Vitamin D vs. Vitamin D3: Are They The Same?

Vitamin D is an essential nutrient that plays a critical role in many bodily functions, from strengthening bones to regulating your immune system. According to the National Institutes of Health, an estimated one billion people worldwide have inadequate levels of vitamin D in their blood, which can lead to a host of health problems, including increased risk of infection, osteoporosis, and autoimmune disorders.

Supplementation provides an attractive strategy to correct low vitamin D status; however, research shows that certain vitamin D forms may be superior. Here, we review the differences between the two forms of vitamin D and discuss their benefits in certain health conditions and diseases.

Is there a difference between vitamin D and vitamin D3?

Yes, there is a difference between vitamin D3 and D. More accurately, vitamin D is the collective term for the group of specific fat-soluble vitamins that include vitamin D2 and vitamin D3.

What is vitamin D?

Vitamin D is a fat-soluble vitamin crucial to maintaining optimal health. It is essential for the absorption of calcium and phosphorus, which are important for bone growth and development, as well as for maintaining strong bones and teeth.

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Beyond skeletal functions, vitamin D also provides other health benefits, but depending on the form, it may have more beneficial effects than the other.

Two forms of vitamin D

There are two main forms of vitamin D:

• Vitamin D2 (ergocalciferol)
• Vitamin D3 (cholecalciferol)

Vitamin D3 is considered the more biologically active form, as it is more efficiently converted by the body into the active hormone form of vitamin D, known as calcitriol. Although vitamin D3 is more efficient, vitamin D2 is also converted into calcitriol.

How the body metabolizes vitamin D

Although the two vitamin D forms — D2 and D3 — have only slightly different chemical structures, they have specific differences in their metabolism and properties.

How vitamin D is synthesized in the body

Vitamin D is naturally synthesized in the body when the skin is exposed to sunlight, but it can also be obtained through certain foods and supplements.

Specifically, when our skin is exposed to sunlight, a compound called cholecalciferol (vitamin D3) is produced. This is then transported to the liver, which converts it into 25-hydroxyvitamin D3. From there, it is further processed in the kidney to form the active hormone form of vitamin D, known as 1,25-dihydrovitamin D3 (calcitriol), the final, most active form of vitamin D.

Meanwhile, when vitamin D2 is taken, it is also transported into the liver and follows the same process.

Differences in absorption and metabolism in the body

Vitamin D2 and vitamin D3 differ in their absorption and metabolism in the body, which can impact their effectiveness in maintaining optimal vitamin D levels.

Here are some key differences in terms of absorption, metabolism, bioavailability, and half-life of vitamin D2 and D3:

What is the best form of vitamin D to take?

A large body of data links vitamin D deficiency to the development of acute and chronic conditions, implicating that supplementation may ameliorate such pathologies.

So, which form of vitamin D is more advantageous? We summarize the research findings assessing vitamin D forms and their impact on several diseases or health conditions.

Vitamin D deficiency

Experimental and clinical studies support vitamin D2 and D3 forms for raising vitamin D levels. However, it is now established that vitamin D3 effectively increases blood levels longer than vitamin D2.

In fact, a report concludes that vitamin D3 has approximately 87% higher potency in increasing and maintaining vitamin D levels by 2 to 3 folds compared to vitamin D2.

While some doctors may prescribe vitamin D2 more often than D3, the reason is higher dosages found in vitamin D2 formulations in the market than in vitamin D3. Additionally, vitamin D2 is more readily available in groceries or pharmacies because vitamin D2 is cheaper to produce.

Bone health and fractures

According to research, vitamin D2 and D3 have fairly equal beneficial effects on bone health and bone mineral density, even though vitamin D3 is more effective at raising and maintaining vitamin D blood levels.

Additionally, vitamin D3 may also effectively reduce the risk of falls and fractures, a major issue in the elderly. More recent data indicates that both vitamin D2 and D3 alone could not reduce fracture rate; however, if combined with calcium, these supplements, especially vitamin D3, significantly reduce fracture rates.

Chronic Kidney Disease (CKD)

Patients with CKD have prevalent vitamin D deficiency. However, supplementation is tricky, and correcting vitamin D status in CKD patients requires stricter guidelines that may depend on patient characteristics and disease stage.

When vitamin D2 and D3 supplementation is compared in hemodialysis patients, results show that vitamin D3 is more effective in improving the patients’ vitamin D status.

However, more recent data warrants caution in choosing vitamin D3 form for supplementation.

In 2021, a systematic review of 22 clinical trials testing vitamin D forms in CKD patients stated the effect of its supplementation is inconclusive. The study showed that vitamin D3 analogs (calcifediol and calcitriol) even have varying effects on markers of CKD severity: while calcifediol suppresses PTH, calcitriol may increase FGF23.

When kidney function in CKD patients progressively declines, circulating levels of parathyroid hormone (PTH) and Fibroblast Growth Factor 23 (FGF23) increase and are associated with more severe disease stages.

Additionally, certain groups of people with CKD may also have resistance to vitamin D3, which is associated with kidney disease progression. Hence, CKD patients must always check with their doctors before taking any vitamins, including vitamin D supplements.

Immune function

Vitamin D deficiency has long been associated with reduced immunity. Vitamin D supplementation may bolster immune defenses against many infections.

Meanwhile, UK scientists recently investigated the effects of Vitamin D2 and D3 on the human immune system and found unequal results.

Regarding IFN activity (a cellular pathway critical in effective response to bacterial and viral infections), only vitamin D3 has a boosting effect. Since reduced IFN activity predisposes people to infection, their findings indicate that vitamin D3 provides a superior boost to immune system processes.

Surprisingly, the researchers also observed some people supplementing with vitamin D2 had lower blood levels than the placebo group. However, since this clinical trial has some limitations, a broader examination of a larger population and a longer time frame is needed.

Cardiovascular disease

A 2019 publication by JAMA Cardiology that meta-analyzed 21 clinical trials with over 83,000 individuals concluded that vitamin D (whether ergocalciferol or cholecalciferol) supplementation does not provide cardiovascular protection or beneficial effects related to major cardiovascular events, individual CVD endpoints (stroke, myocardial infarction, CVD mortality) as well as all-cause mortality.

However, later in the same year, another group of scientists published a literature review by the Journal of Clinical Endocrinology & Metabolism. It argued that although current data do not support vitamin D’s benefits for cardiovascular protection, the evidence is still inconclusive, which warrants more comprehensive investigations and rigorous study designs.

COVID-19

Recently, researchers from Johns Hopkins University published the effects of vitamin D supplementation against COVID-19. Data shows that vitamin D2 and D3 supplementation decreased COVID-19 infection probability by 20% and 28%, respectively.

While both forms significantly reduce the risk of COVID-19 infection, further analysis shows that vitamin D3 is associated with a 33% lower risk of SARS-CoV-2 infection and 30-day mortality following infection. But vitamin D2 does not seem to have this positive effect.

Other findings also indicate the higher severity of COVID-19 in patients with vitamin D deficiency.

All-cause mortality

In 2014, a meta-analysis of 73 cohort studies with over 849,000 participants indicated vitamin D3 supplementation significantly lowers mortality rates in older adults due to cardiovascular disease, cancer, and other causes.

On the other hand, a 2019 meta-analysis of 50 clinical trials with over 74,000 participants suggests vitamin D supplementation alone does not reduce all-cause mortality. Their analysis also showed a 15% reduction in cancer mortality in vitamin D3 supplementation, but not in vitamin D2.

How much vitamin D should I take a day?

The recommended daily vitamin D intake depends on various factors, including age, sex, and overall health. Amounts may also vary depending on whether you get vitamin D from sunlight, food, or supplements.

According to the National Institutes of Health-Office of Dietary Supplements, the recommended vitamin D IU (international units) dosages per day based on age groups are as follows:

However, when it comes to vitamin D2 and D3 specifically, there is no clear consensus on how much of each form you should take. As previously mentioned, both vitamin D forms, effectively increase vitamin D blood levels, but vitamin D3 is more effective.

Where can I get vitamin D?

Since vitamin D deficiency has been linked to various health problems, ensuring you get enough vitamin D through a balanced diet and appropriate sun exposure is important.

Vitamin D2 is primarily found in plant sources, while vitamin D3 is synthesized in the skin when exposed to sunlight and is also found in animal products. You can improve your vitamin D status by taking specific vitamin D-rich sources.

Vitamin D2 sources

• Mushrooms (especially those exposed to UV light)
• Fortified foods such as milk, orange juice, and cereal
• Supplements (in the form of ergocalciferol)

Vitamin D3 sources

• Fatty fish such as salmon, tuna, and mackerel
• Egg yolks
• Beef liver
• Fortified foods such as milk, orange juice, and cereal
• Supplements (in the form of cholecalciferol)