His comments come after two horses had to be put down after falling in yesterday's enthralling race.
"There are risks and we all try to minimise them. No stone is left unturned," Nicholls, who turns 50 on Tuesday, told BBC Radio 5 live.
"There is always risk in sport. A lot of people have to grow up, and realise that it is life."
Nicholls had a National-winning horse for the first time as Neptune Collonges snatched victory by a nose from Sunnyhillboy with the final stride of the race.
The deaths, which mirror two fatalities in last year's race - one of which was Nicholls's own Ornais - are unfortunate consequences of the sport, says Nicholls.
He added: "We've got to be realistic about this. The horses have the best of everything they could have. They probably have better health care than we have.
"If people are going to continue to participate in sport, there is going to be both a human and animal risk.
"The worst thing you can do is to go too far. You make the fences smaller, they go faster and you get more fallers."
New safety measures had been introduced at this year's race but only 15 of the 40 runners crossed the line.