Straight Dope on Medicine: Vitamin C

Linus Pauling won two Nobel prizes: one in chemistry and one in peace. Extraordinaire!

No one does this, and no one has done it save Pauling.

At the time of his award, Pauling was dutifully teaching and conducting research at Caltech. His seminal work involved delineating the nature of the chemical bond. Whenever you see fancy structures, his contribution is the connecting dashes between atoms.

Toward the end of his life, he became enamored with vitamin C, ascorbic acid. No, he did not win a Nobel prize for this affection of his, but he became renowned for pitching it for just about everything.[i]

L-Ascorbic acid, more familiarly known as vitamin C, is widely found in nature. It is particularly abundant in citrus and stone fruits, berries (especially acerola), peppers, and green vegetables.[ii]

Two Nobel Prizes were awarded for the discovery of vitamin C.

In 1928, the legendary Hungarian biochemist Albert Szent-Györgyi, then a student at the University of Cambridge (UK), extracted what he called “hexuronic acid” from the adrenal cortices of oxen. He and colleague Walter Norman Haworth later isolated the molecule from lemons and paprika. Szent-Györgyi was awarded the Nobel Prize in Physiology or Medicine in 1937; the same year, Haworth received the prize in chemistry.

Vitamin C, as ascorbic acid or its salts, is essential for human nutrition. It is a cofactor that permits several enzymes to function properly; it plays a role in the immune system; and it is an antioxidant. Vitamin C deficiency causes the disease scurvy, which, if not treated, results in decreased red blood cell production and excessive bleeding. In extreme cases, it is fatal.

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement. There are fat-soluble vitamins too, and those can be more toxic if taken at higher doses. Humans, unlike most animals, are unable to synthesize vitamin C endogenously, so it is an essential dietary component.[iii] 

Pauling advocated the consumption of large doses of the vitamin to compensate for the body’s inability to produce enough of it for optimum health. Specifically, Pauling espoused taking 2.5 g or more vitamin C per day for general health and to prevent or treat the common cold. He and others also contended that doses as great as 10 g/day helped prevent or cure heart disease and cancers. The so-called vitamin C megadose theory has been largely discredited.

The ACS, American Chemical Society, has added the last line. I wouldn’t be so fast to buy into it. Pauling is more intelligent than most of the people walking the planet and gained a reputation for being right. The inserted line may be a self-righteous addition of scientific dullards who think they know things when they don’t.

But it adds to their infatuation with themselves.

To the point, a relatively recent study was conducted: A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss.[iv]

They concluded that “experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss.”

When a scientist uses the word “suggest,” it typically means “proves.” They are just trying to downplay it and cover their butts just in case something deleterious comes up. Also, it adds to their allure of being humble and not raging narcissists.

It’s expected.

Back to the point, the eye researchers identified their objective: To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity.

Results: Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations.

Conclusions: Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.

What was Pauling recommending?

He developed quite a penchant for taking vitamin C himself. Over the next few years, Pauling upped his intake of vitamin C, eventually taking 18,000 mg per day. Vitamin C became his scientific obsession.

That is quite a lot.

I mean “a lot.”

In 1970, Pauling came out with his book Vitamin C and the Common Cold, where he encouraged Americans to consume 3,000 mg of vitamin C daily.

This all came about because of a particular longevity aspiration of Pauling’s and a chance encounter at a lecture. During a talk in 1960, Pauling mentioned he hoped he could live another 25 years to keep following the exciting discoveries in science. A man in the audience, Irwin Stone, would change the course of Pauling’s career. In a letter to Pauling, Stone recommended he take 3,000 mg of vitamin C each day to live longer.[v] Pauling said he began to feel “livelier and healthier” after taking Stone's advice. "In particular, the severe colds I had suffered several times a year all my life no longer occurred."

Anecdotal evidence can be powerful and convincing, but it must be followed up on in a scientifically responsible and prudent manner.

Pauling did get a bit carried away. He said it would make the common cold disappear completely off the face of the earth. He said vitamins and nutritional supplements could cure everything from retinal detachment to snakebites to the virus that causes AIDS.

The common cold angle really didn’t pan out. There are a few exceptions though.[vi]

Abstract

Background: The role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment.

Objectives: To discover whether oral vitamin C in doses of 200 mg or more daily, reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of cold symptoms.

Main results: Twenty-nine trial comparisons involving 11,077 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold while taking prophylaxis. The pooled RR was 0.96 (95% CI 0.92 to 1.00). A subgroup of six trials that involved a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95%CI 0.38 to 0.66). Thirty comparisons that involved 9,676 respiratory episodes contributed to the meta-analysis on common cold duration during prophylaxis. A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adult participants and 13.5% (95% CI 5% to 21%) for child participants.

Reviewers' conclusions: The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence shows that it could be justified in persons exposed to brief periods of severe physical exercise and/or cold environments. Also, the consistent and statistically significant small benefits on duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defense mechanisms. The trials in which vitamin C was introduced at the onset of colds as therapy did not show any benefit in doses up to 4 grams daily, but one large trial reported equivocal benefit from an 8 gram therapeutic dose at onset of symptoms.

Cancer prevention

Epidemiologic evidence suggests that higher consumption of fruits and vegetables is associated with lower risk of most types of cancer, perhaps, in part, due to their high vitamin C content.[vii] Vitamin C can limit the formation of carcinogens, such as nitrosamines,[viii] in vivo; modulate immune response;[ix] and, through its antioxidant function, possibly attenuate oxidative damage that can lead to cancer.

Conclusion.

No, vitamin C is not going to eradicate the common cold. There are some benefits. Vitamins C and E shortened duration and reduced severity of common cold.[x]

It will prevent you from getting scurvy.

It is also quite an immune booster and antioxidant. It has been shown to regenerate other antioxidants within the body, including alpha-tocopherol (vitamin E).[xi] Oxidative damage builds up over time, meaning aging, and all the aging scientists champion antioxidants.

Humans cannot manufacture vitamin c for themselves, so it must be introduced in the diet. It also is serviceable in age-related macular degeneration and vison loss.

Vitamin C is required for the biosynthesis of collagen, L-carnitine, and certain neurotransmitters; vitamin C is also involved in protein metabolism.

References

[i] https://www.vox.com/2015/1/15/7547741/vitamin-c-myth-pauling

[ii] https://www.acs.org/molecule-of-the-week/archive/a/ascorbic-acid.html

[iii] Li Y, Schellhorn HE. New developments and novel therapeutic perspectives for vitamin C. J Nutr 2007;137:2171-84.

[iv] Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001 Oct;119(10):1417-36.

[v] Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000.

[vi] Douglas RM, Hemila H, D'Souza R, Chalker EB, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2004 Oct 18;(4)

[vii] Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr 1999;69:1086-107.

[viii] Hecht SS. Approaches to cancer prevention based on an understanding of N-nitrosamine carcinogenesis. Proc Soc Exp Biol Med 1997;216:181-91.

[ix] Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care 2002;5:66-74.

[x] Murni IK, Prawirohartono EP, Triasih R. Potential Role of Vitamins and Zinc on Acute Respiratory Infections Including Covid-19. Glob Pediatr Health. 2021 May 31;8

[xi] Jacob RA, Sotoudeh G. Vitamin C function and status in chronic disease. Nutr Clin Care 2002;5:66-74.