Awareness of the ancestral human diet might advance traditional nutrition science. The human genome has hardly changed since the emergence of behaviourally-modern humans in East Africa 100–50×103 years ago; genetically, man remains adapted for the foods consumed then. The best available estimates suggest that those ancestors obtained about 35% of their dietary energy from fats, 35% from carbohydrates and 30% from protein. Saturated fats contributed approximately 7·5% total energy and harmful trans-fatty acids contributed negligible amounts. Polyunsaturated fat intake was high, with n−6:n−3 approaching 2:1 (v. 10:1 today). Cholesterol consumption was substantial, perhaps 480 mg/d. Carbohydrate came from uncultivated fruits and vegetables, approximately 50% energy intake as compared with the present level of 16% energy intake for Americans. High fruit and vegetable intake and minimal grain and dairy consumption made ancestral diets base-yielding, unlike today's acid-producing pattern. Honey comprised 2–3% energy intake as compared with the 15% added sugars contribute currently. Fibre consumption was high, perhaps 100 g/d, but phytate content was minimal. Vitamin, mineral and (probably) phytochemical intake was typically 1·5 to eight times that of today except for that of Na, generally <1000 mg/d, i.e. much less than that of K. The field of nutrition science suffers from the absence of a unifying hypothesis on which to build a dietary strategy for prevention; there is no Kuhnian paradigm, which some researchers believe to be a prerequisite for progress in any scientific discipline. An understanding of human evolutionary experience and its relevance to contemporary nutritional requirements may address this critical deficiency.

The FAO World Food Summit (WFS) in 1996 set the goal of halving the numbers of the global population suffering hunger by the year 2015, which was later incorporated into the UN Millennium Development Goals (MDG) that commit the international community to an expanded vision of development, and one that vigorously promotes human development as the key to sustaining social and economic progress in all countries. The two targets under the first MDG goal to eradicate poverty and hunger call for halving the proportion of individuals who suffer from poverty and from hunger by 2015. This commitment is another instance of the international community through the UN system yet again renewing its efforts and setting a target and a time frame to deal with the global problem of hunger, poverty and malnutrition. To date, the efforts to reduce global hunger in the developing world have fallen far short of the pace required to meet these targets. There has no doubt been some progress and several countries in the developing world have proved that success is possible. The economic and societal costs to developing countries of not taking decisive action, and thus failing to achieve a reduction in hunger and undernutrition, including micronutrient malnutrition costs, are that every year five million children lose their lives, 220 million disability-adjusted life years are lost as a result of childhood and maternal undernutrition and billions of dollars are lost in productivity and incomes in these countries. Alongside this perennial problem in developing societies are emerging new epidemics of diet-related diseases resulting from the profound demographic changes, urbanization and the economic transition that is transforming and globalizing the food systems in these countries. Thus, many developing countries are facing new and additional challenges of co-existing hunger alongside the emergence of other forms of malnutrition. Meeting the WFS and MDG targets of achieving the goal of halving global hunger is urgent, and the question that needs to be addressed is not whether the international community can achieve this goal in time but whether it can afford not to.

Intervention and prospective studies showing no effect of fibre in protection against colo-rectal cancer have challenged consensus recommendations that population intakes of fibre should be increased to reduce the risk of colo-rectal cancer. The European Prospective Investigation of Cancer and Nutrition (EPIC) of 519 978 individuals aged 25–70 years is the largest prospective study of diet and cancer to date worldwide. It incorporates ten different European countries in order to increase heterogeneity in dietary habits and calibration procedures to reduce measurement error. Data for 1065 reported cases of colo-rectal cancer were reported in 2003. There was a 40% reduction in risk for the highest quintile v. lowest quintile of fibre in food after calibration. It has been suggested that these effects were a result of confounding by folate and other factors. Although there are a number of hypotheses to explain why folate should be protective in colo-rectal cancer, a meta-analysis has shown that folate in food may be protective but there is no effect of total folate (i.e. food plus supplements). In a further analysis of 1826 cases in EPIC, identified in the latest follow-up, the inclusion of an additional 761 cases has confirmed the previously published results, with a strong and significant reduction in colo-rectal cancer of approximately 9% reduction in risk for each uncalibrated quintile increase in fibre (P<0·001 for linear trend) compared with an 8% reduction in the previous report, which had not been adjusted for folate. Inclusion of the other covariates (physical activity, alcohol, smoking and red and processed meat) with folate has confirmed this significant inverse association for colon cancer and strengthened the association with left-sided colon cancer (P<0·001).

There is an increasing body of evidence, including that from prospective population studies and epidemiological observational studies, suggesting a strong inverse relationship between increased consumption of wholegrain foods and reduced risk of CVD. This evidence has translated into specific dietary recommendations in the USA to consume at least three servings of whole grain per d, and has informed the development of specific health claims for wholegrain foods both in the USA and in Europe. Wholegrain foods are rich sources of many nutrients and phytochemicals, including complex carbohydrates, dietary fibre, minerals, vitamins, antioxidants and phyto-oestrogens such as lignans. Many of these components are lost from the grain during processing and although some may be replaced (such as in the mandatory fortification of white flour), this practice ignores the possible synergistic effects of the ‘natural’ constituents. The notion that wholegrain foods are simply a source of dietary fibre has been dispelled, although the additional components that contribute to the health benefits have not been clearly identified. In addition, the mechanisms by which wholegrain foods may have their effect are poorly understood. At present there are few strictly-controlled intervention studies that have confirmed a beneficial effect of increased consumption of wholegrain foods, demonstrated the level of consumption required to elicit a beneficial effect or provided evidence of modes of action. Although wholegrain foods are considered amongst the healthiest food choices available, their consumption falls well below current recommendations, which have been based mainly on epidemiological evidence. Well-controlled intervention studies are needed to provide more detailed mechanistic evidence to support the health claims and findings which can be used to develop effective public health strategies to promote whole-grain consumption.

Vegetarian diets do not contain meat, poultry or fish; vegan diets further exclude dairy products and eggs. Vegetarian and vegan diets can vary widely, but the empirical evidence largely relates to the nutritional content and health effects of the average diet of well-educated vegetarians living in Western countries, together with some information on vegetarians in non-Western countries. In general, vegetarian diets provide relatively large amounts of cereals, pulses, nuts, fruits and vegetables. In terms of nutrients, vegetarian diets are usually rich in carbohydrates, n−6 fatty acids, dietary fibre, carotenoids, folic acid, vitamin C, vitamin E and Mg, and relatively low in protein, saturated fat, long-chain n−3 fatty acids, retinol, vitamin B12 and Zn; vegans may have particularly low intakes of vitamin B12 and low intakes of Ca. Cross-sectional studies of vegetarians and vegans have shown that on average they have a relatively low BMI and a low plasma cholesterol concentration; recent studies have also shown higher plasma homocysteine concentrations than in non-vegetarians. Cohort studies of vegetarians have shown a moderate reduction in mortality from IHD but little difference in other major causes of death or all-cause mortality in comparison with health-conscious non-vegetarians from the same population. Studies of cancer have not shown clear differences in cancer rates between vegetarians and non-vegetarians. More data are needed, particularly on the health of vegans and on the possible impacts on health of low intakes of long-chain n−3 fatty acids and vitamin B12. Overall, the data suggest that the health of Western vegetarians is good and similar to that of comparable non-vegetarians.

The first cases of human Zn deficiency were described in the 1960s in the Middle East. Nevertheless, it was not until 2002 that Zn deficiency was included as a major risk factor in the global burden of disease, and only in 2004 did WHO/UNICEF include Zn supplements in the treatment of acute diarrhoea. Despite this recognition Zn is still not included in the UN micronutrient priority list, an omission that will continue to hinder efforts to reduce child and maternal mortality, combat HIV/AIDS, malaria and other diseases and achieve the UN Millennium Development Goals for improved nutrition in developing countries. Reasons for this omission include a lack of awareness of the importance of Zn in human nutrition, paucity of Zn and phytate food composition values and difficulties in identifying Zn deficiency. Major factors associated with the aetiology of Zn deficiency include dietary inadequacies, disease states inducing excessive losses or impairing utilization and physiological states increasing Zn requirements. To categorize countries according to likely risk of Zn deficiency the International Zinc Nutrition Consultative Group has developed indirect indicators based on the adequacy of Zn in the national food supplies and/or prevalence of childhood growth stunting. For countries identified as at risk confirmation is required through direct measurements of dietary Zn intake and/or serum Zn in a representative sample. Finally, in at risk countries either national or targeted Zn interventions such as supplementation, fortification, dietary diversification or modification, or biofortification should be implemented, where appropriate, by incorporating them into pre-existing micronutrient intervention programmes.

Increasing recognition of the importance of the long-chain n−3 PUFA, EPA and DHA, to cardiovascular health, and in the case of DHA to normal neurological development in the fetus and the newborn, has focused greater attention on the dietary supply of these fatty acids. The reason for low intakes of EPA and DHA in most developed countries (0·1–0·5 g/d) is the low consumption of oily fish, the richest dietary source of these fatty acids. An important question is whether dietary intake of the precursor n−3 fatty acid, α-linolenic acid (αLNA), can provide sufficient amounts of tissue EPA and DHA by conversion through the n−3 PUFA elongation–desaturation pathway. αLNA is present in marked amounts in plant sources, including green leafy vegetables and commonly-consumed oils such as rape-seed and soyabean oils, so that increased intake of this fatty acid would be easier to achieve than via increased fish consumption. However, αLNA-feeding studies and stable-isotope studies using αLNA, which have addressed the question of bioconversion of αLNA to EPA and DHA, have concluded that in adult men conversion to EPA is limited (approximately 8%) and conversion to DHA is extremely low (<0·1%). In women fractional conversion to DHA appears to be greater (9%), which may partly be a result of a lower rate of utilisation of αLNA for β-oxidation in women. However, up-regulation of the conversion of EPA to DHA has also been suggested, as a result of the actions of oestrogen on Δ6-desaturase, and may be of particular importance in maintaining adequate provision of DHA in pregnancy. The effect of oestrogen on DHA concentration in pregnant and lactating women awaits confirmation.

A strong and persistent effect of plant-derived foods on the prevention of lifestyle diseases has emerged from observational studies. Several groups of constituents in plants have been identified as potentially health promoting in animal studies, including cholesterol-lowering factors, antioxidants, enzyme inducers, apoptosis inducers etc. In human intervention studies the dose levels achieved tend to be lower than the levels found to be effective in animals and sampling from target organs is often not possible. A controlled dietary human intervention study was performed with forty-three volunteers, providing 600 g fruit and vegetables/d or in the controls a carbohydrate-rich drink to balance energy intake. Surrogate markers of oxidative damage to DNA, protein and lipids, enzymic defence and lipid metabolism were determined in blood and urine. It was found that a high intake of fruit and vegetables tends to increase the stability of lipids towards oxidative damage. Markers of oxidative enzymes indicate a steady increase in glutathione peroxidase (GPX1) activity in erythrocytes during intervention with fruit and vegetables but there is no effect on GPX1 transcription levels in leucocytes. No change occurs in glutathione-conjugating or -reducing enzyme activities in erythrocytes or plasma, and there are no effects on the transcription of genes involved in phase 2 enzyme induction or DNA repair in leucocytes. Fruit and vegetable intake decreases the level of total cholesterol and LDL-cholesterol, but does not affect sex hormones. In conclusion, it has been shown that total cholesterol and LDL-cholesterol, markers of peripheral lipid oxidation, and erythrocyte GPX1 activity are affected by high intakes of fruit and vegetables. This finding provides support for a protective role of dietary fruit and vegetables against CVD.

Many isothiocyanates (ITC), which are available to human subjects mainly through consumption of cruciferous vegetables, demonstrate strong cancer-preventive activity in animal models. Human studies also show an inverse association between consumption of ITC and risk of cancer in several organs. Whereas earlier studies primarily focused on the ability of ITC to inhibit carcinogen-activating enzymes and induce carcinogen-detoxifying enzymes, more recent investigations have shown that ITC inhibit the proliferation of tumour cells both in vitro and in vivo by inducing apoptosis and arresting cell cycle progression. ITC cause acute cellular stress, which may be the initiating event for these effects. These findings shed new light on the mechanism of action of ITC and indicate that ITC may be useful both as cancer-preventive and therapeutic agents. ITC activate caspase 9-mediated apoptosis, apparently resulting from mitochondrial damage, and also activate caspase 8, but the mechanism remains to be defined. Cell cycle arrest caused by ITC occurs mainly in the G2/M phase, and both the G2 and M phases are targetted; critical G2-phase regulators, including cyclin B1, cell division cycle (Cdc) 2 and Cdc25C, are down regulated or inhibited, and tubulin polymerization and spindle assembly are disrupted. Moreover, ITC are metabolized in vivo through the mercapturic acid pathway, giving rise to thiol conjugates (dithiocarbamates). Studies show that these dithiocarbamates are similar to their parent ITC in exerting anti-proliferative activity. Taken together, dietary ITC are highly-promising anti-cancer agents, capable of targetting multiple cellular components that are important for tumour cell survival and proliferation.

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Acetylsalicylic acid (aspirinTM; 2-acetoxybenzoic acid) has been used for >100 years for pain relief and to treat inflammatory conditions and fevers. More recently, regular intake has been associated with decreased incidence of certain cancers, particularly colon cancer. After absorption aspirin is very rapidly hydrolysed to salicylic acid (2-hydroxybenzoic acid). The anti-cancer effects of aspirin may be a result of salicylic acid reducing the transcription of prostaglandin H2-synthase and thereby the synthesis of pro-inflammatory and potentially-neoplastic prostaglandins. Salicylic acid is widely present in plants and functions as a hormonal mediator of the systemic acquired resistance response to pathogen attack and environmental stress. Thus, it is present in a large range of fruit, vegetables, herbs and spices of dietary relevance. Consequently, the recognised effect of consuming fruit and vegetables on lowering risk of colon cancer may be partly attributable to salicylates in plant-based foods. The present review discusses which types of fruit and vegetables are the richest source of salicylates and whether they are sufficiently released from the food matrix to modify the key cellular events associated with the pathogenesis of colon cancer.

The environment encountered in fetal and neonatal life exerts a profound influence on physiological function and risk of disease in adult life. Epidemiological evidence suggests that impaired fetal growth followed by rapid catch-up in infancy is a strong predictor of obesity, hypertension, non-insulin-dependent diabetes and CHD. Whilst these associations have been widely accepted to be the product of nutritional factors operating in pregnancy, evidence from human populations to support this assertion is scarce. Animal studies clearly demonstrate that there is a direct association between nutrient imbalance in fetal life and later disease states, including hypertension, diabetes, obesity and renal disease. These associations are independent of changes in fetal growth rates. Experimental studies examining the impact of micro- or macronutrient restriction and excess in rodent pregnancy provide clues to the mechanisms that link fetal nutrition to permanent physiological changes that promote disease. Exposure to glucocorticoids in early life appears to be an important consequence of nutrient imbalance and may lead to alterations in gene expression that have major effects on tissue development and function. Epigenetic mechanisms, including DNA methylation, may also be important processes in early-life programming.

The increase in CVD incidence following the menopause is associated with oestrogen loss. Dietary isoflavones are thought to be cardioprotective via their oestrogenic and oestrogen receptor-independent effects, but evidence to support this role is scarce. Individual variation in response to diet may be considerable and can obscure potential beneficial effects in a sample population; in particular, the response to isoflavone treatment may vary according to genotype and equol-production status. The effects of isoflavone supplementation (50 mg/d) on a range of established and novel biomarkers of CVD, including markers of lipid and glucose metabolism and inflammatory biomarkers, have been investigated in a placebo-controlled 2×8-week randomised cross-over study in 117 healthy post-menopausal women. Responsiveness to isoflavone supplementation according to (1) single nucleotide polymorphisms in a range of key CVD genes, including oestrogen receptor (ER) α and β and (2) equol-production status has been examined. Isoflavones supplementation was found to have no effect on markers of lipids and glucose metabolism. Isoflavones improve C-reactive protein concentrations but do not affect other plasma inflammatory markers. There are no differences in response to isoflavones according to equol-production status. However, differences in HDL-cholesterol and vascular cell adhesion molecule 1 response to isoflavones v. placebo are evident with specific ERβ genotypes. In conclusion, isoflavones have beneficial effects on C-reactive protein, but not other cardiovascular risk markers. However, specific ERβ gene polymorphic subgroups may benefit from isoflavone supplementation.

Studies have shown that the risk of hypertension in adulthood can be affected by the in utero environment. It is established that hypertension is linked to compromised kidney function and that factors affecting organogenesis can increase the risk of later disease. Prostaglandins (PG) and growth factors are known to play an important role in regulating kidney function and renal organogenesis. The extent, however, to which global energy restriction (where all nutrients are reduced) of the mother can programme later blood pressure control or renal PG and growth factor status is unknown. A study is described that aimed to examine the long-term effects of maternal nutrient restriction (NR) and elucidate their relationship with compromised kidney development. First, it was necessary to establish animal models. A sheep model of 50% NR during specific stages of gestation was used to investigate fetal renal development, whilst a rat model of 50% NR throughout pregnancy was used to investigate postnatal kidney development and adult functioning. Molecular analysis has shown that expression of the growth hormone–insulin-like growth factor (GH–IGF) axis is affected by NR in the fetal sheep kidneys, and that changes are dependent on the timing of NR and whether the fetus is a singleton or a twin. Analysis of the kidneys from the rat model has shown nutritional differences in the expression of PG receptors and the enzymes responsible for PG synthesis and degradation that persist into adulthood. In conclusion, NR does affect the GH–IGF and PG axes, and these changes may be important in the nutritional programming of renal functioning and adult blood pressure control.

There is growing evidence that the type of carbohydrate consumed is important in relation to metabolic disease risk, and there is currently particular interest in the role of low-glycaemic-index (GI) foods. Observational studies have associated low-GI diets with decreased risk of type 2 diabetes and CHD, and improvements in various metabolic risk factors have been seen in some intervention studies. However, findings have been mixed and inconsistent. There are a number of plausible mechanisms for the effects of these foods on disease risk, which arise from the differing metabolic responses to low- and high-GI foods, with low-GI foods resulting in reductions in hyperglycaemia, hyperinsulinaemia and late postprandial circulating NEFA levels. Low-GI foods may also increase satiety and delay the return of hunger compared with high-GI foods, which could translate into reduced energy intake at later time points. However, the impact of a low-GI diet on body weight is controversial, with many studies confounded by dietary manipulations that differ in aspects other than GI. There is currently much interest in GI from scientists, health professionals and the public, but more research is needed before clear conclusions can be drawn about relationships with metabolic disease risk.

Cruciferous vegetables have been studied extensively for their chemoprotective effects. Although they contain many bioactive compounds, the anti-carcinogenic actions of cruciferous vegetables are commonly attributed to their content of glucosinolates. Glucosinolates are relatively biologically inert but can be hydrolysed to a range of bioactive compounds such as isothiocyanates (ITC) and indoles by the plant-based enzyme myrosinase, or less efficiently by the colonic microflora. A number of mechanisms whereby ITC and indoles may protect against colo-rectal cancer have been identified. In experimental animals cruciferous vegetables have been shown to inhibit chemically-induced colon cancer. However, the results of recent epidemiological cohort studies have been inconsistent and this disparity may reflect a lack of sensitivity of such studies. Possible explanations for the failure of epidemiological studies to detect an effect include: assessment of cruciferous vegetable intake by methods that are subject to large measurement errors; the interaction between diet and genotype has not been considered: the effect that post-harvest treatments may have on biological effects of cruciferous vegetables has not been taken into account.