Published Science

This dissertation examines the natural foods and dietary health movement that emerged from the 1960s countercultural context. It traces the history of this food movement to explore larger transformations within the post-1960s U.S. political landscape and to examine the dilemma of using consumerism, the motor of capitalism, to express discontent with the dominant commercial culture. Originally, the 1960s natural foods movement endeavored to overthrow the mass market through counterhegemonic eating and shopping. Yet by the turn of the twenty-first century, natural foodists pursued a less adversarial personal "politics" of self-health, psychic well-being, and socially-conscious materialism. This work argues that the post-war ascendance of the media commercial complex and the baby boom generation's emphasis on the political character of personal acts determined that the post-1960s natural foods movement would eventually be incorporated and industrialized. It also assured that a generation shaped both by post-war materialism and the 1960s cultural rebellion would continue to use natural and organic eating and shopping to express their social discontent and political fortitude.

Although few hunter-gatherers or foragers exist today, they are well documented in the ethnographic record. Anthropologists have been eager to study them since they assumed foragers represented a lifestyle that existed everywhere before 10,000 years ago and characterized our ancestors into some ill-defined but remote past. In the past few decades, that assumption has been challenged on several grounds. Ethnographically described foragers may be a biased sample that only continued to exist because they occupied marginal habitats less coveted by agricultural people.3 In addition, many foragers have been greatly influenced by their association with more powerful agricultural societies.4 It has even been suggested that Holocene foragers represent a new niche that appeared only with the climatic changes and faunal depletion at the end of the last major glaciation.5 Despite these issues, the ethnographic record of foragers provides the only direct observations of human behavior in the absence of agriculture, and as such is invaluable for testing hypotheses about human behavioral evolution.6.

Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P \textless 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P \textless 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P \textless 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min (P \textless 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect.

Recent research suggests that a low-carbohydrate, ketogenic diet is effective for the treatment of obesity.18-22 A consideration of the physiology of low carbohydrate dieting leads to a different perspective of insulin resistance, suggesting that insulin resistance could be treated by reducing glucose appearance and cellular influx, rather than by increasing glucose disposal and cellular influx. Further research should consider a reduction in dietary carbohydrate as a strategy to treat insulin resistance. © Mary Ann Liebert, Inc.

The soy isoflavones daidzein and genistein are believed to reduce prostate cancer risk in soy consumers. However, daidzein can be metabolized by the intestinal flora to form a variety of compounds with different bioactivities. In the current study, we investigated the influence of long-term dietary habits on daidzein metabolism in healthy Caucasian men (19-65 y old). A secondary goal was to compare plasma and prostatic fluid concentrations of 5 isoflavonoids: genistein, daidzein, equol, dihydrodaidzein, and O-desmethylangolensin. Baseline plasma levels of isoflavonoids were quantitated in 45 men by HPLC-electrospray ionization-MS. Participants then consumed a soy beverage daily for 1 wk, and post-soy isoflavonoid levels were quantitated in plasma and prostatic fluid. Equal was the only metabolite that appeared to be influenced by routine dietary habits. Stratified analyses revealed that men who had consumed ≥30 mg soy isoflavones/d for at least 2 y had 5.3-times the probability of producing equal than men who had consumed ≤5 mg/d (P = 0.014). Additionally, those men who consumed animal meat regularly had 4.7-times the probability of producing equal than men who did not consume meat (P = 0.023). Equal production was not linked to age, BMI, or the consumption of yogurt, dairy, fruit, or American-style fast food. Daidzein and its metabolites (but not genistein) were typically present at higher levels in prostate fluid than plasma (median = 4-13 times that in plasma). In conclusion, our data suggest that the ability of Caucasian men to produce equal is favorably influenced by the long-term consumption of high amounts of soy and the consumption of meat. Last, the high concentrations of isoflavonoids in prostatic fluid increases the potential for these compounds to have direct effects in the prostate. © 2005 American Society for Nutritional Sciences.

This review seeks to find support for the hypothesis that (early) environmental factors, notably those of nutritional nature, play important roles in the etiology and severity of at least some psychiatric diseases. Complex diseases, like schizophrenia, autism and depression, do not inherit by Mendel's law, and the search for the underlying genetic basis has to this end been unsuccessful. Schizophrenia and autism relate to low birth weight and pregnancy complications, which predispose to developmental adaptations by 'programming'. Adaptation to the 'conditions of existence' occurs by mutation, epigenetics and interaction of the environment with transcription factors. Folate status, and one-carbon metabolism in general, is intimately involved in epigenetic modification, which refers to modifications of gene expression that do not entail a change of DNA base sequence. Studies in rats and hyperhomocysteinemic patients revealed that DNA methylation is sensitive to dietary folate and other factors in one-carbon metabolism. Early folate status of schizophrenic patients might be compromised as suggested by i) coinciding incidences of schizophrenia and neural tube defects (NTDs) in Dutch hunger winter cohorts, ii) coinciding seasonal fluctuations of birth incidence of patients with schizophrenia and NTDs, and iii) higher incidence of schizophrenia in methylene tetrahydrofolate dehydrogenase 677C→T homozygotes. Recent studies in both schizophrenia and autism point at epigenetic dysregulation by altered methylation of the investigated genes or chromosomal loci. Arachidonic acid (AA, from meat) and docosahexaenoic acid (from fish) are major structural components of brain phospholipids, as well as modulators of signal transduction and gene expression. Schizophrenic patients, and possibly autistic children, exhibit abnormalities in phospholipid metabolism that might cause local AA depletion and impaired eicosanoid-mediated signal transduction. There is a strong inverse relation between national fish intakes and rates of major and postpartum depressions. Four out of 5 randomized controlled trials with fish oil-derived eicosapentaenoic acid have so far produced positive results in schizophrenia, whereas 3/3 produced positive effects in depression and bipolar disorders. Patients with schizophrenia may also benefit from folic acid and fish oil supplements to lower their high risk of cardiovascular disease. It is concluded that folate, other one-carbon metabolite micronutrients, and LCP might play important roles in the etiology of at least some psychiatric diseases in their capacity as modulators of gene expression through epigenetic mechanisms (folate), and as brain structural components, precursors of signal-transducing eicosanoids and ligands to nuclear transcription factors (LCP). The nutrition-gut-brain axis in pregnancy and psychiatric patients is in urgent need of more attention.

The obesity epidemic is among the greatest public health challenges facing the modern world. Regarding dietary causes, most emphasis has been on changing patterns of fat and carbohydrate consumption. In contrast, the role of protein has largely been ignored, because (i) it typically comprises only approximately 15% of dietary energy, and (ii) protein intake has remained near constant within and across populations throughout the development of the obesity epidemic. We show that, paradoxically, these are precisely the two conditions that potentially provide protein with the leverage both to drive the obesity epidemic through its effects on food intake, and perhaps to assuage it. We formalize this hypothesis in a mathematical model. Some supporting epidemiological, experimental and animal data are presented, and predictions are made for future testing.

The purpose of this study was to compare the relative strength of association between symptoms of attention deficit/hyperactivity disorder (ADHD) with sleep disordered breathing (SDB), periodic limb movement disorder (PLMD), and bedtime resistance behaviors (BRBs). The Pediatric Sleep Questionnaire was completed by parents of 283 children. Scales were derived to indicate risk for specific sleep disorders, then correlated with symptoms of ADHD. Strong independent interrelationships between symptoms of PLMD and symptoms of ADHD emerged, with potential additional contributions by bedtime resistance. These interrelationships remained after controlling for age, SDB, sleepiness, or BRBs. These data suggest ADHD symptoms may be especially related to PLMD but that insufficient sleep duration secondary to bedtime resistance and noncompliance may make an independent contribution.

Background: We sought to determine the safety and efficacy of repeated 60°C sauna bathing in patients with chronic systolic congestive heart failure (CHF). Methods and Results: This study included 15 hospitalized CHF patients (New York Heart Association class = 2.8 ± 0.4) in stable clinical condition on conventional treatments. Sauna bathing was performed once per day for 4 weeks. Repeated sauna bathing was safely completed without any adverse effects in all patients. Symptoms improved in 13 of 15 patients after 4 weeks. Sauna bathing decreased systolic blood pressure without affecting heart rate, resulting in significant decrease in the rate-pressure product (6811 ± 1323 to 6292 ± 1093). Echocardiographic left ventricular ejection fraction was significantly increased from 30 ± 11 to 34 ± 11%. Sauna bathing significantly improved exercise tolerance manifested by prolonged 6-minute walking distance (388 ± 110 to 448 ± 118 m), increased peak respiratory oxygen uptake (13.3 ± 1.8 to 16.3 ± 2.1 mL/kg/min), and enhanced anaerobic threshold (9.4 ± 1.2 to 11.5 ± 1.9 mL/kg/min). Four-week bathing significantly reduced plasma epinephrine (40 ± 42 to 21 ± 23 pg/mL) and norepinephrine (633 ± 285 to 443 ± 292 pg/mL). Sauna bathing reduced the number of hospital admission for CHF (2.5 ± 1.3 to 0.6 ± 0.8 per year). Conclusion: Repeated 60°C sauna bathing was safe and improved symptoms and exercise tolerance in chronic CHF patients. Sauna bathing may be an effective adjunctive therapy for chronic systolic CHF. © 2005 Elsevier Inc. All rights reserved.

Abstract: Fructosamine-3-kinase (FN3K) and the more recently discovered fructosamine-3-kinase-related protein (FN3KRP) appear to protect proteins from nonenzymatic glycation. To gain a better understanding of these enzymes we performed a series of investigations including (1) in silico comparisons of their promoters; (2) real-time PCR analysis of their expression in human tissues; (3) effects of hyperglycemia, interleukin-1β (IL-1β), and nuclear factor kappa-B (NFκB) activation on their mRNA levels; (4) effects of small interfering RNA (siRNA) suppression of FN3K expression (knockdown) in cultured cells and (5) search of FN3K and FN3KRP homologs in available genomic and EST (expressed sequence tag) databases. Our results indicate that (1) both FN3K and FN3KRP promoters are TATA-less and CAAT-less and contain several homologous CpG islands and Sp1 binding sites. (2) Both genes are expressed in all human tissue examined, with FN3K showing significantly higher levels in tissues susceptible to nonenzymatic glycation and diabetic complications. (3) Treatment of fibroblasts with high glucose, IL-1β, and activation of NFκB does not affect the expression of either FN3K or FN3KRP. (4) Knockdown of FN3K in cultured cells inhibits or arrests their growth. (5) FN3K-like genes are widely distributed in nature, with the notable exception of insects and yeasts. These data suggest that FN3K and FN3KRP are constitutive “housekeeping” genes and that they play an important role in cell metabolism, possibly as deglycating enzymes.

Tells the story of our struggle to recognise the connections between diet, health, and disease. This book combines the science of nutrition with a history of the fads and quackery that waylay the unwary when it comes to matters of food and health.

A low fat, high carbohydrate diet in combination with regular exercise is the traditional recommendation for treating diabetes. Compliance with these lifestyle modifications is less than satisfactory, however, and a high carbohydrate diet raises postprandial plasma glucose and insulin secretion, thereby increasing risk of CVD, hypertension, dyslipidemia, obesity and diabetes. Moreover, the current epidemic of diabetes and obesity has been, over the past three decades, accompanied by a significant decrease in fat consumption and an increase in carbohydrate consumption. This apparent failure of the traditional diet, from a public health point of view, indicates that alternative dietary approaches are needed. Because carbohydrate is the major secretagogue of insulin, some form of carbohydrate restriction is a prima facie candidate for dietary control of diabetes. Evidence from various randomized controlled trials in recent years has convinced us that such diets are safe and effective, at least in short-term. These data show low carbohydrate diets to be comparable or better than traditional low fat high carbohydrate diets for weight reduction, improvement in the dyslipidemia of diabetes and metabolic syndrome as well as control of blood pressure, postprandial glycemia and insulin secretion. Furthermore, the ability of low carbohydrate diets to reduce triglycerides and to increase HDL is of particular importance. Resistance to such strategies has been due, in part, to equating it with the popular Atkins diet. However, there are many variations and room for individual physician planning. Some form of low carbohydrate diet, in combination with exercise, is a viable option for patients with diabetes. However, the extreme reduction of carbohydrate of popular diets (\textless30 g/day) cannot be recommended for a diabetic population at this time without further study. On the other hand, the dire objections continually raised in the literature appear to have very little scientific basis. Whereas it is traditional to say that more work needs to be done, the same is true of the assumed standard low fat diets which have an ambiguous record at best. We see current trends in the national dietary recommendations as a positive sign and an appropriate move in the right direction.

Increased endogenous generation of advanced glycation endproducts (AGEs) contributes importantly to the vascular complications of diabetes, in part owing to activation of the pro-inflammatory RAGE receptor. However, AGE-altered oligopeptides with RAGE-activating potential can also be absorbed from the diet, and indeed make a significant contribution to the plasma and tissue pool of AGEs; this contribution is especially prominent when compromised renal function impairs renal clearance of AGEs. Perhaps surprisingly, foods rich in both protein and fat, and cooked at high heat, tend to be the richest dietary sources of AGEs, whereas low-fat carbohydrate-rich foods tend to be relatively low in AGEs. Conceivably, this reflects the fact that the so-called "AGEs" in the diet are generated primarily, not by glycation reactions, but by interactions between oxidized lipids and protein; such reactions are known to give rise to certain prominent AGEs, such as epsilonN-carboxymethyl-lysine and methylglyoxal. Although roasted nuts and fried or broiled tofu are relatively high in AGEs, low-fat plant-derived foods, including boiled or baked beans, typically are low in AGEs. Thus, a low-AGE content may contribute to the many benefits conferred to diabetics by a genuinely low-fat vegan diet. Nonetheless, the plasma AGE content of healthy vegetarians has been reported to be higher than that of omnivores - suggesting that something about vegetarian diets may promote endogenous AGE production. Some researchers have proposed that the relatively high-fructose content of vegetarian diets may explain this phenomenon, but there so far is no clinical evidence that normal intakes of fructose have an important impact on AGE production. An alternative or additional possibility is that the relatively poor taurine status of vegetarians up-regulates the physiological role of myeloperoxidase-derived oxidants in the generation of AGEs - in which case, taurine supplementation might be expected to suppress elevated AGE production in vegetarians. Thus, a taurine supplemented low-fat vegan diet may be recommended as a strategy for minimizing AGE-mediated complications in diabetics and in patients with renal failure.

The human mitochondrial genome consists of approximately 1500 genes, 37 encoded by the maternally inherited mitochondrial DNA (mtDNA) and the remainder encoded in the nuclear DNA (nDNA). The mtDNA is present in thousands of copies per cell and encodes proteins that are essential components of the mitochondrial energy generation pathway, oxidative phosphorylation (OXPHOS). OXPHOS generates heat to maintain our body temperature and ATP to do work. The mitochondria also produce much of the cellular reactive oxygen species (ROS) and can initiate apoptosis through activation of the mitochondrial permeability transition pore (mtPTP) in response to energy deficiency and oxidative damage. Mitochondrial ROS mutates the mtDNA and mtDNA mutations have been associated with a wide range of age-related diseases including neurodegenerative diseases, cardiomyopathy, diabetes and various cancers. The cellular accumulation of mtDNA mutations may also be the aging clock. Ancient mtDNA variants have also been adaptive and may influence individual health today. Mutations in nDNA-encoded mitochondrial genes can also disrupt OXPHOS, alter mtDNA replication, and affect mitochondrial division. In an effort to treat mitochondrial disease, both metabolic and genetic interventions have been attempted. Metabolic interventions have been directed at increasing energy output, reducing ROS production and stabilizing the mtPTP. Genetic therapies have attempted introduction of nucleic acids into the mitochondrion, nDNA-mitochondrial genes into the nucleus, and mtDNA-encoded genes into the nucleus. These therapeutic approaches might also be used to enhance performance, but we must be careful that catering to short term individual interests might undermine our capacity to adapt and survive.

Vegetarians have a lower intake of vitamin B12 than omnivores do. Vitamin B12 deficiency (holotranscobalamin II 271 nmol/L) was found in 58% of 71 vegetarians studied. Higher homocysteine levels (>12 micromol/L) found in 45% indicate disturbed remethylation of homocysteine to methionine. The methylation of DNA is strongly linked to homocysteine metabolism. Since DNA methylation is an important epigenetic factor in the regulation of gene expression, alteration of the methylation pattern has been associated with aging, cancer, atherosclerosis and other diseases. Three observations indicate that DNA methylation could be diminished by a vegetarian lifestyle. The vegetarian diet has a low content of methionine, remethylation of homocysteine is reduced by vitamin B12 deficiency and elevated homocysteine levels can induce the generation of S-adenosylhomocysteine (SAH), a potent inhibitor of methyltransferases. In our study we observed a significant correlation between SAH and whole-genome methylation (r=-0.36, p

During World War II, 36 conscientious objectors participated in a study of human starvation conducted by Ancel Keys and his colleagues at the University of Minnesota. The Minnesota Starvation Experiment, as it was later known, was a grueling study meant to gain insight into the physical and psychologic effects of semistarvation and the problem of refeeding civilians who had been starved during the war. During the experiment, the participants were subjected to semistarvation in which most lost \textgreater25% of their weight, and many experienced anemia, fatigue, apathy, extreme weakness, irritability, neurological deficits, and lower extremity edema. In 2003-2004, 18 of the original 36 participants were still alive and were interviewed. Many came from the Historic Peace Churches (Mennonite, Brethren, and Quaker), and all expressed strong convictions about nonviolence and wanting to make a meaningful contribution during the war. Despite ethical issues about subjecting healthy humans to starvation, the men interviewed were unanimous in saying that they would do it all over again, even after knowing the suffering that they had experienced. After the experiment ended, many of the participants went on to rebuilding war-torn Europe, working in the ministries, diplomatic careers, and other activities related to nonviolence.

A growing body of scientific evidence indicates that wholesome vegetarian diets offer distinct advantages compared to diets containing meat and other foods of animal origin. The benefits arise from lower intakes of saturated fat, cholesterol and animal protein as well as higher intakes of complex carbohydrates, dietary fiber, magnesium, folic acid, vitamin C and E, carotenoids and other phytochemicals. Since vegetarians consume widely divergent diets, a differentiation between various types of vegetarian diets is necessary. Indeed, many contradictions and misunderstandings concerning vegetarianism are due to scientific data from studies without this differentiation. In the past, vegetarian diets have been described as being deficient in several nutrients including protein, iron, zinc, calcium, vitamin B12 and A, n-3 fatty acids and iodine. Numerous studies have demonstrated that the observed deficiencies are usually due to poor meal planning. Well-balanced vegetarian diets are appropriate for all stages of the life cycle, including children, adolescents, pregnant and lactating women, the elderly and competitive athletes. In most cases, vegetarian diets are beneficial in the prevention and treatment of certain diseases, such as cardiovascular disease, hypertension, diabetes, cancer, osteoporosis, renal disease and dementia, as well as diverticular disease, gallstones and rheumatoid arthritis. The reasons for choosing a vegetarian diet often go beyond health and well-being and include among others economical, ecological and social concerns. The influences of these aspects of vegetarian diets are the subject of the new field of nutritional ecology that is concerned with sustainable life styles and human development.

In this review the several data concerning phytotoxins as natural harmful substances of plants and phycotoxins--toxicants of algae were described. For example plants are source of pyrrolizidine alkaloids, glycoalkaloids, glucosinolates as well as glycosides, saponine and psolarens. Possible adverse effects of phytoestrogens as endocrine disruptors versus beneficial influence these substances on human organism were mentioned. About lectins as possible factors of some diseases was reported, as well as some proteins as allergens of soy and peanuts was mentioned. Accumulated by shellfish and fish the most important phycotoxins such as saxitoxin, okadaic acid, brevetoxins and ciguatoxins were described. Phycotoxins produced several poisoning symptoms. Microcystins and nodularin--cyanobacterial phycotoxins of freshwater, was mentioned. In conclusion, the need of limitation of permissible levels of some plant toxicants, development of analytical methods as well as knowledge of influence of some technological processes on toxic plant substances was highlighted. The importance of balanced diet as a tool of defense against plant toxicants was concluded.

In this review the several data concerning phytotoxins as natural harmful substances of plants and phycotoxins--toxicants of algae were described. For example plants are source of pyrrolizidine alkaloids, glycoalkaloids, glucosinolates as well as glycosides, saponine and psolarens. Possible adverse effects of phytoestrogens as endocrine disruptors versus beneficial influence these substances on human organism were mentioned. About lectins as possible factors of some diseases was reported, as well as some proteins as allergens of soy and peanuts was mentioned. Accumulated by shellfish and fish the most important phycotoxins such as saxitoxin, okadaic acid, brevetoxins and ciguatoxins were described. Phycotoxins produced several poisoning symptoms. Microcystins and nodularin--cyanobacterial phycotoxins of freshwater, was mentioned. In conclusion, the need of limitation of permissible levels of some plant toxicants, development of analytical methods as well as knowledge of influence of some technological processes on toxic plant substances was highlighted. The importance of balanced diet as a tool of defense against plant toxicants was concluded.

Structural and functional peculiarities of digestive tract's wall depending from the character of nutrition (vegetarian or mixed diets) are interpreted in morphology. Proper facts and results of investigations of other authors about morphological structure of tunica mucosa colonic according of type of nutrition are discussed.

Work make on 84 patients with coronare heart diseases were divided into two groups, equal quantity. The first groups were given athenolol (50 mg daily), the second--hypotiazide (25 mg daily). In every groupspart patients received an antiatherogenic lactoovovegetetarian diet, part--an standard antiatherogenic diet 10c. Time observation--24 daily. By the end of the treatment period with athenolol in backoground the vegetarian diet the level of total cholesterol decreased by 16%, low-density lipoproteins cholesterol decreased by 18%. In groups patients received an standard antiatherogenic diet these parameters practically did'nt change. In the vegetarian group the atherogenic coefficient (KA) decreased by 31%., while in the patients on standard antiatherogenic diet KA showed only a tendency for decreasing. By the end to the treatment period with hypotiazide the slight decrease in total cholesterol, KA levels and a slight increase in HDL cholesterol were observed only the vegetarian group.

This is the year of the chimpanzee genome. Chimpanzee chromosome 22 has been sequenced and soon will be followed by the whole genome, and thousands of chimpanzee cDNA sequences are available for comparative analysis. Not only does this genomic information allow us to identify human-specific changes in particular genes that are potentially under selection, but also to understand molecular evolutionary dynamics characterizing the two most closely related mammalian genomes sequenced so far. Studies comparing gene expression in chimpanzees and other closely related primates reveal significant species differences in brain, liver and fibroblasts. New empirical data, in combination with models of speciation, are giving insight into how humans and chimpanzees speciated.

OBJECTIVE: To investigate the association of red meat and other specific dietary components in predicting the development of inflammatory polyarthritis. METHODS: This nested case-control study was conducted within a prospective population-based study of cancer incidence (European Prospective Investigation of Cancer in Norfolk [EPIC-Norfolk]). EPIC-Norfolk recruited 25,630 subjects ages 45-75 years between 1993 and 1997. Dietary intake was assessed at baseline using a 7-day food diary, and the information was analyzed using dietary analysis software. Patients with new cases of inflammatory polyarthritis were identified by linkage with the Norfolk Arthritis Register, a primary care-based inception study of inflammatory polyarthritis, and were matched for age and sex to 2 controls from EPIC-Norfolk. The risk for development of inflammatory polyarthritis was compared between subjects in the highest and lowest tertiles of dietary intake using conditional logistic regression and was expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Between 1993 and 2002, 88 new patients with inflammatory polyarthritis were identified and matched with 176 controls. Among patients, the level of red meat intake was higher (P = 0.04) and that of vitamin C was lower (P = 0.03) compared with intake among controls, but no difference in total energy intake was observed. Patients were more likely to be smokers. After adjusting for total energy intake, smoking, and other possible dietary confounders, subjects with the highest level of consumption of red meat (OR 1.9, 95% CI 0.9-4.0), meat and meat products combined (OR 2.3, 95% CI 1.1-4.9), and total protein (OR 2.9, 95% CI 1.1-7.5) were at an increased risk for inflammatory polyarthritis. CONCLUSION: A high level of red meat consumption may represent a novel risk factor for inflammatory arthritis or may act as a marker for a group of persons with an increased risk from other lifestyle causes.

Whether regular exercise is beneficial or should be avoided is a question currently unsettled in patients with heteroplasmic mitochondrial DNA (mtDNA) disorders of skeletal muscle. Deleterious effects of habitual physical inactivity superimposed upon impaired mitochondrial oxidative phosphorylation may contribute to varying degrees of exercise intolerance in these patients. Endurance exercise training is widely known to improve exercise capacity in healthy subjects and various chronic-disease patient populations. Although we have shown that beneficial physiological and biochemical responses to training increase exercise tolerance in patients with mtDNA defects, knowledge of the muscle adaptive response to endurance training within the setting of mitochondrial heteroplasmy remains limited. In order to determine advisability of endurance training as therapy, it remains to be established whether potential endurance training-induced increases in mutant mtDNA levels may be offset by increases in absolute wild-type mtDNA levels, and whether chronic inactivity leads to a selective down-regulation of wild-type mtDNA. Resistance training utilizes a different adaptive exercise approach to induce the transfer of normal mitochondrial templates from satellite cells to mature muscle fibers of patients with sporadic mtDNA disorders. The efficacy and safety of this approach needs to be further established. Our current inability to clearly advise patients to "use it or lose it" underscores the immediate urgency of studying the effects of exercise on skeletal muscle of patients with heteroplasmic mtDNA defects. © 2004 Elsevier B.V. All rights reserved.

A well-planned vegetarian diet has been stated to be adequate during pregnancy. The aim of the present study was to compare serum vitamin B-12 and homocysteine concentrations in pregnant women (n = 109) consuming vegetarian and Western diets and to evaluate the adequacy of current dietary reference intakes of vitamin B-12 for these women. Pregnant women adhering to vegetarian diets for at least 3 y, with subgroups of ovo-lacto vegetarians (OLVs; n = 27), low-meat eaters (LME, n = 43), and women eating an average Western diet (control group, n = 39), were recruited. Dietary vitamin B-12 intake, serum vitamin B-12, and plasma total homocysteine (tHcy) concentrations were measured in wk 9-12, 20-22, and 36-38 of pregnancy. During pregnancy serum vitamin B-12 concentrations of ovo-lacto vegetarians (P < 0.001) and low-meat eaters (P = 0.050) were lower than those of the control group. We observed the combination of low serum vitamin B-12 concentrations and elevated plasma tHcy in 22% of ovo-lacto vegetarians, in 10% of low-meat eaters, and in 3% of controls (P = 0.003). In OLVs, serum vitamin B-12 predicted 60% of the plasma tHcy variation (P < 0.001), but in LMEs and controls only

The spinal cord, brain, optic nerves and peripheral nerves may be affected by vitamin B12 (cobalamin) deficiency. Deficiency of vitamin B12 also causes megaloblastic anaemia, meaning that the red blood cells are usually larger than normal. In this paper we report a 16-year old girl who was referred to us for the evaluation of mild paraparesis and paresthesias marked by tingling "pins and needles" feelings and general weakness. The patient, her parents and sisters were on a strict vegan diet, which made us believe that vitamin B12 deficiency may be the possible cause of the neurologic clinical manifestations. The serum level of vitamin B12 was low, but there was no macrocytosis in the routine blood examination. The electrophoresis of haemoglobin was pathologic, there was 3.7% of HbA2 and 11.6% of HbF (heterozygous form of beta-thalassaemia). When megaloblastic anaemia occurs in combination with a condition that gives rise to microcytic anaemia, many megaloblastic features may be masked. Instead of being macrocytic, the anaemia could be normocytic or even microcytic. Vitamin B12 deficiency is a diagnosis that must not be overlooked. This case report turns the light on the fact that increased MCV is a hallmark in vitamin B12 deficiency, but it is not an obligatory sign.

Muscular forces generated during locomotion depend on an animal's speed, gait, and size and underlie the energy demand to power locomotion. Changes in limb posture affect muscle forces by altering the mechanical advantage of the ground reaction force (R) and therefore the effective mechanical advantage (EMA = r/R, where r is the muscle mechanical advantage) for muscle force production. We used inverse dynamics based on force plate and kinematic recordings of humans as they walked and ran at steady speeds to examine how changes in muscle EMA affect muscle force-generating requirements at these gaits. We found a 68% decrease in knee extensor EMA when humans changed gait from a walk to a run compared with an 18% increase in hip extensor EMA and a 23% increase in ankle extensor EMA. Whereas the knee joint was extended (154-176 degrees) during much of the support phase of walking, its flexed position (134-164 degrees) during running resulted in a 5.2-fold increase in quadriceps impulse (time-integrated force during stance) needed to support body weight on the ground. This increase was associated with a 4.9-fold increase in the ground reaction force moment about the knee. In contrast, extensor impulse decreased 37% (P

Objective: To compare the relationships between food (nutrient) intakes and biochemical markers of nutritional status of asymptomatic HIV-infected with HIV-uninfected subjects, to gain more information on the appropriate diet for HIV-infected persons at an early stage of infection.Design: Cross-sectional population-based survey.Setting: North West Province, South Africa.Subjects: Two hundred and sixteen asymptomatic HIV-infected and 1550 HIV-uninfected men and women volunteers aged 15 years and older, recruited as 'apparently healthy' subjects from 37 randomly selected sites.Outcome Measures: Food and nutrient intakes, measured with a validated food-frequency questionnaire, and nutritional status indicated by anthropometric and biochemical variables, measured by a standardised methodology.Results: The prevalence of HIV infection in the study population was 11.9%. The anthropometric indices and nutrient intakes of HIV-infected and uninfected subjects did not differ significantly, indicating that these 216 HIV-infected subjects were at an early stage of infection. Of the biochemical nutritional status variables, high-density lipoprotein cholesterol and total cholesterol, haemoglobin, albumin and triglycerides were significantly lower in infected subjects. They also had higher globulin and liver enzyme levels than uninfected subjects. In infected subjects, serum albumin correlated significantly with serum lipids, serum vitamin A, serum vitamin E, serum iron, total iron-binding capacity and haemoglobin. The significant positive correlations of the liver enzymes with serum lipids, albumin, vitamin A and iron, observed in HIV-uninfected subjects, disappeared in the infected subjects. Polyunsaturated fat intake showed significant positive correlations with the increased liver enzymes in infected subjects. A principal components analysis indicated that, in infected subjects, increased liver enzymes correlated with higher consumption of maize meal and lower consumption of meat and vegetables.Conclusions and Recommendations: This survey indicated that asymptomatic HIV-infected subjects who followed a diet rich in animal foods had smaller decreases in serum albumin, haemoglobin and lipid variables, and smaller increases in liver enzymes, than those who consumed a diet based on staple foods. This suggests that animal foods are associated with improved nutritional status in HIV-infected persons. These results should be confirmed with intervention studies before dietary recommendations for asymptomatic HIV-infected individuals can be made.

Attention-deficit hyperactivity (ADHD) is a common disorder in school-aged children and is associated with significant impairment in social and academic functioning. Its recognition is based on congruent information from different sources, because most ADHD children and adolescents are not completely aware of impairments caused by inattention and/or hyperactivity/impulsivity. Fluctuations in symptom expression may complicate the diagnosis: during clinical examination or tests sessions, ADHD symptoms may be less severe than usual or completely absent. This review examines variations in ADHD symptoms due to environmental context, internal state, circadian factors, development, psychiatric comorbidity and discusses their clinical relevance. Generally, ADHD symptoms are pervasive and identified in different areas of functioning. Despite their chronicity, they show a relative context-dependency. An unfamiliar environment or situation may lessen symptoms. The same happens in dual relations or in calm settings, when the child receives attention and positive reinforcement from the adult. On the contrary, the classroom situation with its high stimulation level (noise, visual distractors, large class size) is likely to reveal or accentuate instability, impulsivity and inattention. Independently from objective symptom fluctuations, the impact of ADHD symptoms, and their consequences on self-esteem may also vary with the degree of environmental mismatch. Recent research in experimental psychology also draws attention to the motivational state of ADHD children: preference for immediate gratification and delay aversion may explain why most of them show satisfactory attentional capacities in certain activities (for instance video games or TV), while showing impairment in school work or in other effortful tasks. The diagnosis of the full ADHD syndrome requires significant impact on functioning in at least two areas. Some children with "situational" ADHD are impaired either in school setting or exclusively at home. Manuzza et al. report long-term outcome of "situational" versus "pervasive" ADHD. School-ADHD, in opposition to home-ADHD shows similarities with the full blown syndrome, as regards proportion of anti-social personality disorder, psycho-social functioning and academic/professional achievements. Moderate seasonal variations have also been identified with less ADHD symptoms in August. This result is likely to reflect a better fit between individual characteristics and environmental demands during school holidays rather than neurobiological changes, as there are no convincing arguments for seasonal fluctuations of serotoninergic tone in ADHD. Another cause for variations in ADHD symptom expression may be the co-occurrence of a mood disorder. Relationships between early-onset mania and ADHD are discussed. The appropriate definition of prepubertal mania is still in debate; its recognition is hindered by symptom overlap and high level of comorbid conditions. Chronic emotional dysregulation with irritability and frequent temper tantrums, sometimes viewed as characteristics of early-onset mania, might reflect a--possibly severe--sub-type of ADHD rather than a prodrome of bipolarity. A marked cyclicity of symptoms, with periodic accentuation of ADHD and mood symptoms, requires careful monitoring and systematic analysis of comorbid conditions. Clarification of the complex interrelations between ADHD and bipolar disorder will be obtained from long-term studies.

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Striding bipedalism is a key derived behaviour of hominids that possibly originated soon after the divergence of the chimpanzee and human lineages. Although bipedal gaits include walking and running, running is generally considered to have played no major role in human evolution because humans, like apes, are poor sprinters compared to most quadrupeds. Here we assess how well humans perform at sustained long-distance running, and review the physiological and anatomical bases of endurance running capabilities in humans and other mammals. Judged by several criteria, humans perform remarkably well at endurance running, thanks to a diverse array of features, many of which leave traces in the skeleton. The fossil evidence of these features suggests that endurance running is a derived capability of the genus Homo, originating about 2 million years ago, and may have been instrumental in the evolution of the human body form.

Purpose of reviewThe purpose of this chapter is to summarize and place into perspective the past year's literature regarding the regulation of gastric exocrine and endocrine secretion.Recent findingsTo prevent acid and pepsin from overwhelming mucosal defense mechanisms and causing injury, the secre

OBJECTIVE: The aim of treatment for attention-deficit/hyperactivity disorder (ADHD) is to decrease symptoms, enhance functionality, and improve well-being for the child and his or her close contacts. However, the measurement of treatment response is often limited to measuring symptoms using behavior rating scales and checklists completed by teachers and parents. Because so much of the focus has been on symptom reduction, less is known about other possible health problems, which can be measured easily using health-related quality-of-life (HRQL) questionnaires, which are designed to gather information across a range of health domains. The aim of our study was to measure HRQL in a clinic-based sample of children who had a diagnosis of ADHD and consider the impact of 2 clinical factors, symptom severity and comorbidity, on HRQL. Our specific hypotheses were that parent-reported HRQL would be poorer in children with ADHD than in normative US and Australian pediatric samples, in children with increasing severity of ADHD symptoms, and in children who had diagnoses of comorbid psychiatric disorders. METHODS: Cross-sectional survey was conducted in British Columbia, Canada. The sample included 165 respondents of 259 eligible children (63.7% response rate) who were referred to the ADHD Clinic in British Columbia between November 2001 and October 2002. Children who are seen in this clinic come from all parts of the province and are diverse in terms of socioeconomic status and case mix. ADHD was diagnosed in 131 children, 68.7% of whom had a comorbid psychiatric disorder. Some children had >1 comorbidity: 23 had 2, 5 had 3, and 1 had 4. Fifty-one children had a comorbid learning disorder (LD), 45 had oppositional defiant disorder or conduct disorder (ODD/CD), and 27 had some other comorbid diagnosis. The mean age of children was 10 years (standard deviation: 2.8). Boys composed 80.9% (N = 106) of the sample. We used the 50-item parent version of the Child Health Questionnaire to measure physical and psychosocial health. Physical domains include the following: physical functioning (PF), role/social limitations as a result of physical health (RP), bodily pain/discomfort (BP), and general health perception (GH). Psychosocial domains include the following: role/social limitations as a result of emotional-behavioral problems (REB), self-esteem (SE), mental health (MH), general behavior (BE), emotional impact on parent (PTE), and time impact on parents (PTT). A separate domain measures limitations in family activities (FA). There is also a single-item measure of family cohesion (FC). Individual scale scores and summary scores for physical (PhS) and psychosocial health (PsS) can be computed. Symptom severity data (parent and teacher) came from the Child/Adolescent Symptom Inventory 4. These checklists provide information on symptoms for the 3 ADHD subtypes (inattentive, hyperactive, and combined). Each child underwent a comprehensive psychiatric assessment by 1 of 4 child psychiatrists. Documentation included a full 5-axis Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis on the basis of a comprehensive assessment. Clinical information for each child was extracted from hospital notes. RESULTS: Compared with both population samples, children with ADHD had comparable physical health but clinically important deficits in HRQL in all psychosocial domains, FA, FC, and PsS, with effect sizes as follows: FC = -0.66, SE = -0.90, MH = -0.97, PTT = -1.07, REB = -1.60, BE = -1.73, PTE = -1.87, FA = -1.95, and PsS = -1.98. Poorer HRQL for all domains of psychosocial health, FA, and PsS correlated significantly with more parent-reported inattentive, hyperactive, and combined symptoms of ADHD. Children with > or =2 comorbid disorders differed significantly from those with no comorbidity in most areas, including RP, GH, REB, BE, MH, SE, PTT, FA, and PsS, and from those with 1 comorbid disorder in 3 domains, including BE, MH, and FA and the PsS. The mean PsS score for children in the ODD/CD group (mean difference: -12.9; effect size = -1.11) and children in the other comorbidity group (-9.0; effect size = -.77) but not children in the LD group were significantly lower than children with no comorbid disorder. Predictors of physical health in a multiple regression model included child's gender (beta = .177) and number of comorbid conditions (beta = -.197). These 2 variables explained very little variation in the PhS. Predictors of psychosocial health included the number of comorbid conditions (beta = -.374) and parent-rated combined ADHD symptoms (beta = -.362). These 2 variables explained 31% of the variation in the PsS. CONCLUSIONS: Our study shows that ADHD has a significant impact on multiple domains of HRQL in children and adolescents. In support of our hypotheses, compared with normative data, children with ADHD had more parent-reported problems in terms of emotional-behavioral role function, behavior, mental health, and self-esteem. In addition, the problems of children with ADHD had a significant impact on the parents' emotional health and parents' time to meet their own needs, and they interfered with family activities and family cohesion. The differences that we found represent clinically important differences in HRQL. Our study adds new information about the HRQL of children with ADHD in relation to symptom severity and comorbidity. Children with more symptoms of ADHD had worse psychosocial HRQL. Children with multiple comorbid disorders had poorer psychosocial HRQL across a range of domains compared with children with none and 1 comorbid disorder. In addition, compared with children with no comorbidity, psychosocial HRQL was significantly lower in children with ODD/CD and children in the other comorbidity group but not in children with an LD. The demonstration of a differential impact of ADHD on health and well-being in relation to symptom severity and comorbidity has important implications for policies around eligibility for special educational and other supportive services. Because the impact of ADHD is not uniform, decisions about needed supports should incorporate a broader range of relevant indicators of outcome, including HRQL. Although many studies focus on measuring symptoms using rating scales and checklists, in our study, using a multidimensional questionnaire, we were able to show that many areas of health are affected in children with ADHD. We therefore argue that research studies of children with ADHD should include measurement of these broader domains of family impact and child health.

OBJECTIVE: We compared plasma biomarkers of antioxidant status, oxidative stress, inflammation, and risk for coronary heart disease in long-term vegetarians and age- and sex-matched omnivores. METHODS: Thirty vegetarians (mean age +/- standard deviation: 44.2 +/- 9.0 y) were recruited. The subjects had been vegetarian for 5 to 55 y (21.8 +/- 12.2 y). The control group comprised 30 adults selected by age-stratified sampling from a community health project (mean age: 44.0 +/- 9.2 y). Fasting plasma total antioxidant status (ferric-reducing antioxidant power), ascorbic acid (AA), alpha-tocopherol (total and lipid standardized), malondialdehyde, total cholesterol, triacylglycerol, uric acid (UA), and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: Plasma AA was significantly higher in the vegetarians than in the omnivores (90.5 +/- 21.0 and 61.8 +/- 17.0 microM; P < 0.001). The vegetarians had lower concentrations of triacylglycerol, UA, and hsCRP. Plasma total and lipid-standardized alpha-tocopherol concentrations were also lower in the vegetarians: 22.0 +/- 5.9 and 27.0 +/- 7.9 microM versus 3.76 +/- 0.57 and 4.23 +/- 0.58 microM per millimoles per liter of total cholesterol plus triacylglycerol, respectively. There was a significant inverse correlation between AA and UA (r = -0.343, P < 0.01; n = 60) and between AA and hsCRP (r = -0.306, P