¹Unilever Corporate Research, Colworth Laboratory, Sharnbrook, Bedford, UK

Correspondence: Dr MR Green, Unilever Corporate Research, Colworth Laboratory, Sharnbrook, Bedford, MK44 1LQ, UK. Tel: +44 1234 222104; Fax: +44 1234 222552; E-mail: martin.green@unilever.com

In spite of concerns about affluence-related conditions such as obesity and diabetes, the Western world has enjoyed extraordinary improvements in health and well-being over the past century. During the last 150 years, the average female life expectancy has increased by 3 months per year and now exceeds 85 years in Japanese women.¹ The main causes of this remarkable phenomenon are improvements in nutrition, sanitation, hygiene and infection control.

Individuals are ever more captivated by opportunities for improved personal health and appearance; therefore, it is not surprising that consumer studies suggest preferences for food products having positive health benefits. At the same time, consumers believe that they are all 'different' so it is reasonable that food choices should reflect this diversity. As we all want to see healthier populations, it is increasingly topical to ask how food companies can further contribute to health and longevity, and how new concepts and techniques from the genomics era can aid the industry to improve healthy living. Indeed, many population studies have concluded that the micronutrients from high fruit and vegetable diets improve health and longevity;^2,3 so how might the food industry further contribute to improvements in human health and what are the pitfalls?

An unconventional vision for the foods industry is (i) that major benefits for society will arise in the future from modest, individual improvements in health and well-being generating a cumulative, significantly improved pattern of health and well-being across entire populations; and (ii) that these accumulated benefits from now on will far outweigh those achieved by new medical treatments. In essence, population benefits bring improved health for all, while medicines, though of irreplaceable and immense value to individuals, only immediately benefit the current proportion of the population with treatable conditions (Figure 1). Indeed, improvements in population health can lead to many people not developing a specific disease at all. The population argument can be illustrated by the role of fluoride in improving dental health. Dental decay affected virtually everyone in developed countries prior to the widespread introduction of fluoride in the early 1960s. The anticaries property of fluoride was discovered in the 19th century and through epidemiological observations in the USA,⁴ but the major benefits for mankind and marked reduction in caries incidence in the Western world were mainly achieved by fluoride delivery to the general public in cheap and/or consumer pleasing forms.^5,6 This was implemented in part through publicly funded research, water fluoridation and education, but mainly by commercial product sales to consumers who appreciated and enjoyed the immediate benefits of the product forms. Extrapolating from the fluoride paradigm, an ideal vision for health care is illustrated in the figure: the ambition for all in society to achieve a fully acceptable lifestyle for the whole of their life aided by consumer desirable foods that promote health. In this respect, public health organisations and the commercial health care and foods industries share a mutual interest and motivation in providing better health and well-being solutions for society.

Figure 1.

Illustration of how foods industries can target the majority of the (relatively healthy) population with products and services to improve health, while the Pharma industries are focused on the smaller proportion of the population with medical needs. Accordingly, the foods industries represent part of the 'solution' for improved population health as illustrated by the left-shifted population distribution.

Full figure and legend (130K)

Turning to some of the issues, there are abundant examples of drugs causing different, sometimes adverse, responses in individuals driving the new area of pharmacogenomics.⁷ Similarly, there are many examples of important food components badly tolerated by some individuals; for instance, lactose intolerance, gluten and nut allergies. In some cases, the mechanisms for these disorders are known, for example, lactase deficiency; in other cases genomic techniques are helping to elucidate the mechanisms underlying these conditions.

There are also diet-linked examples demonstrating that benefits expected from population studies can break down for individuals. In a carefully executed metabolic study, Schaefer et al⁸ observed that the effects of the National Cholesterol Education Program (NCEP) Step 2 diets on serum LDL-cholesterol, HDL-cholesterol and triglyceride levels differed very widely between individuals, with some subjects showing no improvement at all. Responses to diet can also be strongly affected by gene polymorphisms. For example, alcohol has quite different effects on LDL-cholesterol levels dependent on individual ApoE genotype.⁹ ApoE4 carriers show elevation of LDL-cholesterol even with moderate alcohol intake, whereas in ApoE2 carriers the reverse is seen. The incidence of the ApoE4 gene varies markedly between populations, being below 10% in Italy, Greece and Spain and over 30% in New Guinea and some African and Oceanic populations.¹⁰ While the origin of these genotype differences is ancestral, perhaps related to survival factors in harsh environments,¹⁰ these variations should stimulate a debate on optimal country-by-country public health strategies and dietary recommendations. In practical terms, until an early surrogate or phenotypic marker for the genetic risk factor(s) becomes evident, rather than a late, symptomatic risk factor such as angina, the benefits from targeting dietary improvements towards 'genetically' at-risk subgroups will be difficult to implement.

What immediate opportunities are there for foods-based population health improvements? Given that the health benefits could be immense, this question must surely be addressed. Major current problem areas for population health include obesity, cardiovascular health, age-related cognitive decline, metabolic syndrome, insulin resistance and diabetes. To illustrate the last example, recent revised WHO estimates presented at the Third World Congress on the Prevention of Diabetes in September 2002 suggest that the worldwide incidence of diabetes will exceed 450 million people by 2025. More recently, the WHO published estimates that over one billion people are obese and over 400 million people are clinically obese. The American Diabetes Association has estimated that in the US, total direct and indirect medical costs of diabetes and associated disorders reached $98 billion in 1997;¹¹ to these figures must be added the emotional cost of untold human suffering and premature death. The NIH-sponsored Diabetes Prevention Programme suggests that a lifestyle (ie exercise and dietary change¹²) rather than a drug approach is a favoured intervention strategy for diabetes prevention on economic grounds, estimating that the costs required to save a 'quality-adjusted life year' are $99 600 for the drug metformin and $31 700 for lifestyle intervention (http://www.nih.gov/news/pr/aug
2001/niddk-08.htm). Drawing on the 'fluoride' paradigm, we propose that consumer-attractive low glycemic index food products containing biologically effective natural food ingredients^12,13 combined with improved consumer communication and advertising of lifestyle advice could significantly influence the impending diabetes 'epidemic'. In the case of insulin resistance and diabetes, a suitable biological target is provided by the peroxisome proliferator-activated receptor gamma (PPAR) which can be activated by naturally occurring fatty acids found in foods.^13,14 Add to this that type II diabetes genetic risk assays are many years away from the doctor's surgery and that there appears to be no realistic commercial case for genetic screening for the type II diabetes risk factors, a population rather than an individual strategy becomes more compelling.

A second foods-linked benefit example is provided by the enzyme methyltetrahydrofolate reductase (MTHFR). The enzyme is involved in methylene transfer from methionine using folate as a cofactor. Relative deficiency in folate for carriers of an MTHFR allele results in highly significant elevation of blood homocysteine, an independent cardiovascular risk factor and a negative indicator of vascular health.¹⁵ Low folate levels over a lifetime predispose people to vascular dementia and research is underway to examine if there is a link to MTHFR polymorphisms. Such observations promote the case for folate supplementation in foods for at risk groups.

The medical applications and promise of human pharmacogenetics are well elucidated and under intense investigation. Approximately 925 genetic tests from 550 laboratories (www.genetests.org) are currently available, many of which are grouped towards specific disorders, for example Alzheimer's disease. The end of 'trial-and-error' medicine has been predicted taking advantage of genotyping and detailed knowledge on drug mechanisms.⁷ However, much less thought has been given to the role of foods and nutrigenetics in population health, particularly to the benefits that may accrue over time for currently healthy people. It remains to be seen to what extent the potential of genotyping for individual needs will guide healthy food selections in the medium to long term. Much more research into the interaction between genes and nutrients is called for, in part guided by the acceptability of genotyping individuals and obtaining population genotype data.¹⁶ In the near term, the main application of genomics will be to illuminate nutritional and/or dietary interactions as well improving the effectiveness of food safety research. However, in addition we contend that the foods industry has an important role to play in bringing improved health benefits to the public through improved, attractive food products and motivating lifestyle communications. We suggest that the population benefits in affluent countries from the implementation of such an approach will provide great future additional health benefits for humankind.