As food makers increasingly turn to nutrients to fortify and 'functionalise' their food products for a growing consumer market, a new study out of the US find that high doses of vitamin C increase the severity of spontaneous knee osteoarthritis in an animal model of the disease.
Findings from researchers at the US Duke University Medical Center contradict previous short-term studies in guinea pigs and an epidemiologic study in humans that suggested vitamin C might protect against osteoarthritis, said lead investigator Virginia Kraus.
In the Duke study, the researchers fed guinea pigs - which, according to the scientists develop, knee osteoarthritis in a manner similar to humans - low, medium and high doses of vitamin C during an eight-month period.
The researchers found that high-dose guinea pigs developed more cartilage damage and had more bony spurs form in their knee joints than did the medium- and low-dose groups.
'The researchers' examination of the spurs revealed a possible cause for the link between vitamin C and osteoarthritis. They discovered a protein in the spurs that leads to spur formation and can be activated by vitamin C,' report the scientists.
Because the study indicates potential drawbacks to long-term use of high-dose vitamin C supplements, adults should not supplement their dietary vitamin C levels above the recommended dietary allowance (RDA), warned Kraus. The RDA for men is 90 milligrams per day and the RDA for women is 75 milligrams per day. A diet that includes five servings of fruits and vegetables a day supplies about 200 milligrams per day of vitamin C.
"It is possible that brief exposure to high levels of vitamin C offers antioxidant effects with a minimum of side effects, while prolonged exposure results in deleterious effects," Kraus is reported as saying. A randomised, controlled clinical trial in humans would be required to definitely resolve the issue of vitamin C dosing, she added.
Like humans, the Hartley strain of guinea pigs lack a gene for making vitamin C, leaving them dependent on vitamin C in their diet. Each of the 46 guinea pigs followed in the study were fed standard chow supplemented by a custom-made food with three different concentrations of ascorbic acid (vitamin C). The study began when the guinea pigs were 4 months old.
The medium dose, 30 milligrams per day, was the guinea pig equivalent of the RDA for vitamin C in humans - comparable to a person consuming five fruit and vegetable servings. The lower dose, about three milligrams per day, was the minimum necessary to prevent scurvy in the guinea pigs. The high dose was 150 milligrams per day, an amount shown to protect against surgically-induced osteoarthritis in a short-term guinea pig study. The equivalent human dose is 1,500 to 2,500 milligrams per day.
The antioxidant properties of vitamin C were proposed as one explanation for the earlier positive results, because oxygen radicals can degrade collagen and proteoglycan, a connective tissue protein. The vitamin has also been shown to help collagen synthesis and stimulate production of key components of collagen.
The Duke researchers, reports the university, 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 added.
Full findings of the study are published in the June 2004 issue of Arthritis & Rheumatism.
Osteoarthritis more frequently affects humans in later life and with the world's population getting older and older the ailment is likely to become more prolific. In 2000, according to the World Health Organisation there were 600 million people aged 60 and over, set to rise to1.2 billion by 2025 and 2 billion by 2050. Today, about two thirds of all older people are living in the developing world, by 2025, it will be 75 per cent. In the developed world, the very old (age 80+) is the fastest growing population group.