Non-alcoholic fatty liver disease, which is part of the metabolic syndrome, is quietly on the rise among the adult population.
THE ancient Greeks thought that the liver was the seat of dark emotions such as wrath, lust and greed. Traditional Chinese medicine also associates anger with the liver.
However, the Persians and Zulus take a more positive view of the emotional significance of this organ, associating it with courage and strength instead.
Both views might have their merit as our liver, the heaviest and largest internal organ of our body, affects virtually every part of us.
From breaking down toxic substances and waste products, to manufacturing hormones, bile (which is essential for fat digestion and absorption), blood-clotting factors, cholesterol and various functional proteins, and helping to regulate glucose, cholesterol, fats and amino acids, the liver does it all.
In fact, the liver is estimated to perform over 500 vital functions within our body.
So, just imagine what happens if our liver becomes unhealthy.
Too much fat
While most of us might be more familiar with hepatitis, alcohol-related liver disease and liver cancer, there is another condition affecting the liver that is insidiously rising amongst the world population.
According to Universiti Sains Malaysia (USM) senior lecturer Dr Enrico Magosso, non-alcoholic fatty liver disease (NAFLD) is considered the most common non-communicable liver disease worldwide.
As reflected by its name, this condition is caused by the excessive build-up of fat in the liver, which is not a result of alcohol consumption.
According to the American Liver Foundation, while it is normal for the liver to contain some fat, anything more than 5-10% of the liver’s weight is considered excessive. In such cases, the liver would be considered a fatty liver (also called steatosis).
While a fatty liver in itself is harmless, the problem arises when the fat continues to accumulate to the stage where it causes inflammation within the liver. This stage is known as non-alcoholic steatohepatitis (NASH).
If left unchecked, NASH can progress on to liver fibrosis, then cirrhosis, which is irreversible, and finally, liver failure.
Now, the good news is that, according to Britain’s National Health Services Choices website, only a few people with NAFLD go on to develop NASH and the more severe forms of liver damage.
However, NAFLD is believed to be part of the metabolic syndrome, which also includes abdominal obesity, high blood pressure (hypertension), elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein (HDL, or “good”) cholesterol levels.
Dr Magosso, an Italian pharmacist who has lived in Malaysia since his postgraduate studies in USM, says in an e-mail interview: “NAFLD is strongly associated with type 2 diabetes mellitus, obesity, hyperlipidaemia and a sedentary lifestyle. Those are all-too-common conditions amongst Malaysians.”
Unfortunately, like pre-diabetes, hypertension and high cholesterol levels, NAFLD generally presents with no symptoms, meaning that you could have it and not realise it until the damage has progressed to irreversible cirrhosis.
In addition, its association with the metabolic syndrome means that all those who have it are at increased risk of cardiovascular disease, including heart attacks and stroke.
No drugs available
Dr Magosso, who is attached to the Oncological and Radiological Sciences Cluster of USM’s Advanced Medical and Dental Institute (AMDI), shares that data from Western countries estimates that between 10% and 30% of their adult population have NAFLD.
He says: “Similar percentages were reported for Asia, although no systematic studies have been performed, except in Japan. In Malaysia, only a few reports exist about the prevalence of NAFLD.”
However, based on a local prevalence study he and his colleagues did in 2010, Dr Magosso believes that the number of Malaysian adults with NAFLD is similar to that of other nations.
The study, which was published in the July 2010 edition of The Southeast Asian Journal of Tropical Medicine and Public Health, found that 56.7% of the 180 untreated hypercholesterolaemic participants had NAFLD upon blood tests and ultrasound scanning.
There is currently no pharmacological treatment for NAFLD, and such patients are usually encouraged to embrace healthy lifestyle changes like eating a balanced diet and exercising.
Dr Magosso does point out that the American Association for the Study of Liver Diseases, the American Gastroenterological Association and the American College of Gastroenterology have recently jointly released guidelines indicating that a daily dose of 800mg vitamin E, in the form of alpha-tocopherol, helps improve biopsy-proven NASH, but this option is limited to non-diabetics.
However, those guidelines also noted the controversy surrounding the potential link between high doses of such vitamin E and death.
According to the guidelines, some meta-analyses have reported an increase in all-cause mortality with high-dose vitamin E, but others failed to confirm such an association.
But alpha-tocopherol is just one of eight forms of vitamin E.
Explains Dr Magosso: “Vitamin E is a family of eight compounds: four tocopherols and four tocotrienols. Chemically, they all have a common ‘head’, but different ‘tails’.
“The ‘tail’ of the tocotrienol has three double bonds. This small difference gives peculiar biological properties to the tocotrienols, for they have up to 60 times more potent antioxidant activity than tocopherols in the liver.”
With this in mind, Dr Magosso and his colleagues thought it might be a good idea to look into the effects of tocotrienols on NAFLD.
“Moreover, we had access to a unique preparation of tocotrienols that had been shown in earlier human trials to provide a significantly superior bioavailability (e.g. 300% increased absorption compared to normal preparations).
“Increased absorption meant that we were able to provide higher antioxidant activity in the liver. (And) oxidative stress plays an important role in both the onset and progression of NAFLD,” he says.
He adds that previous animal studies using the same preparation of tocotrienols had shown that tocotrienols are preferentially distributed to the liver, indicating that the organ is an excellent target for such therapy.
The research team carried out a randomised, double-blind phase II clinical trial over the course of one year in 2008-09. Sixty-four out of the original 87 participants with NAFLD and hypercholesterolaemia recruited completed the trial.
These participants were divided into two groups: one taking 200mg of mixed tocotrienols twice daily, and the other, a placebo.
The results, published in last December’s Nutrition Journal, indicated that the number of patients taking the mixed tocotrienols whose livers went back to normal at the end of the trial (50%) was significant (i.e. not due to chance), compared to the placebo group (23.5%).
Says Dr Magosso: “Our studies showed the potential of mixed palm tocotrienols in NAFLD and that they are well tolerated. In fact, we did not encounter any serious adverse events during our research.
“Mixed palm tocotrienols may provide a good therapeutic agent for NAFLD patients.
“Moreover, the preparation used in our research is of natural origin and the ratio of the various tocotrienols present in the product reflects the natural ratio present in fruit of the oil palm.”
Palm oil is the richest natural source of tocotrienols.
The next step for him and his team is to expand the clinical studies to include a much larger group of patients. While he notes that USM has recently provided a research grant sufficient for a small study using magnetic resonance imaging (MRI), the fact is larger clinical studies can cost millions of ringgit.
Having submitted a research proposal to the Malaysian Palm Oil Board for a large NAFLD clinical trial targeting about 300 patients, Dr Magosso is hopeful that he can continue to explore the promise of tocotrienols in treating this increasingly common condition.