Garlic for flavour, not cardioprotection

THE LANCET

COMMENTARY Notwithstanding these facts immunisation policies in most developed countries are based on the laboratory finding of reduced concentrations of antitoxin titres with age and the assumption of waning immunity.1,5 Regular decennial boosters through adult life are recommended. The costs are high. First, each booster increases the chance of developing a sensitivity to further toxoid and the production of quite severe reactions, often local, such as pain, redness, and swelling round the injection site persisting for several days, and sometime general, such as headache, malaise, myalgia, and pyrexia. Second, each additional booster reduces the sensitivity of response to tetanus toxoid antigen after three or four challenges. Third, the costs of purchase and administration of the vaccine are substantial. A recent cost-effectiveness analysis6 found that a fully implemented 10-year booster strategy in the USA would cost $143 000 per year of life saved. As a comparison the authors point out that screening for hypertension in older men costs $8000 per year of life saved. Despite the implications of the epidemiology and the costs involved, the national immunisation policies in Australia, the USA, and many European countries still include 10-yearly tetanus toxoid boosters throughout adult life. In the UK the current policy is: “For immunised adults who have received five doses either in childhood or when adult, booster doses are not recommended, other than at the time of tetanus prone injury, since they have been shown to be unnecessary and can cause considerable local reactions. There are data that show that tetanus has occurred only exceptionally rarely in fully immunised individuals despite the passage of many years since the completing dose of a standard course of immunisation, and without subsequent routine boosting. Cases that have occurred were not fatal. There is therefore little justification for boosting with tetanus vaccine beyond the recommended 5 dose regimen”2.

This is an appropriate policy. But is it being followed in practice? The answer is that a vast amount of toxoid is still being given to unsuspecting individuals—probably because of the fee for item of service that UK general practitioners get from the NHS for giving tetanus toxoid boosters. With a sensible dirty-wound policy, which includes a tetanus-toxoid booster at the time of surgical cleaning of the wound in people who have had a primary course, the benefits of regular tetanus boosting throughout adult life are insufficient to justify the costs of the administration of the toxoid, the sensitivity reactions that might occur, and the dulling of the immune system by oversensitisation. Countries that mount a concerted effort to stop tetanus-toxoid boosters for adults can spend some of the money saved on a public and professional education campaign to ensure that everyone has a primary course of tetanus toxoid once in their life and knows what to do with a dirty wound. This advice is clearly laid out in the UK handbook on immunisations.2 For once, there is money and effort to be saved.

Cameron Bowie The Old Farmhouse, Clayhanger, Chard, Somerset TA20 3RD, UK

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Heath TC, Smith W, Capon AG, Hanlon M, Mitchell P. Tetanus immunity in an older Australian population. Med J Australia 1969; 164: 593–96. UK Health Departments. Immunisation against infectious disease. London: HM Stationery Office, 1996. Tetanus—the elderly are at greatest risk. CDR Weekly 1993; 3: 73. Prevots R, Sutter RW, Strbel PM, Cochi SL, Hadler S. Tetanus surveillance—United States, 1989–1990. MMWR CDC Surveill Summ 1992; 41 (SS-8): 1–9. Georgen PJ, McQuillan GM, Keily M, Ezzati-Rice TM, Sutter MS, Virella G. A population-based serologic survey of immunity to tetanus in the United States. N Engl J Med 1995; 332: 761–76. Balestra DJ, Littenberg B. Should adult tetanus immunisation be given as a single vaccination at age 65? J Gen Intern Med 1993; 8: 405–12.

Garlic for flavour, not cardioprotection Garlic (Allium sativum) is promoted as a “miracle nutrient” and “the world’s most ancient, versatile and enjoyable medicine”.1 With this hype, objective evaluation of garlic’s therapeutic potential will be difficult. However, well-designed studies are now appearing, although they are still outnumbered by studies flawed in design, conduct, and analysis. Garlic has been used for the prevention and treatment of an impressive range of diseases from plague to heart disease and cancer, as well as for warding off evil spirits. Garlic is rich in vitamins and antioxidants and garlic extracts are fashionable nutrient supplements. It is available in a variety of forms, but a standardised driedpowder preparation in tablet form is gaining popularity. The principal active ingredient is allicin, a sulphurcontaining component that, with its breakdown products, gives garlic its smell. Several other biologically active ingredients have also been extracted. Garlic is an important component of one of the diets associated with low rates of cardiovascular diseases, the traditional Mediterranean diet. Garlic’s putative cardioprotective effects include lipid and blood-pressure lowering, and antiplatelet, antioxidant, and fibrinolytic actions. Much of the research, especially on the control of cardiovascular disease risk factors, has been presented at sponsored international meetings, and few studies have been published in peer-reviewed journals. The best evidence is on the use of garlic for the treatment of hyperlipidaemia. A recent well-designed and executed randomised controlled trial assessed the effect of dried “odour controlled” garlic powder (900 mg/day) on cholesterol concentrations in a total of 115 men and women (mean age 53 years) recruited from a group general practice in Buckinghamshire.2 Pre-treatment cholesterol concentrations were 6·0–8·5 mmol/L and the trial was of sufficient size to have 90% power to detect a difference of 0·6 mmol/L between the treatment and placebo groups. No significant differences in lipid concentrations were found between groups after 6 months in both the intention-to-treat and the on-treatment analyses. Despite odour control of the preparation, smell attributable to the agent was an important reason for stopping treatment, along with abdominal pain. The results of this trial are concordant with another small but well-designed crossover trial reported recently from Australia,3 but in contrast to a small US study.4 Meta-analysis of the effects of garlic illustrates the strengths and weaknesses of this technique. Confidence in the outcome of these meta-analyses is limited by the general poor quality of the studies. Major problems

Vol 348 • November 2, 1996

THE LANCET

COMMENTARY include lack of description of study methods, inadequate assessment of potential confounders, possible underreporting of side effects (especially the smell of garlic), low power, and inadequate analyses. Two metaanalyses have been reported,5,6 and the second has been updated.2 The first included five of 28 studies identified and found a 9% net reduction in total cholesterol concentration attributable to garlic.5 The second found a greater effect, a 12% lowering of total cholesterol in the treated compared with the placebo group, which was apparent after 1 month of therapy and persisted for at least 6 months.6 The addition of two new well-designed trials to the second meta-analysis reduced the overall estimate of the likely effect of garlic on cholesterol lowering, compared with the earlier results.2 A meta-analysis of the blood-pressure-lowering effect of garlic was limited to eight studies, many of which have methodological shortcomings, and included only 415 participants.7 Although there is some evidence of a bloodpressure-lowering effect, the mechanism is unknown and much more extensive and rigorous evaluation is required. No studies of garlic have had the power to investigate cardiovascular disease endpoints. Publication bias is a strong possibility in this field since there is evidence, from “funnel plot” analysis, that there are fewer published negative studies than expected. This suggests that the meta-analysis gives a false-positive result.2 At this stage, the evidence does not support use of garlic powder for cardioprotection. Further well-designed controlled studies are required to increase our confidence in subsequent meta-analyses. In the meantime, garlic should be enjoyed for its culinary, not its cardioprotective, properties. Efforts to prevent cardiovascular disease should concentrate on lowering population levels of fat intake, smoking, and physical inactivity.

Robert Beaglehole Faculty of Medicine and Health Science, University of Auckland, New Zealand 1 2

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Mindell E. Garlic. The miracle nutrient. New Canaan, Connecticut; Keats Publishing, 1994. Neil HAW, Silagy CA, Lancaster T, et al. Garlic powder in the treatment of moderate hyperlipidaemia: a controlled trial and a metaanalysis. J Roy Coll Physicians 1996; 30: 329-34. Simons LA, Balasubramaniam S, von Konigsmark M, et al. On the effect of garlic on lipids and lipoproteins in mild hypercholesterolemia. Atherosclerosis 1995; 113: 219-25. Jain AK, Vargas R, Gotzkowsky S, et al. Can garlic reduce levels of serum lipids? A controlled clinical study. Am J Med 1993; 94: 632-35. Warshafsky S, Kamer RS, Sivak SL. Effect of garlic on total serum cholesterol: a meta-analysis. Ann Intern Med 1993; 119: 599-605. Silagy C, Neil A. Garlic as a lipid lowering agent—a meta-analysis. J Roy Coll Physicians 1994; 28: 39-45. Silagy CA, Neil HAW. A meta-analysis of the effect of garlic on blood pressure. J Hyperten 1994; 12: 463-68.

Euthanasia and palliative care: a pseudoconflict? Japan is an advanced country where palliative care, euthanasia, and other ethical issues have been little discussed, especially among health professionals. It was therefore noteworthy that Tokai University, one of the three largest private universities in Japan, held an international symposium on these topics at its European Centre in Denmark in September. Half the speakers came from Japan and half from European countries. Much of

Vol 348 • November 2, 1996

the discussion concerned disclosure (“truth-telling”) and decision-making in medicine. The cultural differences between countries are striking. In Japan it is still unusual for individuals to express their opinions openly or to question people in authority such as doctors, bosses, or senior family members; autonomy remains an unfamiliar concept. The diagnosis of cancer is still withheld from an estimated 20% of patients. Many patients with advanced or recurrent cancer complain that bad news is given in an insensitive and mechanical way through a one-way conversation. But practice is changing fast, especially among younger doctors. John Ellershaw, a palliative-care physician from Liverpool, described euthanasia and palliative care as an uneasy partnership and referred to the recent House of Lords Committee, which opposed any change in the law concerning euthanasia.1 The main reasons were the difficulty of setting secure limits to voluntary euthanasia, and the risk that vulnerable people—the elderly, lonely, sick, or distressed—would feel real or imagined pressure to request an early death. Takashi Hosaka, a psychiatrist at Tokai University, had investigated the attitudes of Japanese physicians and liaison psychiatrists to euthanasia and suicide by seriously ill people, to follow up the widely discussed “Tokai euthanasia case”. In April, 1991, a young doctor working at the Tokai University Hospital had given a lethal injection of potassium chloride to his terminally ill patient after repeated requests from the family to ease his suffering. The doctor was charged with murder. In 1995 he was found guilty but received a 2-year suspended prison sentence because the family had pressed him and because no system existed for managing such problems. Asked what they would do in a similar case, two-thirds of physicians said they would have increased the dose of opioid after explaining to the family that it might shorten life (but use of opioids has been low in the past). Most of the psychiatrists did not consider suicide by the patient as reasonable, though the act is accepted more in Japan than in many other countries. In the Netherlands euthanasia is not legal, but is accepted in practice if the doctor informs the prosecutor, and if the doctor can prove that the patient was suffering intolerably and requested it voluntarily. In Switzerland active voluntary euthanasia and mercy killing are punishable, but passive euthanasia and assisted suicide are not: the patient’s living will must be respected. EXIT Switzerland, which has over 60 000 members, has since 1995 helped about 200 seriously ill patients. The fierce exchanges between the advocates of palliative care and of euthanasia or assisted suicide became calmer when Jan Stjernswärd, chief of the WHO Cancer and Palliative Care programme from 1980 until this year, put the debate into perspective. At present 51 million people die yearly, 39 million of them in developing countries. Palliative care is needed everywhere, and great educational and organisational efforts are urgently needed to provide it. Promising starts are being made, for example by removing bureaucratic obstacles to the supply of opioids2 and training more doctors in palliative care. But where unbearable suffering cannot be eased by palliation or in its absence, it is cruel to deny help. Legalisation of euthanasia would, however, be not only difficult but also dangerous because it could inhibit the development and provision of adequate palliative care. It seems much more prudent and 1187