Published Science

It is the position of the American Dietetic Association and Dietitians of Canada that appropriately planned vegetarian diets are healthful, nutritionally adequate, and provide health benefits in the prevention and treatment of certain diseases. Approximately 2.5% of adults in the United States and 4% of adults in Canada follow vegetarian diets. A vegetarian diet is defined as one that does not include meat, fish, or fowl. Interest in vegetarianism appears to be increasing, with many restaurants and college foodservices offering vegetarian meals routinely. Substantial growth in sales of foods attractive to vegetarians has occurred and these foods appear in many supermarkets. This position paper reviews the current scientific data related to key nutrients for vegetarians including protein, iron, zinc, calcium, vitamin D, riboflavin, vitamin B-12, vitamin A, n-3 fatty acids, and iodine. A vegetarian, including vegan, diet can meet current recommendations for all of these nutrients. In some cases, use of fortified foods or supplements can be helpful in meeting recommendations for individual nutrients. Well-planned vegan and other types of vegetarian diets are appropriate for all stages of the life-cycle including during pregnancy, lactation, infancy, childhood, and adolescence. Vegetarian diets offer a number of nutritional benefits including lower levels of saturated fat, cholesterol, and animal protein as well as higher levels of carbohydrates, fibre, magnesium, potassium, folate, antioxidants such as vitamins C and E, and phytochemicals. Vegetarians have been reported to have lower body mass indices than non-vegetarians, as well as lower rates of death from ischemic heart disease, lower blood cholesterol levels, lower blood pressure, and lower rates of hypertension, type 2 diabetes, and prostate and colon cancer. While a number of federally funded and institutional feeding programs can accommodate vegetarians, few have foods suitable for vegans at this time. Because of the variability of dietary practices among vegetarians, individual assessment of dietary intakes of vegetarians is required. Dietetics professionals have a responsibility to support and encourage those who express an interest in consuming a vegetarian diet. They can play key roles in educating vegetarian clients about food sources of specific nutrients, food purchase and preparation, and any dietary modifications that may be necessary to meet individual needs. Menu planning for vegetarians can be simplified by use of a food guide that specifies food groups and serving sizes.

The shift to "living interpretation" in the second half of the 20th century redirected the trajectory of museum work. Living bodies were said to give a more real experience of the past than could historic objects. But what about those pigs, cows, chickens, and sheep found at every major living history museum? Nowadays museums seek rare breeds or they breed contemporary animals to bring them closer to descriptions found in historic documents. What are the ethical and political implications of "backbreeding"? Will museums determine that some backbreeding is legitimate, while others are the stuff of mad-scientist films?

Thousands of chemical structures have been identified in plant foods. Many are found in spices. Typically, spices are the dried aromatic parts of plants-generally the seeds, berries, roots, pods, and sometimes leaves-that mainly, but not invariably, grow in hot countries. Given the wide range of botanical species and plant parts from which spices are derived, they can contribute significant variety and complexity to the human diet. In the past, the medicinal uses of spices and herbs were often indistinguishable from their culinary uses, and for good reason: people have recognized for centuries both the inherent value, as well as the potential toxicity, of phytochemicals in relation to human health. Plants have the capacity to synthesize a diverse array of chemicals, and understanding how phytochemicals function in plants may further our understanding of the mechanisms by which they benefit humans. In plants, these compounds function to attract beneficial and repel harmful organisms, serve as photoprotectants, and respond to environmental changes. In humans, they can have complementary and overlapping actions, including antioxidant effects, modulation of detoxification enzymes, stimulation of the immune system, reduction of inflammation, modulation of steroid metabolism, and antibacterial and antiviral effects. Embracing a cuisine rich in spice, as well as in fruit and vegetables, may further enhance the chemopreventive capacity of one's diet.

Advances in nutrition research during the past few decades have changed scientists' understanding of the contribution of vegetarian diets to human health and disease. Diets largely based on plant foods, such as well-balanced vegetarian diets, could best prevent nutrient deficiencies as well as diet-related chronic diseases. However, restrictive or unbalanced vegetarian diets may lead to nutritional deficiencies, particularly in situations of high metabolic demand. If some vegetarian diets are healthier than diets largely based on animal products, this constitutes an important departure from previous views on dietary recommendations to prevent disease conditions. Based on different paradigms, 3 models are presented depicting the population health risks and benefits of vegetarian and meat-based diets. This series of models encapsulates the evolution of scientific understanding on the overall effects of these dietary patterns on human health. Recent scientific advances seem to have resulted in a paradigm shift: diets largely based on plant foods, such as well-balanced vegetarian diets, are viewed more as improving health than as causing disease, in contrast with meat-based diets.

Advances in nutrition research during the past few decades have changed scientists' understanding of the contribution of vegetarian diets to human health and disease. Diets largely based on plant foods, such as well-balanced vegetarian diets, could best prevent nutrient deficiencies as well as diet-related chronic diseases. However, restrictive or unbalanced vegetarian diets may lead to nutritional deficiencies, particularly in situations of high metabolic demand. If some vegetarian diets are healthier than diets largely based on animal products, this constitutes an important departure from previous views on dietary recommendations to prevent disease conditions. Based on different paradigms, 3 models are presented depicting the population health risks and benefits of vegetarian and meat-based diets. This series of models encapsulates the evolution of scientific understanding on the overall effects of these dietary patterns on human health. Recent scientific advances seem to have resulted in a paradigm shift: diets largely based on plant foods, such as well-balanced vegetarian diets, are viewed more as improving health than as causing disease, in contrast with meat-based diets.

Our knowledge is far from complete regarding the relationship between vegetarian diets and human health. However, scientific advances in the last decades have considerably changed the role that vegetarian diets may play in human nutrition. Components of a healthy vegetarian diet include a variety of vegetables, fruits, whole grain cereals, legumes and nuts. Numerous studies show important and quantifiable benefits of the different components of vegetarian diets, namely the reduction of risk for many chronic diseases and the increase in longevity. Such evidence is derived from the study of vegetarians as well as other populations. While meat intake has been related to increased risk for a variety of chronic diseases, an abundant consumption of vegetables, fruits, cereals, nuts, and legumes all have been independently related with a lower risk for several chronic degenerative diseases, such as ischemic heart disease, diabetes, obesity, and many cancers. Hence, whole foods of plant origin seem to be beneficial on their own merit for chronic disease prevention. This is possibly more certain than the detrimental effects of meats. Vegetarian diets, as any other diet pattern, have potential health risks, namely marginal intake of essential nutrients. However, from the public health viewpoint the health benefits of a well-planned vegetarian diet far outweigh the potential risks.

Wild primates take most of the daily diet from plant sources, eating moderate to small amounts of animal source foods (ASF). Plant materials make up from 87% to >99% of the annual diet of great apes, the closest living relatives of modern humans (Homo sapiens sapiens). Reflecting their close genetic relationship, gut form and nutrient requirements of apes and humans (Hominoidea) are very similar, as is their pattern of digestive kinetics-one predicated on a relatively slow turnover of ingesta. In plant-eating mammals, in contrast to carnivorous mammals, greater body size is associated with lower dietary quality. Turning to ASF as a routine rather than occasional dietary component would have permitted the evolving human lineage to evade the nutritional constraints placed on body size increases in apes. Without routine access to ASF, it is highly unlikely that evolving humans could have achieved their unusually large and complex brain while simultaneously continuing their evolutionary trajectory as large, active and highly social primates. As human evolution progressed, young children in particular, with their rapidly expanding large brain and high metabolic and nutritional demands relative to adults would have benefited from volumetrically concentrated, high quality foods such as meat. Today, many humans, particularly those in high income nations, have a variety of high quality, non-ASF dietary alternatives, but such foods were not generally available to paleolithic human ancestors nor to many people today in low income nations.

Wild primates take most of the daily diet from plant sources, eating moderate to small amounts of animal source foods (ASF). Plant materials make up from 87% to >99% of the annual diet of great apes, the closest living relatives of modern humans (Homo sapiens sapiens). Reflecting their close genetic relationship, gut form and nutrient requirements of apes and humans (Hominoidea) are very similar, as is their pattern of digestive kinetics-one predicated on a relatively slow turnover of ingesta. In plant-eating mammals, in contrast to carnivorous mammals, greater body size is associated with lower dietary quality. Turning to ASF as a routine rather than occasional dietary component would have permitted the evolving human lineage to evade the nutritional constraints placed on body size increases in apes. Without routine access to ASF, it is highly unlikely that evolving humans could have achieved their unusually large and complex brain while simultaneously continuing their evolutionary trajectory as large, active and highly social primates. As human evolution progressed, young children in particular, with their rapidly expanding large brain and high metabolic and nutritional demands relative to adults would have benefited from volumetrically concentrated, high quality foods such as meat. Today, many humans, particularly those in high income nations, have a variety of high quality, non-ASF dietary alternatives, but such foods were not generally available to paleolithic human ancestors nor to many people today in low income nations.

Objectives: To inform the debate over whether human sleep can be chronicall y reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiologi cal functions were monitored and compared to those for total sleep deprivat ion. Design: The chronic sleep restriction experiment involved randomizatio n to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), whi ch were maintained for 14 consecutive days. The total sleep deprivation exp eriment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. Setting: Bo th experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. Participants: A total of n = 48 healthy adults (ages 21-38) participated in the experime nts. Interventions: Nocturnal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibit ed. Results: Chronic restriction of sleep periods to 4 h or 6 h per night o ver 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratin gs showed an acute response to sleep restriction but only small further inc reases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-R EM sleep EEG-a putative marker of sleep homeostasis-displayed an acute resp onse to sleep restriction with negligible further changes across the 14 res tricted nights. Comparison of chronic sleep restriction to total sleep depr ivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of slee p deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). Conclusions: Since chronic restriction of sleep to 6 h or less per night p roduced cognitive performance deficits equivalent to up to 2 nights of tota l sleep deprivation, it appears that even relatively moderate sleep restric tion can seriously impair waking neurobehavioral functions in healthy adult s. Sleepiness ratings suggest that subjects were largely unaware of these i ncreasing cognitive deficits, which may explain why the impact of chronic s leep restriction on waking cognitive functions is often assumed to be benig n. Physiological sleep responses to chronic restriction did not mirror waki ng neurobehavioral responses, but cumulative wakefulness in excess of a 15. 84 h predicted performance lapses across all four experimental conditions, This suggests that sleep debt is perhaps best understood as resulting in ad ditional wakefulness that has a neurobiological cost which accumulates over time.

OBJECTIVES: Although the evidence is strong that fasting has anti-tumor, anti-inflammatory and anti-ageing actions, the mechanisms responsible for these phenomena are still unclear. An ameliorated antioxidative defence with fasting may be the cause of such effects. The objective of the present work was to determine the influence of fasting on antioxidant systems in healthy young vegetarian humans. DESIGN AND METHODS: We measured Trolox Equivalents Antioxidant Capacity (TEAC) of plasma, erythrocytes superoxide dismutase (SOD) activity, blood glutathione peroxidase (GPx) activity, level of total blood non-proteic thiols (TBNT), plasma ceruloplasmin activity, plasma level of NO metabolites (the sum of nitrites and nitrates, NOx), in 18 healthy young humans (age 20-27 years) after 12h (overnight fasting) and 80h of fasting. RESULTS: Trolox Equivalents Antioxidant Capacity of plasma, the level of total blood nonproteic thiols, plasma ceruloplasmin activity and plasma concentration of nitrites and nitrates were significantly increased after 80h of fasting. Superoxide dismutase activity and glutathione peroxidase activity were lower after 80h of fasting. CONCLUSIONS: Our results suggest that fasting induces the "reorganisation" of antioxidative defence lines: fasting increases especially plasma protective systems (total antioxidant capacity of plasma, plasma ceruloplasmin activity) and decreases an erythrocytes antioxidant enyzme (superoxide dismutase) and blood glutathione peroxidase.

The aim of this paper is to examine the factors associated with the belief that vegetarian diets provide health benefits. A random population mail survey about food choice was conducted among a sample of 1000 South Australians. An additional (non-random) survey of 106 vegetarians and semi-vegetarians was also conducted, giving a total of 707 participants from both samples. The main predictors of the belief that vegetarian diets provide health benefits for all respondents were found to be the belief that meat is neither healthy nor necessary and frequent searching for information on healthy eating. However, there were differences between vegetarians, non-vegetarians and semi-vegetarians. In particular, health issues were relatively more important for semi-vegetarians and vegetarians, while knowledge and convenience issues were most important for non-vegetarians. The results have important implications for public health. Many South Australians perceive that health benefits are associated with eating a vegetarian diet, which may also apply to plant-based diets in general. However, if non-vegetarians are to obtain some of the health benefits associated with the consumption of a plant-based diet, they require information on the preparation of quick and easy plant- based meals.

Background: There have been few long-term follow-up studies of older adults who follow different dietary patterns. Methods: We cluster-analyzed data on dietary fat, fiber, protein, carbohydrate, and calorie consumption from the U.S. Cardiovascular Health Study (mean age=73), and examined the relationship of the dietary clusters to outcomes 10 years later. Results: The five clusters were named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat), "Unhealthy diet" (relatively high in protein and fat, relatively low in carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was distinguished by higher alcohol consumption. The clusters were strongly associated with demographic factors, health behaviors, and baseline health status. The Healthy diet cluster had the most years of life and years of healthy life, and the Unhealthy diet cluster had the fewest. The Low 4 cluster had the best cardiovascular outcomes. Differences were not usually large. Conclusions: Older adults who followed the healthy eating pattern had somewhat longer and healthier lives, and the cluster with more alcohol consumption was associated with fewer cardiovascular events. The unhealthy eating pattern had the worst outcomes. © 2003 Elsevier Inc. All rights reserved.

Thiocyanate [SCN-] is a complex anion which is a potent inhibitor of iodide transport. It is the detoxification product of cyanide and can easily be measured in body fluids. Consumption of naturally occurring goitrogens, certain environmental toxins and cigarette smoke can significantly increase SCN- concentrations to levels potentially capable of affecting the thyroid gland. Goiter endemics were reported to develop when the critical urinary iodine/ SCN- ratio decreases below 3 microg iodine per mg SCN-. Iodine supplementation completely reverses the goitrogenic influence of SCN-. SCN- is also generated from cigarette smoking as a detoxifying product of cyanide. During the past two decades many reports dealt with the possible effects of cigarette smoking on thyroid hormone synthesis, thyroid gland size and thyroid autoimmunity including infiltrative ophtalmopathy of Graves' disease. In this mini-review, issues regarding thiocyanate overload and thyroid disease will be summarized.

Based on what is known of the components of plant-based diets and their effects from cohort studies, there is reason to believe that vegetarian diets would have advantages in the treatment of type 2 diabetes. At present there are few data on vegetarian diets in diabetes that do not in addition have weight loss or exercise components. Nevertheless, the use of whole-grain or traditionally processed cereals and legumes has been associated with improved glycemic control in both diabetic and insulin-resistant individuals. Long-term cohort studies have indicated that whole-grain consumption reduces the risk of both type 2 diabetes and cardiovascular disease. In addition, nuts (eg, almonds), viscous fibers (eg, fibers from oats and barley), soy proteins, and plant sterols, which may be part of the vegetarian diet, reduce serum lipids. In combination, these plant food components may have a very significant impact on cardiovascular disease, one of the major complications of diabetes. Furthermore, substituting soy or other vegetable proteins for animal protein may also decrease renal hyperfiltration, proteinuria, and renal acid load and in the long term reduce the risk of developing renal disease in type 2 diabetes. The vegetarian diet, therefore, contains a portfolio of natural products and food forms of benefit for both the carbohydrate and lipid abnormalities in diabetes. It is anticipated that their combined use in vegetarian diets will produce very significant metabolic advantages for the prevention and treatment of diabetes and its complications.

Abattoir workers are occupationally exposed to Toxoplasma gondii by the contact with raw meat. One hundred and seven abattoir workers from the Meat Factory in Lublin were examined for the presence of anti-Toxoplasma antibodies. Sixty-one blood donors were also tested as the reference group. Sera from workers and referents were tested by direct agglutination with 2-mercaptoethanol (DA-2ME), and also by ELFA IgG and ELFA IgM tests (Vidas Toxo IgM, Vidas Toxo IgG, bioMerieux, France). In the workers group, out of 107 tested sera, 70 were found positive (65.4%). The highest percentage of seropositive results was found in the Cured Meat Division--76.2%. In the Meat Production Division 66.6% of seropositive results were found, and in the Slaughter Division--46.1%. Three persons with the presence of IgM antibodies were found in the Cured Meat Division. In the reference group, 34 out of 61 sera (55.7%) were positive. The difference in seropositivity between Cured Meat Division workers and reference group was statistically significant (p

Cardiac rehabilitation programs (CRP) represent comprehensive interventions that are typically limited to four months. Following completion of CRP, it appears that risk factors and lifestyle behaviours may deteriorate. The Extensive Lifestyle Management Intervention (ELMI) Following Cardiac Rehabilitation trial will investigate the benefits of a randomized intervention to prevent these adverse changes. Patients with ischemic heart disease (IHD) were randomized following a standard CRP to the ELMI or to usual care. The ELMI program is a case-managed intervention aimed at individualizing risk factor and lifestyle management based on current treatment guidelines. The program consists of cardiac rehabilitation sessions, telephone follow-up and risk factor and lifestyle counselling sessions. Health professionals work with participants using behavioural counselling and communications with participants' family physicians. Usual care participants return to their family physicians' care, and come to the study clinic only to undergo annual outcomes assessment. The primary outcome is change in IHD global risk after four years. Secondary outcomes include combined cardiovascular events, health care utilization, lifestyle adherence, quality of life and risk factors. Over 28 months, 302 men and women were randomized. This represented 29% of the total population screened. The average age of study participants is 64 years, 18% are women, 53% have had a previous myocardial infarction, 73% have undergone previous revascularization and 20% have diabetes mellitus. Ischemic heart disease risk factors for the entire cohort improved significantly after subjects had gone through previous CRPs. Baseline risk factors, lifestyle behaviours and medications were similar between the groups. This study population is representative of patients completing a standard CRP. Results of the ELMI trial will provide valuable information for the future design of CRPs.

Knowledge of our ancestor's diets is becoming increasingly important in evolutionary medicine, as researchers have argued that we have evolved to specific type of ‘Palaeolithic’ diet, and many modern nutritional disorders relate to the mismatch between the diet to which we have evolved, and the relatively newer agricultural-based ‘Neolithic’ diets. However, what is the archaeological evidence for pre-agricultural diets and how have they changed over the four million years of hominid evolution? This paper briefly introduces the three lines of evidence we have for Palaeolithic and Neolithic diets; morphological changes, archaeological material evidence, and direct measurement of diet from bone chemistry. The morphological changes, increasing gracilization of the mandible and increasing brain size have been interpreted (based on analogies with living primates) as the move from plants to higher-quality, more digestible, animal meat, although this is debated. The archaeological evidence is especially weak, as many organic materials, especially plants, do not survive well, and are therefore invisible in the archaeological record. Artefacts, such as stone tools which are likely to be used for hunting and animal bones with evidence of human processing and butchering do indicate that hunting did occur at many times in the past, but it is impossible to judge the frequency. Direct evidence from bone chemistry, such as the measurement of the stable isotopes of carbon and nitrogen, do provide direct evidence of past diet, and limited studies on five Neanderthals from three sites, as well as a number of modern Palaeolithic and Mesolithic humans indicates the importance of animal protein in diets. There is a significant change in the archaeological record associated with the introduction of agriculture worldwide, and an associated general decline in health in some areas. However, there is an rapid increase in population associated with domestication of plants, so although in some regions individual health suffers after the Neolithic revolution, as a species humans have greatly expanded their population worldwide.

Although preoperative assessment of the length of the intestine may be of interest to avoid postoperative consequences of large intestinal resection, measurements of the intestine are quite rare and results variable in the literature. This anatomical study aimed to assess the length of the different intestinal segments, their variation and their correlation with sex, age, weight and height. Two hundred non-fixed adult cadavers (100 men, 100 women) who willingly gave their bodies for scientific purposes were studied. The post mortem average length of the whole intestine was 795.5+/-129 cm and was significantly longer in men and in young subjects. It was correlated with the subject's weight but not height. Multivariate analysis demonstrated that the factor showing the strongest correlation with intestinal length was body weight. This latter parameter may be useful in the preoperative assessment of intestinal length.

Three cases of diabetic ketoacidosis precipitated by thyrotoxicosis are presented. Two of them are young women with type 1 diabetes mellitus; the third case is a middle-aged woman with type 2 diabetes mellitus. All of them were diagnosed with Graves' disease. They typically showed tachycardia at rest in spite of correction of the metabolic disorder. Hyperthyroidism worsens glycemic control in diabetic patients and may precipitate diabetic ketoacidosis. On the other hand, women with diabetes have a higher prevalence of Graves' disease. Thus, in diabetic ketoacidosis without an obvious triggering factor, the presence of hyperthyroidism should be investigated, particularly in women.

OBJECTIVE: To evaluate measurement error structure in dietary assessment instruments and to investigate its implications for nutritional studies, using urinary nitrogen excretion as a reference biomarker for protein intake. DESIGN: The dietary assessment methods included different food-frequency questionnaires (FFQs) and such conventional dietary-report reference instruments as a series of 24-hour recalls, 4-day weighed food records or 7-day diaries. SETTING: Six original pilot validation studies within the European Prospective Investigation of Cancer (EPIC), and two validation studies conducted by the British Medical Research Council (MRC) within the Norfolk cohort that later joined as a collaborative component cohort of EPIC. SUBJECTS: A sample of approximately 100 to 200 women and men, aged 35-74 years, from each of eight validation studies. RESULTS: In assessing protein intake, all conventional dietary-report reference methods violated the critical requirements for a valid reference instrument for evaluating, and adjusting for, dietary measurement error in an FFQ. They displayed systematic bias that depended partly on true intake and partly was person-specific, correlated with person-specific bias in the FFQ. Using the dietary-report methods as reference instruments produced substantial overestimation (up to 230%) of the FFQ correlation with true usual intake and serious underestimation (up to 240%) of the degree of attenuation of FFQ-based log relative risks. CONCLUSION: The impact of measurement error in dietary assessment instruments on the design, analysis and interpretation of nutritional studies may be much greater than has been previously estimated, at least regarding protein intake.

OBJECTIVE: To illustrate biomarkers of diet that can be used to validate estimates of dietary intake in the study of gene-environment interactions in complex diseases. DESIGN: Prospective cohort studies, studies of biomarkers where diet is carefully controlled. SETTING: Free-living individuals, volunteers in metabolic suites. SUBJECTS: Male and female human volunteers. RESULTS: Recent studies using biomarkers have demonstrated substantial differences in the extent of measurement error from those derived by comparison with other methods of dietary assessment. The interaction between nutritional and genetic factors has so far largely gone uninvestigated, but can be studied in epidemiological trials that include collections of biological material. Large sample sizes are required to study interactions, and these are made larger in the presence of measurement errors. CONCLUSIONS: Diet is of key importance in affecting the risk of most chronic diseases in man. Nutritional epidemiology provides the only direct approach to the quantification of risks. The introduction of biomarkers to calibrate the measurement error in dietary reports, and as additional measures of exposure, is a significant development in the effort to improve estimates of the magnitude of the contribution of diet in affecting individual disease risk within populations. The extent of measurement error has important implications for correction for regression dilution and for sample size. The collection of biological samples to improve and validate estimates of exposure, enhance the pursuit of scientific hypotheses, and enable gene-nutrient interactions to be studied, should become the routine in nutritional epidemiology.

Thyroid hormones exert a range of developmental and physiological actions in all vertebrates. Serum concentrations of L-thyroxine (T4) and 3,5,3 -L-triiodothyronine (T3) are maintained by a negative feedback loop involving T3-inhibition of hypothalamic thyrotrophin releasing hormone (TRH) and pituitary thyroid stimulating hormone (TSH) secretion, and by tissue specific and hormone-regulated expression of the three iodothyronine deiodinase enzymes that activate or metabolise thyroid hormones. T3 actions are mediated by two T3-receptors, TRalpha and TRbeta, which act as hormone-inducible transcription factors. The TRalpha (NR1A1) and TRbeta (NR1A2) genes encode mRNAs that are alternatively spliced to generate 9 mRNA isoforms (TRalpha1, alpha2, alpha3, Deltaalpha1, Deltaalpha2, beta1, beta2, beta3 and Deltabeta3), of which four (TRalpha1, alpha2, beta1 and beta2) are known to be expressed at the protein level in vivo. The numerous TR mRNAs are expressed widely in tissue- and developmental stage-specific patterns, although it is important to note that levels of mRNA expression may not correlate with receptor protein concentrations in individual tissues. The TRalpha2, alpha3, Deltaalpha1 and Deltaalpha2 transcripts encode proteins that fail to bind T3 in vitro. These non-binding isoforms, in addition to TRDeltabeta3 which does bind hormone, may act as dominant negative antagonists of the true T3-binding receptors in vitro, but their physiological functions and those of the TRbeta3 isoform have not been determined. In order to obtain a new understanding of the complexities of T3 action in vivo and the role of TRs during development, many mouse models of disrupted or augmented thyroid hormone signalling have been generated. The aim of this review is to provide a picture of the physiological actions of thyroid hormones by considering the phenotypes of these genetically modified mice.

Epidemiological data suggests a role of dietary cholesterol in the etiology of lung cancer without having a clear biological hypothesis. Although smoking as the outstanding risk factor for lung cancer may enhance lipid peroxidation reactions, this study was planned to assess smoking-independent associations between the extent of cholesterol oxidation and the risk for lung cancer. In the frame of a nested case-control study in European Prospective Investigation on Cancer-Heidelberg, six cholesterol oxidation products (COPs) were determined in plasma samples of 20 incident lung cancer patients obtained 1.9 +/- 0.6 years before diagnosis and in 40 matched (including smoking habits) controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression. Among all COP compounds tested, plasma 7beta-hydroxycholesterol was associated with lung cancer risk. The high crude risk estimate (OR approximately equals 5) became significant after adjustment for sports activity (OR = 6.83, CI = 1.08-43.01, 3rd versus 1st tertile). For the independent effect of 7beta-hydroxycholesterol, i.e., adjusted for other COP compounds, an OR of 8.08 (CI = 1.12-58.54, 3rd versus 1st tertile) was calculated (P = 0.04 for trend). Lung cancer risk adjusted for sports activity significantly increased by 26% (CI = 1.050-1.506, P = 0.01) per unit (1 nmol/mmol plasma cholesterol) of 7beta-hydroxycholesterol. No dietary factor had a significant effect in the regression model, but the dietary intake of meat, eggs, animal fat, cholesterol, and fruits (inversely) correlated with plasma COP concentrations. In this small study, plasma 7beta-hydroxycholesterol appeared to be a smoking-independent predictor of lung cancer risk and might therefore be used as a biomarker. Because of the rather high-risk estimate, research on possible intrinsic biological effects of this compound should be encouraged.

Vegetarians are at risk to develop deficiencies of some essential nutrients, especially vitamin B-12 (cobalamin). Cobalamin occurs in substantial amounts only in foods derived from animals and is essential for one-carbon metabolism and cell division. Low nutritional intake of vitamin B-12 may lead to negative balance and, finally, to functional deficiency when tissue stores of vitamin B-12 are depleted. Early diagnosis of vitamin B-12 deficiency seems to be useful because irreversible neurological damages may be prevented by cobalamin substitution. The search for a specific and sensitive test to diagnose vitamin B-12 deficiency is ongoing. Serum vitamin B-12 measurement is a widely applied standard method. However, the test has poor predictive value. Optimal monitoring of cobalamin status in vegetarians should include the measurement of homocysteine (HCY), methylmalonic acid (MMA), and holotranscobalamin II. Vitamin B-12 deficiency can be divided into four stages. In stages I and II, indicated by a low plasma level of holotranscobalamin II, the plasma and cell stores become depleted. Stage III is characterized by increased levels of HCY and MMA in addition to lowered holotranscobalamin II. In stage IV, clinical signs become recognizable like macroovalocytosis, elevated MCV of erythrocytes or lowered haemoglobin. In our investigations, we have found stage III of vitamin B-12 deficiency in over 60% of vegetarians, thus underlining the importance of cobalamin monitoring in this dietary group.

An almost endless number of observations and experiments have effectively falsified the hypothesis that dietary cholesterol and fats, and a high cholesterol level play a role in the causation of atherosclerosis and cardiovascular disease. The hypothesis is maintained because allegedly supportive, but insignificant findings, are inflated, and because most contradictory results are misinterpreted, misquoted or ignored.

The purpose of the current study was to examine the effects of a very low-carbohydrate diet on weight loss and biochemical parameters in overweight women. Twenty women completed an 8-week trial that reduced their daily carbohydrate intake from 232 to 71 g (p < 0.05) and reduced energy by 2,644 kJ/day (8,384 to 5,740 kJ, p < 0.001). The average weight loss was 5.0 kg (p < 0.0001), with a net decrease in body mass index of 1.82 kg/m2, a loss of 3.4% body fat (4 kg, p < 0.0001), and a loss of 1.0 kg lean mass (p < 0.05). There were no significant changes in fasting blood glucose, fasting serum insulin, oral glucose tolerance, free or total insulin-like growth factor-1, or total IGFBP-3. Systolicblood pressure decreased by an average of 9.0 mmHg (1 mmHg = 133.322 Pa) (p < 0.01) and diastolic blood pressure decreased by 7 mmHg (p < 0.05). Total cholesterol decreased 1.2 mM (p < 0.001), all of which was accounted for by a decrease in low-density lipoprotein cholesterol (p < 0.001) with no change in high-density lipoprotein cholesterol (baseline, 1.17 mM; week 8, 1.22 mM). Total triacylglycerol decreased 0.6 mM (p < 0.01), and the ratio of triacylglycerol/HDL also significantly decreased (baseline, 1.40; week 8, 0.87; p

The KD has been proven an effective alternative epilepsy treatment in children refractory to standard anticonvulsants. Children to be placed on the diet must be carefully selected, monitored, and followed. The diet is to be regarded as a strict medical regimen and requires a comprehensive medical team approach in concert with intensive parental involvement. With better understanding of the scientific principles underlying brain ketosis, we should be able to optimize the KD to achieve even better results.

Epilepsy is a common and heterogeneous neurological disorder arising from biochemical and molecular events that are incompletely understood. To effectively manage epilepsies, it is important to understand the mechanisms underlying both seizure-induced brain damage as well as seizure initiation. Oxidative stress is emerging as a mechanism that may play an important role in the etiology of seizure-induced neuronal death. Conversely, epileptic seizures are a common occurrence in mitochondrial diseases arising from defects in oxidative phosphorylation. This review focuses on the emerging role of oxidative stress and mitochondrial dysfunction both as a consequence and cause of epileptic seizures.

BACKGROUND: Accurate quantification of mRNA in whole blood is made difficult by the simultaneous degradation of gene transcripts and unintended gene induction caused by sample handling or uncontrolled activation of coagulation. This study was designed to compare a new blood collection tube (PAXgene Blood RNA System) and a companion sample preparation reagent set with a traditional sample collection and preparation method for the purpose of gene expression analysis. METHODS: We collected parallel blood samples from healthy donors into the new sample collection tubes and control EDTA tubes and performed serial RNA extractions on samples stored for 5 days at room temperature and for up to 90 days at 4 and 20 degrees C. Samples were analyzed by Northern blot analysis or reverse transcription-PCR (RT-PCR). RESULTS: Specific mRNA concentrations in blood stored in EDTA tubes at any temperature changed substantially, as determined by high-precision RT-PCR. These changes were eliminated or markedly reduced when whole blood was stored in PAXgene tubes. Loss of specific mRNAs, as measured by RT-PCR, reflected total RNA depletion as well as specific mRNA destruction demonstrated by Northern blot analysis. The salutary effects of PAXgene on mRNA stabilization extended to blood samples from eight unrelated donors. CONCLUSIONS: Compared with whole blood collected in EDTA tubes and extracted by an organic method, the PAXgene Blood RNA System reduced RNA degradation and inhibited or eliminated gene induction in phlebotomy whole blood samples. Storage of whole blood samples in PAXgene tubes can be recommended for clinically related blood samples that will be analyzed for total or specific RNA content.

The lower rates of some cancers in Asian countries than in Western countries may be partly because of diet, although the mechanisms are unknown. The aim of this cross-sectional study was to determine whether a plant-based (vegan) diet is associated with a lower circulating level of insulin-like growth factor I (IGF-I) compared with a meat-eating or lacto-ovo-vegetarian diet among 292 British women, ages 20-70 years. The mean serum IGF-I concentration was 13% lower in 92 vegan women compared with 99 meat-eaters and 101 vegetarians (P = 0.0006). The mean concentrations of both serum IGF-binding protein (IGFBP)-1 and IGFBP-2 were 20-40% higher in vegan women compared with meat-eaters and vegetarians (P = 0.005 and P = 0.0008 for IGFBP-1 and IGFBP-2, respectively). There were no significant differences in IGFBP-3, C-peptide, or sex hormone-binding globulin concentrations between the diet groups. Intake of protein rich in essential amino acids was positively associated with serum IGF-I (Pearson partial correlation coefficient; r = 0.27; P

Berry extracts rich in anthocyanins have been linked to protective effects including the modulation of age-related neurological dysfunction and the improvement of the resistance of red blood cells against oxidative stress in vitro. In this study the bioavailability, metabolism and elimination of polyphenols from blackcurrant juice, rich in anthocyanins, flavonols, and hydroxycinnamates, were investigated. The four major native anthocyanidin glycosides of blackcurrant juice, delphinidin-3-glucoside, delphinidin-3-rutinoside, cyanidin-3-glucoside and cyanidin-3-rutinoside, were detected and identified in low amounts by HPLC and LC-MS in plasma and urine post-ingestion. Elimination of the anthocyanins was fast (maximum excretion after 1 h) and plasma levels (0-128.6 nmol/l) and total urinary exretion (0.07-1.35 mg; 0.007-0.133% of the dose ingested) were low. Most significantly, of the hydroxycinnamates, conjugated and free ferulic, isoferulic, p-coumaric, sinapic and vanillic acids were identified in plasma and urine, using GC-MS techniques. Quercetin and kaempferol (as glucuronides) and the proposed colonic metabolite of quercetin, 3-hydroxyphenylacetic acid, were detectable in a minority of subjects. Increased daily urinary hippuric, 4-hydroxyhippuric and 3-hydroxyhippuric acid levels were also observed post-ingestion in all volunteers.

OBJECTIVE: To observe any changes in serum concentrations of lipids, when UK meat-eaters switch to a self selected vegetarian diet for 6 months. DESIGN: Observational study using capillary blood samples and 3-day estimated dietary diary. SETTING: Free-living subjects in the North-West of England. SUBJECTS: Twelve male and 31 female adult volunteers aged between 18 and 42 years. OUTCOME MEASURES: Serum lipids; nutrient intake and anthropometric measurements at baseline and 6 months after switching to a self-selected vegetarian diet. RESULTS: Total energy intake and amount of energy derived from saturated fatty acids decreased significantly after changing to a vegetarian diet (P

OBJECTIVE: To observe any changes in serum concentrations of lipids, when UK meat-eaters switch to a self selected vegetarian diet for 6 months. DESIGN: Observational study using capillary blood samples and 3-day estimated dietary diary. SETTING: Free-living subjects in the North-West of England. SUBJECTS: Twelve male and 31 female adult volunteers aged between 18 and 42 years. OUTCOME MEASURES: Serum lipids; nutrient intake and anthropometric measurements at baseline and 6 months after switching to a self-selected vegetarian diet. RESULTS: Total energy intake and amount of energy derived from saturated fatty acids decreased significantly after changing to a vegetarian diet (P

The extent to which women of reproductive age are able to convert the n-3 fatty acid alpha-linolenic acid (ALNA) to eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) was investigated in vivo by measuring the concentrations of labelled fatty acids in plasma for 21 d following the ingestion of [U-13C]ALNA (700 mg). [13C]ALNA excursion was greatest in cholesteryl ester (CE) (224 (sem 70) micromol/l over 21 d) compared with triacylglycerol (9-fold), non-esterified fatty acids (37-fold) and phosphatidylcholine (PC, 7-fold). EPA excursion was similar in both PC (42 (sem 8) micromol/l) and CE (42 (sem 9) micromol/l) over 21 d. In contrast both [13C]DPA and [13C]DHA were detected predominately in PC (18 (sem 4) and 27 (sem 7) micromol/l over 21 d, respectively). Estimated net fractional ALNA inter-conversion was EPA 21 %, DPA 6 % and DHA 9 %. Approximately 22 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h of the study. These results suggest differential partitioning of ALNA, EPA and DHA between plasma lipid classes, which may facilitate targeting of individual n-3 fatty acids to specific tissues. Comparison with previous studies suggests that women may possess a greater capacity for ALNA conversion than men. Such metabolic capacity may be important for meeting the demands of the fetus and neonate for DHA during pregnancy and lactation. Differences in DHA status between women both in the non-pregnant state and in pregnancy may reflect variations in metabolic capacity for DHA synthesis.

The capacity for conversion of alpha-linolenic acid (ALNA) to n-3 long-chain polyunsaturated fatty acids was investigated in young men. Emulsified [U-13C]ALNA was administered orally with a mixed meal to six subjects consuming their habitual diet. Approximately 33 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h. [13C]ALNA was mobilised from enterocytes primarily as chylomicron triacylglycerol (TAG), while [13C]ALNA incorporation into plasma phosphatidylcholine (PC) occurred later, probably by the liver. The time scale of conversion of [13C]ALNA to eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) suggested that the liver was the principal site of ALNA desaturation and elongation, although there was some indication of EPA and DPA synthesis by enterocytes. [13C]EPA and [13C]DPA concentrations were greater in plasma PC than TAG, and were present in the circulation for up to 7 and 14 d, respectively. There was no apparent 13C enrichment of docosahexaenoic acid (DHA) in plasma PC, TAG or non-esterified fatty acids at any time point measured up to 21 d. This pattern of 13C n-3 fatty acid labelling suggests inhibition or restriction of DHA synthesis downstream of DPA. [13C]ALNA, [13C]EPA and [13C]DPA were incorporated into erythrocyte PC, but not phosphatidylethanolamine, suggesting uptake of intact plasma PC molecules from lipoproteins into erythrocyte membranes. Since the capacity of adult males to convert ALNA to DHA was either very low or absent, uptake of pre-formed DHA from the diet may be critical for maintaining adequate membrane DHA concentrations in these individuals.

BACKGROUND: Hypertension-related diseases are the leading causes of morbidity and mortality in industrially developed societies. Surprisingly, 68% of all mortality attributed to high blood pressure (BP) occurs with systolic BP between 120 and 140 mm Hg and diastolic BP below 90 mm Hg. Dietary and lifestyle modifications are effective in the treatment of borderline hypertension. One such lifestyle intervention is the use of medically supervised water-only fasting as a safe and effective means of normalizing BP and initiating health-promoting behavioral changes. METHODS: Sixty-eight (68) consecutive patients with borderline hypertension with systolic BP in excess of 119 mm Hg and diastolic BP less than 91 mm Hg were treated in an inpatient setting under medical supervision. The treatment program consisted of a short prefasting period (approximately 1-2 days on average) during which food consumption was limited to fruits and vegetables followed by medically supervised water-only fasting (approximately 13.6 days on average). Fasting was followed by a refeeding period (approximately 6.0 days on average). The refeeding program consisted of a low-fat, low-sodium, plant-based, vegan diet. RESULTS: Approximately 82% of the subjects achieved BP at or below 120/80 mm Hg by the end of the treatment program. The mean BP reduction was 20/7 mm Hg, with the greatest decrease being observed for subjects with the highest baseline BP. A linear regression of BP decrease against baseline BP showed that the estimated BP below which no further decrease would be expected was 96.0/67.0 mm Hg at the end of the fast and 99.2/67.3 mm Hg at the end of refeeding. These levels are in agreement with other estimates of the BP below which stroke events are eliminated, thus suggesting that these levels could be regarded as the "ideal" BP values. CONCLUSION: Medically supervised water-only fasting appears to be a safe and effective means of normalizing BP and may assist in motivating health-promoting diet and lifestyle changes.

BACKGROUND: Little is known about changes in thyroid function in obese children. An influence of leptin on thyroid hormone synthesis has been proposed. AIMS: To examine thyroid function and leptin concentrations in obese children. METHODS: Triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), and leptin were measured in 118 obese children (aged 4.5-16 years); thyroid function was also determined in 107 healthy children of normal weight. T3, T4, and TSH were analysed in 55 obese children who had achieved weight reduction and in 13 obese children who had not achieved weight reduction after one year based on normal energy diet. RESULTS: TSH, T3, and T4 were significantly higher in obese children compared to those of normal weight. Twelve per cent of the obese children had TSH, 15% had T3, and 11% had T4 concentrations above the twofold standard deviation of normal weight children. The degree of overweight correlated with T3, T4, and TSH. Thyroid hormones did not correlate significantly with leptin. A reduction in overweight showed a significant decrease in T3, T4, and leptin serum concentrations, but there was no significant change in TSH. CONCLUSION: Peripheral thyroid hormones (T3, T4) and TSH are moderately increased in obese children; weight reduction leads to a long term decrease in the peripheral thyroid hormones but not in TSH. There is no necessity to treat the increased serum TSH.

BACKGROUND: The aim of this study was to prospectively evaluate the magnitude of the variations in lipid levels in a large population of patients admitted for acute myocardial infarction (MI) and unstable angina (UA). Clinical data and blood samples were prospectively collected from consecutive patients with MI and UA. METHODS: The study population consisted of patients with symptoms lasting

Insulin resistance occurs in obesity and Type II (non-insulin-dependent) diabetes mellitus, but it is also a prominent feature of lipodystrophy. Adipose tissue could play a crucial part in buffering the flux of fatty acids in the circulation in the postprandial period, analogous to the roles of the liver and skeletal muscle in buffering postprandial glucose fluxes. Adipose tissue provides its buffering action by suppressing the release of non-esterified fatty acids into the circulation and by increasing triacylglycerol clearance. In particular, the pathway of 'fatty acid trapping' (adipocyte uptake of fatty acids liberated from plasma triacylglycerol by lipoprotein lipase) could play a key part in the buffering process. If this buffering action is impaired, then extra-adipose tissues are exposed to excessive fluxes of lipid fuels and could accumulate these in the form of triacylglycerol, leading to insulin resistance. These tissues will include liver, skeletal muscle and the pancreatic beta cell, where the long term effect is to impair insulin secretion. Adipose tissue buffering of lipid fluxes is impaired in obesity through defects in the ability of adipose tissue to respond rapidly to the dynamic situation that occurs after meals. It is also impaired in lipodystrophy because there is not sufficient adipose tissue to provide the necessary buffering capacity. Thus, the phenotype, at least with regard to insulin resistance, is similar with both excess and deficiency of adipose tissue. Furthermore, this concept could provide a framework for understanding the action of the thiazolidinedione insulin-sensitizing agents.

Résumé Quatre restes humains : une mandibule, deux crânes et un métatarsien ont été découverts entre 1991 et 1999 sur le site de plein air de Dmanissi en Géorgie, dans un contexte stratigraphique, paléontologique et archéologique précis, datés par la présence de cendres volcaniques enrobantes de 1,81 ± 0,05 Ma. Les premières études de ces fossiles ont permis aux auteurs de les rapprocher de la morphologie des Homo erectus archaïques africains, attribués à Homo ergaster, et de constater la présence de l'homme aux portes de l'Europe 300[punctuation space]000 ans plus tôt que le scénario classique ne le prévoyait. En septembre 2000, la mise au jour d'une seconde mandibule D 2600, plus complète, robuste, présente un triple intérêt : paléontologique, fonctionnel et pathologique. Une comparaison avec Homo habilis et Homo erectus permet de reconnaître une nouvelle espèce d'Homo : Homo georgicus sp. nov. Les caractéristiques morpho-fonctionnelles et l'ancienneté de Homo georgicus caractérisent la souche d'une longue lignée eurasiatique.

The concept of manipulating an individuals habitual diet before an exercise bout in an attempt to modify patterns of fuel substrate utilization and enhance subsequent exercise capacity is not new. Modern studies have focused on nutritional and training strategies aimed to optimize endogenous carbohydrate (CHO) stores while simultaneously maximizing the capacity for fat oxidation during continuous, submaximal (60-70% of maximal O(2) uptake [(.)VO(2max)] exercise. Such "nutritional periodization" typically encompasses 5-6 d of a high-fat diet (60-70% E) followed by 1-2 d of high-CHO intake (70-80% E; CHO restoration). Despite the brevity of the adaptation period, ingestion of a high-fat diet by endurance-trained athletes results in substantially higher rates of fat oxidation and concomitant muscle glycogen sparing during submaximal exercise compared with an isoenergetic high-CHO diet. Higher rates of fat oxidation during exercise persist even under conditions in which CHO availability is increased, either by having athletes consume a high-CHO meal before exercise and/or ingest glucose solutions during exercise. Yet, despite marked changes in the patterns of fuel utilization that favor fat oxidation, fat-adaptation/CHO restoration strategies do not provide clear benefits to the performance of prolonged endurance exercise.

High-fat ketogenic diets increase ketones (acetoacetate, beta-hydroxybutyrate, and acetone) and are used to treat refractory seizures. Although ketosis is an integral aspect of these therapeutic regimens, the direct importance of ketosis to seizure control needs further investigation. An examination of this relationship requires a reliable, minimally invasive measure of ketosis that can be performed frequently. In the present study, we examined the use of breath acetone as a measure of ketosis in children with refractory seizures on a classic ketogenic diet. Results were compared with breath acetone levels in epilepsy and healthy controls. Children on the ketogenic diet had significantly higher fasting breath acetone compared with epilepsy or healthy controls (2530 +/- 600 nmol/L versus 19 +/- 9 nmol/L and 21 +/- 4 nmol/L, respectively; p < 0.05). One hour after consumption of a ketogenic breakfast meal, breath acetone increased significantly in epilepsy and healthy controls (p

Insomnia is one of the most prevalent psychological disorders, causing sufferers severe distress as well as social, interpersonal, and occupational impairment. Drawing on well-validated cognitive models of the anxiety disorders as well as on theoretical and empirical work highlighting the contribution of cognitive processes to insomnia, this paper presents a new cognitive model of the maintenance of insomnia. It is suggested that individuals who suffer from insomnia tend to be overly worried about their sleep and about the daytime consequences of not getting enough sleep. This excessive negatively toned cognitive activity triggers both autonomic arousal and emotional distress. It is proposed that this anxious state triggers selective attention towards and monitoring of internal and external sleep-related threat cues. Together, the anxious state and the attentional processes triggered by it tricks the individual into overestimating the extent of the perceived deficit in sleep and daytime performance. It is suggested that the excessive negatively toned cognitive activity will be fuelled if a sleep-related threat is detected or a deficit perceived. Counterproductive safety behaviours (including thought control, imagery control, emotional inhibition, and difficulty problem solving) and erroneous beliefs about sleep and the benefits of worry are highlighted as exacerbating factors. The unfortunate consequence of this sequence of events is that the excessive and escalating anxiety may culminate in a real deficit in sleep and daytime functioning. The literature providing preliminary support for the model is reviewed and the clinical implications and limitations discussed.  2002 Elsevier Science Ltd. All rights reserved.