New Article Re Nutrient Intake, Amyloid & Glucose Metabolism

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circular
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by circular »

So, dark leafy greens, cruciferous vegetables, legumes, grains, and fresh fruit REDUCED glucose metabolism for E4 carriers (especially women & those with a family history) :shock: How do we explain this?
Could this have anything to do with some sort of gene switching, where some E4 communication goes on when healthy foods are eaten that down regulates (term?) glucose metabolism genes because the E4 body thinks it's now getting the lower carb diet it needs? Sort of like E4 is saying yes, it's vegetables I want in *order* to not be processing glucose with all the attendant problems. I don't need the glucose metabolism going strong.

Totally crazy idea but just stretching to understand this.

I think the population size is a serious problem. I wouldn't give it a lot of weight at this point. I don't have time to read the article at all, let alone carefully, so I don't know if all the people also ate a lot of glucose.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by RBK »

I'm glad others have some time to dig deeper for the rest of us to gain some knowledge. The idea of spinach and kale somehow being bad for me makes my brain hurt! Really do appreciate everyone's active work here.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Stavia »

Juliegee wrote:I'm reading it the same way, Stavia.. but you may have missed this relevant nugget:
β-carotene and folate were associated with reduced glucose metabolism for women, apolipoprotein E epsilon 4 (APOE4) carriers and participants with positive AD family history, but not for their risk-free counterparts.
So, dark leafy greens, cruciferous vegetables, legumes, grains, and fresh fruit REDUCED glucose metabolism for E4 carriers (especially women & those with a family history) :shock: How do we explain this?

Oh! Weirrrrd....counter other data....I dont believe it.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by SusanJ »

Another long post...helps me clarify my understanding/thinking, so bear with me.

Since I’ve been looking into macular degeneration (I’m at risk according to 23andme), I’m guessing betacarotene itself may not be the problem, but the interaction with other snp variants that were not identified. (I’ve also been interested because both AD and AMD have the presence of amyloid β - in the plaques of the AD brain and in the drusen of AMD patients. Might there be a common mechanism/cause?)

Here goes my take on betacarotene and blood glucose regulation. Interactions between a zinc transporter gene and betacarotene influences diabetes risk.
...the strongest evidence for interaction in our data was between rs13266634, a non-synonymous coding SNP in the SLC30A8 gene and three nutrient factors, trans- and cis-β-carotene, and γ-tocopherol. SLC30A8 is expressed in pancreatic islets and localized in insulin secretory granules of islet β cells. It appears to modulate insulin secretion and storage (Chimienti et al. 2004, 2005)...Our study enabled us to hypothesize that impaired insulin secretion driven by rs13266634 may increase T2D risk if combined with high or low levels of specific nutrients.
(C is the risk allele)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625410/


In addition, in women, at least one study found a high incidence of a snp that decreases the ability to convert betacarotenes. So you might get high betacarotenes in your diet, but not be able to utilize them.
In double-tracer studies, 27–45% of volunteers have been classified as poor converters (19⇓ 20⇓ 21)⇓ . These individuals have a capacity to form only 9% vitamin A from β-carotene compared with those who are classified as normal converters (21)⇓ . This large interindividual difference might be caused by reduced enzymatic activity as a consequence of genetic polymorphisms in the BCMO1 gene.

Here we describe the screening of the total open reading frame of the BCMO1 coding region that led to the identification of two common nonsynonymous single nucleotide polymorphisms (R267S: rs12934922; A379V: rs7501331) with variant allele frequencies of 42 and 24%, respectively. In vitro biochemical characterization of the recombinant 267S + 379V double mutant revealed a reduced catalytic activity of BCMO1 by 57% (P<0.001). Assessment of the responsiveness to a pharmacological dose of beta-carotene in female volunteers confirmed that carriers of both the 379V and 267S + 379V variant alleles had a reduced ability to convert beta-carotene, as indicated through reduced retinyl palmitate:beta-carotene ratios in the triglyceride-rich lipoprotein fraction [-32% (P=0.005) and -69% (P=0.001), respectively] and increased fasting beta-carotene concentrations [+160% (P=0.025) and +240% (P=0.041), respectively]
rs12934922 and rs7501331 (T is the risk allele on both)
http://www.fasebj.org/content/23/4/1041.long

So, one might have higher circulating betacarotenes from good eating habits, but depending on their snps, still have problems utilizing them!

So, there might have been enough women in this nutrient intake study, with altered betacarotene metabolism, that uncovered this connection with blood glucose regulation.

Throw in the APOE4 lipid transport issues, and betacarotenes and Vitamin A might not be making it to their job sites effectively.
However, an association of vitamin A with the apo E polymorphism was found in women, with apo E2 carriers exhibiting a slightly higher concentration than other subjects (19). These results indicate an influence of the apo E polymorphism on antioxidant vitamins, which may be modulated by sex (19).
http://ajcn.nutrition.org/content/81/3/624.full

And, if possible glucose dysregulation isn't bad enough, not enough Vitamin A (derived from betacarotene or perhaps supplements) impacts amyloid deposition in our mouse friends.
http://www.ncbi.nlm.nih.gov/pubmed/22221326
http://www.ncbi.nlm.nih.gov/pubmed/24582848

Fortunately, it looks like there are clinical trials in humans underway with various retinoids.

In addition, high circulating levels of betacarotenes can have other consequences.
A puzzling finding of this study is that participants with a G allele in rs6564851 had significantly lower levels of lycopene, lutein, and zeaxanthin plasma concentrations. Lycopene, lutein and zeaxanthin are synthesized only by plants and mammals need to consume them in their diet. Because of their molecular structure, there is no reason to believe that these carotenoids are a direct target for BCMO1. However, it has been proposed that carotenoids antagonize absorption of each other, suggesting that uptake by intestinal cells is a protein-transport facilitated process.54 Thus, it may be hypothesized that, through a still-unknown mechanism, higher α- and β-carotene plasma levels directly affect absorption, cell transport, and bio-availability of other carotenoids that are not vitamin A precursors.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668002/

And BTW, low lycopene, lutein and zeaxanthin are also a risk factor in AD (and especially in AMD - in fact they recommend supplementing these for AMD patients).

Serum lycopene, lutein and zeaxanthin, and the risk of Alzheimer's disease mortality in older adults.
http://www.ncbi.nlm.nih.gov/pubmed/24247062

So, the way I see this is that perhaps not a problem with betacarotene per se, but getting it converted so our bounty of antioxidants from food can actually do their jobs.

My guess is that the same problem, a series of folate metabolism / methylation snp variants, might be impacting the results for folate but working on that path will take more brain power than I have left tonight.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by circular »

Wow, thanks SusanJ! Very interesting. My father has early MD and my mother's family has had AD. I was C,C for the first gene, normal for the next two, and had one G for the last. Much to think about, and probably better focus more on the MD/AD nutrients you mention at the end while dialing back beta carotene? I only get these in my diet currently. I supplement Bs, folic acid (the fancy form) but have no MTFR problems that I'm aware of, as well as D and luteolin and curcumin. Think I better print your comments out.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Julie G »

Seems plausible, Susan, especially if these are common variants. Reproducing the study with a larger sample size would be telling.

The researchers seem to have good credentials, Stavia. I'm planning to write to Dr. Lisa Mosconi on our behalf to get her "take" on a possible mechanism. With your permission, Susan; I'll toss your idea to her.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Welcomeaboard »

Susan excellent research as I was on the thought something was amiss on something and my first thought was something with the vitamin a but was looking in other areas as well.

There is also these telling and glaring issues as if you look under dietary assessments. These were self reported under wil let's 116 foods in 30 food groups of which they picked out only 10 known risk foods for AD. Well what if the people fudged on what they reported or remembered something that they thought they did but was not the fact. Then we have the what about the 106 other foods and how they may have effected the absorption of the 10.

To be fair the study said they needed more studies and I whole heartedly agree.

Finally, Susan I think your work on vitamin A conversion is significant as there could be a minor sub group effected by this issue or a larger than expected amount. Either, way as I have stated without the tests you cannot be sure what is happening by your diet and supplements. This is a case where someone could think that I am on the right diet so no need to worry or test and what the hell happened to me. And the answer would be in some cases an unknown malabsorption issue because you did not have a genetic test or this brain scan. So in fact you had scammed yourself into a false belief. There could also be other genetic mutations that are not known at this time genetically to also cause this issue so the brain scan would be required and may indicate looking for those unknown mutations.
I would want to look at food interactions and or cancellations.
The statement about excellent circulating vitamin a in the blood and no test to determine what is actually being used is telling as well, I am not familiar enough to state that there is not. This reminds me of circulating vitamin d being fine but 25 hydroxy vitamin d 3 not showing fine.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Welcomeaboard »

Another point is vitamin a is fat soluble and salmon has fat and vitamin a among other things. We could be seeing a low fat or no fat meal of these vegetables causing no or little absorption of vitamin a. The concept is if all you ate was vegetables with no fat to get vitamin a as you thought that was healthy eating then you may have caused your own demise
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Welcomeaboard »

I eagerly await your folate analysis(Susan).
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Russ »

Susan, Want to note that this point about beta-carotenoids form veggies not being in a form that many people can convert properly into a usable form was central in the recent Chris Masterjohn talk on fat soluble vitamins that I went to. He said that it was genetics, but I don't recall that he said which genes. His main point was that unless you're sure to know you're one with the effectives genes, you must get your vitamin A from animal products (e.g. liver) to ensure you get the form of Vit A you know your body can use.
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