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

Abstract

Background

The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown. This study aimed to examine the associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting.

Methods and findings

In the 2-year POUNDS Lost randomized clinical trial based in Boston, Massachusetts, and Baton Rouge, Louisiana, that examined the 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. RMR and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline and 6 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 6–24 months (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 of PFAS concentrations, the multivariate-adjusted mean weight regain (SE) was 4.0 (0.8) versus 2.1 (0.9) kg for perfluorooctanesulfonic acid (PFOS) ( P _trend = 0.01); 4.3 (0.9) versus 2.2 (0.8) kg for perfluorooctanoic acid (PFOA) ( P _trend = 0.007); 4.7 (0.9) versus 2.5 (0.9) kg for perfluorononanoic acid (PFNA) ( P _trend = 0.006); 4.9 (0.9) versus 2.7 (0.8) kg for perfluorohexanesulfonic acid (PFHxS) ( P _trend = 0.009); and 4.2 (0.8) versus 2.5 (0.9) kg for perfluorodecanoic acid (PFDA) ( P _trend = 0.03). When further adjusted for changes in body weight or thyroid hormones during the first 6 months, results remained similar. Moreover, 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. Limitations of the study include the possibility of unmeasured or residual confounding by socioeconomic and psychosocial factors, 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.

Conclusions

In this diet-induced weight-loss trial, higher baseline plasma PFAS concentrations were associated with a greater weight regain, especially in women, possibly explained by a slower regression of RMR levels. These data illustrate a potential novel pathway through which PFASs interfere with human body weight regulation and metabolism. The possible impact of environmental chemicals on the obesity epidemic therefore deserves attention.

Trial registration

ClinicalTrials.gov NCT00072995

Abstract

Gang Liu and colleagues reveal that perfluoroalkyl substances, often found in food packaging particularly of energy dense foods, contribute to weight regain for those recruited to a weight loss trial. This effect is higher in women.

Author summary

Why was this study done?

• Although many approaches can be used to achieve a short-term weight loss, maintenance of weight loss has become a key challenge for sustaining long-term benefits of weight loss. Accumulating evidence has suggested that certain environmental compounds may play an important role in weight gain and obesity development.

• The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown.

What did the researchers do and find?

• In a 2-year diet-induced weight-loss trial (the POUNDS Lost trial), we measured plasma concentrations of PFASs at baseline in 621 overweight and obese men and women and collected information on changes in body weight, resting metabolic rate (RMR), and other metabolic parameters during weight loss and weight regain over the 2 years the participants were on the study diet.

• Higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. On average, women in the highest tertile of PFAS concentrations regained 1.7–2.2 kg more body weight than women in the lowest tertile.

• Higher baseline plasma concentrations of PFASs, especially perfluorooctanesulfonic acid (PFOS) and perfluorononanoic acid (PFNA), were significantly associated with greater decline in RMR during the first 6 months and less increase in RMR during the period when participants on average regained weight (6–24 months).

What do these findings mean?

• In this diet-induced weight-loss trial, higher baseline PFAS concentrations were associated with a greater weight regain, especially in women, possibly explained by a slower return of RMR levels. These data provide initial evidence suggesting that PFASs may interfere with human body weight regulation and counteract efforts to maintain weight loss in adults.