Improved immunity: Vitamin D3 versus D2

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According to a recent study, D2 and D3 may have different effects on the body. Marco Furia/EyeEm/Getty Images
  • Researchers recently investigated the genetic effects of the two forms of vitamin D: D2 and D3.
  • They found that vitamin D3 is linked to enhanced immune function but that its effects differ among ethnic groups.
  • They say that further research with a larger sample size is necessary to confirm their results.

Vitamin D is crucial for maintaining bone healthcellular function, and immune function.

Multiple studies show that low vitamin D levels are linked to an increased risk of fractures, as well as the development of some cancers, cardiovascular diseases, and inflammatory diseases.

Of the two kinds of vitamin Dvitamin D2, or ergocalciferol, occurs naturally in plants and fungi, whereas D3, or cholecalciferol, occurs in animal products.

Unlike vitamin D2, the body can produce vitamin D3 in the skin when it gets exposure to UVB radiation from sunlight.

Whether vitamin D2 and vitamin D3 have the same effect on human physiology remains unknown. Although some studies suggest that long-term vitamin D2 and D3 supplementation have similar effects on vitamin D blood concentrations, others report that D3 supplements lead to higher concentrations than D2 supplements.

Meanwhile, one study found that vitamin D3 supplements are linked to reduced cancer mortality compared with vitamin D2 supplements. Another study found that D2 and D3 supplements have different effects on depression.

The research on how vitamin D2 and D3 supplements affect gene expression in people is limited. Investigating underlying gene expression following supplementation with these variants could improve the understanding of how they affect the body. This knowledge could improve additional recommendations.

In a recent study, researchers investigated gene expression following vitamin D supplementation. They used data from a previously conducted studythe D2-D3 Study — that found that vitamin D3 increased overall vitamin D levels more than vitamin D2.

Following a genetic analysis, the researchers found that vitamin D3 and vitamin D2 affect different ethnic groups in distinct ways. They also found that vitamin D3 is linked to an improved immune system in white individuals, whereas vitamin D2 is not.

The study appears in Frontiers in Immunology.

The D2-D3 Study included 335 women of South Asian or European descent. The researchers randomized these individuals into three intervention groups for 12 weeks. The groups received 15 micrograms of either vitamin D2, vitamin D3, or a placebo each day.

The team selected 97 of the participants for genetic analysis, including 67 white participants and 30 of South Asian origin. The researchers conducted a genetic analysis at baseline and again 12 weeks after supplementation began.

At the end of the study, the researchers noted that vitamin D levels in the vitamin D3 treatment group increased by 59% and 166% among those of white ethnicity and South Asian descent, respectively.

Meanwhile, vitamin D3 levels dropped by 23% and 29% among those in the placebo group and by 52% and 53% among those who took vitamin D2.

From the genetic analysis, the researchers found that vitamin D2 and D3 supplementation downregulated 13% of the same genes and uniquely downregulated 28% and 59%, respectively.

They also found that different types of vitamin D supplementation had different effects on different ethnicities.

While vitamin D3 supplementation stimulated type I and type 2 interferon signaling in white people, the opposite was true for those of South Asian descent. Type 1 interferon signaling is crucial for the antiviral immune response, whereas type 2 interferon signaling is responsible for adaptive immunity and inflammatory regulation.

In contrast, vitamin D3 supplementation led to increased heme iron metabolism in those from South Asia, while the opposite effect occurred in white participants.

Nevertheless, the researchers found that in both white and South Asian individuals, vitamin D2 reduced interferon type 1 and 2 signaling.

Dr. Micheal Snyder, Ph.D., chair of the Department of Genetics at Stanford University, who was not involved in the study, told Medical News Today:

“Although similar, they are indeed different molecules, and it is likely that they either bind slightly different targets or the same targets with different efficiencies. They are also metabolized differently.”

The researchers note that the stark difference in results among ethnicities might be partially due to the small sample sizes and relatively lower vitamin D levels at baseline for those of South Asian descent.

However, they say that their results highlight the emerging evidence on how ethnicity, skin tone, vitamin D status, and susceptibility to contracting a virus such as SARS-CoV-2 may influence the effects of supplementation.

The researchers conclude that vitamin D2 and D3 may have different physiological effects and that these may vary among different ethnicities.

They also note some limitations to their research. Dr. Colin Smith, lead author of the study, told DTM that a larger sample size of around 2,400 is necessary to verify the findings and that it should include people of different ethnic groups. He added that future studies should also take changes in blood cell composition into account.

When we asked him how these results could influence how people take supplements, Dr. Snyder said that people should start looking into the exact molecules that they take, as even though different molecules may look similar, they will have different effects. He also noted that different supplements will affect individuals in varying ways.

Dr. Smith said: “We think that health policy should change. The food industry should only add vitamin D3 to its products, avoiding vitamin D2. Health policy should be specific about the type of vitamin D that should be used in supplements and fortified foods: vitamin D3.”

He added that vegans, vegetarians, and some religious groups who may use vitamin D2 supplements because D3 supplements are often sourced from animal products should switch to using vegan-friendly sources of vitamin D3.

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