The Digest

Two Sides of the Same Coin

The New England Journal of Medicine recently published a study in which the authors had aimed to identify the components of the ‘Mediterranean diet’ responsible for its association with a reduced risk of cardiovascular disease (namely heart attack and stroke). In the so-called PREDIMED (Prevención con Dieta Mediterránea) trial, Dr Estruch and his team in Spain divided 7447 participants – aged between 55 and 80 years and considered to be at high risk for cardiovascular disease – into three groups, which will be referred to as Groups 1 to 3 herein. The members of each group were requested to follow a Mediterranean-type diet, but with the following modifications:

After monitoring the participants for almost 5 years, it was found that those in Groups 1 and 2 had benefitted from a reduced risk of cardiovascular disease compared with those in Group 3. The magnitude of this reduction in risk was impressive (approximately 30 %), particularly when brought about solely by dietary means.

    Two aspects of the PREDIMED trial have attracted the most discussion. The first is that the diet followed by the participants in Group 3 was not particularly low in fat. With 37 % of their energy (‘calories’) being derived from fat (by the end of the study), those in Group 3 had only a marginally lower total fat intake than those in the other two groups, whose energy intake from fat was 41 %. For comparison, the American Heart Association recommends limiting fat intake to providing between 25 and 35 % of total calories. Similarly, the Food Standards Agency in the UK recommends an upper limit of 35 %. It is all the more noteworthy, then, that the PREDIMED trial demonstrated the importance of the type – rather than amount – of fat in the diet in determining cardiovascular health.

    The subjects in Group 1 would have had a particularly high intake of monounsaturated fatty acids (mostly oleic acid, the principal fatty acid in olive oil). Fatty acids are the building blocks of fats and oils. Compared with sunflower oil, which is one of the main vegetable oils consumed in the United Kingdom, oils rich in ‘monounsaturates’ are far less susceptible to damage by free radicals (short-lived chemical species able to inflict damage to proteins, carbohydrates, fats and indeed DNA). Such damage by free radicals is believed to be involved in the development of many important diseases, including those of the cardiovascular system. What is more, many of the substances formed during the degradation of oils by free radicals are toxic. The intrinsic resistance of monounsaturates to such damage is believed to be one reason why the Mediterranean diet is protective against cardiovascular disease. The second reason – which brings us to the second main point upon which the PRIDIMED trial has attracted discussion – involves the high levels of ‘antioxidants’ present in the typical Mediterranean diet, many of which occur in olive oil itself. Antioxidants are agents that protect other substances from free radicals, a good example being vitamin E.

    In its criticism of the PRIDIMED study, the ‘Physicians Committee for Responsible Medicine’ claimed that the real benefits of the Mediterranean diet stem from its rich provision of antioxidants and not olive oil or fatty fish. The PCRM is correct in its assertion that low-fat, vegetarian diets – rich in fruits, vegetables and whole grains – carry innumerable health benefits, but the Committee does not appear to give proper consideration to the importance of the type of fat or oil in the diet. There is a world of difference between obtaining 35 % of one’s calories from the ‘healthy’ oils in nuts, seeds, olive oil and oily fish and what might be termed the unhealthy oils: namely those containing trans fats (partially-hydrogenated vegetable oils) and, in particular, polyunsaturated vegetable oils that have been degraded into toxins by heating to high temperatures (e.g. during deep-frying). It can be argued that a diet considered high in fat, but with that fat coming from nuts, olive oil and oily fish, is far healthier than a diet lower in fat, but consisting of ‘unhealthy’ fats. The evidence appears to bear this out.

    Whilst the participants in Group 1 are expected to have benefitted from the intrinsic resistance of the fatty acids in olive oil to damage by free radicals (as well as the antioxidants in the oil), those in Group 2 enjoyed a similar level of protection from cardiovascular disease. Like olive oil, hazelnuts and almonds are both rich in monounsaturates (and are also good sources of antioxidants). However walnuts – the nuts consumed in the highest quantity by Group 2 – are rich in polyunsaturated fatty acids, which are far more susceptible to damage by free radicals than monounsaturates. One of the main polyunsaturates in walnuts is alpha-linolenic acid, which belongs to the so-called omega-3 family of fatty acids. In the body, omega-3 fatty acids can be converted into a family of locally-acting ‘chemical messengers’ (prostaglandins) that tend to suppress inflammation, which, along with free radical formation (the two phenomena often go hand-in-hand), plays an important role in many disease processes, including cardiovascular disease. Although only a very small fraction of dietary alpha-linolenic acid is believed to undergo conversion to these beneficial, anti-inflammatory substances, the walnut intake by the participants in Group 2 was substantial. Moreover, the negative, ‘downside’ effects of polyunsaturated fatty acids – namely their ease of damage by free radicals – would probably not have come into play because, firstly, the oils are protected by the high levels of antioxidants present in walnuts and, secondly, the nuts were not fried before being eaten (one would hope), which is often the case with other dietary sources of polyunsaturates.

    We have, therefore, the beginnings of a rational, mechanistic explanation for the protection seen in Groups 1 and 2 when compared with Group 3. There were also differences in the intake of oily fish between the participants: those in Groups 1 and 2 were encouraged to consume three or more servings per week, whereas those in Group 3 were requested to restrict their intake of oily fish to one (or fewer) servings. Once again, we see that the three groups had similar (and relatively high) fat intakes, but marked differences in the types of fat they consumed. Oily fish is believed to be particularly beneficial in protecting from cardiovascular disease because it is rich in omega-3 fatty acids. However, unlike the alpha-linolenic acid present in walnuts, the omega-3 fatty acids in oily fish – particularly one known as EPA (eicosapentaenoic acid) – are converted to those ‘anti-inflammatory substances’ very easily and efficiently. This is because, before it can be converted into such substances, alpha-linolenic acid must first be converted to EPA in the body, which it is not always particularly good at: eating oily fish provides EPA directly, so this first – ‘difficult’ – step in the formation of the anti-inflammatory substances is, in effect, bypassed. (Consumers should keep this in mind when reading food labels extolling the virtues of oils and spreads rich in omega-3 oils derived from seeds.)

    Returning to the criticisms levelled at the PREDIMED trial by the Physicians Committee for Responsible Medicine, the Mediterranean diet is not ‘misleading Westerners’. (And the last time I checked, Spain was still in Western Europe.) The PCRM is not justified in its dismissal of the importance of fatty fish and olive oil in the protection such diets offer against cardiovascular disease. The Committee states: ‘When it comes to fad diets, it’s important to understand the research’. The Mediterranean diet is no fad diet – it is probably the healthiest diet in the world. The Committee is, however, correct in its appreciation of the beneficial effects of dietary antioxidants. This author’s understanding of the research – of the underlying chemical processes, rather than the ‘blind’ statistics – is that we are looking at two sides of the same coin: the monounsaturates in olive oil are less prone to damage by free radicals to begin with (compared with polyunsaturates) and antioxidants, present in generous quantities in Mediterranean diets, serve to suppress further the participation of free radicals in the development of cardiovascular disease. The omega-3 fatty acids in oily fish offer additional protection via their actions on the inflammation ‘arm’ of cardiovascular disease, which in many respects is a response-to-injury phenomenon.


R. Estruch et al. (2013) Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. The New England Journal of Medicine, volume 368, pages 1279 – 1290. [Article]

Discussed, for example, in the Editorial: L. J. Appel and L. Van Horn (2013) Did the PREDIMED Trial Test a Mediterranean Diet? The New England Journal of Medicine, volume 368, pages 1353 – 1354. [Article]

Physicians Committee for Responsible Medicine. ‘Mediterranean Diet is Misleading Westerners’. [Article]

Mark Burkitt

Westcott Research and Consulting [Home Page]

Article published 29 June 2013

If you would like to learn more about the topics discussed in this article, it is recommended you read Dr Burkitt’s book, Healthy Eating Through Informed Choice, where you will find, for example, descriptions of the various types of fats and oils (saturates, monounsaturates, polyunsaturates, trans fats, omega-3 oils etc) and explanations of how they affect health.

Whilst the book is written in non-technical language and is intended primarily for readers with absolutely no background in science, it is hoped that trained scientists and health professionals will also find the material to be of interest – the book is extensive in its scope and challenges some of the conventional views on the role of nutrition in human disease.