Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.

The strong, positive association of urinary sodium with systolic pressure of individuals concurs with Intersalt cross population findings and results of other studies. Higher urinary sodium is also associated with substantially greater differences in blood pressure in middle age compared with young adulthood. These results support recommendations for reduction of high salt intake in populations for prevention and control of adverse blood pressure levels.

Public health campaigns in several countries encourage population-wide reduced sodium (salt) intake, but excessive intake remains a major problem. Excessive sodium intake is independently related to adverse blood pressure and is a key factor in the epidemic of prehypertension/ hypertension. Identification of food sources of sodium in modern diets is critical to effective reduction of sodium intake worldwide. We used data from the INTERMAP Study to define major food sources of sodium in diverse East Asian and Western population samples. INTERMAP is an international, cross-sectional, epidemiologic study of 4, 680 individuals ages 40 to 59 years from Japan (four samples), People’s Republic of China (three rural samples), the United Kingdom (two samples), and the United States (eight samples); four in-depth, multipass 24-hour dietary recalls/person were used to identify foods accounting for most dietary sodium intake. In the People’s Republic of China sample, most (76%) dietary sodium was from salt added in home cooking, about 50% less in southern than northern samples. In Japan, most (63%) dietary sodium came from soy sauce (20%), commercially processed fish/seafood (15%), salted soups (15%), and preserved vegetables (13%). Processed foods, including breads/cereals/grains, contributed heavily to sodium intake in the United Kingdom (95%) and the United States (for methodological reasons, underestimated at 71%). To prevent and control prehypertension/hypertension and improve health, efforts to remove excess sodium from diets in rural China should focus on reducing salt in home cooking. To avoid excess sodium intake in Japan, the United Kingdom, and the United States, salt must be reduced in commercially processed foods.

Blood pressure (BP) above optimal (p120/p80 mmHg) is established as a major cardiovascular disease (CVD) risk factor. Prevalence of adverse BP is high in most adult populations; until recently research has been sparse on reasons for this. Since the 1980s, epidemiologic studies confirmed that salt, alcohol intake, and body mass relate directly to BP; dietary potassium, inversely. Several other nutrients also probably influence BP. The DASH feeding trials demonstrated that with the multiple modifications in the DASH combination diet, SBP/DBP (SBP: systolic blood pressure, DBP: diastolic blood pressure) was sizably reduced, independent of calorie balance, alcohol intake, and BP reduction with decreased dietary salt. A key challenge for research is to elucidate specific nutrients accounting for this effect. The general aim of the study was to clarify influences of multiple nutrients on SBP/DBP of individuals over and above effects of Na, K, alcohol, and body mass. Specific aims were, in a cross-sectional epidemiologic study of 4680 men and women aged 40-59 years from 17 diverse population samples in China, Japan, UK, and USA, test 10 prior hypotheses on relations of macronutrients to SBP/DBP and on role of dietary factors in inverse associations of education with BP; test four related subgroup hypotheses; explore associations with SBP/DBP of multiple other nutrients, urinary metabolites, and foods. For these purposes, for all 4680 participants, with standardized high-quality methods, assess individual intake of 76 nutrients from four 24-h dietary recalls/person; measure in two timed 24-h urine collections/person 24-h excretion of Na, K, Ca, Mg, creatinine, amino acids; microalbuminuria; multiple nutrients and metabolites by nuclear magnetic resonance and high-pressure liquid chromatography. Based on eight SBP/DBP measurements/person, and data on multiple possible confounders, utilize mainly multiple linear regression and quantile analyses to test prior hypotheses and explore relations of multiple dietary and urinary variables to SBP/DBP of individuals. The 4680 INTERMAP participants are equally divided across four age/gender strata: diverse in ethnicity, education, occupation, physical activity; use of cigarettes, alcohol; diagnosed high BP, CVD, diabetes; CVD family history; women vary in parity, use of contraceptive medication and hormone replacement therapy.

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Objective: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. Design and subjects: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fatty acids and total fat in adults andaor the total population using the best available national food consumption data set. Results: A wide variation was observed in the intake of total fat and (clusters) of fatty acids in absolute amounts. The variation in proportion of energy derived from total fat and from clusters of fatty acids was less. Only in Finland, Italy, Norway and Portugal total fat did provide on average less than 35% of energy intake. Saturated fatty acids (SFA) provided on average between 10% and 19% of total energy intake, with the lowest contribution in most Mediterranean countries. TFA intake ranged from 0.5% (Greece, Italy) to 2.1% (Iceland) of energy intake among men and from 0.8% (Greece) to 1.9% among women (Iceland) (1.2 ± 6.7 gad and 1.7 ± 4.1 gad, respectively). The TFA intake was lowest in Mediterranean countries (0.5 ± 0.8 en%) but was also below 1% of energy in Finland and Germany. Moderate intakes were seen in Belgium, The Netherlands, Norway and UK and highest intake in Iceland. Trans isomers of C 18 X1 were the most TFA in the diet. Monounsaturated fatty acids contributed 9 ± 12% of mean daily energy intake (except for Greece, nearly 18%) and polyunsaturated fatty acids 3 ± 7%. Conclusion: The current intake of TFA in most Western European countries does not appear to be a reason for major concern. In several countries a considerable proportion of energy was derived from SFA. It would therefore be prudent to reduce intake of all cholesterol-raising fatty acids, TFA included.

Vegetable protein intake was inversely related to blood pressure. This finding is consistent with recommendations that a diet high in vegetable products be part of healthy lifestyle for prevention of high blood pressure and related diseases.

The significant relation of heavy drinking (3-4 or more drinks/day) to blood pressure, observed in both men and women, and in younger and older men, was independent of and added to the effect on blood pressure of body mass index and urinary excretion of sodium and potassium. The findings indicate the usefulness of targeting those at high risk as well as the general population to reduce the adverse effects of alcohol on blood pressure.