Non Alcoholic Fatty Liver Disease (NAFLD) Treatment In Healthy Food Perspective(3)

By Kyle J. Norton

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition caused by fat accumulated in the liver over time, in the absence of excessive alcohol use. The disease can be classified into the types of non-inflammatory fatty liver (NAFl) and inflammatory nonalcoholic steatohepatitis (NASH)(1).

Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of cirrhosis and liver cancer.

According to world statistics, nonalcoholic fatty liver disease (NAFLD) is normally known as a disease of the Western world(2). However, due to the economic prosperity of Southeast Asian(3), the disease also was found in a large number of population in the cities, causing concerns of many scientists in the region(4)(6).

According to the joint assessment of the prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the US, led by the Stanford University School of Medicine, "The prevalence of NAFLD in the United States (U.S.) has risen from 18% in 1988–1991 to 31% in 2011–2012. Estimates of NAFLD prevalence for adults in Western countries is 20–30%, with much higher prevalence in adults with obesity (80–90%), diabetes (30–50%), and hyperlipidemia (90%)"(5).

Among the more affluent regions of China, the prevalence rate of non-alcoholic fatty liver disease (NAFLD) is approximately 15%(6). The number may decrease substantially if the poor rural populations where obesity is non-existence are also taking into account(7).

The exact causes of NAFLD aren't well understood. Some researchers suggested that certain risk factors such as long-term use of certain medications(8), genetic preposition(8), insulin resistance(8), high cholesterol(8) and triglycerides(8) in the blood, polycystic ovary syndrome(8), metabolic syndrome(8), obesity(8), and type 2 diabetes(8) are associated with the onset of the disease.

Recent studies also found that people with obstructive sleep apnea(11), underactive thyroid (hypothyroidism(10) and underactive pituitary gland (hypopituitarism) (9) also at an increased risk of the NALFD.

Some researchers suggested that unhealthy diet such as high-fat diet may also have a strong implication on NAFLD(12)(13).


Dr. Jensen VS, the lead scientist in the study high-fat diet-induced non-alcoholic fatty liver disease, wrote, "In humans and animal models, excessive intake of dietary fat, fructose, and cholesterol has been linked to the development of non-alcoholic fatty liver disease (NAFLD)"(13).

And, " Only HFr-fed rats developed dyslipidemia as characterized by higher levels of plasma triglycerides compared to all other groups (p < 0.0001). Hepatic dysfunction and inflammation was confirmed in HFD-fed rats by elevated levels of hepatic MCP-1 (p < 0.0001), TNF-alpha (p < 0.001) and plasma β-hydroxybutyrate (p < 0.0001), and in NASH-fed rats by elevated levels of hepatic MCP-1 (p < 0.01), increased hepatic macrophage infiltration (p < 0.001), and higher plasma levels of alanine aminotransferase (p < 0.0001) aspartate aminotransferase (p < 0.05), haptoglobin (p < 0.001) and TIMP-1 (p < 0.01) compared to Control"(13).

According to the statistics, in the US, over 100 million people have non-alcoholic fatty liver disease and the condition is more double over the past 20 years(14). The disease also is the most prevalent liver disease in children(14).

The prevalence rate of NAFLD is varied among different ethnic groups in the US. Dr. Rich NE, the lead scientist in the investigation of the ethnicity and NAFLD, wrote, "NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high-risk cohorts (range 47.6%-55.5%) than population-based cohorts (range, 13.0%-22.9%)(15)".

And, "Among patients with NAFLD, the risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98-1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60-0.87) than Whites"(15).

The progression of NAFLD and NASH led to cirrhosis, the late stage of liver scarring are well defined, as the liver tries to heal itself by halting inflammation(16), leading to symptoms of ascites(16)(18), swell esophageal varices(16)(19), hepatic encephalopathy(16)(17) and complications of liver cancer(16)(17) and liver failure(16)(17).

Most people at the early stage NAFLD are asymptomatic, however, as the disease progression into the later stage, most patients experience symptoms of right upper abdominal discomfort(20), fatigue(20), and/or malaise(20), and jaundice(20) with yellowing of the skin and eyes(20).

Most patients with NAFLD have elevated levels of liver enzymes gamma-glutamyl transferase (GGT)(21) and/or Aspartate Aminotransferase (AST)(21) to platelet ratio index (APRI) score(21), and/or Alanine Aminotransferase (ALT) (21) which are the markers used to predict the severity of liver disease including the fatty liver. A blood test is required if you suspected to have developing nonfatty liver disease.

Conventionally, as of today, there is no effective treatment of NAFLD(22)(23). Weight loss for overweight and obese patients(22) has been recommended through our the industry accompanied by the change of lifestyles(22) such as moderate exercise and reduced intake of alcohol, depending on individuals.

Patients who are hepatitis virus B and C carriers are also recommended to be vaccinated(22).

Given the nature of the nonalcoholic fatty liver disease, the search for effective treatment for NAFLD from the natural sources used over thousands of years in traditional medicine for the treatment of liver disease has been intensified(23). Many secondary metabolites, whole foods, and herbal medicine have been found to be effective in vivo, vitro and small human trials(24). However, most of them were stopped due to a simple reason. Who will spend billions to prove the thing which has no commercial values? Secondary metabolites, whole foods, and herbal medicine cannot be patented.

C. Healthy foods
Eating a healthy diet with a high in vegetables and fruits knowledged by health experts is the best way to prevent diseases including non-alcoholic fatty liver disease, particularly in older adults.

1. Olea europaea (Olive)
Olive Its fruit, is also called the olive and the source of olive oil. Olea europaea L is a small tree, belonging to the family Oleaceae,  native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea(98).

In the evaluation of oxidative stress induced non-alcoholic steatohepatitis (NASH) on hypertensive/NIH-corpulent rats fed a diet of AIN-93G with or without olive leaf extract (500, 1000, 2000 mg/kg diet, and control; 5 rats each) for 23 weeks, oleuropein, the active constituent of olive leaf, exhibited antioxidative stress(99) by enhancing the levels of antioxidant(99) against hepatic fat accumulation(99) in a rat model of NASH.

In other words, a diet of AIN-93G containing more than 1000 mg/kg olive leaf extract had a preventive effect on the occurrence of NASH(99) by improving the levels of thioredoxin-1 expression(99) and decreasing the levels of 4-hydroxynonenal expression(99) associated with hepatic lipid peroxidation(99) in rat with NASH.

Where overexpression of thioredoxin-1 expression is a marker of liver disease.

Based on the findings, researchers said, "olive leaf extract may help prevent NASH,... through its anti-oxidative activity.".


Also, in rats fed a cholesterol-rich diet for 16 weeks, administration of polyphenol-rich olive leaf extracts significantly lowered total cholesterol (TC)(100), triglycerides (TG)(100) and low-density lipoprotein cholesterol (LDL-C)(100) and increased the serum level of high-density lipoprotein cholesterol (HDL-C)(100).

Furthermore, administration of polyphenol-rich olive leaf extracts was found to lower the levels of thiobarbituric acid reactive substances (TBARS)(100), a byproduct of lipid peroxidation upon the injection of in liver, heart, kidneys, and aorta significantly.

Moreover, the also extracts also increased the serum antioxidant potential(100) and the hepatic CAT(100) and SOD activities(100).

Collectively, polyphenol-rich olive leaf extracts protected the liver against the onset of NASH(100) by inhibiting parameters(100)  involved in the production of oxidative stress(100).


2. Punica granatum L. (Pomegranate)
Pomegranates is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time.  Pomegranate flower (PGF) has been used in traditional medicine for the treatment of hyperlipidemia, insulin resistance, and diabetes(101).

In glucose-fed hyperglycaemic and alloxan-induced diabetic rats, oral administration of its aqueous-ethanolic (50%, v/v)extracts of pomegranate led to significant lowering the blood glucose(101)with a maximum dose up to 400 mg/kg, b.w.

On on streptozotocin (STZ) induced diabetic rats, Punica granatum aqueous extract (PgAq)  restored parameters of diabetes(103) including  blood glucose level(103), total cholesterol (TC)(103), triglycerides (TG)(103), low-density lipoprotein cholesterol (LDL-C)(103), very low density lipoprotein (VLDL)(103), and improved  antioxidant profiles(103) including glutathione-S-transferase (GST)(103), superoxide dismutase (SOD)(103) and catalase (CAT)(103).

Additionally, the extract also elevated the levels of HDL-C(103), compared to the diabetic control group.

In other words, Punica granatum aqueous extract (PgAq) processed anti-chronic diseases including NASH associated with atherogenic lipoprotein profile(103), aggravated antioxidant status(103), and impaired glucose metabolism(103).


3. Zingiber officinale (Ginger)
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil, used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, and colitis(104).

On streptozotocin (STZ)-induced type I diabetic rats, oral administration of juice of Z. officinale (4 ml kg-1, p.o. daily) for 6 weeks showed a significant increase in insulin levels(105) and a decrease in fasting glucose levels(105).

 Treatment with Z. officinale also decreased serum cholesterol(105), serum triglyceride(105) and blood pressure(105) in diabetic rats. 

Based on the findings, researchers said, " (The) potential antidiabetic activity of the juice of Z. officinale in type I diabetic rats, possibly involving 5-HT receptors".

In vitro, Zingiber officinale Roscoe was found to reduce the elevation of rat plasma triacylglycerol(106)  levels 1 and 2 h involved in hydrolysis(106) after oral administration of a lipid emulsion containing corn oil by interfering the intestinal absorption of dietary fat.

In vivo, mice fed the high-fat diet containing 3% aqueous extract of Z. officinale Roscoe compared to controls fed the high-fat diet significantly reduced final parametrial adipose tissue weights(106) associated with fat metabolism(106).

4. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China(107).

In male ZF rats fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk,  GTP intervention showed a decreased weight gain(108) and a significantly lowered visceral fat(108).

GTP treatment not only significantly reduced fasting serum insulin(108), glucose(108), and lipids levels(108), but also attenuated the levels of pro-inflammatory cytokines(108) in rats fed a high-fat diet (HFD) by regulating the pathways associated with fat metabolism(108).

Furthermore, GTP treated rats also was found with hepatic lipogenesis(108) and triglycerides outflux(108) from the liver, compared to controls.

SlimTrym®, a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract, and lychee extract administrated in male C57BL/6 mice fed a normal diet (ND), high fat diet (HFD) or HFD containing 0.1% or 0.5% SlimTrym® for 16 weeks, significantly reduced weight gain(109) and relative perigonadal(109), retroperitoneal(109), mesenteric fat weight(109) as well as the size of the adipocyte(109).

Moreover, SlimTrym® supplementation also effectively inhibited the hepatic steatosis(109) and the elevated serum levels of enzymes(109) associated with liver injury or damage, such as glutamate oxaloacetate transaminase (GOT)(109), glutamate pyruvate transaminase (GPT)(109).

Observation of the adipose tissue and liver after injection of SlimTrym®, researchers found that the formula also SlimTrym® exerted its anti-NASH(109) and obesity(109) effect by inhibiting the receptors(109) involved in lipogenesis(109) and lipid accumulation(109).

5. Wolfberry
Wolfberry is the fruit of plant Lycium barbarum of the family Solanaceae, used as a famous drug or supplement by traditional Chinese medicine for the treatment of liver and eyes problems(110).

 In C57BL/6N mice by feeding with MCD diet for 6 weeks, accompanied by the 1 mg/kg Lycium barbarum polysaccharides (LBP) intragastrically fed on a daily basis with or without MCD diet lasting from the 4th to 6th week, LBP,  a major bioactive constituents of wolfberry attenuated the hepatic injury(111) in a non-alcoholic steatohepatitis (NASH)(111) induced by methionine-choline-deficient (MCD)(111) in mouse model.

Additonally, LBP normalized the increased serum ALT(111) and AST levels(111), hepatic oxidative stress(111), fibrosis(111), inflammation(111), and apoptosis(111) in a mouse model fed with MCD diet.

Furthermore, LBP injection also attenuated the overexpression of proteins(111) in facilitating the production of pro-inflammatory cytokines(111) involved in lipid peroxidation(111).

Based on the findings, researchers suggested that the reduction of hepatic injury during the progression of NASH by therapeutic LBP treatment is attributed to the inhibition of proteins and protein receptor associated with proinflammation and inflammatory diseases(111), respectively.

Moreover, on a high‑fat diet (HFD)-induced NAFLD mice model and C57BL/6 mice fed a normal control diet, high‑fat diet (HFD), HFD supplemented with 2 g/kg LRE, or HFD supplemented with 5 g/kg LRE, treatment with LRE markedly decreased the levels of triglycerides(112), total cholesterol(112), aspartate aminotransferase(112) and alanine aminotransferase(112) in the serum of mice fed an HFD, and improved glucose metabolism(112) and insulin sensitivity(112) in NAFLD mice.

Also, treatment with LRE significantly decreased the expression level of proteins(112) involved in the transcriptional regulation of lipid metabolism(112), energy balance(112), and inflammation(112) in the liver tissues through enhancing the hepatic AMPK pathway(112) in preventing liver lipid accumulation and insulin resistance.

6. Garlic
Garlic, or Allium sativum, is a species in the onion genus Allium, native in Asia, Egypt, and the Mediterranean regions, used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic(113).

According to the study by the Huazhong University of Science and Technology, a traditional Chinese medicine formula including resveratrol, Lycium barbarum polysaccharides, dioscin, bergamot polyphenol fraction, capsaicin, and garlic-derived S-allylmercaptocysteine, garlic-derived S-allylmercaptocysteine, inhibit the progression of NAFLD(114) by exhibiting the liver autophagy/lipophagy(114).

In other words, the formula protected the liver against the onset of NAFLD by inhibiting insulin resistance(114), dysfunctional lipid metabolism(114), endoplasmic reticulum stress(114), oxidative stress(114), inflammation(114), and apoptosis/necrosis(114).

Furthermore, in a clinical trial including 110 subjects with NAFLD were randomly assigned to the intervention or the control group. The intervention group received two garlic tablets (containing 400 mg of garlic powder) daily while the control group received placebo tablets, 400 mg of garlic powder showed a significantly greater reduction in body weight(116) and fat mass(116) compared to controls.


7. Uncontaminated  fish oil
Uncontaminated fish oil is derived from the tissues of oily fish, excluding fish which are contaminated and at the top of the food chain(117). 

Fish do not actually produce omega-3 fatty acids, but instead, accumulate them from consuming microalgae that produce these fatty acids.

Compared to the 10 male Sprague-Dawley rats fed a control diet (CON), a Western-style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively, researchers found that fish oil significantly ameliorated WD-induced dyslipidemia(118), transaminase elevation(118), hepatic steatosis(118), inflammatory infiltration(118), and fibrosis(118) induced by the Western diet by correcting the expression levels of genes(118) involved in fatty acid and cholesterol metabolism(118).

Additionally, fish oil also inhibited the expression levels of pro-inflammation genes(118) such as Mcp1, Socs2, Sema4a, and Cd44(118) compared to the WD group.

Collectively, researchers said, " fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation".

In male Sprague-Dawley rats fed with a lab chow (CON), high-fat high-cholesterol diet (WD), or WD supplemented with fish oil (FOH), respectively, fish oil modification of hepatic lipid metabolism(119) and signaling transduction(119) through the alternation of hepatic miRNAs(119) including rno-miR-29c-3p, rno-miR-30d-5p, rno-miR-33-5p, rno-miR-34a, and rno-miR-328a-3p,  compared to differentially expressed miRNAs (DEMs) between FOH and WD groups.

By compared to different expression of miRNAs (DEMs) between FOH and WD groups, researchers said, (The result) reveals that fish oil supplementation alters hepatic expression of miRNAs, which may contribute to fish oil amelioration of NAFLD in rats".


8. Flax seeds
The seeds of the flax plant (Linum usitatissimum) contained both omega-3 and omega-6 fatty acids. 

Its oil used as a supplement generally contains 50% of the omega-3 fatty acid - alpha-linolenic acid and 25 % of the omega-6 fatty acid linolenic acid, 15 % of mainly monounsaturated oleic acid and trace amounts of palmitoleic acid and eicosenoic acid(120).

In the aged laying-hens-a novel and more physiologically relevant model of human disease induced NAFLD, supplemented with whole flaxseed (WFX) reduced steatosis(121) and hepatocellular ballooning(121).

Furthermore, the serum AST(121) associated with liver injury or damage(121) also was reduced in hens provided WFX and defatted flaxseed meal (DFM).

Compared to other group fed with fas seeds, FXO supplementation showed a greater effect in the modification of transcript abundance of genes(121) linked to NAFLD.

Based on the findings, researchers said, "These findings demonstrate the potential use of whole flaxseed for the treatment and prevention of NAFLD in humans".

In a  two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD), assigned to take either a lifestyle modification (LM) or LM +30 g/day brown milled flaxseed for 12 weeks, researchers found that at the end of the study,
 flaxseed supplementation exhibited a significantly greater reduction on body weight(122), liver enzymes(122), insulin resistance(122), and hepatic fibrosis(122) and steatosis(122) compared to LM group.

Flaxseed supplementation also reduced the levels of hepatic markers(122) compared to the control group.

Researchers wrote in the final report, "flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management".

9. Coffee
Coffee, a popular and social beverage all over the world, particularly in the West, is a drink made from roast bean from the Coffea plant, native to tropical Africa and Madagascar. Chlorogenic acids (CGA) are the most abundant phenolic compounds in green coffee beans and in the human diet and have been suggested to mitigate several cardiometabolic risk factors(123).

In ApoE-/- mice fed an atherogenic diet without (vehicle) or with water-based standardized green coffee extract (GCE) by gavage (equivalent to 220 mg/kg of CGA) for 14 weeks, GCE showed to improve metabolic parameters(124), including fasting glucose(124), insulin resistance(124), serum leptin(124), urinary catecholamines(124), and liver triglycerides(124), without affecting the atherosclerotic lesion progression(124) or plasma lipid levels(124).

GCE also reduced weight gain(124), decreased adiposity(124), lower inflammatory infiltration(124) in adipose tissue(124), and protection against liver damage(124) and induced the shifts in favor of good gut microbiota(124), compared to vehicle group.

The levels of liver pro-inflammation cytokines(124) also were decreased by the injection of GCE.

 In a study of patients with metabolic syndrome (Mets) randomly allocated to consume 400 mg GCE or placebo capsules twice per d for 8 weeks with both groups were advised to follow an energy-balanced diet, injection of GCE supplementation,  significantly reduced systolic blood pressure (SBP)(125) compared with the placebo group.

Furthermore, the GCE treatment group showed a significantly reduced fasting blood glucose (FBS)(125), waist circumference(125) and insulin resistance(125) in comparison to placebo.

Based on the findings, researchers said, "GCE administration had an ameliorating effect on some of the Mets components such as high SBP, high FBS, and Mets (metabolic syndrome) main aetiological factors including insulin resistance and abdominal obesity.

10. Broccoli
Broccoli is a mustard/cabbage plant, belonging to the family Brassicaceae. The vegetable has large flower heads, usually green in color and the mass of flower heads surrounded by leaves and evolved from a wild cabbage plant on the continent of Europe(126).

On adult 5-wk-old male B6C3F1 mice received a control diet (AIN-93M) or a Western diet (high in lard and sucrose, 19% and 31%, wt:wt, respectively), with or without freeze-dried broccoli (10%, wt:wt), mice group treated with broccoli exhibited lower hepatic triglycerides(127) and NAFLD scores(127).

Additionally compared to the control group, mice group treated with broccoli decreased liver injured or damaged markers(127) and protected against liver inflammation(127) and slowed the initiation and progression of a hepatic neoplasm(127).

In the sum up, researchers said, "Long-term consumption of whole broccoli countered both NAFLD development enhanced by a Western diet and hepatic tumorigenesis induced by DEN in male B6C3F1 mice".

In mice exposed to the hepatocarcinogen diethylnitrosamine (DEN), Sulforaphane from broccoli exerted significant liver protection against NAFLD and liver cancer.

In male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months, researchers at the end of the experiment showed that dietary broccoli decreased hepatic triacylglycerols(128), NAFLD(128), liver damage(128) and tumor necrosis factor(128) by month 5 without changing body weight(128) or relative liver weight(128), and slowing down the carcinogenesis(128), seen in 100% of mice.

In other words, broccoli, a good source of sulforaphane, is a good candidate to slow the progression of hepatic lipidosis(128).


11. Walnuts
Walnut tree is one of the Genus plants belonging to the family Juglandaceae about 30–130 ft cultivated for its nut and kernel and for the commercial purpose all over the world(129).

On male C57BL/6J mice fed a rodent chow or HFD (45% energy-derived)±walnuts (21.5% energy-derived) for 6 weeks, before injection of walnut, mice fed with HFD showed a significantly elevated fat accumulation(130).

Mice fed a rodent chow or HFD (45% energy-derived)±walnuts (21.5% energy-derived) compared to HFD group prevented HFD-mediated alteration of the levels of key proteins involved in lipid homeostasis(130) in the induction lipid accumulation in the liver(130).

Furthermore, walnut protected the liver against the overexpression of pathways in elevated oxidative stress-induced lipid peroxidation(130) as well as the proteins associated with programming liver cells apoptosis(130) caused by HFD.

Researchers based on the findings wrote, "The beneficial effects of dietary walnut likely result, at least partially, from its antioxidant ingredients and attenuating HFD-induced hepatic steatosis, nitroxidative stress and apoptosis".

Also, on male C57BL/6J mice fed either a regular rodent chow or HFD (45% energy-derived) with or without walnuts (21.5% energy-derived) for 20weeks.dietary walnuts significantly decreased the amounts of hepatic triglyceride (TG)(131)compared to HFD-fed mice.

Similar to the aforementioned results, additional walnuts significantly altered the levels of proteins(131), involved in the hepatic lipid homeostasis(131).

Moreover, in the examined the adipose tissues isolated from mice fed the HFD+walnut diets, researchers found that walnut significantly decreases levels of proinflammatory cytokines(131) compared to those significantly elevated in mice fed HFD alone without affecting the significantly alter HFD-induced peripheral glucose intolerance(131) or insulin resistance(131).

Researchers wrote in the final report, "the protective effects of walnuts against HFD-induced hepatic TG accumulation in mice are mediated, at least partially, by modulating the key proteins in hepatic lipid homeostasis and suppression of the genes related to adipose tissue inflammation and macrophage infiltration as well as prevention of adipocyte apoptosis".

12 Avocado
Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America, and Central America, belonging to the flowering plant family Lauraceae(132). 

On male Sprague-Dawley rats fed high-cholesterol diet for four weeks to induce hypercholesterolemia, followed by the VAO (450 and 900 mg·kg-1 ·day-1 ) and simvastatin (10 mg·kg-1 ·day-1) given orally while maintaining the high-cholesterol diet for another four weeks, according to the assessment of urinary metabolomics using NMR, oral administration of VAO  partially recover the metabolism dysfunction(133)) induced by hypercholesterolemia mainly via lipid, energy(133), amino acid(133), and gut microbiota(133) metabolism.

On Streptozocin-induced diabetic mice, before treatment of avocado oil, a rich source of C18, diabetic mice elicited a noticeable increase in the content of docosahexaenoic acid (DHA)(134) found in the mitochondrial peroxidizability index(134) and higher levels of lipid peroxidation(134).

Furthermore, Mitochondrial respiration(134) and activity were impaired in diabetic rats with a significant increase in reactive oxygen species (ROS) generation(134).

Additional avocado oil not only restored all the alternative parameters(134) in the diabetic mice except by the changes in mitochondrial fatty acid composition(134) but also normalized the hyperlipidemia(134).

However,  avocado oil showed no effect on the prevention of hyperglycemia polyphagia(134).

Based on the findings, researchers said, " These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis".

Summary
Taken altogether, phytochemicals, herbal medicines, healthy foods found in the research paper may be considered remedies for the prevention and treatment of non-alcoholic fatty liver disease, pending to large sample size and multicenter human study.

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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

Sources
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(22) Current treatment options for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis by Melanie D Beaton, MD FRCPC. (PMC)

(23) Herbal medicines and nonalcoholic fatty liver disease by Hong Yao, Yu-Jie Qiao, Ya-Li Zhao, Xu-Feng Tao, Li-Na Xu, Lian-Hong Yin, Yan Qi, and Jin-Yong Peng. (PMC)

(24) An Overview of Herbal Products and Secondary Metabolites Used for Management of Type Two Diabetes by Ajda Ota and Nataša P. Ulrich. (PubMed)

(98) Healthy #Foods - Nuts & Seeds - Olive (Olea europaea) by Kyle J. Norton
(99)Olive leaf extract prevents the spontaneous occurrence of non-alcoholic steatohepatitis in SHR/NDmcr-cp rats by Omagari K1, Kato S, Tsuneyama K, Hatta H, Sato M, Hamasaki M, Sadakane Y, Tashiro T, Fukuhara M, Miyata Y, Tamaru S, Tanaka K, Mune M. (PubMed)
(100) Hypolipidemic and antioxidant activities of oleuropein and its hydrolysis derivative-rich extracts from Chemlali olive leaves by bJemai H1, Bouaziz M, Fki I, El Feki A, Sayadi S.(PubMed)
(101) Super Foods - #Pomegranates(Punica granatum) by Kyle J. Norton
(102) Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan-induced diabetic rats by Jafri MA1, Aslam M, Javed K, Singh S. (PubMed)
(103) Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation, and antioxidant enzymes in experimental diabetes by Bagri P1, Ali M, Aeri V, Bhowmik M, Sultana S. (PubMed)
(104) Popular #Herbs - #Ginger (Zingiber officinale) by Kyle J. Norton
(105) Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats by Akhani SP1, Vishwakarma SL, Goyal RK. (PubMed)
(106) Antiobesity Actions of Zingiber officinale Roscoe by Li-Kun Han, Xiao-Jie Gong, Shiho Kawano, and Masato Saito. (Research Gate)
(107) Healthy #Foods - Green tea - Leaves of Camellia sinensis by Kyle J. Norton

(108) Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats by Tan Y1, Kim J1, Cheng J1, Ong M1, Lao WG1, Jin XL1, Lin YG1, Xiao L1, Zhu XQ1, Qu XQ. (PubMed)

(109) Combination of citrus polymethoxyflavones, green tea polyphenols, and Lychee extracts suppresses obesity and hepatic steatosis in high-fat diet induced obese mice by Pan MH1,2,3,4, Yang G1, Li S1, Li MY5, Tsai ML5, Wu JC6, Badmaev V7, Ho CT8, Lai CS. (PubMed)

(110) Super Foods - Wolfberry by Kyle J. Norton

(111) Lycium barbarum polysaccharides improve hepatic injury through NF-kappa-B and NLRP3/6 pathways in a methionine choline deficient diet steatohepatitis mouse model by Xiao J1, Wang F2, Liong EC3, So KF4, Tipoe GL. (PubMed)

(112) Lycium ruthenicum extract alleviates high-fat diet-induced nonalcoholic fatty liver disease via enhancing the AMPK signaling pathway by Lin J1, Zhang Y1, Wang X1, Wang W. (PubMed)

(113) Popular #Herbs - #Garlic (Allium sativum) by Kyle J. Norton

(114) Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease by Liu C1, Liao JZ1, Li PY. (PubMed)

(116) Effect of garlic powder consumption on body composition in patients with nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial by Soleimani D1, Paknahad Z2, Askari G3, Iraj B4, Feizi A. (PubMed)

(117) Superfoods - Uncontaminated Fish Oil by Kyle J. Norton

(118) Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study by Yuan F1,2, Wang H3, Tian Y4, Li Q5, He L6, Li N7, Liu Z. (PubMed)

(119) Fish Oil Feeding Modulates the Expression of Hepatic microRNAs in a Western-Style Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model by Wang H1, Shao Y1, Yuan F1,2, Feng H1, Li N1, Zhang H1, Wu C3, Liu Z. (PubMed)

(120) Superfoods - Flaxseed oil by Kyle J. Norton

(121) Therapeutic effect of flax-based diets on fatty liver in aged laying hens by Davis JE1, Cain J2, Small C3, Hales DB. (PubMed)

(122) Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open-labeled, controlled study by Yari Z1, Rahimlou M2, Eslamparast T1, Ebrahimi-Daryani N3, Poustchi H4, Hekmatdoost A. (PubMed)

(123) 71 Health Benefits and 28 Adverse Effects of Coffee by Kyle J. Norton

(124) Green Coffee Extract Improves Cardiometabolic Parameters and Modulates Gut Microbiota in High-Fat-Diet-Fed ApoE-/- Mice by Caro-Gómez E1, Sierra JA2, Escobar JS3, Álvarez-Quintero R4, Naranjo M5, Medina S6, Velásquez-Mejía EP7, Tabares-Guevara JH8, Jaramillo JC9, León-Varela YM10, Muñoz-Durango K11, Ramírez-Pineda JR. (PubMed)

(125) Effects of green coffee extract supplementation on anthropometric indices, glycaemic control, blood pressure, lipid profile, insulin resistance and appetite in patients with the metabolic syndrome: a randomized clinical trial by Roshan H1, Nikpayam O1, Sedaghat M2, Sohrab G. (PubMed)

(126) Healthy #Foods - Vegetables - Cabbage (Brassica oleracea) by Kyle J. Norton

(127) Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet by Chen YJ1, Wallig MA2, Jeffery EH. (PubMed)

(128) Dietary broccoli protects against fatty liver development but not against the progression of liver cancer in mice pretreated with diethylnitrosamine by Chen YJ1, Myracle AD1, Wallig MA2, Jeffery EH. (PubMed)

(129)  Healthy #Foods - Nuts & Seeds - Walnuts (Juglans) by Kyle J. Norton

(130) Preventive effects of dietary walnuts on high-fat-induced hepatic fat accumulation, oxidative stress, and apoptosis in mice by Choi Y1, Abdelmegeed MA1, Song BJ. (PubMed)

(131) Dietary walnut reduces hepatic triglyceride content in high-fat-fed mice via modulation of hepatic fatty acid metabolism and adipose tissue inflammation by Choi Y1, Abdelmegeed MA1, Akbar M1, Song BJ. (PubMed)

(132) Healthy #Foods - Fruits - Avocado by Kyle J. Norton

(133) Effect of virgin avocado oil on diet-induced hypercholesterolemia in rats via 1 H NMR-based metabolomics approach by Tan CX1, Chong GH2, Hamzah H3, Ghazali HM. (PubMed)

(134) Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats by Ortiz-Avila O1, Gallegos-Corona MA, Sánchez-Briones LA, Calderón-Cortés E, Montoya-Pérez R, Rodriguez-Orozco AR, Campos-García J, Saavedra-Molina A, Mejía-Zepeda R, Cortés-Rojo C. (PubMed)