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Title:
Ketogenic diets for weight loss: A review of their principles, safety and efficacy
Authors:
Sumithran, Priya; Proietto, Joseph
Abstract:
SUMMARY: Low-carbohydrate "ketogenic" diets have increased in popularity over recent years as a means of weight loss. Published studies of these diets have been highly heterogeneous, and it remains unclear to what degree dietary carbohydrate intake must be restricted in order to induce ketosis. Despite concern that they are often relatively high in fat, ketogenic low-carbohydrate diets have been generally shown to compare favourably with low-fat diets in terms of weight loss and improvements in triglyceride and high-density lipoprotein levels. This review includes a brief overview of ketone body metabolism, and summarises the literature regarding the safety and efficacy of ketogenic diets for weight loss.:
Published:
2008-03
Title:
Subtype differences in adults with attention-deficit/hyperactivity disorder (ADHD) with regard to ADHD-symptoms, psychiatric comorbidity and psychosocial adjustment
Authors:
Sobanski, Esther; Brüggemann, Daniel; Alm, Barbara; Kern, Sebastian; Philipsen, Alexandra; Schmalzried, Hannah; Hesslinger, Bernd; Waschkowski, H.; Rietschel, Marcella
Abstract:
BACKGROUND: To date, nearly all research of subtype differences in ADHD has been performed in children and only two studies, with conflicting results, have covered this subject in adults with ADHD. OBJECTIVE: This study examined subtype differences in the clinical presentation of ADHD-symptoms, related psychopathological features, psychosocial functioning and comorbid psychiatric disorders in adults with ADHD. METHOD: One hundred and eighteen adults with ADHD, diagnosed according to DSM-IV criteria, and a population based control group underwent diagnostic evaluations with clinical interviews for ADHD, DSM-IV disorders and demographic features. Comparisons were made between ADHD combined type (n=64), predominantly inattentive type (n=30) and predominantly inattentive type, anamnestically combined type (n=24), relative to each other and to a community control group (n=70). RESULTS: The four groups did not differ in age and gender composition. All ADHD groups had significantly less education, were significantly more often unemployed and reported significantly more lifetime psychiatric comorbidity than controls. In comparison to each other, the three ADHD groups differed mainly in core symptoms and the pattern of comorbid psychiatric disorders, whereas no prominent differences in associated psychopathological features and most of the assessed psychosocial functions could be found. Patients with ADHD combined type and inattentive, anamnestically combined type both presented with significantly more hyperactive symptoms and also showed more impulsive symptoms than those with the predominantly inattentive type. With a similar overall lifetime psychiatric comorbidity in the three groups, patients with ADHD combined type and inattentive, anamnestically combined type suffered significantly more from lifetime substance use disorders than patients with predominantly inattentive type. CONCLUSION: Our results clearly show impaired psychosocial adjustment and elevated risk for additional psychiatric disorders in adults with all subtypes of ADHD, compared to healthy controls. They provide preliminary evidence that in adult ADHD there might be a subgroup of patients, which is classified as predominantly inattentive subtype according to current diagnostic criteria, but which in its clinical presentation is in between ADHD combined and inattentive type. Further studies are needed to evaluate this finding and to gain a clear picture of its validity.
Published:
2008-03
Title:
The relative impact of a vegetable-rich diet on key markers of health in a cohort of Australian adolescents
Authors:
Grant R; Bilgin A; Zeuschner C; Guy T; Pearce R; Hokin B; Ashton J
Abstract:
Childhood obesity is a widespread health problem in Australia. Overweight in childhood can lead to adult overweight and the development of risk factors for cardiovascular disease (CVD). Effective strategies for reducing childhood obesity are urgently required. A vegetarian diet has been shown to be an effective prophylactic to many lifestyle diseases in the adult population and may therefore be beneficial in children. However the metabolic demands of adolescents are different to adults and the impact of a vegetarian diet on CVD markers in this demographic is not certain. We compared key physiological and biochemical markers of health against responses to a modified, Schools Physical Activity and Nutrition Survey (SPANS) using one-way and two-way Analysis of Variance. 215 adolescents (14-15yrs) from 5 Adventist secondary schools in the Sydney and Hunter regions of New South Wales, Australia, participated in this study. Adolescents consuming predominantly vegetarian foods showed significantly better scores on markers of cardiovascular health, including, body mass index (BMI), waist circumference, Cholesterol/High density lipoprotein ratio and low density lipoprotein. Adolescents consuming nuts more than once per week, also showed lower scores for BMI and serum glucose irrespective of their vegetarian status. Markers of general health including haemoglobin and average height were not different between groups; however a lower serum level of vitamin B12 was apparent in the vegetarian cohort. Surprisingly, exercise on its own was not statistically associated with any of the risk factors tested suggesting that diet may be the most significant factor in promoting health in this age group.
Published:
2008-03
Title:
The stress system in depression and neurodegeneration: focus on the human hypothalamus
Authors:
Bao, A.-M.; Meynen, G.; Swaab, D. F.
Abstract:
The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) release from the pituitary, which subsequently causes cortisol release from the adrenal cortex. The CRH neurons co-express vasopressin (AVP) which potentiates the CRH effects. CRH neurons project not only to the median eminence but also into brain areas where they, e.g., regulate the adrenal innervation of the autonomic system and affect mood. The hypothalamo-neurohypophysial system is also involved in stress response. It releases AVP from the PVN and the supraoptic nucleus (SON) and oxytocin (OXT) from the PVN via the neurohypophysis into the bloodstream. The suprachiasmatic nucleus (SCN), the hypothalamic clock, is responsible for the rhythmic changes of the stress system. Both centrally released CRH and increased levels of cortisol contribute to the signs and symptoms of depression. Symptoms of depression can be induced in experimental animals by intracerebroventricular injection of CRH. Depression is also a frequent side effect of glucocorticoid treatment and of the symptoms of Cushing's syndrome. The AVP neurons in the hypothalamic PVN and SON are also activated in depression, which contributes to the increased release of ACTH from the pituitary. Increased levels of circulating AVP are also associated with the risk for suicide. The prevalence, incidence and morbidity risk for depression are higher in females than in males and fluctuations in sex hormone levels are considered to be involved in the etiology. About 40% of the activated CRH neurons in mood disorders co-express nuclear estrogen receptor (ER)-alpha in the PVN, while estrogen-responsive elements have been found in the CRH gene promoter region, and estrogens stimulate CRH production. An androgen-responsive element in the CRH gene promoter region initiates a suppressing effect on CRH expression. The decreased activity of the SCN is the basis for the disturbances of circadian and circannual fluctuations in mood, sleep and hormonal rhythms found in depression. Neuronal loss was also reported in the hippocampus of stressed or corticosteroid-treated rodents and primates. Because of the inhibitory control of the hippocampus on the HPA-axis, damage to this structure was expected to disinhibit the HPA-axis, and to cause a positive feedforward cascade of increasing glucocorticoid levels over time. This 'glucocorticoid cascade hypothesis' of stress and hippocampal damage was proposed to be causally involved in age-related accumulation of hippocampal damage in disorders like Alzheimer's disease and depression. However, in postmortem studies we could not find the presumed hippocampal damage of steroid overexposure in either depressed patients or in patients treated with synthetic steroids.
Published:
2008-03
Title:
Unlimited energy, restricted carbohydrate diet improves lipid parameters in obese children
Authors:
Dunlap, Brian S.; Bailes, James R.
Abstract:
BACKGROUND: Childhood obesity is a leading health concern. We have previously demonstrated the effectiveness of a restricted-carbohydrate, unlimited energy diet for weight reduction in elementary school-aged children. To our knowledge, there are no studies that have looked at the effect of this diet on lipid profiles in elementary school-aged children. Therefore, the objective of this pilot study was to examine the effect of a restricted-carbohydrate, unlimited protein, unlimited energy diet on lipid profiles in obese children 6 to 12 years of age. METHODS: Overweight children (body mass index >97%) referred to our obesity clinic were treated with a restricted-carbohydrate (
Published:
2008-03
Title:
A comparison of some of the cardiovascular risk factors in vegetarian and omnivorous Turkish females
Authors:
Karabudak, E.; Kiziltan, G.; Cigerim, N.
Abstract:
BACKGROUND: Elevated serum total homocysteine (tHcy) is associated with an increased risk of cardiovascular disease. Homocysteine levels may be influenced by dietary habits. The aim of the present study was to determine the effects of a vegetarian diet on some of the cardiovascular risk factors in Turkish females. METHOD: The study was conducted on 26 vegetarian and 26 omnivore females. Serum tHcy, folate, vitamin B(12) and lipids were determined and dietary data were assessed using a 4-day food intake record at two time points. RESULTS: Compared with omnivores, vegetarians had higher plasma tHcy, 10.8 +/- 3.72 versus 12.6 +/- 5.97, (P < 0.05) and folate (P < 0.05) levels. The prevalence of hyperhomocysteinaemia was higher in vegetarians than in omnivores (34.6% versus 12.0%). In addition, serum vitamin B(12) levels were lower in vegetarians than in omnivores (P
Published:
2008-02
Title:
A very-low-fat vegan diet increases intake of protective dietary factors and decreases intake of pathogenic dietary factors
Authors:
Dewell, Antonella; Weidner, Gerdi; Sumner, Michael D.; Chi, Christine S.; Ornish, Dean
Abstract:
There is increasing evidence that dietary factors in plant-based diets are important in the prevention of chronic disease. This study examined protective (eg, antioxidant vitamins, carotenoids, and fiber) and pathogenic (eg, saturated fatty acids and cholesterol) dietary factors in a very-low-fat vegan diet. Ninety-three early-stage prostate cancer patients participated in a randomized controlled trial and were assigned to a very-low-fat (10% fat) vegan diet supplemented with soy protein and lifestyle changes or to usual care. Three-day food records were collected at baseline (n=42 intervention, n=43 control) and after 1 year (n=37 in each group). Analyses of changes in dietary intake of macronutrients, vitamins, minerals, carotenoids, and isoflavones from baseline to 1 year showed significantly increased intake of most protective dietary factors (eg, fiber increased from a mean of 31 to 59 g/day, lycopene increased from 8,693 to 34,464 mug/day) and significantly decreased intake of most pathogenic dietary factors (eg, saturated fatty acids decreased from 20 to 5 g/day, cholesterol decreased from 200 to 10 mg/day) in the intervention group compared to controls. These results suggest that a very-low-fat vegan diet can be useful in increasing intake of protective nutrients and phytochemicals and minimizing intake of dietary factors implicated in several chronic diseases.
Published:
2008-02
Title:
Dietary cholesterol from eggs increases plasma HDL cholesterol in overweight men consuming a carbohydrate-restricted diet
Authors:
Mutungi, Gisella; Ratliff, Joseph; Puglisi, Michael; Torres-Gonzalez, Moises; Vaishnav, Ushma; Leite, Jose O.; Quann, Erin; Volek, Jeff S.; Fernandez, Maria Luz
Abstract:
Carbohydrate-restricted diets (CRD) significantly decrease body weight and independently improve plasma triglycerides (TG) and HDL cholesterol (HDL-C). Increasing intake of dietary cholesterol from eggs in the context of a low-fat diet maintains the LDL cholesterol (LDL-C)/HDL-C for both hyper- and hypo-responders to dietary cholesterol. In this study, 28 overweight/obese male subjects (BMI = 25-37 kg/m2) aged 40-70 y were recruited to evaluate the contribution of dietary cholesterol from eggs in a CRD. Subjects were counseled to consume a CRD (10-15% energy from carbohydrate) and they were randomly allocated to the EGG group [intake of 3 eggs per day (640 mg/d additional dietary cholesterol)] or SUB group [equivalent amount of egg substitute (0 dietary cholesterol) per day]. Energy intake decreased in both groups from 10,243 +/- 4040 to 7968 +/- 2401 kJ (P < 0.05) compared with baseline. All subjects irrespective of their assigned group had reduced body weight and waist circumference (P < 0.0001). Similarly, the plasma TG concentration was reduced from 1.34 +/- 0.66 to 0.83 +/- 0.30 mmol/L after 12 wk (P < 0.001) in all subjects. The plasma LDL-C concentration, as well as the LDL-C:HDL-C ratio, did not change during the intervention. In contrast, plasma HDL-C concentration increased in the EGG group from 1.23 +/- 0.39 to 1.47 +/- 0.38 mmol/L (P
Published:
2008-02
Title:
Efficacy of the ketogenic diet in the 6-Hz seizure test
Authors:
Hartman, Adam L.; Lyle, Megan; Rogawski, Michael A.; Gasior, Maciej
Abstract:
PURPOSE: Since the ketogenic diet is effective in drug-resistant epilepsies, we sought to determine whether it is active in the 6-Hz seizure test, which identifies agents with a broader spectrum of activity than conventional antiepileptic screening tests. METHODS: Male (3-4 week old) NIH Swiss mice were fed a normal or ketogenic diet ad libitum for 2-21 days. The intensity of the corneal stimulation current required to elicit seizures in the 6-Hz test was measured. Blood glucose and beta-hydroxybutyrate were measured on the day of seizure testing. RESULTS: CC(50) (current intensity producing seizures in 50% of mice tested) was 50.6 mA and 15 mA in mice fed for 12 days with a ketogenic or normal diet, respectively (p
Published:
2008-02
Title:
Factors affecting adherence to a raw vegan diet
Authors:
Link, Lilli B.; Jacobson, Judith S.
Abstract:
The purpose of this study was to evaluate adherence and identify predictors of adherence to a raw vegan diet (i.e., uncooked plant foods) following a stay at a raw vegan institute. In this cohort study of guests at a raw vegan institute, subjects completed written questionnaires upon arrival and 12 weeks later. Of 107 eligible guests, 84 participated. Mean age was 54 years, 23 were male, and 73 white. Fifty-one completed the 12-week follow-up. Eight (16%) reported their diet to be 80% raw vegan at baseline and 14 (28%) at follow-up. Based on a raw vegan dietary adherence score (range 0-42) created for this study, mean adherence (SD) increased from 15.1 (5.4) to 17.0 (5.8) over 12 weeks (p=0.03). Baseline predictors of adherence included: education (beta=0.95), severity of disease (beta=0.98), and self-efficacy to adhere (beta=0.72). Future interventions that evaluate this diet should address self-efficacy, an important, potentially remediable predictor of adherence.
Published:
2008-02
Title:
Fasting-induced changes in the hypothalamus-pituitary-thyroid axis
Authors:
Boelen, Anita; Wiersinga, Wilmar Maarten; Fliers, Eric
Abstract:
Fasting induces profound changes in the hypothalamus-pituitary-thyroid (HPT) axis. The alterations observed in humans and rodents are similar in many ways, although they may be more pronounced and more acute in rodents. The molecular mechanisms underlying the resetting of HPT axis regulation in the framework of caloric deprivation are still incompletely understood. Fascinating studies in rats and mice have shown a dramatic downregulation of thyrotropin-releasing hormone (TRH) gene expression in hypophysiotropic paraventricular nucleus (PVN) neurons during fasting. Direct and indirect effects of decreased serum leptin, as well as effects of increased local triiodothyronine (T3) concentrations, in the hypothalamus during food deprivation contribute to the decreased activity of TRH neurons in the PVN. However, the relative contributions of these complex determinants remain to be defined in more detail. Pituitary thyroid-stimulating hormone (TSH) beta mRNA expression decreases during fasting, and this may be relatively independent of leptin and/or TRH, since leptin administration in this setting does not fully restore pituitary TSH expression, while it does restore TRH expression in the PVN. There may be a role for pituitary peptides, such as neuromedin B, in altered TSH gene expression during fasting. The observed decrease in serum thyroid hormone concentrations results to some extent from diminished thyroidal secretion of thyroid hormones, especially in rodents. Decreased thyroxine (T4) and T3 contribute to the downregulation of T3-responsive genes such as liver D1. The overall result of these complex HPT axis changes in various tissues during fasting is downregulation of the HPT axis, which is assumed to represent an energy-saving mechanism, instrumental in times of food shortage.
Published:
2008-02
Title:
Long-term effects of a diet loosely restricting carbohydrates on HbA1c levels, BMI and tapering of sulfonylureas in type 2 diabetes: a 2-year follow-up study
Authors:
Haimoto, Hajime; Iwata, Mitsunaga; Wakai, Kenji; Umegaki, Hiroyuki
Abstract:
The aim was to assess the long-term effect of a loose restriction of carbohydrate intake (carbohydrate-reduced diet: CARD) compared to a conventional diet (CD) in type 2 diabetes. One hundred and thirty-three type 2 diabetic outpatients followed the CD (n=57, 1734+/-410 kcal, carbohydrate:protein:fat ratio=57:16:26) or CARD (n=76, 1773+/-441 kcal, carbohydrate:protein:fat ratio=45:18:33) according to their own will, and were followed up for 2 years. Glycemic control, body mass index (BMI), serum cholesterols and dose of antidiabetic drugs were assessed at baseline and after 1 and 2 years. At baseline, hemoglobin A1c (HbA1c) and BMI levels were 7.1+/-1.0% and 24.2+/-2.9, respectively, in the CD group, and 7.4+/-1.1% and 25.1+/-3.4 in the CARD group, showing no significant differences. During the 2-year follow-up period, HbA1c levels were significantly improved in the CARD group (CD: 7.5+/-1.3%, CARD: 6.7+/-0.6%, P<0.001), and BMI decreased more significantly in the CARD group (CD: 23.8+/-3.0, CARD: 23.8+/-3.5, P
Published:
2008-02
Title:
Long-term safety of recombinant human growth hormone in turner syndrome
Authors:
Bolar, Katrina; Hoffman, Andrew R; Maneatis, Thomas; Lippe, Barbara
Abstract:
CONTEXT Turner syndrome (TS) affects more than 50,000 girls and women in the United States. The National Cooperative Growth Study (NCGS) has collected efficacy and safety data for 5220 TS children treated with recombinant human GH (rhGH) during the last 20 yr. OBJECTIVES Our objective was to determine frequencies of specific targeted adverse events (AEs) and additional AEs of interest in TS patients. Corresponding safety data in non-TS patients or normal populations were compared for selected AEs. METHODS Patients may be enrolled at rhGH initiation and followed until discontinuation. Investigators submit AE reports describing any event that is potentially rhGH related or is a targeted event. RESULTS The Genentech Drug Safety department received 442 AE reports for TS NCGS patients as of June 30, 2006, including 117 serious AEs. Seven deaths occurred; five resulted from aortic dissections/ruptures. The incidence of certain events known to be associated with rhGH (targeted events), including intracranial hypertension, slipped capital femoral epiphysis, scoliosis, and pancreatitis, was increased compared with other non-TS patients in NCGS. There were 10 new-onset malignancies that occurred, including six in patients without known risk factors. Type 1 diabetes also appeared to be increased compared with other NCGS groups. CONCLUSIONS Children with TS who were treated with rhGH exhibit an increased underlying risk for selected AEs associated with rhGH and for type 1 diabetes, which is likely unrelated to rhGH. The aortic dissection/rupture incidence reflects the higher baseline risk for these events in TS, was consistent with current epidemiological data in smaller TS populations, and is likely unrelated to rhGH. It is not known whether the reported malignancies represent an inherently increased risk in TS patients. Twenty years of experience in 5220 patients indicates no new rhGH-related safety signals in the TS population. The NCGS and similar registries, although focused on the years during rhGH treatment, may also be a window into the natural history of TS in childhood.
Published:
2008-02
Title:
Muscular exercise can cause highly pathological liver function tests in healthy men
Authors:
Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats
Abstract:
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. WHAT THIS STUDY ADDS: Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. AIM: To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. METHODS: Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise. RESULTS: Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P
Published:
2008-02
Title:
The effects of perceived discrimination on diabetes management
Authors:
Ryan, Andrew M.; Gee, Gilbert C.; Griffith, Derek
Abstract:
We investigated whether self-reported racial/ethnic and gender discrimination were associated with lower rates of diabetes management. Analyses focused on 524 respondents with diabetes from the 2001 Commonwealth Health Care Quality Survey. Probit models estimated the marginal effect of self-reported racial/ethnic and gender discrimination on diabetes management, adjusting for racial/ethnic and gender concordance of the patient and physician, as well as a variety of health and sociodemographic indicators. Self-reported racial/ethnic discrimination was associated with a roughly 50% lower marginal probability of receiving a hemoglobin A1c test, foot exam, and blood pressure exam, when accounting for racial/ethnic and gender physician-patient concordance and other factors. Self-reported gender discrimination was associated with 22% lower marginal probability of conducting a hemoglobin test but not associated with the other management indicators. Evidence from this study suggests that racial/ethnic discrimination is an important barrier to diabetes management.
Published:
2008-02
Title:
Vitamin K intake and atherosclerosis
Authors:
Erkkilä, Arja T.; Booth, Sarah L.
Abstract:
PURPOSE OF REVIEW: It has been hypothesized that insufficient intake of vitamin K may increase soft-tissue calcification owing to impaired gamma-carboxylation of the vitamin K-dependent protein matrix gamma-carboxyglutamic acid. The evidence to support this putative role of vitamin K intake in atherosclerosis is reviewed. RECENT FINDINGS: In animal models, multiple forms of vitamin K have been shown to reverse the arterial calcification created by vitamin K antagonists. The human data, however, are less consistent. Phylloquinone, the primary dietary form, has not been associated consistently with the risk of cardiovascular diseases. High menaquinone intake may be associated with lower risk of coronary heart disease mortality, but this needs to be confirmed. SUMMARY: The role of vitamin K in calcification remains controversial. Although biologically plausible, results from the human studies have not consistently supported this hypothesis.
Published:
2008-02
Title:
When do seizures usually improve with the ketogenic diet?
Authors:
Kossoff, Eric H.; Laux, Linda C.; Blackford, Robyn; Morrison, Peter F.; Pyzik, Paula L.; Hamdy, Rana M.; Turner, Zahava; Nordli, Douglas R.
Abstract:
PURPOSE: Parents often expect immediate seizure improvement after starting the ketogenic diet (KD) for their children. The purpose of this study was to determine the typical time to seizure reduction as well as the time after which it was unlikely to be helpful in those children started on the KD. METHODS: Records of all children started on the KD at Johns Hopkins Hospital, Baltimore (n = 83) and Children's Memorial Hospital, Chicago (n = 35) from November 2003 to December 2006 were examined to determine the first day in which seizures were reportedly improved. RESULTS: Of the 118 children started on the KD, 99 (84%) had documented seizure reduction. The overall median time to first improvement was 5 days (range: 1-65 days). Seventy-five percent of children improved within 14 days. In those children who were fasted at KD onset, the time to improvement was quicker (median 5 vs. 14 days, p
Published:
2008-02
Title:
A randomized clinical trial of a standard versus vegetarian diet for weight loss: the impact of treatment preference
Authors:
Burke, L. E.; Warziski, M.; Styn, M. A.; Music, E.; Hudson, A. G.; Sereika, S. M.
Abstract:
BACKGROUND: With obesity rampant, methods to achieve sustained weight loss remain elusive. OBJECTIVE: To compare the long-term weight-loss efficacy of 2 cal and fat-restricted diets, standard (omnivorous) versus lacto-ovo-vegetarian, and to determine the effect of a chosen diet versus an assigned diet. DESIGN, SUBJECTS: A randomized clinical trial was conducted with 176 adults who were sedentary and overweight (mean body mass index, 34.0 kg/m(2)). Participants were first randomly assigned to either receive their preferred diet or be assigned to a diet group and second, were given their diet of preference or randomly assigned to a standard weight-loss diet or a lacto-ovo-vegetarian diet. Participants underwent a university-based weight-control program consisting of daily dietary and exercise goals plus 12 months of behavioral counseling followed by a 6-month maintenance phase. MEASUREMENTS: Percentage change in body weight, body mass index, waist circumference, low- and high-density lipoprotein, glucose, insulin and macronutrient intake. RESULTS: The program was completed by 132 (75%) of the participants. At 18 months, mean percentage weight loss was greater (P=0.01) in the two groups that were assigned a diet (standard, 8.0% (s.d., 7.8%); vegetarian, 7.9% (s.d., 8.1%)) than in those provided the diet of their choice (standard, 3.9% (s.d., 6.1%); vegetarian, 5.3% (s.d., 6.2%)). No difference was observed in weight loss between the two types of diet. Over the 18-month program, all groups showed significant weight loss. CONCLUSIONS: Participants assigned to their dietary preference did not have enhanced treatment outcomes. However, all groups lost weight with losses ranging from 4 to 8% at 18 months.
Published:
2008-01
Title:
A randomized, multicentre, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence
Authors:
Laaksonen, E.; Koski-Jännes, A.; Salaspuro, M.; Ahtinen, H.; Alho, Hannu
Abstract:
Aim: To compare the effects in alcohol-dependent patients of three pharmacotherapies, disulfiram (DIS), naltrexone (NTX), and acamprosate (ACA), when used with a brief manual-based cognitive-behavioural intervention. Method: We conducted a randomized, open label, multicentre naturalistic study in two phases; first, a 12-week continuously supervised medication, followed by targeted medication (TM) up to 52 weeks in addition to a 67-week follow-up period; altogether 119 weeks (2.5 years), in 243 voluntary treatment-seeking alcohol-dependent adult outpatients. Subjects were randomized 1:1:1 to receive supervised NTX, ACA or DIS, 50, 1998, or 200 mg, respectively, per day, plus a brief manual-based cognitive-behavioural intervention. The patients were met in the second and sixth weeks, and then after 3, 6, and 12 months. The primary outcome measures were the time (days) to first heavy drinking day (HDD), and time during the first 3 months to the first drinking day after medication started. Secondary variables were abstinent days/week (0 drinks/day), average weekly alcohol intake, Alcohol Use Disorder Identification Test (AUDIT), Severity of Alcohol Dependence Data (SADD), and quality of life (QL) measures. Results: All three study groups showed marked reduction in drinking, from baseline to the end of the study. During the continuous medication phase, treatment with DIS was more effective in reducing HDDs and average weekly alcohol consumption, and increasing time to the first drink, as well as the number of abstinent days. During the TM period, there were no significant differences between the groups in time to first HDD and days to first drinking, but the abstinence days were significantly more frequent in the DIS group than ACA and NTX. There were no differences between the NTX and ACA groups in either phase of the study of drinking outcomes. However, SADD scores improved more in the NTX group than the ACA group. Conclusions: Patients allocated to ACA, NTX and DIS combined with brief manual-based cognitive behavioural intervention significantly reduce their alcohol consumption and report improved QL. Supervised DIS appeared superior, especially during the continuous medication period, to NTX and ACA.
Published:
2008-01
Title:
An overview of the ketogenic diet for pediatric epilepsy
Authors:
Zupec-Kania, Beth A.; Spellman, Emily
Abstract:
Epilepsy is the most common serious neurological condition in the world, with an estimated prevalence of 1% of the population. The highest incidence occurs in childhood and in the elderly, with lower levels in early adulthood. Traditional epilepsy management includes pharmacological treatment, epilepsy surgery, and vagal nerve stimulation. Despite these therapies, 25% of children continue to have uncontrolled seizures. The ketogenic diet (KD), which has been in use since 1921, is a treatment option for many of these children. A meta-analysis of 19 studies with a combined sample of 1084 pediatric patients was completed in 1998 by Blue Cross Blue Shield. Estimates of the overall efficacy of the KD in controlling seizures were reported as follows: 16% became seizure free, 32% had a >90% reduction in seizures, and 56% had a >50% reduction. The KD is high in fat, moderate in protein, and low in carbohydrates. This combination of energy results in a sustained ketosis that somehow serves to abate seizures through an unknown mechanism. Strict adherence to the diet is required for it to be effective. Newer, more liberal versions of the KDs have been recently introduced and are being studied in children and adults. Administration of all of these metabolically adjusted diets must be medically managed as there can be adverse effects. The focus of this review is on the pediatric application of the KD.
Published:
2008-01
Title:
Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research
Authors:
Spencer, Jeremy P. E.; Abd El Mohsen, Manal M.; Minihane, Ann-Marie; Mathers, John C.
Abstract:
In order to establish firm evidence for the health effects of dietary polyphenol consumption, it is essential to have quantitative information regarding their dietary intake. The usefulness of the current methods, which rely mainly on the assessment of polyphenol intake using food records and food composition tables, is limited as they fail to assess total intake accurately. This review highlights the problems associated with such methods with regard to polyphenol-intake predictions. We suggest that the development of biological biomarkers, measured in both blood and urine, are essential for making accurate estimates of polyphenol intake. However, the relationship between dietary intakes and nutritional biomarkers are often highly complex. This review identifies the criteria that must be considered in the development of such biomarkers. In addition, we provide an assessment of the limited number of potential biomarkers of polyphenol intake currently available.
Published:
2008-01
Title:
Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation
Authors:
Forsythe, Cassandra E.; Phinney, Stephen D.; Fernandez, Maria Luz; Quann, Erin E.; Wood, Richard J.; Bibus, Doug M.; Kraemer, William J.; Feinman, Richard D.; Volek, Jeff S.
Abstract:
Abnormal distribution of plasma fatty acids and increased inflammation are prominent features of metabolic syndrome. We tested whether these components of metabolic syndrome, like dyslipidemia and glycemia, are responsive to carbohydrate restriction. Overweight men and women with atherogenic dyslipidemia consumed ad libitum diets very low in carbohydrate (VLCKD) (1504 kcal:%CHO:fat:protein = 12:59:28) or low in fat (LFD) (1478 kcal:%CHO:fat:protein = 56:24:20) for 12 weeks. In comparison to the LFD, the VLCKD resulted in an increased proportion of serum total n-6 PUFA, mainly attributed to a marked increase in arachidonate (20:4n-6), while its biosynthetic metabolic intermediates were decreased. The n-6/n-3 and arachidonic/eicosapentaenoic acid ratio also increased sharply. Total saturated fatty acids and 16:1n-7 were consistently decreased following the VLCKD. Both diets significantly decreased the concentration of several serum inflammatory markers, but there was an overall greater anti-inflammatory effect associated with the VLCKD, as evidenced by greater decreases in TNF-alpha, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1. Increased 20:4n-6 and the ratios of 20:4n-6/20:5n-3 and n-6/n-3 are commonly viewed as pro-inflammatory, but unexpectedly were consistently inversely associated with responses in inflammatory proteins. In summary, a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet.
Published:
2008-01
Title:
Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum
Authors:
Johnstone, Alexandra M.; Horgan, Graham W.; Murison, Sandra D.; Bremner, David M.; Lobley, Gerald E.
Abstract:
BACKGROUND: Altering the macronutrient composition of the diet influences hunger and satiety. Studies have compared high- and low-protein diets, but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake. OBJECTIVE: We aimed to compare the hunger, appetite, and weight-loss responses to a high-protein, low-carbohydrate [(LC) ketogenic] and those to a high-protein, medium-carbohydrate [(MC) nonketogenic] diet in obese men feeding ad libitum. DESIGN: Seventeen obese men were studied in a residential trial; food was provided daily. Subjects were offered 2 high-protein (30% of energy) ad libitum diets, each for a 4-wk period-an LC (4% carbohydrate) ketogenic diet and an MC (35% carbohydrate) diet-randomized in a crossover design. Body weight was measured daily, and ketosis was monitored by analysis of plasma and urine samples. Hunger was assessed by using a computerized visual analogue system. RESULTS: Ad libitum energy intakes were lower with the LC diet than with the MC diet [P=0.02; SE of the difference (SED): 0.27] at 7.25 and 7.95 MJ/d, respectively. Over the 4-wk period, hunger was significantly lower (P=0.014; SED: 1.76) and weight loss was significantly greater (P=0.006; SED: 0.62) with the LC diet (6.34 kg) than with the MC diet (4.35 kg). The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma (P=0.036 from baseline; SED: 0.62) and 2.99 mmol/L in urine (P
Published:
2008-01
Title:
Egg yolk improves lipid profile, lipid peroxidation and retinal abnormalities in a murine model of genetic hypercholesterolemia
Authors:
Fernández-Robredo, Patricia; Rodríguez, José Antonio; Sádaba, Luis M.; Recalde, Sergio; García-Layana, Alfredo
Abstract:
Carotenoids are believed to inhibit oxidative stress. We investigated the protective effect of lutein and egg yolk supplementation on systemic and retinal alterations in apolipoprotein E-deficient (apoE-/-) mice, an experimental model of hypercholesterolemia and cardiovascular disease. Three-month-old wild-type and apoE-/- mice received one of the following: vehicle, lutein (0.09 mg/kg per day) or egg yolk (0.8 g/kg per day), by gastroesophageal cannula for 3 months. Total cholesterol (TC), triacylglycerol (TG) and lipid peroxidation (TBARS) were measured in plasma. TBARS levels were also determined in retinal homogenates. Ultrastructural morphology was analyzed by electron microscopy. ApoE-/- mice, with increased TC and TG concentrations, had higher systemic (P<.05) and retinal (P<.01) levels of lipid peroxidation than wild-type strains. Electron microscopy showed ultrastructural alterations (basal laminar deposits, open intercellular junctions, increased cytoplasmic vacuoles) in the retinas from apoE-/- mice. Egg yolk significantly reduced plasma TG (P<.05) and, without changes in TC, decreased plasma lipid peroxidation (P<.05). Lutein supplementation marginally affected the parameters. Less severe retinal ultrastructural alterations were observed in apoE-/- mice receiving either egg yolk or lutein. In the apoE-/- mouse model, egg yolk improved the lipid profile and reduced systemic lipid peroxidation (P
Published:
2008-01
Title:
Fish oils for depression?
Authors:
Young, Simon N.
Abstract:
Published:
2008-01
Title:
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy.
Authors:
Twig, Gilad; Elorza, Alvaro; Molina, Anthony J A; Mohamed, Hibo; Wikstrom, Jakob D; Walzer, Gil; Stiles, Linsey; Haigh, Sarah E; Katz, Steve; Las, Guy; Alroy, Joseph; Wu, Min; Py, Bénédicte F; Yuan, Junying; Deeney, Jude T; Corkey, Barbara E; Shirihai, Orian S
Abstract:
Accumulation of depolarized mitochondria within beta-cells has been associated with oxidative damage and development of diabetes. To determine the source and fate of depolarized mitochondria, individual mitochondria were photolabeled and tracked through fusion and fission. Mitochondria were found to go through frequent cycles of fusion and fission in a 'kiss and run' pattern. Fission events often generated uneven daughter units: one daughter exhibited increased membrane potential (delta psi(m)) and a high probability of subsequent fusion, while the other had decreased membrane potential and a reduced probability for a fusion event. Together, this pattern generated a subpopulation of non-fusing mitochondria that were found to have reduced delta psi(m) and decreased levels of the fusion protein OPA1. Inhibition of the fission machinery through DRP1(K38A) or FIS1 RNAi decreased mitochondrial autophagy and resulted in the accumulation of oxidized mitochondrial proteins, reduced respiration and impaired insulin secretion. Pulse chase and arrest of autophagy at the pre-proteolysis stage reveal that before autophagy mitochondria lose delta psi(m) and OPA1, and that overexpression of OPA1 decreases mitochondrial autophagy. Together, these findings suggest that fission followed by selective fusion segregates dysfunctional mitochondria and permits their removal by autophagy.
Published:
2008-01
Title:
Idiopathic central precocious puberty in 28 boys
Authors:
Pigneur, Bénédicte; Trivin, Christine; Brauner, Raja
Abstract:
BACKGROUND: Idiopathic central precocious puberty (CPP) is rare in boys. The aim was to to analyze the presentation and evaluate the frequency of familial factor in boys with idiopathic CPP. MATERIAL/METHODS: Data for 28 boys seen consecutively by the same physician for idiopathic CPP were analyzed. RESULTS: Puberty started after seven years in all the boys. The associations were intrauterine growth retardation in two, one of whom had Silver Russell syndrome, bilateral retinal degeneration (one case), epilepsy (one case), cryptorchidism (two cases), and inguinal hernia (two cases). All patients had normal basal plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The LH/FSH peaks ratio after a gonadotropin hormone-releasing hormone (GnRH) test was <2 in 8/26 and plasma testosterone <0.5 ng/ml in 5/28. Familial early puberty was found in 12 cases (40%). Familial and non-familial forms had similar characteristics, except that body mass index was greater in the familial form (P1 ng/ml despite shortening the interval between GnRH analogue injections. CONCLUSIONS: Puberty started after seven years in all cases of idiopathic CPP, suggesting that pubertal onset before this age suggests organic CPP. Almost half the cases had familial early puberty.
Published:
2008-01
Title:
Restricted-carbohydrate diets in patients with type 2 diabetes: a meta-analysis
Authors:
Kirk, Julienne K.; Graves, Darby E.; Craven, Timothy E.; Lipkin, Edward W.; Austin, Mary; Margolis, Karen L.
Abstract:
Many current popular weight-loss diets advocate restricting carbohydrates, but risks and benefits of these diets for patients with diabetes is unclear. We searched for articles published in English between 1980 and April 2006 regarding carbohydrate-restricted diets that included and reported separate results for adult, nonpregnant patients with type 2 diabetes. Articles were limited to studies completed in the United States and Canada. Available data on study design; carbohydrate composition of diet; duration of diet; and the outcomes of weight, lipid levels (total, low-density lipoprotein and high-density lipoprotein cholesterol, and triglycerides), hemoglobin A1c percent and/or fasting glucose were extracted. A total of 56 studies or reviews were evaluated. Thirteen studies met our inclusion criteria. Meta-regression analyses show that hemoglobin A1c, fasting glucose, and some lipid fractions (triglycerides) improved with lower carbohydrate-content diets. Overall effect on weight was equivocal among the studies evaluated in this meta-analysis. Randomized, controlled studies of restricted-carbohydrate diets in patients with diabetes need to be conducted in order to evaluate the overall sustainability of outcomes and long-term safety.
Published:
2008-01
Title:
Tissue depletion of amoxicillin and its major metabolites in pigs: influence of the administration route and the simultaneous dosage of clavulanic acid
Authors:
Reyns, Tim; De Boever, Sandra; De Baere, Siegrid; De Backer, Patrick; Croubels, Siska
Abstract:
A residue depletion study of amoxicillin (AMO) and its major metabolites, amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione, was performed after a single oral (p.o.) and intravenous (i.v.) administration of amoxicillin (20 mg kg (-1)) and amoxicillin/clavulanic acid (20 and 5 mg kg (-1)) to pigs. Animals were slaughtered 12, 36, 48, 60, 72, and 84 h after dosing. Tissue samples were analyzed using liquid chromatography-tandem mass spectrometry. Kidney samples contained high concentrations of amoxicilloic acid metabolite, which depleted much slower from tissues than amoxicillin, both after p.o. (t1/2AMO = 4.5 h vs t1/2AMA = 8 h) and i.v. (t1/2AMO = 4 h vs t1/2AMA = 8 h) administration. Moreover, after oral administration, significantly higher amoxicilloic acid concentrations were measured in liver and kidney than after i.v. administration. The coadministration of amoxicillin with clavulanic acid provoked no significant differences in amoxicilloic acid tissue concentrations as compared to an amoxicillin dosing. The prolonged presence of residues of amoxicilloic acid in edible tissues can play an important role in food safety, because the compound could give rise to a possible health risk, although it is not included in the maximum residue limit legislation.
Published:
2008-01
Title:
Advanced glycation end products induce in vitro cross-linking of α-synuclein and accelerate the process of intracellular inclusion body formation
Authors:
Shaikh, Shamim; Nicholson, Louise F. B.
Abstract:
Cross-linking of α-synuclein and Lewy body formation have been implicated in the dopaminergic neuronal cell death observed in Parkinson's disease (PD); the mechanisms responsible, however, are not clear. Reactive oxygen species and advanced glycation end products (AGEs) have been found in the intracellular, α-synuclein-positive Lewy bodies in the brains of both PD as well as incidental Lewy body disease patients, suggesting a role for AGEs in α-synuclein cross-linking and Lewy body formation. The aims of the present study were to determine 1) whether AGEs can induce cross-linking of α-synuclein peptides, 2) the progressive and time-dependent intracellular accumulation of AGEs and inclusion body formation, and 3) the effects of extracellular or exogenous AGEs on intracellular inclusion formation. We first investigated the time-dependent cross-linking of recombinant human α-synuclein in the presence of AGEs in vitro, then used a cell culture model based on chronic rotenone treatment of human dopaminergic neuroblastoma cells (SH-SY5Y) over a period of 1–4 weeks, in the presence of different doses of AGEs. Cells (grown on coverslips) and cell lysates, collected at the end of every week, were analyzed for the presence of intracellular reactive oxygen species, AGEs, α-synuclein proteins, and intracellular α-synuclein- and AGE-positive inclusion bodies by using immunocytochemical, biochemical, and Western blot techniques. Our results show that AGEs promote in vitro cross-linking of α-synuclein, that intracellular accumulation of AGEs precedes α-synuclein-positive inclusion body formation, and that extracellular AGEs accelerate the process of intracellular α-synuclein-positive inclusion body formation. © 2008 Wiley-Liss, Inc.
Published:
2008
Title:
Altered lipid metabolism in brain injury and disorders
Authors:
Adibhatla, Rao Muralikrishna; Hatcher, J. F.
Abstract:
Published:
2008
Title:
Associations of usual sleep duration with serum lipid and lipoprotein levels
Authors:
Kaneita, Yoshitaka; Uchiyama, Makoto; Yoshiike, Nobuo; Ohida, Takashi
Abstract:
STUDY OBJECTIVES We examined the individual association between sleep duration and a high serum triglyceride, low HDL cholesterol, or high LDL cholesterol level. DESIGN AND SETTING The present study analyzed data from the National Health and Nutrition Survey that was conducted in November 2003 by the Japanese Ministry of Health, Labour and Welfare. This survey was conducted on residents in the districts selected randomly from all over Japan. PARTICIPANTS The subjects included in the statistical analysis were 1,666 men and 2,329 women aged 20 years or older. INTERVENTION N/A. MEASUREMENTS AND RESULTS Among women, both short and long sleep durations are associated with a high serum triglyceride level or a low HDL cholesterol level. Compared with women sleeping 6 to 7 h, the relative risk of a high triglyceride level among women sleeping \textless5 h was 1.51 (95% CI, 0.96-2.35), and among women sleeping \textgreater or =8 h was 1.45 (95% CI, 1.00-2.11); the relative risk of a low HDL cholesterol level among women sleeping \textless5 h was 5.85 (95% CI, 2.29-14.94), and among women sleeping \textgreater or =8 h was 4.27 (95% CI, 1.88-9.72). On the other hand, it was observed that the risk of a high LDL cholesterol level was lower among men sleeping \textgreater or =8 h. These analyses were adjusted for the following items: age, blood pressure, body mass index, plasma glucose level, smoking habit, alcohol consumption, dietary habits, psychological stress, and taking cholesterol-lowering medications. CONCLUSIONS Usual sleep duration is closely associated with serum lipid and lipoprotein levels.
Published:
2008
Title:
Beneficial effects of Waon therapy on patients with chronic heart failure: Results of a prospective multicenter study
Authors:
Miyata, Masaaki; Kihara, Takashi; Kubozono, Takuro; Ikeda, Yoshiyuki; Shinsato, Takuro; Izumi, Toru; Matsuzaki, Masunori; Yamaguchi, Tetsu; Kasanuki, Hiroshi; Daida, Hiroyuki; Nagayama, Masatoshi; Nishigami, Kazuhiro; Hirata, Kumiko; Kihara, Koichi; Tei, Chuwa
Abstract:
Background: We conducted a prospective multicenter case-control study to confirm the clinical efficacy and safety of Waon therapy on chronic heart failure (CHF). Methods: Patients (n = 188) with CHF were treated with standard therapy for at least 1 week, and then were randomized to Waon therapy (n = 112) or a control group (n = 76). All patients continued conventional treatment for an additional 2 weeks. The Waon therapy group was treated daily with a far infrared-ray dry sauna at 60 °C for 15 min and then kept on bed rest with a blanket for 30 min for 2 weeks.
Published:
2008
Title:
Biochemical effects of consumption of eggs containing omega-3 polyunsaturated fatty acids
Authors:
Ohman, Marie; Akerfeldt, Torbjörn; Nilsson, Ingela; Rosen, Christer; Hansson, Lars-Olof; Carlsson, Martin; Larsson, Anders
Abstract:
Today, eggs with an increased content of -3 fatty acids are available but there are few publications on the effects of consumption of such eggs on the lipoproteins and acute phase markers in humans. The aim of the present study was to evaluate the effects of consumption of standard eggs and -3 enriched eggs on lipoproteins, glucose and inflammation markers. Nineteen healthy volunteers consumed one extra egg per day of either standard eggs or omega-3 enriched eggs in a double-blind, cross-over study. The duration of each period was 1 month. The effects of the different egg diets on apolipoprotein A1 and B (Apo A1 and B), lipoprotein (a), creatinine, cystatin C, C-reactive protein, serum amyloid protein A, interleukin 6, triglycerides, glucose, total-, high-density lipoprotein and low-density lipo-protein cholesterol concentrations were analyzed. Addition of one regular egg per day to the normal diet had no negative impact on blood lipids or inflammation markers. Consumption of omega-3 enriched eggs resulted in higher levels of ApoA1, lower ApoB/ApoA1 ratio and lower plasma glucose. These effects have been associated in previous studies with a reduced risk for cardiovascular mortality and diabetes.
Published:
2008
Title:
Bone mineral density of vegetarian and non-vegetarian adults in Taiwan
Authors:
Wang, Yuh-Feng; Chiu, Jainn-Shiun; Chuang, Mei-Hua; Chiu, Jing-Er; Lin, Chin-Lon
Abstract:
Diet is thought to be one of the leading causes of bone mineral loss in aging people. In this study, we explored the potential impact of a vegetarian diet on bone mineral density (BMD) in adult Taiwanese men and women. This was a cross-sectional study of the relationship between diet (vegetarian versus non-vegetarian) and BMD and the incidence of osteoporosis. Bone mineral density was determined in a cohort of 1865 adult male and female patients who underwent routine examination in a regional teaching hospital in Taiwan between February 2003 and February 2004. Subjects with definite vertebral problems, known osteopathy, or poor posture were excluded. Dual-energy X-ray absorptiometry (DEXA) was used to determine BMD, on the right hip in men and on lumbar vertebrae L2 to L4 in women. The subjects were grouped according to sex and diet, and were then stratified by age within each of the four groups. The outcome measures were the BMD value and the incidence of osteopenia or osteoporosis according to defined criteria. Bone mineral density gradually declined with increasing age in Taiwanese men, while Taiwanese women showed a precipitous decrease in BMD after the 5th decade. However, no statistical differences in BMD were observed between vegetarians and non-vegetarians of either sex. The proportion of subjects with osteopenia or osteoporosis also appeared comparable between vegetarians and non-vegetarians of either sex. BMD shows an age-related decline in Taiwanese men and women, and eating a vegetarian diet does not appear to affect this decline.
Published:
2008
Title:
Closing the Gap in a Generation: Health Equity Through Action on the Social Determinants of Health : Commission on Social Determinants of Health Final Report
Authors:
World Health Organization
Abstract:
The Final Report of the Commission on Social Determinants of Health sets out key areas-of daily living conditions and of the underlying structural drivers that influence them-in which action is needed. It provides analysis of social determinants of health and concrete examples of actions that have proven effective in improving health and health equity in countries at all levels of socioeconomic development. Part 1 lays out the rationale for a global movement to advance health equity through action on the social determinants of health. Part 2 outlines the approach the Commission took to evidence, and to the indispensable value of acknowledging and using the rich diversity of different types of knowledge. Parts 3, 4, and 5 set out in more detail the Commission's findings and recommendations. Part 6, finally, reprises the global networks-the regional connections to civil society worldwide, the growing caucus of country partners taking the social determinants of health agenda forward, the vital research agendas, and the opportunities for change at the level of global governance and global institutions-that the Commission has built and on which the future of a global movement for health equity will depend.
Published:
2008
Title:
Dental remains from Dmanisi (Republic of Georgia): morphological analysis and comparative study
Authors:
Martinón-Torres, M.; Bermúdez de Castro, J. M; Gómez-Robles, A.; Margvelashvili, A.; Prado, L.; Lordkipanidze, D.; Vekua, A.
Abstract:
Published:
2008
Title:
Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats
Authors:
Stranahan, Alexis M.; Norman, Eric D.; Lee, Kim; Cutler, Roy G.; Telljohann, Richard S.; Egan, Josephine M.; Mattson, Mark P.
Abstract:
Overall dietary energy intake, particularly the consumption of simple sugars such as fructose, has been increasing steadily in Western societies, but the effects of such diets on the brain are poorly understood. Here, we used functional and structural assays to characterize the effects of excessive caloric intake on the hippocampus, a brain region important for learning and memory. Rats fed with a high-fat, high-glucose diet supplemented with high-fructose corn syrup showed alterations in energy and lipid metabolism similar to clinical diabetes, with elevated fasting glucose and increased cholesterol and triglycerides. Rats maintained on this diet for 8 months exhibited impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation at Schaffer collateral--CA1 synapses. These changes occurred concurrently with reductions in levels of brain-derived neurotrophic factor in the hippocampus. We conclude that a high-calorie diet reduces hippocampal synaptic plasticity and impairs cognitive function, possibly through BDNF-mediated effects on dendritic spines.
Published:
2008
Title:
Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle
Authors:
Karagounis, L. G.; Simpson, E. J.; Wackerhage, H.; Layfield, R.; Smith, K.; Peirce, N.; Atherton, P.; Greenhaff, P. L.; Hazell, M.; Rennie, M. J.; Selby, A.
Abstract:
We determined the effects of intravenous infusion of amino acids (AA) at serum insulin of 5, 30, 72, and 167 mU/l on anabolic signaling, expression of ubiquitin-proteasome components, and protein turnover in muscles of healthy young men. Tripling AA availability at 5 mU/l insulin doubled incorporation of [1-(13)C]leucine [i.e., muscle protein synthesis (MPS), P \textless 0.01] without affecting the rate of leg protein breakdown (LPB; appearance of d(5)-phenylalanine). While keeping AA availability constant, increasing insulin to 30 mU/l halved LPB (P \textless 0.05) without further inhibition at higher doses, whereas rates of MPS were identical to that at 5 mU/l insulin. The phosphorylation of PKB Ser(473) and p70(S6k) Thr(389) increased concomitantly with insulin, but whereas raising insulin to 30 mU/l increased the phosphorylation of mTOR Ser(2448), 4E-BP1 Thr(37/46), or GSK3beta Ser(9) and decreased that of eEF2 Thr(56), higher insulin doses to 72 and 167 mU/l did not augment these latter responses. MAFbx and proteasome C2 subunit proteins declined as insulin increased, with MuRF-1 expression largely unchanged. Thus increasing AA and insulin availability causes changes in anabolic signaling and amounts of enzymes of the ubiquitin-proteasome pathway, which cannot be easily reconciled with observed effects on MPS or LPB.
Published:
2008
Title:
Do We Need Gastric Acid?
Authors:
Pohl, D.; Fox, M.; Fried, M.; Göke, B.; Prinz, C.; Mönnikes, H.; Rogler, G.; Dauer, M.; Keller, J.; Lippl, F.; Schiefke, I.; Seidler, U.; Allescher, H. D.
Abstract:
Evidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage; however, in modern-day humans the need for gastric acid can be questioned in light of the widespread use of safe and effective pharmacologic acid suppression. The Kandahar Working Group addressed questions concerning the need, production and effects of gastric acid, specifically: (1) motility in the upper gastrointestinal (GI) tract; (2) neuroendocrine factors; (3) digestive and mucosal processes; (4) microbiology, and (5) central processes and psychological involvement. We addressed each topic with the individual models available to answer our questions including animal versus human studies, pharmacologic, surgical as well as pathophysiologic states of acid suppression.
Published:
2008
Title:
Dominique-Jean Larrey, chief surgeon of the French Army with Napoleon in Egypt: notes and observations on Larrey's medical memoirs based on the Egyptian campaign.
Authors:
Wood, M.
Abstract:
Abstract This paper explores the role of vitamin C (ascorbic acid) in the foodways of hunter-gatherers—both ethnohistoric and Paleolithic—whose diet seasonally or over much of the year, of necessity, was comprised largely of animal foods. In order to stave off scurvy, such foragers had to obtain a minimum of about 10 mg per day of vitamin C. However, there is little to no vitamin C in muscle meat, being concentrated instead in various internal organs and brain. Even ruminant stomach contents, despite the abundance of partially digested plants, contains almost none. Moreover, many of the “meatiest” anatomical units in a carcass, such as the thigh muscles or “hams” associated with the femur, are extremely lean in most wild ungulates, making them nutritionally much less valuable to northern foragers than archaeologists commonly assume (for example, Inuit and other indigenous peoples of the arctic and subarctic commonly use the thigh meat as dog food). Vitamin C is also the most unstable vitamin, rapidly degrading or disappearing when exposed to water, air, light, heat, and pH levels above about 4.0. As a consequence, common methods of preparing meat for storage and consumption (e.g., drying, roasting, boiling) may lead to significant loss of vitamin C. There are two effective methods of minimizing such loss: (1) eating meat raw (fresh or frozen); and (2) eating the meat after it has been putrefied. Putrefaction has distinct advantages that make it a common, if not essential, way of preparing and preserving meat among northern latitude foragers and, for the same reasons, very likely also among Paleolithic foragers in the colder climes of Pleistocene Eurasia. Putrefaction “pre-digests” the meat (including the organs), making it much less costly to ingest and metabolize than raw meat; and it lowers the pH, greatly increasing the stability of vitamin C. These observations offer insights into critical nutritional constraints that likely had to be addressed by Neanderthals and later hominins in any context where their diet was heavily meat-based for a substantial part of the year.
Published:
2008
Title:
Dominique-Jean Larrey, chief surgeon of the French Army with Napoleon in Egypt: notes and observations on Larrey's medical memoirs based on the Egyptian campaign.
Authors:
Wood, M.
Abstract:
In 2013, Hardy et al. offered a broad behavioural context for the hypothesis that the ingestion of non-nutritional plants (yarrow and camomile) by Neanderthals was for the purpose of self-medication. Chemical traces of these plants had been detected in samples of dental calculus from Neanderthals at the site of El Sidrón, Spain, along with traces of bitumen and wood smoke, as well as starch granules that showed evidence of roasting (Hardy et al. 2012). Subsequently, the presence of traces of resin and a piece of non-edible conifer wood were also identified from these samples (Radini et al. 2016). Although not rejecting our interpretation for the presence of these two non-edible plants as evidence of medicinal plant use, two recent articles offer alternative scenarios for why and how those plants may have reached the mouth and, eventually, the dental calculus of the individual concerned. Buck and Stringer (2014) suggest that the plants were not deliberately ingested, and that the traces of yarrow and camomile were in fact embedded in the chyme, or stomach contents, of herbivore prey. Krief et al. (2015) propose two hypotheses: first, they suggest that the plants could have been used to flavour meat; second, while not ruling out the possibility that they could be medicinal, they argue on a technical point that the plants were not self-administered but were provided by a caregiver. Here, we examine these suggestions and consider their probability and feasibility as alternatives to our original proposal of self-medication.
Published:
2008
Title:
Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD)
Authors:
Oades, Robert D.
Abstract:
Poor control of attention-related and motor processes, often associated with behavioural or cognitive impulsivity, are typical features of children and adults with attention-deficit hyperactivity disorder (ADHD). Until recently clinicians have observed little need to improve on or add to the catecholaminergic model for explaining the features of ADHD. Recent genetic and neuroimaging studies however provide evidence for separate contributions of altered dopamine (DA) and serotonin (5-HT) function in this disorder. Genetic studies imply that for both DA and 5-HT systems variants may frequently occur in ADHD for neurotransmitter uptake, synthesis and breakdown functions. The separate distributions in the brain of mesolimbic DA transporter and mesocortical DA D4 binding sites, both strongly implicated in ADHD, draws attention to potentially differential contributions from the 5-HT system. However, the evidence here points less towards an anatomical differentiation, as towards one in terms of inhibitory/facilitatory pre/post-synaptic location of receptors in the 5-HT(1) and 5-HT(2) families. While the monoamine metabolite levels excreted in ADHD are often correlated, this may well flow from a starting point where 5-HT activity is anomalously higher or lower than the generally lower than normal levels for DA. It appears that perhaps both situations may arise reflecting different diagnostic subgroups of ADHD, and where impulsive characteristics of the subjects reflect externalizing behaviour or cognitive impulsivity. For these features there is clear evidence that DA and 5-HT neuronal systems can and do interact anomalously in ADHD at the level of the soma, the terminals and at a distance. Interactions mediated by macroglia are also likely. However, it remains difficult to ascribe specific mechanisms to their effects (in potentially different subgroups of patients) from this relatively new field of study that has as yet produced rather heterogeneous results.
Published:
2008
Title:
Effects of Yoga on Inflammation and Exercise Capacity in Patients With Chronic Heart Failure
Authors:
Pullen, Paula R.; Nagamia, Sameer H.; Mehta, Puja K.; Thompson, Walter R.; Benardot, Dan; Hammoud, Ramadan; Parrott, Janice M.; Sola, Srikanth; Khan, Bobby V.
Abstract:
Background: Despite recent advances in pharmacologic and device therapy, morbidity and mortality from heart failure (HF) remain high. Yoga combines physical and breathing exercises that may benefit patients with HF. We hypothesized that an 8-week regimen of yoga in addition to standard medical therapy would improve exercise capacity, inflammatory markers, and quality of life (QoL) in patients with HF. Methods and Results: New York Heart Association Class I-III HF patients were randomized to yoga treatment (YT) or standard medical therapy (MT). Measurements included a graded exercise test (GXT) to over(V, ̇) O2 Peak and the following serum biomarkers: interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and extracellular superoxide dismutase (EC-SOD). The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was administered to assess changes in QoL. A total of 19 patients were enrolled after the initial screening. Of the 19 patients, 9 were randomized to YT and 10 to MT. Patients had a mean EF of 25%. GXT time and over(V, ̇) O2 Peak were significantly improved in the YT versus MT groups (+18% in the YT and -7.5% in MT; P = .03 vs. control and +17 in YT and -7.1 in MT; P = .02, respectively). There were statistically significant reductions in serum levels of IL-6 and hsCRP and an increase in EC-SOD in the YT group (all P \textless .005 vs. MT). MLHFQ scores improved by 25.7% in the YT group and by 2.9% in the MT group. Conclusions: Yoga improved exercise tolerance and positively affected levels of inflammatory markers in patients with HF, and there was also a trend toward improvements in QoL. © 2008 Elsevier Inc. All rights reserved.
Published:
2008
Title:
Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification
Authors:
Wallin, Reidar; Schurgers, Leon; Wajih, Nadeem
Abstract:
INTRODUCTION: The transformation of smooth muscle cells (VSMCs) in the vessel wall to osteoblast like cells is known to precede arterial calcification which may cause bleeding complications. The vitamin K-dependent protein MGP has been identified as an inhibitor of this process by binding BMP-2, a growth factor known to trigger the transformation. In this study, we determined if the vitamin K-dependent Gla region in MGP by itself can inhibit the growth factor activity of BMP-2 and if menaquinone-4 (MK4) regulates gene expression in VSMCs. MATERIALS AND METHODS: A synthetic gamma-carboxyglutamic acid (Gla) containing peptide covering the Gla region in human MGP was used to test its ability to inhibit BMP-2 induced transformation of mouse pro-myoblast C2C12 cells into osteoblasts. MK4 was tested by microarray analysis as a gene regulatory molecule in VSMCs. RESULTS AND CONCLUSIONS: The results show that the Gla - but not the Glu-peptide inhibited the transformation which provide evidence that the Gla region in MGP is directly involved in the BMP-2/MGP interaction and emphasizes the importance of the vitamin K-dependent modification of MGP. From the data obtained from the microarray analysis, we focused on two quantitatively altered cDNAs representing proteins known to be associated with vessel wall calcification. DT-diaphorase of the vitamin K-cycle, showed increased gene expression with a 4.8-fold higher specific activity in MK4 treated cells. Osteoprotegrin gene expression was down regulated and osteoprotegrin protein secretion from the MK4 treated cells was lowered to 1.8-fold. These findings suggest that MK4 acts as an anti-calcification component in the vessel wall.
Published:
2008
Title:
Estimating the Population Burden of Lymphedema
Authors:
Rockson, Stanley G.; Rivera, Kahealani K.
Abstract:
Lymphedema is a complex, regional edematous state that ensues when lymph transport is insufficient to maintain tissue homeostasis. The disorder is remarkably prevalent, but the population implications of lymphatic dysfunction are not well-studied. Prevalence estimates for lymphedema are relatively high, yet its prevalence is likely underestimated. The ability to estimate the burden of disease poses profound implications for current and future lymphedema patients, but the challenge to correctly surmise the incidence and prevalence of lymphedema is complex and the relevant medical literature is scanty. In the absence of the highly desired, prospectively designed and rigorously performed relevant epidemiologic studies, it is instructive to look at the existing studies of lymphedema disease burden. In the current review, the extant literature is examined in the context of the disease setting in which tissue edema is encountered. Incidence or prevalence estimates are provided or inferred, and, where feasible, the size of the subject population is also identified. It is extremely attractive to contemplate that future approaches will entail formal, prospectively designed studies to objectively quantitate incidence and prevalence statistics for individual categories, as well as for the global lymphedema population.
Published:
2008
Title:
Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake
Authors:
Avena, Nicole M.; Rada, Pedro; Hoebel, Bartley G.
Abstract:
[Avena, N.M., Rada, P., Hoebel B.G., 2007. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neuroscience and Biobehavioral Reviews XX(X), XXX-XXX]. The experimental question is whether or not sugar can be a substance of abuse and lead to a natural form of addiction. "Food addiction" seems plausible because brain pathways that evolved to respond to natural rewards are also activated by addictive drugs. Sugar is noteworthy as a substance that releases opioids and dopamine and thus might be expected to have addictive potential. This review summarizes evidence of sugar dependence in an animal model. Four components of addiction are analyzed. "Bingeing," "withdrawal," "craving" and "cross-sensitization" are each given operational definitions and demonstrated behaviorally with sugar bingeing as the reinforcer. These behaviors are then related to neurochemical changes in the brain that also occur with addictive drugs. Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin mRNA expression and dopamine and acetylcholine release in the nucleus accumbens. The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent. This may translate to some human conditions as suggested by the literature on eating disorders and obesity. © 2007 Elsevier Ltd. All rights reserved.
Published:
2008
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