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New study identifies threshold for vitamin D supplementation

Posted on: March 2, 2017   by  Missy Sturges & John Canell, MD


A new RCT published by the journal Medicine and Science in Sports and Exercise determined weekly doses of 70,000 IU vitamin D3 reduced serum 1,25(OH)2D3 (calcitriol) levels among athletes, thereby hindering its ability to carry out its biological functions.

Vitamin D is continuing to gain recognition for its role in optimizing health. No longer merely acknowledged for regulating mineral balance for bone health, vitamin D has proven to initiate a physiologic response in 36 tissues of the body. This is because vitamin affects transcription, which is how proteins are made from your DNA. Vitamin D affects the production of thousands of proteins.

A topic of particular interest among the health-conscious community involves the role of vitamin D in muscle strength and athletic performance. Some research has discovered that vitamin D increases the rate of protein synthesis, enlarges muscle fiber size and improves exercise capacity. As a result, vitamin D supplementation has become widely accepted as a necessary tool for promoting peak physical performance.

There is a lack of consensus regarding the ideal dosing of vitamin D for maintaining optimal health. Despite research showing daily dosing is more beneficial in raising vitamin D levels, large weekly vitamin D doses are routinely provided for professional athletes to improve vitamin D status and optimize physical performance. Since research has not established the effect of high dose supplementation on the vitamin D endocrine system, this common practice has become an area of concern. The vitamin D endocrine system consists of the following major metabolites:

  • Calcidiol or 25(OH)D: The form of vitamin D that has undergone the first activation step in the liver to become a prehormone. This is the form of vitamin D widely measured to determine vitamin D status.
  • Calcitriol or 1,25(OH)2D3: The hormonally active form of vitamin D.
  • 24,25-hydroxylase: An enzyme that breaks down circulating 25(OH)D and 1,25(OH)2D3

A new randomized controlled trial hypothesized that high dose weekly vitamin D supplementation negatively regulates vitamin D metabolites among elite athletes.

A total of 46 professional European athletes were included in the study. The participants were randomly divided into two groups: Group 1 received 35,000 IU/week, while group 2 received 70,000 IU/week for 12 weeks. The researchers measured the participant’s parathyroid levels and three major vitamin D metabolites (25(OH)D, 1,25(OH)2D3 and 24,25-hydroxylase) at baseline, weeks 6, 12 and 18.

Here is what the researchers found:

  • None of the participants experienced adverse side effects from supplementation.
  • Average baseline 25(OH)D levels of the participants was 34 ng/ml.
  • Both supplement doses provided a significant increase in serum 25(OH)D and 1,25(OH)2D3 (p = 0.008).
  • Four weeks after withdrawal from supplementation, the 25(OH)D levels in group 1 returned to levels similar to baseline, whereas group 2 did not (p = 0.007).
  • Group 2 experienced a significant increase in 24,25-hydroxylase at weeks 6 and 12. This remained elevated at week 18, despite the subsequent decrease in 1,25(OH)2D3 at week 12 (p < 0.0001).
  • As suspected, intact parathyroid hormone was decreased in both groups by week 6, which remained throughout the duration of the study.

According to these findings, blanket high dose supplementation of 70,000 IU/week generated a threshold effect. Although 25(OH)D levels remained in the healthy range, this large dose caused the body to start increasing production of the enzyme that degrades vitamin D in an effort to maintain balance in the body. As a result, the higher supplementation group experienced a subsequent decrease in activated vitamin D, thereby inhibiting its availability to carry out important biological functions in the body.

This study supports our stance that 5,000 IU/day (35,000 IU/week) is the ideal dosage to maintain healthy vitamin D levels and adequate intracellular supply of activated vitamin D. Remember, 1,25(OH)2D3 acts as a steroid hormone in the body, meaning it regulates gene expression and facilitates proper cellular function in target tissues. Chronic inadequate intracellular activated vitamin D, whether from deficiency or over supplementation, may place individuals at an increased risk for health complications.

The researchers stated,

“These data imply that lower doses of vitamin D3 ingested frequently may be most appropriate and gradual withdrawal from supplementation as opposed to rapid withdrawal may be favorable.”

RCTs comparing various daily vitamin D supplementation doses are needed to determine the ideal supplement routine for maintaining optimal vitamin D status without stimulating 24,25-hydroxylase to break down vitamin D.


Sturges, M. & Cannell, JJ. Large bolus vitamin D dosing decreases activated vitamin D levels among elite athletes. The Vitamin D Council Blog & Newsletter, 2/2017.


Owens, D. J., J. C. Y. Tang, W. J. Bradley,, A. S. Sparks, W. D. Fraser, J. P. Morton, and G. L. Close. Efficacy of High-Dose Vitamin D Supplements for Elite Athletes. Med. Sci. Sports Exerc., Vol. 49, No. 2, pp. 349–356, 2017.

10 Responses to New study identifies threshold for vitamin D supplementation

  1. JA Larson

    The standard current protocol for raising very lowD levels is 50,000 IU/week for 8 weeks (roughly 7,000 IU/day). Most prescription D is D2. Apparently the medical community thinks weekly doses have higher compliance rates than daily doses.

    I’d suggest 10,000 IU/day D3 for 5-6 weeks, then retest.

    Based on those results, then adjust dosage.

  2. keven50945600

    The medical community prescribes weekly doses rather than daily. Is there an upper threshold where weekly doses either aren’t utilized by the body or become toxic? A daily dosage seems like it would be better absorbed and utilized than a weekly dose.

  3. Ron Carmichael

    Any study that ignores the aspects of “mother nature” and “evolutionary foundations” is derelict. Setting the “sufficiency of 25(OH)D levels to 30 ng/ml is an indictment of ignorance by the designers of the protocol, as is using D2, as is administering anything other than a daily dose of D3. Sole exception is assessing how to aggressively rectify decades of chronic deficiency by using pharmaceutical dosages such as 50,000iu D3 daily, or 5,000iu per 25 pounds body weight to determine how quickly the body establishes a stable level circa 50 to 70 ng/ml. How in the world did “30 ng/ml” become an accepted “sufficient level is a mystery. But it marks stupidity and wasteful science funding.

    • DrPushpa

      I was once in a conversation about this with a radiologist who was doing osteoporosis research at the University of Washington. He said that it was set at the 30-32 range because it had been found that moving serum levels from 20 to 30 made a significant difference to bone health, but that moving serum levels from 30 to 40 made very little difference. Obviously, this doesn’t take into account the many other health benefits of Vitamin D, but does have a certain rationale when considering that Vitamin D was being looked at primarily for its effect on bone density at that time, at least by mainstream medicine.

  4. gustavo48329000

    Points to consider:

    – This Vit.D council article is extremely poor and misleading. It leads the reader to think a high blood 1,25 level is what is needed for gene activation. When, in fact, the blood 25 that gives the pleiotropic effects and is locally hydroxilated in the tissues . It is correctly explained here https://www.vitamindcouncil.org/the-physiology-of-vitamin-d/
    and here

    – 1,25 and 25 blood levels don’t go hand-to-hand. And a 1,25 test will not measure anything meningful https://www.vitamindcouncil.org/activated-vitamin-d-vs-25ohd-levels-what-should-you-measure/

    – The effect observed in this study is due to enzyme kinetics, as explained here https://www.ncbi.nlm.nih.gov/pubmed/15221979

  5. [email protected]

    VDR and 24,25-hydroxylase SNP analysis may help identify those who would benefit from 10,000 IU/d of vitamin D3.

  6. [email protected]

    Definitely agree, daily intake of 5,00 – 10,000 IU of vitamin D3 will be physiologically much more effective than bolus dose of 70,000 IU once a week.
    Whether induced by sun exposure or consumed orally, vitamin D3 is cleared quickly. Large bolus doses of vitamin D3 of 50,000 to 100,000 IU are cleared from the body within 2 days. This has been known for at least 10 years. The vitamin D3 consumed in a bolus dose that is not used within 12-24 hours is simply excreted in bile, feces, and urine.
    For this reason, the only way to sustain needed amounts of vitamin D in the bloodstream is by either daily D3 supplementation and/or daily sunlight exposure (at the right UV wavelength).
    A few supportive references:
    Lips P, Binkley N, Pfeifer M, et al. Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on neuromuscular function and tolerability in older adults with vitamin D insufficiency. Am J Clin Nutr. 2010 Apr;91(4):985-91. doi: 10.3945/ajcn.2009.28113. Epub 2010 Feb 3. PMID: 20130093 (Once-weekly bolus dosing ineffective)
    Lips P, Bouillon R, van Schoor NM, et al. Reducing fracture risk with calcium and vitamin D. Clin Endocrinol (Oxf). 2010 Sep;73(3):277-85. doi: 10.1111/j.1365-2265.2009.03701.x. PMID: 20796001 (Same lead author; daily dosing, effective.)

  7. [email protected]

    Dr. Bruce Hollis has put forth the hypothesis that extra-skeletal cells in the body use parent vitamin D to synthesize calcitriol in an intracellular process. The 24,25-hydroxylase is also produced in the intracellular processes. They are therefore not available to circulate in the body. This nullifies the hypothesis presented above. These extra-skeletal cells cannot use the calcidiol produced in the liver because it binds too tightly to the VDBP and therefore cannot be converted to calcitriol.

    Since the half-life of calcidiol is 2-3 weeks while the half-life of parent vitamin D is a scant 24 hours, weekly dosing doesn’t work for extra-skeletal cells.

    This puts in doubt any of the findings presented above and underscores the value of much higher daily dosing which some doctors are now using therapeutically for other than bone health.

  8. boblistecki

    We use 45 IU x body wt as a starting dose and then test in 6 weeks. There are some 12 or 13 items that effect D absorption and distribution. One is lack of aerobic exercise. In the Pharmacy we had a 60 yof whose dose got her tested to 60 ng/ml. She is a competitive tennis player and the same dose got her test up to 97 when competing. Fat soluble substances move in the lymph system which does not have a pump like the heart for the blood.
    Bob at Glen Ellyn Pharmacy Glen Ellyn , IL

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