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Hundreds of thousands of deaths in the United States every year are attributed to obesity, now overtaking smoking as perhaps the main preventable cause of illness and premature death. In particular, excess body fatness is an important cause of most cancers, according to a meta-analysis of studies done to date. For some cancers, about half of cases may be attributable to just being overweight or obese.

What’s the connection, though? Why do individuals who are obese have increased cancer risk? To answer this question we must consider the biochemical consequences of obesity, like IGF-1, insulin like growth factor one is a cancer-promoting growth hormone associated with a variety of common cancers in adults, as well as children. Kids who got cancer had about four times the levels of IGF-1 circulating in their bloodstream, whereas people growing up with abnormally low levels of IGF-1 don’t seem to get cancer at all. Zero cases of cancer out of 300 people.

I’ve talked about this cancer-proofing mutation, the role animal protein intake plays in boosting IGF-1 production from our liver, which may explain plant-based protection from cancer, and how plant-based one has to eat, but our liver is not the only tissue that produced IGF-1, fat cells produce IGF-1 too. That may help explain this 21st century cancer epidemic caused by obesity.

So of course drug companies have come up with a variety of IGF-1 blocking chemo agents, with cute names like figitumamab, but with not-so-cute side effects such as early fatal toxicities. So perhaps better to lower IGF-1 the natural way, by eating a plant-based diet, as vegan women and men have lower IGF-1 levels. Maybe, though, it’s just because they’re so skinny. The only dietary group that comes close to the recommended BMI of 21 to 23 were those eating strictly plant based diets, but so maybe it’s the weight loss that did it. Maybe we can eat whatever we want as long as we’re skinny.

To put that to the test, we’d have to find a group of people that eat meat—but are still as slim as vegans. Long-distance endurance runners, running an average of 48 miles a week for 21 years. If you run 50,000 miles you too can maintain a BMI of even a raw vegan. So what did they find?

If you look at blood concentrations of cancer risk factors among the groups of study subjects, you see that only the vegans had significantly lower levels of IGF-1. That makes sense given the role animal protein plays in boosting IGF-1 levels.

But the vegan group didn’t just eat less animal protein, they ate fewer calories. And in rodents at least, caloric restriction alone reduces IGF-1 levels. So OK, maybe low IGF-1 among vegans isn’t due to their slim figures, but maybe the drop in IGF-1 in vegans is effectively due to their unintentional calorie restriction. OK, so let’s compare vegans to people practicing severe calorie restriction.

They recruited vegans from the St. Louis Vegetarian Society, and went to the Calorie Restriction Society to find folks practicing severe caloric restriction. What did they find?

Only the vegan group got a significant drop in IGF-1. These findings demonstrate that, unlike in rodents, long-term severe caloric restriction in humans does not reduce the level of this cancer-promoting hormone. It’s not how many calories we eat, Protein intake may be the key determinant of circulating IGF-1 levels in humans, and so reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.