Changes in liver health biomarkers following consumption of energy restricted diets containing almonds compared with carbohydrate-rich snack foods for 9 months

Energy restricted diets improve liver function(1) and habitual nut consumption has been associated with a lower prevalence of fatty liver(2). This study examined the effect of incorporating almonds in an energy restricted diet on liver health biomarkers. One Hundred and forty adults (42M:98F, 47.5 ± 10.8 years, BMI 30.7 ± 2.3 kg/m2) enrolled in a 9-month (9M) dietary intervention comprising 3 months (3M) weight loss (30% energy restriction) followed by 6 months (6M) of weight maintenance. Participants were randomly assigned to consume almonds (n = 68, AED) or isocaloric carbohydrate-rich snacks (n = 72, CRD) which provided 15% of total daily energy. At baseline (BL), 3M and 9M, fatty liver index (FLI) scores (0-100)(3) were calculated using body mass index (BMI), waist circumference (WC), fasting serum gamma-glutamyl transferase (GGT) and triglyceride (TAG) levels, and other liver health biomarkers were assessed by ultrasound (volume, visual appearance and elastography (a marker of stiffness due to fibrosis)). Intention to treat analyses were conducted using mixed effects modelling (fixed effects group and time, with participants as the random effect). Significant reductions from BL occurred over time (all p<0.001 for 3M and 9M) with no difference between groups (AED vs CRD, P>0.05) in BMI (3M: −2.44 ± 0.20 vs −2.32 ± 0.20, 9M: −2.83 ± 0.19 vs −2.81 ± 0.19 kg/m2), WC (3M: −8.04 ± 0.79 vs −7.00 ± 0.81, 9M: −8.72 ± 0.83 vs −9.14 ± 0.81 cm), TAG (3M: −0.24± 0.08 vs −0.22 ± 0.09, 9M: −0.37 ± 0.09 vs −0.21 ± 0.09 mmol/L), FLI score (3M: −23.8 ± 2.0 vs −17.6 ± 2.1, 9M: −23.8 ± 2.0 vs −17.6 ± 2.1), and liver volume (3M: −134.56 ± 38.30 vs −100.96 ± 37.25, 9M: −113.68 ± 37.42 vs −110.64 ± 35.47cm3). Significantly greater reductions occurred for AED compared to CRD at 3M and 9M in GGT (p = 0.003) (3M: −9.68 ± 1.93 vs −0.01 ± 2.00, 9M: −7.75 ± 2.06 vs −2.78 ± 2.15 IU/L) and liver visual assessment scores (p = 0.03) (3M: −0.58 ± 0.24 vs −0.45 ± 0.23, 9M: −1.33 ± 0.23 vs −0.50 ± 0.22). There were no significant changes in liver elastography over time or between groups. Energy restriction improved body composition and reduced the extent of fatty liver and liver size but did not change liver stiffness. The inclusion of almonds in an energy restricted diet demonstrated additional benefits to some liver health biomarkers providing support for almonds being incorporated into lifestyle interventions to improve liver function.

Resveratrol promotes liver regeneration in drug-induced liver disease in mice

Studies suggest that the bioactive polyphenolic compound resveratrol (RESV, trans-isomer), found naturally in certain foods such as red grapes and peanuts, may be able to ameliorate liver damage. However, the effects and efficacy of long-term treatment with RESV remain unclear. Here, we used an acetaminophen (APAP; 400 mg/kg/d for 15 days) overdose model to induce liver damage in C56BL/6 mice. Three days after the intoxication was stopped, we observed biochemical, histological and ultrastructural alterations in the livers of these mice. The APAP-treated animals were then given RESV (10 mg/kg/d) for 60 days. Blood and tissue were analyzed at days 7, 30 and 60. Our data show that long-term RESV treatment (60 days) ameliorates the liver injury caused by APAP intoxication, restoring histological features, ultrastructural organization and serum biochemical parameters (albumin, alanine aminotransferase). Ck18- and F4/80-positive cells (indicators of hepatocyte recovery) were reestablished and the number of α-SMA positive cells was normalized after long-term RESV treatment. Additionally, downregulation of the drug transporter BCRP was observed. Electron microscopy revealed that treatment with RESV was effective in restoring the shape and size of hepatic microvilli and normalizing both the number and viability of mitochondria. Taken together, these results indicate that long-term treatment with RESV is effective in alleviating liver injury caused by APAP administration.

Walnut-Enriched Diet Elevated α-Linolenic Acid, Phytoprostanes, and Phytofurans in Rat Liver and Heart Tissues and Modulated Anti-inflammatory Lipid Mediators in the Liver.

α-Linolenic acid (ALA) and its non-enzymatic oxidized products, namely, phytoprostanes and phytofurans, are found in some nuts. The uptake and deposition of these compounds are not well-defined. Walnut has high ALA and a considerable amount of phytoprostanes and phytofurans compared to other common nuts. When fed to rodents, ALA and eicosapentaenoic acid levels increased in the liver and heart tissues compared to the control diet. Furthermore, phytoprostanes and phytofurans were elevated 3-fold in both tissues after a walnut diet, indicating that they are not only contributed from the diet but also generated through in vivo autoxidation of ALA found in the walnuts. It was further noted that a walnut diet reduced 5-F2t-isoprostanes and 12-hydroxyeicosatetraenoic acid and induced 4-F4t-neuroprostane and significant amounts of anti-inflammatory hydroxydocosahexaenoic acid in the liver only. Altogether, high ALA in a walnut diet elevated phytoprostanes and phytofurans in the liver and heart tissues and showed the regulation of anti-inflammatory lipid mediators in the liver only.

A Walnut Diet in Combination with Enriched Environment Improves Cognitive Function and Affects Lipid Metabolites in Brain and Liver of Aged NMRI Mice.

This in vivo study aimed to test if a diet enriched with 6% walnuts alone or in combination with physical activity supports healthy ageing by changing the oxylipin profile in brain and liver, improving motor function, cognition, and cerebral mitochondrial function. Female NMRI mice were fed a 6% walnut diet starting at an age of 12 months for 24 weeks. One group was additionally maintained in an enriched environment, one group without intervention served as control. After three months, one additional control group of young mice (3 weeks old) was introduced. Motor and cognitive functions were measured using Open Field, Y-Maze, Rotarod and Passive Avoidance tests. Lipid metabolite profiles were determined using RP-LC-ESI(-)-MS/MS in brain and liver tissues of mice. Cerebral mitochondrial function was characterized by the determination of ATP levels, mitochondrial membrane potential and mitochondrial respiration. Expression of genes involved with mito- and neurogenesis, inflammation, and synaptic plasticity were determined using qRT-PCR. A 6% walnut-enriched diet alone improved spatial memory in a Y-Maze alternation test (p < 0.05) in mice. Additional physical enrichment enhanced the significance, although the overall benefit was virtually identical. Instead, physical enrichment improved motor performance in a Rotarod experiment (p* < 0.05) which was unaffected by walnuts alone. Bioactive oxylipins like hydroxy-polyunsaturated fatty acids (OH-PUFA) derived from linoleic acid (LA) were significantly increased in brain (p** < 0.01) and liver (p*** < 0.0001) compared to control mice, while OH-PUFA of α-linolenic acid (ALA) could only be detected in the brains of mice fed with walnuts. In the brain, walnuts combined with physical activity reduced arachidonic acid (ARA)-based oxylipin levels (p < 0.05). Effects of walnut lipids were not linked to mitochondrial function, as ATP production, mitochondrial membrane potential and mitochondrial respiration were unaffected. Furthermore, common markers for synaptic plasticity and neuronal growth, key genes in the regulation of cytoprotective response to oxidative stress and neuronal growth were unaffected. Taken together, walnuts change the oxylipin profile in liver and brain, which could have beneficial effects for healthy ageing, an effect that can be further enhanced with an active lifestyle. Further studies may focus on specific nutrient lipids that potentially provide preventive effects in the brain.

Effects of almond consumption on metabolic function and liver fat in overweight and obese adults with elevated fasting blood glucose: A randomised controlled trial.

BACKGROUND: Almonds are a rich source of bioactive components. This study examined the effects of daily almond consumption on glycaemic regulation, liver fat concentration and function, adiposity, systemic inflammation and cardiometabolic health. METHODS: 76 adults with elevated risk of type 2 diabetes (T2D) or T2D (age: 60.7 ± 7.7 years, body mass index: 33.8 ± 5.6 kg/m2) were randomly assigned to daily consumption of either 2 servings of almonds (AS:56 g/day) or an isocaloric, higher carbohydrate biscuit snack (BS) for 8 weeks. Glycosylated haemoglobin (HbA1c), glycaemic variability (GV), liver fat, serum aminotransferases, body weight and composition, markers of cardio-metabolic risk and systemic inflammation were assessed at baseline and week 8. RESULTS: No group differential effects were observed on HbA1c, GV, body weight and composition, liver fat and aminotransferases, cardio-metabolic health and inflammatory markers (all P > 0.05). For serum TC/HDL-C ratio a significant gender × treatment × time interaction occurred (P < 0.01), such that in women TC/HDL-C ratio was significantly reduced after AS compared to BS (-0.36 [0.26] mmol/L [n = 14] vs. -0.14 [0.32] mmol/L [n = 17]; P = 0.05), but not in men (P = 0.52). CONCLUSIONS: Compared to BS, AS consumed between meals did not substantially alter glycaemic regulation, liver fat or function, adiposity, and metabolic health and inflammatory markers. Serum TC/HDL-C ratio improved in women, but not in men with AS; but as this sub-analysis was not defined a priori the results should be interpreted with caution. Further research should examine the longer-term health effects of regular almond consumption and differential gender responses. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: Australia New Zealand Clinical Trial Registry: ACTRN12616000571471 (

Changes in fatty liver index after consuming a Mediterranean diet: 6-year follow-up of the PREDIMED-Malaga trial.

OBJECTIVE: To analyze the effect of an intervention with a Mediterranean diet supplemented with either extra virgin olive oil or nuts, on the fatty liver index (FLI), compared to a low-fat control diet. METHODS: Participants of the PREDIMED-Malaga trial, free from cardiovascular disease at baseline, but with a high risk to develop it, were included in this study. Anthropometric measurements were assessed and blood samples were taken to calculate participants' FLI at study baseline and after one, 3, 5 and 6 years. Mixed linear models were used to explore the fixed effects of the 3 intervention groups on the FLI as well as their interaction with time. RESULTS: A total of 276 participants were included in the study. Average participant age was 67 years, with 66% of participants being women. The baseline prevalence of NAFL was 57%. The change in the FLI of the control group increased significantly over time (1.13±0.41; P=.006). In the MedDiet+EVOO group, the time trend of the change in the FLI was similar to that of the control group, although it was seen to be lower (-3.90±1.9; P=.038). In the MedDiet+Nuts group, the trend was significantly lower than that of the control group (-1.63±0.62; P=.009). In the MedDiet+Nuts group, the trend of changes in participants' BMI was 0.100 points lower per year compared to the control group (P=.004). In the control group, the change in waist circumference increased significantly over time (0.61±0.16cm/year; P<.001) in contrast to the MedDiet+EVOO group, in which this variable remained stable (-0.51±0.22; P=.019). CONCLUSIONS: A dietary intervention consisting of a Mediterranean diet could delay or slow down the natural progression of NAFL, thus, being beneficial for its prevention and treatment. However, further studies supporting these conclusions have yet to be carried out.

Antioxidant and hepatoprotective properties of dried fig against oxidative stress and hepatotoxicity in rats.

The aim of this study was to investigate the hepatoprotective effect and antioxidant role of dried fig (DF) (Ficus carica L.) against ethanol-induced oxidative stress. Experiment was designed as normal Control, 20% ethanol, 10% DF and 10% DF+20% ethanol groups. The hepatoprotective and antioxidant role of the dried DF supplementation feed against ethanol induced oxidatif stress were evaluated by liver histopathological changes, measuring liver damage serum enzymes (LDSE), antioxidant defense system (ADS) and malondialdehyde (MDA) content in various tissues of rats following the exposure of experimental for 50days. The biochemical analysis showed a considerable increase the LDSE in the ethanol group as compared to that of control group whereas, decreased in 10% DF+20% ethanol group as compared to that of ethanol group. In addition, the DF supplementation diet restored the ethanol-induced MDA and ADS towards to control. The hepatoprotection of DF is further substantiated by the almost normal histologic findings of liver in 10% DF+20% ethanol group against degenerative changes in ethanol group. The results indicated that the DF could be as important as diet-derived antioxidants and antihepatotoxicity in preventing oxidative damage in the tissues by inhibiting the production of ethanol-induced free radicals and hepatotoxicity in rats.

Hepatoprotective effect and antioxidant role of sun; sulphited-dried apricot (Prunus armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats

The present study was carried to evaluate the hepatoprotective effect and antioxidant role of sun; sulphited-dried apricot and its kernel against ethanol-induced oxidative stress. The hepatopreventive and antioxidant potential of the plant's supplementations were evaluated by measuring level of serum liver damage marker enzymes (AST; ALT; GGT and LDH); antioxidant defense systems (GSH; GR; SOD; GST and GPX) and MDA content in various tissues of rats. Eight experimental groups: I (control); II (20% ethanol); III (ethanol+15% sun-dried apricot); IV (ethanol+30% sun dried). V (ethanol+15% sulphited-dried); VI(ethanol+30% sulphited-dried); VII (ethanol+15% kernel) and VIII (ethanol+30% kernel). According to the results; the levels of serum enzymes increased significantly in the II group as compared to those of I group; but they decreased in the III; IV; V and VI groups as compared to those of II group. Also; administration of sun and sulphited-dried apricot supplementation restored the ethanol-induced imbalance between MDA and antioxidant system towards near normal particularly in tissues but not its kernel. It is concluded that apricot has a hepatoprotective effect in rats with ethanol; probably acting by promoting the antioxidative defense systems.

Hepatoprotective effects of almond oil against carbon tetrachloride induced liver injury in rats

This research aimed at evaluating the protective effects of almond oil against acute hepatic injury induced by carbon tetrachloride in rats. The study results showed that animals received almond oil prior to the administration of CCl4 significantly decreased serum alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities; and total cholesterol (TC); triglyceride (TG) and low density lipoprotein (LDL) content; and increased serum high density lipoprotein (HDL) content. Whereas; pre-treatment with almond oil markedly increased rat hepatic superoxide dismutase (SOD); catalase and glutathione peroxidase (GPx) levels; and decreased the malondialdehyde (MDA) level. These results combined with liver histopathology demonstrated that almond oil has potent hepatoprotective effects; and could be developed as a functional food for the therapy and prevention of liver damage.

Walnut Polyphenols Prevent Liver Damage Induced by Carbon Tetrachloride and d-Galactosamine: Hepatoprotective Hydrolyzable Tannins in the Kernel Pellicles of Walnut

The polyphenol-rich fraction (WP; 45% polyphenol) prepared from the kernel pellicles of walnuts was assessed for its hepatoprotective effect in mice. A single oral administration of WP (200 mg/kg) significantly suppressed serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) elevation in liver injury induced by carbon tetrachloride (CCl 4); while it did not suppress d-galactosamine (GalN)-induced liver injury. In order to identify the active principles in WP; we examined individual constituents for the protective effect on cell damage induced by CCl 4 and d-GalN in primary cultured rat hepatocytes. WP was effective against both CCl 4- and d-GalN-induced hepatocyte damages. Among the constituents; only ellagitannins with a galloylated glucopyranose core; such as tellimagrandins I; II; and rugosin C; suppressed CCl 4-induced hepatocyte damage significantly. Most of the ellagitannins including tellimagrandin I and 2;3- O-hexahydroxydiphenoylglucose exhibited remarkable inhibitory effect against d-GalN-induced damage. Telliamgrandin I especially completely suppressed both CCl 4- and d-GalN-induced cell damage; and thus is likely the principal constituent for the hepatoprotective effect of WP.