Vitamin D Absorption                                                          

Part 1

By G. Douglas Andersen, DC, DACBSP, CCN

Vitamin D research has exploded in the past few years. The number of conditions that low or deficient levels of vitamin D can cause and/or exacerbate continues to expand. (See table below.) In the course of this research, focus has included the different types of vitamin D.

Vitamin D comes in five forms - D₁, D₂, D₃, D₄ and D₅. Of these, vitamin D₂(ergocalciferol) and vitamin D₃(cholecalciferol) are bioactive and used in supplements. A simplified summary of the difference is as follows:

• Vitamin D₂ is synthesized by UV irradiation of chemical derivatives from yeast.
     
• Vitamin D₃ is synthesized by UV irradiation of chemical derivatives from lanolin.

Health Conditions Associated With Low Vitamin D Status (below 30 ng/mL)1-3

Osteoporosis Rickets Psoriasis Muscle pain Cognitive impairment Cardiovascular disease Childhood asthma Multiple sclerosis Hypertension Glucose intolerance Type 1 diabetes Type 2 diabetes Seasonal affective disorder Falls (imbalance in seniors) Periodontal disease Senile warts Premature births Gestational immunity

Both vitamin D₂ and vitamin D₃ are used in over-the-counter supplements, but only vitamin D₂is available in pharmacologic preparations. This is because vitamin D₂ was developed in the early 1930s and was grandfathered in as a controlled substance when the FDA (as we know it) was formed in 1938. Vitamin D₃ was developed in the 1950s. Historically, they were considered equal based on the responses of patients with rickets.⁴ This opinion has changed after a number of studies have shown vitamin D3 to be superior to vitamin D₂. This is based on measuring serum 25-hydroxyvitamin D [25(OH)D], which is the gold standard for determining vitamin D status in humans. Researchers believe vitamin D-binding proteins in the plasma prefer vitamin D₃ over D₂.

Among the most commonly cited studies is a two-week study in which 17 subjects were given 4,000 IU vitamin D₂ daily and 55 subjects were given 4,000 IU of vitamin D₃ daily. Serum levels of 25(OH)D were 1.7 times higher with D₃ supplementation.⁵ Another commonly cited study, this one a single-dose study, divided 30 people into three groups: 10 individuals took placebo, 10 were given 50,000 IU of vitamin D2 and 10 took 50,000 IU of vitamin D3. Serum 25(OH)D measurements were performed over 28 days. Both forms of vitamin D showed equal elevations four days after the megadose.

By day seven, 25(OH)D levels in the D₂ subjects began to drop, reaching baseline on day 16 and ending with lower levels than the placebo group and less than they had before the study. 25(OH)D levels in the vitamin D₃ group continued to rise and peaked on day 14. On day 28,25(OH)D remained elevated above baseline in the D₃ group.⁶ The results of these studies and others were summarized in a paper that concluded vitamin D₃ was clearly superior to vitamin D₂ based on its absorption.⁷

In part 2 of this article (Jan. 15, 2010 issue), I will review a study that showed vitamin D₂ may be better than we think.

References

1. Office of Dietary Supplements Fact Sheet: Vitamin D.http://ods.od.nih.gov/factsheets/vitamind.asp
2. Mayo Clinic: Vitamin D. www.mayoclinic.com/health/vitamin-d/NS_patient-vitamind
3. “Vitamin D Deficiency.” WebMD.com. www.webmd.com/diet/vitamin-d-deficiency
4. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest, 2006;116:2062-72.
5. Trang HM, Cole DE, Rubin LA, et al. Evidence that vitamin D₃ increases serum 25-hydroxy vitamin D more efficiently than does vitamin D₂. Am J Clin Nutr, 2006;68:854-8.
6. Armas LAG, Hollis BW, Heaney RP. Vitamin D₂ is much less effective than vitamin D₃in humans. J Clin Endocrinol Metab, 2004;89(11):5387-91.
7. Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr, 2006;84(4):694-7.

Vitamin D Absorption, Part 2

By G. Douglas Andersen, DC, DACBSP, CCN

In recent years, research has indicated that vitamin D₃ appears to have greater bioavailability than vitamin D₂. However,a recent study calls this into question.¹Sixty-eight subjects with vitamin D deficiency were divided into four random, double-blind groups and studied over an 11-week period. One group was assigned a placebo, the second group took 1,000 IU of vitamin D₃ daily, the third group got 1,000 IU of vitamin D₂ daily, and the fourth group received a mixture of 500 IU of D₂ and 500 IU of D₃ every day. For the results of the study, please see Table 1. For how 25-hydroxyvitamin D [25(OH)D] is measured, see Table 2.

Table 1: Vitamin D₂ Versus Vitamin D₃ (nanograms per milliliter)

Treatment	Amount of D3	Number of Subjects	Baseline 25(OH)D	Final 25(OH)D	Increase (ng/ml)
Placebo	N/A	14	18.6	18.8	0.2
Vitamin D2	1,000	16	16.9	26.8	9.9
Vitamin D3	1,000	20	19.6	28.9	9.3
D2 plus D3	500 + 500	18	20.2	28.4	8.2

In this study, vitamin D₂ and vitamin D₃ equally raised serum 25(OH)D levels. Furthermore, the combination of both forms of vitamin D also showed no statistical difference. The most important aspect of this study to me was the fact that after 11 weeks of 1,000 IU daily, none of the groups reached the normal serum range of 30 ng/ml. In fact, the peak serum 25(OH)D concentrations were achieved after approximately six weeks and then leveled out for the remaining five weeks. One thousand IU/day of any form of vitamin D was not enough to raise 25(OH)D to low-normal levels, even though the dose was 2.5 times more than the RDA (400 IU).

Table 2: 25(OH)D Laboratory Measurements

Measurement	Abbreviation	Conversion	Normal Range	Low	Deficient
Nanograms/milliliter	ng/ml	x 2.5 = nmol/L	30-74 ng/ml	<30	<20
Nanomoles/liter	nmol/L	x 0.4 = ng/ml	75-85 nmol/L	<75	<50

In the meantime, studies like this show that more evidence is needed before a blanket recommendation can be made that D₂ is clearly inferior to D₃. Since most supplements use D₃already, the primary concern of patients and providers should be the amount rather than the form. When a patient recently asked me, "Is it better for me to take 400 D₃ instead of the 400 D₂ I use now," I replied, "Instead of buying more, just take more of what you already have."

Reference

1. Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D₂ is as effective as vitamin D₃ in maintaining circulating concentrations of 25-hydroxy vitamin D. J Clin Endocrinol Metab, 2008;93:677-81.