Funnily enough, considering its many purported benefits, vitamin C (ascorbic acid) is one of the vitamins that doctors are least likely to prescribe to patients. Vitamin A is given to all small children in many countries, as is vitamin D. Vitamin D is of course also frequently prescribed to patients with osteoporosis. Vitamin B1 (thiamin) is regularly given to alcoholics, to prevent Wernicke-Korsakoff disease. B3 (niacin) was for years given to people with heart disease, on the assumption that it would be useful because it lowers LDL (“bad cholesterol”) and raises HDL (“good cholesterol”). It has since fallen out of favour, after multiple trials have failed to show benefit, but I still see the odd patient who takes it on a daily basis, “for their heart”. The same goes for vitamin E. B9 (folic acid) is recommended for all women seeking to get pregnant, because it decreases the risk of spina bifida in the child, and is also frequently prescribed to patients with anemia, as is B12 (cobalamin). I’ve seen all these other vitamins many times in patients’ charts. But not once have I ever seen vitamin C.
The one medical condition that vitamin C is widely agreed to be useful for is scurvy, common among 18th century sailors, due to the fact that their diet consisted almost entirely of dried meat and biscuits. Although vitamin C is present in small quantities in fresh meat, it is sensitive enough that it is destroyed by the process of drying. Scurvy is vanishingly rare today. The fact that even people on a “carnivore” diet, who eat nothing but meat, can go years without ever developing the slightest sign of scurvy, suggests that the amount of the vitamin needed to prevent the disease is tiny, far lower than the Recommended Daily Intake (RDA) of 90 mg for men and 75 mg for women.
The idea that vitamin C has a lot of additional beneficial health effects, beyond it’s ability to prevent scurvy, largely originates with Linus Pauling, the two time Nobel prize winner who developed an almost pathological obsession with the vitamin during his last few decades of life. He argued that it was effective against heart disease, cancer, and infection – in other words, most of the major causes of premature death!
A while back, I looked in to the claim that vitamin C is effective against upper respiratory tract infections. My conclusion back then, based on a meta-analysis produced by the Cochrane collaboration, was that it does appear to slightly shorten the duration, but not the frequency, of respiratory infections. However, that conclusion was based almost entirely on old studies, carried out in the 70’s and 80’s, before there was a general expectation that trials be pre-registered at clinicaltrials.gov. What that means is that there is a significant risk of publication bias, i.e. that trials that showed benefit were published, while those that failed to show benefit weren’t, and that this explains the entire benefit seen. Even if the effect is real, it’s questionable whether it’s worth taking a supplement every day of the year in order to shorten the duration of any colds you experience by one day.
In this article I’m going to focus on another of the three major claims about vitamin C, that it protects against heart disease. This has been the subject of two large randomized controlled trials. The first, the Womens Antioxidant Cardiovascular Study, was published in the Archives of Internal Medicine in 2007. This was a randomized double-blind placebo-controlled study that tested the effect of vitamin C supplements on women at high risk of cardiovascular disease. It was carried out in the United States and funded by the National Institutes of Health.
In order to be included in the study, apart from being a woman, you had to be over the age of 40 and either have a history of heart disease or fulfill at least three of the following risk factors for heart disease: high blood pressure, smoking, obesity, high cholesterol, type 2 diabetes, or parental history of heart disease. 4,087 women were randomized to receive the vitamin C supplement, while 4,084 were randomized to placebo. The average age of the participants was 61 years and average BMI was 30.3 (the cut-off for obesity is 30, so the women were mostly overweight or obese).
The dose of vitamin C given was 500 mg. Is this a high dose or a low dose?
As mentioned, the RDA for vitamin C is 75-90 mg, but the fact that people on a carnivore diet can get by on as little as 10 mg without developing scurvy suggests that the RDA might actually be set much higher than necessary. 500 mg is about the amount of vitamin C you would get from eating 80 apples, or six lemons. From that perspective, 500 mg seems like a very high dose. It is certainly much higher than our ancestors would have gotten from their diet on a daily basis. The average amount of vitamin C consumed by an adult American today is around 100 mg per day.
There are of course those who argue that much higher doses are necessary. By the end of his life, Linus Pauling was reportedly consuming several thousand mg per day of vitamin C. However, Pauling died in the early nineties, and research done after his death has found that 400 mg is enough to achieve saturation in the body, at least in healthy young adults, at which point any excess consumption beyond that will simply be peed out. A higher dose might be necessary for elderly people to reach saturation, but on the other hand, there is no evidence that saturation is necessary in order to achieve the full benefit from vitamin C (and when it comes to scurvy, we know it is avoided at a fraction of the dose necessary for saturation). So 500 mg should be enough to see at least some beneficial effect, if one exists, and should be enough to reach tissue saturation and thus the maximal benefit possible in most people.
Let’s get back to the study. The women were followed for an average of 9.4 years, which is an impressively long follow-up. Complicance was good, with 76% reporting taking their supplements as directed at least two thirds of the time at the four year mark. 68% were still doing so at the eight year mark.
So, what were the results?
Overall, 206 women died of cardiovascular disease in the vitamin C group, compared to 189 in the placebo group. This represents a 9% increased relative risk of cardiovascular death in the group treated with vitamin C. The difference was however not statistically significant. Nor was there any statistically significant difference between the groups in terms of frequency of heart attacks or strokes. Overall mortality was also similar, with 504 dead in the vitamin C group, compared with 491 in the placebo group.
In other words, there was no meaningful difference in outcomes between the groups in any of the variables studied. Considering the enormous size of the study (over 8,000 people) and the long follow-up time (over nine years), we can be pretty sure that means that a vitamin C supplement doesn’t impact risk of heart disease or overall longevity in any meaningful way, at least not in overweight middle-aged women.
Let’s move on to the next study, which was published in JAMA in 2008. This was the Physicians’ Health Study II. Like the previous study, it was big. And, like the previous study, it was randomized, double-blind, and placebo-controlled. All the good words I like to hear. 14,641 male physicians over the age of 50 were followed for an average of eight years. 7,329 of these received vitamin C, while 7,312 received placebo. The dose given was the same as in the previous study, 500 mg per day. The study was carried out in the US, and funded by the National Institutes of Health and BASF (a German chemical company that at the time sold vitamin C supplements).
Unlike the previous study, there was no requirement that the participants have a high cardiovascular disease risk to be included in the trial, so while the previous trial was mainly looking at secondary prevention (decreasing risk of further events in those who already have cardiovascular disease), this one was instead mainly looking at primary prevention (preventing cardiovascular disease from developing in the first place).
The average age of the participants at the start of the trial was 64 years, and average BMI was 26 (the cut-off for overweight is 25, so these men were very slightly overweight, on average). Only 5% had a history of cardiovascular disease and over 60% reported exercising at least once a week, so this was a pretty healthy group overall, although 42% had a history of high blood pressure.
As in the previous study, compliance was good. 78% of the participants were still taking the supplements as directed more than two thirds of the time at the four year mark, and 71% were still doing so at the eight year mark.
Ok, let’s get to the results.
There were 256 deaths from cardiovascular disease in the vitamin C group, compared with 253 in the placebo group. This represents a 2% increased relative risk of dying of heart disease among those treated with vitamin C, although, needless to say, the difference wasn’t statistically significant. Overall, 857 people died in the vitamin C group, while 804 died in the placebo group. As with the previous study, there were no statistically significant differences in any of the variables studied.
In other words, the results of the second study line up perfectly with the results of the first study. What can we conclude?
The best available evidence at this point in time suggests that Vitamin C does not have any beneficial effect on heart disease, or on overall longevity for that matter. Considering that these were very big, high quality studies, I think the conclusion can be considered definitive. One could always argue that a beneficial effect would have been seen with a much higher dose, but considering that tissue saturation is usually reached at just 400 mg, I doubt it. If anything, the signal from these two studies is that increasing the dose further might be harmful, since there were actually more deaths in the vitamin C group than in the placebo group in both studies.