The further a society drifts from the truth, the more it will hate those who speak it. ... In a time of deceit, telling the truth is a revolutionary act. George Orwell

Tuesday, October 4, 2011

Is t2 diabetes result of mitochondrial destruction?

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1. A hypothesis:

- Metabolic syndrome and diabetes t2 results from mitochondrial destruction caused by overfeeding with glucose (and fructose but only in the liver), taking place over many years. An individual mitochondrion has (hypothetical assumption!) a fixed maximal total energy yield out of the two main energy sources: glucose (or glucose+fructose in the liver) plus fatty acids.

There is a self-clamping regulatory mechanism preventing mitochondrial overfeeding by fatty acids, by means of Malonyl-CoA/CPT1 feedback (see Peter’s discussion), but there are no very effective self-regulation feedbacks for glucose, only a partial mechanism reducing the glucose transport into in the cells! This partial mechanism is mediated by insulin regulating the transport of glucose into a cell through the cellullar membrane. This regulatory mechanism is not always effective or fast because the insulin secretion is not local to the cell, rather it is produced in the pancreas whose rate of secretion is regulated by the autonomous nervous system and pancreating glucose concentration involving many factors other than some particular mitochondria overload. Furthermore, the insulin regulation (blocking) of glucose can be overriden by high glucose concentration.

2. Conclusions.

A straight conclusion would be that a high carbohydrate diet can indeed be healthy and avoid diabetes as long as it restricts calories to prevent mitichondrial overfeeding. What is the limit? In my guesstimate (based on published literature) - probably around 25kcal/kg for women and 30kcal/kg for men.

A second straight conclusion is that a high fat low carb diet automatically avoids mitochondrial deterioration and thus diabetes among other degenerative diseases, by its built-in biochemical overfeeding protection mechanism. (note: my daily caloric intake on a high animal fat diet, is and has been around 20-25kcal/kg since 1999).

A third conclusion concerns a situation of the cells with the insufficient number of or worn-out mitochondria. Having lower total mitochondrial energy throughput, such cells may be forced to over-rely upon and and over-utilize the Penthose Phosphate Pathway (PPP) (also called the Penthose Shunt) which takes place in the cytosol volume outside of the mitochondria. This has originally been proposed by Dr. Jan Kwasniewski, the author of Optimal Diet in the 1970-ties. I found his idea fascinating, largely because there was no easy or obvious way of proving it at the time, and last but not least - it flew right against the medical dogma! Interestingly the PPP is mainly a synthesis pathways resulting in lipids and lipoproteins manufactured inside the cells, in-situ. Such as the infamous "cholesterol" plaque perhaps? Out of glucose? Like suggested by R.W. Stout in his 1968 and 1969 Lancet papers?

--- Part 2 (9-Oct-2011) ---

3. Declining energy syndrome and carbo-loading trap.

More conclusions can be drawn out of this simple hypothesis. If t2 diabetes is the results of mitochondrial decline caused by overfeeding (carbs or by a combination of carbs and fats) then it should be accompanied by a steadily declining energy yield.

Suppose for the sake of discussion that a healthy individual consumes 30kcal/kg/day, leading active live. If he looses 10% of his mitochondria he would be able to process only 27kcal/kg/day. Less energy to work, more lethargic, getting tired sooner. What do we do when that happens? I was in that situation 15 years ago. Falling energy level at work, especially after 3pm. I snacked! I snacked on carbs! Why on carbs? Because I couldn't snack on fat! (even if I didn't believe that fat is harmful...) Fats don't work if you have mitochondrial deficiency because of the Malonyl-CoA/CPT1 feedback(*). A mitochondrion can only process a certain maximum amount of energy out of fat and that's it! If your total mitochndrial yield declined from 30 to 27 during the first 20 years of dietary abuse, then 27 is all what you can get out of fat! But you can still push your partially worn-out "engine" into overdrive by flooding it with extra glucose! It will sputter and spew out lots of smoke polluting your cells with free radicals, AGE's etc but it would allow you to bring your yield back to the previous level of 30. At least for a time being because the process of mitochondrial decline has accelerated due to the pushing them over the limit and the ensuing end product toxicity. So instead of 27kcak/kg/d, now the maximum available yield drops by another 10%, this time over 2 years. You can now safely draw 24kcal/kg/d out of fat or carbs or a combination of both. However if you want to stay awake at work you have got to load up on carb snack now by 20% not 10% over your maximum limits creating more problems, requiring a lot more insulin to overcame the natural barrier that your body cells have enacted against your plan. It also requires maintaining a high blood glucose level to speed up diffusion across cellular boundaries. Which particular cells of your body will be the first in line to see the high glucose and high insulin? Your arterial endothelium! Your liver!

This appears to be a run-away process where your tissues cells would keep enacting more and more barriers agaisnt excessive metabolism, your conscious brain will make you snack like crazy on carbs to maintain the same energy level, your pancreas will try keeping up with that pumping your insulin, your immune system will work overtime trying to clean up the mess after glucose and eventually it will also try saving your body tissue by attacking the source of the excessive insulin - pancreating beta cells, in some cases it will try even to sequester the excessive insulin floating in your bloodstream, and last but not least your poor mitochondria will keep dying! Eventually one of more of the players described above will give up. If you stop snacking and keep below your maximum metabolic yield, you will feel hungry and lethargic. Especially if you have to work 9-5. If you don's stop snacking your blood glucose would go up until you develop kidney failure. If you force you blood glucose below renal dumping threshold (about 160mg/dl) by injecting insulin you will develop heart failure or arteriosclerosis (or both). What to do? This will be the next subject.

4. The way out - what exactly happens (and when) if you start curing yourself of diabetes using a high fat low carb diet.


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More references, links and thoughts are in this file.

Footnote:

*) I am speculating but there seems to be cases when the fat-clamp mechanism may also be defeated, leading to fatty acids overload(+). This condition is also harmful creating large amount of toxins that require a massive cleanup operation my the immune system (see Masterjohn's article, in my reference file above). I suspect that this is one reason behind the so-called "low-carb flu" syndrome sometimes reported by inexperienced diabetic low carb dieters. It is interesting that fat overload (if that does happen, however unlikely) may be as unpleasant as glucose overload!

Footnote to a footnote:

+) Indeed it does happen! Peter just posted an interesting discussion about this issue here. A must read! It appears that when the adipose tissue develops insulin resistance, it is then capable of releasing fat into triglyceride particles and into the bloodstream under the condition of falling but still higher than normal insulin level! Fatty acids are then forced into the cells and a smaller fraction are then forced into mitochondria. The free fatty acids left-over inside the cell (but outside of the mitochondria) become the main cause of the insulin resistance and the cause of major cellullar cleanup operation. I have a mental picture of my old sputtering "Komar" motorbike with its carburator overflooded with gasoline...


This makes a fascinating fork in the metabolic failure modes under overfeeding. On one hand, the overfeeding with glucose may be wearing off the mitochondria and also forcing the excess fuel into adipocytes. On the other hand releasing those excessive fats from the adipocytes into the bloodstream may be setting up the physiological insulin resistance and still damaging the cells even more through the high free fatty acids level in the cytosol. Interestingly this excessive fatty acids may as likely (if not more so) come from the internal source (adipose tissue) than from a diet! It also explains why many obese people experience a health breakdown only AFTER they undergo a weight loss, especially after a repeatable weight loss and weight gain cycling.


A weight loss diet is therefore ALWAYS a HIGH FAT diet even if a person eats nothing but lean veggies!

--- Part 3 (15-Oct-2011) ---

The reason I am considering this mitochondrial decline model seriously is because of my experience. Back in July 1999 when I started my low carb high animal fat diet (almost by accident) I did experience a noticeable lack of energy, light-headedness and dizziness for a couple of weeks. Also: low blood pressure and reduced blood clotting that showed up by excessive and random bruising on my hands.
The worst part of it (dizziness and weakness) last only for 2 weeks. I didn't have diabetes just metabolic syndrome and hypoglycemic episodes. In my case, I was able to combat those initial low carb startup difficulties by carrying with me some high fat snacks such as Swiss cheese, Polish saussage and nuts.

The main problem is: when you stop consuming excessive carbohydrates then your damaged mitochondria might not be able to deliver enough energy out of fat and carbs to sustain your previous energy expenditure. You do feel the loss of energy immediately, and more hunger, therefore:    You must slow down!

 The only way for your mitochondria to recover or for your tissue to stop deteriorating and then regenerate(**) is to maintain the lower caloric intake compatible with your maximal mitochondrial yield. It will recover! This is the good news. The bad news is that it will take a few years!

Footnote:
**) I am not sure if mitochondria can individually regenerate by themselves or if the only way is for the body to regrow the new cells from stem-cells.

Yes to both, see this comment by Dr. Jack Kruse, on Peter's blog.
The low carb high fat therapy can be divided into 3 stages.

a) Switch-over

This is when the initial difficulty will show up. For diabetics and elderly this could be severe enough to warrant some medical supervision. Your body, digestive system and metabolic apparatus is switching over from carbohydrates to animal fats as the main energy source. There are hundreds of grams of enzymes circulating in your system that are no longer needed and have to be disposed off. Enzymes are protein. you will excrete their end products in urine, during this stage. Ketone bodies will show up in urine since your liver will be producing them more than your body tissue are able (yet) to utilize as fuel. Fortunately ketones in urine are in this case inconsequential but one has to be aware of it because of the rampant scare-mongering propagated by some uninformed people. I have seen many cases of people being scared by ketones and abandoned a low carb high fat diet, to their detriment. This stage last typically from 2 week to 2 months.

b) Rapid at first, then gradual improvement, disappearance of most chronic disease symptomes.

At this stage, most diabetic patients will experience disappearance of all or of most of the symptoms. Also, other chronic disease will show a lesser or stronger reversal, for example: auto-immune diseases, chronic intestinal diseases, arteriosclerosis, cardiac diseases, vascular diseases, neurological etc. However, the energy level may still be lower than on the standard high carb high caloric diet. Good news is that this yield will no longer be deteriorating. It will begin to slowly improve.

Many changes will take place at this stage, for example:
  • Eating and snacking habits will be completely modified.
  •  
  • Hunger will disappear, one will have to eat only once or twice a day. There will be no "toxic" hunger!(***) Total caloric intake will automatically and painlessly come down by about 30%, compared with the previous high carb nutrition. Please notice how close this ties with the Caloric Restriction programme! The low carb high fat diet is the Caloric Restriction program without hunger! For diabetic patients, all symptoms should disappear during this period. Most patients (except dm t1) will no longer need diabetic drugs or insulin. However - if they go back to a high carb diet, their diabetes will return.
  •  
  • Breathing rate will go down. An interesting side effect will be an ability to free-dive for a longer periods of time due to lower carbon dioxide release per calorie due to fat oxidation chemistry and due to an overall lower energy expenditure!.
  •  
  • Ability to better withstand cold temperature and cold weather.
  •  
  • Greater resistant to stress and alleviation of some neurological disorders, mood disorders, bad temper etc. This is a big and important effect! The low carb high fat metabolism is accompanied by a significantly different endocrine reaction against stress stimuli. A stress will no longer trigger a "panic paralyzis" reaction or initiate a panic attack, but will instead stimulate a generally pleasant and always useful rush of energy! The effects of stress hormones upon the neural tissues will be much less harmful in the presence of ketone bodies as in ketogenic diet, than in their absence as is more typical under the high carb diets in metabolic syndrome.  Ketone bodies are not produced when insulin and glucose levels are too high! More on the effect of stress hormones, ketone bodies and glucose upon the neural tissue is discussed here.
  •  
  • Greater resistant against infections, viral and bacterial. No more seasonal flu!
  •  
  • Complete prevention of tooth decay and dental plaque. I have seen cases of molar teeth broken in half self-healed by sealing off of the cleavage.
  •  
  • Improved cholesterol level and profile.  One notable exception: patients with fatty liver disease, the level of LDL may climb to a very high value, I have seen as high as 700md/dl sustained over a couple of years. No adverse health impact, other than scaring a "beejesus" out of some doctors... . Note that after the fatty liver recovers, LDL comes down.
  •  
  • Lower capacity to tolerate a once off high carbohydrate meal (or high intake of alcohol).  At this stage, people with metabolic syndrome and diabetics must still be careful to actually measure their daily intake of carbs and ensure it is within the strictly limited band. Typically about 50g per day.   Failure to observe this limit results in unpleasant symptoms and is hazardous to one's health.

Footnote:
***) The term "toxic hunger" as coined by Fuhrman, is in my opinion probably related to a falling level of glucose and insulin from a high value below the level sufficient to sustain glucose metabolism (in metabolic syndrome) but still too high to allow burning of one's body fat. This leads to a condition where some or all body tissues are temporarily starved of energy.   In a non-diabetic, insulin and glucose levels do not go too high thus insulin can quickly go down in between the meals prompting the release of the stored body fat.

High insulin = low leptin = burning glucose not fat.
Low insulin = high leptin = burning fat not glucose.

A very weak feeling of a slight hunger under ketogenic body fat "burning" can be easily overcome or forgotten, and is totally different from a "panicky" acute and almost painful hunger pangs experienced by diabetics and people with metabolic syndrome.  


c) Long term recovery

After several years on the low carb high fat diet, one's energy level will gradually come back to the previous level (like in one's 30-ties). This is probably due to tissue regeneration from stem cells. In my experience this will take a minumum of 7 years. An ability to tolerate a once-off higher intake of carbohydrates (typ. up to 150g) will come back at this stage. People who had diabetes may probably (I am hypothesizing) be able to come back to some kind of medium carb medium caloric diet if they wanted to, without getting diabetes because they will no longer be insulin resistant.

------
A must-read:
"Metabolic flexibility and the identical twins"


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26 comments :

valerie said...

You eat 20-25 cal per kg? That seems awfully low to me. How do you keep hunger under control? What about food obsession (happens to me when I try to reduce my caloric intake that much)?

Stan (Heretic) said...

The High Fat Low Carb diet! The figures are correct. The caloric intake stabilizes itself by the body, to the level I mentioned!. I measured my food intake once over a period of two weeks, weighing everything and using food tables to calculate calories per each macronutrient.

I am never truly hungry. It feels very differently than when on a high carbohydrate diet. Back then I either had to snack like crazy every 1/2h or pretend to like going hungry every day in between the meals, all the while bullshitting myself that "hungry" is supposed to mean "healthy".

I eat only when I feel like eating and "peckish". Which is typically only once or twice a day! On a high fat diet I am never truly hungry to the extent that I used to feel before, that is before 1999. My weight is stable and my energy level is very good for a 55yo. I think, the older you are the better it works! Why haven't yet more people in this culture discovered that? Beats me! May be they are just ... hard to tell.

I eat mostly natural, unprocessed food. Rarely packaged food. High in animal fat, fatty cuts of meat, cheeses, cream, butter, fish, chicken, and last but not least - VEGETABLES. Almost no bread (may be once a month a small slice).

I would never go back!

J. Stanton said...

Stan:

Thank you for putting together these notes, and for a very interesting hypothesis!

It will take a lot of patient work to investigate the links in the chain you propose, not to mention the myriad other possibilities still available at this point. I further suspect there will be a role for linoleic acid in causing or potentiating mitochondrial dysfunction.

However this all shakes out, it's exciting to be part of an online community that is actually advancing the state of knowledge. What the community needs now is a lot less prescriptive advice based on bold new hypotheses and n=1, and a lot more patient investigation of the facts. Keep working, keep moving forward.

JS

STG said...

Very important topic and thoughtful hypothesis. Anticipating your next post.

Stan (Heretic) said...

STG,

Thanks for the encouragement. I have been wondering about this topic for a long time, ever since being challenged by diabetics on various discussion groups. They make some of the most vocal opponents of the low carb high fat nutrition. I always wondered why. Now I am beginning to understand it better.

JS,

Thanks, I will.
I agree that there is something "fishy" about the popular polyunsaturated seed oils. Even the countries like India that were using veg oils for ever are not using them exclusively. Always with butter or other animal fats.

The only thing now is to find out exactly what is wrong. I am not sure of the mechanism. An impact on the immune system? Probably true (there are studies on linoleic acid immuno-supression) but it has to be something more subtle yet substantial about veg oils, that must be affecting basic metabolism directly.

I agree that n=1 is grossly insufficient but we have no choice. But even n=1 may be still enough to falsify various hypotheses thrown upon us from the "other" side, such as that animal fat is supposed to cause heart disease etc. The fact that guys like me are alive not dead, that is n=1 not n=0, is sure like hell making a lot of titled academic parasites very unhappy... 8-:)

Regards,
Stan

STG said...

Stan:

The people who crticize low carb/high fat for diabetes must be brainwashed by the ADA or AHA. Jenny Ruhl, as your probably know, has a great website about diabetes and she advocates a low carb approach. Recently an important book was published called Sugar Nation. The author, Jeff O'Connell also argues for a low carb diet to deal with prediabetes. There is a Dr. Bernstein's diabetes low carb diet forum on the low carb forum. My point is that there are people who are controlling their blood sugar sucessfully with low carb diets and they are talking/blogging about it.

Stan (Heretic) said...

Re: "The people who crticize low carb/high fat for diabetes must be brainwashed by the ADA or AHA."

May be. People in this culture seem to enjoy being brainwashed by all sorts of public media. 8-:)

In addition, diabetics in particular experience really unpleasant effects initially when they try to restrict carbohydrates and go back to fat. I described some in the part 3 of my article. In addition they seem also to experience some endocrine-triggered mood disorders (typically emotional outbursts). It makes it particularly difficult for them to engage in a normal technical discussion. More often than not, my attempts at passing them some information on various discussion groups (such as webmd diabetes forum) resulted in verbally abusive outbursts.

Stan

john said...

Stan other ways to increase adipocyte mitochondria are and decrease adipocyte counts are synthetic leptin administration, high dose resveratrol, green tea in high doses, and heavy use of quercetin. The best unknown way is PQQ! I have blogged about these supplements in many of my blogs. The key to reengineering humans with leptin problems is tuning up the mitochondria. Most of the paleo bloggers talk about what happens in normal folks. Well normal folks dont come into my office too often. It takes years to rehab the mitochondria but doing it first with a ketogenic paleo diet is critical foundational work in my Leptin Rx. After some years the mtochondria can revert back to burning carbs and BCCA well again. It is not a slam dunk like some bloggers would have you believe. If it were then we would have to explain all the people on everyones blog comments who have problems with the higher carb diets some advise. Normal people can eat carbs and BCCA's because they have normal mitochondria with normal CO2, low HS CRP, good RQ, and excellent leptin function. My focus is on the folks who need a doctor to fix them and not read a research paper and translate it via a biased mind. We are all biased to some degree but when we are trying to repair people we have to try to keep our minds open to all possibilities even if the seem remote. I think much of what has transpired since AHS over this carbohydrate macronutrient nonsense is more about ego than any science. Love your blog to Stan. Keep it up. Dr. K

Morris said...

Stan
I find your hypothesis very interesting. For the last 10 months I have experimented with variation in caloric intake with surprising (to me) results. I have tried posting but the post did not appear. Edited out? If of interest, I will try again.
Best

valerie said...

Morris, please do post!

Stan (Heretic) said...

Morris,

I checked the blogspot spambox but your post wasn't there. It must have been eaten by a PC while you were trying to post. I have added the "anonymous" selection which will allow commenting without a login-in, since some people reported problems, in the past. Sometimes, an automatic spamcop removes the posts if they contain some dodgy links, for example those selling drugs etc. I cannot disable the spamcop or relax otherwise we would be flooded with commercial garbage. However, even if a comment were removed by the spamcop I would still see it forwarded to my email and I would repost it myself.

Regards,
Stan

Morris said...

Stan
I particularly find your energy/ kg values intriguing as I started out much higher and am now approaching your values in an attempt to find an optimum. I lost about 9 lbs over a 48 week period, although weight loss was not the objective My experiment consisted of gradually increasing fat calories while keeping carb + protein calories ~ constant, starting week 0, peaking at week # 17 and then reducing calories (as fat) to the present (week 48). Carbs ranged from 90-110g/d except for a 7 week trial in 130-185g/d range. Carbs include fibre, typically 15-20g/d. I am moderately active.
My results:
Week 0: 2507kcal/23.5BMI/36.9kcal/kg
Week 17: 3307kcal/24.0BMI/47.7kcal/kg
Week 48: 1650kcal/22.1BMI/25.8kcal/kg
As you pointed out, initially the improvements were relatively quick and then slowed. Improvements were in aging biomarkers, I was not clinically sick. But I did notice a decline in endurance exercise fitness, which has not yet returned but strength did not change.
Some unexpected results: I continue to not have hunger or cravings even as I have reduced calories. My body is much quicker/more sensitive to changes in diet composition. Some food aversions appeared early and then disappeared. I estimate a loss of about 4 # of gut microbiota. Microbiota mass seems to go with total calories, so implies presence of eukaryotic parasites.
You say a minimum of 7 years to recover. Do you bas this on cell replication time?
Best

Stan (Heretic) said...

Re: Carbs ranged from 90-110g/d ...

You meant fat? My fat intake was also clipped at ~120g initially. I could not simply make myself to eat more - wasn't hungry! I also had to limit my carbs, to ~25g/d in the first couple of years. I felt it when I exceeded 50g a day. Now - no problem!

I found that I could not increase my caloric intake on my high animal fat diet, other than by increasing carbs! Which I of course would not do! I could not increase my fat intake beyond about 150g (the highest amount in a day I registered was ~180g. I never really understood why is that. especially since I am trying to follow Dr. Kwasniewski's guidelines for the "Optimal Diet" (see for example this). The recommended range is 2.5-3.5g of fat per day. Since my body weight is ~65kg that would mean 160-230g/day. I cannot eat that much!

I couldn't understand why is that, until Peter ( Hyperlipid) posted his recent series of articles about mitochondria.
Stan

Morris said...

@stan
I meant carbs, not fats. For 17 weeks in the calorie increasing phase, fats (weekly averages) exceeded 200g/d and one week hit 300. I reckon that my metabolism is not badly damaged and that I may be able to test for an extended period the low energy/kg levels you practice. This sounds to me like calorie restriction but perhaps without the discomfort of hunger.

Jaego said...

I tried to give up sugar and failed. I collapsed - complete with many strange symptoms and trouble breathing. I think I have candida and was experiencing the so called die off or "Herxheimer Reaction". Didn't know at the time or I would have used anti-fungals. I did have alot of small brown particles in my urine, but were these the ketones you mention or the dead fungus?

I'm going to try again in a few weeks.

Stan (Heretic) said...

Jaego,
You should monitor your blood glucose with a glucometer, next time you try it. If your glucose level goes down below about 80mg/dl as shown by glucometer, then you can remedy it by taking a glucose tablet (not sugar! glucose is better than sucrose).
This will slow down the process of weaning yourself off sugar but it will be much safer.

If the symptoms are more severe you shouldn't attempt that but rather do it only under a medical supervision. Re: particles in urine - I would recommend to ask a doctor. Ketone bodies are invisible and colorless, you cannot see them in urine.

Mark said...

I just want to mention the book: sex power suicide by nick lane. To learn more about mitochondria. Also, Peter does some talk about Mitochondria over at Hyperlipid.

Sam said...

Thank you very much for your blog. I'm most appreciative.
I wonder if a high fat diet that includes a lot of saturated fats wouldn't put you at a risk for heart disease? I've been reading a lot about high fat/ low carb diets and have been impressed. They're is really only one guy who impresses me against this type of diet due to high saturated fat.
I know you said you have filters for ads (this is not one) so I'm going to go about this in a round about way.
Through reading about low carb diets I came upon the book,"Ignore the Awkward.: How the Cholesterol Myths Are Kept Alive by Uffe Ravnskov" on Amazon. I looked at the comments and one guy "D.M." seemed to make extremely good points about high fat diets bad for you. The bad part being high saturated fat. All his post are reasonable and backed with numerous health studies. All his detractors seemed to waffle around and insult him.
I wonder have you made an effort to keep low saturated fat consumption low?
I know your busy but if you're interested in diet the commenter "D.M." on the book I quoted above has a succinct, high content first post reviewing the book.
It's hard to know what to believe. I have seen a study by Stanford M.S. that shows the Adkins diet better than all the other "diet book" diets.
Thank you for your time if you read this.

Stan (Heretic) said...

Re: "I wonder if a high fat diet that includes a lot of saturated fats wouldn't put you at a risk for heart disease?"

No, if it were a slightest of a risk then I would have been dead since I am consuming 150-200g of animal fat every single day since July 1999. I did have a mild angina back then, to start with, probably due to my previous decades of a "healthy" high starch low fat eating. It went away in the first 2 years, by around 2001. I am now 56.

The very fact that are you reading this message regardless of its contents, is the best proof that your fear of fat is irrational and baseless!

Re: Familial Hypercholesterolemia (from the thread you mentioned)

This study showed that FH was associated with the the risks only for some people and only in the recent period spanning the last 1930-60 out of the 200 years of patient's family histories.

That means that some other factor must be at play than the high cholesterol alone. I suspect (my personal opinion) that the mortality risk for FH is modulated by carbohydrates intake. That's why the Dutch families with FH did not experience an increase in mortality until the period of 1930 depression and WWII poverty and malnutrition.

Re: "4. People with an intermediate level of LDL have intermediate levels of heart disease."

Not true! See:
Fat and CHD.

Lipid Level in Patients with CHD

It is not fat but rather excessive carbohydrates which seems to be the problem. See the following:

Refined Carbs

Food Choices

Carbs and Women's Heart Risk

It's the Glucose...

I hope this helps.
Regards,
Stan (Heretic)

Sam said...

Thank you VERY much. I looked my post and it was practically incoherent. Ouch! I was afraid you wouldn't answer at all.

Stan (Heretic) said...

DM wrote: How does LDL cause atherosclerosis?
9. Last but not least elevated LDL is essential to the mechanism of atherosclerosis. Apo B lipoproteins (mostly LDL) diffuse into the artery wall that has been damaged by hypertension (coronary arteries have the highest blood pressure) , smoking or alcohol. They become oxidized and cause inflammation which attracts macrophages. Macrophages devour oxidized LDL and become foam cells which form plaque and produce more inflammatory chemicals. They grow and eventually rupture depositing cholesterol crystals in the plaque. The crystals penetrate the artery wall causing even more inflammation. Elevated LDL also impairs endothelial function, reduces nitric oxide production and promotes platelet aggregation which promotes clotting. There are other factors besides elevated LDL that contribute to heart disease like smoking, hypertension, diabetes, abdominal obesity, stress, inflammation, homocysteine, sedentary lifestyle and excess sucrose but according to the INTERHEART study the ratio of apo-B (mostly LDL) to apo-A1 (HDL) can account for 50% of the risk. (16,17,18,10)


No, if LDL was causing the disease then the correlation factor would have been much closer to 100%. It is not even close.

Cholesterol in the arterial plaque is synthesized and deposited in situ out of glucose and in the presence of insulin (the necessary factor!). See the papers discussed in:
"Arterial plaque = glucose + insulin, C14 traced study"

So is calcium present in the plaque a by-product of excessive glucose metabolism in the arterial tissue, not fat! LDL particles are congregating at the damaged arterial endothelial sites as part of the repair apparatus, mobilized to heal the damaged tissue, rather than being the cause of the injury. LDL presence is coincidental but not causual!

Incidentally, a subpopulation of the LDL particles (small dense, phenotype LDL-B) that correlates with the arteriosclerosis the most are the product of IDL synthesized mostly in the liver out of fructose (alcohol and glucose too). See for example this

Ravnskov is discussing those issues with all the necessary references and more. DM should have read the book before reviewing it.

Heretic

Sam said...

Thanks. Know how you read a lot of varied information and somehow the last piece of data makes it all jell together at once? The last links you posted put it all together for me. Seems you know the answer to the question before I ask.
I read the "Arterial plaque = glucose + insulin, C14 traced study" earlier but didn't understand it's context. Now I see it as equal to carbs causing insulin spikes and what the results of the spikes would be.
The "A Case For High Fat Nutrition" was exceptionally good. I now understand the differences in LDL types and how that's related to diet.
Another post in response to D.M. impressed me,"...The Framingham Heart Study is often cited as proof of the lipid hypothesis. This study began in 1948 and involved some 6,000 people from the town of Framingham, Massachusetts. Two groups were compared at five-year intervals-those who consumed little cholesterol and saturated fat and those who consumed large amounts. After 40 years, the director of this study had to admit: "In Framingham, Mass, the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower the person's serum cholesterol..."

from

http://www.amazon.com/review/R1I48208CNRFQ5/ref=cm_cr_rev_detmd_pl?ie=UTF8&cdForum=FxLEPTN0SMVO9V&cdMsgNo=188&cdPage=19&asin=B004EPYUPI&store=digital-text&cdSort=oldest&cdThread=Tx3JW2BGUJNL5WT&cdMsgID=MxJOGA6E8VCVIM#MxJOGA6E8VCVIM

I've ordered Dr. Ravnskov's book and a lot of Adkin's diet books.
I'm going back and reading your earlier blog posts. It's very interesting. Thank you for your efforts.
I'm still a little nervous about saturated fats. Can't help it. It's been hammered into me for so long that they are bad.

Stan (Heretic) said...

Re: "In Framingham, Mass, the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower the person's serum cholesterol..."

This is William P. Castelli's quote. He stated it, meaning it as the paradox since he himself is a firm believer in the fat and cholesterol theory of heart disease. He was the third director of Framingham Study. They discovered many more such fat and cholesterol related "paradoxes" since then, such as: Spanish, French, Swedish, Russian, Lithuanian, Israeli, Polynesian, Greek and Cretean etc.

Stan (Heretic) said...

Response to Dolores (on another forum's thread). I am posting it here since I do not know if the original will be preserved and for how long.

Regarding diabetics, I agree with you to some extent but my conclusions are different.

There seems to be more going on with diabetes than just "glucose intolerance" or "sugar overload". My current working hypothesis is that they are caught between two crippling conditions:
1) insulin resistance
2) mitochondrial destruction

Condition 1 creates what we refer to as "glucose intolerance", that is it forces them to ingest more and more carbs to burn the same amount of glucose for energy. At the same time it leads to hyperinsulinemia which then leads to overweight, heart disease risk, PCOS risk etc. On the high carb diet they are able to overcome the falling metabolic yield due to insulin resistance by pushing more glucose into their system and by triggering production (or injecting) of more insulin. Notice that glucose metabolism may take place in the mitochondria as well as outside of the mitochondria - that is the crucial point!

Condition 2 on the other hand prevents them from attaining the normal energy level on a high fat diet! Fat is transported throughout the body in the blood stream by VLDL ("Triglycerides") and can only be metabolised in the mitochondria! That poses a metabolic clamp on the maximum energy release for the body function if the mitochondria are depleted, that cannot be overcome by "pushing" more fat from food or by releasing own body fat!

In fact, attempting to consume more fat above the mitochondrial limit, or when loosing weight too rapidly that is accompanied by release of too much own fat into the blood stream - can make one feel really sick! The symptoms are as under an accute infection, that is general weakness, sometimes fever, nausea and typically a massive headache that cannot be remedied with aspirin.

The symptoms are like of an infectious disease because it is the immune system that has to dispose of the excessive fat and clean out the debris from the overloaded cells.

Basically, a diabetic has got a choice of either (a) maintain a normal metabolism and have a normal energy level on a high carbohydrate diet by pushing a lot of carbs into their body, overcomming the resistance with the sheer concentration of glucose and with insulin or diabetic drugs.

(b) They can accept and live with a lower metabolic energy level on a low caloric high carb diet such as Pritikin's etc.

c) They can accept and live with even lower metabolic energy level on a low caloric high fat diet such as Kwasniewski's Optimal diet, Atkins, Paleo etc.

Out of the 3 scenarios only one (a) allow a diabetic to experience and maintain a normal energy level albeit at the cost of continous mitochondrial deterioration, progression of all diabetic symptoms and shortened life span.

Out of the three scenarios only one (c) allows a patients to gradually (over about 7 years) to recover from mitochondrial depletion through a complete cellular rebuilt (from stem cells).

Heretic

P.S.

GTT (oral glucose tolerance test) that uses 100g of glucose, will always be somewhat abnormal for a person on a high fat low carbohydrate diet! Even if you take a perfectly healthy 20 years old! There is nothing pathological about it, just a normal biochemistry and body's adaptation - it is like if you poured 87 octane gasoline to a racing car that requires 91 octane. If you want to measure glucose tolerance on a mix diet population that includes low carbers you have to use 50g tests. The test works just the same except the calibration curves and limits are slightly lower.

Stan (Heretic) said...

- It seems that the problems some (but not all) diabetics experience on an Atkins-like diet stem from the fact that they attempt to increase their metabolic yield through overfeeding!.

If they overfeed using fat it brings the symptoms like I described above. If they try overfeeding with protein it brings other problems, one of them being conversion of excessive protein into glucose and then the body having to deal with excess fat, protein and glucose at the same time.

I realize that a high fat low carb diet is easy for me but it may be quite difficult for a diabetic patient. It requires a certain amount of determination to maintain a discipline because one of the diabetic symptoms is an incessant hunger. There is no easy "fix"! For a type 2 diabetic, the easiest way is perhaps the scenario (a) - the road to "hell". From my own observation of diabetic people than I know, the second easiest path is (c) because of the hunger-quenching property of fat, although it does require an acceptance of low energy level (if you are diabetic). I believe that (b) is actually the hardest.
H.

Anonymous said...

Stan, thank you for posting about overfeeding, the symptoms of too much fat, and mitochondrial yield. Your posting all this has been a great help to me. :)

You explained why, even with keeping constant amounts of PRO and CHO, eating real food, that too much FAT, causes ill.

Even on very low carb, and moderate protein, there really is "no such thing as a free lunch".

Thank you very much. :)