The main issue with NAFLD is that there are no specific biomarkers for it, meaning that a simple blood test will not confirm or exclude NAFLD. Even if the liver function test is normal, the person may still have NAFLD. An ultrasound examination is needed to confirm a NAFLD diagnosis, and NAFLD is highly correlated with other metabolic diseases, such as obesity, diabetes, dyslipidemia (high cholesterol or triglycerides) and hypertension. The more risk factors that are present, the higher the rate of NAFLD in that population of patients. Up to 90% of obese diabetics with high cholesterol may have NAFLD. However, even lean healthy individuals are not spared fatty liver disease.
Focus: Before we get to the success of tocotrienols in NAFLD, can you give us an overview of the disorder?
Magosso: Until the 1980s, NAFLD was not even considered a disease on its own. Because alcoholic and non-alcoholic have an analogous pathological expression, most of the patients presenting with NAFLD were considered “drinkers in denial”. Fat accumulation in the liver was considered an innocuous condition. We had to wait another 20 years before the dangers of NAFLD were proven and it was shown that people with NAFLD have higher mortality, and more strokes and cancers than non-
16 Focus April 2013
NAFLD individuals. NAFLD is actually a range of diseases of increasing severity that can progress to fibrosis, cirrhosis and in a small percentage, hepatocellular carcinoma. NAFLD is predicted to become the leading cause of liver transplants in the next 10 years.
So far, many studies have investigated drugs and supplements for NAFLD, but none resulted in a truly effective treatment. NAFLD can progress into nonalcoholic steatohepatitis (NASH).
NASH includes
accumulation of fat in the liver cells as well as inflammation of the liver. The inflammatory cells
can destroy the liver
cells (hepatocellular necrosis). Recently alpha-tocopherol was studied as a treatment for NASH at very high doses (800mg/day) for two years. But reviews of these studies were contradictory; in one study, known as PIVENS, alpha-tocopherol was superior to placebo. But in another study, known as TONIC, it was not. Both
studies used liver investigated
advanced cases of NAFLD, and
biopsy determine severity.1,2
Focus: What happened when you studied tocotrienols and NAFLD?
Magosso: Blood tests on our study population showed that all three tocotrienols we used— alpha, gamma, and delta—were significantly increased when
to
taking the supplement. We use the blood tests to check compliance with the dosing regimen. We also measured alpha-tocopherol. In our double-blind study of 64 patients, we treated 30 with two capsules a day of 200 milligrams of a balanced, self-emulsifying formula of tocotrienols, and treated 34 with an identical looking placebo. The primary end point of the study was cure, meaning that ultrasound revealed no NAFLD. Fifteen patients on tocotrienols—50%—were completely cured, while another five had improvement—a total of 67% of all those treated with tocotrienols.
As I mentioned, a review of alpha-tocopherol and NAFLD studies is still puzzling and contradictory. Moreover, alpha- tocopherol at high doses (above 400 mg/day) has been shown to increase mortality risk.3
The
advantage of a mixed tocotrienol preparation may be that no single tocotrienol is taken at more than 260 mg/day.
The final paper is in preparation for publication, while an inter- im analysis was presented at the Liver Meeting 2010, in Boston.4 We are now planning animal and cell research to elucidate the mechanisms of action. A simple antioxidant effect is not sufficient to explain the effects of tocotrie- nols against fatty liver. We are also planning another, large scale study in humans, hopefully with about 200 individuals. It is really
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