Can a low-carbohydrate or ketogenic diet prevent or treat cancer? We don't know,of course, but several lines of evidence encourage optimism. First, we've come to appreciate the value of a metabolic approach and, in particular, the importance of the Warburg effect. Warburg described a difference in energy metabolism in cancer tissue: such tissues relied more on glycolysis (using glucose for energy without consuming oxygen -- even if oxygen was present). While it is not a feature of every cancer, it is very common. Control of energy metabolism and the importance of glucose and insulin point to carbohydrate restriction and ketogenic diets. It is also significant that obesity and type 2 diabetes are highly correlated with the development of a wide variety of cancers.
Our lab is one of several specifically taking this approach. Three major lines of attack are in vitro tissue culture studies (cells grown in medium), animal studies and clinical studies. We have made advances along each line of attack although, like the whole field we are at the beginning; the overpowering barrier is still that there are many cancers, sometimes even in the same tissue, and prior emphasis on the genomic approach was not that it was wrong but that it could not have anticipated the multi-headed nature of the monster. Whether the metabolic approach will offer unifying principles remains to be seen but contents oft the glass seems to have exceeded 50 % capacity.
Our 28 day pilot human trial of 10 subjects with advanced cancers on a very low carbohydrate ketogenic diet (KD) was publilshed in the journal Nutrition . We found that patients tolerated the diet well but, in addition, patients with the greatest extent of ketosis had stable cancers or partial remission, while those with the least ketosis showed continued progressive cancer. We have been fortunate in finding an anonymous donor to support the continuation of this part of the research. The current project currently underway at Albert Einstein College of Medicine involves patients scheduled for surgery for breast cancer. Forty-five of the patients will be on ketogenic diets until surgery (typically one month) while a control group of 20 patients will follow a low-fat diet. While this is a small time period, we expect to see difference in several biomarkers.
In cell culture studies we previously showed that acetoacetate (AcAc, one of the ketone bodies (KB)) inhibited growth of 7 different cancers from 20-50%, while leaving normal cells unaffected. Most recently, we studied the effect of AcAc on cells subject to anti-cancer agents. We used a breast and a cancer cell line and treated the cells with one of three potent anticancer agents, rapamycin, methotrexate and PNC-27 a new anticancer drug developed by a member of our team and currently being investigated. It turned out that all three agents had enhanced anti-cancer activity if administered in a ketone-containing solution. The significance is that these drugs have limited applicability because they are toxic or have serious side-effects. The goal is ultimately to couple the drugs with a ketogenic diet in the hope that they will be better tolerated. We presented the work at the Experimental Biology 2019 meeting and we are currently preparing a manuscript for publication. While these studies are very promising, tissue culture must always be considered circumspectly and we have been carrying out animal studies in parallel.
The third branch of our three-pronged approach asks whether a mouse models of cancer will allow us to see the synergy, if any, of drugs and ketogenic diets as suggested by the in vitro studies. We have just established that, in a mouse that spontaneously develops tumors, we can delay death with either a ketogenic diet or the drug rapamycin. In fact, a very low dose of rapamycin was slightly enhanced when the animals were maintained on a ketogenic diet. At a moderate dose, however, there was a greatly enhanced increase in longevity as shown in the title figure. The goal of the project is, again, to see if anticancer drugs which by themselves, are toxic or lead to serious side-effects -- rapamycin is in this class -- can become more useful (that is, safer and better tolerated) if coupled with a ketogenic diet.