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Title:
Effects of β-hydroxybutyrate on cognition in memory-impaired adults
Authors:
Reger, Mark A.; Henderson, Samuel T.; Hale, Cathy; Cholerton, Brenna; Baker, Laura D.; Watson, G. S.; Hyde, Karen; Chapman, Darla; Craft, Suzanne
Abstract:
Glucose is the brain’s principal energy substrate. In Alzheimer’s disease (AD), there appears to be a pathological decrease in the brain’s ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body β-hydroxybutyrate (β-OHB) were observed 90min after treatment (P=0.007) when cognitive tests were administered. β-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For ε4+ subjects, β-OHB levels continued to rise between the 90 and 120min blood draws in the treatment condition, while the β-OHB levels of ε4− subjects held constant (P
Published:
February 29, 2004
Title:
Exploring the intersectoral partnerships guiding Australia's dietary advice
Authors:
Dixon, Jane; Sindall, Colin; Banwell, Cathy
Abstract:
Abstract. In 1986, the Ottawa Charter alerted a new generation of health promotion practitioners to the benefits of working with the non-health sectors, includ
Published:
February 29, 2004
Title:
High-Protein, Low-Fat Diets Are Effective for Weight Loss and Favorably Alter Biomarkers in Healthy Adults
Authors:
Johnston, Carol S.; Tjonn, Sherrie L.; Swan, Pamela D.
Abstract:
Abstract. Although popular and effective for weight loss, low-carbohydrate, high-protein, high-fat (Atkins) diets have been associated with adverse changes in
Published:
February 29, 2004
Title:
Trends in intake of energy and macronutrients--United States, 1971-2000
Authors:
Centers for Disease Control and Prevention (CDC)
Abstract:
During 1971-2000, the prevalence of obesity in the United States increased from 14.5% to 30.9%. Unhealthy diets and sedentary behaviors have been identified as the primary causes of deaths attributable to obesity. Evaluating trends in dietary intake is an important step in understanding the factors that contribute to the increase in obesity. To assess trends in intake of energy (i.e., kilocalories [kcals]), protein, carbohydrate, total fat, and saturated fat during 1971-2000, CDC analyzed data from four National Health and Nutrition Examination Surveys (NHANES): NHANES I (conducted during 1971-1974), NHANES II (1976-1980), NHANES III (1988-1994), and NHANES 1999-2000. This report summarizes the results of that analysis, which indicate that, during 1971--2000, mean energy intake in kcals increased, mean percentage of kcals from carbohydrate increased, and mean percentage of kcals from total fat and saturated fat decreased. An expert advisory committee appointed by the U.S. Department of Health and Human Services and the U.S. Department of Agriculture (USDA) is conducting a review of the Dietary Guidelines for Americans. Revised guidelines will be published in 2005.
Published:
February 5, 2004
Title:
A Critical Review of Atypical Antipsychotic Utilization: Comparing Monotherapy with Polypharmacy and Augmentation
Authors:
Stahl, S.; Grady, M.
Abstract:
The atypical antipsychotics risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole have become first-line treatment for schizophrenia because they reduce the positive symptoms of psychosis but do not have a high incidence of extrapyramidal symptoms. However, these agents, like other antipsychotics, may take as long as 16 or more weeks to produce a response, and even with prolonged treatment are unlikely to evoke responses greater than 50% improvement in symptoms. This has led to the experimental use of high atypical antipsychotic doses, antipsychotic polypharmacy, and augmentation with other psychotropic drugs, all of which occur commonly in clinical practice. This article reviews the current evidence for these increasingly common means of treating schizophrenia and psychosis, with particular emphasis on polypharmacy and augmentation. To date, there are only two controlled studies of antipsychotic polypharmacy involving an atypical antipsychotic; the rest of the data are uncontrolled trials and case reports that describe a mixture of positive and negative findings. One multicenter, double-blind trial shows a faster onset of action when divalproex is added to risperidone or olanzapine than with antipsychotic monotherapy. A small double-blind study demonstrates efficacy when lamotrigine is added to clozapine. The rest of the data on augmentation with anticonvulsants are uncontrolled, and most report adverse effects. With the exception of divalproex, there are currently no compelling data to justify the use of antipsychotic polypharmacy or augmentation. Existing evidence suggests that the best treatments for schizophrenia and psychosis may be long-term trials of a sequence of atypical antipsychotic monotherapies at therapeutic doses.
Published:
January 31, 2004
Title:
Advanced glycation end product ligands for the receptor for advanced glycation end products: biochemical characterization and formation kinetics
Authors:
Valencia, Jessica V; Weldon, Stephen C; Quinn, Douglas; Kiers, Geesje H; DeGroot, Jeroen; TeKoppele, Johan M; Hughes, Thomas E
Abstract:
Advanced glycation end products (AGEs) accumulate with age and at an accelerated rate in diabetes. AGEs bind cell-surface receptors including the receptor for advanced glycation end products (RAGE). The dependence of RAGE binding on specific biochemical characteristics of AGEs is currently unknown. Using standardized procedures and a variety of AGE measures, the present study aimed to characterize the AGEs that bind to RAGE and their formation kinetics in vitro. To produce AGEs with varying RAGE binding affinity, bovine serum albumin (BSA) AGEs were prepared with 0.5M glucose, fructose, or ribose at times of incubation from 0 to 12 weeks or for up to 3 days with glycolaldehyde or glyoxylic acid. The AGE-BSAs were characterized for RAGE binding affinity, fluorescence, absorbance, carbonyl content, reactive free amine content, molecular weight, pentosidine content, and N-ε-carboxymethyl lysine content. Ribose-AGEs bound RAGE with high affinity within 1 week of incubation in contrast to glucose- and fructose-AGE, which required 12 and 6 weeks, respectively, to generate equivalent RAGE ligands (IC50=0.66, 0.93, and 1.7μM, respectively). Over time, all of the measured AGE characteristics increased. However, only free amine content robustly correlated with RAGE binding affinity. In addition, detailed protocols for the generation of AGEs that reproducibly bind RAGE with high affinity were developed, which will allow for further study of the RAGE–AGE interaction.
Published:
December 31, 2003
Title:
Efficacy of the Atkins diet as therapy for intractable epilepsy
Authors:
Kossoff, Eric H.; Krauss, Gregory L.; McGrogan, Jane R.; Freeman, John M.
Abstract:
The ketogenic diet is effective for treating seizures in children with epilepsy. The Atkins diet can also induce a ketotic state, but has fewer protein and caloric restrictions, and has been used safely by millions of people worldwide for weight reduction. Six patients, aged 7 to 52 years, were started on the Atkins diet for the treatment of intractable focal and multifocal epilepsy. Five patients maintained moderate to large ketosis for periods of 6 weeks to 24 months; three patients had seizure reduction and were able to reduce antiepileptic medications. This provides preliminary evidence that the Atkins diet may have a role as therapy for patients with medically resistant epilepsy.
Published:
December 22, 2003
Title:
Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance
Authors:
Xu, Haiyan; Barnes, Glenn T.; Yang, Qing; Tan, Guo; Yang, Daseng; Chou, Chieh J.; Sole, Jason; Nichols, Andrew; Ross, Jeffrey S.; Tartaglia, Louis A.; Chen, Hong
Abstract:
Insulin resistance arises from the inability of insulin to act normally in regulating nutrient metabolism in peripheral tissues. Increasing evidence from human population studies and animal research has established correlative as well as causative links between chronic inflammation and insulin resistance. However, the underlying molecular pathways are largely unknown. In this report, we show that many inflammation and macrophage-specific genes are dramatically upregulated in white adipose tissue (WAT) in mouse models of genetic and high-fat diet-induced obesity (DIO). The upregulation is progressively increased in WAT of mice with DIO and precedes a dramatic increase in circulating-insulin level. Upon treatment with rosiglitazone, an insulin-sensitizing drug, these macrophage-originated genes are downregulated. Histologically, there is evidence of significant infiltration of macrophages, but not neutrophils and lymphocytes, into WAT of obese mice, with signs of adipocyte lipolysis and formation of multinucleate giant cells. These data suggest that macrophages in WAT play an active role in morbid obesity and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance. We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue.
Published:
December 14, 2003
Title:
Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios
Authors:
Clark, Andrew G.; Glanowski, Stephen; Nielsen, Rasmus; Thomas, Paul D.; Kejariwal, Anish; Todd, Melissa A.; Tanenbaum, David M.; Civello, Daniel; Lu, Fu; Murphy, Brian; Ferriera, Steve; Wang, Gary; Zheng, Xianqgun; White, Thomas J.; Sninsky, John J.; Adams, Mark D.; Cargill, Michele
Abstract:
Even though human and chimpanzee gene sequences are nearly 99% identical, sequence comparisons can nevertheless be highly informative in identifying biologically important changes that have occurred since our ancestral lineages diverged. We analyzed alignments of 7645 chimpanzee gene sequences to their human and mouse orthologs. These three-species sequence alignments allowed us to identify genes undergoing natural selection along the human and chimp lineage by fitting models that include parameters specifying rates of synonymous and nonsynonymous nucleotide substitution. This evolutionary approach revealed an informative set of genes with significantly different patterns of substitution on the human lineage compared with the chimpanzee and mouse lineages. Partitions of genes into inferred biological classes identified accelerated evolution in several functional classes, including olfaction and nuclear transport. In addition to suggesting adaptive physiological differences between chimps and humans, human-accelerated genes are significantly more likely to underlie major known Mendelian disorders.
Published:
December 11, 2003
Title:
A Randomized Clinical Trial of a Care Recommendation Letter Intervention for Somatization in Primary Care
Authors:
Dickinson, W. P.
Abstract:
PURPOSE This paper describes the impact of a care recommendation (CR) letter intervention on patients with multisomatoform disorder (MSD) and analysis of patient factors that affect the response to the intervention. METHODS One hundred eighty-eight patients from 3 family practices, identified through screening of 2,902 consecutive patients, were classified using somatization diagnoses based on the number of unexplained physical symptoms from a standardized mental health interview. In a controlled, single-crossover trial, patients were randomized to have their primary care physician receive the CR letter either immediately following enrollment or 12 months after enrollment. The CR letter notified the physician of the patient’s somatization status and provided recommendations for the patient’s care. Patients were followed for 24 months with assessments of functional status at baseline, 12, and 24 months. RESULTS Longitudinal analysis revealed a 12-month intervention effect for patients with multisomatoform disorder (MSD) of 5.5 points (P
Published:
October 31, 2003
Title:
Advanced Glycation Endproducts Induce Changes in Glucose Consumption, Lactate Production, and ATP Levels in SH-SY5Y Neuroblastoma Cells by a Redox-Sensitive Mechanism
Authors:
de Arriba, Susana Garcia; Loske, Claudia; Meiners, Ina; Fleischer, Gerd; Lobisch, Michael; Wessel, Klaus; Tritschler, Hans; Schinzel, Reinhard; Münch, Gerald
Abstract:
Advanced glycation endproducts (AGEs) accumulate on long-lived proteins, including β-amyloid plaques in Alzheimer's disease, and are suggested to contribute to neuronal dysfunction and cell death. We have investigated the effects of a model AGE upon glucose metabolism and energy production in a neuroblastoma cell line. AGEs decrease cellular ATP levels and increase glucose consumption and lactate production. All of the AGE-induced metabolic changes can be attenuated by antioxidants such as (R+)-α-lipoic acid and 17β-estradiol. These antioxidants may become useful drugs against (AGE-mediated) effects in neurodegeneration through their positive effects on cellular energy metabolism.
Published:
October 31, 2003
Title:
Enzymatic deglycation of proteins
Authors:
Wu, Xinle; Monnier, Vincent M
Abstract:
Reducing sugars such as glucose react with amino groups in proteins to form the Amadori product, which can undergo a wide range of chemical modifications and form cross-links in tissue proteins. There is growing evidence to suggest that accumulation of glycation products is associated with aging and disease progression, as in diabetes. Thus, the design and discovery of inhibitors for the glycation cascade would potentially offer a promising therapeutic approach for the prevention of glycation related diseases, especially diabetes. Two types of enzymes, fructosyl lysine oxidase and fructose lysine 3-phosphokinase, catalyze the deglycation reaction and generate free amine groups. This paper reviews the biochemical properties of these “amadoriase” enzymes, such as structural-function relationship, kinetic mechanism, and substrate specificity, as well as their biological roles and applications in the protein deglycation.
Published:
October 31, 2003
Title:
Elevated gene expression levels distinguish human from non-human primate brains
Authors:
Cáceres, Mario; Lachuer, Joel; Zapala, Matthew A.; Redmond, John C.; Kudo, Lili; Geschwind, Daniel H.; Lockhart, David J.; Preuss, Todd M.; Barlow, Carrolee
Abstract:
Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee cortex, and 91 were ascribed to the human lineage by using macaques as an outgroup. Surprisingly, most differences between the brains of humans and non-human primates involved up-regulation, with ≈90% of the genes being more highly expressed in humans. By contrast, in the comparison of human and chimpanzee heart and liver, the numbers of up- and down-regulated genes were nearly identical. Our results indicate that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans and suggests that the human brain is characterized by elevated levels of neuronal activity.
Published:
October 27, 2003
Title:
Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial
Authors:
Rae, Caroline; Digney, Alison L.; McEwan, Sally R.; Bates, Timothy C.
Abstract:
Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p
Published:
October 21, 2003
Title:
Neuropsychiatric Disturbances in Presumed Late-Onset Cobalamin C Disease
Authors:
Roze, Emmanuel; Gervais, David; Demeret, Sophie; Baulny, Hélène Ogier de; Zittoun, Jacqueline; Benoist, Jean-François; Said, Gérard; Pierrot-Deseilligny, Charles; Bolgert, Francis
Abstract:
Background
Combined methylmalonic aciduria and homocystinuria cobalamin C type (cobalamin C disease) is an inborn metabolic disorder consisting of an impaired intracellular synthesis of the 2 active forms of vitamin B12(cobalamin), namely, adenosylcobalamin and methylcobalamin, that results in increased levels of methylmalonic acid and homocysteine in the blood and urine. Most patients present in the first year of life with systemic, hematological, and neurological abnormalities. Late-onset forms are rare and had not been comprehensively characterized. They could be easily misdiagnosed.
Objective
To describe clinical and biochemical features of the disease in 2 siblings affected with presumed late-onset cobalamin C disease.
Design
Case report and review of the literature.
Setting
Neurological intensive care unit of a university hospital.
Observation
We describe 2 patients with neurological deterioration due to presumed cobalamin C disease. A 16-year-old girl was initially seen with psychosis and severe progressive neuropathy requiring mechanical ventilatory support and her 24-year-old sister had a 2-year disease course of subacute combined degeneration of the spinal cord. A metabolic workup displayed increased methylmalonic acid levels, severe hyperhomocysteinemia, and low plasma methionine levels. The diagnosis was then confirmed by demonstration of impaired synthesis of adenosylcobalamin and methylcobalamin in cultured skin fibroblasts and Epstein-Barr virus–infected lymphocytes. Under specific treatment the younger sister's condition dramatically improved.
Conclusions
Although complementation studies have not been conducted, it is most likely these patients had cobalamin C disease. This study emphasizes the possibility of late-onset disease with purely neurological manifestations. Left untreated, this treatable condition can lead to death or irreversible damage to the nervous system. Screening for intracellular vitamin B12dysmetabolism should, therefore, be considered in the investigation of adults with unexplained neurological disease, particularly when they are initially seen with a clinical picture suggestive of vitamin B12deficiency.
Published:
September 30, 2003
Title:
No Effect of 600 Grams Fruit and Vegetables Per Day on Oxidative DNA Damage and Repair in Healthy Nonsmokers
Authors:
Møller, Peter; Vogel, Ulla; Pedersen, Anette; Dragsted, Lars O.; Sandström, Brittmarie; Loft, Steffen
Abstract:
In several epidemiological studies, high intakes of fruits and vegetables have been associated with a lower incidence of cancer. Theoretically, intake of antioxidants by consumption of fruits and vegetables should protect against reactive oxygen species and decrease the formation of oxidative DNA damage. We set up a parallel 24-day dietary placebo-controlled intervention study in which 43 subjects were randomized into three groups receiving an antioxidant-free basal diet and 600 g of fruits and vegetables, or a supplement containing the corresponding amounts of vitamins and minerals, or placebo. Blood and urine samples were collected before, once a week, and 4 weeks after the intervention period. The level of strand breaks, endonuclease III sites, formamidopyrimidine sites, and sensitivity to hydrogen peroxide was assessed in mononuclear blood cells by the comet assay. Excretion of 7-hydro-8-oxo-2′-deoxyguanine was measured in urine. The expressions of oxoguanine glycosylase 1 and excision repair cross complementing 1 DNA repair genes, determined by real-time reverse transcription-PCR of mRNAs, were investigated in leukocytes. Consumption of fruits and vegetables or vitamins and minerals had no effect on oxidative DNA damage measured in mononuclear cell DNA or urine. Hydrogen peroxide sensitivity, detected by the comet assay, did not differ between the groups. Expression of excision repair cross complementing 1 and oxoguanine glycosylase 1 in leukocytes was not related to the diet consumed. Our results show that after 24 days of complete depletion of fruits and vegetables, or daily ingestion of 600 g of fruit and vegetables, or the corresponding amount of vitamins and minerals, the level of oxidative DNA damage was unchanged. This suggests that the inherent antioxidant defense mechanisms are sufficient to protect circulating mononuclear blood cells from reactive oxygen species.
Published:
September 30, 2003
Title:
D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease
Authors:
Tieu, Kim; Perier, Celine; Caspersen, Casper; Teismann, Peter; Wu, Du-Chu; Yan, Shi-Du; Naini, Ali; Vila, Miquel; Jackson-Lewis, Vernice; Ramasamy, Ravichandran; Przedborski, Serge
Abstract:
Published:
September 14, 2003
Title:
An Isoenergetic Very Low Carbohydrate Diet Improves Serum HDL Cholesterol and Triacylglycerol Concentrations, the Total Cholesterol to HDL Cholesterol Ratio and Postprandial Lipemic Responses Compared with a Low Fat Diet in Normal Weight, Normolipidemic Women
Authors:
Volek, Jeff S.; Sharman, Matthew J.; Gómez, Ana L.; Scheett, Timothy P.; Kraemer, William J.
Abstract:
Abstract. Very low carbohydrate diets are popular, yet little is known about their effects on blood lipids and other cardiovascular disease risk factors. We re
Published:
August 31, 2003
Title:
Metabolic correlates of hominid brain evolution
Authors:
Leonard, William R; Robertson, Marcia L; Snodgrass, J. Josh; Kuzawa, Christopher W
Abstract:
Large brain sizes in humans have important metabolic consequences as humans expend a relatively larger proportion of their resting energy budget on brain metabolism than other primates or non-primate mammals. The high costs of large human brains are supported, in part, by diets that are relatively rich in energy and other nutrients. Among living primates, the relative proportion of metabolic energy allocated to the brain is positively correlated with dietary quality. Humans fall at the positive end of this relationship, having both a very high quality diet and a large brain size. Greater encephalization also appears to have consequences for aspects of body composition. Comparative primate data indicate that humans are ‘under-muscled’, having relatively lower levels of skeletal muscle than other primate species of similar size. Conversely, levels of body fatness are relatively high in humans, particularly in infancy. These greater levels of body fatness and reduced levels of muscle mass allow human infants to accommodate the growth of their large brains in two important ways: (1) by having a ready supply of stored energy to ‘feed the brain’, when intake is limited and (2) by reducing the total energy costs of the rest of the body. Paleontological evidence indicates that the rapid brain evolution observed with the emergence of Homo erectus at approximately 1.8 million years ago was likely associated with important changes in diet and body composition.
Published:
August 31, 2003
Title:
The many faces of c-MYC
Authors:
Pelengaris, Stella; Khan, Mike
Abstract:
The proto-oncogene c-MYC is implicated in various physiological processes-cell growth, proliferation, loss of differentiation, and cell death (apoptosis). Oncogenic c-MYC implies constitutive or deregulated expression of c-MYC and is associated with many human cancers often with poor prognosis. Recently, c-MYC has been implicated in the loss and dysfunction of insulin-producing beta cells in diabetes. Intriguingly, this raises the possibility that c-Myc may be a key contributor to disease, not only by deregulating cell proliferation, which is well established, but also by virtue of its opposing role in engendering apoptosis. However, given the fact that human diseases at diagnosis are generally advanced and pathologically complex, it is generally difficult to attribute a specific pathogenic role to c-MYC, or indeed any given single factor, or to assess the potential of therapies targeting individual such factors. Regulatable transgenic mouse models have shed light on these issues, have influenced our thinking about cancer, and have provided encouragement for the future development of cancer therapies based on targeting individual oncogenes such as c-MYC. Although still in its infancy, encouraging results have been reported for several approaches using gene targeting to interfere with c-MYC expression or activity both in vitro and in vivo.
Published:
August 14, 2003
Title:
Vitamin D, Cod-Liver Oil, Sunlight, and Rickets: A Historical Perspective
Authors:
Rajakumar, Kumaravel
Abstract:
Rickets, a disease of vitamin D deficiency, is rarely confronted by the practicing pediatrician in the United States today. At the turn of the 20th century, rickets was rampant among the poor children living in the industrialized and polluted northern cities of the United States. With the discovery of vitamin D and the delineation of the anti-rachitic properties of cod-liver oil by the 1930s, it became possible to not only treat but also eradicate rickets in the United States. Rickets was a common disease in 17th century England. Frances Glisson’s treatise on rickets published in 1650, a glorious contribution to English medicine, described the clinical and anatomic features of rickets in great detail. The exact etiology of rickets had been elusive until the 1920s. During the Glissonian era, rickets was a mysterious disease. By the late 19th and early 20th century, faulty diet or faulty environment (poor hygiene, lack of fresh air and sunshine) or lack of exercise was implicated in its etiology. Animal experiments, appreciation of folklore advocating the benefits of cod-liver oil, and the geographical association of rickets to lack of sunshine were all relevant factors in the advancement of knowledge in the conquest of this malady. In this article, the history of rickets pertaining to the discovery of vitamin D, cod-liver oil, and sunlight is reviewed.
Published:
July 31, 2003
Title:
[Nutrition and health--potential health benefits and risks of vegetarianism and limited consumption of meat in the Netherlands]
Authors:
Dagnelie, P. C.
Abstract:
In the latest Dutch national food consumption survey (1998) just over 1% of subjects (about 150,000 persons) claimed to be vegetarians; however, a much larger group (6% or approximately 1 million persons) ate meat < or = once a week. Vegetarianism can be subdivided into lacto-vegetarianism (a diet without meat and fish) and veganism (a diet without any animal foods whatsoever, including dairy products and eggs). A recent meta-analysis showed that vegetarians had a lower mortality from ischaemic heart disease than omniovorous subjects; however, cancer mortality and total mortality did not differ. Although a high consumption of red meat, which is rich in haeme iron and saturated fat, may increase the risk of cardiovascular disease and some types of cancer, this does not apply to white meat and fish. In fact, the most important protective effect would seem to be derived from the consumption of unrefined vegetable products (whole-grain cereals, vegetables, fruits, nuts and legumes) and fish. In other words, a prudent, omnivorous diet with moderate amounts of animal products, in which red meat is partly replaced by white meat and fish (especially fatty fish), together with the consumption of ample amounts of unrefined vegetable products, is thought to be just as protective as a vegetarian diet. On the other hand, the omission of meat and fish from the diet increases the risk of nutritional deficiencies. A vegan diet, in particular, leads to a strongly increased risk of deficiencies of vitamin B12, vitamin B2 and several minerals, such as calcium, iron and zinc. However, even a lacto-vegetarian diet produces an increased risk of deficiencies of vitamin B12 and possibly certain minerals, such as iron. Data from the latest Dutch food consumption survey suggest that 5-10% of all inhabitants of the Netherlands (up to 1 million persons) actually have a vitamin B12 intake below recommended daily levels. In medical practice, the possibility of vitamin B12 deficiency in subjects consuming meat or fish
Published:
July 4, 2003
Title:
Controversies of the Sweet Urine Disease
Authors:
Guthrie, Richard A.
Abstract:
Before the discovery of insulin, the primary controversy in diabetes was what kind of reductive diet to use—rice diet, rancid fat diet, vegetables “cooked three times in their own water,” and so forth. All were restrictive and essentially treated diabetes by starvation. For type 2 diabetes, they probably worked out, in that they no doubt led to weight loss. (Perhaps we should try some of these again.) With the advent of insulin, the problem of diabetes was thought to be solved, and indeed, those with type 1 diabetes did just fine, for a while. It didn’t take long, however, for those now living longer to begin to develop vascular and neurological complications. And thus began a new round of controversy. This controversy, which began in the 1930s, raged on for the next 60 years and was often very heated. The issue, simply put, was whether the vascular and neurological problems associated with diabetes were a genetic concomitant of the disease (and thus inevitable and unalterable) or instead were associated with the metabolic abnormalities of diabetes, such as high blood glucose levels (and thus preventable). Which side one took on this issue had great ramifications regarding the method of diabetes management one’s practice adopted. A classic debate on this topic took place in New York in the 1940s between Dr. Elliott Joslin and Dr. Edward Tolstoi. The debate, which was recorded and is available at the New York Hospital, Cornell University School of Medicine, was reenacted a few years ago. In the late 1930s, Dr. Robert L. Jackson, then a pediatrician at the University of Iowa …
Published:
June 30, 2003
Title:
Lack of Acculturation Is a Risk Factor for Diabetes in Arab Immigrants in the U.S.
Authors:
Jaber, Linda A.; Brown, Morton B.; Hammad, Adnan; Zhu, Qian; Herman, William H.
Abstract:
OBJECTIVE—To examine the relationship between dysglycemia (impaired fasting glucose, impaired glucose tolerance, and diabetes) and acculturation, physical activity, and perceived stress in Arab immigrants in the U.S. RESEARCH DESIGN AND METHODS—In a cross-sectional population-based study, we examined 520 Arab Americans, aged 20–75 years, who were born in the Middle East and immigrated to southeastern Michigan. Dysglycemia was assessed by history and with a 2-h 75-g oral glucose tolerance test. Acculturation, physical activity, and perceived stress were measured with standardized questionnaires. RESULTS—Associations were found between dysglycemia in men and older age at immigration, unemployment, speaking Arabic with friends, being less active in Arabic organizations, more frequent consumption of Arabic food, and less integration into American society. Dysglycemia in women was associated with being raised in rural areas of the Middle East, older age at immigration, longer length of stay in the U.S., not being employed outside the home, less than high school education, not attending Arabic or American schools, and not being able to read Arabic. Among men, older age at immigration, shorter length of stay in the U.S., less activity in Arab organizations, and eating Arabic food were associated with dysglycemia independent of age and BMI. Among women, acculturation was very low and was confounded with age and BMI as powerful risk factors for dysglycemia. No association was found between physical activity, perceived stress, and the risk of dysglycemia in either sex. CONCLUSIONS—Lack of acculturation is an important risk factor for dysglycemia in immigrant Arab Americans. Intervention programs aimed at diabetes prevention should consider the acculturation process.
Published:
June 30, 2003
Title:
Routine vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the U.S. Preventive Services Task Force
Authors:
Morris, Cynthia D.; Carson, Susan
Abstract:
BACKGROUND: Antioxidant vitamins are thought to play a role in atherosclerosis. Supplementation of these nutrients has been explored as a means of reducing cardiovascular morbidity and mortality. PURPOSE: To assess the evidence of the effectiveness of vitamin supplementation, specifically vitamins A, C, and E; beta-carotene; folic acid; antioxidant combinations; and multivitamin supplements, in preventing cardiovascular disease. DATA SOURCES: Cochrane Controlled Trials Registry and MEDLINE (1966 to September 2001), reference lists, and experts. STUDY SELECTION: The researchers selected English-language reports of randomized trials and cohort studies that assessed vitamin supplementation in western populations and reported incidence of or death from cardiovascular events. They also included reports of good- or fair-quality clinical trials of primary and secondary prevention and good- or fair-quality prospective cohort studies. Studies that examined only dietary nutrients or did not provide separate estimates for supplements were not included. DATA EXTRACTION: Two reviewers abstracted descriptive information and data on cardiovascular outcomes and mortality from included studies. The researchers assessed study quality using predetermined criteria. DATA SYNTHESIS: Evidence tables were constructed to summarize data from included studies. The researchers summarized the strength, level, and quality of the overall evidence for the effectiveness of each of the vitamin supplements in preventing or treating cardiovascular disease. CONCLUSIONS: Some good-quality cohort studies have reported an association between the use of vitamin supplements and lower risk for cardiovascular disease. Randomized, controlled trials of specific supplements, however, have failed to demonstrate a consistent or significant effect of any single vitamin or combination of vitamins on incidence of or death from cardiovascular disease. Understanding the sources of these differences will permit researchers to better analyze the cohort study data and to better design long-term clinical trials.
Published:
June 30, 2003
Title:
Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials
Authors:
Vivekananthan, Deepak P.; Penn, Marc S.; Sapp, Shelly K.; Hsu, Amy; Topol, Eric J.
Abstract:
INTRODUCTION: Oxidised LDL is thought to play an important part in the pathogenesis of atherosclerosis. Observational studies have associated alpha tocopherol (vitamin E), beta carotene, or both, with reductions in cardiovascular events, but not clinical trials. We did a meta-analysis to assess the effect of these compounds on long-term cardiovascular mortality and morbidity. METHODS: We analysed seven randomised trials of vitamin E treatment and, separately, eight of beta carotene treatment; all trials included 1000 or more patients. The dose range for vitamin E was 50-800 IU, and for beta carotene was 15-50 mg. Follow-up ranged from 1.4 to 12.0 years. FINDINGS: The vitamin E trials involved a total of 81788 patients and the beta carotene trials 138113 in the all-cause mortality analyses. Vitamin E did not provide benefit in mortality compared with control treatment (11.3 vs 11.1%, odds ratio 1.02 [95% CI 0.98-1.06] p=0.42) or significantly decrease risk of cardiovascular death (6.0 vs 6.0%, p=0.86) or cerebrovascular accident (3.6 vs 3.5%, p=0.31). Beta carotene led to a small but significant increase in all-cause mortality (7.4 vs 7.0%, 1.07 [1.02-1.11] p=0.003) and with a slight increase in cardiovascular death (3.4 vs 3.1%, 1.1 [1.03-1.17] p=0.003). No significant heterogeneity was noted for any analysis. INTERPRETATION: The lack of a salutary effect was seen consistently for various doses of vitamins in diverse populations. Our results, combined with the lack of mechanistic data for efficacy of vitamin E, do not support the routine use of vitamin E.
Published:
June 13, 2003
Title:
Pleistocene Homo sapiens from Middle Awash, Ethiopia
Authors:
White, Tim D.; Asfaw, Berhane; DeGusta, David; Gilbert, Henry; Richards, Gary D.; Suwa, Gen; Howell, F. Clark
Abstract:
The origin of anatomically modern Homo sapiens and the fate of Neanderthals have been fundamental questions in human evolutionary studies for over a century. A key barrier to the resolution of these questions has been the lack of substantial and accurately dated African hominid fossils from between 100,000 and 300,000 years ago. Here we describe fossilized hominid crania from Herto, Middle Awash, Ethiopia, that fill this gap and provide crucial evidence on the location, timing and contextual circumstances of the emergence of Homo sapiens. Radioisotopically dated to between 160,000 and 154,000 years ago, these new fossils predate classic Neanderthals and lack their derived features. The Herto hominids are morphologically and chronologically intermediate between archaic African fossils and later anatomically modern Late Pleistocene humans. They therefore represent the probable immediate ancestors of anatomically modern humans. Their anatomy and antiquity constitute strong evidence of modern-human emergence in Africa.
Published:
June 11, 2003
Title:
Association of the dopamine beta hydroxylase gene with attention deficit hyperactivity disorder: genetic analysis of the Milwaukee longitudinal study
Authors:
Smith, Karen Müller; Daly, Mark; Fischer, Mariellen; Yiannoutsos, Constantin T.; Bauer, Lorri; Barkley, Russell; Navia, Bradford A.
Abstract:
Attention deficit hyperactivity disorder (ADHD) is a highly heritable and common disorder that partly reflects disturbed dopaminergic function in the brain. Recent genetic studies have shown that candidate genes involved in dopamine signaling and metabolism contribute to ADHD susceptibility. We have initiated genetic studies in a unique cohort of 158 ADHD and 81 control adult subjects who have been followed longitudinally since childhood in the Milwaukee study of ADHD. From this cohort, genetic analysis was performed in 105 Caucasian subjects with ADHD and 68 age and ethnicity-matched controls for the DRD4 exon 3 VNTR, the SLC6A3 (DAT1) 3' UTR VNTR, dopamine beta hydroxylase (DBH) TaqI A polymorphism, and the DBH GT microsatellite repeat polymorphism that has been quantitatively associated with serum levels of DBH activity, but not previously studied in ADHD. Results indicate a significant association between the DBH TaqI A1 allele and ADHD (P = 0.018) with a relative risk of 1.33. The DBH GT repeat 4 allele, which is associated with high serum levels of DBH, occurred more frequently in the ADHD group than controls, but the difference did not reach statistical significance. Associations were not found with the SLC6A3 10 repeat or DRD4 7 repeat alleles. These results indicate that the DBH TaqI A allele, or another polymorphism in linkage disequilibrium with this allele, may confer increased susceptibility towards ADHD.
Published:
May 14, 2003
Title:
Getting it right: industry sponsorship and medical research
Authors:
Baird, Patricia
Abstract:
Published:
May 12, 2003
Title:
Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials
Authors:
Mensink, Ronald P; Zock, Peter L; Kester, Arnold DM; Katan, Martijn B
Abstract:
Background: The effects of dietary fats on the risk of coronary artery disease (CAD) have traditionally been estimated from their effects on LDL cholesterol. Fats, however, also affect HDL cholesterol, and the ratio of total to HDL cholesterol is a more specific marker of CAD than is LDL cholesterol. Objective: The objective was to evaluate the effects of individual fatty acids on the ratis of total to HDL cholesterol and on serum lipoproteins. Design: We performed a meta-analysis of 60 selected trials and calculated the effects of the amount and type of fat on total:HDL cholesterol and on other lipids. Results: The ratio did not change if carbohydrates replaced saturated fatty acids, but it decreased if cis unsaturated fatty acids replaced saturated fatty acids. The effect on total:HDL cholesterol of replacing trans fatty acids with a mix of carbohydrates and cis unsaturated fatty acids was almost twice as large as that of replacing saturated fatty acids. Lauric acid greatly increased total cholesterol, but much of its effect was on HDL cholesterol. Consequently, oils rich in lauric acid decreased the ratio of total to HDL cholesterol. Myristic and palmitic acids had little effect on the ratio, and stearic acid reduced the ratio slightly. Replacing fats with carbohydrates increased fasting triacylglycerol concentrations. Conclusions: The effects of dietary fats on total:HDL cholesterol may differ markedly from their effects on LDL. The effects of fats on these risk markers should not in themselves be considered to reflect changes in risk but should be confirmed by prospective observational studies or clinical trials. By that standard, risk is reduced most effectively when trans fatty acids and saturated fatty acids are replaced with cis unsaturated fatty acids. The effects of carbohydrates and of lauric acid–rich fats on CAD risk remain uncertain. Am J Clin Nutr 2003;77:1146–55.
Published:
April 30, 2003
Title:
Giving Voice to Bear: North American Indian Myths, Rituals, and Images of the Bear
Authors:
Rockwell, David
Abstract:
In this new edition of a classic, David Rockwell describes the captivating and awe-inspiring presence of the bear in Native American rituals. The bear played a central role in shamanic rights, initiation, healing and hunting ceremonies, and new year celebrations. Considered together, these traditions are another way of looking at the world, one in which the mysteries of the universe are revealed through animals.
Published:
April 20, 2003
Title:
New Study: Low-Carb Diets Work Without Boosting Heart Risk : LC Research/Media Forum : Active Low-Carber Forums
Authors:
Abstract:
Low-Carb Diets Work Without Boosting Heart Risk Women lost twice the weight as those on low-fat plans By Kathleen Doheny HealthScoutNews Reporter FRIDAY, April 18 (HealthScoutNews) -- Obese women who are otherwise healthy can lose twice the weight on a low-carbohydrate diet plan as on a traditional low-fat plan. And they can do so without compromising their cardiovascular health, at least in the short term, new research concludes. The new report, published in the April issue of The Journal of Clinical Endocrinology and Metabolism, promises to refuel the diet debate over whether low-carb or low-fat is the better approach. The controversial low-carbohydrate approach to weight loss was popularized by Dr. Robert Atkins, who died Thursday from injuries sustained in a fall during a recent snowstorm. Because low-carbohydrate plans include a high percentage of calories from fat and protein, concern has been expressed over the potential cardiovascular damage such a diet might do. Study author Bonnie Brehm, an assistant professor in the college of nursing at the University of Cincinnati, says the results surprised her: "We had hypothesized that this [low-carb plan] would harm their cardiovascular health." "This was funded by the American Heart Association [as well as other sources]. Our hypothesis was that the low-fat group would lose more weight and body fat for sure." In fact, after six months, the 22 women on the low-carb plan averaged an 18.7-pound loss, while the 20 women on the low-fat plan averaged an 8.5-pound loss. Both groups also showed improvement in markers of cardiovascular health, such as blood pressure, blood lipids and blood cholesterol levels, Brehm says. The women ranged in age from 29 to 58, but most were in their 40s. Their body mass index (BMI) ranged from 29.5 to more than 37. A BMI of 30 marks the beginning of obesity. The low-carbohydrate group, at the three-month mark, was averaging 15 percent of calories from carbohydrates, 28 percent from protein and 57 percent from fat. At the six-month mark, they were eating 30 percent carbs, 23 percent protein and 46 percent fat. The low-fat group was averaging 54 percent of calories from carbohydrates three months into the study, 18 percent from protein and 28 percent from fat. At six months, the totals were 53 percent carbs, 18 percent protein and 29 percent fat. Average calorie intake was similar for both groups -- 1,302 a day for the low-carb group after six months and 1,247 for the low-fat group. Under current recommended guidelines set by the National Academies of Sciences, Americans are advised to take in 45 percent to 65 percent of calories from carbohydrates, 20 percent to 35 percent from fat and 10 percent to 35 percent from protein. Brehm isn't sure why the low-carb group lost more weight. The women agreed they would not change their exercise habits during the study. "I told them, if you are a couch potato today [at the start of the study], you must remain a couch potato for six months," Brehm says. "If you walk four times a week, continue." She plans to research the matter further. Another dietary expert familiar with the new study says she wouldn't advise women to go the low-carbohydrate route to lose weight. "The study was only six months," says Evelyn Tribole, a dietitian and author of numerous nutrition books, including the revised "Intuitive Eating," due out from St. Martin's Press later this year. She points out the pitfalls of low-carbohydrate diets. "When you go on such a low-carb diet, there's not much food left to select from," she says. And exercising for an hour or 90 minutes at a stretch may be more difficult on such a diet, she says, because the body depends on carbohydrates for energy.
Published:
April 17, 2003
Title:
Efficacy and Safety of Low-Carbohydrate Diets: A Systematic Review
Authors:
Bravata, Dena M.; Sanders, Lisa; Huang, Jane; Krumholz, Harlan M.; Olkin, Ingram; Gardner, Christopher D.; Bravata, Dawn M.
Abstract:
ContextLow-carbohydrate diets have been popularized without detailed evidence of their efficacy or safety. The literature has no clear consensus as to what amount of carbohydrates per day constitutes a low-carbohydrate diet.ObjectiveTo evaluate changes in weight, serum lipids, fasting serum glucose, and fasting serum insulin levels, and blood pressure among adults using low-carbohydrate diets in the outpatient setting.Data SourcesWe performed MEDLINE and bibliographic searches for English-language studies published between January 1, 1966, and February 15, 2003, with key words such as low carbohydrate, ketogenic, and diet.Study SelectionWe included articles describing adult, outpatient recipients of low-carbohydrate diets of 4 days or more in duration and 500 kcal/d or more, and which reported both carbohydrate content and total calories consumed. Literature searches identified 2609 potentially relevant articles of low-carbohydrate diets. We included 107 articles describing 94 dietary interventions reporting data for 3268 participants; 663 participants received diets of 60 g/d or less of carbohydrates—of whom only 71 received 20 g/d or less of carbohydrates. Study variables (eg, number of participants, design of dietary evaluation), participant variables (eg, age, sex, baseline weight, fasting serum glucose level), diet variables (eg, carbohydrate content, caloric content, duration) were abstracted from each study.Data ExtractionTwo authors independently reviewed articles meeting inclusion criteria and abstracted data onto pretested abstraction forms.Data SynthesisThe included studies were highly heterogeneous with respect to design, carbohydrate content (range, 0-901 g/d), total caloric content (range, 525-4629 kcal/d), diet duration (range, 4-365 days), and participant characteristics (eg, baseline weight range, 57-217 kg). No study evaluated diets of 60 g/d or less of carbohydrates in participants with a mean age older than 53.1 years. Only 5 studies (nonrandomized and no comparison groups) evaluated these diets for more than 90 days. Among obese patients, weight loss was associated with longer diet duration (P = .002), restriction of calorie intake (P = .03), but not with reduced carbohydrate content (P = .90). Low-carbohydrate diets had no significant adverse effect on serum lipid, fasting serum glucose, and fasting serum insulin levels, or blood pressure.ConclusionsThere is insufficient evidence to make recommendations for or against the use of low-carbohydrate diets, particularly among participants older than age 50 years, for use longer than 90 days, or for diets of 20 g/d or less of carbohydrates. Among the published studies, participant weight loss while using low-carbohydrate diets was principally associated with decreased caloric intake and increased diet duration but not with reduced carbohydrate content.
Published:
April 8, 2003
Title:
Low-Carbohydrate Diets and Realities of Weight Loss
Authors:
Bray, George A.
Abstract:
Obesity is a worldwide epidemic and will be followed by a worldwide epidemic of diabetes.1 While diet, lifestyle, and exercise are the cornerstones of current approaches to treat obesity, they have been ineffective in stemming the current epidemic. In this issue of THE JOURNAL, the article by...
Published:
April 8, 2003
Title:
Functional analysis of the N-terminal domain of the Myc oncoprotein
Authors:
Oster, Sara K.; Mao, Daniel Y. L.; Kennedy, James; Penn, Linda Z.
Abstract:
Myc is a multifunctional nuclear phosphoprotein that can drive cell cycle progression, apoptosis and cellular transformation. Myc orchestrates these activities at the molecular level by functioning as a regulator of gene transcription to activate or repress specific target genes. Previous studies have shown that both the Myc N-terminal domain (NTD) and the C-terminal domain (CTD) are essential for Myc functions. The role of the CTD is relatively well understood as it encodes a basic helix-loop-helix leucine zipper motif important for DNA binding and protein-protein interactions. By contrast, the role of the NTD and the specific domains responsible for different Myc activities are not as well defined. To investigate the regions of the NTD necessary for Myc function and to determine whether these activities are overlapping or independent of one another, we have conducted a detailed structure-function analysis of the Myc NTD. We assessed the ability of a number of deletion and point mutants within the highly conserved regions of the Myc NTD to induce cell cycle progression, apoptosis and transformation as well as repress and activate expression of endogenous target genes. Our analyses highlight the complexity of the Myc NTD and extend previous studies. For example, we show most Myc mutants that were compromised as repressors of gene transcription retained the ability to activate gene transcription, reinforcing the concept that these activities can be uncoupled. Repression of two different target genes could be distinguished by specific mutants, further supporting the notion of at least two different Myc repression mechanisms. Mutants disabled at both inducing and repressing gene transcription could not maximally drive the biological activities of Myc, indicating these functions are tightly linked. Indeed, a close association of Myc repression and apoptosis was also observed.
Published:
April 2, 2003
Title:
A Randomized Trial Comparing a Very Low Carbohydrate Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women
Authors:
Brehm, Bonnie J.; Seeley, Randy J.; Daniels, Stephen R.; D’Alessio, David A.
Abstract:
Untested alternative weight loss diets, such as very low carbohydrate diets, have unsubstantiated efficacy and the potential to adversely affect cardiovascular
Published:
March 31, 2003
Title:
Non-occlusal dental microwear variability in a sample of Middle and Late Pleistocene human populations from Europe and the Near East
Authors:
Pérez-Pérez, Alejandro; Espurz, Vanesa; Bermúdez de Castro, José Marı́a; de Lumley, Marie Antoinette; Turbón, Daniel
Abstract:
Non-occlusal, buccal tooth microwear variability has been studied in 68 fossil humans from Europe and the Near East. The microwear patterns observed suggest that a major shift in human dietary habits and food processing techniques might have taken place in the transition from the Middle to the Late Pleistocene populations. Differences in microwear density, average length, and orientation of striations indicate that Middle Pleistocene humans had more abrasive dietary habits than Late Pleistocene populations. Both dietary and cultural factors might be responsible for the differences observed. In addition, the Middle Paleolithic Neandertal specimens studied show a highly heterogeneous pattern of microwear when compared to the other samples considered, which is inconsistent with a hypothesis of all Neandertals having a strictly carnivorous diet. The high density of striations observed in the buccal surfaces of several Neandertal teeth might be indicative of the inclusion of plant foods in their diet. The buccal microwear variability observed in the Neandertals is compatible with an overall exploitation of both plant and meat foods on the basis of food availability. A preliminary analysis of the relationship between buccal microwear density and climatic conditions prevailing in Europe during the Late Pleistocene has been attempted. Cold climatic conditions, as indicated by oxygen isotope stage data, seem to be responsible for higher densities of microwear features, whereas warmer periods could correspond to a reduced pattern of scratch density. Such a relationship would be indicative of less abrasive dietary habits, perhaps more meat dependent, during warmer periods.
Published:
March 31, 2003
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