Diet confusion

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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jgilberAZ
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Re: Diet confusion

Postby jgilberAZ » Fri Sep 14, 2018 9:37 am

Plumster wrote:https://www.ncbi.nlm.nih.gov/pubmed/12658281
https://www.ncbi.nlm.nih.gov/pubmed/9600988
https://www.ncbi.nlm.nih.gov/pubmed/23813612
https://www.ncbi.nlm.nih.gov/pubmed/11571339
https://www.ncbi.nlm.nih.gov/pubmed/19345313
And the list of studies linking cholesterol and AD goes on and on and on . . . .


Correct ... cholesterol does play a role.

But, cholesterol itself is not the determining factor ... it's cholesterol in a high insulin / high blood sugar environment.

From the link I posted above:

An emerging body of evidence suggests that an increased prevalence of insulin abnormalities and insulin resistance in Alzheimer's disease may contribute to the disease pathophysiology and clinical symptoms. It has long been known that insulin is essential for energy metabolism in the periphery. In the past 2 decades, convergent findings have begun to demonstrate that insulin also plays a role in energy metabolism and other aspects of CNS function. Investigators reported 20 years ago that insulin and insulin receptors were densely but selectively expressed in the brain, including the medial temporal regions that support the formation of memory. It has recently been demonstrated that insulin-sensitive glucose transporters are localised to the same regions supporting memory and that insulin plays a role in memory functions. Collectively, these findings suggest that insulin may contribute to normal cognitive functioning and that insulin abnormalities may exacerbate cognitive impairments, such as those associated with Alzheimer's disease. Insulin may also play a role in regulating the amyloid precursor protein and its derivative beta-amyloid (Abeta), which is associated with senile plaques, a neuropathological hallmark of Alzheimer's disease. It has been proposed that insulin can accelerate the intracellular trafficking of Abeta and interfere with its degradation. These findings are consistent with the notion that insulin abnormalities may potentially influence levels of Abeta in the brains of patients with Alzheimer's disease. The increased occurrence of insulin resistance in Alzheimer's disease and the numerous mechanisms through which insulin may affect clinical and pathological aspects of the disease suggest that improving insulin effectiveness may have therapeutic benefit for patients with Alzheimer's disease. The thiazolidinedione rosiglitazone has been shown to have a potent insulin-sensitising action that appears to be mediated through the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma agonists, such as rosiglitazone, also have anti-inflammatory effects that may be of therapeutic benefit in patients with Alzheimer's disease. This review presents evidence suggesting that insulin resistance plays a role in the pathophysiology and clinical symptoms of Alzheimer's disease. Based on this evidence, we propose that treatment of insulin resistance may reduce the risk or retard the development of Alzheimer's disease


And this one ...

https://insulinresistance.org/index.php/jir/article/view/15/32

Clinically, Alzheimer’s patients present with decreased cognitive function and lapses in memory that decline progressively and ultimately impact performance of everyday life tasks. Physiologically, AD is characterised by several physical hallmarks that can be measured or observed via biopsy, positron emission tomography (PET) scan, or upon autopsy. These include insoluble extracellular plaques made of beta-amyloid peptide (Aβ); intracellular neurofibrillary tangles (NFTs), loss of hippocampal neurons; and a marked decline in the metabolism of glucose in regions of the brain associated with memory and learning. All of these changes can be logically explained as sequelae resulting from long-term dysregulation of insulin signalling and glucose energetics.


A noteworthy feature of AD is the combination of hyperinsulinism in the periphery with hypoinsulinism in the CNS. Patients with advanced AD show higher plasma but lower cerebrospinal fluid (CSF) insulin concentrations than healthy controls and subjects with mild cognitive impairment. Moreover, the ratio of CSF to plasma insulin levels was significantly lower in patients with advanced dementia, with the degree of difference correlating to dementia severity.33 These compartmentalised alterations in insulin concentration were observed in individuals who lacked the strongest currently known genetic risk factor for development of AD: homozygosity for the ε-4 allele of the apolipoprotein E gene (ApoE4). This suggests again that peripheral hyperinsulinaemia/IR is a significant risk factor for AD regardless of genotype.34


The synthesis and secretion of amyloid precursor proteins are normal physiological processes. The formation of the insoluble plaques is what distinguishes an Alzheimer’s brain from a healthy brain. However, there is no evidence that Alzheimer’s patients secrete more Aβ than healthy individuals; rather, in AD patients, these proteins are not properly degraded and cleared away. The enzyme responsible for degrading amyloid proteins in the brain is insulysin, also known as insulin degrading enzyme (IDE) – the same enzyme tasked with degrading insulin (as well as glucagon, atrial natriuretic peptide, and more). Peripheral hyperinsulinaemia – as seen in T2D, metabolic syndrome and other hyperinsulinaemic conditions associated with greater risk for AD – may induce a functional deficiency of IDE.40 The affinity of IDE for insulin is much greater than that for Aβ, such that the presence of even small amounts of insulin completely inhibits the degradation of Aβ.38,40 Thus, when IDE is saturated with insulin as a substrate, Aβ is left to accumulate and form plaques.


Finally, it is crucial to address the strongest and, to date, only known genetic risk factor for Alzheimer’s disease: possession of one or two ε4 (E4) alleles of the APOE gene (ApoE4). Possession of an ε4 allele is so strongly correlated with AD that it has been called the ‘susceptibility gene’.27 Heterozygotes for ApoE4 have a fivefold increased risk of developing AD, while homozygotes are estimated to have a staggering lifetime risk between 50% and 90%.54 Despite this threatening genetic heritage, the ApoE4 allele is neither required nor sufficient for development of AD: 50% of people with AD are not E4 carriers, and many E4 homozygotes never develop the disease. Chronic hyperinsulinaemia/insulin resistance elevates risk independently of ApoE status, with a 43% increased risk for AD from hyperinsulinism alone, regardless of genotype. Among insulin-resistant individuals who were not diagnosed diabetics (normoglycaemic due to hyperinsulinaemia), the risk for AD was double that of those without IR.15 As hyperinsulinaemia occurs in approximately 40% of people over age 60, it is not surprising to find a correlation between IR and a condition that preferentially strikes the aging.55

Although there are strong correlations between the ApoE4 genotype and AD, the majority of AD patients are not ApoE4 carriers. One potential aggravating factor for the ApoE4 genotype is that ApoE4 homozygotes produce 50% less hippocampal IDE compared to healthy controls, as well as AD patients who are not carriers of the ε4 allele.36 Thus, these individuals may have reduced capacity to degrade Aβ peptides relative to other genotypes, which would explain, in part, the severity of AD observed in ApoE4 carriers. However, it has not been determined whether the ApoE4 gene causes reduced IDE synthesis. The ApoE4 gene and reduced IDE expression could both presumably be the result of an overall hunter-gatherer genotype poorly suited for the modern diet’s evolutionarily discordant amount of refined carbohydrates.41,42,43,56


The single amino acid substitutions that differentiate the three ApoE isoforms affect tendency for apolipoproteins to become glycated, as well as determine binding affinity to any number of enzymes and receptors, which is why the isoforms are associated with different trends in serum low-density lipoprotein (LDL), very low–density lipoprotein (VLDL) and triglyceride measurements, with ApoE4 being associated with hypertriglyceridaemia and elevated LDL – common findings in metabolic syndrome and insulin resistance.56,57,58 Pre-agriculturalists presumably would have derived more of their calories from fat, protein and high-fibre, lower-starch, vegetable-based carbohydrates as opposed to grains and acellular carbohydrates, and may therefore have had a lower requirement for both insulin and IDE.41,43,59,60


The focus should be more on insulin, and less on cholesterol.
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Markus
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Re: Diet confusion

Postby Markus » Mon Sep 17, 2018 2:15 am

Science will never be able to tell us the optimal diet for each individual since studies can only point us in a direction, but in the end we will all have to individualize our diet depending on how we feel and respond to different foods.

The only true method of knowledge is experiment.

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Re: Diet confusion

Postby jgilberAZ » Tue Sep 18, 2018 7:13 am

http://www.zoeharcombe.com/2014/03/anim ... -6-deaths/

Here we find the real headline. What the researchers didn’t want us to find out. The “four times more likely to die” global headline grabber was based on a reference group of six deaths. Yes six deaths. And not just six deaths – but six deaths over an 18 year study. And the ‘researchers’ tried to claim that animal protein is as bad as smoking based on this?
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Re: Diet confusion

Postby Brainz » Tue Sep 18, 2018 8:51 pm

jgilberAZ: Love your posts in this thread and agree with your findings 100%. Great summaries!

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Re: Diet confusion

Postby KimC » Sat Sep 29, 2018 7:24 am

Talk about confused! I recognize there are many opinions out there, but, honestly, how is one to know which is the right one? I've been keto for 16 months, but, cholesterol is much higher. Ran across this site today where it prescribes low fat, high carb for APOE4s. https://www.gbhealthwatch.com/GND-High- ... l-APOE.php

As always, I look forward to everyone's perspective and thank you for this wonderful site!

Sincerely,
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Re: Diet confusion

Postby dcox » Sun Sep 30, 2018 12:56 am

KimC wrote:Talk about confused! I recognize there are many opinions out there, but, honestly, how is one to know which is the right one? I've been keto for 16 months, but, cholesterol is much higher. Ran across this site today where it prescribes low fat, high carb for APOE4s. https://www.gbhealthwatch.com/GND-High- ... l-APOE.php


Welcome KimC!!
I have to agree with you, the opinions on eating for E4's can be overwhelming. Even with all the differing opinions out there, a couple of things run true through them all, reduce or eliminate processed foods, sugar and refined grains, and increase whole real foods. I know that sounds way too simplistic, but it is a great foundation to work from. You stated that you have been on a keto plan for 16 months, how do you feel physically and mentally after eating this way? The reason I ask is that our bodies have a way of telling us if we are eating foods that are nourishing us and/or if we are missing something.
You also stated that your cholesterol is much higher on this type of diet. Total cholesterol taken into consideration by itself can be a little misleading, as it's the LDL cholesterol, and specifically the small dense LDL particles that cause increased risk of cardiovascular disease (CVD), also lipoprotein a, Lp(a), can cause even greater damage. If you haven't already, to gain more insight, you might want to have an advanced lipid panel run, as recommended by Dr. Bredesen in the ReCODE protocol. It will test for Lp(a) and the size and density of your LDL particles, along with a few other specific lipid tests. Sometimes we can have an elevated total cholesterol and our LDL particle size is good (large and "fluffy") which decreases our risk. So this test may give you more information about how your body is utilizing the fats your are eating. The link between high blood glucose and glycated-LDL as brought out in previous posts in this thread, might be another area to check out, as knowing your glucose, insulin and Hemoglobin A1C status, can be helpful in determining diet choices also.
I hope I didn't bombard you with too much "lab" talk, I do believe that knowing your numbers can really help in the "diet" decision making process. Another very important point is that you are an individual with unique circumstances and background, and there is no one-size-fits-all "diet". I love how Markus put it in a previous post:
"Science will never be able to tell us the optimal diet for each individual since studies can only point us in a direction, but in the end we will all have to individualize our diet depending on how we feel and respond to different foods.
The only true method of knowledge is experiment."

I want to give you a huge WELCOME to ApoE4.info, as you have probably already seen this site is loaded with information, great discussions and absolutely wonderful, caring, hopeful people. We are glad you are with us on this journey to reversal, prevention and overall hope and joy. To make navigating the site a little easier please take a look at the Wiki Page, where you will find some more in depth topics; the Primer, written by Stavia one of our most active members, a Doctor, and E4/E4 herself, this is an amazing place to start she truly put her heart into writing it; this page will help you learn how to use the site more efficiently "How-To" Get the most out of the ApoE4.info website; here is a direct link to Stavia's section of the primer on Nutrition to get you started. When the time is right for you we would love to hear a little more about your story, you can post it on the Our Stories forum.

Please feel free to reach out to me or any other person with questions as you dive into the site.

We look forward to learning more about your journey as you share and learn along with us.
Find your joy and hope in each day and each new discovery along your path,
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