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A Freshwater Fish-Based Diet Alleviates Liver Steatosis by Modulating Gut Microbiota and Metabolites: A Clinical Randomized Controlled Trial in Chinese Participants With Nonalcoholic Fatty Liver Disease.
He, K, Guo, LL, Tang, H, Peng, X, Li, J, Feng, S, Bie, C, Chen, W, Li, Y, Wang, M, et al
The American journal of gastroenterology. 2022;117(10):1621-1631
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The diagnosis and treatment of non-alcoholic fatty liver disease (NAFLD) is critical, however, there isn’t an effective treatment readily available. On the other hand, lifestyle modifications, particularly a calorie-restricted diet, habitual physical activity, and weight loss, have been advocated for the treatment of NAFLD. The hypothesis of this study was that a freshwater fish-based diet would induce a greater improvement in hepatic steatosis by regulating gut microbiota and its metabolites compared with an alternating combination of freshwater fish-based and red meat-based diets. This study was a randomised, open-label and controlled clinical trial which enrolled participants who were clinically diagnosed of NAFLD with a presence of hepatic steatosis. Participants (n=34) were randomly assigned to either a freshwater fish-based diet or the combination of a freshwater fish-based diet and a red meat-based diet at a daily alternating frequency in a 1:1 ratio. Results showed that dietary freshwater fish consumption: - alleviates liver steatosis in participants with NAFLD; - ameliorates several metabolic phenotypes in participants with NAFLD; - partially redresses gut microbiota dysbiosis in the improvement of the metabolic phenotypes of participants with NAFLD; - improves NAFLD by inducing metabolites alternation. Authors conclude that even though the freshwater fish-based diet showed various positive results for participants with NAFLD, the alternating freshwater fish and red meat consumption may not exacerbate NAFLD, which may be more appropriate to fit the daily eating habits and food diversity for long-term implementation.
Abstract
INTRODUCTION We aimed to assess the effects of 2 isoenergetic intervention diets (a freshwater fish-based diet [F group] or freshwater fish-based and red meat-based diets alternately [F/M group]) on liver steatosis and their relationship with intestinal flora in patients with nonalcoholic fatty liver disease (NAFLD). METHODS In this open-label, 84-day randomized controlled trial, 34 NAFLD patients with hepatic steatosis ≥10% were randomly assigned to the F group or F/M group in a 1:1 ratio using a computer-generated random number allocation by a researcher not involved in the study. Liver fat content and gut microbiota and its metabolites were measured. RESULTS At the end of intervention, the absolute reduction of hepatic steatosis was significantly greater in the F group than in the F/M group (-4.89% vs -1.83%, P = 0.032). Of the 16 secondary clinical outcomes, the improvement in 7 in the F group was greater compared with the F/M group, including alanine aminotransferase and gamma-glutamyl transferase. Furthermore, dietary freshwater fish and red meat consumption alternately did not exacerbate NAFLD. Moreover, changes in the enrichment of Faecalibacterium, short-chain fatty acids, and unconjugated bile acids and the depletion of Prevotella 9 and conjugated bile acids in the F group were significantly greater compared with the F/M group. DISCUSSION Higher intake of freshwater fish may be beneficial to NAFLD by regulating gut microbiota and its metabolites, whereas intake of a similar total of animal protein and fat from the alternating freshwater fish and red meat may not be harmful for NAFLD in the dietary management of patients with NAFLD.
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Healthy Lifestyle Is Associated with Reduced Mortality in Patients with Non-Alcoholic Fatty Liver Disease.
Yu, C, Gao, J, Ge, X, Wang, X, Ding, Y, Tian, T, Xu, X, Guo, W, Wang, Q, Ge, Z, et al
Nutrients. 2022;14(18)
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Non-alcoholic fatty liver disease (NAFLD) has emerged as the predominant cause of chronic liver disease. Given the association between NAFLD and metabolic syndrome [11,12], lifestyle modification can improve patients’ life quality and prognosis. The aim of this study was to assess the joint association of several modifiable lifestyle factors with overall and cause-specific mortality among NAFLD individuals and depict the mortality risk of varied composite modes of lifestyle. This study is a large, nationally representative, population-based study. It is based on the NHANES III (1988–1994, the National Center for Health Statistics, the Center for Disease Control and Prevention), which used a complex multistage probability design to recruit a representative sample of participants. Results show a protective effect among NAFLD participants following a healthy lifestyle, particularly impacting CVD-related mortality. Notably, among the most common lifestyle factor combinations, the effect of risk reduction on mortality was particularly strong when smoking was avoided. Authors conclude that their findings can be a useful tool to help the general public and patients with NAFLD to understand the importance of maintaining a healthy lifestyle.
Abstract
BACKGROUND AND AIMS It is unclear whether a healthy lifestyle impacts mortality in the presence of non-alcoholic fatty liver disease (NAFLD). The present study aimed to examine the joint association of several modifiable lifestyle factors with mortality risk for NAFLD patients. METHODS We collected lifestyle behavior data form the National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and follow-up data form NHANES III-linked mortality data through 2015. We estimated joint association between four healthy lifestyle factors (non-smoking, non-drinking, regular physical activity, a healthy diet) after NAFLD diagnosis and mortality using Cox proportional hazards regression models. RESULTS During a median of 22.83 years of follow-up, 2932 deaths occurred. The risk of all-cause mortality decreased significantly with the healthy lifestyle scores increasing (p < 0.001). NAFLD patients with a favorable lifestyle (3 or 4 healthy lifestyle factors) reduced 36% of all-cause mortality and 43% of cardiovascular disease (CVD) mortality compared with those with an unfavorable lifestyle (0 or 1 healthy lifestyle factor) (HR, 0.64 [95% CI, 0.50-0.81], 0.57 [95% CI, 0.37-0.88]). Compared with the non-NAFLD group, the number of NAFLD patients required to adhere to a favorable lifestyle to prevent one cardiovascular disease death in 20 years was fewer (77 vs. 125). CONCLUSIONS For the NAFLD patients, adopting a healthy lifestyle could significantly reduce their risk of death.
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Association between Mediterranean Diet and Fatty Liver in Women with Overweight and Obesity.
Leone, A, Bertoli, S, Bedogni, G, Vignati, L, Pellizzari, M, Battezzati, A
Nutrients. 2022;14(18)
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Non-alcoholic fatty liver disease (NAFLD) is a condition resulting from excessive lipid accumulation in the liver in individuals with low alcohol consumption. Obesity is an established risk factor for the development of NAFLD, and 50% to 75% of people with obesity also have NAFLD. The aim of this study was to evaluate the association between Mediterranean diet and non-invasive indices of fatty liver in a large sample of women with overweight and obesity. This study is a cross-sectional study of 2967 consecutive women with overweight and obesity. Results show that higher adherence to the Mediterranean diet was associated with lower indices of fatty liver in women with overweight and obesity (particularly obese women than in women who are overweight). Authors conclude that women with obesity, especially during the premenopausal period, may benefit more from following a Mediterranean-style diet.
Abstract
Obesity is a risk factor for NAFLD. However, not all people with obesity have an excessive intrahepatic fat content. Adherence to a high-quality dietary pattern may also promote liver health in obesity. A cross-sectional study of 2967 women with overweight and obesity was carried out to assess the association between a Mediterranean diet and fatty liver. All women underwent clinical examination, anthropometric measurements, blood sampling, ultrasound measurements of abdominal visceral and subcutaneous fat, and assessment of adherence to the Mediterranean diet using the 14-item MEDAS questionnaire. Fatty liver index (FLI), NAFLD fatty liver steatosis (NAFLD-FLS) and hepatic steatosis index (HSI) were calculated. In women with obesity, the MEDAS score was inversely associated with FLI (β = -0.60, 95% CI: -1.04, -0.16, p = 0.008), NAFLD-FLS (β = -0.092, 95% CI: -0.134, -0.049, p < 0.001) and HSI (β = -0.17, 95% CI: -0.30, -0.04, p = 0.011). Stronger associations were observed in premenopausal women with obesity. Mediterranean diet was inversely associated with NAFLD-FLS in women with overweight, independently of menopausal status. In conclusion, Mediterranean diet is associated with a better liver status in women with overweight and obesity. This may have a public health impact and be useful in drafting nutritional guidelines for NAFLD.
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Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans.
Nascimento, EBM, Moonen, MPB, Remie, CME, Gariani, K, Jörgensen, JA, Schaart, G, Hoeks, J, Auwerx, J, van Marken Lichtenbelt, WD, Schrauwen, P
The Journal of clinical endocrinology and metabolism. 2021;106(5):1437-1447
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Brown fat is a type of fat that burns energy to regulate the body’s temperature in cold conditions. A high level of activity in the brown fat has been associated with healthy whole-body metabolism. Several supplements have been investigated for their potential to activate brown fat, however many of these have limiting side effects. Nicotinamide riboside (NR), also known as vitamin B3, is a supplement which can boost energy burning pathways within the body. This randomised control trial was part of a larger trial including a study on human brown fat cells and aimed to determine whether NR supplementation in overweight and obese individuals may act on the activity of brown tissue. The results showed that 6 weeks of NR supplementation had no effect on brown tissue activity or energy expenditure. It was concluded that NR supplementation for 6 weeks in individuals with obesity had no effect on brown fat tissue for reasons unknown, as the cellular study showed an increase in activity. This study could be used by healthcare professionals to better understand the role of brown fat in metabolism.
Abstract
CONTEXT Elevating nicotinamide adenine dinucleotide (NAD+) levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high-fat-diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism, and enhanced cold tolerance. OBJECTIVE Because brown adipose tissue (BAT) is a major source of thermogenesis, we hypothesize that NR stimulates BAT in mice and humans. DESIGN AND INTERVENTION HFD-fed C56BL/6J mice were supplemented with 400 mg/kg/day NR for 4 weeks and subsequently exposed to cold. In vitro primary adipocytes derived from human BAT biopsies were pretreated with 50 µM or 500 µM NR before measuring mitochondrial uncoupling. Human volunteers (45-65 years; body mass index, 27-35 kg/m2) were supplemented with 1000 mg/day NR for 6 weeks to determine whether BAT activity increased, as measured by [18F]FDG uptake via positron emission tomography-computed tomography (randomized, double blinded, placebo-controlled, crossover study with NR supplementation). RESULTS NR supplementation in HFD-fed mice decreased adipocyte cell size in BAT. Cold exposure further decreased adipocyte cell size on top of that achieved by NR alone independent of ex vivo lipolysis. In adipocytes derived from human BAT, NR enhanced in vitro norepinephrine-stimulated mitochondrial uncoupling. However, NR supplementation in human volunteers did not alter BAT activity or cold-induced thermogenesis. CONCLUSIONS NR stimulates in vitro human BAT but not in vivo BAT in humans. Our research demonstrates the need for further translational research to better understand the differences in NAD+ metabolism in mouse and human.
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NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.
Connell, NJ, Grevendonk, L, Fealy, CE, Moonen-Kornips, E, Bruls, YMH, Schrauwen-Hinderling, VB, de Vogel, J, Hageman, R, Geurts, J, Zapata-Perez, R, et al
The Journal of nutrition. 2021;151(10):2917-2931
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Ageing is associated with the progressive loss of muscle, which can result in impaired movement, an increased risk for falls and disrupted energy production. During ageing there is a decrease in one of the substrates involved in producing energy known as NAD+. Studies in animals have shown that supplementing with a precursor of NAD+ promotes longevity and energy production. In humans supplementation with a precursor of NAD+ has been shown to improve heart health and be of benefit to individuals with obesity. This randomised control trial aimed to determine the effect of supplementing the NAD+ precursors, tryptophan, nicotinic acid, and nicotinamide on muscle function in 14 older adults with impaired physical function. The results showed that supplementation had no effect on NAD+ and had no effect on muscular energy production nor exercise performance following a cycling test. It was concluded that supplementation with an NAD+ precursor does not improve muscle function. This study could be used by healthcare professionals to understand that a combination supplement of tryptophan, nicotinic acid, and nicotinamide may not benefit the physical function of older adults.
Abstract
BACKGROUND Boosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function. OBJECTIVES We investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults. METHODS A randomized, double-blind, controlled trial was conducted in 14 (female/male: 4/10) community-dwelling, older adults with impaired physical function [age, 72.9 ± 4.0 years; BMI, 25.2 ± 2.3 kg/m2]. Participants were supplemented with 207.5 mg niacin equivalents/day [intervention (INT)] and a control product (CON) that did not contain niacin equivalents, each for 32 days. The primary outcomes tested were mitochondrial oxidative capacity and exercise efficiency, analyzed by means of paired Student's t-tests. Secondary outcomes, such as NAD+ concentrations, were analyzed accordingly. RESULTS Following supplementation, skeletal muscle NAD+ concentrations [7.5 ± 1.9 compared with 7.9 ± 1.6 AU, respectively] in INT compared with CON conditions were not significantly different compared to the control condition, whereas skeletal muscle methyl-nicotinamide levels were significantly higher under NAD+-precursor supplementation [INT, 0.098 ± 0.063 compared with CON, 0.025 ± 0.014; P = 0.001], suggesting an increased NAD+ metabolism. Conversely, neither ADP-stimulated [INT, 82.1 ± 19.0 compared with CON, 84.0 ± 19.2; P = 0.716] nor maximally uncoupled mitochondrial respiration [INT, 103.4 ± 30.7 compared with CON, 108.7 ± 33.4; P = 0.495] improved under NAD+-precursor supplementation, nor did net exercise efficiency during the submaximal cycling test [INT, 20.2 ± 2.77 compared with CON, 20.8 ± 2.88; P = 0.342]. CONCLUSIONS Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This study was registered at clinicaltrials.gov as NCT03310034.
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Association of resting heart rate with nonalcoholic fatty liver disease in postmenopausal women.
Kim, HB, Lee, YJ
Medicine. 2020;99(14):e19529
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Non-alcoholic fatty liver disease (NAFLD) is characterised by accumulation of fats in the liver and is particularly prevalent in postmenopausal women, due to a decrease in oestrogen, which leads to weight gain. Higher than normal resting heart rate has been shown to be a predictor of heart disease, however studies that look at the relationship between heart rate and NAFLD are lacking. This cross-sectional, observation study of 1315 postmenopausal women aimed to look at the relationship between resting heart rate and NAFLD. The results showed that the overall prevalence of NAFLD was increased with increased resting heart rate. It was concluded that resting heart rate was associated with NAFLD in postmenopausal women and it could be used as an additional predictor for risk of the disease. This study could be used by healthcare practitioners to understand the possible relationship between resting heart rate and the risk of developing NAFLD.
Abstract
Resting heart rate, a simple and useful indicator of autonomic function, and its imbalance has emerged as an independent predictor of cardio metabolic diseases. Nonalcoholic fatty liver disease (NAFLD) is increasingly being diagnosed worldwide and is strongly associated with the features of cardiometabolic diseases. This study aimed to examine the association between resting heart rate and NAFLD in postmenopausal women.The cross-sectional study included 1017 postmenopausal women aged ≥46 years, who attended a health examination program. Resting heart rate and NAFLD were measured in all subjects who underwent a medical examination. Resting heart rate quartiles were categorized as follows: Q1: 56 to 65, Q2: 66 to 71, Q3: 72 to 78, and Q4: 79 to 99 beats/min. The odds ratios and 95% confidence intervals for NAFLD were calculated after adjusting for confounding variables across resting heart rate quartiles using multiple logistic regression analysis.The prevalence of NAFLD increased with increasing resting heart rate quartiles: 28.2% for Q1, 31.5% for Q2, 33.4% for Q3, and 38.1% for Q4 (P < .001). Compared to the 1st quartile, the odds ratio (95% confidence intervals) of NAFLD in the 4th quartile of resting heart rates was 2.11 (1.17-3.42) after adjusting for age, body mass index, cigarette smoking, regular exercise, blood pressure, total cholesterol, triglyceride, aspartate aminotransferase, and alanine aminotransferase levels.Resting heart rate was positively associated with NAFLD in postmenopausal women, suggesting that it could be a useful additional measure to assess the risk for NAFLD in postmenopausal women.
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A Low ω-6 to ω-3 PUFA Ratio (n-6:n-3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth.
Van Name, MA, Savoye, M, Chick, JM, Galuppo, BT, Feldstein, AE, Pierpont, B, Johnson, C, Shabanova, V, Ekong, U, Valentino, PL, et al
The Journal of nutrition. 2020;150(9):2314-2321
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Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of fat in the liver of people who drink very little or no alcohol. NAFLD is a common problem in children with obesity and diet is a contributory factor. Recent research has suggested that the Western diet and its high omega-6 and low omega-3 fat intakes may lead to the development of NAFLD. This quasi-experimental study of twenty children with obesity and NAFLD aimed to determine whether 12 weeks of low omega-6: omega-3 ratio diet affected liver fat content. The results showed that the diet did not affect weight loss but still significantly decreased liver fat content, with one third of the participants returning their liver fat content to normal. In lieu of weight loss, improvements were also observed in markers for liver function, diabetes and blood cholesterol. Interestingly those who carry a certain gene increasing their risk of developing NAFLD, showed greater improvements in liver fat percentage and liver function. It was concluded that in the absence of weight loss, a diet high in omega-3 and low in omega-6 improves fatty liver disease, risk factors for heart disease and has the potential to revert liver fat content to normal levels. This study could be used by healthcare professionals to recommend a low omega-6:omega-3 diet in children with obesity and NAFLD.
Abstract
BACKGROUND Recent literature suggests that the Western diet's imbalance between high ω-6 (n-6) and low ω-3 (n-3) PUFA intake contributes to fatty liver disease in obese youth. OBJECTIVES We tested whether 12 wk of a low n-6:n-3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response. METHODS In a single-arm unblinded study, obese youth 9-19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n-6:n-3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann-Whitney U test, and covariance pattern modeling were used. RESULTS Twenty obese adolescents (median age: 13.3 y; IQR: 10.5-16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time. CONCLUSIONS These data suggest that, independently of weight loss, a low n-6:n-3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113.
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Role of Probiotics in Non-alcoholic Fatty Liver Disease: Does Gut Microbiota Matter?
Xie, C, Halegoua-DeMarzio, D
Nutrients. 2019;11(11)
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Non-alcoholic fatty liver disease (NAFLD) is characterised by an excessive accumulation of fat in the liver tissue, without excessive alcohol consumption, and appears to be related to metabolic syndrome. It is thought to have a prevalence of 25% globally and there are no pharmacological treatments available. This review discusses the connection between the gut microbiota (GM) and NAFLD. Various mechanisms by which the GM may be involved in the development of NAFLD are discussed. As probiotics and prebiotics can normalise GM and reverse dysbiosis their use may benefit patients with NAFLD. This has been confirmed in animal models. The authors review 26 randomised controlled trials (RCTs) of probiotics and/or prebiotics in the treatment of NAFLD which evaluate biochemical markers, as well as five meta-analyses, and found that overall there is strong evidence that probiotics and/or prebiotics can lower ALT and AST (markers of NAFLD), although results for other biochemical markers were mixed. They also reviewed RCTs assessing NAFLD by imaging and histological means, and again found benefits from probiotic and/or prebiotic supplementation.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic inflammation (impairing intestinal integrity, facilitating endotoxemia, and initiating inflammatory cascades with cytokines releasing), and (3) altered biochemistry metabolism and GM-related metabolites (i.e., bile acid, short-chain fatty acids, aromatic amino acid derivatives, branched-chain amino acids, choline, ethanol). Due to the hypothesis that probiotics/synbiotics could normalize GM and reverse dysbiosis, there have been efforts to investigate the therapeutic effect of probiotics/synbiotics in patients with NAFLD. Recent randomized clinical trials suggest that probiotics/synbiotics could improve transaminases, hepatic steatosis, and reduce hepatic inflammation. Despite these promising results, future studies are necessary to understand the full role GM plays in NAFLD development and progression. Additionally, further data is needed to unravel probiotics/synbiotics efficacy, safety, and sustainability as a novel pharmacologic approaches to NAFLD.
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Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial.
Schwimmer, JB, Ugalde-Nicalo, P, Welsh, JA, Angeles, JE, Cordero, M, Harlow, KE, Alazraki, A, Durelle, J, Knight-Scott, J, Newton, KP, et al
JAMA. 2019;321(3):256-265
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The prevalence of non-alcoholic fatty liver disease (NAFLD) among children in the United States is increasing and evidence supports a role for dietary sugar in the development and progression of NAFLD. This open-label, randomised clinical trial using a feeding study design was performed to test the hypothesis that restricting free sugar would improve NAFLD in children. Children in the intervention group, who were provided all food for the 8 week intervention, received less than 3% of daily calories from sugar. The control group continued with their usual diet. Study visits were conducted at baseline and at 4 and 8 weeks after start of the intervention. The mean decrease in hepatic steatosis (a sign of NAFLD) from baseline to week 8 was significantly greater for the intervention diet group compared with the usual diet group. Liver enzymes, total cholesterol, weight/body mass index and systolic blood pressure also improved more in the low sugar group than in the usual diet group. There was no difference in markers for blood sugar control and other lipid parameters. The authors conclude that these findings suggest a potential benefit of a low sugar diet for children with NAFLD, but state that further research is needed to assess long-term and clinical outcomes.
Abstract
Importance: Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment. Objective: To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD. Design, Setting, and Participants: An open-label, 8-week randomized clinical trial of adolescent boys aged 11 to 16 years with histologically diagnosed NAFLD and evidence of active disease (hepatic steatosis >10% and alanine aminotransferase level ≥45 U/L) randomized 1:1 to an intervention diet group or usual diet group at 2 US academic clinical research centers from August 2015 to July 2017; final date of follow-up was September 2017. Interventions: The intervention diet consisted of individualized menu planning and provision of study meals for the entire household to restrict free sugar intake to less than 3% of daily calories for 8 weeks. Twice-weekly telephone calls assessed diet adherence. Usual diet participants consumed their regular diet. Main Outcomes and Measures: The primary outcome was change in hepatic steatosis estimated by magnetic resonance imaging proton density fat fraction measurement between baseline and 8 weeks. The minimal clinically important difference was assumed to be 4%. There were 12 secondary outcomes, including change in alanine aminotransferase level and diet adherence. Results: Forty adolescent boys were randomly assigned to either the intervention diet group or the usual diet group (20 per group; mean [SD] age, 13.0 [1.9] years; most were Hispanic [95%]) and all completed the trial. The mean decrease in hepatic steatosis from baseline to week 8 was significantly greater for the intervention diet group (25% to 17%) vs the usual diet group (21% to 20%) and the adjusted week 8 mean difference was -6.23% (95% CI, -9.45% to -3.02%; P < .001). Of the 12 prespecified secondary outcomes, 7 were null and 5 were statistically significant including alanine aminotransferase level and diet adherence. The geometric mean decrease in alanine aminotransferase level from baseline to 8 weeks was significantly greater for the intervention diet group (103 U/L to 61 U/L) vs the usual diet group (82 U/L to 75 U/L) and the adjusted ratio of the geometric means at week 8 was 0.65 U/L (95% CI, 0.53 to 0.81 U/L; P < .001). Adherence to the diet was high in the intervention diet group (18 of 20 reported intake of <3% of calories from free sugar during the intervention). There were no adverse events related to participation in the study. Conclusions and Relevance: In this study of adolescent boys with NAFLD, 8 weeks of provision of a diet low in free sugar content compared with usual diet resulted in significant improvement in hepatic steatosis. However, these findings should be considered preliminary and further research is required to assess long-term and clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02513121.
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The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease.
Chambers, ES, Byrne, CS, Rugyendo, A, Morrison, DJ, Preston, T, Tedford, C, Bell, JD, Thomas, L, Akbar, AN, Riddell, NE, et al
Diabetes, obesity & metabolism. 2019;21(2):372-376
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Non-alcoholic fatty liver disease (NAFLD) is characterised by an accumulation of fat within the liver, and is strongly associated with obesity. Recent investigations suggest that diet, the gut microbiota and liver fat storage could be linked through a mechanism involving short chain fatty acids (SCFA), in particular the SCFA propionate, which are produced by the gut bacteria. The aim of this randomised controlled study was to evaluate whether an inulin-propionate ester (IPE) has benefits in patients with NAFLD. Subjects with NAFLD received either 20 g/d of inulin (control) or IPE for 42 days. 18 subjects completed the trial. Intrahepatocellular lipids IHCL (a marker of fat accumulation in the liver) increased post supplementation in both groups with no significant difference between control and IPE group. There was a change in insulin resistance (HOMA-IR) which was significantly different between groups, with a non-significant increase in the inulin-control group and decrease in the IPE group. There were no within- or between-group differences in body composition. The authors discuss these unexpected results and suggest that the SCFA acetate, from inulin fermentation by gut bacteria, may have led to an increase in IHCL which was attenuated by the propionate.
Abstract
The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non-alcoholic fatty liver disease (NAFLD). Eighteen adults were randomized to receive 20 g/d of an inulin-propionate ester (IPE), designed to deliver propionate to the colon, or an inulin control for 42 days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between the groups (P = 0.082), however, IHCL significantly increased within the inulin-control group (20.9% ± 2.9% to 26.8% ± 3.9%; P = 0.012; n = 9), which was not observed within the IPE group (22.6% ± 6.9% to 23.5% ± 6.8%; P = 0.635; n = 9). The predominant SCFA from colonic fermentation of inulin is acetate, which, in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate-mediated increase in IHCL.