Nutritelligent Food Supplements UK Organic Vegan non GMO benefits

“Just a bit of homework we’ve done on your behalf. Get a glimpse of what our selected nutrients in our food supplements are about”

“The Nutritelligent Team”

Vitamins

  • Foods rich in Vitamin A:

    Beef Liver, Sweet Potatoes, Carrots, Spinach, Pumpkin, Cantaloupe, Mango

    PMID: 10637381

    Dawson MI. The importance of vitamin A in nutrition. Curr Pharm Des. 2000 Feb;6(3):311-25. doi: 10.2174/1381612003401190. PMID: 10637381.

    Preformed vitamin A (all-trans-retinol and its esters) and provitamin A (beta-carotene) are essential dietary nutrients that provide a source of retinol. Both retinyl esters and beta-carotene are metabolized to retinol. The retinol-binding proteins on binding retinol provide a means for solubilizing retinol for delivery to target tissues and for regulating retinol plasma concentrations. Oxidation of retinol provides retinal, which is essential for vision, and retinoic acid, a transcription factor ligand that has important roles in regulating genes involved in cell morphogenesis, differentiation, and proliferation. The observations that vitamin A can produce cell and tissue changes similar to those found during neoplastic transformation and that vitamin supplementation can reverse this process indicated a potential role for vitamin A in cancer prevention. Thus far, correlative epidemiological studies on vitamin A use and cancer prevention have produced mixed results, as this review indicates. Apparently, in populations deficient in vitamin A (caused by an inadequate diet or tobacco use), supplementation programs appear to be effective in reducing cancer incidence. In groups already having sufficient dietary or supplemental vitamin A, cancer prevention by added vitamin A may not be particularly effective. The most likely reason for the low efficacy in the latter groups is that feedback mechanisms that increase retinol storage in the liver limit retinol plasma levels; whereas, supplementation at higher doses causes toxicity. In addition to serving as a metabolic source of retinol, beta-carotene, along with other dietary carotenoids, function as antioxidants that can prevent carcinogenesis by decreasing the levels of the free-radicals that cause DNA damage.

  • Foods rich in Vitamin B1:

    Wheat Germ, Flax Seed, Sunflower Seed, Hemp Seed, Pine Nuts, Pistachio Nuts, Asparagus, Lentils, Navy Beans

    PMID: 24399744

    Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride

    The absorption rate and extent of benfotiamine systemic availability of thiamine were significantly increased indicating higher bioavailability of thiamine from oral dose of benfotiamine compared to oral dose of thiamine hydrochloride.

    https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/#en1

    Thiamin (or thiamine) is one of the water-soluble B vitamins. It is also known as vitamin B1. Thiamin is naturally present in some foods, added to some food products, and available as a dietary supplement. This vitamin plays a critical role in energy metabolism and, therefore, in the growth, development, and function of cells.

    Benfotiamine is a synthetic thiamin derivative that is used in some dietary supplements. Benfotiamine is not water soluble and is converted to thiamin in the body.

    A few small randomized studies have assessed the effects of benfotiamine supplements on diabetic neuropathy. Three studies found that, compared to placebo, 120–900 mg/day benfotiamine with or without other B-vitamins decreased the severity of neuropathy symptoms and lowered urinary albumin excretion (a marker of early-stage diabetic nephropathy) [43-45]. However, another study found no effect of 900 mg/day benfotiamine on urinary excretion of albumin or kidney injury molecule-1, a marker of kidney injury [46].

  • Foods rich in Vitamin B2:

    Beef Liver, Mushrooms, Spinach, Almonds, Eggs, Milk, Yogurt, Cheese, Salmon

    PMID: 32023913

    Suwannasom N, Kao I, Pruß A, Georgieva R, Bäumler H. Riboflavin: The Health Benefits of a Forgotten Natural Vitamin. Int J Mol Sci. 2020 Jan 31;21(3):950. doi: 10.3390/ijms21030950. PMID: 32023913; PMCID: PMC7037471.

    Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties.

    PMID: 26780280

    Namazi N, Heshmati J, Tarighat-Esfanjani A. Supplementation with Riboflavin (Vitamin B2) for Migraine Prophylaxis in Adults and Children: A Review. Int J Vitam Nutr Res. 2015;85(1-2):79-87. doi: 10.1024/0300-9831/a000225. PMID: 26780280.

    It seems that riboflavin is a safe and well-tolerated option for preventing migraine symptoms in adults, however, there is insufficient evidence to make recommendations regarding vitamin B2 as an adjunct therapy in adults and children with migraine

  • Foods rich in Vitamin B3

    Liver, Chicken Brest, Tuna, Turkey, Beef, Mushrooms, Brown Rice, Peanuts, Avocados, Green Peas

    PMID: 10540864

    Kobayashi M, Shimizu S. [Nicotinic acid and nicotinamide]. Nihon Rinsho. 1999 Oct;57(10):2211-7. Japanese. PMID: 10540864.

    Nicotinic acid and nicotinamide are called niacin. They are the antipellagra vitamin essential to many animals for growth and health. In human being, niacin is believed necessary together with other vitamins for the prevention and cure of pellagra. Niacin is widely distributed in nature; appreciable amounts are found in liver, fish, yeast and cereal grains. Nicotinamide is a precursor of the coenzyme NAD and NADP. Some of the most understood metabolic processes that involve niacin are glycolysis, fatty acid synthesis and respiration. Niacin is also related to the following diseases: Hartnup disease; blue diaper syndrome; tryptophanuria; hydroxykynureninuria; xanthurenic aciduria; Huntington's disease.

  • Foods Rich in Vitamin B5:

    Beef Liver,Shiitake Mushrooms, Sunflower Seeds, Salmon, Avocadoes, Sweat Potatoes, Lentils, Chicken, Turkey, Yogurt

    PMID: 31691401

    Gheita AA, Gheita TA, Kenawy SA. The potential role of B5: A stitch in time and switch in cytokine. Phytother Res. 2020 Feb;34(2):306-314. doi: 10.1002/ptr.6537. Epub 2019 Nov 5. PMID: 31691401.

    Vitamin B5 (VB5), also known as pantothenate or ""anti-stress vitamin,"" is the precursor of coenzyme A, which is essential in every micro-organism. Many pantothenic acid amides acquire persuasive antimicrobial activity. Pantothenic acid improves surgical wounds healing with moisturizing and skin barrier enhancing potential. Its deficiency leads to reduced cortisol production, increased arthritic pain, myalgia, fatigue, headache, depression, insomnia, and widespread ""proinflammatory"" effects on the immune-system

  • Foods rich in Vitamin B6:

    Skipjack Tuna, Wild Atlantic Salmon, Chicken Breast, Potatoes, Yellowfin Tuna, Beef Liver, Sea Bas, Turkey Breast, Grass-fed Beef, Pistachios, Pinto Beans, Avocado, Blackstrap Molasses, Sunflower Seed, Sesame Seed, Sweat Potatoes, Bananas

    PMID: 20110903

    Hellmann H, Mooney S. Vitamin B6: a molecule for human health? Molecules. 2010 Jan 20;15(1):442-59. doi: 10.3390/molecules15010442. PMID: 20110903; PMCID: PMC6257116.

    Vitamin B6 is an intriguing molecule that is involved in a wide range of metabolic, physiological and developmental processes. Based on its water solubility and high reactivity when phosphorylated, it is a suitable co-factor for many biochemical processes. Furthermore the vitamin is a potent antioxidant, rivaling carotenoids or tocopherols in its ability to quench reactive oxygen species. It is therefore not surprising that the vitamin is essential and unquestionably important for the cellular metabolism and well-being of all living organisms

    PMID: 19145213

    Mooney S, Leuendorf JE, Hendrickson C, Hellmann H. Vitamin B6: a long known compound of surprising complexity. Molecules. 2009 Jan 12;14(1):329-51. doi: 10.3390/molecules14010329. PMID: 19145213; PMCID: PMC6253932.

    In recent years vitamin B6 has become a focus of research describing the compound's critical function in cellular metabolism and stress response. For many years the sole function of vitamin B6 was considered to be that of an enzymatic cofactor. However, recently it became clear that it is also a potent antioxidant that effectively quenches reactive oxygen species and is thus of high importance for cellular well-being

    PMID: 29477221

    Bird RP. The Emerging Role of Vitamin B6 in Inflammation and Carcinogenesis. Adv Food Nutr Res. 2018;83:151-194. doi: 10.1016/bs.afnr.2017.11.004. Epub 2018 Feb 1. PMID: 29477221.

    Vitamin B6 serves as a coenzyme catalyzing more than 150 enzymes regulating metabolism and synthesis of proteins, carbohydrates, lipids, heme, and important bioactive metabolites. For several years vitamin B6 and its vitamers (B6) were recognized as antioxidant and antiinflammatory and in modulating immunity and gene expression. During the last 10 years, there were growing reports implicating B6 in inflammation and inflammation-related chronic illnesses including cancer. It is unclear if the deficiency of B6 or additional intake of B6, above the current requirement, should be the focus. Whether the current recommended daily intake for B6 is adequate should be revisited, since B6 is important to human health beyond its role as a coenzyme and its status is affected by many factors including but not limited to age, obesity, and inflammation associated with chronic illnesses

    PMID: 20089286

    Mooney S, Hellmann H. Vitamin B6: Killing two birds with one stone? Phytochemistry. 2010 Apr;71(5-6):495-501. doi: 10.1016/j.phytochem.2009.12.015. Epub 2010 Jan 19. PMID: 20089286.

    Vitamin B6 comprises a group of compounds that are involved in a surprisingly high diversity of biochemical reactions. Actually, most of these reactions are co-catalyzed by a single B6 vitamer, pyridoxal 5'-phosphate, making it a crucial and versatile co-factor in many metabolic processes in the cell. In addition, it has been demonstrated in recent years that vitamin B6 has a second important function by being an effective antioxidant

  • Foods rich in Vitamin B7:

    Egg Yolks, Legumes, Nut/Seeds, Liver

    PMID: 28628687

    Soleymani T, Lo Sicco K, Shapiro J. The Infatuation With Biotin Supplementation: Is There Truth Behind Its Rising Popularity? A Comparative Analysis of Clinical Efficacy versus Social Popularity. J Drugs Dermatol. 2017 May 1;16(5):496-500. PMID: 28628687.

    Biotin, also known as Vitamin B7 or vitamin H, is a water-soluble B vitamin that acts as an essential cofactor for several carboxylases involved in the cellular metabolism of fatty acids, amino acids, and gluconeogenesis. Although there exists an incredible amount of social media hype and market advertising touting its efficacy for the improvement of hair quantity and quality, biotin's efficacy for hair remains largely unsubstantiated in scientific literature. We reviewed all pertinent scientific literature regarding the efficacy of biotin supplementation for hair growth and quality improvement, and we also investigated its popularity in society defined as a function of market analytics. To date, there have been no clinical trials conducted to investigate the efficacy of biotin supplementation for the treatment of alopecia of any kind, nor has there been any randomized controlled trial to study its effect on hair quality and quantity in human subjects. Because of the lack of clinical evidence, its use to improve hair quantity or quality is not routinely recommended

    PMID: 29057689

    Lipner SR, Scher RK. Biotin for the treatment of nail disease: what is the evidence? J Dermatolog Treat. 2018 Jun;29(4):411-414. doi: 10.1080/09546634.2017.1395799. Epub 2017 Nov 9. PMID: 29057689.

    Clinical trials have shown an improvement in firmness, hardness, and thickness of brittle nails with oral biotin. There are some case reports and series demonstrating that oral biotin may improve triangular worn down nails, trachyonychia, and habit tic nail deformity

  • Foods rich in Vitamin B8:

    Mushrooms,, Milk, Cheese, Whole Wheat Bred, Rice Bran, Peanut Butter, Walnuts, Hazelnuts, Oatmeal, Egg White, Beef Liver, Yogurt, Almonds

    PMID: 36703143

    Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, Park S, Hegyi P, Nyirády P, Ács N, Várbíró S, Horváth EM. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023 Jan 26;21(1):10. doi: 10.1186/s12958-023-01055-z. PMID: 36703143; PMCID: PMC9878965.

    Inositol is an effective and safe treatment in polycystic ovary syndrome

    PMID: 33139672

    Chatree S, Thongmaen N, Tantivejkul K, Sitticharoon C, Vucenik I. Role of Inositols and Inositol Phosphates in Energy Metabolism. Molecules. 2020 Nov 1;25(21):5079. doi: 10.3390/molecules25215079. PMID: 33139672; PMCID: PMC7663797.

    Recently, inositols, especially myo-inositol and inositol hexakisphosphate, also known as phytic acid or IP6, with their biological activities received much attention for their role in multiple health beneficial effects. Although their roles in cancer treatment and prevention have been extensively reported, interestingly, they may also have distinctive properties in energy metabolism and metabolic disorders

    PMID: 27351907

    Bizzarri M, Fuso A, Dinicola S, Cucina A, Bevilacqua A. Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease. Expert Opin Drug Metab Toxicol. 2016 Oct;12(10):1181-96. doi: 10.1080/17425255.2016.1206887. Epub 2016 Jul 14. PMID: 27351907.

    Inositol and its derivatives comprise a huge field of biology. Myo-inositol is not only a prominent component of membrane-incorporated phosphatidylinositol, but participates in its free form, with its isomers or its phosphate derivatives, to a multitude of cellular processes, including ion channel permeability, metabolic homeostasis, mRNA export and translation, cytoskeleton remodeling, stress response

  • Foods rich in Vitamin B9:

    Lentils [Lentils, Chickpeas, Black Eyed Peas], Leafy Greens [Spinach, Kale, Collard Greens] , Asparagus, Eggs, Citrus Fruits

    PMID: 28597528

    Martone G. Enhancement of recovery from mental illness with l-methylfolate supplementation. Perspect Psychiatr Care. 2018 Apr;54(2):331-334. doi: 10.1111/ppc.12227. Epub 2017 Jun 8. PMID: 28597528.

    People suffering from depression, schizophrenia, and dementia often have measurably lower levels of serum folate compared to people not experiencing psychiatric disorders. Augmentation of SSRI and SNRI antidepressant medications with l-methylfolate has been demonstrated to increase their effectiveness and onset of action. Even the use of l-methylfolate as a stand-alone monotherapy has been observed to exert antidepressant properties. The role of folate in mental illness has been known for many decades, but the strategic use of l-methylfolate supplementation has not yet been accepted as a standard regimen

    PMID: 31833826

    Jain R, Manning S, Cutler AJ. Good, better, best: clinical scenarios for the use of L-methylfolate in patients with MDD. CNS Spectr. 2020 Dec;25(6):750-764. doi: 10.1017/S1092852919001469. Epub 2019 Dec 13. PMID: 31833826.

    Depression is among the most prevalent mental disorders worldwide, and a substantial proportion of patients do not respond adequately to standard antidepressants. Our understanding of the pathophysiology of depression is no longer limited to the chemical imbalance of neurotransmitters, but also involves the interplay of proinflammatory modulators in the central nervous system, as well as folate metabolism. Additional factors such as stress and metabolic disorders also may contribute. Multiple inflammatory, metabolic, and genetic markers have been identified and may provide critical information to help clinicians individualize treatments for patients to achieve optimal outcomes. Recent advancements in research have clarified underlying causes of depression and have led to possible new avenues for adjunctive treatment. Among these is L-methylfolate, a medical food that is thought to enhance synthesis of monoamines (serotonin, norepinephrine, and dopamine), suppress inflammation, and promote neural health. Clinical studies that assessed supplemental use of L-methylfolate in patients with usual care-resistant depression found that it resulted in improved outcomes

    PMID: 19193337

    Stahl SM. L-methylfolate: a vitamin for your monoamines. J Clin Psychiatry. 2008 Sep;69(9):1352-3. doi: 10.4088/jcp.v69n0901. PMID: 19193337.

    Synthesis of the monoamine neurotransmitters serotonin, dopamine, and norepinephrine is regulated by L-methylfolate, a derivate of the vitamin folate

    PMID: 28272116

    Siscoe KS, Lohr WD. L-Methylfolate supplementation in a child with autism and methyltetrahydrofolate reductase, enzyme gene C677TT allele. Psychiatr Genet. 2017 Jun;27(3):116-119. doi: 10.1097/YPG.0000000000000170. PMID: 28272116.

    Errors in folate metabolism may play a role in the pathology of autism spectrum disorders because of increased vulnerability to oxidative stress. We report a case where L-methylfolate supplementation improved symptoms of aggression and disruptive behavior in a child with autism who tested positive for the C677TT allele of the methyltetrahydrofolate reductase enzyme gene. To our knowledge, this is the first report of L-methylfolate administration in this situation. Further controlled studies of L-methylfolate in this population are warranted

  • Foods rich in Vitamin B10 [PABA]:

    Liver, Brewer’s Yeast, Whole Grains, Mushrooms, Spinach

    orthomolecular.org

    PABA is the shortened name for para-aminobenzoic acid that is often thought of as only an ingredient used in sunscreens, while it is in actual fact a nutritional ingredient as well. Since it is a moiety of PGA, a form of folic acid, some health professionals do not consider it a vitamin, but only a B-complex factor.

    Para-aminobenzoic acid (PABA), a component of pteroylglutamate, was once considered a vitamin and named vitamin B-x because it serves as a provitamin for some bacteria. Later studies in humans demonstrated that it does not have vitamin activity because humans lack the ability to synthesize folate from PABA. This biochemical is very useful in other ways and has been extensively utilized as a sunscreen in topical lotions to protect the skin from harmful ultraviolet radiation upon exposure to the sun. It is also effective in the treatment of vitiligo, a condition that causes discoloration of the skin.

    PABA is used to improve the protein used in the body. It relates to red blood cell formation, as well as assists in the manufacture of folic acid in the intestines. Para-aminobenzoic acid is used in sunscreen preparations since it can help protect the skin against ultra-violet radiation. It has been linked to hair growth as well as reversing the graying of hair, but these results are disappointing. People suffering from vitiligo, over-pigmentation of skin, or without pigment in some spots, have reported an improvement of the skin after more PABA was ingested. PABA also assists with breaking down of protein, the formation of red blood cells and maintaining intestinal flora.

    When PABA is in short supply fatigue, irritability, nervousness and depression might manifest itself, as well as constipation. Weeping eczema has also been noted in people with PABA deficiency, as well as patchy areas on the skin.

    When higher than factor (SPF) 8 sunscreens are used, the manufacture of vitamin D in the body may be reduced. Nausea, skin rashes and vomiting might be indicative of PABA taken in excess. Excessive levels of PABA are stored in the body and may cause liver damage.

    Long term antibiotic use may require more PABA from the body, but take note of PABA affecting the ability of sulfa drugs. Although not documented in medical terms, some women having problems becoming pregnant claim conceiving after increasing PABA in their diet.

    PABA is found in liver, kidney, brewer's yeast, molasses, whole grains, mushrooms and spinach, and can be made by intestinal bacteria.

  • Foods rich in Vitamin B12:

    Beef Liver, Lamb Liver, Sardines, Beef, Eggs, Milk, Cheese, Yogurt

    PMID: 26024497

    Gille D, Schmid A. Vitamin B12 in meat and dairy products. Nutr Rev. 2015 Feb;73(2):106-15. doi: 10.1093/nutrit/nuu011. PMID: 26024497.

    Vitamin B12 is synthesized exclusively by microorganisms; therefore, humans must absorb it from food. Excellent sources of B12 are foods of ruminant origin, so dairy and meat products play an important role in efforts to meet the official daily B12 intake recommendation of 3.0 μg. Concentrations of the vitamin vary within foods of ruminant origin, with the highest concentrations found in offal such as liver and kidney. In comparison, dairy products have much lower quantities of the vitamin. In bovine milk, the B12 concentration is stable with regard to breed, feed, season, and stage of lactation, but in ruminant meat, the amount of B12 can vary based on the feeding and husbandry of the animal as well as the cut of meat chosen and its preparation

    PMID: 25117994

    Thakkar K, Billa G. Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion. Eur J Clin Nutr. 2015 Jan;69(1):1-2. doi: 10.1038/ejcn.2014.165. Epub 2014 Aug 13. PMID: 25117994.

    Vitamin B12 (cyancobalamin, Cbl) has two active co-enzyme forms, methylcobalamin (MeCbl) and adenosylcobalamin (AdCbl). There has been a paradigm shift in the treatment of vitamin B12 deficiency such that MeCbl is being extensively used and promoted. This is despite the fact that both MeCbl and AdCbl are essential and have distinct metabolic fates and functions. MeCbl is primarily involved along with folate in hematopiesis and development of the brain during childhood. Whereas deficiency of AdCbl disturbs the carbohydrate, fat and amino-acid metabolism, and hence interferes with the formation of myelin. Thereby, it is important to treat vitamin B12 deficiency with a combination of MeCbl and AdCbl or hydroxocobalamin or Cbl. Regarding the route, it has been proved that the oral route is comparable to the intramuscular route for rectifying vitamin B12 deficiency

    PMID: 10448529

    Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr. 1999;19:357-77. doi: 10.1146/annurev.nutr.19.1.357. PMID: 10448529.

    Vitamin B12 deficiency is estimated to affect 10%-15% of people over the age of 60, and the laboratory diagnosis is usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels. Although elderly people with low vitamin B12 status frequently lack the classical signs and symptoms of vitamin B12 deficiency, e.g. megaloblastic anemia, precise evaluation and treatment in this population is important

    PMID: 21462117

    Allen LH. Bioavailability of vitamin B12. Int J Vitam Nutr Res. 2010 Oct;80(4-5):330-5. doi: 10.1024/0300-9831/a000041. PMID: 21462117.

    Vitamin B12 deficiency is common in people of all ages who consume a low intake of animal-source foods, including populations in developing countries. It is also prevalent among the elderly, even in wealthier countries, due to their malabsorption of B12 from food

    PMID: 35053277

    Lauer AA, Grimm HS, Apel B, Golobrodska N, Kruse L, Ratanski E, Schulten N, Schwarze L, Slawik T, Sperlich S, Vohla A, Grimm MOW. Mechanistic Link between Vitamin B12 and Alzheimer's Disease. Biomolecules. 2022 Jan 14;12(1):129. doi: 10.3390/biom12010129. PMID: 35053277; PMCID: PMC8774227.

    Alzheimer's disease (AD) is the most common form of dementia in the elderly population, affecting over 55 million people worldwide. Histopathological hallmarks of this multifactorial disease are an increased plaque burden and tangles in the brains of affected individuals. Several lines of evidence indicate that B12 hypovitaminosis is linked to AD

  • Foods rich in Vitamin C:

    Citrus Fruits, Berries, Papaya, Kiwi, Bell Peppers, Broccoli

    PMID: 26808119

    Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis. 2016 Sep;22(6):463-93. doi: 10.1111/odi.12446. Epub 2016 Apr 14. PMID: 26808119; PMCID: PMC4959991.

    Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids

    PMID: 10969031

    Carr AC, Zhu BZ, Frei B. Potential antiatherogenic mechanisms of ascorbate (vitamin C) and alpha-tocopherol (vitamin E). Circ Res. 2000 Sep 1;87(5):349-54. doi: 10.1161/01.res.87.5.349. PMID: 10969031.

    The premise that oxidative stress, among several other factors, plays an important role in atherogenesis implies that the development and progression of atherosclerosis can be inhibited by antioxidants. In this minireview we discuss several mechanisms by which the antioxidants ascorbate (vitamin C) and alpha-tocopherol (vitamin E) may protect against atherosclerosis. These mechanisms include inhibition of LDL oxidation and inhibition of leukocyte adhesion to the endothelium and vascular endothelial dysfunction. Overall, ascorbate appears to be more effective than alpha-tocopherol in mitigating these pathophysiological processes, most likely as a result of its abilities to effectively scavenge a wide range of reactive oxygen and nitrogen species and to regenerate alpha-tocopherol, and possibly tetrahydrobiopterin, from its radical species. In contrast, alpha-tocopherol can act either as an antioxidant or a pro-oxidant to inhibit or facilitate, respectively, lipid peroxidation in LDL. However, this pro-oxidant activity of alpha-tocopherol is prevented by ascorbate acting as a coantioxidant. Therefore, an optimum vitamin C intake or body status may help protect against atherosclerosis and its clinical sequelae, whereas vitamin E may only be effective in combination with vitamin C

    PMID: 22170049

    Kirkwood JS, Lebold KM, Miranda CL, Wright CL, Miller GW, Tanguay RL, Barton CL, Traber MG, Stevens JF. Vitamin C deficiency activates the purine nucleotide cycle in zebrafish. J Biol Chem. 2012 Feb 3;287(6):3833-41. doi: 10.1074/jbc.M111.316018. Epub 2011 Dec 13. PMID: 22170049; PMCID: PMC3281694.

    Vitamin C (ascorbic acid, AA) is a cofactor for many important enzymatic reactions and a powerful antioxidant. AA provides protection against oxidative stress by acting as a scavenger of reactive oxygen species, either directly or indirectly by recycling of the lipid-soluble antioxidant, α-tocopherol (vitamin E). Only a few species, including humans, guinea pigs, and zebrafish, cannot synthesize AA

    PMID: 31336735

    Tada A, Miura H. The Relationship between Vitamin C and Periodontal Diseases: A Systematic Review. Int J Environ Res Public Health. 2019 Jul 11;16(14):2472. doi: 10.3390/ijerph16142472. PMID: 31336735; PMCID: PMC6678404.

    Vitamin C is important for preventing and slowing the progression of many diseases. There is significant evidence linking periodontal disease and vitamin C. We aimed to systematically review the studies addressing the relationship between vitamin C and periodontal disease, and the preventive ability of vitamin C against periodontal disease

  • Foods rich in Vitamin D3:

    Oily Fish, Egg Yolks, Beef Liver, Mushrooms [sun exposed], don’t forget about the sun…!

    PMID: 28866715

    Stefanowski B, Antosik-Wójcińska AZ, Święcicki Ł. The effect of vitamin D3 deficiency on the severity of depressive symptoms. Overview of current research. Psychiatr Pol. 2017 Jun 18;51(3):437-454. English, Polish. doi: 10.12740/PP/66809. Epub 2017 Jun 18. PMID: 28866715.

    Traditional methods of depression treatment with the use of pharmacotherapy with antidepressants have limited effectiveness. Biological, psychological and environmental causes of depressive disorders are known, but pathophysiology of depression has not been fully explained. Many factors and mechanisms play role in the pathophysiology of depression, one of which may be vitamin D3 deficiency. Deficiency or border level of vitamin D3 is fairly common in the general population and may occur even in one billion people globally. Epidemiological studies show that vitamin D3 or its metabolites do not reach an optimal level in most adults. Even lower than the optimal level may cause clinical symptoms and be one of the risk factors for depression. In the population of patients suffering from depressive disorders deficiency or insufficiency of vitamin D3 occur more frequently than in the general population. The use of vitamin D3in patients with depression may have antidepressant effect. Continuous supplementation may also reduce the risk of recurrence

    PMID: 35630002

    Olszewska-Czyz I, Firkova E. Vitamin D3 Serum Levels in Periodontitis Patients: A Case-Control Study. Medicina (Kaunas). 2022 Apr 24;58(5):585. doi: 10.3390/medicina58050585. PMID: 35630002; PMCID: PMC9145192.

    Periodontitis is a multifactorial disease characterized by bacterial-dysbiosis-associated, host-mediated inflammation, which results in the loss of the tooth-supporting tissues. Vitamin D3 plays an important role in the tissue homeostasis and its deficiency might have a negative effect on the periodontitis progression and treatment outcomes. Objectives: The aim of the study was to evaluate the vitamin D3 serum levels among patients with periodontitis and healthy subjects. Materials and Methods: A total of 100 generally healthy adult participants (50 diagnosed with periodontitis, 50 with healthy periodontium) were enrolled in the study. The periodontal clinical parameters were measured, radiographs were performed and the 25-hydroxy vitamin D (25(OH)D) test was used to assess vitamin D3 levels. Results: Vitamin D3 levels were found to be statistically significantly lower among periodontitis patients (31.34; SD = 5.62) compared with healthy controls (39.64; SD = 8.77). Vitamin D3 deficiency was corresponding to the stage and grade of the disease as well as the clinical attachment and bone loss. Conclusion: Adequate monitoring of the vitamin D3 serum levels and supplementation could be of benefit in periodontitis treatment

    PMID: 23277049

    Di Rosa M, Malaguarnera L, Nicolosi A, Sanfilippo C, Mazzarino C, Pavone P, Berretta M, Cosentino S, Cacopardo B, Pinzone MR, Nunnari G. Vitamin D3: an ever green molecule. Front Biosci (Schol Ed). 2013 Jan 1;5(1):247-60. doi: 10.2741/s370. PMID: 23277049.

    Vitamin D3 is a key regulator of vertebrates homeostasis. It is synthesized from the precursor 7-dehydrocholesterol upon UVB exposure in the skin and then hydrolyzed in the liver in position 25, to be finally converted into its active form, 1,25-dihydroxyvitamin D (1,25(OH)2D or calcitriol), in the kidneys. The biological activity of this molecule depends on its binding to the nuclear receptor VDR, which binds VDRE once complexed with RXR-alpha. Despite being present in different types of food, the best way to assume it at physiological levels remains the exposure to UVB radiation at certain hours of the day and at particular angles of the Earth's crust. There is plenty of evidence that altered levels of vitamin D3 are associated with pathological conditions, such as osteoporosis, cancer, immunological and infectious diseases

    PMID: 36145180

    Mazur A, Koziorowska K, Dynarowicz K, Aebisher D, Bartusik-Aebisher D. Vitamin D and Vitamin D3 Supplementation during Photodynamic Therapy: A Review. Nutrients. 2022 Sep 15;14(18):3805. doi: 10.3390/nu14183805. PMID: 36145180; PMCID: PMC9502525.

    Photodynamic therapy is an unconventional yet increasingly common method of treating dermatological diseases and cancer that is implemented more often in adults than in children. Current clinical uses include treatment of actinic keratosis, superficial basal cell carcinomas, and acne. Despite its high efficiency, photodynamic therapy support supplements have recently been reported in the literature, including calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, and vitamin D3 cholecalciferol. In clinical trials, photodynamic therapy enhanced with vitamin D or D3 supplementation has been reported for treatment of squamous cell skin cancers, actinic keratosis, and psoriasis

  • Foods rich in Vitamin E:

    Wheat Germ Oil, Sunflower seeds, Almonds, Hazelnut Oil, Mamey Sapote, Sunflower Oil, Almond Oil, Hazel Nuts, Abalone, Goose Meat, Peanuts, Atlantic Salmon, Avocado, Rainbow Trout, Red Sweet Pepper [raw], Brazil Nuts, Mango, Turnip Greens [raw], Pine Nuts

    PMID: 17628169

    Mustacich DJ, Bruno RS, Traber MG. Vitamin E. Vitam Horm. 2007;76:1-21. doi: 10.1016/S0083-6729(07)76001-6. PMID: 17628169.

    The term vitamin E is used to describe eight lipophilic, naturally occurring compounds that include four tocopherols and four tocotrienols designated as alpha-, beta-, gamma-, and delta-. The most well-known function of vitamin E is that of a chain-breaking antioxidant that prevents the cyclic propagation of lipid peroxidation. Despite its antioxidant function, dietary vitamin E requirements in humans are limited only to alpha-tocopherol because the other forms of vitamin E are poorly recognized by the hepatic alpha-tocopherol transfer protein (TTP), and they are not converted to alpha-tocopherol by humans.

    PMID: 33324057

    Mohd Zaffarin AS, Ng SF, Ng MH, Hassan H, Alias E. Pharmacology and Pharmacokinetics of Vitamin E: Nanoformulations to Enhance Bioavailability. Int J Nanomedicine. 2020 Dec 8;15:9961-9974. doi: 10.2147/IJN.S276355. PMID: 33324057; PMCID: PMC7733471.

    Vitamin E belongs to the family of lipid-soluble vitamins and can be divided into two groups, tocopherols and tocotrienols, with four isomers (alpha, beta, gamma and delta). Although vitamin E is widely known as a potent antioxidant, studies have also revealed that vitamin E possesses anti-inflammatory properties. These crucial properties of vitamin E are beneficial in various aspects of health, especially in neuroprotection and cardiovascular, skin and bone health

    PMID: 27049072

    Caraffa AL, Varvara G, Spinas E, Kritas SK, Lessiani G, Ronconi G, Saggini A, Antinolfi P, Frydas I, De Tommaso Morrison MC, Conti P. Is vitamin E an anti-allergic compound? J Biol Regul Homeost Agents. 2016 Jan-Mar;30(1):11-5. PMID: 27049072.

    Vitamin E is found in eight forms in nature which include four tocopherols (alpha, beta, gamma and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to reduce and prevent oxygen damage to the tissue and is useful for the treatment of pain, inflammation and allergic reactions. In addition to antioxidant activity, vitamin E also has a number of different and related functions. It protects against cancer, improves immune response, lowers the incidence of infectious diseases, cardiovascular diseases and is protective in allergy and asthma risk, and other disorders. Vitamin E increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect that diminishes asthma and allergic diseases. Moreover, vitamin E regulates vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the endothelial function by altering VCAM-1-induced oxidative activation of endothelial cell PKCα. However, vitamin E is not consistently associated with asthma and/or allergy, and in some cases there are conflicting results on allergy and inflammatory diseases. The association of vitamin E and allergy appears to be very complex, and further study needs to clarify this dilemma

  • Foods rich in Vitamin K:

    Kale, Spinach, Broccoli, Brussels Sprouts, Parsley, Collard Greens, Green Beans

    PMID: 28403946

    Palermo A, Tuccinardi D, D'Onofrio L, Watanabe M, Maggi D, Maurizi AR, Greto V, Buzzetti R, Napoli N, Pozzilli P, Manfrini S. Vitamin K and osteoporosis: Myth or reality? Metabolism. 2017 May;70:57-71. doi: 10.1016/j.metabol.2017.01.032. Epub 2017 Feb 4. PMID: 28403946.

    Vitamin K is a liposoluble vitamin. The predominant dietary form, phylloquinone or vitamin K1, is found in plants and green vegetables; whereas menaquinone, or vitamin K2, is endogenously synthesized by intestinal bacteria and includes several subtypes that differ in side chain length. Aside from its established role in blood clotting, several studies now support a critical function of vitamin K in improving bone health.

    PMID: 27732556

    Fusaro M, Gallieni M, Rizzo MA, Stucchi A, Delanaye P, Cavalier E, Moysés RMA, Jorgetti V, Iervasi G, Giannini S, Fabris F, Aghi A, Sella S, Galli F, Viola V, Plebani M. Vitamin K plasma levels determination in human health. Clin Chem Lab Med. 2017 May 1;55(6):789-799. doi: 10.1515/cclm-2016-0783. PMID: 27732556.

    Vitamin K (phylloquinone or vitamin K1 and menaquinones or vitamin K2) plays an important role as a cofactor in the synthesis of hepatic blood coagulation proteins, but recently has also aroused an increasing interest for its action in extra-hepatic tissues, in particular in the regulation of bone and vascular metabolism

    PMID: 34993998

    Gul S, Maqbool MF, Maryam A, Khan M, Shakir HA, Irfan M, Ara C, Li Y, Ma T. Vitamin K: A novel cancer chemosensitizer. Biotechnol Appl Biochem. 2022 Dec;69(6):2641-2657. doi: 10.1002/bab.2312. Epub 2022 Jan 18. PMID: 34993998.

    Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, cost-effective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy

    PMID: 27437760

    Villa JKD, Diaz MAN, Pizziolo VR, Martino HSD. Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences. Crit Rev Food Sci Nutr. 2017 Dec 12;57(18):3959-3970. doi: 10.1080/10408398.2016.1211616. PMID: 27437760.

    Osteoporosis is a public health concern associated with an increased risk of bone fractures and vascular calcification. Vitamin K presents unique benefits on these issues, although understudied. The two main forms of vitamin K are phylloquinone (vitamin K1) and menaquinone (vitamin K2). In this study, it was especially investigated the action of vitamin K2 in bones and vessels. Vitamin K2 has shown to stimulate bone formation by promoting osteoblast differentiation and carboxylation of osteocalcin, and increasing alkaline phosphatase, insulin-like growth factor-1, growth differentiation factor-15, and stanniocalcin 2 levels. Furthermore, vitamin K2 reduces the pro-apoptotic proteins Fas and Bax in osteoblasts, and decreases osteoclast differentiation by increasing osteoprotegerin and reducing the receptor activator of nuclear factor kappa-B ligand. In blood vessels, vitamin K2 reduces the formation of hydroxyapatite, through the carboxylation of matrix Gla protein and Gla rich protein, inhibits the apoptosis of vascular smooth muscle cells, by increasing growth arrest-specific gene 6, and reduces the transdifferentiation of vascular smooth muscle cells to osteoblasts. The commonly used dosage of vitamin K2 in human studies is 45 mg/day and its application can be an interesting strategy in benefitting bone and vascular health, especially to osteoporotic post-menopausal women

Benefits of Nutritelligent Food Supplement

Nutritelligent nutrients list

Minerals

  • Foods rich in Vitamin Zinc:

    Oysters, Beef, Crab, Lobster, Beans, Nuts, Seeds

    PMID: 25096007

    Muhamed PK, Vadstrup S. [Zinc is the most important trace element]. Ugeskr Laeger. 2014 Mar 3;176(5):V11120654. Danish. PMID: 25096007.

    Zinc is one of the most important trace elements. Zinc deficiency is a major health problem worldwide. Causes of zinc deficiency can be nutritional, iatrogenic, genetic or a result of diseases. Severe zinc deficiency results in symptoms like pustular dermatitis, alopecia, weight loss, diarrhoea, infections secondary to immune dysfunction, hypogonadism and problems in ulcer healing. Zinc supplementation is necessary in cases of zinc deficiency, but high doses zinc supplementation through a long time can result in copper deficiency or anaemia. Thus a rational use of zinc supplementation in the required time is necessary

    PMID: 20141096

    Saper RB, Rash R. Zinc: an essential micronutrient. Am Fam Physician. 2009 May 1;79(9):768-72. PMID: 20141096; PMCID: PMC2820120.

    Zinc is an essential micronutrient for human metabolism that catalyzes more than 100 enzymes, facilitates protein folding, and helps regulate gene expression. Patients with malnutrition, alcoholism, inflammatory bowel disease, and malabsorption syndromes are at an increased risk of zinc deficiency. Symptoms of zinc deficiency are nonspecific, including growth retardation, diarrhea, alopecia, glossitis, nail dystrophy, decreased immunity, and hypogonadism in males. In developing countries, zinc supplementation may be effective for the prevention of upper respiratory infection and diarrhea, and as an adjunct treatment for diarrhea in malnourished children

    PMID: 11115789

    Rink L, Gabriel P. Zinc and the immune system. Proc Nutr Soc. 2000 Nov;59(4):541-52. doi: 10.1017/s0029665100000781. PMID: 11115789.

    Zn is an essential trace element for all organisms. In human subjects body growth and development is strictly dependent on Zn. The nervous, reproductive and immune systems are particularly influenced by Zn deficiency, as well as by increased levels of Zn. The relationship between Zn and the immune system is complex, since there are four different types of influence associated with Zn. (1) The dietary intake and the resorption of Zn depends on the composition of the diet and also on age and disease status. (2) Zn is a cofactor in more than 300 enzymes influencing various organ functions having a secondary effect on the immune system. (3) Direct effects of Zn on the production, maturation and function of leucocytes. (4) Zn influences the function of immunostimulants used in the experimental systems

    PMID: 34160751

    Wen S, Li Y, Shen X, Wang Z, Zhang K, Zhang J, Mei X. Protective Effects of Zinc on Spinal Cord Injury. J Mol Neurosci. 2021 Dec;71(12):2433-2440. doi: 10.1007/s12031-021-01859-x. Epub 2021 Jun 23. PMID: 34160751.

    Spinal cord injury is a serious disease of the central nervous system, but there is no effective treatment. And zinc is an essential nutrient for human body and participates in many physiological processes, such as immune response, homeostasis, oxidative stress, cell cycle progression, DNA replication, DNA damage repair, apoptosis, and aging. This article mainly summarizes that zinc could predict the prognosis and treat the spinal cord injury. Especially, zinc could help to inhibit inflammation, regulate autophagy, and reduce oxidative stress. However, excessive zinc will damage neurons

  • Foods rich in Magnesium:

    Pumpkin Seeds, Spinach, Almonds, Cashews, Peanuts, Soy Milk, Rolled Oats, Dark Chocolate

    PMID: 19621856

    Guerrera MP, Volpe SL, Mao JJ. Therapeutic uses of magnesium. Am Fam Physician. 2009 Jul 15;80(2):157-62. PMID: 19621856.

    Magnesium is an essential mineral for optimal metabolic function. Research has shown that the mineral content of magnesium in food sources is declining, and that magnesium depletion has been detected in persons with some chronic diseases. This has led to an increased awareness of proper magnesium intake and its potential therapeutic role in a number of medical conditions. Studies have shown the effectiveness of magnesium in eclampsia and preeclampsia, arrhythmia, severe asthma, and migraine. Other areas that have shown promising results include lowering the risk of metabolic syndrome, improving glucose and insulin metabolism, relieving symptoms of dysmenorrhea, and alleviating leg cramps in women who are pregnant. The use of magnesium for constipation and dyspepsia are accepted as standard care despite limited evidence. Although it is safe in selected patients at appropriate dosages, magnesium may cause adverse effects or death at high dosages. Because magnesium is excreted renally, it should be used with caution in patients with kidney disease. Food sources of magnesium include green leafy vegetables, nuts, legumes, and whole grains

    PMID: 23674807

    Volpe SL. Magnesium in disease prevention and overall health. Adv Nutr. 2013 May 1;4(3):378S-83S. doi: 10.3945/an.112.003483. PMID: 23674807; PMCID: PMC3650510.

    Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation and has been recognized as a cofactor for >300 metabolic reactions in the body. Some of the processes in which magnesium is a cofactor include, but are not limited to, protein synthesis, cellular energy production and storage, reproduction, DNA and RNA synthesis, and stabilizing mitochondrial membranes. Magnesium also plays a critical role in nerve transmission, cardiac excitability, neuromuscular conduction, muscular contraction, vasomotor tone, blood pressure, and glucose and insulin metabolism. Because of magnesium's many functions within the body, it plays a major role in disease prevention and overall health. Low levels of magnesium have been associated with a number of chronic diseases including migraine headaches, Alzheimer's disease, cerebrovascular accident (stroke), hypertension, cardiovascular disease, and type 2 diabetes mellitus. Good food sources of magnesium include unrefined (whole) grains, spinach, nuts, legumes, and white potatoes (tubers)

    PMID: 33959846

    Rondanelli M, Faliva MA, Tartara A, Gasparri C, Perna S, Infantino V, Riva A, Petrangolini G, Peroni G. An update on magnesium and bone health. Biometals. 2021 Aug;34(4):715-736. doi: 10.1007/s10534-021-00305-0. Epub 2021 May 6. PMID: 33959846; PMCID: PMC8313472.

    In 2009 EFSA Panel concludes that a cause and effect relationship has been established between the dietary intake of magnesium (Mg) and maintenance of normal bone. After 2009, numerous studies have been published, but no reviews have made an update on this topic. So, the aim of this narrative review was to consider the state of the art since 2009 on relationship between Mg blood levels, Mg dietary intake and Mg dietary supplementation (alone or with other micronutrients; this last topic has been considered since 1990, because it is not included in the EFSA claims) and bone health in humans. This review included 28 eligible studies: nine studies concern Mg blood, 12 studies concern Mg intake and seven studies concern Mg supplementation, alone or in combination with other nutrients. From the various studies carried out on the serum concentration of Mg and its relationship with the bone, it has been shown that lower values are related to the presence of osteoporosis, and that about 30-40% of the subjects analyzed (mainly menopausal women) have hypomagnesaemia. Various dietetic investigations have shown that many people (about 20%) constantly consume lower quantities of Mg than recommended; moreover, in this category, a lower bone mineral density and a higher fracturing risk have been found. Considering the intervention studies published to date on supplementation with Mg, most have used this mineral in the form of citrate, carbonate or oxide, with a dosage varying between 250 and 1800 mg. In all studies there was a benefit both in terms of bone mineral density and fracture risk

  • Foods rich in Selenium:

    Brazil Nuts, Fish [Tuna, Sardines, Oysters, Clams, Halibut, Shrimp, Salmon, Crab], Beef [including liver], Turkey, Chicken, Eggs

    PMID: 27731835

    Baltaci AK, Mogulkoc R, Akil M, Bicer M. Review - Selenium - Its metabolism and relation to exercise. Pak J Pharm Sci. 2016 Sep;29(5):1719-1725. PMID: 27731835.

    Selenium (Se), which is commonly found in nature, is one of the essential trace elements necessary for the normal development of human and animal organisms. Selenium was first defined in 1818 by the Swedish chemist Berzelius in sulfuric acid residues. At the end of 1960s, the role of selenium in human health began to attract attention and human diseases that resembled animal diseases responding to selenium was started to be investigated. Selenium, which is highly important for human health, is necessary for a variety of metabolic processes, including thyroid hormone metabolism, protection against oxidative stress and immunity functions. Selenium is a molecule that activates glutathione peroxidase, and thus, it is involved in the antioxidant mechanisms that prevent oxidant damage. Exhaustive physical exercise is known to cause oxidant damage, probably by promoting free radical production in many tissues, including muscle, liver, heart and lungs in animals. The increase in oxidative stress during exercise and recognition of selenium's stimulation of antioxidant activity inevitably suggest a relation between selenium and exercise

    PMID: 7478310

    Sanz Alaejos M, Diaz Romero C. Selenium in human lactation. Nutr Rev. 1995 Jun;53(6):159-66. doi: 10.1111/j.1753-4887.1995.tb01543.x. PMID: 7478310.

    The primary factor determining selenium concentration in human milk is the maternal selenium intake. A significant correlation between selenium in human milk and maternal selenium intake has been reviewed in papers from different regions of the world. Infants fed human milk have higher selenium intake than those fed commercially available formula milk or baby foods. Selenium compounds found in breast milk seem to be more biologically available for infant nutrition than those in formulas. Increased requirements of selenium have been observed in pregnant and lactating women. Supplementation of lactating and pregnant women with different selenium compounds has been assayed, and selenium supplementation of soil and cows has been used to increase the selenium status of children fed infant formula made from cow's milk

    PMID: 19325522

    Zeng H. Selenium as an essential micronutrient: roles in cell cycle and apoptosis. Molecules. 2009 Mar 23;14(3):1263-78. doi: 10.3390/molecules14031263. PMID: 19325522; PMCID: PMC6253990.

    Selenium is an essential trace element for humans and animals, and selenium deficiency is associated with several disease conditions such as immune impairment. In addition, selenium intakes that are greater than the recommended daily allowance (RDA) appear to protect against certain types of cancers. In humans and animals, cell proliferation and death must be regulated to maintain tissue homeostasis, and it has been well documented that numerous human diseases are directly related to the control of cell cycle progression and apoptosis

  • Foods rich in Boron:

    Prunes, Avocados, Raisins, Peaches, Grapes, Apples, Pears, Peanuts, Beans [Lentils, Legumes]

    PMID: 18366532

    Nielsen FH. Is boron nutritionally relevant? Nutr Rev. 2008 Apr;66(4):183-91. doi: 10.1111/j.1753-4887.2008.00023.x. PMID: 18366532.

    Evidence from numerous laboratories using a variety of experimental models, including humans, shows that boron is a bioactive beneficial element. Much evidence has come from studies that did not require nutritional or environmental stressors or fastidious methods in diet preparation or environmental control. The evidence includes deprivation studies showing that boron is necessary for some higher animals to complete the life cycle, and that realistic low boron intakes result in impaired bone health, brain function, and immune response. Thus, low boron intake is a relevant nutritional concern, which diets rich in fruits, vegetables, nuts, and pulses can prevent

    PMID: 26770156

    Pizzorno L. Nothing Boring About Boron. Integr Med (Encinitas). 2015 Aug;14(4):35-48. PMID: 26770156; PMCID: PMC4712861.

    The trace mineral boron is a micronutrient with diverse and vitally important roles in metabolism that render it necessary for plant, animal, and human health, and as recent research suggests, possibly for the evolution of life on Earth. As the current article shows, boron has been proven to be an important trace mineral because it (1) is essential for the growth and maintenance of bone; (2) greatly improves wound healing; (3) beneficially impacts the body's use of estrogen, testosterone, and vitamin D; (4) boosts magnesium absorption; (5) reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α); (6) raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase; (7) protects against pesticide-induced oxidative stress and heavy-metal toxicity; (8) improves the brains electrical activity, cognitive performance, and short-term memory for elders; (9) influences the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD(+)); (10) has demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin's lymphoma; and (11) may help ameliorate the adverse effects of traditional chemotherapeutic agents

  • Foods rich in Molybdenum:

    Legumes [Beans, Lentils, Peas, Soybeans], Peanuts, Grains [Oats, Wheat, Rice, Quinoa, Buckwheat], Organ Meat [Liver, Kidney, Heart],Dairy [Milk, Yogurt, Cheese], Potatoes, Banana’s

    "34864981

    Molybdenum (Mo) is an essential element for almost all living organisms. After being taken up into the cells as molybdate, it is incorporated into the molybdenum cofactor, which functions as the active site of several molybdenum-requiring enzymes and thus plays crucial roles in multiple biological processes

    PMID: 9891606

    Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med. 1998 Dec;18(4):673-85. PMID: 9891606.

    Copper, zinc, selenium, and molybdenum are involved in many biochemical processes supporting life. The most important of these processes are cellular respiration, cellular utilization of oxygen, DNA and RNA reproduction, maintenance of cell membrane integrity, and sequestration of free radicals. Copper, zinc, and selenium are involved in destruction of free radicals through cascading enzyme systems. Superoxide radicals are reduced to hydrogen peroxide by superoxide dismutases in the presence of copper and zinc cofactors. Hydrogen peroxide is then reduced to water by the selenium-glutathione peroxidase couple. Efficient removal of these superoxide free radicals maintains the integrity of membranes, reduces the risk of cancer, and slows the aging process. On the other hand, excess intake of these trace elements leads to disease and toxicity; therefore, a fine balance is essential for health. Trace element--deficient patients usually present with common symptoms such as malaise, loss of appetite, anemia, infection, skin lesions, and low-grade neuropathy, thus complicating the diagnosis. Symptoms for intoxication by trace elements are general, for example, flu-like and CNS symptoms, fever, coughing, nausea, vomiting, diarrhea, anemia, and neuropathy

    PMID: 1757880

    Neve J. Importance nutritionnelle et physiopathologie du molybdène chez l'homme [The nutritional importance and physiopathology of molybdenum in man]. J Pharm Belg. 1991 May-Jun;46(3):189-96. French. PMID: 1757880.

    Molybdenum is an essential trace element taking part in the active site of three human enzymes: xanthine oxidase, aldehyde oxidase and sulfite oxidase, playing a role in the detoxification of the organism and/or the production of important intermediary products. The perturbation of the first two enzymes has no established clinical consequence, but a decrease in activity of the third one is harmful for the organism, particularly the nervous system during pre- or post-natal development. The anomalies in the function of these enzymes are generally inherited and linked to the impaired production of the molybdenum cofactor, an organic molecule complexed to the element in the active site. However, several pathological cases in animals and one case in man have been clearly attributed to molybdenum deficiency. It is the reason why molybdenum supplementation has been recommended in long term total parenteral nutrition in infants and adults

  • Foods rich in Chromium:

    Grapes, Whole Wheat Flour, Brewer’s Yeast, Broccoli, Oats, Sweet Potato, Turkey, Eggs

    PMID: 22192535

    Wise SS, Wise JP Sr. Chromium and genomic stability. Mutat Res. 2012 May 1;733(1-2):78-82. doi: 10.1016/j.mrfmmm.2011.12.002. Epub 2011 Dec 13. PMID: 22192535; PMCID: PMC4138963.

    Many metals serve as micronutrients which protect against genomic instability. Chromium is most abundant in its trivalent and hexavalent forms. Trivalent chromium has historically been considered an essential element, though recent data indicate that while it can have pharmacological effects and value, it is not essential. There is no data indicating that trivalent chromium promotes genomic stability and, instead may promote genomic instability. Hexavalent chromium is widely accepted as highly toxic and carcinogenic with no nutritional value. Recent data indicate that it causes genomic instability and also has no role in promoting genomic stability

    PMID: 10500510

    Porter DJ, Raymond LW, Anastasio GD. Chromium: friend or foe? Arch Fam Med. 1999 Sep-Oct;8(5):386-90. doi: 10.1001/archfami.8.5.386. PMID: 10500510.

    Chromium is an essential nutrient with many natural sources, but several investigators have presented evidence that healthy persons often have an inadequate intake of this metal. Advocates of its use as a dietary supplement believe that people with diabetes, lipoprotein abnormalities, and increased risk of cardiovascular disease may benefit from such supplementation. Others suggest a therapeutic role for chromium in obese people and in those who seek to improve their body composition for other reasons, but research provides little support for these uses. For the general public, current data do not warrant routine use of chromium supplements, whose risk-benefit function has not yet been adequately characterized

    PMID: 14983576

    Kleefstra N, Bilo HJ, Bakker SJ, Houweling ST. Chroom en insulineresistentie [Chromium and insulin resistance]. Ned Tijdschr Geneeskd. 2004 Jan 31;148(5):217-20. Dutch. PMID: 14983576.

    Since as early as the 50s of the last century, it has been known that chromium is essential for normal glucose metabolism. Too little chromium in the diet may lead to insulin resistance. However, there is still no standard against which chromium deficiency can be established. Nevertheless, chromium supplements are becoming increasingly popular. Various systematic reviews have been unable to demonstrate any effects of chromium on glycaemic regulation (possibly due partly to the low dosages used), but there is a slight reduction in body weight averaging 1 kg. In a double-blind randomised placebo-controlled trial in a Chinese population with type-2 diabetes mellitus, supplementation with 1000 micrograms of chromium led to a fall in the glycosylated haemoglobin level (HbA1c) by 2%. Toxic effects of chromium are seldom seen; recently, however, the safety of one of the dosage forms of chromium, chromium picolinate, has been questioned. One should be aware that individual patients with type-2 diabetes mellitus may have an increased risk of hypoglycaemic episodes when taking chromium supplements as self-medication

    PMID: 9562138

    Cerulli J, Grabe DW, Gauthier I, Malone M, McGoldrick MD. Chromium picolinate toxicity. Ann Pharmacother. 1998 Apr;32(4):428-31. doi: 10.1345/aph.17327. PMID: 9562138.

    A 33-year-old white woman presented with weight loss, anemia, thrombocytopenia, hemolysis, liver dysfunction (aminotransferase enzymes 15-20 times normal, total bilirubin 3 times normal), and renal failure (serum creatinine 5.3 mg/dL; blood urea nitrogen 152 mg/dL). She had ingested chromium picolinate 1200-2400 microg/d for the previous 4-5 months to enhance weight loss. The patient had chromium plasma concentrations 2-3 times normal. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome were ruled out by clinical findings, peripheral blood smears, and a bone marrow biopsy. The patient was managed with supportive measures and received blood product transfusions and hemodialysis. Hemolysis stabilized and liver function improved over 6 days. Liver function returned to normal prior to discharge. Renal function began to return on day 12 and her serum creatinine on discharge was 1.3 mg/dL. One year later, all laboratory values were within normal limits

    PMID: 30513859

    Willoughby D, Hewlings S, Kalman D. Body Composition Changes in Weight Loss: Strategies and Supplementation for Maintaining Lean Body Mass, a Brief Review. Nutrients. 2018 Dec 3;10(12):1876. doi: 10.3390/nu10121876. PMID: 30513859; PMCID: PMC6315740.

    With over two-thirds (71.6%) of the US adult population either overweight or obese, many strategies have been suggested for weight loss. While many are successful, the weight loss is often accompanied by a loss in lean body mass. This loss in lean body mass has multiple negative health implications. Therefore, weight loss strategies that protect lean body mass are of value. It is challenging to consume a significant caloric deficit while maintaining lean body mass regardless of macronutrient distribution. Therefore, the efficacy of various dietary supplements on body weight and body composition have been a topic of research interest. Chromium picolinate has been shown to improve body composition by maintaining lean body mass. In this paper we review some common weight loss strategies and dietary supplements with a focus on their impact on body composition and compare them to the effect of chromium picolinate

  • Foods rich in Iodine:

    Seaweed, Cod, Dairy [Milk, Cheese, Yogurt], Eggs, Beans [Navy Beans, Lima Beans, Soy Beans], Prunes, Bananas, Strawberries

    PMID: 2670299

    Delange F, Bürgi H. Iodine deficiency disorders in Europe. Bull World Health Organ. 1989;67(3):317-25. PMID: 2670299; PMCID: PMC2491245.

    Recent data on iodine excretion in the urine of adults, adolescents and newborns and on the iodine content of breast milk indicate a high prevalence of iodine deficiency (moderate in many cases and severe in a few) in many European countries. These cases may manifest as subclinical hypothyroidism in neonates and as goitre in adolescents and adults. Lack of iodine causes not only goitre, but also mental deficiency, hearing loss and other neurological impairments, and short stature due to thyroid insufficiency during fetal development and childhood. Although iodinated salt is available theoretically in most countries where it is needed, its quality and share of the market are often unsatisfactory. In many countries where only household salt is iodinated the iodine content has been set too low owing to an overestimation of household salt consumption. Governments are therefore urged to pass legislation and provide means for efficient iodination of salt wherever this is necessary

    PMID: 8748212

    Ali O. Iodine deficiency disorders: a public health challenge in developing countries. Nutrition. 1995 Sep-Oct;11(5 Suppl):517-20. PMID: 8748212.

    Iodine as a trace element is an essential nutrient for human growth and development. Its potential impact on manpower development in third world countries are of special concern, primarily due to iodine deficiency disorders (IDD) such as goiter, hypothyroidism, and cretinism. IDD of mild to moderate severity are still found in Malaysia. The prevalence ranges from almost zero in many developed urban areas to more than 90% in some rural parts of Malaysia, especially in Sabah and Sarawak. The endemias were associated with low urinary excretion of iodine among the population, indicating poor iodine intake and low iodine content in the environment. Water and salt iodination strategies are being planned to eradicate the disease by the year 2000

    PMID: 8427204

    Pharoah PO. Iodine-supplementation trials. Am J Clin Nutr. 1993 Feb;57(2 Suppl):276S-279S. doi: 10.1093/ajcn/57.2.276S. PMID: 8427204.

    Iodine deficiency as a major determinant of endemic goiter has been recognized for several decades. The evidence is also strong that iodine supplementation is effective in preventing both varieties of endemic cretinism, provided it is given before conception; early fetal and infant death may also be prevented. However, the reason for the variation in prevalence of the different types of cretinism is still a matter of conjecture. Iodine supplementation may improve motor and cognitive performance, but the evidence needs to be evaluated in light of the difficulty in transposing tests of intellectual and motor ability developed in one culture to another very different one

    PMID: 31776808

    Delshad H, Azizi F. Iodine nutrition in pregnant and breastfeeding women: sufficiency, deficiency, and supplementation. Hormones (Athens). 2020 Jun;19(2):179-186. doi: 10.1007/s42000-019-00160-2. Epub 2019 Nov 27. PMID: 31776808.

    Iodine is a micronutrient used by the thyroid gland to produce thyroid hormones, which manage different aspects of body metabolism. Humans depend on exogenous sources of iodine to maintain the normal concentration of thyroid hormones. Pregnancy alters iodine turnover and is associated with significant changes in thyroid function. Daily iodine requirement during pregnancy increases to 250 μg, compared with 150 μg for nonpregnant women. According to recent guidelines of scientific organizations, to improve maternal thyroid status and to prevent child neurocognitive defects, all pregnant and breastfeeding women should take 150 μg of iodine supplementation, not only in iodine-deficient regions but also in iodine-sufficient areas. However, some recent studies have confirmed that iodine supplementation of mildly iodine-deficient pregnant women has no clear benefits as concerns maternal thyroid function or child neurodevelopment

  • Foods rich in Manganese:

    Nuts and Seeds, Whole Grains [Brown Rice, Oats, Quinoa, Buckwheat, Millet], Legumes [Black-eyed Peas, Soybeans, Chickpeas, Lentils, Kidney Beans], Leafy Green Vegetables [Spinach, Kales, Collard Greens, Swiss Chard, Turnip Greens], Fruits [Pineapples, Blackberries, Raspberries, Strawberries, Bananas, Kiwis]

    PMID: 30855111

    Erikson KM, Aschner M. Manganese: Its Role in Disease and Health. Met Ions Life Sci. 2019 Jan 14;19:/books/9783110527872/9783110527872-016/9783110527872-016.xml. doi: 10.1515/9783110527872-016. PMID: 30855111.

    Manganese is an essential dietary element that functions primarily as a coenzyme in several biological processes. These processes include, but are not limited to, macronutrient metabolism, bone formation, free radical defense systems, and in the brain, ammonia clearance and neurotransmitter synthesis. It is a critical component in dozens of proteins and enzymes, and is found in all tissues. Concentrated levels of Mn are found in tissues rich in mitochondria and melanin, with both, liver, and pancreas having the highest concentrations under normal conditions. However, overexposure to environmental Mn via industrial occupation or contaminated drinking water can lead to toxic brain Mn accumulation that has been associated with neurological impairment

    PMID: 25974698

    Horning KJ, Caito SW, Tipps KG, Bowman AB, Aschner M. Manganese Is Essential for Neuronal Health. Annu Rev Nutr. 2015;35:71-108. doi: 10.1146/annurev-nutr-071714-034419. Epub 2015 May 13. PMID: 25974698; PMCID: PMC6525788.

    The understanding of manganese (Mn) biology, in particular its cellular regulation and role in neurological disease, is an area of expanding interest. Mn is an essential micronutrient that is required for the activity of a diverse set of enzymatic proteins (e.g., arginase and glutamine synthase). Although necessary for life, Mn is toxic in excess. Thus, maintaining appropriate levels of intracellular Mn is critical. Unlike other essential metals, cell-level homeostatic mechanisms of Mn have not been identified

    PMID: 35121412

    Studer JM, Schweer WP, Gabler NK, Ross JW. Functions of manganese in reproduction. Anim Reprod Sci. 2022 Mar;238:106924. doi: 10.1016/j.anireprosci.2022.106924. Epub 2022 Jan 18. PMID: 35121412.

    Manganese (Mn) is the twelfth most abundant element in the earth's crust and is widely distributed throughout the surface of the planet, naturally occurring in rocks, soil, water, and food. As an essential trace mineral in diets, Mn is required for a variety of metabolic functions including skeletal system development, energy metabolism, enzyme activation, nervous system function, immune system function, and reproductive hormone function. Manganese has effects on reproductive hormone function as a cofactor for enzymes necessary for cholesterol synthesis. Production of steroid hormones necessary for reproduction is dependent on the availability of cholesterol as a precursor. There is also evidence that Mn has effects on reproduction due to actions at the hypothalamus. Because Mn is used for manufacturing of steel, recent research has focused on the effects of Mn toxicity as a result of occupational endeavors rather than evaluating the optimal Mn inclusion rate for mammalian growth and development, reproductive function, immune function, etc.

    PMID: 32298096

    Martins AC, Krum BN, Queirós L, Tinkov AA, Skalny AV, Bowman AB, Aschner M. Manganese in the Diet: Bioaccessibility, Adequate Intake, and Neurotoxicological Effects. J Agric Food Chem. 2020 Nov 18;68(46):12893-12903. doi: 10.1021/acs.jafc.0c00641. Epub 2020 Apr 29. PMID: 32298096.

    Manganese (Mn) is an essential element that participates in several biological processes. Mn serves as a cofactor for several enzymes, such as glutamine synthetase and oxidoreductases, that have an important role in the defense of the organisms against oxidative stress. The diet is the main source of Mn intake for humans, and adequate daily intake levels for this metal change with age. Moreover, in higher amounts, Mn may be toxic, mainly to the brain

  • Foods rich in Potassium:

    Avocados, Sweet Potatoes, Spinach, Apricots, Oranges, Coconut Water, Beans, Lentils, Nuts, Seeds, Tomatoes, Potatoes, Broccoli, Mushrooms, Fish, Dairy

    PMID: 34112360

    McLean RM, Wang NX. Potassium. Adv Food Nutr Res. 2021;96:89-121. doi: 10.1016/bs.afnr.2021.02.013. Epub 2021 May 24. PMID: 34112360.

    Potassium is an essential nutrient that performs a vital role in cellular functions including maintaining fluid balance and osmolality of cells. Potassium balance is maintained by the kidney and the majority of ingested potassium is excreted in the urine. There is strong evidence of a negative association between dietary potassium and blood pressure, and some evidence (much of it indirect) of negative associations between dietary potassium and cardiovascular disease (particularly stroke and coronary heart disease) and kidney disease (chronic renal failure, and kidney stones). Blood pressure lowering is particularly associated with high potassium and low sodium diets. Important dietary sources of potassium include fruit and vegetables (including rice, potatoes, legumes and wholegrains), dairy products, and animal proteins. Worldwide, diets are low in potassium compared to dietary guidelines. Interventions focused on increasing dietary potassium will have major benefits including improvements in diet, reducing non-communicable disease and enhancing planetary health

    PMID: 30478476

    Goldfarb DS. Empiric therapy for kidney stones. Urolithiasis. 2019 Feb;47(1):107-113. doi: 10.1007/s00240-018-1090-6. Epub 2018 Nov 26. PMID: 30478476; PMCID: PMC6361718.

    Careful phenotyping of patients to classify those with kidney stones has a long and important history in revealing the chemical basis for stone formation. Advances in our genetic understanding of kidney stones will lead to incredible insights regarding the pathophysiology of this common disorder. At this time, both evaluation of urine chemistry and genotyping of patients are extremely useful in the setting of a university and research-based kidney stone clinic. For much of the world, in a more clinically focused setting, these techniques are neither available nor absolutely necessary. Careful implementation of an empiric prescription based on stone composition would have an important effect to reduce stone recurrence in the world's many stone formers. Increased fluid intake, generic dietary manipulations, and prescription of potassium citrate and thiazides are all appropriate empiric therapies for people with calcium and uric acid kidney stones

    PMID: 33391747

    Wiegand A, Fischer G, Seeger H, Fuster D, Dhayat N, Bonny O, Ernandez T, Kim MJ, Wagner CA, Mohebbi N. Impact of potassium citrate on urinary risk profile, glucose and lipid metabolism of kidney stone formers in Switzerland. Clin Kidney J. 2019 Aug 19;13(6):1037-1048. doi: 10.1093/ckj/sfz098. PMID: 33391747; PMCID: PMC7769539.

    Background: Hypocitraturia and hypercalciuria are the most prevalent risk factors in kidney stone formers (KSFs). Citrate supplementation has been introduced for metaphylaxis in KSFs. However, beyond its effects on urinary parameters and stone recurrence, only a few studies have investigated the impact of citrate on other metabolic pathways such as glucose or lipid metabolism.

    Methods: We performed an observational study using data from the Swiss Kidney Stone Cohort. Patients were subdivided into two groups based on treatment with potassium citrate or not. The outcomes were changes of urinary risk parameters, haemoglobin A1c (HbA1c), fasting glucose, cholesterol and body mass index (BMI).

    Results: Hypocitraturia was present in 19.3% of 428 KSFs and potassium citrate was administered to 43 patients (10.0%) at a mean dosage of 3819 ± 1796 mg/day (corresponding to 12.5 ± 5.9 mmol/ day). Treatment with potassium citrate was associated with a significantly higher mean change in urinary citrate (P = 0.010) and urinary magnesium (P = 0.020) compared with no potassium citrate treatment. Exogenous citrate administration had no effect on cholesterol, fasting glucose, HbA1c and BMI. Multiple linear regression analysis demonstrated no significant association of 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] levels with urinary citrate excretion.

    Conclusion: Potassium citrate supplementation in KSFs in Switzerland resulted in a beneficial change of the urinary risk profile by particularly increasing anti-lithogenic factors. Fasting glucose, HbA1c, cholesterol levels and BMI were unaffected by potassium citrate therapy after 3 months, suggesting that potassium citrate is safe and not associated with unfavourable metabolic side effects. Lastly, 1,25(OH)2 D3 levels were not associated with urinary citrate excretion

    PMID: 31266277

    Cicerello E, Ciaccia M, Cova G, Mangano M. The impact of potassium citrate therapy in the natural course of Medullary Sponge Kidney with associated nephrolithiasis. Arch Ital Urol Androl. 2019 Jul 2;91(2). doi: 10.4081/aiua.2019.2.102. PMID: 31266277.

    Objectives: The present study was carried out to evaluate the effectiveness of medical therapy with potassium citrate in preventing calculosis complicating Medullary Sponge Kidney (MSK) without renal acidification defects.

    Materials and methods: In a open, uncontrolled, retrospective analysis, 49 MSK patients with nephrolithiasis without renal tubular acidosis, underwent a complete metabolic evaluation and received potassium citrate therapy 4-6 g/day. The course of stone disease before and after citrate therapy was determined in each patient from a combination of clinical history, past records, radiographs and kidney ultrasound. The rate of new stone formation/pt/yr, of endourological and extracorporeal procedures, of urinary tract infection (UTI) and number of hospitalization before and after medical treatment were calculated.

    Results: Metabolic anomalies (hypercalciuria, hypocitraturia, hyperuricuria and hyperoxaluria) were present in 83% of the patients. Follow-up before and after alkali citrate therapy was comparable (4.7+/-1.4 and 4.9+/-1.7 years respectively). Medical treatment significantly reduced rates of stone formation from 2.0+/-1.0 to 0.2+/-0.5 pt/yr, ureteroscopy (URS) from 0.9+/0.8 to 0.4+/-0.5 pt/yr, extratracoporeal lithotripsy (ESWL) from 1.1+/-0.8 to 0.4+/-0.6 pt/yr, urinary tract infections (UTIs) from 0.8+/-1.2 to 0.3+/-0.5 pt/yr and hospitalization from 1.1+/-0.6 to 0.2+/-0.3 pt/yr, p < 0.001. This effect was observed also in MSK patients without metabolic anomalies. In 35 patients the asymptomatic disappearance of calcium stones was also observed.

    Conclusions: Our study documents the effectiveness of potassium citrate therapy in preventing neprolithiasis in MSK patients also in the absence of distal tubular acidosis. It suggests that in MSK patients alkali citrate may promote calcium stone dissolution by oral administration

    PMID: 33397057

    Uçar M, Akkoc A, Topcuoglu M, Ozturk SA, Demir M. The Effect of Potassium Citrate on Overactive Bladder Disease: A Cross-sectional Study. J Coll Physicians Surg Pak. 2020 Dec;30(12):1301-1305. doi: 10.29271/jcpsp.2020.12.1301. PMID: 33397057.

    Objective: To show the effect of potassium citrate treatment on overactive bladder disease in patients with kidney stone and overactive bladder symptoms.

    Study design: Experimental study.

    Place and duration of study: Department of Urology, Alanya Alaaddin Keykubat University and Department of Urology, Süleyman Demirel University, Turkey, from October 2019 to July 2020.

    Methodology: Patients with an indication for starting potassium citrate therapy because of kidney stone, and patients with symptoms of overactive bladder disease were included in the study. At the beginning of the treatment, the overactive bladder-version 8 form was filled and potassium citrate 10 meq 2x2 dose was started to the patients. The effect of potassium citrate on the symptoms of overactive bladder disease was demonstrated by filling the overactive bladder-version 8 form after one month of treatment.

    Results: A total of 82 people, 36 men and 46 women, participated in the study. Potassium citrate treatment caused a significant increase in urine pH levels (p<0.001). After potassium citrate treatment, there was a significant decrease in the score of the overactive bladder-version 8 form. (p<0.001). A positive correlation was found between age and overactive bladder-version 8 score change (p = 0.004).

    Conclusion: Potassium citrate can be used in the treatment of overactive bladder disease. The effect of potassium citrate treatment on ameliorating overactive bladder symptoms is more distinct in elderly patients. Key Words: Renal stones, Potassium citrate, Overactive bladder

Herbs & Spices

  • PMID: 27213821

    Vaughn AR, Branum A, Sivamani RK. Effects of Turmeric (Curcuma longa) on Skin Health: A Systematic Review of the Clinical Evidence. Phytother Res. 2016 Aug;30(8):1243-64. doi: 10.1002/ptr.5640. Epub 2016 May 23. PMID: 27213821.

    Turmeric (Curcuma longa), a commonly used spice throughout the world, has been shown to exhibit antiinflammatory, antimicrobial, antioxidant, and anti-neoplastic properties. Growing evidence shows that an active component of turmeric, curcumin, may be used medically to treat a variety of dermatologic diseases. This systematic review was conducted to examine the evidence for the use of both topical and ingested turmeric/curcumin to modulate skin health and function. The PubMed and Embase databases were systematically searched for clinical studies involving humans that examined the relationship between products containing turmeric, curcumin, and skin health. A total of 234 articles were uncovered, and a total of 18 studies met inclusion criteria. Nine studies evaluated the effects of ingestion, eight studies evaluated the effects of topical, and one study evaluated the effects of both ingested and topical application of turmeric/curcumin. Skin conditions examined include acne, alopecia, atopic dermatitis, facial photoaging, oral lichen planus, pruritus, psoriasis, radiodermatitis, and vitiligo. Ten studies noted statistically significant improvement in skin disease severity in the turmeric/curcumin treatment groups compared with control groups. Overall, there is early evidence that turmeric/curcumin products and supplements, both oral and topical, may provide therapeutic benefits for skin health. However, currently published studies are limited and further studies will be essential to better evaluate efficacy and the mechanisms involved. Copyright © 2016 John Wiley & Sons, Ltd.

    PMID: 28662006

    Zdrojewicz Z, Szyca M, Popowicz E, Michalik T, Śmieszniak B. Kurkuma – nie tylko przyprawa [Turmeric - not only spice]. Pol Merkur Lekarski. 2017 Jun 23;42(252):227-230. Polish. PMID: 28662006.

    The purpose of this article is to introduce the role of turmeric in medicine and summarize the current state of research on its applications. Turmeric (Curcuma longa) has had a wide range of uses in middle eastern and orietnal traditional medicine. Currently, however, its use has been truncated to a common cooking spice, despite numerous studies pointing to its healing properties and possible use in the treatment of many diseases. The main focus is on curcumin, a polyphenol which serves as the biologically active component of turmeric. Curcumin's anti-inflammatory effects have been well documented in medical studies, with wide ranging applications from the treatment of rheumatologic diseases such as arthritis to dermatology, with significant effects in the treatment of psoriasis, acne and in relieving of itching. In addition to the effect of pro-inflammatory cytokines, curcumin can also accelerate healing of skin wounds. Apart from controlling the body's inflammatory response, curcumin has a bacteriostatic effect, which has been shown to be an important factor in the treatment of diseases with complex etiology. Additionally, studies show that curcumin's effects on oncogenesis, the process of metastasis, angiogenesis, apoptosis or response to cytostatic drugs have yielded promising results. It has been confirmed that its antioxidant effect correlates with a decrease in LDL levels in blood and to a reduced risk of atherosclerosis. Curcumin consumption has also been shown to have a vasodilating effect through its indirect impact on prostacyclins and directly on vascular endothelium. Many of the mention medicinal properties of turmeric are still the subject of research and debate; as such, only some of them have entered the phase of clinical trials

    PMID: 34106380

    Zhang HA, Kitts DD. Turmeric and its bioactive constituents trigger cell signaling mechanisms that protect against diabetes and cardiovascular diseases. Mol Cell Biochem. 2021 Oct;476(10):3785-3814. doi: 10.1007/s11010-021-04201-6. Epub 2021 Jun 9. PMID: 34106380; PMCID: PMC8187459.

    Turmeric, the rhizome of Curcuma longa plant belonging to the ginger family Zingiberaceae, has a history in Ayurvedic and traditional Chinese medicine for treatment of chronic diseases, including metabolic and cardiovascular diseases (CVD). This parallels a prevalence of age- and lifestyle-related diseases, especially CVD and type 2 diabetes (T2D), and associated mortality which has occurred in recent decades. While the chemical composition of turmeric is complex, curcuminoids and essential oils are known as two major groups that display bioactive properties. Curcumin, the most predominant curcuminoid, can modulate several cell signaling pathways involved in the etiology and pathogenesis of CVD, T2D, and related morbidities. Lesser bioactivities have been reported from other curcuminoids and essential oils. This review examines the chemical compositions of turmeric, and related bioactive constituents. A focus was placed on the cellular and molecular mechanisms that underlie the protective effects of turmeric and turmeric-derived compounds against diabetes and CVD, compiled from the findings obtained with cell-based and animal models. Evidence from clinical trials is also presented to identify potential preventative and therapeutic efficacies. Clinical studies with longer intervention durations and specific endpoints for assessing health outcomes are warranted in order to fully evaluate the long-term protective efficacy of turmeric

  • PMID: 25912592

    Giacosa A, Morazzoni P, Bombardelli E, Riva A, Bianchi Porro G, Rondanelli M. Can nausea and vomiting be treated with ginger extract? Eur Rev Med Pharmacol Sci. 2015 Apr;19(7):1291-6. PMID: 25912592.

    Ginger (Zingiber officinale) is a spice traditionally used to treat indigestion, nausea and vomiting. Ginger extracts accelerate gastric emptying and stimulate gastric antral contractions. These effects are mainly due to the presence of gingerols and shogaols and their activity on cholinergic M receptors and serotonergic 5-HT and 5-HT receptors. Various researches on this subject have led to controversial results, due to the chemical instability of ginger extracts and particularly of gingerols, which are readily-oxidizable substances. A systematic review of double-blind, placebo-controlled, randomized studies highlighted the potential efficacy of ginger on the prevention and treatment of nausea and vomiting of various origins, even though additional controlled studies are needed. This review focuses on pregnancy-induced nausea and vomiting and on chemotherapy induced nausea, and hypothesizes a therapeutic role for ginger extracts in case of side effects, as an alternative to traditional prokinetic drugs such as domperidone, levosulpiride or metoclopramide

    PMID: 11710709

    Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum. 2001 Nov;44(11):2531-8. doi: 10.1002/1529-0131(200111)44:11<2531::aid-art433>3.0.co;2-j. PMID: 11710709.

    Objective: To evaluate the efficacy and safety of a standardized and highly concentrated extract of 2 ginger species, Zingiber officinale and Alpinia galanga (EV.EXT 77), in patients with osteoarthritis (OA) of the knee.

    Methods: Two hundred sixty-one patients with OA of the knee and moderate-to-severe pain were enrolled in a randomized, double-blind, placebo-controlled, multicenter, parallel-group, 6-week study. After washout, patients received ginger extract or placebo twice daily, with acetaminophen allowed as rescue medication. The primary efficacy variable was the proportion of responders experiencing a reduction in ""knee pain on standing,"" using an intent-to-treat analysis. A responder was defined by a reduction in pain of > or = 15 mm on a visual analog scale.

    Results: In the 247 evaluable patients, the percentage of responders experiencing a reduction in knee pain on standing was superior in the ginger extract group compared with the control group (63% versus 50%; P = 0.048). Analysis of the secondary efficacy variables revealed a consistently greater response in the ginger extract group compared with the control group, when analyzing mean values: reduction in knee pain on standing (24.5 mm versus 16.4 mm; P = 0.005), reduction in knee pain after walking 50 feet (15.1 mm versus 8.7 mm; P = 0.016), and reduction in the Western Ontario and McMaster Universities osteoarthritis composite index (12.9 mm versus 9.0 mm; P = 0.087). Change in global status and reduction in intake of rescue medication were numerically greater in the ginger extract group. Change in quality of life was equal in the 2 groups. Patients receiving ginger extract experienced more gastrointestinal (GI) adverse events than did the placebo group (59 patients versus 21 patients). GI adverse events were mostly mild.

    Conclusion: A highly purified and standardized ginger extract had a statistically significant effect on reducing symptoms of OA of the knee. This effect was moderate. There was a good safety profile, with mostly mild GI adverse events in the ginger extract group

    PMID: 29417850

    Li X, Qin Y, Liu W, Zhou XY, Li YN, Wang LY. Efficacy of Ginger in Ameliorating Acute and Delayed Chemotherapy-Induced Nausea and Vomiting Among Patients With Lung Cancer Receiving Cisplatin-Based Regimens: A Randomized Controlled Trial. Integr Cancer Ther. 2018 Sep;17(3):747-754. doi: 10.1177/1534735417753541. Epub 2018 Feb 8. PMID: 29417850; PMCID: PMC6142108.

    Nausea and vomiting are among the most common and distressing side effects of chemotherapy. Additional antiemetic drugs are urgently needed to effectively manage and ameliorate chemotherapy-induced nausea and vomiting (CINV). The efficacy of ginger as an antiemetic modality for ameliorating CINV has not been established in previous studies. The aim of this study was to examine the efficacy of ginger, as an adjuvant drug to standard antiemetic therapy, in ameliorating acute and delayed CINV in patients with lung cancer receiving cisplatin-based regimens. In this randomized, double-blind, placebo-controlled clinical trial, 140 patients with lung cancer receiving cisplatin-based regimens were enrolled and allocated to receive either ginger root powder or a placebo. Ginger root powder was administered orally (0.5 g, 2 capsules per day, 0.25 g per capsule, every 12 hours) for 5 days beginning on the first day of chemotherapy. The incidence and severity of acute and delayed nausea and vomiting were assessed using the MASCC (Multinational Association for Supportive Care in Cancer) Antiemesis Tool (MAT). Adverse effects and patient adherence were also assessed in this study. No significant difference was observed between the ginger and control groups in the reduction of the incidence and severity of nausea and vomiting ( P > .05). No significant difference in adverse events was observed between the 2 groups ( P > .05). No study-treatment-related adverse events were observed in this study. As an adjuvant drug to standard antiemetic therapy, ginger had no additional efficacy in ameliorating CINV in patients with lung cancer receiving cisplatin-based regimens

    PMID: 30299178

    Wilson PB. A Randomized Double-Blind Trial of Ginger Root for Reducing Muscle Soreness and Improving Physical Performance Recovery Among Experienced Recreational Distance Runners. J Diet Suppl. 2020;17(2):121-132. doi: 10.1080/19390211.2018.1492484. Epub 2018 Oct 9. PMID: 30299178.

    Previous studies indicate that ginger root has pain-relieving properties, but these effects have not been thoroughly examined in the context of distance running. The purpose of this randomized, double-blind, placebo-controlled trial was to determine whether ginger root supplementation reduces muscle soreness and dysfunction from downhill running. Thirty-two runners (10 women, 22 men) were pair-matched and randomized to 1.425 g/day of ginger root or placebo for 5 days. A 40-minute downhill (-7.5%) run was completed on day 3. Before supplementation and at various points throughout a 5-day protocol, muscle soreness, pain-pressure threshold, vertical jump, and 1.5-mile run performance were evaluated. Differences between treatments were assessed using magnitude-based inferential statistics. Soreness while jogging likely increased to a lesser degree with ginger root from baseline to immediately postrun (Cohen's d = -0.69; 90% confidence limit [CL] [-1.50, 0.12]) and from baseline to day 5 (d = -0.72; 90% CL [-1.61, 0.16]). Ginger root had a possible small benefit on vertical jump from baseline to day 5 (d = 0.24; 90% CL [0.05, 0.44]) but likely no meaningful impact on 1.5-mile run performance. Trivial or unclear effects were found for most other outcomes. No significant differences in adverse events were observed between treatments. Ginger root possibly has moderate beneficial effects on running-induced soreness but likely irrelevant effects on recovery of physical performance. Ginger represents one option for runners looking to temporarily reduce pain, although more studies are warranted to clarify its safety profile and its effects on long-term training adaptation

  • PMID: 11749801

    Deyama T, Nishibe S, Nakazawa Y. Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol Sin. 2001 Dec;22(12):1057-70. PMID: 11749801.

    The bark and leaves of Eucommia ulmoides Oliv (Eucommiaceae) and ""Siberian ginseng"" (Ezoukogi in Japanese) prepared from the root bark or stem bark of Eleutherococcus senticosus Maxim (Acanthopanax senticosus Harms) have been used as tonic and anti-stress drug. The extracts of Eucommia showed anti-hypertensive, anti-complementary, anti-oxidative, and anti-gastric ulcer effects, and promoting collagen synthesis, accelating granuloma formation, and other pharmacological effects. The Siberian ginseng exhibited anti-fatigue, anti-stress, immuno-enhancing effect, CNS activity, and anti-depressive effect. By now, 40, 28, and 10 compounds have been isolated from Eucommia ulmoides bark, Eucommia ulmoides leaves, and Siberian ginseng, respectively, and their structures were elucidated. Their pharmacological activities were mainly due to lignans and iridoid glycosides

    PMID: 32065954

    Jin L, Schmiech M, El Gaafary M, Zhang X, Syrovets T, Simmet T. A comparative study on root and bark extracts of Eleutherococcus senticosus and their effects on human macrophages. Phytomedicine. 2020 Mar;68:153181. doi: 10.1016/j.phymed.2020.153181. Epub 2020 Feb 6. PMID: 32065954.

    Background: Eleutherococcus senticosus or Siberian ginseng is a medicinal plant containing adaptogenic substances believed to regulate immune responses. Both, the root and stem bark are commonly used in traditional medicines.

    Purpose: The purpose of the present study is to chemically characterize E. senticosus root and bark extracts and to compare their effects on functions of human primary macrophages.

    Study design and methods: HPLC-DAD-MS analysis was used to characterize chemical constituents of alcoholic extracts from E. senticosus root and bark. The data obtained and available databases were combined for network pharmacology analysis. Involvement of predicted pathways was further functionally confirmed by using monocyte-derived human macrophages and endotoxin-free E. senticosus root and bark extracts.

    Results: Chemical analysis showed that the root extract contained more syringin, caffeic acid, and isofraxidin than the bark extract. At variance, bark extract contained more sesamin and oleanolic acid. Coniferyl aldehyde and afzelin were below the limit of quantification in both extracts. Network pharmacology analysis indicated that constituents of E. senticosus might affect the immune cell phenotype and signaling pathways involved in cell metabolism and cytoskeleton regulation. Indeed, both extracts promoted actin polymerization, migration, and phagocytosis of E. coli by macrophages pointing to macrophage polarization towards the M2 phenotype. In addition, treatment with E. senticosus root and bark extracts decreased phosphorylation of Akt on Ser473 and significantly reduced expression of the hemoglobin scavenger receptor CD163 by macrophages. Neither extract affected expression of CD11b, CD80, or CD64 by macrophages. In addition, macrophages treated with the bark extract, but not with the root extract, exhibited activated p38 MAPK and NF-κB and released increased, but still moderate, amounts of proinflammatory TNF-α and IL-6, anti-inflammatory IL-10, and chemotactic CCL1, which all together point to a M2b-like macrophage polarization. Differently, the root extract increased the IL-4-induced expression of anti-inflammatory CD200R. These changes in monocytes are in agreement with an increased M2a macrophage polarization.

    Conclusion: The ability of E. senticosus root and bark extracts to promote polarization of human macrophages towards anti-inflammatory M2a and M2b phenotypes, respectively, might underlay the immunoregulatory activities and point to potential wound healing promoting effects of this medicinal plant

    PMID: 15207399

    Cicero AF, Derosa G, Brillante R, Bernardi R, Nascetti S, Gaddi A. Effects of Siberian ginseng (Eleutherococcus senticosus maxim.) on elderly quality of life: a randomized clinical trial. Arch Gerontol Geriatr Suppl. 2004;(9):69-73. doi: 10.1016/j.archger.2004.04.012. PMID: 15207399.

    An unspecific feeling of fatigue and asthenia often pushes elderly patients to require any form of help even from non medically trained people. Traditional Chinese medicine suggest that Siberian ginseng could act as safe ""adaptogenic"" substance. Our aim was thus to test the effect of a middle term Eleutherococcus senticosus Maxim. (Araliaceae) administration on elderly, health related quality of life (HRQOL). 20 elderly hypertensive and digitalized volunteers (age >/= 65 years) were randomized in a double -blind manner to E. senticosus dry extract 300 mg/day (n = 10) or placebo (n = 10) for 8 weeks. The short form-36 health survey version 2 (SF-36v2), a validated general health status questionnaire, was used to access HRQOL at baseline and at 4 and 8 weeks. There were no significant differences in baseline demographics and SF-36v2 scores between the groups. At each visit, controls of digitalemia and blood pressure level were carried out. After 4 weeks of therapy, higher scores in social functioning (p = 0.02) scales were observed in patients randomized to E. senticosus; these differences did not persist to the 8-week time point. No adverse event has been observed in both groups of patients. No significant difference in both blood pressure control and digitalemia was observed in both treatment groups. Subjects give E. senticosus (70%) were more likely to state that they received active therapy than subjects given placebo (20%; p < 0.05). In conclusion, E. senticosus safely improves some aspects of mental health and social functioning after 4 weeks of therapy, although these differences attenuate with continued use

  • PMID: 23768180

    Butt MS, Pasha I, Sultan MT, Randhawa MA, Saeed F, Ahmed W. Black pepper and health claims: a comprehensive treatise. Crit Rev Food Sci Nutr. 2013;53(9):875-86. doi: 10.1080/10408398.2011.571799. PMID: 23768180.

    For millennia, spices have been an integral part of human diets and commerce. Recently, the widespread recognition of diet-health linkages bolsters their dietary importance. The bioactive components present in them are of considerable significance owing to their therapeutic potential against various ailments. They provide physiological benefits or prevent chronic ailment in addition to the fundamental nutrition and often included in the category of functional foods. Black pepper (Piper Nigrum L.) is an important healthy food owing to its antioxidant, antimicrobial potential and gastro-protective modules. Black pepper, with piperine as an active ingredient, holds rich phytochemistry that also includes volatile oil, oleoresins, and alkaloids. More recently, cell-culture studies and animal modeling predicted the role of black pepper against number of maladies. The free-radical scavenging activity of black pepper and its active ingredients might be helpful in chemoprevention and controlling progression of tumor growth. Additionally, the key alkaloid components of Piper Nigrum, that is, piperine assist in cognitive brain functioning, boost nutrient's absorption and improve gastrointestinal functionality. In this comprehensive treatise, efforts are made to elucidate the antioxidant, antimicrobial, anti-inflammatory, gastro-protective, and antidepressant activities of black pepper. Moreover, the synergistic interaction of black pepper with different drugs and nutrients is the limelight of the manuscript. However, the aforementioned health-promoting benefits associated with black pepper are proven in animal modeling. Thus, there is a need to conduct controlled randomized trials in human subjects, cohort studies, and meta-analyses. Such future studies would be helpful in recommending its application in diet-based regimens to prevent various ailments

    PMID: 17987447

    Srinivasan K. Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Crit Rev Food Sci Nutr. 2007;47(8):735-48. doi: 10.1080/10408390601062054. PMID: 17987447.

    Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. Black pepper or piperine treatment has also been evidenced to lower lipid peroxidation in vivo and beneficially influence cellular thiol status, antioxidant molecules and antioxidant enzymes in a number of experimental situations of oxidative stress. The most far-reaching attribute of piperine has been its inhibitory influence on enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase. Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property. Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border. Although initially there were a few controversial reports regarding its safety as a food additive, such evidence has been questionable, and later studies have established the safety of black pepper or its active principle, piperine, in several animal studies. Piperine, while it is non-genotoxic, has in fact been found to possess anti-mutagenic and anti-tumor influences

    PMID: 32180294

    Heidari-Beni M, Moravejolahkami AR, Gorgian P, Askari G, Tarrahi MJ, Bahreini-Esfahani N. Herbal formulation "turmeric extract, black pepper, and ginger" versus Naproxen for chronic knee osteoarthritis: A randomized, double-blind, controlled clinical trial. Phytother Res. 2020 Aug;34(8):2067-2073. doi: 10.1002/ptr.6671. Epub 2020 Mar 16. PMID: 32180294.

    Osteoarthritis is the most common articular disease that can lead to chronic pain and severe disability. Curcumin-an effective ingredient in turmeric with anti inflammatory property-plays an important role in protecting the joints against destructive factors. Gingerols and piperine, are the effective ingredients of ginger and black pepper, which may potentially enhance and sustain the effect of curcumin in this direction. To determine the effect of cosupplementation with turmeric extract, black pepper, and ginger on prostaglandin E2 (PGE2 ) in patients with chronic knee osteoarthritis, compared with Naproxen. Sixty patients with two different levels of knee osteoarthritis (Grade 2 and 3) were studied. Individuals were randomly assigned to receive daily turmeric extract, ginger, and black pepper together or Naproxen capsule for 4 weeks. PGE2 was evaluated by ELISA method. 24-hr recall was also assessed. All of participants completed the study. PGE2 decreased significantly in both groups (p < .001), but there was no significant differences between groups. The results of this study indicated that intake of the selected herbs twice a day for 4 weeks may improve the PGE2 levels in patients with chronic knee osteoarthritis similar to Naproxen drug

    PMID: 33884168

    Banerjee S, Katiyar P, Kumar V, Saini SS, Varshney R, Krishnan V, Sircar D, Roy P. Black pepper and piperine induce anticancer effects on leukemia cell line. Toxicol Res (Camb). 2021 Feb 18;10(2):169-182. doi: 10.1093/toxres/tfab001. PMID: 33884168; PMCID: PMC8045589.

    The black pepper, most commonly used in Indian cuisines for ages, is considered as ""king of spices."" The present study evaluates the anticancer potential of black pepper and its main constituent, i.e. alkaloid piperine, against human leukemia cell line, K-562 cells. Gas chromatography-mass spectrometry (GC-MS) analysis confirmed the presence of piperine in black pepper extract. The methanolic extract of black pepper (BP-M) and pure piperine (PIP) showed a strong cytotoxic effect against this cell line. Both BP-M and PIP generated apoptotic bodies in K-562 cells and caused nuclear condensation as visualized by fluorescent microscopy, which was further confirmed by flow cytometry analysis. BP-M and PIP also generated reactive oxygen species in K-562 cells as established by flow cytometry. The translation of Bax, caspase-3 and caspase-9 genes was found to be upregulated with subsequent downregulation of Bcl-2 gene. The anti-proliferative effect of both BP-M and PIP was also observed by trypan blue staining and was further confirmed by the downregulated expression of proliferating cell nuclear antigen (PCNA). The molecular docking studies showed the binding of PIP with PCNA and Bcl-2 and supported the in vitro findings. The docking studies also proposed the binding of PIP to ADP binding pocket of Apaf-1 protein. Taken together, these findings signify the anticancer potential of both black pepper and PIP, thus proposing black pepper as a potent nutraceutical for preventing the progression of chronic myeloid leukemia

  • PMID: 31877551

    Zhang Y, Liu X, Ruan J, Zhuang X, Zhang X, Li Z. Phytochemicals of garlic: Promising candidates for cancer therapy. Biomed Pharmacother. 2020 Mar;123:109730. doi: 10.1016/j.biopha.2019.109730. Epub 2019 Dec 23. PMID: 31877551.

    Of the numerous health benefits of garlic, the anticancer effect is probably the most noticeable. Observations over the past years have shown that the consumption of garlic in the diet provides strong protection against cancer risk. Previous studies involving garlic phytochemicals have usually focused on the cancer chemopreventive properties, but there is little published evidence showing its therapeutic potential in cancer treatment. In view of the multitargeted carcinoma actions and lack of severe toxicity, some components of garlic are likely to play vital roles in the selective killing of cancer cells. However, the rational design of experimental studies and clinical trials are required to verify this concept. This paper discusses the promises and pitfalls of garlic for the treatment of cancer

    PMID: 27748188

    Alali FQ, El-Elimat T, Khalid L, Hudaib R, Al-Shehabi TS, Eid AH. Garlic for Cardiovascular Disease: Prevention or Treatment? Curr Pharm Des. 2017;23(7):1028-1041. doi: 10.2174/1381612822666161010124530. PMID: 27748188.

    Cardiovascular disease (CVD) is the leading cause of global mortality with a substantial economic impact. The annual deaths are expected to increase in the next decade. An array of dietary supplements is being used by people worldwide to ameliorate cardiovascular risk factors. Garlic (Allium sativum L.), a top-selling herbal dietary supplement, is renowned for its wide range beneficial effects, particularly in the treatment and prevention of CVD. This review aims to present a thorough discussion of the available evidence-based data which support the use of garlic in the treatment or prevention of cardiovascular diseases, including atherosclerosis, hypertension, and hyperlipidemia. The molecular mechanisms underlying these effects are dissected as well. This review supports the notion that garlic has the potential to treat mild hypertension, to decrease hypercholesterolemia, and to prevent atherosclerosis. More clinical studies are essential to unequivocally understand the mechanisms underlying treatment or prevention of these cardiovascular conditions

    PMID: 29718835

    Sun YE, Wang W, Qin J. Anti-hyperlipidemia of garlic by reducing the level of total cholesterol and low-density lipoprotein: A meta-analysis. Medicine (Baltimore). 2018 May;97(18):e0255. doi: 10.1097/MD.0000000000010255. PMID: 29718835; PMCID: PMC6392629.

    Background: This study aimed to understand the impact of garlic on improving blood lipids using a meta-analysis.

    Methods: A literature search of the PubMed, EMBASE, and Cochrane Library databases was performed using keywords such as ""garlic"" and ""hypercholesterolemia,"" and the deadline ""July 14 (th), 2017."" After extracting relevant details, each selected literature was evaluated for quality according to the quality evaluation criteria of bias risk recommended by Cochrane Collaboration recommendations and heterogeneity tests were performed. Standardized mean difference (SMD) and 95% confidence interval (CI) were evaluated using R 3.12 software. The publication bias was assessed using Egger method.

    Results: A total of 14 eligible papers published from 1981 to 2016 were included. The quality of the literatures was of moderate to high qualities. The values of TC (SMD = -1.26, 95% CI, -1.86 to -0.66), low-density lipoprotein (LDL) (SMD = -1.07, 95% CI, -1.67 to -0.47), and high-density lipoprotein (HDL) (SMD = 0.50, 95% CI, 0.06-0.94) after taking garlic in the experimental group and the control group have statistical significance, while there was no significant difference of TG in the 2 groups (SMD = -0.16, 95% CI, -0.87-0.55). However, the result of HDL was reversed when removed some of the literatures. No significant publication bias among the eligible studies with values of TC (P = .0625), LDL (P = .0770), HDL (P = .2293), and TG (P = .3436).

    Conclusion: Garlic can reduce the level of TC and LDL instead of HDL and TG, indicating the ability of anti-hyperlipidemia

    PMID: 20120123

    Aviello G, Abenavoli L, Borrelli F, Capasso R, Izzo AA, Lembo F, Romano B, Capasso F. Garlic: empiricism or science? Nat Prod Commun. 2009 Dec;4(12):1785-96. PMID: 20120123.

    Garlic (Allium sativum L. fam. Alliaceae) is one of the best-researched, best-selling herbal remedies and is also commonly used as a food and a spice. Garlic constituents include enzymes (for example, alliinase) and sulfur-containing compounds, including alliin, and compounds produced enzymatically from alliin (for example, allicin). Traditionally, it has been employed to treat infections, wounds, diarrhea, rheumatism, heart disease, diabetes, and many other disorders. Experimentally, it has been shown to exert antilipidemic, antihypertensive, antineoplastic, antibacterial, immunostimulant and hypoglycemic actions. Clinically, garlic has been evaluated for a number of conditions, including hypertension, hypercholesterolemia, intermittent claudication, diabetes, rheumatoid arthritis, common cold, as an insect repellent, and for the prevention of arteriosclerosis and cancer. Systematic reviews are available for the possible antilipidemic, antihypertensive, antithrombotic and chemopreventive effects. However, the clinical evidence is far from compelling. Garlic appears to be generally safe although allergic reactions may occur

  • PMID: 11695882

    Kreydiyyeh SI, Usta J, Kaouk I, Al-Sadi R. The mechanism underlying the laxative properties of parsley extract. Phytomedicine. 2001 Sep;8(5):382-8. doi: 10.1078/0944-7113-00058. PMID: 11695882.

    Parsley has been claimed in folk medicine to possess laxative properties attributed to the presence therein of some volatile oils that are more concentrated in seeds than in stems or leaves. The advocated physiological effect of parsley, does not have, however, any proven scientific background and relies mainly on simple observations and empirical information. This work aims at providing the scientific evidence that would confirm or reject the claimed laxative role of parsley, and at determining its mechanism of action if present. A perfusion technique was used to measure the net fluid absorption from the rat colon. The addition of an aqueous extract of parsley seeds to the perfusion buffer, and the omission of sodium, both reduced significantly net water absorption from the colon, as compared to the control. Parsley, added to a sodium-free buffer did not lead to any further significant change in water absorption as compared to parsley alone inferring that with parsley sodium absorption was already inhibited. Since K+ and Cl- secretion depends on the activity of the NaKCl2 transporter, the latter was inhibited with furosemide which increased significantly net water absorption. When parsley and furosemide were added together, net water absorption was significantly higher than with parsley alone and significantly lower than with furosemide alone. In addition, parsley extract was shown to inhibit the in vitro activity of the Na+-K+ATPase in a colon homogenate and the activity of a partially purified dog kidney ATPase. The results suggest that parsley acts by, inhibiting sodium and consequently water absorption through an inhibition of the Na+-K+ pump, and by stimulating the NaKCl, transporter and increasing electrolyte and water secretion

    PMID: 21854170

    Yousofi A, Daneshmandi S, Soleimani N, Bagheri K, Karimi MH. Immunomodulatory effect of Parsley (Petroselinum crispum) essential oil on immune cells: mitogen-activated splenocytes and peritoneal macrophages. Immunopharmacol Immunotoxicol. 2012 Apr;34(2):303-8. doi: 10.3109/08923973.2011.603338. Epub 2011 Aug 19. PMID: 21854170.

    Introduction: Parsley (Petroselinum crispum) has been traditionally used for the treatment of allergy, autoimmune and chronic inflammatory disorders. The present study aims to investigate the suppressive effects of parsley essential oil on mouse splenocytes and macrophages cells.

    Methods and materials: Parsley essential oil was harvested. It was treated on splenocytes and phytohemagglutinin (PHA) (5 μg/mL) and lipopolysaccharide (LPS) (10 μg/mL) activated splenocytes in different concentrations (0.01-100 μg/mL); then, proliferation was assayed by methyl tetrazolium (MTT) method. Treatment was also performed on the macrophages and LPS-stimulated macrophages (10 μg/ml) and the nitrite levels were measured using the diazotization method based on the Griess reaction and MTT assay for evaluation of the viability of the macrophages.

    Results: Proliferation of splenocytes in all the treated groups was suppressed. In PHA-stimulated splenocytes, the suppression was seen in all the examined concentrations (0.01-100 μg/mL), while in the unstimulated and LPS-stimulated groups suppression was relatively dose dependent and in high concentration (10 and100 μg/mL).The viability of the macrophages in all groups was the same and in the unstimulated groups; NO suppression was significant in all the concentrations but in LPS-stimulated groups, it was significant in the three higher concentrations (1, 10, and100 μg/mL).

    Conclusion: The results of this study indicate that parsley essential oil may be able to suppress the cellular and humoral immune response. It can also suppress both NO production and the functions of macrophages as the main innate immune cells. These results may suggest that parsley essential oil is a proper suppressant for different applications

    PMID: 19919287

    Wahba NM, Ahmed AS, Ebraheim ZZ. Antimicrobial effects of pepper, parsley, and dill and their roles in the microbiological quality enhancement of traditional Egyptian Kareish cheese. Foodborne Pathog Dis. 2010 Apr;7(4):411-8. doi: 10.1089/fpd.2009.0412. PMID: 19919287.

    This study was designed to assess the application of some edible plants including cayenne, green pepper, parsley, and dill to Kareish cheese and to evaluate the antimicrobial activity of these plant materials against natural microflora, coliforms, molds, and Staphylococcus aureus. Twelve different concentrations of ethanol extract of the plants were prepared for determination of the minimal inhibitory concentration. Cayenne and green pepper extracts showed highest activity followed by dill and parsley against S. aureus. Addition of cayenne or green pepper to Kareish cheese during manufacture revealed that both plants were able reduce the S. aureus population to undetectable level within the first and second days of storage. To study the effect of combining plant materials on the microbiological quality of ready-to-eat Kareish cheese, the total bacterial count, coliform count, and yeast and molds counts were determined. It has been found that addition of plant materials to Kareish cheese reduced the total bacterial and coliform populations. All concentrations of cayenne, green pepper, dill, and parsley (9%) completely reduced the yeast count within 2 hours. Cayenne and green pepper completely reduced the mold count within 2 days, whereas parsley and dill were found to be less effective. Kareish cheese prepared with 1% cayenne pepper and 3% and 6% each of green pepper, dill, and parsley were found strongly acceptable to the consumer and considered the most preferable type. Therefore, this study revealed that pepper, parsley, and dill exhibited antibacterial activity against natural microflora, coliforms, yeast and molds, and S. aureus in Kareish cheese, and the addition of these plants is acceptable to the consumer and may contribute to the development of new and safe varieties of Kareish cheese

  • PMID: 32680575

    Yu G, Xiang W, Zhang T, Zeng L, Yang K, Li J. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. BMC Complement Med Ther. 2020 Jul 17;20(1):225. doi: 10.1186/s12906-020-02985-6. PMID: 32680575; PMCID: PMC7368679.

    Background: Osteoarthritis (OA) is the commonest form of inflammatory joint disease. Unfortunately, to date, there is no appropriate treatment for OA. Boswellia serrata was considered as a potent anti-inflammatory, anti-arthritic and analgesic agent that may be a drug for OA.

    Conclusion: Based on current evidence, Boswellia and its extract may be an effective and safe treatment option for patient with OA, and the recommended duration of treatment with Boswellia and its extract is at least 4 weeks

    PMID: 33151656

    LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Boswellia Serrata. 2020 Nov 4. PMID: 33151656.

    Boswellia also called Indian Frankincense is an extract of the gummy oleoresin derived from beneath the bark of the Boswellia serrata tree, which is native to India, the Middle East and Northern Africa. The resin is rich in triterpenic acids and has been used for centuries in traditional Ayurvedic medicine to treat inflammatory conditions. More recently, Boswellia serrata extracts have been marketed as helpful in arthritis, colitis and asthma. Extracts of Boswellia serrata have not been linked to serum aminotransferase elevations during treatment or to instances of clinically apparent acute liver injury

    PMID: 29622343

    Bannuru RR, Osani MC, Al-Eid F, Wang C. Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis. Semin Arthritis Rheum. 2018 Dec;48(3):416-429. doi: 10.1016/j.semarthrit.2018.03.001. Epub 2018 Mar 10. PMID: 29622343; PMCID: PMC6131088.

    Purpose: The unfavorable safety profiles of commonly prescribed knee osteoarthritis (OA) treatments have led clinicians and patients to seek safer alternatives. Research has suggested that curcuminoid and boswellia formulations could moderate key inflammatory pathways that are associated with worsening symptoms and disease progression. We conducted a systematic review and meta-analysis to assess the efficacy and safety of these treatments vs. placebo or NSAIDs for knee OA.

    Conclusions: The results of our study suggest that curcuminoid and boswellia formulations could be a valuable addition to the knee OA treatment regimens by relieving symptoms while reducing safety risks. The current body of evidence is not adequate in size or quality to make any meaningful clinical practice recommendations. Further research through large, high quality RCTs probably investigating the synergistic effect of these products with other OA treatments is warranted

  • PMID: 34770801

    Haro-González JN, Castillo-Herrera GA, Martínez-Velázquez M, Espinosa-Andrews H. Clove Essential Oil (Syzygium aromaticum L. Myrtaceae): Extraction, Chemical Composition, Food Applications, and Essential Bioactivity for Human Health. Molecules. 2021 Oct 22;26(21):6387. doi: 10.3390/molecules26216387. PMID: 34770801; PMCID: PMC8588428.

    Clove (Syzygium aromaticum L. Myrtaceae) is an aromatic plant widely cultivated in tropical and subtropical countries, rich in volatile compounds and antioxidants such as eugenol, β-caryophyllene, and α-humulene. Clove essential oil has received considerable interest due to its wide application in the perfume, cosmetic, health, medical, flavoring, and food industries. Clove essential oil has biological activity relevant to human health, including antimicrobial, antioxidant, and insecticidal activity. The impacts of the extraction method (hydrodistillation, steam distillation, ultrasound-assisted extraction, microwave-assisted extraction, cold pressing, and supercritical fluid extraction) on the concentration of the main volatile compounds in clove essential oil and organic clove extracts are shown. Eugenol is the major compound, accounting for at least 50%. The remaining 10-40% consists of eugenyl acetate, β-caryophyllene, and α-humulene. The main biological activities reported are summarized. Furthermore, the main applications in clove essential oil in the food industry are presented. This review presents new biological applications beneficial for human health, such as anti-inflammatory, analgesic, anesthetic, antinociceptive, and anticancer activity. This review aims to describe the effects of different methods of extracting clove essential oil on its chemical composition and food applications and the biological activities of interest to human health

    PMID: 33810416

    Vicidomini C, Roviello V, Roviello GN. Molecular Basis of the Therapeutical Potential of Clove (Syzygium aromaticum L.) and Clues to Its Anti-COVID-19 Utility. Molecules. 2021 Mar 26;26(7):1880. doi: 10.3390/molecules26071880. PMID: 33810416; PMCID: PMC8036487.

    The current COronaVIrus Disease 19 (COVID-19) pandemic caused by SARS-CoV-2 infection is enormously affecting the worldwide health and economy. In the wait for an effective global immunization, the development of a specific therapeutic protocol to treat COVID-19 patients is clearly necessary as a short-term solution of the problem. Drug repurposing and herbal medicine represent two of the most explored strategies for an anti-COVID-19 drug discovery. Clove (Syzygium aromaticum L.) is a well-known culinary spice that has been used for centuries in folk medicine in many disorders. Interestingly, traditional medicines have used clove since ancient times to treat respiratory ailments, whilst clove ingredients show antiviral and anti-inflammatory properties. Other interesting features are the clove antithrombotic, immunostimulatory, and antibacterial effects. Thus, in this review, we discuss the potential role of clove in the frame of anti-COVID-19 therapy, focusing on the antiviral, anti-inflammatory, and antithrombotic effects of clove and its molecular constituents described in the scientific literature."

    PMID: 32019140

    Batiha GE, Alkazmi LM, Wasef LG, Beshbishy AM, Nadwa EH, Rashwan EK. Syzygium aromaticum L. (Myrtaceae): Traditional Uses, Bioactive Chemical Constituents, Pharmacological and Toxicological Activities. Biomolecules. 2020 Jan 30;10(2):202. doi: 10.3390/biom10020202. PMID: 32019140; PMCID: PMC7072209.

    Herbal medicinal products have been documented as a significant source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Many plant species have been reported to have pharmacological activities attributable to their phytoconstituents such are glycosides, saponins, flavonoids, steroids, tannins, alkaloids, terpenes, etc. Syzygium aromaticum (clove) is a traditional spice that has been used for food preservation and possesses various pharmacological activities. S. aromaticum is rich in many phytochemicals as follows: sesquiterpenes, monoterpenes, hydrocarbon, and phenolic compounds. Eugenyl acetate, eugenol, and β-caryophyllene are the most significant phytochemicals in clove oil. Pharmacologically, S. aromaticum has been examined toward various pathogenic parasites and microorganisms, including pathogenic bacteria, Plasmodium, Babesia, Theileria parasites, Herpes simplex, and hepatitis C viruses. Several reports documented the analgesic, antioxidant, anticancer, antiseptic, anti-depressant, antispasmodic, anti-inflammatory, antiviral, antifungal, and antibacterial activity of eugenol against several pathogenic bacteria including methicillin-resistant Staphylococcusepidermidis and S. aureus. Moreover, eugenol was found to protect against CCl4-induced hepatotoxicity and showed a potential lethal efficacy against the multiplication of various parasites including Giardia lamblia, Fasciolagigantica, Haemonchuscontortus, and Schistosomamansoni. This review examines the phytochemical composition and biological activities of clove extracts along with clove essential oil and the main active compound, eugenol, and implicates new findings from gas chromatography-mass spectroscopy (GC-MS) analysis

  • PMID: 13678141

    Sierpina VS, Wollschlaeger B, Blumenthal M. Ginkgo biloba. Am Fam Physician. 2003 Sep 1;68(5):923-6. PMID: 13678141.

    Ginkgo biloba is commonly used in the treatment of early-stage Alzheimer's disease, vascular dementia, peripheral claudication, and tinnitus of vascular origin. Multiple trials investigating the efficacy of ginkgo for treating cerebrovascular disease and dementia have been performed, and systematic reviews suggest the herb can improve the symptoms of dementia. Ginkgo is generally well tolerated, but it can increase the risk of bleeding if used in combination with warfarin, antiplatelet agents, and certain other herbal medications. Clinical issues of safety, dosing, use in the perioperative period, and pharmacology are addressed in this review

    PMID: 31376068

    Singh SK, Srivastav S, Castellani RJ, Plascencia-Villa G, Perry G. Neuroprotective and Antioxidant Effect of Ginkgo biloba Extract Against AD and Other Neurological Disorders. Neurotherapeutics. 2019 Jul;16(3):666-674. doi: 10.1007/s13311-019-00767-8. PMID: 31376068; PMCID: PMC6694352.

    Alzheimer's disease (AD) is the most common progressive human neurodegenerative disorder affecting elderly population worldwide. Hence, prevention of AD has been a priority of AD research worldwide. Based on understanding of disease mechanism, different therapeutic strategies involving synthetic and herbal approaches are being used against AD. Among the herbal extract, Ginkgo biloba extract (GBE) is one of the most investigated herbal remedy for cognitive disorders and Alzheimer's disease (AD). Standardized extract of Ginkgo biloba is a popular dietary supplement taken by the elderly population to improve memory and age-related loss of cognitive function. Nevertheless, its efficacy in the prevention and treatment of dementia remains controversial. Specifically, the added effects of GBE in subjects already receiving ""conventional"" anti-dementia treatments have been to date very scarcely investigated. This review summarizes recent advancements in our understanding of the potential use of Ginkgo biloba extract in the prevention of AD including its antioxidant property. A better understanding of the mechanisms of action of GBE against AD will be important for designing therapeutic strategies, for basic understanding of the underlying neurodegenerative processes, and for a better understanding of the effectiveness and complexity of this herbal medicine

    PMID: 32097990

    Eisvand F, Razavi BM, Hosseinzadeh H. The effects of Ginkgo biloba on metabolic syndrome: A review. Phytother Res. 2020 Aug;34(8):1798-1811. doi: 10.1002/ptr.6646. Epub 2020 Feb 25. PMID: 32097990.

    The Ginkgo biloba (G. biloba), commonly known as ginkgo, brings considerable benefit to common medicine, including weight loss effects, as well as antidiabetic, antihypertensive, and antilipidemic properties that could be effective in the treatment of Metabolic syndrome (MetS) associated with increased risk of cardiovascular disease events. Major compounds of G. biloba are terpene lactones (bilobalide and ginkgolides A, B, and C) and flavone glycosides (isorhamnetin, quercetin, and kaempferol). We evaluated the most relevant original articles to indicate the effects of G. biloba on different components of MetS, including obesity, high blood pressure, dyslipidemia, and hyperglycemia. Several electronic databases (Scopus, PubMed, Web of Science and Google Scholar) were searched and the articles that included Ginkgo's effect on one or more of the criteria for MetS were selected. This review indicated that G. biloba might be efficient in the improvement of MetS; however, more studies especially clinical trials are needed to evaluate safety and efficacy of G. biloba

    PMID: 32329705

    Sharma G, Sharma N, Nguyen BT, Jeong JH, Nah SY, Yoneda Y, Shin EJ, Kim HC. Protective Potential of Ginkgo biloba Against an ADHD-like Condition. Curr Mol Pharmacol. 2021;14(2):200-209. doi: 10.2174/1874467213666200424152454. PMID: 32329705.

    Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder commonly found in children, which is recognized by hyperactivity and aggressive behavior. It is known that the pathophysiology of ADHD is associated with neurobiological dysfunction. Although psychostimulants are recognized as the therapeutic drugs of choice for ADHD patients, the side effects might be of great concern. Ginkgo biloba is a promising herbal, complementary supplement that may modulate the neuronal system in an ADHD-like condition. The beneficial effect of Ginkgo biloba on ADHD-like symptoms may be related to the modulation of the system by novel molecular mechanisms. Ginkgo biloba is known to modulate dopamine, serotonin, and norepinephrine signaling. Flavonoid glycosides and terpene trilactones are the two major phytochemical components present in the Ginkgo biloba preparations, which can exhibit antioxidant and neuroprotective activities. The pharmacological mechanisms of the phytochemical components may also contribute to the neuroprotective activity of Ginkgo biloba. In this review, we have summarized recent findings on the potential of various Ginkgo biloba preparations to treat ADHD-like symptoms. In addition, we have discussed the pharmacological mechanisms mediated by Ginkgo biloba against an ADHD-like condition

  • PMID: 35010932

    Gómez-Martínez S, Díaz-Prieto LE, Vicente Castro I, Jurado C, Iturmendi N, Martín-Ridaura MC, Calle N, Dueñas M, Picón MJ, Marcos A, Nova E. Moringa oleifera Leaf Supplementation as a Glycemic Control Strategy in Subjects with Prediabetes. Nutrients. 2021 Dec 24;14(1):57. doi: 10.3390/nu14010057. PMID: 35010932; PMCID: PMC8746299.

    Moringa oleifera (MO) is a multipurpose plant with a high polyphenol content, which is being increasingly consumed to lessen the risk of chronic metabolic diseases such as Type 2 diabetes; however, scientific evidence from clinical trials is scarce. A double-blind, randomized, placebo-controlled, parallel group intervention study with MO leaves as a food supplement was conducted in subjects with prediabetes. They consumed six daily capsules of MO dry leaf powder (2400 mg/day) (MO, n = 31) or placebo (PLC, n = 34) over 12 weeks. Glycemia, appetite-controlling hormones and gut microbiota composition were studied. ANCOVA with the fixed factor ""treatment"" and the basal value as covariate was used to compare the change score between the groups. The results showed significant differences between groups in the rate of change of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c), which showed opposite directions during the intervention, decreasing in MO and increasing in PLC. No different change scores were found between the groups in microbiota, hepatic and renal function markers or the appetite-controlling hormones measured. In conclusion, MO supplementation resulted in favorable changes in glycaemia markers compared to placebo in the subjects with prediabetes studied, suggesting that MO might act as a natural antihyperglycemic agent

    PMID: 25808883

    Stohs SJ, Hartman MJ. Review of the Safety and Efficacy of Moringa oleifera. Phytother Res. 2015 Jun;29(6):796-804. doi: 10.1002/ptr.5325. Epub 2015 Mar 24. PMID: 25808883; PMCID: PMC6680322.

    Moringa oleifera leaves, seeds, bark, roots, sap, and flowers are widely used in traditional medicine, and the leaves and immature seed pods are used as food products in human nutrition. Leaf extracts exhibit the greatest antioxidant activity, and various safety studies in animals involving aqueous leaf extracts indicate a high degree of safety. No adverse effects were reported in association with human studies. Five human studies using powdered whole leaf preparations of M. oleifera have been published, which have demonstrated anti-hyperglycemic (antidiabetic) and anti-dyslipidemic activities. These activities have been confirmed using extracts as well as leaf powders in animal studies. A rapidly growing number of published studies have shown that aqueous, hydroalcohol, or alcohol extracts of M. oleifera leaves possess a wide range of additional biological activities including antioxidant, tissue protective (liver, kidneys, heart, testes, and lungs), analgesic, antiulcer, antihypertensive, radioprotective, and immunomodulatory actions. A wide variety of polyphenols and phenolic acids as well as flavonoids, glucosinolates, and possibly alkaloids is believed to be responsible for the observed effects. Standardization of products is an issue. However, the results of published studies to date involving M. oleifera are very promising. Additional human studies using standardized extracts are highly desirable

    PMID: 17089328

    Anwar F, Latif S, Ashraf M, Gilani AH. Moringa oleifera: a food plant with multiple medicinal uses. Phytother Res. 2007 Jan;21(1):17-25. doi: 10.1002/ptr.2023. PMID: 17089328.

    Moringa oleifera Lam (Moringaceae) is a highly valued plant, distributed in many countries of the tropics and subtropics. It has an impressive range of medicinal uses with high nutritional value. Different parts of this plant contain a profile of important minerals, and are a good source of protein, vitamins, beta-carotene, amino acids and various phenolics. The Moringa plant provides a rich and rare combination of zeatin, quercetin, beta-sitosterol, caffeoylquinic acid and kaempferol. In addition to its compelling water purifying powers and high nutritional value, M. oleifera is very important for its medicinal value. Various parts of this plant such as the leaves, roots, seed, bark, fruit, flowers and immature pods act as cardiac and circulatory stimulants, possess antitumor, antipyretic, antiepileptic, antiinflammatory, antiulcer, antispasmodic, diuretic, antihypertensive, cholesterol lowering, antioxidant, antidiabetic, hepatoprotective, antibacterial and antifungal activities, and are being employed for the treatment of different ailments in the indigenous system of medicine, particularly in South Asia. This review focuses on the detailed phytochemical composition, medicinal uses, along with pharmacological properties of different parts of this multipurpose tree

  • PMID: 32106548

    Kosehira M, Machida N, Kitaichi N. A 12-Week-Long Intake of Bilberry Extract (Vaccinium myrtillus L.) Improved Objective Findings of Ciliary Muscle Contraction of the Eye: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial. Nutrients. 2020 Feb 25;12(3):600. doi: 10.3390/nu12030600. PMID: 32106548; PMCID: PMC7146147.

    A 12-week-long randomized, double-blind, placebo-controlled, parallel-group comparison trial was conducted to determine the effects of long-term standardized bilberry extract (SBE) intake on tonic accommodation of ciliary muscle caused by visual display terminal (VDT) tasks. This study was compliant with the accordance with CONSORT 2010 statement. A total of 109 healthy adult men and women aged 20-60 years were recruited and randomized into SBE and placebo groups. The subjects in the SBE and placebo groups were administered 240 mg of SBE and placebo, respectively, once daily for 12 weeks. Tests were performed before and after VDT tasks at week 0, 4, 8, and 12; high-frequency component (HFC)-1 value was the evaluation outcome. Results showed that post-load HFC-1 values at weeks 8 and 12 were significantly improved in the SBE group than in the placebo group (p = 0.014 and 0.017, respectively). Regarding the difference between before and after the task load (ΔHFC-1), the values were significantly better in the SBE group than in the placebo group at week 4 and 12 (p = 0.018 and 0.049, respectively). This study shows that oral consumption of 240 mg SBE extract for 12 weeks relieves the tonic accommodation of the ciliary muscle caused by VDT tasks and near-vision tasks

    PMID: 36225983

    Choo PP, Woi PJ, Bastion MC, Omar R, Mustapha M, Md Din N. Review of Evidence for the Usage of Antioxidants for Eye Aging. Biomed Res Int. 2022 Oct 3;2022:5810373. doi: 10.1155/2022/5810373. PMID: 36225983; PMCID: PMC9550496.

    Oxidative stress is one of the common factors leading to age-related eye diseases in older adults. Factors such as high oxygen consumption, high concentration of polyunsaturated fatty acids, and cumulative exposure to high-energy visible light in the eyes, lead to excessive generation of reactive oxygen species, hence triggering apoptosis of ocular cells and giving rise to ophthalmic diseases. Dietary supplements such as carotenoids, anthocyanins, and vitamins have antioxidant properties which may be of benefit in retaining better vision or reversing vision impairment; thus, studies have been conducted to understand the role of dietary supplements in the treatment or prevention of ophthalmic diseases. While high concentration of carotenoids such as lutein and zeaxanthin decrease the risk of developing age-related macular disease, anthocyanins and vitamins play a role in the treatment and prevention of other ophthalmic diseases: saffron extract reduced intraocular pressure in glaucoma patients; bilberry extract prevented impairments in lenses and retina, as well as alleviate symptoms of dry eye disease; high concentration of beta-carotene may reduce the risk of developing cataract. Further studies with clinical measurements are required to investigate the effectiveness of antioxidants on visual function and ophthalmic diseases

    PMID: 34829135

    Hong J, Kim M, Kim B. The Effects of Anthocyanin-Rich Bilberry Extract on Transintestinal Cholesterol Excretion. Foods. 2021 Nov 18;10(11):2852. doi: 10.3390/foods10112852. PMID: 34829135; PMCID: PMC8624570.

    Hypercholesterolemia is one of the modifiable and primary risk factors for cardiovascular diseases (CVD). Emerging evidence suggests the stimulation of transintestinal cholesterol excretion (TICE), the nonbiliary cholesterol excretion, using natural products can be an effective way to reduce CVD. Bilberry (Vaccinium myrtillus L.) has been reported to have cardioprotective effects by ameliorating oxidative stress, inflammation, and dyslipidemia. However, the role of bilberry in intestinal cholesterol metabolism is not well understood. To examine the effects of bilberry in intestinal cholesterol metabolism, we measured the genes for cholesterol flux and de novo synthesis in anthocyanin-rich bilberry extract (BE)-treated Caco-2 cells. BE significantly decreased the genes for cholesterol absorption, i.e., Niemann-Pick C1 Like 1 and ATP-binding cassette transporter A1 (ABCA1). In contrast, BE significantly upregulated ABCG8, the apical transporter for cholesterol. There was a significant induction of low-density lipoprotein receptors, with a concomitant increase in cellular uptake of cholesterol in BE-treated cells. The expression of genes for lipogenesis and sirtuins was altered by BE treatment. In the present study, BE altered the genes for cholesterol flux from basolateral to the apical membrane of enterocytes, potentially stimulating TICE. These results support the potential of BE in the prevention of hypercholesterolemia

  • PMID: 12674456

    Gordon AE, Shaughnessy AF. Saw palmetto for prostate disorders. Am Fam Physician. 2003 Mar 15;67(6):1281-3. PMID: 12674456.

    Saw palmetto is an herbal product used in the treatment of symptoms related to benign prostatic hyperplasia. The active component is found in the fruit of the American dwarf palm tree. Studies have demonstrated the effectiveness of saw palmetto in reducing symptoms associated with benign prostatic hyperplasia. Saw palmetto appears to have efficacy similar to that of medications like finasteride, but it is better tolerated and less expensive. There are no known drug interactions with saw palmetto, and reported side effects are minor and rare. No data on its long-term usage are available. The herbal product also has been used to treat chronic prostatitis, but currently there is no evidence of its efficacy

    PMID: 28762712

    Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017 Jul 15;96(2):101-107. PMID: 28762712.

    Nearly 25% of U.S. adults report concurrently taking a prescription medication with a dietary supplement. Some supplements, such as St. John's wort and goldenseal, are known to cause clinically important drug interactions and should be avoided by most patients receiving any pharmacologic therapy. However, many other supplements are predicted to cause interactions based only on in vitro studies that have not been confirmed or have been refuted in human clinical trials. Some supplements may cause interactions with a few medications but are likely to be safe with other medications (e.g., curcumin, echinacea, garlic, Asian ginseng, green tea extract, kava kava). Some supplements have a low likelihood of drug interactions and, with certain caveats, can safely be taken with most medications (e.g., black cohosh, cranberry, ginkgo, milk thistle, American ginseng, saw palmetto, valerian). Clinicians should consult reliable dietary supplement resources, or clinical pharmacists or pharmacologists, to help assess the safety of specific herbal supplement-drug combinations. Because most patients do not disclose supplement use to clinicians, the most important strategy for detecting herb-drug interactions is to develop a trusting relationship that encourages patients to discuss their dietary supplement use

    PMID: 35334848

    Yamada S, Shirai M, Ono K, Kageyama S. Beneficial Effects of Saw Palmetto Fruit Extract on Urinary Symptoms in Japanese Female Subjects by a Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. Nutrients. 2022 Mar 11;14(6):1190. doi: 10.3390/nu14061190. PMID: 35334848; PMCID: PMC8953103.

    Saw palmetto berry extract (SPE) is the most commonly consumed supplement by men with benign prostatic hyperplasia (BPH). The oral administration of SPE was previously shown to significantly attenuate urodynamic symptoms in the hyperactive bladders of female rats by increasing bladder capacity and prolonging the micturition interval. The amelioration of urodynamic symptoms by SPE may be partly attributed to its binding to muscarinic receptors in the urinary bladder and its inhibition of vanilloid receptors on afferent nerves. Therefore, SPE may be pharmacologically effective at mitigating lower urinary tract symptoms (LUTS) in women. The efficacy and safety of a 12-week treatment with SPE in adult women with urinary symptoms were examined herein. The daytime frequency score in the core lower urinary symptom score (CLSS) questionnaire was significantly lower in women with LUTS treated with SPE for 12 weeks than in the placebo group. A subgroup analysis revealed that SPE alleviated the symptoms of daytime frequency (CLSS Q1) and nocturia (CLSS Q2) in a subset of subjects with a CLSS Q5 score of 1 or higher. The daytime frequency of urination in overactive bladder symptom score (OABSS) Q1 was also significantly improved by the SPE treatment. In conclusion, the present study is the first to demonstrate the potential of SPE to mitigate LUTS in adult women

  • PMID: 22744951

    Gaweł E. Chemical composition of lucerne leaf extract (EFL) and its applications as a phytobiotic in human nutrition. Acta Sci Pol Technol Aliment. 2012 Jul-Sep;11(3):303-10. PMID: 22744951.

    Lucerne, a valuable plant grown mainly for animal feed, is rich in protein, minerals (Ca, Cu, Fe, Mg, Mn, P, Zn, Si), vitamins (A, B, C, D, E, K, U), phytochemical substances (carotene, chlorophyll, coumarins, isoflavones, alkaloids, saponins), contains secondary metabolites of plants (phytoestrogens: isoflavones and coumestrol), and antinutritional components (phytates, L-canavanine, saponins). It may be used as a dietary supplement in human nutrition. The proteins found in lucerne are comprised of numerous exogenous and semi-exogenous amino acids which are desirable for human body. Extract from the leaves of alfalfa (EFL - l'Extrait Foliaire de Luzerne) practically does not contain mycotoxins and pesticide pollutants. It is a completely natural product, safe even in a long-term supplementation. Extract from the leaves of alfalfa has a positive, multidirectional impact on the human body. It increases the level of estrogen, prevents atherosclerosis, helps blood circulation and strenghtens immunity, protects against the development of dangerous diseases of the digestive tract, combats anemia and many other health ailments. The results of preclinical studies indicate that alfalfa leaf extract enriched with vitamin C (EFL) can be a dietary supplement supporting the human body in fighting malnutrition, ischemic diseases, and various disorders of digestive tract. It also strengthens and enhances immunity

  • PMID: 26561078

    Panahi Y, Darvishi B, Jowzi N, Beiraghdar F, Sahebkar A. Chlorella vulgaris: A Multifunctional Dietary Supplement with Diverse Medicinal Properties. Curr Pharm Des. 2016;22(2):164-73. doi: 10.2174/1381612822666151112145226. PMID: 26561078.

    Chlorella vulgaris is a green unicellular microalgae with biological and pharmacological properties important for human health. C. vulgaris has a long history of use as a food source and contains a unique and diverse composition of functional macro- and micro-nutrients including proteinsChlorella vulgaris is a green unicellular microalgae with biological and pharmacological properties important for human health. C. vulgaris has a long history of use as a food source and contains a unique and diverse composition of functional macro- and micro-nutrients including proteins, omega-3 polyunsaturated fatty acids, polysaccharides, vitamins and minerals. Clinical trials have suggested that supplementation with C. vulgaris can ameliorate amelioration hyperlipidemia and hyperglycemia, and protect against oxidative stress, cancer and chronic obstructive pulmonary disease. In this review, we summarize the findings on the health benefits of Chlorella supplementation and the molecular mechanisms underlying these effects., omega-3 polyunsaturated fatty acids, polysaccharides, vitamins and minerals. Clinical trials have suggested that supplementation with C. vulgaris can ameliorate amelioration hyperlipidemia and hyperglycemia, and protect against oxidative stress, cancer and chronic obstructive pulmonary disease. In this review, we summarize the findings on the health benefits of Chlorella supplementation and the molecular mechanisms underlying these effects

    PMID: 35331862

    Sherafati N, Bideshki MV, Behzadi M, Mobarak S, Asadi M, Sadeghi O. Effect of supplementation with Chlorella vulgaris on lipid profile in adults: A systematic review and dose-response meta-analysis of randomized controlled trials. Complement Ther Med. 2022 Jun;66:102822. doi: 10.1016/j.ctim.2022.102822. Epub 2022 Mar 22. PMID: 35331862.

    Objective: To summarize available findings on the effect of Chlorella vulgaris supplementation on lipid profile in adults.

    Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

    Setting: This study followed 2020 PRISMA guideline. We performed a systematic search in the online databases to identify relevant articles and then, extracted required data from each paper for the meta-analysis. Random-effects models were used to obtain overall mean difference (MD) comparing Chlorella vulgaris supplementation with a control group.

    Main outcome measures: Blood lipids including triglyceride (TG), total cholesterol (TC), LDL-C, and HDL-C.

    Results: In total, 10 RCTs with a total sample size of 539 adults (264 in the Chlorella vulgaris group and 275 in the control group) were included. Of the 10 RCTs, four had a low risk of bias for all aspects of the Cochrane risk of bias tool. Also, only two studies determined the chlorella content, purity, potency, and contamination of the supplements used in the intervention. Combining results from these studies showed a summary MD of -2.11 mg/dL (95% CI: -7.28 to 3.06) for TG, -7.47 mg/dL (95% CI: -12.98 to -1.96) for TC, -7.71 mg/dL (95% CI: -14.05 to -1.37) for LDL-C, and -0.45 mg/dL (95% CI: -0.67 to 1.57) for HDL-C, indicating a beneficial effect of Chlorella vulgaris supplementation on TC and LDL-C levels. Based on the dose-response analysis, the reducing effect of Chlorella vulgaris supplementation on LDL-C levels was seen at the dosages between zero and 1500 mg/d (P for non-linearity= 0.01), whereas in higher amounts, this effect was not significant.

    Conclusion: We found that Chlorella vulgaris supplementation had a beneficial effect on TC and LDL-C levels with no significant effect on TG and HDL-C levels

  • PMID: 32892320

    Gurney T, Spendiff O. Spirulina supplementation improves oxygen uptake in arm cycling exercise. Eur J Appl Physiol. 2020 Dec;120(12):2657-2664. doi: 10.1007/s00421-020-04487-2. Epub 2020 Sep 5. PMID: 32892320; PMCID: PMC7674321.

    Purpose: Spirulina has previously been reported to improve high-intensity exercise performance and hemoglobin. However, spirulina's effect on arm cycling exercise has yet to be investigated. The purpose of this study was to investigate the responses of spirulina supplementation on hemoglobin and on oxygen uptake, RER and HR during seated arm cycling exercise.

    Methods: In a double-blinded randomized crossover design, eleven males untrained in arm cycling ingested 6 g/day of spirulina or placebo for seven days. Seated on the Arm Crank Ergometer, each participant performed a baseline V̇O2max test, and then after supplementation, 2 × 30-min submaximal exercise bouts corresponding to 55% of their V̇O2max, followed by an incremental test to fatigue. A seven-day wash-out period was required between conditions. Oxygen uptake, RER and HR were measured continuously during exercise and hemoglobin measured prior to exercise after both conditions.

    Results: Spirulina significantly (p < 0.05) increased Hb in comparison to Placebo (144.1 g/l ± 10.5 Vs 154.5 g/l ± 6.9). After spirulina supplementation, during the 30-min exercise bouts, oxygen uptake and HR were significantly lower (2170 ml/min ± 173 Vs 2311 ml/min ± 189 and 154 bpm ± 14 Vs 149 bpm ± 17), RER was not significantly different. In comparison to placebo, Spirulina significantly increased oxygen uptake at time of fatigue (34.10 ml/min/kg ± 6.03 Vs 37.37 ml/min/kg ± 5.98). Time taken to fatigue was not different.

    Conclusion: Spirulina supplementation significantly reduces oxygen uptake and HR during arm cycling submaximal exercise, allowing for an increased oxygen uptake during an incremental test to fatigue

    PMID: 34235823

    Naeini F, Zarezadeh M, Mohiti S, Tutunchi H, Ebrahimi Mamaghani M, Ostadrahimi A. Spirulina supplementation as an adjuvant therapy in enhancement of antioxidant capacity: A systematic review and meta-analysis of controlled clinical trials. Int J Clin Pract. 2021 Oct;75(10):e14618. doi: 10.1111/ijcp.14618. Epub 2021 Aug 4. PMID: 34235823.

    Background: Spirulina, a type of blue-green algae, is used as an adjuvant treatment of metabolic and inflammatory diseases. Evidence about the effects of spirulina on antioxidant system are conflicting. Thus, this quantitative review aimed to summarise the effects of spirulina administration on antioxidant status biomarkers.

    Methods: Systematic searches were conducted using the PubMed/Medline, Scopus, Web of Science and EMBASE, up to May 2021. Random effect analysis was applied to perform meta-analysis. Subgroup analyses and multivariate meta-regression were performed to find heterogeneity sources. Quality assessment was conducted using Cochrane Collaboration's tool. Trim and fill analysis were also carried out in case of the presence of publication bias.

    Results: A total of nine articles that enrolled 415 subjects were included in the present meta-analysis. Obtained findings exhibited that spirulina supplementation had marginal significant effect on total antioxidant capacity (TAC) (SMD = 0.49; 95% CI: -0.001, 0.98; P = .05) and superoxide dismutase (SOD) activity (SMD = 0.72; 95% CI: -0.03, 1.46; P = .06), while did not affect glutathione peroxidase (GPx) activity (SMD=0.27; 95% CI: -0.23, 0.77; P = .29).

    Conclusions: Spirulina consumption may exert beneficial effects on enhancement of antioxidant system. A marginal significant increasing effect on TAC and SOD activity were found by spirulina administration. However, it did not affect GPx activity

    PMID: 34107141

    Moradi S, Zobeiri M, Feizi A, Clark CCT, Entezari MH. The effects of spirulina (Arthrospira platensis) supplementation on anthropometric indices, blood pressure, sleep quality, mental health, fatigue status and quality of life in patients with ulcerative colitis: A randomised, double-blinded, placebo-controlled trial. Int J Clin Pract. 2021 Oct;75(10):e14472. doi: 10.1111/ijcp.14472. Epub 2021 Jun 27. PMID: 34107141.

    Background: An emerging body of evidence has highlighted the protective role of spirulina in human health. Thus, we conducted a randomised controlled trial to discern the effects of spirulina supplementation on anthropometric indices, blood pressure, sleep quality, mood, fatigue status and quality of life among ulcerative colitis patients.

    Methods: Eighty participants with ulcerative colitis were randomly allocated to receive, either, 1 g/day (two 500 mg capsules) spirulina (n = 40) or placebo (n = 40), in a clinical trial for eight weeks. Dietary intake, physical activity, sleep quality, mental health, fatigue status and quality of life were assessed for each participant at baseline and trial cessation. Anthropometric indices and blood pressure were also assessed.

    Results: Seventy-three participants completed the intervention. Our results revealed that spirulina supplementation significantly reduced sleep disturbances (P = .03), while no significant changes occurred in the sleep quality score or other sleep parameters, vs the placebo group (P > .05). Furthermore, a significant reduction in stress score (P = .04) and increase in quality of life (P = .03) was detected; but not anxiety, depression or fatigue scores (P > .05). Additionally, anthropometric indices and blood pressure did not significantly change (P > .05).

    Conclusion: An improved quality of life was observed among ulcerative colitis patients following spirulina supplementation, which could be attributed to improved sleep disturbance and stress status. Further clinical studies, with longer duration interventions and suitably powered sample sizes, are necessary to elucidate the veracity of our findings

  • PMID: 34206160

    Aoe S, Yamanaka C, Ohtoshi H, Nakamura F, Fujiwara S. Effects of Daily Kelp (Laminaria japonica) Intake on Body Composition, Serum Lipid Levels, and Thyroid Hormone Levels in Healthy Japanese Adults: A Randomized, Double-Blind Study. Mar Drugs. 2021 Jun 22;19(7):352. doi: 10.3390/md19070352. PMID: 34206160; PMCID: PMC8307228.

    To investigate whether supplementation with iodine-reduced kelp (Laminaria japonica) powder decreases body fat composition in overweight Japanese subjects, a randomized, double-blind, placebo-controlled intervention study was conducted in 50 Japanese subjects with body mass index (BMI) ≥25 and <30 kg/m2. Subjects were randomly assigned to consume thirty tablets/d (10 tablets orally, 3 times/d) containing either iodine-reduced kelp powder (test, 6 g kelp powder corresponding to 3 g alginate/d) or kelp-free powder (placebo) for 8 weeks. Anthropometric measurements, blood lipids, and serum thyroid hormone levels were obtained before and after the trial. Body fat percentage was significantly decreased in male subjects from the test group compared with the placebo group. The same tendency was observed for body weight (p = 0.065) and BMI (p = 0.072) in male subjects. No significant changes in anthropometric measurements or visceral fat area were observed in female subjects. Serum thyroid hormone concentrations did not increase after 1.03 mg/d of iodine supplementation through kelp intake. The intake of iodine-reduced kelp powder led to significant and safe reductions in body fat percentage in overweight male subjects. The consumption of kelp high in alginate may contribute to preventing obesity without influencing thyroid function in Japanese subjects with a relatively high intake of iodine from seaweed

Other

  • PMID: 19419806

    Ferrando AA, Paddon-Jones D, Hays NP, Kortebein P, Ronsen O, Williams RH, McComb A, Symons TB, Wolfe RR, Evans W. EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr. 2010 Feb;29(1):18-23. doi: 10.1016/j.clnu.2009.03.009. Epub 2009 May 5. PMID: 19419806.

    Background & aims: Older individuals are more likely to experience extended hospitalization and become protein malnourished during hospitalization. The concomitant compulsory inactivity results in functional decline. Increasing protein intake in hospitalized patients improves nitrogen balance, but effects on function are unknown. In the present study, we examined the effects of increasing protein intake by essential amino acid (EAA) supplementation in older individuals subjected to 10 d bed rest on LBM and muscle function.

    Methods: Subjects were given a placebo (n=12, 68+/-5 (SD) yrs, 83+/-19 kg) or 15 g of EAA (n=10, 71+/-6, 72+/-8 kg) 3 times per day throughout 10d of bed rest. LBM, muscle protein synthesis, and muscle function were determined before and after bed rest. Due to an imbalance in randomized gender distribution between groups, gender and beginning functional and LBM measures were utilized for analyses by repeated measures analysis of covariance (RMANCOVA).

    Results: Analyses revealed the potential for the preservation of functional outcomes with EAA supplementation.

    Conclusions: Increasing protein intake above the RDA may preserve muscle function in the elderly during compulsory inactivity. EAA supplementation is potentially an efficient method of increasing protein intake without affecting satiety

    PMID: 33315000

    Ispoglou T, Witard OC, Duckworth LC, Lees MJ. The efficacy of essential amino acid supplementation for augmenting dietary protein intake in older adults: implications for skeletal muscle mass, strength and function. Proc Nutr Soc. 2021 May;80(2):230-242. doi: 10.1017/S0029665120008010. Epub 2020 Dec 14. PMID: 33315000.

    The primary aim of this review is to evaluate the efficacy of essential amino acid (EAA) supplementation as a strategy to increase dietary protein intake and improve muscle mass, strength and function in older adults. A sufficient daily protein intake is widely recognised to be fundamental for the successful management of sarcopenia in older undernourished adults. In practice, optimising protein intakes in older adults is complex, requiring consideration of the dose and amino acid composition (i.e. a complete EAA profile and abundant leucine content) of ingested protein on a per meal basis, alongside the age-related decline in appetite and the satiating properties of protein. Recent studies in older adults demonstrate that EAA-based supplements are non-satiating and can be administered alongside food to enhance the anabolic properties of a meal containing a suboptimal dose of protein; an effect magnified when combined with resistance exercise training. These findings support the notion that EAA supplementation could serve as an effective strategy to improve musculoskeletal health in older adults suffering from non-communicable diseases such as sarcopenia. Compliance is critical for the long-term success of complex interventions. Hence, aspects of palatability and desire to eat are important considerations regarding EAA supplementation. In conclusion, EAA-based supplements enriched with l-leucine offer an alternative strategy to whole protein sources to assist older adults in meeting protein recommendations. In practice, EAA supplements could be administered alongside meals of suboptimal protein content, or alternatively between meals on occasions when older adults achieve their per meal protein intake recommendations

    PMID: 31307843

    Randolph AC, Markofski MM, Rasmussen BB, Volpi E. Effect of essential amino acid supplementation and aerobic exercise on insulin sensitivity in healthy older adults: A randomized clinical trial. Clin Nutr. 2020 May;39(5):1371-1378. doi: 10.1016/j.clnu.2019.06.017. Epub 2019 Jun 28. PMID: 31307843; PMCID: PMC6934924.

    Background & aims: The combination of prolonged essential amino acid (EAA) supplementation and aerobic exercise training (Ex) improves muscle protein metabolism, strength and function in healthy older adults. However, excess EAA intake may worsen insulin sensitivity. Here we report the effects of EAA supplementation (EAA, n = 11), placebo (PLA, n = 10), aerobic exercise with placebo (Ex + PLA, n = 11) or Ex with EAA supplementation (Ex + EAA, n = 10) for 22 weeks on insulin sensitivity in non-diabetic older adults.

    Methods: A 2 × 2 design with block randomization and double blinding for supplement or placebo was used. Subjects ingested EAA (15 g) or placebo daily. Exercising subjects participated in supervised progressive vigorous treadmill walking 3 times weekly. Measures of insulin sensitivity by oral glucose tolerance testing were collected at baseline and 22 weeks. Dietary intakes of protein and specific amino acids were determined in a subset of subjects.

    Results: Overall, exercise improved insulin sensitivity, while EAA supplementation had no effect. In the dietary subset, post-intervention insulin sensitivity did not correlate significantly with the total intake of EAA, anti-angiogenic amino acids (cysteine, methionine), or branched-chain amino acids (isoleucine, leucine, valine).

    Conclusions: Overall, we conclude that in healthy older adults with moderate protein intake, EAA supplementation is metabolically safe as it does not decrease insulin sensitivity regardless of its combination with aerobic exercise. Thus, daily protein intake should be controlled for when modeling insulin sensitivity. Future studies should explore the role of increased blood flow as a potential explanatory factor for the observed interaction between aerobic exercise and supplementation

    PMID: 31021358

    Negro M, Perna S, Spadaccini D, Castelli L, Calanni L, Barbero M, Cescon C, Rondanelli M, D'Antona G. Effects of 12 Weeks of Essential Amino Acids (EAA)-Based Multi-Ingredient Nutritional Supplementation on Muscle Mass, Muscle Strength, Muscle Power and Fatigue in Healthy Elderly Subjects: A Randomized Controlled Double-Blind Study. J Nutr Health Aging. 2019;23(5):414-424. doi: 10.1007/s12603-019-1163-4. PMID: 31021358.

    Objective: To counteract muscle mass, muscle strength and power loss during aging, and to study age-related change of neuromuscular manifestation of fatigue in relation to nutritional supplementation.

    Design: randomized controlled double-blind study.

    Setting: Twice-daily consumption for 12 weeks of an Essential Amino Acids (EAA)-based multi-ingredient nutritional supplement containing EAA, creatine, vitamin D and Muscle Restore Complex®.

    Participants: 38 healthy elderly subjects (8 male, 30 female; age: 68.91±4.60 years; body weight: 69.40±15.58 kg; height: 1.60±0.09 m) were randomized and allocated in supplement (SUPP) or placebo (PLA) group. Mean Measurements: Vitamin D blood level; Appendicular Lean Mass (ALM); Visceral Adipose Tissue (VAT); Maximal Voluntary Contraction (MVC) and Peak Power (PP); myoelectric descriptors of fatigue: Fractal Dimension and Conduction Velocity initial values (FD iv, CV iv), their rates of change (FD slopes, CV slopes) and the Time to perform the Task (TtT). Mean Results: Significant changes were found in SUPP compared to baseline: Vitamin D (+8.73 ng/ml; p<0.001); ALM (+0.34 kg; p<0.001); VAT (-76.25 g; p<0.001); MVC (+0.52 kg; p<0.001); PP (+4.82 W; p<0.001). Between group analysis (SUPP Vs. PLA) showed improvements: vitamin D blood levels (+11,72 ng/ml; p<0.001); Legs FFM (+443.7 g; p<0.05); ALM (+0.53 kg; p<0.05); MVC (+1.38 kg; p<0.05); PP (+9.87 W; p<0.05). No statistical changes were found for FD iv, CV iv, FD and CV slopes and TtT, either compared to baseline or between groups. Significant correlations between mean differences in SUPP group were also found.

    Conclusion: The study demonstrates that in healthy elderly subjects an EAA-based multi-ingredient nutritional supplementation of 12 weeks is not effective to change myoelectric manifestation of fatigue and TtT failure but can positively affect muscle mass, muscle strength, muscle power and VAT, counterbalancing more than one year of age-related loss of muscle mass and strength

    PMID: 30280129

    Dreyer HC, Owen EC, Strycker LA, Smolkowski K, Muyskens JB, Kirkpatrick TK, Christie AD, Kuehl KS, Lantz BA, Shah SN, Mohler CG, Jewett BA. Essential Amino Acid Supplementation Mitigates Muscle Atrophy After Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial. JB JS Open Access. 2018 Jun 4;3(2):e0006. doi: 10.2106/JBJS.OA.18.00006. PMID: 30280129; PMCID: PMC6145559.

    Abstract

    Background: Substantial muscle atrophy occurs after total knee arthroplasty (TKA), resulting in decreased strength and impaired mobility. We sought to determine whether perioperative supplementation with essential amino acids (EAA) would attenuate muscle atrophy following TKA and whether the supplements were safe for ingestion in an older surgical population.

    Methods: We performed a double-blind, placebo-controlled, randomized trial of 39 adults (age range, 53 to 76 years) undergoing primary unilateral TKA who ingested 20 g of EAA (n = 19) or placebo (n = 20) twice daily for 7 days preoperatively and for 6 weeks postoperatively. At baseline and 6 weeks postoperatively, magnetic resonance imaging (MRI) scans were obtained to measure quadriceps and hamstrings muscle volume. Secondary outcomes included functional mobility and strength. Data on physical activity, diet, and patient-reported outcomes (Veterans RAND 12-Item Health Survey and Knee injury and Osteoarthritis Outcome Score) were collected. Safety was determined through blood tests evaluating blood urea nitrogen, creatinine, creatinine clearance, homocysteine, and renal and liver function. Laboratory values at baseline, on the day of surgery, and at 2 days, 2 weeks, and 6 weeks postoperatively were compared between treatment groups. Analysis of covariance models, with baseline values as covariates, were used to evaluate outcomes between treatment groups. P values were adjusted for multiple tests.

    Results: Compared with baseline, the EAA group had significantly less decrease in mean quadriceps muscle volume compared with the placebo group in the involved leg (-8.5% ± 2.5% compared with -13.4% ± 1.9%; p = 0.033) and the contralateral leg (-1.5% ± 1.6% compared with -7.2% ± 1.4%; p = 0.014). The hamstrings also demonstrated a greater muscle-volume-sparing effect for the EAA group than for the placebo group in the involved leg (-7.4% ± 2.0% compared with -12.2% ± 1.4%; p = 0.036) and contralateral leg (-2.1% ± 1.3% compared with -7.5% ± 1.5%; p = 0.005). There were no differences between the groups in terms of functional measures or strength. Blood chemistry values varied significantly between assessments periods but did not statistically differ between groups.

    Conclusions: The results of the present study suggest that EAA supplementation is safe and reduces the loss of muscle volume in older adults recovering from TKA

    PMID: 8365971

    MacLean DA, Graham TE. Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans. J Appl Physiol (1985). 1993 Jun;74(6):2711-7. doi: 10.1152/jappl.1993.74.6.2711. PMID: 8365971.

    Abstract

    This study examined the effects of branched-chain amino acid (BCAA) supplementation on amino acid and ammonia (NH3) responses during prolonged exercise in humans. Seven men cycled for 60 min at 75% of maximal O2 uptake after 45 min of either placebo (dextrose, 77 mg/kg) or BCAA (leucine + isoleucine + valine, 77 mg/kg) supplementation. Plasma samples (antecubital vein) were collected at rest and during exercise and analyzed for plasma NH3 and amino acids, whole blood glucose and lactate, and serum free fatty acids and glycerol. After BCAA administration, plasma BCAA levels increased from 375 +/- 22 to 760 +/- 80 microM (P < 0.05) by the onset of exercise and remained elevated throughout the experiment. Plasma NH3 concentrations increased continually during exercise for both trials and were higher (P < 0.05) after BCAA supplementation than after placebo administration. The mean plasma NH3 increase from rest to 60 min was 79 +/- 10 and 53 +/- 4 microM for BCAA and placebo trials, respectively. Plasma alanine and glutamine concentrations were elevated (P < 0.05) during exercise for both treatments. However, only glutamine concentrations were greater (P < 0.05) for BCAA trial than for placebo trial during exercise. There were no significant differences between treatments for glucose, lactate, free fatty acids, and glycerol or any other plasma amino acid. These data suggest that increased BCAA availability before exercise, when initial muscle glycogen is normal, results in significantly greater plasma NH3 responses during exercise than does placebo administration

    PMID: 28285641

    Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults. Metabolism. 2017 Apr;69:120-129. doi: 10.1016/j.metabol.2016.12.010. Epub 2016 Dec 20. PMID: 28285641; PMCID: PMC5351771.

    Background: The development of effective nutritional strategies in support of muscle growth for patients with chronic obstructive pulmonary disease (COPD) remains challenging. Dietary essential amino acids (EAAs) are the main driver of postprandial net protein anabolism. In agreement, EAA supplements in healthy older adults are more effective than supplements with the composition of complete proteins. In patients with COPD it is still unknown whether complete protein supplements can be substituted with only EAAs, and whether they are as effective as in healthy older adults.

    Methods: According to a double-blind randomized crossover design, we examined in 23 patients with moderate to very severe COPD (age: 65±2 years, FEV1: 40±2% of predicted) and 19 healthy age-matched subjects (age: 64±2 years), whether a free EAA mixture with a high proportion (40%) of leucine (EAA mixture) stimulated whole body net protein gain more than a similar mixture of balanced free EAAs and non-EAAs as present in whey protein (TAA mixture). Whole body net protein gain and splanchnic extraction of phenylalanine (PHE) were assessed by continuous IV infusion of L-[ring-2H5]-PHE and L-[ring-2H2]-tyrosine, and enteral intake of L-[15N]-PHE (added to the mixtures).

    Results: Besides an excellent positive linear relationship between PHE intake and net protein gain in both groups (r=0.84-0.91, P<0.001), net protein gain was 42% higher in healthy controls and 49% higher in COPD patients after intake of the EAA mixture compared to the TAA mixture (P<0.0001). These findings could not be attributed to the high LEU content, as in both groups net protein gain per gram EAA intake was lower for the EAA mixture (P<0.0001). Net protein gain was higher in COPD patients for both mixtures due to a 40% lower splanchnic extraction (P<0.0001), but was similarly related to dietary PHE (i.e. EAA) plasma appearance.

    Conclusions: In COPD patients, similarly to healthy older adults, free EAA supplements stimulate whole body protein anabolism more than free amino acid supplements with the composition of complete proteins. Therefore, free EAA supplements may aid in the prevention and treatment of muscle wasting in this patient population

  • Foods rich in Beta Carotene:

    Bakes Sweet Potatoes, Carrots, Dark Leafy Greens [Spinach, Kales, Mustard Greens, Collards, Swiss Chard], Butternut Squash, Cantaloupe Melons, Romaine Lettuce, Red Bell Peppers

    PMID: 15949689

    Palozza P. Can beta-carotene regulate cell growth by a redox mechanism? An answer from cultured cells. Biochim Biophys Acta. 2005 May 30;1740(2):215-21. doi: 10.1016/j.bbadis.2004.12.008. Epub 2004 Dec 31. PMID: 15949689.

    Many studies suggest a protective role of beta-carotene against cancer. However, the ATBC and the CARET trials have shown that beta-carotene increases the incidence of lung cancer in heavy smokers and asbestos workers. To explain this paradox, it can be hypothesized that beta-carotene modulates intracellular redox status and through this mechanism, it affects redox-sensitive molecular pathways involved in the regulation of cell cycle progression and apoptosis. Studies conducted in cultured cells seem to confirm such a hypothesis. At low concentrations, the carotenoid may serve as an antioxidant, inhibiting free radical production, while at relatively high concentrations and/or in the presence of a chronic oxidative stress (i.e. smoke), it may behave as a prooxidant, propagating free radical-induced reactions, consuming endogenous antioxidants and inducing DNA oxidative damage. In this context, it may regulate cell growth and death by the modulation of redox-sensitive genes and transcription factors

    PMID: 14704324

    Bendich A. From 1989 to 2001: what have we learned about the "biological actions of beta-carotene"? J Nutr. 2004 Jan;134(1):225S-230S. doi: 10.1093/jn/134.1.225S. PMID: 14704324.

    Dr. James Allen Olson helped us to define the role of beta-carotene in human health by categorizing these as ""functions, actions and associations."" In the last decade, significant research has shown that beta-carotene acts as an antioxidant in biologically relevant systems, affects several aspects of human immune function and higher intake/serum levels are associated with improvements in certain physiological functions such as lung function. The unexpected findings of increased lung cancer in beta-carotene supplemented smokers in the ATBC and CARET intervention studies have resulted in the need for expanded research efforts to define the mechanism(s) of action of beta-carotene. Recent survey data as well as laboratory animal studies continue to find an inverse association between beta-carotene and cancer risk. Because beta-carotene is the major source of vitamin A for the majority of the world's population, it is critical to define the safe levels of intake from foods and supplements

  • Foods rich in Co-Enzyme Q10:

    Read Meat, Chicken, Fish [Salmon, Eel, Sardines, Trout, Mackerel, Oysters, Squid, Shrimp], Organ Meats [Heart, Liver, Kidney], Oils [Soybean, Canola], Nuts and Seeds [Sesame Seeds, Pistachios]

    PMID: 28762311

    Zhang X, Tohari AM, Marcheggiani F, Zhou X, Reilly J, Tiano L, Shu X. Therapeutic Potential of Co-enzyme Q10 in Retinal Diseases. Curr Med Chem. 2017;24(39):4329-4339. doi: 10.2174/0929867324666170801100516. PMID: 28762311.

    Background: Coenzyme Q10 (CoQ10) plays a critical role in mitochondrial oxidative phosphorylation by serving as an electron carrier in the respiratory electron transport chain. CoQ10 also functions as a lipid-soluble antioxidant by protecting lipids, proteins and DNA damaged by oxidative stress. CoQ10 deficiency has been associated with a number of human diseases in which CoQ10 supplementation therapy has been effective in slowing or reversing pathological changes. Oxidative stress is a major contributory factor in the process of retinal degeneration.

    Method: The related literature was reviewed through searching PubMed using keywords: CoQ10, CoQ10 and oxidative stress, CoQ10 and retinal degeneration. The functions of CoQ10 were summarized and its use in the treatment of age-related macular degeneration and glaucoma highlighted. The therapeutic potential of CoQ10 for other retinal diseases was also discussed.

    Results: CoQ10 has been applied in different types of neurodegeneration. CoQ10 is detectable in retina and declines with ageing. Early studies showed treatment of CoQ10 improved visual function in patients with age-related macular degeneration. In glaucomatous models, CoQ10 exposure protected ganglion cell death from environmental stress; in glaucoma patients, CoQ10 treatment demonstrated beneficial effects on function of inner retina and enhancement of visual cortical response. Since oxidative stress also plays a critical role in the pathogenesis of diabetic retinopathy and retinitis pigmentosa, CoQ10 is a therapeutic target for both conditions.

    Conclusion: A wide range of evidence supports a role of CoQ10 in retinal diseases through inhibiting production of reactive oxygen species and protecting neuroretinal cells from oxidative damage

    PMID: 2202752

    Greenberg S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol. 1990 Jul;30(7):596-608. doi: 10.1002/j.1552-4604.1990.tb01862.x. PMID: 2202752.

    Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardial ischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide

    PMID: 32933108

    Hargreaves I, Heaton RA, Mantle D. Disorders of Human Coenzyme Q10 Metabolism: An Overview. Int J Mol Sci. 2020 Sep 13;21(18):6695. doi: 10.3390/ijms21186695. PMID: 32933108; PMCID: PMC7555759.

    Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extramitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid, pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. In view of the central role of CoQ10 in cellular metabolism, it is unsurprising that a CoQ10 deficiency is linked to the pathogenesis of a range of disorders. CoQ10 deficiency is broadly classified into primary or secondary deficiencies. Primary deficiencies result from genetic defects in the multi-step biochemical pathway of CoQ10 synthesis, whereas secondary deficiencies can occur as result of other diseases or certain pharmacotherapies

    PMID: 32067520

    Lisicki M, Schoenen J. Metabolic treatments of migraine. Expert Rev Neurother. 2020 Mar;20(3):295-302. doi: 10.1080/14737175.2020.1729130. Epub 2020 Feb 19. PMID: 32067520.

    Introduction: Most preventive migraine treatments modify the brain's excitation/inhibition balance and/or serotonin metabolism, which likely accounts for their unfavorable adverse effect profile. Novel biological therapies blocking CGRP transmission are effective and better tolerated, but they are expensive and may not influence brain dysfunctions upstream in the pathophysiological cascade of migraine, including premonitory and aura symptoms. Biochemical and clinical studies suggest that there may be another complimentary treatment strategy, the one that targets the underestimated metabolic facet of migraine pathophysiology.Areas covered: After a brief description of the metabolic abnormalities found in migraine patients, we will review and discuss published data on metabolic treatments of migraine. There is evidence that riboflavin and co-enzyme Q10 are effective for the prevention of migraine and quasi devoid of adverse effects. Response rates are close to those of topiramate, propranolol, and CGRP/CGRPrec mAbs. The evidence is weaker for thioctic acid. Dietary and pharmacological strategies inducing ketosis are novel promising approaches for which preliminary trials with favorable outcomes have been published.Expert opinion: Metabolic treatments of migraine constitute an effective, well-tolerated, inexpensive, and evidence-supported therapeutic option for migraine prophylaxis, and may be considered as first treatment line in many patients, including in children and adolescents

    PMID: 34502447

    Rodríguez-Varela C, Labarta E. Does Coenzyme Q10 Supplementation Improve Human Oocyte Quality? Int J Mol Sci. 2021 Sep 2;22(17):9541. doi: 10.3390/ijms22179541. PMID: 34502447; PMCID: PMC8431086.

    Acquiring oocyte competence requires optimal mitochondrial function and adequate ATP levels. In this context, CoQ10 supplementation may improve human oocyte quality and subsequent reproductive performance given its role in ATP synthesis and mitochondrial protection from ROS oxidative damage. In infertility treatments, CoQ10 therapy can be orally supplied to promote a more favorable environment for oocyte development in vivo or by its addition to culture media in an attempt to improve its quality in vitro. Human clinical studies evaluating the impact of CoQ10 on reproductive performance are summarized in this review, although the available data do not clearly prove its ability to improve human oocyte quality. The main objective is to provide readers with a complete overview of this topic's current status as well as the keys for potential future research lines that may help to take this therapy to clinical practice. Indeed, further clinical trials are needed to confirm these results along with molecular studies to evaluate the impact of CoQ10 supplementation on oxidative stress status and mitochondrial function in human gametes

    PMID: 8702395

    Folkers K. Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun. 1996 Jul 16;224(2):358-61. doi: 10.1006/bbrc.1996.1033. PMID: 8702395.

    In the human, coenzyme Q10 (vitamin Q10) is biosynthesized from tyrosine through a cascade of eight aromatic precursors. These precursors indispensably require eight vitamins, which are tetrahydrobiopterin, vitamins B6, C, B2, B12, folic acid, niacin, and pantothenic acid as their coenzymes. Three of these eight vitamins (the coenzyme B6, and the coenzymes niacin and folic acid) are indispensable in the biosynthesis of the four bases (thymidine, guanine, adenine, and cytosine) of DNA. One or more of the three vitamins required for DNA are known to cause abnormal pairing of the four bases, which can then result in mutations and the diversity of cancer. The coenzyme B6, required for the conversion of tyrosine to p-hydroxybenzoic acid, is the first coenzyme required in the cascade of precursors. A deficiency of the coenzyme B6 can cause dysfunctions, prior to the formation of vitamin Q10, to DNA. Former data on blood levels of Q10 and new data herein on blood levels of B6, measured as EDTA, in cancer patients established deficiencies of Q10 and B6 in cancer. This complete biochemistry relating to biosyntheses of Q10 and the DNA bases is a rationale for the therapy of cancer with Q10 and other entities in this biochemistry

    PMID: 33325173

    Arenas-Jal M, Suñé-Negre JM, García-Montoya E. Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges. Compr Rev Food Sci Food Saf. 2020 Mar;19(2):574-594. doi: 10.1111/1541-4337.12539. Epub 2020 Feb 19. PMID: 33325173.

    World population growth and aging are posing unprecedented challenges in sustaining the health of 9.1 billion people that will be occupying the planet by 2050. Although noncommunicable diseases such as cardiovascular and neurodegenerative diseases, cancer, and diabetes are among the top 10 global causes of death, they can be prevented by risk factor reduction, early detection, and adequate treatment. Since a healthy diet along with dietary supplementation could play an important role to reduce morbidity and cut off its associated health care costs, research in the food and nutrition area is required to find solutions to global challenges affecting health. As a result of the healthy living trend, dietary supplements category is growing fast, leading to an urgent need for dietitians, physicians, and policy makers to broaden the scientific evidence on the efficacy and safety of a wide range of active ingredients. Coenzyme Q10 (CoQ10), as the third most consumed dietary supplement, and as a potential candidate for the treatment of various noncommunicable diseases that are among the global top 10 causes of death, has gained interest over years. Scientific evidence regarding mainly CoQ10 efficacy and safety, as well as formulation challenges, is addressed in this review

    PMID: 22655115

    Wagner AE, Ernst IM, Birringer M, Sancak O, Barella L, Rimbach G. A combination of lipoic acid plus coenzyme Q10 induces PGC1α, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells. Oxid Med Cell Longev. 2012;2012:835970. doi: 10.1155/2012/835970. Epub 2012 May 9. PMID: 22655115; PMCID: PMC3357652.

    A combination of lipoic acid plus coenzyme Q10 induces PGC1α, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells

  • Foods rich in Alpha Lipoic Acid:

    Read Meat, Organ Meats, Spinach, Broccoli, Tomatoes, Brussels Sprouts

    PMID: 7649494

    Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995 Aug;19(2):227-50. doi: 10.1016/0891-5849(95)00017-r. PMID: 7649494

    alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor

    PMID: 19664690

    Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009 Oct;1790(10):1149-60. doi: 10.1016/j.bbagen.2009.07.026. Epub 2009 Aug 4. PMID: 19664690; PMCID: PMC2756298.

    Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation

    PMID: 35234312

    Najafi N, Mehri S, Ghasemzadeh Rahbardar M, Hosseinzadeh H. Effects of alpha lipoic acid on metabolic syndrome: A comprehensive review. Phytother Res. 2022 Jun;36(6):2300-2323. doi: 10.1002/ptr.7406. Epub 2022 Mar 2. PMID: 35234312.

    Metabolic syndrome (MetS) is a multifactorial disease with medical conditions such as hypertension, diabetes, obesity, dyslipidemia, and insulin resistance. Alpha-lipoic acid (α-LA) possesses various pharmacological effects, including antidiabetic, antiobesity, hypotensive, and hypolipidemia actions. It exhibits reactive oxygen species scavenger properties against oxidation and age-related inflammation and refines MetS components. Also, α-LA activates the 5' adenosine monophosphate-activated protein kinase and inhibits the NFκb. It can decrease cholesterol biosynthesis, fatty acid β-oxidation, and vascular stiffness. α-LA decreases lipogenesis, cholesterol biosynthesis, low-density lipoprotein and very low-density lipoprotein levels, and atherosclerosis. Moreover, α-LA increases insulin secretion, glucose transport, and insulin sensitivity

    PMID: 31016198

    Liu W, Shi LJ, Li SG. The Immunomodulatory Effect of Alpha-Lipoic Acid in Autoimmune Diseases. Biomed Res Int. 2019 Mar 20;2019:8086257. doi: 10.1155/2019/8086257. PMID: 31016198; PMCID: PMC6446120.

    Αlpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically. Accumulating evidences suggested that α-lipoic acid might have immunomodulatory effects on both adaptive and innate immune systems. This review focuses on the evidences and potential targets involved in the immunomodulatory effects of α-lipoic acid. It highlights the fact that α-lipoic acid may have beneficial effects in autoimmune diseases once the immunomodulatory effects can be confirmed by further investigation

    PMID: 22655115

    Wagner AE, Ernst IM, Birringer M, Sancak O, Barella L, Rimbach G. A combination of lipoic acid plus coenzyme Q10 induces PGC1α, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells. Oxid Med Cell Longev. 2012;2012:835970. doi: 10.1155/2012/835970. Epub 2012 May 9. PMID: 22655115; PMCID: PMC3357652.

    A combination of lipoic acid plus coenzyme Q10 induces PGC1α, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells

    PMID: 12495372

    Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71. PMID: 12495372.

    Mercury exposure is the second-most common cause of toxic metal poisoning. Public health concern over mercury exposure, due to contamination of fish with methylmercury and the elemental mercury content of dental amalgams, has long been a topic of political and medical debate. Although the toxicology of mercury is complex, there is evidence for antioxidant protection in the prevention of neurological and renal damage caused by mercury toxicity. Alpha-lipoic acid, a coenzyme of pyruvate and alpha-ketoglutarate dehydrogenase, has been used in Germany as an antioxidant and approved treatment for diabetic polyneuropathy for 40 years. Research has attempted to identify the role of antioxidants, glutathione and alpha-lipoic acid specifically, in both mitigation of heavy metal toxicity and direct chelation of heavy metals. This review of the literature will assess the role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

  • Foods rich in N-Acetyl L-Cystene:

    Meats [Chicken, Turkey, Duck, Fish], Dairy [Cheese, Yogurt], Eggs, Legumes [Lentils], Whole Grains [Oatmeal, Whole Wheat Pasta]

    PMID: 33380301

    Raghu G, Berk M, Campochiaro PA, Jaeschke H, Marenzi G, Richeldi L, Wen FQ, Nicoletti F, Calverley PMA. The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. Curr Neuropharmacol. 2021;19(8):1202-1224. doi: 10.2174/1570159X19666201230144109. PMID: 33380301; PMCID: PMC8719286.

    Oxidative stress, which results in the damage of diverse biological molecules, is a ubiquitous cellular process implicated in the etiology of many illnesses. The sulfhydryl-containing tripeptide glutathione (GSH), which is synthesized and maintained at high concentrations in all cells, is one of the mechanisms by which cells protect themselves from oxidative stress. N-acetylcysteine (NAC), a synthetic derivative of the endogenous amino acid L-cysteine and a precursor of GSH, has been used for several decades as a mucolytic and as an antidote to acetaminophen (paracetamol) poisoning. As a mucolytic, NAC breaks the disulfide bonds of heavily cross-linked mucins, thereby reducing mucus viscosity. In vitro, NAC has antifibrotic effects on lung fibroblasts. As an antidote to acetaminophen poisoning, NAC restores the hepatic GSH pool depleted in the drug detoxification process. More recently, improved knowledge of the mechanisms by which NAC acts has expanded its clinical applications. In particular, the discovery that NAC can modulate the homeostasis of glutamate has prompted studies of NAC in neuropsychiatric diseases characterized by impaired glutamate homeostasis

    PMID: 30551603

    Tardiolo G, Bramanti P, Mazzon E. Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules. 2018 Dec 13;23(12):3305. doi: 10.3390/molecules23123305. PMID: 30551603; PMCID: PMC6320789.

    N-acetylcysteine (NAC), which is an acetylated cysteine compound, has aroused scientific interest for decades due to its important medical applications. It also represents a nutritional supplement in the human diet. NAC is a glutathione precursor and shows antioxidant and anti-inflammatory activities. In addition to the uses quoted in the literature, NAC may be considered helpful in therapies to counteract neurodegenerative and mental health diseases. Furthermore, this compound has been evaluated for its neuroprotective potential in the prevention of cognitive aging dementia. NAC is inexpensive, commercially available and no relevant side effects were observed after its administration. The purpose of this paper is to give an overview on the effects and applications of NAC in Parkinson's and Alzheimer's disorders and in neuropathic pain and stroke

    PMID: 24080471

    Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2014 Feb;141(2):150-9. doi: 10.1016/j.pharmthera.2013.09.006. Epub 2013 Sep 28. PMID: 24080471.

    N-acetyl-l-cysteine (NAC) has long been used therapeutically for the treatment of acetaminophen (paracetamol) overdose, acting as a precursor for the substrate (l-cysteine) in synthesis of hepatic glutathione (GSH) depleted through drug conjugation. Other therapeutic uses of NAC have also emerged, including the alleviation of clinical symptoms of cystic fibrosis through cysteine-mediated disruption of disulfide cross-bridges in the glycoprotein matrix in mucus. More recently, however, a wide range of clinical studies have reported on the use of NAC as an antioxidant, most notably in the protection against contrast-induced nephropathy and thrombosis. The results from these studies are conflicting and a consensus is yet to be reached regarding the merits or otherwise of NAC in the antioxidant setting. This review seeks to re-evaluate the mechanism of action of NAC as a precursor for GSH synthesis in the context of its activity as an ""antioxidant"". Results from recent studies are examined to establish whether the pre-requisites for effective NAC-induced antioxidant activity (i.e. GSH depletion and the presence of functional metabolic pathways for conversion of NAC to GSH) have received adequate consideration in the interpretation of the data. A key conclusion is a reinforcement of the concept that NAC should not be considered to be a powerful antioxidant in its own right: its strength is the targeted replenishment of GSH in deficient cells and it is likely to be ineffective in cells replete in GSH

    PMID: 30551603

    Tardiolo G, Bramanti P, Mazzon E. Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules. 2018 Dec 13;23(12):3305. doi: 10.3390/molecules23123305. PMID: 30551603; PMCID: PMC6320789.

    N-acetylcysteine (NAC), which is an acetylated cysteine compound, has aroused scientific interest for decades due to its important medical applications. It also represents a nutritional supplement in the human diet. NAC is a glutathione precursor and shows antioxidant and anti-inflammatory activities. In addition to the uses quoted in the literature, NAC may be considered helpful in therapies to counteract neurodegenerative and mental health diseases. Furthermore, this compound has been evaluated for its neuroprotective potential in the prevention of cognitive aging dementia. NAC is inexpensive, commercially available and no relevant side effects were observed after its administration. The purpose of this paper is to give an overview on the effects and applications of NAC in Parkinson's and Alzheimer's disorders and in neuropathic pain and stroke

    PMID: 27117852

    Pirabbasi E, Shahar S, Manaf ZA, Rajab NF, Manap RA. Efficacy of Ascorbic Acid (Vitamin C) and/N-Acetylcysteine (NAC) Supplementation on Nutritional and Antioxidant Status of Male Chronic Obstructive Pulmonary Disease (COPD) Patients. J Nutr Sci Vitaminol (Tokyo). 2016;62(1):54-61. doi: 10.3177/jnsv.62.54. PMID: 27117852.

    Antioxidant therapy has a potential to be introduced as therapeutic modality for chronic obstructive pulmonary disease (COPD) patients. This study aimed to determine the effect of antioxidant supplementation [ascorbic acid and N-Acetylcysteine (NAC)] on nutritional and antioxidant status in male COPD patients. A parallel and single blind randomised controlled clinical trial (RCT) was conducted at two medical centers in Kuala Lumpur, Malaysia. Seventy-nine subjects were recruited and randomly divided into four trial arms (i.e., NAC, vitamin C, NAC+vitamin C and control groups) for six mo. The primary outcome was changes in body mass index by estimating power of 90% and significance level of p<0.05. Repeated Measure ANOVA showed that there was a significant interaction effect on BMI (p=0.046) and carbohydrate intake (p=0.030), especially in the NAC group. Plasma glutathione (GSH) increased significantly in all intervention groups, especially in vitamin C (p=0.005). A single supplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects

  • Foods rich in Glutathione:

    Asparagus, Avocado, Okra, Garlic, Cabbage, Spinach, Broccoli

    PMID: 33819793

    Asantewaa G, Harris IS. Glutathione and its precursors in cancer. Curr Opin Biotechnol. 2021 Apr;68:292-299. doi: 10.1016/j.copbio.2021.03.001. Epub 2021 Apr 2. PMID: 33819793.

    Buffering oxidative stress is as a crucial requirement for tumorigenesis. Antioxidant is a term reserved for molecules that quench reactive oxygen species (ROS) and alleviate oxidative stress. The details regarding antioxidant synthesis, their utilization to eliminate ROS, and their ability to promote different stages of tumorigenesis are unclear. Here, we focus on glutathione (GSH), the most abundant antioxidant in the cell, and its precursor amino acids (cysteine, glutamate, and glycine). Even though GSH was discovered more than a century ago, continued research into this antioxidant has provided answers to longstanding questions while also posing new ones

    PMID: 32071304

    Wei Y, Lu M, Mei M, Wang H, Han Z, Chen M, Yao H, Song N, Ding X, Ding J, Xiao M, Hu G. Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nat Commun. 2020 Feb 18;11(1):941. doi: 10.1038/s41467-020-14788-x. PMID: 32071304; PMCID: PMC7029000.

    Oxidative stress is a major pathogenic mechanism in Parkinson's disease (PD). As an important cellular antioxidant, glutathione (GSH) balances the production and incorporation of free radicals to protect neurons from oxidative damage. GSH level is decreased in the brains of PD patients. Hence, clarifying the molecular mechanism of GSH deficiency may help deepen our knowledge of PD pathogenesis. Here we report that the astrocytic dopamine D2 receptor (DRD2) regulates GSH synthesis via PKM2-mediated Nrf2 transactivation. In addition we find that pyridoxine can dimerize PKM2 to promote GSH biosynthesis. Further experiments show that pyridoxine supplementation increases the resistance of nigral dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in wild-type mice as well as in astrocytic Drd2 conditional knockout mice. We conclude that dimerizing PKM2 may be a potential target for PD treatment

    PMID: 36707132

    Averill-Bates DA. The antioxidant glutathione. Vitam Horm. 2023;121:109-141. doi: 10.1016/bs.vh.2022.09.002. Epub 2023 Jan 13. PMID: 36707132.

    Reduced glutathione (GSH) is an essential non-enzymatic antioxidant in mammalian cells. GSH can act directly as an antioxidant to protect cells against free radicals and pro-oxidants, and as a cofactor for antioxidant and detoxification enzymes such as glutathione peroxidases, glutathione S-transferases, and glyoxalases. Glutathione peroxidases detoxify peroxides by a reaction that is coupled to GSH oxidation to glutathione disulfide (GSSG). GSSG is converted back to GSH by glutathione reductase and cofactor NADPH. GSH can regenerate vitamin E following detoxification reactions of vitamin E with lipid peroxyl radicals (LOO). GSH is a cofactor for GST during detoxification of electrophilic substances and xenobiotics. Dicarbonyl stress induced by methylglyoxal and glyoxal is alleviated by glyoxalase enzymes and GSH. GSH regulates redox signaling through reversible oxidation of critical protein cysteine residues by S-glutathionylation. GSH is involved in other cellular processes such as protein folding, protecting protein thiols from oxidation and crosslinking, degradation of proteins with disulfide bonds, cell cycle regulation and proliferation, ascorbate metabolism, apoptosis and ferroptosis

    PMID: 12495372

    Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71. PMID: 12495372.

    Mercury exposure is the second-most common cause of toxic metal poisoning. Public health concern over mercury exposure, due to contamination of fish with methylmercury and the elemental mercury content of dental amalgams, has long been a topic of political and medical debate. Although the toxicology of mercury is complex, there is evidence for antioxidant protection in the prevention of neurological and renal damage caused by mercury toxicity. Alpha-lipoic acid, a coenzyme of pyruvate and alpha-ketoglutarate dehydrogenase, has been used in Germany as an antioxidant and approved treatment for diabetic polyneuropathy for 40 years. Research has attempted to identify the role of antioxidants, glutathione and alpha-lipoic acid specifically, in both mitigation of heavy metal toxicity and direct chelation of heavy metals. This review of the literature will assess the role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity

    PMID: 23392865

    Hansen SH, Grunnet N. Taurine, glutathione and bioenergetics. Adv Exp Med Biol. 2013;776:3-12. doi: 10.1007/978-1-4614-6093-0_1. PMID: 23392865.

    Biochemistry textbook presentations of bioenergetics and mitochondrial function normally focus on the chemiosmotic theory with introduction of the tricarboxylic acid cycle and the electron transport chain, the proton and electrical gradients and subsequent oxidative phosphorylation and ATP-production by ATP synthase. The compound glutathione (GSH) is often mentioned in relation to mitochondrial function, primarily for a role as redox scavenger. Here we argue that its role as redox pair with oxidised glutathione (GSSG) is pivotal with regard to controlling the electrical or redox gradient across the mitochondrial inner-membrane. The very high concentration of taurine in oxidative tissue has recently led to discussions on the role of taurine in the mitochondria, e.g. with taurine acting as a pH buffer in the mitochondrial matrix. A very important consequence of the slightly alkaline pH is the fact that the NADH/NAD(+) redox pair can be brought in redox equilibrium with the GSH redox pair GSH/GSSG.An additional consequence of having GSH as redox buffer is the fact that from the pH dependence of its redox potential, it becomes possible to explain that the mitochondrial membrane potential has been observed to be independent of the matrix pH. Finally a simplified model for mitochondrial oxidation is presented with introduction of GSH as redox buffer to stabilise the electrical gradient, and taurine as pH buffer stabilising the pH gradient, but simultaneously establishing the equilibrium between the NADH/NAD(+) redox pair and the redox buffer pair GSH/GSSG

    PMID: 36707136

    Gęgotek A, Skrzydlewska E. Ascorbic acid as antioxidant. Vitam Horm. 2023;121:247-270. doi: 10.1016/bs.vh.2022.10.008. Epub 2022 Nov 29. PMID: 36707136

    Ascorbic acid, as one of the basic exogenous vitamins, is known for its tremendous antioxidant properties. This review has been prepared to show not only the importance of ascorbic acid as a free radical scavenger, but also to summarize its antioxidant action based on other mechanisms, including activation of intracellular antioxidant systems. Ascorbic acid interacts with small molecule antioxidants, including tocopherol, glutathione and thioredoxin, but also can stimulate the biosynthesis and activation of antioxidant enzymes, such as superoxide dismutase, catalase or glutathione peroxidase. Moreover, ascorbic acid promotes the activity of several transcription factors (Nrf2, Ref-1, AP-1), which enables the expression of genes encoding antioxidant proteins. Additionally, it supports the action of other exogenous antioxidants, mainly polyphenols. In this connection, both DNA, protein and lipids are protected against oxidation. Although ascorbic acid has strong antioxidant properties, it can also have pro-oxidant effects in the presence of free transition metals. However, its role in prevention of DNA mutation and cellular apoptosis, especially in relation to cancer cells is controversial

    PMID: 27117852

    Pirabbasi E, Shahar S, Manaf ZA, Rajab NF, Manap RA. Efficacy of Ascorbic Acid (Vitamin C) and/N-Acetylcysteine (NAC) Supplementation on Nutritional and Antioxidant Status of Male Chronic Obstructive Pulmonary Disease (COPD) Patients. J Nutr Sci Vitaminol (Tokyo). 2016;62(1):54-61. doi: 10.3177/jnsv.62.54. PMID: 27117852.

    Antioxidant therapy has a potential to be introduced as therapeutic modality for chronic obstructive pulmonary disease (COPD) patients. This study aimed to determine the effect of antioxidant supplementation [ascorbic acid and N-Acetylcysteine (NAC)] on nutritional and antioxidant status in male COPD patients. A parallel and single blind randomised controlled clinical trial (RCT) was conducted at two medical centers in Kuala Lumpur, Malaysia. Seventy-nine subjects were recruited and randomly divided into four trial arms (i.e., NAC, vitamin C, NAC+vitamin C and control groups) for six mo. The primary outcome was changes in body mass index by estimating power of 90% and significance level of p<0.05. Repeated Measure ANOVA showed that there was a significant interaction effect on BMI (p=0.046) and carbohydrate intake (p=0.030), especially in the NAC group. Plasma glutathione (GSH) increased significantly in all intervention groups, especially in vitamin C (p=0.005). A single supplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects

    PMID: 32071304

    Wei Y, Lu M, Mei M, Wang H, Han Z, Chen M, Yao H, Song N, Ding X, Ding J, Xiao M, Hu G. Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nat Commun. 2020 Feb 18;11(1):941. doi: 10.1038/s41467-020-14788-x. PMID: 32071304; PMCID: PMC7029000.

    Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection.

    NOTE: Pyridoxine = Vitamin B6

    PMID: 21462082

    Richie JP Jr, Muscat JE, Ellison I, Calcagnotto A, Kleinman W, El-Bayoumy K. Association of selenium status and blood glutathione concentrations in blacks and whites. Nutr Cancer. 2011;63(3):367-75. doi: 10.1080/01635581.2011.535967. PMID: 21462082; PMCID: PMC3087599

    Selenium deficiency has been linked with increased cancer risk and, in some studies, selenium supplementation was protective against certain cancers. Previous studies have suggested that selenium chemoprevention may involve reduced oxidative stress through enhanced glutathione (GSH). Our objectives were to examine the relationships between selenium and GSH in the blood and the modifying effects of race and sex in free-living adults and individuals supplemented with selenium. Plasma selenium concentrations and free and bound GSH concentrations and γ-glutamyl cysteine ligase (GCL) activity in the blood were measured in 336 healthy adults (161 Blacks, 175 Whites). Plasma selenium and blood GSH were also measured in 36 healthy men from our previously conducted placebo-controlled trial of selenium-enriched yeast (247 μg/day for 9 mo). In free-living adults, selenium concentrations were associated with increased blood GSH concentration and GCL activity (P < 0.05). Further, selenium was significantly higher in Whites than in Blacks (P < 0.01). After 9 mo of supplementation, plasma selenium increased 114% in Whites and 50% in Blacks (P < 0.05), and blood GSH increased 35% in Whites (P < 0.05) but was unchanged in Blacks. These results indicate a direct association between selenium and GSH in the blood of both free-living and selenium-supplemented individuals, with race being an important modifying factor

    PMID: 14988435

    Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92. doi: 10.1093/jn/134.3.489. PMID: 14988435.

    Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is the most abundant low-molecular-weight thiol, and GSH/glutathione disulfide is the major redox couple in animal cells. The synthesis of GSH from glutamate, cysteine, and glycine is catalyzed sequentially by two cytosolic enzymes, gamma-glutamylcysteine synthetase and GSH synthetase. Compelling evidence shows that GSH synthesis is regulated primarily by gamma-glutamylcysteine synthetase activity, cysteine availability, and GSH feedback inhibition. Animal and human studies demonstrate that adequate protein nutrition is crucial for the maintenance of GSH homeostasis. In addition, enteral or parenteral cystine, methionine, N-acetyl-cysteine, and L-2-oxothiazolidine-4-carboxylate are effective precursors of cysteine for tissue GSH synthesis. Glutathione plays important roles in antioxidant defense, nutrient metabolism, and regulation of cellular events (including gene expression, DNA and protein synthesis, cell proliferation and apoptosis, signal transduction, cytokine production and immune response, and protein glutathionylation). Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many diseases (including kwashiorkor, seizure, Alzheimer's disease, Parkinson's disease, liver disease, cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack, stroke, and diabetes). New knowledge of the nutritional regulation of GSH metabolism is critical for the development of effective strategies to improve health and to treat these diseases

    PMID: 10523398

    Barbagallo M, Dominguez LJ, Tagliamonte MR, Resnick LM, Paolisso G. Effects of vitamin E and glutathione on glucose metabolism: role of magnesium. Hypertension. 1999 Oct;34(4 Pt 2):1002-6. doi: 10.1161/01.hyp.34.4.1002. PMID: 10523398.

    Vitamin E is an antioxidant that has been demonstrated to improve insulin action. Glutathione, another natural antioxidant, may also be important in blood pressure and glucose homeostasis, consistent with the involvement of free radicals in both essential hypertension and diabetes mellitus. Our group has recently suggested that the effects of reduced glutathione on glucose metabolism may be mediated, at least in part, by intracellular magnesium levels (Mg([i])). Recent evidence suggests that vitamin E enhances glutathione levels and may play a protective role in magnesium deficiency-induced cardiac lesions. To directly investigate the effects of vitamin E supplementation on insulin sensitivity in hypertension, in relation to the effects on circulating levels of reduced (GSH) and oxidized (GSSG) glutathione and on Mg([i]), we performed a 4-week, double-blind, randomized study of vitamin E administration (600 mg/d) versus placebo in 24 hypertensive patients and measured whole-body glucose disposal (WBGD) by euglycemic glucose clamp, GSH/GSSG ratios, and Mg([i]) before and after intervention. The relationships among WBGD, GSH/GSSG, and Mg([i]) in both groups were evaluated. In hypertensive subjects, vitamin E administration significantly increased WBGD (25.56+/-0.61 to 31.75+/-0.53 micromol/kg of fat-free mass per minute; P<0.01), GSH/GSSG ratio (1.10+/-0.07 to 1.65+/-0.11; P<0.01), and Mg([i]) (1.71+/-0.042 to 1.99+/-0.049 mmol/L; P<0.01). In basal conditions, WBGD was significantly related to both GSH/GSSG ratios (r=0.58, P=0.047) and Mg([i]) (r=0.78, P=0.003). These data show a clinical link between vitamin E administration, cellular magnesium, GSH/GSSG ratio, and tissue glucose metabolism. Further studies are needed to explore the cellular mechanism(s) of this association

    PMID: 14988435

    Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92. doi: 10.1093/jn/134.3.489. PMID: 14988435.

    Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is the most abundant low-molecular-weight thiol, and GSH/glutathione disulfide is the major redox couple in animal cells. The synthesis of GSH from glutamate, cysteine, and glycine is catalyzed sequentially by two cytosolic enzymes, gamma-glutamylcysteine synthetase and GSH synthetase. Compelling evidence shows that GSH synthesis is regulated primarily by gamma-glutamylcysteine synthetase activity, cysteine availability, and GSH feedback inhibition. Animal and human studies demonstrate that adequate protein nutrition is crucial for the maintenance of GSH homeostasis. In addition, enteral or parenteral cystine, methionine, N-acetyl-cysteine, and L-2-oxothiazolidine-4-carboxylate are effective precursors of cysteine for tissue GSH synthesis. Glutathione plays important roles in antioxidant defense, nutrient metabolism, and regulation of cellular events (including gene expression, DNA and protein synthesis, cell proliferation and apoptosis, signal transduction, cytokine production and immune response, and protein glutathionylation). Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many diseases (including kwashiorkor, seizure, Alzheimer's disease, Parkinson's disease, liver disease, cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack, stroke, and diabetes). New knowledge of the nutritional regulation of GSH metabolism is critical for the development of effective strategies to improve health and to treat these diseases