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The Effect of Moderate Weight Loss on a Non-Invasive Biomarker of Liver Fibrosis: A Randomised Controlled Trial.
Koutoukidis, DA, Jebb, SA, Aveyard, P, Astbury, NM
Obesity facts. 2020;13(2):144-151
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Non-alcoholic fatty liver disease covers a range of conditions from excess fat in the liver through inflammation and fibrosis, to advanced fibrosis, and cirrhosis. The Enhanced Liver Fibrosis (ELF) score is emerging as a promising blood biomarker for fibrosis. The aim of this study was to examine whether a community weight loss programme reduces ELF score over 12 months compared with a weight-loss intervention which is less effective. This study is a secondary analysis of a published randomised controlled trial. Participants (n=73) were equally randomised to a community weight loss programme (WeightWatchers) or usual care. Results indicate that there was no evidence of an effect of a community weight loss programme on changes in the ELF score and no association between weight loss and the ELF score in people who had, on average, an ELF score compatible with moderate fibrosis. Authors conclude that using the ELF test to assess weight loss treatment efficacy in improving liver fibrosis may be of limited value, thus biopsy remains the gold-standard assessment for liver fibrosis.
Abstract
BACKGROUND Referral to weight loss programmes is the only effective treatment for non-alcoholic fatty liver disease (NAFLD). Clinicians should advise weight loss and screen for liver fibrosis using the Enhanced Liver Fibrosis (ELF) score. AIM: To examine if the ELF score changes with weight loss. DESIGN AND SETTING Randomised controlled trial (ISRCTN85485463) in UK primary care during 2007-2008. METHOD Adults with a BMI of 27-35 kg/m2 and ≥1 risk factor for obesity-related disease were randomised to attend a community weight loss programme (n = 45) or receive usual weight loss advice from a practice nurse (n = 28). Weight and the ELF score were measured at baseline and 1 year. Analysis of covariance examined mean changes in the ELF score between groups and its relationship with weight loss. RESULTS Mean (SD) BMI was 31.10 kg/m2 (2.55) with evidence of moderate levels of liver fibrosis at baseline (mean ELF score: 8.93 [0.99]). There was no evidence that the community weight loss programme reduced the ELF score compared with usual care (difference +0.13 points, 95% CI: -0.25 to 0.52) despite greater weight loss (difference: -2.66 kg, 95% CI: -5.02 to -0.30). Mean weight loss in the whole cohort was 7.8% (5.9). There was no evidence of an association between weight change and change in ELF; the coefficient for a 5% weight loss was -0.15 (95% CI: -0.30 to 0.0002). CONCLUSION We found no evidence that the ELF score changed meaningfully following moderate weight loss. Clinicians should not use the ELF score to measure improvements in NAFLD fibrosis following weight loss programmes.
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Estimation of Primary Prevention of Gout in Men Through Modification of Obesity and Other Key Lifestyle Factors.
McCormick, N, Rai, SK, Lu, N, Yokose, C, Curhan, GC, Choi, HK
JAMA network open. 2020;3(11):e2027421
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Gout is prevalent in most Western countries. Modifying the contributary factors such as obesity and alcohol intake could prevent gout, however the impact this could have on prevention is unknown. This cohort study of 44,654 men, aimed to estimate the proportion of gout cases that could be prevented through the modification of risk factors. The results showed that the most important risk factor for gout was body mass index (BMI) and modifying other risk factors did not prevent gout. 77% of gout cases could be prevented if all men had been of normal weight, had no alcohol intake, if they adhered to a diet known as the Dietary Approaches to Stop Hypertension (DASH) diet and if they didn't take drugs to increase urine output. It was concluded that weight loss in men determines their ability to prevent gout, regardless of whether they have modified other contributory factors. This study could be used by healthcare professionals to understand that unless weight loss is achieved in individuals who are overweight and have gout, then other interventions may have minimal impact. Recommending the DASH diet to achieve weight loss, may be more successful in the long-term management of gout.
Abstract
Importance: The population impact of modifying obesity and other key risk factors for hyperuricemia has been estimated in cross-sectional studies; however, the proportion of incident gout cases (a clinical end point) that could be prevented by modifying such factors has not been evaluated. Objective: To estimate the proportion of incident gout cases that could be avoided through simultaneous modification of obesity and other key risk factors. Design, Setting, and Participants: The Health Professionals Follow-up Study is a US prospective cohort study of 51 529 male health professionals enrolled in 1986 and followed up through questionnaires every 2 years through 2012. Self-reported gout cases were confirmed through June 2015. Clean and complete data used for this analysis were available in June 2016, with statistical analyses performed from July 2016 to July 2019. Exposures: From data collected in the validated questionnaires, men were categorized to low-risk groups according to combinations of the following 4 factors: normal body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; <25), no alcohol intake, adherence to Dietary Approaches to Stop Hypertension (DASH)-style diet (highest quintile of DASH diet score), and no diuretic use. Main Outcomes and Measures: Population attributable risks (PARs) for incident gout meeting the preliminary American College of Rheumatology survey criteria, overall and stratified by BMI. Results: We analyzed 44 654 men (mean [SD] age, 54.0 [9.8] years) with no history of gout at baseline. During 26 years of follow-up, 1741 (3.9%) developed incident gout. Among all participants, PAR for the 4 risk factors combined (BMI, diet, alcohol use, and diuretic use) was 77% (95% CI, 56%-88%). Among men with normal weight (BMI <25.0) and overweight (BMI 25.0-29.9), we estimated that more than half of incident gout cases (69% [95% CI, 42%-83%] and 59% [95% CI, 30%-75%], respectively) may have been prevented by the combination of DASH-style diet, no alcohol intake, and no diuretic use. However, among men with obesity (BMI ≥30), PAR was substantially lower and not significant (5% [95% CI, 0%-47%]). Conclusions and Relevance: The findings of this cohort study suggest that addressing excess adiposity and other key modifiable factors has the potential to prevent the majority of incident gout cases among men. Men with obesity may not benefit from other modifications unless weight loss is addressed.
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Prospective association between organic food consumption and the risk of type 2 diabetes: findings from the NutriNet-Santé cohort study.
Kesse-Guyot, E, Rebouillat, P, Payrastre, L, Allès, B, Fezeu, LK, Druesne-Pecollo, N, Srour, B, Bao, W, Touvier, M, Galan, P, et al
The international journal of behavioral nutrition and physical activity. 2020;17(1):136
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The prevalence of type 2 diabetes (T2D) has significantly increased over recent decades, concomitantly to the obesity epidemic. Among the emergent risk factors, exposure to environmental contaminants including pesticides is of major concern. In fact, a recent European Food Safety Authority report indicated that 44% of conventional crop-based food contained at least one quantifiable pesticide residue, vs 6.5% in organic-labelled foods (OF). The aims of this study were (a) to investigate the prospective association between OF consumption and the risk of T2D, and (b) to estimate the mediation effect by the potential healthiness of a plant-based diet. This study is prospective cohort study based on the data from the web-based NutriNet-Santé study with an analysis sample of 33,256 participants. Results indicate an inverse association between organic plant-based food consumption and T2D risk especially in women. The association persisted after accounting for potential confounding effects of various factors, including lifestyles, dietary patterns and adiposity. Authors conclude that further studies are needed to replicate these findings for confirmation purposes and to elucidate underlying mechanisms.
Abstract
BACKGROUND Organic food (OF) consumption has substantially increased in high income countries, mostly driven by environmental concerns and health beliefs. Lower exposure to synthetic pesticides has been systematically documented among consumers of organic products compared to non-consumers. While experimental studies suggest that pesticides currently used in food production may be associated with type 2 diabetes (T2D), no well-conducted prospective studies have investigated the potential association between consumption of organic products and the risk of T2D, controlling for potential confounding factors. The objective of this prospective study was to estimate the association between OF consumption and the risk of T2D. METHODS A total of 33,256 participants (76% women, mean (SD) age: 53 years (14)) of the French NutriNet-Santé prospective cohort study who completed the organic food frequency questionnaire were included (2014-2019). The proportion of OF in the diet (as weight without drinking water) was computed. The associations between the proportion of OF in the diet (as 5% increment and as quintiles) and the risk of T2D were estimated using multivariable Hazard Ratio (HR) and 95% confidence interval (95% CI) derived from proportional hazards models adjusted for confounders (sociodemographic, anthropometric, lifestyle, medical and nutritional factors). RESULTS During follow-up (mean = 4.05 y, SD = 1.03 y, 134,990 person-years), 293 incident cases of T2D were identified. After adjustment for confounders including lifestyle (physical activity, smoking status, alcohol consumption) and nutritional quality of the diet assessed by the adherence to the French food-based dietary guidelines, OF consumption was associated with a lower risk of T2D. Participants with the highest quintile of OF consumption, compared with those with the lowest quintile, had 35% lower risk of T2D (95% CI = 0.43-0.97). Each increment of 5% in the proportion of OF in the diet was associated with 3% lower risk of T2D (HR 0.97, 95% CI = 0.95-0.99). CONCLUSIONS In this large prospective cohort study, OF consumption was inversely associated with the risk of T2D. Further experimental and prospective studies should be conducted to confirm these observations. CLINICAL TRIAL REGISTRY The study was registered at ClinicalTrials.gov ( NCT03335644 ).
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Weight Status and Alcohol Intake Modify the Association between Vitamin D and Breast Cancer Risk.
Deschasaux, M, Souberbielle, JC, Latino-Martel, P, Sutton, A, Charnaux, N, Druesne-Pecollo, N, Galan, P, Hercberg, S, Le Clerc, S, Kesse-Guyot, E, et al
The Journal of nutrition. 2016;146(3):576-85
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Experimental studies suggest that vitamin D may contribute to the prevention of breast cancer. However, population studies have been inconclusive, and it is possible that any relationship is dependent on other factors such as genetics or lifestyle. The objective of this study was to explore associations between blood vitamin D levels and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m(2)) and alcohol intake. The nested case-control study involved 233 women with breast cancer and 466 healthy controls. Overall, no association was found between vitamin D levels and breast cancer risk. However, a higher blood vitamin D concentration was associated with a decreased risk of breast cancer for women with a BMI under 22.4, whereas it was associated with an increased risk for women with a BMI 22.4 or over. A blood vitamin D concentration ≥ 10 ng/mL was associated with a decreased risk of breast cancer for women with alcohol intakes ≥ 7.1 g/day, whereas no association was observed for women with alcohol intakes < 7.1g/day. The authors concluded that BMI and alcohol intake modified the association between vitamin D and breast cancer risk. These lifestyle factors could explain the inconclusive results of previous studies.
Abstract
BACKGROUND Mechanistic hypotheses suggest that vitamin D may contribute to the prevention of breast cancer. However, epidemiologic evidence is inconsistent, suggesting a potential effect modification by individual factors. OBJECTIVE Our objective was to perform exploratory analyses on the prospective associations between the plasma 25-hydroxyvitamin D [25(OH)D] concentration, polymorphisms of genes encoding for the vitamin D receptor (VDR) and vitamin D-binding protein (also known as gc-globulin or group-specific component, GC), and breast cancer risk, along with 2 potential modifiers: body mass index (BMI; in kg/m(2)) and alcohol intake. METHODS A nested case-control study was set up in the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort (1994-2007), involving 233 women with breast cancer and 466 matched controls (mean ± SD age: 49 ± 6 y). The plasma total 25(OH)D concentration and gene polymorphisms were assessed on samples obtained at baseline. Conditional logistic regression models were computed. RESULTS A higher plasma 25(OH)D concentration was associated with a decreased risk of breast cancer for women with a BMI < the median of 22.4 [OR quartile (Q)4 compared with Q1: 0.46; 95% CI: 0.23, 0.89; P-trend = 0.01, P-interaction = 0.002], whereas it was associated with an increased risk for women with a BMI ≥ the median (OR Q4 compared with Q1: 2.45; 95% CI: 1.13, 5.28; P-trend = 0.02, P-interaction = 0.002). A plasma 25(OH)D concentration ≥ 10 ng/mL was associated with a decreased risk of breast cancer for women with alcohol intakes ≥ the median of 7.1 g/d (OR ≥10 compared with <10 ng/mL: 0.50; 95% CI: 0.26, 0.95; P = 0.03, P-interaction = 0.03). The genetic analyses were consistent with the results observed with plasma 25(OH)D. CONCLUSION In this prospective study, BMI and alcohol intake modified the association between vitamin D [plasma 25(OH)D and vitamin D-related gene polymorphisms] and breast cancer risk. These effect modifications suggest explanations for discrepancies in results of previous studies. This trial was registered at clinicaltrials.gov as NCT00272428.
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Silymarin in the prevention and treatment of liver diseases and primary liver cancer.
Féher, J, Lengyel, G
Current pharmaceutical biotechnology. 2012;13(1):210-7
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Non-alcoholic fatty liver disease (NAFLD) is a recognised health problem with no convincing interventions to date. This randomised trial aimed to examine the efficacy of silymarin plus vitamin E in the treatment of NAFLD. 36 patients were randomized to either group Ι or group ΙΙ. Group Ι was treated with 2 tablets of silymarin plus vitamin E per day, hypocaloric diet and exercise. Group ΙΙ was treated only with a hypocaloric diet. Study duration was 3 months for both groups. Diagnosis of NAFLD was confirmed for all participants by liver biopsy. Patients in group Ι showed significant decrease in anthropometric measurements. Both groups experienced reductions in markers of NAFLD, however in group I, these reductions were independent of weight loss, whereas in group II, those who failed to lose 5% of body weight didn’t show a change in biochemical markers. Authors conclude that intervention with silymarin plus vitamin E, alone or along with other treatments, can help NAFLD patients who fail to lose weight with diet.
Abstract
In chronic liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver diseases, drug- and chemical-induced hepatic toxicity), the antioxidant medicines such as silymarin can have beneficial effect. Liver cirrhosis, non-alcoholic fatty liver and steatohepatitis are risk factors for hepatocellular carcinoma (HCC). Insulin resistance and oxidative stress are the major pathogenetic mechanisms leading the hepatic cell injury in these patients. The silymarin exerts membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration; furthermore it reduces the inflammatory reaction, and inhibits the fibrogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies the long-term administration of silymarin significantly increased survival time of patients with alcohol induced liver cirrhosis. Based on the results of studies using methods of molecular biology, silymarin can significantly reduce tumor cell proliferation, angiogenesis as well as insulin resistance. Furthermore, it exerts an anti-atherosclerotic effect, and suppresses tumor necrosis factor-alpha-induced protein production and mRNA expression due to adhesion molecules. The chemopreventive effect of silymarin on HCC has been established in several studies using in vitro and in vivo methods; it can exert a beneficial effect on the balance of cell survival and apoptosis by interfering cytokines. In addition to this, anti-inflammatory activity and inhibitory effect of silymarin on the development of metastases have also been detected. In some neoplastic diseases silymarin can be administered as adjuvant therapy as well.