The potential and limits of functional foods in preventing cardiovascular disease

Cardiovascular disease (CVD) is still a major cause of death in Western populations and is becoming an important cause of morbidity and mortality worldwide. Thanks to advanced medical knowledge and treatments, many patients survive an initial event. Because of that, prevention of secondary CVD is a growing task for nutritionists and other health professionals.

Cardiovascular risk can be reduced by lifestyle changes, one of which is diet. There is now substantial evidence from epidemiological and clinical studies that a diet rich in fruits, vegetables, unrefined grains, fish and low-fat dairy products, and low in saturated fats and sodium, can reduce the risk of coronary heart disease and hypertension. People who have adopted such diets have benefited by way of a much lower risk of heart disease. However, such a prudent diet is not typical of what consumers in Western countries eat.It appears that consumers today are less likely to invest in long-term health if taste

Evidence-based strategies to reduce the risk of coronary heart disease

Substitute nonhydrogenated unsaturated fats for saturated and trans fatsIncrease consumption of omega-3 fatty acids from fish, fish oil supplements, or plant sourcesConsume a diet high in fruits, vegetables, nuts, and whole grains and low in refined grain products

Functional foods, cardiovascular disease and diabetes

and convenience are compromised: in 1998 only 24 per cent of consumers ate `healthy foods’ for long-term prevention of disease, as opposed to 45 per cent in 1990. However, almost all consumers indicated that they sometimes buy foods for health reasons. Food industries are aware of this, and market some of their foods with health claims. Indeed, it has been shown that health claims on foods have a positive influence on consumers’ perception of the healthiness of foods.7 Thus, functional foods in the form of palatable and ready-to-use foods that suggest short- or long-term health benefits have a huge market and health potential.

This post will discuss how functional foods can play a role in choosing a healthy diet.

The term `functional foods’ is not a standard nutritional term in nutrition textbooks. Regulatory agencies and professional associations of nutrition scientists and dieticians all use different definitions. ILSI Europe, an industry-sponsored forum in which representatives from industry, academia and government address nutrition issues, proposed a definition which in abbreviated form runs:

A food can be regarded as `functional’ if it is satisfactorily demon­strated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way that is relevant to either an improved state of health and well-being and/or reduction of risk of disease.

More concise definitions are `foods that provide a health benefit beyond basic nutrition’ or `foods that have health benefits beyond the traditional nutrients provided’. Examples are soy, garlic, and green tea. What these definitions do not include is the link with the food industry, which uses health claims to market functional foods. An alternative definition could therefore be `a food which claims explicitly or implicitly to improve health or well-being’.

Functional foods that are marketed with claims to reduce heart disease focus primarily on the risk factors of blood cholesterol, homocysteine and hypertension. This can be done by a reduced content of food components that are known to increase risk, such as saturated fat or sodium. More recently products have been designed that are enriched in components that are thought to reduce risk. The most common `protective’ ingredients include fibres, soya, omega-3 fatty acids, phytostanols and phytosterols, and (antioxidant) vitamins. These components have cholesterol or homocysteine-lowering abilities in metabolic studies. The added ingredients may be food components that are often deficient in Western diets, such as calcium and folate. Their recommended intake could, however, be achieved by `normal’ foods. The added ingredients may also be nutrients or phytochemicals that are normally not ingested in effective amounts because natural food sources of these ingredients are scarce or not part of out diet. Examples are phytosterols or probiotics. Examples of functional foods include soya drinks, eggs enriched with omega-3 fatty acids, margarines with plant sterols or stanols, and vitamin-enriched cereals.

In this post a distinction will be made between functional foods that help consumers adhere to dietary guidelines and functional foods that offer novel ingredients with claimed or suggested health effects.

Many consumers struggle to meet dietary recommendations. The United States Department of Agriculture (USDA) reported in 1998 that the average intake of added fats and sugars was too high and the intake of fruits, vegetables, dairy products, lean meats and foods made from unrefined grains was too low compared with serving recommendations. Comparable findings in The Netherlands and the rest of Europe (supplement 2 to the British Journal of Nutrition 1999, vol. 81) have been reported.

Functional foods enriched with vitamins, dietary fibres or specific fatty acids, or foods that are designed to be low in sodium or saturated fat, can therefore make a valuable contribution to our diet, as will be discussed in the following paragraphs. The evidence-based strategies for a reduction in CVD risk have been used as a guide.

Replacement of saturated or trans fat in the diet by carbohydrates or other types of fat reduces the risk of coronary heart disease. Margarines were rich sources of trans fat until about a decade ago, but food manufacturers have markedly reduced the trans fat content since reports on adverse health effects.

Fish oils are listed as functional food ingredients because of their remarkable effect on preventing sudden cardiac death. The recommended consumption of fish in Western countries is one or two portions per week. The average intake varies highly between countries, with a six- to sevenfold variation in total fish consumption in countries in Europe, but is lower than the recommendation. Instead of increasing the amount of fish in the diet, functional foods enriched with the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be used. Several foods can be fortified with fish oil, for example margarines, dairy products, sausages, luncheon meat and french onion dip. Adding these products to an ad libitum diet significantly increased plasma and platelet EPA and DHA.

Chicken eggs enriched with n-3 fatty acids may provide an alternative source of EPA and DHA. In populations where egg consumption is higher than fish consumption, in particular, this could be an effective strategy to increase n-3 intake. Chicken eggs can be enriched with n-3 fatty acids by feeding hens diets rich in flax seed or fish meal. It has been shown that consumption of two to four enriched eggs/day significantly increased polyunsaturated fatty acid (PUFA) concentrations in platelet phosplipids. Effects on blood lipids were variously shown to be absent to beneficial. Omega-3 enriched eggs can be a succesful source of n-3 fatty acids only if they are accepted by the consumer. In a sensory evaluation with 78 untrained volunteers no difference in taste was found, and storage life was no different for enriched and `normal’ eggs. Although three enriched eggs need to be consumed to provide approximately the same amount of n-3 fatty acids as one meal with fish, they can be a good source of n-3 fatty acids for consumers who do not like fish.

In the US, vegetable consumption is close to the recommended daily intake but fruit consumption is less than half of the recommended amount. In Europe, fruit and vegetable consumption is also below recommendations (supplement 2 to the British Journal of Nutrition 1999, vol. 81). As a consequence many consumers do not meet dietary recommendations for fibre, folate, vitamin C and other vitamins. For example, it has been estimated that approximately 50 per cent of Dutch consumers do not meet dietary recommendations for folate.

Many consumers believe that a healthy meal takes more time to prepare. Ready-to-eat salads, fruits and ready-to-cook vegetables can increase consumption in consumers with limited time to prepare foods.

Foods enriched with fibres and vitamins can be an alternative to fruits and vegetables, but only to a certain point. For example, different dietary fibres have different effects on CVD risk: water-soluble dietary fibres such as pectin and guar gum appear to have stronger effects than insoluble fibres such as wheat bran. Thus, a mixture of various dietary fibres such as found naturally in fruits and vegetables appears to be necessary for a protective effect on CVD. Also, adding vitamins to foods to compensate for low fruit and vegetable intakes might not have the expected effects. For example, beta-carotene was widely believed to reduce cancer risk in smokers, because intake of carotene-rich foods was associated with less cancer, as were high levels of carotene in blood. However, it was found that carotene supplements increased risk of lung cancer in smokers. Large clinical trials of antioxidants have also had disappointing outcomes. Moreover, several other bioactive components from fruits and vegetables, rather than vitamins, may protect against CVD. Enrichment of foods with known vitamins and minerals might therefore not be enough.

Consumption of functional foods can make an important contribution to nutrient intakes. For example, consumption of micronutrient-enriched cereals was associated with significantly increased intakes of iron, B vitamins, vitamin D and fibre in an adult Irish population.

Although not part of the strategies as proposed by Hu and Willett in their 2002 paper, reduced salt intake is another strategy to lower risk of CVD. Current average salt intake in Western populations is 9±12 g/day and this should be reduced to 5±6 g/day according to most public health recommendations aimed at lowering blood pressure.

Manufactured foods are the largest sources of salt in our diet, whereas cooking salt and table salt provide only 5±35 per cent. Thus, reductions in the amount of salt added by food manufacturers have a much larger impact in salt consumption than the advice to use less salt at home. Functional foods with reduced salt content such as soups and snacks ± could therefore have a considerable impact on CVD risk.

Replacing sodium in the diet with potassium has been shown to reduce blood pressure. Mineral salts such as LoSalt, in which a third of the sodium has been replaced by potassium, could therefore be a good alternative to regular salt.

Most of the claims for benefits from novel ingredients have come from ecological or cohort studies.However, the effects of some ingredients on risk markers have been well investigated in clinical trials, and show promise of reducing disease risk.

Sterols and stanols

Margarines and yogurts have been enriched with plant stanols or sterols, which lower low-density lipoprotein (LDL) cholesterol by 10 per cent and could thus make an important contribution to prevention of coronary heart disease. Many well-controlled trials have documented the efficacy of sterols and stanols for lowering LDL, and no major adverse effects have been noted. However, long­term safety and clinical efficacy have not been evaluated in large-scale clinical trials of the size and duration customary for new drugs. The Health Council of The Netherlands therefore discourages the use of plant sterols by consumers who would not benefit from a cholesterol-lowering effect, e.g. children and pregnant women, and other regulatory agencies have suggested similar limitations.

Polyphenols

High intakes of tea rich in catechins and other flavonoid polyphenols have been associated with a reduced risk of coronary heart disease. A clinical trial to evaluate these effects would seem justified and feasible.

Isoflavones (phytoestrogens)

A high consumption of soy and soy protein has been associated with a low risk of CVD in ecological studies. Besides soy protein, phytoestrogens such as genistein might be responsible for the effects on CVD risk. Phytoestrogens comprise several groups of non-steroidal oestrogens including isoflavones and lignans. There is limited quantitative data on the absorption and metabolism of dietary phytoestrogens. Although it is now known that dietary phytoestrogens are metabolised by intestinal bacteria, absorbed, conjugated in the liver, circulated in plasma and excreted in urine, further clinical trials should determine the potential health effects of these compounds.

Functional foods with isoflavones and other phytoestrogens include breakfast cereals, soft drinks, bakery and dairy products and snack bars.

Potential Synergy of Phytochemicals found in the Mediterranean Diet

The buzz about vitamins and minerals has lately been re-placed by the buzz about phytochemicals. Phytochemicals are non nutritive substances in plants. Thousands exist, and every plant food contains them. What can they do for us? Knowing what they do for plants may shed some light on the question.

Some phytochemicals protect plants from invaders of all kinds. Predators like leaf-munching insects and animals, bacteria, viruses, and fungi can all be put off by the action of phytochemicals, whether that action comes in the form of an unpleasant taste, a repugnant smell, a startling color, or a poisonous effect. Also, the antioxidant action of cer­tain phytochemicals protects plants against an oxygen-rich environment (remember, plants “breathe” carbon dioxide, not oxygen).

What happens when we consume phytochemical-laden vegetables? Only some of the thousands of phytochemicals have been found (to date) to have an effect on the human body, but these few apparently have enough of an effect to make a difference. (The thousands of phytochemicals as yet uninvestigated represent great research potential. The field of phytochemical research is still in its infancy and may well reveal many other benefits to human health.)

When humans consume certain phytochemicals, we ap­pear to enjoy protective effects similar to those plants re­ceive. Phytochemicals, in many ways, seem to defend the human body against free radical damage (see below) and age-related degeneration, not to mention viruses, bacteria, and fungi.

The phytochemical-cancer connection has been widely researched, and results suggest that phytochemicals may disrupt cancer in more ways than one. Phytochemicals may protect DNA or repair damaged DNA, helping to prevent cancer from developing. They may prevent cancerous cells from multiplying and/or spreading through the body. Phyto­chemicals may help the body to help itself, giving carcinogen-blocking enzymes a boost.

Much cancer research has focused more generally on veg­etable and fruit consumption, which implicates phytochemi­cals by association. Raw and green vegetable consumption appears to reduce the risk of stomach, lung, mouth, esoph­ageal, colon, rectal, breast, and bladder cancers. Research in other areas has supported general vegetable and fruit con­sumption as well, suggesting that a diet rich in vegetables and fruits may lower the risk of heart disease and stroke, and boost the effectiveness of the immune system. Some of the phytochemicals more relevant to humans include the allium compounds (in onions and garlic); carotenoids (in dark green and deep orange vegetables), including lycopene (particularly rich in tomatoes and red grapefruit); glucosinolates (in cruciferous vegetables such as broccoli); and flavonoids (in many foods including tomatoes).

Allium compounds, also called organosulfides, exist in onions, garlic, leeks, shallots, and chives. These compounds give these vegetables their unique smell and pungent taste. They also appear to increase the effectiveness of the body’s own cancer-fighting enzymes, halt the production of nitrates into carcinogens, lower cholesterol and blood pressure, and reduce the tendency of the blood to clot. Allium compounds appear to be most potent in raw vegetables, and may be de-stroyed by the cooking process.

Carotenoids are potent antioxidant phytochemicals that fight free-radical cellular damage in the body, possibly guarding against a wide range of chronic diseases. They are the substances in plants that provide their bright red, orange, or deep yellow colors. More than six hundred carotenoids are known, but fewer than fifty have been found to be active in the human body. Examples of beneficial carotenoids found in vegetables are as follows:

Alpha-carotene is a substance that the body converts to vitamin A. Research has linked alpha-carotene to a reduced risk of lung cancer. Carrots are full of it.Beta-carotene (as discussed previously) is another substance the body converts to vitamin A. Well publicized for its anticancer benefits, beta-carotene may also prevent cataracts, slow the progression of heart disease, and boost the immune system. Good sources include most red, orange, and yellow fruits and vegetables, as well as dark, leafy greens.Gamma-carotene is just starting to get attention as an anticancer agent, and research with gamma-carotene is just beginning. The best sources of gamma-carotene are tomatoes and apricots. The above three carotenoids—alpha-carotene, beta-carotene, and gamma-carotene, are thought to be powerful allies against cancer.Lycopene, the carotenoid that gives tomatoes, watermelon, and red grapefruit their rosy hues, has been linked to decreased risk of prostate and breast cancer, and may also protect skin from the damaging effects of ultraviolet radiation.·Lutein and zeaxanthin have been found in the eye and may help prevent age-related macular degeneration by protecting the retina from potentially harmful light exposure, and also by neutralizing the effects of free radicals formed by the negative effects of sunlight on the retina. One study demonstrated a lower incidence of macular degeneration in people who ate increased amounts of spinach and collard greens, both of which contain lutein and zeaxanthin.

Flavonoids include a huge class of compounds (more than four thousand) called phenolic compounds and are found in plants of all types. Flavonoids give plants color, have anti-fungal properties, slow or prevent damaging oxidation, lower cholesterol, prevent the clotting of blood, and protect cells from carcinogens. The most studied flavonoid is quercetin, abundant in onions, wine, and tea. Unlike the allium compounds, quercetin remains intact and available after cooking, and may have an anti­cancer effect in the body.

Other flavonoids available to the human body from food include isoflavones, found primarily in soybeans (although soybeans aren’t part of a traditional Mediterranean diet, they should be consumed in the Mediterranean spirit of eating). Isoflavones are thought to have an estrogenlike effect on the body, possibly guarding against hormone-related cancers like breast cancer. Catechins are another type of flavonoid, which may be responsible for the anticancer properties ap­parently inherent in green tea. Flavonoids may also be a fac­tor in the heart-protective benefits of red wine.

One of the most intriguing qualities of phytochemicals, and the most convincing argument for receiving your phyto­chemicals from food rather than from supplements, is their synergistic nature. Science has only begun to understand the effects of individual phytochemicals on the body. The com­bined nature of phytochemical interactions in the body—of eating a whole plant, rather than a supplement of artificially produced or isolated single compound—is still largely a matter of speculation, but many experts assert that eating plant foods in a form close to their original state (minimally processed) is the best way to ensure receiving the health benefits, both those understood and those not yet under­stood.

Even if the term phytochemical was unknown in the Mediterranean during the time when the traditional Mediterranean diet was the pervasive way of eating, phyto­chemical benefits were at a premium in this diet of locally grown, seasonally consumed, minimally processed plant foods. Understanding the nature of phytochemicals pro­vides one more good reason to return to more traditional di­etary practices.