Interventions such as fasting or the ketogenic diet alone are not sufficient for cancer treatment, because some cancer cells can adapt. However, the triad of the ketogenic diet, a fasting-mimicking diet, and standard of care treatments (such as chemotherapy or immunotherapy) holds promise for particularly aggressive phenotypes, such as gliomas. In this clip, Dr. Valter Longo describes how fasting and the ketogenic diet used together with the standard of care treatment may help treat aggressive cancers.
Rhonda: So you were talking about the development of the fasting-mimicking diet, and how you were looking at all these genetic pathways, and also you mentioned the ketone bodies and...what was the last thing for...
Valter: Ketone bodies and glucose.
Rhonda: And glucose, right.
Valter: IGF-1, IGFBP-1, glucose, and ketone bodies.
Rhonda: And these are all things that regulate cancer growth as well?
Valter: Yes, they can regulate cancer, they do regulate many cancers in different ways. I mean, ketone bodies, you know, some will argue that they hurt cancer cells, but some cancers actually love to use both ketone bodies and sugar.
Rhonda: Yeah, there was a recent publication I think.
Valter: So you can actually accelerate cancer growth with ketone bodies, but you can also hurt cancer cells with ketone bodies. This is why ketogenic diet, you know, I wouldn't get too confident about using ketogenic diet alone against cancer cells because of course even fasting, a lot of cancer cells can adapt to the changed environment. So...
Rhonda: Yeah, cancer is a very...it's so...it's so complicated when it comes to cancer and it seems like really...you really have to be careful when you're trying to treat the cancer.
Valter: Yeah. And I think that there is a lot of, of course interest on the ketogenic diets and cancer treatment, and it's good, I think it can do...there are situations where the ketogenic diet can hurt the cancer growth. But as for fasting, we see that you need to have in most cases the powerful target intervention with the fasting. So like fasting and chemo, fasting and kinase inhibitors, fasting and immunotherapy for example.
So, I will assume that the ketogenic diet alone is going to be a complementary intervention.
So now for example we're very interested in what happens if you do fasting, ketogenic diet, and cancer treatment together, you know? That I think is very promising. Particularly if you do it in the sense of...And we have patients that, with very aggressive phenotypes that are doing this. So they do the periodic fasting-mimicking diet, then in between the ketogenic diet, and then they keep doing the radiotherapy, and particularly like gliomas, radiotherapies and chemotherapy. And this seems to be working, or certainly very promising what we're seeing.
Rhonda: Is this an ongoing trial you're talking about, or is it just...
Valter: We haven't started...I mean, we have trials on cancer, a number of trials on cancer. We don't have one on glioma yet, but I know that some groups in Arizona, they are...But then mostly they have just done it with a ketogenic diet. But because it's so aggressive, and most people...you cannot tell like glioma patient, wait until the clinical trial is ready, right? Because it's a very quick-moving cancer.
So, in some cases we just say, look, go to your oncologist and ask them if they're okay letting you follow a fasting plus ketogenic diet plus standard of care. So they're just adding ketogenic diet and fasting to the standard of care.
Rhonda: Yeah, okay. And that's, so the, for the periodic fasting, is that also including the fasting-mimicking diet which they can talk to…
Valter: Yeah. The fasting-mimicking diet, I mean, not water-only fasting, but FMD, ketogenic diet, and standard of care.
A diet that mimics the effects of fasting on markers associated with the stress resistance induced by prolonged fasting, including low levels of glucose and IGF-1, and high levels of ketone bodies and IGFBP-1. More importantly, evidence suggests these changes in the cellular milieu are associated with a sensitization of cancer cells to chemotherapeutic drugs while simultaneously also conferring greater stress resistance to healthy cells. Evidence also continues to emerge that properties of the fasting-mimicking diet, particularly its ability to cause immune cell turnover, may also make it useful in the amelioration of auto-immune diseases like multiple sclerosis.
 Cheng, Chia-Wei, et al. "Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression." Cell Stem Cell 14.6 (2014): 810-823.  Choi, In Young, et al. "A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms." Cell Reports 15.10 (2016): 2136-2146.
A type of tumor that forms in the brain and spinal cord in neurons called glial cells. Roughly one-third of all brain tumors are gliomas. Malignant gliomas are highly aggressive, and survival rates for patients are poor, at roughly 10 percent after three years. A protein associated with human cytomegalovirus, a common beta-herpes virus, is expressed in more than 90 percent of gliomas.
One of the most potent natural activators of the AKT signaling pathway. IGF-1 stimulates cell growth and proliferation, inhibits programmed cell death, mediates the effects of growth hormone, and may contribute to aging and enhancing the growth of cancer after it has been initiated. Similar in molecular structure to insulin, IGF-1 plays a role in growth during childhood and continues later in life to have anabolic, as well as neurotrophic effects. Protein intake increases IGF-1 levels in humans, independent of total caloric consumption.
A diet that causes the body to oxidize fat to produce ketones for energy. A ketogenic diet is low in carbohydrates and high in proteins and fats. For many years, the ketogenic diet has been used in the clinical setting to reduce seizures in children. It is currently being investigated for the treatment of traumatic brain injury, Alzheimer's disease, weight loss, and cancer.
Molecules (often simply called “ketones”) produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, or prolonged intense exercise. There are three types of ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. Ketone bodies are readily used as energy by a diverse array of cell types, including neurons.
The observable physical characteristics of an organism. Phenotype traits include height, weight, metabolic profile, and disease state. An individual’s phenotype is determined by both genetic and environmental factors.
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