If You Have Fatty Liver Disease, an Israeli-American Team Have Found a Better Way to Treat It

Do you suffer from fatty liver disease (FLD) – also known as hepatic steatosis, a condition where excess fat builds up in the liver? You probably don’t know, because it hardly causes any symptoms except occasional tiredness or pain in the upper-right side of the abdomen. But you risk of having it are quite high, as the global prevalence (the proportion of a population who have a specific characteristic in a given time period) is between 25% and 35%.


It may result from excessive drinking of alcohol (alcoholic liver disease or ALD), in which case, if you stop drinking alcohol for two weeks, your liver should return to normal. But in most cases, it comes from a poor diet and lack of exercise and is called non-alcoholic fatty liver disease (NAFLD). This is a very common disorder and refers to a group of conditions in which there is accumulation of excess fat in the liver of people who drink little or no alcohol. Some people develop simple fatty liver, but the most common form of NAFLD is nonalcoholic steatohepatitis (NASH), which and causes inflammation liver cell damage and can lead to fibrosis (scarring) of the liver. It is unclear why some people with NAFLD develop simple fatty liver and others develop NASH. While some fat is normal in the liver, excessive fat (5% or higher) leads to insulin resistance, type-2 diabetes, cardiovascular risk, as well as decreased gut microbiome diversity and microbial imbalance. Diagnosis is based on the medical history supported by blood tests, medical imaging, and occasionally liver biopsy.

There are no drugs for treating NAFLD, so patients are advised to choose a healthful diet, lose weight (if they are overweight), exercise regularly, control their diabetes (if they have it), lower their “bad cholesterol” level and protect the liver. If NAFLD is chronic and untreated, it can lead to develop into serious fibrosis and liver cancer. 


But what is a healthful diet? Researchers at Ben-Gurion University (BGU) of the Negev in Beersheba and a team of Harvard University colleagues have refined diets recommended until now to create one that is even more effective in fighting fatty liver disease; they found that a “green Mediterranean diet” reduces fatty liver more than other diets and cuts NAFLD in half. The findings have just been published in Gut, a leading international journal focused on gastroenterology and hepatology, under the title “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomized controlled trial.” 


 “Our research team and other groups over the past 20 years have proven through rigorous randomized long-term trials that the Mediterranean diet is the healthiest,” said lead researcher Prof. Iris Shai, an epidemiologist in the BGU School of Public Health who is also an adjunct lecturer at the Harvard T.H. Chan School of Public Health. “Now, we have refined that diet and discovered elements that can make dramatic changes to hepatic fat and other key health factors.” Other Harvard investigators were Profs. Meir Stampfer and Frank Hu, chair of the department of nutrition at the Chan school. 


This MRI-nutritional clinical trial (called Direct-Plus), is rich in vegetables, includes daily intake of walnuts (28 grams), and less processed and red meat. It is enriched with green components, high in polyphenols, including three to four cups of green tea/day and 100 grams (frozen cubes/day) of a Mankai (an aquatic green plant also known as duckweed) green shake., is high in bioavailable protein, iron, B12, vitamins, minerals and polyphenols. 


“Addressing this common liver disease by targeted lifestyle intervention might promote a more effective nutritional strategy,” noted Dr. Anat Yaskolka-Meir, first author and member of the BGU School of Public Health. “This clinical trial demonstrates an effective nutritional tool for NAFLD beyond weight loss.” 


This 18-month trial DIRECT-PLUS began in 2017 at the Nuclear Research Center Negev in Dimona, Israel, when 294 workers in their fifties with abdominal obesity were randomly divided into three groups – healthy dietary regimen, Mediterranean diet and green Mediterranean diet. In addition to the diet, all the participants were given a physical exercise regimen with a free gym membership. The participants underwent MRI scans to quantify the exact proportion of excess intrahepatic fat before and after the trial. The results showed that every diet led to liver-fat reduction. However, the green Mediterranean diet resulted in the greatest reduction of hepatic fat (-39%), as compared to the traditional Mediterranean diet (-20%) and the healthy dietary guidelines (-12%). 


The results were significant after adjusting for weight loss. Overall, the green MED diet produced dramatic reductions in fatty liver. NAFLD prevalence dropped from 62% at baseline to 31.5% in the green Mediterranean group, down to 47.9% in the Mediterranean group and 54.8% in the healthy dietary regimen group. Specifically, greater Mankai and walnut intake and less red/processed meat intake were significantly associated with the extent of IHF loss, after controlling for other variables. Both MED groups had significantly higher total plasma polyphenol levels. More specific polyphenols, found in walnuts and Mankai, were detected in the green Mediterranean diet group; the researchers hypothesize the effect of polyphenols and the reduction in red meat play a role in liver fat reduction. 


The Direct Plus trial consisted of 1,500 calories per day, including 40 grams of carbohydrates and 100grams of protein plus healthful fats such as olive oil.   The major sources of polyphenols were Mankai and walnuts, but these also come from olive oil, almonds, red onion and broccoli. 




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