Loading...
 
Toggle Health Problems and D

Glutathione and Vitamin D synergism - many studies

  1. Increased Glutathione (the master antioxidant) increases cellular and blood vitamin D
  2. Vitamin D increases Glutathione
  3. Glutathione can be increased in many ways, such as using liposomal form
    One company claimstheir liposomal form is 64X more bioavailable


5+ VitaminDWiki pages have GLUTATHIONE in the title

The list is automatically updated

Items found: 5

What is glutathione - Asked Perplexity AI June 2024

Glutathione is a powerful antioxidant naturally produced in every cell of the human body.
Here are the key points about glutathione:

  1. Composition: It is a tripeptide composed of three amino acids - cysteine, glycine, and glutamic acid.
  2. Production: Glutathione is synthesized primarily in the liver and is involved in many bodily processes.
  3. Functions: Glutathione plays critical roles in:
    • Detoxification of xenobiotic and endogenous compounds
    • Tissue building and repair
    • Making chemicals and proteins needed in the body
    • Supporting immune system function
    • DNA synthesis
    • Neutralizing free radicals
    • Regenerating vitamins C and E
    • Facilitating mercury elimination from the brain
  4. Antioxidant properties: As a potent antioxidant, glutathione helps protect cells from oxidative damage and maintains redox homeostasis.
  5. Health implications: Low levels of glutathione have been associated with various health conditions,
    including liver disease, cancer, Parkinson's disease, and other neurodegenerative disorders.
  6. Supplementation: Glutathione levels can be boosted through oral or intravenous supplementation,
    or by taking precursors that stimulate the body's natural production.
  7. Measurement: Assessing glutathione status in cells is important for understanding oxidative stress and redox signaling.
  8. Age-related decline: Glutathione levels tend to decrease with age, which may contribute to various age-related health issues.

While glutathione shows promise in various health applications, it's important to consult with a healthcare professional before starting any supplementation regimen.
Click here for references, images, etc


Describe the top antioxidants in order of importance - Asked Perplexity AI June 2024

Based on the search results and scientific understanding, here are the top antioxidants for the human body, listed in approximate order of importance:

  1. Glutathione: Often called the "master antioxidant," glutathione is the most potent antioxidant produced by our bodies. It supports lung health, liver detoxification, immune function, and can reduce signs of aging skin.
  2. Vitamin C: A powerful water-soluble antioxidant crucial for immune function. It can be found in fruits and vegetables, especially citrus fruits, berries, and red peppers.
  3. Vitamin E: This fat-soluble antioxidant protects cell membranes and can be found in foods like nuts, seeds, and vegetable oils.
  4. Coenzyme Q10 (CoQ10): Found in every cell of the body, CoQ10 protects cell membranes from free radical damage and is essential for energy production.
  5. Selenium: This mineral is required for the production of important antioxidant enzymes in the body. Brazil nuts are an excellent source of selenium.
  6. Carotenoids (including beta-carotene and lycopene): Found in orange and red fruits and vegetables, these antioxidants have been linked to various health benefits, including reduced risk of certain cancers.
  7. Flavonoids: These plant compounds are found in a variety of fruits, vegetables, and beverages like tea and red wine. They have been associated with preventing metabolic diseases and certain cancers.
  8. Anthocyanins: Found in blue and purple fruits like blueberries and blackberries, these antioxidants have been linked to heart health and reduced inflammation

The Ultimate Crash Course on Glutathione! - video April 2024

YouTube, 51 minutes
3:45 Functions
5:45 GSH (Active Form)
7:40 Detox & Repair
9:10 Diseases
11:30 Mental Health
14:15 Inflammation
16:45 Cardiovascular
19:20 Blood Glucose
21:30 Fatty Liver
23:15 Depletion
24:20 Glutathione & Vitamin C
26:30 Alcohol


GLUTATHIONE FOR BEGINNERS - Amazon book, Dec 2023 (free if Kindle Unlimited)

Unlocking Health And Vitality, The Comprehensive Guide To Boost Your Immunity, Detoxify Your Body, Combat Aging, And Rejuvenate Your Cells
33 pages - I have not looked at it


Vitamin D, Glutathione & NAC: new relationships you should know - 2022 video

YouTube, 23 minutes


Increased Vitamin D in both cells and blood when Glutathione (GSH) is increased – June 2024

The Impact of Vitamin D and L-Cysteine Co-Supplementation on Upregulating Glutathione and Vitamin D-Metabolizing Genes and in the Treatment of Circulating 25-Hydroxy Vitamin D Deficiency
Nutrients Volume 16 Issue 13 10.3390/nu16132004
by Sushil K. Jain 1, sushil.jain at lsuhs.edu ORCID, Jeffrey Justin Margret 1ORCID, Steven A. Abrams 2,Steven N. Levine 3 andKamal Bhusal 3
1 Dept of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA
2 Dept of Pediatrics and Dell Pediatric Research Institute, Dell Medical School at the U. of Texas at Austin, Austin, TX 78723, USA
3 Dept of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA

Table of Contents
Image

Image

2 of the 4 genes increase the tested level of Vitamin (red ellipsoids)
Image
Vitamin D receptors are expressed in many organs and tissues, which suggests that vitamin D (VD) affects physiological functions beyond its role in maintaining bone health. Deficiency or inadequacy of 25(OH)VD is widespread globally. Population studies demonstrate that a positive association exists between a high incidence of VD deficiency and a high incidence of chronic diseases, including dementia, diabetes, and heart disease. However, many subjects have difficulty achieving the required circulating levels of 25(OH)VD even after high-dose VD supplementation, and randomized controlled clinical trials have reported limited therapeutic success post-VD supplementation. Thus, there is a discordance between the benefits of VD supplementation and the prevention of chronic diseases in those with VD deficiency. Why this dissociation exists is currently under debate and is of significant public interest.

This review discusses the downregulation of VD-metabolizing genes needed to convert consumed VD into 25(OH)VD to enable its metabolic action exhibited by subjects with metabolic syndrome, obesity, and other chronic diseases. Research findings indicate a positive correlation between the levels of 25(OH)VD and glutathione (GSH) in both healthy and diabetic individuals.
Cell culture and animal experiments reveal a novel mechanism through which the status of GSH can positively impact the expression of VD metabolism genes.
This review highlights that for better success, VD deficiency needs to be corrected at multiple levels:

  • (i) VD supplements and/or VD-rich foods need to be consumed to provide adequate VD, and
  • (ii) the body needs to be able to upregulate VD-metabolizing genes to convert VD into 25(OH)VD and then to 1,25(OH)2VD to enhance its metabolic action.

This review outlines the association between 25(OH)VD deficiency/inadequacy and decreased GSH levels, highlighting the positive impact of combined VD+LC supplementation on upregulating GSH, VD-metabolizing genes, and VDR. These effects have the potential to enhance 25(OH)VD levels and its therapeutic efficacy.
 Download the PDF from VitaminDWiki
Clipped from PDF

  • "Various studies in humans and animals have successfully used LC, N-acetyl-L-cysteine (NAC), and/or LC-rich whey protein supplementation to improve the status of GSH and lower the levels of inflammation and insulin resistance in blood and tissues"

Perhaps they were unaware of the liposomal form of Glutathione - which might be better than L-Cysteine or NAC
References
  1. Holick, M.F The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev. Endocr. Metab. Disord. 2017,18,153-165.
  2. Shapses, S.A.; Calvo, M.S. Health Benefits of Vitamin D Supplementation: Time to Move the Spotlight Away from Bone Health in Vitamin D-replete Individuals? Am. J. Clin. Nutr. 2023,118, 489-490.
  3. Vearing, R.M.; Hart, K.H.; Darling, A.L.; Probst, Y.; Olayinka, A.S.; Mendis, J.; Ribeiro, H.; Thakur, S.; Mendes, M.; Charlton, K.; et al. Global Perspective of the Vitamin D Status of African-Caribbean Populations: A Systematic Review and Meta-analysis. Eur. J. Clin. Nutr. 2022, 76, 516-526.
  4. Neme, A.; Seuter, S.; Malinen, M.; Nurmi, T.; Tuomainen, T.P.; Virtanen, J.K.; Carlberg, C. In vivo transcriptome changes of human white blood cells in response to vitamin D. J. Steroid Biochem. Mol. Biol. 2019,188, 71-76.
  5. Ginde, A.A.; Liu, M.C.; Camargo, C.A., Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch. Intern. Med. 2009,169, 626-632.
  6. Maretzke, F.; Bechthold, A.; Egert, S.; Ernst, J.B.; Melo van Lent, D.; Pilz, S.; Reichrath, J.; Stangl, G.I.; Stehle, P.; Volkert, D.; et al. Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases—An Umbrella Review. Nutrients 2020,12, 969.
  7. Bouillon, R.; Manousaki, D.; Rosen, C.; Trajanoska, K.; Rivadeneira, F.; Richards, J.B. The health effects of vitamin D supplementa­tion: Evidence from human studies. Nat. Rev. Endocrinol. 2022,18, 96-110.
  8. Boucher, B.J. Why do so many trials of vitamin D supplementation fail? Endocr. Connect. 2020, 9, R195-R206. #Wilger-Gahche, J.J.; Bailey, R.L.; Burt, V.L.; Radimer, K.; McDowell, M.; Picciano, M.F.; Dwyer, J.; Sempos, C. Mean daily intake of calcium, folate and vitamin D from dietary supplements and the proportion getting above certain Dietary Reference Intake (DRI) levels, in the US population ages 14 years and older: Third National Health and Nutrition Examination Survey (NHANES III) and NHANES, 1999-2006. FASEB J. 2009,23, 341.7.
  9. Elkhwanky, M.S.; Kummu, O.; Piltonen, T.T.; Laru, J.; Morin-Papunen, L.; Mutikainen, M.; Tavi, P.; Hakkola, J. Obesity Represses CYP2R1, the Vitamin D 25-Hydroxylase, in the Liver and Extrahepatic Tissues. JBMR Plus 2020, 4, e10397.
  10. Roizen, J.D.; Long, C.; Casella, A.; O'Lear, L.; Caplan, I.; Lai, M.; Sasson, I.; Singh, R.; Makowski, A.J.; Simmons, R.; et al. Obesity Decreases Hepatic 25-Hydroxylase Activity Causing Low Serum 25-Hydroxyvitamin D. J. Bone Miner. Res. 2019, 34,1068-1073.
  11. Mokhtari, V.; Afsharian, P.; Shahhoseini, M.; Kalantar, S.M.; Moini, A. A Review on Various Uses of N-Acetyl Cysteine. Cell J. 2017,19,11-17.
  12. Bikle, D.D. The Free Hormone Hypothesis: When, Why, and How to Measure the Free Hormone Levels to Assess Vitamin D, Thyroid, Sex Hormone, and Cortisol Status. JBMR Plus 2021, 5, e10418.
  13. Cheng, J.B.; Levine, M.A.; Bell, N.H.; Mangelsdorf, D.J.; Russell, D.W. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc. Natl. Acad. Sci. USA 2004,101, 7711-7715.
  14. Engelman, C.D.; Meyers, K.J.; Iyengar, S.K.; Liu, Z.; Karki, C.K.; Igo, R.P., Jr.; Truitt, B.; Robinson, J.; Sarto, G.E.; Wallace, R.; et al. Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. J. Nutr. 2013,143,17-26.
  15. Nissen, J.; Vogel, U.; Ravn-Haren, G.; Andersen, E.W.; Madsen, K.H.; Nexo, B.A.; Andersen, R.; Mejborn, H.; Bjerrum, P.J.; Rasmussen, L.B.; et al. Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D(3)-fortified bread and milk during winter in Denmark. Am. J. Clin. Nutr. 2015,101, 218-227.
  16. Speeckaert, M.; Huang, G.; Delanghe, J.R.; Taes, Y.E. Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clin. Chim. Acta 2006, 372, 33-42.
  17. Adams, J.S.; Hewison, M. Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch. Biochem. Biophys. 2012, 523, 95-102.
  18. Miller, W.L. Genetic disorders of Vitamin D biosynthesis and degradation. J. Steroid Biochem. Mol. Biol. 2017, 165, 101-108.
  19. Safadi, F.F.; Thornton, P.; Magiera, H.; Hollis, B.W.; Gentile, M.; Haddad, J.G.; Liebhaber, S.A.; Cooke, N.E. Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. J. Clin. Investig. 1999,103, 239-251.
  20. Robien, K.; Butler, L.M.; Wang, R.; Beckman, K.B.; Walek, D.; Koh, W.P.; Yuan, J.M. Genetic and environmental predictors of serum 25-hydroxyvitamin D concentrations among middle-aged and elderly Chinese in Singapore. Br. J. Nutr. 2013,109,493-502.
  21. Nimitphong, H.; Saetung, S.; Chanprasertyotin, S.; Chailurkit, L.O.; Ongphiphadhanakul, B. Changes in circulating 25- hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D(3) or D(2)supplementation. Nutr. J. 2013, 12, 39.
  22. Fu, L.; Yun, F.; Oczak, M.; Wong, B.Y.; Vieth, R.; Cole, D.E. Common genetic variants of the vitamin D binding protein (DBP) predict differences in response of serum 25-hydroxyvitamin D [25(OH)D] to vitamin D supplementation. Clin. Biochem. 2009, 42, 1174-1177.
  23. Rosen, C.J. Clinical practice. Vitamin D insufficiency. N. Engl. J. Med. 2011, 364, 248-254.
  24. Wang, Y.; Zhu, J.; DeLuca, H.F. Where is the vitamin D receptor? Arch. Biochem. Biophys. 2012, 523,123-133.
  25. Cashman, K.D.; van den Heuvel, E.G.; Schoemaker, R.J.; Preveraud, D.P.; Macdonald, H.M.; Arcot, J. 25-Hydroxyvitamin D as a Biomarker of Vitamin D Status and Its Modeling to Inform Strategies for Prevention of Vitamin D Deficiency within the Population. Adv. Nutr. 2017, 8, 947-957.
  26. Korn, S.; Hubner, M.; Jung, M.; Blettner, M.; Buhl, R. Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency. Respir. Res. 2013,14, 25.
  27. Muindi, J.R.; Adjei, A.A.; Wu, Z.R.; Olson, I.; Huang, H.; Groman, A.; Tian, L.; Singh, P.K.; Sucheston, L.E.; Johnson, C.S.; et al. Serum vitamin D metabolites in colorectal cancer patients receiving cholecalciferol supplementation: Correlation with polymorphisms in the vitamin D genes. Horm. Cancer 2013, 4, 242-250.
  28. Johnson, M.A.; Davey, A.; Park, S.; Hausman, D.B.; Poon, L.W.; Georgia Centenarian, S. Age, race and season predict vitamin D status in African American and white octogenarians and centenarians. J. Nutr. Health Aging 2008,12, 690-695.
  29. Powe, C.E.; Evans, M.K.; Wenger, J.; Zonderman, A.B.; Berg, A.H.; Nalls, M.; Tamez, H.; Zhang, D.; Bhan, I.; Karumanchi, S.A.; et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N. Engl. J. Med. 2013, 369, 1991-2000.
  30. Looker, A.C.; Johnson, C.L.; Lacher, D.A.; Pfeiffer, C.M.; Schleicher, R.L.; Sempos, C.T. Vitamin D status: United States, 2001-2006. NCHS Data Brief 2011, 59,1-8.
  31. Grant, W.B.; Peiris, A.N. Possible role of serum 25-hydroxyvitamin D in black-white health disparities in the United States. J. Am. Med. Dir. Assoc. 2010,11,617-628.
  32. Williams, S.K.; Fiscella, K.; Winters, P; Martins, D.; Ogedegbe, G. Association of racial disparities in the prevalence of insulin resistance with racial disparities in vitamin D levels: National Health and Nutrition Examination Survey (2001-2006). Nutr. Res. 2013, 33, 266-271.
  33. Bikle, D.D.; Malmstroem, S.; Schwartz, J. Current Controversies: Are Free Vitamin Metabolite Levels a More Accurate Assessment of Vitamin D Status than Total Levels? Endocrinol. Metab. Clin. N. Am. 2017, 46, 901-918.
  34. Fang, A.P.; Long, J.A.; Zhang, Y.J.; Liu, Z.Y.; Li, Q.J.; Zhang, D.M.; Luo, Y.; Zhong, R.H.; Zhou, Z.G.; Xu, Y.J.; et al. Serum Bioavailable, Rather Than Total, 25-hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival. Hepatology 2020, 72,169-182.
  35. Zhu, A.; Kuznia, S.; Boakye, D.; Schottker, B.; Brenner, H. Vitamin D-Binding Protein, Bioavailable, and Free 25(OH)D, and Mortality: A Systematic Review and Meta-Analysis. Nutrients 2022,14, 3894.
  36. AlSedairy, S.A.; Al-Harbi, L.N.; Binobead, M.A.; Athinarayanan, J.; Arzoo, S.; Al-Tamimi, D.S.; Shamlan, G.; Alshatwi, A.A.; Periasamy, V.S. Association of CYP2R1 and CYP27B1 genes with the risk of obesity and vitamin D metabolism in Saudi women. J. Genet. Eng. Biotechnol. 2023,21, 59.
  37. Bakos, B.; Szili, B.; Szabo, B.; Horvath, P.; Kirschner, G.; Kosa, J.P.; Toldy, E.; Lakatos, P.; Tabak, A.G.; Takacs, I. Genetic variants of VDR and CYP2R1 affect BMI independently of serum vitamin D concentrations. BMC Med. Genet. 2020, 21,129.
  38. Wamberg, L.; Christiansen, T.; Paulsen, S.K.; Fisker, S.; Rask, P.; Rejnmark, L.; Richelsen, B.; Pedersen, S.B. Expression of vitamin D-metabolizing enzymes in human adipose tissue—The effect of obesity and diet-induced weight loss. Int. J. Obes. 2013, 37, 651-657.
  39. Di Nisio, A.; De Toni, L.; Sabovic, I.; Rocca, M.S.; De Filippis, V.; Opocher, G.; Azzena, B.; Vettor, R.; Plebani, M.; Foresta, C. Impaired Release of Vitamin D in Dysfunctional Adipose Tissue: New Cues on Vitamin D Supplementation in Obesity. J. Clin. Endocrinol. Metab. 2017,102, 2564-2574.
  40. Yuzbashian, E.; Asghari, G.; Hedayati, M.; Zarkesh, M.; Mirmiran, P; Khalaj, A. Determinants of vitamin D receptor gene expression in visceral and subcutaneous adipose tissue in non-obese, obese, and morbidly obese subjects. J. Steroid Biochem. Mol. Biol. 2019,187, 82-87.
  41. Araujo, E.; Lima, S.; Galdino, O.A.; Arrais, R.F.; de Souza, K.S.C.; de Rezende, A.A. Association of CYP2R1 and VDR Polymor­phisms with Metabolic Syndrome Components in Non-Diabetic Brazilian Adolescents. Nutrients 2022, 14, 4612.
  42. Park, J.M.; Park, C.Y.; Han, S.N. High fat diet-Induced obesity alters vitamin D metabolizing enzyme expression in mice. Biofactors 2015, 41,175-182.
  43. Jain, S.K.; Parsanathan, R.; Achari, A.E.; Kanikarla-Marie, P.; Bocchini, J.A., Jr. Glutathione Stimulates Vitamin D Regulatory and Glucose-Metabolism Genes, Lowers Oxidative Stress and Inflammation, and Increases 25-Hydroxy-Vitamin D Levels in Blood: A Novel Approach to Treat 25-Hydroxyvitamin D Deficiency. Antioxid. Redox Signal 2018, 29,1792-1807.
  44. Bonnet, L.; Hachemi, M.A.; Karkeni, E.; Couturier, C.; Astier, J.; Defoort, C.; Svilar, L.; Martin, J.C.; Tourniaire, F.; Landrier, J.F. Diet induced obesity modifies vitamin D metabolism and adipose tissue storage in mice. J. Steroid Biochem. Mol. Biol. 2019,185, 39-46.
  45. Aatsinki, S.M.; Elkhwanky, M.S.; Kummu, O.; Karpale, M.; Buler, M.; Viitala, P.; Rinne, V.; Mutikainen, M.; Tavi, P.; Franko, A.; et al. Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes. Diabetes 2019, 68, 918-931.
  46. Parsanathan, R.; Jain, S.K. Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice. Sci. Rep. 2019, 9,14784.
  47. Feng, M.; Wang, K.; Wei, H.; Zhang, S.; Chen, Y. Serum 25OHD3 of Obese Mice Is Affected by Liver Injury and Correlates with Testosterone Levels and Sperm Motility. Obes. Facts 2021,14, 559-567.
  48. Park, C.Y.; Shin, Y.; Kim, J.H.; Zhu, S.; Jung, Y.S.; Han, S.N. Effects of high fat diet-induced obesity on vitamin D metabolism and tissue distribution in vitamin D deficient or supplemented mice. Nutr. Metab. 2020,17, 44.
  49. Zhu, T.; Zhao, J.; Zhuo, S.; Hu, Z.; Ouyang, S.; Wunier; Yu, S.; Chen, Y.; Li, Y.; Le, Y. High Fat Diet and High Cholesterol Diet Reduce Hepatic Vitamin D-25-Hydroxylase Expression and Serum 25-Hydroxyvitamin D(3) Level through Elevating Circulating Cholesterol, Glucose, and Insulin Levels. Mol. Nutr. Food Res. 2021, 65, e2100220.
  50. Bonnet, L.; Karkeni, E.; Couturier, C.; Astier, J.; Defoort, C.; Svilar, L.; Tourniaire, F.; Mounien, L.; Landrier, J.F. Four days high fat diet modulates vitamin D metabolite levels and enzymes in mice. J. Endocrinol. 2021, 248, 87-93.
  51. Fernandez-Sanchez, A.; Madrigal-Santillan, E.; Bautista, M.; Esquivel-Soto, J.; Morales-Gonzalez, A.; Esquivel-Chirino, C.; Durante-Montiel, I.; Sanchez-Rivera, G.; Valadez-Vega, C.; Morales-Gonzalez, J.A. Inflammation, oxidative stress, and obesity. Int. J. Mol. Sci. 2011,12,3117-3132.
  52. Manna, P.; Jain, S.K. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies. Metab. Syndr. Relat. Disord. 2015,13, 423-444.
  53. Chang, Y.C.; Yu, Y.H.; Shew, J.Y.; Lee, W.J.; Hwang, J.J.; Chen, Y.H.; Chen, Y.R.; Wei, P.C.; Chuang, L.M.; Lee, W.H. Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human. EMBO Mol. Med. 2013, 5, 1165-1179.
  54. Maciejewski, M.; Siodmiak, J.; Borkowski, B.; Lorkowski, M.; Olszewska-Slonina, D.M. Lipid Peroxidation as a Possible Factor Affecting Bone Resorption in Obese Subjects-Preliminary Research. Int. J. Mol. Sci. 2023, 24,11629.
  55. Curtis, J.M.; Hahn, W.S.; Long, E.K.; Burrill, J.S.; Arriaga, E.A.; Bernlohr, D.A. Protein carbonylation and metabolic control systems. Trends Endocrinol. Metab. 2012,23, 399-406.
  56. Dalle-Donne, I.; Rossi, R.; Giustarini, D.; Milzani, A.; Colombo, R. Protein carbonyl groups as biomarkers of oxidative stress. Clin. Chim. Acta 2003, 329, 23-38.
  57. Franklin, C.C.; Backos, D.S.; Mohar, I.; White, C.C.; Forman, H.J.; Kavanagh, T.J. Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase. Mol. Aspects Med. 2009, 30, 86-98.
  58. Rains, J.L.; Jain, S.K. Oxidative stress, insulin signaling, and diabetes. Free Radic. Biol. Med. 2011, 50, 567-575.
  59. Barreiro, E.; Hussain, S.N. Protein carbonylation in skeletal muscles: Impact on function. Antioxid. Redox Signal 2010,12, 417-429.
  60. Evans, J.L.; Maddux, B.A.; Goldfine, I.D. The molecular basis for oxidative stress-induced insulin resistance. Antioxid. Redox Signal 2005, 7,1040-1052.
  61. Akoumianakis, I.; Antoniades, C. Impaired Vascular Redox Signaling in the Vascular Complications of Obesity and Diabetes Mellitus. Antioxid. Redox Signal 2019, 30, 333-353.
  62. Yin, J.; Ren, W.; Yang, G.; Duan, J.; Huang, X.; Fang, R.; Li, C.; Li, T.; Yin, Y.; Hou, Y.; et al. L-Cysteine metabolism and its nutritional implications. Mol. Nutr. Food Res. 2016, 60,134-146.
  63. Jain, S.K.; Velusamy, T.; Croad, J.L.; Rains, J.L.; Bull, R. L-Cysteine supplementation lowers blood glucose, glycated hemoglobin, CRP, MCP-1, and oxidative stress and inhibits NF-kappaB activation in the livers of Zucker diabetic rats. Free Radic. Biol. Med. 2009, 46,1633-1638.
  64. McPherson, R.A.; Hardy, G. Clinical and nutritional benefits of cysteine-enriched protein supplements. Curr. Opin. Clin. Nutr. Metab. Care 2011,14, 562-568.
  65. Hansen, J.G.; Tang, W.; Hootman, K.C.; Brannon, P.M.; Houston, D.K.; Kritchevsky, S.B.; Harris, T.B.; Garcia, M.; Lohman, K.; Liu, Y.; et al. Genetic and environmental factors are associated with serum 25-hydroxyvitamin D concentrations in older African Americans. J. Nutr. 2015,145, 799-805.
  66. Jolliffe, D.A.; Hanifa, Y.; Witt, K.D.; Venton, T.R.; Rowe, M.; Timms, P.M.; Hypponen, E.; Walton, R.T.; Griffiths, C.J.; Martineau, A.R. Environmental and genetic determinants of vitamin D status among older adults in London, UK. J. Steroid Biochem. Mol. Biol. 2016,164, 30-35.
  67. Shaban, N.Z.; Abdel-Alnaby, M.; Atta, M.N.; Abdul-Aziz, A.A.; Megahed, F. The association between body mass index elevation and differentiation in vitamin D receptor gene expression, genetic polymorphism, and oxidative stress in adult Egyptian individuals. Sci. Rep. 2023,13,17696.
  68. Jain, S.K.; Kanikarla-Marie, P.; Warden, C.; Micinski, D. L-Cysteine supplementation upregulates Glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases blood levels of GSH, VDBP, and 25-hydroxy-vitamin D in Zucker diabetic fatty rats. Mol. Nutr. Food Res. 2016, 60,1090-1098.
  69. Jain, S.K.; Micinski, D.; Huning, L.; Kahlon, G.; Bass, P.F.; Levine, S.N. Vitamin D and L-Cysteine levels correlate positively with GSH and negatively with insulin resistance levels in the blood of type 2 diabetic patients. Eur. J. Clin. Nutr. 2014, 68,1148-1153.
  70. Jain, S.K.; Kahlon, G.; Bass, P.; Levine, S.N.; Warden, C. Can L-Cysteine and Vitamin D Rescue Vitamin D and Vitamin D Binding Protein Levels in Blood Plasma of African American Type 2 Diabetic Patients? Antioxid. Redox Signal 2015, 23, 688-693.
  71. Jain, S.K.; McVie, R. Effect of glycemic control, race (white versus black), and duration of diabetes on reduced Glutathione content in erythrocytes of diabetic patients. Metabolism 1994, 43, 306-309.
  72. Jain, S.K.; Micinski, D.; Parsanathan, R. L-Cysteine Stimulates the Effect of Vitamin D on Inhibition of Oxidative Stress, IL-8, and MCP-1 Secretion in High Glucose Treated Monocytes. J. Am. Coll. Nutr. 2021, 40, 327-332.
  73. Alvarez, J.A.; Chowdhury, R.; Jones, D.P.; Martin, G.S.; Brigham, K.L.; Binongo, J.N.; Ziegler, T.R.; Tangpricha, V. Vitamin D status is independently associated with plasma Glutathione and cysteine thiol/disulphide redox status in adults. Clin. Endocrinol. 2014, 81, 458-466.
  74. Mokhaneli, M.C.; Fourie, C.M.; Botha, S.; Mels, C.M. The association of oxidative stress with arterial compliance and vascular resistance in a bi-ethnic population: The SABPA study. Free Radic. Res. 2016, 50, 920-928.
  75. Lu, S.C. Glutathione synthesis. Biochim. Biophys. Acta 2013,1830, 3143-3153.
  76. Weber, D.; Davies, M.J.; Grune, T. Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: Focus on sample preparation and derivatization conditions. Redox Biol. 2015, 5, 367-380.
  77. Grimsrud, P.A.; Xie, H.; Griffin, T.J.; Bernlohr, D.A. Oxidative stress and covalent modification of protein with bioactive aldehydes. J. Biol. Chem. 2008,283, 21837-21841.
  78. Szanton, S.L.; Rifkind, J.M.; Mohanty, J.G.; Miller, E.R., 3rd; Thorpe, R.J.; Nagababu, E.; Epel, E.S.; Zonderman, A.B.; Evans, M.K. Racial discrimination is associated with a measure of red blood cell oxidative stress: A potential pathway for racial health disparities. Int. J. Behav. Med. 2012,19, 489-495.
  79. Montero, D.; Vicente-Salar, N.; Herranz, M.; Micol, V.; Walther, G.; Perez-Martin, A.; Vinet, A.; Roche, E. Glutathione-dependent enzyme activities of peripheral blood mononuclear cells decrease during the winter season compared with the summer in normal-weight and severely obese adolescents. J. Physiol. Biochem. 2019, 75, 321-327.
  80. Abbasalizad Farhangi, M.; Najafi, M. Dietary total antioxidant capacity (TAC) among candidates for coronary artery bypass grafting (CABG) surgery: Emphasis to possible beneficial role of TAC on serum vitamin D. PLoS ONE 2018, 13, e0208806.
  81. Parsanathan, R.; Achari, A.E.; Manna, P.; Jain, S.K. L-Cysteine and Vitamin D Co-Supplementation Alleviates Markers of Musculoskeletal Disorders in Vitamin D-Deficient High-Fat Diet-Fed Mice. Nutrients 2020,12, 3406.
  82. Delerive, P.; Wu, Y.; Burris, T.P.; Chin, W.W.; Suen, C.S. PGC-1 functions as a transcriptional coactivator for the retinoid X receptors. J. Biol. Chem. 2002,277, 3913-3917.
  83. Kliewer, S.A.; Umesono, K.; Mangelsdorf, D.J.; Evans, R.M. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 1992, 355, 446-449.
  84. Jusu, S.; Presley, J.F.; Kremer, R. Phosphorylation of Human Retinoid X Receptor alpha at Serine 260 Impairs Its Subcellular Localization, Receptor Interaction, Nuclear Mobility, and 1alpha,25-Dihydroxyvitamin D3-dependent DNA Binding in Ras- transformed Keratinocytes. J. Biol. Chem. 2017, 292,1490-1509.
  85. Sekhar, R.V.; McKay, S.V.; Patel, S.G.; Guthikonda, A.P.; Reddy, V.T.; Balasubramanyam, A.; Jahoor, F. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care 2011, 34,162-167.
  86. Sekhar, R.V. GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflamma­tion, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging. J. Nutr. 2021,151, 3606-3616.
  87. Borges-Santos, M.D.; Moreto, F.; Pereira, P.C.; Ming-Yu, Y.; Burini, R.C. Plasma Glutathione of HIV(+) patients responded positively and differently to dietary supplementation with cysteine or glutamine. Nutrition 2012,28, 753-756.
  88. Nguyen, D.; Hsu, J.W.; Jahoor, F.; Sekhar, R.V. Effect of increasing Glutathione with cysteine and glycine supplementation on mitochondrial fuel oxidation, insulin sensitivity, and body composition in older HIV-infected patients. J. Clin. Endocrinol. Metab. 2014, 99,169-177.
  89. Vidal, K.; Breuille, D.; Serrant, P.; Denis, P.; Glomot, F.; Bechereau, F.; Papet, I. Long-term cysteine fortification impacts cysteine/Glutathione homeostasis and food intake in ageing rats. Eur. J. Nutr. 2014, 53, 963-971.
  90. Sacco, S.M.; Horcajada, M.N.; Offord, E. Phytonutrients for bone health during ageing. Br. J. Clin. Pharmacol. 2013, 75, 697-707.
  91. Klingberg, E.; Olerod, G.; Konar, J.; Petzold, M.; Hammarsten, O. Seasonal variations in serum 25-hydroxy vitamin D levels in a Swedish cohort. Endocrine 2015, 49, 800-808.
  92. Daly, R.M.; De Ross, B.; Gianoudis, J.; Tan, S.Y. Dose-Response Effect of Consuming Commercially Available Eggs on Wintertime Serum 25-Hydroxyvitamin D Concentrations in Young Australian Adults: A 12-Week Randomized Controlled Trial. J. Nutr. 2022, 152,1702-1710.
  93. Clemente Plaza, N.; Reig Garcia-Galbis, M.; Martinez-Espinosa, R.M. Effects of the Usage of L-Cysteine (l-Cys) on Human Health. Molecules 2018,23, 575.
  94. Chitapanarux, T.; Tienboon, P.; Pojchamarnwiputh, S.; Leelarungrayub, D. Open-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients. J. Gastroenterol. Hepatol. 2009,24,1045-1050.
  95. Sekhar, R.V.; Patel, S.G.; Guthikonda, A.P.; Reid, M.; Balasubramanyam, A.; Taffet, G.E.; Jahoor, F. Deficient synthesis of Glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am. J. Clin. Nutr. 2011, 94, 847-853.
  96. Bizzozero, O.A.; Reyes, S.; Ziegler, J.; Smerjac, S. Lipid peroxidation scavengers prevent the carbonylation of cytoskeletal brain proteins induced by Glutathione depletion. Neurochem. Res. 2007, 32, 2114-2122.
  97. Jersin, R.A.; Jonassen, L.R.; Dankel, S.N. The neutral amino acid transporter SLC7A10 in adipose tissue, obesity and insulin resistance. Front. Cell Dev. Biol. 2022,10, 974338.
  98. Steele, M.L.; Fuller, S.; Patel, M.; Kersaitis, C.; Ooi, L.; Munch, G. Effect of Nrf2 activators on release of Glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells. Redox Biol. 2013,1, 441-445.
  99. Morales Pantoja, I.E.; Hu, C.L.; Perrone-Bizzozero, N.I.; Zheng, J.; Bizzozero, O.A. Nrf2-dysregulation correlates with reduced synthesis and low Glutathione levels in experimental autoimmune encephalomyelitis. J. Neurochem. 2016,139, 640-650.
  100. Leiser, S.F.; Miller, R.A. Nrf2 signaling, a mechanism for cellular stress resistance in long-lived mice. Mol. Cell Biol. 2010, 30, 871-884.
  101. Patti, M.E.; Butte, A.J.; Crunkhorn, S.; Cusi, K.; Berria, R.; Kashyap, S.; Miyazaki, Y.; Kohane, I.; Costello, M.; Saccone, R.; et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc. Natl. Acad. Sci. USA 2003,100, 8466-8471.
  102. Leick, L.; Fentz, J.; Bienso, R.S.; Knudsen, J.G.; Jeppesen, J.; Kiens, B.; Wojtaszewski, J.F.; Pilegaard, H. PGC-1alpha is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2010, 299, E456-E465.
  103. Gannon, N.P.; Schnuck, J.K.; Mermier, C.M.; Conn, C.A.; Vaughan, R.A. trans-Cinnamaldehyde stimulates mitochondrial biogenesis through PGC-1alpha and PPARbeta/delta leading to enhanced GLUT4 expression. Biochimie 2015, 119, 45-51.
  104. Sczelecki, S.; Besse-Patin, A.; Abboud, A.; Kleiner, S.; Laznik-Bogoslavski, D.; Wrann, C.D.; Ruas, J.L.; Haibe-Kains, B.; Estall, J.L. Loss of Pgc-1alpha expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation. Am. J. Physiol. Endocrinol. Metab. 2014, 306, E157-E167.
  105. Eisele, P.S.; Furrer, R.; Beer, M.; Handschin, C. The PGC-1 coactivators promote an anti-inflammatory environment in skeletal muscle in vivo. Biochem. Biophys. Res. Commun. 2015, 464, 692-697.
  106. Lin, L.M.; Peng, F.; Liu, Y.P.; Chai, D.J.; Ning, R.B.; Xu, C.S.; Lin, J.X. Coadministration of VDR and RXR agonists synergistically alleviates atherosclerosis through inhibition of oxidative stress: An in vivo and in vitro study. Atherosclerosis 2016,251, 273-281.
  107. Vaughan, R.A.; Mermier, C.M.; Bisoffi, M.; Trujillo, K.A.; Conn, C.A. Dietary stimulators of the PGC-1 superfamily and mitochondrial biosynthesis in skeletal muscle. A mini-review. J. Physiol. Biochem. 2014, 70, 271-284.
  108. Smith, C.V.; Jones, D.P.; Guenthner, T.M.; Lash, L.H.; Lauterburg, B.H. Compartmentation of Glutathione: Implications for the study of toxicity and disease. Toxicol. Appl. Pharmacol. 1996,140,1-12.
  109. Jain, S.K.; Justin Margret, J.; Zachary, A., Jr.; Lally, M.M.; Vanchiere, J.A.; Mhanna, M.J.; Shi, R.; Levine, S.N. The effects of Vitamin D and L-Cysteine co-supplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free/total testosterone ratio, and inflammatory biomarkers in healthy vitamin D-deficient African Americans: A placebo-controlled double-blind clinical trial. BMJ Nutr. Prev. Health 2024, in press.
  110. Foresta, C.; Strapazzon, G.; De Toni, L.; Perilli, L.; Di Mambro, A.; Muciaccia, B.; Sartori, L.; Selice, R. Bone mineral density and testicular failure: Evidence for a role of vitamin D 25-hydroxylase in human testis. J. Clin. Endocrinol. Metab. 2011, 96, E646-E652.
  111. Blomberg Jensen, M.; Nielsen, J.E.; Jorgensen, A.; Rajpert-De Meyts, E.; Kristensen, D.M.; Jorgensen, N.; Skakkebaek, N.E.; Juul, A.; Leffers, H. Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum. Reprod. 2010,25,1303-1311.
  112. Costanzo, P.R.; Suarez, S.M.; Kozak, A.E.; Knoblovits, P. Seasonal Variations in Sex Steroids in a Young Male Population and Their Relationship with Plasma Levels of Vitamin D. World J. Mens Health 2022, 40, 308-315.
  113. Yeap, B.B.; Almeida, O.P.; Hyde, Z.; Chubb, S.A.; Hankey, G.J.; Jamrozik, K.; Flicker, L. Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The Health in Men Study. Clin. Endocrinol. 2008, 68, 404-412.
  114. Seidell, J.C.; Cigolini, M.; Deurenberg, P.; Oosterlee, A.; Doornbos, G. Fat distribution, androgens, and metabolism in nonobese women. Am. J. Clin. Nutr. 1989, 50, 269-273.
  115. Kravchick, S.; Peled, R.; Dorfman, D.; Agulansky, L.; Ben-Dor, D.; Cytron, S. Predictive criteria for prostate cancer detection in men with serum PSA concentration of 2.0 to 4.0 ng/mL. Urology 2005, 66, 542-546.
  116. Narinx, N.; David, K.; Walravens, J.; Vermeersch, P.; Claessens, F.; Fiers, T.; Lapauw, B.; Antonio, L.; Vanderschueren, D. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology. Cell Mol. Life Sci. 2022, 79, 543.
  117. Laurent, M.R.; Hammond, G.L.; Blokland, M.; Jardi, F.; Antonio, L.; Dubois, V.; Khalil, R.; Sterk, S.S.; Gielen, E.; Decallonne, B.; et al. Sex hormone-binding globulin regulation of androgen bioactivity in vivo: Validation of the free hormone hypothesis. Sci. Rep. 2016, 6, 35539.
  118. Simo, R.; Saez-Lopez, C.; Barbosa-Desongles, A.; Hernandez, C.; Selva, D.M. Novel insights in SHBG regulation and clinical implications. Trends Endocrinol. Metab. 2015,26, 376-383.
  119. Li, H.; Pham, T.; McWhinney, B.C.; Ungerer, J.P.; Pretorius, C.J.; Richard, D.J.; Mortimer, R.H.; d'Emden, M.C.; Richard, K. Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells. Int. J. Endocrinol. 2016,2016, 6437585.
  120. Saez-Lopez, C.; Villena, J.A.; Simo, R.; Selva, D.M. Sex hormone-binding globulin overexpression protects against high-fat diet-induced obesity in transgenic male mice. J. Nutr. Biochem. 2020, 85,108480.
  121. Bourebaba, N.; Ngo, T.; Smieszek, A.; Bourebaba, L.; Marycz, K. Sex hormone binding globulin as a potential drug candidate for liver-related metabolic disorders treatment. Biomed. Pharmacother. 2022,153,113261.
  122. Yamazaki, H.; Kushiyama, A.; Sakoda, H.; Fujishiro, M.; Yamamotoya, T.; Nakatsu, Y.; Kikuchi, T.; Kaneko, S.; Tanaka, H.; Asano, T. Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages. Mediat. Inflamm. 2018, 2018, 3062319.
  123. Jana, K.; Dutta, A.; Chakraborty, P.; Manna, I.; Firdaus, S.B.; Bandyopadhyay, D.; Chattopadhyay, R.; Chakravarty, B. Alpha-lipoic acid and N-acetylcysteine protects intensive swimming exercise-mediated germ-cell depletion, pro-oxidant generation, and alteration of steroidogenesis in rat testis. Mol. Reprod. Dev. 2014, 81, 833-850.
  124. Kim, K.H.; Park, M.J.; Park, N.C.; Park, H.J. Effect of N-acetyl-L-Cysteine on Testicular Tissue in Busulfan-Induced Dysfunction in the Male Reproductive System. World J. Mens Health 2023, 41, 882-891.
  125. Bosgelmez, I.I.; Guvendik, G. Beneficial Effects of N-Acetyl-L-Cysteine or Taurine Pre- or Post-treatments in the Heart, Spleen, Lung, and Testis of Hexavalent Chromium-Exposed Mice. Biol. Trace Elem. Res. 2019,190, 437-445.
  126. Feng, D.; Huang, H.; Yang, Y.; Yan, T.; Jin, Y.; Cheng, X.; Cui, L. Ameliorative effects of N-acetylcysteine on fluoride-induced oxidative stress and DNA damage in male rats' testis. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2015, 792, 35-45.
  127. Zhang, T.; Liu, T.; Shao, J.; Sheng, C.; Hong, Y.; Ying, W.; Xia, W. Antioxidant protects blood-testis barrier against synchrotron radiation X-ray-induced disruption. Spermatogenesis 2015, 5, e1009313.
  128. Ezzat, G.M.; Nassar, A.Y.; Bakr, M.H.; Mohamed, S.; Nassar, G.A.; Kamel, A.A. Acetylated Oligopeptide and N-acetyl cysteine Protected Against Oxidative Stress, Inflammation, Testicular-Blood Barrier Damage, and Testicular Cell Death in Iron-Overload Rat Model. Appl. Biochem. Biotechnol. 2023,195, 5053-5071.
  129. Kemahli, E.; Uyeturk, U.; Cetinkaya, A.; Erimsah, S.; Uyeturk, U.; Gucuk, A. Protective Effects of N-Acetyl Cysteine on Undescended Testis after Orchiopexy: A Rat-model Study. J. Coll. Physicians Surg. Pak. 2023, 33, 319-324.
  130. Abedi, B.; Tayefi-Nasrabadi, H.; Kianifard, D.; Basaki, M.; Shahbazfar, A.A.; Piri, A.; Dolatyarieslami, M. The effect of co­administration of artemisinin and N-acetyl cysteine on antioxidant status, spermatological parameters and histopathology of testis in adult male mice. Horm. Mol. Biol. Clin. Investig. 2023, 44, 207-214.
  131. Acer-Demir, T.; Mammadov, M.; Ocbe, P.; Coruhlu, A.; Coskun, D.; Nazik, Y.; Tufekci, I.; Guney, L.H.; Hicsonmez, A. The long term effects of intrascrotal low dose and high dose N-acetylcysteine on testis damage in rat model of testicular torsion. J. Pediatr. Surg. 2020, 55, 672-680.
  132. Bodur, A.; Alver, A.; Kahraman, C.; Altay, D.U.; Ince, I. Investigation of N-acetylcysteine on contralateral testis tissue injury by experimental testicular torsion: Long-term effect. Am. J. Emerg. Med. 2016, 34,1069-1074.
  133. Jannatifar, R.; Parivar, K.; Roodbari, N.H.; Nasr-Esfahani, M.H. Effects of N-acetyL-Cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men. Reprod. Biol. Endocrinol. 2019,17, 24.
  134. Liddle, L.; Monaghan, C.; Burleigh, M.C.; Baczynska, K.A.; Muggeridge, D.J.; Easton, C. Reduced nitric oxide synthesis in winter: A potential contributing factor to increased cardiovascular risk. nitric oxide 2022,127,1-9.
  135. Siervo, M.; Hussin, A.M.; Calella, P.; Ashor, A.; Shannon, O.M.; Mendes, I.; Stephan, B.C.; Zheng, D.; Hill, T.; Mathers, J.C. Associations between Aging and Vitamin D Status with Whole-Body nitric oxide Production and Markers of Endothelial Function. J. Nutr. 2024,154, 469-478.
  136. Jain, S. L-Cysteine Supplementation Increases Blood Levels of Hydrogen Sulfide and Nitrite, and Decreases Insulin Resistance and Vascular Inflammation in Zucker Diabetic Rats. Curr. Dev. Nutr. 2020, 4 (Suppl. S2), 405.
  137. Golden, S.H.; Selvin, E.; Cunningham, K.E. Glycaemic status and cardiovascular disease in type 2 diabetes mellitus: Re-visiting glycated haemoglobin targets for cardiovascular disease prevention. Diabetes Obes. Metab. 2007, 9, 792-798.
  138. Shah, S.; Iqbal, M.; Karam, J.; Salifu, M.; McFarlane, S.I. Oxidative stress, glucose metabolism, and the prevention of type 2 diabetes: Pathophysiological insights. Antioxid. Redox Signal 2007, 9, 911-929.
  139. Droge, W. Oxidative stress and ageing: Is ageing a cysteine deficiency syndrome? Philos. Trans. R. Soc. Lond. B Biol. Sci. 2005, 360, 2355-2372.
  140. Abu El Maaty, M.A.; Hanafi, R.S.; El-Badawy, S.; Gad, M.Z. Interplay of vitamin D and nitric oxide in post-menopausal knee osteoarthritis. Aging Clin. Exp. Res. 2014, 26, 363-368.
  141. Mahmoud, A.M.; Szczurek, M.; Hassan, C.; Masrur, M.; Gangemi, A.; Phillips, S.A. Vitamin D Improves nitric oxide-Dependent Vasodilation in Adipose Tissue Arterioles from Bariatric Surgery Patients. Nutrients 2019,11, 2521.
  142. Andrukhova, O.; Slavic, S.; Zeitz, U.; Riesen, S.C.; Heppelmann, M.S.; Ambrisko, T.D.; Markovic, M.; Kuebler, W.M.; Erben, R.G. Vitamin D is a regulator of endothelial nitric oxide synthase and arterial stiffness in mice. Mol. Endocrinol. 2014, 28,53-64.
  143. Wolf, S.T.; Jablonski, N.G.; Ferguson, S.B.; Alexander, L.M.; Kenney, W.L. Four weeks of vitamin D supplementation improves nitric oxide-mediated microvascular function in college-aged African Americans. Am. J. Physiol. Heart Circ. Physiol. 2020, 319, H906-H914.
  144. Al-Daghri, N.M.; Bukhari, I.; Yakout, S.M.; Sabico, S.; Khattak, M.N.K.; Aziz, I.; Alokail, M.S. Associations of Serum nitric oxide with Vitamin D and Other Metabolic Factors in Apparently Healthy Adolescents. Biomed. Res. Int. 2018, 2018,1489132.
  145. Kim, D.H.; Meza, C.A.; Clarke, H.; Kim, J.S.; Hickner, R.C. Vitamin D and Endothelial Function. Nutrients 2020,12, 575.
  146. Cordova, A.; Caballero-Garcia, A.; Noriega-Gonzalez, D.; Bello, H.J.; Pons, A.; Roche, E. Nitric-Oxide-Inducing Factors on Vitamin D Changes in Older People Susceptible to Suffer from Sarcopenia. Int. J. Environ. Res. Public Health 2022,19, 5938.
  147. Whiteman, M.; Armstrong, J.S.; Chu, S.H.; Jia-Ling, S.; Wong, B.S.; Cheung, N.S.; Halliwell, B.; Moore, P.K. The novel neuromodu­lator hydrogen sulfide: An endogenous peroxynitrite 'scavenger'? J. Neurochem. 2004, 90, 765-768.
  148. Ali, M.Y.; Ping, C.Y.; Mok, Y.Y.; Ling, L.; Whiteman, M.; Bhatia, M.; Moore, P.K. Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide? Br. J. Pharmacol. 2006,149, 625-634.
  149. Caballero-Garcia, A.; Pascual-Fernandez, J.; Noriega-Gonzalez, D.C.; Bello, H.J.; Pons-Biescas, A.; Roche, E.; Cordova-Martinez, A. L-Citrulline Supplementation and Exercise in the Management of Sarcopenia. Nutrients 2021,13, 3133.
  150. Justin Margret, J.; Jain, S.K. Regulatory Effect of L-Cysteine on Testosterone Biosynthesis Genes in Leydig Cells and THP-1 Monocytes. Physiology 2024, 39, 292.
  151. Lasram, M.M.; Dhouib, I.B.; Annabi, A.; El Fazaa, S.; Gharbi, N. A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development. Clin. Biochem. 2015, 48,1200-1208.
  152. Kanikarla-Marie, P.; Jain, S.K. L-Cysteine supplementation reduces high-glucose and ketone-induced adhesion of monocytes to endothelial cells by inhibiting ROS. Mol. Cell Biochem. 2014, 391, 251-256.
  153. Rhodes, K.; Braakhuis, A. Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis. Sports Med. 2017, 47,1619-1636.
  154. Rizzoli, R. Vitamin D supplementation: Upper limit for safety revisited? Aging Clin. Exp. Res. 2021, 33, 19-24.
  155. Galior, K.; Grebe, S.; Singh, R. Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports. Nutrients 2018,10, 953.
  156. Marcinowska-Suchowierska, E.; Kupisz-Urbanska, M.; Lukaszkiewicz, J.; Pludowski, P.; Jones, G. Vitamin D Toxicity-A Clinical Perspective. Front. Endocrinol. 2018, 9, 550.

Glutathione improved vitamin D levels and 6 Vitamin D genes (more gets to cells) (mice) - 2018

Glutathione Stimulates Vitamin D Regulatory and Glucose-Metabolism Genes, Lowers Oxidative Stress and Inflammation, and Increases 25-Hydroxy-Vitamin D Levels in Blood: A Novel Approach to Treat 25-Hydroxyvitamin D Deficiency
Antioxidants & Redox SignalingVol. 29, No. 17 https://doi.org/10.1089/ars.2017.7462
Sushil K. Jain sjain at lsuhsc.edu, Rajesh Parsanathan, Arunkumar E. Achari, Preeti Kanikarla-Marie, and Joseph A. Bocchini,

Image

Image
Image
Image Image
           Note: the deactivatin of CYP24A1 is a good thing - it means MORE Vitamin D can get to the cells

Aims: 25-Hydroxyvitamin D [25(OH)VD] deficiency/inadequacy is a major public health issue affecting more than 1 billion people worldwide. A convincing association exists between low levels of circulating 25(OH)VD and the poor health outcomes associated with chronic diseases. However, high supraphysiological doses of VD are needed to achieve the required 25(OH)VD levels in the blood, because many subjects respond poorly to supplementation.

Results: This study reports a link between 25(OH)VD deficiency and a reduction in glutathione (GSH) in obese adolescents. The improvement in GSH status that results from cosupplementation with VD and l-cysteine (LC; a GSH precursor) significantly reduced oxidative stress in a mouse model of 25(OH)VD deficiency.
It also positively upregulated VD regulatory genes (VDBP/VD-25-hydroxylase/VDR) in the liver and glucose metabolism genes (PGC-1α/VDR/GLUT-4) in muscle, boosted 25(OH)VD, and reduced inflammation and insulin resistance (IR) levels in the blood compared with supplementation with VD alone. In vitro GSH deficiency caused increased oxidative stress and downregulation of VDBP/VD-25-hydroxylase/VDR and upregulation of CYP24a1 in hepatocytes and downregulation of PGC-1α/VDR/GLUT-4 in myotubes. This study demonstrates that improvement in the GSH status exerts beneficial effects on the blood levels of 25(OH)VD, as well as on the inflammation and IR in a VD-deficient mouse model. Thus, the VD supplements widely consumed by the public are unlikely to be successful unless the GSH status is also corrected.
Innovation: These studies demonstrate a previously undiscovered mechanism by which GSH status positively upregulates the bioavailability of 25(OH)VD.

Conclusion: Supplementation with a combination of VD and LC or GSH precursor, rather than supplementation with VD alone, is beneficial and helps achieve more successful VD supplementation.
 Download the PDF from VitaminDWiki


Study was cited 101 times as of July 2024

Google Scholar

  • Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging- Dec 2023 https://doi.org/10.1016/j.arr.2023.102066 PDF is behind Paywall
  • Image
  • Effects of vitamin D and L-cysteine cosupplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free/total testosterone ratio and inflammatory biomarkers in healthy vitamin D-deficient African Americans: a placebo-controlled double-blind clinical trial - 2024 FREE PDF
  • Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy - March 2022 FREE PDF
  • Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation - NOV 2022 FREE PDF
  • Non-Melanoma Skin Cancer and Vitamin D: The “Lost Sunlight” Paradox and the Oxidative Stress Explanation - 2023 FREE PDF
    • Control group had higher GHS levels
  • Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging - Dec 2023 -https://doi.org/10.1016/j.arr.2023.102066   274 references
  • Image

VitaminDWiki - Genetics chart shows the vitamin D genes

in Visio for 2023


What are possible good ways to increase glutathione levels in the body? Asked Perplexity AI June 2024

There are several effective ways to increase glutathione levels in the body:

  1. Eat sulfur-rich foods: Consuming cruciferous vegetables like broccoli, Brussels sprouts, and cabbage can help boost glutathione levels due to their high content of sulfur-containing compounds called glucosinolates.
  2. Consume glutathione-rich produce: Avocados, asparagus, spinach, squash, melons, grapefruit, and peaches contain plant versions of glutathione that the body can convert to replenish its supply.
  3. Get enough sleep: Adequate sleep is crucial for maintaining glutathione levels. Adults should aim for 7-9 hours of sleep per night.
  4. Exercise regularly: Aerobic exercise, strength training, and yoga can all help build glutathione levels while also boosting the immune system and supporting detoxification.
  5. Eat a healthy diet: Following diets like the Mediterranean or DASH diet, which emphasize fruits, vegetables, nuts, seeds, fish, and olive oil, has been shown to improve glutathione levels.
  6. Supplement with glutathione precursors: N-acetyl cysteine (NAC), alpha-lipoic acid, and selenium can help boost glutathione production in the body.
  7. Consider milk thistle: This herb has been shown to enhance glutathione levels and protect the liver from toxicity.
  8. Increase intake of vitamins C and E: These supporting antioxidants work in tandem with glutathione and can help maintain its levels in the body.
  9. Limit toxic exposure: Reducing your intake of alcohol, processed foods, and exposure to environmental toxins can help preserve glutathione levels.
  10. Consume whey protein: High-quality, grass-fed whey protein can help replenish glutathione by boosting cysteine levels.

Remember to consult with a healthcare professional before making significant changes to your diet or starting any new supplement regimen.


Review of 11 Glutathione Supplements - ConsumerLab June 2024

ConsumerLab
Price of 200 mg ranges from $0.17 cents to $2.88
Swanson and Now were both highly rated
See Excellent reviews of supplements at ConsumerLab - which has a 5 day free trial.

  • VitaminDWiki has subscribed to ConsumerLab for many years - it appears to have zero competition

3 videos by Dr. Anderson on Glutathione


Dr. Anderson REVEALS The 5 MISTAKES You’re Making When Taking GLUTATHIONE - June 2024

12 minute
Synergistic with Vitamin C and Vitamin E - should also take them
Also take co-factors: several Vitamin Bs, Magnesium, Selenium, Zinc


What Happens to Your BODY When You Use GLUTATHIONE? - June 2024

7 minute


The BEST Form of Glutathione - IV, IM, SQ, or LIPOSOMAL - July 2024

7 minute best oral forms: Liposomal, Aceytl


One liposomal Glutathione product was found to be 64X more bio-available than standard

Study on the bioavailability of glutathione
Image


How long does it take for liposomal glutathione to show effects (spoiler: 1 week) - asked Perplexity AI June 2024

Liposomal glutathione can show effects relatively quickly, with significant improvements observed within the first few weeks of supplementation:

  • Initial Effects: In a clinical study, glutathione (GSH) levels were elevated after just 1 week of oral liposomal glutathione supplementation. The study reported maximum increases of 40% in whole blood, 25% in erythrocytes, 28% in plasma, and 100% in peripheral blood mononuclear cells (PBMCs) after 2 weeks of supplementation with doses of 500 mg or 1000 mg per day.
    • Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function - 2017 FREE PDF
  • Oxidative Stress and Immune Function: Alongside the increase in GSH levels, reductions in oxidative stress biomarkers were observed, including a 35% decrease in plasma 8-isoprostane and a 20% decrease in the oxidized:reduced GSH ratio. Enhancements in immune function markers were also noted, with natural killer (NK) cell cytotoxicity elevated by up to 400% and lymphocyte proliferation increased by up to 60% after 2 weeks.
  • Longer-Term Effects: A separate study indicated that liposomal glutathione supplementation over a period of 3 months resulted in reduced oxidative stress and maintained GSH levels in individuals with type 2 diabetes, demonstrating sustained benefits over a longer duration.

Overall, liposomal glutathione can start showing beneficial effects within the first week, with more pronounced and maximum effects typically observed after 2 weeks of consistent supplementation.
References in Perplexity AI


What supplements increase Glutathione levels in the body (NAC best?) - Asked Perplexity AI June 2024

Several supplements have been shown to increase glutathione levels in the body:

  1. N-acetylcysteine (NAC): This is a precursor to cysteine, one of the amino acids needed to synthesize glutathione. NAC is considered one of the most effective supplements for boosting glutathione levels. The recommended dosage is typically 600-1,200 mg per day, divided into multiple doses.
  2. Alpha-lipoic acid (ALA): ALA has been shown to increase glutathione levels. The recommended dosage is 300 mg three times a day or 200-600 mg per day.
  3. Whey protein: Rich in cysteine, whey protein can help boost glutathione production. A typical dosage is around 40 grams per day.
  4. Selenium: This mineral is essential for glutathione production. The recommended dosage is 100-200 μg per day, with caution advised for doses above 400 μg due to potential toxicity.
  5. Vitamin C: This antioxidant can help increase glutathione levels. Dosages of 500-2,000 mg per day have been studied.
  6. Vitamin E: Another antioxidant that may support glutathione levels. Typical dosages range from 100-400 IU per day.
  7. Curcumin: Found in turmeric, curcumin may help boost glutathione levels. Dosages of 1-2 grams per day have been found to benefit antioxidant capacity.
  8. Glutathione itself: While controversial due to potential breakdown in the digestive system, some studies have shown oral glutathione supplementation can increase body stores. Typical dosages range from 250-1,000 mg per day.
  9. Liposomal glutathione: This form may be more bioavailable than standard oral glutathione. Dosages of 500-1,000 mg per day have been studied.
  10. Glycine: An amino acid precursor to glutathione. A dosage of 100 mg/kg/day has been suggested.

It's important to note that while these supplements may help increase glutathione levels, their effectiveness can vary among individuals. Additionally, lifestyle factors such as getting enough sleep, regular exercise, and eating a healthy diet rich in sulfur-containing foods (like cruciferous vegetables) can also support glutathione production. Always consult with a healthcare professional before starting any new supplement regimen.
Perplexity AI references
NAC supplement review at ConsumerLab 5 day free trial of annual subscription


>50 liposomal Glutathoine products on Amazon

I chose a low-cost lipospmal form in capsules with > 400 in monthly sales
Seems good - as of Oct 2024 - I am starting on my 3rd bottle.


Have glutathione levels decreased recently (spolier: YES) - asked Chat-GPT 4.o June 2024

There is some evidence suggesting that glutathione levels have decreased in certain contexts over recent decades. Several factors contribute to these changes, including increased exposure to environmental pollutants, dietary shifts, and the widespread use of certain medications.

  1. Environmental Pollutants: The rise in environmental pollutants, such as heavy metals, pesticides, and industrial chemicals, has been linked to oxidative stress, which depletes glutathione levels. This is because glutathione is a primary antioxidant that neutralizes reactive oxygen species (ROS) induced by these pollutants (MDPI) (MDPI).
  2. Dietary Changes: Modern diets, which are often lower in fruits and vegetables and higher in processed foods, can reduce the intake of glutathione precursors and other antioxidants. Nutrient deficiencies, particularly in vitamins and minerals that support glutathione synthesis, may also play a role in the decline of glutathione levels (MDPI).
  3. Medication Use: Certain medications, including acetaminophen (paracetamol), can deplete glutathione levels. Acetaminophen, when metabolized in the liver, can form toxic intermediates that require glutathione for detoxification, thereby reducing its availability (MDPI).
  4. Aging: Natural aging processes are associated with a decline in glutathione levels. This is due to a decrease in the efficiency of the body's natural antioxidant systems and increased oxidative stress over time (MDPI).

Overall, while it is challenging to pinpoint a precise global trend, these factors collectively suggest that glutathione levels might have decreased in recent decades due to increased oxidative stress from environmental, dietary, and pharmaceutical sources.


Glutathione, cataract and liposomal search found 4,100 items as of Oct 2024

Google Scholar

  • How to Increase Cellular Glutathione - May 2023 [https://doi.org/10.3390/antiox12051094|FREE PDF
  • Antioxidant Nutraceutical Strategies in the Prevention of Oxidative Stress Related Eye Diseases - May 2023 FREE PDF
  • Ferroptosis: a novel mechanism of cell death in ophthalmic conditions - June 2024 FREE PDF
  • Advancing Medicine with Lipid-Based Nanosystems—The Successful Case of Liposomes - Feb 2023 FREE PDF

There have been 1782 visits to this page

Attached files

ID Name Comment Uploaded Size Downloads
21427 Glut arrows.webp admin 16 Jul, 2024 37.75 Kb 147
21426 Genes and Glut.webp admin 16 Jul, 2024 24.18 Kb 143
21425 Obesity & GSH.webp admin 16 Jul, 2024 25.92 Kb 146
21424 Glut ToC.webp admin 16 Jul, 2024 14.69 Kb 165
21423 Glutathione and vitamin D July 2024_CompressPdf.pdf admin 16 Jul, 2024 372.00 Kb 44
21370 Lipo glut bioavailability.webp admin 23 Jun, 2024 11.42 Kb 168
21361 Glut effects.webp admin 21 Jun, 2024 15.37 Kb 174
21360 Glut D Chart.webp admin 21 Jun, 2024 21.81 Kb 229
21359 Glut increase Vitamin D genes.webp admin 21 Jun, 2024 16.13 Kb 173
21358 Glur caption.webp admin 21 Jun, 2024 6.50 Kb 173
21357 Gluathione increases Vitamin D.webp admin 21 Jun, 2024 3.10 Kb 175
21356 Glutathone vs vitamin D.webp admin 21 Jun, 2024 7.43 Kb 178
21355 Glutathione and vitamin D genes_CompressPdf.pdf admin 21 Jun, 2024 845.91 Kb 48