Vitamin D Sufficiency: How Should it be Defined and what are its Functional Indicators?

  • Hollis Broce W. (Departments of Pediatrics, Biochemistry and Molecular Biology, Medical University of South Carolina)
  • Published : 2005.05.01

Abstract

It has been more than three decades since the first assay assessing circulating 25 (OH)D in human subjects was performed That publication as well as several that followed it defined 'normal' nutritional vitamin D status in human populations. Recently, the wisdom by which 'normal' circulating 25 (OH)D levels in human subjects were assigned in the past has come under question. It appears that sampling human subjects, who appear to be free from disease, and assessing 'normal' circulating 25 (OH)D levels by plotting a Gaussian distribution is grossly inaccurate. There are many reasons why this method is inaccurate, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary recommendations for vitamin D. For instance, a 400 IU/day. AI for vitamin D is insignificant when one considers that a 10-15 minute whole body exposure to peak summer sun will generate and release up to 20,000 IU vitamin $D_3$ into the circulation. Recent studies, which orally administered up to 10,000 IU/day vitamin $D_3$ to human subjects for several months, have successfully elevated circulating 25 (OH)D levels to those observed in individuals from sun-rich environments. Further, we are now able to accurately assess sufficient circulating 25 (OH)D levels utilizing specific biomarkers instead of guessing what an adequate level is. These biomarkers include intact parathyroid hormone (PTH), calcium absorption, bone mineral density (BMD), insulin resistance and pancreatic beta cell function. Using the data from these biomarkers, vitamin D deficiency should be defined as circulating levels of 25 (OH)D$\leq$30 ng/mL. In certain cases, such as pregnancy and lactation, significantly higher circulating 25 (OH)D levels would almost certainly be beneficial to both the mother and recipient fetus/infant.

Keywords

References

  1. Haddad JG, Chyu K. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinal Metab 33:992-995, 1971 https://doi.org/10.1210/jcem-33-6-992
  2. Holick MF. Photobiology of vitamin D. In: Feldman D, Glorieux FH, Pike JW (eds.) Vitamin D. Academic Press. San Diego, CA, pp.33-39, 1996
  3. Matsuoka LY, Wortsman J, Haddad JG, Hollis BW. In vivo threshold for cutaneous synthesis of vitamin $D_{3}$. J Lab Clin Med 114:301-305, 1989
  4. Holick MF, MacLaughlin JA, Doppelt SH. Factors that influence the cutaneous photosynthesis of previtamin $D_{3}$. Science 211:590-593, 1981 https://doi.org/10.1126/science.6256855
  5. Matsuoka LY, Wortsman J, Hollis BW. Lack of effect of exogenous calcitriol on cutaneous production of vitamin $D_{3}$. J Clin Endocrinal Metab 66:451-453, 1988 https://doi.org/10.1210/jcem-66-2-451
  6. MacLaughlin JA, Holick MF. Aging decreases the capacity of the skin to produce vitamin $D_{3}$. J Clin Invest 76:1536-1538, 1985 https://doi.org/10.1172/JCI112134
  7. Matsuoka LY, Wortsmann J, Haddad JG, Kolm P, Hollis BW. Racial pigmentation and the cutaneous synthesis of vitamin D. Arch Dermatol 127:536-538, 1991 https://doi.org/10.1001/archderm.127.4.536
  8. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin $D_{3}$ synthesis in human skin. J Clin Endocrinal Metab 67:373-378, 1988 https://doi.org/10.1210/jcem-67-2-373
  9. Matsuoka LY, Wortsman J, Hollis BW. Use of topical sunscreen for the evaluation of regional synthesis of vitamin $D_{3}$. J Amer Acad Dermatol 22:772-775, 1990 https://doi.org/10.1016/0190-9622(90)70107-S
  10. Matsuoka LY, Wortsman J, Dannenberg MJ, Hollis BW, Lu Z, Holick MF. Clothing prevents ultraviolet-B-radiation-dependent photosynthesis of vitamin $D_{3}$. J Clin Endocrinol Metab 75:1099-1103, 1992 https://doi.org/10.1210/jc.75.4.1099
  11. Clemens TL, Henderson SL, Adams JS, Holick MF. Increased skin pigment reduces the capacity of skin to synthesize vitamin $D_{3}$. Lancet 9:74-76, 1982
  12. Haddad JG, Matsuoka LY, Hollis BW, Hu Y, Wortsman J. Human plasma transport of vitamin D after its endogenous synthesis. J Clin Invest 91(6):2552-2555, 1993 https://doi.org/10.1172/JCI116492
  13. Lark R, Lester G, Ontjes D, Blackwood A, Hollis BW, Hensler M, Aris R. Diminished and eratic absorption of ergocalciferol in adult cystic fibrosis patients. Am J Clin Nutr 73:602-606, 2001 https://doi.org/10.1093/ajcn/73.3.602
  14. Haddock L, Corcino J, Vazquez MD. 25 (OH)D serum levels in the normal Puerto Rican population and in subjects with tropical sprue and parathyroid disease. Puerto Rico Health Science 1:85-91, 1982
  15. Matsuoka LY, Wortsman J, Hanifan N, Holick MF. Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D: A preliminary study. Arch Dermatol 124:1802-1804, 1988 https://doi.org/10.1001/archderm.124.12.1802
  16. Sherman SS, Hollis BW, Tobin J. Vitamin D status and related parameters in a healthy population: The effects of age, sex and season. J Clin Endocrinal Metab 71:405-413, 1990 https://doi.org/10.1210/jcem-71-2-405
  17. Gloth FM, Tobin JD, Sherman SS, Honis BW. Is the recommended daily allowance for vitamin D too low for the homebound elderly? J Am Geriatric Soc 39:137-141, 1991 https://doi.org/10.1111/j.1532-5415.1991.tb01615.x
  18. Vieth R, Ladak Y, Walfish P. Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. J Clin Endocrinal Metab 88:185-191, 2003 https://doi.org/10.1210/jc.2002-021064
  19. Heaney R, Dowen M, Hale C, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Amer College Nutr 22(2):142-146, 2003 https://doi.org/10.1080/07315724.2003.10719287
  20. Bischoff-Ferrari H, Dietrich T, Orav E, Dawson-Hughes B. Positive association between 25 (OH)D levels and bone mineral density: A population-based study of younger and older adults. Amer J Med 116:634-639, 2004 https://doi.org/10.1016/j.amjmed.2003.12.029
  21. Chiu K, Chu A, Go V, Soad M. Hypovitaminosis D is associated with insulin resistance and beta cen dysfunction. Amer J Clin Nutr 79:820-825, 2004 https://doi.org/10.1093/ajcn/79.5.820
  22. Mawer E, Davies M. Bone disorders associated with gastrointestinal and hepatobiliary disease. In: Feldman D, Glorieux F, Pike J (eds.) Vitamin D. Academic Press. San Diego, CA, pp.831-847, 1996
  23. Meier C, Woitge H, Witte K, Lemmer B, Seibel M. Supplementation with oral vitamin $D_{3}$ and calcium during winter prevents seasonal bone loss: A randomized controlled open-label prospective trial. J Bone Mineral Res 19:1221-1230, 2004 https://doi.org/10.1359/JBMR.040511
  24. Holick MF. Vitamin D: Importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 79:362-371, 2004 https://doi.org/10.1093/ajcn/79.3.362
  25. Zittermann A. Vitamin D in preventive medicine: Are we ignoring the evidence? Brit J Nutrition 89:552-572, 2003 https://doi.org/10.1079/BJN2003837
  26. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204-210, 2003 https://doi.org/10.1093/ajcn/77.1.204
  27. Chapuy MC, Arlot M, DuBoeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ. Vitamin $D_{3}$ and calcium to prevent hip fractures in the elderly woman. N Engl J Med 327:1637-1642, 1992 https://doi.org/10.1056/NEJM199212033272305
  28. Trivedi D, Doll R, Khan K. Effect of four monthly oral vitamin $D_{3}$ supplementation on fractures and mortality in men and, women living in the community: randomized double blind controlled trial. Brit Med J 326:469-474, 2003 https://doi.org/10.1136/bmj.326.7387.469
  29. Passeri G, Pini G, Troiano L, Vescovini R, Sansoni P, Passeri M, Gueresi P, Delsignore R, Pedrazzoni M, Franceschi C. Low vitamin D status, high bone turnover, and bone fractures in centenarians. J Clin Endocrinal Metab 88:5109-5115, 2003 https://doi.org/10.1210/jc.2003-030515