BEDFORD, Massachusetts–Cartilage strength depends in part on the charge of the sulfate bits in chondroitin sulfate, the vast majority of which is produced within the cartilage itself. In vitro studies have shown that sulphation of chondroitin drops when sulfate concentrations in culture medium are <0.2 mmol/L. C. M. Blinn, MD, and colleagues in the laboratory of Jeremiah E. Silbert, MD, report that human blood levels can drop below this level in some people after an overnight fast, particularly if they then take on a load of sugar and no protein.1 This raises the possibility that cartilage formed during a period of such low sulfate availability might have weak spots that could predispose a joint to osteoarthritis (OA).
This does not translate into support for chondroitin sulfate dietary supplements, however.
"[Ingestion of] chondroitin sulfate makes no sense, as whatever small amounts get to cartilage are not attached to the specific protein called aggrecan that is the functional structure," Dr. Silbert warned. "I would tell rheumatologists that it is a waste of money at best and could be deleterious at worst because of possible effects on glucose levels as described in another publication from our laboratory," he added.
In this study, the researchers collected sera from 14 patients with OA who fasted overnight. On one day of the study the subjects continued to fast for 3 hours in the morning while blood was collected every 15 to 30 minutes. On a different day after another overnight fast, the same subjects were given a challenge of 75 g of glucose, and blood was collected over the subsequent 3 hours. Samples were analyzed for levels of sulfate and glucose.
Baseline sulfate levels ranged from 0.26 mmol/L to 0.45 mmol/L and dropped an average 9.3% after the additional 3-hour fast. Baseline sulfate levels ranged from 0.29 mmol/L to 0.60 mmol/L and dropped an average 18.9% after the glucose challenge.
"I was very surprised at finding this, particularly the doubling of the effect when glucose was ingested. To my knowledge, no one previously had described this, nor had anyone even thought about testing for it. We found it by chance when we were examining the effects of glucose after ingestion of glucosamine sulfate. After seeing this effect we went back to get the information concerning the levels when no glucose was taken. This was another surprise," Dr. Silbert said. He pointed out that this sequence of events might easily occur in a person who fasted all night, had only carbohydrates for breakfast, then ate only a salad for lunch.
"If what we found is important, it probably matters only in a subgroup of patients with OA, but it is interesting," Dr. Silbert said.
Serum sulfate dropped to 0.21 mmol/L and 0.22 mmol/L in two of the 14 subjects after glucose challenge, just above the 0.20 mmol/L level that adversely affected chondroitin sulphation in cultured cells. According to Dr. Silbert, undersulphation could make cartilage that incorporates the resulting abnormal chondroitin compound more susceptible to damage and to enzymatic degradation.
Chondroitin sulfate turnover in the joint cartilage is quite slow, so any such weakened areas of cartilage would persist for some time. Whether this contributes to OA is unknown, but Dr. Silbert described the first step in finding out as "an ideal PhD project". He would like to see a study done comparing damaged and intact cartilage from OA joints. He emphasized that just measuring the sulfate level will not be useful. What is needed is to sample cartilage from the two areas, extract the sulfated chondroitin from both, and compare the levels of chondroitin and of sulfate within each sample. If he is right, the damaged cartilage will show lower sulphation. "If so, a major long-term, double-blinded trial of sulfate utilization would be indicated," Dr. Silbert said.
Table: Serum Sulfate Levels in Patients With Osteoarthritis*
|
Intervention |