Heath Notes

Glucosamine

Glucosamine is an important building block needed by the body to manufacture specialized molecules called glycosaminoglycans, found in cartilage.

Where is it found?

Glucosamine is not present in significant amounts in most diets. Supplemental sources are derived from the shells of shrimp, lobster, and crab, or may be synthesized.

Glucosamine has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings	Health Concerns
	Osteoarthritis (glucosamine sulfate)
	Autism Knee pain (glucosamine HCI)
	Minor injuries Osteoarthritis (glucosamine HCl) Sprains and strains Wound healing (oral)
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

A glucosamine deficiency in humans has not been reported.

Which form is best?

Glucosamine is available in several forms. The glucosamine sulfate (GS) form (stabilized with a mineral salt) is the only form clearly shown in clinical trials to be effective for osteoarthritis. For this reason, it is the preferred form.

GS is stabilized with one of two mineral salts: sodium chloride (NaCl) or potassium chloride (KCl).¹ ² Although they both appear to effectively stabilize GS, the use of KCl as a stabilizer seems preferable since the average Western diet already provides far too much salt (NaCl) and not enough potassium. However, most of the research has been done with the NaCl-stabilized form.

Concerns have been raised about the quality of GS products on the market. In one study, the amount of glucosamine contained in 14 commercially available glucosamine products varied from 41% to 108% of the amount stated on the label.³ Even when the weight of the sulfate molecule was included, 11 of the 14 products contained less than the amount of glucosamine stated on the label. Some manufacturers may include the weight of the stabilizing salts (NaCl or KCl) in the total weight of the product, without stating so on the label.

Glucosamine hydrochloride (GH) has been widely available as a dietary supplement for years, but only one trial has evaluated this form of glucosamine as a single remedy for OA.⁴ This trial found only minor significant benefits from 1,500 mg per day of GH for eight weeks, in people with osteoarthritis of the knee who were also taking up to 4,000 mg per day of acetaminophen. To more fairly evaluate the effects of GH, future research should involve people not taking pain-relieving medication.

Another form of glucosamine, N-acetyl-glucosamine (NAG), has not been studied in people with osteoarthritis.

How much is usually taken?

Healthy people do not need to routinely supplement with glucosamine. Most research with people who have osteoarthritis, uses 500 mg three times per day of GS. Appropriate amounts for other conditions are not known.

Are there any side effects or interactions?

At the amount most frequently taken by adults—500 mg three times per day of GS—adverse effects have been limited to mild reversible gastrointestinal side effects. In one trial, people with peptic ulcers and those taking diuretic drugs were more likely to experience side effects.⁵

Animal research has raised the possibility that glucosamine could contribute to insulin resistance.⁶ ⁷ This effect might theoretically result from the ability of glucosamine to interfere with an enzyme needed to regulate blood sugar levels.⁸ However, available evidence does not suggest that taking glucosamine supplements will trigger or aggravate insulin resistance or high blood sugar.⁹ ¹⁰ Two large, 3-year controlled trials found that people taking GS had either slightly lower blood glucose levels or no change in blood sugar levels, compared with people taking placebo.¹¹ ¹² Until more is known, people taking glucosamine supplements for long periods may wish to have their blood sugar levels checked; people with diabetes should consult with a doctor before taking glucosamine and should have blood sugar levels monitored if they are taking glucosamine.

In 1999 the first case of an allergic reaction to oral GS was reported.¹³ Allergic reactions to this supplement appear to be rare.

Some GS is processed with sodium chloride (table salt), which is restricted in some diets (particularly for people with high blood pressure).

The theory that GS and chondroitin sulfate work synergistically in the treatment of osteoarthritis remains unproven.

At the time of writing, there were no well-known drug interactions with glucosamine.

References
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1. Drovanti A, Bignamini AA, Rovati AL. Therapeutic activity of oral glucosamine sulfate in osteoarthritis: a placebocontrolled doubleblind investigation. Clin Ther 1980;3:260–72.

2. Vaz AL. Doubleblind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthritis of the knee in outpatients. Curr Med Res Opin 1982;8:145–9.

3. Russell AS, Aghazadeh-Habashi A, Jamali F. Active ingredient consistency of commercially available glucosamine sulfate products. J Rheumatol 2002;29:2407–9.

4. Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol 1999;26:2423–30.

5. Tapadinhas MJ, Rivera IC, Bignamini AA. Oral glucoseamine sulfate in the management of arthrosis: report on a multi-centre open investigation in Portugal. Pharmatherapeutica 1982;3:157–68.

6. Virkamaki A, Daniels MC, Hamalainen S, et al. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance in multiple insulin sensitive tissues. Endocrinology 1997;138:2501–7.

7. Rossetti L, Hawkins M, Chen W, et al. In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats. J Clin Invest 1995;96:132–40.

8. Barzilai N, Hawkins M, Angelov I, et al. Glucosamine-induced inhibition of liver glucokinase impairs the ability of hyperglycemia to suppress endogenous glucose production. Diabetes 1996;45:1329–35.

9. Russell AI, McCarty MF. Glucosamine in osteoarthritis. Lancet 1999;354:1641; discussion 1641–2 [letters].

10. Muniyappa R, Karne RJ, Hall G, et al. Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects. Diabetes 2006;55:3142–50.

11. Rovati LC, Annefeld M, Giacovelli G, et al. Glucosamine in osteoarthritis. Lancet 1999;354:1640; discussion 1641–2.

12. Reginster JY, Deroisy R, Rovati L, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001;357:251–6.

13. Matheu V, Bracia Bara MT, Pelta R, et al. Immediate-hypersensitivity reaction to glucosamine sulfate. Allergy 1999;54:643–50.

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires June 2009.

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