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Childhood Cranial Radiation Therapy May Increase Obesity Risk in Adults

sharma-obesity-cancer-cellsAmong all of the possible factors that may contribute to obesity, one that is seldom discussed (and most people are largely unaware of) is surviving cancer.

While this is increasingly being appreciated in adults, data on childhood cancer survivors is rather sparse.

Thus, a study by Carmen Wilson and colleagues, published in Cancer, which follows the development of obesity in individuals treated for cancer as kids is of particular interest.

The study looks at 1996 cancer survivors who previously received treatment for cancer at a large Children’s Research Hospital, who survived ≥10 years from diagnosis (median age at diagnosis, 7.2 years; median age at follow-up, 32.4 years).

Interestingly, 47% of survivors, who received cranial radiation therapy developed obesity compared to only 30% of those who did not.

This risk was greatest in those who also received glucocorticoids or were the youngest at the time of treatment.

The researchers also found a significant modifying effect of genetic markers, some of which are known to be involved in neural growth, repair and connectivity.

Thus, this study shows that survivors of childhood cancer appear to be prone to developing obesity as adults particularly if they were treated with cranial radiation therapy and/or corticosteroids.

Clinicians should be aware of this increased risk and should consider measures to prevent excess weight gain in individuals with a history of childhood cancer.

@DrSharma
Edmonton, AB

ResearchBlogging.orgWilson CL, Liu W, Yang JJ, Kang G, Ojha RP, Neale GA, Srivastava DK, Gurney JG, Hudson MM, Robison LL, & Ness KK (2015). Genetic and clinical factors associated with obesity among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort. Cancer PMID: 25963547

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Post-Weight Loss Fat Gain in US Rangers

army-rangersAnd finally, to conclude this week’s discussion of evidence to support the notion that weight cycling predicts weight (fat) gain especially in normal weight individuals, I turn back to the paper by Dulloo and colleagues published in Obesity Reviews, which quotes these interesting findings in US Rangers:

“…U.S. Army Ranger School where about 12% of weight loss was observed following 8–9 weeks of training in a multi-stressor environment that includes energy deficit. Nindl et al. reported that at week 5 in the post-training recovery phase, body weight had overshot by 5 kg, reflected primarily in large gains in fat mass, and that all the 10 subjects in that study had higher fat mass than before weight lost. Similarly, in another 8 weeks of U.S. Army Ranger training course that consisted of four repeated cycles of restricted energy intake and refeeding, Friedl et al. showed that more weight was regained than was lost after 5 weeks of recovery following training cessation, with substantial fat overshooting (∼4 kg on average) representing an absolute increase of 40% in body fat compared with pre-training levels. From the data obtained in a parallel group of subjects, they showed that hyperphagia peaked at ∼4 weeks post-training, thereby suggesting that hyperphagia was likely persisting over the last week of refeeding, during which body fat had already exceeded baseline levels.”

Obviously, association (even in a prospective cohort) does not prove causality or, for that matter, provide insights into the physiological mechanisms underlying this observation.

All we can conclude, is that these observations in US Rangers (and the other studies cited in Dulloo’s article) are consistent with the notion that weight loss in normal weight individuals can be followed by significant weight gain, often overshooting initial weight.

Incidentally, these findings are also consistent with observational studies in women recovering from anorexia nervosa, famine, cancer survivors and other situations resulting in significant weight loss in normal weight individuals.

Certainly enough evidence to consider a work of caution against “recreational” weight loss, especially in individuals of normal weight.

@DrSharma
Edmonton, AB

ResearchBlogging.orgDulloo AG, Jacquet J, Montani JP, & Schutz Y (2015). How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery. Obesity reviews : an official journal of the International Association for the Study of Obesity, 16 Suppl 1, 25-35 PMID: 25614201

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Are Weight-Cycling Elite Athletes Predisposed To Weight Gain?

powerliftingMy recent reading of the paper by Dulloo and colleagues on post-dieting weight gain in non-obese individuals, reminded me of my clinical observation that a surprisingly large proportion of patients I see in our bariatric clinic report a history of competitive sports.

When I have previously discussed this observation with colleagues, the answer I often get is that this weight gain is simply due to the fact that active athletes are used to eating a lot, which they continue to do after their activity levels decline, thus resulting in weight gain – a theory, I don’t quite buy largely because it appears far too simplistic (and I have yet to see any evidence to support it).

Rather, if the phenomenon of weight-cycling induced weight gain is real, one would assume that not all athletes are at risk, but rather that this phenomenon would be limited to athletes in disciplines where weight cycling (e.g. to meet certain weight criteria), often referred to as “weight cutting”, is part of the culture of that sport. Examples of such sports include wrestling, boxing, and weight lifting.

It turns out that this very issue has been studied by Saarni and colleagues, who, in a paper published in the International Journal of Obesity, report their findings on a large national cohort of 1838 male elite athletes who had represented Finland in major international sport competitions in 1920-1965.

This cohort included 370 men engaged in sports in which weight-related performance classes are associated with weight cycling (boxers, weight lifters and wrestlers) and 834 matched control men with no background in athletics.

Over the 20+ years of follow-up, the weight-cycling gained a whooping 5.2 BMI units from age 20 years to their maximum mean weight (at around age 60) conpared to only 3.3 BMI units in non-weight-cycling athletes or just 4.4. BMI units in the non-athletic controls.

Indeed, weight-cycling athletes were about three times as likely to develop obesity (defined as a BMI > 30), than their non-weight cycling colleagues or controls.

This enhanced risk of developing obesity in weight-cycling athletes remained significant even after correction for a number of potential confounders including health habits (smoking, alcohol use, use of high-fat milk or physical activity) or weight at age 20 years.

While this paper does not prove causality, or for that matter, provide any insights into possible biological mechanisms that would promote weight gain, it is certainly consistent with the hypothesis that repeated cycles of weight loss and regain in people who start out with a normal weight (in this case elite athletes) strongly predicts subsequent weight gain and the development of obesity.

Or, as the authors put it,

“The weight cycling behavior of the former athletes engaged in power sports at a young age resembles that of young dieters who lose weight temporarily and soon regain it. The present observations concerning the enhanced weight gain of these athletes raise the concern that the repeated cycles of weight loss and regain caused by dieting at a young age could similarly affect weight in the long term.”

@DrSharma
Edmonton, AB

ResearchBlogging.orgSaarni SE, Rissanen A, Sarna S, Koskenvuo M, & Kaprio J (2006). Weight cycling of athletes and subsequent weight gain in middleage. International journal of obesity (2005), 30 (11), 1639-44 PMID: 16568134

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Did Dieting Make You Fat? Blame Your ‘Proteinstat’

Skeletal muscle

Skeletal muscle

Yesterday, I posted on the intriguing finding (now documented in 15 prospective studies) that dieting can make you fat – especially if you start out with a normal weight.

In the paper by Dulloo and colleagues published in Obesity Reviews, the authors attribute part of this effect to the so far elusive “proteinstat” – a system, similar but different from the “adipostat” – that is designed to protect your lean body mass.

As the paper nicely delineates, the problem with post-dieting weight regain is that the fat comes back first but that the drive to eat does not cease till you have also regained the lost lean body mass (muscle).

It appears as though there are two complimentary biological systems that regulate weight regain.

The better known system is the “adipostat” that worries about protecting and restoring fat mass – the neuroendocrine players include leptin and perhaps other signals derived from fat tissue that signal fat stores to the brain. This system works (primarily through dropping metabolic rate but also through effects on appetite) to very quickly and effectively restore the depleted fat mass after dieting.

The less known system is the “proteinstat”, that apparenty worries about restoring lean body mass. The system works slower than the “adipostat” but continues its activity (often reaching its peak) even after all the lost fat has been regained and you are back to your original weight. In fact, it continuous working (primarily through appetite and cravings) till lean body mass is restored, even if this means gaining even more fat in the process.

In their careful reanalysis of starvation studies, Dulloo and colleagues also come up with an explanation why this process of “weight overshoot” results in more gain the skinnier the individual is to begin with.

“…the lower the initial adiposity, the greater the proportion of energy mobilized as body protein (referred to as P-ratio) during weight loss. The steep part of the negative exponential curve lies between 8–20% body fat, and a shift from the upper to the lower values in this range, generally considered to reflect a ‘normal’range of adiposity for men living in affluent societies, results in 2.5- to 3-fold increase in the P-ratio; the latter constitutes a proxy of the fraction of weight that is lost as FFM since protein belongs to the FFM compartment. This extremely high sensitivity of the P-ratio with regard to the initial body composition emphasizes the critical importance of even small differences in the initial percentage body fat in dictating the individual’s energy-partitioning characteristic and, hence, the pattern of lean and fat tissue deposition during weight loss and subsequent
weight regain, in turn, determining the extent of fat overshooting.”

In other words, lean dieters are far more susceptible to mobilising energy (and thus losing mass) from their muscle than from their fat stores, resulting in a much greater likelihood of overshooting their original weight.

Eventually, as these dieters get fatter with every diet cycle, they get less and less susceptible to this effect, which matches well with the finding that dieting is a far better predictor of long-term weight gain in people with lower fat percentages than in those who already have overweight or obesity).

As for exactly how the “proteinstat” works, much remains unclear. Early work focussed on the notion that certain amino acids may serve as signals of protein stores, however, now work is focussing on the far more plausible theory that some of the over 100 molecules now known to be secreted by skeletal muscle (myokines) may play a role in this system.

Certainly a topic that will be interesting to watch develop over the coming years.

@DrSharma
Calgary, AB

ResearchBlogging.orgDulloo AG, Jacquet J, Montani JP, & Schutz Y (2015). How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery. Obesity reviews : an official journal of the International Association for the Study of Obesity, 16 Suppl 1, 25-35 PMID: 25614201

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Will Dieting Make You Fatter? Only If You Are Skinny!

Professor Abdul Dulloo, University of Fribourg, Switzerland

Professor Abdul Dulloo, University of Fribourg, Switzerland

At the recent European Congress on Obesity, I had the occasion for a long chat with my friend and colleague Abdul Dulloo, from Friburg in Switzerland, who has worked extensively on the issue of weight regain.

I asked him how much evidence there is to support the common notion that losing weight makes you fatter – something many dieters claim to have experienced.

Indeed, both in animals and humans, weight loss, as a rule, is followed by a more rapid regain of body fat than lean body mass (i.e. preferential catch-up fat) than of lean body mass, as a result of which body composition post-weight regain results in a greater proportion of fat mass than before. But does this increased “fatness” persist over time?

This is where Dulloo made me aware of a recent paper he published in Obesity Reviews that examines this question.

What his analysis of prospective studies on this issue revealed is that paradoxically, people within a the normal weight range appear much more prone to weight gain over time with dieting than people who already have overweight or obesity.

Indeed as he points out,

“…it is dieting to lose weight in people who are in the healthy normal range of body weight, rather than in those who are overweight or obese, that most strongly and consistently predict future weight gain.”

The reasons for this rather unexpected finding are unclear and some have argued that repeated dieting to lose weight in normalweight people may represents unsuccessful attempts to counter genetic and familial predispositions to obesity – these people are genetically prone to weight gain, which is why they are dieting in the first place. Thus, rather than a causal relationship, the association between dieting and subsequent weight gain is just what would have happened to them anyway.

Others have argued that the metabolic effects resulting from the psychological “fear of fatness” (which prompts dieting) per se may increase the risk for weight gain hence a contributing factor to the obesity epidemic.

However, as Dulloo and colleagues discuss at length, based on their reanalysis of a wide range of human studies of weight loss and refeeding on body composition data on fat mass and fat-free mass (FFM) losses and regains, there is increasing support for the biological plausibility that dieting predisposes lean individuals (rather than those with overweight or obesity) to regaining more body fat than what had been lost (i.e. fat overshooting).

Overall the findings suggest that perhaps the reason why lean people regain fat faster is because their feedback signals in response to the depletion of both fat mass (i.e. adipostats) and fat-free mass (i.e. proteinstats), through the modulation of energy intake and adaptive thermogenesis, are more effective than in individuals with overweight or obesity, thus resulting in a faster rate of fat recovery relative to recovery of lean tissue (i.e. preferential catch-up fat).

In fact, it appears that lean people overshoot in terms of weight gain because the state of hyperphagia (in response to weight loss) appears to persist well beyond complete recovery of fat mass and interestingly until fat free mass is fully recovered (which may take months during which time fat gain continues).

Thus, it appears that in lean individuals “fat overshooting” following a diet is a prerequisite to allow complete recovery of fat-free mass (in obese individuals this may be less of an issue as recovery of fat-free mass is stimulated simply by the need to carry around a greater body weight).

Thus, it is easy to understand why repeated dieting and weight cycling would increase the risks for trajectories from leanness to fatness particularly in people who have a normal weight to begin with.

These findings have important public health implications and for promoting a “fear of fat”.

As Dulloo notes,

“Given the increasing prevalence of dieting in normal-weight female and male among young adults, adolescents and even children who perceive themselves as too fat (due to media, family and societal pressures), together with the high prevalence of dieting for optimizing performance among athletes in weight-sensitive sports, the notion that dieting and weight cycling may be predisposing a substantial proportion of the population to weight gain and obesity deserves greater scientific scrutiny.”

Indeed, I wonder how much of the obesity epidemic is directly attributable to normal weight people trying to lose weight for no good reason other than to look better.

@DrSharma
Edmonton, AB

ResearchBlogging.orgDulloo AG, Jacquet J, Montani JP, & Schutz Y (2015). How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery. Obesity reviews : an official journal of the International Association for the Study of Obesity, 16 Suppl 1, 25-35 PMID: 25614201

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