Keto-adaptation: what it is and how to adjust

Originally published on May 27, 2012

What is keto-adaptation?

Keto-adaptation is the process of shifting your metabolism from relying mostly on glucose for fuel, to relying mostly on fat-based sources of fuel. Not only does fat oxidation itself increase, but your body starts producing enough ketones that they can be used as a significant source of fuel as well. Ketones are derived from partially metabolized fat, and they can be used in many of the same tissues of the body as glucose can, including much of the brain. The benefits of using fat and ketones rather than glucose for fuel are many, and are the main subject of this site. However, it takes time for the metabolism to adjust to producing and using ketones at a significant rate. Even though changes are evident within days of carbohydrate restriction, improvements continue for weeks.

In brief:

Carbohydrate-based fueling is a self-perpetuating cycle: it runs out quickly, and every time you eat more carbs you delay adaptation to fat-burning.
Fat-based fueling is sustainable, because it allows access to a very large store of energy without you frequently stopping to refuel. Blood sugar is maintained though precise internal processes without wild swings. These two together create a desirable flow of even, stable energy, mood, and alertness.
There is a delay between first reducing the amount of carbohydrates that you eat, and having a smoothly running fat metabolism. In the intervening days, you may feel slow, or even unwell. These symptoms can be minimized by making sure to eat lots of fat, staying hydrated, and using salt liberally. Other electrolytes may also be helpful to add — homemade broth makes a good supplement. Keep carbs consistently low, or you will never adapt and the process will go on indefinitely.

Carbohydrate-based fueling is a self-perpetuating cycle.

The body can store only relatively small amounts of glucose, in the form of glycogen. About 100 grams can be stored in the liver, and about 400 grams can be stored in the muscles. Muscle glycogen can only be used by the muscle it is stored in — it can’t go back to the bloodstream — so the liver glycogen is the only source that can be used to keep blood sugar stable, and provide fuel for the brain. If you are not making use of ketones for fuel, then this is not enough glucose to get through a typical day, let alone a day when you are doing something strenuous. If you depend on glucose metabolism, then you have to frequently replenish your glycogen stores or you will begin to feel tired, physically and mentally.

There are basically two ways to get the necessary glucose, and only one of them involves eating it. The first is to eat carbohydrate. Unfortunately, every time you ingest more than a small amount of carbohydrate, it stops all progression toward keto-adaptation. So this strategy is a Catch-22. It makes you continually dependent on dietary carbohydrate. It locks you in, because supply is limited, but restocking prevents other fuels from becoming available.

The other way to get glucose is to let the body make its own on demand out of protein. This process is called gluconeogenesis. Gluconeogenesis is the reason that eating carbohydrate is not necessary, even though some amount of glucose is manufactured and used internally. This is analogous to any other internally produced nutrient, such as vitamin D, which we don’t need to ingest, because the body makes it in response to sun exposure, or to a hormone, like adrenaline, that we make and use every day, but don’t need to get from food.

One of the benefits that comes directly from this physiological mechanism is that on a keto diet you will no longer need to eat so often. Skipping a meal does not become an emergency, or even a problem. A lot of people have problems with mood, cognition, and wakefulness if they don’t eat frequently. On a keto diet your blood sugar will naturally become steady, and the advice to eat every 3 hours to prevent hypoglycemia will become irrelevant.

What exactly happens during keto-adaptation?

In their recent book The Art and Science of Low Carbohydrate Living, Volek and Phinney describe two stages of keto-adaptation. In the first few days of a keto diet, your body is still running on glycogen stores. This is the toughest part of the process, because in order to break the vicious cycle of glucose-based metabolism, you have to avoid eating carbohydrates, even though your glycogen stores are dwindling. Fat metabolism is still not optimized, and ketone production hasn’t become significant.

Another noticeable effect in the first days is water loss. One of the inefficiencies of glycogen storage is that it needs to be stored with water. It takes about 3 or 4 grams of water to store a gram of glycogen [1] . This means that as you deplete your glycogen stores you could lose up to 2 kg of water! Not only that, but high circulating insulin levels cause water retention by inhibiting sodium excretion (see e.g. [2]). The keto diet lowers insulin levels and increases insulin sensitivity, allowing excess fluid to be released. These combined effects are the origin of the claim that the weight lost on keto diets is due to water loss. In the very beginning, this is true, but subsequently, of course, it is not.

When glycogen runs out, you start producing ketones, and some are excreted in the urine. This is easy to measure, and some keto dieters use it to know if they are hitting a low enough level of carbohydrate restriction. This also marks the beginning of the second stage of keto-adaptation. Ketones are now becoming available for fuel, but they haven’t yet risen to their stable adapted level. There is an interesting interplay between ketone use in the muscles and the brain. When ketone levels are low, the muscles tend to use them directly for fuel, but as levels increase, the muscles use them less, turning to fat for fuel instead. The brain, on the other hand, uses ketones proportionally to their concentration in the blood. This means that at low levels of ketones, the brain’s supply is not much affected, because the muscles intercede, but above some threshold, the brain’s supply rapidly becomes much higher. At this point, the brain can rely on ketones, and since it is no longer susceptible to running out of fuel, the need to eat frequently throughout the day to maintain mental function disappears. The muscles in turn now rely on fat: they finally have access to a virtually unlimited supply of energy, which is particularly valuable for athletes.

Much confusion has been generated by scientists not recognizing one or both stages of keto-adaptation. A few studies have been publicized claiming that low carbohydrate diets worsen mental or physical performance (e.g. [3], [4]). On reading the details, it turns out that the testing was done in the first few days of carbohydrate restriction. Obviously, these studies are not valid criticisms of the keto diet, except as measurements of the initial adaptation cost. They do not reflect the longer-term outcome.

How to make keto-adaptation as quick and painless as possible

As noted above, the difficult part of keto-adaptation is the first stage. There are two reasons. The first is that glucose is less available, but fat and ketone metabolism haven’t effectively taken over. The best strategy for coping with this is to eat a lot of fat. Even if you eventually wish to get most of your fat from your fat stores, you do not normally need to restrict it in the diet, and especially not now. Fat is an important source of essential fatty acids and nutrients. Moreover, ingesting fat with protein helps to moderate the insulin response. A keto diet is not a high protein diet, it is a high fat diet. Do not fear it. Eat plenty of fat during keto-adaptation to ensure you have energy available.

The second difficulty is a result of the sodium excretion and transient rapid water loss we mentioned. If care is not taken to replenish sodium and water, both sodium and potassium are sometimes lost too rapidly. This can cause tiredness, weakness, and headaches. Be sure to get enough sodium: about 5 grams per day, or 2 teaspoons of table salt, will help prevent these symptoms.

Adequate potassium may be necessary to preserve lean mass [5], and magnesium deficiency can lead to muscle cramps, as well as fatigue and dizziness. Both of these minerals are abundant in meat, but are easily lost though cooking: into the water, if the meat was boiled, or the drippings otherwise. In addition to taking care to preserve the liquid from meat, acute effects can be cut short through supplementing potassium and magnesium by capsule. We recommend regularly drinking broth.

Finally, keep your dietary carbohydrates low. The worst scenario is to eat some every few days — you will set yourself back, and be in perpetual limbo. Now is not the time to experiment with your carbohydrate tolerance, or eat foods you aren’t sure about the content of. Commit to a very low level of carbohydrate intake, and stay with it consistently for at least long enough to get ketone production in full force. Most people we have talked to, if they experienced any discomfort at all, felt fully functional within 4 or 5 days. However, metabolic changes continue for at least two weeks and often more [6]. We recommend a 30 day trial at near zero levels of carbohydrate, to give yourself a chance to experience a completely keto-adapted state.

Tools:

The USDA National Nutrient Database for Standard Reference is a large database of nutrients including carbohydrate levels of whole foods and fast foods both.
Testing strips for urine ketones are useful for figuring out if you are getting into ketosis. We haven’t tried this brand, but it’s currently a good price. We’ve used Ketostix, and they work fine.
A fancier tool is a blood ketone meter. It works just like a glucose meter. In fact it doubles as one. This is better than urine testing, because it is more accurate, and it measures actual blood concentration. However, the test strips are pretty expensive.

References:

[1] Evidence type: experimental.
Olsson, K.-E. and Saltin, B. (1970), Variation in Total Body Water with Muscle Glycogen Changes in Man. Acta Physiologica Scandinavica, 80: 11–18. doi: 10.1111/j.1748-1716.1970.tb04764.x

“19 subjects performed prolonged heavy arm and leg exercise after which they had a protein and fat diet for three days. Thereafter they switched to a carbohydrate enriched diet during a 4-day period. The measurements were performed on the 3rd day and then repeated on the 7th day. The glycogen concentration in the thigh and the arm muscles was 4.5 and 2.6 g/kg wet muscle on the 3rd day and increased with the carbohydrate enriched diet to 19.9 and 16.9 g/kg wet muscle, respectively. Body weight increased 2.4 kg during this period of 4 days. The total body water increased 2.2 1 which is assumed to be caused by the glycogen storage in the muscles and the liver. The amount of glycogen stored was calculated to be at least 500 g, which means that 3-4 g of water is bound with each gram of glycogen.”

[2] Evidence type: review of a variety of experimental conditions.
R. A. DeFronzo (1981) The effect of insulin on renal sodium metabolism: A review with clinical implications. Diabetologia Volume 21, Number 3, 165-171, DOI: 10.1007/BF00252649

“Abstract
Data are discussed which demonstrate that insulin plays an important role in sodium metabolism. The primary action of insulin on sodium balance is exerted on the kidney. Increases in plasma insulin concentration within the physiological range stimulate sodium reabsorption by the distal nephron segments and this effect is independent of changes in circulating metabolites or other hormones. Several clinical situations are reviewed: sodium wasting in poorly controlled diabetics, natriuresis of starvation, anti-natriuresis of refeeding and hypertension of obesity, in which insulin-mediated changes in sodium balance have been shown to play an important pathophysiological role.”

[3] Langfort J, Zarzeczny R, Pilis W, Nazar K, Kaciuba-Uścitko H. The effect of a low-carbohydrate diet on performance, hormonal and metabolic responses to a 30-s bout of supramaximal exercise. Eur J Appl Physiol Occup Physiol. 1997;76(2):128-33.

The aim of this study was to find out whether a low-carbohydrate diet (L-CHO) affects: (1) the capacity for all-out anaerobic exercise, and (2) hormonal and metabolic responses to this type of exercise. To this purpose, eight healthy subjects underwent a 30-s bicycle Wingate test preceded by either 3 days of a controlled mixed diet (130 kJ/kg of body mass daily, 50% carbohydrate, 30% fat, 20% protein) or 3 days of an isoenergetic L-CHO diet (up to 5% carbohydrate, 50% fat, 45% protein) in a randomized order.
…
The main conclusions of this study are: (1) a L-CHO diet is detrimental to anaerobic work capacity, possibly because of a reduced muscle glycogen store and decreased rate of glycolysis; (2) reduced carbohydrate intake for 3 days enhances activity of the sympathoadrenal system at rest and after exercise.

[4] D’Anci KE, Watts KL, Kanarek RB, Taylor HA. Low-carbohydrate weight-loss diets. Effects on cognition and mood. Appetite. 2009 Feb;52(1):96-103. Epub 2008 Aug 29.

In the present experiment, cognitive effects of a low-carbohydrate diet were compared to those of another popular weight reduction diet over a 3-week period.
…
These data suggest that after a week of severe carbohydrate restriction, memory performance, particularly on difficult tasks (e.g., backward compared to forward digit span; spatial memory), is impaired.

Comment: This paper is interesting. The low carb dieters experienced memory deficits one week into the diet, and long term memory problems later, but the long term memory experiments were from memories that were formed at that same one week point, and so the problems were likely to be from poor memory formation, not poor recall ability. The authors suggest that cognition was better after more carbohydrate was added, but in the latter two weeks of the experiment the amount of carbohydrate added was very low, and the subjects were still well within ketogenic levels. So this isn’t a very compelling explanation. It seems much more plausible to us that this improvement was from keto-adaptation. While we don’t completely agree with the analysis of the authors, they did not state such a ridiculous interpretation of their findings in their paper as they did in the press: Science Daily reports:

A new study from the psychology department at Tufts University shows that when dieters eliminate carbohydrates from their meals, they performed more poorly on memory-based tasks than when they reduce calories, but maintain carbohydrates. When carbohydrates were reintroduced, cognition skills returned to normal.

“This study demonstrates that the food you eat can have an immediate impact on cognitive behavior,” explains Holly A. Taylor, professor of psychology at Tufts and corresponding author of the study. “The popular low-carb, no-carb diets have the strongest potential for negative impact on thinking and cognition.”

Whereas the abstract itself was more factual:

“Results showed that during complete withdrawal of dietary carbohydrate, low-carbohydrate dieters performed worse on memory-based tasks than ADA dieters. These impairments were ameliorated after reintroduction of carbohydrates. Low-carbohydrate dieters reported less confusion (POMS) and responded faster during an attention vigilance task (CPT) than ADA dieters. Hunger ratings did not differ between the two diet conditions. The present data show memory impairments during low-carbohydrate diets at a point when available glycogen stores would be at their lowest. A commonly held explanation based on preoccupation with food would not account for these findings. The results also suggest better vigilance attention and reduced self-reported confusion while on the low-carbohydrate diet, although not tied to a specific time point during the diet. Taken together the results suggest that weight-loss diet regimens differentially impact cognitive behavior.”

In other words, except for the memory problems that can be accounted for by keto-adaptation, the low carb dieters had equal or better cognitive performance than the ADA dieters, and yet this is cited as proof of the opposite!

[5] Evidence type: explanation and comparison of experiments.
Stephen D Phinney (2004) Ketogenic diets and physical performance. Nutrition & Metabolism 2004, 1:2 doi:10.1186/1743-7075-1-2

“An example of what happens when these mineral considerations are not heeded can be found in a study prominently published in 1980 [18]. This was a study designed to evaluate the relative value of “protein only” versus “protein plus carbohydrate” in the preservation of lean tissue during a weight loss diet. The protein only diet consisted solely of boiled turkey (taken without the broth), whereas the protein plus carbohydrate consisted of an equal number of calories provided as turkey plus grape juice. Monitored for 4 weeks in a metabolic ward, the subjects taking the protein plus carbohydrate did fairly well at maintaining lean body mass (measured by nitrogen balance), whereas those taking the protein only experienced a progressive loss of body nitrogen.

A clue to what was happening in this “Turkey Study” could be found in the potassium balance data provided in this report. Normally, nitrogen and potassium gains or losses are closely correlated, as they both are contained in lean tissue. Interestingly, the authors noted that the protein only diet subjects were losing nitrogen but gaining potassium. As noted in a rebuttal letter published soon after this report [19], this anomaly occurred because the authors assumed the potassium intake of their subjects based upon handbook values for raw turkey, not recognizing that half of this potassium was being discarded in the unconsumed broth. Deprived of this potassium (and also limited in their salt intake), these subjects were unable to benefit from the dietary protein provided and lost lean tissue. Also worthy of note, although this study was effectively refuted by a well-designed metabolic ward study published 3 years later [20], this “Turkey Study” continues to be quoted as an example of the limitations of low carbohydrate weight loss diets.”

[6] Evidence type: experiment.
Oliver E. Owen, Philip Felig, Alfred P. Morgan, John Wahren, and George F. Cahill, Jr. Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 March; 48(3): 574–583.

“Blood glucose and insulin concentrations fell acutely during the 1st 3 days of fasting, and alpha amino nitrogen after 17 days. The concentration of free fatty acids, β-hydroxybutyrate, and acetoacetate did not reach a plateau until after 17 days.”