I recently posted that a link has been established between grilled meat and fibrogenesis. On the other side of the coin, saturated fats have been shown to be anti-fibrotic. These studies have been done on ethanol-induced fibrosis, but the process of fibrogensis, once activated by NFkappa beta and TNF alpha, is generally considered to be constant, regardless of the cause.
Dietary Saturated Fatty Acids Reverse Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administration
Amin A. Nanji1,
George L. Tipoe3,
Amir Rahemtulla4 and
Andrew J. Dannenberg5
+ Author Affiliations
1. 1Department of Pathology and Center for the Study of Liver Diseases, The University of Hong Kong, Hong Kong, China (A.A.N.); 2Research Unit of Alcohol Diseases, Helsinki University Central Hospital, Helsinki, Finland (K.J.); 3Department of Anatomy, The University of Hong Kong, Hong Kong, China (G.L.T.); 4Department of Pathology, Harvard Medical School, Boston, Massachusetts (A.R.); and 5Department of Medicine, Weill Medical College of Cornell University and Anne Fisher Nutrition Center at Strang Cancer Prevention Center, New York, New York (A.J.D.)
Dr. Amin A. Nanji, Clinical Biochemistry Unit, LG 136, Block K, Queen Mary Hospital, 102 Pokfulam Rd., Hong Kong, China. E-mail: ***@****
We investigated the potential of dietary saturated fatty acids to reverse alcoholic liver injury despite continued administration of alcohol. Five groups (six rats/group) of male Wistar rats were studied. Rats in groups 1 and 2 were fed a fish oil-ethanol diet for 8 and 6 weeks, respectively. Rats in groups 3 and 4 were fed fish oil and ethanol for 6 weeks before being switched to isocaloric diets containing ethanol with palm oil (group 3) or medium-chain triglycerides (MCTs, group 4) for 2 weeks. Rats in group 5 were fed fish oil and dextrose for 8 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, nuclear factor-κB (NF-κB) activation, and mRNAs for cyclooxygenase-2 (Cox-2) and tumor necrosis factor-α (TNF-α). Endotoxin in plasma was determined. The most severe inflammation and fibrosis were detected in groups 1 and 2, as were the highest levels of endotoxin, lipid peroxidation, activation of NF-κB, and mRNAs for Cox-2 and TNF-α. After the rats were switched to palm oil or MCT, there was marked histological improvement with decreased levels of endotoxin and lipid peroxidation, absence of NF-κB activation, and reduced expression of TNF-α and Cox-2. A diet enriched in saturated fatty acids effectively reverses alcohol-induced necrosis, inflammation, and fibrosis despite continued alcohol consumption. The therapeutic effects of saturated fatty acids may be explained, at least in part, by reduced endotoxemia and lipid peroxidation, which in turn result in decreased activation of NF-κB and reduced levels of TNF-α and Cox-2.
Long-term treatment of alcoholic liver disease continues to incorporate vitamins, nutrients, and trace elements (Fulton and McCullough, 1998; McCullough et al., 1998). In fact, the role of specific pharmacological agents remains unproven. Clearly, the development of more effective nutritional or pharmacological therapy will depend on further elucidating the mechanisms that contribute to liver injury.
Several lines of investigation indicate that dietary fat can modulate the severity of alcoholic liver injury (Mezey, 1998). In experimental animals, for example, diets enriched with saturated fatty acids protect against alcohol-induced liver injury, whereas diets containing polyunsaturated fatty acids promote liver injury (Nanji and French, 1989; Nanji et al., 1989, 1994a). Saturated fatty acids have also been reported to reverse established alcoholic liver injury (Nanji et al., 1995, 1996, 1997b). Importantly, in previous studies, use of alcohol was discontinued at the time that dietary treatment was initiated. This model represented the alcoholic patient who stopped drinking at the time of hospitalization (French, 1995).
Discontinuation of alcohol remains pivotal in the treatment of alcoholic liver disease. Although this goal can frequently be achieved in the short-term, the majority of patients resume alcohol consumption, often with sudden deterioration in liver disease (Pares et al., 1986). Hence, it is important to develop therapeutic strategies that simulate the clinical condition in which alcohol use is continued despite the presence of alcoholic liver disease.
Previously, we used the intragastric feeding rat model to study the pathogenesis of alcoholic liver disease (Nanji et al., 1999). In addition to being useful for elucidating mechanisms of injury, this model has been used to evaluate various strategies to prevent or reverse alcoholic liver disease (Nanji et al., 1995, 1997b). The results of previous studies suggest that elevated levels of endotoxin and lipid peroxides in alcohol-fed animals activate nuclear factor-κB (NF-κB), leading to enhanced expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and proinflammatory cytokines (Nanji et al., 1997a, 1999). In the current study, we investigated whether treatment with dietary saturated fatty acids could reverse established alcoholic liver injury despite continued administration of ethanol. We show that diets enriched in saturated fatty acids improved both histological liver injury and biochemical parameters that have been etiologically linked to liver injury.
(The ferretin levels in the livers of the saturated-fat rats were less than half those of the polyunsaturated fat-rats).
Beef Fat Prevents Alcoholic Liver Disease in the Rat
Amin A. Nanji MD, FRCP(C), Charles L.
The amount and type of dietary fat is thought to be important in the pathogenesis of alcoholic liver disease (ALD). We investigated the role of different dietary fats in our rat model for ALD. Liver pathology was evaluated in rats fed ethanol and lard or tallow or corn oil over a period of 2 to 6 months. All experimental animals were pair-fed the same diet as controls except that glucose was isocalorically replaced by ethanol. Rats fed tallow and ethanol developed none of the features of ALD, those fed lard and ethanol developed minimal to moderate disease, rats fed corn oil and ethanol developed the most severe pathology. The degree of histopathological abnormality correlated with the linoleic acid content of fat in the diet (tallow 0.7%, lard 2.5%, corn oil 56.6%). We postulate that linoleic acid facilitates development of ALD and provides an explanation for our previous epidemiological observations.
Effect of Dietary Fat on Ito Cell Activation by Chronic Ethanol Intake: A Long-Term Serial Morphometric Study on Alcohol-Fed and Control Rats
Hisao Takahashi, Kim Wong, Linda Jui, Amin A. Nanji, Charles S. Mendenhall, Samuel W. French
(note: Ito Cells are Hepatic Stellate cells in their normal state. This study is saying that rats fed beef tallow had no loss of Ito cells – that is, no conversion to myofibroblasts – whereas rats fed corn oil went into fibrosis)
We studied the effects of long-term ethanol ingestion and dietary fat on Ito cell activation morphometrically in rats. Sixteen pairs of Wistar male rats were divided into two groups, one fed tallow and the other fed corn oil as the source of dietary fat. Each group of rats were pair-fed a nutritional adequate liquid diet containing either corn oil (CF) or tallow (TF) as fat as well as protein and carbohydrate. Half of each group received ethanol, the rest were pair-fed isocaloric amounts of dextrose via an implanted gastric tube for up to 5 months. Morphometric analysis of the change in fat and rough endoplasmic reticulum (RER) of Ito cells was performed on electron micrographs obtained from monthly biopsies including baseline. Ito cell activation was assessed by a decrease in the ratio of fat/RER in Ito cells. The ratio of fat/RER in Ito cells of alcoholic rats fed the CF diet (CFA) gradually decreased. The ratio war found to be lower than in the pair-fed control rats (CFC) at 5 months of feeding. CFA 1.74 ± 0.57, vs. 7.46 ± 2.05, respectlvely, p < 0.05, mean ± se). Ito cell fat also significantly decreased at 5 months of feeding (p < 0.05). The fat/ RER ratio In CFA significantly decreased only subsequent to the development of fatty change, necrosis, and inflammation followed by fibrosis of the liver. In contrast, the TFA rats did not show a significant decrease in the fat/RER ratio in the Ito cells throughout the study, while TFC rats showed an increase in the fat/RER ratio. Minimal pathological changes were observed in the livers of CFC, TFA, and TFC rats. These results indicate that activation of Ito cells at a significant level occurred only late in the course of feeding alcohol after moderate to severe abnormalities in liver histology had developed, although activation may have begun at an earlier time of ethanol feeding. The results indicate that dietary fatty acid composition may be an important factor in the pathogenesis of ethanol-induced Ito cell activation.
Interesting to read but we still have to limit our fat intake. Diet is often a double edged sword. Loading up on fats that may inhibit the fibrosis could cause us to have new different problems, such as cardiovascular issues.
Further.... I think there are other issues which can come into play. Meat may just be meat, but when you grill it the composition changes. I believe that is one reason that high temperature grilling has gotten some bad press as of late.
I wonder, are nuts not high in saturated fats? It could be that nuts could be a better choice than a grilled 1/4 pounder.
I've always been impressed about you concern for Joe and the level of interest that you take in his care and his health. But, keep in mind that these are RATS and extrapolating to you dear hubby might not be a sound approach. What I find interesting is the lack of follow-up on these poor animals, did their hearts explode and did they expire with little fibrosis but massively clogged arteries?
I think it is obvious, however, that vegetable and corn oil are things to stay far away from. And not just because of these studies. Omega sixes feed directly into the arachidonic acid pathway (inflammation).
The things that drives me nuts (no pun) is some of the counter-intuitivness of some of this stuff. You'd think, in general, that for human purposes that derivitives of plants = good and derivitives of animals = bad (again, in general).
One TBSP (14 g) = one serving
total calories from Fat 120
TOTAL Fat 14 g
saturated fat 1.5 g *
Trans fat 0
Poly unsaturated fat 10 g *
Mono unstaturated fa t 3 g *
Hmmmm ..... not that impressive
Those items with an asterisk contain the disclaimer daily value not established, and the set up seems to emphasize the health, but possibly minimize the less stellar aspects of the product.
On that note...
Omega 3 (alpha linolenic acid, ALA) 8 g
Omega 6 (linoleic acid) 2g
Omega 9 Oleic acid) 3 g
What it means, I do not know...... but I assume that we cannot escape the so called "bad" and that all things in balance it may all work out. WE can eschew the worst of the worst and limit our intake of things we know to be bad.
Thanks, I will definitely keep it in moderation.
I agree with the counterintuitive part too. I really thought I was doing something good for him when I MADE him be a vegetarian for his own good. It turned out to be the wrong move entirely. He ate plenty of eggs and some beans and nuts but as soon as I got convinced that the latest studies say extra protein is needed for cirrhosis, his sorry looking albumin number went up.
In all my zeal to help Joe, I have made some blunders. I also used to be stingy with coffee because I thought it wasn't good for him and that turns out to be a mistake too. Left to his own devices, he would have eaten protein, coffee, and butter for sure. He would have added cherry pie and any day now there will be another article suggesting cherry pie would have helped too. :>) Hopefully, I will get points for trying hard but I have missed the target a lot.
Joe liked nuts all his life and liked them unroasted and raw even. I had him eat them with the riba on his last, long, nauseaus TX and not surprisingly, he doesn't seem to like them much at all now.
About a week ago I was on some nutrition website (not sure which one) and I was looking at some of the health traits of various fruits. Mostly, I was researching "glucose friendly" stuff but several other attributes were discussed too. Although I can't find the site right now my impression was that cherries were more good than bad. Around my house milk chocolate covered cherries are a bit hit and I'm glad that the wife and the kids attack them like mosquitoes on an open cut. When it comes to sweet snacks "more for them and less for me" is probably a good thing for me. Until someone mad a mistake and bought dark chocolate covered cherries. I'm the only one who like dark chocolate.
So my dilemma, convince myself that dark chocolate is a beneficial as coffee and consider eating the glycemic bombs as theraputic or act wisely and eat a chunk of cheddar cheese instead. Sometimes you just can't win.
You brought back an old memory. Joe and I were dating in 1982 and he was stocking and sweeping at Walmart while working on his degree. One night he just happened to mention that he ate an entire box of chocolate covered cherries for his dinner break at Walmart. I knew then that he needed me, bad. :>I
For fats, you need the proper proportion of omega 3, 6 and 9. I have to look up what is the ratio, but an overabundance of omega six is the worst. Steatosis (intracellular fat) is mostly composed of omega sixes. A certain percentage of omega sixes convert directly to arachidonic acid. The arachidonic acid pathway is the biochemical textbook definition of the inflammatory pathway.
Look at this quote from one of the above studies. "The degree of histopathological abnormality correlated with the linoleic acid content of fat in the diet (tallow 0.7%, lard 2.5%, corn oil 56.6%)."
So flax is much closer to the proper proportion of the three omega fatty acids, while vegetable and corn are heavily composed of omega sixes to the exclusion of the others. But no omega sixes is definitely bad for you too. You need the proper proportion.
"Omega-3 fatty acids can be found in far less foods than omega-6 fatty acids. Many people have a very low intake of omega-3s. Since omega-6 fatty acids compete with omega-3 fatty acids for use in the body, it is important to take these fatty acids in the proper ratio. The World Health Organization recommends a ratio of 5:1 to 10:1 omega-6 to omega-3. While a ratio between 1:1 and 4:1 is often considered as being optimal. Since most diets are very rich in omega-6 and low in omega-3, the ratio is often somewhere between 10:1 and 20:1. This is especially a problem with diets that are high in processed foods and oils. Oils like corn, safflower, sunflower and cottonseed are usually low in omega-3s. To balance the fatty acids out, it is important to eat a diet that is low in processed foods and with fat mainly coming from omega-3 fatty acids."
The omega 3,6,9 fatty acids are unsaturated. The harmful effects of saturated fatty acids, the fats studied in the tests above, have actually been overestimated, in my opinion. For instance, one of the amazing benefits of coconut oil include the fact that it helps burn fat, not accumulate it, in the body.
"The things that drives me nuts (no pun) is some of the counter-intuitivness of some of this stuff. You'd think, in general, that for human purposes that derivitives of plants = good and derivitives of animals = bad (again, in general). "
Very good point/advice. It's important to think carefully about what we put in out body, especially when dealing with a chronic disease. 3 cups of coffee a day maybe okay if you don't have high blood pressure, 10 cups of coffee a day probably not good for anyone. Just jumping on the antifibrotic band wagon blindly is not a wise idea. (not saying anyone did)
"He would have added cherry pie and any day now there will be another article suggesting cherry pie would have helped too. :>)"
That really made me smile! All we can do is work with what we know. I know if my husband were left to his own devices and I wasn't doing all this research, he would probably have convinced me that all fruit pies are good for cirrhosis! ;)
Regardless of points or not for trying, your efforts on Joe's behalf have my utmost respect and admiration.
mhudnall: Counter-intuitive but interesting data for sure. Thanks for the article. Though I must admit I'll keep it to myself quietly for comfort -- sharing this info with my cirrhotic husband who already has a debilitating weakness for butter-made confections may be too much of a good thing!
so the frenchies can tarry at the wine trough as long as Bessy comes along???
but hey, lets get real, the long and short of it is the body uses different lipid chains to correct different problems.
Example...for years I had untreated thyroid disease and craved coconut...
then I read all hypothyroid people crave it...coconut, they all do crave it.
couldn't let it go,,,so studied it, and found out that high chain omegas correct thyroid deficiency....somehow, the body knows what the mind does not. Found this out in pubmed.
this same thing has been observed in animals ad nauseum by dept. of agriculture, animals know when they are low in a mineral for example, and go graze on the thing highest in that mineral....how do they know??? We are fearfully and wonderfully made!,
now I won't feel so guilty when I eat eggs...and butter...everyday. (one weakness I cannot quit).
But I think we need to look carefully at the other antioxidants, like cucurmin, like dashan, etc. If we can reduce inflammation without the extra fat it will be better for our heart and other systems don't you think?? Certainly our waistlines!!
I'm not up on the whole of the mechanism, but my guess is any fat is going to reduce oxidation by it's nature, HOWEVER....when we speak of saturated fats, they do NOT have one problem that oils often have, the high omegas don't oxidize at the same rate.
Things like cocoa butter, cocomut oil, etc can last years without refrigeration and without becoming rancid...they are much more stable that way.
And butter of course, and meat as well are much FRESHER fats....meat is consumed within days of slaughter, butter also has a high turnover rate....whereas oils can sit on the shelf for months or longer...and the "idiot health food nuts" made the industry remove the antioxidants BHA and BHT years ago. Which combined means your corn oil etc is much more likely to have a high level on oxidation when you use it....(unless like me you keep it refrigerated and also add your own BHT as I do).
My guess is that this rancidity is the greater reason that the saturates scored better....not because they are better as much as they are fresher and ergo have less peroxide, less free radicals will be formed ergo, and less irritation and inflammation, whereas any amount of rancidity will make any oil or grain more dangerous than healthful.
It's too bad the researchers did not know about the rancidity potion in this equation.
It's too bad the public doesn't know either. This is one case where the presevative in the oils made them far more healthful, but as usual the bigger the whiners, the more our government caves and gives the little pissants what they think is right...even though in this case, their enlightment had nothing to do with chemistry, and they've made us all a lot sicker as a result of their ignorance. Nothing is harder on the body than peroxide.
There are two new new medical studies from the US; one shows that high-fat diets help burn liver fat, the other shows that low-fat diets are much more likely to cause fatty liver and inflammation.
If you try to avoid fat, you will eat more carbohydrate, and you'll get fewer nutrients with that. Animal fat supplies vit A, D, K2 and selenium and these are all things that get depleted in hepatitis, and depletion is a risk factor for HCC.
I think, along with Paul Jaminet and Kurt Harris, that there are three toxic nutrients:
Fructose - from sugar, HFCS, fruit juice (the amount in most fruit is OK in "moderation", whatever that means)
Wheat (and maybe other grains)
Omega 6 oils (other than olive oil which is only 9-11% - which would still be too high without the antioxidants of CPEV).
I am also concerned about galactose from milk, don't recommend low-fat milk or large amounts of milk other than butter, cream and cheese.
But I have less evidence for this.
I'm getting ready to make Joe a fluffy omelette whipped up with a splash of cream and cooked in some butter...mm-good!
In case others aren't aware, George is gifted in the area of research and has built up a lot of information pointing to a lower in carb/higher saturated fat diet as beneficial for HCV and cirrhosis. His own liver health has increased significantly.
My husband has benefited from his knowledge. I really respect his work. It basically points to what many are referring to as a paleo diet although people's definition of that term varies widely. George has summed it up very succinctly above as to what is showing itself to be beneficial to HCV/cirrhosis/fibrosis. Foods with the least amount of processing seem to be the way to go which is not surprising.
My husband isn't very compliant with all this but he has shifted heavily towards these chages and even giving that much has shown benefit.
I want to add a caveat to the above discussion. Pork is not a low carb food that I give Joe anymore because it has been linked pretty heavily to cirrhosis and liver cancer. Even though George didn't include it in his above post, I first learned of it from him. Paul Jaminet has a blog called The Perfect Health Diet and he is doing a series on the subject of pork and George H is mentioned there also because he has gathered a great deal of incriminating evidence that puts a big stamp of disapproval of pork as a liver friendly food. There are some scarey graphs and stats to look at if you are interested.
Not to be contradictory but just as a reminder that we are all different,
I never stopped eating pork, fresh pork, not processed or salted, while sick with cirrhosis. Most my protein came from chicken, fish and tofu and eggs but I ate pork as well.
Never got cancer despite almost dying.
Years ago, we raised our own pork. The meat was entirely different. Personally I wonder if the 'problem' with pork, isn't pork per se but how it's raised, what it's fed, etc.
Organic and close to the source is always going to be the healthiest choice no matter what the food.
Maybe George will be back by sometime and can give you some feedback. The stats we saw made pork look pretty guilty. We will miss bacon but at this point we've both decided it isn't worth the risk for Joe. I wouldn't be so cruel as to cook bacon and tell him he can't eat it...it smells so good. Bacon was way too salty for him anyway and makes ascites worse.
Coffee smells good too and he can have all he wants. :>)
Have a great day,
Here is a section taken from the "Perfect Health Diet" website under the title, "Did Leviticus 11:7 Have It Right?" ----Author- Paul Jaminet (I know his wife contributes to his blog also) The blank spaces are where the graphs are. If you are interested, you should take a look because I found them pretty plain and when I saw it, I knew that bacon was no longer welcome at our house. I hate to bring bad news but it is what it is.
Pork Consumption and Liver Cirrhosis
Pork consumption has a strong epidemiological association with cirrhosis of the liver. Startlingly, pork may be even more strongly associated with alcoholic cirrhosis than alcohol itself!
The evidence was summarized by Francis Bridges in a recent (2009) paper , building on earlier work by Nanji and French . A relation between pork consumption and cirrhosis of the liver is apparent across countries and has been consistently maintained for at least 40 years.
Here is the correlation between pork consumption and mortality from liver cirrhosis in 2003 :
The correlation coefficient of 0.83 is extremely high – rarely seen in epidemiology. Correlation coefficients range from -1.0 to 1.0, and a coefficient of 1.0 would indicate that cirrhosis mortality was strictly proportional to pork consumption. The very low p-value confirms the statistical association.
Here is the relation between alcohol consumption and mortality from liver cirrhosis:
The correlation coefficient is lower than for pork consumption.
In epidemiological studies, beef, lamb, and pork are often grouped together as “red meat.” However, this may conceal differences between pork and the ruminant meats. Bridges found that beef actually appeared protective against cirrhosis:
hate to bring bad news but it is what it is. Pork Consumption and Liver Cirrhosis
Pork consumption has a strong epidemiological association with cirrhosis of the liver.
Personally I don"t know enough about this topic to really comment intelligently..however I would say I have had HCV for 36 years ..eat basically a relatively sound diet from all the different food groups ,including pork and I have ealy stage 1 fibrosis.
Possibly the bad news ..isn"t bad news for everyone..
Thank you so much for this information, very interesting. When I found that it could take days to weeks to digest red meat we stopped red meat and pork, still have other things but it didn't sound good to me.
Good luck Take Care
I have, for many years, leaned towards a vegetarian type of diet, with the occasional chicken and fish. However, while on treatment I started craving meat. So, I listened to my body and have been eating red meat. Amazing how the body knows what it needs.. we just need to listen.
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