Bosses have tended to rest star players in Europe's secondary tournament in order to keep them fresh for domestic duty, with the Portuguese's predecessor, Harry Redknapp, particularly notorious for fielding second-string teams.
|66/1||Tottenham are 66/1 with BetVictor to beat Liverpool 3-0 at Anfield
"I think what Tottenham has shown this season contradicts a lot of science, or science fiction," he told the Daily Mirror. "There is a lot of rest time between a Thursday and a Sunday.
"The intensity of the Premier League is not comparable to the Italian league but the comparisons in terms of mental stress are bigger."
With Spurs in third place going into Sunday's Premier League meeting with Liverpool, Villas-Boas is keen to ensure that his side follow through and secure a top-four finish, which would help in recruiting higher-calibre players in the transfer windows to come.
"If we achieve Champions League qualification in third or fourth place we're playing the preliminary rounds but the money will be different regarding our challenge and the players we can attract, also," he added.
"That's the position we want to be in. We are faced with a difficult calendar in front of us."