June 2018 Issue

Diet and Nutrition for Liver Health
By Densie Webb, PhD, RD
Today's Dietitian
Vol. 20, No. 6, P. 36

Learn what dietary patterns and lifestyle habits can prevent and treat chronic liver disease.

The liver is one of the hardest-working organs in the body, performing more than 500 functions vital for life and health, including carrying away waste and breaking down fats in the small intestine (thanks to bile), producing proteins and cholesterol, converting excess glucose into glycogen for storage, regulating blood levels of amino acids, storing iron, clearing the blood of drugs and bacteria, and regulating blood clotting. If any of these functions go awry, illness that sometimes can lead to death occurs.

According to the Centers for Disease Control and Prevention, 3.9 million adults in the United States are diagnosed with liver disease, which led to 40,326 deaths in 2015, the latest year for which such statistics are available. There are any number of causes of liver disease, from excessive alcohol intake and obesity to autoimmune diseases and damage from prescription drugs and some over-the-counter supplements. However, the most common form of chronic liver disease affecting between 30% and 40% of adults in the United States is nonalcoholic fatty liver disease (NAFLD).1,2

Simply put, NAFLD is the result of a buildup of excess fat in the liver that's unrelated to alcohol intake. Although it begins with a fatty liver, it can and often does progress to nonalcoholic steatohepatitis (NASH), characterized by inflammation of the liver; then to fibrosis, the first stage of liver scarring; and finally cirrhosis, when scarring has damaged most of the liver. NASH presents a 20% to 50% risk of progressive fibrosis, a 30% risk for cirrhosis, and a 5% risk of developing liver cancer.3

While hepatitis C is the most common reason for liver transplants,4 NAFLD is currently on its way to becoming the leading cause of liver transplantation in the United States. In fact, it's estimated that NAFLD could reach the No. 1 position as soon as 2020.5

Common Causes of NAFLD
"Anyone with obesity, prediabetes, type 2 diabetes, or metabolic syndrome is at increased risk of NAFLD,"6 says Jill Weisenberger, MS, RDN, CDE, CHWC, FAND, consultant and author of Prediabetes: A Complete Guide: Your Lifestyle Reset to Stop Prediabetes and Other Chronic Illnesses and Diabetes Weight Loss — Week by Week, "so it's logical to use liver enzymes [as a way] to screen anyone with these conditions."

It's unknown why some people develop NAFLD and others don't. However, overweight and obesity put patients at greater risk. With almost 71% of American adults now either overweight or obese, and 5% being morbidly obese (a 400% increase since 1986),7 all of the metabolic diseases (eg, prediabetes, type 2 diabetes, hypercholesterolemia, and metabolic syndrome) associated with these numbers also are on the rise. And NAFLD is among the most prevalent. Researchers have found NAFLD in 40% to 80% of people who have type 2 diabetes and in 30% to 90% of people who are obese. In research that tested for NAFLD in people who were severely obese and undergoing bariatric surgery, more than 90% had NAFLD.2

About one-half of all patients with NAFLD also have hypertension.8 It's been suggested that the gut microbiota can influence both the development and progression of NAFLD by several mechanisms, including regulation of bile acid metabolism and gut permeability. In addition, the possibility of intestinal microbiota regulation with probiotics and prebiotics could be worthy of further study in the prevention and treatment of NAFLD.9

"While genetics play a small role in the condition, prevention is essential and includes management of a healthy weight, a low- or no-added sugars diet, regular physical activity, and a whole foods diet," according to Kristin Kirkpatrick, MS, RD, LD, president of KAK Consulting in the Denver area and author of Skinny Liver: A Proven Program to Prevent and Reverse the New Silent Epidemic — Fatty Liver Disease.

Diagnosing NAFLD
While symptoms can include fatigue and pain in the upper right abdomen,1 NAFLD is usually asymptomatic, so diagnosis typically results from the incidental finding of abnormal liver enzymes during routine blood work. This is usually mildly raised transaminases (alanine transaminase (ALT) and aspartate transaminase, and/or gamma-glutamyltransferase). However, this is a broad screening tool.

Approximately 80% of patients with NAFLD have normal-range ALT levels, so patients with NAFLD easily can go undiagnosed. And since 70% to 80% of people with central obesity and 50% to 80% of people with type 2 diabetes show NAFLD with an ultrasound, liver enzymes alone aren't the best indicator for the presence of liver disease.10

Overweight, obesity, type 2 diabetes, metabolic syndrome, obstructive sleep apnea, and a BMI of 35 or greater are indicators that NAFLD may be present. An ultrasound may be warranted if liver enzymes are normal but NAFLD is suspected; ultrasound is accurate if >30% of liver cells are steatotic. A liver biopsy may be ordered if more advanced liver disease is suspected.10

If NAFLD has progressed to inflammation and cirrhosis, symptoms may include abdominal swelling, enlarged blood vessels just beneath the surface of the skin, enlarged breasts in men, red palms, and jaundice (yellowing of the skin and eyes).

Can Liver Disease Be Treated?
In the past, cirrhosis of the liver was considered irreversible.11 The definitive answer to the question today is "maybe." Reversal of liver damage depends on the stage of the disease, its causes, and whether patients consistently follow treatment protocols.

Liver disease caused by hepatitis C, for example, often can be treated with antiviral medications. Hemochromatosis, an inherited condition in which the body absorbs and stores too much iron, is one of the most common genetic disorders in the United States. The extra iron builds up in several organs, especially the liver. Hemochromatosis can be treated with therapeutic phlebotomy (routine removal of blood, similar to blood donation), iron-chelation therapy, and avoiding supplements that contain iron.12

While there are no FDA-approved medical treatments or drugs for NAFLD, therapies are geared toward reducing risk factors by improving patients' diets, eliminating alcohol, and increasing physical activity to decrease weight, improve glycemic control, manage dyslipidemia, and improve cardiovascular risk profiles.3,11

"The condition is reversible as long as it has not progressed to the later stages," Kirkpatrick says. "Stabilization of blood sugar and weight loss are absolutely essential to reversal of the condition."

Diet and Lifestyle Factors
NAFLD is a multifactorial disease resulting from a complex interplay of genetics, diet, and lifestyle. However, nutrition is the most important environmental factor.9 Because of the interrelationship of obesity and type 2 diabetes with NAFLD, CVD rather than liver disease is the main cause of death in people with NAFLD.8

Below are some of the primary lifestyle factors that often lead to NAFLD and its complications.

Weight
The majority of people with NAFLD are either overweight or obese. Individuals with morbid obesity typically have greatly enlarged livers as a result of fat accumulation. Gradual weight loss can reverse the condition.

Several studies have found that a reduction in daily calorie intake by 500 kcal results in a significant decrease of fat in the liver.13,14 Weight loss is advisable for overweight (ie, BMI 25 to 30) and obese individuals (BMI >30) but shouldn't exceed 1 kg (2.2 lbs) per week. Very low-calorie diets should be avoided, as they can worsen the condition and increase inflammation in the liver.15

Fat Intake
While there are no human studies linking diets high in saturated fat with NAFLD, animal studies have suggested that diets high in saturated fat worsen NAFLD, as well as insulin resistance and CVD.16,17 On the other hand, polyunsaturated fats, specifically omega-3 fatty acids and monounsaturated fatty acids, may play a protective role in NAFLD.3

Sugar Intake
Simple carbohydrates in the diet, in particular fructose, have been linked to NAFLD.18,19 People with NAFLD consume a larger quantity of soft drinks than those without the disease. Soft drinks are high in fructose (high-fructose corn syrup), and fructose stimulates fatty acid and triglyceride synthesis in the liver.

One study found that individual metabolic reactions to fructose vary, and those reactions can determine whether fatty liver will develop.20 Some researchers have suggested that short-term carbohydrate restriction may be more effective at reducing triglycerides in the liver than calorie restriction.21 However, not all studies have found fructose to be associated with increased risk.22

Protein Intake
Limited evidence exists on the effect of proteins on NAFLD. In animals, researchers have observed a reduction in liver fat content when protein intake was increased.23 Findings from The Rotterdam Study in the Netherlands showed that a diet high in animal protein, but not total protein, was associated with a higher risk of NAFLD.22

Physical Activity
Physical activity has been shown to reduce the risk of diabetes by 35% and CVD by 49% in people with NAFLD.24,25 One study found that reducing weight by 5% and exercising regularly was associated with a significant improvement in NAFLD.26

Recommendations
Lifestyle alteration, including dietary changes, plays a critical role in the prevention and treatment of NAFLD. While no dietary recommendations exist that are tailored specifically to NAFLD, the research to date suggests that following dietary and lifestyle guidelines for maintaining a healthy weight, and reducing the risk of type 2 diabetes, metabolic syndrome, and CVD apply to reducing the risk of and treating NAFLD and its complications.

"Some research suggests a Mediterranean-style diet may be beneficial,"27 Weisenberger says, adding that while there isn't much research on NAFLD and dietary components, there's research on diet and insulin sensitivity, which is closely associated with NAFLD. The healthful DASH (Dietary Approaches to Stop Hypertension) eating pattern presented in the US Dietary Guidelines for Americans should minimize risk of insulin insensitivity and NAFLD in individuals who have no other identifiable causes for the disease.

— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas.

References
1. Nonalcoholic fatty liver disease. Mayo Clinic website. http://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567. Accessed April 20, 2018.

2. Definition & facts of NAFLD & NASH. National Institute of Diabetes and Digestive and Kidney Diseases website. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/definition-facts. Updated November 2016. Accessed April 20, 2018.

3. Nseir W, Hellou E, Assy N. Role of diet and lifestyle changes in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(28):9338-9344.

4. Alcohol-related liver disease. American Liver Foundation website. https://liverfoundation.org/for-patients/about-the-liver/diseases-of-the-liver/alcohol-related-liver-disease/. Accessed April 20, 2018.

5. Jarvis LM. Facing a silent liver disease epidemic. Scientific American. October 4, 2016. https://www.scientificamerican.com/article/facing-a-silent-liver-disease-epidemic/

6. Obesity and overweight. Centers for Disease Control and Prevention, National Center for Health Statistics website. https://www.cdc.gov/nchs/fastats/obesity-overweight.htm. Updated May 3, 2017. Accessed April 20, 2018.

7. Sadek R, Wassef A, Mikhail J, Melman L. Prevalence of non alcoholic fatty liver disease in an obese population: expected versus actual correlation. Surg Obes Relat Dis. 2016;12(7 Suppl):S203.

8. Wójcik-Cichy K, Koślińska-Berkan E, Piekarska A. The influence of NAFLD on the risk of atherosclerosis and cardiovascular diseases. Clin Exp Hepatol. 2018;4(1):1-6.

9. Arslan N. Obesity, fatty liver disease and intestinal microbiota. World J Gastroenterol. 2014;20(44):16452-16463.

10. Dyson JK, Anstee QM, McPherson S. Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging. Frontline Gastroenterol. 2014;5(3):211-218.

11. Jung YK, Yim HJ. Reversal of liver cirrhosis: current evidence and expectations. Korean J Intern Med. 2017;32(2):213-228.

12. Hemochromatosis. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/hemochromatosis. Accessed April 20, 2018.

13. Shah K, Stufflebam A, Hilton TN, Sinacore DR, Klein S, Villareal DT. Diet and exercise interventions reduce intra-hepatic fat content and improve insulin sensitivity in obese older adults. Obesity (Silver Spring). 2009;17(12):2162-2168.

14. Larson-Meyer DE, Newcomer BR, Heilbronn LK, et al. Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Obesity (Silver Spring). 2009;16(6):2162-2168.

15. Adams LA, Angulo P. Treatment of non-alcoholic fatty liver disease. Postgrad Med J. 2006;82(967):315-322.

16. Wang D, Wei Y, Pagliassotti MJ. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. Endocrinology. 2006;147(2):943-951.

17. van den Berg SA, Guigas B, Bijland S, et al. High levels of dietary stearate promote adiposity and deteriorate hepatic insulin sensitivity. Nutr Metab (Lond). 2010;7:24.

18. Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, et al. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J Hepatol. 2007;47(5):711-717.

19. Basaranoglu M, Basaranoglu G, Sabuncu T, Senturk H. Fructose as a key player in the development of fatty liver disease. World J Gastroenterol. 2013;19(8):1166-1172.

20. Beysen C, Ruddy M, Stoch A, et al. Dose-dependent quantitative effects of acute fructose administration on hepatic de novo lipogenesis in healthy humans [published online March 20, 2018]. Am J Physiol Endocrinol Metab. doi: 10.1152/ajpendo.00470.2017.

21. Browning JD, Baker JA, Rogers T, Davis J, Satapati S, Burgess SC. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr. 2011;93(5):1048-1052.

22. Alferink L, Kiefte-deJong JC, Veldt B, et al. Animal protein is the most important macronutrient associated with non-alcoholic fatty liver disease in overweight participants: The Rotterdam Study. J Hepatol. 2017;66(1 Suppl):S50.

23. Pichon L, Huneau JF, Fromentin G, Tome D. A high-protein, high-fat, carbohydrate-free diet reduces energy intake, hepatic lipogenesis, and adiposity in rats. J Nutr. 2006;136(5):1256-1260.

24. Bassuk SS, Manson JE. Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease. J Appl Physiol (1985). 2005;99(3):1193-1204.

25. LaMonte MJ, Blair SN, Church TS. Physical activity and diabetes prevention. J Appl Physiol (1985). 2005;99(3):1205-1213.

26. Suzuki A, Lindor K, St Saver J, et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol. 2005;43(6):1060-1066.

27. Baratta F, Pastori D, Polimeni L, et al. Adherence to Mediterranean diet and non-alcoholic fatty liver disease: effect on insulin resistance. Am J Gastroenterol. 2017;112(12):1832-1839.

RISK FACTORS FOR NAFLD

• Increasing age
• Metabolic syndrome (70% to 90% of those with metabolic syndrome have NAFLD)
• More common in men, but women are at higher risk of advanced fibrosis
• Higher risk in Hispanics
• Lower risk in African Americans
• High intake of saturated fats
• High intake of fructose
• Sedentary lifestyle
• Polycystic ovary syndrome
• Hypothyroidism
• Chronic kidney disease
• Type 2 diabetes

— DW
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