Melatonin Turns off Your Cancer Switch

November 15, 2022

Melatonin Turns off the Cancer Switch In Your Cells

In 1931, Otto Warburg got the Nobel Prize in Medicine for elucidating cellular respiration, and how and where cells burn glucose. He noted that cancer cells could survive without oxygen, provided they had enough glucose. All cells have the capability of chopping glucose into two halves without using any oxygen and thereby getting two ATP molecules. For many cancer cells, that is their principal source of energy, making them dependent on other nutrients. Cancer cells are very inefficient and have to parasitize their hosts, spreading like crazy. Indeed, Thomas Seyfried, at Yale, has made a CT scanner of electron microscopes and demonstrated that mitochondria are broken in all cancers and cannot digest fat and ketones, proving Warburg's hypothesis.

Efficient cellular metabolism needs more energy than that. Glucose needs to be turned into pyruvate, then shuttled into the Krebs cycle inside mitochondria where one molecule of glucose can make 38 ATP instead of the measly 2. That takes oxygen and healthy mitochondria. That represents a 19-fold increase in energy from a single glucose. That's efficient and the basis of all cellular biology.

In a healthy human cell, glucose is made into two pyruvate molecules which are then transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). That is the nexus of metabolism. Making Acetyl CoA is the penultimate step before the entry into the mitochondria where 36 ATP follows. Turning on and off the PDC complex is akin to the circuit board on a computer or your fuse box to your home. Central, first, and important.

Focus on that PDC enzyme. In cancer cells, the PDC enzyme gets inhibited, shifting the cell into "Warburg" metabolism. You don't need to know all that nerdy stuff but it has some advantages for cancer cells because a pentose phosphate pathway makes more DNA molecules for rapidly growing cancer cells. A healthy cell wants to "dis-inhibit" the PDC complex, shifting metabolism back to healthy ATP production, making energy, and closing down the pentose phosphate shunt. And that's what melatonin does. Signaling molecules that "dis-inhibit" the PDC complex usually do it by inhibiting hypoxia-inducible factor-1α which then leads to PDC disinhibition allowing for the intramitochondrial conversion of pyruvate into acetyl coenzyme A. There are several levers of control that wax and wane inside the cell and melatonin is one of the most prominent. In summary, melatonin swings the cell away from the cancer model and towards the healthy cellular model.

This might explain why melatonin is being found to be beneficial in the prevention of many diseases. Everything from metabolic syndrome to COVID in addition to cancer appears to be beneficially affected by melatonin.

It all starts in healthy mitochondria. And the PDC complex.

www.What will Work for me. Whew, heady physiology that comes down to a simple summary. Our melatonin levels drop dramatically as we age. It is safe and easy to buy. There are now multiple authors suggesting that 40 mg a day for cancer is reasonable, and there are more aggressive "thought-leaders" in functional medicine advocating for 200 mg a day of melatonin for anyone with active disease. I haven't found much evidence of toxicity, despite some anxious websites that quote out-of-date references.

References: Int Jr Molecular Sci, BMC, Trials, Frontiers, Oncotarget, MoleculesMDPI,

Pop Quiz

1. What is the "PDC" complex in the human cell?                               Answer: The metabolic switch the makes the last step of molecular preparation before the cascade of the mitochondria. I've likened it to your home's fuse box.

2. In cancer, what happens to the PDC complex?                        Answer: It gets inhibited, so instead of energy molecules with complicated names going into the mitochondria, they head off in directions that help cancer cells grow faster.

3. What does melatonin do to the PDC complex?                         Answer: Aha! Turns it back on. "Dis-inhibits" it.

4. You mean to suggest that higher doses of melatonin might turn cancer off?                  Answer: Yup, yup, yup.

5. If you google and look up cancer care around melatonin, what is the highest dose you might find?                 Answer: 200 mg a day is not hard to find.