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Tuesday, 22 January 2013

Fatty liver and its treatment.

Fatty liver (steatosis) is pretty much the precondition of fibrosis, cirrhosis and hepatocellular cancer.

Steatosis and hepatic IR are closely associated but it is still poorly understood whether it is steatosis which causes IR, or vice versa. It is clear however that steatosis and IR usually precede inflammation, fibrosis, and cirrhosis of the liver.

Steatosis is produced experimentally in animals by a) toxins and alcohol – in which case the effect will be made worse by high-PUFA diets, reversed by diets providing highly saturated fats, usually beef tallow or coconut oil, and kept stable by moderately saturated fats such as olive oil and lard, b) high-fat diets (high PUFA) with round-the-clock feeding (but not with feeding in a time-restricted window), c) diets deficient in choline, or in the raw materials needed to make choline; methionine, folate and B12 (however, deficiencies of B12 and folate have other serious effects which might mask their importance in this regard), d) diets deficient in antioxidants that prevent lipid peroxidation, usually selenium and tocopherol.
Up-regulation of
PPAR-alpha is protective against steatohepatitis and inhibits HCV replication.

PPARα was also reported to be down-regulated by HCV in the liver of infected patients [8889]. Since PPARα blocks the replication and production of infectious viral particles, its downregulation likely confers a replicative advantage to the virus in spite of the resulting metabolic disorders for the host cells [9091].

PPAR-alpha is upregulated by intracellular peroxidation of DHA, by carbohydrate restriction, and by fasting, as well as by the flavanone naringenin, an antioxidant found in grapefruit, oranges and tomatoes.

From this we might be able to construct a diet that prevents or reverses fatty liver, and thus prevents its sequellae:

·         The fats in the diet will be highly saturated; beef and lamb dripping, coconut oil, dairy fats and olive oil, but there will also be optimal amounts of DHA from fish and seafood.

·         The diet will supply ample choline, from offal and eggs, and methylation factors B12 and folate from meat and vegetables (spinach and beetroot are excellent sources of the alternative methylation factor betaine). 

·         Carbohydrate will be restricted (and low GI), caloric intake will not be excessive, and round-the-clock feeding will be avoided.

·         The diet will be high in antioxidants. It is important for the activation of PPAR-alpha that DHA peroxidize in hepatocytes and not in the gut or the blood. In this paper vitamin E protects DHA, but I’ve also read that grape seed extract(*) is effective, so we are probably looking at a general antioxidant effect, such as you’d get from a dish like sardines, tomatoes and spinach, cooked lightly in extra virgin olive oil. In the case of hepatitis C, which is a selenium- and zinc-sequestering virus, special attention should be given to the intake of these minerals and moderate supplementation considered.
(* grape seed extract is a plant polyphenol, contains no fats, and is not to be mistaken for grape seed oil which is high in omega 6 PUFA)

This letter mentions the intriguing possibility that excess accumulation of NADH is a factor in steatohepatitis. This phenomenon is known as reductive stress and may be relieved by choline, betaine and similar molecules through the generation of methane.

In practice, do such diets work? There have already been a few studies of high-fat diets in fatty liver disease. Considering that these have only covered the carbohydrate-to-fat ratio and ignored choline, PUFAs and antioxidants, the results have been thoroughly encouraging (Note, however, that the average patient changing to an “Atkins-type” diet is likely to eat more eggs than they did before, taking care of the choline angle, and probably more greens and fish).

There were no significant associations between either total caloric intake or protein intake and either steatosis, fibrosis, or inflammation. However, higher CHO intake was associated with significantly higher odds of inflammation, while higher fat intake was associated with significantly lower odds of inflammation. In conclusion, present dietary recommendations may worsen NAFLD histopathology.


The findings show that 4 weeks of a very low carbohydrate diet reduces liver fat content and liver size, particularly of the left lobe. This approach may render bariatric surgery or any foregut operations less difficult in morbidly obese patients and may be a useful treatment for nonalcoholic fatty liver disease.

The Effect of a Low-Carbohydrate, Ketogenic Diet on Nonalcoholic Fatty Liver Disease: A Pilot Study

Four of 5 posttreatment liver biopsies showed histologic improvements in steatosis (P=.02) inflammatory grade (P=.02), and fibrosis (P=.07). Six months of a low-carbohydrate, ketogenic diet led to significant weight loss and histologic improvement of fatty liver disease.


Last but not least, some case studies from everyone’s favourite blogger, Stephan Guyenet at Whole Health Source. Stephan is someone who has taken into account choline and all the other factors I’ve mentioned. 

Fatty Liver Reversal

Another Fatty Liver Reversal

Another Fatty Liver Reversal, part II

Post script: exercise and fatty liver
“Neither moderate-intensity exercise nor total exercise per week was associated with NASH or stage of fibrosis. Meeting vigorous recommendations was associated with a decreased adjusted odds of having NASH (odds ratio (OR): 0.65 (0.43-0.98)). Doubling the recommended time spent in vigorous exercise, as is suggested for achieving additional health benefits, was associated with a decreased adjusted odds of advanced fibrosis (OR: 0.53 (0.29-0.97)).”
Exercise significantly elevates PPAR-alpha in rats
this gives us a range of strategies and combinations for fatty liver; paleo diets, carbohydrate restriction, ketogenic diets, calorie restriction, time-restricted feeding, and high-intensity exercise.