15 replies to this topic

[RWhigham]

The Endothelial Glycocalyx

•      The endothelial glycocalyx is a soft layer of molecules that lines the endothelium.
•      It is difficult to stain and visualize, and vanishes when tissue samples are removed for study.
•      It protects the endothelium from damaging molecules in the blood.
•      It blocks the excursion of fluid and lipids from arteries. (In shock the glycocalyx is dissapated).
•      It strongly reduces the incursion of LDL into the arterial wall unless its damaged.

Heart Disease Assumptions

•     Atherosclerotic plaques are caused by the incursion and retension of LDL cholesterol into the arterial wall.
•     Prevention can address either the incursion or the retention or both. Only the incursion is considered here.
•     LDL incursion is increased by higher cholesterol levels, and/or by damage to the endothelial glycocalyx layer.

Diet

•    High-carb dieters have blood glucose spikes after every meal.
•    Blood glucose spikes damage the glycocalyx layer and allows a temporary increase in the LDL influx.
•    Low-carb dieters have higher cholesterol levels. All else equal, this causes higher fasting LDL incursion.
•    But perhaps postprandial glycocalyx damage of high-carb diets may produce higher LDL incursion overall.

Note: There are supplements to help maintain the glycocalyx,  including metformin, hyaluronic acid, N-acetyl cysteine (NAC), chondroitin Sulfate, and nitric oxide boosters, perhaps advisable for those on a high-carb diet along with plenty of L-Carnosine to reduce glycation.

 

References

Endothelial Glycocalyx as a Shield Against Vascular Diabetic Complications

 Glycocalyx 2.jpg   52.45KB   0 downloads

Short-term hyperglycemia increases endothelial glycocalyx permeability ...

Endothelial Glycocalyx: Role in body fluid homeostasis ...

The endothelial glycocalyx: composition, functions, and visualization

Dave Feldman's (CholesterolCode) interview with Ivor Cummings (The Fat Emperor)

 Glycocalyx.jpg   63.33KB   0 downloads

Edited by RWhigham, 09 August 2020 - 10:38 PM.

[RWhigham]

One might ask which likely has the longest life span, a high-carb (plant-based low-fat) or low-carb (animal-based high-fat) diet. The postprandial insulin exposure is quite different.

• Mice with lower exposure to insulin had increased life spans of up to 11%. Reduced Circulating Insulin Enhances Insulin Sensitivity In Old Mice and Extends Lifespan 
• Plant-based low-fat diets have higher postprandial insulin than an animal-based high-fat keto diet.  A plant-based low-fat diet decreases ad libitum energy intake compared to an animal-based ketogenic diet: an inpatient randomized controlled trial  (preprint link which may expire)
•  Low-fat insulin.jpg   17.55KB   1 downloads
• A 11% life extension from lower insulin exposure would be about 9 years for humans

 

Edited by RWhigham, 14 August 2020 - 10:29 PM.

[RWhigham]

The following damage the glycocalyx which can result in atherosclerosis  (ref)

• Hypertension
• Smoking
• Alcohol
• Homocysteine
• Angiotensin II
• Oxidation
•      oxLDL
•      Ferritin - a powerful oxidant, can increase LDL leakage through endothelium 20x (2000%)
•      Copper - another oxidant, water from copper pipes & supplements w the wrong sort of copper
•      ROS - radical oxygen species (copper, ferritin, & poly-unsaturated fats)
•      Refined vegetable oils or transfat
• Glycation
•      High glucose and/or high insulin
•      Diet - too much Omega-6, not enough Omega-3, sugar, sweet drinks, high carb meals  too often
• Inflammation - chronic infection, bacterial, viral, yeast, fungus, etc including
•       Toxins in our food, toxins stored and released from adipose tissue
•       LPS (endotoxin, bacterial debris) from the gut
•       TNF-a

 To prevent atherosclerosis, protect the glycocalyx and minimize oxidation, gllycation, and inflammation in the bloodstream

 

The glycocalyx is the fuzzy glycan coating on all cell membranes with negative charged sialic acid molecules on the end. After removal of sialic acid (de-sialylation) galactose becomes the terminal saccharide.  When intact the glycocalyx provides repulsion between lipoproteins and the endothelium which keeps LDL out of contact with the endothelium and out of the intima media. De-sialylated LDL is atherogenic and readily passes through the endothelium. Atherosclerotic plasma contains 2-5 x less sialic acid than plasma from healthy volunteers.

 

If the glycocalyx is damaged too often, too much LDL will get into the intima media. The intima media grabs onto LDL particles which enter it.  These can oxidize over time and be eaten by white blood cells in such quanity that the white blood cells become non-functional and collect in huge quanity forming the "foam cell" heart of plaques.

 

There are two problems--damaged glycocalyx which allows too much LDL to get into the intima media where it becomes trapped and oxidizes, and oxLDL in the bloodstream which gets removed from the bloodstream by white blood cells. LDL receptors often fail to recognize oxLDL (depending on the exact oxidation) and cannot remove it from the bloodstream. White blood cells have to remove it to control damage. White blood cells crawling along the endothelium grab onto oxLDL and take it out of the bloodstream into the intima media

 

Glycated LDL has similar problems.

 

 

 

Edited by RWhigham, 03 September 2020 - 09:44 PM.

[protoject]

I didn't read the whole thread yet just the first post (im gonna read the other 2 comments right after i post this before I forget) but I'm betting what kind of carbs really matters, and maybe even the degree to which they are cooked. Does glucose spike when you're slowly absorbing carbs that are harder to digest immediately? On a subjective level I feel way better eating brown rice pasta than simpler carbs that cause these wierd crashes. I try to keep the pasta as al-dente as I can as that should slow down any hits of glucose into my body.  But when I eat in the morning i eat like 1800 calories of this pasta because I'm borderline underweight and I found that complex carbs is the only thing that makes me gain weight (after years of experimentation) and my body seems to store that energy in some way. I mean I've maintained the heavier weight even though I haven't been eating as much these days. 

Like when I eat that 1800 morning brown rice pasta, complex carbs, is my blood sugar spiking? I get hella tired doing it but then when I go on a walk for 6 hours my body is totally subsisting on that energy and i feel way healthier. 

Also if you combine other foods, like meats, which I do, does it change what happens with glucose and insulin in the body if it's being co-digested with the carbs? 

[protoject]

Wow 

RWhigham

 this is really good information, thanks for posting this. A lot to think about there. I'm also always thinking about the ketogenic diet. I wonder if benefits outweigh the risks. I never bother committing to it because it seems to hard on the body or hard to follow in real life. I think it's hard on the kidneys, isn't it? Wonder if there's a way around that. I haven't lived a ketogenic life before, not knowingly. I mean I did a few fasts of over 7 days, maybe I went into ketosis for a little while. But that fasting was unhealthy. I wonder what it actually feels like to be on a ketogenic diet, cleaner energy. 

 

[Rosanna]

Great to start a thread on this, I've nothing to add at the moment, I only logged on because I'm totally confused at the moment.  

 

I am over my ideal weight currently but think that's partly because I've been on beta blockers and I've just turned 50, female so body is preparing for menopause, which can lead to weight gain.  I've decided to take HRT after weighing the pros and cons and I've lost some weight already and gained more energy.  Joint pain has gone (all of these symptoms have been very recent and have reduced or gone with intro of HRT).  Also I figure the oestrogen will protect against heart disease.

 

But came here tonight because I haven't a clue anymore about diet.  

 

I used to be skinny and fit on a high complex carb vegan diet.  Yet I listened to an interview with Dr Jason Fung today that suggests that it's hard to keep weight off when insulin is being triggered all the time from dietary carbs.  Well I was always super thin by keeping my saturated fat level below 10g a day (my dad died of a heart attack so I was extreme) and eating a LOT of complex carbs, which you have to to keep the energy and calories up, so that didn't follow for me.  

 

I then tried low fodmap vegan but it's complex.  I tried that just for some mild IBS and found that oligoscaccharides were the main culprit.  But now I've cut them out and started eating other foods and forgetting about fat levels, etc, because who knows, there's the whole keto thing.  I just don't know anymore.  

 

But high protein and fat diets raise mTor.....

 

Dietary fat according the Dr Esselstyn is a culprit in atherosclerosis and using a high complex carb / plant based diet he has reversed heart disease in a number of patients.  

 

So confused.

[TheFountain]

I echo that the types of carbs make a huge difference. The constitution of your plant based regimen in it's entirety makes a boat full of difference. You can't state absolutes in absence of context.

 

Also, never ignore your personal experiences. If you have tried a clean cut Keto diet and a clean cut fully balanced plant based diet with all things within the contexts of said diets being equal, and one of these has more favorable and noticeable physiological physique and blood work results don't listen to anything anyone else here says and pay no mind to their fringe data outside of it being a curiosity of sorts.

 

Try it all and test yourself and see what is best. Nothing else matters. 

[TheFountain]

Great to start a thread on this, I've nothing to add at the moment, I only logged on because I'm totally confused at the moment.  

 

I am over my ideal weight currently but think that's partly because I've been on beta blockers and I've just turned 50, female so body is preparing for menopause, which can lead to weight gain.  I've decided to take HRT after weighing the pros and cons and I've lost some weight already and gained more energy.  Joint pain has gone (all of these symptoms have been very recent and have reduced or gone with intro of HRT).  Also I figure the oestrogen will protect against heart disease.

 

But came here tonight because I haven't a clue anymore about diet.  

 

I used to be skinny and fit on a high complex carb vegan diet.  Yet I listened to an interview with Dr Jason Fung today that suggests that it's hard to keep weight off when insulin is being triggered all the time from dietary carbs.  Well I was always super thin by keeping my saturated fat level below 10g a day (my dad died of a heart attack so I was extreme) and eating a LOT of complex carbs, which you have to to keep the energy and calories up, so that didn't follow for me.  

 

I then tried low fodmap vegan but it's complex.  I tried that just for some mild IBS and found that oligoscaccharides were the main culprit.  But now I've cut them out and started eating other foods and forgetting about fat levels, etc, because who knows, there's the whole keto thing.  I just don't know anymore.  

 

But high protein and fat diets raise mTor.....

 

Dietary fat according the Dr Esselstyn is a culprit in atherosclerosis and using a high complex carb / plant based diet he has reversed heart disease in a number of patients.  

 

So confused.

 

Don't listen to the arm chair experts they don't know diddly squat about what is best for you within your tried and true tested personal context. Do what has and continues to work for you and gives you favorable blood work and physical results. 

[Rosanna]

Thanks.  I'm noticing that olive oil actually inhibits my craving for chocolate.  I've always avoided it because I've considered any oil, even olive oil to be damaging to blood vessels, but I'm not sure there's a lot of science behind that and my personal experience is I eat a lot less with even a tiny amount of olive oil on food.  So I may include it from time to time.  

 

I always did well on strict vegan and very low fat, I might go back to that but include fish and some olive oil now here and there as I think strict low fat might not be necessary (although I'm still pretty much convinced by the work of Esselstyn, mainly because no one else seems to have replicated it).

 

Blood work...not something done in the UK routinely.  I will consider ways of getting this done.

Edited by Rosanna, 09 September 2020 - 09:05 PM.

[TheFountain]

Thanks.  I'm noticing that olive oil actually inhibits my craving for chocolate.  I've always avoided it because I've considered any oil, even olive oil to be damaging to blood vessels, but I'm not sure there's a lot of science behind that and my personal experience is I eat a lot less with even a tiny amount of olive oil on food.  So I may include it from time to time.  

 

I always did well on strict vegan and very low fat, I might go back to that but include fish and some olive oil now here and there as I think strict low fat might not be necessary (although I'm still pretty much convinced by the work of Esselstyn, mainly because no one else seems to have replicated it).

 

Blood work...not something done in the UK routinely.  I will consider ways of getting this done.

 

 

Well your blood work and your physical results are your primary indicators at all times.

 

Without those you're a sitting duck, regardless of what a bunch of studies say. Get it done every year at least. 

[vasra]

"LDL incursion is increased by higher cholesterol levels, and/or by damage to the endothelial glycocalyx layer."

LDL integration into arterial walls is caused only by endothelial glycocalyx damage (which is caused by hypertension, ROS, viral attacks on endothelial cells, destruction of glycocalyx by other means) endothelial repair. This is NOT correlated nor causally linked to higher cholesterol levels. 

 

" reduces the incursion of LDL into the arterial wall unless its damaged"
" Atherosclerotic plaques are caused by the incursion and retension of LDL cholesterol into the arterial wall."
 

LDL does not go into arterial wall through incursion. The LDL associated proteins that are part of the endothelial repair process end up on the "other side" of endothelium, because they are first covering the endothelial damage and the new endothelial growth happens on top of that. There is no "incursion." 

 

The current textbook endothelial plaque model is causally, epidemiologically and pharmacodynamically wrongly modelled and can be demonstrated to be so. It is wrong on causation model ("high cholesterol causes endothelial damage"), it is wrong on the offending biomolecules ("LDL molecule" quantity), it is wrong on how to avoid it ("reduce LDL") it is wrong on treatments ("reduce cholesterol and lower LDL") and it has not succeeded to treat/reverse the damage (all cholesterol medications that succeed in ONLY lowering LDL/cholesterol, have failed 100%).

For all the references, all the reasoning, all the counterfactual proof, listen to this single monologue by Malcom Kendrick c. 90mins of your time:

https://nourishbalan...ing-mystery-he/

 

In summary: concentrating on LDL/cholesterol will miss the mark, use up resources from the real cause and POTENTIALLY cause other detrimental (all cause mortality/disease) issues due to diminishing of cholesterol and LDL.

 

Otherwise glycocalyx is really important. My current take (no time for refs, PubMed is friend):

 

- avoid endothelial damaging gases (smoking, exhaust fumes)

- avoid NO-synthesis reducing processes (too many to mention)

- avoid glycocalyx degrading processes (metabolic syndrome, high / continued glucose spikes)

- avoid heavy metal damages (lead, arsenic, cadmium, mercury intake, esp. intravascular, i.e. injections containing these)

- avoid hypertension (a post onto it's own for reasons that cause this)

- avoid constant stress (as a cause of hyperglycemia and/or hypertension) 

- add potential glycocalyx protecting / building supplements (this is controversial, but : NAG, chondroitin sulfate, higher blood albumin through diet, hyaluronan)

 

 

[Mind]

"LDL incursion is increased by higher cholesterol levels, and/or by damage to the endothelial glycocalyx layer."

LDL integration into arterial walls is caused only by endothelial glycocalyx damage (which is caused by hypertension, ROS, viral attacks on endothelial cells, destruction of glycocalyx by other means) endothelial repair. This is NOT correlated nor causally linked to higher cholesterol levels. 

 

" reduces the incursion of LDL into the arterial wall unless its damaged"
" Atherosclerotic plaques are caused by the incursion and retension of LDL cholesterol into the arterial wall."
 

LDL does not go into arterial wall through incursion. The LDL associated proteins that are part of the endothelial repair process end up on the "other side" of endothelium, because they are first covering the endothelial damage and the new endothelial growth happens on top of that. There is no "incursion." 

 

The current textbook endothelial plaque model is causally, epidemiologically and pharmacodynamically wrongly modelled and can be demonstrated to be so. It is wrong on causation model ("high cholesterol causes endothelial damage"), it is wrong on the offending biomolecules ("LDL molecule" quantity), it is wrong on how to avoid it ("reduce LDL") it is wrong on treatments ("reduce cholesterol and lower LDL") and it has not succeeded to treat/reverse the damage (all cholesterol medications that succeed in ONLY lowering LDL/cholesterol, have failed 100%).

For all the references, all the reasoning, all the counterfactual proof, listen to this single monologue by Malcom Kendrick c. 90mins of your time:

https://nourishbalan...ing-mystery-he/

 

In summary: concentrating on LDL/cholesterol will miss the mark, use up resources from the real cause and POTENTIALLY cause other detrimental (all cause mortality/disease) issues due to diminishing of cholesterol and LDL.

 

Otherwise glycocalyx is really important. My current take (no time for refs, PubMed is friend):

 

- avoid endothelial damaging gases (smoking, exhaust fumes)

- avoid NO-synthesis reducing processes (too many to mention)

- avoid glycocalyx degrading processes (metabolic syndrome, high / continued glucose spikes)

- avoid heavy metal damages (lead, arsenic, cadmium, mercury intake, esp. intravascular, i.e. injections containing these)

- avoid hypertension (a post onto it's own for reasons that cause this)

- avoid constant stress (as a cause of hyperglycemia and/or hypertension) 

- add potential glycocalyx protecting / building supplements (this is controversial, but : NAG, chondroitin sulfate, higher blood albumin through diet, hyaluronan)

 

Like Fountain mentioned earlier, there is always context. If you eat high fiber vegetables/fruits and complex carbs, then you will not have big glucose spikes.

 

Interesting to note that dark chocolate intake is often associated with health and longevity, even though it has higher levels of metals than most foods. As an aside, if anyone knows of a "clean" chocolate product (tested for low metal content), send me a message.

[sensei]

HIGH DIGESTIBLE CARB DIETS will kill you early, -actually accelerating your aging, especially if you have any caloric excess.

[Mind]

HIGH DIGESTIBLE CARB DIETS will kill you early, -actually accelerating your aging, especially if you have any caloric excess.

 

In all of the nutrition and low-carb/low-fat diet discussion, this seems to be the key: caloric excess. After following the research for decades now, it seems you could eat almost any macronutrient ratio and be quite healthy, as long as you are light on the calories and remain thin.

 

Studies have shown that both an extremely low fat diet (less than 10%) and a high fat diet (over 65%) have health and longevity benefits. Here is an interesting review of the research and history behind both: 

 

The trouble is that the most satisfying and enjoyable diet is in the middle of the macronutrient spectrum. Most tasty meals and dishes are equal combos of fat/carbs/protein.

 

In order to enjoy life the most, I have gone with intermittent fasting. In this way, I keep my calories low and enjoy a wide spectrum of food. My second choice would be a ketogenic diet. In third place would be the extremely low fat diet. Even though I grow and eat a ton of vegetables, it is not enjoyable to eat plain low-fat vegetables all the time. Plain potatoes, plain lettuce, plain broccoli, etc...

[Priscilla]

Heart disease is a magnesium and iodine deficiency.

 

 

 

 

Edited by Priscilla, 22 September 2023 - 07:12 AM.

[Mind]

Here is another article from Mercola justifying his switch from a low-carb diet to a bit higher carb diet. He references the Randle cycle in this discussion. Interesting that Mercola is super healthy from eating a low carb diet for decades, yet he still switched to a higher carb diet (mostly from fruits), and now says he was wrong about low carb. I just find it a little weird that one would disparage a diet that kept oneself in great shape for decades.

 

 

One of the foundational concepts of health that I’ve had to radically revise my thinking on, based on Peat’s and Dinkov’s work, is the idea that eating a low-carb diet long-term is the best way to optimize your metabolic and mitochondrial health.

I now realize that this was misguided, and the reason for that has to do with the fact that your body requires glucose, and if you aren’t eating it you will go into a hypoglycemic coma and die. Obviously, your body has safeguards to prevent that, and the major one is the hormone cortisol.

In medical school, we learned that cortisol is a glucocorticoid. Gluco means glucose (sugar) and cortico means it comes from the adrenal cortex. It’s also another word for steroid. We were told that cortisol is responsible for maintaining glucose homeostasis, but led to believe its primary purpose was for inflammation.

Well, that is just not true. While cortisol certainly contributes to glucose balance, its primary purpose is to raise your blood sugar when it is too low and you don’t have enough glycogen reserves in your liver.

How Does Cortisol Work?

But just how does cortisol increase your blood sugar? It does it by breaking down your muscles, bones and brain. It sacrifices your lean muscle mass to release amino acids that your liver converts to glucose in a process called gluconeogenesis.

So, ultimately, cortisol also is going to increase inflammation and impair your immune function. And it increases food cravings. So, you do not want your cortisol to be elevated. For a long time, I was a proponent of a low-carb diet, but now I realize that chronic low-carb is not a good idea.

As a fuel, glucose is vastly superior to fat, and this was something I simply got wrong. The same thing goes for fasting. Both low-carb and fasting are great interventions in the short-term for those who are overweight and metabolically inflexible.

However, once you’ve regained your metabolic flexibility, it is important to revise your strategy and add healthy carbs back in, or these strategies will backfire and lead to decreased metabolic health, compromised mitochondrial function and impaired metabolism.

Cortisol happens to be the primary aging hormone. If it is chronically elevated, you simply will die prematurely as it is highly catabolic, meaning it will break down your body tissues. To stay healthy as you age you need to be anabolic and build healthy tissues like muscle and mitochondria.

Elevated cortisol will seriously impair those efforts. So, it is clear that you need to be doing everything you can to keep your cortisol levels and chronic inflammation low.

 

I have been on a somewhat low carb and somewhat higher fat diet for many years. I did this mainly because of the evidence for low carb diets to improve metabolic and mitochondrial health. But there is another reason: I live in the US where people tend to ingest gargantuan amounts of the worst carbs imaginable. Obesity (and the attendant major health problems) is off the charts!! Seeing this made me want to avoid carbs, however, many types of carbs from fruits, legumes, and vegetables are really good. Like I mentioned earlier, it seems you can be quite healthy on many different types of diets as long as you are not chronically over-consuming calories.

 

In the end though, this discussion has limited value. Optimizing your health through diet is great, but it won't stop you from aging.