Back on the IF bandwagon - and its working

After the rodent study I decided to get back on the IF bandwagon, especially given what we also learnt about diurnal cortisol in the same post. The biggest point about diurnal cortisol is not to eat for atleast 3-4 hours after waking up, let the cortisol come down before you start munching on grub.

Anyway, I have been doing 23/1 IF since, and I was pleasantly surprised that my glucose tolerance was considerably higher. In line with diurnal cortisol, I have been waiting until 4pm-6pm in the evening and then consuming all my calories in one large meal, ive even been sneaking in some carbs in the form of candy and banana's. Im also taking 1000mg metformin with the meal, and pre-loading with 2 teaspoons of white wine vinegar.

I dont restrict myself, I dont count calories, I just eat whatever I want and eat to hunger. My estimate is it comes out to about 2200 calories.

My plan was to continue this for a few days until I became accustomed to the circadian rhythm of feeding, and then transition more into a ketogenic diet but still keeping the 23/1 feeding pattern. I needed to eat higher carb and bit of junk food in the beginning to keep myself satisfied and not strain myself with cravings while my body adjusted to the new 23/1 pattern because ghrelin is also on the circadian clock and it takes time to adjust. Eating ketogenic on 23/1 will inadvertently lead to reduced calorie intake because it wont be easy eating 2200 calories of low-carb in one meal, not unless I start drinking pints of cream.

OK, so yesterday was my first low-carb day on the IF 23/1 and today I had some comments from work colleagues "hey it looks like your losing weight", tbh my trousers do feel noticeably looser. Great! I never weigh myself on the scales because its just playing mind games with yourself, I just go by how I feel and how my clothes fit. I actually did 23/1 back in 2007 and looking back now I remember that's when I also managed to get down to my lowest weight, alas, everything literally went "pear-shaped" though when I started my new job and came under stress and pressure.

Stress and depression make me crave sucrose laden foods. This has been the prime reason I have yo-yo dieted so much. Sucrose is how I artificially raise my mood to cope with stress and depression. Although sucrose tends not to make me gain weight in small amounts, once I get the mood high from sucrose foods I end up binging on huge amounts and its very hard to pull myself away from it.

I cant eat just one strawberry lace or just one drumstick lolly, as soon as I get the taste of sucrose on my tongue I just get completely mind-controlled and consume it all. I.E. hyperphagia , Fruit does not have the same affect at all. Only human engineered foods cause these addictions.

I want to quickly comment on something else aswell, Today I had only bacon and eggs for my meal. Anyway about 30 minutes after the meal I got very drowsy, and it was lights out, I must of napped for about 1 hour. This is post-prandial somnolence, and I was surprised that this happened because I had assumed this phenomenon was primarily a function of the tryptophan:LNAA ratio in the blood, and that only high carb meals that spike insulin were capable of post-prandial somnolence by shunting more tryptophan into the brain.

Sigh, so thats another theory out of the window. Unless the egg white had something to do with it? I ate 4 egg whites in the meal, and egg whites are high in tryptophan ( but they are high in BCAA aswell! ). This study used something called hydrolysed egg protein to raise the tryptophan:LNAA ratio. No idea what that is, and it probably isn't the same as fried egg whites. So meh.

Anyway, the rodent IF study has finally nailed it into my brain, that when you eat is likely just as important as what you eat. I'm sure I wont stay 23/1 forever, but I will keep the lessons that rodents teach us in mind. 23/1 is good for weight loss, and I will probably resume 2 meals per day in a 6 hour window in the future for maintenance.

hhhhmmmm, im sure the government nutrition guidelines of eating 3 meals per day must be causing more harm than good.

high CHO vs high FAT dieting

I stumbled across this old paper ( 1964 ) recently, sometimes these old papers can be real gems because the scientists of old were probably less influenced by bias, political correctness, and corporate/financial motivation. I dont have access to the full paper which is a shame, so im left with decrypting the abstract. BEWARE! He talks about mice again. Extrapolate to humans at your own risk!

The rate of weight loss in mice produced by restricting calorie intake below normal requirements is influenced by the type of food predominating in the diet; fat producing a rapid loss and carbohydrate a slower one.

I.E. a calorie is a calorie.

oh wait..

The amount of weight loss in both instances can be accounted for almost entirely by the extent of the negative carbon balances.

This is just basic common sense. To lose weight, you must expelle more carbon atoms than you ingest.

The varying rates of weight loss are due to differences in the rate of fat loss and not to changes in total body water.

Dont listen to this guy!, common knowledge is right, you only lose water on atkins diet!

In mice on a normal diet and in carbon equilibrium, about half the carbon is excreted as CO₂ and half in the form of organic molecules with an energy value of their own.

I.E. the body wastes calories. This is why its foolish to talk about energy balance and calories in calories out, it only makes sense to talk about carbon balance.

With restricted calorie high carbohydrate diets the proportion excreted as CO₂ rises to over 80 per cent of the total while the proportion excreted in the form of complex molecules falls.

What this basically says is that on a low calorie high carb diet, your body becomes EXTREMELY efficient, and most nearly all carbon atoms are completely oxidated to CO2 before being expelled from the body. Being efficient is not something you want if your to trying to reduce something. ( fat mass )

With restricted calorie high fat diets the proportion excreted as CO₂ remains normal. The half excreted as complex organic moleceules is significantly altered as to its distribution between feces and urine.

Now this is a tricky statement to dissect without the full paper. We know that ketones are excreted in breath and urine on a ketogenic diet, but whats this stuff about feces excretion of carbon atoms? Can you shit out calories? Maybe it only happens if your a mouse?

With restricted calorie feeding the proportion of food and/or tissue totally degraded to CO₂ influences the amount of energy available to the organism.

I would re-word this to "with restricted nutrient feeding". Total calories consumed are not so as important as amount of carb/protein/fat consumed. Things make more sense when you consider the next statement....

The demands on its own fat stores are consequently greater when fat is the major constituent of such a diet.

Again the way I would look at this is that, "the demand on fat stores is greater when protein and carbs are only very small parts of the diet". It does seem to me that researchers are hesitant to admit when the calories in calories out model fails to predict something. Remember the monkey study where the researchers lost some calories?

This next paper is a good example of that.....

The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets.

We have recently reported that obese women randomized to a low-carbohydrate diet lost more than twice as much weight as those following a low-fat diet over 6 months.

All lies, a calorie is a calorie.

The difference in weight loss was not explained by differences in energy intake because women on the two diets reported similar daily energy consumption.

Remember we are scientists! And calories in calories out is a universal truth and law! it must be obeyed at all time! If the groups had the same energy intake, the low-carb group must of had higher energy expenditure!!!!

We hypothesized that chronic ingestion of a low-carbohydrate diet increases energy expenditure relative to a low-fat diet and that this accounts for the differential weight loss.

Yuh, because, calories dont vanish.

So anyway, after this the scientists measure various energy expenditures including basal metabolic rate ( which we have already seen does not predict adiposity ), thermic food affect, and physical activity. The researchers had this to say next....

Mean REE in the two groups was comparable at baseline, decreased with weight loss, and did not differ at 2 or 4 months. The low-fat meal caused a greater 5-h increase in TEF than did the low-carbohydrate meal . Estimates of physical activity were stable in the dieters during the study and did not differ between groups.

OK, OK, that can ONLY mean one thing!, food intake was the same, energy expenditure was similiar, so that means.......................................drum roll

The differential weight loss is not explained by differences in REE, TEF, or physical activity and likely reflects underreporting of food consumption by the low-fat dieters.

I.E. fat people are fucking liars!!!!

Intermittent Fasting and Diurnal Cortisol

A new study that is the buzz in the media is about how restricting feeding to an 8 hour window ( during the afternoon-night phase ) prevents the progression of obesity on a diet that otherwise induces obesity in the same rodents if they are given Ad Lib access to the same food around the clock.

The intermittent fasting rodents consumed the same number of calories as the Ad Lib fed rodents yet remained much more slim. So yes, this proves a calorie is a calorie btw. /sarcasm

This has come at a time that I was thinking about something mentioned on itsthewooo's blog in the comments about diurnal cortisol. Actually, cortisol essentially makes you quite glucose intolerant, ( like melatonin ), and induces insulin resistance, so it is most likely not a good time to eat food when cortisol is high, like first thing in the morning or immediately after exercise.

This is the daily graph of diurnal cortisol for a normal healthy person. It might be slightly different for an obese person, but it quite clearly highlights the problem with eating food immediately after waking up, especially sugary cereal. You should ideally only be eating when cortisol is low, that means during the late afternoon and evening. Could this be one of the reasons that helped the rodents in the IF study above resist obesity? ( maybe not, since rodents are nocturnal animals by nature, it makes sense for them only to be eating during the night. )

Why are obese people starving?

Why do obese people display symptoms of starvation? ( increased hunger, increased food intake, decreased locomotor activity, decreased fertility )

Clearly something is amiss, If Joe has 5 million dollar's in his bank account, would you expect him to display behaviour of poverty? Ofcourse not, if he did display such behaviour, you would think that either he was mentally impaired ( read: low "will power" in the case of obesity ) , or , that there was some kind of catch, some kind of key missing information that you wasn't aware of.

Like maybe, the bank has a daily withdrawal limit on Joe's account of, lets say, 5 dollars.

Bingo!

Suddenly it becomes obvious why Joe is behaving the way he is. Although he has loads of money in the bank, there are rules and regulations in place that only allow him to use $150 dollars per month. Thats poverty!

In a similar fashion, it is probably a mystery as to why obese people display starvation symptoms, until you measure their AgRP levels that is. ( 1 ) Obese people have increased levels of this protein, which is a potent orexin. So just like Joe, who is in poverty because the bank is blocking access to his money, obese people are starving because the AgRP is blocking access to their energy expenditure.

BTW, AgRP is also increased in anorexia nervosa ( 2 ), so increased levels of AgRP is a sign of starvation and emaciation.

OK, so just how potent is AgRP anyway?

Actually, there is evidence that AgRP rivals that of leptin in potency. ( 3 ) We all know the ob/ob mouse, it is one that does not produce any leptin, and thus its body *thinks* that it is starving and has like zero fat mass. But what happens if you take an ob/ob mouse and also destroy its AgRP neurons???

It turns into a normal mouse!!!!! Its bodyweight becomes normal like wild-type mice and its fertility is returned to normal. Wow! So what does this mean, does leptin work by AgRP?

Well no, not quite, as destruction of leptin receptors in AgRP neurons produces no discernible change in phenotype, but all this really means is that leptin doesnt work to directly influence AgRP itself, and that it is more likely their paths cross further down the metabolic highway.

Here are some configurations to think about.......

normal AgRP + normal leptin = normal
normal AgRP + no leptin = obesity
no AgRP + no leptin = normal*
no AgRP + normal leptin = death ( through starvation and hypothermia )

*There appears to be a point of no return, as severely obese and older ob/ob mice that have thier AgRP neurons destroyed do not survive and die of hypothermia. This can be resolved by injection of norepinephrine, indeed, sympathetic nervous system outflow from the brain regulates lipolysis and body temperature via norepinephrine action on fat cells.

Remember that the primary function of AgRP is to block the MC4R. And as we saw in the previous post, activation of MC4R is required for weight loss. This implies that part of achieving successful weight loss is a reduction in AgRP.

Even metformin may work by reducing AgRP ( 4 ). The only question that remains is, what is the exact function of leptin? Clearly it is intimately involved in fertility, but what is the exact mechanism and pathway?!

Ketones do suppress appetite!

Just a quick post, everyone knows ketones suppress appetite, but whats the mechanism? A recent paper has helped shed some light on the mechanics, at physiological blood glucose concentrations of 5.5mM the ketone β-hydroxybutyric suppresses the agouti-related peptide which is a hunger hormone that also blocks the MC4R.

The researchers also tested 25mM and found β-hydroxybutyric increases agouti-related peptide! However I have to ask, what the fuck is the point of that? A blood glucose concentration of 25mM is not exactly possible in vivo is it?

β-hydroxybutyric seems to do this by reducing hypothalamic AMPK. Thats good, because the evidence seems to be that high levels of hypothalamic AMPK put you starvation mode. ( orexigenesis ).

In related research, it seems that MC4R is downstream of both leptin and GLP-1, they work together to act on POMC to produce α-melanocortin stimulating hormone which binds MC4R. Then, binding of MC4R reduces hypothalamic AMPK!

You see, its all connected, love it when a plan comes together. This proves there is more to the ketogenic diet than simply the "satiating power" of protein.

In other news, It seems I was ( kind of ) right about the importance of MC4R, as it is required for weight loss.

Anyway, thanks for coming, you can all go home now.

Fat tissue growth drives over-eating

NOT the other way around.

This is why Taubes is smarter than those who ridicule him. He understands the logic, and has the cause and affect the correct way around. Unlike people such as Guyenet, who think that the obesity epidemic is caused by our average increase in calorie consumption of ~400 per day. What makes Guyenet so sure he has his cause and affect the right way around? Maybe our average calorie intake has increased BECAUSE we are fatter, and maybe we are fatter BECAUSE our food is more insulinogenic than it has ever been.

Does an increase in salary ( income ) of $4000 encourage you to go to the bank and take out a loan? That doesnt make any sense does it? If were getting paid more money, why would we need a loan from the bank?

Alternatively

What does taking out a loan from the bank do? It encourages us to ask our boss for a $4000 increase in salary to help us make the monthly payments on said loan.

The increase in debt ( fat tissue ) causes us to seek increased income ( food intake )

This gets all the more serious when you realise that taking on a loan as debt creates an obligation, you are obligated to repay it. Fat tissue is the same, when new fat tissue grows, you are obligated to maintain it, fat cells do not like to be atrophied.

The monkey study also offers very good evidence for my argument. They administered drugs to obese monkeys that caused apoptosis in their fat tissue, the result was a DECREASE in food intake and probably also an INCREASE in energy expenditure. ( as spoken of in the rodent study )

If gluttony and sloth was the driver of obesity, you would of expected these monkeys to continue their old eating habits. Right? Afterall, they were fat because they were gluttons, right??, and surely melting off some of their fat tissue shouldn't change their lack of "will power" to stop themselves over-eating, should it?

BTW, the researchers in that study appear to have violated the first law of thermodynamics and made some calories vanish. If you destroy a bunch of fat cells by apoptosis, all that fat they are carrying has to go somewhere, right?

Given the rapid loss of adipose tissue over a short period of time, one might have expected an abnormal increase in serum-free fatty acids and possibly dyslipidemia because of rapid fat mobilization. Surprisingly, free fatty acid concentrations showed a decreasing trend throughout the treatment interval

Damn, where the fuck did those calories go??!?

With the rapid reduction in white adipose tissue observed, the possibility of abnormal fecal elimination of lipids was considered.

Maybe the monkeys shit them out?! Usually when you take orlistat the side affects are quite apparent, they include

oily stools, flatulence, fecal incontinence, and diarrhea.

OK, I got a plan, lets see what kind of mess the monkeys leave when they go to bog room.....

the absence of these side effects was considered inconsistent with increased fecal elimination of lipids

Damn! (In other words, the researchers have no idea where the calories went. They lost em. Lesson learnt, Never trust a medical researcher with your calories!)

Your fat cells know things that you do not

This study may or may not be much of a surprise to some people. Basically, they overfed normal healthy people and used tracers to find out where the dietary fat was stored after the meal.

The question the researchers sought to resolve was, does post-meal fat storage predict where the increase in adiposity will occur in the future?

According to the researchers, that is answer NO ( damnit! )

If you store alot of post-meal fat in your belly, theres no garauntee it will be there next week, or even tomorrow. This flies in the face of the calories argument, because it suggests that regardless of what you eat, each of your fat cells have thier own agenda as to how big or small they prefer to be.

Indeed, This next study builds on that theory. The paper is a review describing the infrastructure of adipose tissue. It talks about how long term over-feeding upregulates genes involved with angiogenesis, extracellular matrix deposition, i.e. when your fat cells see they are being forced to store larger amounts of fat for extended periods, they modify themselves to increase vasculature. Think of it like a tree growing. As the tree grows, it also increases its underground root network in size.

There are important implications for people looking to reduce fat mass discussed aswell. Short-term reductions in fat mass do not appear to reduce adipose tissue vasculature, but, it was reported that long-term reductions in fat mass did modulate genes involved with extracellular matrix deposition and cell death at >=33weeks. ( 1 ).

This suggests that a fat reduced state must be maintained for an extended period such to as allow for significant changes in adipose tissue vasculature to occur that favour maintanence of the new reduced size. This makes sense because short-term reductions in fat mass usually only involves reductions in the lipid droplet size in the adipocyte, this probably makes the adipocyte freak out and throw trantrums like a baby ( probably by refusing to make leptin ) and thus create an environment that favors fat storage.

Shrinking the fat cell's lipid droplet is not enough, one must also reduce its vasculature, and perhaps even kill it off completely ( apoptosis ).

Infact, going a step above leptin, the paper has a short mention at how drugs that reduce angiogenesis are able to reduce fat mass in leptin deficient mice that is "on par" with leptin administration itself!

The paper speculates that angiogenic-derived signals in adipose tissue may modify hunger and satiety, this is because reductions in fat mass produced from angiogenesis inhibiting drugs reduce food intake despite reductions in leptin and hypothalamic neuropeptides that modify bodyweight. Could adipose tissue vasculature be downstream of leptin signalling? As in, hypothalamic leptin signalling inhibits adipose tissue vasculature, while lack of hypothalamic leptin signalling promotes adipose tissue vasculature?

Don't forget we have atleast one study showing how leptin injections in the brain cause fat cell death by apoptosis. Sounds a bit convenient to me...... And lets not forget our old friend insulin, AKA insulin injection sites in type 1 diabetics cause localised fat tissue hypertrophy. I can only wonder if angiogenesis is downstream of insulin signalling in fat cells aswell.

It is clear that over a more prolonged period the supportive structures (vascular and extracellular membrane) needed to maintain adipose tissue expansion begin to predominate. This is accompanied by down-regulation of apparent nutrient-sensing pathways that are the permissive to this tissue expansion.