Glutathione is essential for vitamin D metabolism

Garlic is an allium vegetable, that among others contains sulfur-containing compounds. Glutathione, a master antioxidant in the body is a compound that contains sulfur amino-acids. Garlic consumption increases sulfur intake from the diet and stimulates glutathione synthesis. Garlic can be eaten daily, raw or processed.

Many healthy people lack vitamin D and glutathione. Basically, most sick people are deficient in both of those compounds. What is the mistake that I see quite often is that medical specialists and dietitians focus on vitamin D only. At the same time they are forgetting about glutathione.

Why is that matter? Glutathione works together with vitamin D. Without vitamin D glutathione can’t be metabolized properly and you can know about that from another article. In here, I’ll tell you a bit why vitamin D can’t be produced, metabolism, and finally activated to biologically active form when you lack glutathione.

Interesting right?

Highlights

  • Glutathione is necessary for expression of vitamin D metabolism-related genes expression,
  • Low glutathione status correlates with low vitamin D status especially in people with type 2 diabetes,
  • Obese and overweight people have both low glutathione and vitamin D status,
  • Low glutathione status might block completely or blunt effects of vitamin D supplementation therapy,
  • Studies on mice show that vitamin D status increases more with a concomitant increase of glutathione status.

If you follow the blog you know that glutathione is the natural protector of the body against toxins, oxidative stress, or over increased inflammatory processes. It is a “master antioxidant” and there are easy ways to increase its concentration in the body by nutrition and other interventions.

READ: Glutathione – boost your natural protector.

It is now known that glutathione (GSH) is much more than most of us thought. In fact, glutathione takes an active role in vitamin D metabolism. Vitamin D (VD) is an often reported deficient compound in healthy and sick people. One of the most prevalent diseases worldwide related to cardiovascular diseases.

Glutathione interacts with vitamin D genes

Glutathione was found to interact with the expression of genes related to VD metabolism.

Generally, there is a growing interest in food compounds that interacts in gene expressions like resveratrol or omega-3 fatty acids. Although glutathione is also a body producing compound that interacts with epigenetic processes and its level is highly related to the quality of food we eat.

Vitamin D metabolism is highly related to the synthesis of proteins that participates in its transport and activation. There are a few steps of that, first, you have to have produced vitamin D binding protein that binds VD and transports it throughout the body. Then, if needed an inactive VD needs to be activated in the liver and then in the kidney to the active one.

Infographic. Glutathione is essential for vitamin D activity. Glutathione activates vitamin d related genes what in a result increases level of proteins that transports vitamin d throught the body. Besides that, glutathion increases synthesis of enzymes that activates vitamin D. In a result vitamin D serum concentration increases and its activity.

Vitamin D and glutathione interconnection.

If your genes are off, you are lacking proteins that are necessary to access the biological properties of VD. Those genes expression are blocked if you have the low status of GSH.

In Poland, you can choose Vigantoletten or Vigantol – by choosing one of them you can be sure you are taking your dose.

Are you Vitamin D deficient?

As you probably know VD is synthesized in the skin when you expose yourself to sunlight. Then it is transported through the cardiovascular system to the liver where it gets to cholecalciferol which is 25(OH)D or 25-hydroxyvitamin D. That’s the one you measure concentration in the serum to know what you VD status is. Generally it is accepted that:

Vitamin D status. Potentially toxic, more than 100 ng/mL, 200 nmol/L. Normal level 30-100 ng/mL, 75-200 nmol/L. Insufficient 20-29 ng/mL, 50-725 nmol/L. Deficiency, less than 20 ng/mL, 50 nmol/L.

Vitamin D deficiency status is concentration less than 20 ng/mL, <50 nmol/L

Insufficient: 20-29 ng/mL, 50-72.5 nmol/L,

Normal: 30-100 ng/mL, 75-200 nmol/L

Potentially toxic: above 100 ng/mL, above 200 nmol/.

Counts:

  • 1 ng/ml – 2.5 nmol/l,
  • 1 ug = 2.5 nmol,
  • 1 ug = 40 IU.

Glutathione deficiency cause vitamin D deficiency

On human studies, especially in people with diabetes or liver disease GSH status improvement by supplementation increases concomitantly VD status. The low status of both compounds is related to many diseases and with increased risk of developing them.

In type 2 diabetic patients it was found that low GSH level is correlated with VD deficiency. Their level is also decreased in overweight and obese people compared to normal-weight controls.

Even if you are not diabetic but have insulin resistance – GSH and VD serum concentration was correlated positively with insulin sensitivity. Insulin resistance causes an increase in glucose level in the blood and finally yields to diabetes.

Vitamin D supplementation treatment

As pointed out above you can’t expect vitamin D serum concentration increase in the blood if you are lacking proteins that are necessary for that. Secondly, those proteins need to be synthesized by transcription from genes that codes them. And those genes are expressed by glutathione.

Thus it is logical that if you have low GSH status, vitamin D supplementation may not work for you unless you improve your GSH metabolism. But, studies on mice have shown that vitamin D improvement in the blood is better when you combine it with L-cysteine than use VD alone. The former is a substrate for GSH synthesis.

Thus, among others, lack of vitamin D status improvement despite VD supplementation might be caused by low VD-related gene expression. This might completely block the results of supplementation or decrease them. If you don’t know what is responsible for glutathione synthesis check the article I referred at the beginning and last one where I wrote about magnesium involvement in vitamin D metabolism.

READ Vitamin D doesn’t work without magnesium

Another reason might be a source. Vitamin D dietary supplements might not have VD as much as it’s written on the label. They don’t have to be tested and proved to have it as pharmaceutical drugs have. Thus if there is an option in your county – choose pharmaceutical drugs instead of dietary supplements.

Conclusion

Vitamin D metabolism is highly related to vitamin D related genes expression. Their expression is decreased especially in people with type 2 diabetes but also in obese and overweight people. This is highly related to glutathione status in those subjects. Thus you might have problems with vitamin D status improvement without addressing low glutathione status.

Sources & References

Nissen J, Vogel U, Ravn-Haren G 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 D₃-fortified bread and milk during winter in Denmark. Am J Clin Nutr. 2015 Jan;101(1):218-27. doi: 10.3945/ajcn.114.092148. Epub 2014 Nov 5.  PubMed

Jain SK, 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 May;60(5):1090-8. doi: 10.1002/mnfr.201500667. Epub 2016 Apr 14. PubMed

Jain SK, Micinski D, Huning L et al. 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 Oct;68(10):1148-53. doi: 10.1038/ejcn.2014.114. Epub 2014 Jun 25.  PubMed

Jain SK, Kahlon G, Bass P et al. 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 Sep 10;23(8):688-93. doi: 10.1089/ars.2015.6320. Epub 2015 May 29.  PubMed

Alvarez JA, Chowdhury R, Jones DP et al. Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults. Clin Endocrinol (Oxf). 2014 Sep;81(3):458-66. doi: 10.1111/cen.12449. Epub 2014 Apr 15.  PubMed

Parsanathan R, Jain SK. Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice. Sci Rep. 2019 Oct 15;9(1):14784. doi: 10.1038/s41598-019-51377-5.  PubMed

Jain SK, Parsanathan R, Achari AE et al. 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 Dec 10;29(17):1792-1807. doi: 10.1089/ars.2017.7462. Epub 2018 Oct 9.  PubMed