A Therapeutic Ketogenic Diet – treatment and adjunct treatment

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Introduction

A therapeutic diet is used to treat a medical condition, and when prescribed by a Physician and implemented by a Dietitian, it is referred to as Medical Nutrition Therapy (MNT) [1].

Therapeutic ketogenic diets are a form of medical nutrition therapy using a specific ratio of fat to protein plus carbohydrate. These diets are also referred to as ketogenic diet therapy or ketogenic metabolic therapy, and may be used as an adjunct treatment for specific physical health conditions.

Therapeutic ketogenic diets are very high in fat and help the body enter and stay in a state called ketosis. In ketosis, the body burns fat for energy instead of carbohydrates. Nutritional ketosis occurs when the ketone called beta-hydroxybutyrate (BHB) reaches levels between 0.5 and 3.0 mmol/L [2].

In therapeutic ketogenic diets, like those used to treat epilepsy and seizure disorders, BHB levels can go up to 4.0 mmol/L [3], and for conditions such as glioblastoma, where a therapeutic ketogenic diet is used as an adjunct treatment alongside chemotherapy and radiation, BHB levels can reach up to 3.0 mmol/L [4,5,6].

Note: Just because a therapeutic diet may help in glioblastoma does not mean it is suitable for all types of cancer. Most cancers use glucose to grow; a few use ketone bodies.

Types of Therapeutic Ketogenic Diets

Ketogenic diets are a type of low-carbohydrate diet.

Low-carbohydrate diets are defined as diets in which less than 130 grams of carbohydrates per day, or less than 26% of total energy intake, are consumed [7]. This level of carbohydrate intake is considered too high for therapeutic purposes, such as the treatment of epilepsy or seizure disorders, or when used as an adjunct therapy for glioblastoma. However, they are often used to manage type 2 diabetes.

Moderate-carbohydrate diets are defined as diets in which 130–225 grams of carbohydrates per day, or 26–45% of total energy intake, are consumed [7]. While these diets can be used to help manage type 2 diabetes or obesity, the carbohydrate intake is still too high for the treatment of epilepsy, seizure disorders, or as an adjunct therapy in glioblastoma.

A very low-carbohydrate diet is also referred to as a “ketogenic diet.” In this diet, carbohydrate intake is limited to 20–50 grams per day, or about 10% of total energy intake [7]. It is considered safe and effective for the treatment of type 2 diabetes and obesity [2], and it is also used in the treatment of epilepsy, seizure disorders [3], and as an adjunct therapy in glioblastoma [4,5,6]. Because carbohydrate intake is kept very low, protein and fat intake are increased.

In therapeutic ketogenic diets used for obesity management or to help manage type 2 diabetes, protein intake is set between 15% and 35–40% of total calories. Nutritional ketosis is induced because the diet is very high in fat and very low in carbohydrates, allowing beta-hydroxybutyrate (BHB) levels to reach 0.5–3.0 mmol/L [2].

For the treatment of epilepsy, seizure disorders, or as an adjunct therapy in glioblastoma, protein intake is kept as low as 15% of calories to allow BHB levels to rise to between 3.0 and 4.0 mmol/L.

Historic Roots of the Ketogenic Diet

A therapeutic ketogenic diet has been used since the 1920s by Dr. Russell Wilder for the treatment of diabetes and later for the treatment of epilepsy. In fact, the term “ketogenic diet” is credited to Wilder himself. The precise percentages of carbohydrate, fat, and protein in what is now called the “classic” Ketogenic Diet (KD) were calculated by Dr. M.G. Peterman in 1925 [8], and these same ratios are still used today.

Therapeutic ketogenic diets used for epilepsy, seizure disorders, and as adjunct therapy in glioblastoma are very high in fat, low in protein, and low in carbohydrates. Ratios range from 4:1 (4 parts fat for every 1 part protein plus carbohydrate) to 3:1 (3 parts fat for every 1 part protein plus carbohydrate), and for maintenance, ratios as low as 2:1 may be used.

The Clinical Diet Prescription

As a Dietitian who designs therapeutic ketogenic diets, the first step is to determine the amount of energy (calories, in kcal) the individual needs. This is calculated based on the person’s weight, height, activity level, nutritional requirements, and whether weight loss is to be avoided, such as in the treatment of glioblastoma.

The second step is to determine the percentage of calories that needs to come from fat, protein, and carbohydrate based on the specific dietary prescription, whether 4:1 or 3:1. To keep ketone production constant over the day, each meal must contain the exact amounts of fat, protein, and carbohydrate specified. Just as medication has a “dosage,” the specific types and exact amounts of food in the diet prescription are treated as a “food dosage.”

When adults are trialing a 4:1 or 3:1 ketogenic diet for seizure disorders or glioblastoma, a simple breakfast, lunch, and dinner meal plan is designed for use during the first six weeks. For those with glioblastoma, a 2:1 Modified Atkins Diet is usually requested for use between rounds of chemotherapy and radiation. This diet allows for more protein and provides a more pleasant “break” from restrictive 4:1 meals.

The Precision of Meal Planning

For those starting a therapeutic ketogenic diet, a challenge is presented by the requirement that the amounts of food on the final meal plan must be weighed precisely. Even the smallest amount of vegetables, which contain some protein and carbohydrates, can affect the macronutrient ratios and reduce the therapeutic benefit. Therefore, all foods must be weighed to the gram.

In addition, daily monitoring of blood ketone levels is required at the beginning to determine when the desired therapeutic range has been achieved. For epilepsy and seizure disorders, this range is often defined as BHB levels between 3.0 and 4.0 mmol/L. Once the desired levels can be maintained, less frequent testing can be performed.

Standard Protocols: 4:1, 3:1, and 2:1 Ratios

Classic Ketogenic Diet (KD) – 4:1: Matches total calories needed by the person. Protein is usually set at 1 gram per kilogram of body weight, carbohydrate is limited to 10–15 grams per day, and the remaining calories are provided as fat. This ratio means 4 parts fat for every 1 part protein plus carbohydrates; 80% of calories are from fat.

Modified Ketogenic Diet (MKD) – 3:1: This ratio means 3 parts fat for every 1 part protein and carbohydrate. This diet provides 75% of calories from fat, and 25% from a combination of protein and carbohydrate. Protein may be set at 15% of calories, with a maximum of 10% from carbohydrate [5].

Modified Atkins Diet (MAD) – 2:1: Carbohydrate intake is restricted to less than 15 grams per day for children and less than 20 grams per day for adults. For adults, 60% of calories are from fat, 30% from protein, and 10% from carbohydrate [5].

“Chasing Ketones” – The Therapeutic Goal

While people following popular “keto diets” for weight loss are often teased for “chasing ketones,” those following a therapeutic ketogenic diet for epilepsy or seizure disorders are seeking to maintain ketones between 3.0 mmol/L and 4.0 mmol/L. The therapeutic goal is to reach these levels as quickly as possible and maintain them, as the benefit is provided by the ketones themselves.

It is recommended that, for those starting a therapeutic diet, a medical-grade meter be obtained. Blood glucose should not fall below 4.0 mmol/L, and blood ketone levels should ideally measure between 3.0 mmol/L and 4.0 mmol/L—but not higher. If ketone levels exceed 4.0 mmol/L, one’s doctor should be contacted immediately.

For seizure disorders, neurologists seek levels as close to 4.0 mmol/L as possible, as this is where most benefit is seen. To achieve the precise level of ketones required, a certain amount of trial and error in adjusting the diet is involved, but for those seeking to extend life or improve quality of life, the process is often worthwhile.

NOTE: (April 13, 2021): While some research papers indicate that advanced gliomas do not use ketones as a fuel source, a research paper published in September 2020 has called this into question. According to this paper, different types of glioblastoma cells exist, and some are able to oxidize fatty acids and use ketones for energy [9]. Many thanks are extended to Cliff Harvey, PhD, for helping to complete this understanding.

More Info?

Learn about me here. To find out about the types of therapeutic ketogenic diets that I design as adjunct therapy for physical and mental health conditions, view theTherapeutic Diet Services page.

To your good health!

Joy

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References

  1. Centers for Medicare & Medicaid Services (CMS), HHS. Medicare program; revisions to payment policies under the physician fee schedule for calendar year 2002. Final rule with comment period. Fed Regist. 2001 Nov 1;66(212):55245-476. [https://www.govinfo.gov/content/pkg/FR-2001-11-01/pdf/01-27159.pdf]
  2. Bhanpuri NH, Hallberg SJ, Williams PT, et al. Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study. Cardiovasc Diabetol. 2018 May 1;17(1):56. [https://pubmed.ncbi.nlm.nih.gov/29712560/]
  3. Meira ID, Romão TT, Pires do Prado HJ, et al. Ketogenic Diet and Epilepsy: What We Know So Far. Front Neurosci. 2019 Jan 29;13:5. [https://pmc.ncbi.nlm.nih.gov/articles/PMC6361831/]
  4. van der Louw EJTM, Olieman JF, van den Bemt PMLA, et al. Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study. Ther Adv Med Oncol. 2019 Jun 21;11:1758835919853958. [https://pubmed.ncbi.nlm.nih.gov/31258628/]
  5. Schwartz KA, Noel M, Nikolai M, et al. Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned. Front Nutr. 2018 Feb 23;5:11. [https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2018.00011/full]
  6. Klein P, Tyrlikova I, Zuccoli G, et al. Treatment of glioblastoma multiforme with “classic” 4:1 ketogenic diet total meal replacement. Cancer Metab. 2020 Nov 9;8(1):24. [https://pmc.ncbi.nlm.nih.gov/articles/PMC7653752/]
  7. Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015 Jan;31(1):1-13. [https://pubmed.ncbi.nlm.nih.gov/25287761/]
  8. Peterman MG. The Ketogenic Diet. JAMA. 1928 May 5;90(18):1427-1429. [https://jamanetwork.com/journals/jama/article-abstract/269045]
  9. Sperry J, Condro MC, Guo L, et al. Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy. iScience. 2020 Sep 25;23(9):101453. [https://pubmed.ncbi.nlm.nih.gov/32861192/]
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