Roger J. Williams and Linus Pauling on Vitamin C and Collagen

"We have come upon reasons why we require for good health so much larger amounts of vitamin C than are present in the plants we use as food... It has recently been shown by Myllyla and his colleagues that, one molecule of vitamin C is destroyed for each H (hydrogen atom) replaced by OH (during the formation of collagen)... Vitamin C, in the critical reactions that assemble collagen in the tissues, does not serve merely as a catalyst but is destroyed."
Linus Pauling

Linus Pauling HOW TO LIVE LONGER AND FEEL BETTER (1986) Pages 89-91

The synthesis of collagen, for which vitamin C is essential, proceeds in the body as one of its major manufacturing enterprises. A person who is dying of scurvy stops making this substance, and his body falls apart -- his joints fail, because he can no longer keep the cartilage and tendons strongs, his blood vessels break open, his gums ulcerate and his teeth fall out, his immune system deteriorates, and he dies.

Collagen is a protein, one of the thousands of different kinds of proteins in the human body. Most proteins occur in only small amounts: the various enzymes, for example, are so powerful in their ability to cause specific chemical reactions to take place rapidly that only a gram or two or even a few milligrams may be needed in the body. There are a few exceptions. There is a great amount of hemoglobin in red blood cells. There is even more collagen in the skin, bones, teeth, blood vessels, eye, heart, and, in fact, essentially all parts of the body. Collagen as strong white fibers, stronger than steel wire of the same weight, and as yellow elastic networks (called elastin), usually together with macropolysaccharides, constitutes the connective tissue that holds our bodies together.

Like other proteins, collagen consists of polypeptide chains; the long chains of this fibrous molecule contain about one thousand amino-acid residues, about sixteen thousand atoms. It differs from almost all other proteins in being substantially composed of but two amino acids, glycine and hydroxyproline. Collagen is a kind of supermolecule, however, in its three-dimensional architecture. The polypeptide chains of the two amino acids, alternating with one another and punctuated by the presence of certain other amino acids, are coiled in a left-handed helix. Three of these helical strands are twisted around on another, like strands of a rope, in a right handed superhelix, to compose the complete molecule.

Understandably, the synthesis of this structure proceeds in steps. While it has been known for half a century (these words written in 1985) that vitamin C is essential to the manufacture of collagen, the process is only now yielding to inquiry. It appears that vitamin C is involved at every step.

First, a three dimensional stranded structure is assembled, with the amino acids glycine and proline as its principal components. This is not yet collagen but its precursor, procollagen. A recent study shows that vitamin C must have an important role in its synthesis. Prolonged exposure of cultures of human connective-tissue cells to ascorbate induced an eight-fold increase in the synthesis of collagen with no increase in the rate of synthesis of other proteins (Murad et al., 1981). Since the production of procollagen must precede the production of collagen, vitamin C must have a role in this step -- the formation of the polypeptide chains of procollagen -- along with its better understood role int he conversion of procollagen to collagen.

The conversion involves a reaction that substitutes a hydroxyl group, OH, for a hydrogen atom, H, in the proline residues at certain points in the polypeptide chains, converting those residues to hydroxyproline. This hydroxylation reaction secures the chains in the triple helix of collagen. The hydroxylation, next, of the residues of the amino acid lysine, transforming them to hydroxylysine, is then needed to permit the cross-linking of the triple helices into the fibers and networks of the tissues.

These hydroxylation reactions are catalyzed by two different enzymes: prolyl-4-hydroxylase and lysyl-hydroxylase. Vitamin C also serves with them in inducing these reactions. It has recently been shown by Myllyla and his colleagues that, in this service, one molecule of vitamin C is destroyed for each H replaced by OH [Myllyla et al., "Ascorbate is Consumed Stoichiometrically in the Uncoupled Reactions Catalyzed by Prolyl-4-Hydroxylase and Lysyl Hydroxylase. Journal of Biological Chemistry 259:5403-5405. 1984]

We have come upon the two big reasons why we require for good health so much larger amounts of vitamin C than are present in the plants we use as food. First, there is the bodies continuing need for the synthesis of large amounts of collagen for growth and for replacement of the collagen degraded by daily wear and tear. Second, vitamin C, in the critical reactions that assemble collagen in the tissues, does not serve merely as a catalyst but is destroyed."


Roger J. Williams NUTRITION AGAINST DISEASE 1971) Pages 85-86

Vitamin C is essential for the building of collagen, the most abundant protein built in our bodies and the major component of connective tissue.[Wolbach, S. B.., and Howe, P. R. ¤ntercellular substance in experimental scorbutus" Arch. Path., 1:1, 1926] This connective tissue has structural and supportive functions which are indispensable to heart tissues, to blood vessels, --in fact, to all tissues. Collagen is not only the most abundant protein our bodies, it also occurs in larger amounts than all other proteins put together. It cannot be built without vitamin C. No heart or blood vessel or other organ could possibly perform its functions without collagen. No heart or blood vessel can be maintained in healthy condition without vitamin C.

Victims of prison camps who have suffered from vitamin C deficiency have been found to have wide-spread fatty deposits (atherosclerosis) in their arteries. It is quite possible that vitamin C deficiency is directly implicated; it is unlikely that such deposits could have been due to too much fat or cholesterol in diet.

Strong evidence has recently been present that individual needs for vitamin C vary widely, and that some individuals have much higher needs than has hitherto been supposed. While the functioning of vitamin C, except for its role in building collagen, is obscure, it is quite possible that many hearts and blood vessels would be better protected if an abundant environmental supply of this vitamin were available in the circulating fluids that bathe the tissue cells.
Roger J. Williams, Nutrition Against Disease, 1971. Pg 85-86 (paperback)


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