Vitamin D has been implicated for its benefits on both bone and neuromuscular health. Attaining a level >30 ng / mL is optimal for extra-skeletal health. Vitamin D may play a role in immunomodulation.
Vitamin D has been implicated for its benefits on both bone and neuromuscular health. Attaining a level >30 ng / mL is optimal for extra-skeletal health. Vitamin D may play a role in immunomodulation.
Vitamin D has been implicated for its benefits on both bone and neuromuscular health. Attaining a level >30 ng / mL is optimal for extra-skeletal health. Vitamin D may play a role in immunomodulation.
Ian Lind, Marissa Potente, Katherine Ratlif Introduction In 2011 the RDA was established for vitamin D, tripling that of the previous AI from 200 IU to 600 IU for adults age 19-70 (1). This RDA is based on the serum levels of 25 (OH)D that would prevent vitamin D deficiency and maximize bone health (1). A serum level of 20 ng/mL of 25 (OH)D or above was considered sufficient, while levels below 10 ng/mL were considered insufficient (2). Determining vitamin D status in regards to serum levels involves analyzing sun exposure, BMI, age, and skin pigmentation (2). The primary source of vitamin D for most individuals comes from cutaneous synthesis of UV-B irradiation. Food sources of vitamin D include fatty fish, egg yolks, and fortified foods such as milk, orange juice, and breakfast cereals (3). Vitamin D has been implicated for its benefits on both bone and neuromuscular health (3,4). However, the functions of 1,25(OH)2D, the biologically active form, extend far beyond these two benefits. Other cells expressing the vitamin D receptor may also be influenced by 1,25-dihydroxyvitamin D (3). These include skeletal muscle, breast, colon, prostate, and heart. Evidence suggests that vitamin D may play a role in immunomodulation,
Considerations for Increasing the RDA
When researching the efects of vitamin D on extra-skeletal health, it becomes clear that the serum level of 25(OH)D deemed sufficient by the IOM is not what is most often shown to optimize extra-skeletal health. In fact, a common theme among this research is that attaining a level >30 ng/mL is optimal (1,6,7). In a prospective study of >41,000 subjects followed for an average of 1.3 years, there was a significant correlation between vitamin D status <30 ng/mL and risk of hypertension, hyperlipidemia, diabetes, and peripheral vascular disease (p <0.0001) (7). Some of the mechanisms for such improvements in health attributed to vitamin D are inhibition of the reninangiotensin system, improved insulin secretion and sensitivity, inhibition of vascular smooth muscle proliferation, protection of endothelial cell function, and regulation of inflammation (8). Interestingly, both Holick and BischofFerrari present data indicating that even for bone health, levels of 25(OH)D >30 ng/mL are necessary to optimally reduce osteomalacia and increase overall bone mineral density (1,6). In addition, Bischof-Ferrari argues that reducing fall-risk in older adults, via muscular health and balance, begins with at least >24 ng/mL, and prevention of fracture increases most significantly at >30 ng/mL (6). Finally, it is clear that the current RDA is insufficient to reach serum levels of >30 ng/mL of 25(OH)D (1,6,9). For example, in a study conducted in Toronto in winter, supplementation of 4000IU/d for >1 month only brought 88% of the cohort, made up of healthy young men and women, to >30 ng/mL 25(OH)D (6). Therefore, to achieve maximal biological activity of vitamin D, it is suggested that a serum level of > 30 ng/mL of 25(OH)D be used to determine adequacy and that the RDA be increased to match this new level.
Considerations for Maintaining the RDA
Serum levels of 25(OH)D are associated with bone health and according to the IOM the optimal serum level is 20 ng/mL (2). To determine the efect of the current RDA reccommenditons on serum 25(OH)D and skeletal health in post-menopausal women a double blind dose response trial was conducted. Women were randomly assigned to 1 of 7 vitamin D3 doses ranging from 400 IU-4800 IU. The results showed that 97.5% of women were able to achieve serum 25(OH)D levels of 20ng/mL with doses of 400 IU-800 IU. The results from this study show that the IOM recommendations for vitamin D are able to achieve serum levels high enough to optimize bone health (2). The IOM has not taken into account the efects of vitamin D status on extra-skeletal health because current research has been inconsistent and optimal serum levels cannot be determined (2). Although there has been studies that show low 25(OH)D levels are associated with cardiovascular disease and diabetes there has been no determination of a causal relationship from several randomized trials and treatment with high dose vitamin D has shown little efect on lipid and A1c levels (10). A double blind randomized placebo controlled trial was conducted to determine the efect of vitamin D supplementation on HbA1c, and serum lipids levels (10). The experimental groups took vitamin D supplements of either 10ug or 25ug daily for sixteen weeks. After sixteen weeks the experimental groups average 25(OH) D levels increased to 20 ng/mL (p=0.0001), but there was no diference seen in HbA1c, total cholesterol, LDL, HDL, and triglyceride levels (10). Also, high dose Conclusion The current RDA is based on a serum level of vitamin D that prevents osteomalacia (1). No extra-skeletal benefits were taken into account when determining vitamin D adequacy. Given the evidence suggesting the efficacy of vitamin D beyond skeletal health, it is pertinent that we reconsider the serum level of 25(OH)D required to maximize the biological activity of vitamin D. As the proportion of our population that is older and/or overweight continues to rise, both of which predicate a higher vitamin D intake (9,12) and are associated with greater risk of disease, it is of the utmost importance that we reevaluate the RDA necessary to optimize health, particularly as it pertains to extra-skeletal health.
References: 1. Holick MF. Evidence-based D-bate on health benefits of vitamin D revisited. Dermato-Endocrinology. 2012;4(2): 183-190.
2. Gallagher JC, Sai A, Templin T, Smith L. Does Response to Vitamin D Supplementation
in Postmenopausal Women. Annals of Internal Medicine. 2012; 156: 425-437. 3. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006; 81(3):353-73. 4. Moreira- Pfrimer LD, Pedrosa MA, Teixeira L, Lazaretti-Castro M. Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: a randomized double-blind controlled trial. Ann Nutr Metab. 2009;54:291-300. 5. Dalhof K, Dancey J, Astrup L. A phase II study of the vitamin D analogue seocalcitol in patients with inoperable hepatocellular carcinoma. Br J Cancer. 2003;89(2): 252-257. 6. Bischof-Ferrari H. Vitamin D: What is an adequate vitamin D level and how much supplementation is necessary? Clin Rheumatology. 2009;23(6):789-795. doi:10.1016/j.berh.2009.09.005. 7. Anderson JL, May HT, Horne BD, et al. Relation of Vitamin D Deficiency to Cardiovascular Risk Factors, Disease Status, and Incident Events in a General Healthcare Population. Am J of Card. 2010;106(7):963-968. doi:10.1016/j.amjcard.2010.05.027. 8. Wang L, Manson JE, Song Y, et al. Systematic Review: Vitamin D and Calcium Supplementation in Prevention of Cardiovascular Events. Ann Intern Med. 2010;152:315323. doi:10.7326/0003-4819-152-5-201003020-00010. 9. Cashman KD, Wallace JM, Horigan G, et al. Estimation of the dietary requirement for vitamin D in free-living adults 64 y of age. Am J of Clin Nut. 2009;89(5):1366-1374. doi:10.3945/ajcn.2008.27334. 10. Madar AA, Knusten KV, Stene LC, Brekke M, Meyer HE, Lagerlov P. Efects of Vitamin D Supplementation of Glycated Hemoglobin, Fructosamine, Serum Lipids, and Body Mass. Diabetes Research and Care. 2014; 2(1): 1032-1040. 11. Sanders MK, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson. Annual High-Dose Oral Vitamin D and Falls and Fractures in Older Women. Journal of American Medical Association. 2010; 303(18): 1815-1822. 12. Wortsman J, Matsuoka LY, Holick MF, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(3):690-693.