- Vitamin D deficiency is associated with an increased risk of rickets, osteomalacia, cardiovascular conditions, and autoimmune diseases.
- Vitamin D2 and vitamin D3 are the two forms of vitamin D, and both forms are used as supplements to treat vitamin D deficiency.
- A recent meta-analysis, based on data from previous randomized controlled trials, now shows that vitamin D2 can lower the serum levels of vitamin D3.
- These data suggest that vitamin D3 supplements may be more beneficial, and vitamin D2 supplements could counteract some of the benefits of vitamin D3.
Vitamin D deficiency is a widespread health problem, with nearly 1 in 4 individuals in the United States having moderate-to-severe vitamin D deficiency. Vitamin D plays an essential role in bone health and calcium metabolism. Deficiencies in this important nutrient are also associated with a higher risk of cardiovascular conditions, cancer, diabetes, and even depression.
Humans can synthesize their own vitamin D3 in the skin and must obtain the rest through dietary sources. While supplementation can help maintain sufficient levels of vitamin D, whether its two forms, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), are equally effective remains contentious.
Emerging data suggest that vitamin D3 could be more beneficial than vitamin D2 in reducing cancer-related mortality, supporting immune function, and reducing depressive symptoms.
A meta-analysis recently published in Nutrition Reviews shows that vitamin D2 supplementation may negatively impact circulating levels of vitamin D3 and negate the latter’s potential benefits.
The meta-analysis summarized data from 11 randomized controlled trials and found that individuals receiving vitamin D2 supplements experienced a greater decline in circulating levels of vitamin D3 than those who did not receive any supplements.
While both vitamin D2 and vitamin D3 supplements can be used to achieve normal serum 25 (OH)D levels, it is not clear whether one form is more beneficial than the other.
Some studies have shown that vitamin D3 supplements are more effective at increasing 25(OH)D levels, particularly in individuals with a vitamin D deficiency. Moreover, a study reported that vitamin D3, but not vitamin D2, stimulated the expression of interferons, which are immune proteins that provide protection against bacterial and viral infections.
Another study
Besides these differences, several studies with varying timelines and supplementation regimes have also suggested that vitamin D2 supplementation can negatively impact 25(OH)D3 levels and vice versa.
The researchers at Surrey University recently conducted a meta-analysis to systematically synthesize data from the aforementioned studies to examine the effects of vitamin D2 supplementation on 25(OH)D3 levels. Such a meta-analysis involves using statistical methods to synthesize data from previous studies and derive a single conclusion.
The meta-analysis included 11 randomized controlled trials involving healthy participants receiving vitamin D2 supplements compared with those receiving a placebo or no supplementation. The only exception was a trial consisting of participants with an exercise-related muscle injury. The study was included in the meta-analysis because the condition was not expected to impact vitamin D metabolism.
The researchers found that groups receiving vitamin D2 supplementation showed a greater reduction in serum 25(OH)D3 levels than those receiving no supplements or a placebo.
The study’s author, Emily Brown, a PhD research fellow at the University of Surrey, told Medical News Today that their “[m]eta-analysis, published in Nutrition Reviews, is, to the knowledge of the authors, the first to quantify the effect of vitamin D2 supplementation on vitamin D3 concentrations.”
“We discovered that vitamin D2 supplements can actually decrease levels of vitamin D3 in the body, which is a previously unknown effect of taking these supplements. This study suggests that, subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals over vitamin D2.”
— Emily Brown, study author
Given the role of 25(OH)D3 in immune function and mental health, these results suggest that vitamin D3 supplements may be more beneficial in most cases than vitamin D2.
“[These results suggest that] vitamin D3 supplementation may be the preferable supplement over vitamin D2, subject to personal considerations, due to increased efficacy at raising total [serum vitamin D] concentrations and possible additional functionality vitamin D3 has in modifying the immune system to fortify it against viruses and bacteria,” Brown explained.
Vitamin D plays a crucial role in the development and maintenance of Healthy bones by facilitating the absorption of calcium and other minerals from the intestine. Vitamin D deficiency can thus adversely impact calcium metabolism and bone Health, resulting in rickets in children and osteoporosis in adults.
Vitamin D can also modulate the function of immune cells, and a deficiency of this vitamin is associated with increased risk of infection and autoimmune conditions. Moreover, studies have reported an association between low vitamin D levels and the risk of cardiovascular conditions, diabetes, and cancer.
Vitamin D occurs in the form of either vitamin D3 or vitamin D2, with the two forms having slightly different chemical structures. Vitamin D3 is
Vitamin D, synthesized in the body or obtained via supplements and dietary sources, is converted by the body to its active form 1,25-dihydroxyvitamin D [1,25(OH)D] in a two-step process. Vitamin D is initially converted to 25-hydroxyvitamin D [25(OH)D] by enzymes present in the liver and subsequently, to 1,25(OH)D in the kidneys. 1,25(OH) binds to its receptors present on various cells and tissues to exert its biological effects.
Since 1,25(OH)D has a short half-life, serum levels of the more stable 25(OH)D are used to assess vitamin D status. Specifically, vitamin D2 and vitamin D3 are converted to 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3], respectively, by liver enzymes, and both 25(OH)D2 and 25(OH)D3 together contribute to vitamin D status.
Vitamin D deficiency can be caused by insufficient dietary intake of vitamin D or inadequate exposure to sunlight. For instance, darker skin pigmentation, the use of sunscreen, and a decrease in UV radiation during winter months can predispose individuals to insufficient vitamin D levels.
In addition, vitamin D deficiency can also be caused by health conditions or medications that interfere with vitamin D synthesis or absorption. Older adults, individuals with obesity, and those with chronic kidney or liver disease are at an increased risk of vitamin D deficiency.
Some people may take vitamin D supplements to achieve healthy levels of vitamin D and reduce their risk of chronic conditions associated with vitamin D deficiency.
However, it’s important to note that high levels of vitamin D can also have adverse effects, and only individuals who have low vitamin D levels should consider using supplements.
This study has the potential to influence clinical practice. Speaking to Medical News Today, Lina Begdache, PhD, RDN, associate professor of health and wellness studies at Binghamton University, State University of New York, said that doctors should prioritize supplementing vitamin D3 and monitor accordingly.
“Vitamin D3 should be prioritized for supplementation, as D2 can lower circulating D3 levels and is less effective at maintaining total vitamin D status. Clinicians should monitor D3 specifically and consider D2 only for those avoiding animal-derived products,” she said.
Similarly, Malek Cheikh, MD, an endocrinologist at MedStar Health, specializing in endocrinology, diabetes, and metabolism, also noted, “In clinical practice, we always thought that Vitamin D2 and D3 are identical physiologically and replenishing either should suffice to protect the body against low vitamin D levels. This highlights that we should now start to think that not all vitamin D supplements are interchangeable.”
“It may be safer to depend on D3 rather than on D2 to boost vitamin D levels. We should be cautious about taking high doses of D2 for a long duration of time,” Cheikh told MNT.
Cheikh also noted that the study’s results should be interpreted with caution, given the high levels of heterogeneity and lack of long-term data.
“This study serves as a good start to consider future research to further delineate differences between vitamin D2 and vitamin D3 in terms of bone health outcomes and immune markers to help guide clinical decision-making,” he added.
