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Citation reviewed herein: Kimball SM, Mirhosseini N, Holick MF. Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting. Dermatoendocrinol 2017 Apr 13;9(1):e1300213. doi: 10.1080/19381980.2017.1300213 Download PDF here

Reviewed here by: Alex Vasquez DC ND DO FACN

Date of review/posting: 24 May 2017

Overall evaluation of this publication: Excellent, definitely contributes to our understanding of the safety and pharmacology of vitamin D supplementation and how we have to use higher doses in the obese

Key points quoted with commentary: 

• This primary research included data from nearly 4,000 participants who were supplementing with vitamin D3. DrV: Very large group; although this was not a controlled trial, the data is significant and is representative of real-world clinical practice.

• "To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for
  obese." DrV: We have known for many years that obese patients were likely to require additional vitamin D because higher doses would be required to saturate excess adiposity; this study provides a quantification of this increased need so that clinicians and patients can use proper dosing. 

• "Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe." DrV: This documents 1) the increased need of vitamin D in the obese and also 2) excellent safety. 

• "Nearly every cell in the body has a vitamin D receptor and vitamin D is necessary for a myriad of cellular functions. In fact, low vitamin D status reduces the capacity of most tissues to carry out normal physiologic functions." DrV: This is a clear and excellent summary sentence. 

• "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." DrV: Again, excellent articulation of real-world physiology for clinical perspective and context. 

• "Vitamin D3 intakes of at least 6,000 IU/d were required for those with a normal BMI to achieve serum 25(OH)D concentrations above 100 nmol/L, or 7,000 IU/d and 8,000 IU/d for overweight and obese, respectively." DrV: Same as above: very helpful clarity here.

• "...serum 25(OH)D and vitamin D dose were negative predictors of serum calcium." DrV: Excellent refutation of the idea that higher vitamin D = higher serum calcium. One of the main statements by those who discourage vitamin D supplementation is that routine physiologic supplementation is going to lead to higher levels of calcium in serum (where it could promote calcification of tissues) and in urine (where it could promote development of kidney stones); in this research, both of those were disproven. 

• "Urine calcium and creatinine measurements were available for 521 participants. Hypercalciuria (urine calcium:creatinine >0.2 mg/mg) was detected in 17.6% of participants at baseline. There was virtually no increase in the prevalence of hypercalciuria at follow-up (17.7%)." DrV: Again, excellent refutation of the idea that higher vitamin D = higher serum calcium. One of the main statements by those who discourage vitamin D supplementation is that routine physiologic supplementation is going to lead to higher levels of calcium in serum (where it could promote calcification of tissues) and in urine (where it could promote development of kidney stones); in this research, both of those were disproven. 

• "While the present study does not address what is an optimal vitamin D status, it does confirm the safety of serum 25(OH)D concentrations up to 300 nmol/L and intakes of vitamin D up
  to 15,000 IU/d."​ DrV:

Clinical applications/significance: Clinicians and patients should feel comfortable using higher physiologic doses of vitamin D, especially doses up to 10,000 IU per day; this does not mean that such doses will be perfectly tolerated by all patients but it does suggest that these doses will be generally safe for most people. Note that the efficacy of this study is that of dose-response relationships rather than disease-treatment efficacy; the latter is largely dependent on the former. 

Download original article: Download PDF here

Download compilation of DrV's vitamin D articles/excerpts: HERE