Introduction
Evidence suggests that optimal vitamin D status reduces the risk for a long list of chronic health conditions. However, the composite literature is often inconsistent and confusing and has led to heated debates about optimal vitamin D status. To confuse matters more, there is a wealth of expert opinions to support both sides of the argument.1-4
Nearly every cell in the body has a vitamin D receptor and vitamin D is necessary for a myriad of cellular functions.5 In fact, low vitamin D status reduces the capacity of most tissues to carry out normal physiologic functions. Vitamin D is necessary for skeletal, health, immune, developmental, and cardiovascular health and to protect against cancer. As a result, low vitamin D status increases the risk of several diseases including autoimmune disorders, diabetes, cardiovascular disease and cancer.6
Logically, the criteria for determining nutrient intake requirements should be based on the actual function of the nutrient, not disease prevention. The challenges for setting an intake requirement for vitamin D are based in physiology. Three separate lines of evidence, encompassing i) the compensatory mechanism for vitamin D’s role in calcium homeostasis, ii) natural ancestral levels that can be obtained through unhindered sun exposure and iii) levels required for breastmilk to contain adequate vitamin D for the nursing infant, converge to establish an optimal vitamin D status.7,8 Heaney concluded that a 25(OH)D level of 100 to 130 nmol/L is the status best suited for normal physiology.4 The safety of serum 25(OH)D levels as high as 500 nmol/L has been reported9-11 and recently confirmed in large community-based samples.12,13
An adult in a bathing suit exposed to an amount of sunlight that causes a slight pinkness to the skin 24 hours later (1 minimal erythemal dose; MED) is equivalent to ingesting approximately 15,000 IUs of vitamin D.14-16 However physicians remain concerned with intakes above 4,000 IU/d. The Institute of Medicine (IOM) established 4,000 IU/d as the tolerable upper level of intake (the level unlikely to cause harm in almost all adults). Recent studies demonstrate that vitamin D supplement use has increased, whether due to self-selected or physician-directed dosing, and 25(OH)D levels above 150 nmol/L have increased by 200% over 10 y.12-13 In addition, the amount of vitamin D3 supplementation required to achieve a serum 25(OH)D above 100 nmol/L is on average 5,000 IU/d9,17-19 and 2-3 times more for overweight and obese individuals.11,18
Natural levels of 25(OH)D achieved through sun exposure in Maasai herdsman that is in the range of 100-150 nmol/l can also be achieved with oral intake of 5,000-10,000 IU/d.4,17 The Endocrine Society Practice Guidelines recommend that up to 10,000 IUs daily was safe for adults.8,14 This is in contrast to the recommended UL at 4,000 IU/d from the IOM. Thus the safety profile for supplemental intakes above 4,000 IU/d remains uncertain. For an individual with a high body mass index (BMI), doses over 10,000 IU/d may be necessary to achieve a 25(OH)D of at least 100 nmol/L. The present analysis evaluated vitamin D supplementation at intakes up to 15,000 IU/d in a community setting on various parameters of calcium metabolism and potential toxicity.