Can a High Dose Vitamin C Regimen Cause Osteoarthritis?

Any adverse effects of replacement vitamin C will be discuseed here. Topics include kidney stones, gall stones, oxidation, etc.
We plan to move good discussions from the General Topics forum here for posterity.

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quickstep
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Can a High Dose Vitamin C Regimen Cause Osteoarthritis?

Post Number:#1  Post by quickstep » Tue Jan 17, 2006 11:50 pm

Almost all of the research I have found on vitamin C has been positive and in my own experience it has really helped alleviate my allergies and chronic colds.

However, I found a study that was a little disturbing showing that guinea pigs put on a high vitamin C diet comparable to humans resulted in "more cartilage damage and had more bony spurs form in their knee joints than did the medium- and low-dose groups" and it also states "showed a significant worsening of osteoarthritis with increasing levels of vitamin C"

Here is the link: http://www.dukehealth.org/HealthPortals/orthopedic/news/7640

First, is there any rebuttal or contradictory evidence to this study?

Second, what can be done to prevent the cartilage & bony spurs of a high-dose vitamin regimen? (I currently take about 7g per day)

I am really interested given that I intent to qualify for the Olympic Marathon Standard this year or next and Vitamin C has been very beneficial for the short time I have been using it in a high dose regimen.

Thanks

davids

Re: Can a High Dose Vitamin C Regimen Cause Osteoarthritis?

Post Number:#2  Post by davids » Wed Jan 18, 2006 12:45 am

Quickstep,

I read the study. I can only give you my viewpoint. The "system" has been trying to discredit megascorbate therapy for over 50 years. In my opinion, "they" are unconscionable! I, for one, simply do not believe these results, i.e. that they truly conducted an objective study. "They" have a [financial] agenda, and will never have a shortage of people willing to back it, for a price! Many people, like Linus Pauling, including myself, have taken megadoses of ascorbic acid daily for many years and have had no joint problems whatsoever. And in fact, Dr. Cathcart has had success recommending daily megadoses of ascorbic acid for rheumatoid arthritis sufferers in the 15,000 to 100,000 milligram range. http://www.orthomed.com/titrate.htm Gorillas in the wild ingest about 4,000 milligrams of ascorbic acid daily. Do they get [any] arthristis? In the final analysis Quickstep, like most things in life, you will have to come to your own decision, because there will never be a shortage of naysayers!

Best wishes,

David

zucic

Re: Can a High Dose Vitamin C Regimen Cause Osteoarthritis?

Post Number:#3  Post by zucic » Wed Jan 18, 2006 7:07 am

However, I found a study that was a little disturbing showing that guinea pigs put on a high vitamin C diet comparable to humans resulted in "more cartilage damage and had more bony spurs form in their knee joints than did the medium- and low-dose groups"
and it also states "showed a significant worsening of osteoarthritis with increasing levels of vitamin C


It is probably possible to set up the experiment in a way which is reproducible
but still leads to confusion. Something else (not just the ascorbate) might be
missing in a diet of these guinea pigs!

Ken_RN

Post Number:#4  Post by Ken_RN » Wed Jan 18, 2006 7:29 am

This is interesting....

The Duke researchers did find an association between higher levels of vitamin C and increasing collagen in knee cartilage. However, there was also a strong correlation between vitamin C dose and the severity of disease, including the number and size of osteophytes, or bony spurs at the knee joint. The researchers found an important protein in bone growth called active transforming growth factor beta almost exclusively in the osteophytes. The protein is known to cause joint degeneration and spur formation, and vitamin C can convert this protein from an inactive to an active state, Kraus said. This conversion means that vitamin C's ability to enhance collagen synthesis and activate transforming growth factor beta might be the reason guinea pigs fed high doses of vitamin C developed more osteoarthritis, she said.


OK, so I google "active transforming growth factor beta" and one of the first results that pops up is this:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7584958&dopt=Abstract

The serum concentration of active transforming growth factor-beta is severely depressed in advanced atherosclerosis.
Recent evidence has led us to propose that transforming growth factor-beta (TGF-beta) is a key inhibitor of atherosclerosis. We show here that a population of patients with advanced atherosclerosis all have less active TGF-beta in their sera than patients with normal coronary arteries, with a fivefold difference in average concentration between the two groups. This correlation with atherosclerosis is much stronger than for other known major risk factors and it may therefore have important diagnostic and prognostic significance. Aspirin medication correlates with an increase in active TGF-beta concentration, indicating that therapeutic interventions for TGF-beta are possible.


I digress but is the above yet another connection between Vitamin C and decreased athersclerosis perhaps? Back to osteoarthritis..

This seems relevant:

CD69 downregulates autoimmune reactivity through active transforming growth factor-beta production in collagen-induced arthritis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12975472&dopt=Abstract&holding=f1000

CD69 is induced after activation of leukocytes at inflammatory sites, but its physiological role during inflammation remains unknown. We explored the role of CD69 in autoimmune reactivity by analyzing a model of collagen-induced arthritis (CIA) in WT and CD69-deficient mice. CD69-/- mice showed higher incidence and severity of CIA, with exacerbated T and B cell immune responses to type II collagen. Levels of TGF-beta1 and TGF-beta2, which act as protective agents in CIA, were reduced in CD69-/- mice inflammatory foci, correlating with the increase in the proinflammatory cytokines IL-1beta and RANTES. Local injection of blocking anti-TGF-beta antibodies increased CIA severity and proinflammatory cytokine mRNA levels in CD69+/+ but not in CD69-/- mice. Moreover, in vitro engagement of CD69 induced total and active TGF-beta1 production in Concanavalin A-activated splenocyte subsets, mouse and human synovial leukocytes, and Jurkat stable transfectants of human CD69 but not in the parental CD69 negative cell line. Our results show that CD69 is a negative modulator of autoimmune reactivity and inflammation through the synthesis of TGF-beta, a cytokine that in turn downregulates the production of various proinflammatory mediators.


A lot of this is over my head but I understand enough to think that the connection between Vitamin C and osteoarthritis isn't as direct as our Duke University researchers are leading us to believe. There seems to be some autoimmune difficulty that has to be present for the osteoarthritis to be collagen (thus also Vitamin C) induced.

Below is a link to 70 references on PubMed for "active transforming growth factor beta." I haven't the time to go through them all now but if you are curious you can start digging there.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=PubMed&term=%22active+transforming+growth+factor+beta%22&tool=QuerySuggestion

ofonorow
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Low Vitamin C Linked to Inflammatory Arthritis in HUMANS

Post Number:#5  Post by ofonorow » Wed Jan 18, 2006 8:47 am

Lets keep things in perspective. This guinea pig study was in guinea pigs. The pigs on higher ascorbate were LARGER (which is generally regarded as a sign of superior health in animals) and even the authors note that the increase in weight might explain the larger "knobs."

Strangely, a human study that revealed the opposite was just about to be published.

There is a post in the clinical studies forum on this issue

Low Vitamin C Linked to Inflammatory Arthritis in HUMANS
Owen R. Fonorow
HeartCURE.Info
American Scientist's Invention Could Prevent 350,000 Heart Bypass Operations a year

Ken_RN

Post Number:#6  Post by Ken_RN » Wed Jan 18, 2006 9:51 am

I just can't seem to leave well-enough alone..

Here is a study from Arthritis Research and Therapy that seems to illustrate Owen's point exactly:

Susceptibility to Collagen-Induced Arthritis is Modulated by TGFß Responsiveness of T Cells
(Arthritis Res Ther 6(2):R114-R119, 2004)

http://www.medscape.com/viewarticle/466993

The second paragraph of the introduction states:

Transforming growth factor beta (TGFβ) family members are pleiotropic factors produced by a variety of cells and with actions depending on the context of their production.[4] Besides having effects on cell proliferation and differentiation and on matrix regulation and tissue repair, TGFβ1 is a major immunoregulatory factor.[4] TGFβ has been detected in RA synovial tissue, and suppressive effects of synovial fluid have been attributed to its actions.[5] In line with its site-and context-specific action, conflicting results have emerged from the use of exogenous TGFβ1 systemically or locally in joints and from the use of anti-TGFβ antibodies. The systemic administration of TGFβ to mice ameliorated CIA,[6] whereas its local administration to foot pads and joints in rats induced synovitis and aggravated their disease.[4,7] Similarly, blocking endogenous TGFβ by the systemic injection of anti-TGFβ antibody aggravated CIA in mice,[6] whereas it ameliorated the ongoing inflammation when injected into the joints of rats.[8] TGFβ also has important functions in tissue repair and fibrosis and chondrocyte differentiation.[9] These conflicting results underline the need for a better understanding of the role of endogenous TGFβ in the maintenance of joint integrity.


The skinny is that TGF-beta does not have the same effect on the joints of mice as it does rats. Therefore the contention of the Duke study that it would have the same effect upon humans as it does on guinea pigs seems to be a speculation that lacks justification.

JayZee

Post Number:#7  Post by JayZee » Fri Jan 20, 2006 8:10 am

Ken Wahl,
I love reading your posts and always look for them,however the long urls break the page making it difficult to have to scroll both up and down and side to side.It's always those long Gov urls.

I took your long url it was 137 characters and snipped it to 23 like this.
http://snipurl.com/lqz6

Here is the website- http://snipurl.com/

or at this site: Tinyurl.com

I just want to keep this wonderful forum readable. :D

Ken_RN

Post Number:#8  Post by Ken_RN » Fri Jan 20, 2006 1:08 pm

JayZee,

Thanks for the suggestion. I guess I'm spoiled running at 1280x1024. I'm aware of URL-shorteners like TinyURL and url(x) but have been reluctant to use them because some people consider them "blind links." I think what I'll do is link URL's like this from now on..

Linked Article Title Goes Here

So that way people can still see where the link goes if they mouseover it while keeping the forum layout intact.


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