Sterol Absorption and synthesis

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Julie G
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Re: Sterol Absorption and synthesis

Postby Julie G » Tue Oct 23, 2018 12:44 pm

@Julie
I think Dayspring makes the case that
a) phytosterol supplementation is not good versus plant ingestion which is ok.
b) only if you are a hyperabsorber, would potentially ingesting more plant sterols be a potential problem. I assume this to mean if you are NOT a hyperabsorber, your body would not absorb even the additional plant sterol as it has a more natural affinity to cholesterol, not phytosterols or stanols.

Hi Ski!

a.) yep
b.) That's the claim. I guess I'm questioning the validity in a population with a skewed diet- i.e. plant-based keto. This paper is the best I can find. I presume that "validation" is based upon the sheer number in the cohort- 667,718 but that's not exactly the same as using a database of folks all eating the same skewed diet & then measuring hyperabsorption.

Did you ever test your absorption of sterols? If sitosterol is an issue (as it is for many E4s) seems like ezetimibe alone might be enough. :idea:

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Re: Sterol Absorption and synthesis

Postby Ski » Tue Oct 23, 2018 4:27 pm

Julie G wrote:Did you ever test your absorption of sterols? If sitosterol is an issue (as it is for many E4s) seems like ezetimibe alone might be enough. :idea:


No I didnt as to me the end result was important, regardless of whether I was or was not. Having said that though I am going to test on statin therapy to ensure desmosterol is adequate.

Ive done Zetia monotherapy and the drop in lipids was small in comparison. Dayspring ( I believe) mentions that E4's because of the hyperabsorption, do not respond well to a statin because their body naturally down-regulates cholesterol synthesis due to the abundance of cholesterol being absorbed. However, this was not true in my case and I definitely see a bigger response with statin monotherapy over Zetia monotherapy.

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Re: Sterol Absorption and synthesis

Postby Jostmeister » Thu Oct 25, 2018 6:47 pm

Newbie question here.
Is there any consensus on the effect of statins on brain health?
One thing I was a bit disappointed in the Podcast with Peter Attia and Tom Dayspring, was a lack of discussion about the side effects of statins other than dismissing that it's just people on the internet that have no idea what they are talking about.
I have started a kept diet and have had my LDL-C go up significantly with trigs going down.
There seems to be a lot of opinions about this and it's very confusing. Some say it's dangerous (Dayspring for example) others think it's OK if you are on a clean diet with low inflammation. But it doesn't seem anyone really knows how endothelial damage occurs...

Thoughts?

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Re: Sterol Absorption and synthesis

Postby MarcR » Thu Oct 25, 2018 10:52 pm

Jostmeister wrote:Is there any consensus on the effect of statins on brain health?
I don't think so - opinions here run the gamut.

I am not a fan of statins, and I think the lipid hypothesis of heart disease belongs with the other false flags of conventional nutrition and medicine - whole grains are good, fat is bad, saturated fat is especially bad, industrial seed oils like canola and soybean are good, salt intake should be minimized, etc.
One thing I was a bit disappointed in the Podcast with Peter Attia and Tom Dayspring, was a lack of discussion about the side effects of statins other than dismissing that it's just people on the internet that have no idea what they are talking about.
Attia has been dismissive to the point of arrogance of anyone who questions his faith in the lipid hypothesis and in statins. His aggressive interruptions and overtalking of Dave Feldman in a recent podcast signify a level of defensiveness that I associate with cognitive dissonance - unlike Feldman, he seems to have closed his mind entirely to new information.
But it doesn't seem anyone really knows how endothelial damage occurs...
I agree with you. Dayspring and Attia think they know, but from what I have read they actually only understand what happens after damage begins. They beg the question of how and why a particle enters the endothelium - the very first step in the lipid hypothesis - by citing the correlation of particle concentrations with CVD in uncontrolled observational studies. The story seems to be that the particles are like little BB's, and each little BB has a chance of piercing the vascular endothelium. When there are more particles, more of those pesky little BBs veer sideways and open up endothelial wounds. Unfortunately for the credibility of the story, no one has observed this simple analogy in action as an actual phenomenon, and correlation doesn't imply causation any more than visits from fire trucks cause fires to start.

We have discussed this issue from multiple angles over the years. I particularly recommend these topics:

Cholesterol is a passenger, not a driver - Dave Feldman
Rethinking the etiology of CAD
Chris Masterjohn on saturated fat

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Re: Sterol Absorption and synthesis

Postby Julie G » Fri Oct 26, 2018 8:16 am

One thing I was a bit disappointed in the Podcast with Peter Attia and Tom Dayspring, was a lack of discussion about the side effects of statins other than dismissing that it's just people on the internet that have no idea what they are talking about.

Hi Jostmeister! This was actually discussed in great detail near the end of Part IV. Dayspring and Attia were adamant that there is a subset of people for whom statins were NOT appropriate because of the resulting cognitive decline symptoms. They even hypothesized as to the pathway; demsosterol depletion. For folks in this subset, they discussed safer ways of taking a stain or using other lipid lowering medications- ezetimibe and fibrates. I was actually impressed that this was discussed in a very nuanced and detailed manner. So much of the lipid talk on the web, tends to be black and white. Most of this discussion was shades of gray. Take another listen to that section.
I agree with you. Dayspring and Attia think they know, but from what I have read they actually only understand what happens after damage begins. They beg the question of how and why a particle enters the endothelium - the very first step in the lipid hypothesis - by citing the correlation of particle concentrations with CVD in uncontrolled observational studies

To Marc's point, this was the most disappointing part of the entire series for me. Other than observing that people used to die in droves from myocardial infarctions and that occurs less now (implying Pharma has helped) AND vaguely referencing dozens of papers that make the correlation Marc speaks about, they didn't dive into any of the plausible alternative theories. (I do think that some of the correlative papers did attempt to control for other variables, like insulin resistance, but I'd have to scan the transcript to see if they included links to any.) At one point, Dayspring made a comment that guessing a high particle count won't be risky without the presence of insulin resistance is a dangerous proposition. He indicated that we just didn't have the data.

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Re: Sterol Absorption and synthesis

Postby Jostmeister » Sat Oct 27, 2018 11:04 am

Marc,
Thanks for the links to those threads, I will give them a read. I'm trying to stay open to the possible different scenarios that increase cardiovascular disease and trying to do things that will lower my risk.
Exercise is seems is a no brainer for CV health as well as brain health.
Sleep is also a no brainer for overall health.
Diet seems to be the one variable that I'm trying to work out in relation to high lipids. I love the ketogenic diet, feel great on it and have lost weight and it's easy to keep off. I hated the low fat, high carb diet as I was always starving, and it was a bit of a yo-yo diet for me.

I would like to believe that higher lipids in a low inflammatory environment with low trigs is not a problem, but it seems there is also not a lot of proof of this hypothesis either, as far as I have read so far...

There was a post on diet doctor about a study that analyzed LDL-C (I think this was the metric) of numerous studies and they came to the conclusion that it was not correlated as closely as the mainstream medical community would say.

I feel like I need to take a medical statistics course so I can read the actual studies and analyze the data myself, because I have read what someone has said about a study, then read it myself and did not come to even close to the same conclusions...

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Re: Sterol Absorption and synthesis

Postby Jostmeister » Sat Oct 27, 2018 11:14 am

Hi Jostmeister! This was actually discussed in great detail near the end of Part IV. Dayspring and Attia were adamant that there is a subset of people for whom statins were NOT appropriate because of the resulting cognitive decline symptoms. They even hypothesized as to the pathway; demsosterol depletion. For folks in this subset, they discussed safer ways of taking a stain or using other lipid lowering medications- ezetimibe and fibrates. I was actually impressed that this was discussed in a very nuanced and detailed manner. So much of the lipid talk on the web, tends to be black and white. Most of this discussion was shades of gray. Take another listen to that section.


Thanks Julie, I was multitasking in listening to much of the podcast. I will go back and have another listen to that part. I do remember the part about using other lipid lowering medications in addition to a statin, but I think my brain was overflowing by that time :) .


To Marc's point, this was the most disappointing part of the entire series for me. Other than observing that people used to die in droves from myocardial infarctions and that occurs less now (implying Pharma has helped) AND vaguely referencing dozens of papers that make the correlation Marc speaks about, they didn't dive into any of the plausible alternative theories. (I do think that some of the correlative papers did attempt to control for other variables, like insulin resistance, but I'd have to scan the transcript to see if they included links to any.) At one point, Dayspring made a comment that guessing a high particle count won't be risky without the presence of insulin resistance is a dangerous proposition. He indicated that we just didn't have the data.


I agree. I would have liked to heard more about other possibilities for endothelial disfunction.
As I mentioned in my post above, about that paper that postulated that higher LDL was not so strongly correlated with CVD, I would have liked to hear some discussion about some of these other studies that have a differing opinion. Especially ones that are in PubMed.

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Re: Sterol Absorption and synthesis

Postby MarcR » Sun Oct 28, 2018 12:00 pm

Jostmeister wrote:I would like to believe that higher lipids in a low inflammatory environment with low trigs is not a problem, but it seems there is also not a lot of proof of this hypothesis either, as far as I have read so far...
I approach questions like these from an evolutionary standpoint. My baseline assumptions are these:

  • We homo sapiens are functional animals, honed by billions of years of natural selection.
  • Human biology is unfathomably complex - all interventions have unintended consequences.
  • The modern epidemic of chronic disease stems from a mismatch between current circumstances and the ones in which we evolved.
  • Plausible high-impact mismatch candidates include aspects of daily life that have changed recently.
The candidate list is long, but I am especially skeptical of invented products designed for regular ingestion - foods and the subset of drugs intended for chronic use. Foods are the building blocks of our bodies, and chronic use drugs can alter our natural functional state in unexpected ways. The simplicity of invented products does not match the complexity of our bodies.

With that in mind, where should I place the burden of proof? Identifying the idea "that higher lipids in a low inflammatory environment with low trigs is not a problem" as a hypothesis begs two key questions:

  1. Is there really something wrong with how homo sapiens' lipid biochemistry functions?
  2. If so, does manipulating lipid biomarkers with drugs correct what is wrong without so many side effects as to reduce wellbeing and/or lifespan?
It's not a hypothesis that our natural state is functional. It's a full-fledged theory backed by the spectacular success of an entire species. For me the baseline is trusting that our amazing bodies are doing what they should and that our levers for avoiding chronic disease are the choices and activities that align our circumstances more closely with the environment to which we are adapted:

  • Choose minimally processed, nutrient-dense food. Especially avoid industrial seed oils.
  • Fast regularly and avoid overnutrition.
  • Engage each day in substantial physical activity and maintain robust musculature.
  • Prioritize sleep.
  • Reduce stress.
  • Avoid toxins.
For me, the bar for taking any drug chronically is high. All chronic use drugs are in my toxin category until proven otherwise, and I'm deeply skeptical of the evidence offered as proof by profit-seeking corporations with long histories of deceit. The case for lipid biomarker manipulation with drugs seems to me to be exceptionally weak.
I feel like I need to take a medical statistics course so I can read the actual studies and analyze the data myself, because I have read what someone has said about a study, then read it myself and did not come to even close to the same conclusions...
I think a medical statistics course may be overkill - academic incentives are perverse, and most data is hoarded. I think once you understand the usual result metrics - P values and hazard ratios - you will be well equipped to wade in. For a starter project :-), I recommend this 8-year study of 100,000+ people without preexisting diabetes or heart disease. The results associate cholesterol in the 200-300 range with LONGER life. Cholesterol in the sub-200 range recommended by traditional medical authorities is associated with SHORTER lifespans. Besides being exceptionally high powered and lengthy, the study is especially applicable to those of us who are insulin sensitive because it excluded sick people and focused on a cross-section of middle-aged individuals who navigated the contemporary nutritional minefield reasonably well to 1997.

The effect is not small. As per Table I, those with total cholesterol between 193 and 232 experienced death at 73% of the rates of those with TC < 193, and those with TC between 232 and 309 experienced death only 68% as often as those with TC < 193.

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Re: Sterol Absorption and synthesis

Postby SoCalGuy » Sun Oct 28, 2018 6:29 pm

I listened to the podcast series as well. It was super helpful and great timing due to the fact I have an upcoming visit to the doctor to take another look at my lipid panel. After hearing Dr. Dayspring I was planning on getting the panel that Hepoberman had done in the original post. Is this panel called "Sterol Absorption and synthesis" or does it go by another name?

Based on Dr. Dayspring's comments I am most likely to go the "baby statin" + zetia route. I just want to know where my desmosterol is prior to starting so we can track that and make any necessary changes to ensure my brain gets all the cholesterol it needs. With a low-dose statin it may not be an issue but I don't want to take any chances.


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