Metabolic therapy

If cancer runs on two fuels, the strategy follows: cut off the fuels, protect the healthy cells, and use conventional tools more precisely and at lower doses.

The press-pulse strategy is Seyfried’s name for combining a constant “press” - therapeutic ketosis that keeps glucose low and ketones high - with intermittent “pulses” of targeted drugs or fasting, so tumour cells stay under steady pressure and are struck hard at intervals.

The core principle

Put the body into therapeutic ketosis - low blood glucose, elevated ketones. Healthy cells happily switch to burning ketones and actually become healthier. Cancer cells cannot use ketones (their mitochondria are too damaged), so they are starved of one of their two primary fuels. The tumour becomes less inflamed, less angiogenic (fewer abnormal blood vessels), more “indolent” - but not gone, because it still has its second fuel.

The second fuel: glutamine

Diet alone lowers glucose, but the tumour keeps running on glutamine, the most abundant amino acid in the blood. So the strategy adds drugs that target glutamine metabolism. Seyfried highlights repurposed agents - for example mebendazole - noting the value is in showing the mechanism: that it hits both glucose and glutamine utilisation.

The Press-Pulse strategy

Developed with colleagues including Joe Maroon, “press-pulse” is the scheduling logic of the therapy:

Ketosis as a “vehicle” for chemotherapy

Seyfried is explicitly not anti-chemotherapy - he argues it is used in the wrong context. Being in nutritional ketosis, he says, lets you use much lower doses of drugs for a bigger effect:

• Healthy cells enter “bunker mode” - they slow division and build defences, so they survive the toxic hit far better.
• Cancer cells can’t downshift - they keep dividing and take the full force of the chemo.
• Repair is blocked - chemo causes oxidative damage the cancer cell needs glucose to repair; in ketosis that glucose is cut off, so damage becomes lethal.
• Fewer side effects - lower doses mean less hair loss, bleeding gums, and microbiome destruction.

He describes this being applied in clinics in Istanbul and Greece for pancreatic cancer, advanced breast cancer and other “terminal” cancers - pairing standard drugs (cisplatin, carboplatin) at reduced doses with a ketogenic state. The paper framing: a ketogenic diet as a “metabolic vehicle for enhancing therapeutic efficacy.”

Removing the tumour’s shield

The fermentation waste products - lactic acid and succinic acid - form a protective, acidic shield that helps tumours resist chemo, radiation and immunotherapy. Target the two fuels and that shield comes down, making the tumour “super vulnerable” even to low doses. Immunotherapies, he argues, should come after metabolic pressure has shrunk and calmed the tumour - not as a first strike against the beast at full strength.

Metastasis and the hybrid cell

Seyfried argues the deadly step - metastasis - comes from hybrid cells formed when the immune system’s macrophages fuse with tumour stem cells, producing cells “programmed to move around the body.” These hybrids are hard to kill but, he says, are strongly glutamine-driven - which is exactly why glutamine-targeting metabolic therapy may reach them.

Synergies mentioned

• Hyperbaric oxygen therapy - combined with ketosis, drives oxidative stress selectively into cancer cells (published with Dominic D’Agostino).
• Fasting / fasting-mimicking diets - Valter Longo’s work on lowering IGF-1, triggering autophagy, and making therapies more effective.
• The “wall” of fasting - a pre-adaptation week of zero-carb eating makes a subsequent water fast far less traumatic to the brain.