By Dr. Geoffrey Modest
One of the hardest tasks for us and our patients is maintaining weight loss in those who are overweight and obese. A recent NIH study looked at this issue, finding that people who had lost a lot of weight had long-term “metabolic adaptation” leading to a significant lowering of resting metabolic rate (RMR) and much less overall energy expenditure (see doi:10.1002/oby.21538 ). This study looked at 14 of the 16 “Biggest Loser” competitors from this televised weight-loss competition.
Details:
- Baseline: median age 35, 6 men/8 women, weight 149 kg, BMI 49.5
- At the end of the competition (30 weeks), through an aggressive program of diet and exercise, the mean weight loss was 58.3 kg, BMI deceased to 30, and the RMR decreased 610 kcal/day below baseline (this decrease in RMR was expected, as per a multitude of prior studies).
- The following hormone levels improved dramatically after weight loss (at 30 weeks): insulin, C-peptide, triglycerides, HDL, adiponectin, T3, leptin, and the calculated HOMA-IR (which correlates with insulin resistance)
- This weight loss was primarily from fat mass but with relative preservation of fat-free mass [likely from the intensive exercise training]
- After 6 years:
- Participants regained a mean of 41.0 kg (though wide variation: 1 person did not regain weight, though 5 were within 1% of their baseline weight or above), 80% of the weight gain was from fat However, 6 years later the RMR remained 704 kcal/d below baseline (actually non-significantly worse than the RMR after the remarkable initial weight loss), and metabolic adaptation was down 499 kcal/d [I believe this is basically RMR corrected for fat-free mass, but this was never clearly stated in the study]
- The metabolic adaptation at the end of the competition (30 weeks) correlated with the amount of weight loss, did not correlate with the ultimate weight regained, but it did improve some in those who regained the most weight (and metabolic adaptationdid not improve at all in those who maintained the weight loss, with a dose-response curve)
Commentary:
- Background: from the initial studies, the physiologic phenomenon of metabolic adaptation (also called “adaptive thermogenesis”, or AT) reflects the evolutionary imperative that the body readjusts to maximize efficiency in times of starvation by lowering energy expenditure. AT has been found to be independent of changes in fat-free mass and takes weeks to develop; in earlier studies it seemed to be independent of the magnitude of weight loss after reaching the peak of a 10% weight loss threshold (see Muller MJ. Obesity 2013; 21: 218). Adaptive thermogenesis is associated with a variety of changes related to decreases in resting and total energy expenditure, including decreased sympathetic nervous system activity, T3, and leptin. There are some early suggestions from animal studies that giving exogenous leptin restores at least some of the decreased RMR
- Many studies have shown that in the setting of starvation, the body in fact lowers its metabolism to conserve energy and weight. One perhaps interesting issue is the role of genetics (I have seen nothing to answer these questions in searching around on this). For example, is there a difference in the metabolic adaptation/changes in RMR in those who are overweight but coming from families with lots of obesity vs those where there is not an apparent genetic burden for obesity? Overall, obese individuals are more likely to have lower RMR from several studies, but are those who are lean at baseline but have a lower RMR more likely to develop obesity than those with a higher RMR? Not so clear. At least some studies suggest that eating leads to thermogenesis (i.e., it might be that even in those with low metabolic rates, eating increases their metabolic rates enough that they do not become obese; and, therefore, perhaps there is no causal effect of low metabolic rate and eventual obesity). In fact some small studies noting lower RMR in obese women found that the RMR was actually higher in obese women if one corrected for fat-free body mass (see Hoffmans M. Int J Obesity 1979;3(2):111). A bit of a bag of worms….
- Interestingly, bariatric surgery does not create the same issue of metabolic adaptation as does starvation: with surgery there seems to be an effective reset of the body’s weight set-point within a year of bariatric surgery, for unknown reasons (see Hao Z. Obesity (Silver Spring) 2016; 24: 654)
- There were a couple of interesting studies (both from the same group) suggesting that weight loss by a low glycemic diet causes less decrease in RMR:
- One found thatresting energy expenditure in overweight/obese young adults decreased much less with a low glycemic index diet (96 kcal/d, or 5.9%) vs a low fat diet (176 kcal/d, or 10.6%) [Those on low GI diet also had less hunger, improved insulin resistance, triglycerides, CRP and blood pressure]. See Pereira MA. JAMA 2004; 292: 2482
- This was confirmed in another study (see EbbelingJAMA 2012; 307: 2627), finding that isocaloric feeding led to decreases in resting energy expenditure of 205 kcal/d in a low fat diet, 166 kcal/d in a low-glycemic index diet and 138 kcal/d in a very low-carbohydrate diet. Total energy expenditure decreased 423, 297 and 97 kcal/d respectively.
- But, the bottom line from this study: at least in the case of those with severe morbid obesity (median BMI of 50), losing weight had the anticipated decrease in energy expenditure, but even 6 years later, this lowering of RMR through metabolic adaptation did not revert to their baseline. What does that mean? For one thing, it reinforces what many patients and clinicians know: losing weight is really hard to do, and if weight is lost, it is really really hard to keep it off in the long-term. Which doesn’t mean that we all should give up. Just that this understanding is really important, and we all (including patients) should really try to avoid the blame-game (some variant of “if you really want to lose weight, you can” morphing to “if you don’t lose weight, it reflects your lack of will-power, tenacity, ability to get things accomplished….”). and, my suggestion is that, given the remarkable difficulty in losing weight, those so motivated need lots of hand-holding: seeing them frequently to discuss how they are doing and collectively deciding on adjustments, encouraging lots of exercise to help maintain the weight loss, and overall collectively setting often small goals and slowly ramping them up as the patient is capable of doing (understanding that there will be bumps along the way). My guess is that this approach works much better than: “great, you understand what you need to do to lose weight, come back in 3-6 months”.
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