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Fatty Liver or NAFLD

Fatty Liver or NAFLD
April 21, 2011 Patrick Nemechek, D.O.

[Updated December 24, 2011]

Fatty Liver or NAFLD – What is Fatty Liver?

Non-Alcoholic Fatty Liver Disease (NAFLD) is a disorder of fat metabolism within the liver and affects approximately 1/3 of all Americans.¬† The term ‚Äúnon-alcoholic‚ÄĚ is used to clearly separate the liver damage that can occur from NAFLD from somewhat similar damage done by Alcoholic Hepatitis.

NAFLD begins with the accumulation of fat within the liver and over time this can cause liver enzyme blood tests (ALT and AST) to become abnormally elevated. This elevation is the first sign that the liver is being irritated from the fat accumulation.

If the liver fat accumulation continues, chronic inflammation can develop which then causes damage to the individual liver cells and results in permanent damage and scarring of the liver.  This stage is referred to as NASH or Nonalcoholic Steatohepatitis.

If fat accumulation and inflammation continues even further, people can ultimately die from liver failure or the development of liver cancer.  The progression from simple fat accumulation to more serious stages of liver damage often proceeds without any overt symptoms in spite of its potentially deadly consequences.

What Happens Overtime to Patients with Fatty Liver Disease?

There are several distinct stages of NAFLD with each step indicating greater levels of damage to the liver. They occur in the following order:

  1. Fat deposits in the liver (hepatic steatosis)
  2. Fat deposits in the liver with secondary inflammation (steatohepatitis)
  3. Fat deposits in the liver with secondary inflammation and now permanent scar tissue (steatohepatitis with fibrosis), and
  4. Large amounts of scarring in the liver with decreasing liver functioning (cirrhosis)

Hepatic steatosis is the most common presentation and may not always progress to either fibrosis or steatohepatitis.  This observation is however disputed and the true nature of progression may not be known until further observational studies are done.

Some studies indicate the incidence of fibrosis in patients with NAFLD is similar to that seen in other chronic liver disease with 30 to 40% having advanced fibrosis and ~15% having cirrhosis.  Obesity and diabetes as well as increased age are independent predictors of progression to fibrosis.

Two studies (this one and this one) following patients over a period of ~4 years showed that ~30 to 40% developed fibrosis from steatohepatitis.   Similar data have been reported by another study looking at outcomes in patients with NAFLD.

How to Diagnosis Fatty Liver?

Fatty liver can be diagnosed by biopsy, ultrasound and magnetic resonance spectroscopy (MRS).   Ultrasound can sometimes fail to detect moderate cases of fat accumulation.

While many patients are often referred for liver biopsy when they have elevated liver enzymes from an unknown cause, nearly 80 percent of patients with fatty liver have normal levels of these enzymes.

Fatty liver should therefore be suspected on the basis of obesity, diabetes and insulin resistance rather than elevated liver enzymes.

What Causes Fatty Liver? 

NAFLD or ‚ÄúFatty Liver‚ÄĚ as it is commonly referred to, is not simply the result of eating too much fat.¬† It is a consequence of eating too much fructose and sucrose.¬† Sucrose is white table sugar and is metabolized into fructose and glucose.

Fructose is different from other sugar molecules in that it goes straight to the liver rather than dispersing throughout the body.  The liver then responds by converting much of the energy from the fructose into a fat molecule called triglyceride.

Triglycerides can then be released into the blood stream to be used by other cells for fuel as long as the body has another important nutrient known as choline.

Choline is a B vitamin that’s required for the transport of fat out of the liver.¬† It is found in many foods that have fallen out of favor in the standard American diet (liver, gizzards, egg yolks and bacon).

Several studies in both animals and humans (here and here) support the understanding that a deficiency of choline is a critical component for the development of NAFLD.

It doesn’t take much imagination to see why there has been an explosion in the diagnosis of Fatty Liver in the last 30 years.  Combine the fact that Americans were told to pursue a low fat diet (think less meat, eggs and bacon) along with the declining consumption of liver, once considered an important food, along with the introduction of higher and higher amounts of fructose into our food supply.

Studies also point out the fact that excessive alcohol and fat intake are also able to cause fatty liver.  It seems high-fat feeding alone can induce fatty liver disease when the fat is provided as corn oil but not when the fat is butter or coconut oil.

Some fats may even prevent the development of NAFLD. A variety of studies suggest that palm oil is protective compared to fish oil; beef tallow or medium-chain fats from coconut oil are protective compared to corn oil; and cocoa butter is protective compared to corn oil.

While most believe the explosion in NAFLD is being driven predominantly by fructose, it seems that excessive calories from fructose, alcohol or certain fats can lead to NAFLD as long as there is a deficiency of choline in the diet.

Excess Calories + Choline Deficiency = NAFLD

While the combination of excess calories and a deficiency of choline seem to be required to trigger the development the fatty liver, a second step is important in the development of liver inflammation.

What Causes the Liver Inflammation?

The fact that some people with fatty liver never progress to the more destructive phase of liver inflammation (NASH) suggests that 2 steps are required for NASH to occur.

A recent study  tracked people with fatty liver for three years.  A little less than half either stayed the same or got better but almost 40 percent developed borderline NASH and over 20 percent developed the more serious inflammatory stage, NASH.

The first step towards liver damage is the accumulation of liver fat from excess fructose along with a deficient intake of an essential nutrient called choline.  The first step may not lead to permanent liver damage but seems to increase the vulnerability of the liver to insults that trigger the progression to NASH.

The second step involves molecular damage of the accumulated liver fat, a process known as lipid peroxidation.  This then leads to a cascade of inflammation that progressively damages the liver cells.

What exactly triggers the inflammation isn’t as well understood.  There is accumulating evidence that the inflammation required for the transition from Fatty Liver to NASH to related to overgrowth of bacterial in the small intestine known as Small Intestinal Bacterial Overgrowth (SIBO).

The small intestine is not designed to have large numbers of bacteria within it’s environment, especially when they are coliform bacteria such as E. coli.¬† These bacteria are essentially harmless if they remain in the colon further downstream but are being shown to trigger leakage of lipopolysaccharides (LPS) from the intestinal lumen into the tissues surrounding the intestine.

The LPS leakage is referred to as bacteria translocation and triggers the activation of immune cells that seem to fuel the inflammation in the liver that results in the development of NASH.

Additionally, the high omega-6 levels in many common polyunsaturated fatty acids (corn oil, vegetable oil, soy oil) may also be triggering the inflammation.  The use of these oils has greatly increased in recent decades as well.

As liver cells are continually damaged over time, they are replaced by scare tissue known as cirrhosis.  If this continues over many years, the liver progressively loses so many functional cells that it has difficulty in performing its many important metabolic functions.  This late stage is when an individual has liver failure.

Liver failure from NASH can lead to death and is increasingly the reason for liver transplants within the United States.  As liver scarring accumulates, the risk of developing liver cancer also increases.

Diet Can Reverse Fatty Liver

So basically, I think excess sugar (fructose and sucrose) consumption, inadequate dietary choline intake and the use of highly processed oils (corn, soy and vegetable) are the major cause of NAFLD.¬† If you look at dietary trends in the US over the last 40 years, they’re consistent with the idea.¬† A pilot study demonstrated¬†significant improvement in NAFLD with a carbohydrate restricted diet.¬† Additionally, this study¬†also demonstrated a reduction in intrahepatic (i.e., within the liver) triglycerides (a measure of liver fatty deposits).

A potential solution to fatty liver is to reduce sugar intake, replace processed oils with natural fats, increase omega-3 fatty acids (possibly prevents progression to NASH) and supplement the diet with high-choline foods and supplements.

As we discussed in previously, it seems that excessive calories from fructose, alcohol or certain fats can lead to NAFLD as long as there is a deficiency of choline in the diet.

Excess Calories (esp. fructose) + Choline Deficiency = NAFLD

Therefore, a reasonable dietary strategy to reverse NAFLD can be boiled down to 4 steps:

  1. Reduce the excessive sugar and alcohol intake. Total carbohydrate intake should be less than 100 grams per day total with particular avoidance of fructose and sucrose.  Decrease alcohol intake.
  2. Increase omega-3 fatty acids by replacing processed oils (corn, soybean, safflower, sunflower and cottonseed oil) with olive oil.  Olive oil is preferred because blocks the pro-inflammatory linoleic acid that is contained in high amounts within the vegetable oils.
  3. Increase daily intake of choline to 1000 mg per day. Whole foods (egg yolk, liver, pate, meat, seafood, tree nuts) are preferred over supplements.

Common foods or ingredients that contain fructose in our diet include:

  • Fruit
  • Fructose
  • Corn Syrup
  • High Fructose Corn Syrup (HFCS)
  • Sucrose
  • Table Sugar
  • Sugar Cane
  • Beets
  • Cane Juice
  • Rice Syrup
  • Maple Syrup
  • Agave Nectar
  • Fruit Juices or Nectars
  • Soda Pop

If patients have symptoms suggestive of bacterial overgrowth (persistent diarrhea, intermittent abdominal cramping or experiencing the need to defecate shortly after eating), I recommend treatment with a 10-day course of Xifaxan (rifaximin) to reverse this condition.

Addendum: Sources of Choline

Egg yolk, liver and gizzards all have some of the highest concentrations of dietary choline.  Other meats, seafood, and nuts tend to be decent sources of choline as well but vegetables are widely variable.

Liver and eggs, for example, have ten times more choline than most vegetables.  Click on this link (http://www.nal.usda.gov/fnic/foodcomp/Data/Choline/Choline.pdf )(See column with heading Total Chol) to find the choline content of many foods.  Lecithin has a very high concentration of choline as well.

One study was able to prevent liver inflammation and enzyme elevation he minimum by supplementing 500 mg per day of choline. This may be useful from prevention but higher levels may be required for reversal.

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Nicole loftis
Nicole loftis

My son has been on the protocol since October 7th 2018¬† I jusr recently had Donovans (my son) labs done last week because I’ve always wondered if he had any food allergies.¬† Well, the dr informed me that my son has a slew of issues with fatty liver and high cholesterol. His liver number is at a 51 when it should be a 10. I keep him on a strict diet. Should I not let him have fruit anymore either? Please help us dr nemechek, I’m very worried for my 4 year old son. I feel like you’re the only… Read more »

Jim
Jim

Dr. Nemechek, the suggested dosis is 1100 mg daily of rifaximin for 10 days right? One question, could i start the first days with 1200 for the first 9 days and the 10th day the rest of the 200 mg? I am asking this because in my country (Ecuador) i have found rifaximin only in 400 mg presentation.

Erika
Erika

Hello Dr. Nemechek: I would first like to thank you for your work. I read The Nemechek Protocol for Autism and Developmental Disorders a couple of weeks ago. As soon as I finished your book, I started my entire family on your Protocol. I have a question about why canola oil is permitted on the Protocol, since most data I‚Äôve come across suggests it is not a beneficial oil. I just did a search for ‚Äúcanola‚ÄĚ on you blog and this was the article that resulted. A quote from this article: ‚ÄúAdditionally, the high omega-6 levels in many common polyunsaturated… Read more »

Rita
Rita

2 yrs ago my AST and ASL were flagged Hi and the GGT flagged Lo and ultrasound results show mild fatty infiltration in the pancreas and liver. For at least a decade I’ve added fruit to my morning yogurt so will stop doing that. But I’ve also taken a probiotic capsule daily in hopes of helping regularity. My confusion is that in another article regarding the protocol you suggest for eradicating suspected SIBO, (I am starting today), you mentioned getting OFF Probiotics and starting the Inulin instead. Should I bother with exchanging my Probiotic for the Culturelle you mention in… Read more »

Zarra
Zarra

Hi
I have been experiencing soft stool for past year. I had a colonoscopy last week and it showed nothing.
I have slightly fatty liver, could it be the couse?

Dr. Patrick Nemechek and Jean Nemechek
Dr. Patrick Nemechek and Jean Nemechek

You might have bacterial overgrowth of the small intestine (SIBO). This is a common cause of soft stool, is highly associated with fatty liver and is not detected on upper or lower endoscopy.

Supplementing with a prebiotic fiber called inulin often helps.

Dr. N

Debbie
Debbie

When you say to limit total carb intake to 100g daily, that is not very much at all. Does this include vegetables as well? As in salads and fresh vegetables?

Dr. Patrick Nemechek and Jean Nemechek
Dr. Patrick Nemechek and Jean Nemechek

All carbs.

Kevin
Kevin

My granddaughter was recently diagnosed with NAFLD. We were told by the Dr. to reduce fat and sugar intakes. We have no idea exactly what would be the recommended daily amount (we know that little-to-none is best). She continually asks us if this amount or that amount is too much and we really dont know. Could you please help us with this?
Thanks,

Dr. Patrick Nemechek and Jean Nemechek
Dr. Patrick Nemechek and Jean Nemechek

I recommend my patients reduce carbohydrate intake to less than 100 grams per day and try to eliminate all sources of fructose ( see my article for the list of fructose sources).

Importantly, I have them all use 1/2-1 tsp of Inulin (a prebiotic found in a product called Clear and Natural) everyday to reverse bacterial overgrowth syndrome ( BOS). BOS contributes to the inflammatory process that damages the liver.

Good luck- PMN

Jack
Jack

You mentioned eating beets has fructose, but I thought eeating beets is good for the liver. What fruits do I need to completley avoid, or foods for that matter. I beleive that fatty reveral can be acheived, but diet is the key. Also, excersizing helps as well. Please advise.
Regards, Jack

Jeanne McAuliffe
Jeanne McAuliffe

I was diagnosed with NAFLD Sept 2011 after having blood work drawn for pre-op purposes. Had an ultrasound which showed diffuse fat infiltration, referred to a gastro and was basically told to eat better and lose weight. I feel like I was basically given the brush off. I am 5’4″ and 210lbs – obviously I’m overweight but I think my symptoms started about 5 years ago when my weight was only 140lbs- fatigue, vague right upper quadrant pain. I would like more info on what I’m dealing with because obviously the doctor I saw doesn’t think this is a problem.… Read more »

Patrick Nemechek, D.O.
Patrick Nemechek, D.O.

Jeanne, NAFLD is a reflection of abnormal metabolism (insulin resistance) and an increased level of fructose consumption. To help reverse the level of fat and inflammation in the liver, reduce the fructose (and carbs overall) in your diet and increase your consumption of choline as I’ve outlined in this article. The more important question, is what has triggered your hunger to increase so much that you’ve gained 70 lbs? Your consumption of fructose and other carbohydrates are being driven by an abnormal level of hunger. Are you lightheaded or chronically fatigued? Low blood perfusion to the brain (referred to low… Read more »

Ian
Ian

Hey there, really good read. Lots of relevant information for me. In September I went in for a routine physical and got some blood work and I found my ALT and AST were 157 and 66 respectively. I am a 23 yr old male was 202lbs at the time of this test and am 5’11. (overweight) Over the course of the last four months i have monitored my enzymes adjusted my diet, and lost 30lbs. My ALT is now 38 and my AST is 25. About a month ago i went against the wishes of my doctor and had a… Read more »

Dr. Patrick Nemechek and Jean Nemechek
Dr. Patrick Nemechek and Jean Nemechek

Ian, Great question. The real truth is the studies showing a reversal in inflammatory enzymes and fatty liver content in patients with non-alcoholic fatty liver disease translates into improved liver health over the long term is not available. But the close parallel is alcoholic liver disease for which we do have data. Alcoholic fatty liver disease improves substantially over the long term when you minimize the offending toxin, alcohol. Likewise, non-alcoholic fatty liver disease improves with normailzation of liver enzymes and liver fat content by minimizing the offending agent, fructose. These are metabolically so similar, its a good bet reducing… Read more »

Patrick Nemechek, D.O.
Patrick Nemechek, D.O.

Ian, Sorry for the tardy response. Yes, I believe a reduction in carbohydrates intake does in fact reduce the inflammation within the liver. I’ve many patients who have normalized their enzymes with carb reduction and this wouldn’t happen without a reduction in inflammation. There is another liver test called GGT. It is not unusual for this to be elevated while the other 2 main liver enzymes are normal. I would also take high dose fish oil (3000 mg twice daily) and a probiotic (Culturelle, once daily) if you have the slight irregularities with your bowel movements. Keep up the good… Read more »

Cathy
Cathy

I really appreciate this information. One question though: since lactose is metabolized in the liver, should it be avoided as well? I’ve searched and searched and can’t find anything except info about lactose intolerance.

Dr. Patrick Nemechek and Jean Nemechek
Dr. Patrick Nemechek and Jean Nemechek

Cathy,

Actually lactose isn’t absorbed at all. Lactose is a disaccarharide (composed of 2 sugar molecules) and is metabolized in the intestinal tract into 1 glucose molecule and 1 galactose molecule. Both of these are absorbed and taken up by the liver to use as energy or to be later stored by the liver as eergy. Galactose can also be metabolized into galactocerebroside and is used to maintain brain cells.

In regards to NAFLD, milk and lactose are not felt to be a contributing factor and therefore it is safe to drink milk with NAFLD.

PMN

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