The fact that diabetes leads to so many types of tissue damage is evidence of the toxicity of glucose.
Sure enough, there is beautiful literature showing that glucose creates ROS through multiple pathways. So it satisfies my criteria for being a toxin. Hence, according to TST, cancer cells - in doing their job to pull in toxins - should try hard to sequester glucose. This explains cancer’s love for glucose. It’s not because cancer is desperate for energy, it’s because cancer wants to detoxify the body.
Hyperglycemia is a real, tissue-damaging disease. One of cancer’s key tasks is to protect the body from hyperglycemia. Indeed, cancer cells upregulate glucose transporters—primarily GLUT1—to actively pull excess circulating glucose into the tumor, achieving 2- to 10-fold higher glucose uptake rates than normal cells. This protects the body’s vital organs from “glucotoxicity” - the medical term for glucose’s tissue-damaging effects.
(2) Glutamine
The story with glutamine is even more fascinating. Glutamine is essentially the safe way of transporting ammonia in the blood. Ammonia is highly toxic. It is produced in the muscle tissue, and it must be transported from the muscles to the liver for detoxing. But you can’t just dump the ammonia into the blood, as it would cause massive tissue damage.
The body has an elegant workaround: it packages toxic ammonia into glutamine, the most abundant amino acid in blood.
In peripheral tissues (especially muscle during exercise, stress, or illness), the enzyme glutamine synthetase (GS) combines ammonia with glutamate to form glutamine—a non-toxic, stable carrier. This glutamine shuttle safely transports the nitrogen waste through the bloodstream to the liver, where the urea cycle converts it into harmless urea for excretion. It’s a brilliant detox strategy: glutamine acts as the “safe envelope” that keeps ammonia from circulating freely and scorching delicate tissues.
But what happens when the liver is damaged? A long life of exposure to ethanol, fructose, damaged oils, and other toxins damages the liver so that it cannot perform its ammonia detox role anymore. This is when the body recruits cancer tissue to help.
In TST, cancer acts as a backup site for ammonia detox by aggressively pulling in glutamine—the body’s safe ammonia carrier—through massive upregulation of specific transporters. The primary transporter is ASCT2, a neutral amino acid transporter that is dramatically overexpressed in many cancers compared to normal tissues. ASCT2 has high affinity for glutamine.
There is a close analogy between the processing of glutamine by the liver and by cancer cells, as both appear to have the goal of ammonia detox.
I believe this uptake is not merely “addictive” for growth. In fact, glutamine is a relatively poor and unreliable substratefor energy and biomass production. Rather it is a sequestration mechanism: by intercepting the glutamine shuttle, cancer cells contain ammonia and its associated ROS threat within the tumor, preventing widespread oxidative damage in the body.
This view is further supported by the fact that during cachexia, which is an ammonia overload state that requires intense ammonia detox, cancer cells try even harder to pull in glutamine. During cachexia, tumors further increase glutamine transporter expression to capture as much glutamine (and its ammonia payload) as possible, to help with the ammonia detox process.
Glutamine addiction reinterpreted. Tumors dramatically upregulate glutamine transporters (ASCT2) to pull in glutamine, primarily to sequester and process excess ammonia released during cachexia and protein breakdown. The tumor functions as a secondary “ammonia sink,” protecting the rest of the body at the cost of accelerated muscle wasting
This reinterprets a key “fuel source” in Seyfried’s theory as simply a carrier of a toxin. Once again, it fits perfectly into TST: cancer loves glutamine because cancer is working very hard to protect the body from ammonia’s toxicity.
Why tumors form in specific organs
Now that we’ve examined the microscopic biochemistry of cancer cells, let’s zoom out to the bigger picture: organs.
One of the most powerful predictions of the TST is that tumors do not appear randomly. The body strategically chooses where to put tumors.
To understand the body’s strategy in choosing where to put tumors, I have developed the Tissue-Specific Toxin Sequestration Theory (TSTST), which has the following key principles:
The body does not sequester toxins uniformly — it strategically chooses specific tissues as tumor sites.
Tumors often form in tissues that are most heavily burdened by specific toxins.
Tumors also often form in tissues that are best equipped to safely sequester and isolate the toxic load.
Critical organs (such as the heart and spleen) are almost never chosen, as tumors there would immediately threaten survival.
Let’s unpack these principles. The liver, as the primary detox organ, frequently develops tumors when overwhelmed by fructose, ethanol, mycotoxins, or toxic metals —
effectively turning into an expanded “second liver.” The kidneys, which concentrate protein-bound toxins like PFAS, show strong associations with renal cell carcinoma. The lungs, exposed to airborne and blood-borne toxins, often sequester particles and chemicals in pulmonary tumors. These are all good examples of heavily burdened tissues.