We have a good deal of enthusiasm in the keto/paleo/low-carb community. We have the real sense that we can we use carbohydrate restriction to take advantage of the characteristic metabolic features of cancer — inflexible reliance on glucose. Enthusiasm may have outstripped the data, however, and several groups are trying to fill the gap. The barrier rests with the difficulty
for anybody to obtain funding from NIH or other major government or private agencies. On top of this looms the long-standing resistance to low-carbohydrate diets making things particularly difficult. Our group is carrying out some good experiments and we employ a dedicated technician and we can efficiently use limited funds. Your backing can help. A $ 15 donation gets us several days of supplies for the in vitro experiments that provide the biochemical underpinnings for attacking cancer in the clinic. Our project at experiment.com
provides background, a place for discussion and reports from the lab.
The current metabolic point of view in cancer — emphasizing flexibility of fuel choices — derives from renewed interest in the Warburg effect. Warburg saw that many cancer cells were producing lactic acid, the product of glycolysis. In other words, the tumors were not using the more efficient aerobic metabolism even when oxygen was present in the environment. The tumor cell’s requirement for glucose suggests the possibility of giving the host an advantage by restricting carbohydrate and offering ketone bodies as an alternative fuel.
We showed previously that we could inhibit the growth of 7 different cancer cell lines and repress the production of ATP (the”‘energy molecule” in cell culture by adding acetoacetate (one of the ketone bodies) to the medium. Control normal cell lines were not affected. In addition, we showed that ATP reduction was associated with the level of a molecule called uncoupling protein-2 (UCP-2). I explain in other posts what “uncoupling” means and how it figures into energy efficiency. First, the big picture..
What is the context of inhibition by ketone bodies ?
The real context, of course, is human cancer. Our 28 day pilot human trial of 10 subjects with advanced cancers on a very low carbohydrate ketogenic diet (KD) was published in Nutrition (Elsevier) in 2012. A small study — nominally just to show safety and feasibility, it was nonetheless well received. Of note, is that we found that those patients with the greatest extent of ketosis had stable cancers or partial remission, while those with the least ketosis showed continued progressive cancer. Despite a favorable editorial and the Metabolism Award from the journal. Unfortunately, our proposal to scale up to 65 patients was rejected by the NIH/NCI which we find very discouraging perhaps related to a commitment to drug therapy. In any case, we appeal now for help in supporting dietary cancer research.