KETO DIET IN CANCER

 

Principles of ideal cancer treatment

  1. Target cancer cells only
  2. Spare body cells
  3. Protect body cells

The standard of care (SOC) in cancer is presently based on three therapies

  1. Surgical therapy
  2. Radiation therapy
  3. Chemo-therapy

All of the above do NOT target cancer cells exclusively.

The only therapy that targets cancer cells exclusively while not only sparing but also protecting our body cells is dietary therapy.

  1. Surgical therapy – this is an excellent therapy in the early stages of the disease when there is no distant spread and the tumour can be totally removed. However, normal tissue is excised with the abnormal cancer tissue which in itself leads to morbidity. For example, in breast cancer the entire breast is removed. In kidney cancer the kidney is removed with the normal parts of the kidney. Luckily we can live without a breast and with only one kidney. However, we cannot remove the entire liver of an entire half of the brain. The remainder harbours some cancer cells which not only grow but grow more aggressively after the surgery. This is because surgical incisions and wounds result in inflammation, oedema (swelling) and release of substances that promote the growth of cancer cells. Once the tumour has spread to distant sites (metastases) surgery is mostly palliative
  2. Radiation therapy – For all the advances radiation cannot differentiate between cancer and normal cells and will destroy all cells in their path. Of course the side-effects of radiation are many and include radiation burns, damage to mucosal cells. In up to 90% of those with brain tumours who undergo fractionated partial or whole-brain irradiation (fWBI) can have significant cognitive impairment 6 months after irradiation, even in the absence of detectable anatomic abnormalities. More disturbing is the long-term effects of radiation on cancer cells with actually enhancement of their growth, multiplication and spread by angiogenesis and inflammation.
  3. Chemotherapy – this does target cancer cells but also all rapidly multiplying normal body cells, like blood cells (Red- RBC, white- WBC and platelets). All of these carry out vital body functions like carrying oxygen to all body cells (RBCs), protecting us from infections (WBCs) and ensuring clotting of blood (platelets). This in turns causes weakness, fatigue and propensity to develop infections very easily. In fact, this is a major cause of morbidity in those on chemotherapy. Affection of hair cells causes balding so common in those on chemotherapy. Of course the loss of appetite, nausea and vomiting is very common and debilitating. Toxicity of these agents is immense and 5% may succumb to their chemotherapy. Another 20-30% have to stop chemotherapy due to intolerable side-effects. The most sinister is that 80-90% of chemotherapeutic agents can themselves cause gene mutation to a degree that in turn results in recurrence of the cancer at the same site, at a different site or even a new type of cancer.
  4. Steroids (usually dexamethasone) are used during chemotherapy to reduce edema of the brain and with many chemotherapeutic drugs. However, it also enhances neoglucogenesis and increases blood glucose levels. This in turn enhances cancer cell growth.

Cancer and ketogenic diets

The ketogenic diets target the following important aspects

  1. Starves the cancer cells of nutrition (glucose)
  2. Reduces their blood supply (angiogenesis)
  3. Inhibits important protein kinases that enhance cancer cell multiplication
  4. Forces cancer cells to use their defective mitochondrial metabolism
  5. Reduces the production of lactate which is normally in excess and enhances cancer cell proliferation
  6. Forces cancer cells
  7. Reduces oxidants (antioxidant)
  8. Reduces inflammation (cytokines)
  9. Promotes longevity genes leading to neuroprotection (Nrf2 and SIRT1)

Some illustrative cases

Our patients

A young girl of three years had an inoperable pontine (Centre of the brain having all the vital centres and all the important pathways from cerebral hemispheres to spinal cord) glioma. Surgery was out of the question as it would mean instant death. Radiation was given but did not prove useful. The ketogenic diet reduced the tumour by 30%. The girl was fine for two years and going to school and playing with other children. The usual survival is 6-12 months. Unfortunately, sympathetic relatives gave in to the girl’s pleading for rice after two years and within a few months doubled in size and the girl succumbed to her tumour.

A young adolescent age 14 years presented with a dense right hemiplegia (weakness of right upper and lower limbs). She could not walk without help and was unable to raise the arm or hold anything in her right hand. Her MRI showed a brainstem cancerous tumour, namely glioma. Due to its location it could not be operated. She was advised radiation and /or chemotherapy but could not afford either. She came to us and was put on the ketogenic diet only. Within five months she is now able to walk unaided, raise the right arm overhead and able to use her right hand and even write. She is probably the first person in the world with a brain cancer to be treated only with the ketogenic diet. This shows that brain cancer can be treated only with the ketogenic diet. Brain cancers are amongst the most malignant of all cancers.

This following is a first report of treatment of recurrence of adenocarcinoma after surgery and chemotherapy with dietary therapy only.

Female age 41 years, presented with symptoms of abdominal discomfort & change in bowel habits. On PET scan a large intensely metabolically active mass involving hepatic flexure was detected. Hemi-colectomy was performed. Histopathology revealed poorly differentiated adenocarcinoma, Chemotherapy namely Folfox 4 was given for 12 cycles.  During the 7th chemo cycle, recurrence was detected with tumour measuring 4.0 cm. Biopsy was performed. Patient refused any further chemotherapy. Ketogenic Diet (KD) therapy was started. Repeat PET scan after 3 months of KD showed complete resolution of the recurrence.   

Dietary therapy can control cancer even as a single mode therapy.  

Dr. Seyfried’s patient (personal communication)

A middle aged lady has a brain GBM and has been on the ketogenic diet only. She refused surgery, radiation or chemotherapy. She was given 6 months to live. It has been two years now and her leg weakness has improved.

Summary

  1. Cancer cells have a different metabolism.
  2. Targets only cancer cells and spares and protects normal cells.
  3. High fat content protects from cancer cachexia (weight loss and weakness).
  4. Can be taken for several years with no side-effects.
  5. Very unlike surgery, radiation and chemotherapy which affect normal body cells and have a lot of side-effects.
  6. Can be given with above therapies but ideally should be started prior.
  7. Can be combined with hyperbaric oxygen therapy.

Cancer and our lifestyle

For thousands of years the lifestyle of ancient man has been of a hunter-gatherer and the diet has been meat (protein and fat) and roots and berries (carbohydrates). This has changed recently – last thousand years to easily digestible foods, namely, grains, vegetables and fruit most with high carbohydrate and very high glycemic index- GI (change in glucose level following ingestion). This has got even more accentuated in the past twenty to thirty years with the ‘fast food’ culture. Simultaneously, our activity level has gone from physical activity with lot of sunlight to a sedentary life (home- transport- work- transport-home) and little exposure to sun. Both physical activity and sunlight reduce the risk of cancer. Thus the hunter-gatherer diet differed in two basic ways, the high dependence on animal protein (26% of energy) and the ingestion of low GI carbohydrates (roots, berries and nuts). Therefore, protein contributed 26% fat 43% and carbohydrate 31%. This protein is higher and carbohydrate lower than the modern diet parameters. This ‘modern’ high carbohydrate high GI food intake is linked to ‘modern’ diseases like metabolic syndrome, cataract, retinal degeneration, gout and Alzheimer’s disease (AD). Except AD all the rest are associated with a higher incidence of cancer. The Glycemic Index (GI) and the glycemic load of the diet are also positively correlated with cancer incidence.

Therefore, there is a strong case for low CHO diets to prevent and treat cancers.

Pasteur and Warburg first noted the difference in metabolism between cancer cells and our body calls. Pasteur in what is now known as the Pasteur effect discovered that cancer cells convert glucose (converted from carbohydrate in our food) into lactate in spite of the presence of oxygen. On the other hand normal body cells metabolise glucose to CO2 and H2O in the presence of oxygen and only in hypoxic conditions is lactate formed. Thus glucose in cancer cells undergoes anaerobic fermentation. Warburg in 1930 took this discovery further and found conversion of glucose to lactate even in the presence of oxygen (aerobic glycolysis) and this is now called the Warburg effect. This Warburg effect is found in almost all cancer cells. He also found that cancer cells utilised more than 18 times the glucose used by normal body cells. Further, they could not utilise ketones (derived from fat in our food). He hypothesised that the cause of this was abnormal mitochondrial metabolism which he claimed occurs before the normal body cells turn cancerous (malignant). A low carbohydrate diet was postulated for the control of cancer through lowering of blood glucose levels. The evidence for this link was first noted in 1920 when Braunstein noticed that diabetic patients who developed cancer did not have glucose in the urine. Later when muscle tissue and malignant cells were cultured in glucose media he found that the utilization of glucose was much higher in malignant cells, Later, Bierich found that there was a high accumulation of lactate in the milieu of malignant cells. This lactate was essential for the invasiveness of melanoma cells.

What happens at the cellular metabolism level – aerobic glycolysis of one mole of glucose yields two moles pyruvate, 2 ATP and NADH. Each mole of pyruvate in the presence of pyruvate dehydrogenase is converted to acetyl-CoA which in the TCA (Krebs’cycle) yields 36 ATP. This occurs normally in all our body cells. In contrast when one mole of pyruvate is metabolised through lactic dehydrogenase A (LDHA) only 2 ATP are formed. This occurs in anaerobic conditions or in cancer cells – the Warburg effect. The cancer cells make up for this deficit of energy by increasing (upregulating) the glucose transporters (GLUT 1and GLUT 3). This results in a high glcolytic flux even in the presence of low glucose concentrations. This phenomenon is used in the PET FDG as cancer cells preferentially take up more of the glucose rich FDG tracer. The reason for this is four-fold.

  1. Mitochondrial damage by mutation
  2. Genetic alterations in oncogenes and tumour suppressor genes.
  3. Advanced tumorigenesis Solid cancer tumours have relative hypoxia as the circulation is unable to keep with the fast expansion. These hypoxic cancer cells are particularly radio- and chemo-resistant.

 Glucose availability as a promoter of cancer growth

Taken together, increased glucose flux and metabolism promotes several hallmarks of cancer such as excessive proliferation, anti-apoptotic signalling, cell cycle progression and angiogenesis.

Indirect effects of glucose availability

Besides delivering more glucose to the tumor tissue, hyperglycemia has three other important negative effects for the host:

  1. Even modest blood glucose elevations as they typically occur after a Western diet meal competitively impair the transport of ascorbic acid into immune cells. Ascorbic acid is needed for effective phagocytosis and mitosis, so that the immune response to malignant cells is diminished.
  2. Hyperglycemia (high blood glucose) activates monocytes and macrophages to produce inflammatory cytokines that play an important role also for the progression of cancer.
  3. High plasma glucose concentrations elevate the levels of circulating insulin and free IGF1, two potent anti-apoptotic and growth factors for most cancer cells. 

 

Cancer and the ketogenic diet

The treatment of cancer especially of the brain has been largely focused on surgery, radiation and chemotherapy. However, all of these while having short term benefits in the long-term may actually be doing more harm than good. This is especially true for the more malignant brain tunours like glioblastoma multiforme (GBM). Long –term survival has been usually around 1- 2 years with 90% succumbing before 5 years.

A target neglected is the abnormal or different metabolism found in these cancer cells as compared to our body cells. Warburg, and Pasteur before him, pointed out that these cancer cells depend on aerobic glycolysis, that is, they depend on glucose as their only and sole nutrient. (Warburg effect). In contrast our body cells can use either glucose or in conditions like fasting use fat as their primary source of fuel. The ketogenic diet (KD) mimics the effects of fasting. It is a calorically restricted high fat, low carbohydrate normal protein diet that has been long used to control uncontrolled epilepsy. (Since 1920s).

As ketones are metabolized exclusively within the mitochondria, cancer cells with damaged mitochondria are unable to adequately use them for energy. Many cancers do not express the Succinyl-CoA: 3- ketoacid CoA-Transferase (SCOT) enzyme which is required for ketone body metabolism [65,66]. In fact, bHB administration prevents healthy hippocampal neurons but not glioma cells from glucose withdrawal-induced cell death [24]. Furthermore, ketone bodies have anti-cancer effects themselves, possibly through inhibition of glycolytic enzymes [67]. Skinner and colleagues demonstrated that acetoacetate and bHB administration inhibits brain cancer cell viability in vitro [25]. Thus, the elevated ketone levels in the KD+HBO2T mice likely enhanced the efficacy of this combined therapy.

Both of these are not to reduce the blood glucose levels but with other agents in conjunction with the ketogenic diet the following can be useful:

  1. 2 deoxy glucose 2 DG
  2. 3 bromopyruvate

Not available in India.

Metformin may protect against colon cancer. Metformin by lowering the blood glucose level may help to potentiate the ketogenic diet effect. Thus, metformin my be combined with the ketogenic diet.

Hyperbaric oxygen can be used with KD and in animal trials was found to be superior to KD alone or hyperbaric oxygen alone.

Conclusion:

In conclusion we should use surgery, radiation, chemotherapy and ketogenic diet with probably metformin and hyperbaric oxygen in the treatment of brain tumors. However, it is strongly advised that metabolic therapy be used first and in the future may be the only safe treatment.

Thus KD is the only therapeutic approach that simultaneously targets multiple hallmarks of cancer such as energy metabolism, angiogenesis, and inflammation and increases immunity.

 

CASE- Ketogenic diet in Pontine Glioma

We Would like to share one of our patient with a PONTINE GLIOMA (Cancer) views on Ketogenic diet and her pictures.

 

Earlier as you can see below in Jan 2017 we had shared our Pontine Glioma(Cancer) patient- TG’s picture with her views on Ketogenic Diet.

Today we are glad to share her successful journey with us which is not because of Chemotherapy or Radiation therapy or Surgery, Its only because of ‘KETOGENIC DIET’.

TG came with dense hemiplegia and could not walk unaided. She could not make a fist or hold anything. Surgery could not be performed. She could not afford radiation therapy or chemotherapy. She improved on ketogenic diet only.

Here we share her pictures below:-

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Email: janak.nathan@gmail.com

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