Glucosamine: Wonder-Supplement or Marketing-Goldmine
Whilst Glucosamine may not be the big news story at the moment, it is still a billion-dollar industry, “with 2013’s value at $1.823 billion, and the 2015 forecast predicting a market worth $1.770 billion” (nutra), many people still like to take it as a nutritional supplement especially for arthritis.
I did a lot of research into it years back when it was very popular and not much has moved on since then with respect to the science or the research.
Here’s the science bit for those of you who want to know the detail:
The theory is that Glucosamine is involved in the glycoprotein / proteoglycan metabolism and helps form the ground substance in the extra-cellular-matrix ECM of connective tissue.
Glucosamine derivatives are found in hyaluronic acid, keratan sulfate and heparan sulfate – polysaccharide groups called glycosaminoglycans (GAGs). GAGs are vital for the function of articular cartilage, the GAG chains being fundamental components of aggrecan – a substance found in articular cartilage (the stuff that coats the joints and makes them slide smoothly).
Aggrecan provides cartilage with a ‘swelling pressure’ that is restrained by the tensile forces of collagen fibres. This balance confers upon articular cartilage the deformable resilience vital to its function. In normal language; the substance in which you find glucosamine, ‘bulks-out’ the cartilage, which is held in shape by the tough elastic fibres (collagen).
In the early stages of joint degeneration, the body creates more aggrecan, but in the later stages, aggrecan synthesis drops, leading to the cartilage becoming fragile.
With that dealt with, we can move on to what happens when we eat substances containing glucosamine.
~90% of eaten glucosamine is absorbed in the small intestine, it is then transported via the portal circulation to the liver. It appears that a significant fraction, up to ~80%, of the ingested glucosamine is catabolised by first-pass metabolism in the liver.
Beyond that stage, we are only guessing at what happens, as free glucosamine is not detected in blood serum after oral intake, and it is not presently known how much of an ingested dose is taken up in the joints in humans.
So, here’s a little something for the mathematicians out there:
There are three types of glucosamine commercially available: Glucosamine Sulphate (most common) N-Acetyl-Glucosamine and Glucosamine Hydrochloride. All these have different percentages of Glucosamine due to the different chemical make-ups of these ‘carrier’ substances.
- Glucosamine Hydrochloride contains ~83% glucosamine base
- Glucosamine Sulphate contains ~65% glucosamine base
- N-acetyl-Glucosamine contains ~75% glucosamine base
If we take the form with the highest base level and assume we are taking the recommended therapeutic amount (RTA) (1500mg), then we would need 1807mg of Glucosamine HCl. To make the maths easy and give glucosamine a chance, lets say we take 2000mg Glucosamine HCl which will provide 1660mg glucosamine base to the body on eating.
90% is absorbed by the body, so we have 1494mg Glucosamine travelling to the liver (notice it’s above the RTA, so we’re good at this stage).
The liver catabolises (breaks down) 80% of that, which is a bit of a pest, so we end up with just 298.8mg available for the body to use.
Let’s be generous again, and pretend that, actually, because of inefficient measurement and slightly dodgy maths, we end up with 1.2mg more so we have a nice round figure of 300mg available to the body per day.
At the time of writing, the average weight in the UK of a woman was 70.6kg and of a man 83.9kg.
So, to be crass, lets say the average weight of an Adult in the UK, assuming a population of 51% women and 49% men is 77.12kg.
300mg is 0.0003kg and so is approximately 0.000003% of average body weight.
It may seem to be labouring the point, but that isn’t a lot to spread around the body, even if we are just talking about it going to the joints.
It isn’t known what proportion of glucosamine there is in cartilage, but that 300mg, a fraction of a tiny amount of a substance needs to be pretty powerful to make a difference.
If we were talking about toxicity, just 50 grams of botox could kill everyone on the planet, so maybe 300mg of glucosamine daily could have an effect on your joints, but it would need to be pretty efficient at getting in the right place and binding to the right things.
All the science points to it being ‘mostly harmless’. But, from a sample of scientific papers¹ regarding glucosamine from 1980 to 2014 there isn’t really enough evidence for me to say it is definitely, beyond question always beneficial.
The question is therefore… when there is that little available to the body, is it worth taking Glucosamine?
Before I answer that, there are other considerations to make; are there any side-effects, are there other options, what ‘partner substances’ are best, anything else?
I had no intention of this being the case, but it looks like this is part one of a series. I’ll try to answer some of those questions next time.
A Cochrane review of glucosamine therapy for osteoarthritis found 16 RCT’s which met inclusion criteria (1980-1999).
13 RCT’s compared glucosamine to placebo and in all except one glucosamine was found to be superior. (Towheed 1999)
A more recent, even more rigorous meta-analysis (McAlindon 2000) found 6 RCT’s which met more stringent inclusion criteria.
Pooling the results from the 911 patients in these trials yielded an overall effect size highly in favor of glucosamine (p=.05).
Since these two meta-analyses, a high quality study tested glucosamine vs. placebo in 212 patients followed for an average of 3 years (Reginster 2001).
This study found a highly significant benefit from glucosamine in terms of symptom and function scores, as well as prevention of joint space narrowing on knee x-rays.
Glucosamine is able inhibit the action of cartilage-catabolic enzymes (Fenton JI et al)
Glucosamine is no more effective than placebo in treating the symptoms of knee osteoarthritis (McAlindon T Am J Med. 2004 Nov)
A considerable improvement in OA symptoms was observed (Zhonghua Yi et al. 2005)
Glucosamine may be effective in delaying OA progression (Poolsup N et al June 2005 [review of trials])
Glucosamine (sulfate or hydrochloride) does not reduce pain in knee or hip osteoarthritis. (Gonzalez EP 2013 [meta-analysis of double-blind, placebo-controlled trials.])
Oral supplementation of chondroitin sulphate plus glucosamine helps repair the articular surface in osteoarthritis. (Bottegoni C et al. 2014)
Glucosamine postpones the onset of [rheumatoid] arthritic symptoms, reduced their severity and in [some] cases completely prevented their appearance (Richter J et al. 2014)
Glucosamine supplementation demonstrates a small but significant reduction in the rate of joint space narrowing in knee Osteo-Arthritis. (Henrotin Y et al. 2014)
Controversy remains about the use of Glucosamine. (Nelson AE et al. 2014 [systematic review])
There is no evidence of structural benefits from glucosamine supplementation in individuals with chronic knee pain. (Kwoh CK et al. 2014)
High-dose Glucosamine activates autophagy [self-digestion] of the chondrocyte. (Jiang LB et al. 2014)lucosamine (sulfate or hydrochloride) does not reduce pain in knee or hip osteoarthritis. (Gonzalez EP 2013 [meta-analysis of double-blind, placebo-controlled trials.])