ApoE4.Info

Good reminder of the competing theories surrounding our allele, Russ. Thanks for keeping us honest .

Stavia wrote:Russ my understanding is that it was the greater caloric density of animal foods that made brain size increase possible. I believe it is too simplistic and misleading to take one gene and assume that one alone will be the dominant evolutionary driver.

Possibly, but caloric model seems quite counter to all we've learned about food as signaling. I'm an engineer who absolutely started and clung to food as calories model, but I've come to understand it's much more than that. We now even know that chimps do eat meat (although haven't seen them start a BBQ).

One of my favorite posts from Grace Liu (a pharmacist now blogging as 'Gut Goddess') makes a pretty good an provocative case here...
http://drbganimalpharm.blogspot.com/201 ... brain.html

On the other hand, the research is highly demonstrative of apoE4 increasing FATTY ACIDS into our brains, mitochondrial metabolism and enhancement of neural efficiency.

My view:
apoE4 -- Infiniti of cars (same Nissan engine), running on super premium fuel (ancestral allele)
apoE3 -- Nissan Maxima (wild type allele), runs both regular and premium fuels
apoE2 -- Nissan Sentra, on regular unleaded (agarian allele??)
apoE combos -- Prius hybrids (phenotype varying by degrees)

One change of the protein structure of apoE at the 61 spot from T to R/arginine may have set the stage for evolution of other nervous system and housekeeping genes that not only grew a superior engine in the brain but also the chassis/architecture of our hard drives. The ancestral apoE4 allels may be one among several genetic variations that sets us vastly apart from our not so distant primate past.

For other great stuff, see her other APOE-specific posts...
http://drbganimalpharm.blogspot.com/201 ... min-d.html (how superior ability to uptake fat soluble vitamins allowed for migration northward and inland)
http://drbganimalpharm.blogspot.com/201 ... d-ldl.html (one for your LDL is not necessarily bad files)
...which I don't recall we've talked about since we came over here from 23andMe.

In any case, unless the prior paper I cited is flat our factually inaccurate, I think we can dispense with the idea that the ancestral human APOE4 allele is the same as primate APOE therefore we should eat like primates concept. Can't see how there is room for misinterpretation of something that is simply factually incorrect?

Russ

Still plodding through my notes.

Given the connection between toxins and Alzheimer’s (Dr Bredesen’s Type 3 Inhalational) I thought I’d share this website:

http://www.ewg.org/

You can find information on harmful, yet common, chemicals. EWG stands for Environmental Working Group. Dr. Tim Gerstmar recommended this website during his talk: "Obesogens and Endocrine Disrupting Chemicals: Obesity is about more than Diet and Exercise" which was given on Thursday, Aug 11, 2016 at 10:40 am.

Russ wrote:In any case, unless the prior paper I cited is flat our factually inaccurate, I think we can dispense with the idea that the ancestral human APOE4 allele is the same as primate APOE therefore we should eat like primates concept. Can't see how there is room for misinterpretation of something that is simply factually incorrect?

Thanks for summarizing all of that Russ. I fully agree with your perspective. ApoE4 is unique in that it is the only phenotype with R61, R112, and R158. All the simians have Thr61 and ApoE2 and ApoE3 have Cys112. That's what led the Gladstone group to focus on the R61-R112 interaction.

Here is another paper looking at nutrition, inflammation and apoE: http://www.pnas.org/content/107/suppl_1/1718.full. One interesting point is the pleiotropic nature of apoE4:

In hepatitis C infections, apoE4 carriers incurred less fibrotic damage by allele dose (114, 115), whereas Brazilian slum children carrying apoE4 showed less diarrhea and associated impairments of cognitive development (116, 117).

I think this reinforces your point about understanding how the environment interplays with the genotype. Sir Patrick Bateson, a British evolutionary biologist uses the analogy of baking a cake. Genetics are the recipe, but you still have to gather all the ingredients, mix them up, and bake them at the proper temperature.

That ApoE4 tends to be inflammatory bears out in testing. I eat to minimize inflammation as determined by testing, inclusive of sdLDL.

I've been listening in on the dinner conversations with Dr. Gundry & Dr. Wahls. Thanks for posting these -- lots of great information! Whenever their newest books hit the shelves, I'm going to have to grab both of those.

On the Gundry interview (~33m mark) I found it interesting that oats and gluten-containing grains were mentioned to possess lectins that are unable to be destroyed by pressure cooking, even with the heat and pressure on for an hour straight, while the lectins in tomatoes and squash are completely and easily destroyed in just 15 minutes. I could take or leave oats, so I might remove those from my menu. I'm curious how the lectin in another grain like brown rice or sprouted brown rice (or in pseudo grains) compares against the indestructible lectins in foods like oats & barley -- although brown rice (particularly the sprouted variety) has a higher micronutrient & phytonutrient content than white rice, perhaps white rice is still the "healthier" choice? I'm also curious as to the extent of lectin destruction which occurs during fermentation (eg. "Chickpea Miso") vs instant pot cooked beans @ ~ 10.5psi. If I was to regularly (nearly daily?) consume legumes for a source of vegetable protein, am I far in the clear as far as lectins and gut-damaging anti-nutrients go, so long as I simply toss them in an instant pot or use something like miso, or are there still residual amounts that are best avoided or limited in the diet? I usually use Manual Mode @ 30-40m (higher heat / higher pressure / longer cook time than program modes) on the instant pot, where it sounds like Smart Program mode might actually be the recommended way to do it, which kind of pulses the heat.

On the Wahls interview, she mentions consuming around 9 cups of veg+fruit (mostly veg) per day, with lots of spinach, chard, beet greens, etc. I'm curious if there's any concern about long-term oxalate intake. A serving size of beet greens is just 0.5 cups and supplies nearly a gram of oxalate right there.

http://www.westonaprice.org/health-topi ... disorders/

"Oxalates in the gastrointestinal tract have a tendency to bind essential elements. If you have a lot of oxalates, you won’t be able to utilize essential elements like calcium, magnesium and zinc because they will also form deposits with oxalates. If you have excess oxalates, you may have to increase your intake of calcium, magnesium and zinc. In addition, rather than acting as antioxidants, oxalates are prooxidants, so they encourage the oxidation of your fats, forming rancid fats in your body."

"Virtually everybody who eats a large spinach salad every day is going to succumb to kidney stones. I've tested them over and over again and the people who have the highest oxalate values invariably tell me that a cornerstone of their daily diet is a large spinach salad. If they add nuts to their salad and textured soy protein, both of which are very high in oxalates, you’ve got a cocktail made to produce kidney stones. Spinach is so high I would not recommend eating it even cooked, as a main course. Once after I gave a talk a physician came up afterwards and told me that a few months earlier he had decided to get healthy. He decided to forswear all the McDonald's and the like. He was going to start eating healthy and eating healthy meant a very large spinach salad with lots of pecans on it every day. Within two months he had kidney stones. Cooking does not destroy the oxalates; they are extremely stable."

"Even though oxalate crystals are most common in the kidney, they also can form in virtually any other tissue in the body, including the brain and the blood-brain barrier. Oxalate crystals resembling pieces of glass can form in the heart muscle. As the heart muscle contracts, these pieces of oxalate crystals actually tear into the tissue. If these crystals are deposited in skeletal muscle, normal movement and exercise can be very painful. I’m convinced this is also one of the factors responsible for fibromyalgia. Oxalates may also cause thyroid disease as they react in thyroid tissue. Oxalate crystals can form in the bone. The oxalate crystals can become so dense they actually push the bone marrow cells out of the bones, leading to severe anemia. Deficiencies of red blood cells as well as white blood cells may result due to the oxalate depositions in the bones. Oxalates can likewise cause osteoporosis. The oxalates form in the bone marrow and alter the structure of the bone matrix so the bone is much weaker and prone to breakage. Other diseases in which oxalates may play a role include arthritis, joint pain and interstitial cystitis."

apod wrote: I'm curious how the lectin in another grain like brown rice or sprouted brown rice (or in pseudo grains) compares against the indestructible lectins in foods like oats & barley -- although brown rice (particularly the sprouted variety) has a higher micronutrient & phytonutrient content than white rice, perhaps white rice is still the "healthier" choice?

I'm sure Gundry would say to eat the white rice. I recall he made a comment about the billions of people that rely on rice taking the bran off. Also sarcastically about people studying the Okinawans and saying they'd make their diet more nutritious by subbing brown for white rice (as if they knew better).

I'm curious if there's any concern about long-term oxalate intake.

Something like 18 and 16 years ago I had two separate calcium oxalate kidney stones. This raises my probability of reoccurrence dramatically (~85% in the five years after the stone, if memory serves). My diet is VERY high in oxalate now, applying Wahls' 1/3 greens, 1/3 sulfur containing and 1/3 colored all the way through with at least 3 colors to what is allowed on Gundry's Matrix. The primary source of volume in our diet are these veggies. Julie and Stavia can attest to the quantity as we brought our dinner when we met Tuesday night. I've yet to have an issue. I'm guessing the issue before was something else chemically besides oxalate quantity.

GeorgeN wrote:

apod wrote: I'm curious how the lectin in another grain like brown rice or sprouted brown rice (or in pseudo grains) compares against the indestructible lectins in foods like oats & barley -- although brown rice (particularly the sprouted variety) has a higher micronutrient & phytonutrient content than white rice, perhaps white rice is still the "healthier" choice?

I'm sure Gundry would say to eat the white rice.

Perhaps pressure-cooking sprouted brown would be the best of both worlds (if it does in fact destroy the lectin content)? Compared with white rice, sprouted brown rice seems to:

Decrease heavy metal uptake:
http://www.ncbi.nlm.nih.gov/pubmed/20138853

Decrease lipid peroxidation:
http://www.ncbi.nlm.nih.gov/pubmed/23790918

Protect against neurodegenerative diseases:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431823/

Increase endogenous antioxidants:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497306/

Inhibit cancer development and improve the immune system:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551059/

Improve blood sugar:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635206/

Improve blood lipids:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647596/

Lower inflammation (TNF-a / hs-CRP):
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018597/

While rice is relatively high in arsenic, with more of it often found in brown varieties than white, going with a California-grown BR that's been well rinsed and cooked pasta style seems to nearly eliminate this concern. Sprouted brown basmati seems to have the lowest GI, while sprouted red rice seems to have the highest antioxidant content.

GeorgeN wrote:

apod wrote: I'm curious how the lectin in another grain like brown rice or sprouted brown rice (or in pseudo grains) compares against the indestructible lectins in foods like oats & barley -- although brown rice (particularly the sprouted variety) has a higher micronutrient & phytonutrient content than white rice, perhaps white rice is still the "healthier" choice?

I'm sure Gundry would say to eat the white rice. I recall he made a comment about the billions of people that rely on rice taking the bran off. Also sarcastically about people studying the Okinawans and saying they'd make their diet more nutritious by subbing brown for white rice (as if they knew better).

I'm curious if there's any concern about long-term oxalate intake.

Something like 18 and 16 years ago I had two separate calcium oxalate kidney stones. This raises my probability of reoccurrence dramatically (~85% in the five years after the stone, if memory serves). My diet is VERY high in oxalate now, applying Wahls' 1/3 greens, 1/3 sulfur containing and 1/3 colored all the way through with at least 3 colors to what is allowed on Gundry's Matrix. The primary source of volume in our diet are these veggies. Julie and Stavia can attest to the quantity as we brought our dinner when we met Tuesday night. I've yet to have an issue. I'm guessing the issue before was something else chemically besides oxalate quantity.

Don't you supplement with high doses of Mg so you are somewhat offsetting some of the possible side affects?

I also eat a fair bit of the oxalate family, steamed kale and swiss chard from our garden not to the same degree as you, and I recently reduced my Mg supplement to 400mg vs 800mg and notice that it is not enough.
I think some people are more sensitive to oxalates and it might reside on how ones guts microbes handles the issue so I discount MasterJohns hyperbola!

GenePoole0304 wrote:

GeorgeN wrote:

apod wrote:
Don't you supplement with high doses of Mg so you are somewhat offsetting some of the possible side affects?

Yes, I've recently been able to reduce to 2g/day from a high of 5g/day.

For kidney stone risk the best risk reducer is citrate. Potassium citrate in prescription form (Urocit) is marketed for this, but you can use the health food supplements just as well. I've not looked at the Urocit data in 10 or more years, but I recall it was something like an 85% risk reduction.