Non-alcoholic fatty liver disease (NAFLD) is an increasingly common liver condition that primarily affects people who drink little or no alcohol. The incidence of NAFLD appears to be increasing at an alarming rate and can range from simple hepatic steatosis (which is reversible) to non-alcoholic steatohepatitis (NASH) which is characterised by a build-up of fat within the liver cells. Although individuals with NASH can feel generally well, the condition is serious and, as a consequence of a cascade of insults, ultimately leads to cirrhosis and liver failure.
The impact of NAFLD
NAFLD is commonly associated with obesity, metabolic syndrome and insulin resistance, with increasing evidence suggesting that there is a link between high intake of fructose and the development of the disease. Fructose is a simple sugar that fuels the body, and is found naturally in fruit and vegetables (the riper the fruit, the higher the fructose content). However, high fructose corn syrup (a mixture of glucose and fructose) is now used commonly as a sweetener in numerous consumer food and drink products, meaning that our intake of ‘unnatural’ fructose has increased dramatically over the last few decades. The main issue with fructose is that, unlike sucrose, it is metabolised directly by the liver where it can rapidly deplete the energy currency molecule ATP and cause a rise in the levels of uric acid. The balance of uric acid formation and excretion is driven by several enzymatic pathways and because humans are relatively inefficient in clearing uric acid from the body (due to a lack of the enzyme uricase) uric acid levels rise, leading to hyperuricemia. High levels of uric acid act via several metabolic pathways to reduce the entry of fatty acids into the mitochondria whilst enhancing triglyceride synthesis leading to hepatic lipid accumulation. In addition to increasing fatty build up in the liver, increased dietary fructose can therefore alter the body’s metabolism and energy balance.
NAFLD and omega-3
As with many of today’s Western disease states, NAFLD is considered to be associated with dietary excess of omega-6 and a deficiency of omega-3. Indeed, a higher omega-6 to omega-3 ratio (which is associated with high levels of inflammation) is routinely found in the cell membranes of NAFLD patients. Unsurprisingly, increasing the omega-3 levels of patients with NAFLD has been suggested to improve many of the clinical features of the condition, a hypothesis that has been confirmed in a recent meta-analysis. The beneficial effects of omega-3 are numerous and include optimising liver fat, reducing inflammation and lowering liver enzyme levels (GGT), and blood lipid levels of triglyceride and cholesterol – both of which are risk factors for cardiovascular disease (CVD), implying that omega-3 may actually slow down the progress of NAFLD! You can read more about the study findings here. Whilst balancing the omega-6 to omega-3 ratio appears to be important, it is likely that focusing more specifically on the AA to EPA ratio as a biomarker of ‘inflammatory potential’ is more significant, especially given the link between NAFLD and CVD. In this study from 2015, a low EPA to AA ratio ( which is the equivalent of a higher AA to EPA ratio) was not only found to be associated with NAFLD, but the authors suggest that the low EPA to AA ratio found in younger patients was likely to influence their risk of developing CVD in older age. Encouragingly, it’s relatively easy to restore a healthy ratio of AA to EPA as shown in this earlier study from 2008 in which a 12-month intervention with 2.7g/day highly purified EPA found the treatment to be both safe and efficacious for patients with NASH, and that the improvement observed were due to both anti-inflammatory and antioxidative properties.
Increasing omega-3 levels can help reduce the risk of a number of key inflammatory conditions, as is increasing antioxidant status via a good variety of fruit and vegetables. Whilst high fructose intake is one factor that contributes to the development of NAFLD, it appears to be important, however, to keep a ‘healthy’ ratio of fruit to vegetables (ideally one portion of fruit to 4 portions of vegetables);this is in addition to reducing or eliminating foods with high levels of fructose syrup. Both are clearly important as a first step approach to preventing the development of NAFLD. In addition, maintaining a healthy weight and ‘avoiding’ insulin resistance and metabolic syndrome, through improvements in both diet and physical activity, are also important for reducing the risk of debilitating disease.