Wellbeing: Vitamin D2 or D3?
Winter's coming...
Vitamin D3, which is considered a hormone, plays a crucial role in supporting renal function, prenatal health, brain function, immunity, pregnancy, cancer prevention, and cardiovascular health.
However, current guidelines from the US government only emphasize bone health and overlook the other benefits and the importance of maintaining optimal vitamin D levels for overall health, beyond skeletal issues. Of course, what we all learned during the COVIDcrisis is that higher levels of vitamin D may be the best way to fight off respiratory diseases, such as COVID-19.
This is why a recent news article on vitamin D caught my attention yesterday. The basic premise of the Fox News piece is that a new study from the University of Surrey in the U.K. found that taking vitamin D2 can result in reduced levels of vitamin D3 in the body. To be honest, this has been known for a long time. This is old news, and it is also well-documented that vitamin D3 has significant benefits, whereas vitamin D2 is much less potent, shorter-lived, and less stable than D3.
Before I delve into the politics of milk fortification and prescription supplements, let me put out a few facts about the regulatory landscape:
The standard of supplementation of milk with vitamin D (21 CFR 131.110) was codified in the 1970s. The regulation itself does not specify D2 vs D3.
The specialized food additive regulation (§ 172.380), which explicitly authorizes vitamin D3 in milk, was developed later, and it wasn’t until 2018 that the FDA rule-making explicitly mentions D3’s permitted use in milk.
Higher levels of vitamin D in the blood, in general, have historically been associated with an increased risk of overcalcification, and this has been used to deter people from taking supplements. However, toxicity studies on vitamin D were primarily conducted in the 1940s on animals, using very high-level dosing schedules. These side effects are almost always mitigated by taking vitamin D with vitamin K and limiting daily intake to 10,000 IUs.
The current recommended US government guidelines state that a serum vitamin D level of 20 ng/mL (50 nmol/L) is sufficient for 97.5% of the population to maintain bone health. The guidelines are listed for maintaining bone health, without noting any other benefits or recommended dosages for renal health, prenatal health, brain function, immunity, pregnancy, cancer prevention, or cardiovascular health. The truth is that to prevent respiratory diseases, blood levels should be at least 50 ng/ml, and many prefer them to be as high as 100 ng/ml. However, because the US government has not rigorously tested daily dosing of vitamin D levels for any purpose other than “bone health,” it does not recommend it, despite numerous studies showing its benefits. Of course, this is circular logic at best.
The FDA does not differentiate between vitamin D2 and D3. Below is a summary of current government guidelines
The US government does not recommend vitamin D supplementation for immune health:
NIH Office of Dietary Supplements (ODS)
States that vitamin D is important for bone and immune health,
but explicitly states that:
“Evidence is inconsistent about whether vitamin D supplementation reduces the risk of respiratory tract infections, including COVID-19.”
(NIH ODS, Vitamin D Fact Sheet for Health Professionals, updated 2024)
The NIH does not recommend vitamin D supplementation specifically for the prevention or treatment of respiratory diseases.
CDC
The CDC does not include vitamin D in its recommendations for preventing influenza, pneumonia, or COVID-19.
FDA
The FDA allows structure/function claims like “supports immune health,”
but prohibits disease claims such as “prevents respiratory infections” unless proven by clinical trials and formally authorized.
Almost all of the “high-dose” vitamin D random clinical trials conducted have used a high-dose bolus injection of vitamin D given monthly. As vitamin D levels drop over time, this is a bizarre way to conduct a clinical trial. But that is most often what has been done and what is often recommended clinically. Furthermore, some RCTs use vitamin D2, while others use D3 - this is particularly true historically. So results can vary enormously. Then the meta-analysis on such studies does not find a statistically strong signal when the confounding influences are most likely interfering with their analyses.
However, numerous observational/retrospective studies indicate that individuals with higher levels of circulating vitamin D experience less severe outcomes for respiratory diseases, including influenza and COVID-19. It is unethical to cause someone to become vitamin D-deficient, which means that designing a randomized clinical trial (RCT) with that control arm is not ethical. Therefore, a true RCT can never be conducted for vitamin D, and instead, observational studies are the best that can be achieved. These types of observational studies can be extremely useful and should be considered the gold standard when RCTs can not be conducted due to ethical concerns.
How To Take Vitamin D Safely
Other supplements should also be taken in conjunction with vitamin D3. These are listed below - together with the logic behind taking them:
Vitamin K (especially K₂) & Vitamin D₃. D and K are often considered synergistic: D facilitates calcium absorption, and K (especially K₂) helps modulate calcium’s direction into bones (vs soft tissues). Taking D without adequate K may increase the risk of inappropriate calcium deposition (e.g., in arteries) in susceptible individuals.
Vitamin A & Vitamin D₃. Vitamin A and D share some common pathways (both are fat-soluble, share binding proteins, and can influence gene expression). High doses of preformed vitamin A can antagonize or interfere with vitamin D’s effects in some models, so balance matters. Avoid megadoses of vitamin A unless medically indicated. Ensure the dose ratio is reasonable.
Magnesium & Vitamin D₃ - Magnesium is needed for the enzymes that activate vitamin D (i.e., converting D to 25-hydroxyvitamin D and then to the active form). If magnesium is deficient, vitamin D supplementation may not be fully effective. (ref).
Zinc & Vitamin D₃ - Zinc acts as a cofactor in gene transcription involving the vitamin D receptor (via zinc finger domains), meaning that vitamin D’s effects partly depend on zinc. Low zinc levels may blunt vitamin D’s function, so maintaining sufficient zinc is beneficial (ref).
There are two forms of vitamin D used for supplements. Vitamin D2 is plant-based and is still used almost exclusively in nut milks for fortification purposes. It was once the only supplement available.
D3 has become the preferred supplement because:
Vitamin D3 is 2–3 times more potent at raising serum 25(OH)D. Vitamin D3 maintains levels longer after dosing stops.
These facts have been known for decades, and mean that most fortification using vitamin D2 has been a complete waste of resources and money. It also leads people to have a false sense of security, believing they are getting adequate vitamin D levels, when in fact, they may not be.
D2 supplementation can even lower vitamin D3 (the active form) concentrations in the blood, due to competitive metabolism. Hence, a recent meta-analysis (ref) highlighted this result, which is the basis of the “headline news” from Fox above. However, this has been known for many years, with peer-reviewed papers spanning at least a decade (ref, ref, ref).
This means that vitamin D2 actually lowers the beneficial type of vitamin D3 found in the body. Meaning that less vitamin D3 is actually found in the plasma of people who are supplementing with vitamin D2.
Until the last decade, milk and other foods were supplemented with vitamin D2 or D3. This was despite the fact that scientists had known since at least the early 1980s that vitamin D2 had very little activity and broke down quickly in the body, making it almost worthless as a fortification agent. It took the FDA over thirty years to catch up to the science. But gosh darn, that milk label “fortified with vitamins A and D” sure made parents “feel” good - and sold a heck of a lot of fat-free dairy!
Some peer-reviewed papers suggest that D2 was used much more frequently, although I found no evidence that the FDA or state labs were tracking who was using what. FDA rule-making language didn’t specifically add vitamin D3 until 2018.
Prescription Vitamin D2.
Vitamin D2 is still the most commonly prescribed form of vitamin D because it is the only one officially listed in the U.S. Pharmacopeia, and is exclusively covered by insurance. These organizations consider vitamin D2 and vitamin D3 functionally interchangeable for most clinical purposes.
So, the people who need vitamin D3 the most — those who have vitamin D deficiency, Osteoporosis or osteopenia, have malabsorption syndromes, or have chronic kidney disease — are getting a bolus of an inferior product. Near as I can tell, the reason why they are getting an inferior product is 1) it has been historically given, and 2) it is marginally less expensive to make.
A recent study found a link between reduced mortality and vitamin D deficiency. The study authors examined 307,601 records from the UK Biobank over a 14-year follow-up period. They discovered that higher vitamin D levels, up to 50 ng/ml, were associated with a significantly reduced risk of death (ref). Furthermore, vitamin D deficiency has also been linked to brain aging (ref). Approximately 42% of the US population is considered vitamin D deficient.
To Conclude:
Many of the US government’s recommended daily allowances are based on outdated historical data, extracted from studies conducted 75 years or more ago. Vitamin D3 is one such example, but there are many more.
As HHS is revamped by the Trump administration to meet the goals of the MAHA commission, I expect that other dietary guidance will also be modified to eliminate outdated and misleading health information.
Of course, the big kahuna is the food pyramid, which historically has been a complete and utter disaster and has adversely affected the health of many or most everyday Americans. I look forward to seeing what the MAHA commission creates as new dietary requirements - their job won’t be easy, and yet, it is of critical importance.
But the truth is, don’t we all know that avoiding ultraprocessed foods, simple carbohydrates, including white flour, sugar, and alcohol, will improve our health? That increased exercise leads to healthier bodies? That being outdoors, getting exposed to the elements and sunshine is healthy! That more greens, vegetables, fruits, and protein in the diet are good! That eating until you aren’t quite full, is a good habit to live by!
We also know that winter is a season of vitamin D deficiency, so now is the time to supplement, and the sun remains a great source of vitamin D.
So, eat healthy, enjoy a little sunshine, and supplement wisely - particularly if one has cycled around more than a few decades in life.
“What vitamin D and associated supplements do you take?
Having laid this all out, there is a question that I get asked again and again.
This is: “Dr. Malone, what vitamin D and associated supplements do you take?
So, below isn’t my entire list of supplements (I will save that for another day), but it's the list of vitamins A,D,K, magnesium and Zinc - with dosing that Jill and I take daily.
Paywall below this point
Vitamins A,D,K, magnesium and Zinc - daily dosing and brands:
ADK, DAVINCI Labs - Helps Support Bone, Heart & Immune Health - Dietary Supplement with Vitamins A, D3 & K2 (as MK-7) - Vegetarian, Gluten Free & Soy Free.*
Magnesium L Threonate, Magtein, Sleep and Cognitive Support – High Absorption – Most Bioavailable Form of Magnesium – 2,000 mg**
Zinc Triple Play (Bronson) 30mg Triple Coverage Immune Support with Zinc Acetate, Picolinate & Orotate**
Notes:
The vitamin A,D, K supplement is taken in the AM.
** Magnesium L-Threonate and Zinc are taken in the PM, to stop absorption interference. I take magnesium at night because it is also a sleep aid. I prefer the L-Threonate form of magnesium, as studies indicate that L-Threonate supports brain health. Magnesium citrate has a laxative effect.
As a reference, 5000 IU/day vitamin D3 should get serum levels to around 50 ng/ml, while 10,000 IU/day will bump it up to around 80-100 ng/ml, but results from vitamin D supplementation is very person-to-person specific and depend on the season. Consider getting an occasional vitamin D level test - something your physician should recommend anyway. If you don’t regularly visit a physician, at-home tests are available that require a sample to be sent to a laboratory. I routinely have my blood checked and like to see my levels of vitamin D3 at or above 60-80 ng/mL, but no higher than 100 ng/mL.
I personally take 5,000 IUs right now, as that is all I need to maintain my serum level between 80-100 ng/ml. But again, get your levels checked - and consider finding a health care provider who can help guide you in making decisions about correct dosing.
*,** These products are listed for information only. I am not recommending or endorsing any brand, product or dosage. Please consult your health care professional.
Finally, for science nerds
They’re two different units used for measuring vitamin D serum level concentrations:
ng/mL (nanograms per milliliter) — common in U.S. medical labs.
nmol/L (nanomoles per liter) — the SI (international) unit used in most scientific papers and in Europe.
Conflict of Interest Disclosure- Neither Malone.News nor Drs. Robert or Jill Malone receives any sponsorship or advertising revenue from any of the supplement manufacturers listed above, and we do not hold any equity in any of these companies.