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NUTRIENT TIMING I
FASTING & CIRCADIAN RHYTHMS

Bodybuilding has come a long way since the bro age. Traditional bodybuilding wisdom is that
you should eat 6 meals a day on the clock with a high carb breakfast, a slow protein like
casein before going to bed and a fast (whey) protein shake within an hour after your
workout.

Science has shown many of these ideas to be broscience. As a result, many people, especially
in the if-it-fits-your-macros (IIFYM) culture, have become skeptical of the whole concept of
nutrient timing, thinking it doesn’t matter when you consume what, as long as you hit your
daily macros. If you think about it, this is ironic, because the very concept of daily macros
implies that nutrient timing matters: you have to consume the nutrients within a 24 hour
window that happens to coincide with Earth spinning around its axis.

Moreover, it can easily be deduced a priori that nutrient timing matters. If we compare 2
groups of people with one group eating all of their weekly macros on Saturday and the other
group spreading their meals out across the week as most people do, is there really anyone
who believes the person eating only on a single day of the week will gain as much muscle as
the person eating every day?

So there really is no logical debate necessary about whether nutrient timing matters. It
matters. What we’ll focus on in this topic is how much it matters and within which time
frames.

But before we turn to nutrition, let’s talk about your biorhythm and how this relates to
training.

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Circadian rhythm training timing

Given people’s skepticism of nutrient timing, it is no surprise that virtually no one in the
fitness industry had considered the relevance of when you train within a day. Yet there is a
considerable literature finding that your training time is a significant determinant of your
training results.

Recommended reading
The best time to work out

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Intermittent fasting
Often when people say ‘intermittent fasting’, they really mean ‘skipping the first meal of the
day’. Intermittent fasting sounds cooler and more scientific, but it’s actually a deceptive term
here and it’s important to realize this.

Say we take a pretty common intermittent fasting set-up where someone eats her last meal
close to bedtime at midnight, skips the morning meal and then has her first meal at lunch at
work at 12 AM. Compare that to average person that eats dinner at 6 PM and has her
breakfast at 8 AM. The second person actually has a 2 hour longer daily intermittent fast
than the first person that is ‘doing intermittent fasting’.

So everyone practices intermittent fasting. It is only the duration and timing of the fast. In
fact, this is why we call the first meal of the day breakfast: breaking the fast. So technically
the person in the first example above has breakfast at lunchtime AKA brunch.

Now that we’ve got out terms straight, we can delve into the research on the effectiveness
of postponing breakfast or ‘Leangains style intermittent fasting’, as Martin Berkhan
popularized it.

Consistency vs. timing

The first thing opponents of postponing breakfast will point to is that people who postpone
breakfast are generally fatter than people who don’t. Using this as an argument against
postponing breakfast is a classic case of mistaking a correlation for causation. You are
comparing 2 groups of people here that vary in several key ways. On the one hand you have
people with a regular breakfast routine. On the other hand you have people without a plan
for breakfast. You’re talking about people eating on the run to work that are more likely to
snack and consume ready-to-eat convenience foods. In fact, breakfast skipping is the meal
pattern most strongly related to poor diet quality. It’s no surprise that the more irregular
lifestyle is more likely to make you fat. “Failing to plan is planning to fail.”

Moreover, an irregular meal pattern is not just a lifestyle concern. The regularity of your
meal pattern has important physiological effects. By definition, an irregular meal pattern has

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you eating at times when your circadian rhythm is not adapted to digest nutrients. This
causes disruption of postprandial metabolism, i.e. how your body reacts to food. This
disruption from an irregular eating pattern includes all of the following.
• Higher fasting total and LDL (‘bad’) cholesterol. A cross-sectional study found
decreased LDL cholesterol levels though.
• Decreased postprandial insulin sensitivity. When you eat at a time your body
is not accustomed to, you produce more insulin than normally.
• A disruption in the circadian rhythm of your appetite leading to more hunger
[2].
• A disruption in the circadian rhythm of cortisol production and an increase in
total cortisol production across the day.
• Higher blood pressure.
• A lower thermic effect of food (TEF) [2] as a result of decreased insulin
sensitivity. When you eat at irregular times, your body burns less of it. In this study
the thermic effect of food decreased almost 50% during the 2 week transition from a
regular to an irregular meal pattern. That means if your TEF is normally on the high
end of 25%, an irregular meal pattern could drop that cose to 12.5% and thereby
decrease your total daily energy expenditure by 12.5%.

As if this isn’t bad enough, skipping meals tends to result in complete energy compensation
afterwards [2]. This means that you will be hungry to make up for the decreased energy
intake later in the day and often end up consuming the same total amount of energy as if you
had eaten the meal anyway (or you go hungry). Energy compensation isn’t always complete,
but this is mainly found in studies where the early breakfast is low in protein and therefore
not very satiating to begin with.

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How an irregular meal frequency causes metabolic disorders.

So it is crucial to distinguish between an irregular meal frequency and intermittent fasting. An

irregular meal frequency is unquestionably bad for your body, but how is this relevant to
people practising intermittent fasting where macros and the daily fast are meticulously
controlled every day, such as LeanGains?

Actually, Leangains intermittent fasting does not have a regular meal frequency. There are no
set meal times within the 8 hour ‘eating window’. A person can sometimes have 1 enormous
meal and at other times snack more or less continuously throughout the eating window.
This variance will cause all the metabolic disruptions mentioned above. Having an eating
window in your diet is thus generally suboptimal compared to having set meal times.

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Now what about if you control your macros ánd your meal times?

Fasting for fast fat loss?

Several studies have looked at the effects of extending the overnight fast compared to having
breakfast shortly upon awakening for your body composition.

Schlundt et al. (1992) compared obese women on a weight loss diet of 2 or 3 meals a day
with the 2 meal group fasting through the period where the 3 meal group ate their breakfast
and thereby only eating lunch and dinner. Both groups had the same macros throughout the
12 week study.

Both diets were equally effective for fat loss with no significant differences between groups.

 Body fat percentage decreased by 3.2% - as measured by underwater weighing.

 Muscle retention was 75%.
 Weight loss was ~7.2 kg (15.9 lb).
 Basal metabolic rate decreased by 6%.

The improvements in systolic and diastolic blood pressure, serum triglycerides and
cholesterol did not vary between groups either.

At the 6 month follow-up there were again no significant differences between the groups.

These results suggest that there are no special benefits of intermittent fasting for either
health or fat loss. This makes perfect sense from an evolutionary perspective. Humans
should be able to fully adapt to eating few meals and not eating immediately after waking up.

The researchers also extensively studied the psychological response to the diets. Overall
compliance and psychological response was similar between the diets. These were the most
notable findings.

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 The fasting group scored higher on negative emotional eating at the start of the
study, but this difference disappeared over time. This indicates initial difficulty
adjusting to the fasting diet compared to having breakfast early.
 Overall compliance on various measures (diary keeping, analysis of eating behavior
and drop-out rate) did not vary between groups. Once the subjects were used to the
fasting, they had no more difficulty with the diet than the group having an early
breakfast.
 Hunger levels and snacking behavior did not differ between groups, suggesting no
benefit of intermittent fasting for appetite suppression.

When looking at specific types of non-compliance, there were a few subtle differences
between the groups.

 The fasting group suffered more from impulsive eating.

 The early breakfast group suffered more from depressive eating (effectively self-
medicating), but the difference was very small.
 The fasting group had an easier time incorporating social meals into their diet,
because their meals were larger.

Farshchi et al. (2005) compared a group of healthy, relatively lean women eating a breakfast
cereal either shortly upon awakening or around lunchtime during a weight maintenance diet.
This study confirmed that postponing breakfast does not affect resting energy expenditure,
the thermic effect of food, hunger levels or body composition.

As such, fasting without calorie reduction does not result in fat loss, which is to be expected
from the laws of thermodynamics.

Self-reported compliance in the free-living part of the study was similar between groups.
However, compliance must have been worse in the fasting group, because they ended up
eating significantly more calories. The fasting group also developed slight insulin resistance
and their LDL cholesterol increased. The authors attributed this to the fasting, but it’s
probable that both effects were because of snacking, and therefore an irregular meal pattern,

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in the fasting group, since this metabolic response is typical of irregular eating as discussed
earlier.

Taylor & Garrow (2001) are sometimes cited during discussions about intermittent fasting,
but in this study the meal frequency and presence of fasting where randomly alternated on a
daily basis, resulting in a chronically irregular meal pattern and confounding the effects of the
meal frequency and fasting. Still, it’s worth noting that again no difference was found for
energy intake or expenditure or the thermic effect of food. In other words, intermittent
fasting does not affect your metabolism.

The above research was again in women. However, Kobayashi et al. (2014) and the Bath
Breakfast Project replicated many of these findings in men and added some more:
intermittent morning fasting does not affect basal metabolic rate, thyroid hormones (T3 and
T4), body composition (measured by DXA), glycemic or cardiovascular health or appetite
hormones (leptin, total ghrelin, acylated ghrelin, peptide YY, glucagon-like peptide 1, and
adiponectin).

Overall, most research indicates that whether you eat breakfast or not, as long as you do it
consitently, has no special effect on your body composition.

Fasting and muscle growth

Opponents of intermittent fasting tend to portray intermittent fasting as highly unnatural and
extremely bad for your physique. Yet the above studies have already shown us that
intermittent morning fasting often does not negatively affect your body composition
compared to regular diets.

And a different type of fasting may even be beneficial for your body composition. Alternate
day fasting may preserve muscle mass compared to diets with the same caloric intake every
day. This suggests the effects of short and long term fasting are different. Basically,
intermittent morning fasting really isn’t that special for the body from an evolutionary
perspective. Many people in the intermittent fasting crowd obsess over if they should extend
the overnight fast to 10 or 11 hours. The physiological response for your body composition
between those scenarios is virtually identical. As a frame of reference, the longest successful

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weight loss fast lasted more than a year. It is only when you’re fasting for long periods, well
beyond what you’d naturally be inclined to do, that fasting will start to change the signals for
muscle growth.

The first negative effects of intermittent morning fasting seem to occur around the 20 hour
mark. Fasting for 20 hours decreases resting energy expenditure and mTOR signaling, an
important form of anabolic gene expression. This would suggest 20+ hour fasts may
negatively affect your muscle mass and fat loss. However, weight loss, protein balance,
thyroid activity and glucose and insulin metabolism were not yet affected. The decrease in
energy expenditure was only 59 calories compared to the regular diet, but the subjects were
kept in the lab throughout this entire period for repeated blood testing. It is plausible that
fasting for these periods decreases energy expenditure considerably more in free-living
conditions, as we’ll discuss below. The decrease in mTOR activity may also be more relevant
in more advanced, strength training individuals.

Research on Ramadan fasting, where people fast as long as the sun is up, also generally finds
negative effects on athletic performance, though the effects are actually slight and
confounded by poor study designs and fluid restriction.

As a practical upper limit for intermittent fasting, Martin Berkhan’s 16 hour fasting period is
a good guideline. In Menno’s experience with clients, shorter fasts are often better tolerated.

You may wonder how the negative effects of 20 hour fasts can be reconciled with the
potentially muscle sparing effects of alternate day fasting. Varady’s review paper finding
muscle sparing effects of alternate day fasting was in overweight individuals, for whom
muscle retention should still be easy. The 20 hour fasting study was in lean individuals.
Combined with the fact that alternate day fasting by definition creates an irregular meal
frequency, it’s not advisable to implement true alternate day fasting in anyone but
overweight individuals that are still at the novice level in terms of bodybuilding.

Interim conclusion

Intermittent morning fasting generally does not have any different effects on your body
composition than a diet with regular breakfast consumption (but see the section below).

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Alternate day fasting, on the other hand, may actually improve muscle retention, but in
strength training and lean individuals, instead of true alternate day fasting, periods of protein
sparing modified fasting (PSMF) offer a safer alternative. A PSMF is a period where the
regular meal frequency is preserved, but the meals are reduced to the optimal protein intake
with a minimal intake of the other macros. The PSMF is a highly successful medical practice
for obese individuals with few complications, in contrast to what many lay individuals who
have never tried it often argue (more on this in the compliance topic). However, a PSMF
cannot be sustained without excessive muscle loss in leaner individuals. By implementing
short PSMF periods, such as on your rest days (more on this later), you can achieve rapid fat
loss and the benefits of fasting without excess muscle loss.

Fasting’s game changer: activity level

Before you conclude that intermittent morning fasting doesn’t ever change anything and it’s
purely a psychological question of whether to implement it or not, there’s a huge caveat. All
of the aforementioned research looking at the effect of postponing breakfast measured
energy expenditure in metabolic chambers or wards. Except the Bath Breakfast Project.
Here energy expenditure was measured in free-living conditions by linking the data from the
lab to combined heart rate/accelerometry, which can be worn across the chest so that
subjects can go about their daily lives during the study.

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Allowing the subjects to be active was a game changer. Now the early breakfast eating group
had a significantly higher energy expenditure. This was entirely due to a higher spontaneous
physical activity level. They also naturally increased their energy intake, but they burned all of
this energy off.

Betts et al. add, “cross-sectional studies have detected slightly higher self-reported overall
physical activity levels among breakfast eaters (39), and several recent cross-sectional studies
using accelerometry reported correlations between habitual breakfast consumption and
physical activity levels, particularly during the morning (40, 41).”

These results are in line with a randomized controlled trial from Tinsley et al. (2016). In this
study, the intermittent fasting group restricted their food intake to a 4 hour window on
their 4 weekly rest days. This resulted in significantly lower caloric intake than the non-
fasting group. In spite of consuming the same amount of protein and fewer calories, there
was no significant difference in fat loss, muscle growth or strength development between the
groups. The similar fat loss with a lower energy intake suggests that the fasting decreased
energy expenditure. However, it should be noted that while total protein intake was not
different between groups, relative to bodyweight, the fasting group only consumed 1 g/kg/d
compared to 1.4 g/kg/d in the non-fasting group. As such, this may have been the cause of
the lower energy expenditure, not (just) the fasting.

In conclusion, if you are active in the morning, you may be able to significantly increase your
energy expenditure by having an early breakfast. Intermittent morning fasting can thus
needlessly impair energy expenditure in active individuals.

Breakfast: the most important meal of the day... if you’re carb intolerant

Other than having a high activity level, there is another consideration when deciding whether
intermittent morning fasting is right for someone: their carb tolerance.

Intermittent fasting can be harmful for individuals with poor carb tolerance, because glucose
tolerance and muscle insulin sensitivity are higher in the morning than later in the day.
Corresponding with the circadian rhythm of glucose tolerance, in type 2 diabetics, not having

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breakfast impairs insulin production throughout the rest of the day, causing greater increases
in blood sugar after lunch and dinner (postprandial hyperglycemia) than when breakfast was
consumed [2]. In other words, a big breakfast improves glycemic control in type II diabetics.

Intermittent fasting’s negative effects on carb tolerance can impair not just your health but
also fat loss. Type 2 diabetics, both men and women, lose more weight and achieve better
health outcomes when eating only breakfast and lunch than when eating 6 meals a day. This
suggests they may still benefit from intermittent fasting, just not in the mornings. (However,
intermittent evening fasting is difficult to combine with optimal nutrient timing practices, as
we’ll see in the next course topics.)

Intermittent fasting’s negative effect on insulin-glucose dynamics is not just a concern for
type 2 diabetics, because the negative effects of intermittent fasting and poor carb tolerance
go both ways. Poor carb tolerance can make intermittent fasting problematic, but
intermittent morning fasting can in itself cause poor carb tolerance even in healthy
individuals. Specifically, in the Bath Breakfast Project blood sugar levels remained more stable
in the later part of the day in the group having an early breakfast and in Kobayashi’s study
blood sugar levels were also on average higher.

Ironically, intermittent fasting zealots tend to name improved insulin sensitivity as a major
benefit. This is only true in uncontrolled settings where fasting causes fat loss, which then
improves insulin sensitivity. The overall literature on fasting and insulin sensitivity is not very
favorable. Intermittent fasting is generally bad or neutral for insulin sensitivity.

Intermittent fasting’s negative effects in individuals with poor carb tolerance are not just
theoretical. Overweight women lose more fat if they have a big breakfast instead of a big
dinner. This finding is supported by a long term prospective cohort study.

A study in overweight female homemakers also found that having most of the day’s calories
in the AM led to greater fat loss than having most of the day’s calories in the PM. The image
below shows the diet calorie and macro distributions (spelling error courtesy of the
authors).

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Of course, intermittent morning fasting does not rule out a big breakfast: you just consume
the breakfast later in the day. However, given the circadian rhythm of glucose tolerance, this
may not suffice. A different study found that overweight women lose more weight and
achieve a greater improvement in carb tolerance when consuming 50% of their energy intake
at lunch compared to at dinner with the same daily total macronutrient intake. In this study,
both groups consumed an early morning breakfast, but since intermittent morning fasting
inherently shifts energy intake towards dinner, it still suggests that intermittent fasting is not
always a good idea for overweight individuals.

The question remains how intermittent fasting reduces fat loss in overweight women and
type II diabetics. Since several studies reported similar macronutrient intakes between
groups, the mechanism may well be physiological. We know that poor carb tolerance can
impair nutrient partitioning, particularly that of carbohydrates, so that even given the same
energy intake, there is less fat loss or more fat gain than when the body releases appropriate
amounts of insulin to keep blood sugar levels under control (see the course topic on carb
tolerance).

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However, it is also likely that at least part of the reason for intermittent fasting’s slower fat
loss in these studies is psychological. As you should know by now, insulin is an acutely
appetite suppressing hormone, so the lower insulin production and greater fluctuations in
blood glucose levels during intermittent fasting in individuals with poor carb tolerance may
increase their appetite and thereby, unintentionally, their energy intake.

Type 2 diabetics tend to automatically eat less after a large compared to a small breakfast.
Other research has also found that a high protein intake at breakfast is more satiating than
that same protein consumed at other times of the day, at least in overweight individuals [2].

If the increased energy intake is primarly a result of impulsive snacking, this does not easily
show up in self-reported food logs.

For example, in Jakubowicz (2013)’s study, the compliance criteria were quite lenient and
the lack of statistically significant differences in overall compliance rate, based on occasional
self-reported food logs and interviews, wasn’t very convincing. “Dropout from the study was
mainly because of poor ability to follow dietary instructions. In the breakfast group eight
(17%) dropped out and 38 completed the study, whereas form the dinner group 11 (23%)
dropped out and 36 completed the study. Noncompliance of energy intake in drop-outs was
significantly greater only in the dinner group, whereas weight loss was significantly greater in
patients who completed the study in both group (data not shown).” This strongly suggests
that the main reason the big breakfast eaters lost more fat is simply because they consumed
fewer calories. Even so, better appetite control is still a valid reason to avoid intermittent
fasting.

In the controlled study on overweight female homemakers, no compliance data were

reported, but the authors concluded that improved satiety and thereby better diet
compliance was indeed the likely reason that the bigger breakfast group lost more fat.

Moreover, as you can see in the bar graph below, the meals and in particular the snacks
were highly unbalanced in terms of macronutrients. As we saw in the course topic on
protein intake, the leucine threshold may thus be responsible for the different group results

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if the bigger breakfast group consumed a more equal protein distribution. With barely
sufficient protein intakes of 0.9 and 1 g/kg/d, this is a significant confounder.

All in all, the evidence demonstrates that intermittent fasting is generally not a good idea for
individuals with indications of poor carb tolerance, particularly overweight women and type
2 diabetics. For these individuals, the conventional wisdom to eat a large breakfast seems to
be sound advice. That said, intense exercise is so good at improving insulin sensitivity that in
exercising individuals the relevance of the greater insulin sensitivity in the morning is very
slight. As such, a high training frequency can make intermittent fasting more tolerable. And
to emphasize: lean, strength trained individuals with normal carb tolerance don’t need to
have an early breakfast for normal glucose control and should have no problems with
intermittent fasting.

Fasting for women

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It’s worth noting that there appears to be a gender difference in tolerance to fasting.
Anecdotally, women don’t mentally tolerate fasting as well as men and most of the research
finding negative effects of intermittent fasting is in women. Halsey et al. (2012) specifically
found that after morning fasting women are more likely to overeat later in the day than men.
This may be the reason that overweight women lose more weight and achieve a greater
improvement in carb tolerance when consuming 50% of their energy intake at lunch
compared to at dinner. However, in this particular study, as discussed before, the
macronutrients of both groups were the same, at least as assessed by self-reported food
diaries at the start and end of the study. Since these were overweight women not engaging
in strength training, an alternative explanation for the greater weight loss when consuming a
big lunch and smaller dinner may again be the negative interaction between intermittent
fasting and the circadian rhythm of glucose tolerance.

While evidence for physiologically harmful effects of intermittent fasting per se in women is
lacking, it is prudent to be more wary of intolerance to fasting in women and to advise
shorter fasting durations to women than to men.

Fasting and health

An abundance of research shows that intermittent fasting benefits your health. However,
this research is greatly confounded by fat loss. We know that fat loss is generally good for
your health, so any fat loss protocol, whether it’s intermittent fasting or the-big-breakfast-
diet, is expected to improve your health. Overall, the evidence of intermittent fasting’s
health benefits independent of energy restriction is weak.

There do seem to be some unique health benefits. For example, a study of modified
alternate day fasting found slightly higher SIRT3 levels, which are correlated with longevity
and may be protective against cancer.

Interestingly, some of the health benefits of fasting seem to be mediated by ketone

production. This makes sense, since we know that ketogenic diets provide unique health
benefits (see course topic on ketogenic diets).

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If you’re particularly interested in the health effects of fasting, read Bojan’s thesis: The effects
of intermittent fasting on human and animal health – a systematic review (scroll down to the
thesis).

Conclusion

If intermittent fasting got you out of the bro-age of eating 6 meals a day, carrying around
protein powder and Tupperware containers wherever you went, intermittent fasting will feel
like the holy grail of easy dieting. However, for people used to a regular 3-meals-a-day diet,
intermittent fasting can be difficult to adjust to. Objectively, the physiological responses to
intermittent morning fasting and having an early breakfast are not large. There are no
intrinsic metabolic differences up to fasting periods of at least 20 hours, though at that point
muscle growth may be adversely affected. Intermittent fasting can be slightly detrimental to
someone’s insulin sensitivity and it has the potential to seriously limit spontaneous physical
activity and mental energy levels. Hunger levels are generally not affected, but compliance is
worse in many people, especially women and individuals with poor carb tolerance.

The table below summarizes when intermittent morning fasting is suitable for a person.
These criteria generally make intermittent fasting particularly suitable for male office
workers and particularly unsuitable for in-gym personal trainers and overweight women.

Indications Contraindications
Susceptibility to depressive eating Being active in the morning
Having social meals in the evenings with Susceptibility to impulsive eating
non-lifters
(Pre-)metabolic syndrome and indications of
poor carb tolerance

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Alternate day fasting has a better track record in research, but it is not recommended for
lean or strength training individuals. Instead, when alterante day fasting is desired, periods of
PSMFing are advisable to create a large but short term energy deficit while preserving muscle
mass (or growth).

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Meal frequency

In the course topic on protein you already learned that meal frequency per se does not
affect protein balance or energy expenditure. It is only the distribution of nutrients across
the day that matters. Obviously, meal frequency and nutrient distribution are interrelated,
since having a meal creates the presence of nutrients.

In the lecture we discussed the Iwao (1996) boxer study showing improved muscle retention
and a greater decrease in skinfold measurements during a crash diet with 6 compared to 2
meals a day. This study has several key limitations.
 The 1200 kcal liquid crash diet with only 61 g protein makes it questionable if the
results can be extrapolated to less starvation like situations. Liquid meals may not
sustain postprandial protein balance long enough for maximal protein balance across
the day due to their unnaturally fast absorption speed. More substantial meals with
fiber, unprocessed protein and fat make it far easier for the body to regulate protein
balance.
 The subjects were boxers that performed their regular ‘physical training and boxing
exercises’ for 2 hours a day. The 2 meal group ate only at 9 AM and 9 PM. Since
boxing is extremely energy intensive and it’s likely the exercise took place
somewhere along the day, the thus fasted training condition for this type of exercise
may well have been the reason for the greater muscle loss. Unfortunately, no details
or measurements were provided for the physical training, though somehow the
authors feel confident to state in the discussion that the training burned 800 kcal.

Even in these conditions, resting (!) energy expenditure did not differ between the groups
either before or after the diet. However, there was a non-significant trend for greater
energy expenditure in the 6 meal group after the diet, which is to be expected given the
greater muscle retention.

We also discussed the sponsored Arciero et al. (2013) study showing improved body
recomposition and thermogenesis on 6 compared to 3 meals a day. Their study design is
summarized below.

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TEF was higher in the 6 compared to the 3 meal group. This stands in contrast with an
abundance of other research that finds meal frequency per se does not affect energy
expenditure or fat loss [2, 3]. This discrepancy is likely because the 6 meal group ate 3
additional meals that consisted almost purely of protein supplements from the study
sponsor. As you learned in the course section on the TEF, isolated protein has a high TEF,
especially in comparison to the processed foods from the rest of the diet, which included
“no-sugar-added applesauce and other American Heart Association approved cereals and
granola bars”. As such, it’s no surprise that the TEF relative to caloric intake was higher for
the protein snack in the 6 day group than the regular processed meal of the 3 day group.
Also, the TEF was only measured at 1 time point and resting energy expenditure did not
differ between groups, so the higher TEF value may also simply have been a biorhythm effect
without actually higher total thermogenesis across the day.

The higher TEF, if not an artefact, could explain the greater fat loss. The improved muscle
growth and retention rates, however, must have a different reason. Again other research
strongly suggests that the meal frequency per se was not the reason, since meal frequency
does not affect protein balance. However, just like in the boxer study, it may actually be that
meal frequency does affect protein balance in the conditions of this study due to the highly
processed and liquid nature of the meals. The fast absorption speed of the food may
necessitate a high meal frequency to sustain postprandial anabolism, i.e. keep protein balance
high throughout the day.

Alternatively, the 6 meal group had an additional high protein meal pre-bed. This may have
improved circadian rhythm protein timing. This fits with the higher leptin levels found in the
6 meal group (see circadian rhythm carbohydrate timing section below).

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Based on the above studies, you may still be inclined to favor a higher meal frequency.
However, the best research we have shows that the bro rule of eating 6 meals a day is
actually detrimental compared to a more moderate meal frequency.

Enter The Meal Frequency Project from Norway. Finally research with direct real world
relevance: experienced subjects performed controlled strength training while eating a high
protein diet, the study duration was relatively long (12 weeks) and the subjects tracked their
macros during either 3 or 6 meals a day. Surprisingly to many, the 3 meal group gained
significantly more strength and muscle mass after controlling for confounding variables. The
research wasn’t as well controlled as we’d like from scientific research and it’s hard to
explain why 3 meals would lead to more anabolism than 6 meals, but the data are there.
Possible explanations include the leucine threshold, which may require a higher protein
intake per meal to create a clear signal for muscle protein synthesis, and workout nutrition
timing (discussed in its separate course topic).

Another study in elite rugby athletes found no effect of eating 4 vs. 6 meals a day on muscle
growth, although the diets in this study were evidently poorly controlled: the standard
deviation of protein intake was a whopping 0.6 g/kg/d in one group.

Conclusion

Most research suggests that meal frequency per se does not affect energy expenditure or
protein balance and it thus does not matter over how many meals a day you distribute your
macros. However, the limited research we have suggests that 2 meals a day may not suffice
for maximal results during strength training, at least not when cutting. Additionally, The Meal
Frequency Project shows that 3 meals a day may be superior to 6 meals a day, at least when
bulking. As such, meal frequencies of 3 – 5 meals a day are recommended for optimal body
recomposition.

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Circadian rhythm protein timing

CRPT is a form of nutrient timing, specifically protein timing, relative to your circadian
rhythm AKA your biological clock. Simply put, CRPT just refers to how you spread your
protein intake over the day.

Let’s look at the research on protein timing within a day. The following studies all controlled
for daily protein and energy intake.

Burk et al. (2009) used a long term cross-over design to compare 2 groups of men
performing serious resistance training and eating a diet containing more than sufficient
protein. The only difference between the groups was the timing of a protein supplement
containing 70 grams of protein. One group received it 8 hours after awakening, closely
before their workouts, and the other group received it 90 minutes before going to sleep.
The group receiving the protein later in the day gained significantly more muscle mass than
the group receiving it at midday and lost fat to boot.

So, not only can CRPT be beneficial, it cannot be said that nutrient timing is strictly less
important than energy intake or that nutrient timing is below energy intake in the hierarchy

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of dietary importance. It’s not that simple. Improved nutrient partitioning can significantly
change the effects of a given macro intake. So even if you train hard and eat the right things,
eating them at the wrong time can seriously limit your progression.

Keim and bros (1997) used a long term cross-over design to compare two groups on a
weight loss diet in a metabolic ward. The only difference between the groups was when
most of the food was consumed. One group consumed 70% of their total energy intake in
the AM and the other group consumed 70% of their total energy intake in the PM. Both
groups got up before 08:00 h. Both groups performed the same exercise program:

 30-54 minutes of treadmill or cycling cardio at 65 – 70% of V˙O2max in between

09:00 – 11:30 h 5x per week
 a whole body strength training circuit also in between 09:00 – 11:30 h 3x per week
 outdoor walking at 4.8 – 6.4 km/h in between 1330 and 1430 h every day

The PM group had better muscle retention during the diet and a higher reduction in body fat
percentage than the AM group. See the infographic below.

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That’s 2 well controlled studies in favor of eating much of your daily protein intake later in
the day. However, these studies cannot tell us if it was the energy or just the protein timing
that caused the positive effects.

Enter Jordan et al. (2010). These white-coat-wearing amigos compared two groups receiving
a carbohydrate and a protein beverage at breakfast and post-workout about 10 hours after
waking up. They measured nitrogen balance, a measure of daily protein balance and lean
tissue growth. One group received the carbs at breakfast and the protein later in the day
and the other group received the carbs later in the day and the protein at breakfast. The
group receiving the protein later in the day had a significantly more positive nitrogen balance
than the group receiving the protein at breakfast. Because the study authors controlled for
carb and therefore energy timing, only the protein timing could have caused this difference.
The most remarkable thing about this study is that the protein beverage only contained 15
grams of protein in a diet containing more than sufficient protein and still they found a
significant effect. See the infographic below.

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Putting the CR in CRPT

How do we explain these results? One explanation is that it’s better to spread out your
protein intake over the day. However, this theory would also predict that increasing meal
frequency would result in greater protein balance and we know that’s not true.

A possible interpretation is that protein timing relative to your workouts is what it’s
important, regardless of what time of day this is. This interpretation will be discussed in the
course topic on workout nutrition. Suffice to say for now though, the significance of these
findings is hard to reconcile with the close timing of the workout nutrition in these studies in

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untrained individuals. The anabolic window should last at least 48 hours here and the training
sessions were already sandwiched by meals. Moreover, in Keim et al. the AM meal was
actually the post-workout meal rather than the PM meal and in Burk et al. the early meal
was consumed pre-workout, closer to the actual workout than the pre-bed meal. So we can
at least conclude that it’s not simply a factor of consuming your protein or meals closer to
your workouts.

So maybe it’s not the anabolic window and there is another period where the real magic (get
it? Real magic) happens. It’s called sleep.

There is natural diurnal (daily) variation in anabolic hormones like growth hormone and
testosterone. Care should always be taken to interpret transitive changes in these hormone
concentrations, as this kind of reasoning forms the basis for most broscience, but in the case
of the circadian rhythm the changes aren’t insignificant. The variation occurs day in, day out
and is large relative to the mean. Look at the graph below, which shows how growth
hormone fluctuates every day for people sleeping between midnight (00:00 h) and 08:00 h:
you produce most of your growth hormone at night.

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Having a royal supply of amino acids in your blood between 21:00 and 09:00 may be a pretty
good idea to put that growth hormone to use. The same holds for testosterone, which is
shown in the graph below: you produce most of your testosterone at night.

Sleep is like restoration mode for your body, so the advice not to eat before bed doesn’t
make much sense, especially not in strength training individuals that need their recovery
time. As a recent study showed, “protein ingested immediately before sleep is effectively
digested and absorbed, thereby stimulating muscle protein synthesis and improving whole-
body protein balance during postexercise overnight recovery” with the result of promoting
muscle growth.

Also, protein consumed pre-bed does not seem to impair overnight fat burning [2]. Since
any type of energy consumption typically impairs fat oxidation, this suggests a nutrient
partitioning benefit for pre-bed protein. Sleep quality is typically unaffected as well by pre-
bed protein consumption.

In the worst case scenario, consuming protein pre-bed is generally still at least as beneficial
at any other time of day.

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Conclusion

Energy intake and macros are far from all that matters in a diet and can’t be considered
strictly more important than nutrient timing. CRPT, the timing of your protein intake over
the day, may be important in itself. There is still much that needs clarification by future
research, but all current evidence points in the direction that you should consume a
significant amount of your daily protein intake later in the day.

Take home message: Consume at least a single meal with a good portion of protein (i.e.
above the leucine threshold) in the hours before going to sleep to fuel overnight anabolism.

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Circadian rhythm carbohydrate timing

How carbohydrates should be timed across the day is a controversial topic. Conventional
wisdom is that eating late at night makes you fat, but this is due to looking cross-sectionally
at people that eat late night snacks versus people with a more stable and often healthier
lifestyle. Just like breakfast isn’t nearly as important as conventional wisdom suggests, cross-
sectional research also can’t tell us anything definitive about the detrimental effect of eating
late at night. Obviously binging on junk food at night can make you fat, but this is not
comparable to programming regular meals close to bedtime.

In fact, there are good physiological reasons as to why it may actually be beneficial for
strength trainees to ‘backload’ their carbs, as John Kiefer popularized. Insulin’s action may be
more anabolic, leptin’s circadian rhythm may be set more favorably and sleep quality may
improve via the production of more melatonin. These things can improve nutrient
partitioning and thus improve your body composition even at the same macros.

In support of this, Sofer et al. (2011) showed that the timing of carbohydrate can significantly
impact your body composition. Eating carbohydrates mostly at dinner compared to spread
across the day had several positive health effects.
 Greater weight loss with a trend for greater decreases in abdominal circumference
and body fat percentage.
 A greater decrease in fasting insulin levels with a trend towards improved insulin
sensitivity and fasting glucose levels (likely better carb tolerance).
 A greater increase in HDL (‘good’) cholesterol.
 A greater decrease in tumor necrosis factor-α (TNF-α), a marker of inflammation,
with non-sigificantly greater improvements in the other inflammation markers as well
(interleukin-6 (IL-6) and C-reactive protein (CRP)).

All of the health and nutrient partitioning related variables could simply be the result of the
greater fat loss, since the subjects were overweight. However, the study also found that the
circadian rhythm of the 2 hormones leptin and adiponectin changed as a result of the
carbohydrate timing. There was a trend for a lower reduction in leptin levels in the carbs-at-
night group and in this group adiponectin levels actually increased as a result of the diet.

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Normally leptin and adiponectin decrease in proportion with fat loss, since they are secreted
by adipose tissue (fat), so it must have been the carb timing that altered their levels. Leptin
and adiponectin are very beneficial hormones for fat loss. Leptin is a strong appetite
suppressor and adiponectin can improve carb tolerance, inflammation, energy expenditure,
nutrient partitioning and satiety, especially together with leptin. So the more your body
produces of these hormones, the easier it is to lose fat, generally speaking. And indeed, the
late-carb eating subjects were less hungry during the study. See the graph below for the data.

(Remember that the 6-meal group with a pre-bed protein meal was also found to increase
leptin levels by Arciero et al. from the meal frequency topic.)

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Moreover, the daily secretion pattern of leptin and adiponectin changed. Leptin levels were
higher at daytime compared to at breakfast and in the evening. Adiponectin levels also
primarily increased at noon and the afternoon. Both levels decreased in the evening with a
spike in ghrelin levels (‘the hunger hormone’). The authors noted this pattern of hunger
hormones may improve dietary compliance, because hunger levels coincided with the large
dinner. So by consuming your carbohydrates mostly at dinner, you may synchronize your
appetite’s circadian rhythm better to your actual meal times, whereas when you eat your
carbohydrates throughout the day, you may end up hungrier throughout the day. For many
people it can also be inherently beneficial to be hungry during daytime hours, as most people
are occupied with work at those hours. See the graphs below if you’re interested in the
circadian rhythm specifics.

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As impressive as the benefits of late-carb-eating may look on paper, the absolute effects are
small and almost certainly smaller than the effects of protein timing, as you saw in the article
on CRPT. Weight loss was only 2 kg greater after 6 months and the difference in body fat
percentage loss was less than 2%. So carbohydrate timing is true finetuning of the diet.
However, the reduction in hunger can be exceedingly variable. As we’ll discuss in the topic
on compliance, appetite suppression solves most diet adherence problems.

Moreover, as we’ll see in the course topic on sleep, consuming a high carbohydrate meal in
the hours before going to bed can improve sleep quality by i.a. promoting melatonin
production.

So given that consuming a relatively high amount of carbohydrate pre-bed likely benefits
mood, compliance and fat loss all at the same time, there is no reason not to implement
carbohydrate timing in most diets. This means the evening meal(s) should typically contain
more carbohydrate than the morning meal(s), unless exercise, especially endurance exercise,
is performed in the morning.

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Circadian rhythm fat timing

Unfortunately, there is a major scarcity of research on the effects of fat timing. Based on the
research we have, fat appears to be the least time sensitive macronutrient. Its absorption is
slow and relatively unaffected by the circadian rhythms of insulin and glucose. The research
discussed in the previous topics also generally shows that the effect of carbohydrate or
protein timing still apply even when fat timing was also altered. This indicates that when you
consume your fats in the day is relatively unimportant.

For example, Jakubowicz et al. (2012) found that groups with a high carb or a high fat
breakfast lost just as much fat and weight. However, the high carb breakfast group was more
satiated after breakfast and across the study period as a whole.
An important confounder in this study is that the high carb group consumed more protein
and calories at breakfast, as you can see in the table below, though they consumed less
protein in total.
Another confounder is that with the very low carb intake in the high fat breakfast group,
they almost certainly didn’t consume enough fiber. Given that we know how important fiber,
calories and protein are, specifically at breakfast for overweight individuals (see the course
sections on fiber and intermittent fasting), this study mainly just shows that the timing of fat
is not ás important and this study cannot tell us anything about the timing of fat intake per
se.

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Combining fats and carbs?

In the above sections you learned that carbohydrates and fat may have better nutrient
partitioning at different times of day. Upon realizing this, some people take this to extremes
and suggest we should never combine fats and carbs in the same meal. Should you? Based on
the course contents thus far, you should be able to answer this.

The answer is you should absolutely not completely separate carbs and fats from each other
in your meals. Dissocating carbs from fats in your meals does not result in greater fat loss
than consuming all 3 macronutrients within each meal. There are in fact several good
reasons why you want to combine all 3 macronutrients in each meal.
 As you learned in the course topic on protein, certain whole foods like milk can have
synergistic nutrient compositions that make the whole food more effective at
increasing protein balance than you would expect from its macronutrient
composition.
 As you learned in the course topic on human metabolism, balanced meals increase
your metabolism (DIT) more than you would expect based on their macronutrient
composition.
 Plus, we have the evolutionary argument. Many whole foods have all 3
macronutrients. Not metabolizing such foods optimally would be a hugely
disadvantageous trait that should be eliminated from the gene pool via natural
selection.

So nutrient timing isn’t a matter of excluding certain macros at certain times of day. It’s
about the ratios. Circadian rhythm carbohydrate timing doesn’t require you to completely
avoid carbs in the morning and save all your carbs for the later part of the day. It’s about the
macro ratios in your meals and the distribution of your macros across the day.

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As a recap of some of this week’s course contents, the following lecture discusses fasting
and circadian rhythms.

lecture
Intermittent fasting and circadian rhythms

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