Perturbed Fatty Acid Metabolism in E4 carriers

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
Silverlining
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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby Silverlining » Mon Apr 20, 2015 4:56 am

Another recent paper on the protein(mfsd2a) mentioned in Julie's posted link above. MFSD2A affects DHA uptake and also appears to affect BBB integrity. Researchers are looking at this protein as a future therapeutic target.

Mfsd2a is critical for the formation and function of the blood-brain barrier.
http://www.ncbi.nlm.nih.gov/pubmed/24828040

Also, here is an ongoing clinical trial re: LC Omega 3 and cognition in apoe4 subjects as well as mice. This will be a good one for us to take a look at when complete in 2017. They are still recruiting, however, I certainly don't want to be one of their placebo subjects!

Causal Relationships Between LC-omega-3-enriched Diet and Cognition (MOP201109)

https://clinicaltrials.gov/ct2/show/NCT01625195

Purpose: "Nutrition is key to healthy aging for a number of diseases but the investigators have reported imbalances in the distribution of long chain omega-3 fatty acids (LC-omega-3) in the elderly and in the carriers of apolipoprotein E epsilon 4 (APOE4) isoform. Carrying APOE4 isoform is currently recognized as being the most important genetic risk factor of cognitive decline. The investigators believe that dysregulation of LC-omega-3 metabolism is intimately link with higher risk of cognitive decline. The current project will investigate whether there is a causal relationship between LC-omega-3-enriched diet and cognition using, on the one hand, a randomized double-blind placebo-controlled design and on the other hand, transgenic mice carrying human APOE4. In both study, the investigators will focus specifically on the distribution (level) of LC-omega-3 into lipoproteins with age and/or APOE4 isoform to evaluate whether dysfunctional transport of LC-omega-3 is associated with lower cognitive scores on visuospatial capacity, verbal fluency or working memory. In APOE4 mice, the investigators will evaluate LC-omega-3 brain uptake together with the level of LC-omega-3 in the brain membranes and the level of APOE protein within the brain. The present investigation will provide key basis for understanding how to develop nutritional strategies for healthy aging and the preservation of cognitive function".

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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby Tincup » Mon Apr 20, 2015 9:16 am

rep wrote:GeorgeN - How much of the change do you attribute to niacin you have been taking recently?

What do you think of Dr. Dayspring's warnings against niacin?


I think there is some reduction in LDL-P and a significant reduction in small LDL-P.

I think Dayspring was looking at the Niaspan (prescription w/antihistamine) studies. I am following Dr. Gundry's take, which is to use Slo-Niacin (nicotinic acid) with pychnogenol (60 mg/day) and grape seed extract (200 mg/day). He also recommends niacinimide. According to his support group - he sometimes prescribes one, the other, or both, depending upon lab results.

Stavia, I'll look at the bottle of fish oil to see what is in it. Since I wasn't keeping records, I don't know how much I was taking. However, knowing me, I probably was taking an excessive amount. I recall donating blood at that time and my donation went very quickly - I'm sure due to reduced blood viscosity from the fish oil. There is a mechanical theory of heart disease - why calcification shows up where there is turbulence. Reducing viscosity reduces shear forces. I was aiming for reduced shear and got it. I also got an off the chart NMR. After the NMR, I quit any fish oil for a while. I'll report on the contents later.
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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby Ski » Mon Apr 20, 2015 9:42 am

GeorgeN wrote:He also recommends niacinimide. According to his support group - he sometimes prescribes one, the other, or both, depending upon lab results.

That form does not lower cholesterol so thats puzzling if true.

Niacin is used for high cholesterol.

Niacinamide is used for treating diabetes and two skin conditions called bullous pemphigoid and granuloma annulare.

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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby Tincup » Mon Apr 20, 2015 11:48 am

Ski wrote:
GeorgeN wrote:He also recommends niacinimide. According to his support group - he sometimes prescribes one, the other, or both, depending upon lab results.

That form does not lower cholesterol so thats puzzling if true.

Niacin is used for high cholesterol.

Niacinamide is used for treating diabetes and two skin conditions called bullous pemphigoid and granuloma annulare.


I understand. I know he talks about Slo Niacin on his website. Could be a reporting error from a group member. Or perhaps he is using it to treat diabetes. I know he individualizes his treatments depending upon the patient & test results.
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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby Julie G » Mon Apr 20, 2015 5:27 pm

REALLY interesting hearing your fish oil results, George. Out of curiosity, how much EVOO do you think you use a day? I'm still flummoxed that my LDL-P went UP 300 points on Gundry's plan... but suspect I used too much :oops:

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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby Tincup » Tue Apr 21, 2015 9:47 am

Stavia, the fish oil is Carlson's Norwegian Cod Liver Oil (I might have been taking as much as 2 Tablespoons/day, so material) Image

GeorgeN wrote:
Ski wrote:
Niacinamide is used for treating diabetes and two skin conditions called bullous pemphigoid and granuloma annulare.

[/quote]

Ski, Hoffer http://www.amazon.com/Niacin-Real-Story-Abram-Hoffer-ebook/dp/B0074NDA1W/ref=sr_1_1?s=digital-text&ie=UTF8&qid=1429629178&sr=1-1&keywords=niacin+the+real+story talks about using niacinimide for various mental issues. Perhaps Gundry is using it for another purpose than cholesterol issues (AD prevention???) I just know his patients report he prescribes it.

Juliegee wrote:REALLY interesting hearing your fish oil results, George. Out of curiosity, how much EVOO do you think you use a day? I'm still flummoxed that my LDL-P went UP 300 points on Gundry's plan... but suspect I used too much :oops:


Julie, I'm not very good at measuring everything. I use a bit in the morning to cook my two eggs & I put a bit on the big salad but don't drench it. I was eating a fair amount of nuts (macadamia, brazil & hazelnuts), so that would increase my sat fat, too.

I continue to notice high levels of ketones while taking niacin. Last night I decided to take an additional gram before bed and this morning had serum ketone levels of 2 mmol/L. While my diet is fairly low carb, I usually need to really restrict everything (carb & protein) to get to this level. Unusually high levels (40 mg/dL) of urine ketones (for me) for the diet I'm eating seem to be a consistent feature of the niacin intake. These urine ketone levels usually correlate with serum ketones in the 1-2 mmol/L range in me.
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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby LAC1965 » Tue Apr 21, 2015 12:02 pm

George, how much niacin were you taking when you saw the increase in ketones? I’m asking because I’m trying to keep my ketone level more stable. I’ve been getting increasingly large fluctuations and I just recently started taking niacin. Thanks, Liz

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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby circular » Tue Apr 21, 2015 12:45 pm

Not sure what the O3 was doing in my system, but for years now I've eaten very high amounts of salmon (no omega 3 supplements so far), probably 4-6 times a week or more. I'm long overdue for labs, but my last ones (HDLabs = extensive) returned a 2:1 ratio (28%:15%) O6 to O3. "Free fatty acids" were "optimal". I had DHA at 9.4% where the range was .1-8.4%. My saturated was high end of range at 41.6% (36.6-42). Everything else was in their "optimal" zone other than:

Apo B at 73 (intermediate)
Myeloperoxidase at 403 (intermediate; inflammation/oxidation)
hs-CRP at 1.4 (intermediate; inflammation/oxidation)

I wonder if the tradeoff for achieving a healthy O6:O3 ratio is inflammation/oxidation?

I continue to believe that extremely high levels of dietary antioxidants are crucial to offset the fatty acid oxidation and whatever carb burning we have. I was not *as* focused on that when these labs were done. I've increased dietary antioxidants significantly (read Eating on the Wild Side) and added daily vit C. I wonder if would still have the good ratio but less inflammation/oxidation. Unfortunately I can't afford their labs - got them free last time. Back to that drawing board. Where else can we get detailed fatty acid profiles????
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby Stavia » Tue Apr 21, 2015 2:27 pm

Thanks George. If you were taking two tablespoons a day, thats already 6grams saturated fat. Plus its three grams DHA at that amount plus what you get from food!
Circ, your apob struck me as excellent :)

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Re: Perturbed Fatty Acid Metabolism in E4 carriers

Postby circular » Tue Apr 21, 2015 8:45 pm

Oh really Stavia? That's nice to know! It was the only thing not "optimal" in the whole lipoprotein particles and apolipoproteins category. All regular lipids also optimal. Just the dang inflammation markers. Maybe now that I'm treating the mast cell activation with medicine those will come down some too.
ApoE 3/4 > Thanks in advance for any responses made to my posts.


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