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 D3
(cholecalciferol) 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). (It is only called a vitamin
because we do not get enough sunlight and therefore need to obtain it dietarily).
This process leads to the upregulation of numerous 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 D3 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 for 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 exacerbated 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 margarine restores vitamin D status to clinically healthy
levels in deficient populations. Biofortification of eggs from hens fed vitamin
D3-enriched feed is as effective at correcting this deficiency as using fortified
foods. It has even been shown that cows fed a diet containing 4,000 IUs of
vitamin D3 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 ergocalciferol
(vitamin D2), 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 individuals who cannot digest dairy
there are many other dietary options. (Be sure to check food labels!). Keep in
mind that the only way to be absolutely sure that you are consuming enough
vitamin D, either through food or a supplement, is to have your blood levels
and functional activity checked annually. You are welcome to book an appointment for blood testing from our website at www.egglrock.com.
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
Martin, T. and Campbell, K.. (2011) Vitamin D and
diabetes. Diabetes Spectrum. Retrieved from: https://spectrum.diabetesjournals.org/content/24/2/113
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
*This
article was published in Integrative Practitioner on November 26, 2019 and
can be retrieved here: https://www.integrativepractitioner.com/patient-care-planning/2019-11-26-annual-testing-vitamin-d-serum-levels-and-functional-activity
Thanks for sharing this article on vitamin D levels and their functional activity. It was very useful. I found the best neurology hospital in Chennai offer the best neurologic treatment in Chennai. They provide excellent care and support for the patients. Their medication and treatment are one of the best in Chennai.
ReplyDelete