How the Keto Diet Can Improve Cognitive Function with Dr. Dale Bredesen (Ketoflex 12/3)
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Diet plays a key role in the prevention of Alzheimer's disease. The Ketoflex 12/3 diet, a form of time-restrictive eating that limits the period during which a person eats to a 12-hour window at least three hours before bedtime, promotes the production of ketones. These molecules, which are produced by the liver during the breakdown of fatty acids. induce physiological and metabolic responses that cleanse the brain and promote brain health. In this clip, Dr. Dale Bredesen describes his novel dietary protocol, the Ketoflex 12/3, and how it improves cognitive function.
Dale: So then the 12/3 part of Ketoflex 12/3, a minimum of 12-hour fasts between when you finish dinner and when you start breakfast or brunch or lunch, if you are ApoE4 positive you're actually a better fat absorber, as you know, so you want to make that 14 to 16 hours. If you're ApoE4 negative, 12 to 14 hours. And be careful, if you have a very low BMI, you can lose weight on this Ketoflex 12/3 diet and so you have to liberalize typically once a week, have some sweet potatoes or something that's a little more carbohydrate-related. And of course, in the book we talk about the various things that you want to do with this diet, but 12 hours, that gives you time for autophagy, it gives you time essentially at night to induce your ketosis, to clean out your brain, of course, the glymphatic system, you actually have a change in the architecture of your brain as you're sleeping, you're actually essentially sweeping this stuff out, it's kind of amazing, actually.
And so, if you're eating with these very small windows of sleep and very small windows of fasting you're actually doing yourself harm and putting yourself at greater risk. And then similarly, you want three hours before bed after you finish your dinner. You don't want to eat right up until bedtime because your insulin's high, and again, that's hurting your cognition. That's again, giving you the same sort of insulin resistance problem, storing fat, you're doing all the things that are not helpful. So that's the dietary approach. And of course, you want to have organic. There are toxins in our food, it's unfortunate. We've got a tremendous a life-long exposure to toxins.
Of course, Bruce Ames, with whom you've trained, developed the Ames Test, which allows us now to look at carcinogens, but nobody has ever told us, "Well, hey, what about dementogens?" You're exposed every day to various dementogens, things like mercury, things like some of the organics that are in some of the health and beauty aids, and things like biotoxins. If you're living in a home that has leaks, you are exposed to dementogens and you need to know about that.
So that's the Ketoflex 12/3. We want it be...it's a plant-rich diet that Mark Hyman calls plant-rich as opposed to plant-based, but either way it is a plant-rich diet that can use some animal products, it's up to you. You want to be vegetarian, that's fine, you don't, that's fine too. That minimizes the toxins, you want to have a high, typically 70% or so calories from fat, and you can start out with using things like MCT oil or coconut oil to get your ketones up. We're finding that people who have higher ketone levels, 1.5 millimolar to 4 millimolar more beta-hydroxybutyrate tend to do better than those who are down lower.
Rhonda: ApoE4 positive or negative?
Dale: And ApoE4 positive or negative. Now interestingly, for the ApoE4s what we typically suggest, and this was actually originally suggested by Julie G. who started the website, apoe4.info. You essentially start with using the MCT oil to help you get your ketosis, but then switch after a month or two to more monounsaturates and polyunsaturates. Now you can essentially balance, so you have the best of both worlds. You follow your LDL particle number, your LDLP. You want to keep it below 1,000 so you can adjust how much MCT oil and how much of the monounsaturates and polyunsaturates so they have the best heart outcome, the best cardiovascular outcome, at the same time have the best cognitive outcome.
Be careful, if don't get your ketones up and you get your carbs down you're starving your brain, and so then people will say, "Oh my gosh, I just have no energy." So you want to use that. You want to basically be changing over to a more ketone-based metabolism for your brain. And then, as you indicated, you want to go back more toward the monounsaturates and polyunsaturates to make it heart healthy.
Rhonda: So for this, for the ApoE4 positive people you do recommend lowering the saturated fat intake because of the LDL.
Dale: After you become insulin sensitive, so after you want to drive yourself into insulin sensitivity, so you're able now to convert, because it takes a few weeks, as you know, to convert from a largely carbohydrate-based metabolism to a largely fat-based metabolism. So if you try to do it in a day you may end up with so-called keto flu, and it takes some time and you're now producing, it's a whole set of things you're producing, it's going to be less inflammatory, you're lowering your reliance on glucose, you're becoming metabolically flexible, and you're now essentially developing a use of the ketones and it does takes a few weeks. And it's helpful to do things like exercise and things at that time to help you convert.
Rhonda: And then the fasting, the overnight fasting of at least 12 hours, or like you said, if you're ApoE4 positive possibly even increase that to 14 hours.
A neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Most cases of Alzheimer's disease do not run in families and are described as "sporadic." The primary risk factor for sporadic Alzheimer's disease is aging, with prevalence roughly doubling every five years after age 65. Roughly one-third of people aged 85 and older have Alzheimer's. The major genetic risk factor for Alzheimer's is a variant in the apolipoprotein E (APOE) gene called APOE4.
One of three common genetic variants of the APOE (apolipoprotein E) gene. The APOE4 allele, which is present in approximately 10-15% of people, increases the risk of developing Alzheimer's disease and lowers the age of onset. Having one copy of E4 increases risk 2- to 3-fold, while having two copies increases risk as much as 15-fold.
An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.
The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.
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.
Important for the endocrine enhancing properties of exercise. Exerkines are exercise-induced hormonal-like factors which mediate the systemic benefits of exercise through autocrine, paracrine, and/or endocrine properties.[1]
A system that clears the brain of metabolites and other waste. The glymphatic system comprises a vast arrangement of interstitial fluid-filled cavities surrounding the small blood vessels that serve the brain. During sleep, these perivascular structures increase in size by more than 60 percent. This allows a “flushing” operation in which waste products can be eliminated. The glymphatic system also facilitates the distribution of essential nutrients such as glucose, lipids, and amino acids, as well as other substances, such as growth factors and neuromodulators.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
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 physiological condition in which cells fail to respond to the normal functions of the hormone insulin. During insulin resistance, the pancreas produces insulin, but the cells in the body become resistant to its actions and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level.
A measure of how sensitive the body's tissues are to the effects of insulin. Insulin sensitivity defines a relationship between insulin production and glucose uptake. Poor insulin sensitivity promotes increased pancreatic insulin production, which can lead to increased risk for high blood pressure, heart disease and heart failure, obesity, osteoporosis, and even cancer.
An essential mineral present in many foods. Iron participates in many physiological functions and is a critical component of hemoglobin. Iron deficiency can cause anemia, fatigue, shortness of breath, and heart arrhythmias.
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 class of saturated fats. Medium-chain triglycerides are composed of medium-length fatty acid chains (six to 12 carbons long) bound by a glycerol backbone. They occur naturally in coconut oil, palm oil, and butter, but they can also be synthesized in a laboratory or food processing setting. Evidence suggests that MCT therapy improves cognitive function in older adults with Alzheimer's disease.[1] Examples of MCTs include caprylic acid (C8), capric acid (C10), and lauric acid (C12).
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
A chemical that causes Parkinson's disease-like symptoms. MPTP undergoes enzymatic modification in the brain to form MPP+, a neurotoxic compound that interrupts the electron transport system of dopaminergic neurons. MPTP is chemically related to rotenone and paraquat, pesticides that can produce parkinsonian features in animals.
The highest level of intake of a given nutrient likely to pose no adverse health effects for nearly all healthy people. As intake increases above the upper intake level, the risk of adverse effects increases.
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