CVD is a major cause of mortality and morbidity in the Western world. In recent years its importance has expanded internationally and it is believed that by 2020 it will be the biggest cause of mortality in the world, emphasising the importance to prevent or minimise this increase. A beneficial role for vitamins in CVD has long been explored but the data are still inconsistent. While being supported by observational studies, randomised controlled trials have not yet supported a role for vitamins in primary or secondary prevention of CVD and have in some cases even indicated increased mortality in those with pre-existing late-stage atherosclerosis. The superiority of combination therapy over single supplementation has been suggested but this has not been confirmed in trials. Studies have indicated that β-carotene mediates pro-oxidant effects and it has been suggested that its negative effects may diminish the beneficial effects mediated by the other vitamins in the supplementation cocktail. The trials that used a combination of vitamins that include β-carotene have been disappointing. However, vitamin E and vitamin C have in combination shown long-term anti-atherogenic effects but their combined effect on clinical endpoints has been inconsistent. Studies also suggest that vitamins would be beneficial to individuals who are antioxidant-deficient or exposed to increased levels of oxidative stress, for example, smokers, diabetics and elderly patients, emphasising the importance of subgroup targeting. Through defining the right population group and the optimal vitamin combination we could potentially find a future role for vitamins in CVD.

Protein synthesis is affected when an insufficient level of sulfur amino acids is available. This defect may originate from dietary amino acid deficiency and/or excessive amino acid utilisation for other purposes such as the synthesis of glutathione and acute-phase proteins during catabolic stress. Sulfur amino acids are recognised to exert other significant functions since they are precursors of essential molecules, are involved in the methylation process, participate in the control of oxidative status, and may act as mediators affecting metabolism and cell functions. Despite this increased understanding of the role of sulfur amino acids, many questions still remain unanswered due to the complexity of the mechanisms involved. Moreover, surprising effects of dietary sulfur amino acids have been reported, with the development of disorders in cases of both deficiency and excess. These findings indicate the importance of defining adequate levels of intake and providing a rationale for nutritional advice. The aim of the present review is to provide an overview on the roles of sulfur amino acids as regulators of nutrient metabolism and cell functions, with emphasis placed on the implications for nutrition.

Aged rats show decrements in performance on motor and cognitive tasks that require the use of spatial learning and memory. Previously we have shown that these deficits can be reversed by the polyphenolics in fruits and vegetables. Walnuts, which contain the n-3 fatty acids α-linolenic acid and linoleic acid, are a dietary source of polyphenols, antioxidants and lipids. Thus, the present study examined the effects of walnut supplementation on motor and cognitive ability in aged rats. Fischer 344 rats, aged 19 months, were fed a control, or a 2, 6 or 9 % walnut diet for 8 weeks before motor and cognitive testing. Results for the motor testing showed that the 2 % walnut diet improved performance on rod walking, while the 6 % walnut diet improved performance on the medium plank walk; the higher dose of the 9 % walnut diet did not improve psychomotor performance and on the large plank actually impaired performance. All of the walnut diets improved working memory in the Morris water maze, although the 9 % diet showed impaired reference memory. These findings show for the first time that moderate dietary walnut supplementation can improve cognitive and motor performance in aged rats.

Elevated C-reactive protein (CRP), IL-6 and retinol-binding protein 4 (RBP4) levels are associated with insulin resistance and diabetes mellitus. Phytoestrogens (including lignans and isoflavones) may enhance the management of diabetes and are hypothesized to act through inflammation pathways. The present study explored the effects of flaxseed-derived lignan on inflammatory factors and RBP4 concentrations in type 2 diabetics, who have higher levels of these biomarkers. Seventy community-dwelling diabetic patients (twenty-six men and forty-four post-menopausal women) with mild hypercholesterolaemia completed a randomized, double-blind, placebo-controlled, cross-over trial of supplementation with flaxseed-derived lignan capsules (360 mg/d) or placebo for 12 weeks, separated by an 8-week wash-out period. The participants maintained their habitual diets and levels of physical activity. Baseline to follow-up concentrations of CRP increased significantly within the placebo group (1·42 (sem 0·19) v. 1·96 (sem 0·22) mg/l, P < 0·001), but were comparatively unchanged in the lignan-supplemented group (1·67 (sem 0·19) v. 1·90 (sem 0·26) mg/l, P = 0·94); a significant difference was observed between treatments ( − 0·45 (95 % CI − 0·76, − 0·08) mg/l, P = 0·021). This effect was confined to women (P = 0·016), but not observed in men (P = 0·49). No between-treatment differences were found with regard to IL-6 or RBP4; though IL-6 concentrations increased significantly from baseline to follow-up in both groups (P = 0·004 and P < 0·001 following lignan and placebo treatments, respectively). The study suggests that lignan might modulate CRP levels in type 2 diabetics. These results need to be confirmed by further large clinical trials of longer duration.

Haem carrier protein 1 (HCP1) was originally identified and characterised as a mammalian haem transporter. However, recent evidence has shown that it is also a proton-coupled folate transporter (PCFT) and mutations in the gene cause hereditary folate deficiency in humans. We therefore investigated haem and folate transport characteristics of PCFT/HCP1 both in vivo and in vitro in CD-1 mice and in the presence or absence of a blocking antibody for PCFT/HCP1, and also in cultured cells (which express PCFT/HCP1 endogenously) to elucidate the specificity and selectivity of PCFT/HCP1. The in vivo study showed that the addition of folic acid inhibited 59Fe-labelled haem transport in hypoxic mice but had no effect in normal mice. Using in vitro methods, the results showed increased [3H]folate uptake into everted duodenum from hypoxic mice but uptake was reduced by the addition of haem or PCFT/HCP1 antibodies to the medium. Caco-2 cells transiently transfected with small interfering RNA (siRNA) PCFT/HCP1 duplex oligos resulted in a 69 % reduction in PCFT/HCP1 mRNA when compared with the control siRNA. Both haem and folate uptake were significantly (P < 0·05) reduced in cells transfected with PCFT/HCP1 siRNA; however, the magnitude of reduction with folic acid uptake was greater (48 %) than that of haem (22·5 %). Overall the data support PCFT/HCP1 as a primary folate transporter with a lower affinity for haem. PCFT/HCP1 could therefore play a physiological role in Fe nutrition and the data highlight the potential for the interaction of folate and haem at the level of intestinal absorption.

Hydroxytyrosol acetate (HT-AC) is a polyphenol present in virgin olive oil (VOO) at a proportion similar to hydroxytyrosol (HT) (160–479 μmol/kg oil). The present study was designed to measure the in vitro platelet antiaggregating activity of HT-AC in human whole blood, and compare this effect with that of HT and acetylsalicylic acid (ASA). The experiments were designed according to the standard procedure to investigate the activity of ASA. HT-AC and HT inhibited platelet aggregation induced by ADP, collagen or arachidonic acid in both whole blood and platelet-rich plasma (PRP). ASA and HT-AC had a greater effect in whole blood than in PRP when ADP or collagen was used as inducer. ASA and HT-AC had a greater effect in PRP+leucocytes than in PRP alone. All three compounds inhibited platelet thromboxane B2 and leucocyte 6-keto-prostaglandin F1α (6-keto-PF1α) production. The thromboxane/6-keto-PGF1α inhibition ratio (as an indirect index of the prostanoid equilibrium) was 10·8 (se 1) for HT-AC, 1·0 (se 0·1) for HT and 3·3 (se 0·2) for ASA. All three compounds stimulated nitric oxide production, although HT was a weaker effect. In our experiments only concentrations higher than 500 μm (HT) or 1 mm (HT-AC and ASA) inhibited 3-nitrotyrosine production. All three compounds inhibited the production of TNFα by leucocytes, with no significant differences between them. In quantitative terms HT-AC showed a greater antiplatelet aggregating activity than HT and a similar activity to that of ASA. This effect involved a decrease in platelet thromboxane synthesis and an increase in leucocyte nitric oxide production.

Diabetes mellitus is an important risk factor for CVD. A previous study showed that high glucose induced the apoptosis of human umbilical vein endothelial cells (HUVEC) via the sequential activation of reactive oxygen species, Jun N-terminal kinase (JNK) and caspase-3. The apoptosis cascade could be blocked by ascorbic acid at the micromolar concentration (100 μm). In addition to ascorbic acid, quercetin, the most abundant dietary flavonol, has been recently actively studied in vascular protection effects due to its antioxidant effect at low micromolar concentrations (10–50 μm). Quercetin sulfate/glucuronide, the metabolite of quercetin in blood, however, has been rarely evaluated. In the present study, we investigated the effect of quercetin sulfate/glucuronide on the prevention of high glucose-induced apoptosis of HUVEC. HUVEC were treated with media containing high glucose (33 mm) in the presence or absence of ascorbic acid (100 μm) or quercetin sulfate/glucuronide (100 nm, 300 nm and 1 μm). For the detection of apoptosis, a cell death detection ELISA assay was used. The level of intracellular H2O2 was measured by flow cytometry. JNK and caspase-3 were evaluated by a kinase activity assay and Western blot analysis. The results showed that high glucose-induced apoptosis was inhibited by quercetin sulfate/glucuronide in a dose-dependent manner. The effect of quercetin sulfate/glucuronide on H2O2 quenching, inhibition of JNK and caspase-3 activity at the nanomolar concentration (300 nm) was similar to that of ascorbic acid at the micromolar concentration (100 μm). The findings of the present study may shed light on the pharmacological application of quercetin in CVD.

Dietary non-digestible carbohydrates (NDC) play an important role in large-bowel health and one form of NDC, resistant starch (RS), can promote low levels of DNA damage and other markers of colonic health. The objective of the present study was to determine whether the ability of dietary RS or other NDC to influence colonic health, particularly DNA damage, is dependent on the type of dietary oil. We compared the effects of diets containing 10 % of NDC from cellulose, wheat bran, high-amylose maize starch (HAS, a rich source of RS type 2) or a retrograded HAS (RHAS, a rich source of RS type 3) on DNA damage, SCFA production and bacterial changes in the large bowel of rats. Each carbohydrate source was combined with 10 % fish oil (FO) or Sunola™ oil (SO; rich in oleic acid). There was a significant interaction between NDC and oil treatments on single-strand DNA breaks in colonocytes isolated from the colon. The damage in rats consuming RHAS was greater for FO consumption than for SO consumption. There was a significant interaction between NDC and oils on caecum weights and treatment effects of NDC and oils were observed for the weights and lengths of other gut tissues. Significant differences were found in colonic SCFA pools and caecal numbers of lactobacilli, bifidobacteria, Escherichia coli and Bacteroides fragilis with the various NDC and oil treatments. The present results demonstrate that the effects of NDC and oils, particularly on colonic DNA damage, can depend on how they are combined within the diet.

In search of an adequate model for the human metabolic syndrome, the metabolic characteristics of Wistar rats were analysed after being submitted to different protocols of high fructose ingestion. First, two adult rat groups (aged 90 d) were studied: a control group (C1; n 6) received regular rodent chow (Labina, Purina) and a fructose group (F1; n 6) was fed on regular rodent chow. Fructose was administered as a 10 % solution in drinking water. Second, two adult rat groups (aged 90 d) were evaluated: a control group (C2; n 6) was fed on a balanced diet (AIN-93G) and a fructose group (F2; n 6) was fed on a purified 60 % fructose diet. Finally, two young rat groups (aged 28 d) were analysed: a control group (C3; n 6) was fed on the AIN-93G diet and a fructose group (F3; n 6) was fed on a 60 % fructose diet. After 4–8 weeks, the animals were evaluated. Glucose tolerance, peripheral insulin sensitivity, blood lipid profile and body fat were analysed. In the fructose groups F2 and F3 glucose tolerance and insulin sensitivity were lower, while triacylglycerolaemia was higher than the respective controls C2 and C3 (P < 0·05). Blood total cholesterol, HDL and LDL as well as body fat showed change only in the second protocol. In conclusion, high fructose intake is more effective at producing the signs of the metabolic syndrome in adult than in young Wistar rats. Additionally, diet seems to be a more effective way of fructose administration than drinking water.

Poor quality of nutrition during fetal development is associated with adverse health outcomes in adult life. Epidemiological studies suggest that markers of fetal undernutrition are predictive of risk of the metabolic syndrome and CHD. Here we show that feeding a low-protein diet during pregnancy programmed the development of atherosclerosis in ApoE*3-Leiden mice. ApoE*3-Leiden mice carry a mutation of human ApoE*3 rendering them prone to atherosclerosis when fed a diet rich in cholesterol. It was noted that fetal exposure to protein restriction led to a greater degree of dyslipidaemia in mice when fed an atherogenic diet, with low-protein-exposed ApoE*3 mice having elevated total plasma cholesterol (34 % higher; P < 0·001) and TAG (39 % higher; P < 0·001) relative to offspring exposed to a control diet in utero. The low-protein group developed more severe atherosclerotic lesions within the aortic arch (2·61-fold greater lesion area; P < 0·001). Analysis of a targeted gene array suggested a potential role for members of the LDL receptor superfamily, along with similar programmed suppression of the mRNA expression of hepatic sterol regulatory element-binding protein-1c. This indicates that disordered lipid metabolism may play a role in the fetal programming of atherosclerosis in this model. Whereas earlier studies have shown early programming of cardiovascular risk factors, these results demonstrate for the first time that the interaction of prenatal undernutrition with a postnatal atherogenic diet increases the extent of atherosclerotic disease.

The consumption of mineral waters is increasing in industrialised countries. High intakes of Ca and other alkalising cations as well as a low acid intake are beneficial to bone. We examined which components of mineral waters are conditioning their Ca content and their alkalinising power, in order to define the optimal profile. European mineral waters were randomly selected on the Internet: 100 waters with less than 200 mg Ca/l (9·98 mEq/l) and fifty with more than 200 mg/l, all with complete data for SO4, P, Cl, Na, K, Mg and Ca, and most also for HCO3. For comparison, forty North American mineral waters were randomly chosen. The potential renal acid load (PRAL) was calculated for each mineral water. North American waters did not reveal significant results because of their low mineralisation. We performed correlations between all eight components in order to explore the properties of the mineral waters. In the European waters, twenty-six out of twenty-eight correlations showed a P value of ≤ 0·01. In waters with PRAL >0 (acidifying waters), PRAL was positively correlated with SO4, Ca, K and Mg (P < 0·001). In those with PRAL < 0 (alkalinising waters), PRAL was negatively correlated with HCO3, Na, Mg, Ca, K, Cl and SO4 (P < 0·001). SO4 and HCO3 were not found together in high quantities in the same water for geochemical reasons. A high Ca content is associated with either a high SO4 or a high HCO3 content. SO4 theoretically increases Ca excretion, while HCO3 and low PRAL values are associated with positive effects on bone. Therefore, the best waters for bone health are rich in both HCO3 and Ca, and by consequence low in SO4.

The significant role of trace elements in human health is well documented. Trace elements are those compounds that need to be present in the human diet to maintain normal physiological functions. However, some microelements may become harmful at high levels of exposure, or, on the other hand, may give rise to malnutrition, when their exposure is too low. The aim of the present study was to provide a reliable estimate of the dietary exposure of twenty-one trace elements in a Northern Italian area. For this purpose, trace element analyses were undertaken on total diet samples collected from a university cafeteria in Pavia, Northern Italy. The average daily exposure for the adult people was calculated on the basis of food consumption frequency, portion size and trace element levels in foodstuffs. The mean exposure values satisfy the Italian RDA for all the essential trace elements, except for Fe exposure in females, and are well below the Provisional Tolerable Daily Intake for all the toxic compounds, showing that the probability of dietary exposure to health risks is overall small. As far as Fe exposure is concerned, a potential risk of anaemia in the female adult population should be considered, then studies aimed at evaluating the Fe nutritional status of adult Italian women should be addressed. In conclusion, while not excluding the possibility that the daily exposure determined in the present study may not be representative of the population as a whole, this study provides a good estimate of the Italian adult consumer exposure to twenty-one trace elements.

The aim was to identify the important sources of added sucrose and determinants of high intake, and to evaluate what impact a high proportion of energy from added sucrose has on the intake of foods and nutrients. The subjects consisted of children invited to the nutrition study within the Type 1 Diabetes Prediction and Prevention birth cohort and born in 2001 (n 846). Of these, 471 returned 3 d food records at 3 years of age. The average daily intake of added sucrose was 35 (sd 17) g (11·3 % of energy intake) and that of total sucrose was 41 (sd 18) g (13·3 % of energy intake). Sucrose added by manufacturers accounted for 82 %, naturally occurring sucrose for 15 % and sucrose added by consumers for 3 % of the total sucrose. Juice drinks, yoghurt/cultured milks, and chocolate and confectionery were the main contributors to added sucrose intake. Consumption of rye bread, porridge, fresh vegetables, cooked potatoes, skimmed milk, hard cheeses, margarine and fat spread as well as intake of most nutrients decreased across the quartiles of added sucrose (P < 0·05). Being cared for at home, having a father with a vocational school degree, having at least two siblings and a milk-restricted diet increased the risk for a high-sucrose diet. The study implied that a high proportion of added sucrose in the diet had mainly an unfavourable impact on the intake of recommended foods and key nutrients in Finnish children. The rationale for the recommendation to reduce the intake of refined sugars to ensure adequate intakes of nutrients seems reasonable.

The purpose of the present study was to test the usefulness of dish items selected in developing a dish-based FFQ (DFFQ) to be used for epidemiological studies in Korea. The dietary data of 6817 subjects from the 2001 Korean National Health and Nutrition Examination Survey were used for the analysis. The 24 h recall method was employed for the dietary survey. Initially, ninety-five dish items were selected in developing the DFFQ based on consumption frequency, contribution of selected nutrients and coverage of between-person variations. The usefulness of the selected ninety-five dish items was tested based on their degree of contribution in supplying nutrients in the cumulative percentage contribution (cPC), as well as on their degree of explanation for between-person variation in the cumulative regression coefficient (cMRC). According to the results, the ninety-five selected dish items accounted for an average of 92·3 % of seventeen nutrients consumed by the study subjects based on cPC estimation. The top twenty items among the ninety-five dish items covered 70 to 91 % of the between-person variation for the seventeen nutrients based on cMRC estimation. Thus, the results suggest that the ninety-five items would be useful in developing a FFQ for use in epidemiological studies of Koreans, within less than 10 % underestimation.

An increased risk of renal cell carcinoma (RCC) has been linked with obesity. However, there is limited information about the contribution of dietary fat and fat-related food groups to RCC risk. A population-based case–control study of 406 cases and 2434 controls aged 40–85 years was conducted in Iowa (1986–89). For 323 cases and 1820 controls from the present study, information on dietary intake from foods high in fat nutrients and other lifestyle factors was obtained using a mailed questionnaire. Cancer risks were estimated by OR and 95 % CI, adjusting for age, sex, smoking, obesity, hypertension, physical activity, alcohol and vegetable intake and tea and coffee consumption. In all nutrient analyses, energy density estimates were used. Dietary nutrient intake of animal fat, saturated fat, oleic acid and cholesterol was associated with an elevated risk of RCC (OR = 1·9, 95 % CI 1·3, 2·9, Ptrend < 0·001; OR = 2·6, 95 % CI 1·6, 4·0, Ptrend < 0·001; OR = 1·9, 95 % CI 1·2, 2·9, Ptrend = 0·01; OR = 1·9, 95 % CI 1·3, 2·8, Ptrend = 0·006, respectively, for the top quartile compared with the bottom quartile of intake). Increased risks were also associated with high-fat spreads, red and cured meats and dairy products (OR = 2·0, 95 % CI 1·4, 3·0, Ptrend = 0·001; OR = 1·7, 95 % CI 1·0, 2·2, Ptrend = 0·01; OR = 1·8, 95 % CI 1·2, 2·7, Ptrend = 0·02; OR = 1·6, 95 % CI 1·1, 2·3, Ptrend = 0·02, respectively). In both the food groups and nutrients, there was a significant dose–response with increased intake. Our data also indicated that the association of RCC with high-fat spreads may be stronger among individuals with hypertension. These findings deserve further investigation in prospective studies.

The objectives of the study were to investigate whether the health conditions of mothers with short stature differed from those with normal stature, and to establish if these aspects were associated with the health of the offspring. Data relating to health and socio-economic, demographic and anthropometric conditions were collected from a probabilistic sample population consisting of 1180 mothers and 1511 children ( < 10 years) living in the semi-arid region of the State of Alagoas, Brazil. Mothers were categorised according to stature, with those in the 1st quartile being defined as of short stature and those in the 4th quartile being defined as of normal stature and serving as a reference for the comparison of variables of interest. Following verification that maternal stature fulfilled parametric assumptions, its associations with the other variables were determined by calculating Pearson correlation coefficients. After excluding strongly self-correlated variables (r ≥ 0·70), the remaining variables were analysed by multiple linear regression. The results showed that low maternal stature was independently associated with obesity (percentage body fat ≥ 30; P = 0·045), abdominal adiposity (waist:hip ratio ≥ 0·85; P = 0·007) and high systolic blood pressure ( ≥ 140 mmHg; P = 0·006). Short maternal stature was associated with low birth weight ( < 3000 g; P = 0·01) and stunting (height-for-age Z score < − 2; P = 0·019) in the offspring. Thus, in the semi-arid region of Alagoas, women of short stature presented a higher prevalence of chronic degenerative diseases and produced less healthy children than women of normal stature.

The present study was undertaken to assess the beneficial effects of a daily consumption of 8 % freeze-dried red-pigmented leafy lettuce (Lactuca sativa) on CVD. C57BL/6J mice were fed a high-fat high-cholesterol diet supplemented with or without red-pigmented leafy lettuce for 4 weeks. The present results showed that the red-pigmented leafy lettuce-supplemented diet significantly decreased the level of total and LDL-cholesterol and TAG in the plasma of the mice. The atherosclerotic index was calculated to be 46 % lower in the mice fed with the lettuce diet compared with the control diet. Lipid peroxidation measured by 2-thiobarbituric acid-reactive substances was markedly reduced in the plasma, liver, heart and kidney of the mice fed the lettuce diet. The content of antioxidants (total glutathione and β-carotene) was significantly increased by lettuce supplementation. The antioxidant defence system by antioxidant enzymes including glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase and paraoxanase in blood or liver tissues was also increased, and showed the improved oxidative stress in the mice fed the lettuce diet. The measurement of tail DNA (%), tail extent moment and olive tail moment indicated that the lettuce diet increased the resistance of hepatocyte and lymphocyte DNA to oxidative damage. The present study showed that the supplementation of a high-cholesterol high-fat diet with 8 % red-pigmented leafy lettuce resulted in an improvement of plasma cholesterol and lipid levels, prevention of lipid peroxidation and an increase of the antioxidant defence system and, therefore, could contribute to reduce the risk factors of CVD.

We have previously shown that adult female rats exposed to intra-uterine malnutrition were normophagic, although obese and resistant to insulin-induced hypophagia. The present study aimed at examining aspects of another important catabolic component of energy homeostasis control, the hypothalamic serotonergic function, which inhibits feeding and stimulates energy expenditure. Pregnant dams were fed ad libitum or were restricted to 50 % of ad libitum intake during the first 2 weeks of pregnancy. Control and restricted 4-month-old progeny were studied. The restricted rats had increased body adiposity with normal daily food intake but failed to respond with hypophagia to an intracerebroventricular injection of serotonin (5-hydroxytryptamine; 5-HT). Stimulation, by food ingestion, of extracellular levels of serotonin in medial hypothalamus microdialysates was more pronounced and lasted longer in the restricted than in the control rats. In the restricted group, hypothalamic levels of 5-HT2C receptor protein tended to be reduced (P = 0·07) while the levels of 5-HT1B receptor and serotonin transporter proteins were significantly elevated (36 and 79 %, respectively). In conclusion, female rats undernourished in utero had normophagic obesity as adults but had an absence of serotonin-induced hypophagia and low hypothalamic levels of the 5-HT2C receptor. Compensatory adaptations for the functional serotonergic impairment were evidenced, such as an enhanced release of serotonin in response to a meal allied to up-regulated hypothalamic 5-HT1B and transporter expression. Whether these compensations will persist in later life warrants further investigation. Moreover, it cannot be ruled out that the serotonergic component of energy expenditure was already impaired, thus contributing to the observed body-fat phenotype.

Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Our aim was to determine the relationship between serum leptin and clinical and biochemical features in overweight children and adolescents. Overweight children and adolescents followed in this Unit with serum leptin ascertained were included. Clinical, biochemical and abdominal ultrasound data were analysed. Statistical analysis was performed by t test, χ2, Pearson's correlation and linear regression. One outlier of serum leptin was excluded to perform correlation and regression. Serum leptin was determined in 357 patients. At the first visit, the mean age was 9·5 (sd 3·2) years and mean BMI z-score was 1·72 (sd 1·34) (girls 1·71 (sd 1·16); boys 1·72 (sd 1·11)). Serum leptin levels were significantly related to: sex (mean: girls 48·0 ng/ml, boys 34·4 ng/ml; P = 0·003); Tanner stage (mean: I–II 37·0 ng/ml, III–V 45·2 ng/ml; P = 0·035); systolic blood pressure (mean: normal 41·3 ng/ml, high 44·0 ng/ml; P = 0·009); BMI z-score (r 0·136; P = 0·010); C-peptide (r 0·17; P = 0·002); insulin (r 0·34; P < 0·001); homeostasis model assessment of insulin resistance (HOMA-IR) (r 0·25; P < 0·001) and aspartate aminotransferase (r − 0·12; P = 0·023). In the multivariate analysis (with leptin as the dependent variable and sex, Tanner stage, BMI z-score, systolic blood pressure, aspartate aminotransferase, C-peptide, insulin and HOMA-IR as independent variables), sex and BMI were determinant factors. The present study in overweight children and adolescents showed that being female and greater BMI were significantly and independently associated with increased serum leptin. In this large cohort other associations with leptin described in the literature can be discharged.