She links to Ruderman's mini review, which we will come back to in some detail in future, and there we find this excellent graph:
I rather like this graph, although it could theoretically be reduced to one line of text. The bit I like best about it is that you can play Pin the Donkey Tail on it. We'll play later.
The graph shows that lipid oxidation, as indicated by respiratory quotient, is well below normal in both pre-obese and post-obese people.
But not in the obese.
No, the RQ of an obese person is, from the graph, somewhere around 0.825, ie an obese person actually runs their whole body metabolism slightly more using fat vs carbohydrate than a non obese person, who has their RQ at around 8.5 when on a mixed diet.
It is only the pre-obese or post-obese who run their metabolism on carbohydrate (poorly) and fail to oxidise fat, their RQ panning out up at 0.875.
If we ignore causes of mitochondrial dysfunction for the time being, we can look at these situations logically. I'm loathe to use analogies but they are useful on occasions. Here's one, highly factual and probably quite relevant:
Take a type 1 diabetic with complete failure to produce any pancreatic insulin. Ask them to volunteer to skip their exogenous insulin, become both profoundly hypoinsulinaemic and markedly hyperglycaemic. Then use a tracer to measure their glucose metabolism. Can they use glucose? Of course they can. This was done back in 1978 and the results are quite clear cut. Acute hypoinsulinaemia can be compensated for by acute hyperglycaemia.
Now, the question is whether there is a situation existing at the mitochondrial surface, as relates to fatty acids, which is analogous to that at the cell membrane surface as regards glucose. Glucose uptake is controlled at the cell surface. Fatty acid uptake is (predominantly) controlled at the mitochondrial surface.
Can we increase intracellular free fatty acid derivatives to the point where energy production can be forced back up to a semblance of normality in the abnormal mitochondria of a pre-obese person?
The graph of RQs suggests to me that this can indeed be done.
However it requires an increase in FFA delivery to the tissues well in excess of what a normal person might oxidise. There needs to be enough of an increase in FFA delivery to the tissues to reach the point where FFA derivatives can be "pushed" down an adequate concentration gradient in to mitochondria to restore adequate ATP production.
The cost of this maneuver is in increased FFA intermediary-derived insulin resistance and even greater failure to use glucose.
If you are having even more problems using glucose because you have managed to get your fat oxidation up by increased lipid derivatives within the cytosol, where would you expect your RQ to be compared to someone who has free choice in metabolic substrate utilisation? More fat, less glucose. So the RQ will be.....
Lower of course. Somewhere around 0.825 I would guess, looking at the graph.
You can see why I like this graph...
So we know that the pre-obese and post-obese have problems burning fatty acids in their mitochondria. We know the currently-obese have corrected this defect by increasing fatty acid delivery to their mitochondria at the cost of worsening insulin resistance.
How do we increase fatty acid delivery to the cytosol? Fatty acid delivery is primarily controlled at the adipocyte level. Insulin, acting on normal adipocytes, inhibits lipolysis. Have I ever said that before?
Adipocyte insulin resistance is the direct equivalent of relative hypoinsulinaemia. If we simply stretch our adipocytes to the point where they no longer listen adequately to insulin we can increase FFAs delivery to the blood stream and so increase their delivery to cytosol and get to work pushing them in to whatever mitochondria we have.
In the state of established obesity energy production is, in fact, normalised.
Let's just set this out:
Mitochondrial dysfunction leads to cytosolic fatty acid derivative accumulation.
This leads to chronic hyperinsulinaemia via insulin resistance.
This leads to adipocyte distension.
This leads to adipocyte insulin resistance.
This leads to increased plasma FFA delivery at a given level of insulin.
This leads to increased cytosolic FFA derivatives.
This leads to mitochondrial ATP production being normalised.
The cost is increased insulin resistance. Oh, and the MECHANISM for improved ATP production is OBESITY. Call this a cost if you wish.
BTW: Of course there is a second set of discussions related to adipocyte mitochondrial dysfunction but I'll leave that out to keep it simple here.
Okaaaaaay.
Time to play Pin the Donkey Tail.
Everybody needs a drawing pin (thumb tack?). And a piece of string attached to it to represent the donkey's tail. It is traditional to have a picture of a tail-less donkey taped to a cork board and to try and pin the tail in the correct place, while blindfolded. I'll let everyone off of the blindfold and we can have this nice blue balloon as a substitute for the picture of the tail-less donkey.
It would be very helpful, if you are doing this at home, to write "Adipostat Hypothesis" on the balloon, most easily done before you inflate it. I couldn't be *rsed to do this, as always.
Now pin the tail, using the thumb tack, on to the balloon.
Pop!
Oops. Did you just pop the set point hypothesis of obesity? Clumsy of you, but easily done.
Obesity is a method of normalising ATP production. The concept of an adipose tissue "set point" is an artefact of how much adipocyte distension-induced insulin resistance is needed to normalise tissue ATP production at a given level of mitochondrial dysfunction.
Confession time. I never meant anyone to pop a real balloon. You don't have to actually do it. What I really wanted everyone to do was to pin a hypothetical donkey tail to the graph at the top of the post.
You need to guess what the respiratory quotient is for a person who, for the last seven days, has been eating a diet which included less that 20 grams per day of carbohydrate, around 60 grams of protein and as much butter as they like.
All you have to oxidise outside of your brain is fat. Your RQ will plummet to the lowest value possible short of full starvation. FFA delivery to non neural tissue will rocket. Glucose delivery will be irrelevant and the role of insulin in energy production will be sidelined. Cytosolic FFA derivatives will sky rocket too, to keep you alive using physiological insulin resistance, dontcha-no.
Perhaps you will normalise your ATP production?
Might you normalise your appetite too as you normalise your ATP production? It happens for many who try it...
Peter
I think ATP, AMP and AMPK might be an interesting subject to move on to next.
130 comments:
Is this the reason Rosedale insists on supplementing with n-acetyl carnitine on a low carb diet?
This is a phenomenal post, Peter. The "set point" theory (or settling point) always gave me the willies. People who use the term seem to do so to explain something they don't fully understand or can't explain (FR hypothesis anyone?). It has a religious connotation that I don't fancy in science. But I never could pinpoint what it was that made this concept fall flat. Everything else in the body seems to come down to homeostasis. Seems like it still does. Kudos.
@Miki,
"Carne" means meat. Meat (particularly organs) is chock full of carnitine.
OMG epic response/discussion ahead sorry :(
The graph only seems to plot pre obese and obese people, and non obese controls. ... I do not see a point where post obese are represented. Am I reading it incorrectly?
The direction of this discussion of mitochondria seems to be missing a piece of info: cell level mitochondrial activity is controlled by neurotransmitter and hormones: changes in metabolism are not always attributed to irreparable mitochondrial damage.
It has been shown that in a post obese person, leptin can restore these oxidative defects. They are not permanent, they are not mitochondrial "damage", the cells are refusing to work normally as a downstream effect of low leptin and low dopamine.
It has also been shown that lack of dopamine signaling will cause functional mitochondrial-level metabolic switch; a lack of dopamine signaling leads to an inability to suppress fat oxidation in the presence of glucose at a meal (result, hyperinsulinemia), combined with an inability to oxidize fat in general (result, higher RQs and a paucity of energy at all times)
The post obese person is leptin insufficient, and by definition, dopamine insufficient, as leptin is a crucial prerequisite which must be in place if your brain ever hopes to make normal levels of dopamine.
People with congenital leptin deficiency, have never known leptin, go through almost instantaneous personality changes when they get their first injection. They go from passive, child like beings to assertive, aggressive and adult like. The personality changes rapidly exhibited by completely leptin naive humans is awfully suggestive of normalizing dopamine in the brain, as these personality traits are associated with dopamine activity (dopamine tends to make people more active and aggressive/assertive and motivated, and is naturally higher in men due to testosterone bolstering dopamine... females are more serotonin dominant, and serotonin has the opposite effect on personality, creating inhibition and hesitation/anxiety lack of motivation/ assertiveness. The dopamine and serotonin balance is another reason why males effortlessly lose weight and fast whereas females cannot do this as easily and struggle with weight loss... nature is SMARTZ, female physiology freaks out from food deprivation much more so than male physiology, that fetus thing again).
Also, the obese person is in a state of chronic dopamine insufficiency as dopamine receptor downregulation is required for obesity to occur. When normal people have their dopamine receptors blocked (e.g. HALDOLIFYQUEL) or lost pathologically (bad meth habit; coke, nicotine) they rapidly find themselves becoming fat and diabetic and apathetic/depressed and fatigued and difficulty moving/energy with lower blink rates with lower rates of facial movements and quite hungry -- all dopamine mediated effects. Obesity is unique as this is a condition where the dopamine receptors spontaneously downregulate - no one took haldol, zyprexa, no one used coke or meth.
The food addiction/reward people would state BUT ITS FOOD REWARD, however it should be mentioned that the obese downregulate dopamine receptors not in response to tasty food, but to GLUCOSE IN GENERAL. The tastiness of food merely controls how assaulting (dopamine downregulating) will be the glucose bolus in your CNS. Tastier food leads to more eating, leads to higher glucose spikes, leads to buh byez dopamine receptors. The taste/reward did not do it. The glucose did. If you lavage glucose down the throat of an obese person, sans perception of food, the dopamine receptors will be lost all the same, because this is an effect of glucose specifically. Low taste/disgusting diets merely prevent people from lavaging glucose down their throats. If they lavaged brie cheese and walnuts instead, enjoying yumminess along the way, this downregulation process WILL NOT OCCUR, because brie cheese and walnuts = fat, with no ability to cause dopamine receptor site downregulation.
Food restriction rapidly restores dopamine sensitivity in an obese person, and I think another reason the reason LC is so palliative and long term efficacious is because it allows people to eat energy without down regulating dopamine receptors. Quite the opposite, ketosis and fat metabolism preserves and augments dopamine as it is a fat-metabolism based intervention, and normal dopamine function is absolutely required for ketosis. Dopamine rules fat oxidation.
I've long considered that a proper "low carb' diet is less than 20g/day. The metabolic differences between say 10g and 100g of carbohydrate daily are staggering.
I'm very suspicious of this group of people so-called identified as "pre-obese".
So far I have not seen this defined? Is a pre-obese person someone who will gain 30 pounds in the next year? Next 5 years? next month? Is the definition of a preobese person consistent between studies?
It seems we are extrapolating findings from this so called "preobese" person , and then concluding things about what does or does not cause obesity (e.g. "if pre obese people are oxidizing a lot of carbs, that means / evidences that obesity is a state of fat oxidation deficiency, and once the person becomes obese, they oxidize fat normally") This is not appropriate, because actively gaining body fat is not the same condition as being obese and weight stable.
Given that a "preobese" person isn't really defined, in the way an obese person or post obese person is (these have obvious immutible definitions)... and given that being in a state of body fat gain is quite different than being in a state of energy balance...it stands to reason that the "preobese" person may be exhibiting the metabolic abnormalities they are because they are rapidly gaining weight and this has no relevence to the baseline mitochondrial potential of an obese person.
If you are eating a ton of carbohydrate and calories , fat and glucose because you are getting fat (hypothetically), I would expect the basal blood sugar, insulin, thus the RQ to be higher while "fasting" .
The general idea that an 8 hr fast sets us into a fasted state is only true when the person isn't eating excessive amounts of food and their glucose/insulin dynamics are not subsequently exacerbated. RQ is typically measured after an overnight fast.
Think about it.
Imagine you are a 130 pound woman, who falls into the category of "preobese", i.e. you are about to gain like 30 pounds of fat.
Your glucose tolerance & insulin levels just went to utter shit (you started solumedrol/you started taking a SSRI or antipsychotic for depression/you started a new job and stopped sleeping normally/you are under a lot of psych stress/ just started taking prednisone based birth control or just got pregnant/ etc etc etc).
This new found shit glucose tolerance/higher insulin levels will lead to EATING A LOT MORE calories. You will be in chronic energy surplus, which is actively being shunted into body fat as you are not diabetic. You will be oxidizing a lot more glucose than a weight stable person, whether that weight stable person has a large adipocyte storage volume or not.
Even if you are asked to fast so that some nice scientists can measure your RQ, the fact you are "preobese", eating 3000 calories due to symptomatic glucose intolerance/hyperinsulinemia means your RQ is not going to dip as low as the person in body fat equilibrium. Your insulin and basal blood glucose does not drop the way it does after 8 hrs sleep for a weight stable person, as you are "preobese", which means you are eating a ton and have higher insulin.
The solumedrol/depoprovera/abiliquel is keeping your blood glucose higher, and your insulin higher, and your RQ also higher, even if you are fasting for 8 hrs.
So, when stating that this "preobese " group has a higher RQ, and then concluding that fat oxidation defects mediate obesity...it's a big leap. Theres a lot being supposed as fact that should not be.
Kind of like when the food rewardists view the lack of dopamine receptors in the obese, and IRRATIONALLY conclude the obese must be addicted to food. Duh factory.
peter:
"Carbing up immediately post workout could help you to make the most of the feeding window"
peter ^tis^ right? ( i know this is not your thing, but it might be related, lots of AMPK bs talk there)
http://suppversity.blogspot.com/search?updated-max=2011-10-02T17%3A04%3A00%2B02%3A00&max-results=20
btw, still etin^ teh evil sugars @ milk... hows do u think my mitochondria is dooing, haven't ballooned yet,wouldn't be able to fit this XD
http://img274.imagevenue.com/img.php?image=361380348_DSCN0344_122_591lo.jpg
ups, wrong link
here...
http://suppversity.blogspot.com/2011/09/intermittent-thoughts-on-intermittent_25.html
I agree with woo that the issue in food addiction-like overeating wrt dopamine is not taste, but I believe that taste does contribute to learned aspects of eating ... we associate the taste with the benefit the sugar (or the opiod peptides in wheat or dairy) delivers. So we remember the connection and go back to that food again as a result. J Stanton is doing a pretty good job hashing this out over on gnolls.org.
And yes, low-carbing restores dopamine sensitivity, but going paleo/PHD (removing wheat and dairy) seems to work as well for a lot of folks.
So while I have my own semantic issues with the concept of "raising the fat setpoint" I don't really understand completely discounting the idea that some (a lot?) of obesity is being driven by appetites being disrupted by modern, high-palatable food and that what Peter is describing here is the downstream effect of that overnutrition.
Brilliant.
Peter, thank you for putting the word "mechanism" in big block letter where I can easily see it. It's a word I keep looking for in explanations of obesity by other means, but haven't found yet. Maybe if I treat these other explanations like a word scramble puzzle I can find it?
Woo,
You didn't read the graph wrong in terms of not seeing 'post-obese'. It's not on the graph itself, but in the description. It says pre-obese and formerly obese.
Anyways, it's a stupid graph as elegantly pointed out by Peter. The build up and lead up to the fun pin the tail on the donkey game was brilliant!
Their explanation for being obese helps mediate fat oxidation just sounds like becoming diabetic...That is not 'normalization' at all.
In "Power, Sex, Suicide," Nick Lane makes a pretty convincing argument that mitochondria are subject to selection pressures within the body--which is why (to most researchers' surprise) mitochondrial defects do not accumulate at high rates; defective mitochondria are weeded out. (The main mechanism is pretty drastic: cells with a high proportion of dysfunctional mitochondria commit apoptosis.)
It would be interesting to know if dietary changes select for differently adapted mitochondria.
Peter,
I can't satisfactorily reconcile these two statements.
1. "Fatty acid uptake is (predominantly) controlled at the mitochondrial surface."
2. "Mitochondrial dysfunction leads to cytosolic fatty acid derivative accumulation."
Statement 1 seems to imply that the exchange of FFAs and their derivatives between the cytosol and the extracellular environment is tolerably efficient. I understand that this exchange does not depend upon transporter molecules, unlike in the case of glucose, so we're talking about a process that looks like diffusion and maintains the intra- and extracellular concentrations about even.
Why then does mitochondrial dysfunction lead to cytosolic fatty acid derivative accumulation? What's stopping them from diffusing out?
Maybe we need a critical mass of dysfunctional cells, so that extracellular/palsma FFA concentrations track upward because there's a whole body bottleneck on FA oxidation, leading to the consequences you enumerate. Is it as simple as that?
Loved the balloon. I like balloons.
When somebody is loosing weight, it could be illustrated by several inflated balloons assembled like nest-dolls (progressively smaller inserted into bigger ones)and got punctured one after another through intervals of time. Such intervals are often not short.I personally spent 2 years on a weight-loss plateau. I thought I was moving through "set-points". I was always wondering what was going on , and the therm "set point" or the image of changing "set points" sort of explained for me some of it.
@TheWooo
I could be an illustration for your description of a pre-obese individual 5 years ago when I moved from 172lb (5'6") to 198 lb during one year. I remember being hungry in 2 hours after each meal and energy crashes after meals. Food was tasting amazingly then. I tried to compensate my appetite with 1.5 hours of exercise daily - it didn't work of course. Many things happened then - I started a new demanding job, decided to live healthier life and substituted most of my red meat with soy staff, limited fat in my diet, turned 45 years old. Each of things could be blamed for my weight gain. In a hint sign, it looks like a perfect storm. I am on LC now and unemployed. Luckily, my husband's provides a good income. Like you, I am enjoying great metabolic health - most of my fat is going into legs, butt and upper arms, all blood work always looks perfect, never ever even a hint of a high blood pressure.
I just wanted to clarify since my previous 3 epic rambling posts were not clear and tangential...
I do not disagree with what is written here, it is absolutely brilliant.
It does, make sense, that the point in which obese people become weight stable, is the point where their fat cell insulin resistance reaches a point that their fat tissue is leaking "enough" FFAs to mimic a state of hypoinsulinism/normal metabolism.
It could also be assumed they are borderline or actively diabetic at this point, as leaking FFAs inappropriately with fat tissue unresponsive to insulin is certainly going to bring on diabetes.
I clearly never reached this state, interesting to contemplate.
I had very good glucose levels while fasting and I never stopped rapidly gaining weight in spite of extreme obesity. I probably could have made it well over 300 pounds, egads. Mah fat tissue is the stuff of 1000 pounders I guess, oh lord.
I don't know if I would specifically say obesity is a method of normalizing ATP production; that assumes people are eating until they no longer feel fatigued and crappy; I don't know if there are any obese people, even if weight stable, even if they are young, who can state that they feel anywhere near as energetic as I am (now) or any other thin healthy person w/o glucose metabolism disorders.
My cousin who has glucose intolerance and prediabetes, she is relatively energetic for a very obese person but she is WAY more lethargic now than she was before her metabolic problems set in (she was one of those people who was thin as a rail when she was young, then magically became obese and rapidly gained weight in late 20s/early 30s... late onset food reward?).
At points when her glucose tolerance was worsened (pregnancy - progesterone induced) she describes the condition of being like lead unable to stand from the couch because her energy was so abysmal. She could correlate the fatigue with the points where her blood sugar was very high.
She also gained extreme weight with her pregnancy.
I still like the idea that obesity is the point where pancreatic insulin output can not compete/overcome fat cell insulin resistance.
I don't necessarily think the obese are normalizing their energy state with obesity. Most of these conclusions are based off the metabolic state of "preobesity", but as I said I don't think we can relate or conclude anything from this. Very different mechanisms seem to be at play to affect the metabolism of people who are going to gain a lot of weight, people who already have gained a lot of weight, and people who have lost a lot of weight. There does not seem to be a linear relationship between these conditions, as if fluxing levels of fatty acids explain the differences observed.
Miki and blogblog, I think you need functional mitochondria as well as adequate transport molecules...
Stipetic, my view is that the brain fine tunes metabolism which should be doing what is basically functional with minimal interference. Our politicians appear to have some sort of metabolism with no functional brain.
pablo, you can email me in 50 years time and let me know how you got on!
Its, I am the first to admit that my knowledge of leptin and dopamine metabolism is in need of improvement. I find it an interesting prospect to look at glucose metabolism in dopaminergic neurones from the metabolic flexibility perspective too. There are obviously a lot of interesting thoughts there. Thanks for the input.
I would also agree that we would need to follow the refs to find a definition of pre-obese. No time on that one, but I suspect they are looking at non obese but insulin resistant people as pre-obese. But it needs checking.
The feeling crap under severe hyperglycaemia makes me think of free radicals beyond any benefit. Goodness knows how mitochondria function under these conditions but I think they might vote with cytochrome C...
Beth, it would be quite hysterical for the world to pan out so that Stephan is correct. I would find it ironic in the extreme should this occur and that I be convinced. My own current interest is towards the effects of ATP levels in neurones as drivers of appetite at the moment.
I think we are probably looking at the downstream effects of mitochondrial dysfunction. This does not strike me as the result of overconsumption of food per se. Especially if the food has a capital F. It doesn't happen in the forced overfeeding rituals described by Stephan. I find the idea that certain foods trigger mitochondrial damage without the need for overconsumption of calories much more entertaining. This leaves the weight gain to be independent of food reward. I fully accept I could be wrong in this but it would be great fun to be correct. I keep wondering if adding bisphenol A to your food makes it a high reward item.
I keep ending up at the pentose shunt plus fructose as one line forwards and/or trans fats causing damage to lipid metabolism as another. These look like interesting areas to me. As does the GLUT5 transporter of course.
Correct me if I am wrong but I understood that high reward foods did not necessarily need to be palatable, just needed make you come back for more. Hmmmmmmmm.
Gladina, I agree. This is not "normalisation" of metabolism. It is a bodge to normalise ATP production at a serious cost to metabolism and health.
David, I don't recall much on diet except he suggested reduced fertility on high fat diets but it was one of the weaker points in an excellent book. I really must re read.
Strontium Pup, I have a post on CD36 deficiency I ought to write for those who have commented in the past "LC didn't work for me, the adipostat hypothesis must be correct". The have to be some people who resemble the OLETF rat.
I just looked up that post on the OLEFT rat and found I'd written this:
"Fatty acids enter mitochondria as acyl CoA moieties. The place to be looking for explanations for the syndrome seen in the OLETF rat is in fatty acid processing. My guess is that lipid molecules get in to myocytes but never get effectively passed to the mitochondria."
Sweet.
Re whole body bottleneck, probably yes. Re accumulation of lipids in muscles etc. I think it's the level of mono and diglycerides which cause the insulin resistance. Quite how this tracks with increasing plasma FFAs would need more magnetic resonance spectroscopy studies to pick apart.
Peter
@Beth,
opioid proteins have a negligible effect compared with any conventional opioid such as morphine. Opioid proteins are also completely degraded within 10 minutes by monamine oxidase. As a result they They are very unlikely to have a major effect on mood.
A more likley effect of wheat and dairy proteins is inflammation and excess histamine production.
Some antihistamines are quite powerful stimulants.
Anti-inflammatory corticosteroids are know to cause stimulation and even mania
Before the 20th century grains and dairy foods were typically fermented (sourdough, cheese) or boiled for long periods (porridge) before consumption. This would have substantially denatured any potentially allergenic proteins.
Fresh milk was rarely consumed in western countries before the 20th century because refrigeration was non-existent. Milk was nearly always made into butter or cheese. Traditional butter-making involved boiling and skimming milk. The leftover skim milk was nearly always used as pig food rather than human food.
Couple minor points: 1) red blood cells only use glucose for fuel and 2) the increase in transmembrane flux that occurs as a result of an increase in adipocyte size goes both ways, which I don't believe was explicitly stated. I suppose the latter point is obvious when you think about it, because otherwise your adipocytes would cross a threshold and then spill all of their contents into the blood stream and never become very large. Rather, the pool of FFA/NEFA in the blood increases as does the adipocyte depots and there is a largely equivalent in/out flux of FFAs (though for someone gaining body fat, it's obviously more in than out). That increased serum pool is likely pathological, I would think.
More importantly, I wonder how much of this initial mitochondrial dysfunction is due to a magnesium deficiency. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1172515/
Mg deficiency is fairly common these days and fairly easily rectified with supplements.
When somebody is loosing weight, it could be illustrated by several inflated balloons assembled like nest-dolls (progressively smaller inserted into bigger ones)and got punctured one after another through intervals of time. Such intervals are often not short.I personally spent 2 years on a weight-loss plateau. I thought I was moving through "set-points". I was always wondering what was going on , and the therm "set point" or the image of changing "set points" sort of explained for me some of it.
Are you saying that while you got stuck at a level eventually you would burst through to a lower weight.
That is terrific news since I have been stuck at 205 since coming down from 235 for 6 or 7 months. Or did I misunderstand what you were saying?
Hi Travis,
I'm boiling bones right now and have a great supply of offal in the freezer. I'm looking for minerals from Food...
We bought a whole grass fed ewe last week. 34kg of meat. Fatty!
Peter
Peter,
CD36. Very cool.
@blogblog
The stimulant effect of corticosteroids is related to a number of factors, not just antiinflammatory action.
It should be noted that depression can also occur, suggesting that the steroids are not stimulant, they merely are mood destabilizing (brain energy use disrupting) and promote crazy times for people with crazy brainz.
http://www.jfponline.com/Pages.asp?AID=4147
Discusses a case of a high profile person who took corticosteroids for illness; first she developed mania, then in the second course of treatment, depression. You can go either way with steroids, if you have beepoo.
Following steroids, depression is actually more common of a reaction than mania; mania is just more widely discussed as it is so obviously abnormal when you are sick and on steroids (depression, however, may get mistaken for a psychological reaction to being sick when it is really just corticosteroid induced).
@blogblog
I do agree that I do not buy, believe the wheat is bad/opioid peptides are a problem.
I tend to think that psychological attachments to the diets we grew up with are responsible for people being unable to start and continue with a paleo/low carb eating program, not some magic properties in wheat or dairy. Some people are more emotional than others, some form deep emotional attachments and can not give up their traditional diet. That's sort of normal, far more normal than being able to eat a radically culturally different diet for over a decade plus.
For what it is worth, I have noticed that people who tend to have problems altering diet they grew up with, are almost invariably of an emotional nature, people who are very sensitive and form attachments which are strong.
I am a callous robot who barely cares about people, so it is beyond easy for me to be like "I am never eating carbs again". Even someone like myself, I struggled with cravings and fondness for my traditional childhood diet for months if not YEARS into low carb (I never do now, but the first 2 years was very difficult, even the first 5 years I would say I still craved my holiday meals and treats and stuff).
I have never observed a person claim they had "wheat/opioid protein addiction", and fail to also have this sensitive attached sort of personality.
This is sort of how Kruse is saying he is curing people with a leptin protocol, meanwhile his diet is nothing but an awesome LC diet.
The inability to stop wheat/dairy/carbs is being attributed to opioid peptides, when in reality it is probably more of a psychological disposition on behalf of the dieter.
Diet is like language - it is a way humans communicate and differentiate one group from the other. We are programmed, from birth, to eat certain things and not eat other things. This is as acquired, and as essential to identity, as is language. Some people have brains which can learn 40 languages at all stages of life, most people find it impossible to learn a new language after childhood. It is totally normal to find it extremely difficult and painful to give up the foods you were raised on, your brain is programmed to view that as nurturing and food. Your mother did not know she was feeding you poison.
The ironic thing is an endorphin like reaction may be occurring in response to eating traditional/chidhood food, but it would be endogenously created (a reaction to the perception/visual/texture/smells indicating traditional familiar food). Endorphins rule attachment and nurturing loving feelings.
Animals abandoned at birth cry and are miserable, opiates can calm them and make them placid and happy. Sucrose can as well, as it raises the endorphins they lack due to isolation and deprivation of nurturance.
Cruel psychologists took baby monkies and raised them on a "wire mother"; the babies rock for stimulation and suck their thumb desperate for comfort, these all raise endorphins they are bottomed out on from being motherless.
Human babies abandoned in russian orphanages left alone in isolation also demonstrate this rocking behavior.
Interesting, autistic children frequently rock and self stimulate - it is as if their endorphin receptors do not work even when they have loving parents. This could also explain lack of acquiring/understanding human group signifiers like language, nonverbal communication, these may require normal endorphin function.
It does give credence to the idea that "refrigerator mothers" cause autism. well, no, that idea is completely wrong, but it does suggest they are on the right path - love, and endorphins, are required to not be an isolated robot.
Peter, So damage and consumption rigth? you are thinking "days and hours" here and im thinking weeks and months. Also, The air damages you (pollution? oxygen?) does that mean i have to stop breading?
I rather have better / greater insulin sensitivity, health, strength, stamina, fuel metabolism, satiety, muscles, etc etc. ALWAYS CONSUMING LESS "foodstuff" overall. So yes . I let you know im 45 years. Right now im doing great!
Loved the post. Don't really like posting links to studies, but I found these interesting and relevant:
http://www.ncbi.nlm.nih.gov/pubmed/18256136
http://www.ncbi.nlm.nih.gov/pubmed/2240203
http://www.ncbi.nlm.nih.gov/pubmed/17618960
http://www.ncbi.nlm.nih.gov/pubmed/17823426
http://chemse.oxfordjournals.org/content/30/suppl_1/i182.long
"I tend to think that psychological attachments to the diets we grew up with are responsible for people being unable to start and continue with a paleo/low carb eating program, not some magic properties in wheat or dairy."
Just throwing in my datapoint here: I have no "cravings" whatsoever for potatoes or rice (most def. childhood staples). Wheat and dairy though are another story.
so its ok to eat dat meat but no no on the milk? BS. dairy is harmless. eat it, drink it, bath in it. rub it on your skin. cant digest it?
stop- eating - gluten. try again. without casein i wouldn't be able to fast 30 hours a day. oh, that and calcium in milk inhibits iron absorption. "safe starches" like Potatoes + meat =increase your iron stores...
With reference to the wheat and behavior. From the observation of my 5 year old who suffers some severe asthma attacks, some of the medication which was prescribed would turn her a little psychotic. Removal of that would return her normal behaviour.
She was gluten and dairy free for a long time due suggestions from the allergy clinic. Anyway gluten and dairy started going back into the diet and after while behavior changes were noticed and it gets put down to usual child behavior. However, recently we withdraw the gluten again and it's quite obvious that her behavior has changed for the better.
@Makro,
as a I child I hated all vegetables, most fruit and bread. Obviously my body knew what is good for me.
From my late teens to my late 30s I managed to destroy my health by eating a "healthy balanced low fat diet".
A decade later I eat nothing but meat, cheese, cream and a tiny amount of berries (plus some vitamin and mineral supplements as insurance). The result is superb health.
Hi Peter,
Did you see this study:
http://www.ncbi.nlm.nih.gov/pubmed/21673053
@ PierreLegrand
Unfortunately, each time I had to change something in my diet in order to burst next balloon. When I just started LC , I never thought twice about eating a lot of mayonnaise with eggs and cheese , sugar-free candies, at least one fruit a day, a lot of nuts, some paper-thin wheat or rye things as sandwich base. Why not, if I lost 20 lb on it? At least I had staff to trim off. The major trimming occurred after I had a foot surgery (result of over-doing high-impact aerobic classes for years) . I thought I would regain all what was lost during the after-surgery period, got scared and went completely grain-free, no more than 20 gram of carbs a day, a lot of sleep(because I couldn't move much). Next step - I started to practice intermittent fasting inspired by Todd Becker blog, particularly the post "Learning to fast"
http://gettingstronger.org/2010/11/learning-to-fast/. My diet now contains more than 20 gram of carbs, but no snacks, two meals a day. First meal is around noon and contains couple eggs and some butter. During my second meal I get my variety, meat, veggies, some starches, sometimes some fruits. If I eat something that doesn't fit my diet for social reasons, I usually fast around it.
Each austerity measure worked like a burst of balloon at first, until the next balloon was reached. I don't think I would be able to loose 100 lb if I had to. Fortunately, I am where I want to be now weight-wise, my health is very good and I look much younger than my age. High-fat diet made wonder to my skin. But I am a pre-menopausal female with low-thyroid function. Looks like males usually have on easier ride.
Peter, so are you saying you give little to no credence to brain-mediated overfeeding theories aside from neurons/ATP? Or just Stephan's in particular?
It's alluded to above, but here goes:
It appears (from this post) that the whole process starts with mitochondrial dysfunction. What causes the mitochondrial dysfunction?
Also, I don't think it is fair to assume that all post-obese will have mitochondrial dysfunction - important to remember that for unsuccessful dieters, post-obese is often also pre-obese.
@Stipetic
Don't confuse set point with settling point.
Settling point is basically the observation of where one's weight "settles at" due to a competition of forces, which can include RQ, insulin secretion, insulin resistance, or problems burning fatty acids in the mitochondria.
Set point is the idea of a central regulator that detects when levels of fat get too high or too low (which would also suggest that we wouldn't become obese).
Settling point is somewhat borne out of the idea that we appear to have a set point, but it's really just various mechanisms, feedback loops, and possible dysregulation that is at play when it seems like there is some sort of creature that resides within our brain that pulls the strings and levers.
About boiling bones.
There is a traditional dish in Eastern Europe that is basically a jellied meat broth. Jello consistency is achieved by cooking for hours bones and pieces of meat with dissent amount of connective tissue (low parts of feet. tails, jowl) until meat separates from bones. I cook it with carrots and onion.Cheapest version - pigs feet and beef heart combined. Pig parts are cheaper, but the resulting broth is not transparent, if somebody minds. In case if after cooling in a refrigerator the broth is not solid enough, you can cheat - worm it up again and add some gelatin. When the broth is almost done, it is a good idea to add some bay leaf and other spices and cook an additional 30 minutes. When it is not hot anymore, remove bones and spent onion, chop meat and carrots, place it in some wide but shallow dishes or bowls. At that point you can add crashed garlic and some fresh chopped herbs. When it is firm, it is ready to eat. We eat it sliced with horseradish or mustard. If you find it too exotic to eat (most Americans do), just turn it into soup.
After arriving into Canada from Russia 15 years ago, our family started enthusiastically try and eat all new and interesting food. Me and my husband grow up and reach 35 years of age without eating fast food. The food enthusiasm lasted a year or too, we got tired of very strong and artificial flavors, and return to the foods, normal for us. Not out of sentiment of for health, it just happened.Luckily, I like to cook. Things like cabbage or beat soups, homemade sauerkraut and pickles are always in my fridge.My son is the only one out of the group of boys who he grow up with who doesn't have some degree of a spare tire around his middle.
guys, guys boiling bones sounds like the shitiest most disgusting food evar... are you sure you are not following Guyenet ideas here Peter?... Anyway my massive rib eye steak usually has a rather large bone sticking out. does it help with dat minerals if i suck it?
honest question btw.
Why is it that throwing bones in a garbage feels better than saving it in a freezer and slowly boiling it in a salted water later in order to get a beef or a lamb stock? It requires almost no effort. Just a lot of time and zero attention.Probably, some very squeamish folks may find it to be desirable to filter that stock after it is ready because it will contain little bits of coagulated protein and small bone pieces. You could drink it and cook with it. It is not bones versus rib-eye, it is about not wasting nutritious animal parts. Peter just bought a half of a cow. Does he suppose to cut out some steaks, stew meat, give liver to his cats and then throw away the rest?
Just as an experiment, I ate a high carb (500-1000g/day), moderate-low protein (100g/day), low fat (<100g/day) diet for the last month. The results were not good for me: the most noticeable thing was poor sleep*, which is the main reason I gave up; I was constantly thinking about food and my next meal; my exercise performance and body composition worsened slightly.
I ate mostly sweet potato varieties, some vegetables, and shellfish--small amounts of cheese, fruit, butter, and meat, which I strongly craved throughout [meat].
*I suspected the decrease in sleep was due to insufficient calorie intake, so I tried getting down almost 10lbs of sweet potatoes each day, but I ended up adding a bit of butter to the 5lbs--neither worked.
The main reason was an attempt to increase speed and strength, but as I have assumed in the past, my training style is minimally glycogen intensive, and it seems I was not in need of more glucose.
Also, my weight decreased by a couple pounds, but that always happens if I cut down fat/protein too much.
blogblog,
Since I know you consume very few carbs, what kind of workouts do you do?
John,
I'd like to chime in here, because of some recent material I've been reading.
The preface is that I've been an athlete for a long time, as well as low-zero carbing (20 some-odd years). I am now much more of a coach than athlete, but my workouts are of great intensity - the kind that should put me on the floor if my diet was causing low glycogen. And I perform well at them for a few days on end too.
I have no explanation for it - we all know that my performance should be much worse.
(I'm sure that I'll receive some sharp-shooting now). Ready to respond.
-Al
@John
I don't do any workouts. I simply walk up and down steep hills, carry home heavy bags of shopping etc.
It takes about 18 months to fully adapt to <20g/day carbs.
Hi Bob. If settling point is the state of today's homeostatic affairs, and it seems it is, then I'm fine with it. See -> :-) Thanks for the thorough explanation.
Hi Al(berto). I too have been training low carb and have been startled by some fairly bright folks proclaiming you need extra carbs in your diet if you are exercising. I think Phinney et al debunked that 30 years ago. I hit the proverbial "wall" fairly rapidly, but that doesn't stop me from doing whatever I'm doing at the time. Sure, I go slower, but the effort is the same before and after the "wall," so I'm assuming the benefits are at least the same (probably more beneficial when glycogen depleted as my body is likely compensating by creating more mitochondria). So, I'm a bit perplexed by this "you need extra carbs if you exercise" dogma(?). Don't know if this was what you were alluding to, but that's my take.
"Correct me if I am wrong but I understood that high reward foods did not necessarily need to be palatable, just needed make you come back for more. Hmmmmmmmm."
Great point! Whether they really taste good or not they will be carbs. I rarely eat bread, and I find the taste is bland even of the high fat varieties like brioche. I can remember bingeing on fast food, bready things, then within mnutes thnking, That really didn't taste good. And wondered for years why I felt driven to over eat carb foods. Since going very low carb I never suffer that constant craving.
AL and Stipetic,
I mostly do shorts sprints with long rest or strength training with low reps and long rest.
My thoughts on higher carb revolved around muscle fiber type, as more fat should lead toward type i expression, but there isn't much literature.
@John,
you can't grow new muscle fibres (hyperplasia) as an adult.
Lack of high intensity exercise will eventually cause the permanent loss of type II (fast twitch) fibres.
@ blogblog,
"you can't grow new muscle fibres (hyperplasia) as an adult."
You usually have some very profound ideas that I agree with, but this one is out in left field. Everyone of my exercise physiology texts disagrees with this statement, as well as my experience as a coach.
What compels you state this?
-Al
Isn't very low carb dangerous to the thyroid? Don't isocaloric diets with differing macro ratios have the same effects on body composition?
@berto,
The current understanding is that skeletal muscle growth in adult mammals is due to enlargement (hypertrophy) of individual muscle fibres not to an increase in the number of fibres (hyperplasia).
J Physiol 570.3 (2006) pp 611–627
Skeletal muscle hypertrophy and structure and function
of skeletal muscle fibres in male body builders
Different modes of hypertrophy in skeletal muscle fibers
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174086/
blogblog,
although satellite cell activation in older humans is difficult to measure, there is much that indicates a potential for hyperplasia albeit not as great as in the younger.
http://www.ncbi.nlm.nih.gov/pubmed/20092696
@ Blogblog,
From the study you provided:
“The neuromuscular anatomy of human muscles is therefore distinct from that of animals used in laboratory experiments (e.g., rabbit and cat), bred for their meat (e.g., cattle), or sporting performance (e.g., horses).”
And still discussing humans:
“… hypertrophy is defined as an increase in the ratio of cytoplasm to nucleus, whereas hyperplasia is defined as nuclear division and an increase in the number of cells. In contrast, hypertrophy of skeletal muscle is thought to involve an increase in the number of nuclei, as well as an increase in cytoplasmic volume. Hypertrophy of skeletal muscle therefore incorporates part of the definition for hyperplasia, an increase in the number of nuclei.”
Not too mention the stimulus was aerobic exercise on a wheel, and not heavy resistance training.
As an aside, is the purpose of blog comments to search for a study, choose a statement somewhere within that study which supports one's opinion, and come back to comment as if this is science?
My Professors would take me to task if I did that on an essay. I appreciate the folks that comprehensively read through studies and offer conclusions (thanks for your work, Peter), but this "one-liner study slinging" just for dissent is an incredible phenomena.
-Al
First, this was a great post. Peter you said,
"Stipetic, my view is that the brain fine tunes metabolism which should be doing what is basically functional with minimal interference. Our politicians appear to have some sort of metabolism with no functional brain."
Peter as a neurosurgeon, I can assure the brain does this. This is the basis o fmy leptin Rx reset. The protocol allows for neurplastic development of the leptin receptor using alternative pathways to stimulate the hypocretin neurons to respond appropriately to leptin and insulin over time. This does not happen fast. If you are not familiar with the work of Paul Bach-y-rita work on neuro-plasticity please read it when you can. His work showed me about ten yrs ago how we can reengineer damaged parts of the brain if we understand first how the brain and its circuits were damaged and when "we develop special exercises" for the alternative pathways that currently do function, but are not selected for or utilized well by the persons neurological circuits.
My Leptin Rx is constructed in this fashion. About 7 yrs ago I began to think about leptin resistance and Dr. Bach-y-rita's work in making the deaf hear again, the blind see again, and the balance challenged be able to walk again using their tongue and other organs to become their new sensory organs. The leptin receptor of the arcuate nucleus is how humans sense energy from all foods. But it is not the only pathway. There is a circadian leptin pathway that is present but not well used. The newer pathway, seated at the hypocretin neurons is phylogenetically quite new in mammals and has essentially replaced many of the older energy thermostatic circuits that were tied to circadian rhythms. I am not sure if you have read my blogs in my mitochondrial series or any of my leptin blogs but your post here summarized about 15 of mine in a very succinct fashion. I went into minute detail of things you explained in a few paragraphs. Excellent post and please come and visit my site. I would appreciate your voice on it. I would love for you to comment on it and learn a ton about leptin. I think it dovetails perfectly with what you have uncovered in this paper using your discerning thought process. Dr. Jack Kruse
Strontium Pup and Peter. Ironic that I am working now on a future blog about CD 36.
Several authors have reported the participation of CD36 (a fatty acid transporter and scavenger receptor for oxidized Low Density Lipoprotein in the mouth). It is found as a taste receptor for fatty acids in lingual papillae, leading to spontaneous fat preference and digestive secretions. More interesting to me is that CD36 receptors are also in close proximity to the leptin receptors on the tongue that project to the brainstem through parasympathetic afferents of the vagus nerve adn synapse in the Solitary tract and in some circumventricular organs. These organs have no BBB and are another place the brain "samples FFA and leptin levels"
The general postulate that food intake is affected by plasma glucose levels is quite old and dated. “Glucostatic hypothesis” by Mayer et al., in 1953. We do know that decreased glucose plasma levels stimulate appetite by influencing the firing rate of specialized neuronal populations in the ventromedial and lateral hypothalamus as their responses increase following application of glucose (Oomura et al., 1969, Levin, 2002).
Moreover, there are several lines of evidence support the notion that lipid metabolism in neurons plays a critical role in mediating hypothalamic responses to fuel availability. This is where CD36 plays its hand in my mind. Two metabolites, malonyl-conenzyme fatty acyl-CoA (malonyl-CoA) and long- chain fatty acyl-CoAs have emerged as probable signaling molecules in the hypothalamus. These are what leptin receptors are monitoring in normal folks. These hypocretin neurons that use leptin are the ones that are knocked out in obesity and in anorexia. The role for malonyl-CoA in regulating food intake was first recognized through the discovery that intraperitoneal or intracerebral administration of inhibitors of fatty acid synthase (FAS), such as cerulenin and C75, causes an accumulation of malonyl-CoA in the hypothalamus and has a profound appetite suppresant effect (Loftus et al., 2000).
I know as a neurosurgeon that intracerebral administration of long-chain fatty acids, e.g. oleic acid, reduces food intake. I see this when we administer certain drugs into the CSF that contain these compounds for treatment purposes and consequently patients just wont eat post op no matter the circumstance or duration until the drugs have cleared the CSF. This demonstrates that certain fatty acids do have an inhibitory central effect on feeding control (also found by Morgan et al., in 2004). It appears that under physiological conditions hypothalamic malonyl-CoA is an important determinant of feeding behavior in humans and is coupled to the leptin system in the hypothalamus, but first sensed in the CD36 receptor in the oral cavity. (recently reviewed in Prodi and Obici, 2006)
@berto,
An increased number of nuclei within muscle fibres is NOT the same as an increase in the number of muscle fibres.
In exercise physiology HYPERPLASIA is defined as the increase in fibre number as a result of an exercise stimulus. It is unknown in humans (but may occur in cats and chickens).
I didn't even need to back up my statement with any references because every current exercise physiology student knows that exercise induced increases in skeletal muscle bulk is due to hypertrophy (mostly due to more mitochondria and capillaries).
I politely suggest you buy some new exercise physiology books because your knowledge is way out of date.
I personally recommend Wilmore and Costill's Physiology of Sport and Exercise. It is probably the most widely used undergraduate exercise physiology textbook.
http://www.humankinetics.com/products/all-products/physiology-of-sport-and-exercise-4th-edition-wweb-study-guide
John (Dr. Jack Kruse), your comments are fascinating. Please post a link to your blog. Thanks.
Peter i could not sleep after reading your blog last night. I wrote five blogs surrounding your blog here and much of my mitochondrial series of blogs linking it to leptin and telomere biology. This blog maybe the most important one written in all of 2011. The implications are tremendous when you layer the science we know upon its foundation.
My blog address is jackkruse.com.
Peter, one more comment for you to think about. Please read wrights article in Nature. It meshes gorgeously with your balloon analogy.
Most research today is gene centric. It would appear that defected genes cause all of our diseases and maladies. A study in 2004 in Nature Genetics by Alan Wright has shown that belief may be false. He showed that if you could extend lifespan you could postpone all the disease of aging with an ingeneous experiment. He asked a simple question. What happens to different animals with different lifespans when you knock out the same nuclear DNA gene? He looked at Huntington’s, Parkinson’s, and Alzheimer’s disease in this experiment among seven others. They found a tight correlation between disease progression and the leakiness of the mitochondria. It was irrespective of the nuclear gene deletion! It is now clear to us that our old beliefs about nuclear DNA dominance is no longer applicable. It appears that disease onset is married to the cellular physiology of longevity. In all degenerative diseases it appears cells are lost by apoptosis and mitochondrial leakiness is what determines this cellular fate. This was a correlative study and not a causative one but the link was very tight. Later in 2004 another study appeared in Nature from the Karolinska Institute that suggests strong causation. I suggest you read it.
@bopes
Dr Kruse posts at http://www.jackkruse.com
Blogblog......i like frank booth's work in this area a lot more. What his career has given us in excerise molecular biology is a gift. Dr. K
If an organ has mostly defective mitochondria, the organs function will be suboptimal, but the organ can amplify the least damaged mitochondria for years. This is common in kidney failure and heart failure. Mitochondria usually last about 3 weeks. The choice for mitochondria in life is limited; divide or die. In this fashion, defective power plants are constantly weeded out. Let me give you an example. Take a brain neuron. They usually are as old as we are and are rarely replaced. Their function does not crash if there is a power plant mutation. Instead, its function is diminished to a very small degree over time. The more defective mtDNA is, the more oxidation will be found in the cell. Ironically, this oxidation does not effect proteins, fats, or carbohydrates from the diet, in the cell as we once thought. Studies have been done in damaged organs and cannot find evidence for oxidative damage. What is effected is the generation of transcription factors and genes by the new cellular redox state. This redox state is the warning system for the cell of possible impending doom over time. Nuclear regulatory factors 1 and 2 get activated (NRF 1 and 2). NRF1 is what signals the nucleus to manufacture of new mitochondria and NRF2 shuts it off. This signaling system accounts for the chronic inflammation that underscores aging and disease propagation in humans. The level of oxidation chronically resets itself depending upon the current cellular terroir. (Levee 1) We know in humans that this state can exists for decades. I follow this trend with a highly sensitive CRP test, intracellular Mg levels (coupling to the ATPase), and serum CO2 levels which tells us what is likely going on at the mitochondrial levels from electron transport. We may notice we have less energy, take longer to recover from exercise, but it generally won’t kill us. With this explanation it should be clear that the trade off for removing bad mitochondria is long term organ failure slowly over time. We call this aging. (Endurance athletes beware)
john, I am very surprised to hear the following:
'..Ironically, this oxidation does not effect proteins, fats, or carbohydrates from the diet, in the cell as we once thought. Studies have been done in damaged organs and cannot find evidence for oxidative damage.'
Can you give references please? There is a large literature on oxidative damage in degenerative disease.
'..This signaling system accounts for the chronic inflammation that underscores aging and disease propagation in humans.'
No, it's the oxidative damage that accounts for the chronic inflammation. Oxidative stress means misfolded proteins, and inflammation becomes necessary if they cannot be cleared by the 'unfolded protein response'.
'..With this explanation it should be clear that the trade off for removing bad mitochondria is long term organ failure slowly over time.'
No. Bad mitochondria are removed by autophagy, which is perfectly compatible with good organ function and indeed PREVENTS organ failure.
The problem is not that the system is badly designed but that it is short of the tools and raw materials it needs. Look up 'Alzheimer's disease as copper deficiency'.
blogblog:
I tried finding your email address but unsuccessfully. Got a good review of muscle growth from 2007 (Folland et al.)
Anyway, they conclude that methodological difficulties makes it near impossible to say whether hyperplasia occurs, but they write:
The quantitative contribution of hyperplasia to changes in human muscle CSA in response to exercise remains largely unknown. However, the study of human and mammalian muscle suggests hyperplasia accounts for, at most, a small proportion of the increase in muscle CSA in response to increased loading.
lol, what a clusterfuck, just eat your carbs people. then move dat ass. and by carbs i mean chocolate ice cream, chocolate truffles, chocolate milk, chocolate chocolate etc.
@ Blogblog,
I'm not sure why we're debating such a trivial matter on the practical level, but the textbook that you recommended was my undergrad text, and the one I was referring to.
On page 208-09, Wilmore, Costill, and Kenney discuss mucle fiber hyperplasia. There are many studies in animals showing hyperplasia; only a few studies in humans. Seems inconclusive at best, though your original comment on the matter was fairly certain that hyperplasia does not exist:
"you can't grow new muscle fibres (hyperplasia) as an adult. "
and is what I took most of my argument against.
Respectfully,
-Al
@Jane
Mainline scientific theories may have long lifespans but are inevitably overturned as accumulating evidence renders them obsolete and brings alternative theories to the fore. This happened in physics in 1905 with the advent of the theory or relativity and it happened 150 yrs ago in biology when many diseases became explainable not in the established terms of “spontaneous generation” but instead in terms of germs and then viruses. It has now happened in molecular biology with ROS and antioxidants.
When such a major change in paradigm happens there is usually a period of significant and often bitter controversy between scientists seeking to hold on to the theories of the older paradigm and those espousing the newer one. I think your comment reflects that. This is followed gradually by changes in basic thinking patterns and a subsequent long period of fertile discovery. This is what I am trying to convey a bit here.
Here are few links off my current hard drive at home. My master list is at my office and I don't have access to it.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869479/
http://www.gpb.sav.sk/2005_03_263.pdf
http://www.signaling-gateway.org/update/updates/200910/nrc2742.html
http://www.ncbi.nlm.nih.gov/pubmed/19693011
http://medind.nic.in/iaf/t09/i4/iaft09i4p324.pdf
john, have you actually read the papers you linked? The very first one says the following:
'..The significance of ROS as aggravating or primary factors in numerous pathologies and senescence is firmly established, widely recognized, and extensively reviewed elsewhere..'
Your second link is about the failure of antioxidant therapy. You may not be aware that the 'antioxidant cocktails' did not contain the metals (copper and manganese) which activate the most important antioxidant enzymes. One might ask why they did not, since modern diets are very low in these metals.
Your third link suggests antioxidants can be bad. Of course they can. The system is delicately balanced between oxidation and reduction, and an excess of any redox-active entity will disturb this balance.
Your fourth link says antioxidants help tumour cells survive. This is because tumour cells are normally killed by ROS.
Your last link says this:
'..Initial hurriedly planned and executed experimental
and clinical studies showed promising results of antioxidant therapies, but recent studies indicate that excess intake/
supplement may have adverse outcomes including increased mortality.'
I do not see how this can be interpreted to mean that oxidative damage does not play the role in degenerative disease your first link says it does.
john,
Nick Lane discusses Alan Wright's work in PSS in the aging chapter, if you haven't read it.
@Jane I know what the link says, it came of my hard drive in a folder............I am merely pointing out that there are many articles that support your position in the literature but those theories are dying a slow death. Just because something is published does not make it true. We can find many articles about dark ether prior to Einstein. Does that make it true? The same goes for Watson and Cricks original work on DNA. Again its published and most of it has been obliterated by the science of epigenetics. Scientific theories you hold dear are now being replaced dramatically. I am just pointing out the shift for you here. I think you need to read more on what you may not know and less on what you do. IF we focus only on what we know how can we grow in knowledge. Science progresses once we get out from under our comfort zone of what we now know.
I think I have a pretty good handle on minerals and their biochemical effects. I have written a lot about neurodegenerative diseases and what the new theories are showing and where many of the dead ends (AL and CU led us)
@John Thanks I will look in to it.
john,
'Scientific theories you hold dear are now being replaced dramatically.'
I spend most of my time reading the scientific literature, and have done for 30 years. I have not come across any evidence for this, and nor have my colleagues at the university in whose library I do my reading.
You have failed to provide any.
@Dr Kruse
You describe leptin as regulating/detecting food availability; this is actually insulin & ghrelin's job. Acute rises and drops in these lead to food intake. Ghrelin literally programs the brain to detect meal times and become hungry at those times; it feeds into the brian's circadian rhythm.
Yes, leptin suppresses ghrelin (so you could say leptin also affects short term feeding) ... but insulin suppresses it more directly.
Congenitally leptin deficient humans experience only trivial increases in ghrelin after leptin replacement and MASSIVE weight loss, meanwhile obese humans experience overwhelmingly large increases after just trivial weight loss.
This suggests that insulin is the primary regulator of ghrelin; the congentially deficient people didn't have their ghrelin values much change in spite of extreme reductions in insulin levels/glucose intolerance/body fat levels, because they were replacing the leptin they do not naturally make (and this then suppresses ghrelin normally).
On the other hand, in fat people who are not leptin deficient, their ghrelin shoots up fabulously after minor weight loss - this is becausem inor weight loss is specific for significant reductions in insulin levels, thus disinhibition of the nocturnal rise of ghrelin consistent with being metabolically/endocriniologically normal and healthy. It also suggests that fat people are not leptin resistant.
Anyway, considering the primary regulator of leptin is the size of adipocytes (secondary regulator, insulin levels) this suggests leptin is a long term regulator of food intake. Leptin levels do not change profoundly until weight starts to drop, and weight starts to drop only if you have long-term energy imbalance.
"Acute hypoinsulinaemia can be compensated for by acute hyperglycaemia."
you're a very non-linear thinker Peter.
-Bill
Peter's posts always generate thought provoking discussions. I hope Dr. K and Jane will continue their debate.
On a trivial note: after eliminating the "safe starches" and truly following a lower carb diet my HbA1c is now in a healthy, normal range!
@Jane........Your criticism is dually noted. Might I respond to you now.
You have failed to find contrary evidence by your own admission in 30 years as well. It is awfully tough to find any contrary evidence when you dont think the theories you hold dear might be incomplete. I am telling you they are in a big way. One might find fault with that thinking an behavior as well. I don't cling to dogma. I look for evidence. I suggest you do so. Science is best studied from the boundry of our comfort zones. That is where the frontier of new knowledge lies. I cant do all your work for you. I have surgery and patients to heal. But I have shared with you a taste of that boundary. It is your choice to remain in you comfort zone or evolve. With your attitude we might all fall off the edge of the map past Hawaii.
john, I thought we were discussing oxidative damage. Have you changed your mind about it, having seen that your key reference supports my position and not yours?
'..you dont think the theories you hold dear might be incomplete. I am telling you they are in a big way.'
What theories do you mean?
@john/DrKruse
No offense, but everything you just said to jane can be applied to your own approach toward research.
Multiple times I have pointed out inconsistencies in your belief that leptin resistance is responsiblef or obesity. You do not acknowledge, for example, that hypoleptinemia is even possible. When I brought this to your attention, you ignore me, and continue onward with your "obesity is leptin resistance" ideas. YOu describe anorexia nervosa as a model for leptin resistance, when this is an insane statement as anorexia nervosa is a model of leptin insufficiency, unless you consider serum leptin <5 in a reproductive female to be sufficient. YOu refuse to acknowledge that, in weight reduced obese people, leptin replacement reverses all adaptations to reduced body weight, and I first hand experienced this. If the problem was leptin resistance, a low dose physiological replacement would be ineffective (0.04mg/kg).
It seems pretty obvious you are merely ignoring all evidence that does not support the idea of leptin resistance, which would be precisely what you are accusing jane of doing.
I think it's great that you are helping obese people lose weight, but I think you need to reexamine why it is your protocol works; there is research which supports bolusing large amounts of amino acids in the AM and keeping carbs low to help blood sugar/weight problems for reasons totally unrelated to leptin.
Peter (or other authorities who may be reading), do you think it would be premature to jump to soundbites such as "it's the mitochondria, stupid", when feeling for rules of thumb with regards to general anti-ageing and overall health?
Regards,
Richard
Wooo, you are placing an impossible burden on Dr Kruse asking him to respond to your questions as well as mine. Leptin resistance does exist. It is closely associated with oxidative stress and oxidative damage, which is what Dr Kruse and I have been discussing.
Oxidative stress impairs endoplasmic reticulum (ER) function, leading to unfolded/misfolded proteins. Accumulation of misfolded proteins is what you see in many degenerative diseases, for instance Alzheimer's. This is 'oxidative damage'. In fact it could just as well be called 'reductive damage', because protein folding requires the ER to maintain an oxidising environment. Oxidative stress goes together with reductive stress, and of course other molecules besides proteins get damaged.
Recent work links ER stress to leptin resistance.
'..In recent years, “leptin resistance” has been considered to be one of the main causes of obesity. However, the detailed mechanisms of leptin resistance are poorly understood. Increasing evidence has suggested that stress signals, which impair endoplasmic reticulum (ER) function, lead to an accumulation of unfolded proteins, which results in ER stress. ... these findings suggest that the pathological mechanism of leptin resistance is derived from ER stress.'
http://molpharm.aspetjournals.org/content/74/6/1610.full
@Jane
This is not the first time I have addressed him, in the past I questioned somethings he wrote which were suspect and he ignored my valid concerns.
You can post links about leptin resistance all you want, they are all circular. "Everyone knows fat people are leptin resistant". This really hasn't been demonstrated in real obese people, it's sort of just inferred based on a lack of response to very high levels of leptin. But as I said many times before, this is idiotic, as high levels of leptin do not prevent obesity, obesity is a distinct state seperate from leptin where disordered insulin (perhaps totally unrelated to leptin dynamics) encourages fattening and feeding.
Clinical example: Leptin in obesity would be like observing, in heart failure, the BNP keeps going up and up -BNP is made from cardiac tissue stretch; it is a sign of the heart muscle not working properly to eject fluid volume. Normally this substance, BNP, when physiology is otherwise working as intended, helps antagonize fluid volume in the heart, just as leptin antagonizes further fat gain in a normal person.
The fact people go into heart failure in spite of very high BNP does not mean they are resistant to BNP, it only means the heart failure is unrelated to the BNP, and the BNP can not reduce the fluid volume in the heart as it is not a result of low BNP.
Obesity and leptin are just like this. The fact the obese do not respond to leptin with weight loss does not mean they are resistant to leptin - it just means leptin does not do anything for obesity, any more than BNP does not do anything for heart failure. The fact leptin deficiency causes obesity does not mean obesity is caused by leptin signalling deficiency. This is grossly illogical.
Again, throw some more articles opening with the fact "everyone knows that obese people are leptin resistant", I've seen hundreds of them, it doesn't make it true.
20 yrs ago I could find and throw out tons of articles talking about how high cholesterol and dietary fat will give you heart attacks. Today we now all know this is BS, almost no one takes that position anymore. We now realize dietary fat does not cause heart attacks, and cholesterol isn't as simple as "always bad".
I repeat, this leptin resistance thing in obese people has not been proven and linking articles stating that "everyone knows the obese are leptin resistant" doesn't serve as evidence that, I, for example, have leptin resistance. If I have leptin resistance, which must be true by definition as I was a morbidly obese person, why do I respond rapidly to 0.04mg/kg leptin replacement with a full reversal of symptoms associated with weight loss maintenance?
The fact is leptin is the last exciting real thing we discovered remotely related to obesity. This is the only reason this "leptin resistance" idea thrives as it has. If we admit it is bullshit, then we are as ignorant as we were when banting wrote that not eating carbs made him lose weight, or the diabetic dogs who became emaciated without insulin, and were able to grow fat tissue only when insulin was present in their systems.
Not much has been discovered. And I'm sorry to be the barer of bad news, but most likely obese people do not have a leptin problem, they have an insulin problem, and insulin problems are RARELY leptin problems.
Wooo, I have heard what you have to say on leptin resistance so many times I just go to sleep now.
That's nice jane, it's sort of how I feel when you start saying minerals cause obesity and diabetes (LOL)
Hi all,
I just got a little time to post a few replies but I have a problem. The battery is non functional on my Mac and the cat sat on the power cable for a split second so it shut down, replies gone!
No time for re posting but I would just reply to Beth.
Stephan may be correct on minor points of obesity, time will tell. It doesn't matter, so long as the correct ideas come out.
His destruction of the ideas carried in GCBC was done so badly that I have very little hope that he will make much progress. You only have to look at the citation of Barnard's diabetes paper to see how little benefit will come from manipulating food palatability in people with mitochondrial dysfunction.
I'm tempted to comment that he is hampered by a PhD in neurobiology, but that might be interpreted as inflammatory and I try not to be. I usually fail of course...
Peter
Wooo, you need to start doing your homework on mitochondria. That's where the minerals do a lot of their work, and if you don't like what I say about them, it's because you don't know enough about mitochondria.
Mac? Ok, now i have to question the validity off ALL your theories @ claims... lets see what u have to say bout dat AMPK...
Jane:
You and thewoo2 are incredibly sharp, intelligent women! Please don't let this interesting discussion/debate between the two of you lapse into attacks on each other's intelligence or knowledge.I learn from and look forward to reading your posts and the Woo's.I think both of you can continue to provide evidence (theoretical and empirical) to support your ideas. Please keep the debate going!
I think I'm suffering from Food Reward resistance.
STG, I entirely agree with you. I never normally attack people, and I regard Wooo as a friend, sometimes anyway.
I have been trying to get certain things across to her for a long time, without success. She uses extreme language herself, and I am trying the same tactic on her to see if it works.
I was not pleased that she interrupted my conversation with Jack Kruse.
Let me check if I get this leptin thing right.
So, it's an anti-starvation hormone, secreted by adipose cells, telling body (and mind) how much fat is available.
Leptin is (abnormally) high in the obese, but they keep eating, thus hypothesis of leptin resistance.
Itsthewoo's (and Peter's) position is that insulin trumps leptin, so even if leptin is telling you that there is plenty of fat in the body, insulin roars 'plenty is not enough!'... and you keep eating to obesity and beyond.
Then you go low-carb paleo, fix your fasting insulin, drop to overweight BMI level and plateau.
Now that insulin is silent, you can "hear" your leptin, but your leptin is now generally lower than in a comparable person of your height/weight/age/sex who has never been obese. That's, presumably, due to you now having lots of small adipose cells as opposed to fewer bigger ones (total weight of the cells being the same). The resultant lower leptin levels keep you hungry and you keep eating until your adipose cells grow enough to bring leptin output back to normal. Or leptin replacement therapy. Or go hungry all day.
So, is it generally correct, or am I missing something?
bes-voprosov;
your not missing anything.except that this is only a hypothesis and has certainly not been proven.don,t latch onto unproven theorys,read them and watch for further studies but don,t take them as fact.
cj
@Peter,
Next, you'll be telling us the dog ate your homework :-) (I hope it was smeared with grass-fed butter).
@bes-voprosov,
I suppose I would be one of those people who "successfully" low-carbed down through many tens of pounds and then plateaued, remaining overweight (but no longer obese).
But the thing is, although I'm overweight, I am not hungry all the time. In fact I'm hardly ever hungry. I usually eat twice a day (occasionally only once, only rarely thrice), don't snack, take in virtually no carbs, all real home-cooked food.
So if it's my still-numerous shrunken, leptin-deficient adipocytes that are the problem, whatever they are doing, they are not screaming out to me "eat, damn you", and they are also not screaming at me to eat carbs. I just don't get carb-cravings. (All right, just occasionally, I'll get a sugar craving, but it's fairly unusual, and 99% of the time it just gets squashed, unanswered, and if it is answered, it is by fruit. (But that's ok, according to Dr Lustig, not that I agree).
@bes-voprosov
That is precisely correct, based on my understanding as a person who has lived, clinically verified, and studied all of this.
Thank you for understanding so it is not as if I am screaming into a black hole.
@Jane
I don't see how I "interrupted" your discussion with Dr Kruse. It's not unreasonable to expect him to answer two comments?
Kruse always does this whenever I ask him to explain how it is I can exist (very low leptin after weight loss; complete restoration with a low-physiological replacement, and yes history of morbid obesity).
He just stops speaking because as I clearly do not fit a model of leptin resistance, I refute his general idea that obesity is related to leptin resistance or that leptin is important to the pathogenesis of common obesity.
On another forum, not directly commenting to me, he interpreted my case that I "fried" my hypocretin system and so required very high leptin to maintain normal functioning, but this is not interpreting the reality of my condition corectly. I did not use a high dose leptin protocol (at the highest dose, I was only taking 0.08mg/kg, and this had to be reduced as I was responding with significant weight loss).
Even without leptin replacement, with a low basal level of leptin, I am able to maintain my low body fat, which suggests my leptin sensitivity is quite good (albeit, without leptin, I exhibit numerous signs of starvation/metabolic thriftiness, most obvious of which is infertility).
Since stopping leptin, now 6 months post, I am still thin, I gained only 5 lbs (now I weigh 118ish)... however my body fat is higher and my lean mass is lower. Leptin adequate state makes your fat just melt off, when combined with the diet I eat (which is why so many obese people effortlessly lose weight on low carb, until they get thin... then leptin is low enough that it is no longer effortless, they are at their "maintenance" weight).
Also, it is much easier to gain weight if I try to eat junk food, and I have become infertile again. I also am fatigued and my glucose becomes destabilized more easily, as compare to a leptin adequate state. The most obvious change is the return of hypothalamic amenorrhea, the other changes are subtle.
Basically, I chronically run low leptin (absolutely low, low for any reproductive aged female) and so my physiology is programmed to adapt to starvation. This is in spite of the fact I am not starving, I do no exercise at all, my nutrition/zinc status is fabulous... I merely used to be obese and own a lot of hypotrophic adipoctyes. My fat cells do not make as much leptin as they should.
This is not something I invented, I had a nice lab slip telling me that my leptin level was like <2.
Kruse will not even acknwoeldge leptin insufficiency is possible, and this will seriously harm his ability to help obese people especially females, females are more sensitive to leptin dropping after body fat loss. If you research sex steroids and their interactions with leptin, it is abundantly clear female physiology evolved to be dependent upon it, for obvious reasons. Tesosterone replaces a lot of effects ordinarily controlled by leptin such as IGF functionality ( protein syntehsis ) and basal dopamine (metabolic use of fat/appetite). This also explains why males are often like "I lost 200 pounds and feel great" but you rarely hear women saying this. Even if they do manage to lose a lot of body fat, it's always a struggle with hunger and fatigue.
This is another factor missing in diet gurus and theire understanding of leptin: leptin is sexually dimorphic. Unlike insulin for example, which does not exhibit any differences between males and females and is only dependent on body weight and sensitivity and nutrient status... leptin absolutely follows a significant difference between males and females, females naturally have high leptin, and require it, males do not. When you observe a female with low leptin, she is underweight and probably not fertile or healthy. The reverse is true for a male, as a healthy male should not have high body fat and should have high free testosterone, which suppresses leptin.
@ bes-voprosov
After my BMI changed from 31 to 27, I feel like I had my wish and I reached my goal. However, technically I am still overweight. It seems to me, my adipose cells don't scream "Eat", they just communicate to my body something like-"That is it! No more giving up ! If you decide to go without any food for a week - don't count on us like we are not here any more." They are on a strike led by leptin, I guess.
I have the same experience as montmorency . No hunger , I eat 2 times a day LC, sometimes one, no snacks. A while ago I would loose at least a lb a week on such regiment. Now it is how I keep the statuesque. My doctor thinks I will regain because it is how it usually is. I am sort of curious what is next. If I start regaining, should I eat every other day?
+1 for losing and maintaining a huge amount of body fat (male, 365-230lbs). I've always been an intense athlete and experience the same relationship with food as the two above posters - i.e., a healthy one.
So what are we to do now? Either love our bodies for what they are; calorie reduce down to goal weight (which I assume would come right back once cals are increased; or take letpin shots?
-Al
@Galina and berto
I have benefited from doing everything I can to maximize dopamine neurotransmission and fat oxidation, as leptin replacement works downstream dopamine.
Studies of leptin deficient mice suggest that giving the mice more dopamine will fix a lot of the crap lack of leptin breaks. Taking dopaminergic substances is a great way for weight reduced people to more easily maintain weight or even lose more.
My regimen is as follows:
1) I take dl-phenylalanine 500mg in the am and at night. This raises endorphins, as well as catecholamines.
2) I take l-tyrosine 1000mg in the am. This is the direct precursor to catecholamines. Studies of leptin deficient mice found that increasing tyrosine in their diet can actually block the push to metabolic disorder/obesity induced by leptin deficiency. This is more evidence that leptin controls body fat/appetite via dopamine.
3) I take OTC multiple reuptake inhibitor hyperforin/hypericin 900mg in the am and 600mg at night. SJW weakly raises a lot of neurotransmitters, among them dopamine and norepi. SJW also improves glucose tolerance by making GLUT4 more functional.
4) Recently I discovered the power of green tea catechins to augment dopamine and norepinephrine - this has been a HUGE help and almost makes me feel just the way low dose leptin did. EGCG is a COMT inhibitor, and in research it consistently leads to higher levels of catecholamines in the brain and body, with subsequent improvements in fat oxidation, energy and mood/energy. It feels very similar to leptin, from my experience having used both.
5) Caffeine, if you can tolerate it, is another simple OTC intervention to help augment sympathetic tone, fat oxidation, catecholamines and counter the effects of leptin insufficiency. Ignore those who would say caffeine is the DEBIL, real clinical research actually supports the utility of caffeine for keeping weight/appetite low and energy high.
6) Avoid interventions that suppress dopamine, such as eating a high carbohydrate diet or taking medications that suppress/block dopamine. SSRIs cause weight gain long term for the same reason as antispsychotics: they are dopamine suppressive.
7) Though I have not found research to support it, I suspect bright light therapy augments catecholamine levels and so can help reduce glucose metabolism dysfunction and body fat gain. My glucose tolerance is much better now that i use light therapy.
8) Acetyl-l-carnitine helps raise dopamine sensitivity and level in the brain. I take 500 in the am and 500 at night.
9) Magnesium citrate results in better glucose tolerance as well as better functionality of dopamine. I noticed huge improvements when I started taking extra magnesium. I take 200% RDV in the am and also at night, and I eat 3 ounces of nuts per day.
The key to weight maintenance is this: Leptin works to keep weight down by hot wiring your dopamine in your body and brain. You can get the weight control of higher leptin, by raising dopamine through other means. The above are just a few suggestions anyone can easily incorporate into their life without the risks of stimulants like phentermine, amphetamine, and other hard drugs that raise catecholamines too much.
Since figuring this out it has become very very easy to maintain my low body fat and feel quite good doing so.
3 years ago I struggled way more, before I knew any of this.
Now, raising dopamine will not correct hypogonadism induced by leptin insufficiency status post massive weight loss (it may even make it worse), and it will not correct the low thyroid state either. However, it WILL correct the energy, mood, and body fat problems, so for all practical purposes you will feel very well.
Basically, the key is to keep dopamine, thus fat oxidation as high as possible, as these are the mechanisms by which the body fights starvation.
I'm coming to the conclusion that the whole obesity/inflammation/diseases of civilisation conundrum is due almost entirely to individual differences in the gut biota.
Sloth and greed has essentially no supporting evidence.
Poo transplants cause weight loss in the obese without changing the diet.
Closely related species can have radically different diets eg giant pandas and polar bears.
Woo,
If you haven't looked into it, Masterjohn has an article called "The Pursuit of Happiness" that discusses dopamine and vitamin A. There are some good references there, but there are many in general regarding retinol & retinoic acid and dopamine & fat oxidation (by several means).
blogblog,
How easy is it to make a drastic change though? I think competitive eaters for example have high bifidobacterium and bacteroidetes; but, I don't think it's as easy as simple supplementation, or maybe it just takes a long time? Does a fecal transplant last long term even if the original obese person continues the same diet? Also, what do you say about the gut bacteria of someone who eats whatever, stays lean, but has hair loss or acne or erectile dysfunction?
John,
Per Dr. Ayers, the gut flora is not changed by diet, the ratios of particular gut species are. The only way to actually introduce new bacteria is to take them directly in through persistently eating soluble fibers that are not cleaned excessively and not being too hygienic. SImply supplementating is not adequate, because the diversity of bacteria is not present and your just contributing to the already existing gut flora population, not introducing new ones. Clue in the hygiene hypothesis here as well...
Further, in the case of a fecal transplant, I would assume that if one continues on the diet that causes the issues in the first place, the ratios would be restored to levels similar to what was previously experienced when a person had all hsi problems, thus the benefits of the fecla transplant would be temporary if no dietary adjustments were made.
I would also harbor to guess that one may also perform an 'enema', to break up the pre-existing gut biofilm for a fecal transplant to be absolutely effective.
Another point per Dr. Ayers is simply how one feeds infants, i.e. formula has 'killed' the health of babies. The reason is precisely related to gut flora, i.e. the babies digestive tract has not developed enough to handle the diversity of gut flora created by formula. One is creating inflammation from the very beginning for a child, which effects them in the long-run. Maybe this can be linked to obesity as well.
Further, this is precsiely why formula has nutrional values of vitamins and minerals equivalent to what adults would be getting, because the gut flora ae competing.
Breast milk on the other hand provides the gut flora the baby needs, which is one species. When the digestive system has developed enough, normally around 6 months or so, than the diet should be diversified.
Asim,
If you take in new bacteria with food, then you can change it with diet... but in general, yes, most people have the same common species but different amounts. What foods affects positive ones though? It's assumed that it's mostly soluble fibers, but vegans and vegetarians have less bifidobacteria and bacteroides. Certain fruits (apples, oranges, bananas) and tubers do okay, but whey and fish oil also work. There is one study that showed a B12 broth with meat trimmings was a good medium for bifidobacterium growth, but Lucas once linked a study showing low carb decreased it.
Art Ayers Cooling Inflammation blog is mostly nonsense that shows no real understanding of microbiology. Ayers is notoriously eccentric and has been 'let go' by a succession of institutions. He is now a private researcher (ie unemployed).
The gut bacteria is readily altered by diet, probiotics and antibiotics. Any reading of the scientific literature (as distinct from blogs) will tell you this quite clearly.
Fecal transplants involve almost totally eliminating the original biota by a combination of fasting, irrigation with PEG solution and powerful broad spectrum antibiotics. The donor feces are treated with a variety of antimicrobial chemicals and infused into the upper colon by a gastoenterologist. AFAIK the new biota remains intact for a long term.
Prebiotics such as soluble fibre only work if you already have the right gut biota. If you have the wrong biota - eg high levels of clostridia - it makes inflammation much worse.
@blogblog
But what would cause the gut dysbiosis? This seems reactive to something else, as immune system and diet largely control the microbes in your intestines. Fungal overgrowths and such are primarily symptomatic, not causative, of high blood sugar and poor immune system. However, once in place, it is not unreasonable to assume they worsen the trend.
Sort of like, carbs do not cause glucose intolerance, but once glucose intolerance is started, eating potatoes excessively makes things worse by adding stress to broken physiology.
It is found, for example, tha tpeople with diabetes easily develop oral infections, but this is a result of having high blood sugar, not a cause of it. If your sugar is too high and your immune system does not work properly as a result, you become a buffet for germs and fungus. This allows you to develop all sorts of horrible problems that normal people with lower sugar and healthy immune systems never have to worry about. If you stub your toe, it turns into gangrene. If you get dental work, you might die of endocarditis or meningitis. Your teeth, with high blood sugar, rot away under bacteria that your immune system is powerless to stop. The sugar encourages their growth; the immune system works impotently to stop it. It's a double sided problem.
Speaking as a nurse, it's remarkable how a diabetic patient can have a tiny meaningless wound, and you observe it turn into this horrid infection. If I had that same wound, it would heal rapidly with no signs of infection. Diabetic patients are always ending up with overwhelming sepsis and pneumonia and such things. THey can't fight off infections.
The poor feet of diabetics. Change the foot dressing of a patient with diabetes. This is one of the least pleasant things in the world to do, and it really makes you appreciate just how horrible diabetes is. They can not heal. Literally, they can't heal, and they can't fight infections. Sores stay open and worsen, become infested with bacteria.
When your blood sugar system does not work, you are basically half dead, physically speaking. Diabetes in a lot of ways is like living death, the body decays and fails to regenerate, much like a corpse, bacteria eat it alive, any and all injuries worsen without healing.
I also think it is quite likely that bacterial and fungal overgrowths, once they start, affect metabolism to encourage higher blood sugar and worse insulin resistance, as this was an evolutionary adaptation allowing them to thrive.
Sort of how toxoplasmosis gondii has evolved the ability to hijack the nervous system, lead to insane fearless behavior in rats, allowing the rats to be consumed by cats, where t. gondii lives happily in a symbiotic relationship.
t. gondii also affects the nervous system of humans and is associated with psychosis and disordered thinking, when one has such an infection.
This is probably much how many germs and fungi induce slightly worse insulin resistance, slightly higher blood sugar... it benefits the metabolism and growth of the microorganism to do so, and was selected for.
It really isn't a problem unless the person has an underlying blood sugar pathology to begin with, which allows for such massive overgrowth, and a progressive worsening of the blood sugar dynamics FROM the bacterial/fungal overgrowth.
@john
I have heard of a relationship between vitamin a metabolism and depression, which I presume is the basis behind the terrible side effect/severe depression occasionally induced by accutane.
I have not researched it much. I will read more based on your recommendations.
An obesity-associated gut microbiome
with increased capacity for energy harvest.
Vol 444 | 21/28 December 2006 | doi:10.1038/nature05414
http://www.fbmc.fcen.uba.ar/materias/ga/seminarios/Gut_environ_genomics.pdf
Free full text
964 citations!
The basic premise of the paper is that the wrong gut bacteria cause obesity and that obesity is a contagious disease.
@Woo,
the gut dysbiosis is most likely due to a lack of breast feeding and the early introduction of solids to infant diets. Non-human milk favours clostridia rather than bacterioides.
Clostridia = potent neurotoxins.
@Woo,
caesarian births also result in a gut dysbiosis.
My son(now 18) was born through a vaginal delivery and was breastfeed till 6 months. He suppose to get a lot of mine micro-flora, right? So far he is like his dad - naturally thin, can eat an enormous amount of food without gaining an ounce, but not interested in food too much and prone to spontaneous fasts. I must say I am completely different.
Woo,
Yea, he covers some of the literature on vitamin A and depression, Accutane, dopamine and presents counter evidence to the idea that vitamin A is a problem.
"The gut bacteria is readily altered by diet, probiotics and antibiotics. Any reading of the scientific literature (as distinct from blogs) will tell you this quite clearly."
1. Dr. AYers clearly acknowledges that antibiotics destroys the gut flora and heavy usage of it leads to problems of inflammation in the long run.
2. Dr. Ayers clearly acknowledges that gut flora can be 'altered' by prebiotics and probiotics. Again, the issue is not the ratios, but the diversity. And he makes this point clear.
"Prebiotics such as soluble fibre only work if you already have the right gut biota. If you have the wrong biota - eg high levels of clostridia - it makes inflammation much worse."
And the Doctor makes this point clear in multiple posts.
I think your projecting or you just don't read properly.
"But what would cause the gut dysbiosis? This seems reactive to something else, as immune system and diet largely control the microbes in your intestines. Fungal overgrowths and such are primarily symptomatic, not causative, of high blood sugar and poor immune system. However, once in place, it is not unreasonable to assume they worsen the trend."
1. Not necessarily 'reactive. The 'causative' factor, for example, could be past use of anitbiotics which disrupted the the gut flora, allowing for the promotion of problems like fungal growth as well as 'resistant' evil flora, which in turn cause inflammation. In this case, the gut flora is the cause.
2. The immune system and gut flora share a symbiotic relationship, i.e. to argue one controls the other isn't true.
http://www.nytimes.com/2011/08/16/health/16cancer.html?_r=1&pagewanted=2
"As the various cells are colluding, they may also be trading information with cells in another realm — the micro-organisms in the mouth, skin, respiratory system, urogenital tract, stomach and digestive system. Each microbe has its own set of genes, which can interact with those in the human body by exchanging molecular signals.
“The signaling these microbes do is dramatically complex,” Dr. Nicholson said in an interview at Imperial College. “They send metabolic signals to each other — and they are sending chemicals out constantly that are stimulating our biological processes.
“It’s astonishing, really. There they are, sitting around and doing stuff, and most of it we don’t really know or understand.”
People in different geographical locales can harbor different microbial ecosystems. Last year scientists reported evidence that the Japanese microbiome has acquired a gene for a seaweed-digesting enzyme from a marine bacterium. The gene, not found in the guts of North Americans, may aid in the digestion of sushi wrappers. The idea that people in different regions of the world have co-evolved with different microbial ecosystems may be a factor — along with diet, lifestyle and other environmental agents — in explaining why they are often subject to different cancers.
The composition of the microbiome changes not only geographically but also over time. With improved hygiene, dietary changes and the rising use of antibiotics, levels of the microbe Helicobacter pylori in the human gut have been decreasing in developing countries, and so has stomach cancer. At the same time, however, esophageal cancer has been increasing, leading to speculation that H. pylori provides some kind of protective effect."
"If you take in new bacteria with food, then you can change it with diet... but in general, yes, most people have the same common species but different amounts. What foods affects positive ones though? It's assumed that it's mostly soluble fibers, but vegans and vegetarians have less bifidobacteria and bacteroides. Certain fruits (apples, oranges, bananas) and tubers do okay, but whey and fish oil also work. There is one study that showed a B12 broth with meat trimmings was a good medium for bifidobacterium growth, but Lucas once linked a study showing low carb decreased it."
The point is this... Bacteria FEED off of soluble fiber, they don't introduce bacteria. As Dr. Ayers says, when your excessively cleaning vegetables, your washing the bacteria that would be eating the vegetables off, thus reducing the probability one would be introducing new and diverse
bacteria. Further, when your overly hygienic and don't play in dirt, then your also not providing oppurtunities for one to introduce diverse species... Further, we excessively cook food, without taking in only foods that have limited bacteria, and eat processed food as well, which leads to simplified gut flors.
"Probiotics are not retained in the gut, but they can contribute a few of the genes needed for a healthy gut flora. The source of bacteria for a healthy gut flora may range from minimally washed garden vegetables, to the more aggressive total replacement of gut flora with a fecal transplant from a healthy donor."
Think of traditional societies and how they dealt with foods. They would eat foods directly off the tree, dusting them off.
Blogblog,
Dr. Ayers was speaking about gut flora way before you even acknowledged it in any of your posts. Your way late to the ball game to be 'criticizing'...
In fact, I remember one post within the last 2 months where you argued that antibiotic use in cattle wasn't done to increase the wight of cattle in response to my point, which Dr. Ayers clearly stated, that it was, i.e the disruption of gut flora through the introduction of antiobiotics in cattle leads to their FATTENING.
The fact that your changing your tune in line to pretty much what Dr. Ayers has been saying for the past 3 years makes me wonder how on earth you would even criticize what you call his 'eccentricity'...
Your even recounting about breast feeding and gut diobysis, like your mimicking him, along with the fact that your now calling obesity 'contagious'...
It's like I'm reading his posts...
As far as processed foods, I think this quote from Dr. Ayers is highly relevant:
"Modern diets consist of processed foods that are made of fat, protein and starch, all of which are digested and absorbed before reaching the colon. These simplified foods produce a SIMPLIFIED GUT FLORA that may also produce more CFAs rather than stool forming gut bacteria. In other words, eating larger amounts of simpler foods can result in more of the nutrients being absorbed and making it easier to gain weight on less food with a tendency toward constipation. These diets may also select for bacteria that maintain the simplified, "efficient" gut flora community and provide the potential for the spread of obesity through a population. Having friends and relatives who are obese and presumably have gut bacteria that favor obesity, increases the risk of obesity. It seems likely that obesity is contagious."
Asim,
I'm not really sure what you're getting at. I read Art's blog, and it has lots of good stuff.
I was making the point that there is more to growing bacteria populations than soluble fibers; certain species populate more with certain foods. As for "simple" foods, I think traditionals generally make foods as "simple" as possible, by spending time processing nuts, spitting out fiber, etc. They prefer meat and honey because they're energy dense and "simple." But, they do have more bacteroidetes and bifidobacterium than industrialized people; I suspect it's not just because they eat more soluble fiber and play in dirt.
Glucose uptake is controlled at the cell surface. Fatty acid uptake is (predominantly) controlled at the mitochondrial surface.
Glucose uptake is controlled at the cell surface...via insulin.
Fatty acid uptake is (predominantly) controlled at the mitochondrial surface...via ???
John, I was actually referring primarily to blogblog's post for calling out Dr. Ayers as eccentric, when as of late, blogblog is simply parroting, almost "word for word" what the Dr. has been saying for many years..
John,
"As for "simple" foods, I think traditionals generally make foods as "simple" as possible, by spending time processing nuts, spitting out fiber, etc."
By simple, Dr. Ayers was referring to PROCESSED foods, which are not 'traditional' by any stretch of the imagination...
"But, they do have more bacteroidetes and bifidobacterium than industrialized people; I suspect it's not just because they eat more soluble fiber and play in dirt."
1.
Oh, no doubt.. that again, is about ratio, not diversity.. The more one eats a particular type of food that a species 'thrives' on, the more one is increasing the chance the particular bacteria that has the enzyme to break down the food thrives on... they'll go where they can eat...
2.
It's the same thing with 'lactose'... many people that have lactose intolerance is more so do to their lack of persistence in taking in lactose to cultivate the necessary gut flora that have the enzyme to break it down. Fermented products like yoghurt, by consistenly eating them, would introduce more of these species you mentioned above.
I wonder, is something we consume while eating animal flesh, contributes to gut bacteria? May be connective tissue or cooked to softness bones?
http://www.nytimes.com/2011/11/01/health/scientist-examines-possible-link-between-antibiotics-and-obesity.html
"His lab has since produced a stream of findings supporting his suspicion. Dr. Blaser and his colleagues discovered, for instance, that the stomach behaves differently after a course of antibiotics eradicates resident H. pylori.
After a meal, levels of ghrelin, a hunger hormone secreted in the stomach, are supposed to fall. But in subjects without H. pylori, the amount of ghrelin in the bloodstream held steady, in essence telling the brain to keep eating."
Antiobiotics is disrupting how hunger is regulated.
@Itsthewoo2:
Taking one item from one of your long lists, caffeine:
Does this not promote cortisol, which in turn promotes belly fat?
@Galina: Sounds like we are similar: by low, and then very-low-carbing, I got down from about BMI 32 to BMI ~27, but foolishly allowed myself to creep back up to ~28.something.
I'm currently trying to crash down through the 28.0 barrier, and it's tough.
When I first started low-carbing, I read on some forum or other that basically you get one easy shot at low-carbing, and if you allow yourself to regain, your second and subsequent shots will always be harder. I suspect there are several good biological reasons for this (if it's true, and it seems to be for me), although I don't think it has anything to do with "set point" :-)
Just to follow up on the RQ estimate: in "Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet" (http://www.ajcn.org/content/90/3/519.full), they measure RQ after 1.5 days on a keto diet, and it was even lower than one might guess -- 0.76. Of coures, this could change with keto-adaptation.
Hi Amber, thngs will change over the long term undoubtedly as muscles come to reject ketones and run primarily on fatty acids, sparing ketones for the brain. Not sure what the mechanism will be here but certainly happens. But the RQ from metabolism usuing ketones should ultimately be the same as from fat, even if the locations for CO2 and O2 production have been separated by hepatic ketogenesis. Interestingly it turns out the glial cells of the brain are ketogenic too...
Peter
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