HomeBorum LabPrecision Ketogenic Therapy Path to Precise, Personalization and Proven

Precision Ketogenic Therapy Path to Precise, Personalized, and Proven

1. Optimize Precision of Precision Ketogenic Therapy

Precision Ketogenic Therapy (PKT) is today’s precision medicine approach to the use of food as medicine. The therapy known as the ketogenic diet was introduced to the medical literature a century ago. Advances in food science, analytical chemistry, computer science, and medicine during the past 100 years allow us to provide food as medicine that meets today’s precision medicine criteria. 

The nutrients in food are the chemicals that maintain health and prevent disease. The precision of administration of nutrients needed to treat disease is usually greater than required to maintain health. The precision of PKT administration requires that the nutrient composition of each food item and the total daily intake be monitored to be able to determine the therapy that is being received. The nutrients are in brand-name foods, fresh foods from the farm, and non-foods containing added nutrients. Data for total groups of nutrients such as fat are required but need to be broken down to the group’s constituents such as families of fatty acids, individual fatty acids, etc. Certification of foods for special diets such as vegan must be documented. Creation and maintenance of the foodomics database is very labor intensive and should begin to incorporate supervised automation of many of the steps in the process. 

Maintenance and Use of Foodomics Database

The purpose of the foodomics database is to list the identity and quantity of each nutrient or chemical in 100 grams of the food or product. Government databases including FoodData Central are our best source for non-brand-name products. We use their Legacy database for foods that do not have a Nutrition Facts Label and that have not yet been added to the Foundation Foods database with its improved analytical approach. Only Nutrition Facts Labels on food products for sale are covered by the food label law. Nutrition Facts Labels listed in advertisements and on the web are frequently out of date. Our experience is that the data on the Nutrition Fats Label changes frequently enough that the database needs to be updated yearly. 

Incorporation of Non-Food Substances Containing Nutrients

Vitamin and mineral supplements, medical foods, and medications received enterally or intravenously may contain nutrients and must be included in the Foodomics database. The Supplement Facts Label on the product or the Food and Drug Administration Ingredient list on the package insert are frequent sources of nutrient composition. 

Extension PKT Foodomics Database to Macronutrient Individual Constituents

The keto ratio has traditionally been (grams of fat/grams of protein plus grams of carbohydrate). Such an equation implies that all fat is the same, all protein is the same, and all carbohydrate is the same. We know that this simply is not true. Within each macronutrient, families of compounds have characteristics more similar than others in that macronutrient. The individual members of each family of compounds in a macronutrient are also different. They differ both in chemical structure and the way the compounds are used in the body. We are learning that the effects of individual members of a macronutrient on symptoms that we are trying to prevent or treat also differ. Therefore, it is important that the Foodomics database includes the identity and quantity of each of the individual compounds of each macronutrient. 

Customization of PKT Foodomics Database for Specific Types of Diets

Before beginning PKT, individuals may already be on a medical diet (such as gluten free), prefer a particular type of diet (such as lacto-ovo-vegetarian), be a member of a family that prefers a cuisine reflective of a particular geographical location in the world. The goals of PKT include facilitating everyone’s ability to continue to eat in a manner that meets their nutritional needs and food preferences. Therefore, PKT recipes for the individual need to administer the PKT Diet Prescription while maintaining their nutritional needs and food preferences. In some cases (such as vegan and kosher) each food in the Foodomics database must include which foods carry the appropriate certification before such recipes can be created. 

Supervised Automation of Foodomics Database Updating

Creation, maintenance, and expansion of the Foodomics database require many steps that are very labor intensive when performed manually. We would like to work with the USDA (United States Department of Agriculture) to update the Foodomics database as quickly as data are released from Foundation Foods. In conjunction with the USDA, we would like to import digitized copies of the nutrition facts labels of products as they are being released to the public. Inclusion and updating of other nutrient containing products including supplements, medical foods, and intravenously administered products will also be automated. 

The PKT diet prescription is calculated to provide the current nutritional needs of the individual. Often dietary recommendations are not available for individuals with the individual’s phenotype, but the window of tolerance for dietary intake of the individual receiving PKT is narrower than that of the reference population. Continuous optimization of a diet prescription for a person on PKT requires nutrient composition data that is more precise than data needed for a general population. 

Precise Personalized Calculation of the Optimal Intake of Calories, Protein Carbohydrate, and Fat

The same compounds used to maintain optimal nutritional status are the compounds that are used to stop seizures. Available recommendations for optimal intake of calories, protein, carbohydrate, and fat are for healthy individuals to maintain health. There are no recommendations for optimal nutrition intake for the specific neurological diagnoses carried by these patients. Therefore, recommendations and the dietary intake before PKT can be a starting point to calculate each patient’s dietary prescription. However, the only way to optimize the diet prescription for a particular patient is to carefully monitor that patient and to alter the diet prescription as needed to improve both nutritional status and seizure control. Improved nutrient composition of foods data must be combined with patient’s food preferences and response to PKT to implement a precise and personalized calculation of the patient’s diet prescription. 

Precise Personalized Calculation of the Optimal Intake of Individual Amino Acids, Fatty Acids, and Carbohydrate Types

As we improve our nutrient database to include individual amino acids fatty acids and carbohydrate types we can combine that with our increasing understanding of how these individual nutrients affect nutritional status and seizure status. We will need to improve our diet prescription tools to include this extended list of nutrients. 

Precise Personalized Calculation of the Optimal Intake of Vitamins, Minerals, and Other Required Nutrient Molecules

Like with the macronutrients, dietary recommendations for micronutrients are for healthy individuals to maintain health. There is a large literature to indicate that vitamin and mineral intake as well as other nutrient molecules may need to be increased for certain types of seizures. Thus, it is critical that we have a foodomics database listing precise information concerning vitamins, minerals, and other nutrient molecules and that we combine this with current information concerning the effect of each nutrient on the brain. Our tools to calculate the diet prescription must be expanded to include all nutrient molecules in addition to the usual macronutrients. 

Creation of AI Approach to Diet Rx Calculation

Currently the steps of calculating a diet prescription are performed in a manual manner. We need to expand our tools to enable a more automated integration of data from different sources of different types and include more nutrient parameters in the diet prescription. The PKT prescription needs to expand the PKT ratio (grams of fat to grams of carbohydrate plus grams of protein) to include the individual components of each of those macronutrients. In addition, the diet prescription should include vitamins, minerals, and any other nutrients that we find to affect either nutritional status or seizure control. 

The PKT meal equivalent calculation results in the recipes that are the tool required for PKT administration. Not only does the recipe need to meet the nutritional needs of the individual and provide the therapy for the symptoms being treated, but it also must create a meal that is pleasing to the eye and the palette. As we understand the importance of more and more parameters in PKT, the precision of calculating these parameters of the recipe must increase. 

  • Improved Robustness, Ease of Use, and Inclusion of More Nutrients in PKT Meal Equivalent Calculator 
  • Integration of Meal Equivalent Calculation and Daily Supplement Calculation 
  • Extension of PKT Meal Equivalent Calculator to Include Non-Food Substances Containing Nutrients 
  • Extension of PKT Meal Equivalent Calculator to Macronutrient Individual Constituents 
  • Creation of AI approach to Meal Equivalent calculation 

2. Optimize Personalization of Precision Ketogenic Therapy

People receiving PKT differ widely in nutritional needs, food preferences, and pathologies. During treatment, symptoms change, nutritional needs change, and the individual’s feeding abilities may change. The initial PKT Diet Prescription needs to be carefully personalized and continuously adapted to the individual’s changing needs. 

PKT modulates an individual’s metabolism in ways that reduce many kinds of symptoms, but that power can also create adverse effects if not done in a precise and personalized manner. PKT has many moving parts that require commitment from caregivers and the patient. Thus, potential recipients of PKT must be evaluated as a single person and not simply as a member of a larger population with some diagnosis.

  • Evaluate Literature Data Relevant to Use of PKT for a Variety of Diagnoses 
  • Create PKT General Guidelines for Each Diagnosis Initiated to PKT 

The PKT diet prescription must supply needed nutrients and the right mix of chemicals needed to reduce symptoms being treated. As we use PKT to treat different kinds of symptoms, the need to personalize PKT increases. Although the desired change in metabolism occurs when nutritional ketosis is induced, it is not clear what changes in metabolism are causing the changes in the symptoms. Therefore, the necessity to personalize the PKT diet prescription is a hallmark of the therapy. 

  • Calories, Grams Protein, PKT Ratio 
  • Vitamins and Minerals

Since PKT uses food as medicine, nutritional parameters are monitored as part of the therapy. Current nutritional status determines the most important nutritional parameters to be monitored and will differ from patient to patient. As we use PKT for different types of symptoms, the parameters monitored will be determined by the specifics of the symptoms being treated. Even for patients with the same diagnosis, the details of the symptoms will vary and thus the parameters that need to be monitored must be personalized. 

  • Personalized Nutritional Status 
  • Personalized Clinical Lab Value Status 
  • Personalized Seizure Status 
  • Personalized Neurological Status 
  • Personalized Quality of Life 

Age of the patient, feeding skills, food preferences, economic access to food, and many other parameters determine the types of meals that are appropriate for a patient. When using food as medicine in PKT, we strive to maintain the cultural and nurturing aspects so closely associated with food. Thus, the tools for administration of PKT are presented as a cookbook that is personalized for the patient and provides the caregiver with the details of exactly how much of what food to use including suggestions for preparation of the meal. 

  • Personal Restrictions/Preferences of Foods 
  • Route of Administration of Food 
  • PKT Cookbook Basis for PKT Patient Cookbooks 

3. Increase Evidence Documenting the Outcome of Precision Ketogenic Therapy

Although the symptoms that cause a person to consider PKT are usually seizures, the person is often experiencing other symptoms that may be due to the disease or side effects of treatment for the disease. PKT is the use of nutrients to change metabolism in all of the body.  Thus, a holistic approach to monitoring the outcome of PKT is needed to both optimize and personalize it. 

Since the first medical publication of the ketogenic diet 100 years ago, there have been many variations of the therapy developed and used by different centers. During the past quarter century of ketogenic therapy, some centers have moved in the direction of less emphasis on the precise documentation of dietary intake and others including our center have moved in the direction of greater precision in documenting nutrient intake and in documenting specific outcomes of therapy. Many publications state that a person is treated with ketogenic diet as though that defines what they are receiving. It would be instructive to formally compare and contrast protocols for the different ketogenic therapies. 

  • Classical Ketogenic Diet 
  • Medium-Chain Triglyceride Diet 
  • Low Glycemic Index Treatment 
  • Modified Atkins Diet 

Many parameters should be monitored when evaluating PKT outcome including seizures, need for anti-seizure medications, growth and development, and many other parameters of health. Publications sometimes simply compare the number of times a parameter occurs during a day or some other time period. Better defined parameters are needed to evaluate the outcome of PKT and other ketogenic therapies. 

  • Nutritional Status 
  • Clinical Lab Value Status 
  • Seizure Status 
  • Neurological Status 
  • Quality of Life 

Our ongoing natural history study of PKT has provided longitudinal data for patients receiving the therapy for more than 20 years. These data need to be interrogated to evaluate the outcome of PKT. 

  • Interrogation of Our Anthropometric Data During PKT 
  • Interrogation of Our Anti-seizure Medication Score Data During PKT 
  • Interrogation of Our Blood Glucose, Blood Beta-Hydroxybutyrate, and Urine Ketone Dat During PKT 
  • Interrogation of Our Blood Lipid Data During PKT 
  • Interrogation of Our GI Issues Data During PKT 
  • Interrogation of Our Nutrient Intake Data During PKT 
  • Interrogation of Our Seizure Score Data During PKT 
  • Interrogation of Out Meal Challenge Data During PKT 

4. Increase Evidence Documenting the Mechanism of Precision Ketogenic Therapy

Ketogenic Therapy was originally created to mimic fasting or starvation in an attempt to recreate the reduction in seizures observed during fasting. Since both fasting and PKT induce ketosis, the obvious first hypothesis for mechanism of action was the effect of ketones. After thousands of published papers, we still have a very incomplete understanding of the mechanism. It is expected that a better understanding of the mechanism will facilitate improved PKT for each individual at a particular point in time.

Thousands of papers have been published using ketogenic therapy in different species at different ages for different symptoms, but the mechanism of action is still not understood. Different hypotheses have been proposed by different groups using ketogenic therapies that are likely not the same. Association of the different hypotheses with the type of ketogenic therapy administered will be used to search for a pattern and to evaluate the different hypotheses against our longitudinal data. 

  • Interaction of Macronutrients and Ketones as Fuel Sources in Ketogenic Therapy 
  • Interaction of Individual Ketones, Fatty Acids, Acylcarnitines, Amino Acids, and Carbohydrates in Energy Metabolic Homeostatis in Ketogenic Therapy 
  • Interaction of Individual Ketones, Fatty Acids, Acylcarnitines, Amino Acids, and Carbohydrates in Inflammation in Ketogenic Therapy 

There is a consensus that fasting for a period of time or consuming a low carbohydrate diet for a period of time often results in a reduction in seizures. Since these situations result in the induction of nutritional ketosis, it is tempting to assume that induction of ketosis causes this reduction in seizures. However, we do not have data to conclude this. We simply know that these two situations change metabolic homeostasis in some manner that reduces seizures. Therefore, we need to revisit the literature data to compare and contrast fed and fasted metabolic homeostasis in normal and pathological states. 

  • Interaction of Macronutrients and Ketones as Fuel Sources 
  • Interaction of Individual Ketones, Fatty Acids, Acylcarnitines, Amino Acids, and Carbohydrates in Energy Metabolic Homeostatis 
  • Interaction of Individual Ketones, Fatty Acids, Acylcarnitines, Amino Acids, and Carbohydrates in Inflamation 
  • Influence of Gut Microbiota on each Interaction Listed Above 

5. Improve Communication Concerning Precision Ketogenic Therapy

Ketogenic diet means as many different things as there are people receiving it. Therefore, the term ketogenic therapy must be followed by a definition and detailed descriptionThe name Precision Ketogenic Therapy indicates use of food to induce nutritional ketosis using a very precise approach. Communication of the details of PKT is essential to its successful adoption for those who would benefit from it. 

The vision of our PKT website is to communicate details of our understanding of PKT to different audiences including researchers trying to better understand PKT, individuals and families who are considering PKT for treatment, and healthcare professionals who are considering administering PKT. 

  • Improve PKT Communication Via Blogs 
  • Improve PKT Communication Via Videos 
  • Improve PKT Communication Via Podcasts 

Abstracts at regional national and international meetings provide an opportunity to communicate early data to support individual PKT principles. 

  • PKT Abstracts Presented to Local and Regional Groups 
  • PKT Abstracts Presented to National and International Organizations

Peer reviewed scientific papers provide a forum for full length investigations of PKT to be made available to the entire community. 

  • Systematic and Narrative Reviews 

Although the primary role of funding proposals is to obtain the funding needed to conduct a study, proposals for PKT funding that are reviewed by other investigators provide an opportunity to communicate ideas about PKT and to receive the thoughts and reactions of the reviewers to those ideas. 

  • National Funding 
  • University of Florida Funding