The idea of the 'Polypill' was first mooted in 2003 by Professors Nick Wald and Malcolm Law of London’s Wolfson Institute of Preventive Medicine (1), suggesting that if everyone over age 55 and anyone with existing cardiovascular disease took a single pill per day without screening, ischaemic heart disease events would be reduced by 88% and stroke by 80%. Side effects would be “minimal” (only 15% of those taking the pill).

The polypill proposed by Wald and Law would have six ingredients: a statin, aspirin, folic acid, and three antihypertensives (a thiazide, a ß blocker, and an angiotensin converting enzyme inhibitor), all at half dose. The combination, the authors said, would prevent heart disease and stroke by reducing four different risk factors—blood pressure, lipid concentration, homocysteine concentration, and platelet function. Financial considerations reduce the cost-benefit ratio: if the Polypill included the three classes of blood pressure lowering drugs with the lowest prevalence of adverse effects (thiazide, angiotensin II receptor antagonist, and calcium channel blocker) instead of the three with the cheapest ingredients (thiazide, ß blocker and ACE inhibitor) only 8% of those taking the pill would suffer adverse symptoms.

At a recent meeting of experts organised by the US Centers for Disease Control in Atlanta it was suggested that three powerful groups are threatened by the Polypill idea: the drug industry, doctors, and the public health lobby, which “generally favours lifestyle change over mass drug treatment”. The drug industry and doctors obviously stand to lose income and clientele from removing individualised diagnosis, treatment and prescription, as the Polypill will no longer need consultations and can use generic components that are not subject to patent protection. The public health lobby however could lose the option of personalised healthcare, and the right to take control of their own health and prevent disease through the natural self-healing ability of the body when using appropriate diet and natural medicine according to individual need without any side effects.

The fact that while statins can perform the dubious task of lowering cholesterol levels in healthy individuals, it can also cause cardiomyopathy by depletion of coenzyme Q-10, is one of the ironies of both statins and the Polypill concept, apart from the rarer side-effects of rhabdomolysis, memory loss and hepatitis, however statins are now available over the counter in the UK without prescription, with no inclusion of or recommendation to take co Q-10. Beta-blockers are well known for their mind-numbing effects as well as their unsuitability for those with asthma. Hypokalaemia (potassium deficiency) may occur with thiazide diuretics. ACE inhibitors can cause acute renal failure, more common in the older population. Aspirin is unsuitable for those with salicylate intolerance, and causes internal bleeding, particularly in individuals of blood group O, however the authors say that the risk of increase in haemorrhagic stroke (from bleeding) would be exceeded by the reduction in thrombotic strokes (from a blood clot), giving the all-important cost-benefit ratio. The authors failed to mention natural medicines that prevent strokes from bleeding without any side-effects. The authors say about a third of people taking the Polypill would ‘benefit’ overall (at the expense of half of this number of people having side-effects).

The only useful thing about this concept is that it raises the profile of the significance of homocysteinaemia in cardiovascular disease. [The role of folic acid for reduction of homocysteine is well documented, however research suggests that synthetic folate supplementation (pteroyl-L-monoglutamic acid, a product of the pharmaceutical industry which rarely occurs in nature) could cause an increase in the incidence of breast cancer (2). The authors of this paper would wish that it be considered as nothing more than a 'research pointer', as the number of deaths in the study was small (31 actual deaths), and the findings were balanced with commentary and several notes of caution, although the article has already caused front page headline reactions in the tabloid press. Although we are told in the research that the "tablets were supplied in six colours, two of which contained folate in 0.2 mg and 5 mg daily doses”, what is not reported is which colouring agents were used, and whether carcinogenic azo dyes had an influence on the results].

Interestingly a version of the polypill is likely to appear on the market in India by the end of 2005, as the authors stated “widespread use would have a greater impact on the prevention of disease in the Western world than any other single intervention”. Is it that resistance would be less from the three major groups who could influence the acceptability of the Polypill idea would have less influence in India? The recipients of the pill are unlikely to be monitored for side-effects due to the fact that “the tests lack specificity, so the increased risk of cardiovascular disease after stopping the drug in people positive on monitoring may outweigh any benefit” – the cost-benefit ratio again.

Based on the potential costs and adverse effects of the Polypill, the concept of the Polymeal was raised in 2004 (3) with the objective of identifying “an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population”. The ironic tone of this article suggests that an “evidence based recipe” includes wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds. Using similar analysis to that of the Polypill study, the authors state that “combining all the ingredients of the Polymeal resulted in cardiovascular disease being reduced by 76%. Whether increasing the amount of each ingredient would increase the effect of the Polymeal is uncertain”.

The article was published just before Christmas and makes amusing reading: if the Polypill ingredients were used to fortify flour used in Polymeals, “redundant cardiologists could be retrained as Polymeal chefs and wine advisers”. There are however some serious conclusions: “Pharmacological interventions are not the only option for preventing heart disease; a healthy diet and an active lifestyle reduce cardiovascular disease as well”. It is unfortunate that the idea of a healthy diet is not taken seriously by the medical community at large, and the article had to be presented as a joke.

The concept behind the Polymeal article could also be applied to the idea of the Polypill: “The preventive strategy outlined here is radical. But the ‘healthy person’ is an outdated concept from the era before scientific prevention. We should recognise that in Western society we all have cardiovascular risk factors, so everyone is at risk, and the diseases they cause are common and often fatal.”

What the authors of both Poly- studies fail to appreciate (or admit) is that some individuals are at greater risk of heart disease than others, and the cost-benefit ratio of many foods are different according to some easily-measured factors, not least ABO blood group and salivary secretor status. If individuals were given access to the information about simple food choices on a large scale they could take control of their own health.

References:

1. A strategy to reduce cardiovascular disease by more than 80%.

Wald N J and Law M R, BMJ 2003 326: 1419.

2. Taking folate in pregnancy and risk of maternal breast cancer.

Charles D, Ness AR, Campbell D et. al., BMJ 2004;329:1375-1376.

3. The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%.

Franco OH, Bonneux L, de Laet C et. al., BMJ 2004;329:1447-1450