The last several years have seen a revolution in the treatment of arthritis with the discovery that cell communication takes place through carbohydrates (sugars) attached to amino acids in the proteins located on the surface of every cell in your body.
Glucosamine is among the eight sugars required to make these 'glycoproteins'. Researchers have theorised that arthritis is the result of abnormal glucosamine metabolism, a malformation in their glycoforms.
As a chief component of proteoglycans (which make cartilage), glucosamine seems able to stop proteoglycan breakdown, rebuild damaged cartilage (Orthop Praxis, 1970; 9: 225) and stimulate the production of glycosaminoglycans such as chondroitin, another building block of cartilage.
For years, we've known that sulphur is vital for preventing joint degeneration (J Bone Joint Surg, 1934; 16: 119-25). For this reason, glucosamine is usually given with sulphate to strengthen its effects on connective tissue. In a large Portuguese study, glucosamine sulphate improved pain and symptoms in 95 per cent after two months, and markedly so in 59 per cent (Int J Tissue React, 1992; 14: 243-51). A microscopy study of cartilage from patients treated with glucosamine sulphate found evidence of new growth (Clin Ther, 1980; 3: 260-72).
With one in three of us suffering from arthritis of some variety, supplement manufacturers were quick to spot an opportunity in a potentially enormous market, particularly as arthritis sufferers have to take supplements more or less for life.
Indeed, ever since the publication of Dr Jason Theodosakis's The Arthritis Care Book, which recommends glucosamine and chondroitin for arthritis, such preparations have become the number one bestselling supplement in America.
Glucosamine sulphate is often paired with chondroitin sulphate, shown to modify the structure of joints and not just alleviate symptoms (Osteoarth Cartilage, 1998; 6 [Suppl A]: 39-46). Injected chondroitin sulphate results in visible improvements in the joints on X-rays (Semin Arth Rheum, 1987; 17: 2 [Suppl 1]: 35-53).
Glucosamine and chondroitin appear to work synergistically. Chondroitin inhibits enzymes that destroy cartilage and reduces arterial clogging, improving the supply of nutrients to cartilage (Townsend Lett Docs, January 1994). This allows glucosamine to make more glycosaminoglycans.
To test the leading brands of these products, PROOF! sent a cross-section of the most popular ones to Somerset Scientific Services Laboratory in Taunton, Somerset, one of the EC's official laboratories for food law enforcement as well as a testing laboratory for standards and quality for the government and private industry.
Of our chosen eight products, purchased as usual through The Nutri Centre in London, four were glucosamine alone, three were glucosamine/chondroitin and one was chondroitin alone. Thus, to be fair, we had two winners: the best combination product and the best single product. We were mainly looking for the product that delivered the best dosage of glucosamine or chondroitin at the best price.
However, Somerset's repeated efforts to test for chondroitin proved unsuccessful at the time of press. This was disappointing, given the relative instability of chondroitin. (If they do manage to produce results, we will report them in our next issue.)
To determine value for money, we compared:
* the price per tablet, which varied from 12 p to more than five times that - 67 p
* the total glucosamine or chondroitin per lb, which also varied more than fourfold - from 1200 mg per lb to more than 5000 mg per lb
* the amount of active ingredients present compared with the amounts stated on the label.
We were pleasantly surprised to find that most manufacturers included more than was stated.
All of the combination products shared a single fault. As glucosamine works best at 500 mg three times a day, and chondroitin works best with a single 800-mg serving once a day, no combination product was able to give the optimal dose of both.
Some of the products include other micronutrients - usually manganese and vitamin C, which aid glucosamine/chondroitin absorption. Others include calcium and magnesium for their beneficial effects on bones, with the rationale that glucosamine and chondroitin will work even better on cartilage if you strengthen bone. Although we acknowledge these good intentions, in many cases, too little of either nutrient was included to do much good.
Above all, be patient and maintain a leap of faith as it could be three months or more of regularly taking supplements before you see any improvement, since the effects of glucosamine get better over time.
You also shouldn't put all your eggs in this single basket. Glucosamine works best as part of an all-embracing treatment programme that also includes diet, other supplements and exercise.
Glucosamine sulphate 600 mg
Price: lb6.95 for 60 tablets
Unusually for a quality vitamin manufacturer, Lamberts has managed to slash the cost of glucosamine to a price none of the other manufacturers can compete with. This product costs 12 p per tablet, or slightly more than 5 g of glucosamine per lb. In fact, our sampling found 400 mg more per lb than declared, making Lamberts an even better deal than it claims.
Although Lamberts calls this a hypoallergenic product, remember that all tablets require binders to stay in one piece.
Each tablet contains glucosamine sulphate as potassium chloride, which is useful if you have high blood pressure.
The only 'fault' we could find was the choice of making each tablet 600 mg rather than the optimal 500 mg; if you take three tablets a day, you'd receive 300 mg above the optimal daily dosage. The result of such 'overdosing' is anybody's guess.
This is a no-frills product with no other cofactors included, which may be a bonus if you're already taking other supplements (multivitamins, say) and don't want to duplicate unnecessarily. But if you need to take glucosamine for life and budgetary considerations loom large, Lamberts' product is a clear frontrunner.
GlucOsamine & Chondroitin
Manufacturer: Health Perception
Price: lb12.99 for 30 tablets
This combo offers the best value for money of all the combination products. At 43 p per tablet and more than 2000 mg of glucosamine/chondroitin per lb, this UK company manages to undercut its US competitors.
Health Perception claims to have the only product which has 'undergone a double-blind placebo-controlled clinical trial at a British hospital', but it's hard to know whether this is the only product to have had such a trial or the only such product to have had a trial in the UK.
Information on their glucosamine is sparse. This glucosamine is sodium-derived but 'salt-free'. As for chondroitin sulphate, all they admit to is a 'fish source'. For some reason, the product also includes tiny amounts of bioflavonoids and manganese.
This is as good as a combo product can be, with 500 mg of glucosamine and 400 mg of chondroitin per tablet - giving you at least a fighting chance of getting the correct amount of each. However, the size of the bottle means replenishment every 10 days.
Manufacturer: Thorne Research
Price: lb23.20 for 90 capsules
US vitamin manufacturer Thorne has produced a no-frills winner, containing the optimal amount of glucosamine to alleviate symptoms. Thorne's is also competitive in cost and the sole manufacturer to deliver its product in a capsule rather than tablet, thus avoiding all binders, coatings or allergens. This is most likely the most hypoallergenic of all the products in our road test.
Although not the cheapest at 26 p per capsule, this has a total delivery of 2370 mg of glucosamine per lb - nearly 400 mg more than the 1940 mg declared.
Thorne is also the only manufacturer besides Lamberts to not include cofactors, which means you may have to take additional supplements - a good multivitamin and mineral tablet, for instance - to achieve the optimal effect.
One nice touch is the size of the package. With 90 capsules per bottle and a dosage of three a day, you have a clear month's supply.
Price: lb38.39 for 60 tablets
Of the three combination products, quality vitamin manufacturer Solgar offers a close runner-up. This version contains 500 mg each of glucosamine and chondroitin per tablet - optimal for the former, slightly too much of the latter, according to the literature (see box, p 3).
The problem with having both in a single tablet is that you need to take too much chondroitin to get enough glucosamine. The manufacturer doesn't specify where the chondroitin comes from, but the glucosamine derives from shellfish, so vegetarians beware. Mystifyingly, this combo is slightly cheaper than its single-product cousin (see below). This also contains calcium ascorbate (buffered vitamin C) and calcium, vegetable cellulose, vegetable stearic acid, manganese, silica and vegetable glycerin.
At 64 p per tablet, this isn't the best value for money of the combinations, and was the second worst bargain in terms of amount of glucosamine/chondroitin per lb. Solgar is often competitively priced but, clearly, not in this case. Nevertheless, by adding decent amounts of vitamin C and manganese, Solgar may, in the end, save you money if you don't want to supplement further.
Manufacturer: Health Perception
Price: lb9.99 for 30 tablets
This UK company has produced an outstanding single-product preparation, but at a price (33 p per tablet). Each tablet contains the recommended 500 mg of glucosamine sulphate made from potassium salts and also includes generous amounts of vitamin C (300 mg) and calcium carbonate (300 mg), plus 5 mg of manganese to aid absorption, so you should factor in these amounts when supplementing with other micronutrients.
Although Health Perception gets full marks for a generous well-conceived label, we were concerned on one point. It implies that this product may be useful for joints and muscles, but also for those who participate in sports and fitness training. This might encourage anyone involved in any sort of fitness training to supplement with glucosamine, to unknown long-term effect. (Health Perception does distinguish between 'normal use' - two tablets a day - and 'additional requirement' (read 'arthritis') - three tablets a day.
There is no mention of what else is in the tablets (binders, fillers), but we can't fault this company on the active ingredients - what it claims (1500 mg per lb) is just about what you get, although our sample tablets had slightly less vitamin C (220 mg) than declared. In terms of value for money, this delivers 1523 mg of glucosamine per lb - the worst of the four glucosamines.
Glucosamine sulfate 1000 mg
Price: lb39.95 for 60 tablets
American vitamin giant Solgar has gone for high potency with their single-ingredient offering, which is probably meant to be paired with their other single product, chondroitin sulphate (see below).
But if you intend to do that, you're in for a large dent in your purse. At 67 p per tablet, this is by far the most expensive of the single-product offerings. However, you do get as much glucosamine sulphate for your money (around 1500 mg) as you do with Health Perception's product.
This product may be more expensive because of its natural source, but the formulation lets it down. Having a 1-g tablet is awkward. If you want to take 500 mg three times a day, you have to break a tablet in half for each serving, so the average punter is likely to end up taking more glucosamine than he ought to.
There are also those fillers that you usually find in a tablet: powdered cellulose, silica and magnesium stearate. There seems to be no scientific justification for having a higher potency other than allowing Solgar to charge a good deal more per bottle.
Glucosamine Chondroitin Rx-Joint
Manufacturer: Nature's Plus
Price: lb34.95 for 60 tablets
US vitamin company Nature's Plus calls this an 'extended delivery' product which dripfeeds the two glycoproteins to your joints, allowing for gradual 'natural' absorption. The means of delivery is not clear, but the company claims it is a 'special base' which allows a gradual release of ingredients over an extended period of time.
This product also includes vitamin C and manganese as cofactors for improved absorption.
Nature's Plus has roughly got the ratio of glucosamine to chondroitin right, offering 500 mg at 58 p per tablet. It also offers slightly more glucosamine/chondroitin per lb (1717 mg) than Solgar's preparation. Nevertheless, extended-release capsules have spotty reputations and could be ineffective. It's also unnecessary as divided doses of glucosamine appear to be well absorbed. Nature's Plus has opted for the N-acetyl version of chondroitin, which may be better at healing a leaky gut than the joints.
Chondroitin Sulfate 600 mg
Price: lb29.39 for 60 tablets
Solgar's final product is pure chondroitin sulphate in a 600-mg tablet. Like the glucosamine, it is expensive - 49 p per tablet - with the least amount of chondroitin for your lb of any product we've seen.
It's also not the optimal dosage. Solgar would have done better to produce 800 mg tablets, or at least 400 mg, to ensure that patients take the right number. As Solgar is usually fastidious about formulation, it's also odd to see a decided absence of cofactors other than a tiny amount of magnesium, largely to bind the product.
If you're thinking of taking glucosamine and chondroitin separately from Solgar, you're in for an unnecessarily expensive deal. If you'd rather take a single product, all the latest studies point to chondroitin as the more effective of the two. For this reason, we have to give Solgar points for providing you with the choice.
Until the publication of Dr Jason Theodosakis's book, taking chondroitin and glucosamine was controversial. A number of researchers concluded that chondroitin, taken orally, cannot be absorbed (Rheumatol Int, 1992; 12: 81-8). Nevertheless, according to Dr Theodosakis, in the only head-to-head study published so far, a combination of glucosamine and chondroitin in a ratio of five to four, respectively, was significantly more effective than either substance alone. Furthermore, only the combination, rather than either single ingredient, prevented the most severe cartilage damage. The study also confirmed that the two substances work synergistically by stimulating cartilage cells to produce the proteoglycans that build further cartilage (J Clin Orthop Rel Res, 2000; 381: 229-40).
The major problem with this study is that it involved animals, so the results may not apply to humans.
Nevertheless, in a review of 37 major studies (including 15 in humans) of glucosamine and chondroitin, the researchers concluded that chondroitin's 'high' effect was almost twice that of glucosamine (JAMA, 2000; 283: 1469-75).
Some early research contended that the amount of chondroitin absorbed from supplements is extraordinarily low - between 0 and 8 per cent - but these results were from rabbits which, as vegetarians, are incapable of absorbing animal-derived products (Townsend Lett Docs, January 1994).
Numerous studies have shown that 500 mg of glucosamine sulphate three times a day is an optimum daily dosage (Clin Ther, 1980; 3: 260-72; Lancet, 1989; i; 1275) with no side-effects.
With chondroitin, in one study, daily doses of 800 mg or 400 mg twice a day increased blood levels, but the one-a-day dose of 800 mg was more effective (Arzneim Forsch, 1995; 45: 918-25). Most other studies since then have confirmed this as the optimal daily dosage.
Besides dosage, the type of salt used as a stabiliser may also be a consideration. Most supplements contain glucosamine as glucosamine NCl (sodium chloride) or KCl (potassium chloride), so even though the products may be listed as 'pure', they contain table salt or potassium chloride. The sodium chloride variety could be especially dangerous to hypertensive patients who have been medically advised to limit their salt intake.
Another variety is N-acetyl glucosamine which, according to Stephen Terrass, a senior researcher at Solgar, when digested, immediately goes towards replenishing the gut wall so that less is available for repair work on joints.
Although glucosamine sulphate has always been marketed as the superior product, this is largely, says glucosamine expert Dr Luke R. Bucci of Houston, Texas, because they were patented first. Nevertheless, research has shown glucosamine hydrochloride (HCl) and hydroiodide to be equally effective. Indeed, a comparative study showed a greater production of proteoglycans with the HCl form than the sulphate (Pharmacology, 1971; 5: 337-45).
Supplements of chondroitin are usually derived from an animal source, usually green-lipped mussels or bovine, whale and shark cartilage, so you may wish to forego this supplement if you are vegetarian.
Another problem with chondroitin is its apparent instability. Products containing the supplement degrade readily so that the amount stated on the label often bears no resemblance to what is inside. Dr Bucci found that the amount of chondroitin in different batches from different manufacturers ranged from 100 per cent to 0 (Townsend Lett Docs, January 1994).
Finally, although there is no toxicity or interactions yet reported with glucosamine salts, there is evidence that glucosamine can cause severe toxicity when given intramuscularly (Lancet, 1989; i: 1275). Other evidence of toxicity is generally thought to be related to unpurified forms of chondroitin, and nausea at higher doses has also been reported. If you do experience nausea, it may be a good idea to lower the dose or get yourself checked for any signs of toxicity, and come off chondroitin completely if it doesn't agree with you.