Lifestyle intervention for metabolic dysfunction-associated fatty liver disease: a 24-h integrated behavior perspective.

INTRODUCTION: The prevalence, health and socioeconomic burden of metabolic dysfunction-associated fatty liver disease (MAFLD) is growing, increasing the need for novel evidence-based lifestyle approaches. Lifestyle is the cornerstone for MAFLD management and co-existing cardiometabolic dysfunction. The aim of this review was to evaluate the evidence for lifestyle management of MAFLD, with a specific lens on 24-hour integrated behaviour and provide practical recommendations for implementation of the evidence. RESULTS: Weight loss ≥ 7-10% is central to lifestyle management; however, liver and cardiometabolic benefits are attainable with improved diet quality and exercise even without weight loss. Lifestyle intervention for MAFLD should consider an integrated '24-h' approach that is cognisant of diet, physical activity/exercise, sedentary behavior, smoking, alcohol intake and sleep. Dietary management emphasises energy deficit and improved diet quality, especially the Mediterranean diet, although sociocultural adaptations to meet preferences should be considered. Increasing physical activity and reducing sedentary behavior can prevent MAFLD, with strongest evidence in MAFLD supporting regular structured moderate-vigorous aerobic exercise for 150-240 min/week. Resistance training in addition to aerobic exercise should be considered and prioritised for those who are losing body mass via diet and/or pharmacological approaches and those with sarcopenia, to minimise bone and lean mass loss. Limited evidence suggests that sleep is important for MAFLD prevention. Emerging novel approaches to diet and exercise may address some of the key barriers to behaviour change (e.g. lack of time, access to resources and social support). FUTURE DIRECTIONS: Large-scale multidisciplinary trials in people with MAFLD with long-term follow-up, that can be scaled up into mainstream healthcare, are required. Future management guidelines should consider the heterogeneity of MAFLD and specialised models of care that coordinate the health workforce to manage the increased and growing MAFLD population.

Mediterranean-style dietary interventions in adults with cancer: a systematic review of the methodological approaches, feasibility, and preliminary efficacy.

BACKGROUND: Cancer and its treatments can lead to excess body fat, decreases in lean mass, cardiotoxicity, and other side effects. The Mediterranean diet (MED-diet) has the potential to improve clinical and supportive care outcomes. The aim of this systematic review was to evaluate the feasibility, safety, and efficacy of the MED-diet on health outcomes in adults with cancer. METHODS: Three databases were searched from inception to February 2023. Eligible studies included randomised controlled trials testing a MED-diet intervention among adults with cancer. Within- and between-group differences for adherence, dietary intake and health outcomes were extracted. RESULTS: Fifteen studies describing fourteen interventions were included, and there were considerable differences in study design and implementation of the MED-diet. Studies were predominately in women with a history of breast cancer. The MED-diet was safe with no adverse events reported, and feasible with high adherence and/or increases in MED-diet-compliant foods. The MED-diet when applied with an energy restriction below estimated requirements for weight loss demonstrated reductions in body weight (range: -3.9 kg to -0.7 kg). Interventions that showed significant reductions in body weight also improved quality of life. There is limited evidence to evaluating the MED-diet on cardiovascular and inflammatory markers, and heterogenous MED-diet prescriptions impede definitive conclusions on these health outcomes. CONCLUSION: The MED-diet was feasible and safe for adults with cancer. There were reported benefits for weight loss following a MED-diet when an energy restriction was applied, however further evaluation to determine the effects on cardiometabolic biomarkers and other outcomes are required.

Adherence to a Mediterranean diet may improve serum adiponectin in adults with nonalcoholic fatty liver disease: The MEDINA randomized controlled trial.

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of adults worldwide, with chronic low-grade inflammation being a key pathophysiological feature of progression. The Mediterranean diet (MedDiet) is recognized for improving metabolic and hepatic outcomes in people with diabetes and NAFLD, in part, via anti-inflammatory properties. The aim of this study was to determine the effect of an ad libitum MedDiet versus low-fat diet (LFD) on inflammatory markers in adults with NAFLD. It was hypothesized that the MedDiet, and its individual components, would improve inflammation. This multicenter, randomized controlled trial, randomized participants to a MedDiet or LFD intervention for 12 weeks. Primary outcomes included change from baseline to 12 weeks for serum high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, adiponectin, leptin, and resistin. Forty-two participants (60% female; age 52.3 ± 12.6 years; body mass index, 32.2 ± 6.2 kg/m²) were randomized to the MedDiet (n = 19) or low-fat diet (n = 23). At 12 weeks, the LFD showed a greater decrease in leptin compared with the MedDiet (-1.20 ± 3.9 ng/mL vs 0.64 ± 3.5 ng/mL, P = .010). Adiponectin significantly improved within the MedDiet (13.7 ± 9.2 µg/mL to 17.0 ± 12.5 µg/mL, P = .016), but not within the LFD group. No statistically significant changes were observed for other inflammatory markers following the MedDiet or LFD. Adherence to the MedDiet significantly improved in both study arms, although greater improvements were seen in the MedDiet group. Adiponectin significantly improved following a Mediterranean diet intervention, in the absence of weight loss. The low-fat diet did not elicit improvements in inflammatory markers. High-quality clinical trials appropriately powered to inflammatory markers are required in this population.

Effect of Dietary Intervention, with or without Cointerventions, on Inflammatory Markers in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease from simple steatosis to nonalcoholic steatohepatitis, with inflammatory cytokines and adipokines identified as drivers of disease progression. Poor dietary patterns are known to promote an inflammatory milieu, although the effects of specific diets remain largely unknown. This review aimed to gather and summarize new and existing evidence on the effect of dietary intervention on inflammatory markers in patients with NAFLD. The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane were searched for clinical trials which investigated outcomes of inflammatory cytokines and adipokines. Eligible studies included adults >18 y with NAFLD, which compared a dietary intervention with an alternative diet or control (no intervention) group or were accompanied by supplementation or other lifestyle interventions. Outcomes for inflammatory markers were grouped and pooled for meta-analysis where heterogeneity was allowed. Methodological quality and risk of bias were assessed using the Academy of Nutrition and Dietetics Criteria. Overall, 44 studies with a total of 2579 participants were included. Meta-analyses indicated intervention with an isocaloric diet plus supplement was more effective in reducing C-reactive protein (CRP) [standard mean difference (SMD): 0.44; 95% CI: 0.20, 0.68; P = 0.0003] and tumor necrosis factor-alpha (TNF-α) (SMD: 0.74; 95% CI: 0.02, 1.46; P = 0.03) than an isocaloric diet alone. No significant weighting was shown between a hypocaloric diet with or without supplementation for CRP (SMD: 0.30; 95% CI: -0.84, 1.44; P = 0.60) and TNF-α (SMD: 0.01; 95% CI: -0.43, 0.45; P = 0.97). In conclusion, hypocaloric and energy-restricted diets alone or with supplementation, and isocaloric diets with supplementation were shown to be most effective in improving the inflammatory profile of patients with NAFLD. To better determine the effectiveness of dietary intervention alone on a NAFLD population, further investigations of longer durations, with larger sample sizes are required.

Extra virgin olive oil improves HDL lipid fraction but not HDL-mediated cholesterol efflux capacity: a double-blind, randomised, controlled, cross-over study (OLIVAUS).

Olive oil (OO) polyphenols have been shown to improve HDL anti-atherogenic function, thus demonstrating beneficial effects against cardiovascular risk factors. The aim of the present study was to investigate the effect of extra virgin high polyphenol olive oil (HPOO) v. low polyphenol olive oil (LPOO) on the capacity of HDL to promote cholesterol efflux in healthy adults. In a double-blind, randomised cross-over trial, fifty participants (aged 38·5 (sd 13·9) years, 66 % females) were supplemented with a daily dose (60 ml) of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for 3 weeks. Following a 2-week washout period, participants crossed over to the alternate treatment. Serum HDL-cholesterol efflux capacity, circulating lipids (i.e. total cholesterol, TAG, HDL, LDL) and anthropometrics were measured at baseline and follow-up. No significant between-group differences were observed. Furthermore, no significant changes in HDL-cholesterol efflux were found within either the LPOO and HPOO treatment arms; mean changes were 0·54 % (95 % CI (0·29, 1·37)) and 0·10 % (95 % CI (0·74, 0·94)), respectively. Serum HDL increased significantly after LPOO and HPOO intake by 0·13 mmol/l (95 % CI (0·04, 0·22)) and 0·10 mmol/l (95 % CI (0·02, 0·19)), respectively. A small but significant increase in LDL of 0·14 mmol/l (95 % CI (0·001, 0·28)) was observed following the HPOO intervention. Our results suggest that additional research is warranted to further understand the effect of OO with different phenolic content on mechanisms of cholesterol efflux via different pathways in multi-ethnic populations with diverse diets.

Extra virgin olive oil high in polyphenols improves antioxidant status in adults: a double-blind, randomized, controlled, cross-over study (OLIVAUS).

PURPOSE: Olive oil polyphenols have been associated with cardiovascular health benefits. This study examined the antioxidant and anti-inflammatory effect of extra-virgin high polyphenol olive oil (HPOO) vs. low polyphenol olive oil (LPOO) in healthy Australian adults. METHODS: In a double-blind cross-over trial, 50 participants (aged 38.5 ± 13.9 years, 66% females) were randomized to consume 60 mL/day of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for three weeks. Following a 2-week wash-out period, participants crossed-over to the alternate treatment. Plasma oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), high-sensitivity C-reactive protein (hs-CRP) and anthropometrics were measured at baseline and follow-up. RESULTS: Fourty-three participants completed the study. Although there were no significant differences between treatments in the total sample, plasma ox-LDL decreased by 6.5 mU/mL (95%CI - 12.4 to - 0.5) and TAC increased by 0.03 mM (95% CI 0.006-0.05) only in the HPOO arm. Stratified analyses were also performed by cardiovascular disease risk status defined by abdominal obesity (WC > 94 cm in males, > 80 cm in females) or inflammation (hs-CRP > 1 mg/L). In the subgroup with abdominal obesity, ox-LDL decreased by 13.5 mU/mL (95% CI - 23.5 to - 3.6) and TAC increased by 0.04 mM (95% CI 0.006-0.07) only after HPOO consumption. In the subgroup with inflammation, hs-CRP decreased by 1.9 mg/L (95% CI - 3.7 to -0.1) only in the HPOO arm. CONCLUSIONS: Although there were no significant differences between treatments, the changes observed after HPOO consumption demonstrate the antioxidant and anti-inflammatory effect of this oil, which is more pronounced in adults with high cardiometabolic risk (Clinical Trial Registration: ACTRN12618000706279).

The Evidence Surrounding Non-Alcoholic Fatty Liver Disease in Individuals with Cancer: A Systematic Literature Review.

Emerging evidence indicates an association between non-alcoholic fatty liver disease (NAFLD), cancer development and mortality. Cancer treatment-induced metabolic and hepatic dysfunction may be associated with increased rates of NAFLD. The review aims to investigate current evidence surrounding NAFLD in adults (≥18 years) with cancer including prevalence, effect of cancer treatments, metabolic co-morbidities, and mortality. Embase, Scopus, PubMed, and CINAHL were searched from inception to December 2021 including randomized controlled trials and observational studies. Twenty-three articles were included, comprising 142,218 participants. The overall risk of bias for observational studies was determined as low for 10 studies and neutral for 12 studies, and the RCT was determined as some concerns. The prevalence of NAFLD, based on imaging or histology, in adults with cancer ranged from 0.5 to 81.3%, with higher prevalence in breast, colorectal and gynecological cancers. Higher rates of NAFLD were also seen in patients who (i) underwent treatments-including chemotherapy and hormone therapy and/or who (ii) had higher BMI or other metabolic co-morbidities. NAFLD was associated with an increase in all-cause and cancer-related mortality. Based on review results, it is recommended that further assessment is carried out to determine whether liver screening in high-risk patients is cost effective and if interventions can be implemented to improve hepatic and health outcomes in adults with cancer.

The Association between Diet and Hepatocellular Carcinoma: A Systematic Review.

Globally, liver cancer is the sixth most common cause of cancer mortality, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. Emerging evidence states that diet is recognised as a potential lifestyle-related risk factor for the development of HCC. The aim of this systematic review is to determine whether there is an association between diet and the development of HCC. Using the PRISMA guidelines, three databases (MEDLINE Complete, CINAHL and Embase) were systematically searched, and studies published until July 2020 were included. Thirty observational studies were selected. The protocol was registered with PROSPERO (CRD42019135240). Higher adherence to the Mediterranean dietary pattern, Alternative Healthy Eating Index-2010, the Urban Prudent Dietary Pattern, the Traditional Cantonese Dietary Pattern, intake of vegetables, wholegrains, fish, poultry, coffee, macronutrients such as monounsaturated fats and micronutrients such as vitamin E, vitamin B9, ß-carotene, manganese and potassium were associated with a reduced risk of HCC. The results suggest a potential role of diet in the development of HCC. Further quantitative research needs to be undertaken within a range of populations to investigate diet and the relationship with HCC risk.

The Effect of High Polyphenol Extra Virgin Olive Oil on Blood Pressure and Arterial Stiffness in Healthy Australian Adults: A Randomized, Controlled, Cross-Over Study.

Extra virgin olive oil (EVOO) is suggested to be cardioprotective, partly due to its high phenolic content. We investigated the effect of extra virgin high polyphenol olive oil (HPOO) versus low polyphenol olive oil (LPOO) on blood pressure (BP) and arterial stiffness in healthy Australian adults. In a double-blind, randomized, controlled cross-over trial, 50 participants (age 38.5 ± 13.9 years, 66% female) were randomized to consume 60 mL/day of either HPOO (360 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for three weeks. Following a two-week washout period, participants crossed over to consume the alternate oil. Anthropometric data, peripheral BP, central BP and arterial stiffness were measured at baseline and follow up. No significant differences were observed in the changes from baseline to follow up between the two treatments. However, a significant decrease in peripheral and central systolic BP (SBP) by 2.5 mmHg (95% CI: -4.7 to -0.3) and 2.7 mmHg (95% CI: -4.7 to -0.6), respectively, was observed after HPOO consumption. Neither olive oil changed diastolic BP (DBP) or measures of arterial stiffness. The reductions in SBP after HPOO consumption provide evidence for a potentially widely accessible dietary intervention to prevent cardiovascular disease in a multiethnic population. Longer intervention studies and/or higher doses of EVOO polyphenols are warranted to elucidate the potential effect on DBP and arterial stiffness.

Effect of high polyphenol extra virgin olive oil on markers of cardiovascular disease risk in healthy Australian adults (OLIVAUS): A protocol for a double-blind randomised, controlled, cross-over study.

BACKGROUND: Previous clinical studies have suggested that high polyphenol extra virgin olive oil (EVOO) provides a superior cardioprotective effect compared to low polyphenol olive oil. However, further studies are required to replicate these results in non-Mediterranean populations. AIM: To investigate the effect of high polyphenol EVOO versus low polyphenol olive oil with known polyphenol composition on markers of cardiovascular disease risk in a healthy non-Mediterranean cohort. METHODS: In a double-blind randomised cross-over trial, the present study will examine the effect of high polyphenol EVOO versus low polyphenol olive oil in 50 healthy participants. Each intervention phase will be 3 weeks long with a 2-week washout period between each phase. Outcomes to be assessed include HDL cholesterol efflux, oxidised LDL, blood lipids, C-reactive protein, arterial stiffness, blood pressure and cognitive function. Dietary intake, physical activity levels and anthropometry will also be collected. DISCUSSION: Because of the rigorous trial design, novel and clinically relevant outcomes, the use of a well-characterised EVOO, and, in contrast to the current literature, the non-Mediterranean study population, the present study will provide a significant contribution to the understanding of the clinical importance of polyphenol intake in the Australian sociocultural context.

Effect of dietary intervention, with or without co-interventions, on inflammatory markers in patients with nonalcoholic fatty liver disease: a systematic literature review.

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver disorders, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with inflammation acting as a key driver in its pathogenesis and progression. Diet has the potential to mediate the release of inflammatory markers; however, little is known about the effects of various diets. OBJECTIVE: This systematic review aimed to evaluate the effect of dietary interventions on cytokines and adipokines in patients with NAFLD. DATA SOURCES: The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane Library were searched for clinical trials investigating dietary interventions, with or without supplementation, on cytokines and adipokines in NAFLD patients. DATA EXTRACTION: Basic characteristics of populations, dietary intervention protocol, cytokines, and adipokines were extracted for each study. Quality of evidence was assessed using the American Dietetic Association criteria. DATA ANALYSIS: Nineteen studies with a total of 874 participants were included. The most frequently reported inflammatory outcomes were C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), adiponectin, and leptin. Hypocaloric, isocaloric, or low-fat diets significantly (P < 0.05) lowered levels of CRP, TNF-α, and adiponectin. The addition of nutraceutical or pharmacological supplementation to dietary interventions appeared to elicit additional benefits for all of the most frequently reported inflammatory markers. CONCLUSIONS: Hypo- or isocaloric diets alone, or with co-interventions that included a nutraceutical or pharmacological supplementation, appear to improve the inflammatory profile in patients with NAFLD. Thus, anti-inflammatory diets may have the potential to improve underlying chronic inflammation that underpins the pathophysiological mechanisms of NAFLD. In the absence of any known liver-sensitive markers, the use of cytokines and adipokines as a surrogate marker of liver disease should be further investigated in well-controlled trials.

The effect of high-polyphenol extra virgin olive oil on cardiovascular risk factors: A systematic review and meta-analysis.

The polyphenol fraction of extra-virgin olive oil may be partly responsible for its cardioprotective effects. The aim of this systematic review and meta-analysis was to evaluate the effect of high versus low polyphenol olive oil on cardiovascular disease (CVD) risk factors in clinical trials. In accordance with PRISMA guidelines, CINAHL, PubMed, Embase and Cochrane databases were systematically searched for relevant studies. Randomized controlled trials that investigated markers of CVD risk (e.g. outcomes related to cholesterol, inflammation, oxidative stress) were included. Risk of bias was assessed using the Jadad scale. A meta-analysis was conducted using clinical trial data with available CVD risk outcomes. Twenty-six studies were included. Compared to low polyphenol olive oil, high polyphenol olive oil significantly improved measures of malondialdehyde (MD: -0.07µmol/L [95%CI: -0.12, -0.02µmol/L]; I2: 88%; p = 0.004), oxidized LDL (SMD: -0.44 [95%CI: -0.78, -0.10µmol/L]; I2: 41%; P = 0.01), total cholesterol (MD 4.5 mg/dL [95%CI: -6.54, -2.39 mg/dL]; p<0.0001) and HDL cholesterol (MD 2.37 mg/dL [95%CI: 0.41, 5.04 mg/dL]; p = 0.02). Subgroup analyses and individual studies reported additional improvements in inflammatory markers and blood pressure. Most studies were rated as having low-to-moderate risk of bias. High polyphenol oils confer some CVD-risk reduction benefits; however, further studies with longer duration and in non-Mediterranean populations are required.

Non-alcoholic fatty liver disease patients attending two metropolitan hospitals in Melbourne, Australia: high risk status and low prevalence.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally, with increased rates in high-risk populations, including type 2 diabetes and obesity. The condition increases the risk of end-stage liver disease, hepatocellular carcinoma and all-cause mortality. NAFLD is asymptomatic and often remains undiagnosed as routine screening in high-risk groups is not practised. AIMS: The aim of this study was to determine the rates and characteristics of NAFLD patients attending liver clinics at two Melbourne metropolitan hospitals. METHODS: Liver clinics were prospectively screened for 10 consecutive months and participants with a diagnosis of NAFLD were further evaluated using pathology and imaging results obtained from medical records. RESULTS: Of the 2050 patients screened, 148 (7%) had NAFLD predominantly diagnosed using ultrasound (81%). NAFLD patients were obese (mean body mass index 30.7 ± 5.9 kg/m2 ), insulin resistant (median HOMA 4.2 (3.2) mmol/L) and had elevated liver enzymes (ALT median, males 47.0 (34.3), females 36.0 (28.0) U/L), and 18% of patients had liver stiffness measuring >12 kPa, suggesting a moderate probability of cirrhosis. Patients with liver stiffness measuring ≥9.6 kPa had significantly higher: glucose (median 5.5 (1.2) vs 6.2 (5.3) mmol/L, P = 0.007), aspartate aminotransferase levels (median 25.5 (26.0) vs 41.0 (62.0) u/L, P = 0.0005) and HOMA (3.1 (3.0) vs 5.4 (5.5) mmol/L, P = 0.040). CONCLUSIONS: NAFLD constituted a minority of liver clinic patients, most of who were obese, insulin resistant and hypertensive, and many had an elevated liver stiffness measurement. NAFLD poses added adverse health outcomes to high-risk patients, and therefore, early detection is warranted.

Randomization to 6-month Mediterranean diet compared with a low-fat diet leads to improvement in Dietary Inflammatory Index scores in patients with coronary heart disease: the AUSMED Heart Trial.

A higher dietary inflammatory index (DII®) score is associated with inflammation and incidence of coronary heart disease (CHD). We hypothesized that a Mediterranean diet (MedDiet) intervention would reduce DII score. We assessed dietary data from a randomized controlled trial comparing 6-month MedDiet versus low-fat diet intervention, in patients with CHD. We aimed to determine the DII scores of the prescribed diets' model meal plans, followed by whether dietary intervention led to lower (i.e., more anti-inflammatory) DII scores and consequently lower high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (hs-IL-6). DII scores were calculated from 7-day food diaries. The MedDiet meal plan had a markedly lower DII score than the low-fat diet meal plan (-4.55 vs. -0.33, respectively). In 56 participants who completed the trial (84% male, mean age 62 ±â€¯9 years), the MedDiet group significantly reduced DII scores at 6 months (n = 27; -0.40 ±â€¯3.14 to -1.74 ±â€¯2.81, P = .008) and the low-fat diet group did not change (n = 29; -0.17 ±â€¯2.27 to 0.05 ±â€¯1.89, P = .65). There was a significant post-intervention adjusted difference in DII score between groups (compared to low-fat, MedDiet decreased by -1.69 DII points; P = .004). When compared to the low-fat diet, the MedDiet non-significantly reduced hs-IL-6 (-0.32 pg/mL, P = .29) and increased hs-CRP (+0.09 mg/L, P = .84). These findings demonstrated that MedDiet intervention significantly reduced DII scores compared to a low-fat diet. However, in this small cohort of patients with CHD this did not translate to a significant improvement in measured inflammatory markers. The effect of improvement in DII with MedDiet should be tested in larger intervention trials and observational cohorts.