What's the "D"eal with Vitamin D?

Updated: Jun 5, 2020

We often think of Vitamin D as the "sunshine vitamin", as it's produced in our body when our skin is exposed to ultraviolet rays from the sun. Vitamin D often makes the spotlight with its importance in calcium metabolism and prevention of osteoporosis and rickets, but did you know that there are Vitamin D receptors located throughout the body, and it can affect somewhere around 3,000 different genes? Did you know it's actually a steroid hormone (like cortisol, estrogen, progesterone and testosterone), and not a vitamin?

There is a lot we've learned about Vitamin D over the last few decades, but there is a lot more we still need to learn. Many physicians overlook the importance of Vitamin D in immune system function and prevention of chronic disease including cancer, type 2 diabetes, age-related macular degeneration and even Alzheimer's disease (and more!).

Deficiency of Vitamin D is prevalent around the world and especially in the United States. Living in the higher latitudes of the Pacific Northwest, we have the challenge of getting enough Vitamin D in the winter and fall as our sun levels are greatly reduced compared to other parts of the country. If you have more skin pigmentation (darker skin color), this also makes it harder for you to absorb the UV B rays which trigger production of the hormone. It's estimated around 85% of Americans are deficient in Vitamin D, and the drop in Vitamin D that occurs in the fall and winter is one suggested contributor to increased colds and flus.

What does the Research Say? A few highlights...

"Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection. As immune cells in autoimmune diseases are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D deficient individuals with autoimmune disease may extend beyond the effects on bone and calcium homeostasis."

Aranow C. Vitamin D and the immune system. J Investig Med. 2011;59(6):881–886. doi:10.2310/JIM.0b013e31821b8755

This is only one study of many showing benefit from Vitamin D supplementation in autoimmune disease. In particular, Type 1 diabetes, Systemic lupus, Multiple Sclerosis, Psoriasis and Rheumatoid Arthritis have then the most common subjects of study.

"Studies in both human and animal models add strength to the hypothesis that the unrecognized epidemic of vitamin D deficiency worldwide is a contributing factor of many chronic debilitating diseases. Greater awareness of the insidious consequences of vitamin D deficiency is needed. Annual measurement of serum 25(OH)D is a reasonable approach to monitoring for vitamin D deficiency. "

Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79(3):362-371.

"Chronic vitamin D deficiency may have serious adverse consequences, including increased risk of hypertension, multiple sclerosis, cancers of the colon, prostate, breast, and ovary, and type 1 diabetes. There needs to be a better appreciation of the importance of vitamin D for overall health and well being."

Holick MF. Vitamin D: A millenium perspective. J Cell Biochem. 2003;88(2):296-307. 

"All patients with persistent, nonspecific musculoskeletal pain are at high risk for the consequences of unrecognized and untreated severe hypovitaminosis D."

Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc. 2003;78(12):1463-1470.

I have seen chronic muscle and joint pain resolve with Vitamin D supplementation alone in two patients. Their serum levels were 5 ng/ml and 8 ng/ml (normal is >30 ng/ml).

"Low vitamin D status is a significant risk factor for cardiometabolic disease in U.S. adults based on standardized serum 25(OH)D results, irrespective of ethnic background."

Al-Khalidi B, Kimball SM, Rotondi MA, Ardern CI. Standardized serum 25-hydroxyvitamin D concentrations are inversely associated with cardiometabolic disease in US adults: a cross-sectional analysis of NHANES, 2001-2010. Nutr J. 2017;16(1):16.

"Vitamin D deficiency is particularly frequent in patients with chronic kidney disease, in whom it is associated with increased mortality. Studies indicate that treatment with vitamin D analogues reduces proteinuria, suppresses the renin-angiotensin-aldosterone system (RAAS), and exerts anti-inflammatory and immunomodulatory effects."

Doorenbos CR, van den Born J, Navis G, de Borst MH. Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism. Nat Rev Nephrol. 2009;5(12):691-700.

"We conclude, percentage body fat content is inversely related to the serum 25-OHD levels in healthy women."

Arunabh S, Pollack S, Yeh J, Aloia JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab. 2003;88(1):157-161. 

Higher levels if serum Vitamin D are seen in those with healthier weights.

"The meta-analysis suggests a moderate inverse association of 25(OH)D concentration with total cancer incidence and mortality."

Yin L, Ordonez-Mena JM, Chen T, Schottker B, Arndt V, Brenner H. Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: a systematic review and meta-analysis. Prev Med. 2013;57(6):753-764. 

Higher Vitamin D levels are seen with less cancer incidence and mortality.

"Higher 25OHD concentration is associated with better cancer outcome, and the observed association of functional variants in vitamin D pathway genes with outcome supports a causal link."

Vaughan-Shaw PG, O'Sullivan F, Farrington SM, et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. Br J Cancer. 2017;116(8):1092-1110.

"These findings suggest that vitamin D3 may be an important pathogenic factor in type 1 diabetes independent of geographical latitude, and that its supplementation should be considered not only at birth, but also at diagnosis of type 1 diabetes with the aim of favouring a Th2 immune response and protecting residual beta cells from further destruction."

Pozzilli P, Manfrini S, Crino A, et al. Low levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes. Horm Metab Res. 2005;37(11):680-683. 

"Vitamin D supplementation during pregnancy was associated with increased circulating 25(OH)D levels, birth weight, and birth length, and was not associated with other maternal and neonatal outcomes."

Perez-Lopez FR, Pasupuleti V, Mezones-Holguin E, et al. Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2015;103(5):1278-1288.e1274.