Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat accumulates in the liver without excessive alcohol consumption. In the United States, NAFLD is particularly prevalent among older adults. You may not experience any symptoms at first, but as NAFLD progresses, it can lead to liver inflammation, scarring, and even liver failure. If left untreated, NAFLD can progress to more serious liver diseases such as nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer.
Study published in BMC Gastroenterology1 It was found that 40.3% of people aged 60 to 74 years and 39.2% of people aged 74 years or older had NAFLD. For those aged 60 to 74, NAFLD is associated with a 60% higher risk of death from all causes within 5 years and a 22% higher risk within 10 years.
Cardiovascular mortality also more than doubled in this age group over five years. However, this increased risk is not observed in people older than 74 years, indicating that the impact of the disease may diminish with age.
In 2023, the term NAFLD was replaced by MASLD (metabolic dysfunction-related fatty liver disease) to more accurately emphasize the underlying cause: metabolic dysfunction.2 Ongoing research continues to expand our understanding of this condition, now revealing two distinct forms: one that is specific to the liver and one that affects the entire body.
From NAFLD to MASLD — What’s Changed?
While NAFLD is defined by the absence of alcohol-related liver damage, MASLD highlights the role of common metabolic factors, such as obesity, type 2 diabetes, and metabolic syndrome, in driving liver fat accumulation and inflammation. MASLD also introduces a more accurate diagnostic framework. Unlike NAFLD, which primarily excludes other causes of liver disease, MASLD requires evidence of metabolic disorders along with liver fat accumulation.3
MASLD is caused by a combination of genetic, metabolic, and lifestyle factors. While genetic predisposition has a huge impact on how the body processes fat and sugar, insulin resistance, a hallmark of metabolic syndrome, worsens this process by impairing the liver’s ability to manage glucose and fat and promoting fat storage.
Overloading the liver with fat causes inflammation and damage to liver cells. Causes also include poor eating habits, lack of physical activity, and certain medications that increase liver fat accumulation. Diagnosing MASLD presents unique challenges, especially in the early stages when symptoms are subtle or absent.
Liver biopsy remains the gold standard for diagnosis, but its invasive nature limits its widespread use. Noninvasive tests, such as imaging and blood tests, can help identify liver fat but are often inadequate in differentiating between simple steatosis and more severe forms, such as NASH. Diagnosis is further complicated by the lack of accurate biomarkers and the overlap of symptoms with other liver diseases.
New insights into MASLD reveal distinct disease types
A study recently published in Nature Medicine4 We uncovered the genetic basis of MASLD and differentiated its various forms. By analyzing genetic data from a large cohort of 36,394 people and validating the results in four additional groups of 3,903 participants, researchers identified genetic signatures that provide insight into why MASLD manifests differently in individuals.
One of the most important discoveries was the identification of 27 new loci associated with MASLD. These specific locations in the genome influence how liver cells process and store fat, influencing the development and progression of the disease. Researchers identified two types of MASLD using a polygenic risk score that aggregates the effects of multiple genetic variants.
The first type is limited to the liver and causes more aggressive liver disease. The second is systemic, meaning it affects multiple organs and greatly increases the risk of cardiometabolic problems, including heart failure. This distinction is important because it means that treatment and management strategies should be tailored to the specific type of MASLD a patient suffers from, rather than treating it as a single disease.
Another key insight is the strong link between body fat distribution and liver health. Visceral fat stored around organs was found to be the strongest predictor of liver triglyceride content and inflammation. Other metrics, such as body mass index (BMI) and waist-to-hip ratio, which are indicators of overall fat distribution, were also associated with liver health, but were less predictive of liver damage than visceral fat.5
At the genetic level, the researchers found that certain genetic mutations disrupt the way liver cells process and secrete lipids, leading to increased liver fat. In particular, some genes that impair the secretion of very low-density lipoprotein (VLDL) cause triglycerides to accumulate in the liver and increase the risk of liver-related diseases.
Paradoxically, the retention of these triglycerides appears to lower the levels of circulating lipoproteins in the blood, thereby reducing the risk of cardiovascular disease (CVD), such as high blood pressure and heart failure. This suggests that the relationship between MASLD and heart disease is more complex than previously thought.6
research7 Additionally, we found that discordant polygenic risk scores focusing on liver-specific genetic variants such as PNPLA3 and TM6SF2 explained a greater portion of the genetic diversity in MASLD compared to concordant scores. This reflects genes that affect liver and systemic health. This highlights the role of liver-specific genetic factors in the pathogenesis of MASLD.
Both risk scores were associated with an increased risk of MASLD and serious complications, such as hepatocellular carcinoma, a type of liver cancer, but the association was stronger for the discrepancy score. Interestingly, discordant polygenic risk scores were associated with reduced risk of CVD, whereas concordant scores showed a strong association with increased risk of CVD and heart failure.
Understanding these pathways is essential to develop targeted treatments and ultimately improve outcomes and reduce the burden of this complex disease. For example, treatments that enhance VLDL secretion alleviate liver-related MASLD without affecting cardiovascular risk. On the other hand, interventions aimed at modulating systemic lipid metabolism address the broader cardiometabolic risks associated with other forms of MASLD.8
Distinguish between simple steatosis and NASH
Study published in Current Hepatology Reports9 It provides important context to the progress of MASLD. Researchers looked at the two main subtypes classified as NAFLD at the time: simple steatosis and nonalcoholic steatohepatitis (NASH), now known as metabolic dysfunction-related steatohepatitis (MASH).
Although this study predated the reclassification, it laid an important foundation by determining the differences between these two conditions in terms of pathophysiology, management, and long-term outcomes.
Researchers found that simple steatosis, defined as fat accumulation in the liver without inflammation or scarring, was largely benign and had no significant impact on survival. Most individuals with steatosis live normal lifespans because excess fat alone does not cause liver damage.
In contrast, NASH is a more serious condition that involves liver inflammation and scarring (fibrosis), increasing the risk of cirrhosis, liver failure, and liver cancer. Although NASH has become one of the leading causes of liver transplantation in the United States, simple steatosis rarely requires such drastic interventions. The study also found a strong link between NASH and metabolic syndrome, noting that individuals with obesity, type 2 diabetes or high triglycerides were at higher risk.
Distinguishing between simple steatosis and NASH is essential for effective management and improved long-term outcomes. “As the prevalence of NAFLD continues to increase, further research is needed to develop non-invasive diagnostic approaches and management algorithms,” the researchers concluded.10
Useful Strategies to Address the Root Cause of MASLD
Adopting a healthy lifestyle and eating habits to address the root causes of metabolic disorders not only supports optimal liver function and reduces the risk of MASLD, but also promotes long-term health and vitality. Here are some key strategies I recommend:
1. Eliminate harmful fats from your diet — Eliminate all vegetable oils from your diet, including canola oil, soybean oil, corn oil, and sunflower oil. This is because it interferes with mitochondrial function and promotes inflammation. Instead, use healthier fats such as grass-fed tallow, ghee, or butter. Also minimize “healthy” oils like olive oil. This is because excessive consumption of monounsaturated fats also impairs metabolic function.
2. Optimize your carbohydrate intake —Aim to consume at least 200-250 grams of carbohydrates each day, and if you are very active, adjust this amount based on your microbiome. Start with fruit juices that contain pulp and whole fruit. Fiber and natural sugars help your gut heal.
Switch to pulp-free juices only after your digestion has improved, and drink slowly to avoid metabolic stress. This is similar to glucose water for severely impaired gut health. As digestion strengthens, gradually introduce complex carbohydrates and starches to maintain balanced energy and support metabolic function.
3. Balance your protein sources — Make sure one-third of your daily protein intake consists of collagen. This aims for about 0.8 grams of protein per pound of lean body mass, which should account for about 15% of your total calorie intake. To reduce exposure to harmful linoleic acid (LA) and support optimal metabolic health, choose grass-fed ruminant meat over traditional chicken or pork.
4. Prioritize choline-rich foods — Choline is important in moving fat out of the liver and lowering the risk of fatty liver disease. To increase your intake of this nutrient, increase your intake of foods such as organic pasture-raised egg yolks, grass-fed beef liver, and arugula.
5. Focus on eating nutritious whole foods — Eliminate ultra-processed foods, including fast food, from your diet as they contain refined carbohydrates, vegetable oils, preservatives and other harmful ingredients that overwhelm the liver and cause it to malfunction. Instead, replace them with minimally processed, nutrient-dense, whole foods to stabilize blood sugar, reduce inflammation, and reduce strain on the liver.
6. Maintain a healthy weight — Regular exercise is essential for boosting your metabolism and maintaining a healthy weight. If you are overweight, losing 7 to 10 percent of your body weight can help improve NAFLD, including lowering liver fat content, liver inflammation, and fibrosis.11
7. Consider taking supplements to support your liver — Supporting the liver with targeted nutrients not only prevents damage, but also improves its ability to detoxify and regenerate. Vitamin B12 and folic acid work together to regulate homocysteine levels, reducing inflammation and preventing fibrosis.12
To further protect and detoxify the liver, n-acetylcysteine (NAC) promotes the production of glutathione, a powerful antioxidant that neutralizes toxins and reduces oxidative stress.13
In addition to antioxidants, supplements like milk thistle and CoQ10 offer unique benefits. The active compounds in milk thistle, silymarin and silybin act as protection against harmful toxins while also promoting the repair and regeneration of damaged liver cells.14 Meanwhile, CoQ10 plays a role in supporting mitochondrial health, ensuring the liver has the energy it needs to function efficiently, while reducing inflammation and oxidative damage.15
Magnesium is another important nutrient for liver health, especially as it plays an important role in cellular energy production. To determine the ideal dosage, first take magnesium citrate and gradually increase the dosage until loose stools appear, then reduce it slightly. This is the ideal dosage. After that, switch to magnesium threonate, which doesn’t cause loose stools like magnesium citrate.
