Bloggo Science ~ FIRKO-ized!
I have long since ceased reading Peter/Hyperlipid's blog for meaningful information. There are too many examples of him openly manipulating data and misrepresenting science for me to take him seriously anymore. Still, our blogs share a certain readership and his readers do participate in other internet realms where I linger or participate. As such, his blog remains on my feed reader. Peter has been on a FIRKO mouse kick lately and it has caused me to dust off a few posts from the draft bin where this mouse fits into the discussion. But his latest latest offering on FIRKO (Fat Insulin-Receptor Knock Out) just tripped my epigenetic BSA* gene switch. *BSA = Bull Sh!t Alert
In FIRKO-ise, Peter actually compares a genetically modified mouse to putting a mouse on a ketogenic diet. Really! To review, the FIRKO mouse lacks insulin receptors. As a result, this mouse is resistant to obesity on the usual obesogenic diet for rodents (high fat). This mouse's fat cells do not "see" insulin and this is the low carbers favorite gen mod rodent because it so *clearly* shows that it's all about insulin signaling in fat tissue, and Taubes is right. I'll have at the various IRKO's in an upcoming post, but the case is hardly airtight for TWICHOO.
So in this post, Peter spins a tale of how one can create a FIRKO mouse from an ordinary C57BL/6. You first "break" it by feeding it high fat crap in a bag, then switch it to a ketogenic diet. The data actually came from such a study where the mice denoted by the triangles were switched to a KD at 60 days, and as you can see, they rapidly drop weight. As Peter tells you:
Ketosis renders adipocytes insulin resistant, just like those of FIRKO mice.
This is not true, and it is misleading. The KD doesn't do anything of the sort of knocking out insulin receptors. It may down-regulate them, but there's no indication that this even occurs. There's no evidence that the adipose tissue sensitivity to insulin is altered in any way, but what's a little making shit up between friends, right? Indeed, smaller adipocytes are more insulin sensitive than larger ones, so a case could be made that the KD rapidly resolves whatever adipose-IR the obese mice are exhibiting. In any case, Peter cites this study (website seems to be down at the moment) that I discussed HERE. The KD mice lost weight to stabilize out at approximately 85% of normal body weight comparable to the calorie restricted (black dots) mice. This too, would counter what you would expect if KD actually did anything of the sort of FIRKO-ising. Peter says:
We know that simply not eating for a while induces whole body physiological insulin resistance. We also know we can do exactly the same thing, without all the pesky death involved in sustained not-eating, by simply going in to deep ketosis without cutting calories.
This is readily explained by the KD mice having a 15% higher resting metabolic rate than even the CR group ... and something that has the ketogenic crowd (all of which are eating single digit percent protein I'm sure) crowing over their metabolic advantage! But speaking of the fatty fairy tales, look at the insulin levels in the table in my post. If anything, the KD diet made these mice functionally Type 1 diabetic (insulin deficient) ... not FIRKO. Peter seems unconcerned that the KD mice lose lean and are relatively "fattier" than their CR peers. Whatever ... but the KD's avoid that pesky death? Really? Well, if they were actually FIRKO-ised, we can expect that they would live longer. As Peter rightly points out, the FIRKO mouse lives 18% longer than ad libitum fed mice on standard chow. But how about the KD mice from this study? But:
What about these ketogenic fed, pseudo-FIRKO mice? Alas the sad story of their premature demise will have to be left for the next post...
Yes, alas. Because we wouldn't want to spoil our sarcastic gloat session with the reality of what happens to these FIRKO-ised mice. The "excess fat" that may have escaped it's insulin-stimulated chains in the adipose tissue doesn't make the workings for urine derived salad dressing -- but it makes for FIRKO foie gras. These mice develop fatty livers. Surely this is a relic of the high fat crap in a bag they were fed for roughly two months. But no ... Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. I cited this study in my prior post (I have the full text now and will be blogging on this at some future date). The mice in this study were fed KD for 12 weeks and the results were not favorable. Hepatic steatosis. You can blame it on the composition of the diet, type of fat, etc.etc. It won't be explained away.
Near as I can tell, it is Peter who coined this term "physiological IR" and deemed it the "good IR". Sure, the insulin resistant state is beneficial to the organism in the glucose-deprived state. Otherwise the brain would starve. But that does not mean it is a beneficial state for any organism in the long term. Urine and beer might be beneficial hydrators if you're stranded in the desert, doesn't make them beneficial for everyday imbibing. More recently I've seen Peter question whether fatty liver is good for the person in ketosis who needs lots of fats at the ready for their liver to produce ketones. Sounds like rationalizing to me, and dangerous thinking out loud. Will we be hearing about BKNAFL (Benign Ketotic Non-Alcoholic Fatty Liver) soon courtesy of Peter? Sigh.
Do I think most humans on VLC diets have to worry? Probably not ... probably ... because most are not eating a lot more food at <10% protein and essentially ZC. Well ... except for the new leader of the Insurgency. Hope he gets this memo...
Comments
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how many went low carb specifically because of the promise of unrestricted food?
IMHO there's a very good chance some VLC-ers are damaging themselves severely.
Can you elaborate on why KD mice had +15% higher RMR relative to CR mice?
Do you mean after a meal of "oatmeal, quark and bananas" you dont feel any hunger again for 16 hours?
Is that how it is all the time? Is that all you ever eat? So you practice calorie restriction then?
Why does it seem to anger people that someone can fast or doesn't get gnawingly hungry after eating carbs? If I eat a bowl of steel cut oatmeal, it fills me up fast and lasts a good long time. We're all different, but I gotta tell you, when I was VLC I was petrified of eating more carbs daily for fear I would be hungry all the time. What bunk.
I'm currently eating well above maintanence which is hard to do in just 8 hours and would be even harder without high reward food like ice-cream and candy.
Wonder what the difference is biochemically speaking? Could I 'over-respond' with insulin to carbs, why do certain carbs make some people hungry really quickly even if they are supposedly low GI?
My understanding is that carbs and fat are equally satisfying but protein trumps both.
this is because some people dont produce GLP-1 in response to dietary carbs, ( itsthewoo first brought this to my attention ).
GLP-1 is a crucial incretin. To give you an idea of how important the incretin affect is, consider this....
Whats the difference between feeding someone a meal through thier mouth, compared to grinding the same meal up into microscopic pieces and injecting it directly ( and slowly ) into thier bloodstream?
In case 1, the person is happy, experiences pleasure from eating, and feels full and satisfied after the meal. He gets the incretin affect.
In case 2, the person most likely will not experience ANY of the above, only the pain from the needle being injected. There is NO incretin affect.
In case 2, is the person going to full after his "meal"? Most likely NOT.
But case 2 is VERY similiar to what obese people experience, they eat carbs, get a severely reduced incretin response, and remain hungry. As far as the body is concerned, The glucose was injected straight into the bloodstream. The body is like "whoa where the fuck did that glucose come from? we didnt eat anything!, maybe the liver is playing glucose leakage games again!, lets squirt out some insulin and get that excess blood sugar into the fat cells quickly before bad things from hyperglycemia happen!"
"Lc makes it easier for YOU too fast. Not everyone. I fast for 16 ours after a meal of oatmeal, quark and bananas."
I don't know what quark is exactly [I'm pulling from context it's some sort of supplemental protein powder?] but I find the mixture of oatmeal and bananas extremely satiating. If I eat a serving of oatmeal with banana chopped up in it and a splash of milk I won't be interested in eating again until dinner so...maybe not really a fast but I'll skip a meal at the very least.
"Kindke: Noone fasts for 16 hours without feeling hunger regardless of food choice. I usually get hungry after 14 hours but it only last a few minutes and after that I get more alert."
Right, I agree. That "alert" feeling is pleasant and of much greater magnitude than the 20 second hunger twinge that comes occasionally when it's almost dinner time.
I'm inclined to think it's not really about certain carbs ....rather about certain foods. I find oatmeal very satiating...some people don't. Some foods satiate others very reliably and the result is unremarkable for me. I'm not certain of the exact mechanism but I do think the insulin model is hindering the process of investigation rather than aiding it.
All I know is that if a carby meal doesnt make you feel full ( which is very common in obese people, ) its because you didnt get any GLP-1.
It certainly has nothing to do with "greed" or "gluttony".
"All I know is that if a carby meal doesnt make you feel full ( which is very common in obese people, ) its because you didnt get any GLP-1."
How can you be so certain of that mechanism? What about a mixed [c/p/f] meal that did make you feel full but you wanted more of anyway?
It certainly has nothing to do with "greed" or "gluttony".
I agree that moralizing something that is amoral is a huge hindrance. Probably more so than any impact the food itself could possibly have independently.
you can google it ...
For the commercial ones I've tried anyway - haven't made it myself. I'll try it someday.
Isnt it well documented, especially by the readers of this blog, that low-carb diets only work because you eat less. And in general, people eat less because they are less hungry.
So what do we have here?
We have meals of only [p/f], but also meals providing less calories than mixed meals of [c/p/f], yet somehow, the participants are less hungry?
How can people be less hungry eating fewer calories?
Spot on bentleyj74 !
Here's a little experiment to make your case: (1) take a Lay's potato chip ("Betcha can't eat just one" - an exemplar of a high-reward food) and break it up into its macro-nutrient and micro-nutrient components (e.g. 40% complex carbs, 55% fat, 10 mg sodium chloride/20gms etc.). Now, (2) re-create that same nutrient environment with separate single-source food ingredients like potato flour, canola oil, and table salt; (3) eat the caloric equivalent of one serving of Lay's chips and; (4) note the effects on appetite!
Clearly, the same amount (and type) of carbs, but a very different effect on satiation and appetite.
In fact, I would go so far as to say that it isn't even foods that are 'addictive', but the individuals' 'experience when eating certain foods'. That is, it's the way John experiences Lay's chips as being "wow, that's yummy!" that is the addictive element, not the chip itself.
Now, of course, John's disposition to respond to Lay's chips in such manner is based on an underlying chemical structure in the chip itself; but the key point is that it is John's internal response to the chip that determines the extent, if any, of the chip's addictive potential (this explains why people of different cultures respond differently to different tastes, textures etc. with respect to food reward).
Cheers
Harry
body weight control by endogenous GLP-1.
Reversal of obesity and insulin resistance by GLP-1 agonist in diet-induced obese mice.
Is there any evidence that the lack of GLP-1 response CAUSES obesity? NO. It would be incongruent with the insulin theory as well. Insulin doesn't make you hungry, GLP-1 = more insulin = more fat accumulation supposedly. That's the problem with swiss cheese hypotheses.
"And in general, people eat less because they are less hungry."
I've heard that theory but it is not what I have observed first hand. What I usually see first hand is that people decide to eat less then realize in retrospect that they weren't as hungry and miserable as they expected to be.
Granted that doesn't mean they are never hungry and it doesn't mean that they always eat less every day without any variability but people do realize that their "hunger" cues and signals are not entirely the result of physiological hunger. I recognize that I eat for reasons other than a clear hunger signal...recreation, boredom, enticing aromas, blah blah blah. Ice cream sandwiches have their own category :) and are absolutely a good reason to eat. Especially the grasshopper ones. Especially on the tail end of a chipotle-esque meal.
In general I observe that people eat less and then become less hungry not vice versa. I'm sure there are exceptions particularly for people who are already at very low body fat but in general that seems to be the pattern.
Yeah, that lady put two loaves of bread, a box of biscuits, a box of pasta, and a bag of flour in her shopping cart. They're sitting right next to the three or four 2-liter bottles of Pepsi and the box of Little Debbie Snack Cakes, Twinkies, cakes, pies, apple juice, corn chips, potato chips, kettle chips, nacho chips, chocolate bars, chocolate-covered almonds... etc.
And aside from the amount of carbs, whether as sugar or those EVIL (read in a deep, echoy voice) starches, is the fact that a lot of that food will NOT be eaten when the people who bought it are hungry. They'll be eaten because they happen to be within easy reach and require no preparation time.
I agree that it is an overlooked factor in weight loss on any diet plan. I think that whenever a person embarks on a new diet plan, whether LC or LF or whatever, they are making a conscious commitment. So the first thing to go are the snacks and drinks. And they get replaced with fruits and celery sticks and water with a dash of self-control. And for as long as the dieter is being self-conscious and exercising a bit of discipline, the diet works. Once they hit a target and feel good about themselves, they lose focus and soon they have a counter full of snack foods within easy reach.
So yeah, the whole "and the best part is, I don't feel hungry" epiphany is probably a bit of unintentional self-deception. If we don't recognize the part it plays in our weight loss, it will hurt our efforts to lose more weight and/or maintain the losses.
"Three quarks for Muster Mark!
Sure he has not got much of a bark
And sure any he has it's all beside the mark."
—James Joyce, Finnegans Wake
I don't think Tonus said anything eliciting hate!
The fact is, self deception and lack of discipline are pretty common traits in humans...and since dieters are human...well, you can see where this is going, right?
That's not to say that all diets fail due to 'human error'. Some are straight up poorly conceived, while others are fine in theory, but are not compatible with the individual needs of the dieter.
But I think it would be excessively charitable to claim that all dieters are equally committed and honest with themselves with respect to their diet efforts.
Diets do fail dieters...but sometimes, dieters fail diets.
Cheers,
Harry
Probably I was too tired yesterday when I left my previous comment, but reading what Tonus said left me as frustrated as when my mother in low kept telling me that the allergy on fish was all in my head. Not everybody is equally committed to their efforts but usually people know pretty well how they feel or react on something. They may be not honest enough when they voice it, of course.
Pointing out the beneficial effects of self-discipline does not mean that it's easy to do. I struggle with my weight as well, after all. The issue for most of us is not in recognizing that we need to be more disciplined, it's in finding ways to achieve it. If you have found a diet and eating plan that is working for you (and from your past comments, it seems that you have) then you are being more disciplined.
As for the self-deception, again I was using my own experience as the basis. As obvious as it is that I have a habit of eating when I am not hungry, it's something that I often do not take into account when trying to find ways to manage my diet and weight. So I wind up talking about hunger when hunger is not really the issue-- unnecessary eating is.
I think you may be taking my comments a bit too personal, Galina. Mostly, I try to understand human behavior from the perspective that our subconscious mind exerts a great deal more influence on us than we believe, even when we're aware of it. If you see comments where I am speaking in the general sense and using "we" then I am using my own experience and my own motives and actions as the basis. I believe that by stating and studying the way I (and other people) think, I can identify those mental obstacles and try to find a way around them.
And I like you Galina, you seem like a nice person. Even if you hate me a little bit. :)
I agree that people DO know how they feel or react but I do also suspect that they do not know whether their perception is objective. Let me compare for the sake of example a person who avoids conflicts to a person who overeats. The over eater and conflict avoider both know intellectually that their behaviors are not helping them BUT they don't know how to endure what they feel if they try to do otherwise. People get disoriented when they don't know what to DO in response to what they ARE feeling.
If I feel hunger should I disregard it? To what degree? When do I have permission to eat again and on what authority is that limit set? We all know we won't roll over and immediately die if we are hungry for a few hours or even a few days but at some point everyone finds it unpleasant and has to decide to get something to eat. That is all determined by perception and perception is a tricky b*tch to contend with. There are a lot of moving parts and sophisticated conditioned responses, trap doors, and blind sides when dealing with perception.
It'd be so much easier for everyone if it really was as simple as any diet would like to suggest.
I think your work with people could make you sort-of pessimistic about human nature. Also, people who hire a personal trainer may be from passive variety(some of them, of course), who think they would pay you to do some of the job instead of practicing self-discipline and observe what works and what doesn't. I believe the majority of health problem people experience could be improved through life-style choices , sometimes significantly improved. My hobby is to find how to do it, and sometimes I give an advice when asked. It is amazing how rarely people follow it. For example, my former mother-in-law, she suffers from rheumatoid arthritis, I keep bringing her as a gift various topical remedies when I visit Russia. I told her(because she asked) to avoid certain things that get all autoimmune issues worse, start taking D3, do not drink a vine for any reason. Just because she is facing the perspective of a wheel-chair in a nearest future, she follows my advise probably 20% of the time. I am not pushing a strict Paleo on her, btw because it would be unrealistic.
Here is my personal summary, if you aim for fasting window at least 16 hours and try to eat not sooner than in 4 hours after you finished your last meal(preferably at different times in order to avoid Pavlov's effect), practice a weekly 22 - 24 hour fast, it will be it. You will decide when you eat in advance, not your hunger or your perception.
Here is my personal summary, if you aim for fasting window at least 16 hours and try to eat not sooner than in 4 hours after you finished your last meal(preferably at different times in order to avoid Pavlov's effect), practice a weekly 22 - 24 hour fast, it will be it. You will decide when you eat in advance, not your hunger or your perception."
Sure, he covers them...but so do a lot of people. My question is broader reaching and sort of overlaps the lab rat question. Things like food reward can inform decisions but unless you actually ARE a lab rat it can't make them for you and doesn't take into account the DQ, McDs, "insert fast food joint here" probably walking distance from your home and on every main road from your home to wherever you are going. It doesn't take social situations, celebrations, self soothing, pleasure, or any of the other varied reasons people eat for reasons other than to satisfy nutrient needs.
All of these plans basically exist for the purpose of placing some sort of arbitrary limit on peoples eating behaviors then backpedaling with some pseudo scientific explanation for why eating at ...say...an 8 hr window as opposed to a 4 or a 10 makes all the difference in the world. Or replacing calorie dense donuts with calorie sparse apples under the premise of "health" but promising you can eat whenever you want. Everyone has their pet method but it all seems to boil down to finding ways to limit those behaviors that work with the individual personality, lifestyle constraints, and preferences. It would not suprise me in the slightest to uncover some personal journaling of Dr Atkins [or anyone really] who designed a diet on a specific premise knowing full well the premise was objectively bullsh*t but that it worked anyway because of the psychological conditioning.
There lies the crux for me personally and my primary objection. These conditioning beliefs designed to do nothing other than reduce intakes have unintended consequences. Self delusion, orthorexia, ocd, ED, and a whole host of other neurotic behaviors which can all by themselves hijack the original goal and displace it with vague ideals, moving targets, and irrational fears. Freedom is a marketing nightmare.
1 I'm already a regular faster but I just find it convenient...I don't believe it offers any magical benefits.
2 I'm irritated by what I consider unethical behavior from people using their credentials to give authority to unproven and occasionally even falsifiable pseudo science by utilizing behavior psychology techniques/conditioning but keeping it veiled.
It get's complicated because I'm not opposed to conditioning per say, in fact I find it a very effective technique for just about anything. When used in an above board manner with a qualified professional who is working 1:1 to deal with unintended consequences it's probably the gold standard. When used willy nilly it's VERY dangerous imo.
Thank you for the clarification, it was really difficult to get a logic from your previous comment, English is my second language, but when I was tested for reading I got the highest possible score, so I am less impaired in reading than in writing, for example, and - o, my ascent!
About what you said - it is the internet, a blogger even if he/she is a real doctor doesn't have the responsibilities or obligations of the real doctor, and the freedom of speech allows him to share his or her ideas and blog readers are thous who are left responsible for unintended consequences because it was their decision to conduct the n=1. As almost everything around us(health care system is a good example), it is the unperfect situation, and there is no means available to make it perfect. The only possible solution - to make it illegal to share the ideas which may be taken as a medical advice. I would rather live it the way it is now because I believe in personal responsibility and the freedom of sharing ideas. Besides, I have less idealized view on doctors who are not so insightful. I insisted on checking my thyroid function while doctor resisted, I got myself a diagnosis of the Rosacia which was later confirmed, the Neuropathologist who I was sent to was absolutely useless for the help with migraines. I am managing my health and deal with medical problems of my family members by myself when it doesn't require a surgery. It is a valuable survival skill, part of being strong and stronger, as opposite to rely on personal trainers, dietitians, doctors , personal cooks to deal with a lifestyle choices. Who relies on other people too much is a weak person , usually have too little will-power, and faith instead of the ability to think and make choices. Usually life is less kind to the weak, and I am not very moved to protect them from themselves at the price of possibly limiting my personal choices to read anything I want.
A large part of my discomfort with the diet gurus is that they set up this very dependency by the design of their programs. People CAN choose to disregard it but they [the writers] know full well unless they've been asleep at the switch for the last hundred years that the majority of people who have significant lifestyle issues also have significant executive function/decision making problems. In other words it is marketed directly to a population known to have a frailty there under the guise of being "help".
"About what you said - it is the internet, a blogger even if he/she is a real doctor doesn't have the responsibilities or obligations of the real doctor, and the freedom of speech allows him to share his or her ideas and blog readers are thous who are left responsible for unintended consequences because it was their decision to conduct the n=1."
True, also true that I think they are @ssholes for using their freedom to exploit the known weakness of a vulnerable population.
"The only possible solution - to make it illegal to share the ideas which may be taken as a medical advice. I would rather live it the way it is now because I believe in personal responsibility and the freedom of sharing ideas."
Snake oil salesman always find a way around the law anyhow. I disagree with SG that it's a viable solution is to attempt to sanitize the environment via litigation/regulation.
Bottom line...I'm wary of reckless conditioning at the hand of an amateur. I've seen bad outcomes for people who were on the business end of the type of conditioning that helps you follow orders like "charge that machine gun nest" or "jump out of this airplane while people shoot at you because I say so" when the person in the drivers seat is not taking their responsibility seriously or has too little accountability. If people are opening themselves up to that willingly...fine, buyer beware. However when it's hidden under the guise of something else...what then?
It is unrealistic to aim for perfection. Often when we get what we want there is some unwanted baggage. I love to go to my yoga classes, I enjoy it a lot, but often yoga instructors preach something what is a complete BS from my perspective. It is life.
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