Perfluoroalkyl substances and changes in body weight and resting metabolic rate (RMR) in response to weight-loss diets: A prospective study

This is a “correlation ––> inferred-causation” epidemiological study, and I would appreciate any comments/criticisms about these findings. Perfluoroalkyl substances (PFASs) –– especially perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) –– have been in the news a lot lately, and identified as plausible endocrine disruptors with the potential to perturb weight regulation. Evidence from animal studies has suggested that PFASs may be involved in altering energy metabolism and thyroid hormone homeostasis, likely through activation of various transcriptional factors such as the peroxisome proliferator-activated receptors. However, given species-specific toxicokinetics and tissue distribution of PFASs, extrapolation from animals to humans is always difficult.

Authors [see attached] examined associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. In the 2-year “POUNDS Lost” randomized clinical trial –– based in Boston, Massachusetts, and Baton Rouge, Louisiana –– which examined effects of energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants (aged 30-70 years). Body weight was measured at baseline and 6, 12, 18, and 24 months. Participants lost an average of 6.4 kg of body weight during the first 6 months (weight-loss period) and subsequently regained an average of 2.7 kg of body weight during the period of 6 to 24 months (weight-regain period). [Note that the annoying television ads for “weight-loss programs” describe enthusastically the ‘weight-loss period’, but fail to mention the ‘weight-regain period’.] 🙁

After multivariate adjustment, baseline PFAS concentrations were not significantly associated with concurrent body weight or weight loss during the first 6 months. In contrast, higher baseline levels of PFASs were significantly associated with a greater weight-regain, primarily in women. In women, comparing the highest to the lowest tertiles (statistical divisions of any population into three equal parts, the two extreme groups being divided by the middle group) of PFAS concentrations, the multivariate-adjusted mean weight-regain was: 4.3 vs 2.2 kg for PFOA; 4.0 vs 2.1 kg for PFOS; 4.7 vs 2.5 kg for perfluorononanoic acid (PFNA); 4.9 vs 2.7 kg for perfluorohexanesulfonic acid; and 4.2 vs 2.5 kg for perfluorodecanoic acid.

Higher baseline plasma PFAS concentrations, especially for PFOS and PFNA, were significantly associated with greater decline in RMR during the weight-loss period and less increase in RMR during the weight-regain period in both men and women. Caveats (limitations of the study) include the possibility of unmeasured or residual confounding by socioeconomic and psychosocial factors (i.e. greater obesity among the poor), as well as possible relapse to the usual diet prior to randomization, which could have been rich in foods contaminated by PFASs through food-packaging and also dense in energy.

Authors conclude that, in this diet-induced weight-loss study, higher baseline plasma PFAS concentrations were associated with a greater weight-regain, especially in women, possibly explained by a slower return to their normal RMR levels. These data convincingly illustrate a potential novel pathway through which PFASs interfere with clinical body weight regulation and metabolism. Possible impact of environmental chemicals on the obesity epidemic thus deserves more attention.

PLoS Med Feb 2o18; 15: e1002502

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