Why Vitamin C Intake Should Not Be a Primary Focus of Cardiovascular Disease Prevention

A popular theory exists, proposed by respected scientists like Linus Pauling and Matthias Rath, that insufficient vitamin C intake is one of the main factors driving cardiovascular disease. But if low vitamin C intake is a significant driver of atherosclerosis and heart disease, where is the supportive evidence?

One variation of this theory is that high levels of uric acid cause heart disease and vitamin C is of central importance in lowering uric acid. Studies show vitamin C does indeed reduce uric acid levels (1) and greater vitamin C intake is associated with lower uric acid levels (2), so that aspect of the theory works. However, if uric acid causes heart disease, why did the Framingham Heart Study (3) fail to find a connection between uric acid levels and heart disease death? Why did the NHANES study (4) also fail to find such a connection in men? Why did the Tecumseh Community Health Study (6) find uric acid was not higher in people with coronary heart disease?

What about the effects of supplementing vitamin C? If low vitamin C intake brings about heart disease, shouldn’t supplementing vitamin C bring about a decrease in the rates of heart disease?

The ASAP study (6), at first glance, seems to support the beneficial effect of vitamin C on heart disease. It found that supplementing vitamin C and E slowed atherosclerosis progression significantly in men and non-significantly in women.

Atherosclerosis progression, determined by CCA-IMT, in both groups.
Atherosclerosis progression, determined by CCA-IMT, in both groups.

However, because this was a trial on vitamin C and E, rather than vitamin C alone, we have to consider whether this effect could have been mediated by the vitamin E.

Sure enough, there is evidence that this is possible. The SPACE trial (7) found that supplementing vitamin E reduced the rates of cardiovascular events and myocardial infarctions in heamodialysis patients with a history of cardiovascular disease. The CHAOS trial (9) gave subjects with coronary atherosclerosis either a vitamin E supplement or a placebo and noted a significant reduction in the rates of myocardial infarction in the group given vitamin E. Finally, the Women’s Health Study (8) found that vitamin E supplementation reduced cardiovascular disease mortality in women.

Picture 10
Incidence of major cardiovascular event by group (dark line=vitamin E, lighter line=placebo)

Does this mean vitamin C isn’t beneficial to atherosclerosis? Of course not, but it does show their may be serious limitations of the ASAP study in demonstrating the benefits of vitamin C on atherosclerosis progression.

Furthermore, an often unreported fact about the ASAP study is that the subjects in the supplementation group, while experiencing decreased atherosclerosis progression, also died twice as much as the placebo group. This effect wasn’t statistically significant, but it should cause some reservations when citing this study to support the benefits of vitamin C.

Additionally, the WAVE trial (10) had a different conclusion than the ASAP study. It found that post menopausal women given a supplement of vitamin C and vitamin E experienced greater coronary lesion progression than the placebo group, though this effect was not quite significant. The antioxidant group also had higher all cause mortality and higher mortality from cardiovascular deaths (P=0.047 and P=0.09 respectively).

A number of studies have also been performed which used combined vitamin and mineral supplements, including vitamin C, and failed to find these supplements had heart disease benefits. In the SU.VI.MAX Study (11) supplementing vitamin C, vitamin E, beta carotene, selenium, and zinc for a median time of 7.5 years produced no differences in the rates of ischemic cardiovascular disease. The MRC/BHF Heart Protection Study (12) was another trial testing vitamin C and E against a placebo and found no differences in the rates of heart attack or stroke between the two groups. Finally, the Physicians’ Health Study II (13) found that a vitamin supplement containing vitamin C did not reduce the risk of major cardiovascular events, myocardial infarction, stroke, or cardiovascular disease mortality after a median follow up of over 11 years.

As far as I’m aware only two studies test the effects of vitamin C alone on actual cardiovascular disease events, one on women and the other on men. The WACS trail (14), failed to find a benefits of 500 mg of the vitamin on the rates of heart attack, stroke, coronary revascularization, or cardiovascular disease deaths compared to placebo:

Picture 5
Incidence of cardiovascular disease between the vitamin C and placebo groups were….the exact same!

The Physicians Health Study II (15) likewise found a daily 500mg vitamin supplement produced no apparent cardiovascular benefit compared to a placebo:

Again, the rates of CVD events between the vitamin C and placebo group were the exact same.
Again, the rates of CVD events between the vitamin C and placebo group were the exact same.

Ultimately, we must acknowledge that there is a lack of evidence supporting the proposed central importance of vitamin C in preventing heart disease. Vitamin C is likely beneficial in preventing cardiovascular disease, especially when its deficiency is avoided, but it is doubtful that vitamin C is a central player in preventing atherosclerosis and there does not exist compelling reason to aim for >1000 mg megadose intakes of this vitamin to prevent heart attacks.

References:

1. http://onlinelibrary.wiley.com/doi/10.1002/art.21105/full
2. http://www.jrheum.org/content/35/9/1853.short
3. http://europepmc.org/abstract/MED/10391820
4. http://aje.oxfordjournals.org/content/141/7/637.short
5. http://www.sciencedirect.com/science/article/pii/000293436890168X
6. http://www.ncbi.nlm.nih.gov/pubmed/12600905
7. http://www.ncbi.nlm.nih.gov/pubmed/11072938
8. http://www.ncbi.nlm.nih.gov/pubmed/15998891
9. http://www.ncbi.nlm.nih.gov/pubmed/8622332
10. http://www.ncbi.nlm.nih.gov/pubmed/12435256
11. http://www.ncbi.nlm.nih.gov/pubmed/15557412
12. http://www.ncbi.nlm.nih.gov/pubmed/12114037
13. http://jama.jamanetwork.com/article.aspx?articleid=1389615
14. http://www.ncbi.nlm.nih.gov/pubmed/17698683
15. http://jama.jamanetwork.com/article.aspx?articleid=1028653

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