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Q: Vitamin C and Collagen ( Answered 5 out of 5 stars,   0 Comments )
Subject: Vitamin C and Collagen
Category: Health
Asked by: jat-ga
List Price: $15.00
Posted: 26 May 2003 10:32 PDT
Expires: 25 Jun 2003 10:32 PDT
Question ID: 208945
I want to know all about the connection between Vitamin C and
Collagen.  What is collagen, it's role, it's purpose?  How is it that
Vitamin C is so critical to proper collagen synthesis and maintenance?
 Is there a way to calculate the amount of C necessary to produce a
given quantity of collagen?  (What I'm getting at here is that I
suspect the RDA's for C do not take into account what may be a much
greater need by the body than just enough to avoid symptoms of
scurvy.)  Thanks...
Subject: Re: Vitamin C and Collagen
Answered By: tehuti-ga on 26 May 2003 14:05 PDT
Rated:5 out of 5 stars
Hello jat

Collagen is the most abundant protein in the body, since it is a major
constituent of connective tissue, which holds everything together:
“Cartilage is composed of fibrous collagen in an amorphous gel. The
organic (nonmineral) content of bone is made up largely of collagen
fibers with calcium salt crystals lying adjacent to each segment of
the fiber; the fibers and salt crystals combined form a structure with
compressional and tensile strength comparable to that of reinforced
concrete.” (The Columbia
Encyclopedia, Sixth Edition.  2001)

“Nature's most abundant protein polymer is collagen. More than a third
of the body's protein is collagen. Collagen makes up 75% of our skin.
The more science learns about the body, the more integral we see
collagen to be.
Acts as a scaffolding for our bodies.
Controls cell shape and differentiation.
Is why broken bones regenerate and wounds heal.
Why blood vessels grow to feed healing areas.
The Collagen mesh provides the blueprint, the road map and the way.
Collagen is the fibrous protein constituent of skin, cartilage, bone,
and other connective tissue.” (BioSpecifics
Technologies Corp)

Linus Pauling, winner of the Nobel Prize for Chemistry in 1954 and the
Nobel Peace Prize in 1962,  in his later years became a champion of
the need for high doses of vitamin C. Pauling wrote about the
connection between vitamin C and collagen in 1986.  The relevant
extract from his book is reproduced on the web site of the Vimain C

Basically, Pauling points out that scurvy is a condition in which the
body cannot produce collagen due to a lack of vitamin C. As a result,
cartilage and tendons become weaker, causing joints to fail, blood
vessels deteriorate and break open, and ulcers form on the gums,
making the teeth fall out.
Collagen is normally present in large quantities in the body, because
it makes up the connective tissue that holds together all body
tissues. Vitamin C is involved at every stage of the synthesis of
collagen.   The first step is the synthesis of procollagen, from which
collagen is ultimately formed. Procollagen is a 3-D stranded structure
made up mainly of the amino acids glycine and proline. Pauling quotes
a study that showed that cultures of  human connective-tissue cells
exposed for a prolonged period to ascorbate increased their synthesis
of collagen eight-fold.

The study is “Regulation of collagen synthesis by ascorbic acid” by
Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A, Pinnell SR,
published in 1981 in Proceedings of the National Academy of Science U
S A, Volume 78(5), pages 2879-82.  You can read a summary at:

Therefore, as Pauling says, “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.”

He goes on to explain the reaction that takes place: “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.”.
Pauling then quotes a paper which appeared in 1984 in Journal of
Biological Chemistry, Vol 259(9), pages 5403-5, “Ascorbate is consumed
stoichiometrically in the uncoupled reactions catalyzed by prolyl
4-hydroxylase and lysyl hydroxylase.” by Myllyla R, Majamaa K, Gunzler
V, Hanauske-Abel HM, Kivirikko KI.
This paper showed that, in the hydroxylation reactions described
above, “one molecule of vitamin C is destroyed for each H replaced by
You can read the full text of this article at (Acrobat Reader will be
needed to read the pdf format.  You can download this at )

Pauling concludes. “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

I have found an estimate that: “Fifty molecules of vitamin C are
consumed in the production of one molecule of collagen.” This
statement is not documented and appears on the web site marketing
dietary supplements, so might not be totally reliable.

Ascorbic acid (Vitamin C) has the formula C6H8O6.  Its molecular
weight is 176.  That means that 1 mole of vitamin C equals 176 grams.
One mole of a substance contains 6 x 10 to the power of 23 molecules.
Therefore there are 34 x 10 to the power of 20 molecules in 1 gram of
vitamin C.

Working on the 50-molecule estimate given above, 1 gram of vitamin C
is sufficient for the production of 68 x 10 to the power of 18
molecules of collagen.  The molecular weight of collagen is 300,000
So one mole of collagen (6 x 10 to the power of 23 molecules) weighs
300,000 grams.
68 x 10 to the power of 18 molecules of collagen will therefore weigh
34 grams.
Therefore, 1 gram of vitamin C will be consumed in the production of
34 grams of collagen.

Water makes up about “60% of total body weight – varies with age,
gender and body composition
(remainder: 18% protein, 15% fat, 7%mineral)”
(Introduction and Basic Physiological Principles, web site of Ohio
Northern University)

We saw above that more than a third of the body’s protein is collagen.
That means collagen must account for at least 6% of body weight. The
average body weight of an adult is usually taken to be 70 kg. That
means about 4.2 kg or 4200 grams of this average weight will be

The US RDA for collagen is 60 mg (Ohio State

According to the calculations above, 60 mg of vitamin C will result in
the production of just over 2 grams of collagen. Of course, this does
make any allowance for its other functions in the body:
“Vitamin C is a strong reducing agent and as an antioxidant is
involved in prevention of the damaging effects of free radicals.
Vitamin C is involved in the synthesis of collagen, neurotransmitters
and carnitine; it is an enzyme co-factor and also increases the
gastrointestinal absorption of non-haem iron.” (UK Food
Standards Agency)

However, the final piece of the puzzle is missing. Vitamin C at the
RDA will stop the occurrence of scurvy, but scurvy is an extreme state
of collagen depletion.  The problem is that other factors also affect
collagen production and loss.

A paper written in 1987 reported that collagen turnover in some
tissues can be quite rapid: “In skin of adult rats, the mean rate lies
between 3 and 5%/day, but rates of greater than 10%/day have been
reported in some tissues, such as lung and periodontal ligament.”
American Journal of Physiology, Volume 252(1 Pt 1), pages C1-9 
Dynamic state of collagen: pathways of collagen degradation in vivo
and their possible role in regulation of collagen mass.  By Laurent

Factors other than vitamin C are important: for example the collagen
content of skin decreases after menopause, but this can be reversed by
hormone replacement therapy.
American Journal of Clinical Dermatology, 2003,  Volume 4(6), pages
Skin aging and menopause : implications for treatment. By
Raine-Fenning N, Brincat M, Muscat-Baron Y.

A comment in the Journal of Physiology (1999), 521.1, p. 1, “Teasing
out the truth about collagen” by Michael J. Rennie made the point:
“we do not know much about what governs collagen synthesis or its
breakdown in the human body…   We need to understand collagen
metabolism in order to understand how we grow, adapt to the
environment, maintain our adult shapes and then wrinkle and crumble as
we age. Collagen diseases are relatively common and almost certainly
if we knew more about how, for example, the collagen framework of bone
is laid down and turned over we would understand much more about
osteopenia of old age.  The problem in finding out has been that
collagen is so difficult to study. It turns over relatively slowly,
and that part of it that is cross-linked and forms mature collagen is,
it seems, with us for life come hell, high-water or famine. The body
reduces to mainly skin and bone-collagen in extremis. Because the
system as a whole is so sluggish, it is difficult to see changes in
indices of collagen metabolism. However, not all the body collagen
seems to be as fixed, and indeed collagen in some tissues must turn
over, enabling remodelling and adaptation, rather quickly.” 

As already cited above, Pauling believed we needed large quantities of
vitamin C to compensate for its destruction during collagen synthesis
and also because it is required for other purposes.  In his last
years, he was taking more than 10 grams of vitamin C per day.  On the
other hand, there has been quite a lot of controversy about his ideas,
and others have claimed that excessive consumption of vitamin C is not
just ineffective, but could even be harmful.  Here is one such
opinion:  On the other hand,
moderate supplementation does no harm.  In 2000, a panel convened by
the US National Academy of Sciences suggested that the recommended
daily dose of vitamin C should be 90mg for men and 75mg for women.,
and that the maximum dose from all sources should not exceed 2000mg. 
The panel was of the opinion that the recommended dose should be
easily obtained by eating 5 servings of fruit and vegetables per day. (BBC news item,
Wednesday, 12 April, 2000)

So, in the end, not enough is known yet about collagen synthesis and
degradation to provide an absolute answer to your question, although
it has provided a fascinating journey through the facts that are

Search strategy: searches on Google and Medline at using combinations of
the following search terms: collagen “vitamin C” “molecular weight”
“turnover” “degradation” “synthesis”

Clarification of Answer by tehuti-ga on 26 May 2003 16:40 PDT
"According to the calculations above, 60 mg of vitamin C will result in
the production of just over 2 grams of collagen. Of course, this does
make any allowance for its other functions in the body:"

Should read "does NOT make any allowance"
jat-ga rated this answer:5 out of 5 stars
I don't hand 5*'s out very often or very easily.  You're one of the
better researchers I've had.  And, if you'll look over my history,
you'll notice that I use GA fairly often.  Thanks for your assistance.
 This will give me a good place to start following the different
rabbit trails having to do with collagen...

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