ACRI’s caloric restricted whole plant and ketogenic (fat-abundant ( 1) mediteranean diet (CRVKMD) is a selective combination of what has been shown to be the most safe and efficient in the field of nutritional oncology. It uses only plant-based foods, 75 percent are fat-based (2) with low carbohydrates, thanks to which we can mimic the metabolic state of starvation, forcing the body to utilize fat as its primary source of energy.
WHY GOLDEN STANDARD
The calorie restricted ketogenic diet (KD-R) is an anti-angiogenic, anti-inflammatory and pro-apoptotic metabolic therapy that also reduces fermentable fuels in the tumor microenvironment. Metabolic therapy, as an alternative to the standard of care, has the potential to improve outcome for patients with GBM and other malignant
of CR without a need for overall reduced food intake these authors focused on CR-mimicking drugs that have several limitations.
I propose carbohydrate restriction as probably the best way to mimic CR in humans without the need to restrict energy intake.
(1). The ketogenic diet is used therapeutically for pharmacoresistant epilepsy and for “rare diseases” of glucose metabolism (glucose transporter type 1 and pyruvate dehydrogenase deficiency).
(2). metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells
For this diet to work (and we have instruments to measure its efficiency (3)), we need to reach a critical mass of MCTs (medium-chain triglycerides), which are largely missing from typical diets, are saturated fats easier to digest than the more common LCTs (long-chain triglycerides). Your body sends them straight to your liver, where they raise your metabolism and are burned as fuel instead of being stored as fat.. Medium chain fats help you feel full more than long-chain fatty acids you’d find in vegetable oils. You will find trace amounts of MCTs in butter, but the richest source is coconut, and to a lesser extent, palm kernel oil.
COCONUT, LAURIC ACID, PALM KERNEL OIL NAD CAPRIC ACID
Coconut oil is about 65 percent MCTs,, but 80% of the fat in coconut oil is just one (of four) type of MCT. The four kinds of MCT differ by the number of carbons on the molecules, ranging between 6 to 12 carbons long. There are caprioc (C6:0), caprylic (C8:0), capric (C10:0), and lauric (C12:0) acids. All of them are good for you, but the shorter the chain, the faster the transformation to ketones for energy. If you are counting on coconut oil for your MCTs, you’re going to get a lot of lauric acid, and only about 5% of the really good shorter chain MCTs.
MECHANISM OF ACTION
Glucose and glutamine are major fuels for myeloid cells, as well as for the more rapidly proliferating cancer stem cells. ( ) See below ?
Therapies that increase inflammation and energy metabolites in the GBM microenvironment can enhance tumor progression. In contrast to current GBM therapies, metabolic therapy is designed to target the metabolic malady common to all tumor cells (aerobic fermentation), while enhancing the health and vitality of normal brain cells and the entire body.
WHAT ARE MITOCHONDRA, KETONES AND THE KETONIC DIET
Mitochondria are the energy-producing organelles of the cell, generating ATP via oxidative phosphorylation mainly by using pyruvate derived from glycolytic processing of glucose.
Ketone bodies generated by fatty acid oxidation can serve as alternative metabolites for aerobic energy production.
“Cancer is not a genetic disease it is a disease of the mitochondria.” Thomas Seyfried’s lecture on using metabolic therapies such as the ketogenic diet for the treatment of brain cancer.
Picture licensed via PD
CASE IN POINT
Anticancer Res. 2015 Oct;35(10):5525-32.
Effects of Pre-surgical Vitamin D Supplementation and Ketogenic Diet in a Patient with Recurrent Breast Cancer.
Branca JJ1, Pacini S2, Ruggiero M3.
A woman, mother of one at the age of 19 years, was diagnosed with mammary adenocarcinoma in the right breast in 1985 at the age of 37 years. The patient underwent surgery (quadrantectomy), lymphadenectomy and radiotherapy. In 1999, an adenocarcinoma was diagnosed in the left breast, followed by adequate resection, radiotherapy and anti-oestrogen receptor treatment for 6 years. In March 2014, an infiltrating adenocarcinoma was diagnosed in the remaining part of the right breast that had been operated on and irradiated in 1985.
The pre-surgical biopsy, showed weak positivity for progesterone receptor (PgR) (<1%), high positivity for oestrogen receptor (ER) (90%), high positivity for human epidermal growth factor receptor (HER2) (>10%, score 2+), and high positivity for the nuclear protein Ki67 (30%). In the three weeks between diagnosis and operation, when no other treatment had been planned, the patient decided to self-administer high doses of oral vitamin D3 (10,000 IU/day), and to follow a strict ketogenic diet.
Following right mastectomy, analysis of the surgical specimen showed no positivity for HER2 expression (negative, score 0), and significant increase in positivity of PgR (20%). Positivity for ER and Ki67 were unaltered.
This observation indicates that a combination of high-dose vitamin D3 and ketogenic diet leads to changes in some biological markers of breast cancer, i.e. negativization of HER2 expression and increased expression of PgR.
Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
ADDITIONAL PEER REVIEWED PRECLINICAL TRIALS.
Pharmacol Res. 2010 Mar;61(3):208-12. doi: 10.1016/j.phrs.2009.11.007. Epub 2009 Nov 30.
Medium-chain fatty acids: functional lipids for the prevention and treatment of the metabolic syndrome.
Nagao K1, Yanagita T.
Metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose, that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and the precise mechanisms have not been elucidated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. This review explores the physiological functions and molecular actions of medium-chain fatty acids (MCFAs) and medium-chain triglycerides (MCTs) in the development of metabolic syndrome. Experimental studies demonstrate that dietary MCFAs/MCTs suppress fat deposition through enhanced thermogenesis and fat oxidation in animal and human subjects. Additionally, several reports suggest that MCFAs/MCTs offer the therapeutic advantage of preserving insulin sensitivity in animal models and patients with type 2 diabetes.
Clin Nutr. 2015 Jan 23. pii: S0261-5614(15)00035-7. doi: 10.1016/j.clnu.2015.01.013. [Epub ahead of print]
Toward a cancer-specific diet.
Bozzetti F1, Zupec-Kania B2.
BACKGROUND & AIMS:
It is widely acknowledged that the energy metabolism of cancer cells mainly relies on anaerobic glycolysis and this has prompted many researchers to try to reduce the malignant cells growth of experimental tumours through a programme of calorie restriction. Recently this approach has been proposed also to cancer patients. In the meantime it was demonstrated that the effects of calorie restriction on tumour growth are mediated through the toxic effect of ketone bodies on cancer cells which have a defective mitochondrial function, while these substrates are well-utilized by the normal cells.
This review analyzes the main available data regarding the tumour growth in patients undergoing a period of starvation or of normal/artificial nutrition as well as the recent approach through special normocaloric ketogenic diets which are well utilized by cancer patients while may be unfavourable for cancer cells.
Despite the paucity of data it appears that modulation of tumour growth by the calorie restriction/nutritional support is unlikekly in humans for several reasons: the different tumour cells growth rate and different tumour/host carcass ratio and duration of treatment, between tumour-bearing animals and patients.
There is a large consensus in literature that maintaining a normal body weight and preserving the lean body mass through an adequate nutrition is beneficial in cancer patients. The nutritional approach through a ketogenic diet which may be toxic for the cancer cells while is well utilized and tolerated by the patient seems promising in a next future.
Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Int J Biochem Cell Biol. 2015 Jun;63:55-9. doi: 10.1016/j.biocel.2015.01.022. Epub 2015 Feb 7.
Mitochondria: The ketogenic diet–A metabolism-based therapy.
Vidali S1, Aminzadeh S1, Lambert B2, Rutherford T2, Sperl W3, Kofler B4, Feichtinger RG1.
Mitochondria are the energy-producing organelles of the cell, generating ATP via oxidative phosphorylation mainly by using pyruvate derived from glycolytic processing of glucose. Ketone bodies generated by fatty acid oxidation can serve as alternative metabolites for aerobic energy production. The ketogenic diet, which is high in fat and low in carbohydrates, mimics the metabolic state of starvation, forcing the body to utilize fat as its primary source of energy. The ketogenic diet is used therapeutically for pharmacoresistant epilepsy and for “rare diseases” of glucose metabolism (glucose transporter type 1 and pyruvate dehydrogenase deficiency). As metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells; there is increasing evidence that the ketogenic diet may also be beneficial as an adjuvant cancer therapy by potentiating the antitumor effect of chemotherapy and radiation treatment. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Redox Biol. 2014 Aug 7;2C:963-970. doi: 10.1016/j.redox.2014.08.002. [Epub ahead of print]
Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism.
Allen BG1, Bhatia SK2, Anderson CM2, Eichenberger-Gilmore JM2, Sibenaller ZA2, Mapuskar KA2, Schoenfeld JD2, Buatti JM2, Spitz DR2, Fath MA2.
Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•-and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses
J Cell Biochem. 2015 Aug 7. doi: 10.1002/jcb.25305. [Epub ahead of print]
Acetate as a Metabolic and Epigenetic Modifier of Cancer Therapy.
Jaworski DM1, Namboodiri AM2, Moffett JR2.
Metabolic networks are significantly altered in neoplastic cells. This altered metabolic program leads to increased glycolysis and lipogenesis and decreased dependence on oxidative phosphorylation and oxygen consumption. Despite their limited mitochondrial respiration, cancer cells, nonetheless, derive sufficient energy from alternative carbon sources and metabolic pathways to maintain cell proliferation. They do so, in part, by utilizing fatty acids, amino acids, ketone bodies and acetate, in addition to glucose. The alternative pathways used in the metabolism of these carbon sources provide opportunities for therapeutic manipulation. Acetate, in particular, has garnered increased attention in the context of cancer as both an epigenetic regulator of posttranslational protein modification, and as a carbon source for cancer cell biomass accumulation. However, to date, the data have not provided a clear understanding of the precise roles that protein acetylation and acetate oxidation play in carcinogenesis, cancer progression or treatment. This review highlights some of the major issues, discrepancies and opportunities associated with the manipulation of acetate metabolism and acetylation-based signaling in cancer development and treatment. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Cancer Lett. 2015 Jan 28;356(2 Pt A):289-300. doi: 10.1016/j.canlet.2014.07.015. Epub 2014 Jul 25.
Metabolic therapy: a new paradigm for managing malignant brain cancer.
Seyfried TN1, Flores R2, Poff AM3, D’Agostino DP3, Mukherjee P2.
Little progress has been made in the long-term management of glioblastoma multiforme (GBM), considered among the most lethal of brain cancers. Cytotoxic chemotherapy, steroids, and high-dose radiation are generally used as the standard of care for GBM. These procedures can create a tumor microenvironment rich in glucose and glutamine. Glucose and glutamine are suggested to facilitate tumor progression. Recent evidence suggests that many GBMs are infected with cytomegalovirus, which could further enhance glucose and glutamine metabolism in the tumor cells. Emerging evidence also suggests that neoplastic macrophages/microglia, arising through possible fusion hybridization, can comprise an invasive cell subpopulation within GBM. Glucose and glutamine are major fuels for myeloid cells, as well as for the more rapidly proliferating cancer stem cells. Therapies that increase inflammation and energy metabolites in the GBM microenvironment can enhance tumor progression. In contrast to current GBM therapies, metabolic therapy is designed to target the metabolic malady common to all tumor cells (aerobic fermentation), while enhancing the health and vitality of normal brain cells and the entire body. The calorie restricted ketogenic diet (KD-R) is an anti-angiogenic, anti-inflammatory and pro-apoptotic metabolic therapy that also reduces fermentable fuels in the tumor microenvironment. Metabolic therapy, as an alternative to the standard of care, has the potential to improve outcome for patients with GBM and other malignant brain cancers.
Copyright © 2014. Published by Elsevier Ireland Ltd.
Trends Mol Med. 2014 Sep;20(9):471-2. doi: 10.1016/j.molmed.2014.07.001. Epub 2014 Jul 21.
Mimicking caloric restriction: what about macronutrient manipulation? A response to Meynet and Ricci.
As ongoing research continues to reveal the links between metabolism, cancer, and aging it is good to see non-toxic interventions such as caloric restriction (CR) coming into focus. Recently, Meynet and Ricci provided a timely review summarizing the current state of research on the possible role of CR in cancer treatment. In discussing ways to implement clinically the beneficial effects of CR without a need for overall reduced food intake these authors focused on CR-mimicking drugs that have several limitations. I propose carbohydrate restriction as probably the best way to mimic CR in humans without the need to restrict energy intake.
Copyright © 2014 Elsevier Ltd. All rights reserved.
wine resveratrol also mimickes CR
We have modified it so that its nutrition element is based on a caloric restricted whole plant and fat-directed foods diet that used in combination with metabolic supplements, botanicals, herbs, exercises, meditation, energy medicine and acupuncture.
In this perspective, we have evidence that just the nutrients dense, hypo-caloric fat-based diet triggers the malignancy to transition from glucose and glutamine fermentable metabolites to respiratory metabolites, primarily ketone bodies. At that point, tumor vascularity and inflammation are decreased while tumor cell death skyrockets.
As a direct consquence, metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells; there is increasing evidence that the ketogenic diet may also be beneficial as an adjuvant cancer therapy by potentiating the antitumor effect of chemotherapy and radiation treatment.