Published Science

OBJECTIVE: High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of cardiovascular risk. We hypothesised that n-3 fatty acids reduce underlying inflammatory processes and consequently CRP concentrations in healthy middle-aged subjects. DESIGN: Placebo-controlled, double-blind study. SUBJECTS: A total of 43 men and 41 postmenopausal women aged 50-70 y. Before and after intervention, we measured serum CRP concentrations with an enzyme immunoassay. INTERVENTIONS: Capsules with either 3.5 g/day fish oil (1.5 g/day n-3 fatty acids) or placebo for 12 weeks. RESULTS: The median CRP change in the fish oil group did not significantly differ from that in the placebo group (0.01 vs -0.17 mg/l, P = 0.057). CONCLUSION: The currently available data--including ours--do not support that beneficial effects on CRP are involved in a mechanism explaining the protective effect on heart disease risk of n-3 fatty acids as present in fish.

AIMS/HYPOTHESIS: This study compared the long-term weight loss and health outcomes at 1-year follow-up, after a 12-week intensive intervention consisting of two low-fat, weight-loss diets, which differed in protein content. METHODS: We randomly assigned 66 obese patients (BMI: 27-40 kg/m2) with type 2 diabetes to either a low-protein (15% protein, 55% carbohydrate) or high-protein diet (30% protein, 40% carbohydrate) for 8 weeks of energy restriction (approximately 6.7 MJ/day) and 4 weeks of energy balance. Subjects were asked to maintain the same dietary pattern for a further 12 months of follow-up. RESULTS: The study was completed by 38 of the subjects, with equal dropouts in each group. At Week 64, weight reductions against baseline were -2.2+/-1.1 kg (low protein) and -3.7+/-1.0 kg (high protein), p<0.01, with no diet effect. Fat mass was not different from baseline in either group. At Week 12, both diets reduced systolic and diastolic blood pressure by 6 and 3 mm Hg respectively, but blood pressure increased more with weight regain during follow-up in the low-protein group (p< or =0.04). At Week 64, both diets significantly increased HDL cholesterol and lowered C-reactive protein concentrations. There was no difference in the urinary urea : creatinine ratio at baseline between the two groups, but this ratio increased at Week 12 (in the high-protein group only, p

BACKGROUND: Endothelial dysfunction is one of the mechanisms linking diet and the risk of cardiovascular disease. OBJECTIVE: We evaluated the hypothesis that dietary patterns (summary measures of food consumption) are directly associated with markers of inflammation and endothelial dysfunction, particularly C-reactive protein (CRP), interleukin 6, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1). DESIGN: We conducted a cross-sectional study of 732 women from the Nurses' Health Study I cohort who were 43-69 y of age and free of cardiovascular disease, cancer, and diabetes mellitus at the time of blood drawing in 1990. Dietary intake was documented by using a validated food-frequency questionnaire in 1986 and 1990. Dietary patterns were generated by using factor analysis. RESULTS: A prudent pattern was characterized by higher intakes of fruit, vegetables, legumes, fish, poultry, and whole grains, and a Western pattern was characterized by higher intakes of red and processed meats, sweets, desserts, French fries, and refined grains. The prudent pattern was inversely associated with plasma concentrations of CRP (P = 0.02) and E-selectin (P = 0.001) after adjustment for age, body mass index (BMI), physical activity, smoking status, and alcohol consumption. The Western pattern showed a positive relation with CRP (P < 0.001), interleukin 6 (P = 0.006), E-selectin (P < 0.001), sICAM-1 (P < 0.001), and sVCAM-1 (P = 0.008) after adjustment for all confounders except BMI; with further adjustment for BMI, the coefficients remained significant for CRP (P = 0.02), E-selectin (P

BACKGROUND: Bone loss is a critical concern for space travelers, and a dietary countermeasure would be of great benefit. Dietary protein and potassium-associated bicarbonate precursors may have opposing effects on the acid-base balance in the body and therefore on bone loss. OBJECTIVE: In 2 studies, we examined the ability of dietary protein and potassium to predict markers of bone metabolism. DESIGN: In the first study, 8 pairs of male identical twins were assigned to 1 of 2 groups: bed rest (sedentary, or SED, group) or bed rest with supine treadmill exercise in a lower-body negative pressure chamber (EX group). In a second study, groups of 4 subjects lived in a closed chamber for 60 or 91 d, and dietary data were collected for two or three 5-d sessions. Urinary calcium, N-telopeptide, and pyridinium cross-links were measured before bed rest; on bed rest days 5-6, 12-13, 19-20, and 26-27; and daily during the chamber studies. Data were analyzed by Pearson's correlation (P

Toll-like receptors (TLR) sense microbial compounds and bridge innate and adaptive immunity by activation of antigen-presenting cells. TLR-induced signaling via intracellular adaptor molecules, including MyD88 and TRIF, drives transcriptional activation of genes including pro-inflammatory cytokines and cell activation markers. To globally assess the activation programs triggered by individual TLR in macrophages, we used microarray-based gene expression profiling of the murine macrophage cell line RAW264.7. Here we describe that the TLR4 ligand LPS more strongly modulates gene expression compared to ligands for TLR 2, 3, 7, and 9. Taking advantage of the known dependency of TLR on given adaptor molecules, we operationally define sets of MyD88 and TRIF "private" genes. We conclude with a TLR signaling model that incorporates both negative and synergistic interactions of MyD88- and TRIF-controlled signaling pathways as deduced from the microarray data presented.

The A8344G mitochondrial DNA (mtDNA) mutation is best known for the MERRF phenotype (myoclonic epilepsy, myopathy, and ragged red fibers). We describe a sporadic case of an infant with the A8344G mtDNA mutation who presented with failure to thrive and sudden unexpected death at 11 months of age. The autopsy revealed a histiocytoid cardiomyopathy, diffuse steatosis of the liver, and bilateral retinal hypoplasia. Electron micrographs of cardiac myocytes showed striking mitochondrial hyperplasia, dispersing the sarcomeres. Special stains of frozen heart muscle showed an absence of complex IV (cytochrome c oxidase) in many of the myocytes. Both complexes I and IV of the respiratory chain were reduced in cardiac muscle. The A8344G mtDNA mutation was detected in both liver and cardiac muscle tissue. To our knowledge, this is the first description of the A8344G mtDNA mutation presenting as a sporadic case of fatal infantile cardiomyopathy and the first occurence of this mutation associated with histiocytoid cardiomyopathy.

BACKGROUND: In previous studies, dietary patterns were derived in different populations without regard to a specific outcome. OBJECTIVE: The objective was to apply a new statistical method to construct a specific dietary pattern that is strongly associated with the risk of coronary artery disease (CAD). DESIGN: We applied reduced rank regression to a sample of 200 cases and 255 controls from the Coronary Risk Factors for Atherosclerosis in Women (CORA) Study. The CAD-specific dietary pattern was constructed by choosing intake data for 49 food groups as predictors and 5 established biomarkers for CAD as responses. RESULTS: A high score for the constructed dietary pattern was characterized by high intakes of meat, margarine, poultry, and sauce and low intakes of vegetarian dishes, wine, vegetables, and whole-grain cereals. After adjustment for known CAD risk factors, the relative risks from the lowest to the highest quintiles of the pattern score were 1.0, 1.1, 3.6, 6.2, and 12.3 (95% CI: 4.9, 30.9; P for trend

There has been interest in the effect of various types and amounts of dietary carbohydrates and proteins on blood glucose. On the basis of our previous data, we designed a high-protein/low-carbohydrate, weight-maintaining, nonketogenic diet. Its effect on glucose control in people with untreated type 2 diabetes was determined. We refer to this as a low-biologically-available-glucose (LoBAG) diet. Eight men were studied using a randomized 5-week crossover design with a 5-week washout period. The carbohydrate:protein:fat ratio of the control diet was 55:15:30. The test diet ratio was 20:30:50. Plasma and urinary beta-hydroxybutyrate were similar on both diets. The mean 24-h integrated serum glucose at the end of the control and LoBAG diets was 198 and 126 mg/dl, respectively. The percentage of glycohemoglobin was 9.8 +/- 0.5 and 7.6 +/- 0.3, respectively. It was still decreasing at the end of the LoBAG diet. Thus, the final calculated glycohemoglobin was estimated to be approximately 6.3-5.4%. Serum insulin was decreased, and plasma glucagon was increased. Serum cholesterol was unchanged. Thus, a LoBAG diet ingested for 5 weeks dramatically reduced the circulating glucose concentration in people with untreated type 2 diabetes. Potentially, this could be a patient-empowering way to ameliorate hyperglycemia without pharmacological intervention. The long-term effects of such a diet remain to be determined.

OBJECTIVE: This study investigated the nutrient intake of overweight postmenopausal women assigned to a low-fat vegan diet or a Step II diet. METHODS: Fifty-nine overweight (body mass index, 26 to 44 kg/m2) postmenopausal women were randomly assigned to a self-selected low-fat vegan or a National Cholesterol Education Program Step II diet in a 14-wk controlled trial on weight loss and metabolism. Nutrient intake, which was measured per 1000 kcal, was the main outcome measure. Statistical analyses included within-group and between-group t tests examining changes associated with each diet. RESULTS: Consumption of a low-fat vegan diet was associated with greater decreases in fat, saturated fat, protein, and cholesterol intakes and greater increases in carbohydrate, fiber, beta-carotene, and total vitamin A intakes than was a Step II diet. The low-fat vegan group also increased thiamin, vitamin B6, and magnesium intakes more than the Step II group, and both groups increased folic acid, vitamin C, and potassium intakes. If considering only food sources of micronutrients, the low-fat vegan group decreased vitamin D, vitamin B12, calcium, selenium, phosphorous, and zinc intakes compared with baseline. However, with incidental supplements included, decreases were evident only in phosphorous and selenium intakes. No micronutrient decreases were found in the Step II group. CONCLUSIONS: Individuals on a low-fat vegan or Step II diet should take steps to meet the recommended intakes of vitamin D, vitamin K, folic acid, calcium, magnesium, and zinc. Individuals on a low-fat vegan diet should also ensure adequate intakes of vitamin B12, phosphorous, and selenium.

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited form of colorectal cancer, caused mostly by mutations in the APC gene. Due to the wide variety of mutations found and the large size of the APC gene, several methods of mutation detection are used, which can be time consuming and costly. Here we demonstrate a new method of mutation detection in the APC gene using an array-based approach termed combinatorial sequencing-by-hybridization (cSBH). In cSBH, a universal probe set is attached to a support and a second one is in solution. Two-probe ligation occurs when a DNA strand from the target PCR product consecutively anneals to both unlabeled array-bound and solution-phase dye-labeled probe, creating all target-complementary long-labeled probes attached to the surface. A standard array reader scores fluorescent signals at each array position. Cell lines and patient DNA with known APC gene mutations were analyzed using a cSBH-based HyChip trade mark product. Results show that this universal hexamer (6-mer) chip can successfully detect a range of mutations. Results are very robust for a continuous readout of 3.6 kb from a PCR target, with 99.97% accuracy on a single HyChip trade mark slide. cSBH is a fast, cost-efficient method for first stage mutation screening in the APC or any other gene.

PURPOSE: This study aimed to assess the acceptability of a low-fat vegan diet, as compared with a more typical fat-modified diet, among overweight and obese adults. METHODS: Through newspaper advertisements, 64 overweight, postmenopausal women were recruited, 59 of whom completed the study. The participants were assigned randomly to a low-fat vegan diet or, for comparison, to a National Cholesterol Education Program Step II (NCEP) diet. At baseline and 14 weeks later, dietary intake, dietary restraint, disinhibition, and hunger, as well as the acceptability and perceived benefits and adverse effects of each diet were assessed. RESULTS: Dietary restraint increased in the NCEP group (P <.001), indicating a greater subjective sense of constraint with regard to diet requirements, but was unchanged in the vegan group. Disinhibition and hunger scores fell in each group (P <.001 and P <.01, respectively). The acceptability of both diets was high, although the vegan group participants rated their diet as less easy to prepare than their usual diets (P <.05) and the NCEP participants foresaw continuation of their assigned diet to be more difficult than continuation of their baseline diets (P

With the growing interest in the potential health benefits of plant-based diets, it is relevant to consider whether vegetarian dietary practices could influence athletic performance. Accordingly, this review examines whether nutrients that may differ between vegetarian and omnivorous diets could affect physical performance. We also describe recent studies that attempt to assess the effects of a vegetarian diet on performance and comment on other nutritional aspects of vegetarianism of relevance to athletes. Although well-controlled long-term studies assessing the effects of vegetarian diets on athletes have not been conducted, the following observations can be made: 1) well-planned, appropriately supplemented vegetarian diets appear to effectively support athletic performance; 2) provided protein intakes are adequate to meet needs for total nitrogen and the essential amino acids, plant and animal protein sources appear to provide equivalent support to athletic training and performance; 3) vegetarians (particularly women) are at increased risk for non-anemic iron deficiency, which may limit endurance performance; and 4) as a group, vegetarians have lower mean muscle creatine concentrations than do omnivores, and this may affect supramaximal exercise performance. Because their initial muscle creatine concentrations are lower, vegetarians are likely to experience greater performance increments after creatine loading in activities that rely on the adenosine triphosphate/phosphocreatine system. 5) Coaches and trainers should be aware that some athletes may adopt a vegetarian diet as a strategy for weight control. Accordingly, the possibility of a disordered eating pattern should be investigated if a vegetarian diet is accompanied by unwarranted weight loss.

Ghrelin is an orexigenic hormone that is implicated in meal initiation, in part because circulating levels rise before meals. Because previous human studies have examined subjects fed on known schedules, the observed preprandial ghrelin increases could have been a secondary consequence of meal anticipation. A causal role for ghrelin in meal initiation would be better supported if preprandial increases occurred before spontaneously initiated meals not prompted by external cues. We measured plasma ghrelin levels among human subjects initiating meals voluntarily without cues related to time or food. Samples were drawn every 5 min between a scheduled lunch and a freely requested dinner, and hunger scores were obtained using visual analog scales. Insulin, glucose, fatty acids, leptin, and triglycerides were also measured. Ghrelin levels decreased shortly after the first meal in all subjects. A subsequent preprandial increase occurred over a wide range of intermeal intervals (IMI; 320-425 min) in all but one subject. Hunger scores and ghrelin levels showed similar temporal profiles and similar relative differences in magnitude between lunch and dinner. One subject displayed no preprandial ghrelin increase and was also the only individual whose insulin levels did not return to baseline between meals. This finding, along with a correlation between area-under-the-curve values of ghrelin and insulin, suggests a role for insulin in ghrelin regulation. The preprandial increase of ghrelin levels that we observed among humans initiating meals voluntarily, without time- or food-related cues, and the overlap between these levels and hunger scores are consistent with a role for ghrelin in meal initiation.

The ideal timing of anticonvulsant reduction for a child started on the ketogenic diet is unclear. The records of 81 children started on the ketogenic diet consecutively over a 2-year period were reviewed for a 6-month period after diet initiation. During their first 6 months on the ketogenic diet, medications were tapered in 53 of 81 (65%) patients, with 30 of 53 (57%) considered "early" (tapered during diet initiation or within the first month afterward). No differences were seen between the early and late groups with respect to percentage with > 90% seizure reduction at 3 months (47% vs 48%), diet duration (1.1 vs 0.9 years), percentage remaining on the ketogenic diet to date (73% vs 65%), or improved alertness (63% vs 57%). Nine of fifty-three (17%) had transient seizure increases during medication tapering, with no correlation to the timing in which this occurred; however, five were taking benzodiazepines or barbiturates. All had > 50% seizure reduction at 3 months despite the transient worsening. Early reduction of anticonvulsants in children initiated on the ketogenic diet appears to be safe and well tolerated. However, it offers no specific advantage compared with a later taper.

Feedlot steers (n = 36) from three biological types (Bos indicus, Bos taurus-Continental, and Bos taurus-English) were used to determine the Ca, P, and vitamin D3 status of feedlot cattle. The USDA yield and quality grade traits were measured at slaughter, and the concentrations of vitamin D3 (VITD) and the metabolites 25-hydroxyvitamin D3 (25-OH D) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D) were determined in LM, liver, kidney, and plasma. Plasma and muscle Ca and P concentrations also were determined. Biological type of cattle affected a number of carcass traits. Carcasses from Bos taurus-English cattle had more marbling, resulting in higher quality grades (P < 0.05). Carcasses from Bos taurus-Continental cattle had lower calculated yield grades (P < 0.05) than did carcasses from cattle in the other biological types. In general, differences in carcass traits resulting from biological type were consistent with other reports. Plasma and LM Ca and P concentrations were not affected (P = 0.06) by biological type of cattle, indicating that Ca and P homeostasis is a conserved trait across the different types of cattle. Plasma VITD and 25-OH D concentrations were not affected (P = 0.41) by biological type, whereas plasma 1,25-(OH)2 D concentration was lower (P < 0.05) in Bos taurus-English cattle than in Bos taurus-Continental and Bos indicus cattle. Liver VITD and 25-OH D were not affected by biological type (P = 0.76), but liver 1,25-(OH)2 D concentration was greater (P < 0.05) in Bos indicus cattle than in Bos taurus-Continental cattle. Kidney vitamin D metabolite concentrations were not affected by biological type of cattle (P = 0.21). Muscle VITD concentration was greater (P < 0.05) in Bos taurus-English cattle than in the other two biological types, and muscle 25-OH D concentrations were greater (P < 0.05) in Bos taurus-English cattle than in Bos indicus cattle. Muscle 1,25-(OH)2 D concentration was less (P

The ketogenic diet is a high-fat, adequate protein, low carbohydrate diet that has been used for the treatment of intractable childhood epilepsy since the 1920s. The diet mimics the biochemical changes associated with starvation, which create ketosis. Although less commonly used in later decades because of the increased availability of anticonvulsants, the ketogenic diet has re-emerged as a therapeutic option. Only a decade ago the ketogenic diet was seen as a last resort; however, it has become more commonly used in academic centres throughout the world even early in the course of epilepsy. The Atkins diet is a recently used, less restrictive, therapy that also creates ketosis and can lower the number of seizures. Dietary therapies may become even more valuable in the therapy of epilepsy when the mechanisms underlying their success are understood.

The study of Haap et al. (1) on two patients with multiple symmetric lipomatosis (MSL), also known as the Launois-Bensaude Syndrome, adds interesting new insights into a condition still poorly understood. As for the conclusions drawn concerning insulin sensitivity in patient 1, we would like to suggest some caution. Our study group has also measured the insulin sensitivity index (ISI) in three subjects with MSL with the euglycemic-hyperinsulinemic \ldots

Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders. Genetic factors contribute to the underlying liability to develop ADHD. Reports implicate variants of genes important for the synthesis, uptake, transport and receptor binding of dopamine in the etiology of ADHD, including DRD4, DAT1, DRD2, and DRD5. In the present study, we genotyped a large multiplex sample of ADHD affected children and their parents for polymorphisms in genes previously reported to be associated with ADHD. Associations were tested by the transmission disequilibrium test (TDT). The sample is sufficient to detect genotype relative risks (GRRs) for putative risk alleles. The DRD4 gene 120-bp insertion/deletion promoter polymorphism displayed a significant bias in transmission of the insertion (chi(2)=7.58, P=0.006) as suggested by an analysis of a subset of these families. The seven repeat allele of the DRD4 48-bp repeat polymorphism (DRD4.7) was not significantly associated with ADHD in the large sample in contrast to our earlier findings in a smaller subset. We replicate an association of a dinucleotide repeat polymorphism near the DRD5 gene with ADHD by showing biased nontransmission of the 146-bp allele (P=0.02) and a trend toward excess transmission of the 148-bp allele (P=0.053). No evidence for an association was found for polymorphisms in DRD2 or DAT1 in this sample. The DRD5 146-bp (DRD5.146) allele and the DRD4 240-bp (DRD4.240) allele of the promoter polymorphism emerge as the two DNA variants showing a significant association in this large sample of predominantly multiplex families with ADHD, with estimated GRRs of 1.7 and 1.37, respectively.

Chemically, isoflavones belong to the group of polyphenols. The most important food source is soy, which contains mainly genistein and daidzein in the form of glycosides. The absorption rate ranges from 20-55%. Isoflavones are selectively incorporated in certain tissues like the breast and ovaries. They are able to bind to the estrogen receptors alpha (ER-alpha) and beta (ER-beta). However, the binding affinity for genistein to ER-alpha is only 4%, the affinity to ER-beta is 87% compared to 17beta-estradiol. Thus, depending on the estradiol concentration, they exhibit weak estrogenic or antiestrogenic activity. Isoflavones can influence transcription and cell proliferation. They modulate enzyme activities as well as signal transduction, and have antioxidant properties. Epidemiological studies have shown that the prevalence of hot flashes is lower in women from countries with high dietary isoflavone intake such as Japan than in Western nations with low isoflavone intake. Results of clinical studies on the effects of soy products or isolated isoflavones on vasomotor symptoms are contradictory. Due to a strong placebo effect and a time-dependent reduction of hot flashes, phytoestrogens were seen to have no significant effect in most studies. The use of soy isoflavones could, however, be considered for women with intense disorders. Because of contradictory data from in vitro and animal studies, a definite safety assessment of isoflavone intake cannot be made to date. While moderate isoflavone consumption seems to be safe in the majority of the population, women with breast cancer should avoid long-term use of soy products or isolated isoflavones.

The objective of this experiment was to determine the effects of age and diet on serum chemistry, hematology, and nutrient digestibility in healthy dogs. Twelve senior (11 yr old; six males and six females) and 12 weanling (age = 8 wk old; six males and six females) beagles were randomly assigned to one of two dietary treatments: 1) an animal product-based (APB) diet or 2) a plant product-based (PPB) diet. The APB diet was primarily composed of brewer's rice, chicken by-product meal, and poultry fat, whereas the primary ingredients of the PPB diet included corn, soybean meal, wheat middlings, and meat and bone meal. Dogs remained on experiment for 12 mo. A 4-d total fecal collection was performed to determine apparent macronutrient digestibilities after 3 and 10 mo. Blood samples were collected at baseline and after 3, 6, 9, and 12 mo on study. After 3 mo, dogs fed the APB diet had greater (P < 0.001) DM (6 percentage units) and OM (7 percentage units) digestibilities than dogs fed the PPB diet. Senior dogs had greater DM (2.5 percentage units; P = 0.07) and OM (3 percentage units; P < 0.01) digestibilities than young dogs. Dogs fed the PPB diet had a lower (P < 0.001) fecal DM percentage (7.5 percentage units) and greater (P < 0.001) fecal output (253 vs. 97 g/d, as-is basis). After 10 mo, age did not affect nutrient digestibility or fecal characteristics. However, the effect of diet after 10 mo was similar to that observed after 3 mo, as dogs fed the PPB diet had a lower (P < 0.001) fecal DM percentage (7 percentage units), lower OM (4 percentage units; P = 0.09) and fat (6 percentage units; P < 0.001) digestibilities, and greater (P < 0.005) fecal output (235 vs. 108 g/d, as-is basis). At baseline, most serum metabolites were different between age groups, with weanlings having several metabolite concentrations outside the reference ranges for adult dogs. Blood cholesterol, red blood cells, hemoglobin, hematocrit, creatinine, total protein, albumin, bilirubin, sodium, chloride, and alanine transaminase were present in greater (P < 0.05) concentrations in senior dogs, but weanling dogs had greater (P < 0.05) concentrations of glucose, platelets, Ca, P, K, and alkaline phosphatase. Over time, blood cholesterol concentrations were affected by age (P < 0.05) and diet (P < 0.01). Senior dogs had greater (P < 0.05) cholesterol concentrations than weanling dogs. Moreover, dogs fed the APB diet had greater (P

BACKGROUND: Vegetarians are often a little leaner compared with nonvegetarians and suffer less from obesity and its associated complications than nonvegetarians. Whether this is because of not eating meat specifically is unclear. OBJECTIVE: We investigated whether changing to a self-selected vegetarian diet resulted in changes to anthropometric measurements. Design Subjects (n = 33; seven males and 26 females) who were in the earliest stages of becoming vegetarian were observed for 6 months. Data on dietary intake, using a 3-day estimated dietary diary, and body composition were obtained at baseline and after 6 months of following a self-selected vegetarian diet. RESULTS: Dietary calculations showed that on changing to a self-selected vegetarian diet, there was a significant reduction (P < 0.05) in energy intake (8.9 MJ day(-1) versus 8.1 MJ day(-1)), and in the proportion of energy from saturated fatty acids (12.9% versus 11.3%) and a significant increase (P

The aim was to investigate socio-demographic characteristics, and attitudes to food and health of vegetarians, non-vegetarian consumers of meat substitutes, and meat consumers in The Netherlands. The sample used for this study (participants > or =18 years) was taken from the Dutch National Food Consumption Survey, 1997/1998. Vegetarians (n = 63) and consumers of meat substitutes (n = 39) had similar socio-demographic profiles: higher education levels, higher social economic status, smaller households, and more urbanised residential areas, compared to meat consumers (n = 4313). Attitudes to food were assessed by the food-related lifestyle instrument. We found that vegetarians (n = 32) had more positive attitudes towards importance of product information, speciality shops, health, novelty, ecological products, social event, and social relationships than meat consumers (n = 1638). The health consciousness scale, which was used to assess attitudes to health, supported earlier findings that vegetarians are more occupied by health. Food-related lifestyle and health attitudes of meat substitute consumers (n = 17) were predominantly in-between those from vegetarians and meat consumers. The outcome of this study suggests that in strategies to promote meat substitutes for non-vegetarian consumers, the focus should not only be on health and ecological aspects of foods.

The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with reduced expression after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. This is followed by induction of stress response, antioxidant and DNA repair genes. DNA damage is markedly increased in the promoters of genes with reduced expression in the aged cortex. Moreover, these gene promoters are selectively damaged by oxidative stress in cultured human neurons, and show reduced base-excision DNA repair. Thus, DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a programme of brain ageing that starts early in adult life.

The influence of a high-cholesterol diet on the atherogenicity of the low-density lipoprotein (LDL) particle was examined by measuring LDL peak diameter and composition, LDL susceptibility to oxidation, and the distribution of cholesterol between LDL subclasses. The crossover intervention randomly assigned 27 premenopausal women and 25 men (18 to 50 years) to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) diet for 30 days, followed by a 3-week washout period. Subjects were classified as either hyperresponders (>2.5 mg/dL increase in plasma cholesterol for each 100 mg additional dietary cholesterol consumed) or hyporesponders to dietary cholesterol. Sex was found to have a significant effect on 3 of the parameters examined. LDL peak diameter was significantly larger (P <.005) in females (26.78 +/- 0.59 nm, n = 27) as compared with males (26.52 +/- 0.49 nm, n = 25), regardless of response to dietary cholesterol. The LDL particles of the male participants also had a higher number of triglyceride (TG) and cholesteryl ester (CE) molecules (P <.01); however, cholesterol ester transfer protein (CETP) activity was higher in females (P <.05). Response classification also revealed significant differences in the determination of LDL subclasses. Independent of sex, the LDL-1 particle (P <.05), which is considered to be less atherogenic, was predominant in hyperresponders and this finding was associated with increased cholesterol intake (interactive effect, P <.001). In addition, CETP and lecithin: cholesterol acyltransferase (LCAT) activities were higher in hyperresponders during the egg period (interactive effect, P 0.5). Because LDL peak diameter was not decreased and the larger LDL-1 subclass was greater in hyperresponders following egg intake, these data indicate that the consumption of a high-cholesterol diet does not negatively influence the atherogenicity of the LDL particle.

The influence of a high-cholesterol diet on the atherogenicity of the low-density lipoprotein (LDL) particle was examined by measuring LDL peak diameter and composition, LDL susceptibility to oxidation, and the distribution of cholesterol between LDL subclasses. The crossover intervention randomly assigned 27 premenopausal women and 25 men (18 to 50 years) to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) diet for 30 days, followed by a 3-week washout period. Subjects were classified as either hyperresponders (>2.5 mg/dL increase in plasma cholesterol for each 100 mg additional dietary cholesterol consumed) or hyporesponders to dietary cholesterol. Sex was found to have a significant effect on 3 of the parameters examined. LDL peak diameter was significantly larger (P <.005) in females (26.78 +/- 0.59 nm, n = 27) as compared with males (26.52 +/- 0.49 nm, n = 25), regardless of response to dietary cholesterol. The LDL particles of the male participants also had a higher number of triglyceride (TG) and cholesteryl ester (CE) molecules (P <.01); however, cholesterol ester transfer protein (CETP) activity was higher in females (P <.05). Response classification also revealed significant differences in the determination of LDL subclasses. Independent of sex, the LDL-1 particle (P <.05), which is considered to be less atherogenic, was predominant in hyperresponders and this finding was associated with increased cholesterol intake (interactive effect, P <.001). In addition, CETP and lecithin: cholesterol acyltransferase (LCAT) activities were higher in hyperresponders during the egg period (interactive effect, P 0.5). Because LDL peak diameter was not decreased and the larger LDL-1 subclass was greater in hyperresponders following egg intake, these data indicate that the consumption of a high-cholesterol diet does not negatively influence the atherogenicity of the LDL particle.

Novel techniques for acquiring metabolomics data continue to emerge. Such data require proper storage in suitably configured databases, which then permit one to establish the size of microbial metabolomes (hundreds of major metabolites) and allow the nature, organisation and control of metabolic networks to be investigated. A variety of algorithms for metabolic network reconstruction coupled to suitable modelling algorithms are the ground substances for the development of metabolic network and systems biology. Even qualitative models of metabolic networks, when subject to stoichiometric constraints, can prove highly informative, and are the first step to the quantitative models, which alone can allow the true representation of complex biochemical systems.

OBJECTIVE: With the increasing knowledge about the antioxidant potential of many micronutrients such as zinc and vitamin C, their roles in oxidative stress related health disorders have been postulated. This study therefore investigated low micronutrient status as a predisposing factor for hypertension in a traditionally lacto-vegetarian population like Indians. METHODS: Micronutrient profile was assessed in 109 hypertensives with age-gender-socio-economic status matched 115 healthy normotensives (30-58 years of age). Food intakes were estimated through a semi-quantitative food frequency questionnaire. Nutrient intakes were then evaluated by previous estimates of cooked foods from our laboratory. Systolic and diastolic blood pressure (SBP, DBP), age, weight, height, waist and hip circumference, occupation, physical activity, smoking habits were recorded. Fasting blood samples were analyzed for hemoglobin, serum level of glucose, triglycerides, total cholesterol, HDL, ceruloplasmin, plasma level of ascorbic acid, folic acid, retinol, erythrocyte glutathione reductase activity coefficient (EGRAC) and erythrocyte membrane zinc. RESULTS: There were no significant differences between protein, fat intakes of normal and hypertensive individuals, though intakes of men were higher than those of women (p 0.2) in these subjects. Conditional logistic regression analysis indicated that intakes of vitamin C, folic acid and zinc were associated with 18% (OR = 1.18, 95% CI:1.08, 1.26), 51% (OR = 1.51, 95% CI 0.94, 2.1) higher odds for hypertension, and 3% lower odds for hypertension (OR = 0.97, 95% CI 0.92, 1.01), respectively. Mean plasma vitamin C and folic acid were significantly higher (p

Regulatory monitoring for most antibiotic residues in edible poultry tissues is often accomplished with accurate, although expensive and technically demanding, chemical analytical techniques. The purpose of this study is to determine if a simple, inexpensive bioassay could detect fluoroquinolone (FQ) residues in chicken muscle above the FDA established tolerance (300 ppb) comparable to a liquid chromatography-fluorescencemass spectrometry(n) method. To produce incurred enrofloxacin (ENRO) tissues (where ENRO is incorporated into complex tissue matrices) for the method comparison, 40-d-old broilers (mixed sex) were orally dosed through drinking water for 3 d at the FDA-approved dose of ENRO (50 ppm). At the end of each day of the 3-d dosing period and for 3 d postdosing, birds were sacrificed and breast and thigh muscle collected and analyzed. Both methods were able to detect ENRO at and below the tolerance level in the muscle, with limits of detection of 26 ppb (bioassay), 0.1 ppb for ENRO, and 0.5 ppb for the ENRO metabolite, ciprofloxacin (liquid chromatography-fluorescence-mass spectrometry(n)). All samples that had violative levels of antibiotic were detected by the bioassay. These results support the use of this bioassay as a screening method for examining large numbers of samples for regulatory monitoring. Positive samples should then be examined by a more extensive method, such as liquid chromatography-fluorescence-mass spectrometry(n), to provide confirmation of the analyte.

OBJECTIVE: The study aimed to evaluate the homocysteine and cobalamin status of German vegans and determine whether the intake of very small amounts of foods of animal origin can improve this status. DESIGN AND SETTING: Cross-sectional study, Germany. SUBJECTS: The dietary and nutritional intakes of 131 vegans (73 women, 58 men; age range: 20.2-82.1 years) were evaluated using a general questionnaire and two food-frequency questionnaires. RESULTS: The prevalence of inadequate cobalamin status in volunteers of the German Vegan Study was 28.2%, and that of hyperhomocysteinaemia, 38.1%. Moderate vegans were affected to a lesser extent than were strict vegans. Duration of veganism and cobalamin concentration were inversely correlated (Spearman's r=-0.175, P=0.047). Folate concentration and erythrocyte aspartic acid aminotransferase activity were not correlated with plasma homocysteine concentration, but duration of veganism correlated positively with homocysteine concentration (Spearman's r=0.319, P<0.001). Cobalamin and homocysteine concentrations were inversely correlated (when controlling for duration of veganism; r=-0.602, P

OBJECTIVE: Very low-carbohydrate diets are widely used for weight loss yet few controlled studies have determined how these diets impact cardiovascular risk factors compared to more traditional low-fat weight loss diets. The primary purpose of this study was to compare a very low-carbohydrate and a low-fat diet on fasting blood lipids, LDL subclasses, postprandial lipemia, and insulin resistance in overweight and obese women. METHODS: Thirteen normolipidemic, moderately overweight (body fat >30%) women were prescribed two hypocaloric (-500 kcal/day) diets for 4 week periods, a very low-carbohydrate (<10% carbohydrate) and a low-fat (<30% fat) diet. The diets were consumed in a balanced and randomized fashion. Two fasting blood draws were performed on separate days and an oral fat tolerance test was performed at baseline, after the very low-carbohydrate diet, and after the low-fat diet. RESULTS: Compared to corresponding values after the very low-carbohydrate diet, fasting total cholesterol, LDL-C, and HDL-C were significantly (p

Diets with higher protein (1.5 g x kg(-1) x d(-1)) and reduced carbohydrates (120 to 200 g/d) appear to enhance weight loss due to a higher loss of body fat and reduced loss of lean body mass. While studies of prolonged use of moderate protein diets are not available, short-term studies report beneficial effects associated with increased satiety, increased thermogenesis, sparing of muscle protein loss, and enhanced glycemic control. Combined impacts of a moderate protein diet are likely derived from lower carbohydrates resulting in lower postprandial increase in blood glucose and lower insulin response, and higher protein providing increased BCAA leucine levels and gluconeogenic substrates. A key element in the diet appears to be the higher intake of BCAA leucine with unique regulatory actions on muscle protein synthesis, modulation of the insulin signal, and sparing of glucose use by stimulation of the glucose-alanine cycle. This review focuses on the contributions of leucine and the BCAA to regulation of muscle protein synthesis and glycemic control.

The aim of the present study was to evaluate Mg absorption from a test meal served with an oxalate-rich vegetable, spinach, as compared with a test meal served with a vegetable with a low oxalate content, kale. Mg absorption was measured by a stable-isotope technique based on extrinsic labelling of the test meals and faecal monitoring of the excreted isotope labels. Nine healthy adults participated in the study. The test meals were based on 100 g phytate-free white bread, served with 300 g spinach (6.6 mmol oxalate; 0.7 mmol (25)Mg label added, 5.0 mmol total Mg) or 300 g kale (0.1 mmol oxalate; 1.2 mmol (26)Mg label added, 4.8 mmol total Mg). The test meals were served on days 1 and 3, at breakfast and lunch, using a cross-over design. The results from the present study demonstrated that apparent Mg absorption was significantly lower from the meal served with spinach (26.7 (sd 10.4) %) than the meal served with kale (36.5 (sd 11.8) %) (P=0.01). However, the lower fractional apparent Mg absorption from the test meal served with spinach can be assumed to be, at least partly, counterbalanced by the higher native Mg content of spinach as compared with kale. Although based on indirect evidence, i.e. not based on an evaluation of added (or removed) oxalic acid, the difference in Mg absorption observed in the present study is attributed to the difference in oxalic acid content between the two vegetables.

Estrogen produced by aromatization of gonadal androgen has an important facilitative role in male-typical aggressive behavior that is mediated through its interaction with estrogen receptors (ER) in the brain. Isoflavones found in soybeans and soy-based dietary supplements bind ER and have dose- and tissue-dependent effects on estrogen-mediated responses. Yet, effects of isoflavone-rich diets on social and aggressive behavior have not been studied. We studied the effects of long-term (15 months) consumption of diets rich in soy isoflavones on spontaneous social behavior among adult male cynomolgus macaques (Macaca fascicularis) (n = 44) living in nine stable social groups. There were three experimental conditions which differed only by the source of dietary protein: casein and lactalbumin (no isoflavones), soy protein isolate containing 0.94 mg isoflavones/g protein, and soy protein isolate containing 1.88 mg isoflavones/g protein. In the monkeys fed the higher amount of isoflavones, frequencies of intense aggressive (67% higher) and submissive (203% higher) behavior were elevated relative to monkeys fed the control diet (P's < 0.05). In addition, the proportion of time spent by these monkeys in physical contact with other monkeys was reduced by 68%, time spent in proximity to other monkeys was reduced 50%, and time spent alone was increased 30% (P's

Cyanogenic glucosides are naturally present in plant foods especially in staple foods (cassava) consumed by millions of people in tropical countries. Most traditional processing methods are effective in detoxifying such goitrogens to safe levels of consumption. Nevertheless, residual cyanide (CN) is rapidly metabolized to thiocyanate (SCN) by existing metabolic pathways. There are concerns that goitrogens may reach the nursing infants through breast feeding or cow's milk based formulas. SCN adverse effects are commonly observed in relation to cigarette smoking. Breast-feeding is effective in protecting infants from anti-thyroid effects of eventual or habitual maternal exposure to CN exposure in food (cassava) or recreation habits (cigarette smoking). SCN goitrogenic effects occur secondary to iodine deficiency in special circumstances of high consumption of incomplete detoxified cassava and insufficient protein intake. Only during inadequate protein nutrition can SCN aggravate endemic iodine-deficient disorders (IDD).

OBJECTIVES: To investigate the changes in post-meal plasma ghrelin levels in people with different breakfast hours. DESIGN AND INTERVENTIONS: The subjects adhered to strict breakfast times starting 2 weeks before the study. Blood was drawn hourly from 0530 or 0630 until 1130. Plasma ghrelin, leptin, and insulin levels were measured by radioimmunoassay. SETTING: Medical Research Institute, Pusan National University Hospital, Korea. SUBJECTS: A total of 16 healthy volunteers. RESULTS: The mean plasma ghrelin level in subjects consuming breakfast was 548.7 +/- 239.6 fmol/ml before breakfast and 384.8 +/- 168.7 fmol/ml 1 h after breakfast, with leptin levels of 6.8 +/- 2.6 and 6.5 +/- 2.5 ng/ml, respectively. Plasma ghrelin levels were lowest 1 h after the meal, although the breakfast times differed. The plasma ghrelin level was lowest at 0730 in subjects not eating breakfast. CONCLUSIONS: These findings suggest that the plasma ghrelin levels are lowest 1 h after breakfast despite the variance in breakfast times. This timing might best reflect an individual's plasma ghrelin level and enable reasonable comparisons.

The authors present a case of severe megaloblastic anemia and neurologic damage due to vitamin B12 deficiency in a 6-month-old infant. The cause of the vitamin deficiency was a maternal dietary deficiency because of a strict vegetarian diet and prolonged breast-feeding. The importance of early recog …

Leptin, a hormone from adipose tissue, regulates feeding behavior, satiation rate, energy expenditure and also plays an important role in maturation and reproduction. Recent studies support the concept that several factors such as a diet may influence on leptin levels. The aim of this study was to investigate serum concentration of leptin and lipids status in prepubertal children aged from 2 to 10 years with two different nutritional habits: vegetarian (n = 24) and omnivorous diet (n = 20). Serum leptin concentration was determined by immunoenzymeassay (ELISA). Serum lipids (cholesterol, HDL- and LDL-cholesterol, triglyceride) were measured by enzymatic and apolipoproteins by immunoturbidimetric methods. We noticed that in vegetarian diet there is a high rate of fiber (nearly twice as high as in omnivorous diet) and polyunsaturated acids (35% as much). In our study vegetarian children had lower total cholesterol and cholesterol in fractions HDL and LDL than meat eaters did. Also the apolipoproteins levels in vegetarian children were significantly below that of nonvegetarians. There is no differences in triglyceride concentration between the two groups of children. The mean serum leptin level in vegetarian children was significantly lower (3.1 +/- 1.2 ng/mL) as compared with the omnivores (5.6 +/- 2.1 ng/mL) (p

OBJECTIVE: The objective of this study was to evaluate differences in the pharmacodynamic (PD) profile of 2 second-generation extended-release (ER) formulations of methylphenidate (MPH): Metadate CD (MCD; methylphenidate HCl, US Pharmacopeia) extended-release capsules, CII, and Concerta (CON; methylphenidate HCl) extended-release tablets, CII. Little empirical information exists to help the clinician compare the PD effects of the available ER formulations on attention and behavior. Previous studies have shown that the near-equal doses of MCD and CON provide equivalent, total exposure to MPH as measured by area under the plasma concentration time curve, yet their pharmacokinetic (PK) plasma concentration versus time profiles are different. We previously offered a theoretical PK/PD account of the similarities and differences among available ER formulations based on the hypothesis that all formulations produce effects related to MPH delivered by 2 processes: 1) an initial bolus dose of immediate-release (IR) MPH that is expected to achieve peak plasma concentration in the early morning and have rapid onset of efficacy within 2 hours of dosing, which for the MCD capsule is delivered by 30% of the total daily dose as uncoated beads and for the CON tablet is delivered by an overcoat of 22% of the total daily dose; and 2) an extended, controlled delivery of ER MPH that is expected to achieve peak plasma concentrations in the afternoon to maintain efficacy for a programmed period of time after the peak of the initial bolus, which for the MCD capsule is delivered by polymer-coated beads and for the CON tablet by an osmotic-release oral system. According to this PK/PD model, clinical superiority is expected at any point in time for the formulation with the highest MPH plasma concentration. METHODS: This was a multisite, double-blind, double-dummy, 3-way crossover study of 2 active treatments (MCD and CON) and placebo (PLA). Children with confirmed diagnoses of attention-deficit/hyperactivity disorder were stratified to receive bioequivalent doses of MCD and CON that were considered to be low (20 mg of MCD and 18 mg of CON), medium (40 mg of MCD and 36 mg of CON), or high (60 mg of MCD and 54 mg of CON), and in a randomized order each of the study treatments was administered once daily in the morning for 1 week. On the seventh day of each treatment week, children attended a laboratory school, where surrogate measures of response were obtained by using teacher ratings of attention and deportment and a record of permanent product of performance on a 10-minute math test at each of the 7 classroom sessions spread across the day at 1.5-hour intervals. Safety was assessed by patient reports of adverse events, parent ratings on a stimulant side-effects scale, and measurement of vital signs. RESULTS: The analyses of variance revealed large, statistically significant main effects for the within-subject factor of treatment for all 3 outcome measures (deportment, attention, and permanent product). The interactions of treatment x session were also highly significant for all 3 outcome measures. Inspection of the PD profiles for the treatment x session interactions suggested 4 patterns of efficacy across the day: 1) PLA > MCD approximately CON (PLA superiority) immediately after dosing; 2) MCD > CON > PLA during the morning (MCD superiority); 3) MCD approximately CON > PLA during the afternoon (PD equivalence of MCD and CON); and 4) CON > MCD approximately PLA in the early evening (CON superiority). The effect of site was significant, because some study centers had low and some high scores for behavior in the lab classroom, but both the low- and high-scoring sites showed similar PD patterns across the day. The interaction of dose x treatment was not significant, indicating that the pattern of treatment effects was consistent across each dose level. There were no statistically significant overall differences among the 3 treatments for the frequency of treatment-emergent adverse events, ratings of side effects, or vital signs. Two additional PK/PD questions were addressed: 1. The a priori hypothesis called for a comparison of the average of sessions (removing session as a factor) during a time period that corresponds to the length of a typical school day (from 1.5 through 7.5 hours after dosing). For the planned contrast of the 2 treatment conditions (MCD versus CON), the difference was significant, confirming the a priori hypothesis of superiority of near-equal daily doses of MCD over CON for this predefined postdosing period. 2. In the design of the study, the dose factor represented the total daily dose, consisting of 2 components: the initial bolus doses of IR MPH, which differ for the near-equal total daily doses of MCD and CON, and the reservoir doses of ER MPH, which were the same for the 2 formulations. To evaluate the moderating effects of the bolus component of dose on outcome, average effect size (ES) was calculated for the efficacy outcomes at the time of expected peak PK concentration times of the initial bolus component for each formulation at the 3 dose levels. The correlation (r) of ES with IR MPH bolus dose was significant for each of the 3 outcome measures (r approximately .9), indicating that the magnitude of effects in the early morning may be attributed to the dose administered by the IR MPH bolus of each formulation. For the 2 dose conditions with equal 12-mg IR MPH boluses (MCD 40 and CON 54), the ESs were large and indistinguishable (eg, deportment ES approximately 0.75 for both). CONCLUSIONS: Once-daily doses of MCD and CON produced statistically significantly different PD effects on surrogate measures of behavior and performance among children with attention-deficit/hyperactivity disorder in the laboratory school setting. As predicted by the PK/PD model, superiority at any point in time was achieved by the formulation with the highest expected plasma MPH concentration.

This article examines the existence, description, perception, treatment, and outcome of symptoms consistent with autistic disorder in nineteenth-century London, England, based on case histories from the notes of Dr William Howship Dickinson at Great Ormond Street Hospital for Children. Three cases meeting the DSM-IV criteria for autistic disorder are described in detail. Other cases in which autistic traits are described are briefly summarized. The article explores the environment of contemporary medical practice, beliefs about childhood brain disorders, and social practice regarding children with brain disorders, and the impact of these factors on assessment and treatment. It correlates Dickinson's observations with current research on autism, providing information about children with autism before the condition was formally named in 1943.

The chimpanzee life span is shorter than that of humans, which is consistent with a faster schedule of aging. We consider aspects of diet that may have selected for genes that allowed the evolution of longer human life spans with slower aging. Diet has changed remarkably during human evolution. All direct human ancestors are believed to have been largely herbivorous. Chimpanzees eat more meat than other great apes, but in captivity are sensitive to hypercholesterolemia and vascular disease. We argue that this dietary shift to increased regular consumption of fatty animal tissues in the course of hominid evolution was mediated by selection for "meat-adaptive" genes. This selection conferred resistance to disease risks associated with meat eating also increased life expectancy. One candidate gene is apolipoprotein E (apoE), with the E3 allele evolved in the genus Homo that reduces the risks for Alzheimer's and vascular disease, as well as influencing inflammation, infection, and neuronal growth. Other evolved genes mediate lipid metabolism and host defense. The timing of the evolution of apoE and other candidates for meat-adaptive genes is discussed in relation to key events in human evolution.

The effects of ketone body metabolism suggests that mild ketosis may offer therapeutic potential in a variety of different common and rare disease states. These inferences follow directly from the metabolic effects of ketosis and the higher inherent energy present in d-beta-hydroxybutyrate relative to pyruvate, the normal mitochondrial fuel produced by glycolysis leading to an increase in the DeltaG' of ATP hydrolysis. The large categories of disease for which ketones may have therapeutic effects are:(1)diseases of substrate insufficiency or insulin resistance,(2)diseases resulting from free radical damage,(3)disease resulting from hypoxia. Current ketogenic diets are all characterized by elevations of free fatty acids, which may lead to metabolic inefficiency by activation of the PPAR system and its associated uncoupling mitochondrial uncoupling proteins. New diets comprised of ketone bodies themselves or their esters may obviate this present difficulty.