Coconut Oil, MCT oil, and other Ketone/Cognition Boosters (salts, esters)
Ketones, also known as ketone bodies, are a source of fuel for the body, especially the brain. With today’s diet most individuals burn just glucose as a source of fuel, but ketones can also be made by the body for energy. Making ketones in the body for fuel was something our ancestors did with great regularity given their active lifestyle and unpredictable/seasonal availability of food. Today there are products that can be consumed for rapid conversion to ketones" coconut oil, MCT oil, salts, esters etc.
While glucose is typically an individual’s primary fuel, those with Alzheimer’s Disease have glucose uptake impairment in the brain. This is a condition that starts decades before cognitive impairment is evident and especially so in ApoE ε4s (Brain Glucose Hypometabolism and Oxidative Stress in Preclinical Alzheimer’s Disease, Mosconi, et al 2008). But the brain is a fuel “hybrid” it can burn ketones even if glucose uptake is impaired. In fact, there are many who argue that because ketones burn cleaner and more efficiently, the brain prefers ketones even though it’s not the main fuel of the brain. The brain is not a pure hybrid, it must burn some glucose, it cannot run on ketones alone. As is often the case, the brain can be swimming in glucose but if its glucose uptake capability is impaired, it can't use the glucose it so desperately needs for fuel. Ketones can offer a needed boost of energy for the brain. Ketones are often advocated for ApoE ε4s. For more information, see Ketosis_and_Ketogenic_Diet
In the presentation Can Ketones Slow Down Alzheimer’s? Dr Stephen Cunnane, who has researched omega-3 fatty acids and ketones in human brain development and function for over 30 years, posits two possibilities for Alzheimer’s:
(1) That the brain’s cells are alive but glucose uptake is impaired, so unless ketones are available, they are starved for fuel. (2) That the brain’s cells are dead/dying and thus unable to uptake any form of fuel either glucose or ketones. He has found the first scenario to be more accurate: those with Alzheimer’s are able to use ketones even though they are unable to use glucose. Thus the rationale for providing ketones to enhance cognitive function. This of course is only accurate when intervention to provide ketones occurs early enough that the brain cells haven’t died due to a lack of an energy source and exposure to oxidizing agents.
Coconut oil and MCT oil
Coconut oil and MCT oil help boost ketones/brain function because, unlike other fats and oils, they are high in Medium Chain Triglycerides. In fact that’s what the MCT stands for: Medium Chain Triglyceride. The name just refers to the length of carbon atoms in the oil (C8 or C10). The fat in most food consists of long chain triglycerides. When you eat fat in the form of long chain triglycerides it is broken down in the small intestine. But the medium-chain triglycerides, caprylic (C8) and capric (C10), bypass that process by directly penetrating the small intestine. They then go to the liver where they are quickly converted into ketones, which are then released back into your bloodstream and transported throughout the body, including the brain, to be used as fuel.
Coconut/MCT Oil and ApoE ε4
While both Coconut oil and MCT oil can boost brain function, ApoE ε4s are often advised to use them judiciously with the preferred source of ketones coming endogenously, i.e. made in the body by the liver through a process called ketogenesis. See Ketosis and Ketogenic Diet. In his book The End of Alzheimer’s Dr Dale Bredesen, internationally recognized expert in the mechanisms of neurodegenerative diseases, refers to coconut oil and MCT oil by saying, ”But both may also have drawbacks for ApoE4-positive individuals …If you are ApoE4 positive, think of MCT and coconut oil as temporary crutches to ease your segue into fat burning mode.”
What Dr Bredesen is referring to when he says “segue into fat burning mode” is the keto adaptation process. When we are born, we are efficient ketone burners but as we approach adulthood, and especially with eating a mostly carbohydrate diet, our ability to produce/burn ketones goes into “sleep mode.” When reawakening this ability to burn fat for fuel in the body, the brain has to be weaned off the glucose and a person can feel bad (keto flu) during this adaptation process. Adding MCT or coconut oil can ease the transition.
Coconut oil or MCT oil does seem to be particularly useful for anyone with cognitive issues and insulin resistance. (A person can be insulin resistant without being Type 2 Diabetic (T2D), but if Type 2 Diabetic, a person is by definition insulin resistant.) If not diabetic but insulin resistant, a person is on the path to Type 2 Diabetes and/or other significant health concerns whether or not diabetes develops. Intervention can reverse insulin resistance/Type 2 Diabetes. Unfortunately, insulin resistance often goes undiagnosed. For more info Insulin Resistance). Studies show a strong association between insulin resistance and/or diabetes with dementia and Alzheimer’s. If an ApoE ε4 carrier with insulin resistance or diabetes, this association with dementia and Alzheimer’s is particularly strong. At about the 33 minute point of this lecture, Can Ketones Slow Down Alzheimer’s?, Dr Cunnane discusses insulin resistance. He notes that if on a ketogenic diet but insulin resistant, the insulin resistance prevents the body’s fat tissue from releasing the fatty acids that are used to make ketones, thus preventing ketones from getting into the brain. But coconut oil and MCT bypass the glucose and Long Chain Fatty acid metabolism (that requires insulin) by going directly to the liver thereby providing ketones for the brain.
While helpful, there are areas of concern for ApoE ε4s when it comes to relying solely on supplementation of substances that convert rapidly to ketones (such as coconut oil or MCT oil) or exogenous ketones to aid cognition versus addressing insulin resistance and using ketones produced by the body.
- Providing fuel to the brain in the form of exogenous ketones, coconut oil or MCT oil can be considered a “band-aid” approach. It works around the problem but does not resolve the fuel impairment issue nor the insulin resistance. Insulin resistance/diabetes is associated with a number of other health concerns besides Alzheimer’s including vascular dementia and cardiovascular disease to which ApoE ε4s also have a greater predisposition.
- For ApoE ε4 carriers, coconut oil and MCT worsens lipid profiles, particularly LDL-P and ApoB. LDL and ApoB, used as markers for cardiovascular health, also appear to correlate with cognitive impairment Ratio of apoB/LDL: a potential clinical index for vascular cognitive impairment, Cheng Qian and Fei Tan, 2016. It may be better for ApoE ε4s to use other unsaturated fats (such as olive oil), to resolve insulin resistance, and become ketogenic in order to produce and use their own ketones.
- Oils high in medium chain triglycerides are also high in saturated fats. Granted, saturated fats have been demonized more than they’ve deserved, see the subheading write-up A short history regarding contemporary attitudes about fat Fats, Omega -3(ω-3) & -6(ω-6), DHA and More. But there are studies that indicate saturated fats do have a more pronounced negative effect on ApoE ε4s, see the subheading Deeper Dive into the Science Fats, Omega -3(ω-3) & -6(ω-6), DHA and More
- Oils high in medium chain triglycerides are also high in Omega-6s. Omega-6s are inflammatory when overconsumed, something to which ApoE ε4s are already highly susceptible. On the other hand, Omega-3s, found predominantly in unsaturated fats are critical contributors to cell structure and function in the central nervous system suggesting supplementation may slow early memory decline in ε4 carriers. For further discussion see the Omega -3s and Omega -6s subheading Fats, Omega -3(ω-3) & -6(ω-6), DHA and More. In balance, Omega-3s and Omega-6s work well together. In the Primer: An introduction to ApoE4, biochemistry, and possible prevention strategies a 3:1 ratio of Omega-6s to Omega 3-s is recommended, but most modern diets don’t support that. Coconut oil has a poor Omega -6 to -3 ratio of 88:1. Palm kernel oil is even worse with no Omega-3s whatsoever. Trying to counterbalance the Omega-6s by supplementing with Omega-3s might not work since Omega-3s and Omega-6s compete for the same conversion enzymes and the Omega-6s can “crowd out” the beneficial Omega-3s.
- Ketone Supplementation may not be of assistance for ApoE ε4s. This study Effects of beta-hydroxybutyrate on cognition in memory-impaired adults (M A Reger, et al, 2004) separated its findings between ApoE4 positive and negative. The study found that while MCT supplementation aided those who were ApoE ε4 negative, it wasn't beneficial for ApoE4s.
- There's also this larger study, Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731764/ (S T Henderson, et al, 2009) (AC-1202 is an MCT composed almost entirely of C8 fatty acids.) It also separated by ApoE4 status and found:
- The improved cognitive function was only in the E4 negative people
- As soon as the ketone supplementation was stopped, everyone’s function went back to the same poor baseline as before.
- ApoE4s tend to be more predisposed to inflammation and introducing agents that encourage ketone production externally (exogenously) vs making ketones in the body (endogenously) can raise inflammation. From this interview of Dr Bredesen by Dr Mercola, https://player.fm/series/take-control-of-your-health-with-dr-mercola-2394791/dr-mercola-interviews-dr-bredesen published on July 28, 2019, at about the 24:25 mark, Dr Bredesen said:
- "As a simple example, endogenous ketones will be inhibitory of NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome, so you’re turning down that inflammation, which is involved not only with Alzheimer’s, but also things like macular degeneration. Whereas if you take exogenous ketones and flood that system, you can actually create some degree of inflammation". (bold font added for emphasis)
Comparison of Coconut oil to MCT oil
Advisability for ApoE ε4
Coconut Oil -- ApoE ε4s can use coconut oil topically on skin or hair for its antibacterial, antifungal, and moisturizer qualities, or swished in the mouth for the oral health benefits of “oil pulling.” However, for ApoE ε4s, digesting coconut oil for brain function enhancement may be best when just restricted to using it as an aid in transitioning to being a fat burner, i.e. ketogenic
MCT Oil -- For ApoE ε4s, it may be best to restrict consumption to using MCT oil as an aid when transitioning to a fat burner, i.e. ketogenic. It’s less controversial than coconut oil, but full effects on ApoE ε4 are uncertain.
Coconut Oil -- Lauric acid (C12) makes up roughly 50%-75% of the fatty acids in solid coconut oil. Metabolism of lauric acid is different than the other three MCTs in Coconut Oil, it acts more like a long-chain fatty acid making it less ketogenic. Lauric acid does have immune boosting properties and other health promoting properties but it also raises cholesterol more than any other fatty acid, an issue of concern to ApoE ε4s.
MCT Oil -- MCT oil is derived from coconut oil and other sources by removing the longer chain Lauric Acid (C12) to offer a product that more efficiently produces ketones.
Use for cooking
Coconut Oil -- Good for cooking, as long as it is not used at high temperatures. At 350ᴼ F /171ᴼ C it has a lower smoke point in comparison to some other cooking oils.
MCT Oil -- MCT is not usually used for cooking (lower smoke point than coconut oil). It should not be heated to temperatures above 300ᴼ F/150ᴼ C or the oil will oxidize and break down. It can be added to recipes, smoothies, salad dressing, coffee, tea, etc. or just consumed as an oil by spoon.
Coconut Oil -- Not as likely to cause stomach upset
MCT Oil -- Consumption should start low and slow, one teaspoon at first, building up the dosage over time. If too much, too fast, the liver may not be able to process the fat and will dump some of it back to the intestines, where it can cause stomach upset and loose stools.
Effect on Sleep
Coconut Oil -- Usually doesn’t affect sleep
MCT Oil -- If taken at night, may be hard to sleep
Impact on Liver
Coconut Oil -- Individuals with liver cancer, elevated liver enzymes, extensive liver metastases, or liver disease can use coconut oil.
MCT Oil -- Individuals with liver cancer, elevated liver enzymes, extensive liver metastases, or liver disease should not use MCT oil.
Coconut Oil -- Coconut oil has been a dietary and beauty staple for ages. Unrefined coconut oil, also known as "virgin" or "pure," is made without chemical processing. Cold-pressed coconut oil is made in a heat-controlled environment and processed at temperatures that never exceed 120 degrees. Expeller-pressed coconut oil is processed at higher temperatures, typically around 210 degrees. Refined coconut oils are processed at upward of 400 degrees, which degrades the quality of the oil and requires further processing methods such as bleaching and deodorizing.
MCT Oil -- MCT oil is a relatively new introduction and not naturally expressed, but made through an industrial process. Many MCTs on the market are manufactured via chemical/solvent refining, which can require using chemicals like hexane and different enzymes and combustion chemicals, such as sodium methoxide. Be careful with the brand of MCT oil you purchase as it is important to get one that is tested for purity and heavy metals. To make MCT oil, the manufacturer starts with coconut oil or palm kernel oil. Corn oil and goat milk may also be used. Then these steps are followed: 1. Fractionation. Where the caproic (C6) caprylic (C8) and capric (C10) acid are extracted and separated, (no more lauric acid (C12)) the resulting oil is a fraction of what it was (fractionated). Fractionated coconut oil is a product that can be purchased but is for skin care, not consumption. The remaining steps are what makes fractionated coconut oil edible. 2. Lipase Esterification. A chemical process that produces triglycerides, with the help of an enzyme called lipase. 3. Filtration to remove lipase. 4. Deacidification. 5. Bleaching and Deodorizing. 6. Packing
Other products to enhance ketones
Palm Kernel oil
Not to be confused with palm oil, is also a source of Medium Chain Triglycerides. Good for cooking, lower in cost, can be stored longer than other vegetable oils, and remains stable at high cooking temperatures, smoke point of 450°F/232°C. However, it is less advisable for ApoE4 ε4s than coconut oil. Palm kernel oil is high in saturated fats: approximately 82%, and contains no Omega-3s, see Fats, Omega -3(ω-3) & -6(ω-6), DHA and More subheading Omega -3s and Omega -6s. It is high in lauric acid which has been shown to raise blood cholesterol levels, both LDL-C and HDL-C, see Cholesterol, Lipids and Treatments, including statins
MCT Oil powder
MCT powder is a powdered form of medium-chain triglycerides. It is made via a process similar to how protein powders are made: spray drying. The product is then micro-encapsulated with a powder “carrier shell” to give it the appearance and convenience of a powder. MCT oil powders are generally composed of starch/ starch derivatives and milk proteins that can raise insulin levels. MCT powders need to be selected carefully to prevent insulin spikes.
Advantages of the powdered form of MCT:
- Easier to incorporate into certain foods, such as baking recipes
- Often used as a “creamer” in coffee offering a more traditional taste
- More convenient to carry with you (say to the coffee shop) or travel with than a liquid
- Less gastrointestinal distress than the oil
It should be noted that virtually all research on the benefits of MCT supplementation has used MCT oil, and not MCT oil powder.
For more information on MCT powders and a comparison of products: MCT Powder: How it Works, Comparison to MCT Oils, and Review of MCT Powder Products
XCT is made with only C8 Caprylic acid and C10 Capric acid which increase ketone levels more efficiently than coconut or MCT oil.
The most effective supplemental oil to raise ketone availability for the brain and improve cognitive outcomes in both Mild Cognitive Impairment and Alzheimer’s is Caprylic acid (C8). Constituting only 6% of coconut oil, the eight carbon atom (C8) Caprylic Acid holds anti-viral properties to help maintain a healthy gut. It is also the fastest to directly pass through the lining of the gut, metabolize in the liver and deliver ketones to the brain. As such it is is very different than other saturated fats including its negligible impact on lipid profiles.
Sometimes referred to as “Ketone Mineral Salts” or “BHB Mineral Salts.” Consists of Beta Hydroxybutyrate (BHB) (a ketone) bound to an electrolyte: such minerals as sodium, potassium, calcium, or magnesium. Made into a powder that tastes good for consumption. Commercially available supplements made from ketone salts include KetoForce, KetoCaNa and Keto OS.
Synthetically-made compounds that link an alcohol to a ketone body. Unpleasant in taste. Primarily used in research. There is only one known commercial product available: HVMN According to Dr Dom D’Agostino, researcher on exogenous ketones, ketone esters need to be further studied and evaluated.
Effects of Exogenous Ketones
Effects of exogenous ketone on cognition
Ketones do not cure or prevent Alzheimer’s disease. There is no noticeable effect on amyloid or tau. Once ketogenic interventions are halted, the brain reverts to relying primarily on glucose for energy. Any boost in mental faculties that accompanies ketogenic supplementation disappears when supplementation is stopped or halted.
The response to exogenous ketones seems to be individual. Some report noted improvement in clarity of thought, others report no effects whatsoever.
Even if not experiencing cognitive impairment, sometimes ketones supplementation can enhance mental sharpness. In an interview with Dr Rhonda Patrick, Joe Rogan Experience #1178 - Dr. Rhonda Patrick, posted Oct 4, 2018 at about the 1:54:30 mark of the interview, the young, healthy, not cognitively impaired Dr Patrick discusses her experience with exogenous ketones. She said she is not ordinarily in ketosis and found using an exogenous Beta Hydroxybutyrate (BHB) ester gave her energy, made her less anxious, and sharpened her mental processing such that she would use them before podcasts or big talks. But she went on to say the experience was a double edged sword, because after a couple hours the exogenous ketones wore off, her blood sugar lowered and she would crash. This would occur because without following a ketogenic diet because her body didn't produce ketones to compensate. She said this happened to her repeatedly and is something that also happens to others.
Effects of exogenous ketones on the body
In a healthy, metabolically flexible body, there’s a reciprocal relationship between ketones and glucose. If glucose is high, ketones are not produced, conversely if ketones are high that's because the body is compensating for low blood glucose levels. This is what the body does to meet its energy needs, sort of like a hybrid car, the body pulls from the fuel source that is most efficient given the circumstance. It should be noted having a full tank of gas (glucose in the body) is different than having unimpaired access to that fuel. If a person has insulin resistance in the brain, it’s like having dirty, clogged spark plugs, the tank can be full but the fuel can’t burn freely and effectively, which is why ketones come in handy. Brain cells must have glucose, but can also run on ketones up to a certain point. (For more info seeInsulin Resistance in the brain
So what does adding ketones do to a body when the body senses that it already has plenty of glucose (fuel) in the bloodstream for energy? The body will eliminate the unnecessary exogenous ketones in expensive urine and this extra energy which is not immediately needed will stimulate the production of insulin (the energy storage hormone) which is not a good thing.
Exogenous ketones are insulinogenic, that is they can stimulate the production of insulin. But it’s the overproduction of insulin in the first place that results in insulin resistance in the brain thereby lowering brain’s ability to use glucose which in turn can be helped by providing ketones to the brain an energy source to compensate for the impaired glucose uptake. So in the short term, the exogenous ketones may aid cognition by providing a fuel for the brain, but in the long run, if there are no other adjustments to diet and lifestyle, the exogenous ketones may be exacerbating the insulin resistance.
This article Are Ketones insulinogenic and does it Matter, accessed March 25, 2019, explains the situation more eloquently:
- "On the left-hand side of the chart, when our blood glucose levels drop, we get a rise in ketones, but an increase in autophagy and all the good stuff that comes with fasting and ketosis.
- On the right-hand side of the chart, when we drive our total energy high with excess energy (be it from processed carbs, Bulletproof Coffee, or exogenous ketones) the body releases insulin to stop stored body fat and glucose being released into our bloodstream.
- People with the highest levels of metabolic health tend to walk around with a lower total energy in their bloodstream. It seems you don’t need to buffer lots of energy in the blood if you can easily mobilise body fat and glycogen stores quickly when required.
Having high levels of energy sitting around in the blood stream is far from ideal and leads to glycation in the case of high blood glucose levels and oxidation in the case of free fatty acids.
- The total energy concept also seems to hold up with laboratory testing in rat pancreas islet cells, where exogenous ketone bodies promoted insulin secretion when there was greater than 5.0 mmol/L of glucose.
- It appears that if your blood glucose levels are greater than 5.0 mmol/L (or 90 mg/dL), then exogenous ketones will be insulinogenic (at least if you’re a rat, but we have no reason to believe this wouldn’t occur in humans as well).
So if your blood glucose levels are greater than 5.0mmol/L (or 90 mg/dL), then those expensive exogenous ketones will be working just like a quick burning insulinogenic fuel, just like a dose of carbs."
Deeper Dive into the Science
Recognized experts on ketones/exogenous ketone use
There are many videos, interviews, podcasts, blogs, books, etc. on ketosis and the use of supplementation to enhance ketone levels. With the wide number of sources comes varying degrees of quality. If any of the sources include one of the below listed individuals, the information can be considered sound. Do recognize that while these are all experts on ketones, not all have cognition, much less ApoE status, as a point of emphasis. This is not an all-inclusive list, just a good starting point if looking for more information.
Dominic D’Agostino, Ph.D
University of Southern Florida, likely the foremost researcher on exogenous ketones, particularly as ketones apply to cancer prevention and in the neuroprotective qualities of ketone therapy especially as it applies to severe environments (space, undersea diving) through his work with the Department of Defense and NASA. Videos and interviews: https://www.ketonutrition.org/https://www.ketonutrition.org/ blog link: http://ketonutrition.blogspot.com/
Peter Attia, M.D
A surgeon who studied at Stanford Medical School and did his residency at Johns Hopkins University. His expertise is in weight loss, increasing longevity, and improving physical and mental performance. He has experimented heavily with ketosis, exogenous ketones and ketogenic diets. https://peterattiamd.com/start-here/
Dr. Richard Veech
Dr Veech was a senior researcher and the laboratory chief at the National Institute of Health (NIH). He passed away in February 2020 at the age of 84. He was active in his research until the day he died. His lifelong research focused heavily on the role of ketone bodies in regards to preventing metabolic diseases, such as type-2 diabetes. A link to his papers:https://irp.nih.gov/pi/richard-veech. Interview with Dr Veech Could This Ketosis-Based Elixir Hold The Key To Weight Loss, World Record Performances, Brain Healing and More?
Stephen Cunnane, Ph.D
Dr. Stephen Cunnane is a fellow of the International Society for the Study of Fats and Lipids. He earned a PhD in Physiology at McGill University in 1980, followed by post-doctoral research on nutrition and brain development in Aberdeen, London, and Nova Scotia. He was a faculty member in the Department of Nutritional Sciences, University of Toronto, from 1986 – 2003, where his research was in two overlapping areas – (i) the role of omega-3 fatty acids in brain development and human health, and (ii) the relation between ketones, the very high fat ketogenic diet and brain development. In 2003, Dr. Cunnane was awarded a senior Canada Research Chair at the Research Center on Aging and became a full professor in the departments of Medicine and Physiology & Biophysics at the Université de Sherbrooke. The main themes of his current research are to use brain imaging techniques to study changing brain fuel metabolism and cognitive function during aging, and to understand how and why omega-3 fatty acid homeostasis changes during aging. He has published over 280 peer-reviewed research papers and was elected to the French National Academy of Medicine in 2009. He is a fellow of the International Society for the Study of Fats and Lipids.
Steven Phinney, MD, Ph.D
Stanford MD, PhD Nutritional Biochemistry MIT, Fellowship Harvard, Professor of Medicine Emeritus at the University of California-Davis. Currently co-founder of Virta Health. Dr. Phinney is an internationally recognized expert on obesity, carbohydrate-restricted and ketogenic diets, diet and performance, and essential fatty acid metabolism. Virta Health
Mary Newport, MD
Neonatologist, practiced in newborn intensive care units where MCTs are added to infant formula to help with ketosis. When her husband was diagnosed with early onset Alzheimer's disease, Dr Newport discovered the benefits of using coconut oil/ketone supplementation for Alzheimer’s treatment. She has written the books, The Complete Book of Ketones, and Alzheimer's Disease: What If There Was a Cure?: The Story of Ketones. Also the paper A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease
Former research biochemist, health expert, and author of the New York Times bestselling The Paleo Solution. He has been a review editor for the Journal of Nutrition and Metabolism and Journal of Evolutionary Health; he serves on the board of Directors of Speciality Health Medical Clinic in Reno, Nevada and is a consultant for the Naval Special Warfare Resiliency program. His website: https://robbwolf.com/ His podcast website: https://robbwolf.com/podcast/ Offers a Keto Masterclass https://ketomasterclass.pages.ontraport.net/ketogains?oprid=14
Tech entrepreneur and biohacker. Before the age of 30 he was a successful executive, but he was also three hundred pounds, chronically fatigued, and struggled with focus and forgetfulness. He was inflamed, had damage from toxic mold, and two traumatic brain injuries. He started researching and experimenting with strategies to upgrade his brain’s performance. Through this he discovered lifestyle changes that lead to higher brain energy. He is the creator of "Bulletproof Coffee," founder of Bulletproof 360, Inc. and Bulletproof Nutrition Inc. He is also the host of Bulletproof Radio, and author of the books: The Better Baby Book, The Bulletproof Diet, Bulletproof: The Cookbook, and Head Strong.
References on ketones and the brain
See Subheading: Additional references on ketosis or the introduction of ketones on cognition /Alzheimer’s from this link Ketosis and Ketogenic Diet