The Basics of the Ketogenic Diet, Exogenous Ketones, and Metabolic Flexibility

Although the clinical use of the ketogenic diet dates back over a century, the mainstream “keto” diet has only made its way into popular culture in the past decade or so. Now well-known in the low-carb and wellness world, “keto” refers to ketosis, a biochemical pathway that burns fat rather than sugar for fuel. In this article, we’ll explore what ketosis is, what a keto diet entails, and how increasing your metabolic flexibility can be beneficial for your health and longevity. 

What Is Ketosis? 

The primary basis of the ketogenic diet is that it is very low in carbohydrates and high in fat, which puts your body into a state of ketosis. 

Ketosis is a different metabolic state from what our bodies typically use, which is breaking down carbohydrates into sugar. When you’re in ketosis, your body produces molecules called ketone bodies. Ketone bodies are only made when we don’t consume a lot of carbohydrates. Rather than turning carbohydrates into glucose for fuel, ketone bodies are produced by a different metabolic path derived from fat breakdown. 

The primary ketone bodies are acetoacetate, beta-hydroxybutyrate, and acetone, which are made during times of limited glucose availability. When carbs are restricted, your body’s fuel comes from fat rather than sugar. It’s also important to note that overconsumption of protein can be converted into glucose, limiting your ability to enter ketosis, which is why fat is the primary macronutrient consumed on a keto diet. It can take up to three weeks of limited carbohydrate consumption for your body to fully expend its glucose stores and enter ketosis.  

The Ketogenic Diet 

Ketogenic diets are very low in carbohydrates, low to moderate in protein, and high in fat. Most keto dieters follow a macronutrient ratio of approximately 5% carbohydrates, 20% protein, and 75% fat. This level of carbohydrates typically translates to 20 to 50 grams per day, with 20 grams being more extreme. To put that in perspective, one medium-sized banana contains about 25 grams of carbs. 

Foods to Eat on the Keto Diet

Examples of keto-friendly foods include: 

• Non-starchy vegetables: leafy greens, lettuce, broccoli, bell pepper, asparagus, celery, zucchini, mushrooms, tomatoes, etc. 
• Meat and poultry: chicken, turkey, pork, beef, etc. 
• Other animal proteins: eggs, fish, and seafood 
• Full-fat dairy: cheese, yogurt, and butter
• Small portions of some fruit: berries, lemons, and limes
• Moderate amounts of nuts and seeds: Almonds, cashews, pistachios, walnuts, pecans, macadamia nuts, chia seeds, sunflower seeds, hemp seeds, flaxseeds, sesame seeds, and nut butter. As nuts and seeds have carbohydrates, be mindful of the amount consumed.
• Healthy fats: avocado, coconut oil or butter, ghee, olive oil, and avocado oil

Keto-friendly drinks include: 

• Water
• Sparkling water with no artificial sweeteners
• Unsweetened coffee
• Unsweetened tea 
• Limited, low-sugar alcohol: tequila or vodka 

Foods to Avoid on the Keto Diet

Foods to avoid on keto are higher in carbohydrates and sugar, including: 

• Grains: bread, pasta, rice, crackers, tortillas, cereals, and oatmeal
• Legumes: beans, lentils, chickpeas, and peas
• Starchy vegetables: potatoes, sweet potatoes, winter squash, root vegetables, and corn
• Most fruit: Bananas, oranges, grapes, pineapple, mango, papaya, apples, pears, plums, etc. 
• Desserts: Sugar-sweetened cakes, cookies, ice cream, and pastries
• Ultra-processed and refined foods: most snack foods, frozen meals, packaged foods, fast foods, etc.
• Condiments with added sugar: ketchup, most salad dressings, barbeque sauce, etc. 

Drinks to avoid on keto: 

• Fruit-based juices and smoothies
• Sweetened beverages: soda, fruit juice cocktails, sports drinks
• Sweetened teas and coffee
• Most alcohol: beer, wine, and alcohol mixed with high-sugar ingredients

What Are Exogenous Ketones?

Exogenous ketones are synthetic ketones produced outside your body and taken as a supplement, while ketone bodies are endogenous (made inside the body). 

Ketone supplements are only made from the ketone body beta-hydroxybutyrate (BHB) and come in the form of ketone salts or ketone esters.

You’ll usually see ketone salts in powdered form that you can mix into liquids, while ketone esters are in liquid form. However, ketone esters are typically only used in research and not available for the general public to use; therefore, if you use exogenous ketones they will almost always be ketone salts. 

Exogenous ketones can be beneficial if you have trouble getting into ketosis, as they increase blood ketone levels similarly to a very low-carbohydrate diet. 

While you won’t be able to get into ketosis if you use exogenous ketones on a high-carb diet, they can help you to get into ketosis faster while following a low-carb diet. They may also reduce the potential side effects of getting into ketosis, commonly referred to as the “keto flu,” which has symptoms of headaches, constipation, diarrhea, bad breath, and muscle aches. 

Using ketone supplements may also help reduce appetite, similar to the keto diet. In one very small study, people who drank an exogenous ketone drink had 50% less hunger after an overnight fast compared to those drinking a sugary beverage. Those having the exogenous ketone drinks had reductions in ghrelin (our main hunger hormone), perceived hunger, and desire to eat.

Why Metabolic Flexibility Is Beneficial for Longevity

Metabolic flexibility is the ability to respond or adapt to changes in metabolic demand. Essentially, your metabolism is flexible in terms of what fuel it can use (glucose versus fat) based on what is available.

While most people run solely on glucose from their most recent meal, being more metabolically flexible means that your body can readily use fat for energy and switch between the two. Flexibility also entails being able to use energy that’s already in your body, like stored fat and sugar.

Greater metabolic flexibility has been studied primarily for its role in supporting healthy weight management, cognitive function, and cardiometabolic health. One way to support metabolic flexibility is to follow a ketogenic diet (another way is intermittent fasting).

There are several benefits of having better metabolic flexibility that translate to longer healthspans, including weight management, cardiometabolic health, and cognitive function. 

Weight management

Being in a state of ketosis has been found to suppress hunger hormones and help with satiety or feelings of fullness, which can translate to healthy weight management. 

In a meta-analysis, researchers concluded that people following keto diets were less hungry and had reduced appetite, which is much different than other restrictive diets.

Another study found that overweight people following a keto diet had significantly more weight loss than those eating a low-carb but non-ketogenic diet. 

Cardiometabolic health

Most of the metabolic benefits can be attributed to the keto diet’s low carbohydrate levels, as chronically high blood glucose levels caused by excess carbohydrate intake are linked to worse health outcomes.

The most substantial evidence for the benefits of ketogenic diets is in people with excess weight or metabolic dysfunction.

One study followed overweight and obese women on a very-low-calorie ketogenic diet for 24 weeks, finding that this diet improved cardiometabolic parameters, including reductions in HOMA-IR (a marker of insulin resistance) and a 14.6% reduction in BMI (Body Mass Index).

Another study compared the effects of a ketogenic diet with a low-calorie diet for 24 weeks, finding that the keto diet improved metabolic control better than the low-calorie diet, including reductions in ​​blood glucose and hemoglobin A1C (a standard diagnostic biomarker for metabolic dysfunction).

One of the main criticisms of the keto diet is that it can cause unfavorable changes to blood cholesterol and lipid levels. Despite the increased fat consumption and increases in total and LDL cholesterol, research has shown that people on keto diets have reduced particle size of LDL (which is a more accurate measure of heart health) and higher levels of HDL cholesterol.

Cognitive function  

The brain-based benefits of the keto diet may stem from the anti-inflammatory properties of beta-hydroxybutyrate, one of the ketone bodies generated during ketosis, which is known to offer protection to the brain and central nervous system.

Although the research here is more limited, some studies have found that being in ketosis may improve symptoms related to neurological conditions. 

For example, one small study found that people with memory-related neurological dysfunction who followed a modified keto diet (a Mediterranean diet plus coconut oil) had increased ketone body production and improvements in episodic memory, temporal orientation, and semantic memory. However, most studies in this area are small, and more research is needed. 

Are There Downsides to the Keto Diet?

Of course, nothing in nutrition is black-and-white, and there are several potential downsides of a keto diet to consider. As with all diets, the keto diet may not work for everyone—especially in people who are genetically sensitive to high fat intake, as they may experience adverse effects related to cardiovascular health. 

Another concern is the low sustainability of this diet, meaning it is hard to follow for a long time. It also is naturally low in fiber, which is found in high amounts in fruits, vegetables, beans, legumes, and whole grains. While it’s not impossible to meet your fiber needs on a keto diet, you have to plan carefully—eating solely eggs and cheese all day won’t get you there. Due to lower fiber intake, people following a keto diet long term can experience digestive issues like constipation or diarrhea, likely due to disruptions to the gut microbiome. 

There are also some concerns about kidney health on the keto diet, including an increased risk of kidney stones, which are made of excess calcium and uric acid deposits in the kidneys. It is understood that an increase in acidic ketone bodies from a ketogenic diet leads to a more acidic internal environment. This alteration impacts the body's ability to reabsorb and excrete calcium and reduces urinary pH, thereby leading to conditions that are more favorable for the formation of uric acid crystals..

Lastly, while the health benefits of a short-term keto diet are better understood, the long-term effects still need to be fully elucidated. In an animal study, rats who were on a ketogenic diet for 60 days (which is approximately six human years) experienced anemia, acidic body pHs, and greater levels of oxidative stress. However, the rats did not experience any adverse effects on liver or kidney health. 

Key Takeaways

Greater metabolic flexibility is an excellent way to support cardiovascular, metabolic, and cognitive health with age, and following a ketogenic diet is one way to get there. While a keto diet is not for everyone, research has found several health benefits related to this style of eating. However, as with all diets, there are also downsides to consider. 

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