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Diet & Fatty Liver - Part I

Liver

 The liver is the largest internal organ and the largest gland in the human body and can weigh about 1500 gm (1.5kg) in men and 1200 gm (1.2kg) in women. Liver is also the most complex organ, performing multiple functions like detoxification, bile formation, protein carbohydrate & lipid metabolism, erythropoietic function, vitamin & mineral metabolism, storage site for some micronutrients, etc.  

 

 Fatty Liver Disease (FLD)

 Fatty Liver as it is commonly called, refers to the excess accumulation of fat in the liver cells which may overtime impact liver function and cause injury to the liver. Fatty Liver Disease can be of two types Non-Alcoholic Fatty Liver Disease (NAFLD) and Alcoholic Fatty Liver Disease (ALD). Usually, fat accumulation of more than 5 – 10% by weight in the liver is classified as fatty liver.

 Non-Alcoholic Fatty Liver Disease (NAFLD) is the buildup of fat deposits within the liver cells without alcohol consumption. NAFLD can be of two types:

 

  1. Non-Alcoholic Fatty Liver (NAFL): In NAFL, there is fat accumulation within the liver accompanied by negligible or no inflammation and no liver damage. This can lead to liver enlargement but usually does not progress to liver damage or major complications.
  2. Non-Alcoholic Steatohepatitis (NASH): NASH is usually identified with fatty deposits accompanied by inflammation and liver damage. This can lead to fibrosis or scarring of the liver, cirrhosis and permanent damage to the liver. Cirrhosis can further progress to liver cancer and/or failure.

  

Common causes of Fatty Liver Disease (FLD)

  • Obesity
  • Overweight
  • Type 2 Diabetes
  • Oxidative Stress
  • Insulin Resistance
  • Overconsumption of calories (overeating/force-feeding/stress-eating)
  • Genetic Causes
  • Dyslipidemia
  • Regular consumption of processed foods and/or sugary beverages (junk food)
  • Alcohol Consumption
  • Side effect of medications
  • Changes in gut microbiome
  • Night shift work
  • Poor sleep

Symptoms of Fatty Liver Disease (FLD):

Usually, patients of fatty liver disease may not feel or experience any symptoms. However, as the disease progresses it may lead to certain common identifiable signs like: 

  • Tiredness/Fatigue/Weakness
  • Abdominal Discomfort
  • Enlargement of Liver
  • Loss of Appetite
  • Changes in gut functioning 

 

Diagnosis 

While there are many ways of diagnosing fatty liver disease such as a physical exam to check for liver enlargement, the most common and widely used method are blood tests for liver function.
 
In the liver function test (LFT), markers of liver enzymes i.e., Aminotransferase (ALT) and Aspartate Aminotransferase (AST) are checked to see if ALT > AST (for NAFLD). Other markers such as GGT, Bilirubin, Albumin, etc. as also checked.
 
FIB-4 calculation based on markers obtained through LFT can be done to check for advanced liver fibrosis or scarring.
 
Ultrasonography is helpful in deriving informative conclusions.
 
Fibroscan is another noninvasive technique being used to detect fatty liver.
 
Advanced testing such as CT scan, MRI and Liver biopsy can be done to check if further deterioration of the liver is taking place. 
 
 
 
A few years ago, a new term MAFLD was coined i.e., Metabolic dysfunction associated fatty liver disease. We won’t be going into discussing MAFLD today, in case you want to know the difference between MAFLD and NAFLD feel free to read PMID: 36443926. Today our focus is non alcoholic fatty liver disease (NAFLD).
 
 
 

Recent trends in Diet & Fatty Liver Disease Research


 

Metabolic Profile and Associated Risk Factors of NAFLD

 
In a cross-sectional study (PMID: 36820120) conducted in Bhopal (India), all the 236 adults were community screened and subjected to Fibro scan testing. 43.6% of the participants were detected with NAFLD. Based on the test and screening results the markers significantly associated with NAFLD were high body weight, high waist circumference, high waist-to-hip ratio, high fasting sugar, high serum glutamate pyruvate transaminase (SGPT), high triglyceride levels and very high low-density lipoproteins (VLDL) along with obesity, diabetes and dyslipidemia.


Researchers conducted a Mandelian Randomization study (PMID: 35488966) and found that genetic predisposition to smoking, obesity, type 2 diabetes, high blood pressure and dyslipidemia were associated with an increased risk of NAFLD, with the association of type 2 diabetes, systolic blood pressure and triglycerides independent of genetically predicated BMI. Additionally, an inverse association between moderate alcohol consumption, coffee, caffeine consumption and vigorous physical activity with NAFLD was found.
 
In addition to anthropometric measurements, blood testing and Fibro scan can be used to appropriately diagnose fatty liver disease. While a predisposition to diseases like type 2 diabetes, hypertension and dyslipidemia increase the risk for fatty liver disease, a thorough evaluation through liver function tests and ultrasonography can lead to a better diagnosis by the health care professional.
 


 
Probiotics and FLD
 

In this (PMID: 29931231) randomized controlled clinical trial 102 patients with a mean age of 40 years were randomly assigned to one of the three groups, where two were intervention groups and one control group. One intervention group was given a synbiotic yogurt containing Bifidobacterium animalis and Inulin, the other conventional yogurt while the control group was instructed to follow a healthy lifestyle alone. The study lasted 24 weeks after which researchers found that there was decrease in ALT, GGT, ALP, TG, TC, Fatty Liver Index and insulin resistance. Researchers concluded that synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD.

In another (PMID: 30952918) randomized, double blind, placebo-controlled study lasting 12 weeks, 68 obese NAFLD patients were randomized to probiotic and placebo groups. The probiotic mixture contained Lactobacillus, Pediococcus, Bifidobacterium. Researchers found a decrease in Total Cholesterol, Hepatic Steatosis, Inflammatory markers and BMI in the obese NAFLD patients.


In a study (PMID: 29148175) on 75 patients with NASH was an open-label trial where the participants were randomly divided into two groups i.e., low fat/low calorie for the control group while a probiotic cocktail was given to the experimental group once daily for 12 weeks. Researchers found that the group taking the probiotic cocktail containing Lactobacillus, Streptococcus, Bifidobacterium saw significant improvement of liver inflammation without any adverse events and led to decrease in TC, ALT and liver stiffness.
 
Use of probiotics has increased exponentially in the past decade, in research, to help with management of numerous diseases. As the evidence piles up, we are hopeful to arrive at a better recommendation strategy for different individuals based on their specific gut microbiota composition and deficiencies, in the near future.


 
Resistant Starch and NAFLD

 
In this recently published study (PMID: 37673036), researchers conducted a randomized double-blind placebo controlled clinical trial which included a total of 200 participants (145 males and 55 females) diagnosed with liver steatosis. Participants were divided into two groups of 100 each and were given either a high amylose maize corn starch or equal energy control starch for 4 months. Calories and macronutrient intake was not significantly different between both groups and all participants were counselled by a nutritionist at the start and during follow ups. Anthropometric measurements, serum markers for liver, kidney, glucose, inflammation and NAFLD severity were measured on Day 0 and Day 120. Researchers reported a significant reduction in liver enzymes, IHCT, body weight, BMI, fat percentage and fat mass. The researchers didn’t stop here, they further went on to analyze the fecal samples collected before and after the intervention and found that the resistant starch group post intervention, had lower alpha diversity, decreased abundance of Bacteroides stercoris and Parabacteroides merdae, for this analysis 50 participants were randomly selected from each group. Further on the researchers transplanted the fecal microbiota (FMT) collected from the participants into antibiotic treated mice fed with high fat, high cholesterol diet and found that the FMT from resistant starch group resulted in significant reduction in liver weight and body weight, improvements in insulin sensitivity, reduction in liver enzymes, reduction in hepatic triglycerides and cholesterol.

 

 

Nutrient Intake and FLD

Chaturvedi S, et al., 2023, in their study conducted on 320 Gastro and Medicine OPD patients at All India Institute of Medical Sciences (India), found that the 160-control group (non-NAFLD) participants had higher intakes of Vitamin K, Vitamin B6, Magnesium and Calcium while the other 160 (NAFLD group) participants showed higher intakes of saturated fatty acids, polyunsaturated fatty acids, n6/n3 ratio compared to controls during the 24 hr., 2-day dietary recall questionnaire. Researchers found that percent carbs and percent SFA’s emerged as significant risk factors for Liver steatosis whereas percent proteins, magnesium and vitamin C were inversely associated with it.


This food group tree-based analysis study (PMID: 35889764) which included 993 NAFLD patients and 973 healthy controls from Trivandrum (India) found that the NAFLD patients consumed more cereals (refined rice), fats and edible oils (animal fat), meat (red meat) and sugars (refined sugars). These patients also consumed fewer vegetables, pulses, legumes, nuts and dairy products. Researchers also found a positive association between nut consumption (coconut and cashew nuts as roasted and fried) and NAFLD.


In a systematic review and meta-analysis of fifteen cross-sectional and nine case control studies (PMID: 32138796), the authors note that a high to moderate intake of nuts, legumes, fish, whole grains and vegetables were inversely associated with NAFLD while consumption of red meat and soft drinks were positively associated with NAFLD. Milk and cheese may have an adverse effect on the likelihood of NAFLD.
 

Micronutrient deficiencies are common, along with an increased energy intake from saturated fats, refined grains and simple sugars in NAFLD patients. It is observed that most patients with NAFLD consume less of vegetables and whole grains.
 
 

Nuts and NAFLD

 Two groups of participants, one with 396 NAFLD patients and the other with 803 controls were analyzed in this study (PMID: 32789149) for nut intake and its prevalence of NAFLD. Nuts intake considered here were sum of almonds, peanuts, walnuts, hazelnuts and pistachios. After adjusting for age, sex, BMI, alcohol consumption, smoking, diabetes and physical activity researchers found that while there was no significant relationship between nut intake and NAFLD, higher nut consumption can be a higher risk factor for NAFLD mediated by a higher energy intake.
 
Nuts as such are considered a source of many nutrients like magnesium, vitamin E, alpha linolenic acid, monounsaturated fats, etc. Being classified into the category of dietary fats, nuts such as almonds, walnuts, pistachios (except of peanuts which in spite of having similar profile are classified as legumes) they tend to have higher calories per serving and overconsumption of nuts is quite easy and may even go unnoticed. Nuts as such when consumed in moderation as part of a healthy and balanced diet may not be a risk factor for fatty liver disease when overall calories are controlled. Some people tend to consume nuts by frying or roasting in oil/ghee/butter along with salt, this practice is not recommended as it would not only increase the caloric load but also lead to excess consumption of salt (sodium) which is a risk factor for many diseases like hypertension, cardiovascular disease, etc.


 
Sugar and Fatty Liver Disease


In this randomization intervention study (PMID: 22205311) lasting 6 months, 47 overweight participants were randomly assigned to either 1L regular cola per day (100gm sucrose), 1L aspartame sweetened diet cola (0 kcals), 1L semi skim milk (47gm milk sugars) and 1L water (0 kcals). At the end of the study researchers observed that while the total fat mass was not significantly different between groups, the regular cola group showed significant increase in liver fat (around 132 – 143%), increased skeletal muscle fat (117 – 221%), increased visceral fat (24 – 31%), increased blood triglycerides and total cholesterol. While the dose of both calories and sugar between the groups were different, researchers did see a decline in systolic blood pressure by 10 – 15% in the milk and diet cola groups compared to regular cola.   


In a study (PMID: 22952180) the participants (16 NAFLD patients) were overfed with 1000 extra calories coming from added sugars for 3 weeks post which the participants went on a hypo-caloric diet (calorie deficit) for 6 months. During the 3 week carbohydrate overfeeding period the participants gained weight by around 2% and saw an increase in liver fat by around 27%, while post the 6 month hypo-caloric phase the participants lost 4% of their weight and 25% of their liver fat.
 

While a lot of research on fatty liver disease has come through from epidemiology, we have recently just scratched the surface with more in depth clinical trials on FLD. Overfeeding trials, for example are a great way to find probable cause and effect relationships. Although, simple sugars come out as a clear outlier when it comes to increasing liver fat, the combination of fructose and saturated fat along with an increased energy intake seems to have the highest effect on increasing liver fat. Dieting (calorie deficit diet) post an overconsumption period does seem to bring down the liver fat levels over a longer period of time.
 


 
Fructose, Saturated Fat and Fatty Liver Disease
 

Thirty healthy non-obese young male participants were evaluated (PMID: 20483648) after a 7-day isocaloric control diet of 55% carbohydrate (10% simple sugar), 30% fat (10% saturated fat) and 15% protein. Post this, the participants were put on a high fructose diet for 7 days, a high saturated fat diet for 4 days and a high fructose + high saturated fat diet for 4 days. Researchers observed that VLDL triacylglycerols significantly increased after the fructose diet but decreased after the saturated fat diet. Intrahepatocellular levels (IHCL) measured using the magnetic resonance spectroscopy, were increased by all the three hyper calorie diets with fructose diet increasing it by 16%, saturated fat diet by 86% and the fructose + saturated fat diet by 133%. Both the high fructose and high saturated fat diets had an increased energy intake by 30 – 35% while the high fructose + saturated fat diet had an energy intake increase of 65%. The increase in the liver fat was 70% more in the saturated fat diet in comparison to the fructose diet.

 


 
Eggs and Fatty Liver Disease
 

In this case control study (PMID: 28443155), 169 patients with NAFLD and 782 controls were assessed for dietary intake using a quantitative food frequency questionnaire. For egg consumption the participants were divided based on their egg intake per week as <2, 2 – 3 and 4+ eggs per week. While the total energy intake between the cases and controls was similar the total energy intake between the egg intake groups was different with the >4 eggs per week group having the highest energy intake. Researchers here observed that participants who consumed 2 – 3 eggs per week were 3.56 times more likely to have NAFLD in comparison to <2 eggs per week. Additionally, 4+ eggs per week consumption was not significantly associated with the risk of NAFLD.  

Researchers divided a cohort of 6734 non-NAFLD participants (PMID: 37500513) into three groups with the first group consuming 0 – 4 eggs per week, second consuming 5 – 7 eggs per week and the third consuming >7 eggs per week. Diet and egg consumption data was collected using a food frequency questionnaire. 1484 participants ended up developing NAFLD during a median follow up of 45 months, with the incidence rates of 27.1%, 19.9% and 29.6% respectively in the three groups after the 4-year period. Researchers concluded that eating 5 – 7 eggs per week may have the lowest risk of developing NAFLD.


In this cross-sectional study (PMID: 38337714), 980 participants aged over 60 completed clinical, dietary and lifestyle assessment including blood testing and were divided into four groups i.e. (a) No steatosis and No Hypertension; (b) No steatosis and Yes Hypertension; (c) Yes steatosis and No Hypertension; (d) Yes steatosis and Yes Hypertension. More than 70% participants in all groups had egg intake of <2 per week. Researchers found that as egg consumption increased to >3 per week, the risk of developing hypertension only and associated with steatosis, decreased linearly.


Researchers conducted a randomized control trial (PMID: 23911216) spanning 12 weeks, participants spread over 3 groups consumed either their regular number of eggs per week of 1 – 2 (control group) while the other two groups consumed one extra egg per day or a buttermilk drink containing one egg yolk. Blood samples were drawn on day 1 and day 90 to check for changes in serum lipids, inflammation markers, endothelial activity and liver function. Markers of total cholesterol and LDL-C did increase in women with daily egg consumption over the control group, however markers of inflammation, endothelial activity and liver function showed no effects. When the egg yolk was consumed in the buttermilk drink, the total cholesterol and LDL-C did increase but didn’t reach significance.
 
Egg consumption has been at the center of debate for many years in fatty liver research as the yolk in the egg is a major source of saturated fat and cholesterol. 1 medium size raw egg (44gm) has about 7% of the daily value of saturated fat (1.4gm) and a whopping 54% (163.7mg) of the daily value of cholesterol (data taken from the USDA). Egg consumption as such did not lead to significant increase in liver fat however, we do have to consider here that maybe people who consume eggs daily as part of their diet might also be consuming vegetables regularly or even cooking eggs along with vegetables & eating them and/or have other lifestyle parameters that would assist in better management of their health. If someone is not an egg eater, it would be prudent to mention here that they don’t have to start eating eggs for fatty liver management, however if a NAFLD patients is eating eggs regularly (assuming they are not overindulging) perhaps adding vegetables to their eggs and consuming them together as part of a wholesome meal is better than having eggs alone. Additionally, watching how much oil/ghee/butter is used while cooking eggs is much more important as that can significantly increase the overall calories being consumed.
 

 

Coffee and Fatty Liver Disease

 

Researchers performed a meta-analysis of 11 epidemiological studies (PMID: 32920163) from a total of 321 articles to find out the effect of coffee consumption on NAFLD. Researchers observed that the risk of developing NAFLD reduced by a statistically significant 23% among regular coffee drinkers, while the risk of developing fibrosis decreased by 32% in NAFLD diagnosed patients drinking coffee daily.


Likewise, two studies PMID: 27824642 and PMID: 34371891 found similar results indicating that coffee consumption significantly decreased the risk of developing liver fibrosis in NAFLD patients and higher coffee intake is inversely associated with severity of hepatic fibrosis in NAFLD patients.  

  
Inspite of the previous convincing evidence, in this double-blind randomized placebo controlled clinical trial (PMID: 33838673), 101 participants were divided into four groups with either 200mg chlorogenic acid + 200mg caffeine, or 200mg caffeine + placebo, or 200mg chlorogenic acid plus placebo, or placebo only, for six months. All participants were diagnosed with type 2 diabetes and NAFLD, additionally they were treated with anti-hyperglycemic agents. Hepatic markers such as AST, ALT, GGT showed no significant differences between groups leading the researchers to conclude that the two main components of coffee had no significant impact on markers of hepatic steatosis and fibrosis, liver biochemistry, inflammatory and metabolic parameters in patients with NAFLD and type 2 diabetes.


Additionally, in this systematic review of seven studies (PMID: 30573353), researchers wanted to explore the relationship between number of cups of coffee consumed per day with the risk of NAFLD. It was observed that more than 3 cups of coffee per day lowered the risk of NAFLD significantly in comparison to less than 2 cups per day.
 
Coffee & caffeine, just like eggs has received multiple positive and negative associations for fatty liver disease. While the distinct difference between the two being that coffee due to its very nature is a calorie free beverage while eggs are classified as food with calories. Most research on coffee consumption and NAFLD risk has come from epidemiology which leads to the conclusion that coffee is negatively associated with NAFLD risk and might even lead to a reduction in risk when regularly consumed. Caffeine and chlorogenic acid paint a different picture though. 
 
 
From the above-mentioned references on recent published research in the field of diet, lifestyle and fatty liver disease it is evident that while certain nutrients like fructose and saturated fat clearly show an increasing trend for the risk of fatty liver disease (NAFLD) with higher intakes. However, when calories are controlled, intake of foods like nuts (almonds, walnuts) might not have a meaningful impact for NAFLD risk. Researchers in their recently published study (PMID: 30901929) point out the nutrients beneficial for NAFLD having good clinical evidence include whole grains, MUFA’s, Omega-3’s, vegetable protein, prebiotic fiber along with nutrients like probiotics, resveratrol, taurine, choline and coffee which have insufficient evidence, while the nutrients to be avoided are simple sugars (fructose), saturated fats and trans fats along with animal protein (red and processed meat). Research in the field of probiotics has come out in the recent past, however we still lack clear guidelines on whom to recommend them to and for how long. Similarly, sweet potato intake has been inversely associated with NAFLD risk in males (PMID: 35403524).
 
 
In future posts we would be going over certain foods which may or may not have beneficial effects on NAFLD like vitamin E, sunflower seeds, garlic, turmeric, etc. With these its more so about the supplementation that has been reported to elicit beneficial effects. Choosing these options as a means to reduce or treat fatty liver risk is not recommended without a thorough analysis of one’s diet, health and lifestyle by a qualified professional. Sunflower seeds, for example may help with fatty liver (NAFLD) they however contain toxic metals like cadmium (PMID: 7792263), aflatoxins (PMID: 29486657) and may cause allergies. One important point to note here is that the recommendation for consumption of sunflower seeds for managing liver fat comes from traditional course of action rather than scientific evidence.


As for what might require some restriction or even complete avoidance in certain scenarios and can potentially increase the risk of liver disease are herbal supplements, herbal products, detoxes, alcohol (in higher amounts), green tea (mostly as supplements), saturated and trans fats especially from processed foods, high amounts of fructose and environmental pollution (this one goes unnoticed). We would delve into these separately in future post and articles.
 
 
As a thumb rule, choosing minimally processed whole foods, which are lower in saturated/trans fat and higher in vegetable protein, and can provide sufficient micronutrients should be the course of action. Supplementation, where the individual needs are not being met for both macro and micro nutrients can be considered in a clinical setting under the supervision of a qualified dietitian.
 
 

 


 
 
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Clinical Dietitian Keshav || MSc Dietetics (DFSM), PGND, CNCC

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