The vitamin D hype is not supported by scientific evidence – GWC Mag

Over the past few years, vitamin D supplements have become trendy. We always knew that maintaining healthy levels of the vitamin was critical to preventing some bone diseases.

Then, in the early 2000s, researchers began amassing a pile of studies suggesting that low vitamin D levels could be a factor in cancer, cardiovascular disease, dementia, depression, diabetes, autoimmune diseases, fractures, respiratory illnesses, COVID-19, and Parkinson’s disease. It seemed reasonable to think that raising our levels of vitamin D — which our bodies make when we stand in the sunshine and which we can consume in supplements — could cure practically whatever ailed us.

But something happened along the way to proclaiming this the most wonderful supplement ever — we were able to show that low levels of vitamin D might occur alongside the diseases I mentioned above, but research provided no evidence that vitamin D supplements could reverse those diseases. In other words, vitamin D supplements were a bust.

It’s the old problem that correlation is not equivalent to causation. We can find that someone with diabetes might have low vitamin D levels, but we have zero evidence that low vitamin levels cause diabetes.

Taking this supplement may appear to be trendy, but the science supporting its use in treating or preventing medical conditions, other than certain bone diseases, is not supported by robust and repeated clinical trials.

The purpose of this article is to review some of the old and new information about vitamin D supplements. It’s about scientific articles that either support or refute a claim, that’s it. It’s not about what we believe or we do not believe, it’s about evidence.

What is vitamin D

Vitamin D is a group of fat-soluble secosteroids (it’s a scientific name for steroids with a “broken” ring). The most important chemicals in this group are vitamin D₃ (known as cholecalciferol) and D₂ (known as ergocalciferol).

Very few foods contain either of the important types of vitamin D. However, some foods can be good sources of the vitamin:

• Fatty fish, like tuna, mackerel, and salmon
• Foods fortified with vitamin D, like some dairy products, orange juice, soy milk, and cereals
• Beef liver
• Cheese
• Egg yolks

Many people with broad diets that include a lot of fish, eggs, and other foods can get sufficient amounts of the vitamin without supplementation. As I’ve repeated often, short of chronic malnutrition, we get plenty of it in a normal, healthy diet.

Moreover, vitamin D is produced by a process called dermal synthesis. That is, sunlight, specifically UV-B radiation, causes the synthesis of vitamin D in the skin. Technically, vitamin D isn’t a vitamin, because we can manufacture it, it is a hormone. For this article, we’ll just call it a vitamin, even though scientifically it is not — I hope that makes some sense.

Although we can manufacture sufficient vitamin D by sunbathing every day, the body has a feedback loop that shuts down production to prevent toxicity. Yes, excess vitamin D is quite dangerous leading to many conditions such as over-absorption of calcium which can lead to hypertension and fatigue. It also can lead to some dangerous chronic conditions that we’ll discuss later.

Although humans can manufacture the vitamin by sitting in bright sun, there’s one major problem – the risk of skin cancer. As I’ve written before, there are very few ways to prevent cancer, but staying out of the sun is one of them.

Finally, the vitamin D we consume or produce in sunlight is not biologically active. It is generally activated by enzymatic conversion (in a process called hydroxylation) in the kidneys and liver so that the body can use it.

What does vitamin D do or don’t do?

Based on real scientific evidence, vitamin D has a very narrow, but important, set of effects.

First, it is responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc, important minerals for the continued health of any human being. Many of these minerals (and vitamin D itself) are necessary for good bone health.

Second, since vitamin D is important to calcium homeostasis and metabolism, a deficiency of the vitamin results in rickets, or the adult form of the disease, osteomalacia. Rickets, because it happens in immature bones, leads to frequent fractures and skeletal deformities. Osteomalacia, because it occurs in adults with fully formed bones, usually results in numerous fractures.

At this point, that’s it. Robust evidence only supports those two beneficial physiological effects of the vitamin.

Here are a few claims made recently about the benefits of vitamin D:

• The claim that it prevents breast cancer – no evidence.
• The claim that it prevents breast cancer – no evidence again.
• The claim that it reduces blood pressure – no again.
• The claim that it reduces the risk of death – no evidence.
• The claim that it improves cardiometabolic outcomes – systematic review says no.
• The claim that it reduces the risk of colorectal cancers – no evidence.
• The claim that it improves skeletal, vascular, or cancer outcomes – meta-analysis says no.
• The claim that it improves mortality outcomes for elderly patients – a massive meta-review says there is weak evidence, but that’s clouded by various reporting biases that make the data almost worthless.
• The claim that it boosts the immune system — given the complexity of the immune system, which is an interconnected network of cells, biomolecules, and organs, I have seen no biologically plausible mechanism that vitamin D magically improves or boosts the immune system. However, someone with a low blood level of vitamin D may experience some level of immune suppression, but that doesn’t mean a handful of vitamin D capsules will magically boost your immune system.
• The claim that it improves COVID-19 outcomes — very weak evidence and even weaker evidence, both, at best, marginally convincing. Both studies use very small patient populations that lack analysis of potential confounding data.
• The claim that it may reduce the risk of type 2 diabetes — several studies (here, here, here, here, and here) show either weak or no link between vitamin D supplementation and preventing the development of type 2 diabetes.

New research

Over the past few years, several articles have been published that reviewed vitamin D supplements and various health conditions. Let’s take a look.

• A June 2019 meta-analysis of 21 randomized clinical trials (n=83,291 participants) showed that vitamin D supplements offer no benefit for cardiovascular disease (CVD) prevention. These results represent fairly conclusive evidence that vitamin D is useless for the prevention of CVD.
• In the accompanying editorial to the article above, the authors concluded that “The popularity of vitamin D supplementation is at least partly owing to the misinterpretation of impressive epidemiologic associations between vitamin D status and a breadth of health metrics, leading to a potentially flawed assumption of causality.” This goes to the adage that correlation does not equal causation. 
• An August 2019 randomized clinical trial showed that vitamin D supplements might not be much help for strengthening bones among healthy adults without osteoporosis, even at doses far higher than recommended daily allowances. Moreover, patients on the highest dose of vitamin D experienced the most instances of hypercalciuria and hypercalcemia, both conditions could become serious health issues.

Vitamin D and cancer

One of the big claims in some miraculous way, vitamin D can reduce the risk of cancer. There isn’t a lot of good data for a few reasons:

• There are hundreds of cancers, each with a different etiology and pathophysiology — and there are thousands of different ways to treat them.
• Cancer can take decades to appear, so correlation, let alone causation, may be difficult to establish when vitamin D levels need to be measured over many years.
• Over 67% of cancers are random mutations. You could have perfect levels of the vitamin, and you still have a significant risk of cancers that happen randomly.
• Although some studies show a small reduction in risk for some cancers by keeping a normal blood level of the vitamin, most studies show no effect. And there are certainly no studies that show taking huge doses of vitamin D prevents any cancer.

Vitamin D supplements don’t harm, right?

That’s the appropriate question. All evidence-based medicine should weigh the evidence that a particular treatment has a benefit against any potential harm.

Right now, we know that vitamin D does two things – helps the absorption of minerals and prevents calcium homeostasis which causes bone damage. Most people in developed countries get sufficient vitamin D from sunlight or food.

And even if a person doesn’t, there are blood tests that can confirm a vitamin D deficiency and an appropriate supplementation level should be prescribed. In other words, if an issue is discovered through a real diagnosis, then a healthcare plan can be implemented to prevent any consequences of low vitamin D.

But let’s say you refuse to accept my evidence that vitamin D is more or less useless, except for those very few who have low levels. You just believe in the charlatans who are pushing megadoses of vitamin D, even if you have not been diagnosed with a chronic deficiency. I would almost say, no harm, no foul.

Except for a small little issue. There is a lot of evidence that these supplements not only have no benefit (except again in two physiological situations) but they might also actually cause harm. Here are just some of the risks of vitamin D supplements:

And I barely touched the surface of the body of research that establishes the potential dangers of excess vitamin D. And unless you have had blood tests to determine the level of vitamin D in your blood, even a small supplement may push you over into the toxic range.

I want to reiterate that people may need vitamin D supplements to get their blood levels up and to benefit from them. But just because a small dose works well, it does not mean that over-supplementation is a good idea. It isn’t.

A summary of vitamin D supplements

Without any doubt, vitamin D is necessary for human health. It is critical for the absorption of some minerals and maintaining proper calcium homeostasis, necessary for bone health.

In developed countries, vitamin D insufficiency is relatively rare. We either produce sufficient amounts of the vitamin while exposed to sunlight (not a safe way to do it)  or through a varied diet. But if one has a low level of vitamin D, it is very easy to diagnose and treat through a properly measured dose of the vitamin.

There is very little evidence that vitamin D supplements have any effect on any other medical condition. It doesn’t prevent cancers or cardiovascular disease. It does not reduce your risk of death. It doesn’t do much of anything, except in the two, very narrow, physiological aspects.

And no, if a little vitamin D helps maintain some aspects of your health, a lot will not make it better. It might make it worse.

Key citations

• Barbarawi M, Kheiri B, Zayed Y, Barbarawi O, Dhillon H, Swaid B, Yelangi A, Sundus S, Bachuwa G, Alkotob ML, Manson JE. Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis. JAMA Cardiol. 2019 Aug 1;4(8):765-776. doi: 10.1001/jamacardio.2019.1870. Erratum in: JAMA Cardiol. 2019 Nov 6;: PMID: 31215980; PMCID: PMC6584896.
• Baron JA, Barry EL, Mott LA, Rees JR, Sandler RS, Snover DC, Bostick RM, Ivanova A, Cole BF, Ahnen DJ, Beck GJ, Bresalier RS, Burke CA, Church TR, Cruz-Correa M, Figueiredo JC, Goodman M, Kim AS, Robertson DJ, Rothstein R, Shaukat A, Seabrook ME, Summers RW. A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. N Engl J Med. 2015 Oct 15;373(16):1519-30. doi: 10.1056/NEJMoa1500409. PubMed PMID: 26465985; PubMed Central PMCID: PMC4643064.
• Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014 Jan 10;1:CD007470. doi: 10.1002/14651858.CD007470.pub3. Review. PubMed PMID: 24414552.
• Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol. 2014 Apr;2(4):307-20. doi: 10.1016/S2213-8587(13)70212-2. Epub 2014 Jan 24. Review. PubMed PMID: 24703049.
• Braganza SF, Ozuah PO. Fad therapies. Pediatr Rev. 2005 Oct;26(10):371-6. Review. PubMed PMID: 16199591.
• Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA. 2019 Aug 27;322(8):736-745. doi: 10.1001/jama.2019.11889. PubMed PMID: 31454046; PubMed Central PMCID: PMC6714464.
• Cummings SR, Kiel DP, Black DM. Vitamin D Supplementation and Increased Risk of Falling – A Cautionary Tale of Vitamin Supplements Retold. JAMA Internal Med. 2016 Jan. 4. doi: 10.1001/jamainternmed.2015.7568.
• Dror AA, Morozov N, Daoud A, Namir Y, Yakir O, Shachar Y, Lifshitz M, Segal E, Fisher L, Mizrachi M, Eisenbach N, Rayan D, Gruber M, Bashkin A, Kaykov E, Barhoum M, Edelstein M, Sela E. Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness. PLoS One. 2022 Feb 3;17(2):e0263069. doi: 10.1371/journal.pone.0263069. PMID: 35113901; PMCID: PMC8812897.
• Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, Alcalá Díaz JF, López Miranda J, Bouillon R, Quesada Gomez JM. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. J Steroid Biochem Mol Biol. 2020 Oct;203:105751. doi: 10.1016/j.jsbmb.2020.105751. Epub 2020 Aug 29. PMID: 32871238; PMCID: PMC7456194.
• Jorde R, Sollid ST, Svartberg J, Schirmer H, Joakimsen RM, Njølstad I, Fuskevåg OM, Figenschau Y, Hutchinson MY. Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes. J Clin Endocrinol Metab. 2016 Apr;101(4):1647-55. doi: 10.1210/jc.2015-4013. Epub 2016 Feb 1. PMID: 26829443.
• Kawahara T, Suzuki G, Mizuno S, Inazu T, Kasagi F, Kawahara C, Okada Y, Tanaka Y. Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population. BMJ. 2022 May 25;377:e066222. doi: 10.1136/bmj-2021-066222. PMID: 35613725; PMCID: PMC9131780.
• McKenna MJ, Flynn MAT. Preventing Type 2 Diabetes With Vitamin D: Therapy Versus Supplementation. Ann Intern Med. 2023 Feb 7. doi: 10.7326/M23-0220. Epub ahead of print. PMID: 36745887.
• Nowak MA, Waclaw B. Genes, environment, and “bad luck”. Science. 2017 Mar 24;355(6331):1266-1267. doi: 10.1126/science.aam9746. PMID: 28336626.
• Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, Lichtenstein AH, Lau J, Balk EM. Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010 Mar 2;152(5):307-14. doi: 10.7326/0003-4819-152-5-201003020-00009. Review. PubMed PMID: 20194237; PubMed Central PMCID: PMC3211092.
• Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, Brodsky I, Ceglia L, Chadha C, Chatterjee R, Desouza C, Dolor R, Foreyt J, Fuss P, Ghazi A, Hsia DS, Johnson KC, Kashyap SR, Kim S, LeBlanc ES, Lewis MR, Liao E, Neff LM, Nelson J, O’Neil P, Park J, Peters A, Phillips LS, Pratley R, Raskin P, Rasouli N, Robbins D, Rosen C, Vickery EM, Staten M; D2d Research Group. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med. 2019 Aug 8;381(6):520-530. doi: 10.1056/NEJMoa1900906. Epub 2019 Jun 7. PMID: 31173679; PMCID: PMC6993875.
• Pittas AG, Kawahara T, Jorde R, Dawson-Hughes B, Vickery EM, Angellotti E, Nelson J, Trikalinos TA, Balk EM. Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials. Ann Intern Med. 2023 Feb 7. doi: 10.7326/M22-3018. Epub ahead of print. PMID: 36745886.
• Quyyumi AA, Al Mheid I. The Demise of Vitamin D for Cardiovascular Prevention. JAMA Cardiol. 2019 Jun 19;. doi: 10.1001/jamacardio.2019.1906. [Epub ahead of print] PubMed PMID: 31215963.
• Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010 May 12;303(18):1815-22. doi: 10.1001/jama.2010.594. Erratum in: JAMA. 2010 Jun 16;303(23):2357. PubMed PMID: 20460620.
• Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56. Review. PubMed PMID: 10232622.
• Vogiatzi MG, Jacobson-Dickman E, DeBoer MD; Drugs, and Therapeutics Committee of The Pediatric Endocrine Society. Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. J Clin Endocrinol Metab. 2014 Apr;99(4):1132-41. doi: 10.1210/jc.2013-3655. Epub 2014 Jan 23. Review. PubMed PMID: 24456284.
• Voutilainen A, Virtanen JK, Hantunen S, Nurmi T, Kokko P, Tuomainen TP. How competing risks affect the epidemiological relationship between vitamin D and prostate cancer incidence? A population-based study. Andrologia. 2022 Jul;54(6):e14410. doi: 10.1111/and.14410. Epub 2022 Feb 28. PMID: 35229338; PMCID: PMC9540471.