Is Vitamin D3 Superior to D2?

Vitamin D3 (cholecalciferol) is superior to vitamin D2 (ergocalciferol) when it comes to health effects and should be the favored form for fortified foods and supplements say researchers from the Universities of Surrey and Brighton.

In their study, published in Frontiers in Immunology the researchers set out to investigate the effect of vitamin D2 and vitamin D3 supplementation on the activity of human genes.

The study involved 97 participants selected for transcriptome analysis and was built on a previous study, in which participants had been randomised to receive either 15 μg (600 IU) vitamin D2 or 15 μg vitamin D3 daily supplementation within fortified foods, or to a placebo group for a period of 12 weeks during UK wintertime (October to March). Analysis took place at baseline and at 12 weeks after the start of treatment, with serum measurements of total 25(OH)D, 25(OH)D2, and 25(OH)D3 determined from fasting blood samples at baseline, week 6, and week 12. Of the 97 participants, aged 20-64 years and living in Surrey, 67 were white European and 30 were South Asian.

Research Showed How Vitamin D3 Boosted the Immune System

Two types of vitamin D do not have the same effect, the authors explained. The research enabled them to identify how vitamin D3 had a modifying effect on the immune system that could fortify the body against bacterial and viral diseases, including COVID-19.

Gene expression associated with type I and type II interferon activity, critical to the body’s innate response to bacterial and viral infections, differed following supplementation with vitamin D2 and vitamin D3, they said. Only vitamin D3 had a stimulatory effect. Following vitamin D3 supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes “potentially shifting the immune system to a more tolerogenic status”.

Prof Colin Smith, lead-author of the study from the University of Surrey, who began this work while at the University of Brighton, said: “We have shown that vitamin D3 appears to stimulate the type I interferon signaling system in the body – a key part of the immune system that provides a first line of defense against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body.”

COVID Has Contributed to Vitamin D Deficiency

Foods like some breakfast cereals, yoghurts, and bread, are fortified with vitamin D, but few naturally contain the vitamin. Many people have insufficient levels of vitamin D3 because they live in locations where sunlight is limited in the winter, such as the UK. The COVID-19 pandemic response has also limited people’s natural exposure to the sun due to people spending more time in their homes. The British Nutrition Foundation has highlighted that the National Diet and Nutrition Survey reported in October 2021 that about 1 in 6 adults in the UK had low vitamin D blood levels. Furthermore, 49% of British adults were unaware of the Government’s recommendation to consider taking vitamin D supplements during the autumn and winter months.

“Our study suggests that it is important that people take a vitamin D3 supplement, or suitably fortified foods, especially in the winter months,” said Prof Smith.

The researchers acknowledged that their ability to detect differences in the effects of vitamin D2 and vitamin D3 may have been negatively impacted by the relatively low statistical power; by the inclusion of two different ethnic groups among the 97 participants, and by the limited number of participants. They pointed out that, therefore, “the biological interpretation of our findings should be considered as preliminary, requiring independent verification.”

Prof Susan Lanham-New, co-author of the study and head of the department of nutritional sciences at the University of Surrey, said: “While we found that vitamin D2 and vitamin D3 do not have the same effect on gene activity within humans, the lack of impact we found when looking at vitamin D2 means that a larger study is urgently required to clarify the differences in the effects.

“However, these results show that vitamin D3 should be the favored form for fortified foods and supplements,” she concluded.


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