Vitamin D3 vs D2: The Hidden Downside 18 of 20 Trials Found
Go to your kitchen cabinet, pick up your bottle of vitamin D and turn it around. Somewhere on that label is a small detail most people never notice: the letter and number after the “D.” It will say either D3 (cholecalciferol) or D2 (ergocalciferol).
For years, most of us assumed the two were interchangeable. But when it comes to vitamin D3 vs D2, new research suggests that tiny detail may matter more than we thought. A review of randomized trials from the University of Surrey and its research partners found that taking vitamin D2 was linked to lower blood levels of vitamin D3, the form your own skin makes in sunlight.
The findings were highlighted this week in a ScienceDaily report on a popular vitamin D supplement’s hidden downside. With fall here and the sun sitting lower in the sky, this is the perfect time to look closely at what you are taking. Let me walk you through what the study found, what it does not prove, and the practical steps I share with my own patients.
🔬 What the Vitamin D3 vs D2 Research Found
This was not a single small experiment. It was a systematic review and meta-analysis, which means the researchers gathered every qualifying study they could find and combined the results. All of the studies were randomized controlled trials in people, the type of study we trust most for cause and effect.
The team, led by scientists at the University of Surrey with colleagues from the John Innes Centre and the Quadram Institute, searched the medical literature from 1975 to early 2023. They found 20 randomized trials, involving about 1,080 people, including 60 children. The results were published in the journal Nutrition Reviews.
The key results
- A consistent pattern: 18 of the 20 trials found that vitamin D2 supplementation was associated with a drop in blood levels of 25(OH)D3, the main circulating form of vitamin D3.
- The pooled numbers: In 11 trials that could be combined (655 mostly healthy adults, 342 taking D2 and 313 taking a placebo or nothing), people on D2 ended up with D3 levels about 18 nmol/L lower than the comparison groups.
- Change over time: When the researchers looked at how much levels shifted during each trial, D3 fell by about 9 nmol/L more in the D2 groups.
- A wide range of use: The trials lasted 3 to 25 weeks and used doses from 300 IU all the way to 50,000 IU.
Recent Research
This is not the first study to favor D3. A 2012 meta-analysis in the American Journal of Clinical Nutrition and a 2024 meta-analysis of 20 comparative studies in Advances in Nutrition both found that D3 raised total blood vitamin D more effectively than D2.
An honest look at the limitations
I always want you to know the strengths and the weaknesses of a study, because one study is never the final word. Here are the cautions the authors themselves raised.
- The results varied a great deal from trial to trial. Scientists call this “heterogeneity,” and it was high here (83 percent for the end-of-trial data).
- Most of the trials were designed to study something else. D3 levels were often recorded as a side finding.
- Seven of the 11 pooled trials did not report how many people dropped out, and only 8 of the 11 were double-blinded.
- The researchers could not check whether studies with unexciting results went unpublished.
- Most importantly, nobody yet knows whether a lower D3 level matters for long-term health when a person’s total vitamin D is already adequate. The authors call for more research before D3 is formally preferred.
In the spirit of full transparency, one author reported a conflict of interest: she serves as research director for a company that holds patents on UVB material for vitamin D deficiency. The other authors declared none. That does not erase the findings, but it is the kind of detail I want my readers to have.
🧬 Why One Form May Lower the Other: The Science in Plain English
To understand this, it helps to know what your doctor measures. When you get a vitamin D blood test, the lab checks a compound called 25-hydroxyvitamin D, written as 25(OH)D. This is the storage form your liver makes from the vitamin D you get from sunlight, food and supplements. It is the best single marker of your vitamin D status.
There are two versions of this marker. If you take D3, your body makes 25(OH)D3. If you take D2, it makes 25(OH)D2. Many labs add them together and report a “total.” The measurement unit you will see in this research is nmol/L (nanomoles per liter), while many U.S. labs report ng/mL.
Here is the twist. Vitamin D2 does raise 25(OH)D2, so it still adds to your total. But at the same time, the D3 portion goes down. One form rises while the other falls.
Why would that happen? The authors suggest your body has a built-in regulating system. When vitamin D levels rise, the body may speed up how quickly it clears 25(OH)D, and the D3 form gets swept out along with it. They are careful to call this a proposed explanation, not a proven one. I appreciate that honesty.
D2 is not useless
I want to be fair to vitamin D2. According to the ScienceDaily report, a separate 2026 meta-analysis of 26 randomized trials (Lai and colleagues, also in Nutrition Reviews) found that D2 still lowers parathyroid hormone and slightly raises blood calcium. In other words, D2 is active in the body. The newer research does not say D2 is harmful. It says D2 may be less effective and may lower your D3.
An interesting immune clue
The ScienceDaily report and the study’s discussion also mention a 2022 study by Durrant and colleagues in Frontiers in Immunology. Looking at gene activity in blood, the researchers found that D3, but not D2, stimulated something called type I interferon signaling. That is one of your immune system’s early alert signals against viruses.
This is fascinating, but please keep it in perspective. Gene activity in a blood sample is not the same as fewer colds in real life. It is a clue that deserves more study, not a promise. If you want to go deeper on this subject, read my earlier article on a common vitamin D and immune system mistake.
Fast Fact
The National Institutes of Health (NIH) states that both D2 and D3 raise blood 25(OH)D, but D3 raises it more and may keep it up longer.
🏷️ Cholecalciferol vs Ergocalciferol: How to Read Your Label
In my practice I often see patients who are faithfully taking vitamin D every day but have never looked at which form it is. Here is the simple decoder I give them.
- Vitamin D3 = cholecalciferol. This is the form your skin makes when sunlight touches it. It is also found in animal foods such as fatty fish and egg yolks. Some vegan products use D3 made from lichen.
- Vitamin D2 = ergocalciferol. This form comes from UV-exposed fungi or yeast. Mushrooms are its main food source.
Check more than your stand-alone vitamin D bottle. Look at your multivitamin, any fortified foods you eat often, and combination products. And here is an important point: high-dose prescription vitamin D is often D2. If your doctor prescribed it, please do not switch it on your own. Bring this article to your next visit and ask whether D3 is right for you.
This label lesson matters most for adults over 40 and 50. As we age, our skin makes less D3 from sunlight, and in the fall and winter months many of us get far less sun to begin with. The form you choose becomes a bigger part of the picture.
🌞 The Key Pieces of the Best Form of Vitamin D Plan
Choosing the right form is only one piece. Here is how I think about a wise, whole-person vitamin D supplement plan for adults over 50.
Vitamin D3 (Cholecalciferol)
The form your skin makes in sunlight. NIH says it raises blood 25(OH)D higher and for longer than D2, and the new review found D2 lowered blood D3 by about 9 to 18 nmol/L. Food sources include fatty fish and egg yolks.
Vitamin D2 (Ergocalciferol)
Comes from UV-exposed fungi and yeast, with mushrooms as the main food source. It still raises 25(OH)D2 and remains an option for vegans who do not use lichen-derived D3. It is not harmful, simply less effective in comparison studies.
A Meal With Healthy Fat
NIH notes that vitamin D is best absorbed with a meal that contains some fat. Take yours with breakfast eggs, avocado, olive oil or a handful of nuts rather than on an empty stomach.
Sensible Sunlight
God designed your skin to make D3 from sunlight. Even in cooler months, time outdoors in the light is a gift for body and spirit. Just remember that skin makes less D3 with age, so sunlight alone may not be enough.
A 25(OH)D Blood Test
NIH links levels below 30 nmol/L to deficiency and calls 30 to under 50 nmol/L generally inadequate. Testing before and after a change takes the guesswork out.
Nutrient Partners
Vitamin D does not work alone. In my practice I like to pair D3 with vitamin K2, which supports healthy calcium utilization, and I pay attention to overall mineral intake as part of a balanced plan.
If you are building a simple daily foundation, you may also enjoy my thoughts on the top 5 supplements I recommend for living longer and stronger, and my guide to the benefits of magnesium, another nutrient many adults fall short on.
Dr. Colbert Recommends
Divine Health Immune Support
Immune Support uses vitamin D3, the cholecalciferol form discussed in this research, rather than D2. It brings D3 together with vitamin C, zinc, quercetin and elderberry in one daily formula designed to support healthy immune function as the days grow shorter.*
- ✔ Supports healthy immune function*
- ✔ Provides vitamin D3 (cholecalciferol), the form your skin makes
- ✔ Combines vitamin C and zinc with quercetin and elderberry*
- ✔ A simple addition to your fall and winter wellness routine
D3 does not work alone
One lesson I have learned over 30 years of practice is that nutrients work as a team. That is why I often suggest pairing vitamin D3 with vitamin K2, especially the MK-7 form. K2 supports healthy calcium utilization, which makes it a natural companion to D3 in a thoughtful supplement plan.
Dr. Colbert Recommends
Divine Health Hormone Zone
Hormone Zone pairs vitamin D3 with vitamin K2 (MK-7) and adds DIM. If you want your daily vitamin D in the D3 form alongside its K2 partner, this formula is designed to support healthy hormone balance for adults in midlife and beyond.*
- ✔ Supports healthy hormone balance*
- ✔ Provides vitamin D3 in the cholecalciferol form
- ✔ Pairs D3 with vitamin K2 (MK-7)
- ✔ Includes DIM as part of a complete formula*
Whichever product you choose, please do not stack several vitamin D sources without checking your total. More is not always better, as we will see next.
⚖️ How Much Vitamin D, and Who Should Check With a Doctor First
According to the NIH, adults ages 19 to 70 need 600 IU (15 mcg) of vitamin D per day, and adults 71 and older need 800 IU (20 mcg). The FDA Daily Value you see on labels is 800 IU (20 mcg). These recommendations do not distinguish between D2 and D3.
Your personal needs may be different, which is why I recommend a 25(OH)D blood test and working out your amount with your physician. Too much vitamin D can be harmful. NIH reports that very high blood levels (over 375 nmol/L, or 150 ng/mL) can cause nausea, weakness, confusion and kidney stones, and these levels are almost always caused by taking too many supplements.
Please talk with your doctor before changing your vitamin D if any of these apply to you:
- You take prescription vitamin D (often the D2 form).
- You have kidney disease, sarcoidosis, a parathyroid condition or high calcium.
- You take thiazide diuretics or heart medications.
- You are pregnant or nursing, or you are choosing vitamin D for a child.
✝️ Stewardship, Sunlight and Testing What We Take
✦ Dr. Colbert’s Faith Perspective
The Light He Designed Us to Use
I never cease to be amazed that God built our skin to turn sunlight into vitamin D3. Truly, we are fearfully and wonderfully made (Psalm 139:14). It moves me that the research keeps pointing back to the very form He designed our bodies to make.
Scripture also calls us to be wise, not careless. Proverbs 14:15 reminds us that the prudent consider their steps well. Reading a label, testing your level and asking good questions is not a lack of faith. It is faithful stewardship of the temple God has entrusted to you.
This fall, I invite you to step outside in the morning light, lift your face to the sun and spend a few minutes in prayer and gratitude. Let your body and your spirit be refreshed together.
“Test all things; hold fast what is good.” (1 Thessalonians 5:21, NKJV)
“Your vitamin D bottle deserves a second look. Choose the form your Creator designed your skin to make, then test, don’t guess.”
Dr. Don Colbert, MD
📋 Your Vitamin D3 vs D2 Action Plan
- Read every label this week. Check your vitamin D, multivitamin and combination products for “D3 (cholecalciferol)” or “D2 (ergocalciferol).”
- Add up your total. Write down how much vitamin D you get from all supplements combined so you do not double up.
- Get a baseline 25(OH)D test. Ask your doctor for a vitamin D blood test before you make any change.
- Talk with your doctor about D3. If your current product is D2, ask whether D3 is a better fit for you. Never switch a prescription on your own.
- Take it with a meal that has some fat. Eggs, avocado, olive oil or nuts help absorption, according to NIH.
- Pair it wisely. Consider D3 with vitamin K2 as part of a balanced plan built with your physician.
- Get outside in the morning light. Even 10 to 15 minutes of fresh air, movement and prayer is a wonderful way to start the day.
- Retest in a few months. A follow-up test shows whether your plan is working and keeps you safely within healthy limits.
❓ Frequently Asked Questions
Is vitamin D3 better than D2?
Several meta-analyses, including reports from 2012 and 2024, found that D3 raises total blood vitamin D more effectively than D2. The NIH agrees that D3 raises levels higher and may keep them up longer. Whether that difference changes long-term health outcomes is still being studied.
Is vitamin D2 bad for you?
No. The research does not show that D2 is harmful. D2 still raises 25(OH)D2 and remains active in the body. The new finding is that it may be less effective than D3 and may lower your blood D3 at the same time.
How much vitamin D do adults over 50 need?
NIH recommends 600 IU daily for adults up to age 70 and 800 IU for adults 71 and older. Many people need a personalized amount based on their blood level, so a 25(OH)D test and a conversation with your doctor are the best guide. Avoid taking large amounts without testing, since too much vitamin D can be harmful.
What is the best way to take vitamin D?
NIH notes that vitamin D is best absorbed with a meal containing some fat. Many of my patients simply take it with breakfast. Consistency matters more than the exact time of day.
What should vegans take: D2 or D3?
Most D3 comes from animal sources, which is why many vegan products have used D2. However, D3 made from lichen is a plant-based option. If you follow a vegan diet, look for “lichen-derived D3” on the label and ask your doctor to help you track your level.
🙏 A Final Word
Sometimes the most meaningful health changes are the smallest ones. Turning a bottle around and reading the label takes ten seconds, yet it can help you make a wiser choice for the months ahead.
Here is the honest bottom line: the research suggests D3 is the more effective form for raising and keeping your vitamin D levels, while D2 may lower your blood D3. We do not yet know whether this changes long-term health, so I am not asking you to fear D2. I am asking you to be informed, to test your level and to work with your doctor.
As the Apostle John wrote, “Beloved, I pray that you may prosper in all things and be in health, just as your soul prospers” (3 John 1:2, NKJV). That is my prayer for you this season. Step into the light, care for the body God gave you, and walk forward in hope.
Dr. Don Colbert, MD
Sources
- Scientists warn a popular vitamin D supplement may have a hidden downside, ScienceDaily (source: University of Surrey), 2026
- Effect of Vitamin D2 Supplementation on 25-Hydroxyvitamin D3 Status: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Brown EIG, Lanham-New SA, Elliott RM, et al., Nutrition Reviews, 2025
- Vitamin D: Health Professional Fact Sheet, NIH Office of Dietary Supplements
- Vitamin D: Consumer Fact Sheet, NIH Office of Dietary Supplements
- Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25(OH)D: A Systematic Review and Meta-Analysis, Advances in Nutrition, 2024
- Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis, American Journal of Clinical Nutrition, 2012
- Vitamin D2 vs. D3: Differences, benefits, sources, Medical News Today
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