A 20-year investigation by Harvard University revealed that the most successful dieters were those genetically predisposed to being overweight.
Researchers found that those with the highest genetic risk were able to improve their BMI approximately 70 per cent better than those who were not.
They believe the act of dieting itself may be blunting the effect of genetic predisposition at a molecular level.
Published in the British Medical Journal, the study tracked nearly 14,000 people between 1986 and 2006.
Dr Louisa Ells, of Teesside University in Middlesbrough, who reviewed the findings for the journal, said: "Genetic predisposition is no barrier to successful weight management and no excuse for weak health and policy responses.”
Obesity is a complex disorder involving a mix of genes and environmental influences.
Previous research has shown that diets high in sugar sweetened drinks and fried foods may amplify the genetic associations with higher body weight.
The first genes associated with putting on weight were discovered 10 years ago, since when more than a 100 new genes have been found.
Between 40 and 44 per cent of people carry the FTO gene variant, and around 16 per cent have two copies, making it roughly 70 per cent more likely that they will become obese.
The new research is the first to assess the interactions between diet quality and genetic predisposition to obesity on a long-term basis.
“Long term, dramatic weight loss is difficult to achieve, even in the context of weight loss interventions,” said Dr Tiange Wang, from Tulane University in Louisiana.
"Therefore, even modest weight loss or simply maintaining weight from adulthood onward - compared with gaining weight - may have a substantial effect on population health."