Tuesday, August 27, 2013

Vegetable Oils Increase Tumor Growth

[This post derives from a post on cancer just put up by Peter Dobromylskyj at Hyperlipid.]

I just want to make two points in this post.

Vegetable Oils Increase Tumor Growth

I'm sure that a book or two could be written exploring all of the ways in which vegetables are horrible for human health (a cursory look on Amazon didn't reveal any, which is kind of surprising). Or one could dedicate a blog just to exploring all of the research and mechanisms involved. There is a lot of information out there already if one is interested and I don't have the time or energy to pull it all up and summarize it.

However, it makes sense to illustrate at least one example of the dangers of vegetable oils. Peter's post highlights some research by Sauer et al in the 1980's which found that vegetable oils but not other fats promoted tumor growth in mice. The following graph illustrates the data in Table 3 of Sauer's paper. The dotted line represents tumor growth in the mice in the control condition (the first bar).



You can more than double the growth of these mouse tumors by providing them with linoleic and arachidonic acid. Linoleic acid is found primarily in vegetable oils. For example, soybean oil is 51% linoleic acid, whereas butter is only 2%. Arachidonic acid is found in some animal products and is also made from linoleic acid in the body. In contrast, palmitic, stearic and oleic acids did not promote tumor growth relative to the control condition. Palmitic and stearic acids are the most common saturated fats found in animal fats (stearic is also the main fat found in cocoa butter). Oleic acid is found in both animal fats and plant sources such as olive oil.

In the chart below, the blue bars represent the percentage of fatty acids that DON'T promote tumor development, and the red bars represent the percentage of fatty acids that DO promote tumor development according to the Sauer study above. Arachidonic acid percentages weren't listed, so I assume they must be small. I left out any fatty acids not included in the above study.


If you don't want to promote tumor development, it looks like a BAD idea to eat soybean oil or even supposedly healthy flax oil. Butter on the other hand looks great.

Current Trials of Ketogenic Diets for Cancer Treatment in Humans are Seriously Misguided

[Adapted from a comment I left on Hyperlipid.]

I haven't gotten to the logic of using a low-carb ketogenic diet as a cancer treatment, but that's where I've been heading. A low-carb ketogenic diet is by necessity a very high fat diet (80% fat or so usually). There are reasons to think it may be therapeutic for cancer patients. However, only a few human studies have been completed, although several clinical trials are in the works.

Unfortunately, despite the cancer-promoting effects of vegetable oils, all but one of the human trials of ketogenic diets for cancer I can get my hands on about have put patients on high vegetable oil diets. For example Schmidt et al 2011 had their participants eat two "liquid meals" a day composed of the following ingredients.

Highly fermented yoghurt-drink:
  • skimmed milk
  • plant oil mixture
  • pectin
Vegetable oil mixture:
  • line seed oil
  • canola oil
  • walnut oil
  • MCT
  • grape seed oil
  • argan-oil
  • pumpkin seed oil
Protein preparation:
  • milk-protein

Additionally: "patients were encouraged to add additional servings (1 tablespoon each) of the oil mixture or other oils from olives, flaxseed and hempseed to the three principle meals." This is a crazy amount of vegetable oil. Of course, they got poor compliance and lots of adverse reactions. Nevertheless, they concluded the diet "might improve aspects of quality of life and blood parameters in some patients with advanced metastatic tumors."

A recent research protocol from Dr. Eugene Fine, who appears to be a thoughtful scientist, nevertheless stipulates "unsaturated oils for cooking."

Two clinical trials are starting up, aiming to investigate the use of a ketogenic diet for lung cancer (see KETOLUNG) and pancreatic cancer (see KETOPAN).

There is a good explanation of the lung cancer trial here, DEFINITELY READ IT. It explains the basic logic behind the use of ketogenic diets for cancer treatment. They will be implementing a 90% fat diet. HOWEVER, if you read the fine print in the study design you will see that they intend to use "Ketocal" shakes to implement the diet. Ketocal is a commercial product you can buy on Amazon. You can read the list of ingredients here. The first three ingredients are:
  • Hydrogenated soybean oil
  • Whole milk
  • Refined soybean oil
Unbelievable. This is exactly what you would feed a mouse in order to give it cancer, or encourage its existing tumors to grow rapidly. It is truly amazing. If this trial were going on at M.D. Anderson I would fly down there and physically prevent you from participating in it. It is incredibly disappointing that good studies of this topic don't even seem to be in the hopper yet, so we can't expect answers for who knows how many more years.

To end on a more positive note, the one exception to the above studies used medium chain triglycerides (MCTs). MCTs are technically a vegetable oil I think, but one which is highly ketogenic and not an omega-6 oil, which is what you want to avoid. The trial was only in two pediatric patients, but the results seemed pretty positive compared to the vegetable oil trials.

Luckily you don't need to enroll in a clinical trial to implement a not insane version of a ketogenic diet yourself. At the very least, stop eating all sources of vegetable oils ASAP. Not easy when you are living in a hotel, but what can you do. Unfortunately that means no more fried calamari.

Sunday, August 25, 2013

Normal vs Cancer Cell Metabolism and How PET Scans Work


 [This is my current understanding of the latest ideas on how cellular metabolism works with respect to cancer based on reading a few articles.]


Cells require ATP in order to survive, as well as fulfill whatever duties they have to the organism as a whole. ATP isn't just floating around for free in unlimited amounts for cells to take up and use, so each cell has to manufacture it's own supply. For people eating a normal diet, glucose is the primary raw material used by cells to manufacture ATP. However there are two different methods the cell can use to generate ATP using glucose.

  1. Mitochondria: A single glucose molecule can be processed by mitochondria in the presence of oxygen to produce 32 molecules of ATP.
  2. Cytosol: Cellular machinery exists in the cytosol which is capable of rapidly producing 2 molecules of ATP from a single molecule of glucose without requiring oxygen as part of the process.


These two processes correspond to the "aerobic" vs "anaerobic" pathways. Running glucose through the mitochondria takes extra time, but is massively more energy efficient than processing glucose directly in the cytosol (specifically, you get 16 times more energy from a given amount of glucose if you process it through the mitochondria). But you need oxygen to process glucose through mitochondria, so if the cell runs short of oxygen (ie. you are running the 400 yard dash) processes in the cytosol will kick in to assist in the production of ATP. However, as a side effect they will also put out lactate and hydrogen ions, which change the pH of the cell and lead ultimately to inability of the muscle cell to contract, the sensation muscle burn, and huffing and puffing.

[Processing glucose through mitochondria also produces byproducts such as reative oxygen species (ROS) but we're not worrying about that right now.]

Cancer cells, however, appear to have dysfunction mitochondria, so they are unable to generate ATP by running glucose through mitochondrial processes.


This puts the cancer cell in a difficult position. All cells need a certain amount of ATP just to survive. For the sake of argument, let's say these example cells need to be able to manufacture 96 molecules of ATP per minute or else they will die. To achieve that, the non-cancerous cell simply needs to transport three molecules of glucose from the extracellular fluid and use oxygen in the mitochondria to produce 96 molecules of ATP.



On the other hand, because its mitochondria doesn't work, a cancer cell has to transport 48 molecules of glucose across the cell membrane and process all of them in the cytosol to produce the same 96 molecules of ATP that only required 3 molecules of glucose for the normal cell. In the process, the cancer cell generates a lot of lactate and hydrogen ions, which alter the pH of the environment and according to some of the articles I've read may contribute to some of the pathological traits of tumors including encouraging them to metastasize.



So, compared to normal cells, cancer cells are like mutants which burn through enormous amounts of glucose. One of the early clues that cancer was related to glucose metabolism came from patients with uncontrolled type I diabetes (prior to insulin therapy I assume). Researchers could tell when these diabetic patients got cancer because the excess glucose normally spilling out in their urine would disappear because it was being devoured by their cancer cells.

[BTW that implies that cancer cells are able to transport the glucose across the cell membrane without the action of insulin, which I think I've heard is possible, but I'm not familiar with the details of how glucose transporters and insulin work.]

With this background you can see why tumors can be detected using radioactively labeled glucose. If you imagine that each glucose molecule comes with a radioactive tag (little red stars in the figures below), here is what the normal cell would look like after producing 96 molecules of ATP.


In contrast, here is the cancer cell after making 96 molecules of ATP.


So the important question is whether or not it is possible to fight cancer by limiting the availability of the large amounts of glucose it needs to survive.