Dr. Ron’s Research Review – July 25, 2018


This week’s research review focuses on one time high dose vitamin D therapy.

The Endocrine society consensus statement recommended 50,000 for 6 weeks for children and adolescents with vitamin D deficiency. Much higher dosing was recommended for obese adults at least 6,000-10,000 per day for 8 weeks.
A study of insulin metabolism in obese adolescents used 300,000 IU as a “stoss dose” (the German word stossen means “to push”), a practical choice to improve compliance. Each subject got 6 capsules totaling 300,000 IU of ergocalciferol (vitamin D2) or no ergocalciferol at all in the placebo capsules. Unfortunately no beneficial effects were found. (Brar et al., 2018)
This one-time loading dose, however, is one-seventh (14.29%) the recommended total dose.
50,000/day x 6 weeks = 2,100,000 IU        300,000 ÷ 2,100,000 IU = 1/7
Vitamin D2 (Ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D3 (Cholecalciferol) is made in the skin following UVB light exposure. Both are converted into 1,25(OH)2D in the liver by 25-hydroxylase. In the kidneys, 1α –hydroxylase converts 25OHD into 1,25(OH)2D. (Bikle, 2014)
Ergosterol ↔︎ pre-D2 ↔︎ D2
7-Dehydrocholesterol  ↔︎ pre-D3 ↔︎ D3
D2/D3 → 25OHD → 1,25(OH)2D
A study found that vitamin D2 potency is less than one third that of vitamin D3, and D2 has a much shorter duration of action. In the study, 20 healthy males were given single 50,000-IU doses of either D2 or D3, and serum levels were measured over a 28-day period. Although the two forms demonstrated similar rises in serum 25(OH)D levels over three days, the D2-treated group experienced a rapid decline to baseline levels at day 14 and were well below baseline by day 28. By contrast, 25(OH)D levels in the D3-treated group peaked at day 14 and remained significantly elevated throughout the study. (Armas et al., 2004)
A meta-analysis found that vitamin D3 is more efficacious at raising serum 25(OH)D than vitamin D2. Vitamin D3 is the preferred choice for supplementation. (Tripkovic et al., 2012)
A recent article stated that vitamin D2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification. (Houghton and Vieth, 2006)

Dr. Ron



Effect of one time high dose "stoss therapy" of vitamin D on glucose homeostasis in high risk obese adolescents.
            (Brar et al., 2018) Download
OBJECTIVE:  To study the effect of using a one time high dose "stoss therapy" of vitamin D2 (ergocalciferol: VD2) on indices of insulin sensitivity (Brar et al., 2018) and secretion (Brar et al., 2018) measured during an oral glucose tolerance test (OGTT) in obese adolescents with VDD (25 OHD; serum metabolite of vit D: < 30 ng/dL). SUBJECTS AND METHODS:  In a randomized placebo controlled cross over design 20 obese adolescents with vitamin D deficiency (VDD) had baseline OGTT. Arm A received one time high dose 300,000 IU of ergocalciferol and Arm B received placebo. After 6 weeks the adolescents were reassigned to Arm A if they were in Arm B and vice versa. 25OHD, calcium, parathyroid hormone, comprehensive metabolic panel, urine calcium creatinine ratio were measured at each study visit. OGTTs to assess indices of sensitivity and secretion were done at baseline, 6 weeks and 12 weeks respectively. RESULTS:  Adolescents were obese and insulin resistant (mean ± SD: mean age = 15.1 ± 1.9 years; BMI: 32.7 ± 9.8; homeostatic model of insulin resistance: HOMA-IR: 4.2 ± 2.8). Stoss therapy with VD2 increased 25OHD from baseline (16.7 ± 2.9 to 19.5 ± 4.5; p = 0.0029) when compared to the placebo. WBISI (2.8 ± 1.9) showed a trend towards improvement in Rx group (p = 0.0577) after adjustment for covariates. IGI (3 ± 2.2) showed an improvement in both Rx and placebo groups. CONCLUSIONS:  Our study demonstrated that using a high dose of VD2 (300,000 IU) did not have any beneficial effect on insulin sensitivity (whole body sensitivity index (Brar et al., 2018)) and secretory indices (insulinogenic index (Brar et al., 2018)) in obese adolescents. High dose "stoss therapy" of VD2 did not appear to have any beneficial effect on glucose homeostasis on obese adolescents.

Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis
            (Tripkovic et al., 2012) Download
BACKGROUND: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. DESIGN: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. RESULTS: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. CONCLUSIONS: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3) could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.



Armas, LA, BW Hollis, and RP Heaney (2004), ‘Vitamin D2 is much less effective than vitamin D3 in humans.’, J Clin Endocrinol Metab, 89 (11), 5387-91. PubMed: 15531486
Bikle, DD (2014), ‘Vitamin D metabolism, mechanism of action, and clinical applications.’, Chem Biol, 21 (3), 319-29. PubMed: 24529992
Brar, PC, et al. (2018), ‘Effect of one time high dose “stoss therapy” of vitamin D on glucose homeostasis in high risk obese adolescents.’, Arch Endocrinol Metab, 62 (2), 193-200. PubMed: 29641737
Houghton, LA and R Vieth (2006), ‘The case against ergocalciferol (vitamin D2) as a vitamin supplement.’, Am J Clin Nutr, 84 (4), 694-97. PubMed: 17023693
Tripkovic, L., et al. (2012), ‘Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis’, Am J Clin Nutr, 95 (6), 1357-64. PubMed: 22552031