Annual testing of vitamin D serum levels and functional activity

Photo Cred: Pietro Jeng/Pexels

By Laura Rokosz, PhD

The correlation between vitamin D and bone health is well-recognized by the medical community. However, its role in immune health is not nearly as appreciated. 

The functional importance of vitamin D is deep-rooted in human evolution. When humans in Africa lost their hair, their skin darkened to protect them from sun burn and skin cancer. As humans migrated to Europe and Asia, skin pigmentation lightened to facilitate UV-B-induced vitamin D production needed not only for bone health but for immunity.

The activated form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), acts as a nuclear hormone that binds to and stimulates the vitamin D receptor (VDR). This process leads to the upregulation of many immune system-related genes and has fueled the hypothesis that a vitamin D deficiency is a risk factor for autoimmune diseases such as inflammatory bowel disease (IBD), type 1 diabetes, rheumatoid arthritis, and multiple sclerosis.

Data also exist to correlate vitamin D deficiency with metabolic diseases, cancer, and Alzheimer’s disease. Although the mechanism for these associations is not clear, it is likely related to VDR activation.

Given the criticality of vitamin D function, it is recommended to quantify both the serum levels and activity during a yearly physical. I have been using a functional cell-based assay, which propagates T cells from blood samples, to measure the activity of vitamin D. This assay informs on VDR signaling by looking at the growth of immune cells in a defined culture medium.

Functional activity is always more informative than checking levels alone. Clinically, a vitamin D deficiency is defined as serum levels less than 20 ng/mL. Vitamin D insufficiency is defined as serum levels between 21 and 29 ng/mL. If the serum levels are below 30 ng/mL, then supplementation with 1,000 to 4,000 international units (IUs) of vitamin D is recommended. Keep in mind, levels of at least 50 ng/mL are advised to thwart immunodeficiency. If vitamin D levels are adequate but the functional activity is below the acceptable threshold, then the dose may be increased to 5,000 IUs per day or 50,000 IUs once per week.

Since vitamin D is fat-soluble, care should be taken to avoid toxicity which occurs when serum levels exceed 150 ng/mL. Functional activity should be rechecked again in six months, which is roughly the amount of time it takes to completely replenish a new generation of T cells that have been exposed to the higher vitamin D levels.

If supplementation does not correct the functional deficiency, then it is possible that the VDR has been desensitized, meaning it has been over-stimulated and no longer responds to activation by vitamin D. This is a common receptor-mediated mechanism, and therefore supplementation should be discontinued several weeks to one month to restore sensitivity. Although there may be unknown genetic factors that effect VDR function manipulating vitamin D levels with a supplement is a straight-forward and economical strategy to help resolve the problem.

With the advent of antiseptics, antibiotics, and vaccines, the human immune system has greatly evolved. Chronic immune-related diseases far outpace infectious disease as a cause of death. This phenomenon has been acerbated by economic expansion that modified human behaviors contributing to vitamin D deficiency. We no longer spend adequate time outdoors and we eat less vitamin D-rich foods like fish and dairy. For the sake of our immune system perhaps, it is time to revisit food fortification efforts.

Such measures with B vitamins including B12, riboflavin, niacin, and thiamin have improved children’s heath, folate fortification has reduced neonatal spinal cord defects, and iodized salt has improved thyroid health. Dietary efforts to reduce vitamin D deficiency are sure to have a similar impact on immune health.

Multiple studies have shown that fortified milk, cereals, wheat flour, and butter restores vitamin D status to clinically healthy levels in deficient populations. Biofortification of eggs from hens fed vitamin D-enriched feed is as effective at correcting this deficiency as using fortified foods. It has also been shown that cows fed a diet containing 4,000 IUs of vitamin D for 30 days prior to slaughter significantly increased vitamin D content of the resulting beef steak. Other biofortified foods include UV-treated mushrooms and baker’s yeast, which are plant-based sources of vitamin D, for those who do not consume animal products.

Our dietary needs for vitamin D will vary on time of year and geographic location. Therefore, food industries world-wide should adjust food product production strategies according to these variables. Current fortification and biofortification efforts are aimed at ensuring that upper limits for consumption are not exceeded. For those patients who cannot digest dairy there are many other dietary options. Encourage patients to check food labels. Keep in mind that the only way to be sure someone is consuming enough vitamin D, either through food or a supplement, is to have blood levels and functional activity checked annually.

References

Carlberg, C. (2019) Nutrigenomics of vitamin D. Nutrients. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/30901909

Carlberg, C. (2019) Vitamin D signaling in the context of innate immunity: Focus on human monocytes. Frontiers in Immunology. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/31572402

Harrison, SR.., Li, D., Jeffery, L.E., Raza, K., and Hewison, M.. (2019) Vitamin D Autoimmune Disease and Rheumatoid Arthritis. Calcified Tissue International. Retrieved from https://link.springer.com/article/10.1007%2Fs00223-019-00577-2

Holick, M.F.. (2007) Vitamin D defiency. New England Journal of Medicine. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/17634462

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Moulas, A.N. and Vaiou, M. (2018) Vitamin D fortification of foods and prospective health outcomes. Journal of Biotechnology Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/30176270

Littlejohns, T.J., Henley, W.E., Lang, I.A., Annweiler, C., Beauchet, O., Chaves, P.H., Fried, L., Kestenbaum, B.R., Kuller, L.H., Langa, K.M., Lopez, O.L., Kos, K., Soni, M., and Llewellyn, D.J. (2014) Vitamin D and the risk of dementia and Alzheimer disease Neurology. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/25098535

Venkatramanan, S., Armata, I.E., Strupp, B.J., and Finkelstein, J.L. (2016). Vitamin B-12 and Cognition in Children. Advances in Nutrition. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/27633104

Walsh, J.S., Bowles, S., and Evans, A.L. (2017) Vitamin D in Obesity. Current Opinion in Endocrinology, Diabetes and Obesity. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/28915134

Young, M.R.I. and Xiong, Y. (2018) Influence of vitamin D on cancer risk and treatment: Why the variability? Trends in Cancer Research. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/30369773

About the Author

Laura Rokosz, PhD

Laura Rokosz, PhD, is a pharmacologist and food scientist with 28 years of experience in the pharmaceutical and biotechnology industries. She received her Bachelor’s, Master’s and PhD in Food Science from Rutgers University and is the current Chair of the Rutgers Food Science Advisory Board.

Rokosz was employed with Schering-Plough, Merck, and Pharmacopeia where she supported drug discovery efforts related to metabolic diseases, Infectious disease, autoimmune disorders, Alzheimer’s disease, and cancer. She is the author of over 40 peer-reviewed journal articles including five expert opinion articles on obesity and cancer. Several her blogs on fitness and nutrition have recently been published on the syndicated website, Mind Body Green. Rokosz is currently the owner of EGGLROCK Nutrition, LLC, an integrative healthcare practice providing dietary and lifestyle guidance for disease prevention and health maintenance. EGGLRock Nutrition recently received the Rising Growth Success Award from the Small Business Development Center at Kean University and was named Business of the Year for 2016 by the Union Chamber of Commerce. 

Rokosz also teaches a variety of nutrition courses at Kean University, Rutgers University, and Stevens Institute of Technology and she teaches group fitness classes at the Gateway Family YMCA of Union, New Jersey.  She also hosts a weekly podcast, “Eat Right with Laura” which can be found on her website at www.egglrock.com.