How to change size of lipid particles

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
circular
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How to change size of lipid particles

Postby circular » Mon Dec 30, 2019 6:24 am

I have pattern A on the Cardio IQ (TM) Lipoprotein Fractionation, Ion Mobility test, which is good, but if I wanted to improve even more, are there ways to increase my large HDL particles, decrease my small LDLs, and increase my LDL peak size?
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: How to change size of lipid particles

Postby Vikingman » Wed Feb 26, 2020 12:07 pm

I am current working on increasing my large HDL Particles. I should now if what I am doing works over the next 4 months.

Fiver
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Re: How to change size of lipid particles

Postby Fiver » Thu Mar 12, 2020 6:59 pm

What I know, there are *correlated* with greater HDL: niacin, statins, higher estrogen/lower testosterone patterns in females vs. males (up until menopause). This is from memory, I haven't red about this in a year or so.
Four relatives with AD. Concerned, but hopeful. Introverted, but will talk about science.

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Re: How to change size of lipid particles

Postby Eric » Sat Mar 28, 2020 12:14 pm

I wonder if certain statins could be helpful is resisting dementia for those of us who have two APOE e4 genes. I ask this based on a paper which reanylzed the data on tests of statins that did not work in general to slow Alzheimer’s. The statistics on us homozygotes were actually pretty positive. I think it can be looked up at the following url. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316146/

In the abstract of that paper is::

Results
Re-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes.

The charts in that study are stunning. It seems to virtually prevent decline, though it seems there are only about twenty people that fit into this re-analysis. Still...


I personally had my doctor prescribe me 80 milligrams of atorvastatin because I was taking 20 milligrams without any problem. I think this is equivalent to simvastatin because it is one of the so-called lipophilic statins that probably goes through the blood brain barrier. My LDL went way down, to about a third of what it was with no statin, which I think is probably protective against vascular problems, which is also good.

Anyway, I wonder what others might think of my choice.

Thanks, Eric

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Re: How to change size of lipid particles

Postby NF52 » Sat Mar 28, 2020 5:33 pm

Eric wrote:I wonder if certain statins could be helpful is resisting dementia for those of us who have two APOE e4 genes. I ask this based on a paper which reanylzed the data on tests of statins that did not work in general to slow Alzheimer’s. The statistics on us homozygotes were actually pretty positive. I think it can be looked up at the following url. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316146/

In the abstract of that paper is::

Results
Re-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes.

The charts in that study are stunning. It seems to virtually prevent decline, though it seems there are only about twenty people that fit into this re-analysis. Still...


I personally had my doctor prescribe me 80 milligrams of atorvastatin because I was taking 20 milligrams without any problem. I think this is equivalent to simvastatin because it is one of the so-called lipophilic statins that probably goes through the blood brain barrier. My LDL went way down, to about a third of what it was with no statin, which I think is probably protective against vascular problems, which is also good.

Anyway, I wonder what others might think of my choice.

Thanks, Eric
Welcome, Eric!

You have obviously done some serious reading on this topic! For the sake of those who are curious about the study you quoted, here's the link, with the title of the 2017 article, written by a group of scientists from the US and UK: Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease. This is a community that loves a good discussion about topics on which reasonable people can reasonably disagree--and the use of statins is one of them! So expect some lively responses, since many of our members (and professionals they consult) feel that insulin resistance is the real risk for ApoE 4/4 and so they focus on that. But we greatly respect that it is up to each of us to determine our own choices!

I'm guessing that you might be Apoe 4/4, like me. I happen to know of someone taking 80 mg.day of atorvastatin who is also ApoE 4/4, with very high level of total cholesterol diagnoses in her teen years and a devastating family history of early deaths from heart attacks and strokes.

In contrast, I had high LDL-C and LDL-P diagnosed just a few years ago, with family history for late coronary artery disease and vascular dementia and strokes in addition to Alzheimer's. i opted for a 10 mg dose of atorvastatin, which has brought my levels down to normal (along with healthier eating). I'm curious about your doctor's reasoning to quadruple your dose, since I thought the usual practice was to increase gradually and monitor liver function and any side effects.

I'm taking the liberty of copying an excerpt of a previous post by "Fiver", one of our Senior Contributors and a scientist himself. {Note: "Quoting" someone using the single quotation mark in the upper right corner of any post is how they get notified by email of a reply. Always good to use a "quote" to be sure your comment is seen!]

Fiver wrote:The debate about statins is a long one. The best course of action almost certainly depends on our own situations.

I've been on low dose statins, of various sorts, for 3-4 years now. The research convinced me that overall the benefits outweighed the side effects for me. I like that they have an anti-inflammatory effect. They also prevented the usual spike in "bad" cholesterols and TGs when I began a ketogenic diet and was eating lots of nuts and chocolate - yes, this felt a bit like cheating but it worked.

Hope this helps start some good conversation!
4/4 and still an optimist!

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Re: How to change size of lipid particles

Postby Eric » Sat Mar 28, 2020 8:14 pm

Thanks for writing back. I don’t necessarily want to post this, but I want to acknowledge your comment. I have already lost some intellect and expect to fail if I don’t stop it I don’t trust my instincts but do think I can still read the literature, sort of. This was my job, though in economics. This strikes me as an important finding and unbiased. It does not have a large sample but the finding is statistically unlikely unless true, and it makes some sense. And what I have to do to see if it works is minor. Honestly, I don’t think taking statins is worth arguing over. Possibly, it is bad for a tiny few, but the risk seems so small compared to what I face from dementia, particularly as I have already slipped a good bit. Anyway, thanks for taking the time to write.

Eric

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Re: How to change size of lipid particles

Postby NF52 » Sat Mar 28, 2020 8:19 pm

Your intellect and education are both enormously associated with continued normal cognition. I agree that reading articles is thought-provoking, and I was an English major!

Thanks for replying! Hope the forum is helpful.
4/4 and still an optimist!

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Re: How to change size of lipid particles

Postby Eric » Sun Mar 29, 2020 10:25 am

Hi, I do not mean to be too chatty,Fiver, but I like how you wrote and you seem like a nice person; also I did not really answer your questions.

I certainly do not want to argue that anybody's point of view is wrong. They could well be right, whether I agree or not. But I am basically a stats nerd (with a PhD), and I tend to be more persuaded by a peer-reviewed and published paper; that seems careful, honest, and unbiased; and is based on relevant data (by far the best is other e4/e4). I also think I have limited time because I am e4/e4. I am MCI now, my older brother (also e4/e4) has it much worse, my Dad died of it and lots of ancestors died of it, etc. etc. I have scoured the whole field, using my son the doctor's ID (so I can do my best to read/browse all the papers). I am impressed when there are multiple papers supporting a point, when I can mostly follow the logic, and when it has worked on people, particularly e4/e4. I think there are a few good things that meet all my tests. One is at least 40 mg of lipophilic statin. It could be a false positive, but probably not. I am not a big devotee of statins but the evidence against them is fairly minor (from reading of the literature) and the chance it might help in a big way seems strong. I went to my doctor to give me 40mg, cause that was the number in the study I read, and he asked me if I would like to just go to 80. I don't know if he was worried about my liver, but I did it (along with several other things) and I have about bi-monthly blood tests and no weird numbers of any sort, including liver things. (I always have my son and other doctors check it out too!) Since you are taking a statin, please tell me which. It might as well be simvastatin, the one with the most data regarding e4/e4, and you can take 40mg. If you want to go up a little slowly, that would be fine in my mind. -- Eric

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Re: How to change size of lipid particles

Postby Eric » Sun Mar 29, 2020 10:46 am

Oh, I reread your post - you are taking atorvastatin, like me. I think that works too. My son thinks that is OK. Still, I wonder if I should switch to simvastin. The paper is about a 40 mg dose, and there is better data on simvastatin. Is 10 enough for the same effect? Possibly, but the paper is about a 40 mg dose. The keto might be also be good. I could not find much real research on it - just lots of people having opinions. I have used keto sporadically for decades to lose weight, as has a lot of my family. I know it works for that, from experience. If you have any real research about dementia though, please send. I will read it for sure.

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Re: How to change size of lipid particles

Postby NF52 » Sun Mar 29, 2020 1:43 pm

Eric wrote: If you have any real research about dementia though, please send. I will read it for sure.
Hi Eric,

My choice for atorvastatin is based on my doctor's recommendation, the apparent safety and efficacy numbers and my own results. It gets my numbers down into a good range and I have a clear coronary artery scan, so from a cardiac standpoint, I feel fairly confident about avoiding major issues.

As for brain health, it's much harder to know! I am a strong believer in lifestyle, environmental and judicious supplement choices for prevention or amelioration of risk, although I'm far from perfect in my habits. I take 500 mcg of methylcobalamin, recommended by the Generation Study Site Doctor to bring my levels above 500. I also take 2000 mg of Vitamin D3 daily to get that above 50, which seems to be important to brain health. (Don't have the citation at my finger tips.)

I also think clinical trials are a necessary path to expand knowledge of mechanisms of pathology, development of blood-based biomarkers to reduce the need for PET scans and MRI for clinical diagnosis, and determination of the efficacy of numerous "novel targets" for prevention and therapeutic treatment. I was in the Generations I clinical trial of people with ApoE 4/4 for two years. It involved a double-blind, randomized (32% placebo vs 68% CNP520 pill) study of a BACE-1 inhibitor of abnormal cleaving of the amyloid precursor protein. I will find out in early summer if I was on CNP520 or placebo, but was shown various test results early this month that confirmed my cognitive skills had not changed over the trial period. Which also means that I couldn't draw before and still can't, but have decent verbal skills!

Since you have MCI, and asked for "real research about dementia", I'll copy a few things that seem relevant to those of us with ApoE 4/4, who are likely to have elevated amyloid beta, considered to be a key biomarker signifying 'preclinical Alzheimer's disease". Like coronary plaques signifying preclinical heart disease, they are neither necessary nor sufficient for dementia, but seem to me to be a clear canary in the coal mine of increased risk.

This is from a February 2020 paper in the journal Aging, studying "association of job demand-control combinations with dementia, ...APOE ɛ4 and work duration... A total of 2,579 dementia-free individuals aged 60+ years from Sweden were followed over 12 years." Here are their encouraging result for someone with a Ph.D in economics:
...it has been shown that education, job complexity, leisure activities, and social network may attenuate the genetic risk of dementia due to APOE ɛ4 [14], possibly by enhancing cognitive reserve and reducing stress levels. Similarly, in this study, active jobs appeared to nullify the detrimental effect of genetic predisposition, as the risk of dementia among APOE ɛ4 carriers with active jobs was similar to that of the non-APOE ɛ4 carriers with active jobs.
The role of Apolipoprotein E epsilon4 in the association between psychosocial working conditions and dementia

If you are interested in clinical studies directly targeting intervention in people with MCI, this is from the 2018 CTAD (Clinical Trials for Alzheimer's Disease) conference, with a report on tramiprosate, an anti-amyloid drug that specifically targets amyloid beta oligomers, not the monomers targeted in earlier anti-amyloid trials. Here is the link, with the topic title, and an excerpt: CLINICAL BENEFITS OF TRAMIPROSATE IN ALZHEIMER’S DISEASE ARE ASSOCIATED WITH HIGHER NUMBER OF APOE4 ALLELES: THE “APOE4 GENE-DOSE EFFECT”
Results: Highest efficacy was observed in APOE4/4 homozygotes receiving 150 mg BID of tramiprosate, showing statistically significant effects on ADAS-cog and positive trends on CDR-SB (respectively, 40-66% and 25-45% benefit compared to placebo). APOE4 heterozygotes showed intermediate efficacy, and non-carriers showed no benefit. In 426 patients with MRI scans, no cases of treatment-emergent vasogenic edema were observed. In the three subgroups, the most common adverse events were nausea, vomiting, and decreased weight.
Conclusions: The “APOE4 Gene-Dose effect” is likely explained by the high prevalence of amyloid pathology in symptomatic APOE4 carriers. In APOE4/4 Alzheimer’s disease patients, the high dose of tramiprosate showed favorable safety and clinically meaningful efficacy in addition to standard of care.


This isn't research, but it is a link to a summary of the development of ALZ-801. the current
trial drug for tramiprosate, that includes a link to the company website and the NIH Clnical Trials. gov website. https://www.alzforum.org/therapeutics/alz-801

Here's a February 2020 summary of an adopted 2018 revised framework to guide research (not clinical practice) in diagnosing and studying Alzheimer's disease (AD). It's not specifically about ApoE 4/4, but does have useful information about thinking of AD progression as likely to involve a triad of key biomarkers (and maybe many more), which may signal important variations in what we call "Alzheimer's Disease".
In 2018, the National Institute on Aging and Alzheimer’s Association (NIA-AA) proposed a new research framework focusing on diagnoses of AD with biomarkers for living persons (17). The scheme [which is labeled AT (N)] is based on grouping biomarkers into 3 categories: β amyloid deposition (A), pathologic tau (T), and neurodegeneration (N) (17). ...ApoE ε 4 (+) prodromal AD participants had lower levels of CSF Aβ 1-42, higher levels of t-Tau, more memory and global cognitive impairment, and faster decline of global cognition, compared to ApoE ε 4 (−) prodromal AD. ApoE ε 4 (+) prodromal AD participants had a thinner cortical thickness of bilateral entorhinal, smaller subcortical volume of the left amygdala, bilateral hippocampus, and left ventral diencephalon (DC) relative to ApoE ε 4 (−) prodromal AD. Furthermore, the cortical thickness average of bilateral entorhinal was highly correlated with memory and global cognition.
The effect of ApoE ε 4 on clinical and structural MRI markers in prodromal Alzheimer’s disease

Another source of information on clinical trials, as well as information I only recently came to appreciate as important on pre-planning for those of us at risk. The Alzheimer's Association spends millions each year to support research on prevention and treatment of AD, and has a Trial Match of studies that include non-drug trials. You can read more here:
Trial Match

The Alzheimer's Clinical Trial Consortium (ACTC) is a network of dozens of academic research centers collaborating to accelerate research, with funding from the National Institute on Aging (NIA/NIH). They have an online Alzheimer's Prevention Trial web study called for people who are 50 years or older. You can find information about it here: APT Webstudy Welcome (Full disclosure: I am on the Research Participant Advisory Board for the ACTC, although I am not in any ACTC-sponsored clinical trial.)

To search for clinical trials (large and small) by your region, try the advanced search function on the NIH Clinical Trials website. Each trial has detailed information about its purpose, the criteria to join and contacts for study sites. Clinical Trials.gov

Apologies for a very long reply! I would love to hear what you think are the best textbooks or sources for people like me to develop some competency with statistics. I have read a great short book on reading medical studies, written by a British researcher based on his work with primary care docs seeking to be better consumers of research. I have the privilege to sit with researchers and biostatisticians once a year as a reviewer of grant proposals, They are always kind to this "consumer reviewer", and make me regret my decision to avoid statistics in favor of psychology in college!

If you have specific areas of dementia research you're looking into, let me know. We can both show that people with ApoE 4/4 continue to learn throughout our lives!
4/4 and still an optimist!


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