Tag Archives: energy balance

Missing: 300 kilocalories

or
Weight-loss maintenance, part II (as promised)

Effects of dietary composition on energy expenditure during weight-loss maintenance (Ebbeling et al., 2012)

A three-way crossover study!  Excellent study design.  In brief, the participants lost 30 pounds in 12 weeks on a pseudo-Zone diet (the official version) consisting of 45% carbs, 30% fat, and 25% protein, then switched to one of 3 “weight-loss maintenance” diets for 4 weeks.  (FTR “weight-loss maintenance” cannot even be remotely assessed in 4 weeks, but what the heck, it was a THREE-WAY CROSSOVER.)

To put the issue to bed before it is even raised, the volunteers were given professionally prepared food for about half a year and paid ~$2,500 if they stuck to the plan.  They STUCK to the plan.

or more simply: 

The diets were classified by the authors as high glycemic load (high carb low fat), low glycemic index (e.g., Mediterranean Diet), & low carb (e.g., Atkins Diet).

These “glycemic” indices in general are primarily determined by the carb & fat contents.  A low carb diet will always have a low glycemic index and low glycemic load, and the opposite is true for a low fat high carb diet.  Any high glycemic index food turns into a low glycemic index meal when it’s combined with other foods (like we normally eat).  The only way to make a strictly high GI diet is with low fat; the easiest way to make a low GI diet is with low carb.

The major outcome measurements dealt with energy expenditure, with the premise being that preservation of metabolic rate after weight loss should improve “weight-loss maintenance.”

Resting energy expenditure (REE) is measured by indirect calorimetry.  It’s the amount of calories that a total couch potato would burn daily and is usually determined by body composition (more muscle = higher REE).  While body composition was similar in each group, REE was modestly higher in subjects on the low carb diet.

RQ (respiratory quotient) measures the relative amount of fat and carbs you’re burning: 0.7 = fat oxidation; 1.0 = carb oxidation.  It is determined by diet (eat more carbs, burn more carbs), body composition (have more body fat, burn more body fat), and exercise intensity (marathons burn fat; sprints burn carbs).  The higher carb oxidation on the low fat diet and higher fat oxidation on the low carb diet likely reflect the respective dietary compositions.

 

 

Total energy expenditure (TEE) is exactly what its name implies.  It’s the total amount of calories you burn in a day.  If your body weight is stable, then this is also approximately how many calories you’re eating.  This result is actually pretty interesting.  TEE on the low carb diet was over 300 kcal higher relative to the low fat diet.  This is probably at least partially due to the higher protein content of the diet (30% vs. 20% of total calories or 150 vs. 100 grams per day).  TEE of the intermediate low GI diet was in between low fat and low carb diets (2937 kcal/d), so TEE increased as carb intake declined and fat intake increased across all 3 diet groups.  Follow the blue boxes in the figure below to see the averages, and since this was a THREE-WAY CROSSOVER (!), you can follow the lines to see how each person fared individually:

300 kcal is equivalent to an hour of exercise, yet subjects on low carb weren’t exercising more (although the slowly-losing-his-wits-Dr Bray suggested otherwise in an editorial, arguing that the increased TEE/REE ratio meant increased physical activity, despite the actual data, which showed if anything, slightly lower total and moderate-vigorous intensity physical activity in the low carb group).

Burning an additional 300 kcal per day is like losing over 2 pounds of fat per month by doing exactly nothing.  BUT

to be clear (e.g., disclaimer, mea culpa, evidence of heresy, etc.):

  1. all participants in the study ate the same amount of calories
  2. low carbers burned over 300 more calories per day compared to low fat dieters
  3. body composition  and body weight were similar between the groups

300 calories per day is a LOT of calories, why didn’t it impact weight loss?

This seemingly paradoxical conclusion suggests energy intake is the primary determinant of weight loss, independent of energy expenditure and diet composition.  It is either a violation of The Laws of Energy Balance, experimental error, or evidence of dark magic.

Moving on,

the authors were quick to note urinary cortisol (an anti-inflammatory and stress hormone) and CRP (a marker of systemic inflammation) were highest on low carb, and this could cause insulin resistance.  However, I’d note 2 things: 1) CRP declined in ALL groups relative to baseline, but the reduction was less in low carbers compared to the other groups; and 2) CRP was low and within the normal range in all subjects throughout the entire study. But most importantly, hepatic and peripheral insulin sensitivity improved most in low carbers, in whom CRP and cortisol was the highest.

Similar to the Jakubowicz study (dessert for breakfast), the Ebbeling study was interesting but not groundbreaking; nothing to write home about.  Both showed modest benefits for low carb over low fat.  The news media haven’t feasted on these studies yet, but when they do, however, I’m sure they’ll disagree.  “Weight-loss maintenance” is a riddle wrapped in a mystery inside an enigma, not a simple question to be elucidated by a mere 4-week diet study, even if it’s a three-way crossover.  even if it has dark magic.

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calories proper

 

 

 

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Resveratrol, energy balance, and another reason to distrust health journalism, Op. 79


The great red wine compound “resveratrol,” at it again.  Disclaimer: 150 mg of resveratrol per day is too low and 30 days is too short to detect anything close to what was seen in the infamous resveratrol mouse study (Baur et al., 2006 Nature), which showed resveratrol to be the best drug ever on the planet.

This study, on the other hand, utilized the highest quality study design and was published in a great journal, but was a flop.   And the media got it wrong too:  “Resveratrol holds key to reducing obesity and associated risks.”  No, it doesn’t.

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans (Timmers et al., 2011 Cell Metabolism)

The study design was pristine.  Kudos.

Sample size too small (n=11) and study duration too short (30 days), but it was a randomized, double-blind, placebo-controlled, crossover study.  And although this type of drug study does not require such a thorough assessment of compliance (a pill count would’ve sufficed), the authors tested blood levels of resveratrol and its metabolites… cool.

On the docket: resVida, DSM Nutritional Products, Ltd.

Divide and conquer

The table above shows baseline characteristics in placebo and treatment groups, but this is peculiar because although the study was randomized (which is confirmed by the high degree of similarity between the two groups), it was also a crossover.

Brief review of my Prelude to a Crossover series (I  & II):

phase 1) half the subjects get drug and half gets placebo

phase 2) both groups get nothing for a washout period

phase 3) everybody switches and gets the other treatment

There are technically two baseline periods (before phase 1 and before phase 2), and all the subjects are in both.  As such, there is only one set of baseline values, so I’m not sure what the data in the above chart actually reflect.  Is this a mistake? or are these data only representative of one of the treatment sessions (which would be an egregious insult to the prestigious crossover design).

In any case, the subjects were all clinically obese, ~100 kg (220 pounds), BMI > 30, body fat > 25%, but otherwise metabolically healthy (fasting glucose levels of < 100 mg/dL).

But here’s where it starts going from technically flawed to weird:

Insulin levels may have been statistically significantly lower after resveratrol compared to placebo, but not after considering baseline insulin was ~15-16 mU in both groups.

insulin proper

The authors noted that after treatment, insulin levels were 14% lower in resveratrol compared to placebo (green circle).  BUT whatever was in that placebo pill was almost twice as good!  The placebo reduced insulin levels by 27% (red circle)!  (take THAT!)  I’m glad the authors reported these data instead of burying them, but they illustrate yet another flaw.

150 mg resveratrol (10-15 bottles of red wine) for a 220 pound person = 1.5 mg/kg; 200x less than what Baur gave his mice (300 mg/kg). Interestingly, however, this produced plasma levels of resveratrol almost 3x higher (180 vs. 65 ng/mL). I have no idea how this happened, but the benefits and lack of toxicity [at such a low dose] bode well for recreational resveratrol supplementation.

As mentioned above, resveratrol was totally safe, but how to interpret this is unclear.  Our options are: 1) good; 2) meaningless; or 3) simply not bad (which I suppose is kind-of-like #2).  It could be interpreted as meaningless because resveratrol, the anti-aging drug, is meant to be taken for a very VERY long time (i.e., forever).  This study proved that resveratrol was safe when taken for 30 days which is considerably shorter than forever.

Furthermore, the dose was phenomenally low, ~150 mg/d, so anything other than “totally safe” would be a huge red flag.

Does resveratrol in fact mimic calorie restriction, as stated in the title?  During calorie restriction, food intake declines (by definition), metabolic rate and insulin levels also decline, but free fatty acids and fat oxidation increases.  In the resveratrol group metabolic rate and insulin declined (recall however that the placebo was pretty impressive also in this regard), but free fatty acids and fat oxidation decreased.  Although proper calorie restriction trials in humans haven’t happened yet, some of these  effects don’t jive.  A decline in metabolic rate will reduce the amount of fat burned.  But relative fat oxidation also declined, leading to what could be a profound reduction in fat burning… coupled with no change in food intake (noted by the authors) this will result in increased fat mass.  Energy Balance 101- no ifs, ands, or buts.  This study was far too short-term to detect a meaningful increase in fat mass, but if these preliminary findings are true (and my interpretation of the data are correct), then this drug might just make you fat.

Oddly enough, they did detect an increase in fat accumulation in skeletal muscle:

(perhaps instead of calling it a calorie restriction-mimetic, the authors should’ve gone with exercise-mimetic, citing the athlete’s paradox (e.g., van Loon and Goodpaster, 2006)

In contrast to the popular antidiabetic drug rosiglitazone, which shifts fat storage from liver (where it causes a host of health maladies), to adipose, where it can be stored safely indefinitely, resveratrol shifted fat storage from liver to skeletal muscle.  This is interesting because while the fat storage capacity of adipose is seemingly unlimited, I doubt the same is true for skeletal muscle, which needs to do a lot of stuff, like flex.

If these findings are true, which I seriously question, then it would be interesting to see what happens to skeletal muscle fat stores after a few months, considering they doubled in only 30 days (this is unbelievable, literally).

The authors try to make the case that the increased muscle fat came from adipose, but until they report body composition data, this is a tough sell.  The elevated fasting free fatty acids support their claim, but the accompaniment of unchanged meal-induced FFA suppression with lower adipose glycerol release don’t; perhaps the missing glycerol is being re-esterified to nascent adipose-derived free fatty acids?  Increased adipose tissue glucose uptake would be supported by the lower glucose levels, but that is already more-than-accounted for by the increased RQ (indicative of increased skeletal muscle glucose oxidation).

There are some mysteries in these findings, and the improper handling of crossover data do not help.  If this paper is true and my interpretation of the energy balance data are correct, resveratrol might just make you fat :/

Unless of course you’re a mouse, in which case it’ll make you better in every quantifiable measure.

calories proper

p.s. I don’t think resveratrol will really make you fat, I think this study elucidates nothing.

The curious perils of crappy sleep

Don’t try this at home

Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption (Buxton et al., 2012)

The most utterly abnormal sleep structure was studied- for 3 weeks, the subjects were subjected to: 1) a 28-hour day; 2) 6.5 hours of sleep per night (equivalent to 5.6 hours in a normal 24-hour day); and 3) dim lighting during the days.  This was done to completely destroy circadian rhythms, and accordingly, metabolic calamity ensued: insulin response went down and hyperglycemia went up (compare black to red bars). 

B, baseline; SRCD, sleep-restricted circadian-disrupted; R, recovery period

Other notable findings:

1) sleep-restricted subjects ate 6% more

2) their metabolic rate declined 8%

3) body temperature went down 0.09 degrees

All of these things point to one common endpoint: weight gain.  Indeed, the authors even concluded that sleep restriction and disrupted circadian rhythms should increase the risk of obesity… except for one thing: everyone in the study lost weight (1.7% of initial body weight).

 

…suspense…

 

How, you ask?  during the increased waking hours, physical activity actually went up (a LOT).  This may have been because the researchers didn’t recruit an average lot, or group of subjects who were generally representative of the population at large.  No, this was a highly selective group of “healthy people.”  And what do healthy people do when their awake?  It’s probably what they don’t do that matters.  Healthy people spend less time sitting around (in general).  Had the researchers recruited a group of overweight subjects with their X-Boxes, I imagine the increased food intake would not have been adequately balanced by increased physical activity and they would’ve gained weight.

like this guy

I do NOT recommend sleep restriction for weight loss.  Even though glucose metabolism was completely restored after 10 days of recovery (gray bars in the figure above), lingering signs of metabolic dysregulation were still apparent (scary).

RMR and leptin

Perhaps not necessarily video game junkies, but those who are otherwise at increased risk of developing obesity do tend to move around less during the day if they sleep less at night (in contrast to the very healthy people mentioned above).

Reduced physical activity in adults at risk for type 2 diabetes who curtail their sleep (Booth et al., 2012)

This is not a “very healthy” group of subjects; accordingly, those who slept <6 a night were 27% less physically active and spent over an hour more per day sitting around.  In this study, short sleepers weren’t obese [yet]; but they were predisposed to weight gain.  (even the media seems to agree with this one).

If you DID want to try sleep restriction for weight loss, and even vowed to decrease food intake (in contrast to the highly active subjects in Buxton’s study), the results still might not turn out so good…

Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss (Nedeltcheva et al., 2012)

In this study, food intake was intentionally reduced to a similar extent (-10%) in sleep restrictors and non-restrictors, and in agreement with Buxton, metabolic rate declined in sleep restrictors.  And although it was only measured at baseline, physical activity during sleep restriction must have increased because weight loss was similar in both groups.  But here’s the catch:  compared with those who slept 8.5 hours per night, the weight lost by those who slept 5.5 hours per night was primarily fat free mass (which is probably what caused their metabolic rate to go down), whereas it was primarily fat mass in those who got adequate sleep.  This finding alone is reason enough to get a good night’s sleep.

In sum:

Exhibit A, Buxton study: sleep-restricted HEALTHY people ate more but moved around WAY more during sleep restriction = weight loss.

Exhibit B, Booth study: those pre-disposed to obesity moved around LESS during sleep restriction = imminent weight gain.

Exhibit C, Nedeltcheva study: the weight lost by sleep restricted overweight dieters was comprised of muscle mass = not good.

In other words, if you think you’re a healthy person who wouldn’t sit around playing video games in your extra waking hours, or even if you promised not to eat more, the effects of sleep restriction on body composition wouldn’t be pretty (no pun intended).  Maybe you wouldn’t get fatter, but you’d probably get fattier.

 

calories proper