Scientists fear the effects of extended weightlessness on skeletal muscle will pose a significant safety risk for future manned Mars missions.
Nasa estimates that it would take a crew 10 months to reach Mars. With a one-year stay, a mission could take as long as three years.
Professor Robert Fitts, from Marquette University in Wisconsin, and colleagues wrote in the Journal of Physiology: ''The main findings were that prolonged weightlessness produced substantial loss of fibre mass, force, and power.
''An obvious conclusion is that the exercise countermeasures employed were incapable of providing the high-intensity needed to adequately protect fibre and muscle mass, and that the crew's ability to perform strenuous exercise might be seriously compromised.
''Our results highlight the need to study new exercise programmes on the ISS that employ high resistance and contractions over a wide range of motion to mimic the range occurring in Earth's 1G environment.''
Prof Fitts believes if astronauts tried to travel to Mars today they would have trouble performing even routine work in a space suit.
The most affected muscles, such as the calf, could weaken by as much as 50 per cent.
Nine American astronauts and Russian cosmonauts were tested before and after spending 180 days on the International Space Station.
Analysis showed ''substantial'' losses caused by muscle atrophy.
Starting the space flight in good physical shape did not help, the scientists found. Crew members who began with the biggest muscles also showed the greatest declines.
Despite the findings Prof Fitts does not believe plans for long-distance space travel should be abandoned.
''Manned missions to Mars represent the next frontier, as the Western hemisphere of our planet was 800 years ago,'' he said.
''Without exploration, we will stagnate and fail to advance our understanding of the universe.''
He added that in the short term, efforts should focus on fully utilising the ISS so that better ways of protecting muscles and bones can be developed.
Nasa and the European Space Agency needed to develop a space shuttle replacement so at least six crew members could stay on the ISS for six to nine months.
''Ideally, the vehicle should be able to dock at the ISS for the duration of the mission so that, in an emergency, all crew could evacuate the station,'' said Prof Fitts.