New Article Re Nutrient Intake, Amyloid & Glucose Metabolism

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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Russ
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Russ »

I agree this is a very good paper, but it is difficult to parse, and I still find some other things at least confusing if not contradictory.

For example, the matching of food with nutrient for B12. The abstract says…
The associations of vitamin B12, vitamin D and ω-3 PUFA with PiB retention were independent of gender, APOE and family history. The identified nutrient combination was associated with higher intake of vegetables, fruit, whole grains, fish and legumes, and lower intake of high-fat dairies, meat and sweets.
…but if we go to bottom of page 5, we find…
Correlations between nutrients associated with PiB and food groups showed that vitamin B12 was mainly from meat, eggs and butter with correlation coefficients of 0.35, 0.31 and 0.36, respectively, (p<0.04). Vitamin D was mostly from low-fat dairies and fish (0.64 and 0.55, p<0.001), and ω-3 PUFA EPA from fish and other vegeta- bles (0.36 and 0.31, p<0.01).
So I would think that their data suggest that meat, eggs and butter were good because they are good for B12, but no. Later on on page 6 in the Discussion, the authors make a general statement anchored by references, but do not reference the data… then follow it with a 'consistent with' statement that does reference their own data and a call to get more data...
Despite differences in the analytic approaches, high adherence to dietary patterns charac- terised by higher intakes of fruits, vegetables, fish, nuts and legumes, and lower intake of meat, high-fat dairies and sweets, is consistently associated with reduced risk for AD.3 4 21 55–59 The food sources associated with the nutrients identified as being AD protective using brain PET in this study are consistent with prior epidemio- logical findings. Other studies are needed to test for spe- cific associations between PET biomarkers, specific food groups and risk for AD.
So isn't there an inconsistency in their own data and conclusions? Do I miss something? On this aspect, although I think they gathered good data, it's one of those cases where actually digging deeper into the data would be required. Specifically, the details of how they mapped foods to nutrients may be key.

On another aspect, I, too, was at first confused by whether increased or decreased brain glucose metabolism was good or bad. The authors do make it clear that they (and the literature) think that increased glucose metabolism is desirable. Seems like it might be important to understand what exactly this FDG-PET Scan is actually measuring. Off to do a little googling...
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

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Got enough on FDG-PET at Wikipedia and now it makes sense anyway. In short, and insulin-resistant brain would show decreased uptake of this glucose-based marker FDG, and thus correlate as a sign of Alzheimer's. There may be some subtleties, but the basic idea seems sound.

For those interested to understand, here's the wiki and a few key quotes…

http://en.wikipedia.org/wiki/Positron_e ... tomography
PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), called FDG-PET, is widely used in clinical oncology. This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly growing malignant tumours). A typical dose of FDG used in an oncological scan has an effective radiation dose of 14 mSv.[22] Because the oxygen atom that is replaced by F-18 to generate FDG is required for the next step in glucose metabolism in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the phosphate added by hexokinase. This means that FDG is trapped in any cell that takes it up, until it decays, since phosphorylated sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the brain, the liver, and most cancers. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin's lymphoma, non-Hodgkin lymphoma, and lung cancer. Many other types of solid tumors will be found to be very highly labeled on a case-by-case basis—a fact that becomes especially useful in searching for tumor metastasis, or for recurrence after a known highly active primary tumor is removed. Because individual PET scans are more expensive than "conventional" imaging with computed tomography (CT) and magnetic resonance imaging (MRI), expansion of FDG-PET in cost-constrained health services will depend on proper health technology assessment; this problem is a difficult one because structural and functional imaging often cannot be directly compared, as they provide different information. Oncology scans using FDG make up over 90% of all PET scans in current practice[citation needed].
In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer's disease greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to differentiate Alzheimer's disease from other dementing processes, and also to make early diagnosis of Alzheimer's disease.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

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I just read one. Why cells starved of iron burn more glucose. Eating a diet high in iron could be the issue?
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

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Another is iron and diabetes revisited. Where iron overload is associated with diabetes and it states women have a three? times risk of GDM with high iron, etc. May be worth looking into since the foods they were eating were high in iron and who knows maybe they had hemochromatosis to boot or bad iron genes.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by SusanJ »

Thanks everyone for the feedback. Keep me honest, that's all I ask.

Julie, send away. It's my working theory, and have I been supplementing accordingly because I don't want to go blind. So I'd love to hear from others farther up the scientific food chain if this need tweaking.

Russ, I would love to know what snps might be related to Vitamin A in Masterjohn's talk. A quick search didn't turn up anything for me. And good point about liver - have some planned for tomorrows dinner, since the hubs is out of town and can't stand it. ;)

WA, I think we all have these glitches in different metabolic pathways that can express themselves poorly or well depending on environment factors. Iron is another one. And eating some fat with fat-soluble vitamins, well, its a good reminder for all of us. And I also eagerly await my folate analysis... :lol:

Generally, I think there needs to be another, larger study, but maybe a little more robust in terms of tracking diet, and the genetic and lab testing they perform. They have some hints coming out of this research, and need to broaden/deepen their thinking a bit. If it turns out that specific metabolic pathways (including snps and nutrients) can be pinpointed, then we all have a chance to fiddle with our diet/supplements to stay as healthy as possible.

Circ, check for the AREDS 2 work on macular degeneration. If your dad isn't supplementing, you'll know which ones he needs.
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

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So isn't there an inconsistency in their own data and conclusions? Do I miss something? On this aspect, although I think they gathered good data, it's one of those cases where actually digging deeper into the data would be required. Specifically, the details of how they mapped foods to nutrients may be key.
My point exactly! Meat, butter & eggs are apparently beneficial for all (including E4s) due to the B12. Yet saturated fat (processed meat, salad dressings, and sweets) are harmful for E4s. By using their data, could we deduce SFA is beneficial and nitrates, trans fats, white flour & sugar are harmful? I think we need to go back to the raw data on this one.

Yes WA, Susan & Russ, insufficient fat or genetics could help explain the negative association of beta carotene and folic acid with glucose metabolism. Thanks Susan for your comprehensive explanation. I will share your idea with the corresponding author.
On another aspect, I, too, was at first confused by whether increased or decreased brain glucose metabolism was good or bad. The authors do make it clear that they (and the literature) think that increased glucose metabolism is desirable.
I hear you. Others have made the same comment. This is an area that I've delved into fairly deeply. Non-symptomatic E4 carriers years/decades before symptoms show demonstrate impaired glucose metabolism per PET scans in the same regions of the brain as AD patients- that's huge. So, yes- increased glucose metabolism is desirable. This is another reason why producing some daily ketone bodies (via lower carbs, CR, exercise) has been speculated to be neuroprotective in our population. The ketones provide an alternate cerebral energy source staving off neuronal death.

Pal, my smart friend, what say YOU on this perplexing paper?
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

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Susan, Found my notes from Masterjohn talk. Citation was to this paper from Leung et. al. (2009) in FASEB Journal…

http://www.fasebj.org/content/23/4/1041.short

According to my notes, bottom line rule of thumb is that people of European descent convert poorly, and Chinese/Japanese convert better. From abstract of paper, looks like key gene is BCMO1 gene, but I know you will digest this one better than me… ;-)

Abstract
The key enzyme responsible for β-carotene conversion into retinal is β-carotene 15,15′-monoxygenase (BCMO1). Since it has been reported that the conversion of β-carotene into vitamin A is highly variable in up to 45% of healthy individuals, we hypothesized that genetic polymorphisms in the BCMO1 gene could contribute to the occurrence of the poor converter phenotype. 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 β-carotene in female volunteers confirmed that carriers of both the 379V and 267S + 379V variant alleles had a reduced ability to convert β-carotene, as indicated through reduced retinyl palmitate:β-carotene ratios in the triglyceride-rich lipoprotein fraction [−32% (P=0.005) and −69% (P=0.001), respectively] and increased fasting β-carotene concentrations [+160% (P=0.025) and +240% (P=0.041), respectively]. Our data show that there is genetic variability in β-carotene metabolism and may provide an explanation for the molecular basis of the poor converter phenotype within the population.—Leung, W. C., Hessel, S., Méplan, C., Flint, J., Oberhauser, V., Tourniaire, F., Hesketh, J. E., von Lintig, J., Lietz, G. Two common single nucleotide polymorphisms in the gene encoding β-carotene 15,15′-monoxygenase alter β-carotene metabolism in female volunteers.
Edit: This newer paper that cites Leung looks like it might be more inclusive and holistic…

http://www.mdpi.com/2072-6643/3/1/63/htm
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by pal »

In the context of the entire article and the tables cited, I believe there is a typo in the summary and it should say "increased" glucose metabolism (see below). So yes you can continue to eat your green leafy vegetables, fruit, and legumes. :-)

Keep in mind there are two independent studies discussed in this article: (1) tests re the amount of amyloid in the brain, and (2) tests re glucose metabolism. The results re B12, vitamin D, and ω-3 polyunsaturated fatty acid are not in connection with the glucose metabolism tests. As I understand it, here are the results:

Amyloid Test Results:
Increased B12, less amyloid,
Increased vitamin D, less amyloid.
Increased ω-3 polyunsaturated fatty acid (PUFA), less amyloid.

"Correlations between nutrients associated with PiB and food groups showed that vitamin B12 was mainly from meat, eggs and butter with correlation coefficients of 0.35, 0.31 and 0.36, respectively, (p<0.04). Vitamin D was mostly from low-fat dairies and fish (0.64 and 0.55, p<0.001), and ω-3 PUFA EPA from fish and other vegetables (0.36 and 0.31, p<0.01)."

Glucose Metabolism Results:
Increased β-carotene, increased glucose metabolism (good) for at least E4 women and those with a family history.
Increased folate, increased glucose metabolism (good) for at least E4 women and those with a family history.
Increased saturated fats, decreased glucose metabolism (bad) for at least E4 women and those with a family history.

"Additionally, FDG-PET metabolic reductions occur prior to dementia onset and correlate with clinical symptoms."

"Correlations between nutrients associated with FDG uptake and food groups showed that β-carotene was mainly from dark leaf, green leafy and cruciferous vegetables and fresh fruit, with correlation coefficients of 0.82, 0.77, 0.69 and 0.53, respectively, (p≤0.001). Folate was from grains, legumes, cruciferous vegetables and fresh fruit (0.44, 0.34, 0.32 and 0.30; p≤0.04), and saturated fats were from high fat dairies, salad dressing, fried potatoes, sweets and processed meat (0.65, 0.52, 0.5, 0.45, 0.41, p≤0.003)."

Typo in following:
"Results: Controlling for age and total caloric intake, higher intake of vitamin B12, vitamin D and ω-3 polyunsaturated fatty acid (PUFA) was associated with lower Aβ load in AD regions on PiB-PET, while higher intake of β-carotene and folate was associated with higher glucose metabolism on FDG-PET. β-carotene and folate were associated with should say "increased" [typo: 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. The associations of vitamin B12, vitamin D and ω-3 PUFA with PiB retention were independent of gender, APOE and family history. The identified nutrient combination was associated with higher intake of vegetables, fruit, whole grains, fish and legumes, and lower intake of high-fat dairies, meat and sweets."
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Julie G »

Rather badly misplaced typo :shock: Thank you, Pal, for setting our world right side up again! That certainly clears up a part of the contradiction. I couldn't fathom a veg/fruit prohibition...
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Re: New Article Re Nutrient Intake, Amyloid & Glucose Metabo

Post by Russ »

Pal, Good catch… but still begs the question about the inherent contradiction w/r B12. Body would suggest meat, eggs and butter are a help, but summary contradicts?
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