Implementing A Ketogenic Diet Based on Medium-chain Triglyceride Oil in Pediatric Patients with Cancer

doi:10.1016/S0002-8223(95)00189-1

Journal of the American Dietetic Association

Volume 95, Issue 6, June 1995, Pages 693-697

https://doi.org/10.1016/S0002-8223(95)00189-1 Get rights and content

Abstract

Traditionally, a ketogenic diet is given to drug-resistant children with epilepsy to improve seizure control. Inducing a ketogenic state in patients with cancer may be a useful adjunct to cancer treatment by affecting tumor glucose metabolism and growth while maintaining the patient's nutritional status. A ketogenic diet consisting of 60% medium-chain triglyceride (MCT) oil, 20% protein, 10% carbohydrate, and 10% other dietary fats was provided to a select group of pediatric patients with advanced-stage cancer to test the effects of dietary-induced ketosis on tumor glucose metabolism. Issues of tolerance and compliance for patients consuming an oral diet (consisting of normal table foods and daily MCT oil “shakes”) and for patients receiving an enteral formula are reviewed. Preliminary use of the MCT oil-based diet suggests a potential in pediatric patients with cancer. J Am Diet Assoc. 1995; 95:693-697.

Section snippets

Why We Selected an Mct Oil-Based Ketogenic Diet

A high-fat, low-carbohydrate ketogenic diet has been used since the 1920s as an effective method of controlling epileptic seizures in prepubescent children (10). Unfortunately, this type of diet is not without side effects — poor tolerance, hyperlipidemia, and elevated serum cholesterol and triglyceride levels (11). The diet, consisting predominantly of heavy cream and butter fat, is often quite unpalatable, and some patients complain of hunger between meals (11), (12). Fluid restrictions are

Thy Mct Oil–Based Kethogenic Diet

The diet consists of 60% MCT oil, 20% protein, 10% carbohydrate, and 10% other dietary fats as percentage of total kilo-calories (Table 1, Table 2). Other sources of dietary fats are included in the diet to prevent a deficiency in essential fatty acids. The percentages of carbohydrate, protein, and dietary fats may be modified slightly to satisfy patient preferences; however, they should not exceed 40% of total kilocalories to maintain ketosis (21), (22).

The diet is designed to promote weight

Enteral Formula

The MCT oil–based ketogenic diet may be provided as an enteral formula for tube feedings. The oil is blended with a variety of commercially available products to create formula of 60% MCT oil, 20% protein, 10% carbohydrate, and 10% other dietary fat. Suggested products include Portagen (Mead Johnson/Bristol-Myers Co, Evansville, Ind), Casec Protein powder (Mead Johnson/Bristol-Myers Co) and Pro-mod powder (Ross Laboratories, Columbus, Ohio). Liquid supplements containing MCT oil may also be

Supplements

Use of vitamin/mineral supplements is essential to maintain nutrient adequacy in the ketogenic diet. Generally, over-the-counter supplements are provided on a daily basis. Unfortunately, these products do not always provide recommended levels of certain minerals, especially trace minerals, for pediatric patients with cancer.

Nutrients such as vitamin E, beta carotene, selenium, and zinc inactivate certain enzymes involved in carcinogen metabolism or decrease enzyme activities that play a role in

Tolerance and Compliance Issues

Tolerance to the diet may be established with minimal difficulty if the diet is introduced to the patient in a gradual manner. Periods of illness may require slight modifications in the composition of the diet. Certain medications or a common cold may alter the patient's tolerance. Depending on the situation, total energy requirements may be reduced to 75% for 24 to 48 hours to allow the episode to resolve. Sugar-free liquids and flavored gelatin can be provided as desired to sustain hydration

Applications

This article describes the successful implementation of an MCT oil–based ketogenic diet in a select pediatric population. The oral or enteral form of the diet, combined with use of broad-spectrum supplements, is designed to meet the overall energy and nutrient needs of pediatric patients with cancer without compromising nutritional status. Tolerance issues are minimal when implementation is done carefully and gradually. Minor adjustments in dietary composition can be made to improve a child's

References (26)

W.L Dills et al.
Effects of diet deficient in glucose and glucose precursors on the growth of the Walker carcinosarcoma 256 in rats
J Nutr.
(1984)
K.C.H Fearon et al.
Cancer cachexiainfluences of systemic ketosis on substrate levels and nitrogen metabolism
Am J Clin Nutr.
(1988)
A.T Gasch
Use of the traditional ketogenic diet for treatment of intractable epilepsy
J Am Diet Assoc.
(1990)
R.C Johnson et al.
Medium chain triglyceride lipid emulsionmetabolism and tissue distribution
Am J Clin Nutr.
(1990)
A.C Bach et al.
Medium chain triglyceridesan update
Am J Clin Nutr.
(1982)
J.M Signore
Ketogenic diet containing medium chain triglycerides
J Am Diet Assoc.
(1973)
J.F Dorgan et al.
Antioxidant micronutrients in cancer prevention
Nutr Cancer.
(1991)
D Herber et al.
Hormonal and metabolic abnormalities in the malnourished cancer patienteffects on host-tumor interaction
JPEN.
(1992)
J.A Tayek
A review of cancer cachexia and abnormal glucose metabolism in humans with cancer
J Am Coll Nutr.
(1992)
W.L Dills
Nutritional and physiological consequences of tumor glycolysis
Parasitology.
(1993)

J.A Norton et al.

In vivo utilization of substrate by human sarcoma-bearing limbs

Cancer.

(1980)

M Rothkopf

Fuel utilization in neoplastic diseaseimplications for the use of nutritional support in cancer patients

Nutrition.

(1990)

L Nebeling

Effects of Dietary Induced Ketosis on Tumor Metabolism, Nutritional Status and Quality of Life in Pediatric Oncology Patients

(1992)

Cited by (68)

From antiepileptic therapy to promising adjuvant in medical oncology: A historical view of the ketogenic diet
2023, PharmaNutrition
Despite recent advances that have been made in cancer treatment, we still lack complementary approaches to significantly improve the effectiveness of current anti-cancer therapies. The high-fat, low-carbohydrate ketogenic diet can cause metabolic changes in the tumor microenvironment, thus targeting cancer metabolism, making it an attractive candidate for adjuvant cancer therapy. This review is an attempt to explore the origin and trace the historical use of the ketogenic diet as a metabolic therapy in medical oncology.
A detailed literature review was conducted through specialized databases. Only those articles pertinent to the specific needs of the review were included. Relevant references in those articles were also followed.
There is a sound biological rationale for the anti-tumor force of the ketogenic diet primarily manifested through its anti-Warburg effect. It is no less true that Otto Warburg’s experiments have based the ketogenic diet in cancer research on solid footing. However, precisely tracing the initial, original anti-tumor use of the ketogenic diet in medical oncology literature has indeed proved to be a hard needle to thread. The currently available data are considered promising in the pre-clinical rodent models. Yet, the number of rigorous human trials is small and suffers from methodological limitations.
Further research, both pre-clinical and clinical, is needed to accurately define the anti-tumor effect of the ketogenic diet and to overcome the current methodological limitations that hinder us from deriving a sound judgment about the use of the ketogenic diet in clinical practice.
Ketogenic diet in the treatment of cancer – Where do we stand?
2020, Molecular Metabolism
Citation Excerpt :
However, especially in patients, use of the KD should be meticulously planned and monitored by physicians and qualified dieticians. Because the classic KD (ratio 4:1) and KDs based on artificial foods potentially lack vitamins and minerals such as vitamin B, vitamin D, calcium, and iron, adequate supplementation of these micronutrients is essential [44,45]. This is a literature review in which we highlight some major findings from preclinical and clinical studies which have used some variations of KD as a single or combination therapy in cancer.
Cancer is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of standard anticancer therapies. The ketogenic diet, a high-fat, low-carbohydrate diet with adequate amounts of protein, appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy.
To critically evaluate available preclinical and clinical evidence regarding the ketogenic diet in the context of cancer therapy. Furthermore, we highlight important mechanisms that could explain the potential antitumor effects of the ketogenic diet.
The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy. The majority of preclinical and several clinical studies argue for the use of the ketogenic diet in combination with standard therapies based on its potential to enhance the antitumor effects of classic chemo- and radiotherapy, its overall good safety and tolerability and increase in quality of life. However, to further elucidate the mechanisms of the ketogenic diet as a therapy and evaluate its application in clinical practice, more molecular studies as well as uniformly controlled clinical trials are needed.
Wilhelm Brünings' forgotten contribution to the metabolic treatment of cancer utilizing hypoglycemia and a very low carbohydrate (ketogenic) diet
2019, Journal of Traditional and Complementary Medicine
Citation Excerpt :
While first preclinical studies into the effect of different forms of diet or macronutrient manipulation on cancer growth have roughly paralleled the early studies on cancer and metabolism,29–31 the first clinical application of a KD to cancer patients is usually assumed to be much more recent, and usually attributed to Kenneth Fearon and co-workers who described the administration of a medium chain triglyceride-rich KD to five cachectic cancer patients in 1988.32 Others mention the case study of two pediatric brain tumor patients by Nebeling et al.33,34 from 1995 as the first clinical KD study (for example Hyde et al.,35 Poff et al.36 or we ourselves in our 2011 review22). Nevertheless, as I describe in the remainder of this paper, both assumptions are not correct: The first clinical study which included the description of a KD to treat cancer patients was published in 1941 by Wilhelm Brünings, a scientist and physician whose obituary has its 80th anniversary this year.
The growing interest in the alterations of tumor cell metabolism and their possible therapeutic exploitation also spurred new complementary and integrative approaches such as treating patients with a ketogenic diet (KD). KDs aim at inhibiting glycolytic tumor metabolism and growth, and have therefore been proposed as adjuncts not only to standard-of-care, but also to other therapies targeting tumor metabolism. Here I describe the life and forgotten work of one of the earliest researchers who realized the importance of altered tumor cell metabolism and its possible exploitation through metabolic modifications: Wilhelm Brünings. Brünings was a German natural scientist and physician famous for his innovative contributions to the fields of physiology and otorhinolaryngology. Based on the findings of Otto Warburg and his physiological reasoning he started to experiment with insulin administration and KDs in his patients with head and neck cancers, aiming to maximally lower blood glucose concentrations. He obtained encouraging short-term results, although most tumors became refractory to treatment after several weeks. His pioneering work is worth revisiting, especially for an international readership that may be unaware of his efforts, as hypoglycemic treatments, including the use of insulin injections and KDs, are currently being re-investigated as complementary and integrative cancer treatments.
Impact of a ketogenic diet intervention during radiotherapy on body composition: II. Protocol of a randomised phase I study (KETOCOMP)
2016, Clinical Nutrition ESPEN
Citation Excerpt :
The reason is that due to their water solubility, after absorption in the gut MCTs are directly transported to the liver via the portal vein where they stimulate ketogenesis. Several studies on a KD in tumor patients have therefore specifically substituted with MCTs [12–14]. The administration of non-glucogenic amino acids could further make a valuable contribution to the diet of tumor patients without leading to increased hepatic glucose production and nitrogen waste.
We have found that a ketogenic diet (KD) during the course of radiotherapy (RT) was feasible and led to a preservation or favorable changes of body composition. Based on these observations and theoretical considerations, we initiated a study to investigate the impact of a KD or a ketogenic breakfast intervention in patients undergoing RT.
All patients presenting for curative RT with age between 18 and 75, body mass index between 18 and 34 kg/m² and a histologically confirmed cancer of the breast, colorectum or head and neck region are considered for inclusion. Exclusion criteria are Karnofsky index <70, pregnancy, metallic body parts that interfere with bioimpedance analysis (BIA), type I diabetes, known enzyme defects that contradict a KD and renal insufficiency. Randomization is achieved by all consecutive patients first entering the control group and then an intervention group 1 until both groups contain 15 breast, 15 colorectal and 5 head and neck cancer patients. Intervention group 1 will receive each radiotherapy fraction after an overnight fast and subsequently ingest a ketogenic breakfast consisting of (i) 50–250 ml of a medium-chain triglyceride drink (betaquick^®, vitaflo, Bad Homburg, Germany) plus (ii) 5–15 g amino acids (MAP, dr. reinwald healthcare gmbh+co kg, Schwarzenbruck, Germany). If willing to undertake a complete KD for the duration of RT, patients are entered into intervention group 2. Intervention group 2 does not have to fast prior to RT fractions but will be supplemented with MAP analogous to intervention group 1. The control group will not receive dietary advice to follow a KD or reduce carbohydrate intake. The objective is twofold: (i) to test whether the ketogenic interventions are feasibly, as measured by the number of dropouts; (ii) to see whether intervention groups 1 and 2 attain a better preservation of BIA phase angle than the control group.
Primary endpoints are the feasibility of the interventions (measured through dropout rates), and changes in body weight and composition (measured through BIA). Secondary endpoints are changes in quality of life (EORTC questionnaires) and blood parameters as well as the occurrence and grade of toxicities and grade of regression after surgery in case of colorectal carcinomas.
Registered under ClinicalTrials.gov Identifier no. NCT00123456.
The Ketogenic Diet for the Adjuvant Treatment of Malignant Brain Tumors
2015, Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and Therapy
Malignant brain tumors are nearly uniformly fatal due, in part, to the limitations of current treatment including surgery, radiation, and chemotherapy. Improvements in survival and quality of life require new approaches, especially those that potentiate currently available therapies without increasing toxicity. Tumor cells have an increased reliance on glucose, and it is now known that many of the pathways that promote tumor cell growth and therapy resistance intersect with metabolic pathways. This suggests that alteration of metabolism through the use of a ketogenic diet, which reduces blood glucose and increases blood ketones, may be beneficial for the treatment of malignant tumors. Current research shows that the ketogenic diet reduces tumor growth, affects growth factor-signaling pathways, reduces angiogenesis and inflammation, and may potentiate the activity of currently used therapies without increased side effects or toxicity. Targeting the metabolism via dietary means offers a new and effective paradigm for the treatment of malignant cancers.
Ketogenic Diet Therapy for Glioma: Combined Effects
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Implementing A Ketogenic Diet Based on Medium-chain Triglyceride Oil in Pediatric Patients with Cancer

Abstract

Section snippets

Why We Selected an Mct Oil-Based Ketogenic Diet

Thy Mct Oil–Based Kethogenic Diet

Enteral Formula

Supplements

Tolerance and Compliance Issues

Applications

J Nutr.

Am J Clin Nutr.

J Am Diet Assoc.

Am J Clin Nutr.

Am J Clin Nutr.

J Am Diet Assoc.

Nutr Cancer.

Hormonal and metabolic abnormalities in the malnourished cancer patienteffects on host-tumor interaction

JPEN.

A review of cancer cachexia and abnormal glucose metabolism in humans with cancer

J Am Coll Nutr.

Nutritional and physiological consequences of tumor glycolysis

Parasitology.

In vivo utilization of substrate by human sarcoma-bearing limbs

Cancer.

Fuel utilization in neoplastic diseaseimplications for the use of nutritional support in cancer patients

Nutrition.

Effects of Dietary Induced Ketosis on Tumor Metabolism, Nutritional Status and Quality of Life in Pediatric Oncology Patients