Of Scurvy, Colds and Cancer

Captain Cook gave it, sort of, to English sailors to prevent death from scurvy. Today many take high doses for a cold. And two Nobel Prize winners believed it could treat cancer. Only Captain Cook was even close to right. Herewith is a short biography of Vitamin C—ascorbic acid. 

Scorbutic and Ascorbic

The term “scorbutic”—an adjective meaning “of, like, or having scurvy”—goes back to Medieval Latin. Ascorbic acid, same root, is the antiscorbutic, known commonly as Vitamin C. Casimir Funk, studying rice, coined the term “vital amines” or “vitamins”, which early on were named by lettering them in order of discovery. Vitamin C was discovered in 1912, isolated in 1928, and first made in 1933. (It is not an amine.)

Vitamin C is a simple molecule, water soluble and if taken in excess is excreted in the kidney with virtually no toxicity, at less than experimental doses. It is an anti-oxidant, much touted by the nutraceutical industry. But its real benefit is in collagen formation, for which it is a cofactor for related enzymes. Poor collagen synthesis leads to poor wound healing and bleeding tendencies. 

A deficiency causes bleeding from mucous membranes, gum disease, inflammation of the tongue and open skin wounds. The affect on the junction of bone in cartilage can cause a deformity known as the scorbutic rosary. Death can result from infection and bleeding, usually preceded by prolonged malaise, then lethargy.

But let’s reach back to when nothing of Vitamin C’s biochemistry was known, back to when scurvy was a scourge that could stay explorers and slay armies. It took centuries to discover that humans cannot make vitamin C and so must get it in their diet, or die.

English Sailors and French Soldiers

The term “Limey” for an English sailor is well known, from the use of limes (more likely lemons, both rich in Vitamin C) to prevent and treat scurvy. The French soldiers used fresh horse meat for the same purpose. Even though Captain Cook was awarded the Copley Medal for his management of shipboard nutrition, he was guided by the wrong principles and, in essence, got lucky. Cook was influenced by Dr. McBride and Sir John Pringle, the later a giant of English science, later to become President of the Royal Society. 

Captain James Cook

Captain James Cook

HMS Endeavour - replica

HMS Endeavour - replica

Pringle advocated malt and wort to facilitate digestion. This Cook implemented during a world circumnavigation in 1768-1771. Modern historians believe his success in minimizing scurvy amongst his crew was more due to cleanliness, resupply of fresh food and prohibiting skimming of fat from copper pots, which generated compounds that inhibit absorption of vitamins.

Despite the speculations of Hippocrates, and ancient Egyptians, the practical experience of earlier voyagers like Vasco de Gama (1497), the specification of oranges in a housewife’s scurvy remedy (1707), a book by Dr. Bachstrom (1734) in which he states “scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease”, and the pioneering experiment by Dr. James Lind in 1747—despite all this—the British medical establishment was unconvinced of how best to deal with scurvy.

That is until 1794 when Rear Admiral Gardner commanded the HMS Suffolk to stock up on lemons and sugar for a four month voyage to India. By the turn of the century, citrus fruits had won the battle against scurvy, although it took over a hundred years more before the practice was universal. And even then, the implementation was sometimes undermined by light exposure, boiling or percolation through copper tubing, any of which can destroy Vitamin C. The Merchant Marine’s lime juice in 1918 contained no antiscorbutic property.

Merck

Dr. Lind Gets a Clue

In reviewing the science behind Vitamin C’s role in human health, we should return to Lind’s experiment of 1747. It is widely regarded as the first documented use of the modern clinical trial method. It doesn’t matter here that Lind’s hypothesis of scurvy was that it is multifactorial. His trial was designed to test if acidic food would aid digestion and alleviate scurvy. He never promoted citrus juice as the curative agent.

Lind evaluated twelve sailors, all of whom had developed signs of scurvy on the same diet during two months at sea. He divided them into six pairs, each pair then got in addition: 

James Lind

James Lind

 
James Lind's Scurvy Experiment

James Lind's Scurvy Experiment

After 6 days the two sailors in group V ran out of fruit, but had already become fit for duty, or nearly so, in stark contrast to all other participants.

Nonetheless, other theories persisted, including ptomaine poisoning from tainted meat. On the other hand, the ability of meat to treat/prevent scurvy confounded the science, throwing people off the scent, as it were. 

Albert and the Guinea Pig

Further human trials were not conducted until WWII, on conscientious objectors in Britain, and in the 1960s on prisoner’s in Iowa. But in between, two things came along to sort things out: an animal model and a biochemist.

In 1907 Holst and Frohlich, Norwegian doctors decided to use Guinea Pigs in their studies of beriberi amongst fishermen. Their discovery that Guinea Pigs can get scurvy from dietary deficiency supported the hypothesis of an anti-scorbutic factor in food. 

Albert Szent-Gyorgyi and his colleagues had extracted hexuronic acid from adrenal gland as a candidate agent. His former colleagues from another lab had been looking for the agent in lemon juice. Szent-Gyorgyi gave them his hexuronic acid to test on Guinea Pigs. It was a success, and his colleagues published the findings without acknowledging Szent-Gyorgyi’s contribution.

Ascorbic Aci

Ascorbic Aci

Guinea Pigs

Guinea Pigs

Paprika was an instrument of justice here. As a Hungarian, it occurred to Szent-Gyorgyi to assay paprika for hexuronic acid. It was rich in the stuff. He got his friend Walter Haworth, to synthesize it. For this work, Szent-Gyorgyi got the Nobel Prize for Medicine and Haworth the Nobel for Chemistry, both In 1937. They renamed hexuronic acid to ascorbic acid. Synthesis was also achieved independently by Tadeusz Reichstein, who won a Nobel in 1950. His process, involving bacterial fermentation, is the basis for commercial production, (original brand name, Redoxon: Hoffmann-LaRoche). 

About 100 mg a day will keep an adult healthy. A 500 mg tablet can be had for about a penny, even if you buy brand–name Vitamin C derived from rose hips. (Which is not necessary—ascorbic acid is a chemical, not a fashion statement.)

Albert Sent–Gyorgyi

Albert Sent–Gyorgyi

Walter Haworth

Walter Haworth

Thadeus Reichstein

Thadeus Reichstein

Cold Comfort and The Big C

Despite its popularity for treatment and prevention of the common cold, there is no repeatable, robust data to suggest that this is true. Nonetheless, given that Vitamin C is cheap and well tolerated, most doctors shrug there shoulders and acquiesce to a lay public attached to the belief.

Szent-Gyorgyiwas great friends with another Nobel Prize winner, the great Linus Pauling. They shared a deep conviction that, on theoretical grounds, Vitamin C should have anti-cancer properties. Many studies since the 1970s, including modern ones with high doses intravenously, fail to support this concept. To quote an expert from the Mayo Clinic, “There are still no well-done, controlled clinical trials that have shown a substantial effect of vitamin C on cancer”.

Coda

Here’s but one example of how dependent we humans are on Vitamin C intake, given that we can’t make it. Pasteurization of cow’s milk destroys Vitamin C. This can lead to infantile scurvy, for which some mothers compensated by feeding their baby onion juice!

Such vulnerability makes one wonder at the evolutionary circumstances surrounding it. We humans are in a small minority of animals that can’t make Vitamin C. Although we have the needed enzyme, L-gulonolactone oxidase, it is deactivated. There are two major branches of primates. The more primitive branch, the Strepsirrhini (wet-nosed primates) can make Vitamin C. We Haplorrhini (dry–nosed primates)—man, apes and tarsiers—cannot. 

There must be an explanation. Is this simply a 60 million year old mutation that is non-lethal because we live in a bounty of Vitamin C rich foodstuffs? Then again, perhaps we have done so well because we have a more clever metabolism: “in essence, the red cells of animals that can't make vitamin C recycle what little they've got.

Rose Hips

Rose Hips

Limes

Limes

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