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Non-alcoholic fatty liver disease (NAFLD) is a condition where fat deposits build up in the liver in patients with little or no alcohol intake and with no other known cause. NAFLD is closely associated with obesity. While poor dietary choices are often to blame, genetic factors may also contribute.
As the condition is generally asymptomatic or has very mild symptoms initially, many people do not know they have it unless a blood test detects abnormal levels of liver enzymes. NAFLD may progress to nonalcoholic steatohepatitis (NASH), which can then progress to cirrhosis, fibrosis, liver failure, and even liver cancer.
Natural interventions such as vitamin E and milk thistle may help protect the liver and even halt or reverse disease progression.
What are the Risk Factors for Non-Alcoholic Fatty Liver Disease?
- • Obesity
- • Insulin resistance/diabetes
- • Metabolic syndrome
- • Increased fructose consumption
What are Conventional Treatments for Non-Alcoholic Fatty Liver Disease?
Note: NAFLD is generally treated with dietary and lifestyle changes, not pharmaceutical interventions. Health practitioners may encourage patients with NAFLD to:
- • Engage in slow and steady weight loss
- • Engage in regular physical activity
- • Refrain from drinking alcohol
What are Emerging Therapies for Non-Alcoholic Fatty Liver Disease?
- Metformin, a drug generally used to treat diabetes, has been shown in several studies to dramatically improve liver blood flow, reduce markers of liver cell death, and reduce the prevalence and severity of fatty liver.
What Natural Interventions May Be Beneficial for Non-Alcoholic Fatty Liver Disease?
- Vitamin E. People with fatty liver disease and NASH have depressed levels of vitamin E. Vitamin E has been shown to reduce levels of liver cell-injury markers, liver fat levels, and inflammation, and improve the appearance of liver tissue on biopsies.
- Omega-3 fatty acids. People with insufficient dietary intake of omega-3 fatty acids are more prone to NAFLD. A clinical trial revealed that supplementation decreased serum markers of liver cell damage, triglyceride levels, and fasting glucose. Supplemented patients also showed improvement of their livers’ appearance and blood flow.
- S-adenosylmethionine (SAMe). Oxidative damage depletes liver glutathione levels. Supplementation with SAMe increased glutathione levels in patients with NAFLD and prevented relatively mild NAFLD from progressing to NASH.
- N-acetylcysteine (NAC). NAC boosts glutathione levels. The combination of NAC with metformin improved liver appearance and reduced fibrosis in patients with NAFLD.
- Milk thistle. Milk thistle has long been used for protecting the liver. Silymarin, an extract of milk thistle, combined with vitamin E and phospholipids (like phosphatidylcholine), improved insulin resistance, reduced liver fat accumulation, and decreased markers of liver scarring.
- Phosphatidylcholine. Higher amounts of phosphatidylcholine in cell membranes help limit the progression of NAFLD to NASH. A rich source of phosphatidylcholine derived from soybeans, polyenylphosphatidylcholine (PPC) supplements in animals attenuated nonalcoholic liver fibrosis and even accelerated its regression.
- Resveratrol. Resveratrol can protect liver tissue from alcoholic fatty liver disease, and its mechanisms may also apply to NAFLD. In animal studies, resveratrol reduced liver fat accumulation and insulin resistance.
Introduction
Roughly one-third of the American population suffers from non-alcoholic fatty liver disease or NAFLD. Many of its victims do not know they have it. NAFLD can go undetected for years and may eventually progress to inflammation and scarring of the liver (cirrhosis) and, in some cases, full-blown liver failure.
A formerly rare condition, its rapid emergence has been linked to skyrocketing rates of metabolic syndrome and “diabesity,” the term many experts use for co-occurring diabetes and obesity.
While poor dietary choices are often to blame, cutting-edge research suggests that hidden genetic factors may also play a role, as some people do not metabolize polyunsaturated fats properly, resulting in fatty deposits in the liver.
As mainstream medicine continues to struggle in the search for drugs to manage this widespread condition, emerging scientific evidence has shed light on effective natural interventions that may halt or even reverse its progress.
Fat Overload, Liver Damage, and the Inflammatory Storm
NAFLD is defined as deposition of fat in the liver cells of patients with minimal or no alcohol intake and with no other known cause. The term “NAFLD” refers to a group of related and progressive conditions closely associated with overweight and obesity.
NAFLD usually does not cause symptoms, but some people with NAFLD report feeling tired or experiencing mild discomfort in their upper-right abdominal quadrant. Early NAFLD can ultimately progress to a more serious condition, non-alcoholic steatohepatitis or NASH.9 About a third of people with NAFLD will develop NASH, and about 20% of people with NASH will go on to liver fibrosis and cirrhosis, with its accompanying risk of liver failure and even liver cancer. Overall, people with NAFLD stand a 12% increased risk of liver-related death over 10 years.
NAFLD has multiple interrelated causes. Primary mechanisms include obesity leading to steadily increasing insulin resistance coupled with an overabundance of circulating fatty acids. These factors fuel one another in a destructive cycle. Together with advanced glycation end-products (AGEs), these events lead to increased oxidant stress and ultimately inflammation, cell death, and fibrous destruction of liver tissue.
An overload of fatty acids and abnormal lipid profiles factor so heavily in the onset of NAFLD that they’re now referred to as “lipotoxicity” because of the ways they directly poison liver tissue. And as fat builds inside liver cells, they begin churning out a storm of fat-related cytokines known as adipokines, which fan the inflammatory flames of the metabolic syndrome and NAFLD.
Of course, what we eat is as important as the calories it contains. One of the major bad actors in today’s world is fructose, found in high quantities in high-fructose corn syrup. Fructose promotes formation of new fat molecules in the liver, blocks breakdown of existing fats, stimulates free radical production, and promotes insulin resistance. An increasing number of studies are linking increased fructose consumption with NAFLD, and even with its deadlier consequence, non-alcoholic steatohepatitis (NASH). Patients with NAFLD consume 2‒3 times as much fructose as do control patients, even corrected for body weight.
Diagnosis of NAFLD
In order to make a diagnosis of NAFLD, a physician considers both clinical data about the patient, and, when appropriate, data from a liver biopsy (for definitive diagnosis). The first indication that NAFLD might be present is rarely a symptom, but rather a finding of elevated levels of liver enzymes in the blood, indicating early liver cell damage. Other treatable causes of liver disease must be ruled out by appropriate testing (eg, hepatitis B or C), and other liver functional parameters (eg, blood clotting factors) should also be measured. Some physicians will do an imaging study such as a liver ultrasound, but normal appearance of the liver does not rule out NAFLD. Alcoholic fatty liver, which can closely resemble NAFLD, must be ruled out. This can be done by reliably establishing the absence of substantial alcohol intake (less than 20‒40 grams of alcohol per day, equivalent to 2‒3 drinks). If and when there is concern that the more dangerous condition, NASH, is present, then liver biopsy must be performed to establish a definitive diagnosis.
Treatment of NAFLD
Despite a growing understanding of the pathology of NAFLD, scientists have been persistently baffled in their attempts to prevent and treat it with drug therapies. Lifestyle interventions such as steady, gentle weight loss and regular exercise have been the only interventions that offered any hope at all. Insulin-sensitizing drugs, while theoretically of value, have proved disappointing in clinical trials.
The only successful pharmaceutical intervention for dealing with NAFLD has been metformin, which is examined further in this section.
Cholesterol-lowering drugs like statins have no proven benefit to date.4 Further studies are needed to determine if bariatric surgery to induce weight loss benefits patients with NAFLD.
Metformin
Because of the central role of insulin resistance in the development of NAFLD and NASH, it makes sense to evaluate insulin-sensitizing drugs for their prevention. No oral antidiabetic drug has as broad a spectrum of action, and as hefty a safety record, as the drug metformin, which is finding a host of new applications outside of diabetes itself.
Studies of metformin for NAFLD and NASH have multiplied in the past few years. Metformin, 500 mg three times daily for six months, produced dramatic improvements in liver blood flow and velocity as detected by Doppler ultrasound exams. A similar dose of metformin (20 mg/kg body weight for one year, or approximately 1,450 mg/day for a 160-lb individual) produced reductions in blood markers of liver cell death. On the other hand, improved insulin sensitivity has repeatedly been shown in patients with NASH and NAFLD who take metformin, and many studies have now shown sustainable improvements in liver chemistry measurements. And a recent study showed significant reduction in the prevalence and severity of fatty liver after six months’ treatment with 850 mg metformin twice daily in obese adolescents.
Metformin is an ideal drug for combination studies because of its safety and compatibility with other therapies. The combination of metformin with the potent antioxidant N-acetyl cysteine (NAC) for 12 months improved liver chemistry results, measurements of insulin resistance, and liver appearance on biopsy.
Recent evidence shows that metformin blocks the induction of cellular stress proteins in cultured liver cells, protecting them from death induced by fatty acids. This novel mechanism adds to metformin’s already impressive array of multitargeted effects on metabolism and fatty liver disease.
What You Have Learned So Far
- • One in three Americans now suffers from the stealth condition known as non-alcoholic fatty liver disease or NAFLD.
- • NAFLD may go undetected for years, and may progress to liver inflammation and scarring (cirrhosis) or full-blown liver failure.
- • While chiefly driven by poor dietary choices linked to metabolic syndrome and “diabesity,” genetic factors can also play a role in NAFLD’s progress.
- • Medical science has proved relatively helpless at preventing or treating NAFLD and NASH, leaving millions of Americans vulnerable to their effects.