I like to reason from first principles and move down the chain of reasoning.
One of the characteristics of physiology I remember from medical school is that most of the structural molecules are made on-site from primitive precursors. The food we eat is broken down to its smallest components which are transferred to where they are needed and then these building blocks are altered or strung together with other chemicals to form more complex structures.
Simplistic, I know, but a reasonable rule of thumb.
That is one of the issues about glucosamine and chondroitin for osteoarthritis that bother me. Both products are made on site by cartilage, not imported complete into the joint. So why would taking them help joint disease? Unless you are eating a diet rich in pig snout and cows ears, most peoples diets have little of either glucosamine or chondroitin.
So I have always wondered, at a basic biochemical level, why taking glucosamine and chondroitin would help osteoarthritis. It seems more sympathetic magic than a real therapeutic intervention, the equivalent of eating hair to treat baldness.
This lack of a good biochemical basis isf why studies that show very marginal benefit from glucosamine and chondroitin are even more unimpressive:
allocation to the dietary supplement combination (glucosamine–chondroitin) resulted in a statistically significant (p=0.046) reduction of 2-year JSN compared to placebo: mean difference 0.10 mm (95% CI 0.002 mm 0.20 mm); no significant structural effect for the single treatment allocations was detected. All 4 groups demonstrated reduced knee pain over the first year, but no significant between-group differences (p=0.93) were detected."
When there is no physiologic reason for why an intervention would work, I am more inclined to suspect the weakest of p values is noise, all sound and fury signifying nothing.