Why Vitamin C? The Scurvy Connection

James Lind

[Reading Cancer and Vitamin C, part 3 of 9]

In their 1979 book, Cancer and Vitamin C, Ewan Cameron and Linus Pauling made clear that vitamin C was uniquely suited to fight cancer, but the duo still needed to address some unanswered questions. Namely, what was so special about vitamin C, and how did that specialness help it to fight disease?  For Pauling and Cameron, part of the answer was connected to vitamin C’s protective factor against scurvy.

By the time that they were working on their book, it had been long understood that the body could store vitamin C. It was likewise well-known that, without any new infusions, these stores would deplete and symptoms of vitamin C deficiency would begin to manifest. Scurvy is the disease that arises once the stores have dropped below a critical level, with symptoms including drops in weight, loss of teeth, bleeding gums, poor wound healing, seizures, jaundice, disorientation, and eventually death. Scurvy was quite common among sailors because the food they took with them on their long voyages often lacked adequate levels of vitamin C. These foods, which were selected because they wouldn’t spoil, generally featured biscuits and cured or salted meats. But after months at sea, eventually their vitamin C concentrations would diminish, and disease would set in.

For a long while it wasn’t well understood what the exact source of scurvy might be, though many suspected it had something to do with one’s diet. As early as 1536, French explorer Jacques Cartier found that he was able to prevent scurvy by drinking a tea made from arborvitae leaves, which was great from a practical viewpoint but still didn’t unravel the root cause of the illness. Almost two centuries later, in 1747, Scottish physician James Lind initiated a concerted effort to uncover the secret. By manipulating the diets of scurvy patients, Lind soon discovered that those who were given an orange and a lemon were cured, while others who consumed diets lacking oranges and lemons continued to decline. But what exactly was in lemons and oranges that could help stave off scurvy remained a mystery.

Almost two-hundred years passed before the secret ingredient in oranges and lemons was finally unlocked, when Albert Szent-Györgyi isolated the substance in 1928 and correctly identified it as vitamin C in 1932. As a result of Lind’s discovery and Szent- Györgyi’s subsequent work, scurvy is now an entirely preventable disease.

As they continued their review of the literature, Pauling and Cameron came to realize that there is also a connection between scurvy and cancer; a connection that was also made centuries earlier by James Lind. When Lind was conducting his scurvy work, part of his search for a cure involved performing autopsies on those who had died of the disease, and he was interested to find that many patients with scurvy also suffered from cancerous tumors. This intriguing connection between cancer and scurvy was not more fully explored at the time, because when people contracted scurvy, they typically died shortly thereafter, meaning that cancer was rarely their cause of death.

In 1954 however, a Canadian physician, W.J. McCormick, reached the conclusion that both scurvy and cancer were diseases of collagen, and that scurvy damaged cells in a manner almost identical to the changes wrought by cancer cells as they replicate. McCormick also pointed out that late-stage cancer symptoms are very similar to those of late-stage scurvy, including anemia, hemorrhaging, formation of ulcers, increases in infections, and low levels of plasma and leukocytes. These connections added weight to Pauling and Cameron’s belief that vitamin C held secrets to fighting cancer, and encouraged them to keep pressing their case.

Irwin Stone: An Influential Man

Irwin Stone. (Image by Oscar Falconi)

Irwin Stone. (Image by Oscar Falconi)

[Part 1 of 2]

Dr. Irwin Stone was a biochemist and chemical engineer who maintained a particular interest in and enthusiasm for vitamin C. Stone was the person who first raised Linus Pauling’s interest in vitamin C, leading to Pauling’s extensive program of research on vitamin C and its uses for the prevention and treatment of disease. Pauling’s contributions to the field are one of the big reasons why many people believe in taking vitamin C for the prevention and treatment of colds today.  But for Pauling, it all started with Irwin Stone.

Stone was born in 1907 and grew up in New York City. He attended the College of the City of New York and then worked at the Pease Laboratories, a well-known biological and chemical consulting lab, from 1924 to 1934. Stone started out as a bacteriologist, but was promoted to Assistant to the Chief Chemist and then to Chief Chemist.

In 1934 the Wallerstein Company, a large manufacturer of industrial enzymes, recruited Stone to set up and direct an enzyme and fermentation research laboratory. Ascorbic acid, or vitamin C, had just been identified and synthesized by a Hungarian research team led by Albert Szent-Györgyi, who later won the 1937 Nobel Prize in Medicine for his work. Stone pioneered processes for implementing the antioxidant properties of ascorbic acid in industrial settings. One specific application that Stone developed was the use of ascorbic acid as a preservative for food – an innovation that landed him three patents.

Stone’s interest in vitamin C lasted throughout his life. He began to study scurvy intensely and by the late 1950s he had formulated a hypothesis that scurvy was not merely a dietary issue, but a flaw in human genetics. (He called it “a universal, potentially-fatal human birth defect for the liver enzyme GLO.”) Stone considered the amount of vitamin C that nutritionists recommended in a healthy diet – the Recommended Daily Allowance (RDA) – to be far from sufficient. In 1968 that recommendation was 55 mg for women and 60 mg for men. The current standard is slightly increased at 75 mg for women and 90 mg for men, with higher recommendations for pregnant and lactating women. But none of these figures are anywhere near Stone’s recommendations.

Stone believed that humans suffer from “hypoascorbemia,” a severe deficiency of vitamin C, caused by our inability to synthesize the substance the way that virtually all other mammals do. Most other mammals synthesize vitamin C in large quantities relative to body weight; proportionately, humans theoretically should be taking between 10-20 grams daily. Stone suggested that about 25 million years ago the primate ancestors of human beings lived in an environment in which they were able to consume relatively massive amounts of ascorbic acid, compared with what we get from our diets today. These material circumstances created an environment in which a genetic mutation occurred that allowed these human ancestors to stop synthesizing the substance. In present day, Stone noted, these amounts of ascorbic acid are not readily available in our diets, so humans may only be getting 1-2% of what they need.

This hypothesis initially led Stone to propose a vitamin C intake of 3 grams for optimal health, 50 times the RDA, and as he further researched ascorbic acid, he recommended increasingly higher doses. He was convinced that taking less than the amount that he recommended would cause “chronic subclinical scurvy,” a state of lowered immunity that increased susceptibility to a variety of illnesses. He felt that large doses of ascorbic acid should be used to prevent and treat infectious and cardiovascular diseases, collagen breakdown, cancer, SIDS, birth defects, AIDS, and health problems normally associated with aging.

Practicing what he preached, Stone and his wife began taking megadoses of vitamin C and they found that it greatly improved their overall health. When the couple both incurred injuries from a serious car accident, they treated themselves in part with large doses of vitamin C and reported a swift recovery. Stone attributed their rapid healing to the large doses of vitamin C.

Letter from Irwin Stone to Linus Pauling, April 4, 1966.  This is the communication that spurred Pauling's interest in vitamin C.

Letter from Irwin Stone to Linus Pauling, April 4, 1966. This is the communication that spurred Pauling’s interest in vitamin C.

In March 1966, Linus Pauling gave a speech on the occasion of his receiving the Carl Neuberg Medal for his work in integrating new medical and biological knowledge. In the speech, Pauling – who was 65 years old at the time – mentioned that he hoped to live for another fifteen years so that he might see several advances of science in medicine that he anticipated to be emerging during that time period.

Irwin Stone was in the audience at this lecture and, on April 4, 1966, he wrote Pauling a fateful letter in which he noted

You expressed the desire, during the talk, that you would like to survive for the next 15 or so years….I am taking the liberty of sending you my High Level Ascorbic Acid Regimen, because I would like to see you remain in good health for the next 50 years.

Pauling was initially skeptical of Stone’s advice, but he had recently learned about other uses of megavitamin therapy and their successes, so he decided to give the regimen a try. It was at that point that Linus and Ava Helen Pauling began taking 3 grams of vitamin C a day.

In July Pauling wrote back to Stone: “I have enjoyed reading your paper and manuscript about hypoascorbemia. I have decided to try your high level ascorbic acid regimen, and to see if it helps me to keep from catching colds.”

Pauling, as it turned out, was impressed by the results. For most of his adult life, he had suffered from severe colds several times a year and had taken a daily dose of penicillin off and on from 1948 to the early 1960s. Pauling thought that the penicillin doses were his primary defense against colds but, in all likelihood, he was probably just killing off his good bacteria and making himself more susceptible to colds through his overuse of antibiotics. Once the Paulings started taking vitamin C, they reporting a noticeable uptick in their physical and emotional energy, and seemed to suffer from fewer colds.

Two years after their initial communications, Stone noticed that Pauling had cited him in a recently published journal article. Stone described his difficulties in getting his research published and the backlash that he was experiencing from physicians. He also asked about Pauling’s health.

The last time I wrote you in 1966, you mentioned that you were going to try my high level ascorbic acid regimen to see if it would help prevent your catching colds. How did it work? At the time you also had a broken leg. I know from personal experience [a reference to his car accident] that it is excellent in bone healing.

Pauling replied

I can report that both my wife and I have been less troubled by colds during the last two years, during which we have been taking 3 to 5 grams of ascorbic a day, than we had been before beginning your regimen.

He also asked about Stone’s research on ascorbic acid and leukemia.

During the late 1960s, Pauling did not make a point of promoting vitamin C megadoses, though he did support the use of megavitamin therapy for the treatment of schizophrenia. But by 1969, he was finally fully convinced of Irwin Stone’s arguments as well as his own personal successes with vitamin C, and he began to promote vitamin C publicly.

Casimir Funk and a Century of Vitamins

Casimir Funk, 1884-1967

One hundred years ago, in 1911, the Polish-born biochemist Casimir Funk published his first work on vitamins, titled “Experiments on the causation of Beri-Beri,” in the British Medical Journal, The Lancet.  Curiously, the word “vitamin,” coined by Funk, was missing from this paper as the Lister Institute in London, for which Funk was working at the time, did not accept the designation. It was not until 1912 that Funk was able to use his new word in a formal publication, the term appearing for the first time in the Journal of State Medicine.

And so began a new path of scientific inquiry into vitamins as constituents of food necessary to the maintenance of good health – an entire discipline whose start can be attributed in large part to Funk, the “father of vitamin therapy.” That said, even one-hundred years ago, it is apparent that Funk drew from what was already known about deficiency-related diseases as he charted his own experiments.

Before Funk’s time, it had already been established that certain foods acted like drugs in their capacity to prevent certain diseases. In the mid-1700s, Scottish physician James Lind conducted an experiment on sailors suffering from scurvy, a disease which is characterized by spots on the skin, spongy gums, and bleeding from mucous membranes. This ailment plagued many sailors who were at sea for longer than fruit could be preserved, and was suspected to be caused by a lack of fresh foods.

Lind tested this hypothesis by feeding one group of sailors two oranges and one lemon every day, while several other groups of sailors consumed a different diet that included garlic, mustard seed, cider and sea water. The two sailors who were given citrus fruits recovered from their symptoms of scurvy, while the others remained in the same condition or worsened. Lind came to the conclusion that citrus fruits were the cure for scurvy. Casimir Funk later discovered that diseases similar to scurvy, such as beriberi and pellagra, were likewise the physical manifestation of a nutritional deficiency.

Kazimierz Funk (“Casimir” is an anglicized form of his given name) was born in Warsaw, Poland, in 1884. He became interested in pathology and physiology at the age of fourteen, and at sixteen he went to Geneva, Switzerland to study the natural sciences – just the start of what would prove to be a peripatetic academic career. Funk later studied chemistry at Berne for three years, eventually focusing on organic chemistry under the supervision of Stanislaw Kostanecki.

His interests in the human body and chemistry eventually led to a program of research on “trace elements” in humans, carried out in 1904 at the Pasteur Institute with Gabriel Bertrand.  Funk’s trace elements work relied upon his ability to synthesize both organic bases and amino acids. Two years later he moved to Berlin, which was the world’s most scientifically vital city at the time. In Berlin, Funk and Nobel laureate Emil Fischer, a leading organic chemist of the period, undertook an analysis of amino acids – the building blocks of proteins – specifically focusing on the structures of cysteine and alanine.

Emil Fischer

At the same time that he and Fischer were analyzing amino acids, Funk accepted a position as a biochemist working for the municipal hospital in Wiesbaden. It was there that he came to the conclusion that foods could be divided into two categories: food that encouraged tumors and that which discouraged them. Funk also observed that “poor” proteins seemed to be poisonous to animals.  In an experiment conducted with Emil Abderhalden  – at the time one of Fischer’s assistants – one dog was fed horsemeat mixed with glucose and butter, while another dog was fed gliadin with glucose and butter. In fifteen days, the first dog gained 150 grams of protein while the second dog lost 450 grams. Based on this data, the American duo of Thomas Osborne and Lafayette Mendel showed that gliadin and edestin are “poor” proteins.

In 1910 Funk began the studies that led to his discovery of the vitamins when he traveled to London to work at the Lister Institute, and met its director, Charles Martin. Martin and Funk discussed the disease beriberi, which is found in populations of people who eat polished rice but not in those who eat the rice polishings. Beriberi was at one time fairly common among populations where rice is a staple, specifically in east Asia, and in its final stages caused paralysis and death.

Funk knew of a disease in pigeons called polyneuritis that is equivalent to beriberi in humans – it occurred in pigeons that had been fed exclusively polished rice. It had been previously supposed by the English scientist Leonard Braddon, and later the Dutchman Christiaan Eijkman, that the endosperm of rice contains a poison, while the cortical layers – the “polishings” – contain the antidote. Funk, however, conducted preliminary experiments in which he administered a diet of various pure carbohydrates – such as starch, insulin, cane sugar and dextrin – and found that they all induced polyneuritis when administered alone. He came to the conclusion that there was no toxic agent at fault; rather, polyneuritis and beriberi were caused by a deficiency of some essential ingredient missing in polished rice.

From there, Funk performed a series of tests which fractured rice polishings into two sections, A and B. He gave one set of polyneuritis-stricken pigeons fraction A, and another set of pigeons fraction B. The pigeons which were given fraction A died, while the group that was given fraction B recovered. Funk further broke down fraction B, and discovered that very small “trace elements” of fraction B could cure pigeons of polyneuritis. He named this trace element a vitamin: “vita” meaning life and “amine” meaning a nitrogen-containing compound.  The word “vitamin” then, stands for “a life-sustaining compound containing nitrogen.” (Though as it turns out, Funk was mistaken about the “amine” part.) Funk named this first vitamin “B1,” now known as thiamine. He published his second paper on the vitamins, “On the Chemical Nature of the Substance which Cures Polyneuritis in Birds Induced by a Diet of Polished Rice,” in 1911.

Funk was sure that more than one substance like Vitamin B1 existed, and in his 1912 article for the Journal of State Medicine, he proposed the existence of at least four vitamins: one preventing beriberi (“antiberiberi”); one preventing scurvy (“antiscorbutic”); one preventing pellagra (“antipellagric”); and one preventing rickets (“antirachitic”). From there, Funk published a book, The Vitamines, in 1912, and later that year received a Beit Fellowship to continue his research.

For several years following the publication of his book, Funk served as director of the Hygiene Institute in Warsaw. At the Institute, he cured dementia symptoms in patients who suffering from pellagra by giving them vitamin B1 and adding yeast to their diet. Funk was correct in his supposition that vitamins are required for the proper metabolism of nervous tissues, and that the lack of vitamins causes the body to extract nutrients from its tissues, thus leading to weight loss as those vital resources are depleted. In 1922 Funk and Harry Dubin successfully created and marketed the first vitamin supplement containing vitamins A and D, found in cod liver oil. It was called “Oscodal” and was sold widely as a product used mostly in infant therapy.

Casimir Funk died in New York in 1967 at the age of 83.  His discovery of the vitamins is widely acknowledged as having catalyzed many more studies on and discoveries related to nutrition and health.  Among them was a 1928 project in which, after a number of efforts, physiologist Albert Szent-Györgyi was able to separate vitamin C from citrus fruits – the first instance of success in obtaining a pure vitamin. Within a few years, vitamin C (ascorbic acid) became recognized as a substance that greatly improved one’s health, and in the 1960s Linus Pauling began to take a special interest…

[Ed Note: Over the next four weeks we will mark the centenary of Casimir Funk’s discovery of the vitamins by examining a number of specific aspects of Pauling’s Vitamin C and the Common Cold.]