Meal frequency, intermittent fasting, and dietary protein

Dietary protein “requirements” are some of the most context-dependent nutrient levels to decipher, and depend largely on energy balance and even meal frequency.

An objective look at intermittent fasting (Alan Aragon, 2007)

Meal frequency and energy balance (Lyle McDonald, 2008)

New study: “Increased meal frequency attenuates fat-free mass losses and some markers of health status with a portion-controlled weight loss diet” (Alencar et al., 2015)

This wasn’t well-received in social media because bro-science & many low carb advocates say grazing is no longer in vogue — “it’s much better/healthier/whatever to eat once or twice daily, because intermittent fasting and all that jazz” …however, this may be problematic when it comes to meeting overall protein needs, which is particularly important when you’re losing weight.

 

 

The study: 2 vs. 6 meals per day, crossover.  

Conclusion: “On average, fat-free mass (FFM) decreased by -3.3% following the 2 meals/d condition and, on average, and increased by 1.2% following the 6 meals/d condition (P<.05).”  

 

fat-free mass

 

In other words, 6 meals per day was better for body composition than 2 meals per day.  But context is everything, and this hypothesis has been tested from a variety of different angles, so what does it mean?  

The relevant context here: 1) big energy deficit (1200 kcal/d for obese women is a pretty low calorie intake); and 2) “adequateTM” protein intake (75 g/d).

The standard dogma says that in the context of an adequate protein hypocaloric diet, meal frequency matters a LOT, whereas with high protein, it doesn’t matter as much.  Theory being that with an “adequate” (read: too low?) overall protein intake, the fasting periods are simply too long with only two meals per day; you need either: 1) higher protein intake; 2) increased meal frequency; or 3) more calories (ie, smaller energy deficit).  

In this study, BOTH diets suppressed insulin and induced weight loss, but the increased protein feeding frequency skewed the weight loss to body fat while preserving fat-free mass.   I actually agree with a lot of the bro-science in this case, and also think that 75 grams of protein is not enough in the context of a big energy deficit (if body composition is a goal).    




 

Historical precedence?

 

Meal frequency and weight reduction of young women (Finkelstein et al., 1971)

Relevant context:  6 vs. 3 meals per day (3 meals per day may not seem like that many more than 2, but it significantly cuts down on the duration of time spent with no food or protein).

Smaller energy deficit: 1700 kcal/d in overweight patients is less of a deficit than 1200 kcal/d in obese patients.

Higher protein intake: 106 – 115g/d.

Result: nitrogen balance (a surrogate for the maintenance of muscle mass) and fat loss were similar in both groups.  This study fixed two problems in the abovementioned study: 1) 3 meals is better than 2 in the context of an energy deficit; and 2) protein intake was higher.

 

And again here, with 3 vs. 6 meals per day (Cameron et al., 2010), just to make the point that 3 meals per day is better than 2 for preserving lean mass in the context of an energy deficit.

 

The effect of meal frequency and protein concentration on the composition of the weight lost by obese subjects (Garrow et al., 1981)

This study tested the opposite extremes: super-low calorie intake (800 kcal/d), much lower protein intakes (20g – 30g/d), and 1 vs. 5 meals per day.

Result: “a diet with a high-protein concentration, fed as frequent small meals, is associated with better preservation of lean tissue than an isoenergetic diet with lower-protein concentration fed as fewer meals.”

It basically confirmed all of the above.

 

Protein feeding pattern does not affect protein retention in young women (Arnal et al., 2000)

1 vs. 4 meals per day; and 70 grams of protein but no energy deficit (~2000 kcal/d isn’t very hypocaloric for lean young women).  In this study, no effect of meal frequency was seen, likely because 70 grams of protein isn’t inadequate when energy intake isn’t restricted.

 

 

 

1. PROTEIN “NEEDS” ARE HIGHLY CONTEXT-DEPENDENT

2. NEED =/= OPTIMIZATION

3. MEAL FREQUENCY & meal timing and peripheral circadian clocks > “MACRONUTRIENTS”

 

If you’re losing weight (ie, in an energy deficit), then intermittent fasting is cool if protein intake is high (above “adequateTM“)… the bigger the energy deficit, the more protein is necessary to optimize changes in body composition.

 

How much is ‘enough?’  Sorry, can’t give you a gram or even gram per pound of body weight answer… but if you’re losing weight and seeing no discernible effect on body composition (muscle vs. fat mass), then it may be prudent to consider eating more protein-rich foods… and paying more attention to sleep quality (which also greatly impacts nutrient partitioning).

No amount of protein will help you if circadian rhythms aren’t intact!!!

 

 

further reading:

Yes, it’s a high protein diet (Tom Naughton, 2015)

Protein requirements, carbs, and nutrient partitioning

Dietary protein, ketosis, and appetite control 

 

 

calories proper

 

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  • Thomas Hemming Larsen

    Another good one Bill!

    So if I’m hypercaloric there is no need for more than three meals per day?

    • http://www.caloriesproper.com/ Bill Lagakos

      Thanks, Thomas!

      right (I think)… are you making gainz? :-)

      • Thomas Hemming Larsen

        Haha, especially my upper body is growing (I’ve even torn a shirt :) ). My weight isn’t changing much but I ‘feel’ more muscular. Now we’re changing my programming to be more focused on mass instead of strength. Its just so damn hard to eat even 3000kcal on low carb…

  • rs711

    Interesting write-up Bill. Your comparisons between hypo & isocaloric context is welcome & necessary.

    Did the results surprise you? If so, in what way?

    Off the cusp, it’d makes sense to me that in a severe hypocaloric context multiple pulses of amino acids would help preserve FFM compared to fewer pulses. In a state of abundance (i.e. iso/hypercaloric) it’d also make sense to me that amino acid pulsatility provides marginal returns up to the point of making no difference (& just being an extra burden, beyond that!).

    As always, looking forward to the next blog post :)

    PS: do you think Fungs’ point on study duration has merit when it comes to comparing FFM changes? I’m not sure I see an obvious reason why…maybe I’m missing something.

    • http://www.caloriesproper.com/ Bill Lagakos

      Thanks. It didn’t really surprise me because this has been floating around in the bro-science soup since forever.

      As to study duration:
      1) these are weight loss studies, and people aren’t going to be in a negative energy balance FOREVER, so the standard criticism (study too short) doesn’t fully apply. Some people lose weight in a month, so we’re interested in FFM dynamics for that month (and maybe check in a month or 2 later).

      2) look at the wide range of study designs — the effect on FFM is incredibly consistent, which suggests to me that it is a true phenomenon

      • rs711

        1) yes, “too short” must have some mechanistic motivation (mitochondrial adaptations to our entire range of exercise modalities for e.g.). In this case it doesn’t seem warranted.
        2) yes, there are many tangentially supportive angles for this type of management in humans (I won’t justify them but will briefly list a few): OFS (Optimal Foraging Strategy) considerations, glucogenic/ketogenic amino acids pathways, metabolic rates (humans vs mice) etc.

        Don’t worry though, someone will read this and run with “OMG OMG OMG I haven’t eaten in 4hrs, IF’ing kills, I need intravenous glucose+whey”.

        • http://www.caloriesproper.com/ Bill Lagakos

          Hahaha I hope not.

          “glucogenic/ketogenic amino acids pathways”
          are you thinking of something specific or just general speculation?

          • rs711

            more general speculation.

            SNPs amongst TCA cycle enzymes dealing with amino acid catabolism *may* plausibly explain some of the variation in individual FFM gains/losses. Or the extent to which individuals can enter/exist ketosis or high FFA ox. states with ease.

            Ultimately muscle is very expensive to gain or maintain, so it it makes me wonder at what level these ‘decision points’ are.

          • Jack Kruse

            SNP’s are abused by alternative practitioners and mis understood by people with them. Single Nucleotide Polymorphisms (SNP’s): Recently 23andme and many alternative practitioners have been touting the predictive power of SNP’s in disease. “Raising awareness” is like medical screening tests, neither is enough to make people healthier. They just create belief that enrich the messenger. If you have some SNP’s in your genome here is the key point most practitioners and patients with them misunderstand: Your steepness of decline with illnesses tied to these SNP’s will be tied to the resultant ubiquitin rates in cells. Some SNP’s can help you in some environments and some will hurt you in others. The key point is, look at your environment and then put your SNP’s in context. “Well-controlled studies” will not mesh with your N-1 because without control of the environment, especially in nutrition studies and SNP trials. Why? ubiquitin rates are never controlled for in these studies and SNP’s expression is linked to the relationship of light and nitrogen coupling in exponential fashion. When someone with bad SNP’s is really sick it tells me ALWAYS LOOK OUTSIDE OF YOU AND NOT INSIDE your cells.This is why I get so angry with alternative paleo providers who deal with patients with SNP’s data from 23andme; they immediately think, and make those with SNP’s believe, they can change the inside of their genome with supplements, and they can’t. When you;re sick in this case it tells you your biology is uncoupled. It tells you light and nitrogen cycling in you is badly broken. This is akin to the story of the KT event and why geologist did not believe the asteroid story for so long. When Dr. Alvarez postulated the sequence of events that occurred 65 million years ago do you know why other geologist thought he was crazy? Because prior to 1990, no one had ever thought that rocks could be changed from outside forces from space……..they just thought climate weathering of the matter in rocks was the only key event. His ideas made them realize they had to look further outside for another possibility. I am telling people that SNP’s are not tied to endogenous breakdown in your nucleic acids or the way you work. It is reflective of how your genome ties you to the flow of energy in the environment you allow and via ubiquitination rates they cause. SNP’s manifest their effects only after they become expressed; that is when they are a problem. If you’re environment is controlled you can tolerate most SNP’s If you don’t control your environment, you’ll harbor the belief the SNP’s are a demon. SNP’s treatment requires an environmental clean up. The Rx should not be prescribing to do things the other way around trying to solve the SNP presence. It is similar to the KT event. It is an environmental epigenetic issue tied to an altered environment increasing ubiquitin rates. SNP’s just slow down epigenetic changes and this is why in environments with higher exogenous energy flows they get sicker faster than other people.

          • http://www.caloriesproper.com/ Bill Lagakos

            “ubiquitin rates are never controlled for in these studies”

            I’m holding my breath for this one.

          • rs711

            Thanks for that perspective Jack!

            “I am telling people that SNP’s are not tied to endogenous breakdown in your nucleic acids or the way you work.”

            If by that you mean that the clinical significance of SNPs involved in nucleic acid catabolism is dwarfed compared to those potentially mediated by epigenetic factors, that may well be true. Maybe even in a majority of cases! I don’t know. But at this point, how can we measure the apportioning of effects from ubiquitin rates & SNPs respectively?

            “The Rx should not be prescribing to do things the other way around trying to solve the SNP presence.”

            Solve SNP presence? Who said that? It implies a faulty assumption that a SNPs are always a problem. They’re no more obligate problems than evolk

          • Jack Kruse

            I have had the pleasure of seeing 4 people in the last 4 months who visit two prominent paleo practitioner’s who got this ridiculous advice. That is where it comes from.

          • rs711

            that is crazy. all you need is a genetics text book & a drop of sanity to know that ‘solving SNPs’ is snake-oil salesman speak right now.

          • Jack Kruse

            When the “practitioner” is in bed with a paleo god lemmings get led off a cliff regularly.

  • This Old Housewife

    I just read this today about how protein calories can be as much as 25% too high when going solely by the nutrition label: http://well.blogs.nytimes.com/2015/04/27/on-food-labels-calorie-miscounts/?partner=rss&emc=rss

    kilocalories (label) vs. calories ACTUALLY DIGESTED AND ASSIMILATED

    From the article: An alternate and more accurate system of counting calories has been devised by Mr. Livesey and has been presented to the United Nations Food and Agriculture Organization, which provides recommendations to member nations. The new method has been discussed but not officially adopted.

    It counts not just how much energy (or calories) are available in a food, but what the body can actually use of that energy. Additional calculations are made to consider the energy expended by the body in digestion and the degree to which the food is processed.

    People ask me, ‘if we know what is wrong, why hasn’t it been changed?’ ” said Rachel Carmody, a postdoctoral researcher at the University of California, San Francisco. “Because the old system is in place in most developed countries, and it would be a massive administrative and political undertaking to coordinate changes.”

    Once again, politics gets in the way of our food and health!

  • Jack Kruse

    I think all these studies suffer from one big issue that Bill eluded to at the end……ubiquitination rates are key and you cannot know anything about nitrogen cycle without getting the light cycle issue organized in a patient. Ubiquitin rates determines how carbon cycles in all living things. I think it is the biggest piece most of these studies miss. I think Fung critic is standard boilerplate response of an MD who advocates and Evidence based medicine approach. I wonder why he did not apply some of his own critic to himself when he advocated the use of the ACCORD trial in some of his opinion pieces. For those who don’t know ACCORD is a horribly flawed trial to draw any conclusions on. This is just a small peek into why all MD’s and researcher need to be careful with what we call evidence.

    • http://www.caloriesproper.com/ Bill Lagakos

      some people respond to growth factors with a rapid suppression of proteolysis (presumably largely via downregulation of ubiquitin rates), whereas this response is much less robust in others.

      there is likely a strong circadian component to it as hinted by studies on meal timing & peripheral circadian clocks (this may also at least partially explain the large interindividual variation).

      • http://www.caloriesproper.com/ Bill Lagakos

        definitely strong link between circadian signaling and ubiquitination; eg, http://1.usa.gov/1Jz10Dr & http://bit.ly/1bBcYht. The two are inseparable.

        • Jack Kruse

          I hope people realize the more they exercise the LESS PROTEIN they actually need. This is why they can expand carbs……..as long as it TOO is linked to light’s natural cycles. This is how nature balances mTOR and IGF1 pathways naturally. The Paleo community breaks both of these rules daily.

          • http://www.caloriesproper.com/ Bill Lagakos

            exercise and protein are two anabolic stimuli: do more of one, need less of the other.

            this seems so very basic, but I guess when the dogma runs so deep…

          • rs711

            i’ve never seen it put as simply – could you expand on that Bill?

            i get the idea in terms of 2 similarly oriented stimuli requiring less of each individually to achieve their intended response…so by that do you mean that it is the efficiency with which amino acids are used to build muscle that is improved? & thus by that token, absolute grams of amino acids won’t *necessarily* need to increase?

          • http://www.caloriesproper.com/ Bill Lagakos

            nitrogen balance becomes positive when you begin an exercise program
            (even if protein intake doesn’t change)

    • rs711

      From Bill’s 1st link: “our data reveal an essential and conserved role of UBE3A in the regulation of the circadian system in mammals and flies and identify a novel mechanistic link between oncogene E6/E7-mediated cell transformation and circadian (BMAL1) disruption.” OK i get that.

      And I get his point about proteolysis response partially stemming from ubiquitin ‘tagging’ dynamics.

      Jack: so far I’ve seen Dr.Fung criticize the ACCORD trial. But, he also uses it to make a point about the dangers associated with intensive pharmaceutical approaches for lowering blood glucose – NOT about intensively lowering blood glucose in & of itself (or via dietary/lifestyle management). This point has recently come up again in a recent JAMA (I think) study. What am I missing about his interpretation of ACCORD? Maybe I’ve not come across some of his other material where he misuses it – if so, I’d be interested in seeing that so please link to it.

      As I said to Bill earlier, I agree that the “too short” critique hear doesn’t seem appropriate.

      • http://www.caloriesproper.com/ Bill Lagakos

        Lemme summarize this shitstorm lol:

        everyone is pro-LC

        if blood glucose isn’t adequately managed via diet/lifestyle, is it good enough that insulin is low, or is medication necessary?

        • http://www.caloriesproper.com/ Bill Lagakos

          shitstorm, part II:

          The original ACCORD study showed that intensively lowering blood glucose was dangerous because more people in the intervention group died. Ergo, “insulin (not blood glucose) is the bad guy.”

          The follow-up analysis showed (I think) that some people in the intervention group weren’t getting their glucose levels down whereas some in the control group were.

          So if the data were analyzed as blood glucose vs. outcomes, instead of group vs. outcomes, a different picture emerged: blood glucose (not insulin) is the bad guy.”

          • rs711

            That’s the gist of what I remember from it.

            Surprised by steve’s anger on this one.

            The recommendations I’ve seen Fung give about diabetes management seem to take this into account and don’t promote cooky stuff. I haven’t seen that much of his material (2-3 videos and an article or 2).

          • http://www.caloriesproper.com/ Bill Lagakos

            I think it comes down to these two opposing viewpoints:

            1. hyperglycemia is the bad guy, so it’s beneficial to use insulin for blood glucose control.

            2. hyperinsulinemia is the bad guy, so using insulin to control blood glucose is counter-productive.

          • http://www.diabetes-warrior.net/ Steve Cooksey

            Actually I know both hyperglycemia and hyperinsulinemia are harmful.

            The responsible approach is to reduce insulin as your blood sugars begin to fall within normal rangs.

            If the diabetic is not on insulin at diagnosis and If very low carb and exercise work, as it does in many circumstances… no insulin would be needed.

          • rs711

            I remember him saying in 1 of his videos (paraphrasing) ‘although everyone knows/agrees hyperglycemia is bad, hyperinsulinemia is also very bad’.

            It seems that we all agree on this here -opposing BG to Insulin is a false dichotomy.

            We’ve all used data from bad trials to make a different point from the original one, nothing new here. But maybe Fung is misusing the ACCORD trial data – but without going into specifics I can’t judge that. I *think* (although I’m not entirely sure) he also pointed out how this study was misrepresented by the concerned governmental agencies. Granted, that doesn’t certify that the conclusions he takes from it are valid – again, we’d need to see the specific claims. I just can’t be bothered now hehe.

          • erdoke

            This controversy can easily be resolved if you know the etiology of the disease:
            http://profgrant.com/2013/08/16/joseph-kraft-why-hyperinsulinemia-matters/
            It seems that insulin resistance is key and insulin is high well before blood glucose starts getting close to problematic levels. In fact high blood glucose is way too late a manifestation for a timely diagnosis. Consequently, restoring insulin sensitivity automatically resolves BG issues. Another fact is that fasting turns out to be one of the most powerful interventions to significantly improve insulin sensitivity.
            In this respect I believe Dr. Fung is correct. I am not sure about his claims that usually even those T2DM patients’ symptoms go into remission who already had failing beta cell function, as I am not a clinician. I do not think though that he is lying, especially considering the 200 or so T2 patients he has first hand experience with.
            As a side note, I’m hesitant to accept that insulin controls blood glucose. It controls glucagon which controls glycolysis and gluconeogenesis in the liver and the liver sets blood glucose level. :o)
            Regarding the study discussed in the article, my experience tells me that proper fat/keto-adaptation through diet takes 2-4 weeks, via starvation much less, and then lean mass is preserved (or increased!) much more efficiently. One of the mechanisms is increased GH secretion.

          • Jack Kruse

            They don’t but here is the point. Fung in a recent LC circle jerk in South Africa used ACCORD data to construct his theories. As Bill laid out above that trial has some big problems if you are a diabetic. I think criticizing Bill and not looking at your own issues is awfully myopic. Fung has some nice ideas but using ACCORD is like looking for data that matches your beliefs: Ie confirmation bias. LC community does this way too much. There are tons of places to look other than ACCORD.

          • http://www.diabetes-warrior.net/ Steve Cooksey

            Thanks for sharing, I did not know this Jack.

            I based my opinion on his public tweets using Accord as evidence blood sugar control is wrong.

            Accord only showed that an ADA or SAD diet and intense control was harmful.

            EVEN I saw that 5 years ago….

          • http://www.diabetes-warrior.net/ Steve Cooksey

            I explained the reasons for my anger to you many times and wrote two posts about it.

            Fung is wrong on many issues including demonizing insulin, stating intense control is harmful (per Accord) and stating that the 2nd biggest lie in diabetes care is controlling blood sugar.

            Fung claims A1c sub 7 is “diabetes-cured”. On and on the Fung deceptions go.

            And I haven’t even gotten to his hyping his protocols as ‘ancient secrets’.

            He’s based his protocols on the Accord (and similar studies). He’s shared public tweets with you Raphi, which you retweeted or favorited, stating Accord etc as proof blood sugar control is useless.

          • Jack Kruse

            I’m with Steve on this.

    • Jack Kruse
      • http://www.caloriesproper.com/ Bill Lagakos

        lol I generally dislike reviewing papers, but feel obligated to accept when asked.
        wouldn’t mind if it was done away with!

        • rs711

          open-access unleashes the critical eye of crowd sourcing…so i’m betting on that power rather than a handful of reviewers, ultimately. transition is already happening and interesting

          • Jack Kruse

            not in big time journals in in specialty journals. PEER review in my specialty is a train wreck and very broken.

  • Ken

    Interesting, I wonder how effective old bodybuilding suggestions are (6-8 meals per day and consuming 1-2g protein/ lb bodyweight)

    • http://www.caloriesproper.com/ Bill Lagakos

      that’s a lot of protein! probably beyond the point of saturating protein-induced anabolism… check out this study by Jose Antonio (who also chimed in the comment section):

      http://caloriesproper.com/nutrient-partitioning-a-very-high-protein-diet/

      suggests that such high doses might still have a favorable effect on nutrient partitioning, in some contexts

      • Ken

        Thats a super interesting article and paper; my general experience with people in a caloric surplus with very hight protein diets isn’t usually fat loss haha. I wonder how different results are in heavily muscled individuals at low bodyfat in a caloric deficit? I wonder if there’s any merit to old bodybuilding dogma where they eat 6-8 meals per day, each with 30+ grams of protein

  • 1tie.net

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