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The ease of implementing and following a ketogenic diet varies from person to person, depending on several factors, including fitness level, disease state, and lifestyle. The gold standard to determine whether someone has achieved a state of nutritional ketosis is to measure blood ketone levels. For those who have difficulty reaching and sustaining ketosis, ketone supplementation may be beneficial. In this clip, Dr. Dominic D'Agostino describes the parameters that affect an individual's response to ketosis.
Rhonda: At the root, or at the heart of a lot of these neurological disorders is a metabolic dysfunction and how, first of all, when we talk about nutritional ketosis, to me, it's so, it's such a broad way of describing.
Dom: Very broad.
Rhonda: What is nutritional ketosis? Like, and how do you achieve it?
Dom: So nutritional ketosis could be, it's defined...they, kind of, have the same definition in my mind. It's achieving and sustaining a level of blood ketones. And I think when people say they've done the ketogenic diet, they did that it didn't work for them or it did work for them, I would ask the question, "Well, did you measure blood ketones? Did you confirm, in fact, that you were able to achieve a state of ketosis?" Defined as an elevation of blood ketones above 0.5 millimolar at the very least. Ideally, you want to stay between one and three millimolar of ketones. And when you've achieved that state...
Rhonda: You're talking about blood ketones?
Dom: I'm talking about blood ketones, yeah, which is, kind of, the gold standard. And this can be measured. There's a number of different devices out there that measure blood ketones. And when that...the state of nutritional ketosis is achieved, you're also, not only not only that biomarker is, kind of, there and we have technologies to measure it, but it would also be important to measure your blood glucose and maybe insulin levels, too. The suppression of the hormone insulin drives hepatic ketogenesis and drives the body's ability to make ketones. And that has therapeutic implications for type 2 diabetes, obviously.
So my definition of nutritional ketosis would be an elevation of blood ketones and the, kind of, the difficulty in prescribing that or telling someone to do it is that the way to implement that is, kind of, similar with everyone, but everyone responds differently depending on where you're coming from. So if you have an obese subject that's type 2 diabetic, it's going to be different than an athlete. And women, there's some differences between women and men, I think. So defining nutritional ketosis is relatively easy with an elevation of blood ketones, but implementing it and being able to, for the individual to commit to it and have that, kind of, ability to control their diet, which is very linked to lifestyle, has been, sort of, a difficult thing to do. And that's where ketone supplementation, kind of, comes in and can allow someone to rapidly achieve nutritional ketosis and sustain it and perhaps get many of the therapeutic benefits that we're just finding out now. We know that ketones are more than just a metabolite. They are more than just an energy metabolite that the brain can use, but they are metabolites, especially beta-hydroxybutyrate, are very powerful signaling molecules. And we're just beginning to understand, sort of, the therapeutic effects of these metabolites as signaling molecules and that's a big thrust of our lab right now.
A chemical produced in the liver via the breakdown of fatty acids. Beta-hydroxybutyrate is a type of ketone body. It can be used to produce energy inside the mitochondria and acts as a signaling molecule that alters gene expression by inhibiting a class of enzymes known as histone deacetylases.
A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.
A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.
A metabolic pathway in which organisms produce ketones. Ketogenesis occurs primarily in the mitochondria of liver cells via the breakdown of fatty acids and ketogenic amino acids. Insulin is the major hormonal regulator of ketogenesis; however, glucagon, cortisol, thyroid hormones, and catecholamines can induce greater breakdown of free fatty acids, thereby increasing the substrates available for use in the ketogenic pathway. The primary ketones used by the body for energy are acetoacetate and beta-hydroxybutyrate.
A diet that causes the body to oxidize fat to produce ketones for energy. A ketogenic diet is low in carbohydrates and high in proteins and fats. For many years, the ketogenic diet has been used in the clinical setting to reduce seizures in children. It is currently being investigated for the treatment of traumatic brain injury, Alzheimer's disease, weight loss, and cancer.
Molecules (often simply called “ketones”) produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, or prolonged intense exercise. There are three types of ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. Ketone bodies are readily used as energy by a diverse array of cell types, including neurons.
A molecule that allows cells to perceive and correctly respond to their microenvironment, which enables normal cellular function, tissue repair, immunity, cognition, and more. Hormones and neurotransmitters are examples of signaling molecules. There are many types of signaling molecules, however, including cAMP, nitric oxide, estrogen, norepinephrine, and even reactive oxygen species (ROS).
A metabolic disorder characterized by high blood sugar and insulin resistance. Type 2 diabetes is a progressive condition and is typically associated with overweight and low physical activity. Common symptoms include increased thirst, frequent urination, unexplained weight loss, increased hunger, fatigue, and impaired healing. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, diabetic retinopathy (and subsequent blindness), kidney failure, and diminished peripheral blood flow which may lead to amputations.
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