Food nutrients and metabolic supply–demand dynamics constitute environmental factors that interact with our genome influencing health and disease states. These gene–environment interactions converge at the metabolic–epigenome–genome axis to regulate gene expression and phenotypic outcomes. Mounting evidence indicates that nutrients and lifestyle strongly influence genome–metabolic functional interactions determining disease via altered epigenetic regulation. The mitochondrial network is a central player of the metabolic–epigenome–genome axis, regulating the level of key metabolites [NAD + , AcCoA (acetyl CoA), ATP] acting as substrates/cofactors for acetyl transferases, kinases (e.g. protein kinase A) and deacetylases (e.g. sirtuins, SIRTs). The chromatin, an assembly of DNA and nucleoproteins, regulates the transcriptional process, acting at the epigenomic interface between metabolism and the genome. Within this framework, we review existing evidence showing that preservation of mitochondrial network function is directly involved in decreasing the rate of damage accumulation thus slowing aging and improving healthspan.

Although weight loss can usually be achieved by restricting food intake, the majority of dieters regain weight over the long-term. In the hypothalamus, hormonal signals from the gastrointestinal tract, adipose tissue and other peripheral sites are integrated to influence appetite and energy expenditure. Diet-induced weight loss is accompanied by several physiological changes which encourage weight regain, including alterations in energy expenditure, substrate metabolism and hormone pathways involved in appetite regulation, many of which persist beyond the initial weight loss period. Safe effective long-term strategies to overcome these physiological changes are needed to help facilitate maintenance of weight loss. The present review, which focuses on data from human studies, begins with an outline of body weight regulation to provide the context for the subsequent discussion of short- and long-term physiological changes which accompany diet-induced weight loss.

Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61±8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3–30 μg/min) and SNP (sodium nitroprusside; 0.3–3 μg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanolrich cocoa does not modify vascular function in patients with established CAD.

Obesity is associated with metabolic syndrome and increased incidence of and mortality from myocardial infarction. The aim of the present study was to develop an animal model with metabolic syndrome and examine how that influences size of myocardial infarcts induced by occlusion and reperfusion of the left anterior descending coronary artery. Sprague–Dawley rats ( n =105) were fed either LF (low-fat) or MHF (moderately high-fat) diets for 13 weeks before coronary occlusion for 45 min, followed by reperfusion for 60 min. Compared with LF-fed and lean MHF-fed rats, obese MHF-fed rats developed metabolic disturbances similar to those seen in the metabolic syndrome, including being overweight by 24% (compared with lean MHF-fed rats), having 74% more visceral fat (compared with LF-fed rats), 15% higher blood pressure (compared with LF-fed rats), 116% higher plasma insulin (compared with lean MHF-fed rats), 10% higher fasting plasma glucose (compared with LF-fed rats), 35% higher non-fasting plasma glucose (compared with lean MHF-fed rats), 36% higher plasma leptin (compared with lean MHF-fed rats) and a tendency to lower plasma adiponectin and higher plasma non-esterified fatty acids. Infarct size was similar in the three groups of rats (36±14, 42±18 and 41±14% in obese MHF-fed, lean MHF-fed and LF-fed rats respectively). In conclusion, rats fed a MHF diet developed metabolic syndrome, but this did not influence myocardial infarct size.

A new simple criterion for diagnosing metabolic syndrome was proposed in the third report of the NCEP (National Cholesterol Education Program). In the present study, we analysed the association between metabolic syndrome and insulin resistance to investigate the effects of the latter on the prevalence of metabolic syndrome based on the new criteria recommended in the ATP (Adult Treatment Panel) III report. A total of 7057 participants (4472 men and 2585 women), who underwent medical screening at the Sungkyunkwan University Kangbuk Samsung Hospital, were investigated. Fasting insulin levels were measured and components of the metabolic syndrome as defined by the ATP III report were determined. We also applied the criteria for abdominal obesity as defined by APC-WC (Asia–Pacific criteria for waist circumference). The prevalence of metabolic syndrome as defined by ATP III was 5.3% (5.0% in men and 5.8% in women) and 8.9% (8.1% in men and 10.3% in women) by APC-WC. The odds ratio for the metabolic syndrome was significantly higher in subjects with higher insulin resistance than in those with lower insulin resistance. The mean levels of HOMA (homoeostatic model assessment) and fasting insulin were significantly higher in those with more of the components of the metabolic syndrome. A high HOMA (≥2.56) and fasting insulin concentration (≥9.98 μIU/ml; where IU is international unit) were found to be independent risk factors of the metabolic syndrome by multiple regression analysis after adjusting for age, sex and body mass index ( P <0.001). These results show that the metabolic syndrome is significantly correlated with the insulin resistance index, and that appropriate values of HOMA and fasting insulin concentration may serve as a helpful guide for the management of metabolic syndrome.

Dietary factors have been implicated in the difference in the risk of cardiovascular disease observed between populations. However, clinical trials and mechanistic studies of dietary modification are difficult to undertake, and the data set on dietary intervention for cardiovascular disease is now much smaller than that for pharmacological interventions. Moreover, the precise mechanism by which dietary modification might alter the risk of cardiovascular disease is uncertain. In this issue of Clinical Science , Ambring and co-workers investigate the effect of a Mediterranean-inspired diet on endothelial function and lipid fractions.

Mediterranean-inspired diets have been shown to decrease cholesterol levels in patients with hypercholesterolaemia, who frequently exhibit endothelial dysfunction. The aims of the present study are to improve endothelial function by dietary intervention in healthy subjects with lipid levels representative of a Western population. Twenty-two healthy subjects (mean total cholesterol, 5.6 mmol/l) were given a Mediterranean-inspired diet rich in ω-3 fatty acids and sterol esters, but low in saturated fat, or an ordinary Swedish diet, for 4 weeks in a randomized cross-over study. The composition of the diets were: in the Swedish diet, 2090 kcal (where 1 kcal=4.184 kJ; 48% of energy from carbohydrate, 15% from protein and 36% from fat) and 19 g of fibre; in the Mediterranean-inspired diet, 1869 kcal (48% of energy from carbohydrate, 16% from protein, 34% from fat) and 40 g of fibre. After each dietary period, fasting blood lipids, insulin and glucose levels, as well as apo B (apolipoprotein B) and LDL (low-density lipoprotein) particle size, were analysed. Endothelial-dependent and -independent vasodilation was measured invasively by venous occlusion plethysmography, and arterial distensibility was assessed by echocardiography tracking. Fibrinolytic capacity across the forearm, as well as oxidative stress measured through urinary F 2 -isoprostane, were evaluated. Total, LDL- and apo B-cholesterol and triacylglycerol (triglyceride) concentrations were decreased by 17%, 22%, 16% and 17% respectively, after the Mediterranean-inspired diet compared with the Swedish diet ( P <0.05 for all). However, no differences in plasma concentrations of insulin and glucose and LDL particle size, endothelial function, arterial distensibility, fibrinolytic capacity or oxidative stress were detected. Treatment for 4 weeks with a Mediterranean-inspired diet decreased blood lipids in healthy individuals with a low-risk profile for cardiovascular disease. This beneficial effect was not mirrored in vascular function or oxidative stress evaluation.

Poor early growth is associated with Type II diabetes, hypertension and other features of the metabolic syndrome in adulthood. It has been suggested that this results from the development of a thrifty phenotype by a malnourished fetus. Such a phenotype would predispose the offspring to the development of obesity if born into conditions of over-nutrition. The present study aimed to determine if early nutrition affected subsequent development of obesity. Mice were established as follows: (a) controls (offspring of control dams), (b) recuperated (offspring of dams fed a low-protein diet during pregnancy, but nursed by control dams) and (c) postnatal low-protein (offspring of control dams nursed by low-protein-fed dams). Mice were weaned on to standard laboratory chow or a cafeteria diet. Recuperated offspring, although smaller at birth ( P <0.01), caught up and exceeded the weight of control offspring by 7 days of age ( P <0.001). Postnatal low-protein offspring were smaller than controls by 7 days of age ( P <0.001). Recuperated animals gained more weight than controls when given free access to a highly palatable diet ( P <0.01). Postnatal low-protein animals showed no additional weight gain when given a highly palatable diet compared with chow-fed litter-mates. These results suggest that the early environment has long-term consequences for weight gain. These programmed responses are powerful enough to block excess weight gain from a highly palatable diet and, thus, have major implications for the drug-free regulation of food intake and obesity.

Adiponectin levels are decreased in subjects with obesity, diabetes and coronary artery disease. In the present study, we have investigated whether the decrease in the levels and mRNA expression of adiponectin is due to obesity or to the diet itself. Wistar rats were either fed standard laboratory chow throughout (controls) or given a fat-enriched, glucose-enriched diet (diet-fed) for 2 days or 16 weeks. After 2 days of diet feeding, total body weight, fat pad masses and the plasma levels of glucose, insulin and leptin were all comparable between the two groups, while plasma NEFA (non-esterified fatty acid) and triacylglycerol levels were increased in the diet-fed animals ( P <0.01 for both). There was a marked ( P <0.01) decrease in plasma adiponectin levels. After 16 weeks of diet feeding, diet-fed rats had significantly higher body weight, fat pad mass and plasma levels of leptin, adiponectin, NEFA and triacylglycerol ( P <0.001 for all) compared with chow-fed controls, whereas plasma levels of glucose and insulin were similar in the two groups. After 2 days of diet feeding, there were no significant changes in Ob mRNA levels in epididymal fat, whereas there was a marked decrease in adiponectin mRNA levels. After 16 weeks of diet feeding, rats had significantly increased levels of Ob mRNA, but decreased adiponectin mRNA levels, in epididymal fat compared with the chow-fed group ( P <0.001 for both). These findings suggest that obesity per se is not a factor in the decreased adiponectin levels observed in obese subjects. We propose that the lipid profile of the plasma and/or the constituents of the diet consumed by rats may contribute to adiponectin levels more than obesity per se .

A growing number of studies indicate an association between obesity, insulin resistance, dyslipidaemia and cardiovascular disorders, collectively known as Syndrome X. In this study we have aimed to produce a model of Syndrome X by voluntary feeding of Wistar rats with a highly palatable cafeteria diet, and examined its effects on metabolic changes and vascular reactivity of Wistar rats. At the end of the experiment, the cafeteria-diet fed group was divided into two groups of low weight gain (LWG) and high weight gain (HWG). Both LWG and HWG groups had significantly ( P < 0.01) higher fat-pad mass than their chow-fed counterparts, while gastrocnemius muscle mass were comparable. All cafeteria-diet fed rats had significantly ( P < 0.01) raised plasma triacylglycerol (TG) levels whereas plasma non-esterified fatty acids, glucose and insulin levels were similar between chow-fed and cafeteria-diet fed rats. Vasorelaxation responses to acteylcholine, insulin and sodium nitroprusside were significantly ( P < 0.01) attenuated in cafeteria-diet fed animals; however, there were no differences in contractile responses of the mesenteric arteries to noradrenaline or KCl between the groups. Multiple regression analysis showed a significant ( P < 0.05) negative association between plasma TG levels and reduction in acetylcholine-induced vasorelaxation. Acetylcholine-induced vasorelaxation was also significantly ( P < 0.05) associated with the amount of fat-pad mass. These data suggest that diet-induced vascular dysfunction can occur in the absence of insulin resistance, and that plasma TGs may have a detrimental effect on vascular reactivity.

1. Intervention trials in free-living populations have shown relatively small reductions in risk factors for cardiovascular disease, including lipid levels, and have led some to question whether diet is an effective treatment for hyperlipidaemia. However, behaviour change is a complex process and it is possible that standard intervention methods fail to motivate people sufficiently to comply with dietary advice. 2. This study applied motivational interviewing, a style of behaviour change counselling, to dietary education for people with hyperlipidaemia. One-hundred and twenty-one patients with hyperlipidaemia who had been referred to a hospital dietetic department for dietary advice were randomized to receive either standard or motivational dietary interventions for a period of 3 months. Outcomes assessed included dietary knowledge, stage of change, dietary intakes, lipid levels and body mass indices. 3. From baseline, both methods of dietary intervention resulted in self-reported changes in dietary habits and knowledge, statistically significant reductions in intake of total fat (from 32.8% to 28.4%), saturated fat (from 11.4% to 9.2%) and energy intakes [-239 ;kcal (-999.98 ;kJ)/day], and in body mass indices (-0.45 ;kg/m 2 ). Serum cholesterol did not change significantly in either intervention group. 4. Motivational and standard dietary interventions achieved statistically significant changes in reported dietary knowledge and behaviour, and led to a reduction in body weight, but not serum cholesterol. Whether this lack of effect is real or due to subjects overestimating true dietary change cannot be determined. Change in body weight was associated with a reported change in energy intake; this provides some support for there having been a real change in intake.

1. Dietary calcium restriction, an efficient practice in reducing urinary calcium excretion, has been reported to induce either an increase or no change in oxalate excretion, questioning its use in hypercalciuric stone-forming patients. In addition, calcium restriction has been previously demonstrated to induce other urinary changes which might influence the relative supersaturation of calcium oxalate. So the overall effect of calcium deprivation on the relative supersaturation of calcium oxalate is unpredictable. 2. The aim of the study was to evaluate the effect of dietary calcium restriction on the relative supersaturation of calcium oxalate in the urine of stone-forming patients utilizing a computer methodology which takes into account the main soluble complex species of oxalate. 3. We studied 34 stone-forming patients on both a free-choice diet, whose Ca and oxalate content (24 and 1.2 mmol respectively) was assessed by dietary inquiry, and after 30 days on a prescribed low-calcium and normal oxalate diet (11 and 1.1 mmol respectively). Under both conditions, the excretion of the main urinary parameters related to dietary composition, electrolytes, oxalate and daily citrate urinary excretion, were measured. The relative supersaturation of calcium oxalate was calculated by means of an iterative computer method which takes into account the main soluble complex species on which the solubility of calcium oxalate is dependent. In addition, intact parathyroid hormone and 1,25-dihydroxyvitamin D blood levels were also evaluated. In 13 of the patients intestinal calcium absorption was evaluated during both a free- and a low-calcium diet, utilizing kinetics methodology. 4. The low-calcium diet induced, together with an expected reduction of calcium excretion, a marked increase in oxalate urinary output. This finding was independent of the presence or otherwise of hypercalciuria and of the serum levels of parathyroid hormone and vitamin D. Intestinal calcium absorption was also stimulated by calcium deprivation and its levels were well correlated with oxalate excretion. Minor changes in magnesium and citrate excretion were also observed. The overall effect on the relative supersaturation of calcium oxalate consisted in a substantial increase in this parameter during the low-calcium diet. 5. In conclusion, our data reinforce the concept that dietary calcium restriction has potentially deleterious effects on lithogenesis, by increasing the relative supersaturation of calcium oxalate.

1. Dystrophin-deficient hindlimb muscles of mdx mice undergo necrosis at the time of weaning when the motor activity of the mice greatly increases and muscle energy metabolism becomes more dependent on insulin and carbohydrates. 2. We have attempted to determine if the onset of myofibre necrosis in mdx mice at the time of weaning is related to the development of motor activity and/or the change in diet. 3. Fourteen-day-old mdx mice were divided into two groups after weaning. One group was trained to run on a treadmill and the other group was kept on a high-fat diet. Muscle necrosis was assessed histologically in the soleus and extensor digitorum longus muscles of mice in both experiments. 4. Keeping mice on a high-fat milk diet from the time of weaning up to 42 days of age did not influence the occurrence of necrosis in the soleus and extensor digitorum longus muscles of the mdx pups. In contrast, treadmill exercise greatly increased necrosis in both muscles. 5. We conclude that an increase in motor activity exacerbates the degeneration of hindlimb muscles of mdx mice at the time of weaning.

1. Plasma sodium concentration may influence renal sodium excretion. We have examined the possibility that the fall in plasma sodium that occurs during salt restriction in man might be an important stimulus for renal sodium conservation. 2. In order to prevent the fall in plasma sodium that usually occurs during dietary salt restriction, we water restricted (200 ml/day) six normal subjects for the 2 days after the transition from 260 (high-sodium diet, day 3) to 20 mmol (low-sodium diet, days 4 and 5) sodium per day. In the control (hydrated) group water intake was held constant at 1800 ml/day. 3. Plasma sodium fell during the low-sodium diet in the hydrated group but remained constant in the dehydrated group (141.3 ± 0.2 to 140.2 ± 0.2 mmol/l versus 141.1 ± 0.3 to 141.3 ± 0.3 mmol/l). Plasma arginine vasopressin concentration was significantly higher and urine flow lower during the low-sodium diet in the dehydrated group (arginine vasopressin on day 5: hydrated group, 0.72 ± 0.1 pmol/l; dehydrated group, 2.18 ± 0.5 pmol/l). Weight fell by a similar amount in both groups (hydrated group, 1.23 ± 0.17 kg; dehydrated group, 1.45 ± 0.19 kg). 4. On the low-sodium diet there were no differences between groups in changes in plasma renin activity (hydrated group, 1.6 ± 0.24 to 4.78 ± 0.65 nmol angiotensin I h −1 ml −1 ; dehydrated group 1.57 ± 0.18 to 5.14 ± 0.56 nmol angiotensin I h −1 ml −1 ) or atrial natriuretic peptide (hydrated group, 23 ± 2.3 to 14.7 ± 1.6 pg/ml; dehydrated group, 26.8 ± 3.6 to 12.7 ± 1.3 pg/ml). Salivary aldosterone concentration increased further in the dehydrated study, but only on day 5. 5. Sodium excretion fell further in the dehydrated group over the first 16 h of the low-sodium diet on day 4 (hydrated group, 8.62 ± 0.76 mmol/h; dehydrated group, 6.57 ± 0.38 mmol/h). Creatinine clearance fell on day 5 (low sodium) in the dehydrated group but did not change significantly in the hydrated group (hydrated group, 152 ± 7 to 137 ± 7; dehydrated group, 157 ± 7 to 123 ± 7 ml/min). 6. We conclude that the fall in plasma sodium during salt restriction is not an important trigger for renal sodium conservation in man. The principal difference between studies was the elevation of arginine vasopressin in the dehydrated study. Differences in salivary aldosterone concentration occurred on day 5 only, too late to account for the differences in sodium excretion on day 4. Under the conditions of this study, our findings could be explained if physiological range elevation of arginine vasopressin has an antinatriuretic effect.

1. We have previously described a progressive antidiuresis in response to low-dose vasopressin infusion during salt restriction in man, despite stable or even declining plasma vasopressin concentration. In the present study we examine the hypothesis that renal sensitivity to the antidiuretic effect of arginine vasopressin may be enhanced by salt restriction. 2. Extremely low-dose infusions of arginine vasopressin were given to normal subjects after equilibration to high (260 mmol/day) and low (20 mmol/day) sodium intakes. 3. Salt restriction increased the antidiuretic effect of arginine vasopressin (2 fmol min −1 kg −1 arginine vasopressin increased urine osmolality from 67.8 ± 2.6 to 196.3 ± 35.7 mosmol/l in the high-salt study and from 268.3 ± 49 mosmol/l in the low-salt study; P < 0.05 between sodium intakes). Glomerular filtration rate, estimated from inulin clearance, was unchanged during arginine vasopressin infusion irrespective of salt intake (high salt 116.5 ± 9.4 to 118.9 ± 6.4 ml/min; low salt, 135.1 ± 9.2 to 111.2 ± 12.4 ml/min). Renal plasma flow, estimated from para-aminohippurate clearance, fell further during infusion of 2 fmol min −1 kg −1 arginine vasopressin in the low-salt study than in the high-salt study (low salt, from 555.7 ± 22.7 to 298.3 ± 27.6 ml/min; high salt, from 544.5 ± 30.2 to 452.9 ± 28.9 ml/min; P < 0.05 between sodium intakes) . 4. Plasma atrial natriuretic peptide concentration increased during infusion of 2 fmol min −1 kg −1 arginine vasopressin in the low-salt study (to 136.5% ± 19.9% of baseline, P < 0.05), if anything falling in the high-salt study (to 90.5% ± 13.6% of baseline). Packed cell volume fell during arginine vasopressin infusion in the low-salt study (high salt, to 98.2% ± 0.4% of baseline; low salt, to 95.7% ± 0.4% of baseline, P < 0.05 for the low-salt study only) . 5. Plasma arginine vasopressin concentration was constant throughout each study (high salt 0.48 ± 0.12 to 0.48 ± 0.1 pmol/l; low salt, 0.38 ± 0.05 to 0.4 ± 0.04 pmol/l) . 6. Our findings suggest that renal sensitivity to the hydro-osmotic and vascular effects of arginine vasopressin is enhanced by salt restriction.

1. We have studied the response of six patients with cranial diabetes insipidus and six age-matched control subjects to dietary sodium restriction during constant administration of the synthetic vasopressin analogue desamino-[8-D-arginine]vasopressin. 2. Urine flow increased on the first low salt day in the normal control subjects but not in the patients with cranial diabetes insipidus. Body weight fell 1.35 kg in the control subjects but was constant in the patients with cranial diabetes insipidus. 3. Urinary sodium excretion fell at the same rate in both groups. Diurnal variation of urinary sodium excretion and creatinine clearance was present in the control subjects but not in the patients with cranial diabetes insipidus. 4. Changes in plasma sodium concentration and osmolality were similar. Plasma protein concentration increased more in the control subjects (from 69.1 + 13 to 73 + 1.2 versus from 71.7 + 1 to 73.2 + 1.1 g/l). The responses of plasma atrial natriuretic peptide, plasma renin activity and salivary aldosterone concentration were similar between the two groups. Salivary aldosterone concentration levels were consistently higher in the patients with cranial diabetes insipidus. 5. We confirm that the low salt diuresis is triggered by release from the antidiuretic activity of arginine vasopressin. In the patients with cranial diabetes insipidus extracellular fluid osmoregulation appeared to be achieved by the movement of water out of and sodium into the extracellular fluid. 6. Absent posterior pituitary function and hypothalamic disturbances did not alter renal sodium conservation. Total extracellular fluid sodium appeared to be lower in the patients with cranial diabetes insipidus than in the control subjects. Disturbances of hypothalamic and pituitary function may have caused resetting of overall sodium balance and altered diurnal cycles of urinary sodium excretion and creatinine clearance.

1. A diuresis occurs within the first 36 h of salt restriction. A decline in plasma arginine vasopressin concentration may contribute to both the diuresis and antinatriuresis. 2. We have studied six normal human subjects during 36 h of dietary sodium restriction. In one study subjects received an intravenous infusion of D-glucose, and in the other an infusion of arginine vasopressin (6 fmol min −1 kg −1 ). 3. In the D-glucose phase plasma arginine vasopressin concentration fell (1.77 +034 to 1.02 +0.13 pg/ml), urine flow increased (67.9 +113 to 89.8 + 17.1 ml/h), haemoconcentration occurred (packed cell volume 40.8 +0.3 to 42.8 +03%, protein concentration 71.6 +03 to 74.5 + 0.6 g/l), plasma sodium concentration fell (140 +0.2 to 138 +0.2 mmol/l) and plasma renin activity increased (1600+153 to 3700 + 356 pg of angiotensin I h −1 ml −1 ). 4. In the arginine vasopressin phase plasma arginine vasopressin concentration remained constant (13 + 0.13 to 134 +0.11 pg/ml), the diuresis was reversed (65.7 +9.9 to 52.1 +8.9 ml/h), plasma sodium concentration fell further (139.8 +0.4 to 136.1 +0.4 mmol/l), the rise in plasma renin activity was reduced (arginine vasopressin 2552 + 292; D-glucose, 3700 + 356 pg of angiotensin I h −1 ml −1 ) and creatinine clearance was lower in the last 12 h of salt restriction (arginine vasopressin, 96.1 +6.9; D-glucose 116.5 + 6.8 ml/min). Renal sodium excretion was unaffected by arginine vasopressin infusion. 5. We conclude that the fall in plasma arginine vasopressin concentration during dietary salt restriction, whilst not affecting renal sodium excretion, may be important in the regulation of plasma sodium concentration, plasma renin activity and glomerular filtration.

1. Diene-conjugated fatty acids are one of the products of free-radical attack upon lipids and therefore have been used as markers of such attack. The major diene-conjugated fatty acid in human tissue and serum is an isomer of linoleic acid (9,12-octadecadienoic acid), namely 9,11-octadecadienoic acid. Diet may be another source of this isomer, raising questions as to its value as a free-radical marker. The aim of this study was to determine the importance of diet as a source of 9,11-octadecadienoic acid in phospholipid esterified fatty acids in human serum. 2. Foodstuffs rich in 9,11-octadecadienoic acid were identified. Fourteen subjects volunteered to alter their diets, either increasing ('high diet') or decreasing ('low diet') their intake of these foodstuffs for 3 weeks. Where subjects undertook both diets, a washout period of at least 3 weeks was allowed between phases. 3. Seven-day diet histories were kept and scored with respect to their content of 9,11-octadecadienoic acid. The concentrations of 9,11-octadecadienoic acid and linoleic acid in serum phospholipids were measured by h.p.l.c. with u.v. detection. 4. The percentage molar ratio of 9,11-octadecadienoic acid to linoleic acid was calculated. The percentage molar ratio rose significantly on the ‘high diet’ [1.3(0.4) versus 1.9(0.7), P =0.01, mean (SD)] and fell significantly on the ‘low diet’ [1.6(0.4) versus 1.1(0.4), P =0.004, means (SD)]. There was a significant correlation between the change in dietary intake of 9,11-octadecadienoic acid and the change in the percentage molar ratio ( r = 0.829, P = 0.001). 5. The concentration of 9,11-octadecadienoic acid in serum phospholipids is influenced by diet. Its use as a marker of free-radical activity is questionable and at least in need of careful interpretation.

1. Some patients with the emphysematous type of tobacco-related chronic obstructive pulmonary disease are hypermetabolic. Since the likely mechanism is the increased work of breathing, other groups of patients with chronic obstructive pulmonary disease should be similar. We have now measured basal metabolic rate and diet-induced thermogenesis in six patients with chronic obstructive pulmonary disease with an arterial partial pressure of CO 2 of <5kPa (emphysematous), nine patients with chronic obstructive pulmonary disease with an arterial partial pressure of CO 2 of >6kPa (bronchitic), eight patients with chronic obstructive pulmonary disease due to chronic asthma and seven control subjects. Diet-induced thermogenesis was measured for 4h after a meal of 87% carbohydrate, 11% protein and 2% fat as energy, with a total energy content of 40% of basal metabolic rate. 2. There was no difference between measured and predicted basal metabolic rate in the control (5541 ± 272 versus 5881 ± 245 kJ/24h) or emphysematous (5552 ± 370 versus 6239 ± 197 kJ/24 h) groups, but measured basal metabolic rate was significantly higher than predicted in the bronchitic (6126 ± 387 versus 5405 ± 250 kJ/24 h) and asthmatic (6293 ± 197 versus 5701 + 245, mean ± SEM, P <0.01) groups. All the control subjects had measured basal metabolic rates within 10% of predicted, whereas two out of six emphysematous patients, four out of nine bronchitic patients and five out of eight asthmatic patients were hypermetabolic. The contributions of fat, carbohydrate and protein oxidation rates to the overall basal metabolic rate were similar between groups. 3. Diet-induced thermogenesis was similar between groups. The postprandial fuel mix oxidized was also similar between all four groups. 4. Thus, some patients with both types of smoking-related chronic obstructive pulmonary disease and other patients with chronic asthma were hypermetabolic. This could not be predicted from detailed lung function tests, arterial blood gases or anthropometric measurements, and suggests that the increased work of breathing may not be the only cause of the hypermetabolism and weight loss seen in these patients.

1. The effects of a diet rich in protein and fat, compared with a control diet, with or without chronic ingestion of ethanol on the pancreatic response to cholecystokinin were studied in rats after a 7-month treatment period. The acute effects of intraduodenal administration of 20% (v/v) ethanol were also analysed under these experimental conditions. 2. Animals receiving a diet rich in protein and fat showed a greater percentage increase in pancreatic output in response to cholecystokinin. 3. Chronic ethanol consumption reduced the basal secretion of protein and amylase; and even though the response capacity to cholecystokinin (considered as the percentage secretion on cholecystokinin stimulation with respect to basal secretion) was maintained, this led to hormone-stimulated secretion being decreased in comparison with the animals receiving water. In contrast, a lack of inhibition of basal volume flow and flow after cholecystokinin stimulation was seen after long-term ingestion of ethanol. 4. Acute administration of ethanol generally depressed cholecystokinin-stimulated pancreatic secretion. 5. On stimulation with cholecystokinin, the diet rich in protein and fat combined with long-term ingestion of ethanol led to non-parallel changes in the release of pancreatic enzymes, since an increase in trypsin secretion and a decrease in amylase secretion occurred concomitantly.

1. The fall in renal sodium excretion after dietary sodium restriction is prompt and reproducible. The importance of increased aldosterone secretion during the early phase (within 48 h) of this response is unclear. Using two indirect measures of aldosterone secretion (in urine and saliva), we have tried to relate changes in excretion and concentration of this hormone to renal sodium excretion during the abrupt transition from a normal (approximately 150 mmol/day) or high (260 mmol/day) to a low (5–25 mmol/day) sodium intake in 11 and seven male volunteers, respectively. 2. All subjects showed reduced renal sodium excretion within 36 h of dietary restriction, but the times at which increases in renal aldosterone excretion, saliva aldosterone concentration and plasma renin activity became statistically significant varied widely (8–72 h, 2.5–>62.5 h and 38 h for renal aldosterone secretion, saliva aldosterone concentration and plasma renin activity, respectively). Circadian fluctuations in saliva aldosterone concentration were apparent and increased in amplitude during sodium restriction. 3. Urine flow rate tended to increase on the first day of sodium restriction and this reached statistical significance in the group initially on a high sodium intake (64.0 ± 8.8 to 84.3 ± 11.2 ml/h, P <0.01); although the pattern of urine flow did correlate with plasma arginine vasopressin concentration ( r = −0.49, P <0.01), there was no significant decrease in mean plasma arginine vasopressin concentration [1.15 (0.92–1.44) to 0.90 (0.72–1.12) pmol/l, P = 0.08; geometric mean and 95% confidence limits]. Renal arginine vasopressin excretion fell significantly after the change from a normal or high to a low sodium diet [2.70 (2.38–8.69) to 2.19 (1.72–4.00) and 3.80 (2.92–5.01) to 2.50 (1.26–2.35) pmol/h, respectively, P <0.05]; in four subjects assayed, plasma atrial natriuretic peptide concentration also fell significantly [20.1 (16.3–24.9)to 13.1 (10.6–16.2) pmol/l, P <0.05]. 4. We conclude that after acute dietary sodium withdrawal: (1) unless enhanced renal sensitivity to aldosterone develops rapidly, increased secretion alone is unlikely to account for the initial decline in renal sodium excretion; (2) decreased atrial natriuretic peptide secretion may have a permissive role in ‘low-sodium’ adaptation; (3) the early ‘low-sodium’ diuresis is probably vasopressin-dependent and is an important mechanism in the preservation of normal plasma osmolality.

1. Salt restriction is recommended in the treatment of hypertension and is included in national dietary guidelines, but its effect on exercise in hot conditions has not been extensively studied. 2. The effects of 2 weeks on two levels of salt intake (50 and 150 mmol/day) on the ability to exercise (60% of maximal oxygen uptake) in a hot environment (35°C) were studied in eight healthy normotensive subjects. 3. All subjects were able to complete the exercise load on the two levels of salt intake. No differences in mean oxygen uptake, heart rate or rectal temperature during exercise were observed between the two salt intakes. 4. Plasma sodium, potassium and osmolality were similar on the two salt intakes both before and during exercise. Plasma renin activity and aldosterone concentration were elevated after 2 weeks on the reduced salt intake and remained so during exercise. 5. The estimated sweat rate during exercise was similar on the two salt intakes but the loss of sodium was less on the low salt intake. 6. On the basis of these results it is concluded that moderate salt restriction does not impair the ability to exercise in a hot environment.

1. Blood pressure was measured after treatment with a high K + , a low Na + and a combined high K + /low Na + diet in young spontaneously hypertensive rats (SHR). 2. A high K + diet reduced blood pressure by approximately 10 mmHg during the development of hypertension. This decrease was accompanied by a significant increase in water intake and urine volume and a significant decrease in plasma renin activity (PRA). 3. A low Na + diet also decreased blood pressure significantly, but, in contrast to the high K + diet, water intake and urine volume significantly decreased and PRA increased. 4. When both diets were given together, the antihypertensive effects of both were eliminated. Thus while an increase in dietary K + and a decrease in dietary Na + are both effective antihypertensive regimens in SHR, the mechanism of action of each appears to be different and may be antagonistic in these animals.

1. Eighty-eight healthy omnivores with normal blood pressure participated in a randomized, controlled, cross-over trial of the effect on blood pressure of increasing dietary fibre intake. Subjects were randomly allocated to a control group eating a low fibre diet throughout, or to one of two experimental groups eating a high fibre diet for one of two 6-week experimental periods. Changes in body weight, other dietary constituents and lifestyle factors were avoided as far as possible. 2. Twenty-four hour diet records showed a substantial increase in dietary fibre when subjects were on the high fibre diet. 3. There was no consistent effect of change in dietary fibre intake on group mean systoloic or diastolic blood pressures. Adjusting blood pressures for changes in other dietary components, plasma lipids, electrolytes, body weight and other lifestyle variables did not alter this result. 4. These findings do not support the hypothesis that the blood pressure lowering effect of a vegetarian diet is solely due to an increase in fibre intake.

1. Normal diet and a simple short term prescribed diet were compared with respect to mean excretion of urine electrolytes and the variability in these responses in 12 healthy male subjects. Urine was collected from 7 to 15 h (overnight) and 15 to 25 h (daytime) after the start of dietary control. 2. Differences in mean responses were slight. For sodium and potassium excretion, however, there were tendencies for responses in subjects with high excretion on normal diet to decrease and for responses in those with low excretion on normal diet to increase towards the overall mean during the prescribed diet. 3. The prescribed diet reduced markedly the variability in electrolyte responses and for log transformed data reductions in variability were statistically significant in the daytime urine collections. 4. The results of this study have confirmed quantitatively the benefit of a short period of simple dietary control. The marked reduction in the variability of sodium and potassium excretion improves considerably the precision and sensitivity of studies of urine electrolyte composition.

1. Resting metabolic rate, measured by the ventilated hood technique in 11 obese subjects before weight loss was 6.5 ± 0.3 kJ/min, not significantly different from the value predicted by regression equations relating metabolic rate to body weight (established from measurements in 106 subjects). 2. After 34.5 kg mean weight loss, and during continued dieting, resting metabolic rate fell an average of 25% to 5.0 ± 0.18 kJ/min, significantly below that predicted for the new slimmed weight. 3. The fall in metabolic rate, over and above that expected from weight loss alone, suggests that the slimmed obese are hypometabolic compared with subjects of the same weight who have not lost weight. 4. The failure of the slimmed obese to maintain their weight loss is unlikely to be due solely to this excessive fall in resting metabolic rate, since they still had quantitatively higher energy expenditure than lean subjects.

1. This study was designed to examine the effect of dexamethasone treatment on tissue and urinary prostanoids, and to determine whether inhibition of prostaglandin biosynthesis by manipulation of dietary fatty acids accelerates the development of glucocorticoid hypertension. 2. Forty-eight rats were placed on either a 2-series prostaglandin ‘inhibitory’ diet (cod liver oil/linseed oil) or a control diet of saturated fat for an initial period of 4 weeks. The groups were then divided into two so that half of each received dexamethasone in their drinking water (2.5 mg/1) for 1 week whilst continuing their respective dietary regimens. 3. Rats on the cod liver oil diet incorporated eicosapentaenoic acid into tissue stores with a corresponding decrease in arachidonic acid, and significantly impaired ability to generate serum thromboxane B 2 (33%), aortic 6-oxo-prostaglandin F 1α (44%), renal homogenate prostaglandin E 2 (45%) and 6-oxo-prostaglandin F 1α (74%) and urinary prostaglandin E 2 (84%) and 6-oxo-prostaglandin F 1α (79%). 4. Despite the diminished levels of vasodilator 2-series prostaglandins, the cod liver oil diet prevented the development of glucocorticoid induced hypertension. 5. Relative to their respective dietary controls, dexamethasone treatment resulted in decreased serum thromboxane B 2 (20%) but increased aortic 6-oxo-prostaglandin F 1α (186%), renal homogenate prostaglandins (127–230%) and urinary excretion of prostaglandin E 2 (640–860%) and 6-oxo-prostaglandin F 1α (230–365%) in both dietary groups. 6. It therefore seems unlikely that glucocorticoid induced hypertension is a consequence of inhibition of vasodilator prostaglandin synthesis.

1. Fifty-four healthy, omnivore normotensive volunteers aged 20-59 years were randomly allocated either to a control group eating a low polyunsaturated to saturated fat ratio (P/S ratio) diet (0.3) throughout, or to one of two experimental groups eating a high P/S ratio diet (1.0) for one of two 6-week experimental periods. Changes in other components were avoided. 2. Twenty-four hour diet records showed substantial changes in the P/S ratio for experimental groups when on the high P/S ratio diet (0.3 to 1.0). 3. There were significant increases in relative concentrations of linoleic acid in plasma phospholipids when on the high P/S ratio diet. 4. There was no consistent effect of dietary P/S ratio elevation from 0.3 to 1.0 on group mean systolic and diastolic blood pressures. Adjustment of blood pressure changes for changes in electrolytes, other dietary components, plasma lipids, weight and other lifestyle variables did not alter this result. 5. It was concluded that the blood pressure lowering effect of a vegetarian diet reported previously was unlikely to have been due to changes in dietary P/S ratio.

1. The fatty acid composition of membrane phospholipids of stimulated and unstimulated platelets was studied in six normal volunteers given a daily dietary supplement of a fish oil rich in eicosapentaenoic acid (EPA) for 4 weeks. The supplement was equivalent to 1.8 g of EPA daily. Thromboxane synthesis and platelet aggregation responses to sodium arachidonate, thrombin and the ionophore A23187 were also investigated. 2. A marked increase in the relative EPA content of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was noted after 2 and 4 weeks fish oil supplementation. However, there was no incorporation into phosphatidylinositol (PI) or phosphatidylserine (PS). The relative arachidonic acid (AA) content of PC and PE was significantly reduced at 2 and 4 weeks but that of PI and PS remained unchanged. Significant reductions in the relative linoleic acid content of total phospholipids, PC and PE were also noted. 3. Stimulation of platelets obtained after 4 weeks fish oil supplementation by thrombin and A23187 was associated with a marked reduction in the AA content of PI and a minor reduction in that of PE. There was no change in the relative proportions of EPA in PI, PS, PC or PE after stimulation. Throughout the study there were no significant changes in platelet aggregation responses or in platelet thromboxane production. 4. Our results indicate that the incorporation of EPA into the platelet membrane phospholipids is selective and that if PI is the major source of AA for platelet prostaglandin biosynthesis then the reported beneficial effects of EPA on haemostasis cannot be explained on the basis of its incorporation into and mobilization from the platelet membrane phospholipid pool.

1. The thermic response of five lean and five obese subjects was measured by indirect calorimetry before, and for 157.5 min after a meal of protein, carbohydrate or fat, each of which provided 1.25 MJ. The change in plasma glucose, insulin and (in the case of the carbohydrate meal) the rate of exogenous glucose oxidation was also measured. 2. There was no significant difference between the lean and obese groups in the magnitude of the thermic response to any of the three meals. In both weight groups the response was largest and most prolonged after the protein meal ( P < 0.01). 3. The obese group showed a higher concentration of fasting plasma insulin ( P < 0.01) and a larger increase in plasma glucose ( P < 0.05) after the carbohydrate meal, but there was no significant difference in the oxidation of exogenous glucose when compared with the lean group. 4. Previous studies on dietary-induced thermogenesis in lean and obese subjects have given conflicting results. In general reports of decreased thermogenesis in obese subjects are characterized by either (a) high pre-meal metabolic rates in the obese group, especially in diabetic subjects, or (b) a group classified as ‘normal’ who have been selected for their high thermogenic capacity.

1. Five healthy subjects took a daily supplement of 20 ml of linseed oil for 2 weeks. After a break of at least 6 weeks, the same subjects took a similar amount of MaxEPA (a fish oil fraction) for 2 weeks. The linseed oil supplement provided 9.38 g of linolenic acid (18:3 ω3) and the MaxEPA supplement provided 3.03 g of eicosapentaenoic acid (20:5 ω3) and 2.93 g of docosahexaenoic acid (22:6 ω3). The effects of the supplements on plasma lipid concentrations and on the fatty acid composition of platelet phosphoglycerides were studied. 2. In a second experiment, five male subjects took 5, 10 and 20 g of MaxEPA/day in random order for 3 week periods; each experimental period was separated by a break of at least 6 weeks. These doses of MaxEPA provided 0.83, 1.67 and 3.33 g of 20:5 ω3 and 0.80, 1.61 and 3.22 g 22:6 ω3 respectively. The effects of these supplements on plasma lipid concentrations, the fatty acid composition of platelet phosphoglycerides, template bleeding time and platelet aggregation induced by collagen and the prostaglandin analogue compound U46619 were studied. 3. In the platelet lipids, the proportion of 20:5 ω3 was increased by the 20 ml linseed oil supplement but the increase was small compared with the increase brought about by even 5 g of MaxEPA/day. The proportion of arachidonic acid (20:4 ω3) was substantially decreased by the MaxEPA supplement but not by the linseed oil supplement. The ratio of 20:4 ω6/20:5 ω3 fell from 32:1 in the control periods to 11:1 with 5 g, 7:1 with 10 g and 5:1 with 20 g of MaxEPA/day. The MaxEPA supplement also led to increases in the proportions of 22:5 ω3 and 22:6 ω3 and decreases in those of 20:3 ω6 and 22:4 ω6. 4. Bleeding times tended to be prolonged with the MaxEPA supplement but did not follow any dose-dependent trend. Platelet aggregation induced by both collagen and compound U46619 was not inhibited in vitro . 5. Plasma triglyceride concentrations were lowered by the MaxEPA supplement but not by the linseed oil supplement. Plasma triglyceride concentrations were substantially lowered by 10 g and 20 g of MaxEPA/day. Total plasma cholesterol concentrations were slightly lowered and HDL cholesterol concentrations were slightly increased by 20 g of MaxEPA/day. No other significant differences were noted.

1. Twenty young subjects with borderline hypertension were studied to evaluate the effects of moderate salt restriction and/or of a high potassium intake on intralymphocytic sodium content and blood pressure. Blood pressure was measured after 1 min (casual) and after 5 min (baseline) of rest and during handgrip. 2. Moderate sodium restriction (from 170 to 100 mmol of sodium/day) decreased both intralymphocytic sodium content and diastolic blood pressure at rest and during handgrip. During a high potassium diet (130 mmol of potassium/day) both intralymphocytic sodium content and baseline diastolic blood pressure rose significantly whereas casual diastolic blood pressure remained unchanged and pressor response to handgrip was reduced by 50%. 3. The increase in intralymphocytic sodium content induced by the high potassium diet was dose-dependent. A daily dose of 0.8 mmol of potassium/kg body weight produced the maximal protective effect on blood pressure during exercise with minimal effects on intralymphocytic sodium content and baseline blood pressure. 4. In borderline subjects a low sodium/high potassium diet seems to produce the most favourable effect, since intralymphocytic sodium content and baseline blood pressure remain unchanged whereas the pressor response to handgrip is reduced.

1. Twelve healthy male subjects took a daily supplement of 20 ml of cod-liver oil for 6 weeks. This provided 1.8 g of eicosapentaenoic acid (20:5ω3) and 2.2 g of docosahexaenoic acid (22:6ω3). The effects of the supplement on blood lipids, haemostatic variables, bleeding time and plasma vitamin A and carotene were studied. In seven subjects platelet aggregation induced by adenosine 5′-pyrophosphate (ADP) was also studied. 2. The proportions of 20:5ω3 and 22: 6ω3 in platelet and erythrocyte phosphoglycerides were substantially increased by the supplement mainly at the expense of ω6 polyunsaturated fatty acids. 3. Mean plasma triglyceride concentrations were reduced and those of high-density-lipoprotein (HDL) cholesterol were increased by the supplement. 4. The mean bleeding time was significantly prolonged after 3 weeks of taking the supplement, but had returned to the presupplementation value 5 weeks after withdrawal of the supplement. 5. The maximum estimated response to platelet aggregation induced by ADP was increased by the supplement. 6. The mean levels of antithrombin III (immunological) and blood pressure were lower at the end of the period of supplementation and remained so 5 weeks after withdrawal of the supplement. No significant changes in other variables were noted.

1. The thermogenic response and changes in plasma substrates and hormones were tested after a liquid meal in lean, obese and formerly obese women. 2. Subjects with a family history of obesity tested either while obese or after slimming to a normal weight had a thermogenic response, which was only half that of the lean group. 3. The immediate response in plasma glucose and insulin was greater in the lean subjects, but the sustained changes in circulating substrates did not differ in the three groups. Thyroidal hormone concentrations did not alter postprandially: venous noradrenaline levels rose in the obese groups only. 4. The differences in postprandial thermogenesis at rest would reduce the energy requirements of subjects with familial obesity, but they still had a metabolic rate estimated to be nearly 1MJ (240 kcal)/day in excess of the lean group so additional thermogenic defects must exist for familial obesity to be explained solely on a metabolic basis.

1. Urinary composition was studied in nine healthy adults on unrestricted diet and low-oxalate diet with and without individual oxalate-rich foods. 2. Urine oxalate was constant on the low-oxalate and constant high-oxalate diets and only fluctuated greatly on unrestricted diet. 3. Urine oxalate was mainly due to dietary oxalate which accounts for up to two-thirds of urinary oxalate. 4. Urine oxalate was unaffected by urine volume. 5. Varying percentages of dietary oxalate were absorbed depending on the nature of the foodstuff. 6. Although tea was the main source of dietary oxalate in some people it, like strawberries, did not represent a real risk factor. Chocolates, peanuts, beetroot, rhubarb and spinach were considered as high-risk foods. 7. Calcium oxalate crystalluria at 4°C was increased significantly when the oxalate-rich foods were taken. When urine was examined at 37°C no increase in crystalluria was found.

1. Changes in serum total and lipoprotein fraction triglyceride and cholesterol levels were studied in 24 adults on home haemodialysis. Half the patients were randomly allocated to a low cholesterol (mean 200 mg/day), fat-modified diet (mean polyunsaturated/saturated fat ratio of 1.0 with a mean of 43% of the total energy content derived from fat). 2. Before dietary manipulation, triglyceride levels in all lipoprotein fractions were significantly higher ( P < 0.02) than in a control group of age and sex matched normal subjects. Total cholesterol, very-low-density-lipoprotein (VLDL) and low-density-lipoprotein (LDL) cholesterol were also significantly raised ( P < 0.02), but high-density-lipoprotein (HDL) cholesterol was normal. In the patients on a fat-modified diet triglyceride levels did not alter in any of the lipoprotein fractions. Total cholesterol and LDL cholesterol levels fell significantly into the normal range ( P < 0.002 and < 0.001 respectively) but VLDL and HDL cholesterol levels did not change. 3. Hypertriglyceridaemia is the most common lipid abnormality in patients with renal failure and a long-term fat-modified diet is, therefore, of limited therapeutic importance in these patients unless there is a low HDL/LDL cholesterol ratio.

1. To establish whether 3-methylhistidine in food is quantitatively excreted in the urine, five normal adults on a vegetarian diet were given known amounts of 3-methylhistidine in meat or fish. The mean cumulative 5-day increment in 3-methylhistidine excretion in non-hydrolysed urine accounted for an average of 90% of the 3-methylhistidine given during the first 3 days of this period. 2. To define the variation in urinary 3-methylhistidine on a constant mixed intake, the daily 3-methylhistidine excretion was measured for 6 days in four patients on a metabolic ‘balance’ diet. The mean daily variation was less than 10%. 3. The results show that under the conditions of this study the increase in urinary 3-methylhistidine above basal levels can be quantitatively accounted for by the 3-methylhistidine content of additional food; in subjects on a constant diet it should be possible to detect relatively small changes in 3-methylhistidine excretion.

1. The possible roles of the diet and of intestinal absorption in the increased excretion of oxalate by patients with renal calcium stones have been studied. 2. Dietary surveys showed that the mean daily intake of oxalic acid by stone-formers was not significantly different from that of non-stone-formers. 3. The mean urinary excretion of oxalate, expressed as an oxalate/creatinine molar ratio, was significantly reduced by fasting, the change being more marked in the stone-formers than in the normal subjects. Moreover, fasting abolished the difference in mean oxalate/creatinine ratios between stone-formers and control subjects. 4. These results are compatible with the hypothesis that the small increases in urinary oxalate excretion which occur in some idiopathic calcium oxalate stone-formers are due to increased absorption of oxalate from the intestine, which may be due to a reduction in intraluminal calcium concentration.

1. High-salt, high-carbohydrate and low-protein diet induces remarkable elevation of blood pressure in spontaneous hypertensive rats (SHR). 2. These animals have low serum potassium, low blood urea nitrogen and high blood sugar. 3. Heart weight is increased in proportion to the elevation of blood pressure. 4. Kidney weight of rats receiving the high-salt, high-carbohydrate and low-protein diet was, by contrast, smaller than SHR receiving a normal diet. 5. The kidneys of SHR receiving a high-salt, high-protein diet were twice as heavy as the kidneys of normal rats. 6. Similar dietary modifications in Goldblatt hypertensive rats to those in SHR produced similar changes in blood pressure and heart weight.

1. Epidemiological studies in Iwate, Northern Japan, have confirmed a higher incidence of cerebrovascular accidents and a lower incidence of ischaemic heart diseases in Japan than in North America and Western Europe. 2. The average daily diet in Iwate is relatively low in animal proteins and fat, but relatively high in sodium. 3. Serum cholesterol is relatively low in inhabitants of Iwate. 4. The higher incidence of cerebrovascular accidents may be related to the higher sodium intake, whereas the lower incidence of ischaemic heart disease may be related to the lower intake of animal protein and fat and probably consequent lower serum cholesterol.