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I recently received the question from a reader that I have paraphrased below. My answer follows.
Q. In John Barron’s Heart Health Program Newsletter from February 24, 2004 and December 21, 2009, he writes that excess fats in the diet can clog the liver and cause cholesterol to clog up the membranes of liver cells, completely stopping the function of the LDL receptor and preventing the liver from taking up LDL from the blood. From what I have read, this should caused LDL oxidation, which is a bad thing. Is it true that too much fat and cholesterol in the diet clogs liver cells, and if so, how much fat and cholesterol should we eat so that we get the nutrients we need without clogging our livers?
A. There are two issues here. First, the issue of fatty liver (build up of fatty deposits). Second, the role of the LDL receptor in health and of cholesterol in regulating that receptor.
There are a few animal models used to induce fatty liver. One is alcohol, but it has been shown that if animals consume 40% of their diet as cocoa butter instead of corn oil, as much as 30% of calories from alcohol does not cause fatty liver. In the same model, medium-chain triglycerides, derived from coconut oil, and beef fat, have dose-dependent protective effects against the alcoholic damage. Another model is methionine- and choline-deficient diets, which cause fatty liver disease. Methionine is an amino acid especially abundant in meat, and choline is found most abundantly in liver and egg yolks. Saturated fat protects against this model of fatty liver disease, although not completely. The third model usually used is a very high fat diet (about 60% of calories), but highly saturated fats have shown very little ability to cause fatty liver disease in this model and polyunsaturated fats have shown a very high ability to do so.
You can find a more detailed review of these studies with references in my other blog over at The Daily Lipid by using this link:
The second issue is the role of the LDL-receptor and the role of cholesterol in the liver. It is true that liver clearance of LDL-cholesterol plays a huge role in heart disease risk. This is clear from the fact that people with a defective gene for the LDL-receptor get heart disease very early — in infancy in the most extreme case — and people with a defective gene for an enzyme that degrades the LDL-receptor have virtual immunity to heart disease.
However, LDL-receptor is not suppressed by “clogging” per se. When the cholesterol level in the liver goes up, it expresses less LDL-receptor for the simple reason that it does not need any more cholesterol. The principal issue with high LDL-receptor function is thyroid hormone status. This is the main determinant among people who do not have genetic defects. Also, oxidative stress, which is promoted by intake of polyunsaturated fatty acids and is protected against by intake of saturated fatty acids and to some extent by monounsaturated fatty acids (and wihch is also influenced by many other factors, such as toxins and heavy metals), decreases LDL-receptor function.
I have reviewed this subject in greater detail here:
High Cholesterol And Heart Disease — Myth or Truth?
Intake of cholesterol has no effect on cholesterol levels in 70% of people, and in the other third, it raises LDL and HDL similarly and does not affect the ratio. This is more consistent with the concept that the ingested cholesterol is being sent into the blood, rather than that the LDL-cholesterol is not being cleared. When this is the case, the LDL-to-HDL cholesterol ratio will tend to increase because the longer the time LDL spends in the blood, the more cholesterol is transferred from HDL to LDL.
Dr. Maria-Luz Fernandez of the University of Connecticut has reviewed this subject in greater detail here:
Dietary Cholesterol Provided by Eggs and Plasma Lipoproteins in Healthy Populations
Intake of certain fatty acids increases cholesterol levels, but again this is more consistent with greater cholesterol synthesis. For example the most powerful increaser of total cholesterol is probably lauric acid, but lauric acid is also the most powerful reducer of the LDL-to-HDL-cholesterol ratio — this is consistent with lauric acid being burned for quick energy, thus increasing the energy state of the liver cell and allowing for greater cholesterol synthesis. Not “blocking” the LDL receptor.
For more information on this subject, see my blog post over at The Daily Lipid:
The Total-to-HDL Cholesterol Ratio — What Does it Mean?
In any case, experimental evidence has shown in humans that saturated fats protect against in vivo LDL oxidation. You can see this by looking at the rightward most column in this graph: Dietary Fat and LDL Oxidation.
This shows a graded increase in LDL oxidation occuring within the blood of live humans as the diet goes from 1) butter and palm oil to 2) olive oil to 3) sunflower oil and finally 4) sunflower oil and fatty fish, all diets being about 35% of calories from fat. The first two diets were statistically significant from the second two diets, but the increase between butter/palm and olive oil was not significant, nor was the increase between sunflower and sunflower/fatty fish. So what we can conclude here is that it is primarily dietary polyunsaturated fats from seed oils and excess amounts of fatty fish that contribute to LDL oxidation.
In summary, eating traditional saturated and monounsaturated fats does not clog the liver and does not promote LDL oxidation.
Read more about the author, Chris Masterjohn, PhD, here.
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Great article, Chris.
I’ve heard that high cholesterol used to be considered a marker for hypothyroidism back in the 60s and 70s. In other words, if a doctor saw high cholesterol on a lab test the first thing suspected would have been hypothyroidism. Functional medicine practitioners are getting hip to this again and have found that treating the thyroid problem brings cholesterol levels down.
Chris,
According to Cordain, saturated fats cause downregulation of the LDL receptors and via that mechanism can promote heart disease. Please see the quote below from his web site. Your thoughts?
“My research group and I believe that the high amounts of dietary saturated fats in the western diet promote atherosclerosis because they down-regulate the LDL receptor (a concept for which the Nobel prize in medicine was awarded in 1984). We do not believe that dietary saturated fats are the sole or even main cause of atherosclerosis, but rather are a part of many dietary elements that promote heart disease”.
My grandfathers both lived to be in their teninies and my mother 99, and as far back as I can remember all three of them ate large quantities of beef (at least 6 times a week) and the word cholesterol meant nothing to them. Most of the beef was produced by them as they lived on farms. Perhaps the animals ate more naturally than the feed they are fed today which contains toxins, steroids,etc. Added to the beef dinners we must include the fatty gravies consumed as well. Makes one wonder what the cause is or if the cardiovascular problems are more related to our sedentary type lifestyles.
Second the last sentence says,
“primarily dietary polyunsaturated fats from seed oils and excess amounts of fatty fish that contribute to LDL oxidation.”
The very next (last) sentence says,
“eating good fats does not clog the liver and does not promote LDL oxidation.”
Either there is a tipping point, or there is a contradiction, no?
Hi Chris,
Thanks! That’s true, and in fact several decades before that it was shown that natural thyroid extract supplementation was a very safe and effective way to normalize cholesterol concentrations and eliminate heart disease risk whether there was any other evidence of hypothyroidism or not. I agree that people with high cholesterol should have their thyroid functioning checked.
Chris
David,
Does Dr. Cordain provide a reference for this? I can only address his comments directly if he provides a reference.
However, for now I can address them in general.
His parenthetical remark indicates that the Nobel prize was awarded for the discovery of the LDL receptor and its associated pathway, not for the statement about saturated fats. Saturated fats were shown to increase LDL-cholesterol and decrease its turnover in the blood, mostly when compared to PUFA. No one to my knowledge has shown that this is due to reduced LDL receptor activity. It could be due to decreasing LDL oxidation and thus decrease the clearance of oxidized LDL through scavenger receptors, which would be a good thing. It could also be due to simply displacing PUFAs. Linoleic acid from vegetable oil causes increased esterification of cholesterol in the liver — that means it binds to cholesterol in a complex — and by reducing the free unbound cholesterol, the liver will think it needs more cholesterol and thus take it in from the blood. But the effect is cholesterol accumulation in the liver and it’s not obvious that this is a good thing.
Either way it is a moot point because as the last graph I linked to shows very clearly, saturated fats decrease LDL oxidation. The whole reason we care about the LDL receptor is that if LDL is not cleared from the blood in a timely fashion it will oxidize! So it is not logical to indict saturated fats on the basiss that they decrease the LDL receptor activity, which is unproven, when in fact their overall effect is to decrease LDL oxidation, the vary thing we want to see happen.
Much more importantly, clinical trials have already refuted the concept that saturated fats increase the risk of heart disease. I will be discussing this in an upcoming WAPF article.
Chris
Ben,
Thanks for writing!
You have a good point. I had poorly formulated the last sentence and I have now changed it to “eating traditional saturated and monounsaturated fats…”
I do believe that fatty fish should be eaten in moderation and in the context of a diet overall low in total PUFA and rich in a broad spectrum of antioxidants. Fish oils, do, in fact, increase oxidative stress in the body.
Chris
Chris,
I typically consume a serving of wild Alaskan salmon 2 or possibly 3 times a week and supplement with between 3 and 6 grams of combined EPA and DHA on the other days. Do you think I should reconsider the amount of supplementary EPA and DHA that I am consuming and scale back?
Dear Peter,
Personally I think that is way too much fish oil. Unless you are using it to treat something pharmacologically and have clear evidence that it is working for you, I think you should limit total consumption of DHA/EPA from all sources to 1 gram/day. This is my opinion, of course, based on research — I am not qualified to give out medical advice. Nevertheless I believe that this is based on the best available evidence.
Chris
I always thought omega-6 pufas were pro-inflammatory, ldl oxidizers, while the omega-3 pufas, like the ones from fatty fish, were the healthy anti-inflammatory non-oxidating type.
But perhaps this above is a gross over-simplification.. and its more accurate to say that both omega6 AND omega3s cause oxidation?
Dear Ben,
That is incorrect. All PUFAs are vulnerable to oxidation and their vulnerability is proportional to their number of double bonds. In this respect, omega-3 PUFAs are worse than omega-6 PUFAs because they have more double bonds. Fish oil trials have clearly established that supplementation with fish oil increases the vulnerability of LDL to oxidation.
However, modest amounts of the essential PUFAs, arachidonic acid (omega-6) and DHA (omega-3) have benefits. Most people have a relative deficient intake of DHA (omega-3), and reversing this can help with inflammation. DHA also has some antioxidant functions depsite its vulnerability to oxidation.
Nevertheless, we do not need large amounts of these fatty acids and “more is better” in this case will get us into trouble.
I’ll be writing an article on this issue in either the fall or winter Wise Traditions.
Chris
Sounds like coconut oil would be good to cook with.. I just wish it was a liquid at room temperature!!
In terms of oxidation, can a mono or polyunsaturated oil be used *IF* it has a high smoke point, like macadamia or grape seed oil?
Is this the mechanism how PUFA’s reduce LDL, by increasing LDL oxidation and thus increasing the clearance of oxidized LDL through scavenger receptors?
Where can I read up on this thought?
thanks so much.
awesome write up. i’ll be using more coconut oil from now on
Chuck, macadamia oil is actually low in PUFAs. A low smoke point is a separate issue — it basically ensures the oil won’t burn, but that doesn’t mean its fatty acids will not peroxidize. More importantly, eating too many PUFAs increases oxidative stress even if they are fresh and uncooked, because they can oxidize in the body.
Sam, thanks! Enjoy!
Thanks for writing everyone!
Chris
Rabbi Hirsch, I do not think this line of reasoning has been expounded on. I was just mentioning it as one of the logical hypothetical possibilities. The current mainstream opinion about how PUFAs lower cholesterol levels is by esterifying cholesterol in the liver, leading to a decrease in free cholesterol and thus convincing the liver that it needs more cholesterol. So, cholesterol accumulates in the liver instead of the blood.
Hello Chris,
When you refer to excess oily fish in this blog, is that inclusive of cod liver oil (which assumably is “oily”)? Or, is cod liver oil okay? I guess if you are only have a tablespoon per day then that is not much (compared to several salmon steaks per week, etc.). Perhaps I am being dense here, and apologies if so!
Warm regards,
Will
Will,
This includes cod liver oil, although cod liver also contains protective vitamins that are not found in fish oil. One tablespoon is a huge amount. Price used 3/4 tsp for children and noted that toxic effects can develop with prolonged use of more than one teaspoon. He does not comment on adult doses but I have never seen any evidence that adults require more fat-soluble vitamins or more essential fatty acids than children do, and in the case of essential fatty acids the cases is quite certainly the opposite, that their requirement is significant for children but extremely low to the point of infinitesimal for the adult except in certain disease states, during periods of growth (bodybuilding) or tissue repair (after injury or sickness) or during pregnancy and lactation.
Chris
Chris, great article. In the animal model could high O-3 conceptually create fatty liver in the same way as high O-6 consumption does? I ask because over the last year I upped my fish oil to 3.5g/day and coconut oil consumption to 10 Tbs/day and at my latest physical I had elevated liver enzymes.