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Best Of Natural Liver Protection

November 10, 2010 Written by JP       [Font too small?]

The word “detoxification” is frequently mentioned in holistic circles. Perhaps the most important organ involved in this process is the liver. Without it, the body could not handle exposure to alcohol, environmental contaminants, junk food and even medications. The liver is responsible for promoting healthy blood (via the production of albumin and clotting factors) and combats fatigue by storing fat as an source of energy. Furthermore, it also aids in the absorption of life promoting nutrients such as CoQ10, Vitamins A, D, E and K. Simply put, without a properly functioning liver, one cannot live a vigorous life.

An herb known as milk thistle (Silybum marianum) is probably the best known natural remedy that supports healthy liver function. It has garnered this reputation with good reason. But there are some other lesser known ways to protect the liver as well. (1,2,3)

Liver Protector #1 – Coffee

A new study appearing in the journal Hepatology examined a proposed link between coffee consumption and hepatitis C outcomes. 766 Hep C patients were medically evaluated every 3 months for almost 4 years. During that time, they reported their average coffee and tea intake. Researchers found a dose dependent protective effect afforded by regular coffee use. The relative risk of disease progression was 30% lower in those drinking 1-3 cups of coffee per day and 53% lower in participants drinking 3 or more cups daily. An interesting side note is that black and green tea did not appear to confer the same benefit. Prior population studies appear to support the superiority of coffee vs. tea in this particular circumstance. The exact mechanism by which coffee imparts this protective effect isn’t clear at this time. However, some scientists suspect that certain phytochemicals in coffee (cafestol, diterpenes and kahweol) may block the damaging effects of toxins on this vital organ. (4,5,6)

Liver Protector #2 – Coenzyme Q10

Coenzyme Q10 is a vitamin-like substance produced by the body that plays an integral role in maintaining a healthy cardiovascular system and supporting cellular energy. The liver is one of the richest sources of CoQ10. Perhaps this is why a recent study presented in the journal Biochemical Pharmacology points to its application in protecting against liver damage caused by a poor diet.

  • A group of mice was fed a junk food diet or a “balanced diet” for 8 weeks.
  • The unhealthy diet was higher in fat and included 21% added fructose in the water supply.
  • Some of the mice receiving the unhealthy drink and food were also supplemented with CoQ10.

The researchers reported that the junk food mice ate more, gained weight and demonstrated elevated blood sugar and “impaired glucose tolerance”. There was also a significant increase in inflammation and oxidative stress – particularly with regard to liver metabolism. On the other hand, CoQ10 supplementation countered some of these ill effects by decreasing liver inflammation and stress markers via altered gene expression in the liver. This is not the first mention of a hepatoprotective effect of CoQ10 in the medical literature. Other trials have concluded that this coenzyme may combat symptoms of cirrhosis and even mitigate the harmful effects of certain medications on the liver. (7,8,9)

Liver Protector #3 – Krill Oil

Krill oil is a valuable source of omega-3 fatty acids, phospholipids and a potent antioxidant known as astaxanthin, a carotenoid that gives wild salmon its distinctive pink color. The October 2009 edition of the Journal of Agricultural Food Chemistry points to a relatively new method for shielding the heart and liver against dietary insults. Much like the previous study using CoQ10, the mice in this experiment were fed two different types of diet: 1) a “standard feed” that was used for comparison purposes; and 2) a heavily processed feed that was intended to tax the cardiovascular system and liver. The researchers then added krill oil to the chow of some of the lab animals that were fed the unhealthy diet.

  • The mice who received krill oil while eating the unhealthy diet showed a reduction in liver fat content and liver weight.
  • Lower levels of blood sugar, cholesterol and triglycerides were also detected in the krill supplemented group.

It’s also interesting to note that krill oil provoked an increase in adiponectin levels. This is a substance released by fat cells that helps to regulate lipids (cholesterol and triglycerides) and promotes insulin sensitivity. Higher levels of this hormone are connected to improved cardiovascular health and a reduced risk of diabetes. In general, marine-based omega-3 fats have been shown to support hepatic health. But krill oil appears to be more effective than fish oil in this regard. However, this conclusion needs to be interpreted with caution because it’s based on a very limited number of studies. (10,11,12)

Source: Can Fam Physician 2007;53:857-863 (link)

The single best way to support the liver is to avoid harming it in the first place. We all understand that abusing alcohol and drugs can ruin virtually any organ or system in the body. But not everyone is aware of the damage caused by consuming excessive carbohydrates on a regular basis. Even moderate amounts of carbs in the form of added sweeteners can lead to harmful shifts in lipid profiles and liver health markers. This is according to a new study conducted at the VA Puget Sound Health Care System in Seattle, Washington. The worst sweeteners appear to be the fructose based variety – agave nectar, crystalline fructose and high fructose corn syrup. A recent review in the Journal of Nutritional Biochemistry again points to fructose as a primary culprit in the development of nonalcoholic fatty liver disease. On the flip side of the coin, the October 2009 issue of the American Journal of Clinical Nutrition explains that higher protein intake may actually lower fatty deposits in the liver – via increased bile acid production. (13,14,15)

There may never be a drug, food or supplement that allows us to eat and live recklessly without suffering the consequences. However, I am a realist and do understand that most people don’t always eat and exercise as they should. Coffee, CoQ10 and krill oil may help overcome genetic weaknesses or the occasional dietary indulgence. But ultimately it’s important to remember that “supplements are meant to supplement an otherwise healthy lifestyle”. When used in that fashion, they can often be the body’s best friend.

Update: November 2010: An analysis in the September 2010 issue of the journal Digestive Diseases and Sciences determined that as many as 92% of patients with chronic liver disease are deficient in Vitamin D. A lack of D or cholecalciferol is most commonly associated with poor bone density. However, new evidence details a much more direct role for this nutrient in the management of the liver disease hepatitis C. A recent Italian trial evaluated the connection between Vitamin D concentrations and the response rate to conventional treatment of recurrent hepatitis C (RHC). A total of 42 patients with RHC took part in the 48 week examination. Fifteen of the study volunteers were given supplemental Vitamin D in order to address an overt deficiency and prevent further bone loss. In this subset of participants, 13 responded well to treatment by exhibiting “sustained viral response”. This compared favorably to the remainder of the non-supplemented participants: only 1 in 10 patients with severe Vitamin D deficiency (</= 10 ng/ml) responded to treatment; 6 in 20 of the D deficient (>10 to </20 ng/ml) volunteers were successfully treated; and 6/12 “near normal” patients (>20 ng/ml) demonstrated sustained viral response. The conclusion of the study states that “Vitamin D deficiency predicts an unfavorable response to antiviral treatment of RHC. Vitamin D supplementation improves the probability of achieving a SVR following antiviral treatment”. This suggests that anyone concerned about or living with a liver condition would do well to monitor 25-OH Vitamin D serum levels. (16,17,18)

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page. You can find the latest research about this topic there!

Be well!

JP

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36 Comments & Updates to “Best Of Natural Liver Protection”

  1. Janet Says:

    Can you tell me if artichokes protect the liver? I have heard rumors that they do but have not read anything authoritatively on the matter.
    Janet

  2. JP Says:

    Janet,

    Artichoke leaf extracts have some scientific and traditional evidence to support their use as liver protectants. A recent study:

    http://www.minervamedica.it/en/journals/gastroenterologica-dietologica/article.php?cod=R08Y2010N02A0093

    Be well!

    JP

  3. JP Says:

    A reason to consider Chlorella:

    http://www.ncbi.nlm.nih.gov/pubmed/25097844

    Health Promot Perspect. 2014 Jul 12;4(1):107-15. doi: 10.5681/hpp.2014.014. eCollection 2014.

    The Effect of Chlorella vulgaris Supplementation on Liver En-zymes, Serum Glucose and Lipid Profile in Patients with Non-Alcoholic Fatty Liver Disease.

    Ebrahimi-Mameghani M1, Aliashrafi S2, Javadzadeh Y3, AsghariJafarabadi M4.

    BACKGROUND:

    Non-alcoholic fatty liver disease (NAFLD) is becoming a public health problem worldwide and using microalgae is a new approach on its treatment. The aim of this study was to investigate the effect of Chlorella vulgaris supplementation on liver enzymes, serum glucose and lipid profile in patients with NAFLD.

    METHODS:

    This double-blind randomized placebo-controlled clinical trial was conducted on 60 NAFLD patients from specialized clinics of Tabriz University of Medical Sciences from December 2011 to July 2012. The subjects were randomly allocated into 2 groups: 1) “intervention” (n=30) received 400 mg/day vitamin E plus four 300 mg tablets of Chlorella vulgaris and, 2) “placebo” (n=30) received 400 mg/day vitamin E and four placebo tablets per day for 8 weeks. Weight, liver enzymes and metabolic factors were assessed in fasting serum and dietary data was collected at baseline and end of the study.

    RESULTS:

    Weight, liver enzymes, fasting blood sugar (FBS) and lipid profile decreased significantly in both groups (P<0.05). The differences in weight, ALP and FBS between the two groups were statistically significant (P=0.01, P=0.04 and P=0.02, respectively).

    CONCLUSION:

    C. vulgaris seems to improve FBS and lipid profile and therefore could be considered as an effective complementary treatment in NAFLD.

    Be well!

    JP

  4. JP Says:

    Update: More support for the role that coffee in fatty liver protection …

    http://www.nature.com/ejcn/journal/vaop/ncurrent/full/ejcn201523a.html

    Eur J Clin Nutr. 2015 Mar 25.

    Coffee but not green tea consumption is associated with prevalence and severity of hepatic steatosis: the impact on leptin level.

    BACKGROUND/OBJECTIVES: Most of the studies that have investigated the association between coffee consumption and hepatic steatosis have been experimental and small-scale clinical studies. As a result, epidemiological studies are scarce. To clear the association, we conducted a cross-sectional study and investigated the effects of coffee consumption with those of green tea consumption.

    SUBJECTS/METHODS: We analyzed 1024 Japanese male workers. The diagnosis of hepatic steatosis was based on ultrasonography. We divided coffee and green tea consumption into the following three categories: non-drinker; 1-2 cups/day and ⩾3 cups/day. To investigate the association between hepatic steatosis and coffee or green tea consumption, we calculated the odds ratio (OR) and adjusted the means of leptin levels on each severity of hepatic steatosis.

    RESULTS: A total of 265 of our subjects (25.9%) were diagnosed with hepatic steatosis. The ORs of the group of subjects who drank >3 cups of coffee/day was significantly lower compared with that of the noncoffee drinker group (OR 0.59, 95% confidence intervals 0.38-0.90, P=0.03). Although there was a significant difference between coffee consumption and leptin level only in the asymptomatic group, we found a decreasing trend in the asymptomatic and moderate-severe hepatic steatosis group. We did not find the same relationships in green tea consumption.

    CONCLUSIONS: Although we did not find an association between hepatic steatosis and green tea consumption, coffee may have beneficial effects on hepatic steatosis. In addition, we produced one possible hypothesis that coffee consumption negatively associates with leptin levels in hepatic steatosis.

    Be well!

    JP

  5. JP Says:

    Update 06/01/15:

    http://www.nmcd-journal.com/article/S0939-4753%2815%2900103-9/abstract

    Nutr Metab Cardiovasc Dis. 2015 Apr 25.

    A double-blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexaenoic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease.

    BACKGROUND AND AIMS: Very little information is available on whether docosahexaenoic acid (DHA) supplementation has a beneficial effect on liver fat and cardiovascular disease (CVD) risk factors in children with nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled randomized trial we investigated whether 6-month treatment with DHA improves hepatic fat and other fat depots, and their associated CVD risk factors in children with biopsy-proven NAFLD.

    METHODS AND RESULTS: Of 58 randomized children, 51 (25 DHA, 26 placebo) completed the study. The main outcome was the change in hepatic fat fraction as estimated by magnetic resonance imaging. Secondary outcomes were changes in visceral adipose tissue (VAT), epicardial adipose tissue (EAT), and left ventricular (LV) function, as well as alanine aminotransferase (ALT), triglycerides, body mass index-standard deviation score (BMI-SDS), and insulin sensitivity. At 6 months, the liver fat was reduced by 53.4% (95% CI, 33.4-73.4) in the DHA group, as compared with 22.6% (6.2-39.0) in the placebo group (P = 0.040 for the comparison between the two groups). Likewise, in the DHA group VAT and EAT were reduced by 7.8% (0-18.3) and 14.2% (0-28.2%), as compared with 2.2% (0-8.1) and 1.7% (0-6.8%) in the placebo group, respectively (P = 0.01 for both comparisons). There were no significant between-group changes for LV function as well as BMI-SDS and ALT, while fasting insulin and triglycerides significantly decreased in the DHA-treated children (P = 0.028 and P = 0.041, respectively).

    CONCLUSIONS: DHA supplementation decreases liver and visceral fat, and ameliorates metabolic abnormalities in children with NAFLD.

    Be well!

    JP

  6. JP Says:

    Update 07/10/15:

    http://www.ncbi.nlm.nih.gov/pubmed/26156412

    J Am Coll Nutr. 2015 Jul 9:1-8.

    Functions of Coenzyme Q10 Supplementation on Liver Enzymes, Markers of Systemic Inflammation, and Adipokines in Patients Affected by Nonalcoholic Fatty Liver Disease: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder related to inflammation. Coenzyme Q10 (CoQ10) is a natural compound that has recently been considered as an anti-inflammatory factor. In the current study we aimed to evaluate the effects of CoQ10 supplementation on liver enzymes, inflammation status, and adipokines in patients with NAFLD.

    METHODS: Forty-one subjects with NAFLD participated in the current randomized, double-blind, placebo-controlled trial. The participants were randomly divided into 2 groups: one group received CoQ10 capsules (100 mg once a day) and the other received placebo for 12 weeks. Blood samples of each patient were taken before and after the 12-week intervention period for measurement of liver aminotransferases, inflammatory biomarkers, and adipokines (adiponectin and leptin).

    RESULTS: Taking 100 mg CoQ10 supplement daily resulted in a significant decrease in liver aminotransferases (aspartate aminotransferase [AST] and gamma-glutamyl transpeptidase [GGT]), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor α, and the grades of NAFLD in the CoQ10 group in comparison to the control group (p < 0.05). In addition, patients who received CoQ10 supplement had higher serum levels of adiponectin (p = 0.016) and considerable changes in serum leptin (p = 0.053). However, no significant changes occurred in serum levels of interleukin-6 in both groups.

    CONCLUSION: The present study suggested that CoQ10 supplement at a dosage of 100 mg could be effective for improving the systemic inflammation and biochemical variables in NAFLD.

    Be well!

    JP

  7. JP Says:

    Update 07/14/15:

    http://www.ncbi.nlm.nih.gov/pubmed/26153591

    MMW Fortschr Med. 2014 Dec 15;156 Suppl 4:120-6.

    [Effect of silymarin on liver health and quality of life. Results of a non-interventional study].

    BACKGROUND: Many drugs are known to have hepatotoxic side effects. The effect of silymarin on liver function and liver-injury-impaired quality of life under daily practice conditions in patients with elevated values of liver enzymes was evaluated in the present non-interventional study.

    METHOD: Patients with drug-induced elevated aminotransferase levels and indication for silymarin (Legalon forte) treatment for 2 to 3 months were documented prospectively over 4 months. At baseline, after 2 and 4 months, respectively, the following parameters were documented: alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), alkaline phosphatase, total bilirubin, presence of liver-related skin symptoms and discoloured urine, severity of liver-related symptoms and quality of life.

    RESULTS: In total, 190 patients (53.2% male, median age 60.0 years [range 19-81]) from 48 centres participated in the non-interventional study. Among potentially hepatotoxic drugs, analgesics/anti-inflammatory drugs were used most frequently (45.8%). These drugs have been administered for a median period of 2.8 years (range 0.0-26.1). At baseline, all patients had elevated levels of ALT, AST or GGT. Fatigue, flatulence, upper abdominal discomfort, lethargy, and joint complaints were the most severe liver-related symptoms and prevalent in over 62% of patients. Quality of life was affected in 88.7% of patients. Significant reductions were achieved in all documented laboratory parameters (p < 0.001), leading to marked improvement in liver-related symptoms and increased quality of life already after 2 months. The percentage of patients with liver enzymes in the normal range increased considerably within 4 months. No adverse drug reactions were observed.

    CONCLUSIONS: Silymarin is a safe and efficacious treatment option for patients with elevated liver enzymes. A benefit in terms of liver-related symptoms as well as quality of life and performance was demonstrated already after 2 months of treatment.

    Be well!

    JP

  8. JP Says:

    Updated 07/20/15:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465602/ (full text)

    Hepatobiliary Surg Nutr. 2015 Jun;4(3):161-71.

    Carotenoids and non-alcoholic fatty liver disease.

    Non-alcoholic fatty liver disease (NAFLD) is a growing health problem around the world, especially in developed countries. NAFLD includes all cases of fatty liver disease from simple steatosis to cirrhosis, without excessive alcohol intake, use of steatogenic medication or hereditary disorders. Pathogenesis is associated with dietary high fat intake, decreased free fatty acid (FFA) oxidation, increased hepatic lipogenesis and lipolysis from the adipose tissue. These metabolic alterations contribute to the hepatic fat accumulation. Consequently, stimulated oxidative stress and inflammation play a major role in hepatocellular damage. Therefore, antioxidant and anti-inflammatory agents may have a role in the prevention of this disease. Carotenoids are potent antioxidant and anti-inflammatory micronutrients, which have been investigated in the prevention and treatment of NAFLD. The main sources of the carotenoids are fruits and vegetables. In this article we review the potential role and possible molecular mechanism of carotenoids in NAFLD.

    Be well!

    JP

  9. JP Says:

    Updated 07/30/15:

    http://onlinelibrary.wiley.com/doi/10.1111/jhn.12327/abstract

    J Hum Nutr Diet. 2015 Jul 27.

    n-3 polyunsaturated fatty acid supplementation reduces insulin resistance in hepatitis C virus infected patients: a randomised controlled trial.

    BACKGROUND: Insulin resistance promotes liver disease progression and may be associated with a lower response rate in treated hepatitis C virus (HCV) infected patients. n-3 polyunsaturated fatty acid (PUFA) supplementation may reduce insulin resistance. The present study aimed to evaluate the effect of n-3 PUFA supplementation on insulin resistance in these patients.

    METHODS: In a randomised, double-blind clinical trial, 154 patients were screened. After applying inclusion criteria, 52 patients [homeostasis model assessment index of insulin resistance (HOMA-IR ≥2.5)] were randomly divided into two groups: n-3 PUFA (n = 25/6000 mg day-1 of fish oil) or control (n = 27/6000 mg day-1 of soybean oil). Both groups were supplemented for 12 weeks and underwent monthly nutritional consultation. Biochemical tests were performed at baseline and after intervention. Statistical analysis was performed using the Wilcoxon Mann-Whitney test for comparisons and the Wilcoxon test for paired data. Statistical package r, version 3.02 (The R Project for Statistical Computing) was used and P < 0.05 (two-tailed) was considered statistically significant.

    RESULTS: Comparisons between groups showed that n-3 PUFA supplementation was more effective than the control for reducing HOMA-IR (P = 0.015) and serum insulin (P = 0.016). The n-3 PUFA group not only showed a significant reduction in HOMA-IR 3.8 (3.2-5.0) versus 2.4 (1.8-3.3) (P = 0.002); serum insulin 17.1 (13.8-20.6) μIU mL-1 versus 10.9 (8.6-14.6) μIU mL-1 (P = 0.001); and glycated haemoglobin 5.4% (5.0-5.7%) versus 5.1% (4.8-5.6%) (P = 0.011), but also presented an increase in interleukin-1 97.5 (0.0-199.8) pg mL-1 versus 192.4 (102.2-266.8) pg mL-1 (P = 0.003) and tumour necrosis factor 121.2 (0.0-171.3) pg mL-1 versus 185.7 (98.0-246.9) pg mL-1 (P = 0.003).

    CONCLUSIONS: n-3 PUFA supplementation reduces insulin resistance in genotype 1 HCV infected patients.

    Be well!

    JP

  10. JP Says:

    Updated 09/16/15:

    http://www.ncbi.nlm.nih.gov/pubmed/26367736

    Eur Rev Med Pharmacol Sci. 2015 Aug;19(16):3118-3124.

    Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study.

    OBJECTIVE:

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized health problem. Various treatment strategies such as thiazolidinediones, metformin, lipid-lowering agents and antioxidants have been evaluated. So far, no single intervention has convincingly improved liver histology. Experience of using silymarin alone or in combination with other agents in patients with NAFLD is limited in the medical literature. The present study was conducted to evaluate the efficacy of silymarin plus vitamin E in the treatment of NAFLD.

    PATIENTS AND METHODS:

    A sample of 36 patients was enrolled. The diagnosis of NAFLD was confirmed by percutaneous liver biopsy. All patients were randomized to one of the following intervention groups: group I: treated with 2 tablets per day of silymarin plus vitamin E (Eurosil 85®, MEDAS SL) and a lifestyle modification program consisting of hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins) and exercise for 3 months and group II (only with the hypocaloric diet). Anthropometric variables as waist circumference, weight, body mass index (BMI) were measured. Biochemical parameters: Glucose, triglycerides, AST, ALT, GGt levels and insulin resistance (HOMA-IR) were determined under fasting conditions. Non-invasive NAFLD-index were applied before and after the treatments: Fatty liver index (FLI), liver accumulation product (LAP) and NAFLD-Fibrosis score (FS).

    RESULTS:

    The mean age was 47.4 ± 11.2 years old (range 18-67); 22 men and 14 women. In group I, 11 patients (61%) have a NAS-score > 5 and 10 (55.5%) in the group II (NS). Anthropometric parameters decreased after treatment in both groups. Patients in both groups showed a decrease in GGt levels after treatment (group I: 68 IU/L vs. 46.2 ± 27 IU/L; p < 0.05 and group II 80.5 ± 46 IU/L vs. 50.3 ± 27 IU/L; p < 0.05). Only in group II we observed a significant decrease in AST and ALT levels. In both groups, we observed a decrease in: FLI index (group I: 86.2 ± 19 vs. 76.9 + 20; p < 0.05 and in group II: 85.2 ± 18 vs. 77.5 ± 23; p < 0.05), and NAFLD-FS index (group I: -1.6 ± 1.8 vs. -2.1 ± 1.5; p < 0.05 and in group II -1 ± 1.9 vs. -1.5 ± 2.1; p < 0.05). Patients in group I who did not get a 5% loss of weight also displayed decreased GGt levels, and in the FLI and NAFLD-FS indexes; whereas patients in group II without decrease of 5% by weight showed no improvement in any of the analyzed parameters.

    CONCLUSIONS:

    Treatment with silymarin plus vitamin E and a hypocaloric diet ameliorate function hepatic test, and non-invasive NAFLD index. Silymarin can be an alternative valid therapeutic option particularly when other drugs are not indicated or have failed or as a complementary treatment associated with other therapeutic programs.

    Be well!

    JP

  11. JP Says:

    Updated 1/28/16:

    http://www.nature.com/ijo/journal/vaop/naam/abs/ijo20164a.html

    Int J Obes (Lond). 2016 Jan 20.

    Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention.

    BACKGROUND/OBJECTIVES: Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet was compared to a conventional, low-fat diet.

    SUBJECTS/METHODS: Seventy healthy, obese, postmenopausal women were randomized to either a Paleolithic diet or a conventional, low-fat diet. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as HOMA-IR/Liver IR index for hepatic insulin sensitivity and OGIS/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6, and 24 months. 41 women completed the examinations for liver fat and were included.

    RESULTS: Liver fat decreased after 6 months by 64% (95% CI: 54-74%) in the Paleolithic diet group and by 43% (27-59%) in the low-fat diet group (P<0.01 for difference between groups). After 24 months liver fat decreased 50% (25-75%) in the Paleolithic diet group and 49% (27-71%) in the low-fat diet group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the low-fat diet group (rs=0.66, P<0.01) but not in the Paleolithic diet group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the Paleolithic diet group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association to liver fat changes.

    CONCLUSIONS: A Paleolithic diet with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional low-fat diet at six months. This difference may be due to food quality, e.g. a higher content of mono- and polyunsaturated fatty acids in the Paleolithic diet. Changes in liver fat did not associate to alterations in insulin sensitivity.

    Be well!

    JP

  12. JP Says:

    Updated 02/27/16:

    http://www.ncbi.nlm.nih.gov/pubmed/26916997?dopt=Abstract

    Br J Nutr. 2016 Feb 26:1-8.

    High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

    Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

    Be well!

    JP

  13. JP Says:

    Updated 03/18/16:

    http://www.ncbi.nlm.nih.gov/pubmed/26983396?dopt=Abstract

    Int J Food Sci Nutr. 2016 Mar 17:1-9.

    Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study.

    A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p < 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

    Be well!

    JP

  14. JP Says:

    Updated 05/30/16:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879762/

    Iran Red Crescent Med J. 2016 Mar 6;18(3):e23628.

    A Randomized Controlled Trial of the Effects of an Almond-enriched, Hypocaloric Diet on Liver Function Tests in Overweight/Obese Women.

    BACKGROUND: Gradual weight reduction has been shown to be associated with improvements in liver enzymes. However, some evidence demonstrated that liver enzymes may transiently increase immediately after a diet-induced weight loss.

    OBJECTIVES: This study was designed to assess the effects of a hypocaloric, almond-enriched diet (AED) compared with a hypocaloric nut-free diet (NFD) on liver function tests in the context of a three-month weight reduction program in overweight/obese women.

    PATIENTS AND METHODS: This randomized controlled clinical trial was registered at Iranian Registry of Clinical Trials with ID number of IRCT2013062313751N1. Overweight and obese Iranian women [n = 108; age = 42.7 y, body mass index = 29.6 kg/m(2)] were randomly assigned to consume an AED or NFD. The carefully planned hypocaloric diets were identical for both groups except for the AED group who consumed 50 grams of almonds daily for three months. Anthropometric measurements and laboratory measurements including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) were assessed before and immediately after the intervention.

    RESULTS: Of 108 participants, 50 women in AED group and 50 women in NFD group completed the protocol of the study (response rate: 92.6 %). The AED led to a median weight loss of 3.79 kg (interquartile range: 4.4 kg). Significant decreases within AED and NFD were observed in ALT (-16.6 ± 16.3 and -11.7 ± 16.8, P < 0.001, respectively). Similar significant decreases were observed in AST (-13.6 ± 15.7 and -7.7 ± 16.1; P < 0.001, respectively). The decrease in GGT was also significant in both groups (-11.4 ± 21.6 and -6.2 ± 19.8; P < 0.001 respectively). ALT, AST and GGT decreased significantly in the AED group compared to the NFD group (P < 0.001).

    CONCLUSIONS: AED improved liver enzymes in obese women. However, mild, transient increases in ALT and AST values can be observed immediately after an NFD in women.

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    JP

  15. JP Says:

    Updated 06/11/16:

    http://www.ncbi.nlm.nih.gov/pubmed/27270872

    Phytother Res. 2016 Jun 8.

    Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial.

    Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70-mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin.

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    JP

  16. JP Says:

    Updated 06/13/16:

    http://onlinelibrary.wiley.com/doi/10.1111/apt.13687/full

    Aliment Pharmacol Ther. 2016 Jun 6.

    Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis.

    BACKGROUND: Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non-alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans.

    AIM: To analyse the effect of cocoa polyphenols on NADPH oxidase isoform 2 (NOX2) activation, oxidative stress and hepatocyte apoptosis in a population affected by NASH.

    METHODS: In a cross-sectional study comparing 19 NASH and 19 controls, oxidative stress, as assessed by serum NOX2 activity and F2-isoprostanes, and hepatocyte apoptosis, as assessed by serum cytokeratin-18 (CK-18) levels, were measured. Furthermore, the 19 NASH patients were randomly allocated in a crossover design to 40 g/day of dark chocolate (>85% cocoa) or 40 g/day of milk chocolate (<35% cocoa), for 2 weeks. sNOX2-dp, serum isoprostanes and CK-18 were assessed at baseline and after 2 weeks of chocolate intake.

    RESULTS: Compared to controls, NASH patients had higher sNOX2-dp, serum isoprostanes and CK-18 levels. A significant difference for treatments was found in subjects with respect to sNOX2-dp, serum isoprostanes and serum CK-18. The pairwise comparisons showed that, compared to baseline, after 14 days of dark chocolate intake, a significant reduction in sNOX2-dp serum isoprostanes and CK-18 M30 was found. No change was observed after milk chocolate ingestion. A simple linear regression analysis showed that ∆ of sNOX2-dp was associated with ∆ of serum isoprostanes.

    CONCLUSION: Cocoa polyphenols exert an antioxidant activity via NOX2 down-regulation in NASH patients.

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    JP

  17. JP Says:

    Updated 06/14/16:

    http://www.ncbi.nlm.nih.gov/pubmed/27293900

    Int J Hepatol. 2016;2016:4030476.

    The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis.

    Background. Based on recent basic and clinical investigations, the extract of artichoke (Cynara scolymus) leaf has been revealed to be used for hepatoprotective and cholesterol reducing purposes. We aimed to assess the therapeutic effects of artichoke on biochemical and liver biomarkers in patients with nonalcoholic steatohepatitis (NASH). Methods. In a randomized double blind clinical trial, 60 consecutive patients suffering NASH were randomly assigned to receive Cynara scolymus extract (as 6 tablets per day consisting of 2700 mg extract of the herb) as the intervention group or placebo as the control group for two months. Results. Comparing changes in study markers following interventions showed improvement in liver enzymes. The levels of triglycerides and cholesterol were significantly reduced in the group treated with Cynara scolymus when compared to placebo group. To compare the role of Cynara scolymus use with placebo in changes in study parameters, multivariate linear regression models were employed indicating higher improvement in liver enzymes and also lipid profile particularly triglycerides and total cholesterol following administration of Cynara scolymus in comparison with placebo use. Conclusion. This study sheds light on the potential hepatoprotective activity and hypolipidemic effect of Cynara scolymus in management of NASH.

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    JP

  18. JP Says:

    Updated 06/15/16:

    http://www.tandfonline.com/doi/abs/10.3109/09637486.2016.1161011?journalCode=iijf20

    Int J Food Sci Nutr. 2016 Jun;67(4):461-9.

    Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study.

    A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p < 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

    Be well!

    JP

  19. JP Says:

    Updated 07/26/16:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947506/

    Evid Based Complement Alternat Med. 2016;2016:3593951.

    The Therapeutic Effect of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis.

    Aim. To assess the efficacy of berberine in the treatment of nonalcoholic fatty liver disease through meta-analysis. Method. We searched Embase, Pubmed, Cochrane Library, and so forth, until March 2016 for randomized controlled trials using berberine to treat NAFLD. Result. Six randomized controlled trials involving 501 patients were included in this study. The results showed that the efficacy of reducing TC, LDL, ALT, 2hPG, and HbA1c in NAFLD patients of the berberine group were significantly higher than that of control group. The subgroup analyses on TG, AST, and FBG indicated that treatment combined with berberine decreased TG level in NAFLD patients significantly. Compared with other drugs, berberine alone decreased TG level in NAFLD patients significantly. We also conducted a descriptive analysis on insulin resistance and radiography results that berberine can improve NAFLD patients’ insulin resistance and fatty liver. Conclusion. According to analysis result, berberine has positive efficacy on blood lipids, blood glucose, liver function, insulin resistance, and fatty liver condition of NAFLD patients. However, due to the limitation of number and quality of trials included, more clinical randomized controlled trials with high quality are needed for further verification of the efficacy of berberine on NAFLD patients.

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    JP

  20. JP Says:

    Updated 08/22/16:

    http://onlinelibrary.wiley.com/wol1/doi/10.1002/ptr.5699/abstract

    Phytother Res. 2016 Aug 19.

    Hepatoprotective Effects of a Proprietary Glycyrrhizin Product during Alcohol Consumption: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

    Traditionally, licorice has been used to treat liver problems. Glycyrrhizin, the primary active compound, has been shown to suppress elevations in liver enzymes that occur when the liver becomes diseased or damaged. This randomized, double-blind, placebo-controlled, crossover study evaluated the hepatoprotective effects of a proprietary glycyrrhizin product during alcohol consumption. Twelve healthy individuals (six male and six female subjects) in a clinic setting consumed vodka nightly for 12 days with the glycyrrhizin product or placebo (blank control), achieving a blood alcohol level of 0.12%. Liver function enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase and serum reduced glutathione were measured at overnight visits 1, 6, and 12. In the alcohol only group, AST, ALT, and GGT significantly increased from baseline (overnight visit 1) to overnight visit 12. In the active group, no statistically significant increases were observed for AST, ALT, and GGT, while alkaline phosphatase significantly decreased and plasma glutathione decreased relative to the alcohol control group. These results suggest that consumption of the proprietary glycyrrhizin study product during alcohol consumption may support improved liver health.

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    JP

  21. JP Says:

    Updated 09/16/16:

    http://www.ncbi.nlm.nih.gov/pubmed/27631178

    Arch Iran Med. 2016 Sep;19(9):631-638.

    Regression of Non-Alcoholic Fatty Liver by Vitamin D Supplement: A Double-Blind Randomized Controlled Clinical Trial.

    OBJECTIVE: Evidence indicates that NAFLD patients are vitamin D deficient. Vitamin D has new roles in lipid and glucose metabolism. The aim of this study was to examine the effects of calcitriol supplementation on the NAFLD progression based on liver lipid accumulation, serum lipid profile and insulin resistance.

    METHODS: We randomly assigned 73 patients with NAFLD-confirmed by ultra-sonography to 12 weeks of treatment with hypocaloric diet (reduction of 500 kcal per day) plus 25 µg of calcitriol supplement or a hypocaloric diet plus placebo. Before and after treatment, we assessed anthropometric parameters, grade of fatty liver, serum lipoproteins, liver enzymes and insulin level.

    RESULT: Baseline variables were not significantly different between groups. A statistically significant reduction in anthropometric measures was observed over the 12 weeks in both groups. However, no significant differences were seen between groups after intervention. Compared with the placebo, reductions in triglyceride and an increase in HDL cholesterol were seen over the 12 weeks of intervention in the calcitriol group (P = 0.002 and P = 0.004). AST level was decreased in the calcitriol group (-4.2 ± 4.3 µmol/L, P < 0.001), but increased in the placebo group (12.6 ± 6.1 µmol/L, P = 0.02) after 12 weeks. Reductions in mean difference of ALT, insulin and HOMA were significantly higher in the calcitriol than placebo group (P = 0.01, P = 0.007 and 0.01).

    CONCLUSIONS: Calcitriol supplementation combined with weight loss diet showed no significant effects on anthropometric measures in NAFLD patients. However, it may have positive effects on lipid profile, liver enzyme tests and insulin sensitivity during a weight-loss program.

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    JP

  22. JP Says:

    Updated 09/26/16:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024486/

    J Transl Med. 2016 Sep 15;14:266.

    Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease.

    BACKGROUND: We recently demonstrated a positive effect of berberine on nonalcoholic fatty liver disease patients after 16 weeks of treatment by comparing mere lifestyle intervention in type 2 diabetes patients with berberine treatment, which decreased the content of hepatic fat. However, the potential mechanisms of the clinical effects are unclear. We used a lipidomic approach to characterize the state of lipid metabolism as reflected in the circulation of subjects with nonalcoholic fatty liver disease (NAFLD) before and after berberine treatment.

    METHODS: Liquid chromatography-mass spectrometry evaluated the various lipid metabolites in serum samples obtained from the participants (41 patients in the berberine group and 39 patients in the mere lifestyle intervention group) before and after treatment.

    RESULTS: A total of 256 serum lipid molecular species were identified and quantified. Both treatments regulated various types of lipids in metabolic pathways, such as free fatty acids, phosphoglycerides and glycerides, in metabolic pathways, but berberine induced a substantially greater change in serum lipid species compared with mere lifestyle intervention after treatment. Berberine also caused obvious differences on ceramides. Berberine treatment markedly decreased serum levels of ceramide and ceramide-1-phosphate.

    CONCLUSIONS: Berberine altered circulating ceramides, which may underlie the improvement in fatty liver disease.

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    JP

  23. JP Says:

    Updated 10/08/16:

    https://www.ncbi.nlm.nih.gov/pubmed/27714002

    Food Funct. 2016 Oct 6.

    The effect of minimal dietary changes with raisins in NAFLD patients with non-significant fibrosis: a randomized controlled intervention.

    Aiming at investigating the potential effect of minimal dietary changes in NAFLD patients with non-significant fibrosis, 55 patients with NAFLD were enrolled in a randomized controlled clinical trial. Patients were assigned into two isocaloric dietary treatment groups for 24 weeks: (a) nutritional counseling (Control arm, N = 27), (b) nutritional counseling with currants included (two fruit servings, 36 g per day), substituting snacks of similar caloric content (Currant arm, N = 28). Clinical tests, anthropometrics, inflammatory and oxidative stress markers were conducted pre- and post-intervention. A total of 50 patients completed the trial. Significant differences between the two arms post-intervention were observed in fasting glucose and in IL-6 levels, these being significantly decreased only in Currant patients. Body weight, BMI, HbA1c, CRP and EUS values decreased in both arms, differences being insignificant between the two arms post-intervention. Participants in the Currant arm had significantly reduced total body fat, WC and trunk fat. Ultrasound scanning improved significantly in patients snacking currants daily. Also, volunteers enrolled in the Currant arm showed a reduced intake of saturated fatty acids. Because BW regulation has been officially recognised as a treatment approach in NAFLD an additional analysis was repeated in patients adhering to this. Post-intervention, the decrease in IL-6 and in fasting glucose was significantly higher in Currant patients who lost BW compared to their counterparts in the Control arm. Conclusively, minimal modifications in snacking choices, such as the inclusion of dried grapes in diet, are beneficial in NAFLD patients with non-significant fibrosis.

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    JP

  24. JP Says:

    Updated 10/19/16:

    http://link.springer.com/article/10.1007/s00394-016-1318-6

    Eur J Nutr. 2016 Oct 14.

    Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

    PURPOSE: Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease.

    METHODS: In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model.

    RESULTS: Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events.

    CONCLUSIONS: Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.

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    JP

  25. JP Says:

    Updated 10/26/16:

    http://www.xiahepublishing.com/ArticleFullText.aspx?sid=2&jid=1&id=10.14218%2fJCTH.2016.00021

    J Clin Transl Hepatol. 2016 Sep 28;4(3):228-233.

    Supplementing Conventional Treatment with Pycnogenol® May Improve Hepatitis C Virus-Associated Type 2 Diabetes: A Mini Review.

    Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) present a significant health burden, with increasing complications and mortality rates worldwide. Pycnogenol® (PYC), a natural product, possesses antidiabetic and antiviral properties that may improve HCV-associated T2DM. In this review, we present previously published data on the effectiveness of PYC against HCV replication and T2DM. We believe that supplementing conventional treatment with PYC may improve the current HCV therapy, attenuate HCV-associated T2DM, and reduce the risk of complications such as cirrhosis or hepatocellular carcinoma and cardiovascular disease.

    Be well!

    JP

  26. JP Says:

    Updated 11/03/16:

    https://www.ncbi.nlm.nih.gov/pubmed/27904598

    J Res Med Sci. 2016 Jul 29;21:53.

    The effects of low carbohydrate diets on liver function tests in nonalcoholic fatty liver disease: A systematic review and meta-analysis of clinical trials.

    BACKGROUND: Although several observational and experimental studies have examined the effects of low carbohydrate diets (LCDs) on nonalcoholic fatty liver disease (NAFLD), there are considerable inconsistencies among studies. We summarized the effect of LCDs on liver function tests, including intrahepatic lipid content (IHLC), alanine transaminase (ALT), aspartate aminotransferases (AST), and gamma-glutamyl transferase (GGT) in patients with NAFLD.

    MATERIALS AND METHODS: PubMed, ISI Web of Science, Scopus, and Google Scholar databases were searched for relevant publications until July 2014, resulting in ten relevant papers that were included in meta-analysis. Related articles were found by searching Medical Subject Heading terms of “NAFLD” in combination with “low carbohydrate”. For this meta-analysis, we used mean differences and standard errors of liver function biomarkers. Summary effect and corresponding confidence interval (CI) were estimated using random effect models. Heterogeneity between studies was assessed using Cochran’s Q- and I-squared tests.

    RESULTS: Our search led to ten eligible papers that evaluated serum ALT levels (n = 238), nine reported serum AST levels (n = 216), five reported serum GGT concentrations (n = 91), and four assessed IHLC (n = 50). LCD decreased IHLC by -11.53% (95% CI: -18.10, -4.96; I2 = 83.2%). However, the effect of LCD on liver enzymes was not significant. Mean differences for the effects of LCDs on ALT, AST, and GGT were -4.35 IU/L (95% CI: -12.91, 4.20; I2 = 87.9%), -1.44 IU/L (95% CI: -4.98, 2.10; I2 = 61.4%), and -7.85 IU/L (95% CI: -29.65, 13.96; I2 =
    99.4%), respectively.

    CONCLUSION: LCD consumption in subjects with NAFLD led to a significant reduction in IHLC, but did not significantly affect the concentration of liver enzymes.

    Be well!

    JP

  27. JP Says:

    Updated 02/03/17:

    http://www.nrcresearchpress.com/doi/abs/10.1139/apnm-2016-0492?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

    Appl Physiol Nutr Metab. 2016 Nov 8:1-7.

    A “healthy diet-optimal sleep” lifestyle pattern is inversely associated with liver stiffness and insulin resistance in patients with nonalcoholic fatty liver disease.

    Several lifestyle habits have been described as risk factors for nonalcoholic fatty liver disease (NAFLD). Given that both healthy and unhealthy habits tend to cluster, the aim of this study was to identify lifestyle patterns and explore their potential associations with clinical characteristics of individuals with NAFLD. One hundred and thirty-six consecutive patients with ultrasound-proven NAFLD were included. Diet and physical activity level were assessed through appropriate questionnaires. Habitual night sleep hours and duration of midday naps were recorded. Optimal sleep duration was defined as sleep hours ≥ 7 and ≤ 9 h/day. Lifestyle patterns were identified using principal component analysis. Eight components were derived explaining 67% of total variation of lifestyle characteristics. Lifestyle pattern 3, namely high consumption of low-fat dairy products, vegetables, fish, and optimal sleep duration was negatively associated with insulin resistance (β = -1.66, P = 0.008) and liver stiffness (β = -1.62, P = 0.05) after controlling for age, sex, body mass index, energy intake, smoking habits, adiponectin, and tumor necrosis factor-α. Lifestyle pattern 1, namely high consumption of full-fat dairy products, refined cereals, potatoes, red meat, and high television viewing time was positively associated with insulin resistance (β = 1.66, P = 0.005), although this association was weakened after adjusting for adiponectin and tumor necrosis factor-α. A “healthy diet-optimal sleep” lifestyle pattern was beneficially associated with insulin resistance and liver stiffness in NAFLD patients independent of body weight status and energy intake.

    Be well!

    JP

  28. JP Says:

    Updated 03/03/17:

    https://www.ncbi.nlm.nih.gov/pubmed/28250783

    J Res Med Sci. 2016 Nov 2;21:106.

    Do symbiotic and Vitamin E supplementation have favorite effects in nonalcoholic fatty liver disease? A randomized, double-blind, placebo-controlled trial.

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Oral administration of symbiotic and Vitamin E has been proposed as an effective treatment in NAFLD patients. This study was carried out to assess the effects of symbiotic and/or Vitamin E supplementation on liver enzymes, leptin, lipid profile, and some parameters of insulin resistance (IR) in NAFLD patients.

    MATERIALS AND METHODS: We randomly assigned sixty NAFLD adult patients to receive (1) symbiotic twice daily + Vitamin E-like placebo capsule; (2) 400 IU/d Vitamin E + symbiotic-like placebo; (3) symbiotic twice daily + 400 IU/d Vitamin E; and (4) symbiotic-like placebo + Vitamin E-like placebo for 8 weeks.

    RESULTS: Symbiotic plus Vitamin E supplementation led to a significant decrease in concentrations of liver transaminase (P ≤ 0.05). Mean difference of apolipoprotein A-1 was more significant in symbiotic group compared to control. However, mean difference of apolipoprotein B100/A-1 was only significant in symbiotic group compared to control. At the end of the study, significant differences in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were seen between the symbiotic plus Vitamin E and control groups (P < 0.001). Furthermore, intake of symbiotic plus Vitamin E supplements led to a significant decrease in concentrations of triglycerides (TG) after the intervention. Significant differences in leptin, fasting blood sugar (FBS), and insulin levels were seen between the symbiotic plus Vitamin E and control groups at the end of the study (P < 0.001). In contrast, symbiotic and/or Vitamin E supplementation did not affect high-density lipoprotein cholesterol and homeostasis model assessment for IR levels.

    CONCLUSION: In our study, symbiotic plus Vitamin E supplementation was the most effective treatment in lowering liver enzymes, leptin, FBS, insulin, TG, TC, and LDL-C among NAFLD patients.

    Be well!

    JP

  29. JP Says:

    Updated 03/29/17:

    https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/synbiotic-supplementation-in-lean-patients-with-nonalcoholic-fatty-liver-disease-a-pilot-randomised-doubleblind-placebocontrolled-clinical-trial/EAB63C291F310282D1DE56ADD2A47433

    Nutrients. 2017 Jan 10;9(1).

    Soluble Fibre Meal Challenge Reduces Airway Inflammation and Expression of GPR43 and GPR41 in Asthma.

    Short chain fatty acids (SCFAs) are produced following the fermentation of soluble fibre by gut bacteria. In animal models, both dietary fibre and SCFAs have demonstrated anti-inflammatory effects via the activation of free fatty acid receptors, such as G protein-coupled receptor 41 and 43 (GPR41 and GPR43). This pilot study examined the acute effect of a single dose of soluble fibre on airway inflammation-including changes in gene expression of free fatty acid receptors-in asthma. Adults with stable asthma consumed a soluble fibre meal (n = 17) containing 3.5 g inulin and probiotics, or a control meal (n = 12) of simple carbohydrates. Exhaled nitric oxide (eNO) was measured and induced sputum was collected at 0 and 4 h for differential cell counts, measurement of interleukin-8 (IL-8) protein concentration, and GPR41 and GPR43 gene expression. At 4 h after meal consumption, airway inflammation biomarkers, including sputum total cell count, neutrophils, macrophages, lymphocytes, sputum IL-8, and eNO significantly decreased compared to baseline in the soluble fibre group only. This corresponded with upregulated GPR41 and GPR43 sputum gene expression and improved lung function in the soluble fibre group alone. Soluble fibre has acute anti-inflammatory effects in asthmatic airways. Long-term effects of soluble fibre as an anti-inflammatory therapy in asthma warrants further investigation.

    Be well!

    JP

  30. JP Says:

    Updated 04/16/17:

    https://www.ncbi.nlm.nih.gov/pubmed/28408059

    Rev Gastroenterol Mex. 2017 Apr 10.

    Effect of a high-protein, high-fiber diet plus supplementation with branched-chain amino acids on the nutritional status of patients with cirrhosis.

    INTRODUCTION AND OBJECTIVES: The potential benefits of branched-chain amino acids (BCAAs) in cirrhosis extend beyond just the improvement of nutritional status. Their effects include improvement of glucose tolerance, oxidative stress, and inflammatory markers, as has been shown in several studies. A dual nutritional approach of a high-protein, high-fiber diet plus BCAAs in cirrhosis could have additional benefits, compared with BCAAs alone. Such an approach has not been explored and therefore the aim of the present study was to evaluate the effect of a combination of a high-protein, high-fiber diet plus BCAA supplementation over a 6-month period of time on the nutritional status of patients with cirrhosis, as well as its safety and tolerability for those same patients.

    METHODS: An open, randomized clinical trial was conducted. Patients were randomized to one of two groups: the BCAAs+HPHF diet intervention group: a high-protein, high-fiber diet with 1.2g/kg protein and 30g of fiber plus supplementation with oral branched-chain amino acids 110g daily and the HPHF diet control group: a high-protein, high-fiber diet with 1.2g/kg protein and 30g of fiber. The differences between the treatment groups were compared using the unpaired T test and the differences at the end of treatment were compared using the paired T test.

    RESULTS: A total of 72 patients were included, 37 in the intervention group and 35 in the control group. At the end of the study period, ammonia and glucose levels showed no significant increase in either group, reflecting the safety of the BCAA supplement. Furthermore, muscle and fat mass were evaluated through triceps skinfold thickness and mid-arm muscle circumference measurements. There was an increase in muscle mass and a decrease in fat mass in the BCAA group, but not in the control group. After the intervention, there were no significant changes in the Psychometric Hepatic Encephalopathy Score or the Critical Flicker Frequency score results in either group, and no episodes of hepatic encephalopathy were observed during the treatment period.

    CONCLUSION: Supplementation with branched-chain amino acids plus a high-fiber, high-protein diet is a safe intervention in patients with cirrhosis. It helps increase muscle mass and does not raise the levels of ammonia or glucose, nor is it associated with the development of hepatic encephalopathy.

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    JP

  31. JP Says:

    Updated 08/03/17:

    https://www.ncbi.nlm.nih.gov/pubmed/28765194

    Cancer Prev Res (Phila). 2017 Aug 1.

    Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a Randomized Intervention Study in the United States.

    Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk. The present analysis examined the effect of GTE consumption on liver injury in 1021 participants (513 in GTE and 508 in placebo arm) with normal baseline levels of liver enzymes. Among women in the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence interval (CI) =3.6-7.1] and aspartate aminotransferase increased by 3.8 U/L (95% CI=2.5-5.1), which were significantly higher than those among women in the placebo arm (both P <0.001). Overall, 26 (5.1%) women in GTE developed moderate or more severe abnormalities in any liver function measure during the intervention period, yielding an odds ratio of 7.0 (95% CI = 2.4-20.3) for developing liver function abnormalities as compared with those in the placebo arm. ALT returned to normal after dechallenge and increased again after one or more rechallenges with GTE. The rise-fall pattern of liver enzyme values following the challenge-dechallenge cycles of GTE consumption strongly implicates the effect of high-dose GTE on liver enzyme elevations.

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    JP

  32. JP Says:

    Updated 09/30/17:

    http://www.mdpi.com/2072-6643/9/8/897/htm

    Nutrients. 2017 Aug 18;9(8). pii: E897.

    Resveratrol in Hepatitis C Patients Treated with Pegylated-Interferon-α-2b and Ribavirin Reduces Sleep Disturbance.

    BACKGROUND: Hepatitis C virus infection and interferon treatment have shown to be risk factors for sleep disorder health-related quality of life.

    AIM:To determine whether the effects of resveratrol on sleep disorders w ere associated with different tests in subjects with chronic hepatitis C treated with Peg-IFN-α and RBV.

    PATIENTS AND METHODS: In this prospective, randomized, placebo controlled, double blind clinical trial, 30 subjects (Group A) with chronic hepatitis received Pegylated-Interferon-α2b (1.5 mg/kg per week), Ribavirin and placebo (N-acetylcysteine 600 mg and lactoferrin 23.6 g), while 30 subjects (Group B) received the same dosage of Pegylated-Interferon-α2b, Ribavirin and association of N-acetylcysteine 600 mg, lactoferrin 23.6 g and Resveratrol 19.8 mg for 12 months. All subjects underwent laboratory exams and questionnaires to evaluate mood and sleep disorders (General Health Questionnaire (GHQ), Profile of Mood States (POMS), Pittsburgh Sleep Quality Inventory (PSQI), Epworth Sleepiness Scale (ESS)).

    RESULTS: The comparison between Group A and Group B showed significant differences after six months in C-reactive protein (p < 0.0001); after 12 months in aspartate aminotransferase (AST) (p < 0.0001) Viremia (p < 0.0001), HAI (p < 0.0012) and C-reactive protein (p < 0.0001); and at follow up in AST (p < 0.0001), Viremia (p < 0.0026) and C-reactive protein (p < 0.0001). Significant differences were observed after 12 month and follow-up in General Health Questionnaire, after 1, 6, 12 and follow-up in Profile of Mood States, after 6, 12, follow-up in Pittsburgh Sleep Quality Inventory and Epworth Sleepiness Scale.

    CONCLUSIONS: Supplementation with Resveratrol decreased General Health Questionnaire score and reduced sleep disorders in patients treated with Peg-IFN-α and RBV.

    Be well!

    JP

  33. JP Says:

    Updated 11/09/17:

    https://www.ncbi.nlm.nih.gov/pubmed/29114108

    Acta Inform Med. 2017 Sep;25(3):169-174.

    Therapeutic Effects of Curcumin on Ultrasonic Morphological Characteristics of Liver in Patients with Metabolic Syndrome.

    Introduction: Metabolic syndrome (METS) represent a simultaneous presence of multiple metabolic disorders in one person. Prevalence is increasing worldwide, which is probably related to increased obesity and sedentary lifestyle. Non-alcoholic steatosis or “fatty liver” is a metabolic disease caused by fat dysfunction. It can be a sign of some other disease, and can often be found in patients with metabolic disorders. Ultrasound is an acceptable method for the identification of fatty steatosis. There is evidence that when turmeric is used as a herbal diet, with its active metabolite of curcumin, can repair fatty acidosis and thus prevent progression of fatty steatosis complications such as cirrhosis and liver cancer. Goal. The aim of the study was to determine the effects of 400 mg curcumin addition to the nutrition on ultrasound morphological characteristics of the liver in METS patients.

    Methodology: A prospective cohort study was conducted on 100 subjects with METS, treated in the family medicine practice of the Tuzla Canton, aged 35-70 years. The therapeutic effects of 400 mg curcumin on ultrasound-morphological characteristics of the liver were followed, validated by ultrasound in 50 respondents of experimental groups with METS. The data were processed by the IBM SPSS Statistics 21 statistical analysis program using parametric techniques andStudent’s t-test for paired samples.

    Results: There were 65% of women in the study. There were no statistically significant differences in the age of respondents within the analyzed groups. The use of 400 mg curcumin per day was statistically significantly improved ultrasound morphological characteristics of the liver in subjects with METS.

    Conclusion: All respondents with METS who used curcumin had beneficial effects on the morphological characteristics of the liver. Curcumin had stronger effects on subjects with METS and DM type 2 than others.

    Be well!

    JP

  34. JP Says:

    Updated 12/13/17:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414412/

    Adv Biomed Res. 2017 Apr 17;6:40.

    The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial.

    BACKGROUND: This study was designed to evaluate the effect of melatonin on nonalcoholic fatty liver disease (NAFLD) in compared to placebo.

    MATERIALS AND METHODS: A total of 100 patients with histopathological diagnosis NAFLD in two groups of case and control received oral melatonin or placebo thrice daily for 3 months. Collected data were weight, waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitive C-reactive protein (hsCRP), fatty liver grade, and side effects which were measured at baseline and after treatment period using standard clinical chemistry techniques.

    RESULTS: Before treatment the mean of weight, waist, SBP, DBP, ALT, AST, and hsCRP between cases and controls were similar (P > 0.5). After treatment, only the differences in the mean of hsCRP in cases was significantly lower than controls (P = 0.003). In case group, all variables after treatment were significantly decreased compare to baseline (P > 0.5) and only AST after treatment was similar to before treatment (P > 0.5). The mean of a decrease in the level of weight, waist, SBP, and ALT were not statistically significant between groups (P > 0.5). In the case group in compare to control group the level of DBP, AST, and hsCRP significantly more decreased. After treatment fatty, liver grade was statistically improved in more cases than controls (P = 0.001). Side effects were similar between the two groups.

    CONCLUSION: Melatonin significantly decreases liver enzymes, so the use of melatonin in patients with NAFLD can be effective.

    Be well!

    JP

  35. JP Says:

    Updated 2/7/18:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768057/

    Biomed Rep. 2018 Jan;8(1):85-90.

    Effect of branched-chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients.

    The incidence rate of insulin resistance (IR) in patients with chronic hepatitis C (CHC) is high. Recently, branched-chain amino acids (BCAA) have been shown to attenuate IR in CHC patients; however, their effect on patient quality of life remains unclear. Therefore, the aim of the current prospective study was to determine the effects of BCAA supplement on IR and health-related quality of life (HR-QoL) in patients with CHC. In the study, 20 non-diabetic patients with CHC, who were non-responders to peginterferon-α and ribavirin, were recruited. Patients took a BCAA supplement once a day (30 g, after a minimum 10-h overnight fast) for 3 months. Serum levels of glucose, insulin, albumin, triglycerides and cholesterol were measured at 0 and 3 months. Additionally, IR was measured using the Homeostasis Model Assessment-IR, HR-QoL was assessed using the 36-item Short Form Health Survey and viral load was measured by reverse transcription polymerase chain reaction using Taqman probes. The Wilcoxon signed-rank test was used to determine statistical significance. The results indicated that 70% of the subjects were positive for IR, which decreased to 50% by the end of the study; furthermore, 85% of the subjects demonstrated some level of improvement. Overall, the BCAA treatment significantly decreased IR (P=0.006) and augmented serum albumin concentration (P=0.008) compared with basal values. Additionally, by the end of the treatment, viral load and triglycerides levels had decreased, though these results were not significant (P=0.084 and P=0.080, respectively). BCAA treatment also improved HR-QoL regarding role limitations due to physical health problems (P=0.017), role limitations due to emotional problems (P=0.026) and social function (P=0.008). In conclusion, BCAA supplementation reduced IR and improved HR-QoL in patients with CHC. These findings support the application of IR therapy as a possible therapeutic strategy for hepatitis C infection.

    Be well!

    JP

  36. JP Says:

    Updated 03/21/18:

    https://www.ncbi.nlm.nih.gov/pubmed/29557414

    J Gastrointestin Liver Dis. 2018 Mar;27(1):41-49.

    A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial.

    BACKGROUND: Probiotics have a beneficial effect on nonalcoholic fatty liver disease (NAFLD) in animal models. Randomized placebo-controlled trials (RCTs) in NAFLD are still lacking in humans despite a large number of data from animal research.

    AIM: We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD.

    METHODS: A total of 58 patients met the criteria for inclusion. They were randomly assigned to receive the multi-probiotic “Symbiter” (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment. The primary main outcomes were the changes in fatty liver index (FLI) and liver stiffness (LS) measured by Shear Wave Elastography (SWE). Secondary outcomes were the changes in aminotransferase activity, serum lipids and cytokines (TNF-α, IL-1β, IL-6, IL-8, and IFN-γ) levels. Analysis of covariance was used to assess the difference between groups.

    RESULTS: In the probiotic group, FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 (p<0.001) but it did not change in the placebo group (82.57+/-2.45 to 81.6 +/-2.36; p=0.367). In both groups a slight but not significant reduction of LS measured by SWE was detected. Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT. Among the markers of chronic systemic inflammatory state, only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic.

    CONCLUSION: The probiotic “Symbiter” reduces liver fat, aminotransferase activity, and the TNF-α and IL-6 levels in NAFLD patients. Modulation of the gut microbiota might represent a new therapy for NAFLD, which should be tested in larger studies.

    Be well!

    JP

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