Glucose, Ketosis, Glutamine and Cancer

I know I’ve touched on these items before but I’ve recently been excited by the ways they tie together to show an exploitable weakness in cancer. I can’t deny that I also love how they validate my ketogenic, moderately low-protein way of eating.

Cellular Metabolism Refresher [skip to next section if this stuff doesn’t turn you on]

You probably remember this all from high school biology but healthy cells are metabolically flexible and can create energy in the form of ATP via multiple pathways. Oxidative phosphorylation, which takes place in the mitochondria (oh! The dreaded Krebs cycle!), is a fairly efficient pathway and creates up to 38 – though usually 29-30 – ATP molecules per molecule of glucose. OxPhos is therefore the most commonly used method of energy production but can only be completed in the presence of oxygen.

When oxygen isn’t available (think hard core sprinting), the body tends to rely on fermentation which creates only 2 usable ATP per glucose molecule. Both these processes begin with glycolysis, or the breakdown of a glucose molecule, which happens in the cell’s cytoplasm.

If no glucose is available, healthy cell can utilize fatty acids via ketone bodies (or directly). A significant portion of this process, called ketosis, also takes place in the mitochondria and can create 120-160+ ATP per fatty acid molecule. I think it’s pretty cool that we can not only burn our fat stores but get more energy molecule for molecule while doing it.

Cancer Metabolism

Otto Warburg won the Nobel prize in 1931 for his discovery that the vast majority of cancers are distinguished by metabolic damage that prevents them from using these multiple pathways. Cancer cells need tremendous energy to grow and spread but for some reason only use the inefficient anaerobic glucose fermentation pathway even when oxygen is available. Since this is the only form of cellular energy production that doesn’t involve the mitochondria, it’s led to speculation that this organelle is somehow damaged in cancer cells.

Regardless of the reason why, the fact is that most cancer cells require glucose to survive. High glucose levels also trigger an increase in insulin which causes cells to proliferate and can inhibit apoptosis, or programmed cell death. [2] Cancer is defined by uncontrollable growth and anti-apoptosis so high insulin levels probably aren’t a good thing. In fact, many cancers cells are all about the insulin and have an unusually high number of insulin receptors [3].

To add more ammunition to my ketogenic diet argument, studies have shown that exposure to ketone bodies will slow tumor grown in vitro and prolong life in mouse models – even in the presence of sufficient glucose [1]. Note that there are no large scale human test results available although studies are underway.

Glutamine Addiction

What I haven’t talked about on this blog yet is the fact that, in addition to being dependent on glucose, cancer cells are also distinguished by their glutamine addiction. Glutamine is a non-essential amino acid (meaning the body can synthesize it, if needed) and the most abundant amino acid in human blood. Several studies in vitro and animal models have shown that cancer cells require access to glutamine for survival [4]. Glutamine provides the building material for cancer’s wild growth while glucose provides the energy.

No one can cut out glutamine completely since it also provides critical functions including immune support – and the body can make it, anyway, though not always in sufficient quantities. Given this, I feel good about limiting the glutamine in my diet but not obsessively. It turns out, I’ve already been doing that since the best dietary sources include meat, seafood, eggs, dairy and beans, none of which I eat. Cabbage, leafy greens, and nuts are also excellent vegetable sources and you know I eat tons of those.

Another reason not to go overboard on the protein is that the liver can convert protein into glucose using a process called gluconeogenesis. I’ve read multiple n=1 accounts of individuals on low carb diets unable to get their blood sugar down until they also reduce dietary protein. (My favorite was posted by an MD and can be found here.)

My Dietary Approach

My approach to starving out the cancer is therefore multifold: minimize blood glucose and insulin levels, increase ketone bodies, and reduce the availability of glutamine. This is the basis for my ketogenic, moderately low protein diet.

In his book Cancer as a Metabolic Disease (which I have not yet read), Dr. Thomas Seyfried proposes the Glucose Ketone Index (GKI) to measure the optimal ratio of blood glucose to ketone bodies. GKI is simply blood glucose in mmol/L divided by ketones in mmol/L.

This chart paraphrased from the keto mojo website.

In his book, Dr. Seyfried advises a GKI of 1 as optimal for cancer care although anything from 0.7 to 2 can be therapeutic.

Note that a blood ketone level above 5 mmol/L is dangerous and can lead to ketoacidosis for some folks like those with Type 1 diabetes. As always, doctors should be consulted before any new diet.

A few days ago I picked up a glucose/ blood ketone meter so I can track my progress. I’d been floating around between 2 and 4, dropping as low as 1.8 one morning. This was during my last week in the states so my diet wasn’t quite as strict as in Hong Kong. Since coming home, I’ve been able to achieve a GKI of 0.7. I talk about how I did it here.

I guess the main point of all this is to say that I’m stoked about my diet and happy to have a way to quantify and track my progress.