SynopsisGuar gum is a dietary fibre advocated for use in lowering serum total cholesterol levels in patients with hypercholesterolaemia. Its mechanism of action is proposed to be similar to that of the bile-sequestering resins. Although guar gum is also employed as an adjunct in non-insulin-dependent diabetic patients this review is restricted to its efficacy as a hypolipidaemic agent. Clinical trials indicate that, when used alone, guar gum may reduce serum total cholesterol by 10 to 15%, although some studies show no significant response. An attenuation of this effect during longer term treatment has been seen but evidence of this effect is equivocal. As an adjunct to established therapies (bezafibrate, lovastatin or gemfibrozil) guar gum has shown some promise: it may produce a further reduction in total cholesterol of about 10% in patients not responding adequately to these drugs alone. Gastrointestinal effects, notably flatulence, occur relatively frequently and may be considered unacceptable by some patients. Standardisation of formulations and methods of administration of guar gum is required to clarify its pharmacological and clinical properties.Thus, on the basis of presently available evidence guar gum as monotherapy may be considered at most modestly effective in reducing serum cholesterol levels. Nonetheless, further investigation of guar gum is warranted, particularly its use as an adjunct to produce additional reductions in serum cholesterol in patients not responding optimally to other lipid-lowering agents.Pharmacological PropertiesGuar gum is a dietary fibre obtained from the endosperm of the seeds of the Indian cluster bean (Cyamopsis tetragonolobus), which forms a highly viscous gel on contact with water, and undergoes colonic fermentation to short-chain fatty acids. It may significantly delay gastric emptying time and/or gastrointestinal transit and reduce small intestinal absorption, although this appears highly dependent on the nature of the diet. While this action may in part explain the mechanism of action whereby it reduces blood glucose and insulin levels, and consequently its use as an adjunct in the treatment of non-insulin-dependent diabetic patients, this has not generally been accepted as part of the mechanism of action in reducing cholesterol levels. Guar gum has been shown to reduce serum total cholesterol (by about 10 to 15%) and low density lipoprotein (LDL)-cholesterol (by about 15 to 25%) in hypercholesterolaemic animals, healthy subjects and diabetic patients, without producing any significant effect on serum high density lipoprotein (HDL)-cholesterol or triglyceride levels. These effects are also seen in patients with hyperlipidaemia (see below). More generally accepted hypothese concerning its antihypercholesterolaemic mechanism of action include reduced cholesterol absorption and increased bile acid excretion, leading to increased hepatic cholesterol turnover. It is also proposed that appetite and dietary intake may be affected since significant weight loss has occurred in some, although not the majority, of patients treated with guar gum.Therapeutic TrialsThere have been relatively few clinical trials of guar gum in the treatment of patients with hypercholesterolaemia, and few of these included comparison with placebo and/or appropriate controls to reduce bias and variation. Indeed, double-blind conditions may be difficult to maintain because of the high frequency of unwanted gastrointestinal effects with some formulations. These studies usually included small numbers of patients (generally 10 to 30). When used alone, guar gum 15 to 30g daily reduced serum total cholesterol by 10 to 15% and LDL-cholesterol by 10 to 20%, although some studies showed a lack of any clinically or statistically significant effect. Serum HDL-cholesterol levels were not significantly affected, and most studies found no change in triglyceride levels. Evidence of attenuation of the antihypercholesterolaemic effect of guar gum is equivocal: rises in cholesterol levels toward baseline values have occurred after 8 to 12 weeks' therapy, but significantly reduced levels have also been measured after 9 to 12 months.The addition of guar gum to bezafibrate, gemfibrozil or lovastatin monotherapy has resulted in a further reduction of 7 to 13% in total cholesterol and 14 to 19% in LDL-cholesterol. Further investigation of such strategies seems warranted.Adverse Effects and Drug InteractionsThe tolerability of guar gum may vary greatly depending on many factors including dosage, formulation and method of administration. As it is not absorbed from the gastrointestinal tract guar gum does not appear to produce systemic adverse effects. Unwanted effects are thus restricted to the gastrointestinal tract and include flatulence, pain or discomfort, nausea and diarrhoea. Although the severity of these effects may necessitate a reduction in dosage or withdrawal from treatment, usually they are transient or diminish during continued treatment. While some trials have reported a low incidence of mild, transient adverse effects, others have reported flatulence in up to 50%, and sometimes 100%, of patients, with dosage reduction sometimes necessary.Guar gum may affect the absorption of certain concomitantly administered drugs: often only the rate of absorption is affected [e.g. paracetamol (acetaminophen), digoxin, bumetanide] and this is consequently of little clinical significance. However, the extent of absorption of certain drugs (e.g. phenoxymethylpenicillin, metformin, oral contraceptives and some galenic formulations of glibenclamide) may be reduced by a clinically significant degree.Dosage and AdministrationGuar gum should be administered initially at a dosage of 2.5g 2 or 3 times daily during the first week of treatment. Thereafter, the dosage may be increased gradually to 5g 3 times daily, to reduce the possibility of unwanted gastrointestinal effects. Numerous formulations are available including powder and coated granules, but plain granules have been used most frequently and appear more palatable. Guar gum has also been incorporated into various foodstuffs including bread, crispbread, pasta and snack bars. The effects of the source, formulation and method of administration of guar gum on its efficacy and tolerability have not been well studied.