Cholesterol targets and genetic risk for chronic liver disease

[circular]

We often debate whether high cholesterol is bad for us even when our particle counts and oxidized cholesterol markers are okay. I've been leaning in the direction that high cholesterol is fine, even healthy because needed for so many things, if it's not oxidized or too abundant in harmful forms.

I'm finally focusing on the fact that in my Promethease results, sorted by magnitude, right below my apoe4 glitch showing at the top, is rs738409(G;G) on GMAF. SNPedia says:

While found in 55%+ of all people, alcohol seems to be 3x more damaging to your liver than typical. 5x higher risk for developing fatty liver, and 6x risk of fibrosis. [Emphasis mine]

This must be showing up in many of our results.

When I look up lifestyle risk factors for fatty liver disease, high cholesterol is mentioned. I'm thinking this might mean the cholesterol levels themselves are implicated, independent of one's level of cholesterol oxidation, density, particle counts etc.

Has anyone looked into this issue?

[NewRon]

I'm rs738409(C;G) according to Promethease...can I crack open a Cabernet?

[TheresaB]

When I look up lifestyle risk factors for fatty liver disease, high cholesterol is mentioned. I'm thinking this might mean the cholesterol levels themselves are implicated, independent of one's level of cholesterol oxidation, density, particle counts etc.

If I understand correctly, I think what you’re saying is you think (or your Promethese test is saying) high cholesterol is a risk factor for developing fatty liver disease, in other words, cholesterol first, then fatty liver. Well, according to what I just heard at the Low Carb conference this past weekend, not exactly.

Specifically I’m referring to Dr. Nicolai Worm’s talk on Non-Alcoholic Fatty Liver Disease (NAFLD), he said just the opposite, cholesterol issues come from Fatty Liver. (Dr Worm is German, and has studied “Nutritional Sciences“ at the University of Munich. He is also scheduled to talk at our annual meet-up in San Diego, although eventually his talk from this past weekend at Low Carb Breckenridge is supposed to be placed on YouTube after being edited.)

In his presentation, Dr Worm is quite convinced that cholesterol (as well as cardiovascular disease and other metabolic problems) comes from a NAFLD, not the other way around.

He cited this study, “A concise review of non-alcoholic fatty liver disease” Atherosclerosis 239 (2015) 192-202
https://www.researchgate.net/publicatio ... er_disease
In this study it says, “An increasing body of data suggest that NAFLD is also an independent risk factor of cardiovascular disease, which remains the commonest cause of mortality in such patients.”

Dr Worm said NAFLD comes from 3 sources, in this order: adipocytes (your own fat cells), dietary carbohydrates, and, lastly dietary fat.

He explained that when your fat cells lose their ability to store fat you have an overflow situation and the body looks for other storage places, so it delivers the fat to visceral fat and other organs.

I think what your genetic markers may be saying is something about your fat cells. From another talk this weekend by Dr Ted Naiman, I learned that everyone has a “Personal Fat Threshold” (PFT), in other words, not everyone has fat in the same locations on the body (and we know visceral fat is more dangerous than subcutaneous fat, but not everyone is built with the same fat distribution) nor do the fat cells all respond the same. In most people, when their adipocytes (fat cells) get overstuffed, the cells can’t get oxygen, they become inflamed, and then insulin resistance develops. Some of these insulin resistant people can LOOK THIN (I’m thinking of that buff Biggest Loser Trainer who recently had a heart attack), it’s just their fat cells can’t suck up any more fat. But in 10% of obese people, their adipose just creates more baby fat cells which suck up more fat and these folks don’t become insulin resistant.

Dr Worm said folks with high triglycerides, low HDL, small dense LDLs, including lean/normal weight people, are almost sure to have fatty liver. He also said that with exercise you can increase your angiogenesis (formation of new blood vessels), so people should exercise to keep their muscles AND fat cells fit.

Lastly, about your comment,

I've been leaning in the direction that high cholesterol is fine, even healthy because needed for so many things, if it's not oxidized or too abundant in harmful forms.

I have the same inclination. In another talk given by Dr Dawn Lamanne, who addresses cancer with nutrition and other regimens to enhance conventional treatments, she talked briefly about cholesterol. On one of her slides it said that Higher Total and LDL cholesterol levels seem to be protective against certain types of cancer and that Triglycerides (TGs) are a proxy for carbohydrates and high TGs are detrimental in at least one type of breast cancer. This wasn't the main thrust of her talk, so she didn't go into this but she did say this has been known a long time, but hasn’t been studied much.

[circular]

NewRon I think you'll find some company here to help you uncork that bottle, whatever their genetics

TheresaB, wow, thanks. Great timing for me for that post Now I have got to find a way to exercise those fat cells more My triglycerides and Lp(a) and quite good, my HDL moderately good, and LDL high end of normal. Particle counts that have been measured are good. I think I'm on the right track. My biggest challenge right now is finding enough time for enough exercise to offset the additional fat calories in my diet.

There's also information online about NAFLD and metabolic issues vis diabetes and the like, but I haven't had time to get into it. I imagine the talk covered that as well?

[Hepoberman]

In my mind, there really is no doubt about it, total cholesterol over 150 predisposes us ~4's for trouble down the road. Look for RCT's where they have did angiograms or autopsies -real data with metrics. It becomes pretty obvious.

Very often, cancer patients have low cholesterol. Their bodies are going haywire. If you graph out TC over death with this cohort, this phenomena appears as a "U" graph, misleading the average laymen to assign causation where it does not belong. Low cholesterol does not kill us, high cholesterol does, slowly.

[slacker]

I just finished my thrice weekly BrainHQ session to exercise the fat cells in my brain. And now off to Zumba (shout out to Jafa)!

[Julie G]

In my mind, there really is no doubt about it, total cholesterol over 150 predisposes us ~4's for trouble down the road. Look for RCT's where they have did angiograms or autopsies -real data with metrics. It becomes pretty obvious.

I admire your certainty, Hep. When you get a chance, I’d appreciate links to those studies that definitively prove TC is the biomarker to chase for E4s. From everything I’ve learned, I think TC is a red herring in terms of both CVD and AD. Looking “under the hood” of TC provides information that may be more relevant. We see some members with very low TC (but high LDL-P or ApoB) that may actually predispose them to CVD. TC alone is simply a piece of a larger clinical picture. From the MESA data below, you can see those with low LDL-C, hence TC, when combined with high LDL-P were at the highest risk of a cardiac event.

LDL-P-and-LDL-C-Discordance.jpg

I suspect that LDL-P may be more significant in terms of CVD risk simply because higher levels may be indicative of chronic infection, poor gut health, and thyroid dysfunction. All of which contribute to to both CVD and AD. Tinkering with thyroid may be especially important for E4s as suboptimal function affects LDL-receptor binding capacity that also plays a part in abeta clearance, already a known issue for E4 carriers. Downregulating glycemic markers and upregulating antioxidant status, may also be an important part of the puzzle in terms of keeping cholesterol free from oxidation.