Extreme diets and their beneficial effects during cancer treatment

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Published: 23 Jul 2015
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Dr Valter Longo - University of Southern California, Los Angeles, USA

Dr Longo talks to ecancertv at IFOM EMBL about his study of the positive effects of fasting, extreme diets and drugs that mimic them on the prevention and treatment of cancer. 

My laboratory for a number of years has been very interested in the mechanisms of cellular protection, in particular we’ve been interested in the connection between nutrients and protection and the entry of a cell into a protective state.

So about ten years ago I started thinking about how to utilise this knowledge and this discovery that we had made many years ago that if you starve a cell, a yeast cell, a simple cell, that cell becomes highly protected.

But then we also discovered that if you express an oncogene in the same cell now that cell becomes very sensitive and from that came the idea of a differential status resistance which was really about what if we starve a mouse and that’s originally what we did and then eventually a person, would their cells in a co-ordinated way go into this protected mode and yet every cancer cell, by virtue of having an oncogene, disobeys and continues on to the sensitised mode which makes them actually more sensitive to chemotherapy rather than less sensitive.

So this was a very nice way to separate the normal cells, all normal cells and all cancer cells, no matter where they were in the body.

Do you propose that patients about to undergo chemotherapy should use this starvation technique?

We have a number of clinical trials ongoing at USC, the Mayo Clinic, Leiden University, the University of Genova, Charité University in Berlin.

The preliminary results look good, very promising.

So these combine maybe about thirty or forty patients but they’re still preliminary and I think we need to wait at least until the Charité study is completed, it has fifty patients randomised.

That should be published probably in the next three or four months.

But I certainly think there are already now patients that don’t feel they have a viable option can certainly talk to their oncologist and ask is this something that may be beneficial to me considering that they are out of options or options that even the oncologist thinks could work.

How does it work?

The clinical trials, in most cases we have either two days of fasting before chemotherapy and one day after or three days of fasting before chemotherapy and one day after.

We believe that the three plus one is probably the most beneficial.

We’ve also developed, because every cancer patient asked us the same question – “What can I eat instead of fasting? Or is there anything that I can eat?” – we developed a fasting mimicking diet with funding from the National Cancer Institute.

Now  most of the trials are actually using the fasting…virtually all are using the fasting mimicking diet and not the fasting itself.

Now, for people… obviously this is not available to people yet, to patients yet, so for the time being fasting is an OK option instead of the fasting mimicking diet.

What kinds of food does the fasting mimicking diet include?

We try to stay as close as possible to normal food, so it contains soups and bars and chips but all of them, they look like regular food but they’ve really been screened and tested in mice first and then in people for their ability to allow the changes that we look for.

There are a number of changes, major ones, that are in growth factors, IGF-1 and IGFBP-1 and glucose and ketone bodies.

So basically it’s all foods that don’t interfere with the fasting dependent changes in those markers.

What about prevention?

By virtue of working on aging we also work on cancer prevention and ageing.

Of course the major risk factor for cancer is ageing and so whether we look at yeast ageing or mouse ageing and lately human ageing the genes and pathways that control longevity also seem to control DNA damage.

So we’ve been very interested in that aspect.

We have published a long time ago on the relationship between the TOR pathway, TOR assist kinase pathway, and protection, so the deletion of genes in this TOR pathway which responds to amino acids and the DNA damage.

We have shown that simple cells that lack this TOR assist kinase signalling are very much longer lived, they live two or three times longer but they’re also very protected against DNA damage, not just point mutation but also growth chromosome rearrangement and small insertions and deletions, etc.

So we’ve then followed up with mouse studies and human studies and in mice we’ve actually just published that and shown that by using dietary manipulations, in this case we used this fasting mimicking diet periodically every couple of weeks in mice and once a month in people, but in mice we showed that by controlling this protein in amino acid signalling pathways even periodically we were able to reduce the cancer incidence in the mouse by about 50%.

Then we also looked, because again proteins are controlling this TOR signalling and also another key gene in promoting aging or aging promotion which is called IGF-1, insulin-like growth factor 1, because that protein controlling this IGF-1/mTOR we looked at the role of protein intake in mortality from all causes and from cancer in the US population.

So last year we published that people that had a high protein intake, so people that had a protein intake over 20%, over 20% of calories coming from protein compared to people that had less than 10% of calories coming from protein.

They displayed a 75% increase in the risk of overall mortality and a three- to four-fold increase in the risk to develop cancer.

Now, this is a relatively small population, about 6,000 people, so we cannot use that in a conclusive manner but certainly that was remarkable that we saw a significant three- to four-fold increase in the chance of developing cancer for people that had the highest protein intake.

In support of that there is also a study from three years ago with this population in Equador that lacks the growth hormone IGF-1, that has a mutation in the growth hormone receptor IGF-1 access, and these subjects also turned out to be protected from cancer and also diabetes.

So if you put it all together also with the mouse data showing that the protein affects cancer in mice and the growth hormone IGF-1 signalling very much affects cancer in mice, I think if you put it all together you get a pretty solid picture about the role of this protein dependent pro-aging pathways which involve IGF-1/mTOR assist kinase signalling, the role of this in cancer incidence in both mice and humans.

What about carbohydrate intake?

Carbohydrate intake is a little bit trickier.

We have described a long time ago the role of glucose in activating a second pathway which is the Ras/PKA pathway in yeast and then others have shown similar effects in drosophila and mice.

The problem is that the carbohydrate intake, high carbohydrate intake, is also associated with longevity in mice, meaning that… this is work by the Simpson group in Australia and others, the low protein, high carbohydrate diet seems to be the best for longevity.

Now, that doesn’t mean it’s low protein high sugar diet, it’s a low protein high complex carbohydrate diet; this is also what we saw in the population studies that I mentioned earlier.

So, most likely, keeping sugar levels low is important but carbohydrate intake still appears to be the best… so carbohydrate still appears to be the best source of calories.

Of course the only other option would be high fat, low carb, low protein and both animal studies and human studies suggest that that’s probably not a good way to go.

What is the take home message for people attempting to avoid cancer by diet?

The take-home message, if you put it all together with a lot more studies and also centenarian studies, you look at the populations from around the world that are particularly long-lived and they have very low cancer, where there’s Okinawans and some of the Southern Italians, the group in Loma Linda, the studies support the role for a low protein high complex carbohydrate diet with low sugar and high healthy fats, the fats from nut consumption, olive oil consumption and these combined with a mostly plant based diet.

This seems to be by far the ideal diet to minimise cancer risk.