Vitamin C—Can a Tablet a Day Keep Colds Away?

January 1999; Volume 2: 1-3

By Barak Gaster, MD

Winter means one thing for most primary care physicians. Colds, colds, colds. And if you’re like me, it also means an almost ritualistic, somewhat paranoid, chap-inducing commitment to hand washing. It’s a desperate attempt to achieve the impossible—to spend each and every day surrounded by upper respiratory infections while not catching one myself.

As every "winter care" patient handout says, hand washing is the only sure-fire way to prevent colds. Or is it? If you remember Linus Pauling, not only as a Nobel-winning chemist but also as a crusader, you’re also probably aware of one of the oldest controversies in evidence-based medicine: Can vitamin C prevent the common cold? Twenty-six years after the publication of Pauling’s book Vitamin C and the Common Cold, the answer is quite clear. High doses of vitamin C do not prevent colds, although they may slightly lessen their severity and duration.

Pharmacology and Mechanism of Action

Vitamin C (ascorbic acid) is an essential, water-soluble vitamin. It is found in high quantities in citrus fruits, strawberries, kiwi fruit, and tomatoes, and in lower quantities in potatoes and green leafy vegetables.

It is required for collagen formation and tissue repair and also plays a role in the metabolism of carbohydrates and the synthesis of proteins. It is this latter function that has been most widely linked to fighting infection, although specific effects of vitamin C on the immune system are unknown. Vitamin C has been shown to have both antioxidant and pro-oxidant effects.1

Vitamin C is well absorbed after oral dosing, although its bioavailability drops off considerably at doses greater than 1.5 g. At high serum concentrations, it is excreted unchanged in the urine. Serum levels tend to plateau at doses greater than 3 g per day.2 Although vitamin C’s clearance is proportional to its concentration at lower serum levels, once high serum levels are achieved, its t½ is long and relatively constant (about 14 days). High intake may stimulate the metabolism of vitamin C so that relative deficiency may occur if long-term administration of megadoses is abruptly discontinued.3

Clinical Studies

Over the past 25 years, there have been more than 60 randomized, controlled trials of vitamin C to prevent and treat the common cold. A recent meta-analysis, published as part of the Cochrane Library Project, pooled the data from 21 of the best of these trials, including more than 4000 subjects who had experienced a total of 5438 upper respiratory infections.4

The main conclusion of this meta-analysis was that vitamin C had no benefit on the incidence of the common cold, but that it did have a small, consistent benefit in decreasing the duration and severity of symptoms. This benefit was very modest, however, averaging no more than 0.5 symptom days per cold episode, or about 8% of symptom days.

This small benefit was seen equally in studies that used prophylactic treatment throughout the winter months and in those that simply initiated high doses at the first signs of a cold (abortive therapy). There was also no clear evidence that one dosing regimen was better than another, although there was some suggestion from the abortive therapy trials that doses of 1 g or higher may be more effective than lower doses.

In the trial that received the highest methodological quality score in the Cochrane review, Anderson et al randomized 818 adults to take either 1 g of vitamin C daily for three months plus 4 g for the first three days of any illness or to take an identical number of placebo tablets.5 The average number of cold episodes was 1.4 for those taking vitamin C vs. 1.5 for those taking placebo, a difference that was not significant. Those taking vitamin C had 21% fewer days of missed work (P < 0.05).

This same group of researchers from Toronto, Canada went on to publish two large follow-up studies to this one.6,7 All three studies came to similar conclusions.

Dosage

Most trials of prophylactic therapy have used 1 g once daily of vitamin C and most trials of abortive therapy have used 2 g or more per day divided into two-four equal doses. The ideal frequency of dosing has not been well-studied, although daily dosing has been shown to raise basal serum levels over time. In abortive therapy, where the objective is to raise serum levels very quickly, bid or tid dosing is probably appropriate. Cigarette smokers should use somewhat higher doses since smoking increases the metabolic turnover of vitamin C.8

The Reference Daily Intake (RDI), formerly the Recommended Daily Allowance (RDA), of vitamin C is 60 mg per day. An eight-ounce glass of orange juice contains about 100 mg of vitamin C.

Formulation

Vitamin C tablets come most commonly in 500 mg sizes. There is no difference in biologic activity or bioavailability between vitamin supplements that claim to be "natural" and those that are synthesized chemically. Likewise, because vitamin C is so readily absorbed in any form, there is no indication that powders or citrus fruits have an advantage over tablets.

Adverse Effects

Although mild side effects have been reported from doses of vitamin C greater than 1 g,3 the medication appears to have been very well tolerated in the randomized trials. A few subjects report experiencing nausea, heartburn, gas, or diarrhea, especially with doses over 2 g, but they represent a very small percentage of the total number of study subjects.

About 5% of individuals who take more than 1000 mg per day of vitamin C on a regular basis will develop hyperoxaluria, which could lead to kidney stones. Caution should be used in patients with a history of kidney stones or renal dysfunction.

Interactions

Vitamin C has been shown to facilitate the absorption of iron and to decrease the excretion of aspirin. There are conflicting reports of vitamin C’s effect on prothrombin times in patients taking warfarin. Vitamin C can cause false negative results in both stool occult blood testing and in routine urine dipstick tests for glucose.

Conclusion

There is no evidence that vitamin C can prevent the common cold. Almost all studies, however, have demonstrated a small decrease in the duration of cold symptoms with either daily dosing through the winter months or with abortive therapy at the first signs of a cold.

Recommendation

Given the benefit of slightly decreasing the time missed from work and the apparent safety and low cost of vitamin C, I would recommend abortive therapy for motivated patients, especially for those whom you suspect have a low dietary intake of vitamin C, such as college students and the elderly.9,10

Dr. Gaster is an Acting Assistant Professor of Medicine at the University of Washington in Seattle.

References

1. Anonymous. Vitamin supplements. Med Lett Drug Ther 1998;40:75-77.

2. Angel J, et al. Effect of oral administration of large quantities of ascorbic acid on blood levels and urinary excretion of ascorbic acid in healthy men. Int J Vitam Nutr Res 1975;45:237-243.

3. Ascorbic Acid. In: Drug Information. 40th ed. Bethesda, Md: American Hospital Formulary Service; 1998:3013.

4. Douglas RM, et al. Vitamin C for the common cold. Available in The Cochrane Library [database on disk and CD-ROM]. The Cochrane Collaboration; Issue 3. Oxford: Update Software; 1998.

5. Anderson TW, et al. Vitamin C and the common cold: A double-blind trial. Can Med Assoc J 1972;107:503-508.

6. Anderson TW, et al. The effect on winter illness of large doses of vitamin C. Can Med Assoc J 1974;111:31-36.

7. Anderson TW, et al. Winter illness and vitamin C: The effect of relatively low doses. Can Med Assoc J 1975;112:823-826.

8. Kallner AB, et al. On the requirements of ascorbic acid in man: Steady-state turnover and body pool in smokers. Am J Clin Nutr 1981;34:1347-1355.

9. Johnston CS, et al. Vitamin C status of a campus population: College students get a C minus. J Am Coll Health 1998;46:209-213.

10. Pfitzenmeyer P, et al. Vitamin B6 and vitamin C status in elderly patients with infections during hospitalization. Ann Nutr Metab 1997;41:344-352.