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What Is The Science Behind the Keto Diet?

Carina Wolff
6 - 8 MIN.

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  • The Keto Diet in a Nutshell
  • Ketosis Unpacked
  • The Path to Ketosis
  • Physiological Changes in Ketosis
  • The Health Benefits of Ketosis
  • How to Know You’ve Achieved Ketosis
  • Side Effects and Precautions
  • Long-Term Health Effects

Science of Keto


The ketogenic (or keto) diet is one of the most popular diet trends of the last two years. From Pinterest to Instagram, from the grocery aisle to restaurant table – it’s everywhere! Proponents are a mixed bag of celebrities on the quest for the perfect body, athletes motivated to gain a performance edge, and executives trying to biohack their body to be smarter and faster in the workplace.

Interestingly this so called “fad” diet isn’t a fad at all, it’s been around for nearly a century and was initially used in combination with fasting to treat neurological disorders like epilepsy. While the science and use of the diet have slowly evolved over time, the mechanisms of action have remained the same. To appreciate the benefits of keto and why it might be a good tool to reach your health goals, it’s helpful to first understand what it is and the science of how it works.

The Keto Diet in a Nutshell

A ketogenic (or keto) diet is a low carbohydrate pattern of eating that is commonly also high in fat. There are many variations of a keto diet but generally carbohydrates are restricted to less than 10% of your total caloric intake with fat and protein making up the difference. A typical distribution of the macronutrients (also known as macros) is shown below:

Science Behind the Keto Diet Macros, HighKey Snacks

In the absence of carbohydrates, your body shifts from burning primarily sugar (or glucose) for energy to burning fat. In this fat-burning mode, the liver uses dietary and body fat to produce fuel molecules called ketones. This is where the metabolic state of ketosis and the ketogenic diet get their names.

Ketosis Unpacked

If you’ve skipped a meal, exercised for more than an hour or reduced your carb intake for a period of time, you’ve likely been in ketosis before. Generally, when you’re short on carbs, you’ll dip into ketosis. Your body, needing fuel, will tap into its stored energy (fat) and use it to create ketone bodies in your liver. Both the fat and the ketone bodies will then be used for your body’s energy needs. While your muscles and other tissues can utilize fat and ketones for energy during times of carb restriction or fasting, your brain must rely primarily on ketones to function.

To understand why the supply of cellular energy is so important to optimal physiological functioning, let’s take a quick detour back to anatomy and physiology 101. Our entire body is made up of cells. Groups of cells form tissues, tissues form organs and organs work together in organ systems to keep the body running properly. The well-oiled machine that is our body requires energy (aka calories) for every metabolic reaction, from keeping the heart beating to running a marathon. Carbohydrates are the preferred energy source for the body. In absence of carbohydrates, fat and ketones take over this job.

The Path to Ketosis

As mentioned before, carbohydrates are your body’s primary source for fuel on regular diets. Most of the carbohydrates people are broken down into glucose, which then is used  

When you eat carbohydrates, your body breaks down most of those carbs into glucose (sugar) which provides fuel for your cells to function. However, the rest of the carbs are stored in your muscle and liver as glycogen that your body can tap into for additional energy later. Ketosis happens when all the glycogen stores in your body are gone. You can kick your body into ketosis by fasting or starting a low carb diet.

Every person’s glycogen stores are different, but generally speaking, it only takes a few days of rapidly-reduced carb intake to empty your body’s glycogen stores and start the process of ketosis. Once your body has no more glycogen, your liver will kick sugar production into high gear to make sure there is enough circulating glucose to maintain homeostasis. Homeostasis is just a fancy term that means your body is stable and in good working order. During this period of time, your liver will make sugar from dietary and internal fat and protein. After several days of your body using protein for energy, it will begin to use fat as its primary fuel source.

Physiological Changes in Ketosis

A number of physiological changes occur when your body enters ketosis, starting with a shift in your fluid and electrolyte balance. As your carb intake is restricted and your body loses its carb stores of glycogen, your body will also start to lose stored water. For every gram of glycogen stored in your  muscle there are three grams of stored water! When fluid is lost, there is also an interruption in the balance of your body’s electrolytes including sodium, potassium, and magnesium. This shift is responsible for the initial weight loss, frequent urination, muscle cramps and constipation commonly reported as initial side effects of the keto diet. This physiological change is also why fluid and electrolyte supplementation can be helpful in reducing some of the less-than-favorable side effects of entering ketosis.

When many people enter ketosis, they will also notice a decline in their appetite and food cravings. The increase of circulating ketones in your body impact your appetite by suppressing ghrelin, the hunger hormone. This is great if your primary goal for starting the ketogenic diet is weight loss.

The Health Benefits of Ketosis

The keto diet gets a lot of attention for being an effective way to lose weight but there are a wide range of reported health benefits that research is starting to explore.

The oldest and most established use of the keto diet is in the treatment of epilepsy. In fact, this is how the diet was created in the first place. It evolved after fasting was shown to reduce seizures in epileptic patients. The keto diet mimics the physiological effects of fasting while still providing patients with ongoing food and nourishment which is more realistic and sustainable option for reducing seizures on a day-to-day basis than continued fasting. The keto diet is still used today in both the pediatric and adult populations as a therapy for epilepsy.

More recently, the keto diet has been used for management of some chronic disease states like obesity and type II diabetes. Research shows that the keto diet is effective at both reducing body fat and improving blood sugar levels. The keto diet is ideal for weight loss as the body is forced to use stored fat for energy. With adequate calories and protein, your body’s muscle mass and function will also be unaffected. This is great because more muscle = better metabolic rate and calorie burning potential. The more calories you can burn, the better your chances for achieving and sustaining a healthy weight long-term. As your body composition changes, you will find it  easier to get to the recommended, healthy range for body fat.

Some studies show the keto diet is more effective at promoting weight loss than a  traditional low-fat diet. In my experience as a dietitian, I do find this to be true and believe it’s because the keto diet does a great job at suppressing appetite. Because keto helps control hunger and cravings, it is far easier for people to maintain and reach their health and weight goals like lowering their blood sugar or blood pressure.

The keto diet can also be used for prevention of chronic disease by supporting blood sugar and insulin levels, reducing circulating levels of triglycerides, LDL cholesterol (aka bad cholesterol) and increasing HDL cholesterol (aka good cholesterol).

Beyond chronic disease, the keto diet shows promise in improving neurological conditions in addition to epilepsy, particularly in individuals with dementia and mild cognitive impairment. In patients with Alzheimer’s disease, the most common form of the dementia, research showed that plaque formation in the brain (a hallmark of the disease) was reduced when they followed a keto diet.

In ALS and Parkinson’s Disease, keto diets were shown to enhance mitochondrial function. The mitochondria are the little metabolic engines within the cells and that are crucial for your body to be performing its best. In a pilot study on people with Multiple Sclerosis (MS), the keto diet was shown to be safe and effective at reducing fatigue, depression and some markers of inflammation.

There are several other common health conditions that the keto diet has been helpful in treating including  cancer, PCOS and acne. One of the proposed mechanisms of action for all of these conditions is the reduction in circulating glucose and insulin which drive certain aspects of the disease process.

In summary, research has shown promising signs that the keto diet can be helpful in improving and managing a variety of medical conditions, including:

  • Epilepsy
  • Obesity
  • Type II Diabetes
  • Alzheimer's Disease
  • Amyotrophic Lateral Sclerosis (ALS)
  • Parkinson's Disease
  • Multiple Scerlosis (MS)
  • Cancer
  • Polycystic Ovary Syndrome (PCOS)
  • Acne

How to Know You’ve Achieved Ketosis

Ketosis can be monitored by observing common symptoms or actually measuring the amount of ketones that are present in your body. Simple, less invasive, signs of ketosis include:

Science Behind the Keto Diet, HighKey Snacks

  • Fruity breath
  • Rapid weight loss
  • Absence of hunger
  • Improved mental clarity

When your body is in ketosis, your liver will produce three types of ketones: beta hydroxybutyrate (BHB), acetone and acetoacetate.  You can actually measure the levels of these ketones in your body to see if you’re in ketosis by testing your blood, urine and breath. 

  • Blood Testing - A simple finger prick can measure the levels of serum betahydroxy butyrate (BHB) in your blood, much like an ordinary blood glucose monitor.
  • Breath Testing - By blowing into a keto breath analyzer, you can measure the levels of acetone present on your breath.
  • Urine Testing Acetoacetate can be detected and measured in your urine by simply peeing on a keto urine test trip. This testing is most accurate when you are in the beginning stages of ketosis. The best time of day to test your urinary ketones is first thing in the morning or right after dinner. 

All of these test methods can usually be purchased at your local pharmacy or online so you can track your ketone levels from the comfort of your own home. The most accurate and reliable methods are blood and breath testing. A test reading of 0.5-3 mmol/L is considered positive for ketosis.

Side Effects and Precautions

Many people report feeling sick and tired during the first week to 10 days of adopting the keto diet. As your body begins shifting into fat-burning mode, it will continue to use some sugar (carbs) for energy. This in-between phase is known as the keto flu. Common symptoms you may experience with the keto flu include:

  • Feeling sluggish
  • Achy muscles
  • Muscle cramps
  • Sugar cravings
  • Nausea
  • Irritability
  • Difficulty concentrating

These negative symptoms are because of the changes happening in your body as a result of your new diet. The keto diet changes the way your body fuels itself and part of that change involves the loss of water and electrolytes that were being stored in your body before from your high-carb diet. Many of the symptoms you’ll experience during this transition are because of your body’s withdrawal from addicting high-carb foods like gluten and sugar and this withdrawal can trigger temporary increases in stress hormones.

Symptoms of the keto flu can be limited by:

Science Behind the Keto Diet, HighKey Snacks

  • Drinking plenty of water
  • Supplementing your diet with electrolytes
  • Starting your keto diet with a fast
  • Managing your stress levels
  • Getting adequate sleep  

The keto diet can result in drastic and immediate reductions in your blood sugar and blood pressure. If you are taking medications for these conditions, it is important that you speak to a qualified health professional before you start the keto diet so they can talk to you about adjusting your medication dosages. Without close management and adjustment, the diet can be unsafe for you.

If you have fat malabsorption issues, difficulty maintaining a healthy body weight or are pregnant, you should also consult with medical professional before starting the keto diet because it might not be the right choice for you. 

Long-Term Health Effects

There is limited health research on the long-term effects of low carbohydrate diets like the keto diet and the research that is available is generally mixed, showing both positive and negative outcomes. Further, most research on low-carb diets does account for the quality of food that’s being consume. Keto eaters feasting on salads, avocados and salmon could have different outcomes than those eating pepperoni and cheese – as these two variations of a low-carb diets look very different at the micro-nutrient level.

The keto diet should be designed strategically to reap the benefits of foods associated with health and longevity. With careful planning, it can offer many of the same benefits as the Mediterranean diet.  Incorporating plenty of fiber, leafy greens, olive oil, nuts seeds and wild fatty fish into your diet  is important, as these types of foods are associated with good health outcomes independent of the keto diet. Less healthful foods like processed meat products, fried foods and artificial sweeteners should be avoided or limitied due to their association with poor health outcomes.


Taking into account both my own clinical experience and the available research, the keto diet can be a remarkably effective way to reach specific health goals. To achieve ketosis, you will need to restrict how many carbohydrate-rich foods you eat like bread, potatoes and fruit so your body can switch from burning sugar to burning fat for energy. This metabolic shift can take some time, a few days to a week or more, and you might experience some flu-like symptoms as your body adjusts.

Careful consideration should be given to your own health history, eating patterns and preferences before starting the keto diet. Undertaking a restrictive diet when you are unprepared can you set up for failure and can be unsafe if you have certain chronic health conditions.

It will take more quality research to draw informed conclusions about the long-term impact of the keto diet, but in the interim, benefits can be maximized and risks minimized by making sure you incorporate plenty of the nutrient-dense foods associated with positive health outcomes that I mentioned above.

If you’re trying to determine if keto is a good fit for you, start by making some simple changes towards fewer carbs. You could begin by eating nuts for a snack instead of pretzels or chips, by replacing starches with vegetables (e.g.  zucchini noodles for pasta, cauliflower rice for regular rice etc.) and  by cutting back on your consumption of added sugars commonly found in beverages and ready-to-eat foods. You can also try a few recipes and start building a list of favorite meals and snacks that are low-carb.

If you have any health conditions, have a simple conversation with a qualified health provider like your primary care doctor or a registered dietitian to evaluate if the keto diet would be reasonable and safe to address your health goals. When you’re ready to begin keto and you’ve laid some groundwork, give it a shot to see if it’s a good fit. We’re cheering for you!

Carina Wolff
Carina Wolff is a health and wellness writer and food blogger based out of Los Angeles. She graduated from New York University with a degree in journalism and psychology. She writes for a number of websites, including Bustle, FabFitFun, Reader's Digest, and more. She also runs a healthy food blog called Kale Me Maybe, where she develops clean-eating recipes.



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