93 replies to this topic

[Dolph]

For what reason would anybody think it was??? There is no connection whatsoever.

[James Cain]

It might be worth mentioning that I posted these results in another forum specific to ApoE4 here. There is some excellent discussion about my results, as well as those of some others.

[James Cain]

I'd guess that 20 - 30 g of cashews would provide the saturated fats to get you close to 10 g per day. Of course it comes at the cost of a slightly worse Omega ratio, but I live with that and a high(er) HDL level.

I also eat no fish oil and get everything from ALA conversion. My 23 and me profile suggests that I may be extra sensitive to warfarin and other blood thinners and I find if I go over 4 g per day in my diet of Omega-3 fatty acid consumption, I get nose bleeds within a week or so. If I stay below 3.5g everything's good. While you probably don't have the same SNP's, I think it's validation enough about keeping a reasonable enough level of ALA in one's diet and thus following the recommendation I sited. What I worry about is that the first sign for you, or someone else reading this, is a bleeding on the brain issue instead of the early warning nose bleeds like I get.

I mirror your concern over covert bleeding issues. My 23andMe does actually indicate warfarin/similar sensitivity, and I seem to respond robustly to even baby aspirin, adding further impetus to lower my omega-3 consumption. While it's honestly not a major concern, I have considered lowering my flaxseed from 20 to 10 g/day mostly to lower ALA and lignan intake. I've considered going back to chia in place of the flaxseed, but I think flax is more convenient, less expensive, and easier to digest for me. I do also think there may be some benefit to consuming some extra lignan from flax, though 20 g/day might be pushing this too high. I'm very open to suggestions here.

[Dolph]

OK, some update from me. Just got my new numbers.

The last few months I tried to be a little bit more liberal about MUFAs, so I roughly doubled my olive oil and peanut butter consumption. My weight and workout regime is stable and I had a few glasses of wine or beer per week as always. Still take 1g of Niacin every day.

 

November 2013

TC 153 mg/dl

LDL 74 mg/dl

HDL 62 mg/dl

Triglycerides 100 mg/dl

 

April 2014

TC 157 mg/dl

LDL 84 mg/dl

HDL 54 mg/dl

Triglycerides 98 mg/dl

 

Well, not too much of a change of course. And I'm not sure how large is the measurement error...

On the other hand I had hoped that the increase in MUFA would at least help keeping the HDL high. Non-HDL-C also seems to have risen a little...

 

Not sure what I will do next. Suggestions are welcome as always. But my first impulse is to reduce the MUFA and in the process the total fat content of the diet again.

Edited by Dolph, 24 April 2014 - 11:42 AM.

[timar]

I think it is highly unlikely that there would be any further advantage in having better lipid values than those. With LDL < 100 and LDL/HDL < 2 both of the test are comfortably in the optimum range. Only the triglycerides are a bit on the high side, but at least both are consistently below or at 100, which is the acceptable maximum.

 

I would stay with the diet that you like better irrespective of these values. And don't forget that extra virgin olive oil provides powerful health benefits that don't show up in one's lipid values (think of the PREDIMED trial).

[Dolph]

Of course, these are still results that are better than those I had for the last 15 years or so... I guess my "Type A"-personality makes me want to improve even more, even so this might be asking for diminishing returns. (Of course it is to some degree...) 

Really, I'm somewhat handeling this as a kind of sport by now. I did bodybuilding until a few years ago and now I do "bloodwork-building".

 

When I state I gonna reduce MUFAs this doesnt mean "eliminate". They (including olive oil) still will make up the majority of my FA intake for the reasons you stated. But it seems to be kind of consensus that fat of all kinds raises LDL-C in APOE4 carriers.

[timar]

I understand your motivation. The question is where it is reasonable to stop, though. We all know that more doesn't always equal better, but the opposite is just as true. With an LDL of 0 you are as dead as a dodo. The physiological optimum is probably somewhere between 50 and 100. Many studies show an U-shaped mortality curve for LDL and total cholesterol, which is in most part due to reverse causation, but probably not completely, given the important physiological functions of cholesterol. So there is definitely a point at which any futher LDL-mediated decrease in CVD risk comes at at disproportionate increase in other risk factors, resulting in an increased overall mortality risk. This is why I'm completely satisfied with an LDL of 90-100. I wouldn't want it much lower. The PROCAM study has shown that the maximum reduction of CVD risk is reached with an LDL/HDL ratio of 2.5 (the first graph for smokers gives an example of the reverse causation issue):

 

 

 

Edited by timar, 25 April 2014 - 09:19 PM.

[Dolph]

It's all reverse causation. So far I'm at least pretty convinced after reading about every paper I could get my hands on. Given the studies with populations that have nonsense mutations causing very low LDL-C around ~25 mg/dl they have extraordinary low CVD and longevity I guess it's safe to say that lower is better in any case.

 

 

[timar]

I'd be cautious with drawing conclusions from such studies of small groups of people carrying rare genetic polymorphisms. You don't know in which ways other than by the given biomarkers such supposed "nonesense mutations" may affect disease and mortality risks.

 

Don't get me wrong: I'm certainly not in the cholesterol-skeptics camp. Not at all. I think, however, that just as for every other endogenous substance there is a optimum physiological range for LDL, too and that most of the literature suggest this range to be in the upper double-digits.

Edited by timar, 25 April 2014 - 09:36 PM.

[Dolph]

I think, however, that just as for every single other endogenous substance there is a optumum physiological range and that most of the literature suggest this range to be in the upper double-digits.

 

Well, that's most certainly not the case, at least when you differenciate between papers that look at spontanously(!) low LDL-C and those that look at deliberately lowered LDL-C. This discrepancy can be explained very well through reverse causation.

On the other hand I also somewhat appreciate your rather conservative position. Being to aggressive with anything can be a curse once you discover you were wrong. I always cringe when I glance at the supplement "stacks" that some people use over here. God knows what consequences some of that stuff may have one day. Especially considering some substances are actually unstudied drugs rather than "supplements"...

 

Regarding atherosclerosis at least there seems to be more and more hints that at a level of ~40 mg/dl it finally stops to occur at all. On the other hand - obviously - of course not many peoply in any culture (if any) over the age of ~15 are able to reach this level. So I think we may have to accept that some amount of atherosclerosis is actually hereditary in the end, at least if not treated whole life long with drugs. Well, in the end we all have to die of some cause, right?

 

I guess a certain amount of stoicism is never wrong, while trying the best we can. Doing everything "about right" is better than what most do...

[APBT]

Pilfering Darryl's post from here http://www.longecity...es/#entry657422
 

Optimal low-density lipoprotein is 50 to 70 mg/dl: Lower is better and physiologically normal

http://www.sciencedi...735109704007168

[Dolph]

Yes, I knew that interview with Castelli Darryl links in his post. It's absolutely worth the read by the way.

[timar]

On the other hand I also somewhat appreciate your rather conservative position. Being to aggressive with anything can be a curse once you discover you were wrong. I always cringe when I glance at the supplement "stacks" that some people use over here. God knows what consequences some of that stuff may have one day. Especially considering some substances are actually unstudied drugs rather than "supplements"...

 

Amen to that! It's easy to get carried away with enthusiasm (NR or C60OO anyone? )

 

Pilfering Darryl's post from here http://www.longecity...es/#entry657422
 

Optimal low-density lipoprotein is 50 to 70 mg/dl: Lower is better and physiologically normal

http://www.sciencedi...735109704007168

 

Yes, I know that paper and it is certainly worth reading. The name Loren Cordain, however, always evokes some skepticism in me, as "Mr. Paleo" Cordain has shown a clear penchant for the appeal to nature fallacy. Just because a few hunter gatherer tribes (and, ahem, horses and elephants!?) tend to have low cholesterol levels, that doesn't mean that those levels are necessarily optimal. It is an argument that they may be, but only if it fits within the overall framework of the evidence.

 

I think in this case it does pretty well. I agree with the lower LDL limit of 50 and that the upper limit of 70 may be a sensible target for secondary prevention, when you already have substantial plaque build up and you want to reverse that atherosclerosis as soon as possible. I think, however, that 100 is absolutely sufficient for primary prevention, especially given a LDL/HDL ratio of 2 or less (even if that is far above the cholesterol levels that have been measured in the black rhinoceros )

 

A pretty much conclusive paper on this question was published only recently, describing a highly sophisticated mathematical model of atherosclerosis, build upon an exhaustive set of data:

 

Atherosclerosis, the leading death in the United State, is a disease in which a plaque builds up inside the arteries. As the plaque continues to grow, the shear force of the blood flow through the decreasing cross section of the lumen increases. This force may eventually cause rupture of the plaque, resulting in the formation of thrombus, and possibly heart attack. It has long been recognized that the formation of a plaque relates to the cholesterol concentration in the blood. For example, individuals with LDL above 190 mg/dL and HDL below 40 mg/dL are at high risk, while individuals with LDL below 100 mg/dL and HDL above 50 mg/dL are at no risk. In this paper, we developed a mathematical model of the formation of a plaque, which includes the following key variables: LDL and HDL, free radicals and oxidized LDL, MMP and TIMP, cytockines: MCP-1, IFN-γ, IL-12 and PDGF, and cells: macrophages, foam cells, T cells and smooth muscle cells. The model is given by a system of partial differential equations with in evolving plaque. Simulations of the model show how the combination of the concentrations of LDL and HDL in the blood determine whether a plaque will grow or disappear. More precisely, we create a map, showing the risk of plaque development for any pair of values (LDL,HDL).

 

This is the LDL to HDL risk map that derives from their model. III is the "no risk" area, with a mathematical risk <= 0%.

 

 

The points on the map correspond to the curves on this graph. It shows that regression of atherosclerosis begins with a LDL/HDL ratio of about two, although it is much more rapid when the ratio approaches one:

 

Edited by timar, 26 April 2014 - 09:07 AM.

[Dolph]

Interesting model, but very theoretical.

I also think there is almost consensus now that the sheer amount of HDL-C doesn't tell much about it's functionality and impact on risk. (Although of course the failures of AIM-High and HPS-Thrive would seem to have been predictable if this graph was found to be correct. The participants all had very low levels of LDL-C to begin with.)

Edited by Dolph, 26 April 2014 - 09:23 AM.

[albedo]

Good finding Timar and nice plot. Thank you. It has been the struggle of my life but with my LDL at 135, HDL at 58 and ratio 2.3 I am slowly approaching.  Hope to do better in my next test this summer.

[James Cain]

Here are some updated results. I had great results previously with higher-fat intake and wanted to experiment with the often prescribed low-fat diet, so I did this and tested after 3 and 5 weeks, both basically the same very-low-fat [CFP 72/14/14%] mostly whole-foods vegan diet.

 

           - 6/11/2014 - 6/23/2014
Chol/HDL-C - 3.4 - 3.5
Triglycerides - 106 - 87
Cholesterol, total - 116 - 112
HDL-C - 34 - 32
LDL-C - 61 - 63
LDL-P - 646 - 884
HDL-P - 25.2 - 24.6
Small LDL-P - 473 - 629
LDL Size - 20.2 - 20.2
LP-IR Score - 38 - 47

 

I could explain some minor differences in diets between these (and my other two) tests, but I think it's pretty obvious that most of these seem largely unaffected by diet so long as long as I stick to the variables that were unchanged across trials: 1) I maintain a mostly whole-foods vegan diet, 2) stay weight-stable or mildly CRed, 3) maintain some amount of physical activity and/or stay lean. I think that these are in order of importance based on my results and published literature.

 

Across the vegan tests I've varied alcohol, amount and sources of fats (flaxseed, nuts, olive oil, 100% cacao chocolate, and soy products), amount and sources of carbs (fruit, grains/starch, bread, with veggies constant), sources of protein (protein powder, beans/grains, and soy products), ratios of macronutrients (15-30% fat and 55-70% carbs, with protein always around 15%), and alcohol intake (from 40g alcohol/day to none).

[Dolph]

Great results once more. Especially amazing trigs for such a very low fat approach!

 

I have a side question in the context of your post. As you write you use protein powder. I do so, too, especially to "compose" regenerative shakes post workout. I recently changed from whey to soy, to further increase my relative intake of vegetable proteins and to reduce dietary oxidized cholesterol. (Although I'm still not sure how relevant the latter really is.)

I know soy is somewhat controversial over here, but after carefully weighing the evidence it at least 90% of it seems to be another case of FUD-management by the WAPF and there seem to be more possible benefits than drawbacks of soy protein. 

Nevertheless I'm curios to know what you do use and what your thougths on the different available sources are. 

[timar]

I am wary of protein powders, as they may contain extremely high AGE levels (protein isolates processed by dry heat, providing the optimum condition for the formation of AGEs - whey protein even has a suspiciously brownish color). I haven't found any measurements of AGE levels in protein powders but it is known that infant formulas have very high levels of AGEs.

 

 

[Dolph]

whey protein even has a suspiciously brownish color

 

Mmm, what??? I have used a lot of different brands of whey protein in the past, but neither of them ever was even slightly brown, the chocolate flavored ones aside, of course.

[James Cain]

Great results once more. Especially amazing trigs for such a very low fat approach!

 

I have a side question in the context of your post. As you write you use protein powder. I do so, too, especially to "compose" regenerative shakes post workout. I recently changed from whey to soy, to further increase my relative intake of vegetable proteins and to reduce dietary oxidized cholesterol. (Although I'm still not sure how relevant the latter really is.)

I know soy is somewhat controversial over here, but after carefully weighing the evidence it at least 90% of it seems to be another case of FUD-management by the WAPF and there seem to be more possible benefits than drawbacks of soy protein. 

Nevertheless I'm curios to know what you do use and what your thougths on the different available sources are. 

I agree about the soy protein. In general, unless you are just barely meeting your protein needs or relying on a single protein source, plant-based protein is of adequate quality in the context of a varied diet. If you're adding protein shakes on top of normal foods you will likely notice no physiological differences.

 

I use rice and pea protein powders from TrueNutrition, and most often their Vegan Protein Optimizer Formula which is a pre-mixed 45/45/10 pea/rice/hemp protein. I don't buy soy protein powders, but I sometimes consume soy milk or tempeh for extra protein.

[Zaul]

[Dolph]

I agree about the soy protein. In general, unless you are just barely meeting your protein needs or relying on a single protein source, plant-based protein is of adequate quality in the context of a varied diet. If you're adding protein shakes on top of normal foods you will likely notice no physiological differences.

 

 

Yes that was my impression, too.

What I'm currently also thinking about is if leucine (or BCAA) supplementation could be useful to prevent or at least alleviate age related sarcopenia in the long run, if started at middle age. This seems to be a controversial topic over here, too, because of the obvious mTOR activating properties of leucine...

I'm not entirely sure what to think about that, especially given the fact that leucine at the same time, and at least in certain circumstances, also seems to stimulate AMPK. 

http://www.fasebj.or...upplement/269.7

http://www.ncbi.nlm....pubmed/24551237

 

Do you have any opinion about that aswell? (Might be a bit off-topic, sorry for that...)

Edited by Dolph, 03 July 2014 - 08:16 AM.

[James Cain]

What I'm currently also thinking about is if leucine (or BCAA) supplementation could be useful to prevent or at least alleviate age related sarcopenia in the long run, if started at middle age. This seems to be a controversial topic over here, too, because of the obvious mTOR activating properties of leucine...

I'm not entirely sure what to think about that, especially given the fact that leucine at the same time, and at least in certain circumstances, also seems to stimulate AMPK. 

http://www.fasebj.or...upplement/269.7

http://www.ncbi.nlm....pubmed/24551237

 

Do you have any opinion about that aswell? (Might be a bit off-topic, sorry for that...)

 

To be honest, I just finished up my PhD and haven't branched out as much as I'd like with non-essential reading, but I've looked into the leucine/mTOR thing a little bit so I'll give my initial impressions. I found and article that sum up my thoughts fairly well.

 

Dietary protein recommendations and the prevention of sarcopenia

http://www.ncbi.nlm....classic#S8title (this section is great, but the whole article is worth a read)

 

I think adequate resistance training (even on a low protein diet) goes a lot further than supplemental leucine, or even a high-protein diet, without resistance training. Though it does seem that supplemental leucine or a high-protein diet does partially ameliorate sarcopenia in non-exercising elderly. Protein timing also becomes much more relevant in the elderly, which the article discusses as well.

 

As far as aging goes, there are a number of variables that have trade-offs such as the mTOR pathway. Stimulate mTOR and possibly reduce the anti-aging effects of certain diets (CRON, protein restriction) or supplements, though I see no reason why consuming leucine or BCAA would enhance aging. At some point (at least with CR and similar) you have to decide if statistically you're better off maintaining a state of low cellular nutrient status and enhanced autophagy, or improving lean mass and reduced frailty.

[APBT]

Looking for this article if anyone can help:

http://link.springer...0044-011-9595-3

Structure-based drug discovery of ApoE4 inhibitors from the plant compounds

Apolipoprotein E4 (ApoE4) is a potential target for developing new therapeutics for Alzheimer’s disease (AD). Till now there is no drug available to inhibit this protein and cholinesterase inhibitor was given for almost all the AD patients. In this study, we have approached to identify the potential ApoE4 inhibitor from the plant compounds. Rigid docking study was performed for 18 plant compounds and 11 cholinesterase inhibitors. Based on the docking score, binding energy and number of hydrogen bonding curcumin posses the best scoring function. For further validation induce fit docking was performed and it also shows that curcumin binds to the same binding pocket of ApoE4 protein. Biological activity prediction reveals that curcumin has a potential therapeutic activity against AD. Pharmacokinetic properties of this compound are under the acceptable range. From the results we concluded that the plant compound curcumin could be a potential inhibitor of ApoE4 and it can control the AD.

 

 

Better late, than not at all FULL TEXT: Structure-based drug discovery of ApoE4 inhibitors from the plant compounds

[JR7]

I find this thread tremendously fascinating! I will come right out and say that I do not have near the level of knowledge shown by the OP and several thread responders. With that said, Id like to ask a few questions:

 

1) Do you think a high carbohydrate diet could eventually lead to high blood glucose levels > insulin resistance > diabetes?

 

2) Have you found low fat/cholesterol has affected your testosterone numbers? Is it possible to maintain and build a fairly high level of muscle while eating a vegan diet?

 

3) Do you suffer from any GI distress from legumes/wheat/high carbs? I want so badly to mirror your diet, but I bloat and gas immediately on wheat and legumes. As a result, Ive had to go low carb paleo which alleviates the GI issues but has negatively affected my heart related blood work 

 

 

Thank you in advance

[Dolph]

1. No, if anything a high carb diet reduces the long term risk suffering high BG/T2 diabetes tremendously.
The single most importent nutrient reproducably causative of insuline resistance and T2 diabetes are saturated fatty acids. Some people here don't like to hear that, but it's beyond doubt and a scientifically verified fact.
EDIT/ This might be different if you ALREADY HAVE a problem with glucose tolerance! But I'm sure James is much better qualified to comment on this one.

2. I actually had my hormone levels tested by my internal specialist roughly half a year ago next to other things and I have another panel from 2007 when I was still eating rather(!) LCHF. Numbers didn't change much at all, but I doubt they are representative. Curiously cortisol, testosterone, free testosterone and DHEA were and are all very slightly higher than the "normal" range, estrogen being perfectly normal. This was even more surprising to me as I was a user of anabolic steroids in the past and would have thought that this might have reduced my T permanently.
It must be stressed though that there is no serious hint that a low normal level of T could cause any symptoms at all. The dose/response curve of testosterone is EXTREMELY flat in the lower part which makes up more than the "normal" lab range!

3. It depends on what you consider GI distress. I don't suffer any stomach pain or excessive flatulence, but I have several bowel movements a day. Up to four on extreme days and if I had lots of whole grains and legumes the day(s) before. This could be defined as "distress" if there is no bathroom around...
If you had problems in the past and want to try again, maybe don't jump into it and add fibrous food only slowly time after time. The body definitely get's used to it as the intestinal flora adapts to its "food" sources.

Edited by Dolph, 12 July 2014 - 06:20 AM.

[JR7]

1. No, if anything a high carb diet reduces the long term risk suffering high BG/T2 diabetes tremendously.
The single most importent nutrient reproducably causative of insuline resistance and T2 diabetes are saturated fatty acids. Some people here don't like to hear that, but it's beyond doubt and a scientifically verified fact.
EDIT/ This might be different if you ALREADY HAVE a problem with glucose tolerance! But I'm sure James is much better qualified to comment on this one.

2. I actually had my hormone levels tested by my internal specialist roughly half a year ago next to other things and I have another panel from 2007 when I was still eating rather(!) LCHF. Numbers didn't change much at all, but I doubt they are representative. Curiously cortisol, testosterone, free testosterone and DHEA were and are all very slightly higher than the "normal" range, estrogen being perfectly normal. This was even more surprising to me as I was a user of anabolic steroids in the past and would have thought that this might have reduced my T permanently.
It must be stressed though that there is no serious hint that a low normal level of T could cause any symptoms at all. The dose/response curve of testosterone is EXTREMELY flat in the lower part which makes up more than the "normal" lab range!

3. It depends on what you consider GI distress. I don't suffer any stomach pain or excessive flatulence, but I have several bowel movements a day. Up to four on extreme days and if I had lots of whole grains and legumes the day(s) before. This could be defined as "distress" if there is no bathroom around...
If you had problems in the past and want to try again, maybe don't jump into it and add fibrous food only slowly time after time. The body definitely get's used to it as the intestinal flora adapts to its "food" sources.

Thank you for this wonderful reply. 

Today is day 1 for my transition from Low carb Paleo to a Lacto Ovo vegetarian diet and hopefully onto Vegan. Already, though, the GI distress I mentioned earlier has begun. Grains and legumes seem to cause gut distention and all day gas. As my post workout meal (I do strength training style lifting), I ate black beans and brown rice. Ive had horrible gas all day. I would really love to get beyond this as the OP's version of eating is where Id like to get to. 

Edited by Jreinhal, 27 July 2014 - 09:51 PM.

[scottknl]

Dude,  Make diet changes slowly over weeks and months.  Not just overnight.  Your body needs time to adjust and your gut biome needs to adjust it's biological make up in order to properly digest the food.  Otherwise it's just torture and you're setting up yourself for failure.  My suggestions are 

1) track your current diet using cronometer.

2) change it food by food at most one different food per day or several days

3) don't eat massive quantities of a new food.  start small and work up to larger portions if required.

4) don't drink beverages with your meal.  It will dilute the stomach acids and lead to poor digestion.

5) eat probiotic foods like yogurt (soy or almond if lactose intolerant), sauerkraut or other fermented foods.  This will build your gut biome up.

6) slowly morph your diet towards your desired end goal

 

No need to hurry.  If you get it right, there will be plenty of life left for you to enjoy your new diet.

[Matthew Duhamel]

I would be curious to see results if you resumed just egg or fish consumption. Several recent studies have said that egg and fatty fish consumption do not contribute to lipid cholesterol levels, but none of them have investigated a group transitioning from low-fat vegan to one that simply incorporates eggs into the same diet.

 

[Matthew Duhamel]

If you have a study that shows that precisely then post it. I don't see how I am "ill informed"