Background: The effect of the macronutrient composition of the usual diet on long term weight maintenance remains
controversial.
Methods: 373,803 subjects aged 25–70 years were recruited in 10 European countries (1992–2000) in the PANACEA project
of the EPIC cohort. Diet was assessed at baseline using country-specific validated questionnaires and weight and height
were measured at baseline and self-reported at follow-up in most centers. The association between weight change after
5 years of follow-up and the iso-energetic replacement of 5% of energy from one macronutrient by 5% of energy from
another macronutrient was assessed using multivariate linear mixed-models. The risk of becoming overweight or obese
after 5 years was investigated using multivariate Poisson regressions stratified according to initial Body Mass Index.
Results: A higher proportion of energy from fat at the expense of carbohydrates was not significantly associated with
weight change after 5 years. However, a higher proportion of energy from protein at the expense of fat was positively
associated with weight gain. A higher proportion of energy from protein at the expense of carbohydrates was also
positively associated with weight gain, especially when carbohydrates were rich in fibre. The association between
percentage of energy from protein and weight change was slightly stronger in overweight participants, former smokers,
participants $60 years old, participants underreporting their energy intake and participants with a prudent dietary pattern.
Compared to diets with no more than 14% of energy from protein, diets with more than 22% of energy from protein were
associated with a 23–24% higher risk of becoming overweight or obese in normal weight and overweight subjects at
baseline.
Conclusion: Our results show that participants consuming an amount of protein above the protein intake recommended by
the American Diabetes Association may experience a higher risk of becoming overweight or obese during adult life.