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I have compiled a mix of biological, physiology information, articles and studies etc that will hopefully give everyone an understanding on the body's digestion processes, maconutrient functions and insulin responses and some other useful facts.

That in turn will clear up the myths of needing to eat 6 meals a day every 3 hours for metabolic function and 'keeping protein up', that identical macronutients/ calories from your typical 'clean' and 'dirty' are the SAME (Yes micronutrients - vitamins and minerals - content will vary but that is not the point of this) and that the GI of carbohydrates and the typical thoughts on their insulin response is of little meaning once a mix of multiple macronutrients is added.

Please note that how your body reacts in a 'fed' state (with food) compared to a 'fast' state (without food) is different. Many of the typically 'bodybuilding' and 'broscience' protocols, that as a few people tend to promote as being 'done for 20,30 or even 40 years and that is why it works' , are and have been based on either lack of understanding of the digestive system as well as focusing on studies that have been done after a fasting period and or a fasting period followed by exercise.

To expand on that more, when a Fast (usually 24 hours) is done, our metabolic rate actually INCREASES, see link to studies -

Enhanced thermogenic response to epinephrine after... [Am J Physiol. 1990] - PubMed result

Resting energy expenditure in short-term starvatio... [Am J Clin Nutr. 2000] - PubMed result

Our metabolic rate does not DROP until between the 60-92 hour mark. See link to study -

Leucine, glucose, and energy metabolism after 3 da... [Am J Clin Nutr. 1987] - PubMed result

As you will read, you should be able to see why due to the digestion process why we are continuously in a 'fed' state and how all the 'myths' simple hold no bearing and are of no relevance. Most times the only real application some of the typical 'bodybuilding' protocols are if you have completed a 'fast' and then going to train or have a number of back to back events in the same day.

Before moving on to the info, I must say that if you want to eat 6 times a day and every 3 hours, YOU CAN but YOU DON'T NEED TO. If you want to eat 'clean', YOU CAN but YOU DON'T NEED TO. If you want to go by the GI, YOU CAN but YOU DON'T NEEDED TO. This is merely for the understanding that for body composition, those sorts of minor details and protocols DO NOT determine what your BODY COMPOSITION is/ will be.
How long does it take food to digest - Overview

Food digestion varies depending upon the type of food. I will break down the process into its steps and provide a timeline for each step.

First we see the food. This stimulates our brain to ready our stomach to receive food, by increasing gastric secretions. Then, we eat the food. Amylase is a digestive enzyme in our saliva that helps to break down carbohydrates. Mechanical manipulation by chewing breaks the food into smaller pieces which provide more surface area. This increased surface area helps the enzymes in the small intestine absorb the nutrients in our food better. This is why it is important to chew your food well. Next, we swallow and food arrives at the stomach.

The stomach is responsible for further mechanical breakdown of food and some chemical breakdown. Proteins are broken down by pepsinogen into peptide chains and fat is broken by gastric lipase (to help you navigate through these terms, any word with “ase” at the end generally denotes an enzyme responsible for some kind of digestion). When food has been through the stomach, it becomes chyme; an acidic mixture of hydrochloric acid from our stomach, pepsinogen, lipase and amylase. The entrance to the small intestine from the stomach is controlled by the pyloric sphincter; a controlled doorway that prevents too much chyme from entering the small intestine at once.

The duodenum is the first part of the small intestine. The duodenum’s job is to neutralize the acidic chyme before allowing it to continue through the rest of the small intestine by way of bicarbonate from pancreatic juice. The food then enters the jejunum, the part of the small intestine that is responsible for the majority of nutrient absorption. Fat, peptides and carbohydrates are further broken down by enzymes into units that are small enough to be transferred in the bloodstream to the target organs. The primary fuel the body needs to run properly is glucose; so much of the food is broken down and recombined into glucose.

At this point, the food has spent between 30 minutes and 2 hours in the stomach and between 2 and 6 hours in the small intestine and 90% of the nutrients have been extracted. The left over material has lots of water and sodium left in it. The body wants to reclaim these substances before defecation; food takes 72 hours to be processed in the large intestine. The jobs of the large intestine are to reclaim the water from the food, reclaim the sodium from the food, and provide healthy bacteria to ferment fiber that has not been digested. This fermentation provides nutrients to keep the cells in the large intestines healthy. Fiber that has not been digested adds bulk to the waste products to facilitate elimination.
Fates of Ingested Nutrients: Oxidation or Storage

So what happens after nutrients get through the stomach and intestines and into the body? Broadly speaking, there are two primary fates for nutrients at this point which are oxidation or storage. A third that I should at least mention is that, under certain conditions, nutrients will sort of ’sit’ in the bloodstream either causing problems there or eventually being excreted in the urine. Outside of various pathophysiologies (e.g. runaway diabetes where glucose is lost in the urine in large amounts), the urine excretion route is generally minimal approaching insignificant and I won’t focus on it further here.

Oxidation simply refers to the direct burning of fuels for energy. This can occur in the liver, skeletal muscle and a few others places and all 4 macronutrients can strictly speaking undergo oxidation after ingestion. So fatty acids from dietary fat ingestion can be used to produce energy, carbohydrate can be burned off, a little appreciated fact is that under normal circumstances as much as half of all dietary protein ingested gets metabolized in the liver via a process called deamination with some of it simply being burned off for energy.

Storage should be fairly clear and the nutrients (with the exception of alcohol) can be ’stored’ in the body for later use. Carbohydrates can be stored as liver or muscle glycogen, under rare circumstances they are converted to and stored as fat. Dietary fat is stored either in fat cells or can be stored within muscle as intra-muscular triglyceride (IMTG). Under certain pathological conditions, fat gets stored in places it’s not supposed to go, a situation called ectopic fat storage. In a very real sense there’s no true store of dietary protein although amino acids from protein digestion are used to make various proteins and hormones in the body. Skeletal muscle is, in essence, a ’store’ of protein in the body.

As it turns out, the size of a nutrient’s store in the body is inversely related to the body’s propensity to oxidize it after ingestion. This is especially true in terms of the size of the store relative to the amount consumed on a daily basis.

Put a little more clearly, the better the body’s ability to store a given nutrient, the less it tends to alter/increase oxidize that nutrient after ingestion. And vice versa, the smaller the store in the body of a given nutrient relative to intake levels, the more likely the body is to oxidize that nutrient after ingestion.

The body’s total protein stores (and note again that this isn’t a true store in the sense of body fat and glycogen) is maybe 10-15kg or so when you add it all up. Which is pretty high compared to an average daily intake. The ‘RDI’ for protein is only about 50-60 grams per day for the average person and even people eating 200-300 grams per day are still eating far less protein than stored. Which is why protein oxidation rates can change with intake.

As mentioned above, an under-appreciated fact is that about half of all ingested dietary protein is metabolized in the liver. Some of it is oxidized for energy while others are converted into other things (including glucose and ketones) for use elsewhere. But, protein oxidation rates do change in response to intake. So, when protein intake goes up, oxidation will increase; when protein intake goes down, oxidation rates decrease. This change isn’t immediate (as it more or less is for carbohydrates) and takes 3-9 days to occur but mis-understanding of this process has led to some goofy ideas such as protein cycling.

It also explains one other issue of importance to protein which has to do with speed of digestion. Early studies, including the oft-cited study on whey and casein by Boirie find that fast proteins are burned off for energy to a greater degree than slower digesting proteins. Since the body doesn’t have anywhere to store the rapidly incoming amino acids, it simply burns off more for energy. This, along with differences in handling e.g. the fact that fast proteins are absorbed by the gut are a big part of why slower digesting proteins invariably lead to better overall protein retention in the body; not only does more make it into the bloodstream but less is burned for fuel.
Protein Digestion

Protein hits the stomach where digestion and breakdown occurs via hydrochloric acid and the enzyme pepsinogen.

The majority of protein digestion occurs in the small intestine where protein is broken down into smaller and smaller amino acid (AA, the building blocks of protein) chains via a variety of protein digesting enzymes. You can think of proteins as being a long chain of the AAs, the enzymes basically act like scissors, cutting the chains into smaller and smaller bits.
Prior to absorption into the bloodstream, whole proteins have been broken down to provide single AAs along with two and three AA chains (called di- and tri-peptides); further breakdown occurs in the intestinal cells themselves, finally releasing individual amino acids into the bloodstream.

Generally speaking, AA chains larger than three in length will not be absorbed to any appreciable degree. Note that occasionally very small amounts of longer amino acid chains can slip through and this is especially the case in situations like leaky gut syndrome where the normal functioning of the gut has been compromised.

This is actually a very bad thing as the body tends to launch immune/allergic responses to the presence of undigested protein in the bloodstream; which is a big part of why the gut is set up to not allow larger protein chains into the bloodstream under normal circumstances.

Related to this is a recurrent idea, usually in sports nutrition, of supplements containing protein based hormones such as Growth Hormone (GH), Insulin-Like Growth Factor 1 (IGF-1) or others being orally consumed. This can’t work due to the way human digestion of protein works, such peptide hormones will simply be digested in the gut and lose their biological availability.

Put this a different way: major pharmaceutical companies have been trying to make an oral insulin (another protein based hormone) for diabetic treatment and have basically given up on it; it took weirdly functioning drugs and there were huge problems with implementation. If the big drug companies haven’t figured out how to do it, neither has the protein powder company claiming it in their ads.

Food Source Protein Digestibility (%)
Egg 97
Milk and Cheese 97
Mixed US Diet 96
Peanut Butter 95
Meat and Fish 94
Whole Wheat 86
Oatmeal 86
Soybeans 78
Rice 76
Source: National Research Council. Recommended Dietary Allowances, 10th ed. National Academy Press, 1989.

Speed of Digestion

One researcher collected what is available –

Protein Absorption Rate (g/hour)
Raw Egg Protein * 1.4
Cooked Egg Protein * 2.9
Pea Protein 3.5
Milk Protein 3.5
Soy Protein Isolate 3.9
Casein Isolate 6.1
Whey Isolate 8-10
Tenderloin Pork Steak * 10.0

* Measurements marked with an asterisk should be considered as the roughest estimates as the studies used indirect measurements of protein digestion.

Clearly there is a large variety for protein digestion rates although, as noted, some of the above values should be taken as very rough estimates.

Note again that this has some implication for the idea that you must eat protein every three hours. With the exception of whey, where 40 grams of protein would take roughly 4 hours for complete absorption), all proteins listed would still be digesting for far longer than the magic 3 hour period.

Most whole food proteins were on the slow end of the digestion scale. This actually makes perfect sense. Whole food proteins are generally contained within a matrix of connective tissue and such (e.g. think of the chewing that you have to put into eating meats such as beef, tuna, or chicken) and that alone will slow the process of digestion down.

Body fat stores are effectively unlimited as individuals reaching 1000 lbs (and 70-80% body fat) have demonstrated. Even a relatively lean male at 180 lbs and 12% body fat is carrying 21 pounds of fat. Each pound contains maybe 400 grams of actual stored fat and that means about 8500 grams of fat stored in the body. Contrast this to a relatively high daily intake of perhaps 100-150 grams per day and you can see that the body’s store of fat is much, much higher than what you eat on a day. And most people aren’t 12% body fat.

But for the most part, ingested dietary fat has little impact on fat burning in the body; that is, when you eat dietary fat, your body doesn’t increase fat oxidation. One exception is if an absolutely massive amount of fat (like 80 g) is consumed all at once but even then the effect is fairly mild. Some specific fats, notably medium chain triglycerides, are somewhat of an exception to this; they are oxidized in the liver directly. Rather, the primary controller of dietary fat oxidation in the body is how many carbohydrates you’re eating.

Fat Digestion

Fats and other lipids do not dissolve in water, instead they tend to congeal together and line the stomach. This separation from water within the stomach makes it much harder for the lipase enzymes to start the breakdown process. The liver is then forced to product bile which aides in the digestion process (by this time has passed into the small intestine where much of the digestion process occurs) as is both water and fat soluble. It can be over 4 hours for fat to pass through to final digestional process.

For carbohydrate, the body’s stores are relatively close to the daily intake. A normal non-carb loaded person may store 300-400 grams of muscle glycogen, another 50 or so of liver glyogen and 10 or so in the bloodstream as free glucose. So let’s say 350-450 grams of carbohydrate as a rough average.

For this reason, the body is extremely good at modulating carbohydrate oxidation to carbohydrate intake. Eat more carbs and you burn more carbs (you also store more glycogen); eat less carbs and you burn less carbs (and glycogen levels drop). This occurs for a variety of reasons including changing insulin levels (fructose, for example, since it doesn’t raise insulin, doesn’t increase carbohydrate oxidation) and simple substrate availability. And, as it turns out, fat oxidation is basically inversely related to carbohydrate oxidation.

So when you eat more carbs, you burn more carbs and burn less fat; eat less carbs and you burn less carbs and burn more fat. And don’t jump to the immediate conclusion that lowcarb diets are therefore superior for fat loss because lowcarb diets are also higher in fat intake (generally speaking). You’re burning more fat, but you’re also eating more.

Carbohydrate Digestion

All carbohydrates absorbed in the small intestine must be hydrolyzed to monosaccharides prior to absorption. The digestion of starch begins with the action of salivary alpha-amylase/ptylin, although their activity is slight in comparison with that made by pancreatic amylase in the small intestine. Amylase hydrolyzes starch to alpha-dextrin, which are then digested by gluco-amylase (alpha-dextrinases) to maltose and maltotriose. The products of digestion of alpha-amylase and alpha-dextrinase, along with dietary disaccharides are hydrolyzed to their corresponding monosaccharides by enzymes (maltase, isomaltase, sucrase and lactase) present in the brush border of small intestine. In the typical Western diet, digestion and absorption of carbohydrates is fast and takes place usually in the upper small intestine. However, when the diet contains carbohydrates not easily digestible, digestion and absorption take place mainly in the ileal portion of the intestine.
Continue the digestion of food while their simplest elements are absorbed. The absorption of most of digested food occurs in the small intestine through the brush border of the epithelium covering the villi. Carbohydrates that are not digested in the small intestine, including resistant starch foods such as potatoes, beans, oats, wheat flour, as well as several non-polisacacáridos oligosaccharides and starch, are digested in a variable when they reach the large intestine.

Fibre slows gastric emptying because Soluble fibers tend to form a gel-like substance in liquids and one consequence of a high soluble fiber intake is that gastric emptying (the rate at which foods empty the stomach) is slowed when they are eaten. Basically, they cause the chyme (the partially digested nutrients in the gut) to form this big gel which empties the stomach more slowly. This, along with the physical stretching of the stomach tends to keep people fuller in the longer term because the food stays in the gut longer.


All forms of carbohydrate must be metabolized into sugar or glucose for cellular energy. Sugar is the easiest of the macronutrients to digest. When mixed with other macronutrient that are slower in digesting, the enzymes production is slower causing the sugars to sit in the stomach and ferment while the ‘slower’ digesting macronutrients start to move out of the stomach.
Glycemic index

Many bodybuilders follow the gylcemic index (GI) religously, and they shouldn't! Why so? Well, the GI is based on eating carbohydrates on an empty stomach without the addition of protein, lipids, fiber, water, etc. Therefore, it obviously has it's shortcomings and is not the be all end all choice for chosing our carbohydrate sources. Truth is, it's quite irrelevant when it comes to bodybuilding purposes. Let's take white potatoes for example. This food species is often avoided mainly because of it's high GI rank. Foolish. White potatoes are a very nutritious food and should be incorporated in a sound nutrition program. See, we're already spotting shortcomings challenging the elements and principles of the GI. But wait, there's more. The GI of that white potato can be drastically altered by combining it with the addition of protein, lipds, fiber, and other carbohydrates. In conclusion, the GI should not be followed religiously by bodybuilders and nutrient-density should be the main principle in one's nutrition plan, not the GI.
Glycemic index studys and review of study by lyle mcdonald

Hormonal Responses to a Fast-Food Meal Compared with Nutritionally Comparable Meals of Different Composition – Research Review
Title and Abstract
Bray GA et. al. Hormonal Responses to a Fast-Food Meal Compared with Nutritionally Comparable Meals of Different Composition. Ann Nutr Metab. 2007 May 29;51(2):163-171 [Epub ahead of print]


Fast food is consumed in large quantities each day. Whether there are differences in the acute metabolic response to these meals as compared to ‘healthy’ meals with similar composition is unknown. Design: Three-way crossover. Methods: Six overweight men were given a standard breakfast at 8:00 a.m. on each of 3 occasions, followed by 1 of 3 lunches at noon. The 3 lunches included: (1) a fast-food meal consisting of a burger, French fries and root beer sweetened with high fructose corn syrup; (2) an organic beef meal prepared with organic foods and a root beer containing sucrose, and (3) a turkey meal consisting of a turkey sandwich and granola made with organic foods and an organic orange juice. Glucose, insulin, free fatty acids, ghrelin, leptin, triglycerides, LDL-cholesterol and HDL-cholesterol were measured at 30-min intervals over 6 h. Salivary cortisol was measured after lunch. Results: Total fat, protein and energy content were similar in the 3 meals, but the fatty acid content differed. The fast-food meal had more myristic (C14:0), palmitic (C16:0), stearic (C18:0) and trans fatty acids (C18:1) than the other 2 meals. The pattern of nutrient and hormonal response was similar for a given subject to each of the 3 meals. The only statistically significant acute difference observed was a decrease in the AUC of LDL cholesterol after the organic beef meal relative to that for the other two meals. Other metabolic responses were not different. Conclusion: LDL-cholesterol decreased more with the organic beef meal which had lesser amounts of saturated and trans fatty acids than in the fast-food beef meal.

LYLE’s Comments

For a couple of decades, there has been an ongoing argument regarding the issue of ‘is a calorie a calorie’ in terms of changes on body composition and other parameters.

Fundamentally, my belief is that, given identical macro-nutrient intakes (in terms of protein, carbs, and fats) that there is going to be little difference in terms of bodily response to a given meal. There may be small differences mind you (and of course research supports that) but, overall, they are not large. And certainly not of the magnitude that many make it sound like.
It’s worth nothing that there are a couple of built-in assumptions to my argument, all of which are detailed in the article I linked to above but I want to briefly reiterate them here.

A tediously typical argument of the ‘a calorie isn’t a calorie’ types is usually something along the lines of “Clearly eating 3000 calories of jelly beans isn’t the same as eating 3000 calories of chicken breast and vegetables.” Well…no shit.

But at that point, the argument is about more than food quality, it’s also about the macro-nutrient content. And of course the diet containing zero protein will be bad. But, again that has zip to do with it being clean and everything to do with there being no protein.

My basic assumptions in this argument are that both protein and essential fatty acid requirements are being met. Beyond that, I find most of the obsession over food quality to be pretty pointless.

Clearly, someone eating a 2000 calorie fast food meal will obviously get a different response than someone eating a 500 or even 1000 calorie clean meal. But as with the argument above, at this point there is more than one variable changing; it’s not just about clean vs. unclean, you’re comparing meals of drastically different caloric value.

A far more logical comparison would be to look at ‘unclean’ vs ‘clean’ meals containing the same caloric value and the same macro-nutrient content; by controlling those two variables, the only thing being examined will be the quality of the food (rather than the total quantity or the macro-nutrient profile).

Especially when you’re talking about bodybuilders and athletes who are typically controlling their caloric content. Under those conditions, I argue that there will be no significant difference between the two; given identical macros and calories, there is simply no real-world difference in a clean vs. unclean meal in terms of its effects on body composition (health and other effects such as hunger control are separate, albeit important, issues).
However, even there the clean freaks will make the counter-argument: they contend that even if the macros and calories are identical, the unclean meal will still be worse. This is usually based on an assumed difference in hormonal response (usually insulin).

So who’s right? Unfortunately, very little research has actually examined this topic in any sort of controlled way (there are at least two studies showing that high sucrose diets generate identical weight and fat losses as lower sucrose diets). At least until this paper came along

The study’s explicit goal was to see if the metabolic response to a fast-food meal would differ to a ‘healthy’ meal of similar macro-nutrient and caloric value.

Towards this end six overweight men and two women were recruited to take part in the study although the data in the women was excluded due to the low number and possible gender effects.

Each subject consumed each of the three test meals on different days with one week in between trials. A standard breakfast was provided at 8am and the test meal was given at exactly 12pm and blood samples were taken every 30 minutes for the first 4 hours and every 60 minutes for the next two hours. Blood glucose, blood lipids, insulin, leptin, ghrelin and free fatty acids were measured.

The test meals consisted of the following:.
 Fast food meal: A Big Mac, french fries and root beer sweetened with high fructose corn syrup purchased at the restaurant itself.
 Organic beef meal: this meal used certified organic rangefed ground beef; cheddar cheese; hamburger bun made with unbleached all purpose naturally white flour, non-iodized salt, non-fat powdered milk, natural yeast, canola oil, and granulated sugar; sauce made from canola mayonnaise and organic ketchup; organic lettuce, onion and dill pickles; French fries made from organic potatoes and fried in pure pressed canola oil; and root beer made with cane sugar.
 Organic turkey meal: this consisted of a turkey sandwich made from sliced, roasted free-range turkey breast with no antibiotics or artificial growth stimulants; cheddar cheese; 60% whole wheat bread made with whole wheat and unbleached all-purpose naturally white flours, non-iodized salt, non-fat powdered milk, yeast, vital wheat gluten, canola oil, and granulated sugar; pure pressed canola oil and canola mayonnaise, stone ground mustard; organic lettuce; accompanied by a granola made with Blue Diamond whole natural almonds, Nature’s path organic multigrain oatbrain flakes, wholesome sweeteners evaporated cane juice, Spectrum Naturals pure pressed canola oil, clover honey, Sonoma organically grown raisins and dried apples. The beverage was an organic orange juice.

So the study was comparing a commercial fast food meal to two carefully designed organic meals (one beef, one turkey) from the above list of ingredients.
The composition of each meal was as follows:

Meal Calories Protein Carbs Fat
Fast Food 1044 28.2 151 53
Organic Beef 1154 28 163 60.2
Organic Turkey 1260 34 170 49

It’s important to note that while the meals were similar, they were not identical in composition; it would have been better if the meals had been completely identical.
The biggest difference between meals had to do with the fatty acid composition: the fast food meal contained twice as much saturated and nearly 8 times as much trans-fatty acids with half of the oleic acid compared to the organic beef meal (which is no surprise). Interestingly, the fast food meal actually contained more linoleic acid than the organic beef meal. The turkey meal had less saturated fat but similar amounts of linoleic and linolenic acid to the fast food meal, with the lowest amount of trans fats.

So what happened? In terms of the blood glucose and insulin response, no difference was seen between any of the meals and this is true whether the data was presented in terms of percentage or absolute change from baseline. The same held true for the ratio of insulin/glucose, no change was seen between any of the meals. Please read those sentences again: the blood glucose and insulin response were identical for all three meals despite one being a fast food ‘unclean’ meal and the other two being organic ‘clean’ meals.

Fatty acid levels showed slight differences, dropping rapidly and then returning to baseline by 5 hours in the beef meals but 6 hours in the turkey meal. Blood triglyceride levels reached a slightly higher peak in the organic beef and turkey meals compared to the fast food meal but this wasn’t significant.

Changes in leptin were not significant between groups; ghrelin was suppressed equally after all three meals but rose above baseline 5 hours after the fast-food lunch but returned only to baseline in the other two meals.

The only significant difference found in the study was that LDL cholesterol decreased more after both of the organic meals compared to the fast food meal, HDL and total cholesterol showed no change after any of the meals. This was thought to be due to differences in the fatty acid content of the meals (saturated fat typically having a greater negative impact on blood lipid levels than other types of fat).

However, beyond that, there were no differences seen in the response of blood glucose, insulin, blood fatty acids or anything else measured.

Now, the study does have a few limitations that I want to mention explicitly.
1. The study only looked at a single meal. It’s entirely possible that a diet based completely around fast food would show different effects.
2. The sample size was small: 6 overweight men and two women. It’s possible that differences would have shown up with more subjects. A related question is whether lean individuals would respond differently. Perhaps but I doubt it. GI and insulin response are even less relevant in trained individuals.
3. However, with that said (along with the fact that the meals weren’t exactly identical), the basic fact is this: the metabolic response between the three meals was essentially identical. There were no differences in either insulin or blood glucose, the fatty acid profile makes perfect sense given the composition of the meals and blood lipids showed basically no change
Glycaemic Index Effects on Fuel Partitioning in Humans – Research Review
Title and Abstract
Diaz EO et. al. Glycaemic index effects on fuel partitioning in humans. Obes Rev. (2006) 7:219-26.
The purpose of this review was to examine the role of glycaemic index in fuel partitioning and body composition with emphasis on fat oxidation/storage in humans. This relationship is based on the hypothesis postulating that a higher serum glucose and insulin response induced by high-glycaemic carbohydrates promotes lower fat oxidation and higher fat storage in comparison with low-glycaemic carbohydrates. Thus, high-glycaemic index meals could contribute to the maintenance of excess weight in obese individuals and/or predispose obesity-prone subjects to weight gain. Several studies comparing the effects of meals with contrasting glycaemic carbohydrates for hours, days or weeks have failed to demonstrate any differential effect on fuel partitioning when either substrate oxidation or body composition measurements were performed. Apparently, the glycaemic index-induced serum insulin differences are not sufficient in magnitude and/or duration to modify fuel oxidation.


The glycemic index (GI) of foods is yet another place where endless argument and debate exists in the world of nutrition, especially as it applies to body composition.

In the early days of nutrition, as many may recall, carbohydrates were rather simplistically divided into simple and complex sources with the even simpler belief that ’simple = bad’ and ‘complex = good’. While this was applied to general health and such, one of the major applications and concerns over carbohydrate intake had to do with diabetic meal planning.
When it became clear that simple vs. complex was insufficient, researchers went looking for more accurate methods of measuring the differences between carbohydrates. Sometime in the 80’s, the GI was born.

Conceptually, the GI refers to the blood glucose response to a given carbohydrate food. A little more technically, the GI of a food relates to the area under the curve (AUC for nerdy types) of blood glucose versus time after the ingestion of a fixed amount of a test food.

Researchers would first test a fixed amount (currently 50 grams digestible carbohydrate) of some standard food, they originally used pure glucose but switched to white bread years later. The blood glucose response to that standard food was defined as having a GI value of 100. I want to make it clear that this value has no inherent meaning, it was simply a defined value.
Then other foods were tested, again 50 grams of digestible carbohydrate (perhaps baked potato or cereal) were given by itself after an overnight fast and the blood glucose response was measured. The GI of that food was then defined relative to the 100 value of the test standard. So a GI of 80 meant that the test food had 80% of the blood glucose response of the test food; a GI of 120 means that it had 120% the blood glucose response of the test food. Again, keep in mind that these values don’t really ‘mean’ anything, they are just relative value.

In any case, from the standpoint of diabetic meal planning, the GI seemed important as it would let diabetics decide which foods would have the best effect on blood glucose levels without causing problems. Of course, for a variety of reasons, the GI concept was also adopted by athletes and the physique obsessed.

I’d note that there is much more to the GI than I have space to go into here, I’ll be writing a full article on it soon enough. Sufficed to say that GI becomes much more complicated when you start mixing foods together, or the person isn’t fasted (e.g. you’ve eaten a meal). Even the aerobic training status of a person modifies the GI as I detail in the research review The Influence of the Subject’s Training State on the Glycemic Index.
In any event, the big argument over the GI of foods at least with regards to body composition usually involves the insulin response and potential impact on things like fat mass and fuel utilization. It was usually inferred that a higher GI value (remember, larger and/or longer blood glucose response) meant a bigger insulin response and for the physique obsesses, insulin equals badness.

I’d note that things aren’t this simple and at least one study suggests that foods with a lower GI may have a lower GI because of a LARGER initial insulin response as detailed in Different Glycemic Indexes of Breakfast Cereals Are Not Due to Glucose Entry into Blood but to Glucose Removal by Tissue.

The Paper

But I’m getting off topic. What today’s paper looks at is the idea of whether differences in the insulin response (from foods differing in GI) actually have meaningful differences in terms of their effect on insulin, fuel utilization or body composition.

Because that’s the real issue: there’s no debate that foods differing in GI generate different blood glucose responses, there is indication that this impacts on the insulin response. But the bottom line question is whether those differences in hormonal response actually meaningfully affect anything.

In looking at the topic, the researchers examined a variety of different data sets including more acute studies along with those looking at actual changes in body composition.

The short-, mid- and long-term studies typically examined things like blood glucose, insulin, blood fatty acid levels, carb and fat oxidation and/or energy expenditure over periods ranging from 6-24 hours (or longer) after the ingestion of foods or meals differing in GI. I’m not going to detail each and every one but, with one or two exceptions, the majority simply found no significant difference in things like fatty acid suppression or fuel oxidation despite significant differences in blood glucose and insulin response. Even longer term intervention studies of 30 days to 10 weeks found no significant impact on weight or body composition for diets designed with different GI levels.

So in terms of data directly examining the topic, the researchers comment that:
High fasting serum insulin concentration or high first-phase serum insulin response to intravenous glucose has been proposed as a risk factor for weight gain.This may have led Ludwig to state that ‘functional hyperinsulinemia associated with high-GI diets ma promote weight gain by preferentially directing nutrients away from oxidation in muscle and towards storage in fat’. Evidence for this hypothesis is still lacking since no effects of GI on fuel partitioning have been demonstrated to date.

Of course, there are studies suggesting that lower GI diets generate more weight loss than higher GI but there are often subtle confounds including the fact that typically GI is not the only difference between diets. Often, with changes in the GI come differences in fiber intake, energy density of the diet, at least one study I can think of changed protein intake between groups. So concluding that the GI per se is having an impact is incorrect.

It’s worth mentioning that low GI foods are often claimed to better control appetite than higher GI foods. And about half of the studies examining this do find this effect, with the other half finding no real effect. This is another confound, if eating lower GI foods causes someone to eat less total food, they will tend to lose weight but it’s not due to the GI of the foods per se. As well, if high GI foods make people eat more, they will tend to gain fat, as a function of eating more.

But this is far different than claiming that high GI foods will make someone gain fat (and/or lose muscle) at an identical caloric intake, an argument that does not seem to be supported by the above studies looking at fuel utilization directly.

I should note that there is at least some indication of an interaction between high and low GI diets and insulin sensitivity, as I discuss in Insulin Sensitivity and Fat Loss, at least one study has shown that people with insulin resistance lose more weight with lower GI diets while those with higher insulin sensitivity actually do better with higher GI diets.

Wrapping up the paper, the researchers examine the impact of insulin on fuel utilization in general terms mentioning that both the magnitude and duration of insulin response has the potential to affect fuel and fat utilization. Without detailing all of the information, they conclude
Taking into account all of the above arguments, we speculate that under postprandial conditions, GI-induced serum insulin differences are not sufficient in magnitude and/or duration to modify fat oxidation.

Given that even tiny increases in insulin pretty much shut off fat oxidation, this actually isn’t surprising. As I discussed in The Stubborn Fat Solution, even fasting levels of insulin inhibit fat cell lipolysis by 50% from maximal rates and almost any increase in insulin is sufficient to shut off lipolysis completely.

As this research review points out, it simply doesn’t appear that some vs. more insulin has any major impact on this. I’d note, mind you, that fat cell metabolism can also be impacted by eating even if insulin doesn’t increase; oral ingestion of pure dietary fat also shuts down lipolysis but that’s beyond the scope of this article.

Summing Up

From the standpoint of fuel utilization, fat oxidation and the rest, there appears to be no meaningful differences in the impact of higher vs. lower GI foods in humans (the study also examined animal data where things, as usual, are different but simply don’t apply to non-rats).
What happens in the end

After consumption and digestion, nutrients have a couple of primary fates in the body which are oxidation (burning) and storage (for use later). And, as it turns out, the propensity for the body to store or oxidize a given nutrient is related to the body’s built-in store relative to intake. In the case of dietary fat, where stored fat is much higher than daily intake, the body tends to store incoming fat and burn very little. Fat intake per se has very little impact on fat oxidation rates.

Rather, the rate of fat oxidation is related to carbohydrate intake as the body is able to precisely alter carbohdyrate oxidation to changing intake. Eat more carbs and burn more carbs (and less fat); eat less carbs and burn less carbs (and more fat). Protein is somewhere in the middle, oxidation can increase or decrease relative to intake but the effect takes time (3-9 days).
Meal frequency & energy balance

Meal Frequency and Energy Balance/ Thermic Effect of Food (TEF)
Each time you eat, metabolic rate increases slightly for a few hours. Paradoxically, it takes energy to break down and absorb energy. This is the Thermic Effect of Food (TEF). The amount of energy expended is directly proportional to the amount of calories and nutrients consumed in the meal.

Let's assume that we are measuring TEF during 24 hours in a diet of 2700 kcal with 40% protein, 40% carbohydrate and 20% fat. We run three different trials where the only thing we change is the the meal frequency.

A) Three meals: 900 kcal per meal.

B) Six meals: 450 kcal per meal.

C) Nine meals: 300 kcal per meal.

What we'd find is a different pattern in regards to TEF. Example "A" would yield a larger and long lasting boost in metabolic rate that would gradually taper off until the next meal came around; TEF would show a "peak and valley"-pattern. "C" would yield a very weak but consistent boost in metabolic rate; an even pattern. "B" would be somewhere in between.

However, at the end of the 24-hour period, or as long as it would take to assimilate the nutrients, there would be no difference in TEF. The total amount of energy expended by TEF would be identical in each scenario. Meal frequency does not affect total TEF. You cannot "trick" the body in to burning more or less calories by manipulating meal frequency.
Study of meal frequency & energy balance review by lyle mcdonald

Bellisle F et. al. Meal frequency and energy balance. Br J Nutr. (1997) 77 (Suppl 1):S57-70.


Several epidemiological studies have observed an inverse relationship between people’s habitual frequency of eating and body weight, leading to the suggestion that a ‘nibbling’ meal pattern may help in the avoidance of obesity. A review of all pertinent studies shows that, although many fail to find any significant relationship, the relationship is consistently inverse in those that do observe a relationship.

However, this finding is highly vulnerable to the probable confounding effects of post hoc changes in dietary patterns as a consequence of weight gain and to dietary under-reporting which undoubtedly invalidates some of the studies.

We conclude that the epidemiological evidence is at best very weak, and almost certainly represents an artefact. A detailed review of the possible mechanistic explanations for a metabolic advantage of nibbling meal patterns failed to reveal significant benefits in respect of energy expenditure.

Although some short-term studies suggest that the thermic effect of feeding is higher when an isoenergetic test load is divided into multiple small meals, other studies refute this, and most are neutral. More importantly, studies using whole-body calorimetry and doubly-labelled water to assess total 24 h energy expenditure find no difference between nibbling and gorging. Finally, with the exception of a single study, there is no evidence that weight loss on hypoenergetic regimens is altered by meal frequency. We conclude that any effects of meal pattern on the regulation of body weight are likely to be mediated through effects on the food intake side of the energy balance equation.

LYLE’s comments

Perhaps one of the longest standing dogmas in the weight loss and bodybuilding world is the absolute necessity of eating frequently for various reasons. Specific to weight loss, how many times have you heard something along the lines of “Eating 6 times per day stokes the metabolic fire.” or “You must eat 6 times per day to lose fat effectively.” or “Skipping even one meal per day will slow your metabolic rate and you’ll hoard fat.” Probably a lot.

Well, guess what. The idea is primarily based on awful observational studies and direct research (where meal frequency is varied within the context of an identical number of calories under controlled conditions) says that it’s all basically nonsense. The basic premise came, essentially out of a misunderstanding of the thermic effect of food (TEF) also called dietary induced thermogenesis (DIT) which are the calories burned in processing of the food you eat.

While TEF differs for the different nutrients, on average it constitutes about 10% of a typical mixed diet (this varies between nutrients and slight differences may be seen with extreme variations in macronutrient intake). So every time you eat, your metabolic rate goes up a little bit due to TEF.

Aha! Eat more frequently and metabolic rate goes up more, right? Because you’re stimulating TEF more often. Well, no. Here’s why:

Say we have two people, both eating the same 3000 calories per day from identical macronutrients. One eats 6 meals of 500 calories/meal while the other eats 3 meals of 1000 calories/meal and we’ll assume a TEF of 10%. So the first will have a TEF of 50 calories (10% of 500) 6 times/day. The second will have a TEF of 100 calories (10% of 1000 calories) 3 times/day. Well, 6X50 = 300 calories/day and 3X100 = 300 calories/day. There’s no difference.
Of course, if you increase food intake from, say, 1500 calories to 2000 calories, you will burn more with TEF; but this has nothing to do with meal frequency per se, it has to do with eating more food. I only bring this up because I’ve seen people (try to) argue the positive effect of TEF by dredging up studies where folks ate more total calories. Of course TEFgoes up, but not because they are eating more frequently; rather it’s because they are eating more food in total.
I want to address that last bit a little bit more since the fact that TEF goes up with increasing food intake is often used to argue that “metabolism chases intake” and to make arguments for eating more to get lean. Here’s the problem with this ‘logic’. Assuming an average 10% TEF, increasing food intake from 1500 calories to 2000 calories per day will increase caloric expenditure by 50 calories. But you had to eat 500 more calories to get it. So even if you burn 50 calories more, you’re still consuming 450 more calories than you would have otherwise. Basically, the logic is akin to saying “I saved $100 by spending $1000 because what I bought was 10% off”. Right, but you’re still out $900 that you wouldn’t have spent and you’d have saved $1000 if you hadn’t bought it in the first place. The same logic applies here.

Which brings me, the long way around, to the above review paper which examined not only earlier observational work but also direct studies of varying meal frequency on either weight loss (during such studies) or metabolic rate. And, with the exception of a poorly done study on boxers (which I’ll discuss a bit below), they found no effect of varying meal frequency on any of the examined parameters. No increase in metabolic rate, no increase in weight loss, no nothing.

What’s going on? They concluded that earlier studies finding an effect of meal frequency on weight gain (or loss) had more to do with changes in appetite or food intake, not from a direct impact on metabolic rate. For example, early observational studies found that people who skipped breakfast were heavier and this still resonates today with the idea that skipping breakfast makes you fatter. However, the review points out that this may be confusing cause and effect: people often start skipping meals to lose weight.

I’d note, tangentially and I’ll come back to this below, that there is no data in humans that skipping a single meal or even a day’s worth of meals does anything to metabolic rate. Human metabolism simply doesn’t operate that quickly and various research into both fasting and intermittent fasting show, if anything, a slight (~5% or so) increase in metabolic rate during the initial period of fasting. The idea that skipping breakfast or a single meal slows metabolic rate or induces a starvation response is simply nonsensical.

Basically, there are a lot of confounding issues when you start looking at observational work on diet and body weight. As I discussed in detail in Is A Calorie A Calorie, you often find that certain eating patterns impact on caloric intake. And it’s those changes in caloric intake (rather than the eating patterns themselves) that are causing changes in weight
For example, some early studies actually found that eating more frequently caused weight gain, mainly because the foods being added were snacks and were in addition to normal food intake. In that situation, a higher meal frequency led to greater food intake and weight gain. But it wasn’t the meal frequency per se that caused the weight gain, it was the fact that folks were eating more.

Other studies have shown that splitting one’s daily calories into multiple smaller meals helps to control hunger: people tend to eat less when they split their meals and eat more frequently. But, again, this isn’t an issue of meal frequency per se, it’s because food intake is decreased. When folks eat less, they lose weight and IF a higher meal frequency facilitates that, it will cause weight loss. But, at the risk of being repetitive, it’s not because of effects on metabolic rate or any such thing; it’s because folks ate less and eating less causes weight loss.

I’d note that the above observation isn’t universal and some people report that the simple act of eating makes them hungrier. Many people are finding that an intermittent fasting protocol, where they don’t eat anything for most of the day followed by one or two big meals works far far better for food control than the standard of eating many small meals per day. Again, this isn’t a universal and I’m currently examining differences between people to determine who will respond best to a given pattern.

I’d also note that there is a fair amount of literature that eating more frequently has benefits in terms of blood glucose control, blood lipid levels and other health markers. I’d add to that the recent work on caloric restriction and intermittent fasting (a topic I’ll look at in a later article) is finding massive benefits (especially for the brain) from less frequent meals. So even this topic isn’t as simple as ‘more frequent meals is healthier’.

However, this is all tangential to the claims being made for metabolic rate. Whether you eat 3 meals per day or 6, if your daily caloric intake is identical, you will expend the same number of calories per day from TEF. While work in rats and mice, for whom everything happens faster, has found that a single meal can lower metabolic rate, this is irrelevant to humans. Skipping a meal will not affect human metabolic rate at all.

Quite in fact, it takes at least 3-4 days of fairly strict dieting to impact on metabolic rate (and some work on fasting shows that metabolic rate goes UP acutely during the first 72 hours of fasting); a single meal means nothing. You will not go into ’starvation mode’ because you went more than 3 hours without a meal. Nor will your muscles fall off as an average sized food meal takes 5-6 hours to fully digest, as I discuss in The Protein Book.

Now, all of the above is only looking at the quantity of weight loss, not the quality. For athletes and dieters, of course, sparing lean body mass and losing fat is a bigger goal than how much weight is actually lost. Which brings me to the boxer study that everybody loves to cite and nobody seems to have read (except me as I spent years tracking down the full text of the paper).

In this study, boxers were given either 2 or 6 meals per day with identical protein and calories and examined for lean body mass lost; the 2 meal per day group lost more lean body mass (note: both groups lost lean body mass, the 2 meal per day group simply lost more). Aha, higher meal frequency spares lean body mass. Well, not exactly.

In that study, boxers were put on low calories and then an inadequate amount of liquid protein was given to both groups and the meals were divided up into 2 or 6 meals. But the study design was pretty crappy and I want to look at a few reasons why I think that.
First and foremost, a 2 vs. 6 meal per day comparison isn’t realistic. As discussed in The Protein Book, a typical whole food meal will only maintain an anabolic state for 5-6 hours, with only 2 meals per day, that’s simply too long between meals and three vs. six meals would have been far more realistic (I would note that the IF’ing folks are doing just fine not eating for 18 hours per day).

Additionally is the use of a liquid protein that confounds things even more. Liquids digest that much more quickly than solid foods so the study was basically set up to fail for the low meal frequency group. They were given an inadequate amount of rapidly digesting liquid protein too infrequently to spare muscle loss. But what if they had been given sufficient amounts of solid protein (e.g. 1.5 g/lb lean body mass) at those same intervals? The results would have been completely different.

As discussed in The Protein Book in some detail, meal frequency only really matters when protein intake is inadequate in the first place. Under those conditions, a higher meal frequency spares lean body mass. But when protein intake is adequate in the first place (and again that usually means 1.5 g/lb lean body mass for lean dieters), meal frequency makes no difference. And that’s why the boxer study is meaningless so far as I’m concerned. An inadequate amount of liquid protein given twice per day is nothing like how folks should be dieting in the first place.
In any case, let me sum up the results of this review: Meal frequency per se has essentially no impact on the magnitude of weight or fat loss except for its effects on food intake. If a high meal frequency makes people eat more, they will gain weight. Because they are eating more. And if a high meal frequency makes people eat less, they will lose weight. Because they are eating less. But it’s got nothing to do with stoking the metabolic fire or affecting metabolic rate on a day to day basis.

As the researchers state above:
We conclude that any effects of meal pattern on the regulation of body weight are likely to be mediated through effects on the food intake side of the energy balance equation.
And that’s that.

Practical Application

The take home of this paper should be fairly clear and I’m going to focus primarily on dieting and weight/fat loss here. I’m also going to assume that your protein intake is adequate in the first place; if you’re not getting sufficient protein during your diet, you have bigger problems than meal frequency can solve.

Before summing up, one last thing, from a practical standpoint, I sometimes wonder if the people who are adamant about 6 meals/day have ever worked with a small female athlete or bodybuilder. A 120 lb female may have a daily food intake of 1200 calories/day or less on a diet.
Dividing that into 6 meals gives her 200 calorie ‘meals’. More like a snack. 4 meals of 300 calories or even 3 meals of 400 calories is a much more livable approach than a few bites of food every 3 hours.

By the same token, a very large male with very high caloric requirements (for dieting or mass gaining for example) may find that fewer larger meals are difficult to get down or cause gut discomfort, eating more frequently may be the only way to get sufficient daily calories.
But again, these are all completely tangential to any (non-existent) impacts of meal frequency on metabolic rate or what have you.

So here’s the take home:
 If eating more frequently makes it easier to control/reduce calories, it will help you to lose weight/fat.
 If eating more frequently makes it harder to control/reduce calories, or makes you eat more, you will gain weight.
 If eating less frequently makes it harder for you to control/reduce calories (because you get hungry and binge), it will hurt your efforts to lose weight/fat.
 If eating less frequently makes it easier for you to control/reduce calories (for any number of reasons), then that will help your efforts to lose weight/fat

I personally consider 3-4 meals/day a workable minimum for most, 3 meals plus a couple of snacks works just fine too. High meal frequencies may have benefits under certain conditions but are in no way mandatory. And, in case you missed it the first time through: eating more frequently does NOT, I repeat DOES NOT, ’stoke the metabolic fire’.
Post-workout anabolic window – real or not

The postexercise "anabolic window" is a highly misused & abused concept. Preworkout nutrition all but cancels the urgency, unless you're an endurance athlete with multiple glycogen-depleting events in a single day. Getting down to brass tacks, a relatively recent study (Power et al. 2009) showed that a 45g dose of whey protein isolate takes appx 50 minutes to cause blood AA levels to peak. Resulting insulin levels, which peaked at 40 minutes after ingestion, remained at elevations known to max out the inhibition of muscle protein breakdown (15-30 mU/L) for 120 minutes after ingestion. This dose takes 3 hours for insulin & AA levels to return to baseline from the point of ingestion. The inclusion of carbs to this dose would cause AA & insulin levels to peak higher & stay elevated above baseline even longer.

So much for the anabolic peephole & the urgency to down AAs during your weight training workout; they are already seeping into circulation (& will continue to do so after your training bout is done). Even in the event that a preworkout meal is skipped, the anabolic effect of the postworkout meal is increased as a supercompensatory response (Deldicque et al, 2010). Moving on, another recent study (Staples et al, 2010) found that a substantial dose of carbohydrate (50g maltodextrin) added to 25g whey protein was unable to further increase postexercise net muscle protein balance compared to the protein dose without carbs. Again, this is not to say that adding carbs at this point is counterproductive, but it certainly doesn't support the idea that you must get your lightning-fast postexercise carb orgy for optimal results.

To add to this... Why has the majority of longer-term research failed to show any meaningful differences in nutrient timing relative to the resistance training bout? It's likely because the body is smarter than we give it credit for. Most people don't know that as a result of a single training bout, the receptivity of muscle to protein dosing can persist for at least 24 hours:Enhanced amino acid sensitivity of myofibrillar pr... [J Nutr. 2011] - PubMed result

More from earlier in the thread:

Here's what you're not seeming to grasp: the "windows" for taking advantage of nutrient timing are not little peepholes. They're more like bay windows of a mansion. You're ignoring just how long the anabolic effects are of a typical mixed meal. Depending on the size of a meal, it takes a good 1-2 hours for circulating substrate levels to peak, and it takes a good 3-6 hours (or more) for everythng to drop back down to baseline.

You're also ignoring the fact that the anabolic effects of a meal are maxed out at much lower levels than typical meals drive insulin & amino acids up to. Furthermore, you're also ignoring the body's ability of anabolic (& fat-oxidative) supercompensation when forced to work in the absence of fuels. So, metaphorically speaking, our physiology basically has the universe mapped out and you're thinking it needs to be taught addition & subtraction.
Properly done preworkout nutrition EASILY elevates insulin above and beyond the maximal threshold seen to inhibit muscle protein breakdown. This insulin elevation resulting from the preworkout meal can persist long after your resistance training bout is done. Therefore, thinking you need to spike anything is only the result of neglecting your preworkout nutrition"

There's no need for quickly absorbed carbs postworkout unless you fulfill all of the following 3 criteria: 1) you have NOT ingested any pre or mid-training carbs, 2) you train to complete glycogen depletion, 3) you're forced to exhustively train those same glycogen-depleted muscles again within the same day.
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Hierarchy of Importance

When speaking of nutrition for improving body composition or training performance, it's crucial to realize there's an underlying hierarchy of importance. At the top of the hierarchy is total amount of the macronutrients by the end of the day. Distantly below that is the precise timing of those nutrients. With very few exceptions, athletes and active individuals eat multiple times per day. Thus, the majority of their day is spent in the postprandial (fed) rather than a post-absorptive (fasted) state. The vast majority of nutrient timing studies have been done on overnight-fasted subjects put through glycogen depletion protocols, which obviously limits the applicability of the outcomes. Pre-exercise (and/or during-exercise) nutrient intake often has a lingering carry-over effect into the post-exercise period. Throughout the day, there's a constant overlap of meal digestion & nutrient absorption. For this reason, the effectiveness of nutrient timing does not require a high degree of precision.

The Primary Laws of Nutrient Timing
The First Law of Nutrient Timing is: hitting your daily macronutrient targets is FAR more important than nutrient timing.
The Second Law of Nutrient Timing is: hitting your daily macronutrient targets is FAR more important than nutrient timing.
I have compiled a mix of biological, physiology information, articles and studies etc that will hopefully give everyone an understanding on the body's digestion processes, maconutrient functions and insulin responses and some other useful facts.

That in turn will clear up the myths of needing to eat 6 meals a day every 3 hours for metabolic function and 'keeping protein up', that identical macronutients/ calories from your typical 'clean' and 'dirty' are the SAME (Yes micronutrients - vitamins and minerals - content will vary but that is not the point of this) and that the GI of carbohydrates and the typical thoughts on their insulin response is of little meaning once a mix of multiple macronutrients is added.

Please note that how your body reacts in a 'fed' state (with food) compared to a 'fast' state (without food) is different. Many of the typically 'bodybuilding' and 'broscience' protocols, that as a few people tend to promote as being 'done for 20,30 or even 40 years and that is why it works' , are and have been based on either lack of understanding of the digestive system as well as focusing on studies that have been done after a fasting period and or a fasting period followed by exercise.

To expand on that more, when a Fast (usually 24 hours) is done, our metabolic rate actually INCREASES, see link to studies -

Enhanced thermogenic response to epinephrine after... [Am J Physiol. 1990] - PubMed result

Resting energy expenditure in short-term starvatio... [Am J Clin Nutr. 2000] - PubMed result

Our metabolic rate does not DROP until between the 60-92 hour mark. See link to study -

Leucine, glucose, and energy metabolism after 3 da... [Am J Clin Nutr. 1987] - PubMed result

As you will read, you should be able to see why due to the digestion process why we are continuously in a 'fed' state and how all the 'myths' simple hold no bearing and are of no relevance. Most times the only real application some of the typical 'bodybuilding' protocols are if you have completed a 'fast' and then going to train or have a number of back to back events in the same day.

Before moving on to the info, I must say that if you want to eat 6 times a day and every 3 hours, YOU CAN but YOU DON'T NEED TO. If you want to eat 'clean', YOU CAN but YOU DON'T NEED TO. If you want to go by the GI, YOU CAN but YOU DON'T NEEDED TO. This is merely for the understanding that for body composition, those sorts of minor details and protocols DO NOT determine what your BODY COMPOSITION is/ will be.

I thought there were benefits due to spreading out meals other than keeping the body in a 'fed state'. The stomach processes food through enzymes and acids and then the pyloric sphincter (i think that's right, been a while since I was at uni), 'sips' the juices from your stomach - then the intestines absorb the nutrients. It stands to reason that an extremely large amount of food might pass through your body at least partially undigested. Do you have any studies on the effect of large meals on digestive efficiency? Does food pass through undigested/wasted? This is the commonly cited problem with liquid diets... the food goes through so quick it isn't broken down and absorbed.
I am not trying to be controversial... i find what you're saying to be intriguing, but there is something I dont think has been rationalised fully.

What seems important is the cue responsible for releasing the chyme into the intestines... If you ingest a large amount of food, the body probably(?) recognises this and releases more digestive enzymes than for a smaller amount. There must be some effect created by having a larger mass with smaller surface area (food congeals, sticks together) on digestion. I know the stomach isn't just a sack, it contracts and squishes food around. Still, I wonder if there is an effect.

Do you know of the mechanism that exists in the stomach that allows the body to recognise when the food is ready to be passed through the pyloric sphincter? Is it based on consistency, or is there some other mechanism that recognises that the food is broken down?

There is another common belief that not chewing your food means you won't digest it as well. This again makes me believe that there is no ability for the stomach to recognise when food is ready to pass to the intestines, and hence the size of meal is important.
I thought there were benefits due to spreading out meals other than keeping the body in a 'fed state'. The stomach processes food through enzymes and acids and then the pyloric sphincter (i think that's right, been a while since I was at uni), 'sips' the juices from your stomach - then the intestines absorb the nutrients. It stands to reason that an extremely large amount of food might pass through your body at least partially undigested. Do you have any studies on the effect of large meals on digestive efficiency? Does food pass through undigested/wasted? This is the commonly cited problem with liquid diets... the food goes through so quick it isn't broken down and absorbed.
I've not seen any studies or literature on that with supportive evidence. If that was true, the weight loss/fat loss would be higher in the lower amounts of meals due to more nutrients/ calories being lost in the digestion process.

Being the body is an adaptive organism and has the ability to super-compensate in the production of enzymes, hormones and tissues etc. ;)

The only thing that will effect nutrients being lost is the fibre content.

Impaired Nutrient Absorption
Another effect, again primarily seen with soluble fibers, is an impairment of nutrient absorption, and this holds for carbohydrates, fats and dietary protein. Essentially, due to the gel-like mass that is formed, digestive enzymes can’t get access to the other nutrients so that more is carried out of the body. This means that high-fiber diets will result in less total caloric absorption, basically the left-hand side of the equation discussed in The Energy Balance Equation will be lower when a large amount of soluble fiber is consumed.
I’d note that the effect isn’t massive, fiber may reduce total fat absorption by about 3%, protein by 5%. I can’t find a good value for carbohydrates at the moment. Put more concretely, an increase in dietary fiber from 18 to 36 grams per day might reduce total caloric absorption by 100 calories per day.
Now, depending on how you want to look at this, it can be seen as either a good or bad thing. For individuals trying to lose weight, higher fiber diets will not only have positive effects on fullness and the rest but will result in less total calories being absorbed from the diet. Again, the high-fiber nature will reduce the Energy In side of the equation (which only counts calories which are actually absorbed).
On the other hand, for athletes or bodybuilders, the impact of a high-fiber intake could be seen as detrimental, especially given that soluble fibers impact on protein absorption. While it would be nice if fiber only impacted on carb or fat absorption, that simply isn’t the case. As well, for athletes with very high energy demands, losing digestible energy due to a high fiber intake might not be the best thing. Again, I’d note that the total impact isn’t massive but it is worth considering.

Impairment of Mineral Absorption
In addition to global impacts on carbohydrate, protein and fat absorption, dietary fibers can also negatively affect mineral absorption especially calcium, magnesium, sodium and potassium. I’d note that, in general, this isn’t really an issue for concern unless the intake of those nutrients is insufficient in the first place.
As well, when fiber intake is increased from foods (as opposed to dietary supplements), there is generally an increase in mineral intake in the first place which should help to offset any issues. For example, the fiber intakes of our evolutionary diet is thought to be massive (some have estimated it at 100-150 grams per day) but nutrient deficiencies aren’t seen; this is most likely due to the fact that the fiber is coming from nutrient dense fruits and vegetables.
However, when people start adding horse-doses of fiber supplements to their diet, problems can start. Older readers may remember the bran craze in the 80’s, when bran was found to lower cholesterol, people starting eating it in massive amounts. But they were often doing it from purified sources rather than whole foods. While this may have improved cholesterol levels, it ended up causing issues with mineral imbalances because the massive fiber intake was not accompanied by an increase in nutrient intake.
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