Alexander Michels, Ph.D., Research Associate, Oregon State University, Linus Pauling Science Center, Oregon, USA
“When Pauling wrote his book ‘Vitamin C and the Common Cold’ and advocated for the antiviral activity of vitamin C, there were only a few clinical studies that could be evaluated. Furthermore, scientific studies with ascorbic acid at the time were still in their infancy because the biological roles of ascorbic acid, such as its enzymatic functions and antioxidant activities, were poorly understood. In the decades since Pauling’s initial review of the field, dozens of studies have been conducted and published on the topic – many inspired by Pauling’s claims – but many still lack the level of sophistication needed to definitively study vitamin C in human subjects. Indeed, without a radical change in the experimental design of such studies and evidence from basic studies examining the potential mechanisms of action of vitamin C, we will not see scientific consensus on the effectiveness of vitamin C in the prevention and treatment of colds.
One of the issues that plague supplement trials on the common cold is fairly fundamental: What is a cold? There are a whole host of viruses that cause symptoms associated with the cold, from rhinovirus and coronaviruses to parainfluenza. It is estimated that over 200 different types of viral infections can cause cold symptoms. It is difficult to detect an effect of vitamin C in clinical studies if it is only most effective against a subset of these viral infections. Furthermore, bacterial infections, especially of the respiratory tract, can induce symptoms that closely mimic a viral infection. The effectiveness of vitamin C supplementation in the prevention or treatment of bacterial infections of the respiratory tract is currently unclear.
In 1970, Pauling noted that the mechanism of vitamin C’s effectiveness against viral infection, such as a common cold, is not yet known. He speculated that the effectiveness of ascorbic acid in providing protection against viral diseases results from its function in preventing the entry of virus particles into the cells. Even though more than 40 years have passed since Pauling wrote those lines, controlled laboratory trials with vitamin C and viral infection are exceedingly rare. As a consequence, we still do not know what dose of vitamin C might be effective at slowing or preventing many types of viral transmission in cells. However, Pauling and colleagues did identify some mechanisms by which vitamin C protected against HIV infectivity and replication in cell cultures, work that was published in the Proceedings of the National Academy of Sciences in 1990. The data collected to date suggest that supplemental vitamin C most likely works by strengthening the immune system.
These data are controversial as they are often conducted in animal models that may poorly mimic the human immune system response. Although Pauling advocated the use of multiple-gram doses of vitamin C per day for health with increasing doses to battle a cold infection, there are very few studies that attempt to follow this regimen. Doses used in clinical trials on vitamin C vary greatly and are likely a reflection of the uncertainly surrounding this field. Vitamin C is obtained from the diet, and nutritional status can play a large role in determining the amount of supplemental vitamin C that may have an influence. Similarly, comparisons are difficult to make with individuals who are deficient in vitamin C, insufficient (not yet saturating the plasma), or saturated (taking vitamin C in excess of that needed to saturate the plasma). Many studies do not make this distinction, as it is a concept few researchers fully understand.
In 2013, 70 years of clinical research on vitamin C and the cold were reviewed (1). The results showed that regular supplementation with 200 mg or more of vitamin C reduced the duration of colds, with a greater benefit in children than in adults. In addition, regular vitamin C supplementation with 250 mg to 2,000 mg/day reduced the incidence of colds, but these results did not reach statistical significance except in those individuals under heavy physical stress (e.g., marathon runners, skiers, or soldiers in subarctic conditions). In conclusion, regular daily supplementation appears to be very important in reducing the severity and duration of colds. It is certainly possible that continuous supplementation with vitamin C for long periods prior to a viral challenge is important to ensure optimal immune system response, which takes time.
A Japanese study deserves special mention in this regard (2). This study was a five-year trial designed to evaluate the effect of a daily dose of a low (50 mg) or high (500 mg) amount of vitamin C on the development of gastric cancer among 244 subjects. The researchers evaluated the effects of the vitamin C supplements on the common cold at the completion of the study and concluded that the risk of contracting three or more colds in the five-year period was decreased by 66% through the daily intake of the high-dose vitamin C supplement versus taking the lower dose of vitamin C. However, it is important to note that these individuals in Japan were consuming a significant amount of vitamin C in the diet before the study started. Plasma measurements of ascorbic acid showed that these individuals were not deficient in the vitamin, and many had likely achieved vitamin C saturation of their blood. This could be why it took approximately two to three years of supplementation before the difference in cold incidence was apparent, covering many cold seasons in which subjects were likely exposed to repeated attacks by cold viruses. It is also possible that the effect of vitamin C supplementation is more effective against repeat infections, as it supports an activated immune system, rather than the first cold encountered after supplementation has begun.
The importance of plasma saturation was touched upon earlier this year in a study (3), which was not included in the review (1) but deserves special attention due to its sophisticated approach to the subject of vitamin C insufficiency. Unlike the majority of studies on vitamin C supplementation and the cold, including the Japanese paper described above, this study was limited to men who all had plasma vitamin C below 45 μM and were considered to have insufficient vitamin C status. During the eight-week trial, the vitamin C-supplemented individuals received 1,000 mg/day. The vitamin C-supplemented subjects (but not those receiving placebo supplements) demonstrated elevated plasma ascorbic acid levels to near saturation. By the end of the study, the researchers found that subjects taking vitamin C supplements were 40% less likely to get a cold, and the duration of colds was decreased nearly 60%. In effect, this paper suggested that consuming a diet with inadequate vitamin C is possibly a factor in determining cold susceptibility. A greater and more immediate benefit on the common cold could be seen in individuals who correct inadequate vitamin C status with supplementation.
The Linus Pauling Institute recommends that all adults consume at least 400 mg/day of vitamin C, which is a dose that will likely achieve plasma saturation in the population. It’s been proposed that vitamin C improves symptoms due to its antihistamine effect. While previous studies showed that vitamin C doses of 2,000 mg/day decreased blood histamine levels by 60% (4), doses of 1,000 mg/day in the recent study (3) had no effect on histamine levels in blood. It should be noted that supplementation taken only after the cold symptoms have begun, such as consuming vitamin C supplements at the first sign of a sore throat or runny nose, seems to have little appreciable effect. The beneficial effects of vitamin C supplementation on the common cold are more apparent when vitamin C is taken on a regular basis, when a cold is present or not, as Linus Pauling advocated. This is likely because of the amount of time taken for vitamin C to have its full effect on the immune system, as mentioned above. Despite some claims to the contrary, the clinical evidence does support an effect of vitamin C supplements against the common cold, similar to Pauling’s assessment 44 years ago. However, more rigorously-controlled studies are needed to solidify this association.”
Based on: Michels A. Vitamin C and the Common cold: Current Status. The Linus Pauling Institute. Research Newsletter. Fall/Winter 2014.