Liver Disease (MAFLD) and Functional Nutrition

Introduction

Formerly known as non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD) is a new definition of liver disease. It’s a liver disease with known metabolic dysfunction and is the most common chronic liver disease worldwide (1), affecting about a quarter of the world’s population. Sedentary behavior, low physical activity, and high-calorie intake relative to energy expenditure have all contributed to the prevalence of the disease (2,3).

 

Why did the name change from NAFLD to MAFLD?

At the beginning of 2020, an international panel of experts proposed a name change from NAFLD to MAFLD to reflect the evolving understanding and pathophysiology of the disease. The change in terminology shifts the focus toward liver disease with the presence of metabolic dysfunction rather than liver disease in the absence of alcohol intake. (4,5)

 

Non-Alcoholic Fatty Liver Disease	Presence of hepatic steatosis in the absence of known causes of liver disease (eg, alcohol, autoimmune liver disease, viral hepatitis, etc). (4)
Metabolic-Associated Fatty Liver Disease	Presence of hepatic steatosis in the presence of one or more of overweight/obesity, type 2 diabetes mellitus, or evidence of metabolic dysregulation (4)

 

Figure 1: Timeline of fatty liver nomenclature (6)

Diagnosis

MAFLD is diagnosed  in people who have confirmed hepatic steatosis (detected either by imaging techniques, blood biomarkers, or liver histology) and any of the following:

• overweight/obesity
• type 2 diabetes
• evidence of metabolic dysregulation in lean individuals (increased waist circumference, arterial hypertension, hypertriglyceridemia, low high-density cholesterol (HDL-C), prediabetes, insulin resistance, and subclinical inflammation) (7, 8)

 

A 2021 study found that of participants with MAFLD, 28.51% were diagnosed by a single metabolic condition, 50.23% were diagnosed by two conditions, and 21.26% were diagnosed by all three metabolic conditions. The same study revealed that those diagnosed with diabetes alone had the highest proportion of advanced fibrosis and were at the most risk for end-stage liver disease. (7)

Figure 2: Flowchart for  diagnostic criteria for MAFLD (2)

Pathophysiology of MAFLD

The pathophysiology of MAFLD is driven by many contributing factors, including genetics, insulin resistance, glucotoxicity, lipotoxicity, oxidative stress, and mitochondrial dysfunction. (3,5,9) Studies suggest that fat accumulation in the liver caused by insulin resistance is the leading cause of MAFLD. (9, 10, 11)

Obese individuals are at a greater risk of MAFLD due to increased visceral adipose tissue, which can lead to insulin resistance and hyperinsulinemia, enhancing adipose tissue lipolysis. (9)

From a nutrition perspective, high-carbohydrate or high-fat diets can contribute to developing hepatic steatosis via glucotoxicity and lipotoxicity. (9) In particular, a diet high in sugar (e.g., fructose and sucrose) increases the risk of MAFLD, primarily because the increased blood glucose from large carb intake exerts harmful effects on cells.

Various nutrition and lifestyle interventions can help support liver health for at-risk or already diagnosed with MAFLD.

 

Diet and MAFLD

 

Role of Fructose

Fructose, a monosaccharide, occurs naturally in ripe fruits and honey and small amounts in some vegetables, such as carrots, onions, and sweet potatoes. It’s also found in ultra-processed manufactured foods via high fructose corn syrup (a mixture of fructose with sucrose or glucose) and table sugar (one glucose molecule plus one fructose molecule). Unlike glucose, the liver clears fructose from circulation via glucose-transporter type 5 (GLUT-5). According to Drodżdż et al., “a large amount of acetyl-CoA is produced following fructose uptake because fructose clearance omits glycolysis, which is the rate-limiting step in acetyl-CoA production. Some acetyl-CoA is used for ATP production, but the excess amount is used for de novo lipogenesis, one of the mechanisms proposed for how consuming fructose leads to NAFLD.” (12)

Human and animal studies also show that high fructose intake, i.e., 25% of energy requirement, can increase visceral adiposity, postprandial hypertriglyceridemia, and insulin resistance by acting on de novo lipogenesis. All of which increase the risk of MAFLD.

 

Role of Microbiota

MAFLD is a multisystem disease that includes the microbiome. By-products created in the gut microbiota can cross the intestinal mucosa to the portal circulation and directly to the liver (gut-liver axis). A 2021 Clinical Liver Disease Journal article states that “some microbial metabolites are suspected to stimulate inflammation or cause hepatocellular injury. Most notable in this regard is LPS, which has been reportedly detected in the serum of obese patients and correlated with the degree of liver injury, suggesting a link between microbiota-derived LPS and progression to fatty liver disease.” (13)

Studies are examining the use of probiotics, prebiotics, symbiotic supplements, antidiabetic drugs, and fecal microbiota transplantation as possible MAFLD treatments.

 

Role of Dietary Fat

A diet high in saturated fat is connected to an increase in liver fat due to de novo liver lipogenesis and an increase in adipose tissue lipolysis. A high saturated fat diet is also associated with impaired glutathione metabolism and oxidative stress, which can contribute to the development of MAFLD. However, the jury is still out on whether or not the source of saturated fat matters (dairy vs. meat). On the contrary, consumption of unsaturated fat (e.g., EVOO) is associated with a decrease in lipolysis and less fat accumulation in the liver. A 2012 randomized controlled study showed that in people with type 2 diabetes, an isocaloric diet enriched in MUFAs compared to a diet higher in carbohydrates and fiber was associated with a clinically relevant reduction of hepatic fat. (14,15)

Studies have also evaluated the impact of polyunsaturated fats, specifically alpha-linolenic acid (omega-3) and linoleic acid (omega-6). Linoleic, in particular, is metabolized to arachidonic acid (AA) which can produce proinflammatory and prothrombotic metabolites. On the other hand, EPA and DHA can improve liver composition by reducing insulin resistance and increasing anti-inflammatory modulators. (15)

 

Role of the Mediterranean Diet

Foods considered beneficial for the prevention and progression of MAFLD are integral to the Mediterranean Diet. This is unsurprising given the unequivocal scientific evidence supporting the Mediterranean Diet for various medical conditions. Whole grain cereals, fruits and vegetables, omega-3-rich fatty fish, and EVOO are critical players in the Mediterranean diet. On the other hand, foods typically associated with a Western diet adversely impact MAFLD, including red meat, processed meats, cakes, pastries, refined oils, and other ultra-processed foods. (15,16,17)

Studies have looked at the effect of EVOO on liver health specifically because it’s known to enhance insulin sensitivity, reduce triglycerides, and downregulate lipogenic genes. A recent double-blind, randomized controlled trial with NAFLD patients (n = 66) found that consumption of 20 grams EVOO per day (approximately 1.5 tablespoons) attenuated fatty liver grade and reduced body fat percentage. (16,18,19)

Figure 3: The Western Diet is associated with a higher risk of NAFLD/MAFLD diagnosis. (15)

 

Case Study – A Functional Nutrition Approach

A 51 year old female with high cholesterol, hypertension, type 2 diabetes, and a BMI of 32 was diagnosed with fatty liver in February 2022. She took simvastatin for cholesterol, valsartan and metoprolol for blood pressure regulation, and supplemented with magnesium, vitamin D, and melatonin gummies.

She often struggled with sleep and rarely exercised due to her demanding corporate job. Ridges in her fingernails and multiple skin tags were evident.

Based on food records in MyFitnessPal, her diet aligned closely with a standard American diet, including fast food multiple times per week, diet soda, and frozen, pre-made convenience meals.

Her initial goals included a 30 lb weight loss and better glucose control to avoid more medication. Her long-term goals include getting off at least one blood pressure medication, improving liver health, and losing an additional 30 lbs.

 

The initial diet and lifestyle plan:

1. She wore a Freestyle Libre 14-day continuous glucose monitor for three months to observe her glucose response to various foods. She activated a new CGM every 14-days.
2. She shifted her diet toward a modified Mediterranean-style diet with a modest goal of 75-80 grams of high-quality protein per day, 3-4 cups of non-starchy vegetables per day, and minimal ultra-processed carbohydrates. Her diet soda consumption was reduced to 3 per week on Wednesday, Friday, and Saturday. She signed up for a local organic meal prep company to help customize her weekday lunches.
3. During the week, she consumed most of her calories at breakfast and lunch and finished her last meal by 5 pm. She fasted from 5 pm-8 am. For sustainability, her weekend fasting schedule remained flexible to accommodate family events and outings.
4. For exercise, she aimed for a minimum of 6k steps per day with a 15-minute walk after lunch and dinner. The goal was to work up to 8k steps per day, then 10-12k steps per day. Resistance training was also discussed and planned to start at a later date.
5. She added breathwork to help manage her stress using the Wim Hof method.

Supplement plan:

• She omitted melatonin gummies from her nightly routine and added 200mg of magnesium bisglycinate and chamomile tea.
• She added Pure Encapsulations LVR Formula (3 per day, with meals), Kaneka Ubiquinol (100mg per day), VSL#3 probiotic (4 per day), and Nordic Naturals Ultimate Omega (2 per day).

After three months, she had lost 12 pounds, noticed less afternoon fatigue and sugar cravings, and could get her daily step count of 6k steps per day on most days. The next phase of the nutrition intervention includes:

• Updated lab work, specifically A1c, fasting glucose, fasting insulin, comprehensive thyroid panel, liver enzymes, and a lipid panel.
• Continue with CGM glucose monitoring for real-time feedback.
• Complete elimination of diet soda.
• Inclusion of 8-12 ounces of wild-caught seafood each week.
• A goal of 100 grams of high-quality protein and 25-35 grams of fiber.
• A beginner’s at-home body weight program three times per week.

While this is a slow-and-steady approach, her readiness to change and commitment to improving liver health and overall metabolic function continued to improve.

 

Conclusion

Many nutrition interventions can help support overall metabolic health. When considering the multisystem impact of MAFLD, a holistic, client-centered approach is essential. While many different nutrition interventions exist, a low-glycemic, Mediterranean-style diet rich in omega-3s and EVOO is a good starting point. And, of course, consider essential micronutrients and supplements for liver and mitochondrial support.

To learn more, SIGN UP TODAY to take your nutrition knowledge to the next level as an Integrative and Functional Nutrition Certified Practitioner (IFNCP)!

 

Tori Eaton, RDN, LDN, IFNCP

 

References

1. Chen Yl, Li H, Li S, et al. Prevalence of and risk factors for metabolic associated fatty liver disease in an urban population in China: a cross-sectional comparative study. BMC Gastroenterol. 2021;21 (212). https://doi.org/10.1186/s12876-021-01782-w
2. Eslam M, Newsome P, Sarin S, et al. A new definition for metabolic dysfunction associated fatty liver disease: an international expert consensus statement. J. Hepatol. 2020;73(1):202-209. https://doi.org/10.1016/j.jhep.2020.03.039
3. Nucera S, Ruga S, Cardamone A, et al. MAFLD progression contributes to altered thalamus metabolism and brain structure. Sci Rep. 2022;12(1207). https://doi.org/10.1038/s41598-022-05228-5
4. Kenneth Z, Fan J, Shi J, et al. From NAFLD to MAFLD: a “redefining” moment for fatty liver disease. Chin. Med. J. 2020;133(19):2271-2273. doi: 10.1097/CM9.0000000000000981
5. Kuchay MS, Choudhary NS, Mishra SK. Pathophysiological mechanisms underlying MAFLD. Diabetes Metab Syndr. 2020;14(6):1875-1887. DOI:10.1016/j.dsx.2020.09.026
6. Targher G, Byrne C. From nonalcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease: is it time for a change of terminology? Hepatoma Res. 2020;6(24). http://dx.doi.org/10.20517/2394-5079.2020.71
7. Huang J, Ou W, Wang M, et al. MAFLD criteria guide to subtyping of patients with fatty liver disease. Risk Management Health Policy. 2021;14:491-501. doi: 10.2147/RMHP.S285880
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19. Rezaei S, Akhlaghi M, Sasani M, Boldaji R. Olive oil lessened fatty liver severity independent of cardio metabolic correction in patients with non-alcoholic fatty liver disease: a randomized clinical trial. Nutrition. 2019;57:154-161. https://doi.org/10.1016/j.nut.2018.02.021