The 1970s advice of two-time Nobel Prize Winner Linus Pauling to take megadoses of vitamin C to combat everything from colds to cancer may not have been entirely innocuous. A Swedish study links regular supplements of vitamin C to an increased risk of men getting kidney stones. The association is not a causal relationship, but for safety’s sake, consumers should refrain from taking high doses, says Agneta Åkesson, principal author of the study, Karolinska Institutet, Stockholm.
The findings of the large prospective study appear in JAMA Internal Medicine. It comprises 23 355 men who were followed for 11 years. The men had not previously had kidney stone, and had either not used supplements at all (n=22 448), or only taken supplements of vitamin C (n=907).
The researchers had already excluded men who had had the disease previously as well as 12 873 men who took supplements other than vitamin C, from a larger study group of 48 850 men.
During the study period, 436 men got kidney stones, requiring hospital care. Then, the researchers compared the risk of men who took vitamin C supplements of having a kidney stone to the risk for men not taking them. The same analysis was made for men taking multivitamins – supplements which included smaller amounts of vitamin C.
Risk almost doubled
The risk of kidney stones in the men who took vitamin C supplements regularly almost doubled (relative risk 1.95, 95% CI, 1.35–2.81) and increased for those who took one or more pills daily compared to those who took less.
However, no connection was seen between intake of multivitamins and kidney stones. Furthermore, the findings could not be translated to applying to women, for whom the risk of kidney stone is considerably less. Neither does it apply to the vitamin C found in food such as vegetables, potatoes and fruit. In Sweden, the recommended daily vitamin C level is 75 mg. Supplements, however, typically contain vitamin C levels of 1000 mg per pill.
Pauling´s theories discredited
The American Nobel Prize winner Linus Pauling, is perhaps best known to the general public during the 60s and 70s for his forceful promotion of megadoses of vitamin C to combat both colds and cancer, and later also atherosclerosis. However, these claims were founded on studies, which were subsequently disqualified by other scientists, and by his death in 1994, the theories about large doses of vitamin C had by and large been discredited.
Pauling’s Institute at the University of Oregon is still alive and well. In a text (last updated in November 2009), Administrative Officer Stephen Lawson at the Institute specifically addresses the kidney stone question, citing some studies allegedly acquitting the substance and concluding that: “…the concern about the role of vitamin C in kidney stone formation, a source of speculation for several decades, appears to be no longer justified.” In another article on the website, this one anonymous, updated June 2006, on cancer and vitamin C, a peripheral finding in a study warrants the concluding comment: “Only minor adverse effects were observed, except for one patient with a prior history of kidney stones who developed one after 13 days of therapy, suggesting that high-dose intravenous vitamin C is generally safe unless there is a predisposition to kidney stone formation.”
No evidence of a causal connection
The Swedish study was led by Dr. Agneta Åkesson, Institute of Environmental Medicine, Karolinska Institutet, who explained to I C that scientists regularly seek to eliminate or minimize possible confounding factors behind their results. Thus, men with a prior history of kidney stones were excluded from the current study. Nevertheless, we still do not know if vitamin C causes kidney stones.
– Observational epidemiological studies of this kind are by definition unable to resolve issues of causal links, instead indicating statistical associations between phenomena seen in the patient cohort under study – using vitamin C supplements – and kidney stone events in the patient registry.
However, other types of data offer some support that kidney stone may arise this way. In the study, the researchers refer to an as yet unpublished Stockholm study of 3 176 men with kidney stones treated with shockwave (sound) therapy, where calcium oxalate proved to be the main constituent of 92.6 percent of kidney stones. High vitamin C doses may be eliminated in urine as oxalate, responsible for a large part of calcium oxalate formation.
Refrain from large doses
Agneta Åkesson emphasizes that the results from Karolinska Institutet must be replicated by other researchers in order to gain greater clarity. Neither can the researchers speculate on whether the risks for women might be as great as for men. But the study is important, she stresses. There is little research in the area, many people take supplements, and there is a widespread belief in high doses of vitamin C being harmless. Meanwhile, her advice is to refrain from taking large doses.
– We are dealing with serious side effects of something which by no means can be said to be life-supportive medicine or the like. And given the lack of well-documented benefits of taking high doses of vitamin C in the form of supplements, it might be wisest not to, especially if you have had a kidney stone before, Agneta Åkesson says..
David Finer
Laura D K Thomas, Carl-Gustaf Elinder, Hans-Göran Tiselius, Alicja Wolk, Agneta Åkesson. Ascorbic acid supplements and kidney stone incidence among men: A prospective study. JAMA Internal Medicine, online first 4 February 2013.
Karolinska Institutet. Press release (in Swedish) 2013-02-05. Koppling mellan C-vitamintillskott och ökad risk för njursten. (Link between vitamin C supplements and increased risk of kidney stone).
Tags: causality, David Finer, Karolinska Institutet, kidney, observational study, supplements, vitamin C
