Ketosis (In Progress)

Ketosis refers to the state in which ketone bodies form the body’s primary energy source when carbohydrates have been restricted to less than 50g per day or the overall energy consumed is less than 800kcal per day (very low calorie diet). If the body is functioning normally, it will be in mild ketosis after an 8 hour sleep. The more obese the individual, the slower the onset of ketosis. 

Ketone body levels in the blood:

• <0.2: No ketosis
• 0.2-0.5: Mild ketosis
• 0.5-3.0: Ketosis caused by food consumption
• 2.5-3.5: Post-exercise ketosis
• 3.0-6.0: Ketosis caused by starvation
• 15-25: Ketoacidosis

Ketosis is induced incrementally after 3-4 days of low calorie intake, fasting, or limited carbohydrates, once the body’s glucose stores in the liver and muscles are depleted. It may be accelerated by consuming MCT oil. MCT fatty acids are rapidly used for energy and readily absorbed. They are also quickly moved into mitochondria and unlike long-chain fatty acids, they do not require carnitine to oxidize fats.

Fasting or restricting carbs lowers insulin levels in the circulation while increasing glucagon and adrenaline. This leads to the release of free fatty acids and glycerol form into acetyl coenzyme A which in turn enters the citric acid cycle in the mitochondria.

The production of ketone bodies is activated by the excessive production of acetyl coenzyme A. The process is activated when the malate has been used for gluconeogenesis and there is insufficient amount of oxaloacetate available for the normal citric acid cycle. Acetyl coenzyme A is used to form acetoacetate and beta-hydroxybutyrate (BHB), the primary ketone body. The ketone bodies produced by the liver are released into the circulation and delivered into the mitochondria of the brain, internal organs, and muscles for ATP. BHB is restored to acetyl coenzyme A which is utilized in the citric acid cycle.

Potential health benefits of ketosis:

• Effective weight loss method in the short term
• An effective method in the treatment of epilepsy
• May reduce the risk of CVD
• May reduce the risk of type 2 diabetes
• May help treat acne
• May be helpful in the adjuvant therapy for cancer
• May help treat polycystic ovary syndrome
• May help treat degenerative neurological diseases (AD and PD)

No long-term studies have been done so it isn’t recommended as a long-term strategy.

Boundless

Ketosis makes for healthier mitochondria. When mitochondria malfunction, they can’t produce enough energy. Tissues with high demands, such as brain, muscles, and the heart suffer, resulting in complications like blindness, deafness, movement disorders, dementia, cardiomyopathy, myopathy, renal dysfunction, and accelerated aging. Ketosis is effective at reversing mitochondria dysfunction because it increases the number of mitochondria and the production of oxidative ATP, particularly in neurons.

After fasting for 16-72 hours or limiting your daily carb intake to 20-60g per day, after 2-3 days, your remaining glucose reserves are insufficient for normal fat oxidization and fueling the brain. The mitochondria in your liver then produce three ketone bodies: acetone, acetoacetate, and beta-hydroxybutyric acid. These are derived from excess acetyl-CoA (a key molecule in the metabolism of proteins, carbohydrates, and lipids). These are converted into other compounds and metabolized into energy in your cells. Ketone metabolism is known to create much less oxidative stress than glucose metabolism, resulting in reduced inflammation and improved mitochondrial health (helping to reduce demyelination in neurodegenerative disorders like multiple sclerosis).

Metabolic Autophagy

Ketosis and keto-adaptation aren’t mutually inclusive, and they have their differences.

• Being in ketosis is the actual metabolic state with the appropriate levels of blood sugar and ketone bodies. It’s said that ketosis begins at 0.5 mmol-s of blood ketones but having 0.3 mmol-s already is quite good. You can be in mild ketosis already after fasting for 24-hours but it doesn’t necessarily mean you’re successfully using fat and ketones for fuel.
• The keto-adaptation process makes your body adapt to utilizing fat and ketones as a primary source of energy. It means you don’t have to rely on glucose and can thrive on consuming dietary fat or by burning your own stored body fat.

To become keto-adapted, you have to go through a period of being in ketosis where your liver’s enzymes and metabolic processes change so you could have the ability to burn fat for fuel, but it’s not necessary to be in ketosis all the time to maintain keto adaptation. You can briefly dip in and out of ketosis for a day or two without fully losing it. After keto-adaptation you can be less strict with the macros.

• Carbs should still be quite low around 5-15%
• Protein can be increased for the muscle building benefits up to 25-30%
• Fat will stay around 55-65%, which will cover the essentials and gives extra energy.

How much fat you’re able to burn and how much protein you’ll compensate with depends on your level of keto-adaptation.

• Eating the high-carb-low-fat-high-protein diet is making your body quite dependent on glucose and frequent eating. The same applies to a high carb, high fructose diet. You have to eat very often to not go catabolic.
• Eating slightly lower carb, like a paleo approach where 30-50% of your calories come from carbs leaves some room for burning fat but it’s still making you burn some glucose because you’re eating more of it.
• Eating a strict low carb high fat ketogenic diet is the furthest you can promote keto-adaptation with diet. It’ll keep you in a state of nutritional ketosis wherein the body is geared towards using ketones as a primary fuel source.

Here’s how the keto-adaptation process looks like:

• Carb Withdrawal – you go on a low carb ketogenic diet and remove all carbohydrates from your diet. On keto, you eat leafy green vegetables, fatty meat, fish, eggs, and some other fats.
• Keto Flu Period – you may experience some fatigue and exhaustion because the brain doesn’t know how to use ketones for energy that efficiently yet. This may last from a few days up to several weeks, depending on your sensitivity.
• Getting Used to Ketones – you begin to feel better and more energized from eating low carb high-fat foods. The process can be accelerated by implementing intermittent fasting and making sure you’re not starving yourself. This may last from 2 weeks up to several months and the longer you do it the better it gets.
• Fat Burning Mode – your exercise performance will improve or at least you’ll regain the vigor you might have initially lost during keto flu. Here you can begin to see increased time to exhaustion, faster recovery from workouts, less fatigue during the day, mental clarity, and reduced hunger.
• Keto Adaptation – you can run very efficiently on dietary fat as well as your own body fat without needing carbohydrates to perform or feel energized. Thanks to burning ketones, you don’t get that hungry and whenever you do it’s temporary.
• Metabolic Flexibility – you can also use carbohydrates for fuel and you’re not going to get brain fog from being kicked out of ketosis. This is the ultimate goal of keto-adaptation – to not be dependent on ketones nor carbs and to use both in various situations.

The process of becoming keto-adapted takes about 2-4 weeks or even up to 3-6 months. How long it’s going to end up taking depends on how easily your body begins to accept ketones and fatty acids as a fuel source.

Some of the side-effects you may experience include losing water weight because of low levels of insulin, increased thirst, a slightly metallic and fruity keto breath, slight fatigue, and lack of appetite. Some of the good signs of proper keto-adaptation include no hunger whatsoever, mental clarity, high levels of energy all the time, increased endurance, reduced inflammation, stable blood sugar, and no muscle catabolism.

If you’re fasting blood glucose is under 80 mg/dl and you’re not feeling hypoglycemic then you’re probably in ketosis. Ketoacidosis occurs over 10 mMol-s, which is quite hard to reach.

Ketone Breath Meters indicate the amount of acetone in your breath. Acetone gets produced by the breakdown of acetoacetate in the blood. This measurement means that your mitochondria actually take the initial ketone body and then convert it further into an additional source of energy.

• For the best results, you’d want to know your blood ketones, blood glucose as well as the amount of acetone in your breath.
• Urine strips are generally useless because you can have higher amounts of acetoacetate in your urine because of dehydration or nitrogen overload as well but it doesn’t really tell you much about how well you’re using ketones for energy.
• The advantage of using breathalyzers is that they’re easier, more convenient, and much cheaper to use than using a lot of blood test strips.

There are a few reasons why you should occasionally get out of ketosis:

• Some people get hormonal imbalances, like low thyroid or testosterone, if they restrict their carbs for too long or if they fail to adapt fast enough.
• Your energy levels may also suffer from time to time because of overtraining or too much stress. In that case, carbs will speed up recovery and lower cortisol.
• Low mucous production of the ketogenic diet will prevent your body from creating enough mucus that surrounds and moisturizes your gut and eyes. That can be the cause of too low insulin and other growth pathways.
• Some carbohydrate foods can promote a healthy gut by increasing diversity in your microbiome. Changing up your menu will help to reset food intolerances and prevent them from developing in the first place. Too restrictive diets all the time may develop autoimmune disorders.
• Carbs can be used to boost your performance while working out but they can also be used for better sleep. Sometimes being low carb for too long may lead to some serotonin deficiencies and carbs can help to fix that.
• Eating carbs seasonally will fit better with the circadian rhythms and your own individual genetic blueprint. During some seasons it’s natural to be eating more carbohydrates and at others less.
• And of course, it’s nice to sometimes eat foods that aren’t bacon or vegetables. 

Why Bother with Keto?

Despite glucose being the body’s default main fuel source, most of the day you’re still using fat for fuel because doing daily chores, walking, or even low-intensity cardio maintains aerobic respiration. You only tap into your glycogen stores whenever you’re sprinting, lifting heavy stuff or training hard. Even then the degree of how much glycogen you’ll end up burning depends on your level of keto-adaptation because as we’ve seen ketones can be used at even higher intensities of exercise. Even people with 7% body fat have over 40,000 calories with them at all times.

High-intensity training, such as HIIT cycles, CrossFit, sprints, bodybuilding, and gymnastics are anaerobic by nature and span the creatine-phosphate system which requires you to be using glycogen in the presence of no oxygen. Because of that anaerobic environment, you can’t maintain it for any longer than a few seconds. You’re only burning glycogen for that specific time length and will revert back to using other fuel sources during rest.

When it comes to high-intensity training, then there are still some implications and constraints that have to be kept in mind:

• If you’re performing high-intensity exercise for longer and with fewer rest intervals, then your body will have troubles resynthesizing its glycogen with just fatty acids. Examples would include Ironman triathlon, a competitive sports game, a 2-hour high volume bodybuilding workout, a CrossFit game event, or having more than 2 workouts a day.
• Workouts that aren’t as taxing or frequent don’t require the addition of carbohydrates although they may still help. Examples include Olympic weightlifting, powerlifting, gymnastics, endurance, cycling, or short HIIT cardio.

Carbohydrate restriction has been shown to have many health benefits, starting from fat loss, neuroprotection of the brain, better biomarkers, stable energy, and ending with mitochondrial density and longevity. Burning fat causes less damage to the mitochondria and it produces more energy per calorie, which has benefits on cellular survival. Being dependent of carbohydrate refeeding is also quite a fragile position to be – you’re always limited by your glycogen stores and have to structure your entire day around eating. After becoming keto-adapted, you can tap into your stored body fat very fast and easily, which keeps you energized even while fasting for 5 days or more.

You don’t have to be in strict ketosis all the time to stay keto-adapted but you do need to maintain a semi-ketogenic state of glycogen depletion to build up these fat oxidation pathways into your metabolism.

How to Increase Metabolic Flexibility

• You have to establish nutritional ketosis by doing a low carb ketogenic diet for at least 2-4 weeks.
• After the first period of keto-adaptation, you can start tinkering with some carbohydrates to improve your performance.
• The fact of the matter is that you still want to be eating relatively low carb, especially at times when you’re not exercising.
• If you’re able to go without food for over 24 hours and not experience hypoglycemia or muscle weakness, then that’s a good indicator of keto-adaptation.
• At this point, your physical performance at all intensities is generally the same and you don’t need carbs to fuel your training. However, you can still use a few hacks that include strategic carbohydrate consumption.
  • The Targeted Ketogenic Diet (TKD) involves consuming a small dose of carbohydrates during your most intense workouts.
  • The Cyclical Ketogenic Diet (CKD) involves eating keto for 5-6 days, then having a day of eating more carbohydrates, and then returning back to keto.
  • There’s also something called Carb Backloading (CBL) where you eat low carb all day, then you go to the gym to have a muscle glycogen depleting workout that makes you more insulin sensitive, and then have dinner with a few extra carbs like a sweet potato, a bit of fruit, or some rice.

The Cyclical Ketogenic Diet:

• Training 4 or more times per week with mostly resistance training.
• Examples: bodybuilding, powerlifting, weightlifting, Crossfit, obstacle course racing
• Goals: build muscle, increase strength and power, have your cake and eat it too
• Refeeds either on your harder training days or the night before.
• If you feel like you’re feeling sh#t the entire following week because of keto flu then dial down on the amount of carbs you’re consuming and have less frequent refeeds.

The Targeted Ketogenic Diet

• Training 4 or more times per week with mostly resistance training or ultra-long endurance.
• Examples: bodybuilding, powerlifting, weightlifting, Crossfit, obstacle course racing, Ironman, rowing, marathon running, swimming
• Goals: build muscle and lose fat while improving performance, power, and endurance
• Have small amounts of easily digestible carbohydrates with protein during your workouts, such as a shake or ripe bananas.
• Adjust your carb intake according to your performance requirements and how you feel. Start off with just 5 grams and slowly keep adding an additional 5 grams per 30 minutes of intense physical activity.
• Hard training athletes can consume up to 30-50 grams of carbs during training while staying in ketosis.
• If you’re training twice a day then have a larger shake during the first workout and a smaller one during the second one. Still, eat keto in between training sessions.
• Eat low carb keto when you’re not exercising and in the post-workout scenario.

The Standard Ketogenic Diet

• Training 3-4 times per week with either resistance training or cardio.
• Examples: powerlifting, fitness, weightlifting, endurance, jogging, cycling, yoga
• Goals: lose fat, build strength, stay fit, improve health, battle diabetes, reverse insulin resistance
• If you’re not feeling tanked or feeble during workouts then you don’t need to be consuming carbs. Also, if you’re not planning on pushing yourself extra hard at the gym on that particular day, then you shouldn’t feel the need to eat carbs either.
• If you’re feeling hypoglycemic and are about to pass out during exercise then it’s a sign of not being keto-adapted. You’re simply in a state of still running on a sugar burning engine and you need to build up your fat burning pathways through diet before trying the TKD or CKD. Adding more electrolytes can also help.
• Eat low carb keto the entire time with enough protein and healthy fats.

Carb Backloading

• Training 4 or more times a week with primarily resistance training and anaerobic exercise.
• Examples: powerlifting, weightlifting, CrossFit, bodybuilding, competitive sports
• Goals: build strength, gain muscle, increase performance, train more frequently at higher intensities, eat carbs more often
• If you don’t want to do the targeted ketogenic diet or prefer to workout with low glycogen, then you can safely eat more carbohydrates the night before your heavier training. This will fill up glycogen stores and primes you to perform more intensely the next day.
• If you’re having heavier training sessions throughout the week, then it’s even better to have 1-2 nights of carb backloading.
• The best time to eat carbs is post-workout with depleted glycogen.
• Carb backloading is great if you don’t want to eat the keto diet all the time.
• Eat low carb keto in the earlier parts of the day before training. After working out have some carbs. Adding fasting is a great idea for sure.

The problem with strict therapeutic ketosis is that it’s not necessarily going to ensure keto-adaptation as you can be in ketosis without using those ketones for fuel and you can have very high ketones without being able to perform at your best. More ketosis doesn’t equal more keto-adaptation as it has to involve the aspect of mitochondrial density and energy production. It can also neglect some of the performance-enhancing benefits of carbs.

Fat Loss Forever Notes

It has its purposes and can be used to sustainably lose weight. The issues arise when zealots tell everybody that it’s THE way to do it. All that matters is adherence and reduced caloric intake. Exceptions being those who don’t respond favorably to a high fat diet. Genetics and the microbiome may come into play here.

History

Fasting was likely a condition that our ancestors experienced on a relatively regular basis through the greater part of the past 70 thousand years. If they lacked foods highly enriched in carbs, they would be able to rely on their fat stores to survive. 

It wasn’t until the 1900s that fasting ketosis was medically explored in patients suffering from the burden of epilepsy.

Today, the ketogenic diet has been explored as a therapeutic tool against a variety of conditions ranging from rare metabolic disorders to neurodegenerative diseases, diabetes, cancer, and weight loss.

What is the Ketogenic Diet?

The definitive goal of the diet is to enter the metabolic state of ketosis, where the body transitions from burning glucose as the primary fuel to burning fatty acids and ketones. Most people following a “keto diet” for weight loss seldom achieve, much less sustain, a state of ketosis. Ketosis itself is defined by an elevation of blood ketones (beta-hydroxybutyrate; BHB) above 0.5 millimoles per liter; getting to 0.5-3.0 millimoles per liter is optimal.

Variations of the Ketogenic Diet

The classical ketogenic diet equates to roughly 90% of your calories coming from fat, relatively low in protein (6% to 9%), and next-to-no carbohydrates (0% to 4%).

Modified versions of the ketogenic diet can range from:

• Carbohydrates: 0-10% (ideally fibrous veggies)
• Protein: 15-35% (ideally fatty meats and fish)
• Fat: 65-85%

Generally speaking, the daily macronutrient recommendations are:

• Carbohydrates: no more than 50 grams total
• Protein: 1-1.5 g/kg LBM (1.8 g/kg may be more optimal under some conditions)
• Fat: remaining daily calories or to satiety (ideally counting macros, which shouldn’t be surprising at this point)

Understanding How the Body Enters Ketosis

1. Within the first one to 12 hours, you’ll burn through most circulating or previously ingested glycolytic fuel. The length depends on the type and amount of foods ingested.
2. The body will next tap into its stored liver glycogen to sustain blood glucose levels for up to 12 to 24 hours, via glycogenolysis.
3. Upon liver glycogen depletion, gluconeogenesis increases to supply glucose for the brain, primarily from gluconeogenic amino acids in muscle or dietary protein. Gluconeogenesis is typically elevated for a week or more following transition into nutritional ketosis.
4. Gluconeogenesis overlaps with ketogenesis, which is typically elevated after three days (less than 0.5 millimolars). Glucose is progressively spared for the brain by the prevention of glucose utilization in tissues such as muscle and adipose. Reduced insulin and increased glucagon lead to a high glucagon-to-insulin ratio, upregulating the fat oxidation machinery required for the production of ketones in the liver, as well as the liberation of free fatty acids from adipose to the liver. Free fatty acids are then converted to acetoacetate and beta-hydroxybutyrate and exported to peripheral tissues. Liver and muscle can use free fatty acids as fuel directly. The glycerol backbone liberated from triglycerides serves as a gluconeogenic substrate in the liver.
5. As you sustain ketosis, your reliance on glucose for fuel diminishes, ketones are preferentially taken up by the brain (fewer cravings for sugar), muscles will primarily use free fatty acids, and the liver will be poised towards ketone production and gluconeogenesis.

Ketone Bodies

There are two primary ketone bodies produced in the liver: acetoacetate (AcAc) and beta-hydroxybutyrate (BHB). A greater abundance of BHB is favored, accounting for ~78% of total ketones. AcAc is the primary intermediate between the production and utilization of ketones for fuel; BHB is produced from AcAc and converted back to AcAc before being used for energy. Acetone is produced by the spontaneous breakdown of AcAc and is mostly excreted through our urine and breath.

Insulin

• The presence or absence of insulin has the power to dictate whether we use glucose for fuel or fatty acid and ketones, respectively. When carbohydrates are restricted, and as a consequence insulin is suppressed, the doors now open for the transition into ketogenesis.
• Insulin increases: glucose uptake, glycolysis, glycogen synthesis, adipogenesis (with total fat gain or loss dictated by overall calorie intake), and protein synthesis
• Insulin decreases: gluconeogenesis, glycogenolysis, lipolysis, ketogenesis, and protein breakdown.

In the Presence of Insulin

When you consume a carbohydrate-based meal, your body will primarily metabolize glucose as a result of increased insulin levels, which in turn suppresses the hormone glucagon. In the presence of insulin, the liver will take in some of this glucose, and either store it as liver glycogen or metabolize it into acetyl- CoA to be used in the generation of energy. DNL is generally low and contributes very little to overall fat storage, but can be higher with excess fructose consumption. These fatty acids are then used in the production of triglycerides and stored in the liver, or sent for storage in our adipose tissue. Lipolysis, or the breakdown of stored triglycerides in our adipose tissue, is inhibited by insulin. Muscle will also take up glucose in the presence of insulin and use it directly as fuel, or store it as glycogen.

Suppression of Insulin

When you restrict carbohydrates, insulin levels are then suppressed, and it stimulates the release of the hormone glucagon. The ratio of glucagon to insulin is an important contributor to ketogenesis. A higher glucagon-to-insulin ratio is required for the production of ketones. In addition, this ratio alters liver metabolism in a way that ultimately halts glycogen synthesis, and favors the breakdown of liver glycogen and gluconeogenic substrates, which occurs with caloric restriction outside of a ketogenic diet. With that said, muscle glycogen is spared if and when ketones are elevated, based on the transitional use of fatty acids and ketones for fuel. Muscle glycogen is used (and lost) at a much faster rate following a carbohydrate-based diet, especially under conditions of calorie restriction. Thus, being in ketosis has practical implications when it comes to preserving muscle glycogen.

Macronutrients Metabolism and their Respective Hormonal Response

Carbohydrates:

• Carbohydrates are broken down through a series of enzymatic steps until their final conversion to individual glucose molecules in the liver. These glucose molecules are either stored as liver glycogen or enter circulation, providing fuel to the rest of the body. The blood glucose response of carbohydrates depends on dose, and the source of carbohydrate consumed dictates how rapid or delayed the response (e.g. high-fiber foods such as fibrous vegetables can essentially be non-glycemic, although they contain carbohydrates).
• Glucose Response: Dose-dependent and rapid
• Insulin Response: Elevated (depending on fiber content)
• Glucagon Response: Suppressed

Protein:

• Protein can stimulate the release of the hormone glucagon, which triggers the breakdown of liver glycogen to raise blood glucose. Gluconeogenic amino acids can also be converted to glucose in the liver, contributing to an elevation in blood glucose. Protein’s impact on blood glucose levels is very small compared to that of carbohydrates, and the response can be delayed up to 5 hours after consumption, especially in the presence of high fat and fiber.
• Glucose Response: Moderate and delayed
• Insulin Response: Dose-dependent
• Glucagon Response: Elevated

Fat:

• Fats are typically consumed (and stored in adipose) in triglyceride form, which contains a glycerol backbone and three fatty acid chains. The length of the fatty acid chains matter in how they’re metabolized in the body, both in general and in terms of ketogenesis. For example, when long-chain triglycerides (LCT) are ingested, they’re packaged into chylomicrons, which enter our lymphatic system and are delivered to adipose tissue. Whereas medium-chain triglycerides (MCT) bypass this process and are delivered directly to the liver through hepatic portal circulation. MCTs can be rapidly converted to ketone bodies in the liver (under ketogenic conditions), and can be used directly for energy (even by the brain). In terms of glucose response, once liberated from triglycerides, free fatty acids cannot be converted to glucose. The glycerol backbone, however, can be. When keto-adapted, this is the body’s primary source of glucose for cell types that cannot metabolize fat or ketones, but this conversion will have no noticeable effect on insulin.
• Glucose Response: No response
• Insulin Response: No response
• Glucagon Response: Elevated (in response to low insulin)

Glucose, Insulin, and Appetite Control:

If you find that eating carbohydrates causes large fluctuations in your energy, a ketogenic approach might help control this. You could eat a 500-calorie ketogenic meal with little to no elevation of blood glucose, translating to little to no elevation of insulin and perhaps even energy and increased satiety. So, while you’re supplying the body with energy (calories), the body for the most part will be in the “fed” state while the liver will remain in the “semi-fasted” state. This is important for the maintenance of blood glucose. The liver is the master regulator of metabolism, so to sustain ketosis, the liver must maintain this “fasted” state. What’s more important is that after this ketogenic meal, you will remain satiated for two-five+ hours. In addition, fat in combination with moderate protein is very satiating, and for many, a well-formulated ketogenic diet is difficult to overconsume. Can be a good thing or bad thing…

Meal Frequency on the Ketogenic Diet:

• 3-5 protein-containing meals throughout the day are advised for optimizing lean body mass, recommended on the assumption that you’re in a glycolytic state. The ketogenic diet makes room for less frequent feedings due to delayed gastric absorption from consuming high fat. You may find your hunger feels different when you’re in ketosis versus when the body is craving glucose. Instead of eating five times a day, you may find you only want/need to eat two or three times.
• Practicing intermittent fasting or time-restricted feeding (TRF) may become much easier when following a ketogenic diet, and some people find that TRF makes creating and sustaining a calorie deficit easier over time. When you’re in ketosis, you’re no longer a slave to food; one reason being that you’re wearing your food. Even lean athletes can hold ~40,000 calories in stored body fat, and keto-adaptation (over months) makes it easier to access that fat for fuel.
• Leptin and ghrelin are also differentially regulated in a state of ketosis. While the amount of leptin decreases, our sensitivity typically increases, meaning only a small release of leptin will reduce hunger cravings. The suppression of ghrelin has been reported in calorie-restricted subjects who maintained BHB levels above 0.3 millimolars per liter. Additionally, drinking exogenous ketones lowers plasma ghrelin levels compared with isocaloric dextrose, perceived hunger, and desire to eat.
• Dextrose ingestion also lowers ghrelin, just not as much as exogenous ketones. Dextrose has very little satiety value in the short term, so it’s unknown whether exogenous ketones would be better than isocaloric protein or lower-glycemic, carbohydrate-containing fiber. Further, it’s important to note that exogenous ketones have caloric value and thus are not “free calories” but may have some beneficial effects. This effect on ghrelin may help improve satiety in a keto-adapted state.

Signaling Roles of Ketones

Research has found beta-hydroxybutyrate (BHB) to be anti-inflammatory, through the inhibition of the NLRP3 inflammasome. The NLRP3 inflammasome controls the activation of pro-inflammatory molecules, and dampening this pathway can reduce systemic inflammation. Chronic inflammation is also a characteristic of metabolic dysfunction, which is tightly linked to insulin resistance. The ketogenic diet can enhance insulin sensitivity, as well as reduce the inflammation that could be contributing to insulin resistance. If anything, this anti-inflammatory effect may reduce inflammation-associated pain, thereby enhancing performance. What’s less clear, however, is if this anti-inflammatory effect is due to unique properties of ketones, or simply the weight loss associated with caloric restriction.

BHB is a histone deacetylase (HDAC) inhibitor, and generally speaking, HDACs inhibit the gene expression. Through ketone-induced HDAC inhibition, BHB has been shown to induce the expression of genes involved in oxidative stress resistance. This means BHB can enhance our own cellular and physiological protection against oxidative stressors that cause cellular damage. These ketone-induced adaptations may enhance performance resilience, especially under conditions of a calorie deficit and high endurance-training demands.

The Ketogenic Diet and Muscle Maintenance:

Nitrogen excretion slows with keto-adaption, indicating a reduction in protein breakdown since fats and ketones become the primary fuel sources. However, there’s evidence that some LBM is lost during the initial keto-adaptation period until the body reaches keto adaptation. During the transition into ketosis, the brain begins preferentially utilizing ketones for fuel, and therefore relies less on glucose. This decreased reliance on glucose for fuel significantly reduces the breakdown of gluconeogenic amino acids in skeletal muscle, explaining this muscle-sparing effect. Additionally, fatty acids are oxidized as fuel for muscles, sparing ketones for the brain while simultaneously maintaining muscle protein by a reduction in branched chain amino acid oxidation.

It’s important to note that muscles can only use ketones for fuel under aerobic conditions, whereas anaerobic exercise will have obligate glucose usage. Thus, the ketogenic diet may not be optimal for athletes who do high-intensity exercise for muscle sparing. Recently, it was demonstrated that BHB IV infusion in humans has potent anticatabolic effects, preventing muscle-wasting under conditions of induced inflammation.

What to Eat on a Ketogenic Diet

Carbohydrates (0-10%):

• All leafy greens and lettuces
• Cruciferous vegetables (broccoli, cauliflower, Brussel sprouts, cabbage)
• Celery
• Cucumber
• Zucchini
• Bok choy
• Mushrooms

Protein (15-35%):

• Fatty cuts of red meat
• Poultry with skin on
• Fatty fish such as sardines, salmon, mackerel
• Eggs and egg yolks
• Nuts and seeds such as hemp seeds, macadamia nuts, and pecans
• Tempeh

Fat (60-90%):

• Majority from saturated and monounsaturated sources. Emphasis on omega-3s, while minimizing omega-6s.
• Oils: coconut oil, butter, ghee, MCT oil, cacao butter, extra-virgin olive oil, avocado oil, and macadamia nut oil
• Whole foods: avocados, eggs, fatty cuts of meat, poultry with skin on, coconut butter, coconut meat, olives, nuts, and some seeds

Limit:

• Soybean oil
• Corn oil
• Cottonseed oil
• Peanut oil
• Canola oil
• Grapeseed oil
• Safflower oil
• Sunflower oil

How to Test Ketones

• Blood: Most expensive but accurate
• Urine: Accuracy varies
• Breath: Cost effective and non-invasive

Caveats of a Ketogenic Diet:

• A strong argument against the ketogenic diet is that ketones cannot fuel anaerobic activity. However, the ketogenic diet has a glycogen-sparing effect, and thus glycogen should not be depleted (after keto-adaptation) unless anaerobic training volume is high.
• Supplements like creatine may be more beneficial for those on a keto diet, especially during the first few weeks of initiation.
• Another issue people may experience is adherence to the diet based on personal food preferences. If you don’t enjoy ketogenic foods, then this diet isn’t feasible for you.

Summary

• An energy deficit drives fat loss
• While the diet didn’t start as a fad, the language surrounding it now, for the most part, is similar to that of fad diets
• It has clinical applications for neurodegenerative diseases and other ailments
• The original ketogenic diet recommends approximately 90% of your calories come from fat, but some of the modified versions we see today lessen the fat requirement (sometimes as low as 65% of total calories) to allow for more protein. You can attain and sustain nutritional ketosis with both
• Dietary adherence still matters, along with tracking your intake