More on hydroxychloroquine

John Gee was kind enough to forward this to me:

This is a good look at the science, and sort of echoes what I’ve been talking about on this blog.

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Have the French cured COVID-19? Not so fast

There has recently been suggestion that a combination of two medications (azithromycin, a macrolide antibiotic) and hydroxychloroquine (a drug which targets malaria parasites, and which is also used in rheumatic disease like rheumatoid arthritis and lupus) may help COVID-19.

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So, doc, should I take vitamins?

People often get told they should take vitamins for the health, or to feel better. People often take vitamin supplements. Much less often, they ask me if they should take vitamins.

As is often the case, the answer to this question isn’t a simple yes or no answer.

Note that everything I say here presumes at least two things:

  • the patient lives in the developed world and has a reasonably healthy, balanced diet.
  • the patient is healthy and does not have a specific disease that either requires supplementation or for which supplementation could cause problems. Check with your doctor about your own situation.

I have included links to reliable websites for further information, recommended doses, etc.

Part 1 – Worthwhile supplementation

Folic acid

There is substantial evidence that women of childbearing age should take folic acid. This reduces the development of neural tube defects (e.g., spina bifida) and cleft lip/palate. There is the most benefit if the mother-to-be is taking the folic acid before she conceives. So, if you are sexually active and aren’t using birth control, taking folic acid is a good practice.

Vitamin D

For people in northern latitudes, like Alberta, we often lack adequate sunshine, which is necessary for the body’s synthesis of Vitamin D.

Vitamin D deficiency can be detected by lab testing, but given that it is a relatively common problem in Alberta, it isn’t recommended routinely. You can just take supplementation. Milk is supplemented with it, but people who don’t eat a lot of dairy may need other sources, including supplementation.


Women’s peak bone mass is at about age 25; adequate calcium intake is necessary to prevent problems later in like life osteoporosis and fragility fractures. As patients age, they may also benefit from supplementation to make sure they reach proper calcium targets. There’s also some evidence for endometrial cancer prevention.


Iron supplementation may be needed for people if they have low iron. This is a bit of an exception to the “healthy patient” rule I pointed out above. Women who menstruate are most at risk. Once you are iron deficient, it is essentially impossible to eat enough iron from food sources to catch up, so you will be anemic forever without supplementation.

Summary: Aside from these relatively few exceptions, there is very little evidence for help using vitamin supplementation in healthy, well-nourished populations. We explore a few of the details in the next section.

Part 2 – Cases in which supplementation has not shown any effect

  • A recent (2013) meta-analysis of multi-vitamin and multi-mineral supplements showed no change in death rates with supplementation.[1]
  • Vitamin supplementation did not affect all-cause mortality, cancer rate, or cardiovascular disease in the Women’s Health Study: “the study provided convincing evidence that multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease, or total mortality in postmenopausal women.”[2]
  • No change in cancer rate for women over age 40 taking B6, B12, and folic acid.[3]
  • No change in cancer rate for men using Vitamin E, Vitamin C, or a daily multivitamin.[4]
  • Vitamin E had no effect on rates of heart attack, while taking daily aspirin did.[5]
  • Vitamin C has no effect on whether you catch the common cold. It may shorten the duration of symptoms slightly, but the effect is so slight that it probably doesn’t have much to notice or use in clinical practice.[6] (This was an analysis of 30 trials containing 11,350 people.)
  • Vitamins A, C, beta-carotene, selenium (all are anti-oxidants) and folic acid, B6, and B12 are all shown no influence on the progression of coronary artery disease.[7]

Part 3 – Cases in which supplementation has been shown to cause harm

In randomized controlled trials, the following harmful effects have been observed:

  • Patients taking cholesterol-lowering drugs alone had lower risks of heart attack and a decrease in clogged arteries compared to patients taking such drugs with Vitamins E, C, beta-carotene, and selenium (all anti-oxidants). Thus, the anti-oxidants likely blocked some of the benefit of these medications.[8]
  • Use of Vitamin E supplementation (400 IU) showed a 17% increase in prostate cancer.[9] Combining selenium with Vitamin E showed no change in cancer rates.[10]
  • Use of Vitamin E raised the risk of hemorrhagic stroke (bleeding) by 22%, while decreasing the risk for embolic (small clot) stroke by 10% in a set of 118,765 patients.
    • This equals one bleeding stroke for every 1,250 people taking vitamin E, and prevention of one clot-based stroke every 476 people.
    • Bleeding is usually far more serious, and causes worse outcomes, so Vitamin E is probably a bad bet on balance.[11]
    • High vitamin A use linked to higher hip fractures in women.[12]
  • Using Vitamin C and E in women with coronary artery disease resulted in higher rates of both death and non-fatal heart attack.[13]
  • Women with kidney disease from diabetes had higher rates of heart attack, continuing kidney failure, and stroke when taking folic acid, vitamin B6, and vitamin B12.[14]
    • This was despite a lower homocysteine level (which has a link to cardiovascular disease). Thus the supposed protective effect of lower homocysteine (if any) was outweighed by some other factor(s).
  • Use of Vitamin C supplementation showed a rise in the risk of cataracts in women (no men were studied in this trial).[15]
  • Vitamin supplementation may increase the risk of breast cancer in women.[16]


The Medical Letter on Drugs and Therapeutics is a well-regarded resource. They accept no advertising, and are strictly evidence-based. Their conclusion in 2005 for recommendations included:

  • Folic acid supplementation, with possible addition of Vit D and B12 in the elderly [I would add that northern latitudes like Canada should probably think about Vit D for all members of the population.]
  • Vitamin C shows no evidence for prevention of any disease.
  • Beta-carotene should not be supplemented.
  • Women should avoid Vitamin A supplementation during pregnancy and after menopause.
  • Balanced diets are probably better than supplementation.[17]

One editorial hoped that

the exuberant use of vitamin-mineral supplements may be tempered by such findings, which carefully separate facts from faith.[18]

One can hope. But, people who sell and push supplements have a vested interest in continuing to sell their wares. And we are often inclined to think, “Well, at least it can’t hurt.” But, we must remember that taking anything with possible good effects opens us up to possible bad effects.

There is an irony too in that doctors are sometimes accused of being “pill pushers,” but then get in trouble when we encourage people to get their nutrients from a healthy, balanced diet (which has shown benefits for things like cancer and heart disease) rather than just popping a pill.

But, now you at least know why your doctor probably isn’t advising you to take much by way of vitamin supplements if you’re healthy—there is a lot of evidence, on hundreds of thousands of patients in randomized placebo-controlled trials, that shows that it simply doesn’t help. And, sometimes it can harm.

Caveat emptor—let the buyer beware.

Useful links

[1] Helen Macpherson et al., “Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials,” American Journal of Clinical Nutrition 97/2 (February 2013): 437-444.

[2] ML Neuhauser, “Multivitamin use and risk of cancer and cardiovascular disease in the Women’s Health Initiative cohorts,” Archives of Internal Medicine 169 (2009):294-304.

[4] J Muntwyler et al., “Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality,” Archives of Internal Medicine 162 (2002):1472-1476.

[6]  RM Douglas et al., “Vitamin C for preventing and treating the common cold,” Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD000980.

[7] J Bleys et al., “Vitamin-mineral supplementation and the progression of atherosclerosis: A meta-analysis of randomized, controlled trials,”  American Journal of Clinical Nutrition 84 (2006):880-887.

[8] [BG Brown, “Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease,” New England Journal of Medicine 345 (2001): 1583-1592.

[10]Review of prostate cancer prevention study shows no benefit for use of selenium and vitamin E supplements,” (27 October 2008) NCI news release.

[12] D Feskanich and others, “Vitamin A intake and hip fractures among postmenopausal women,” JAMA 287 (2002):47-54.

[14] AA House et al., “Effect of B-vitamin on progression of diabetic nephropathy,” JAMA (2010) 303:1603-1609.

[15] S Rautiainen et al., “Vitamin C supplements and the risk of age-related cataract: a population-based prospective cohort study in women,” (18 November 2009) American Journal of Clinical Nutrition.

[16] Susanna C Larsson et al., “Multivitamin use and breast cancer incidence in a prospective cohort of Swedish women,” American Journal of Clinical Nutrition (May 2010).

[17] “Vitamin supplements: Who should take them and who should not,” The Medical Letter 47 (2005): 57-58.