Non-Alcoholic Fatty Liver Disease

What Is Non-Alcoholic Fatty Liver Disease?

[dropcap]N[/dropcap]on-alcoholic fatty liver is a non-inflammatory liver disorder characterized by degenerative changes in the liver caused by excessive accumulation of lipid (fat) in hepatocytes (liver cells) that is called free fatty acid-generated lipotoxicity.

Non-alcoholic fatty liver shows an increase in liver enzymes called transaminases.

Q: What are the enzymes that increase?

A: The transaminases that increase are ALT and AST. ALT is the abbreviation for alanine aminotransferase enzyme and AST is the abbreviation for aspartate aminotransferase enzyme. They are commonly measured in blood tests to determine liver function and when elevated indicate inflammation.

What Is Non-Alcoholic Fatty Liver In Celiac Disease and/or Gluten Sensitivity?

• Relationship between non-alcoholic fatty liver and celiac disease. Non-alcoholic fatty liver is a complication of celiac disease. A nationwide study found excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years beyond diagnosis with celiac disease. The highest risk estimates were seen in children.¹
• Relationship between non-alcoholic fatty liver and gut symptoms. Because most patients do not have overt gastrointestinal symptoms, a high index of suspicion for celiac disease is required.²
• Relationship between non-alcoholic fatty liver and DHA. DHA omega-3 fatty acid is needed for liver health and protects against fatty liver disease.³ Unfortunately, DHA deficiency is common in untreated celiac disease.

How Prevalent Is Non-Alcoholic Fatty Liver In Celiac Disease and/or Gluten Sensitivity

There is a statistically significant occurrence of fatty liver disease in celiac disease.⁴

The prevalence of silent celiac disease is 3.4% in patients with non-alcoholic fatty liver disease.²

What Are The Symptoms Of Non-Alcoholic Fatty Liver?

Non-alcoholic fatty liver is marked by these three symptoms:

• Non-tender, diffuse liver enlargement called hepatomegaly.
• Elevated liver enzymes.
• Low blood proteins called hypoproteinemia.

How Does Non-Alcoholic Fatty Liver Develop In Celiac Disease and/or Gluten Sensitivity?

• Non-alcoholic fatty liver results from malnutrition, especially protein deficiency in celiac disease.²
• Omega-3 fatty acid deficiency such as DHA and vitamin K deficiency contribute.

Does Non-Alcoholic Fatty Liver Respond To Gluten-Free Diet?

Yes. After 6 months on gluten free diet, liver enzymes normalized in study patients.⁵

• Lipoic acid supplementation improves fat composition within the liver and free cholesterol distribution by opposing free fatty acid-generated lipotoxicity or intracellular lipid partitioning by free fatty acid. The nutritional supplement is called L-Alpha Lipoic Acid.⁶
• Green tea extract reduces fat build-up in the liver and inflammation during nonalcoholic fatty liver disease.⁷
• DHA omega-3 fatty acid protects against nonalcholic fatty liver disease.

6 Steps To Improve Non-Alcoholic Fatty Liver Disease In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both liver and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.⁸
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.⁹
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.⁹
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.⁹.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.⁹
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.⁹
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.⁹[/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes green leafy vegetables such as lettuce and kale, also onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

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Certain medications deplete one or more of these nutrients that contribute to non-alcoholic fatty liver disease: protein, omega-6 fatty acids, and vitamin K. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

This is not a complete listing.

ANTACIDS / ULCER MEDICATIONS

• Alka Seltzer®, Baking Soda deplete Protein.

ANTIBIOTICS disrupt intestinal permeability which complicates celiac disease.

• Gentomycin, Neomycin, Streptomycin, Cephalosporins, Penicillins deplete Vitamin K.

ANTICONVULSANTS

• Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon® deplete  Vitamin K.

CHOLESTEROL DRUGS

• Colestid® and Questran® deplete Vitamin K.

WEIGHT LOSS DRUGS THAT BIND FAT also interfere with absorption of some nutrients.

• Zenicol (Orlistat®) depletes Vitamin K.

 [/box]

• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

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The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.
• Vitamin K as prescribed following blood test for status.
• DHA, an omega-3 fatty acid, comes in liquid capsule and syrups.
• L-Alpha Lipoic Acid as prescribed to combat fat toxicity in the liver.
• Green tea extract.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps: Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Non-Alcoholic Fatty Liver In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Increased Risk of Nonalcoholic Fatty Liver Disease After Diagnosis of Celiac Disease.“ This population-based cohort study comparing the risk of nonalcoholic fatty liver disease diagnosed from 1997-2009 in 26,816 individuals with celiac disease to 130,051 matched reference individuals found that Individuals with celiac disease are at increased risk of nonalcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years beyond diagnosis with celiac disease.

Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of nonalcoholic fatty liver disease. Cox regression estimated hazard ratios for nonalcoholic fatty liver disease were determined.

During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of nonalcoholic fatty liver disease (21/100,000 person-years) in comparison with 85 reference individuals diagnosed with nonalcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95%CI=2.0-3.8), with the highest risk estimates seen in children (HR=4.6; 95%CI=2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95%CI=3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR=2.5; 95% CI 1.0-5.9).¹

“Lipoic acid prevents the changes of intracellular lipid partitioning by free fatty acid.” This study investigating whether lipoic acid could alter intrahepatic [within the liver] lipid composition and free cholesterol distribution in the pathogenesis of non-alcoholic steatohepatitis found that lipoic acid opposes free fatty acid-generated fat toxicity by altering the intracellular lipid composition and free cholesterol distribution.

HepG2 cells were cultured with palmitic acid with and without lipoic acid. Apoptosis, changes of the mitochondrial structure, intracellular lipid partitioning, and reactive oxygen species (ROS) activity were measured.

Free fatty acid  increased apoptosis [cell death], and lipoic acid co-treatment prevented this lipotoxicity.  Lipoic acid also restored the intracellular mitochondrial DNA copy number (553±33.8 copies vs 291±14.55 copies vs 421±21.05 copies, p<0.05) and reversed the morphological (form and structure) changes caused by palmitic acid. In addition, ROS was increased in response to palmitic acid and was decreased in response to lipoic acid co-treatment (41,382 relative fluorescence unit [RFU] vs 43,646 RFU vs 41,935 RFU, p<0.05). Lipoic acid co-treatment increased the monounsaturated and polyunsaturated fatty acid concentrations and decreased the total saturated free fatty acid fraction. It also prevented the movement of intracellular free cholesterol from the cell membrane to the cytoplasm.¹⁰

“Searching for coeliac disease in patients with non-alcoholic fatty liver disease.” This study demonstrated high prevalence of celiac disease (3.4%) in 59 consecutive patients with fatty liver disease ( hypertransaminasemia and non-alcoholic fatty liver disease), 38 (64%) with steatohepatitis. Serology screening for celiac disease should include tests for anti-endomysium antibodies, in addition to anti-transglutaminase antibodies, since positivity for tissue transglutaminase antibodies in the absence of confirmatory anti-endomysium antibodies, is not sufficient to perform diagnostic endoscopy.²

CASE REPORT SUMMARIES

“Large-droplet liver steatosis in celiac disease.” This case report of a 25 year old woman with swelling of the lower limbs documents development of serious diffuse large droplet steatosis as a result of malnutrition due to unrecognized Celiac Disease, later confirmed by small bowel biopsy finding of total villous atrophy. Albumin, prothrombin time, and trace elements normalized with gradual improvement in amino transferase levels on Gluten Free Diet.¹¹

Sources:

1. Reilly NR, Lebwohl B, Hultcrantz R, Green PH, Ludvigsson JF. Increased Risk of Nonalcoholic Fatty Liver Disease After Diagnosis of Celiac Disease. J Hepatol. 2015 Jan 21. pii: S0168-8278(15)00019-7. doi: 10.1016/j.jhep.2015.01.013. [↩] [↩]
2. Bardella MT, Valenti L, Pagliari C, et al. Searching for coeliac disease in patients with non-alcoholic fatty liver disease. Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. May 2004;36(5):333-6. [↩] [↩] [↩] [↩]
3. Espinosa A, Valenzuela R, González-Mañán D, D’Espessailles A, Guillermo Gormaz J, Barrera C, Tapia G. Prevention of liver steatosis through fish oil supplementation: correlation of oxidative stress with insulin resistance and liver fatty acid content. Arch Latinoam Nutr. 2013 Mar;63(1):29-36. [↩]
4. Delco F, El-Serag HB, Sonnenberg A. Celiac sprue among US military veterans: associated disorders and clinical manifestations. Digestive Diseases and Sciences. May 1999;44(5):966-72. [↩]
5. Bardella MT, Valenti L, Pagliari C, et al. Searching for coeliac disease in patients with non-alcoholic fatty liver disease. Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. May 2004;36(5):333-6. [↩]
6. Kim DC, Jun DW, Jang EC, Kim SH, Kim EK, Lee SP, Lee KN, Lee HL, Lee OY, Yoon BC, Choi HS. Lipoic acid prevents the changes of intracellular lipid partitioning by free fatty acid. Gut Liver. 2013 Mar;7(2):221-7. doi: 10.5009/gnl.2013.7.2.221. [↩]
7. Li J, Sapper TN, Mah E, Rudraiah S, Schill KE, Chitchumroonchokchai C, et al. Green tea extract provides extensive Nrf2-independent protection against lipid accumulation and NFκB pro- inflammatory responses during nonalcoholic steatohepatitis in mice fed a high-fat diet. Mol Nutr Food Res. 2015 Dec 17. doi: 10.1002/mnfr.201500814. [↩]
8. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
9. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
10. Kim DC1, Jun DW, Jang EC, Kim SH, Kim EK, Lee SP, Lee KN, Lee HL, Lee OY, Yoon BC, Choi HS. Lipoic Acid prevents the changes of intracellular lipid partitioning by free Fatty Acid. Gut Liver. 2013 Mar;7(2):221-7. doi: 10.5009/gnl.2013.7.2.221. [↩]
11. Husova L, Senkyrik M, Lata J, et al. Large-droplet liver steatosis in celiac disease. Vnitrni Lekarstvi. Mar 2004;50(3):244-8. [↩]