Nonalcoholic fatty liver disease (NAFLD) affects a significant portion of the global population, with doctors expressing concern over its increasing prevalence. Hugo Rosen, a liver disease specialist, notes a shift in his patient base, with fatty liver disease now being more common than hepatitis C. NAFLD, often called a "silent killer," is frequently asymptomatic, making awareness and appropriate management crucial. While lifestyle interventions, including diet and exercise, are considered critical in managing NAFLD, the role of specific diets like the ketogenic diet remains a topic of ongoing research and debate.
Understanding NAFLD and its Management
NAFLD is characterized by the buildup of extra fat in the liver, and its prevalence is estimated to affect a quarter of the global population, possibly even higher in the United States. Scientists have linked this condition to an increased risk of liver cancer, even without the presence of cirrhosis.
When NAFLD progresses to nonalcoholic steatohepatitis (NASH), the liver becomes inflamed and damaged, potentially leading to scarring, an elevated risk of cancer, or liver failure. For individuals concerned about NAFLD or NASH, seeking liver blood tests and imaging tests like MRI or ultrasound is crucial.
While some patients have found benefit from Vitamin E and the diabetes drug pioglitazone, results have been inconsistent, and no drugs have yet been approved by the FDA for the direct treatment of NAFLD. This is why poor eating habits and fad diets that boost fat intake are particularly worrisome.
The Allure and Concerns of the Keto Diet
The ketogenic diet, or keto diet, is attractive to many due to its allowance of foods like butter, red meat, and cheese. However, Rosen cautions against consuming 80% of caloric intake from fat, particularly from processed foods. He also identifies fructose and other sugars as major concerns, particularly in sodas, candy, sugary cereals, sweetened juices, and fast food.
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Instead, Rosen suggests a well-balanced diet rich in high-fiber foods, vegetables, fruits, fish, lean meats, nuts, eggs, seeds, and unrefined oils. He also points out the challenges of adhering to fad diets, especially those that eliminate entire food groups. Rapid weight loss, he notes, is rarely sustainable.
Beyond dietary changes, moderate exercise is recommended to avoid sarcopenia, or low muscle mass and strength, and alcohol consumption should be limited, as even moderate intake can cause issues.
Exploring Ketogenic Diets and Intermittent Fasting for NAFLD
Given the lack of approved therapeutic medications for NAFLD, lifestyle interventions such as dietary modification and physical exercise are vital. The Mediterranean diet is often recommended, but ketogenic diets and intermittent fasting (IF) have recently gained attention for weight management. Clinical practice guidelines typically recommend a 7-10% weight reduction for overweight or obese patients with NAFLD through a hypocaloric diet, combined with increased physical activity.
Ketogenic Diet: Mechanisms and Evidence
A ketogenic diet induces ketosis, where the body produces ketone bodies in response to carbohydrate restriction. Nutritional ketosis may facilitate weight loss by promoting satiety and reducing total energy intake. Ketone bodies may also inhibit obesity-induced inflammation and oxidative stress, potentially modulating NAFLD pathophysiology.
Early studies on very-low-carbohydrate ketogenic diets (VLCKD) showed promising results, with patients experiencing significant reductions in hepatic steatosis. Mardinoglu et al. observed a 43.8% reduction in hepatic fat content despite minimal weight loss in patients consuming less than 30 g/day of carbohydrates without total energy restriction. However, most data on VLCKD comes from studies combining it with calorie restriction, making it difficult to determine whether the reduction in hepatic fat content was caused by the VLCKD pattern or weight loss in general.
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A randomized controlled trial (RCT) by Kirk et al. observed a similar degree of weight loss in patients in VLCKD and low-calorie control diet. The intrahepatic triglyceride content decreased significantly from baseline but was not different in the two groups at the end of the study.
Another RCT conducted by Holmer et al. found that patients in the VLCKD arm experienced a significantly greater weight loss and intrahepatic fat content reduction, despite a smaller reduction in daily total energy intake.
Gepner et al. conducted the largest RCT with a long-term follow-up duration, with 139 patients on a VLCKD with 40 g/day of carbohydrates for 2 months and was gradually increased to 70 g/day for a total of 18 months with a Mediterranean-style diet (Med/LC). The reduction in liver fat content was significantly greater in the Med/LC group than in the low-fat diet group.
Overall, current evidence suggests that VLCKD can reduce intrahepatic fat content in patients with NAFLD, especially when combined with calorie restriction. However, the beneficial effect of VLCKD without a hypocaloric diet is yet to be definitively established.
Intermittent Fasting: Types and Outcomes
Intermittent fasting (IF) involves voluntary abstinence from food and/or drink for caloric restriction or no caloric intake over a specified period. Common types of IF include alternate-day fasting (ADF), periodic fasting (e.g., the 5:2 schedule), and time-restricted fasting (TRF) (e.g., 16:8).
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IF has gained traction as a weight loss strategy for people with NAFLD. People following IF tend to have lower energy intake compared to those on normal diets.
One observational study in Iran found that individuals who fasted during Ramadan experienced greater weight loss and improved hepatic steatosis grade on ultrasound compared to those who did not fast.
However, RCTs investigating the effect of IF on NAFLD patients have yielded mixed results. Cai et al. found that ADF with a 25% caloric intake on fasting days led to lower daily energy intake and weight loss, but no improvement in liver fibrosis. Johari et al. reported greater weight loss, reduction in hepatic steatosis grade, and improved liver fibrosis with modified ADF.
Cai et al. compared the outcomes of TRF using the 8:16 h method with SoC outcomes. The TRF group had a greater weight loss than the SoC group even though the daily caloric intake appeared to be a little higher in the TRF group.
Hodge et al. conducted an RCT using TRF as IF. Patients in IF arm had a significant reduction in both liver steatosis and liver fibrosis measured by liver stiffness.
Holmer et al. found that patients in the IF group had a greater reduction in daily caloric intake, lost more weight, and had a greater reduction in hepatic steatosis than those in the SoC group.
While IF shows promise, it is unclear whether the improved outcomes result from IF itself or from weight loss. IF is generally considered safe, but potential concerns include hypoglycemia in diabetic patients and hypotension in those taking antihypertensive medications. It may also aggravate starvation effects in patients with liver cirrhosis.
Potential Therapeutic Mechanisms of Ketogenic Diet in MAFLD
The ketogenic diet may offer therapeutic benefits in MAFLD through various mechanisms, including reduction in insulin resistance, weight loss, elimination of fructose and monosaccharides, limitation of total carbohydrate intake, induction of an anti-inflammatory ketosis state, and modulation of the gut microbiome and metabolome.
Reduction in Insulin Resistance
Insulin resistance is a key factor in MAFLD development, and the ketogenic diet can improve insulin sensitivity through several mechanisms. These include:
- Body weight reduction: Achieving a calorie deficit on a ketogenic diet is often easier, leading to improved insulin sensitivity, increased adiponectin levels, and reduced glycemia and insulin concentrations.
- Absence of monosaccharides: The ketogenic diet's restriction of carbohydrates prevents excessive fluctuations in glucose levels and insulin spikes.
- Elimination of fructose: The ketogenic diet eliminates fructose, which can disturb insulin signaling in the liver.
- Effect of ketone bodies: Ketone bodies, as an alternative energy source, can reduce glucose utilization and improve insulin sensitivity.
Weight Loss and Body Composition
Weight loss is a cornerstone of NAFLD management. Studies show that both ketogenic diets and intermittent fasting can lead to significant weight reduction, which in turn reduces liver fat and improves liver enzymes. The ketogenic diet's high-fat content can promote satiety, leading to reduced calorie intake. Intermittent fasting, by restricting eating windows or days, also creates a calorie deficit.
Reduction of Lipogenesis
Lipogenesis is the process of converting carbohydrates into fatty acids, which are then stored as fat in the liver and around the midsection. The ketogenic diet reduces lipogenesis by limiting carbohydrate intake. This can lead to less fat accumulation in the liver.
Increasing Fatty Acid Oxidation
In addition to reducing lipogenesis, the ketogenic diet can increase the rate at which fatty acids are broken down, or their oxidation rate. This can help reduce oxidative stress and inflammation in the liver.
Addressing the Rise of NAFLD: A Call to Action
The prevalence of NAFLD is increasing globally, making it a significant public health concern. Alarmingly, many patients with NAFLD are unaware of their condition. This underscores the need for increased awareness, education, and effective treatment strategies.
Caveats and Considerations
While the ketogenic diet and intermittent fasting show promise for managing NAFLD, it is important to acknowledge the limitations and potential risks:
- Nutrient deficiencies: Ketogenic diets can be restrictive and may lead to micronutrient deficiencies if not carefully planned.
- Adverse effects: Some individuals may experience adverse effects such as muscle cramps, dyspepsia, nausea, headache, or vertigo on a ketogenic diet.
- Suitability for cirrhosis: Ketogenic diets may not be suitable for patients with cirrhosis, as some studies suggest they could worsen liver injury.
- Long-term sustainability: The long-term sustainability and safety of ketogenic diets for NAFLD management remain uncertain.
Keto and Fatty Liver: What Does the Research Say?
Research suggests the keto diet can assist in weight loss, help prevent fatty liver disease, and reverse fatty liver damage. The goal of the keto diet is to achieve ketosis, or ketogenesis, which happens when your body uses fat instead of carbohydrates for energy. During ketogenesis, ketone bodies are formed, which assist with weight loss thanks to their ability to induce satiety.
Additional benefits of the keto diet include a reduction in triglycerides, abdominal fat, and risk for Metabolic Syndrome.
A 2018 study evaluated the effects of carbohydrate-restricted induced ketosis in 262 obese or overweight patients. After one year, participants had improved their blood sugar parameters, reduced their cardiovascular risk factors, and reduced the need for medications to manage high blood pressure and diabetes. Liver enzymes (ALT) used to measure liver health also improved in this trial. A 2020 meta-analysis of 154 articles reviewed the benefits of the keto diet on Fatty Liver Disease and concluded that macronutrient distribution also plays a role in NAFLD treatment.