Vitamin D3, Not D2, Is Key to Tackling Vitamin D Deficiency

Liam Davenport

July 05, 2017

Vitamin D3 is significantly more effective at raising the serum biological marker of vitamin D status than vitamin D2 when given at standard doses in everyday food and drink, say UK researchers — findings that could have major implications for both current guidelines and the supplement industry.

In a randomized controlled trial of vitamin D supplements, vitamin D3, which is derived from animal products, was associated with significantly higher serum total 25-hydroxyvitamin D [25(OH)D] levels after 12 weeks than vitamin D2, which is plant-based and currently used in the vast majority of vitamin D supplements.

The research was published online July 5 in the American Journal of Clinical Nutrition.

"The importance of vitamin D in our bodies is not to be underestimated, but living in the UK it is very difficult to get sufficient levels from its natural source, the sun, so we know it has to be supplemented through our diet," explained lead author Laura Tripkovic, PhD, department of nutritional sciences, University of Surrey, Guildford, United Kingdom, in a press release.

She added, "Our findings show that vitamin D3 is twice as effective as D2 in raising vitamin D levels in the body, which turns current thinking about the two types of vitamin D on its head."

"Those who consume D3 through fish, eggs, or vitamin D3-containing supplements are twice as likely to raise their vitamin D status [compared with those] consuming vitamin D2-rich foods, such as mushrooms, vitamin D2-fortified bread, or vitamin D2-containing supplements, helping to improve their long-term health."

Senior researcher Susan Lanham-New, PhD, head of the department of nutritional sciences at the University of Surrey, added: "This is a very exciting discovery that will revolutionize how the health and retail sector views vitamin D."

"Vitamin D deficiency is a serious matter, but this will help people make a more informed choice about what they can eat or drink to raise their levels through their diet."

Approached for comment, Robyn Lucas, MD, PhD, College of Medicine, Biology and Environment, Australian National University, Canberra, told Medscape Medical News: "I do think that this study really does show that vitamin D2 doesn't raise total 25(OH)D levels as effectively as vitamin D3."

"Clearly that has implications for any food fortification," she added, stressing that all vitamin D supplements in Australia are vitamin D3-based.

Dr Lucas continued, "Personally, I think the evidence suggests that it is only quite severe vitamin D deficiency that is problematic for health, so levels below, say, 30 nmol/L. In Australia, those levels are uncommon because we have so much sun."

"A higher proportion of the UK population will be in that category and should think about supplementation. This study shows that quite a modest dose of vitamin D3 was sufficient to raise levels well above 50 nmol/L. So it is also useful in showing that you really don't need big doses to achieve and maintain sufficient levels of 25(OH)D."

Current Guidelines State D3 and D2 Are Equivalent

Current guidelines by the US National Institutes of Health, UK Department of Health, and various other government bodies state that vitamins D2 and D3 are equivalent and achieve the same effect. However, emerging evidence suggests that vitamin D3 may be more effective in increasing serum total 25(OH)D levels.

Dr Tripkovic and colleagues therefore conducted a randomized, double-blind, placebo-controlled fortification trial in which 335 South-Asian and white European women aged 20 to 64 years were assigned to placebo or one of four groups:

  • Placebo juice with placebo biscuit (placebo, n = 65).

  • Juice supplemented with 15-µg vitamin D2 with placebo biscuit (D2J).

  • Placebo juice with biscuit supplemented with 15-µg vitamin D2 (D2B).

  • Juice supplemented with 15-µg vitamin D3 with placebo biscuit (D3J).

  • Placebo juice with biscuit supplemented with 15-µg vitamin D3 (D3B).

The treatments were given daily for 12 weeks, and 59 placebo patients completed the study, alongside 60 D2J patients, 58 D2B patients, 59 D3J patients, and 55 D3B patients. All patients who started the study were included in the analysis, however, on an intention-to-treat basis.

Combining the two ethnic groups, researchers found that the placebo group experienced a 25% reduction in serum total 25(OH)D levels over the 12-week intervention, a mean absolute change of -11.2 nmol/L (P < .0001).

In contrast, the D2J and D2B groups saw increases in total 25(OH)D levels of 33% and 34%, respectively, while increases in the D3J and D3B groups were 75% and 74%, respectively.

Furthermore, the D3J group showed significantly higher increases in serum total 25(OH)D levels vs the D2J (16.9 nmol/L, P < .0005), D2B (16.0 nmol/L, P < .0003) and placebo (42.9 nmol/L, P < .0005) arms.

The D3B group was also associated with significantly higher increases in serum total 25(OH)D levels vs the D2B (15.2 nmol/L, P < .0003), D2J (16.3 nmol/L, P < .0005) and placebo (42.3 nmol/L, P < .0003) groups.

There were no significant differences between the D3B and D3J groups over the course of the intervention, and there were no significant interactions for ethnicity. However, South-Asian women appeared to have a greater response to both vitamin D2 and D3 than European women, which researchers ascribed to their lower baseline total 25(OH)D levels.

Findings May Also Help in Quest for Vitamin D to Reduce Diseases

Dr Tripkovic told Medscape Medical News that, in addition to potentially shaking up the supplement industry, their findings may help in the quest to link vitamin D supplementation to measurable clinical outcomes.

She said, "If other researchers want to understand the health benefits of vitamin D, with a hard outcome like bone health or cardiovascular disease...shoring up things like what we know about vitamin D is really important so that those who then take the research forward to look at health outcomes have a sound evidence base to design their study on."

The next steps required in terms of research to take the concept of food fortification forward include casting the net wider to determine which other foods containing vitamin D3 will be effective — as well as acceptable — to the general population, she said.

Moreover, Dr Tripkovic would like see more dose-response data to obtain a better sense of the lower end of the dose spectrum.

"We gave 600 IU, which was basically benchmarked against the American recommendation because, at the time we were drawing together the study, the UK didn't have a recommendation for vitamin D," she explained.

"Now the UK has come out with 10 µg/day, which is 400 IU."

She summarized, "So, it's understanding the lower doses, and it's understanding how food fortification can work with vitamin D in the population. It's bigger numbers, basically."

"The fact that we've managed to pull a lot of women out of deficiency over the wintertime has been really incredible to see and it's very exciting, so we're very hopeful, for the future, that we can keep getting research funding and carry on with our work," she concluded.

What About Bioavailability of Different Forms of Vitamin D?

One issue this study does not address, said Dr Lucas, is the question of whether 25(OH)D derived from vitamin D2 [25(OH)D2] is less bioactive than 25(OH)D3.

"The challenge here is knowing what the outcome might be against which to measure bioactivity. It is the same problem that we have in being able to measure how much 25(OH)D is 'sufficient,' and hence the arguments about what level of 25(OH)D we should aim for."

"This is probably the most important outstanding question, but I'm not sure that it is going to be able to be answered," she said.

The study was supported by the UK-based Biotechnology and Biological Sciences Research Council (BBSRC) as part of a BBSRC Diet and Health Research Industry Club grant. Dr Lanham-New is research director for D3Tex Ltd, which holds the UK patent (with Gulf Corporation Council patent pending) for the use of any UV-B material for the prevention of vitamin D deficiency in women who dress for cultural style. The other authors have reported no relevant financial relationships.

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Am J Clin Nutr. Published online July 5, 2017. Abstract


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