I recently researched and reviewed the Carnivore Diet so I thought it would be fitting to research and review its big brother, the Keto Diet.
The Origin Story
The Keto Diet originated as a diet for epileptic children. In 1921 it was found that "acetone and beta-hydroxybutyric acid (ketone bodies) appear in a normal subject by starvation or a diet containing too low a proportion of carbohydrate and too high a proportion of fat." It was also found that "the benefits of fasting could be obtained if ketonemia was produced by other means." It was later determined in 1925 by Dr. Peterman at the Mayo Clinic that the keto diet would consist of "1 g of protein per kilogram of body weight in children, 10–15 g of carbohydrates per day, and the remainder of the calories in fat. The use of the KD was recorded in almost every comprehensive textbook on epilepsy in children that appeared between 1941 and 1980." (source).
So how did the keto diet gain popularity as a weight loss diet?
Well first came the low-carb craze from the Aktins diet in the 1970s that was later revised and rediscovered in the early 2000s. Then in 2013, Science Magazine published a study that showcased the anti-aging and health benefits of a ketogenic diet. "Scientists at the Gladstone Institute, a San Francisco–based research center, found that powerful antioxidant and anti-inflammatory genes are activated by beta-hydroxybutyrate, a ketone body produced when you limit calories or carbs." (source). A diet that fights free radicals and lowers inflammation in the body can be advertised as a diet that could possibly assist with cancer prevention, neurological disorders like Alzheimer's, heart disease, arthritis, skin conditions, irritable bowel syndrome and more.
Tim Ferris, a California-based podcaster and author of The 4-Hour Work Week was one of the first to try out the keto diet for the proposed health benefits. He stated that the diet is "incredible for simultaneous fat loss and lean muscle gain, though perhaps needlessly complicated for non-athletes.” Tim shared a video on his blog from Dr. Peter Attia MD. a longevity expert who claimed the keto diet "changed his body and health in ways that exercise and vegetables could not." This caused many of the million followers of Tim Ferris to try the diet for themselves and the number of people searching for the keto diet exploded.
It's important to highlight the fact that a low carbohydrate diet IS NOT THE SAME AS a keto diet. Generally people will claim they're following a keto diet but still are consumed too many carbohydrates impairing their ability to truly reach ketosis. The keto diet should remain a medical-grade dietary protocol and patients/clients should be followed by a medical professional.
What Does Keto Even Mean?
Keto is short for Ketosis which is a metabolic state of burning fat as a fuel source instead of the body's preferred fuel source, carbohydrates or rather, glucose. This metabolic state is not easy to get into but it's possible for everyone.
When we eat carbohydrates our bodies break that macronutrient down into simple sugars, glucose, fructose and galactose. These sugars can then either be used for immediate energy by the body, converted and stored as glycogen in the liver and muscle tissues for later energy use, or converted and stored as fat if there are no more glycogen storage spots available and no energy is needed at that time.
If we have limited carbohydrate intake, thus a limited intake of primary fuel, then our body needs to find energy elsewhere. It can take protein (specifically the amino acids alanine, serine, glycine and cysteine) from our muscles and convert it to glucose for energy production in cases of carbohydrate famine/depletion. The body can also use fat molecules to make glucose for energy production if no carbohydrates are available. Both methods of making new glucose in a process called gluconeogenesis (I covered that topic more in depth HERE).
But what happens when we chronically under eat or completely eliminate
carbohydrates from our diet?
This is when the body works to transition itself to burn fat (in the form of ketone bodies) for fuel instead of fighting to find carbohydrates that we aren't eating and we are having a hard time making now because the body does not want to break down muscle protein for fuel as this is not advantageous to survival.
In the absence of glucose, the body will use dietary fat and stored fat in adipose tissue to make a fat fuel source called ketones or ketone bodies. This process is called ketogenesis and it's outlined in the photo below. The three main ketones the body produces are made by our mitochondria and are acetoacetate, acetone and 3-β-hydroxybutyrate.
"During overnight fasting, the level of circulating ketones is supplying 2–6% of the energy, while after three days of starvation this value increases to 30–40%" (source). Acetone actually should not be present in the blood when testing for a state of ketosis as this compound is volatile and is usually eliminated via respiration. Once ketones are made from fat, they are then used to make energy (ATP) in a process called ketolysis, AKA the destruction of ketones. Both ketogenesis and ketolysis are controlled by the hormones glucagon (released from the liver) and insulin (released from the pancreas).
What's all the hype about keto anyways?
The keto diet resembles a primal way of eating. Many people believe that we should be eating in a manner that resembles how our ancestors ate. Before industrialization and agriculture was even a thing, humans were hunter/gathers, forging and hunting for food. This meant our diet was primarily meat, fish, tuberous and rooted vegetables, seeds and some fruit if they grew and were safe to eat. With agriculture and industrialization, humans were able to grow crops and grains and a lot of them faster, which brought the introduction of processed foods. We know ultra-processed and processed foods have been deemed unhealthy and a primary cause of inflammation in the Standard American Diet, leading to many comorbid conditions like diabetes, heart disease, and autoimmune conditions. This is why advocates of the Keto, Paleo, and Carnivore diets (KD, PD, CD) truly believe that limited or eliminating carbohydrates all together and eating as our ancestors did, is the way to achieve optimal health and eliminate dis-ease in the body.
It has also been advertised as a quick way to lose weight and burn fat as well as curb your appetite and improve satiety. While it does burn fat as fuel, that doesn't necessarily mean you'll lose body fat because of it. The main reason why anyone loses weight on a diet isn't because you eliminated carbs or went low-fat or stopped eating X and Y, it's because you put yourself into a caloric deficit; i.e. you're eating less than you're burning. This means whether you're primarily burning fat or carbohydrates as your main fuel source (whether you're in ketosis or not) you still need to be eating less than you're body needs in order to lose actual body fat.
Disclaimer: the above claims typically only work in someone who is generally metabolically healthy, meaning they aren't already chronically undereating, they don't have gut or hormonal issues and they have their stress regulated well. If these things are not met when starting a caloric deficit on any type of diet, then you'll be hard-pressed to see results from a caloric deficit. Proponents of the KD, CD and PD would argue otherwise I'm sure, and there might be some merit there...
So, how can one even get into a state of ketosis?
You need to completely change up your diet.
A keto diet is a very restrictive and regimented diet consisting of 80-90% of your calories coming from fat and the remaining 10-20% coming from protein and carbohydrates (2021, source). In other words, the diet should be a 4:1 ratio of fats to carbohydrates and protein (sometimes 3:1 ratio can achieve ketosis). So, let's look at what that means if you consume a standard 2000 calories. That means a minimum of 1600 calories come from fat which is 178 grams of fat and the remaining 400 calories would come from a mix of protein and carbohydrates; this could be 75 grams of protein and 25 grams of carbohydrates. Some people consume even less carbohydrates, around 10-15 grams only per day.
Reminder: not everyone is eating 2000 calories nor is that ideal for everyone which means if you wanted to attempt keto, you should still consult a nutrition professional or registered dietitian to determine your caloric needs based on your anthropometric data, dieting history, medical history, current health and physique goals, etc.
It's important to note that "up to 58% of amino acids are glucogenic, preventing the occurrence of ketosis" (2021, source). This means that 58% of amino acids found in protein can be converted into glucose in the body therefore preventing ketosis. So, it would be advantageous to drop protein even lower to help the body enter ketosis quicker and more efficiently provided that's the goal. There's always the risk of adverse outcomes with dropping your protein too low as protein is essential for muscle growth and maintenance as well as cellular health and metabolic reactions.
How do you know you're in ketosis?
In order to measure whether you are in a state of ketosis, blood and urine are used to measure ketones. Ketones can often be found in the urine even if you aren't in sustained ketosis so blood is a better marker.
According to the Global Diabetes Community, "The sweet spot for weight loss is 1.5 to 3.0 mmol/l. This level of nutritional ketosis is recommended by researchers Stephen Phinney and Jeff Volek. Ketone levels of 0.5 to 1.5 mmol/l, light nutritional ketosis, is also beneficial although not to the degree of full nutritional ketosis. The longer you stay within these levels, particularly within the sweet spot of nutritional ketosis, the more fat you will burn..." According to the NIH, "The hallmark of nutritional ketosis is blood ketone levels of 0.5 to 3 mg/dL."
As I said earlier, entering a state of ketosis isn't typically easy. It's characterized by something called "the keto flu." When the body works to make the transition to burning fat instead of carbs for fuel this takes a toll on the brain and subsequently nerve conduction. When the brain becomes deprived of carbohydrates (it's favorite fuel source), this can lead to headaches, fatigue, and feeling like you the flu without the fever. The 'keto flu' can last anywhere from a week to a month depending on how your body handles the transition.
The keto diet and cardiovascular outcomes:
With a diet as high in fat as this one, it's inevitable that medical professionals will be concerned about high cholesterol levels and adverse cardiovascular outcomes. A systematic review (PMID: 22905670) that looked at the effects of a low carbohydrate diet on cardiovascular risk factors and found that a low carb diet had "positive effects on body weight, BMI, abdominal circumference, blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides, glycemia, hemoglobin A1c (HbA1c), insulin, and C-reactive protein (CRP). However, despite the positive impact on cardiovascular risk factors, there is insufficient data to support KD in the long term as the studies were of relatively shorter duration, ranging from three to 36 months only."
Another meta analysis by Bueno et. al. 2013 found statistical significance of a ketogenic diet decreased at 12-24 months. However, the authors did find that there was a greater increase in LDL levels in those on a keto diet compared to those on a low fat diet (not surprising) which can lead to the development of atherosclerosis and increased risks in cardiovascular disease IF LDL is needed for vascular repair.
"In a randomized controlled trial performed at the outpatient care of the Philadelphia Veterans Affairs Medical Center among adults of ≥18 years old with a BMI of ≥35 kg/m2, 64 participants were assigned to an LCD [low carb diet] and 68 participants were assigned to a conventional diet. Analysis at one year of initiating the study found favorable metabolic effects on atherogenic dyslipidemia and glycemic control with participants on an LCD compared to participants on a conventional diet" (PMID: 32923239). This study highlights the impact of a low carb diet in regards to heart health, meaning carbohydrates may play a role in cardiovascular risk outcomes.
So, should I do the keto diet then??
Well, let's see what the research says...
Looking at the clinical trials performed in the last five years, the duration of those studies varied from 25 days to one year (not long enough to see long-term outcomes), had a small amount of participants, and some of the studies didn't implement a control group. The results of the studies showed a "significant reduction in body weight, BMI and fat mass content, after following a KD (keto diet). However, it is not confirmed that it is a result of a ketosis state, but an extremely reduced calorie intake." The majority of the studies used a very low calorie approach (or didn't mention calorie amount at all), as little as 600-800 calories per day which makes it tough to determine whether the weight loss was a result of the caloric restriction (I think so) vs. the actual composition of the diet. Other studies put participants through phases of caloric intakes, reaching as high as 2000 calories per day but these higher caloric phases weren't keto.
A randomized, prospective study done by Moreno et. al. 2016 looked at 45 obese patients who followed a very low calorie keto diet (VLCKD) for two years. A state of ketosis was only maintained for 45-60 days with a 12.5 kg. decrease in body weight, 11.6 cm. reduction in waist circumference and 8.8 kg. loss in actual body fat mass.
In another study done by Albanese et. al. 2019 comparing a standard low calorie diet and the keto diet, the keto diet resulted in double the reduction in body weight at the 15th day of the intervention. In both groups, losses slowed down at the 12 month marker but both diets were still effective after two years (I'm not sure how their defining 'effective' but I'm assuming as sustained weight loss).
Sajoiux et al. 2019 was able to show the anti-inflammatory benefits of a VLCKD which was "manifested by more pronounced changes in the circulating myokines levels, including IL-6, IL-8 and metalloproteinase 2."
Luis et. al. 2016 used a VLCKD in conjunction with DHA supplementation (omega-3s) which showed a reduction in the "concentrations of insulin, triglycerides, total cholesterol, LDL cholesterol, C-reactive protein, tumour necrosis factor-alpha (TNF-α) and resistin."
In regards to appetite control and improved satiety, Nymo et. al. 2017 found that a VLCKD had no effect on GLP-1, cholecystokinin and ghrelin levels which are hormones that stimulate appetite. However, ghrelin levels increased when carbohydrates were slowly reintroduced into the diet.
Another study by Castro et. al. 2018 found that a "four-month intervention with VLCKD resulted in reductions in food craving when the ketosis state was obtained, however, it did not affect the level of ghrelin."
Regardless of whatever diet you're on, leptin (satiety hormone) will decrease and ghrelin levels increase with the more weight you lose. Ghrelin is a hormone that is released from the stomach in response to low energy and low nutrient availability in an attempt to tell your body to eat because there isn't enough energy. This is a protective mechanism the body undergoes to make sure we don't die, love that for us. But we don't love that when we are trying to drop body fat.
To summarize the clinical trials conducted in the last five years, "available scientific literature indicates that following a KD (keto diet) could be beneficial toward the management of obesity. Still, there is a lack of big-scale and comprehensive studies warranting the safety of using KD for bodyweight loss. To date, most of the studies had small sample sizes, lack of control groups and the intervention period was short term without any follow-up-assessment... More randomized, controlled studies on the physiological and metabolic effects of diet composition should be designed, with better controls put in place for to adhere to the diets" (2021, source). Also, with limited available research, it's difficult to know what kinds of implications a keto diet can have on the gut microbiome, nutrient deficiencies and long-term hormonal side affects.
HOWEVER, nutrition research is tough enough as it is and I'd argue the data we have on the diets and ways of eating we already implement aren't the best either. Most of the nutritional guidelines we create are based on cohort studies, animal clinical trials, or retrospective data pulled from large databases like NHANES and nurse cohorts. It's very hard to perform RCTs on humans in an ethical manner and control all the necessary variables in order to isolate what you're studying. Humans are too dynamic, highly variable, inconsistent and unpredictable for such a controlled study, but sometimes we can get decent data out of certain study designs.
There is a great need for metabolomic research in regards to the 'perfect diet' for each individual. We are all so different meaning our needs are different from others as well. Metabolomics "is defined as the comprehensive analysis of metabolites in a biological specimen [and] is an emerging technology that holds promise to inform the practice of precision medicine" (PMID: 27148576). Precision medicine, rather precision nutrition, would allow professionals to tailor a dietary protocol based on your genetics and your personalized needs. This would allow us to tell patients what diet is best for them, rather, what macronutrient ratio and profile is best for them in regards to their genetics and their goals. For now, the easiest way to obtain the results from a metabolomic diagnostic tool is to reach out to a registered dietitian or nutrition professional for help! ; )
To wrap up and offer my concluded thoughts on the keto diet...
I don't hate it, and to be honest, it seems like a decent option for someone who is looking to improve their metabolism and drop some weight faster than traditional methods of macro tracking and slowly chipping away. But research is showing that results and effects from the diet tapper off after 12 months which means this isn't a sustainable diet and transitioning out of it is something that should be monitored carefully.