Q:I am reading so much about vitamin D and cancer. How much daily vitamin D should we recommend to patients?

TON - October 2011 Vol 4 No 7 — October 19, 2011

Although there is no straightforward answer to this question, the current recommended daily allowances for adults—600 IU for children and adults, and 800 IU for those older than 70 years— are probably too low.1,2 To provide a little background, vitamin D should be considered a prohormone rather than a vitamin (a substance humans need in small amounts and usually cannot synthesize).3 Animals convert 7-hydrocholesterol to calciferol (D3) in the dermis via a photochemical reaction with ultraviolet B (UVB) sunlight. Similarly, plants convert sterols to ergocalciferol (D2). Humans convert both D3 and D2 to calcidiol by hepatic hydroxylation.4 Serum calcidiol is a relatively stable, measurable intermediate metabolite. In the kidneys and other tissues, calcidiol is further hydroxylated to calcitriol, the active metabolite of vitamin D. Calcitriol is short-lived and is synthesized as necessary to bind with vitamin D receptors (VDRs) in the nucleus of most cells. VDR binding ultimately affects many critical cell and tissue functions. For instance, calcitriol influences cell division, differentiation, and apoptosis—functions that are important in cancer occurrence, invasion, and metastasis. Calcitriol also facilitates absorption of dietary calcium in the gut and influences synthesis and secretion of insulin and parathyroid hormone, calcium regulation, immune function, bone homeostasis, and other important functions.3,4

UVB sunlight is the major source of vitamin D, and most American diets provide only 150 to 200 IU per day. However, avoidance of sun exposure, living in latitudes north of 37 degrees (an imaginary line extending from Santa Rosa, California, to Cape Hatteras, North Carolina), increasing age, darker skin color, obesity, and other factors decrease D3 formation.5 At least 50% of Americans are vitamin D–insufficient or –deficient, which has been associated with some cancers (ie, colon, prostate, ovary, pancreas, lymphomas, and others), as well as decreased cancer survival.6,7 Deficiency also may exacerbate treatment- related bone loss and the risk for osteoporosis, and increase the likelihood of bisphosphonate-related hypocalcemia and renal dysfunction.8

Drawing a serum calcidiol level is the only way to assess nutritional vitamin D status. A level of 32 to 100 ng/mL is considered normal, whereas 15 to 31 ng/mL is considered insufficiency, and <15 ng/mL deficiency. Optimal levels to prevent particular diseases, however, are not known but may be 40 to 70 ng/mL—levels in people living close to the equator or working as lifeguards.9

It would be prudent to check the serum calcidiol level in all cancer patients (and perhaps all Americans) once a year. There are no guideline recommendations regarding the optimal calcidiol level for cancer patients, so clinicians need to individualize patient management. Garland and colleagues suggest that maintaining a calcidiol level of ≥34 ng/mL would decrease the risk for colon cancer by 50%, but a consistent level of ≥52 ng/mL would be necessary to decrease the risk for breast cancer by 50%.10 The calcidiol level should be rechecked every 1 to 2 months after starting supplemental vitamin D to assess response. The level may plateau and the dose may need to be titrated up (or down) to maintain the target level. In addition, patients with a normal level should be evaluated every 6 or 12 months to make certain they have not become deficient.

Vitamin D3 is an over-the-counter product available in several dosages (ie, 500 IU, 1000 IU, 2000 IU), whereas D2 is a prescription agent. D3 is more potent than D2, but adherence to a planned dosing schedule is probably most important. Daily doses of 1000 to 2000 IU (or greater) are considered safe, and deficient patients might need higher doses. Maximum daily doses should not exceed 10,000 IU, as higher doses taken for several months may lead to vitamin D toxicity in some people.9

So, how much vitamin D should we tell our patients to take? It depends on clinical judgment. You will need to incorporate knowledge regarding the multiple physiologic roles of vitamin D, the potential negative effects of deficiency in cancer occurrence and mortality, each patient’s calcidiol level, and the “optimal” level for that patient.

References

  1. Ross AC, Taylor CL, Yaktine AL, Del Valle HB, eds. Dietary Reference Intakes for Calcium Vitamin D. Washington, DC: The National Academies Press; 2010.
  2. Bischoff-Ferrari H. Vitamin D: what is an adequate vitamin D level and how much supplementation is necessary? Best Pract Res Clin Rheumatol. 2009;23:789-795.
  3. DeLuca HF. Evolution of our understanding of vitamin D. Nutr Rev. 2008;66(10 suppl 2):S73-S87.
  4. Wang S. Epidemiology of vitamin D in health and disease. Nut Res Rev. 2009; 22:188-203.
  5. Bordelon P, Ghetu MV, Langan R. Recognition and management of vitamin D deficiency. Am Fam Physician. 2009;80:841-846.
  6. Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: how and when to treat. Mayo Clin Proc. 2010;85:752-758.
  7. Krishnan AV, Trump DL, Johnson CS, Feldman D. The role of vitamin D in cancer prevention and treatment. Endocrinol Metab Clin North Am. 2010;39:401-418.
  8. Wang-Gillam A, Miles DA, Hutchins LF. Evaluation of vitamin D deficiency in breast cancer patients on bisphosphonates. Oncologist. 2008;13:821-827.
  9. Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev. 2008;13:6-20.
  10. Garland CF, Grant WB, Mohr SB, et al. What is the dose-response relationship between vitamin D and cancer risk? Nutr Rev. 2007;65(8 pt 2):S91-S95.

  


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