Dr. Seyfried's Press-Pulse Protocol and the Possible Etiology of its Effects
Dr. Seyfried, et al, describe the details of the research used in proposing the Press-Pulse Protocol in the article below, based on the knowledge that "cancer cells are largely dependent on glucose and glutamine for survival and growth... This strategy can be used for the non-toxic management and possible resolution of cancer... The novelty of the metabolic approach is the synergistic combination of nutritional ketosis, cancer metabolic drugs and hyperbaric oxygen therapy." Of note, the Press-Pulse Protocol does not include either traditional chemotherapy or radiation therapy. It interesting that there are a number of studies that treat a variety of cancers with radiation and/ or chemotherapy, and include pieces of the Press-Pulse Protocol such as a ketogenic diet or repurposed drugs that seem to have an enhanced response compared to the standard of care therapy alone. But the question still remains: why and how does this Press-Pulse Protocol affect cancer cells when it is impossible to completely eradicate glucose and glutamine from the diet? It would seem that any amount of glucose and glutamine would still feed an "energy hungry" cancer, even preferentially over normal tissue demands. So the mechanism is probably not due to the reduction in glucose and glutamine, but to an effect that they have on another metabolic process. Further research seems to indicate that this is most likely due to deuterium-depleting effect of the ketogenic diet in combination with increasing molecular hydrogen in the body. The deuterium/ hydrogen (D/H) ratio is important in cell cycle regulation and cellular metabolism. Low deuterium in a ketogenic diet can impact tumor growth by preventing the cells from reaching a deleterious D/H ratio.
Press and Pulse
The mainstay of the Press-Pulse Protocol is starving the cancer of its' two fuel sources: glucose and glutamine. The first is accomplished with the ketogenic diet: decreasing glucose and increasing ketones. The "Press" is creating a sustained metabolic stress in the body with a calorie restricted ketogenic diet or dietary energy reduction. The "Pulse" is the addition of hyperbaric oxygen therapy and metabolic drugs (I.e. a glutamine blocker) to result in a mass elimination of tumor cells. Not only will this weaken and damage tumor cells, but it will enhance the health of normal cells. It is important to note that to obtain results seen in previous studies it is imperative to very strictly achieve and maintain the glucose/ ketone/ hyperbaric levels as described. Unfortunately this strict diet is very difficult to maintain day after day, week after week, and month after month. In addition, such strict calorie restriction often leads to cachexia and muscle wasting, which is counter-productive to improving overall health and wellness. Studies indicate that the ketogenic diet is actually decreasing deuterium. It would appear that a less restrictive diet can be followed and supplemented with deuterium depleted water and molecular hydrogen to achieve similar results. Studies of deuterium depletion and cancer are ongoing and very exciting.
Ketogenic Diet
The mainstay of the Press-Pulse Protocol is decreasing the sugar available for cancer cells by implementing the ketogenic diet. The ketogenic diet is a reduction in daily calories to reduce average blood glucose levels to a sustained value of approximately 55-65 mg/dL or 3-3.5 mM/L. This can be measured with a continuous glucose monitor that pairs via Bluetooth to a smart phone for 24 hour glucose readings. As there are sometimes discrepancies with these monitors, it will be necessary to confirm readings with a twice daily finger stick assessment of blood glucose. In addition ketones need to be measured twice daily, and the glucose ketone index (GKI) calculated for an optimum range of less than 1.5. With the collaboration of your physician, it may be necessary to add medications/ supplements to help lower the blood glucose , such as metformin or berberine. A ketogenic diet has been shown to overcome resistance to immune checkpoint blockade therapy as well (https://pubmed.ncbi.nlm.nih.gov/38588411/). It is important to note that muscle mass should be maintained, and this therapy will be difficult for those who are anorexic or cachectic. An optimal diet consists of eating 5 times per day (roughly 3 meals of 3 oz. of meat and 1 cup of low carb vegetables, interspersed with 2 high fat "snacks"), with a ratio of 80% Fat, 15% Protein, and 5% Carbohydrates. The question still remains, why choose a blood glucose level of 60 mg/dL instead of 70, 80 or 90mg/dL? Even at 60 mg/dL, there is still glucose available for both the cancer cells and the normal tissues. If cachexia and muscle wasting are such an issue with these mandatory low numbers, and the mechanism of the ketogenic diet is lowering deuterium, maybe a combination of diet and deuterium depletion may be just as effective.
Glutamine blockers
Glutamine is the other fuel source for cancer cells. You cannot use a glutamine blocker chronically as glutamine is also a fuel source for skeletal muscle tissue. Therefore, it has to be "pulsed" strategically to help starve the cancer. DON, or 6-Diazo-5-Oxo-L-Norleucine (mechanism of action: glutaminolysis inhibition), has been timed with the Hyperbaric Oxygen Therapy to further "starve" the cancer while subjecting the cancer cells to oxygen. This is basically "chemo- light", as a glutamine blocker is inhibiting mitosis just like other chemotherapy agents. There is associated toxicity with glutamine because it is necessary for normal cell function, especially in the skeletal muscle tissue as noted above.
Hyperbaric Oxygen Therapy (HbOT)
Cancer cells live in an oxygen free milieu, and a higher concentration of oxygen may make cancer cells easier to kill by other means, even radiation therapy and chemotherapy. Once optimal glucose/ ketone levels are consistently achieved for one to two weeks, hyperbaric oxygen therapy can be added three times a week at 2.2 atm for a total of 90 minutes per Thomas Seyfried's Press-Pulse Protocol. It will likely be necessary to start at a lower atmosphere and duration, and work up to these the optimal numbers. It may also be necessary to take a minute or two break from 100% oxygen during the "dive" if one starts to feel ill or disoriented. This can be discussed with the doctor administering the HbOT. Hyperbaric oxygen therapy can decrease blood glucose, but this is usually well tolerated if the ketone levels are elevated consistently. There are contraindications to hyperbaric oxygen therapy, so this must be discussed with your health care provider before starting this type of therapy. There are many interesting articles on HbOT and cancer, although there is still much research to be done. (See Hyperbaric oxygen therapy and cancer- a review; Moen and Stuhr https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510426/
Repurposed Drugs
Repurposed drugs are medications that have been used in the past for one therapy or treatment, but may be able to be used for another purpose. One example is the metabolic approach to cancer treatment being studied at Care Oncology. They are using medications to fight inflammation, reduce nutrients to and place stress on cancer cells, induce programmed cell death, block cancer cell DNA repair and tumor-feeding blood vessel growth. Some of these medications may include fenbendazole or mebendazole, doxycycline, a statin drug such as lovastatin / fluvastatin/ or atorvastatin, and/ or metformin. These are being used in particular studies, so again you should discuss these with your physician or perhaps contact CareOncology. https://careoncology.com/the-science/
Standard of care therapies and Stress Management
Chemotherapy
Chemotherapy may be recommended depending upon the type of cancer. Cancer cells love sugar (glucose), so one consideration is to maintain a lower glucose level prior to the administration of chemotherapy. If a small amount of glucose is given concomitantly with the chemotherapy, theoretically the cancer would be more likely to take up the chemotherapy agent when it is gobbling up the sugar. This way the cancer cells would be more likely to be targeted by the chemotherapy agent, rather than the healthy cells that are using the ketones generated by a low sugar diet. There is also insulin potentiated chemotherapy, in which a small amount of insulin is administered during glucose/ chemotherapy administration, which would theoretically generate the same scenario.
Radiation Therapy
Radiation therapy may be recommended by your health care provider. Again, studies have shown improved results with radiation therapy when administered on patients maintaining a ketogenic diet, particularly in those with brain tumors. Similar results have been seen with the new
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Stress Management
Stress management is key to addressing cancer. Numerous studies have shown an impact on cancer,, particularly affecting to the immune variables in cancer: cellular immune function and inflammation (Impact of Psychosocial Stress and Stress Management on Immune Responses in Cancer Patients, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467795). There are a variety of ways to modify stress, such was meditation, yoga, massage, acupuncture, relaxation and stress reduction exercises, and more recently neurolofeedback and Brain Training with devices such as Sens.ai.