Non-alcoholic fatty liver disease (NAFLD) occurs when excess fat builds up in your liver without consuming too much alcohol. In the United States, NAFLD is particularly prevalent among older adults. There may be no 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 serious liver conditions such as nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer.
A study published in BMC Gastroenterology1 It found that 40.3% of those aged 60 to 74 and 39.2% of those over 74 had NAFLD. Among those aged 60 to 74 years, NAFLD was associated with a 60% higher risk of all-cause mortality at five years and a 22% higher risk at 10 years.
Cardiovascular death more than doubles in this age group over a five-year period. However, these increased risks were not seen in those over 74 years of age, suggesting that the incidence may decrease with age.
In the year In 2023, the term NAFLD was replaced by MASLD (metabolic disorder-associated steatotic liver disease) to more accurately emphasize the cause – metabolic disorder.2 Ongoing research continues to expand our understanding of this condition, now showing two different forms – one based on the liver and the other with systemic effects.
From NAFLD to MASLD – What Changed?
While NAFLD is characterized by the absence of alcohol-related liver damage, MASLD emphasizes the role of liver in driving fat accumulation and inflammation in common metabolic conditions such as obesity, type 2 diabetes and metabolic syndrome. MASLD has also introduced a more accurate diagnostic framework. Unlike NAFLD, which primarily involves other causes of liver disease, MASLD requires evidence of metabolic abnormalities alongside liver fat accumulation.3
MASLD develops from a combination of genetic, metabolic, and lifestyle factors. Genetic predisposition greatly affects how your body processes fat and sugars, but insulin resistance, a hallmark of metabolic syndrome, worsens the process by impairing the liver’s ability to handle glucose and lipids and promoting fat storage.
When the liver is overloaded with fat, inflammation is triggered, which leads to liver cell damage. Contributing factors include poor nutrition, lack of exercise, and certain medications that increase liver fat storage. MASLD diagnosis presents unique challenges, especially in the early stages when symptoms are subtle or absent.
While liver biopsies remain the gold standard for diagnosis, their invasive nature limits their widespread use. Non-invasive tests such as imaging and blood tests can help detect fatty liver, but often fail to differentiate between mild steatosis and more severe forms such as NASH. The lack of accurate biomarkers and the overlap of symptoms with other liver diseases complicates the diagnosis.
New insights into MASLD reveal distinct disease subtypes
A recent study published in Natural Medicine4 He uncovered the genetic basis of MASLD and identified its different forms. By analyzing genetic data from a cohort of 36,394 people and confirming the findings with four additional cohorts of 3,903 participants, they identified genetic markers that provide insights into why MSLD manifests in individuals.
One of the most important findings was the identification of 27 new genetic loci associated with MASLD. These specific locations on the genome affect how liver cells process and store fat, influencing the development and progression of the disease. The researchers identified two different types of MASLD using polygenic risk scores, which combine the effects of multiple genetic variants.
The first type is confined to the liver and leads to more severe liver disease. The second is systemic, which means it affects many organs and significantly increases cardiometabolic problems, including heart failure. This distinction is important because it indicates that treatment and management strategies should be tailored to the specific type of MASLD that a patient has rather than treating the disease as a single disease.
Another key insight is the strong link between body fat distribution and liver health. Visceral fat, liver triglyceride content, and inflammation were found to be the strongest predictors. Indicators of overall fat distribution, such as body mass index (BMI) and waist-to-hip ratio, are associated with liver health, although they are less influential than visceral fat in predicting liver damage.5
At the genetic level, the researchers found that certain gene variants disrupt how liver cells handle and secrete fats, leading to increased liver fat. In particular, certain genes that impair the secretion of very low-density lipoproteins (VLDL) cause triglycerides to accumulate in the liver, increasing liver-related conditions.
Paradoxically, this triglyceride reduction lowers circulating lipoproteins, which appear to reduce the risk of cardiovascular disease (CVD), such as hypertension or heart failure. This suggests that the relationship between MASLD and heart disease is more complex than previously thought.6
The study7 Furthermore, the polygenic risk score, which focuses on liver-specific genetic variants, such as PNPLA3 and TM6SF2, revealed that a large portion of the genetic variability in MASLD reflects genes affecting liver and systemic health. This suggests a role for liver-specific genetic factors in the development of MASLD.
Both risk scores were associated with an increased risk of MASLD and serious complications such as liver cancer, such as hepatocellular carcinoma, although the association was robust to bias. Interestingly, the discrepant polygenic risk score was associated with a reduced risk of CVD, whereas the composite score showed a stronger association with a higher risk of CVD and heart failure.
Understanding these pathways is important for developing targeted therapies, ultimately improving outcomes and reducing the burden of this complex condition. For example, therapies that improve VLDL secretion may reduce liver-specific MASLD without affecting cardiovascular risk. On the other hand, interventions aimed at regulating systemic lipid metabolism address the broader cardiometabolic risks associated with other forms of MASLD.8
Differentiate between simple steatosis and NASH
A study published in Current Hepatology Reports9 It provides an important context for the development of MASLD. The researchers examined the two main types of NAFLD classified at the time: mild steatosis and nonalcoholic steatohepatitis (NASH), now known as metabolic dysfunction-associated steatohepatitis (MASH).
Although this study was before the reclassification, it laid an important foundation by determining the difference between the pathology, management and long-term results between these two conditions.
The researchers found that mild steatosis, which is defined as inflammation and scarring in the liver due to fat accumulation, was generally healthy and did not significantly affect survival. Because excess fat alone does not cause liver damage, most people with steatosis expect a normal life expectancy.
NASH, on the other hand, is a more serious disease that causes inflammation and scarring of the liver (fibrosis), increasing the risk of cirrhosis, liver failure, and liver cancer. NASH has become one of the leading causes of liver transplants in the US, but mild steatosis rarely requires such serious interventions. The study also found a strong link between NASH and metabolic syndrome, with individuals with obesity, type 2 diabetes, or high triglycerides at increased risk.
Distinguishing between simple steatosis and NASH is important for effective management and improving long-term outcomes. “As the prevalence of NAFLD increases, more research is needed to develop uncomplicated diagnostic methods and management algorithms,” the researchers said.10
Strategies to help solve MASLD from the root
Adopting healthy lifestyle and dietary habits to address the underlying causes of metabolic disorders not only supports good 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, soybean, corn, and sunflower oils, as they disrupt mitochondrial function and promote inflammation. Instead, use healthy fats like grass-fed tallow, ghee or butter. Limit even “healthy” oils like olive oil, as their monounsaturated fat content can impair metabolic function if consumed in excess.
2. Improve your carbohydrate intake:Aim for at least 200 to 250 grams of targeted carbs daily, adjusting upwards if you’re very active based on your microbiome. Start with whole grains and fruit juices, as these support gut healing with fiber and natural sugars.
Transition to pulp-free juice only after your digestion improves, drinking slowly to avoid metabolic stress, like dextrose water for serious gut health. As digestion improves, gradually introduce complex carbohydrates and starches to maintain balanced energy and support metabolic function.
3. Balancing Protein Sources- Make sure one-third of your daily protein intake consists of collagen, which aims for approximately 0.8 grams of protein per pound of lean body weight, which accounts for 15 percent of total calories. Choose grass-fed beef over conventional chicken or pork to reduce your exposure Linoleic Acid (LA) And they support good metabolic health.
4. Prioritize choline-rich foods: Choline is important for removing fat from the liver and reducing the risk of liver disease. Add foods like organic, pasture-raised egg yolks, grass-fed beef liver, and arugula to increase your intake of this nutrient.
5. Focus on eating whole foods that are rich in nutrients – Eliminate refined carbohydrates, vegetable oils, preservatives, and other harmful ingredients from your diet, including fast foods. Instead, replace them with whole, minimally processed, nutritious foods to stabilize your blood sugar, reduce inflammation, and reduce the burden on your liver.
6. Maintaining a healthy weight Regular exercise is important to increase metabolism and support a healthy weight. If you are overweight, losing 7% to 10% of your body weight can help improve NAFLD, which includes fatty liver, liver inflammation, and fibrosis.11
7. Consider taking supplements that support the liver: Supporting your liver with targeted nutrients not only protects it from damage, but also strengthens its ability to detoxify and regenerate. Vitamin B12 and folate work together to reduce inflammation and prevent fibrosis by regulating homocysteine levels.12
To further protect and detoxify the liver, n-acetylcysteine (NAC) increases production of glutathione, a powerful antioxidant that detoxifies and reduces oxidative stress.13
In addition to antioxidants, supplements such as milk thistle and CoQ10 offer unique benefits. The active compounds in milk thistle, silymarin and silybin, act as a shield against harmful toxins while promoting the repair and regeneration of damaged liver cells.14 Meanwhile, CoQ10’s role in supporting mitochondrial health ensures your liver has the energy it needs to function efficiently by reducing inflammation and oxidative damage.15
Magnesium is another important nutrient for liver health, particularly in its role in cellular energy production. To determine your correct dose, first take magnesium citrate, and gradually increase your dose until you feel stools, and then decrease slightly – this is your ideal dose. Then switching to magnesium threonate, which doesn’t produce stools like magnesium citrate.
