Non-Alcoholic Fatty Liver Disease (NAFLD)
Non-Alcoholic Fatty Liver Disease (NAFLD)
Roughly one-third of the American population suffers from nonalcoholic fatty liver disease or NAFLD (Polyzos et al 2010, Schuppan et al 2010, Younossi 2008). 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 (Younossi 2008, Kaser et al 2010, Bondini and Younossi 2006).
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 (Puri et al 2009).
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 (Lirussi et al 2007). The term “NAFLD” refers to a group of related and progressive conditions closely associated with overweight and obesity (Schuppan et al 2010).
NAFLD starts off as a low-level disturbance characterized by dull right upper-quadrant abdominal discomfort and fatigue in most patients, but it is hardly benign (Raszeja-Wyszomirska et al 2008). Early NAFLD can ultimately progress to a more serious condition, nonalcoholic steatohepatitis or NASH (Musso et al 2010). About a third of people with NAFLD will develop NASH (Raszeja-Wyszomirska et al 2008), 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 (Schuppan et al 2010, Raszeja-Wyszomirska et al 2008, Mark et al 2010). Overall, people with NAFLD stand a 12% increased risk of liver-related death over 10 years (Raszeja-Wyszomirska et al 2008).
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 (Kaser et al 2010). 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 (Younossi 2008, Kaser et al 2010, Raszeja-Wyszomirska et al 2008).
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 (Musso et al 2010, Schaffer 2003, Perez-Martinez 2010). 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 (Polyzos et al 2010).
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 (Parker-Pope 2010). Fructose promotes formation of new fat molecules in the liver, blocks breakdown of existing fats, stimulates free radical production, and promotes insulin resistance (Lim et al 2010). An increasing number of studies are linking increased fructose consumption with NAFLD, and even with its deadlier consequence, non-alcoholic steatohepatitis (NASH) (Abdelmalek et al 2010). Patients with NAFLD consume 2-3 times as much fructose as do control patients, even corrected for body weight (Ouyang et al 2008).
Diagnosis of NAFLDIn 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 (e.g., hepatitis b or c), and other liver functional parameters (e.g., 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 20-40g 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 (Nugent and Younossi, 2007).
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 (Schuppan et al 2010, Musso et al 2010). Insulin-sensitizing drugs, while theoretically of value, have proved disappointing in clinical trials (Adams and Lindor 2007, Park 2008).
The only successful pharmaceutical intervention for dealing with NAFLD has been metformin, which will be examined below.
Cholesterol-lowering drugs like statins have no proven benefit to date (Kaser et al 2010). Further studies are needed to determine if bariatric surgery to induce weight loss benefits patients with NAFLD (Musso et al 2010, Chavez-Tapia et al 2010).