This is the first chapter of a series on ketosis.
I've been experimenting with ketosis for some time, periodically posting my thoughts and findings to immediate family and interested friends. Some of them have urged me to share my experiments with a wider audience, so here we are. If you are unfamiliar with ketosis, not to worry - it's easy to understand and hopefully by the end of this article that unfamiliarity will have been superseded by curiosity.
In essence, ketosis is a metabolic state that occurs when the liver converts large amounts of fat into molecules called ketones which the body may use for energy. High ketone levels are generated when glucose levels are really low, which usually occurs under conditions of excessive caloric restriction, prolonged vigorous exercise, fasting, and ketogenic diets. Modest ketone levels may also be generated by consuming ketogenic products such as pure cream, coconut oil, medium chain triglyceride (MCT) oil, and ketone ester. Since these are all unusual situations and products, significant ketosis is rarely or never experienced by most people.
My preoccupation with ketosis lies in the fact that it confers numerous physiological benefits to the human body, especially the brain. Indeed, a growing body of evidence shows that ketosis may be effective not only as a symptomatic therapy (a treatment that temporarily ameliorates the symptoms of a condition) but also as a disease modifying therapy (a treatment that modifies the progression of a condition - slows it down or reverses it). In an era where the bulk of medical treatments for chronic conditions such as obesity, type II diabetes, hypertension, dyslipidemia, epilepsy, Alzheimer's disease, and Parkinson's disease are merely symptomatic therapies with no capacity to strike at the heart of the condition, the addition of a single disease modifying therapy with powerful applicability to all of them would be a great thing indeed.
My plan over the next several weeks is to provide some background on ketosis while comparing different methods of achieving it. With very rare exceptions I will reference only human studies - while numerous animal studies have found some spectacular benefits of ketosis on body and brain metabolism, we are not mice or rats or monkeys and so the relevance of animal studies to humans is questionable. Moreover, I will try to stick to randomized controlled trials (the gold standard for clinical trials) and systematic reviews (literature reviews that collect and criticize randomized controlled trials) as much as possible. My aim is to find a "best method" for achieving ketosis that is simple to follow, effective at achieving ketosis, and enhancing to the body and brain.
I've been experimenting with ketosis for some time, periodically posting my thoughts and findings to immediate family and interested friends. Some of them have urged me to share my experiments with a wider audience, so here we are. If you are unfamiliar with ketosis, not to worry - it's easy to understand and hopefully by the end of this article that unfamiliarity will have been superseded by curiosity.
In essence, ketosis is a metabolic state that occurs when the liver converts large amounts of fat into molecules called ketones which the body may use for energy. High ketone levels are generated when glucose levels are really low, which usually occurs under conditions of excessive caloric restriction, prolonged vigorous exercise, fasting, and ketogenic diets. Modest ketone levels may also be generated by consuming ketogenic products such as pure cream, coconut oil, medium chain triglyceride (MCT) oil, and ketone ester. Since these are all unusual situations and products, significant ketosis is rarely or never experienced by most people.
My preoccupation with ketosis lies in the fact that it confers numerous physiological benefits to the human body, especially the brain. Indeed, a growing body of evidence shows that ketosis may be effective not only as a symptomatic therapy (a treatment that temporarily ameliorates the symptoms of a condition) but also as a disease modifying therapy (a treatment that modifies the progression of a condition - slows it down or reverses it). In an era where the bulk of medical treatments for chronic conditions such as obesity, type II diabetes, hypertension, dyslipidemia, epilepsy, Alzheimer's disease, and Parkinson's disease are merely symptomatic therapies with no capacity to strike at the heart of the condition, the addition of a single disease modifying therapy with powerful applicability to all of them would be a great thing indeed.
My plan over the next several weeks is to provide some background on ketosis while comparing different methods of achieving it. With very rare exceptions I will reference only human studies - while numerous animal studies have found some spectacular benefits of ketosis on body and brain metabolism, we are not mice or rats or monkeys and so the relevance of animal studies to humans is questionable. Moreover, I will try to stick to randomized controlled trials (the gold standard for clinical trials) and systematic reviews (literature reviews that collect and criticize randomized controlled trials) as much as possible. My aim is to find a "best method" for achieving ketosis that is simple to follow, effective at achieving ketosis, and enhancing to the body and brain.
Diets: Now And Then
Before launching more into ketosis, some historical background is needed.
Modern western society is plagued by an obesity epidemic. Since the 1970s, the prevalence of obesity in North America has risen from 11.9% to 33.4% in men and from 16.6% to 36.5% in women (1). Most health professionals lay the blame for the obesity epidemic on the usual whipping boys - excessive caloric intake and lack of exercise. However, since the 1970s caloric intake in North America and Europe has only increased marginally, by 200 calories at most (1), and physical activity has actually increased (2). Therefore excess caloric intake and lack of exercise play a minor role at best in the rising obesity epidemic.
There are more fundamental shifts in dietary trends over the past half-century - namely increases in meal frequency, particularly snacking, and increases in carbohydrate consumption, particularly processed carbohydrates. Regarding meal frequency, since the 1970s three meals a day plus snacking has become the norm (3) and in that time the calories derived from those snacks have doubled (4). Regarding carbohydrate consumption, since the 1970s the percentage of energy derived from carbohydrates has increased by 5-10% while that derived from fat has decreased by roughly the same percentage (5) but what has changed the most is that the majority of carbohydrates consumed today are processed carbohydrates in which the protective fiber is removed, some big offenders being bread, pasta, rice, juice, and sugar (6). The pernicious tag-team of snacking and processed carbohydrates stimulates the body to constantly produce the hormone insulin leading to a continuous state of fat deposition (6).
It was not always this way - if we look back even further in time, up until 12,000 years ago all humans were hunter-gatherers. The hunter-gatherer period occupied at least 90% of human history and the hunter-gatherer strategy represented humanity's first and most successful adaptation (7), There are still well over 200 hunter-gatherer societies living today and they rarely, if ever, suffer from obesity or any of the other chronic diseases (8).
There are two major differences between hunter-gatherer diets and modern western diets. First, food was not always readily available to hunter-gatherers so they adapted to fasting for days or even weeks at a time, and during the fast their bodies and brains continued to function at a high level (3). There was no paradigm of three meals a day plus snacking. Second, a 2002 review of all modern hunter-gatherer diet studies to date showed that their diets were generally higher in fat and lower in carbohydrate compared to the modern western diet (8) - of course there would have been exceptions, as a 2011 review of 229 modern hunter-gatherer diets demonstrated that carbohydrate content varied anywhere from 3-50% of the total energy intake (9) - but in general, a higher proportion of fat was consumed by hunter-gatherers compared to modern times. Moreover, we can be certain that none of the carbohydrates during this pre-agricultural era were processed. Therefore the traditional hunter-gather diet, which is the diet that the human body evolved towards, was characterized by alternating periods of fasting and feasting, two revolving states in which the energy needs were largely supplied by body fat or dietary fat, respectively.
Modern western society is plagued by an obesity epidemic. Since the 1970s, the prevalence of obesity in North America has risen from 11.9% to 33.4% in men and from 16.6% to 36.5% in women (1). Most health professionals lay the blame for the obesity epidemic on the usual whipping boys - excessive caloric intake and lack of exercise. However, since the 1970s caloric intake in North America and Europe has only increased marginally, by 200 calories at most (1), and physical activity has actually increased (2). Therefore excess caloric intake and lack of exercise play a minor role at best in the rising obesity epidemic.
There are more fundamental shifts in dietary trends over the past half-century - namely increases in meal frequency, particularly snacking, and increases in carbohydrate consumption, particularly processed carbohydrates. Regarding meal frequency, since the 1970s three meals a day plus snacking has become the norm (3) and in that time the calories derived from those snacks have doubled (4). Regarding carbohydrate consumption, since the 1970s the percentage of energy derived from carbohydrates has increased by 5-10% while that derived from fat has decreased by roughly the same percentage (5) but what has changed the most is that the majority of carbohydrates consumed today are processed carbohydrates in which the protective fiber is removed, some big offenders being bread, pasta, rice, juice, and sugar (6). The pernicious tag-team of snacking and processed carbohydrates stimulates the body to constantly produce the hormone insulin leading to a continuous state of fat deposition (6).
It was not always this way - if we look back even further in time, up until 12,000 years ago all humans were hunter-gatherers. The hunter-gatherer period occupied at least 90% of human history and the hunter-gatherer strategy represented humanity's first and most successful adaptation (7), There are still well over 200 hunter-gatherer societies living today and they rarely, if ever, suffer from obesity or any of the other chronic diseases (8).
There are two major differences between hunter-gatherer diets and modern western diets. First, food was not always readily available to hunter-gatherers so they adapted to fasting for days or even weeks at a time, and during the fast their bodies and brains continued to function at a high level (3). There was no paradigm of three meals a day plus snacking. Second, a 2002 review of all modern hunter-gatherer diet studies to date showed that their diets were generally higher in fat and lower in carbohydrate compared to the modern western diet (8) - of course there would have been exceptions, as a 2011 review of 229 modern hunter-gatherer diets demonstrated that carbohydrate content varied anywhere from 3-50% of the total energy intake (9) - but in general, a higher proportion of fat was consumed by hunter-gatherers compared to modern times. Moreover, we can be certain that none of the carbohydrates during this pre-agricultural era were processed. Therefore the traditional hunter-gather diet, which is the diet that the human body evolved towards, was characterized by alternating periods of fasting and feasting, two revolving states in which the energy needs were largely supplied by body fat or dietary fat, respectively.
Ketosis
Let's return to ketosis.
When glucose stores become low enough for long enough, the human body enters a catabolic state whereupon fat is burned and the liver (and possibly brain cells known as astrocytes) (10,11) begin converting fat into ketones, molecules that may be consumed for energy by the body and brain. There are three different types of ketones - acetone, acetoacetate, and beta-hydroxybutyrate (BHB) (12). The last one, BHB, is the primary circulating ketone in the blood (12). The heart, skeletal muscles, and brain consume large quantities of ketones; the human brain must have at least some glucose, but up to 75% of its total energy needs can be supplied by ketones (13,14). The only major organ that cannot utilize ketones for energy is the one that generates them - the liver.
The blood BHB concentration in humans can range from negligible to downright toxic. In a person eating a typical modern western diet, the blood BHB concentration remains below 0.3 mmol/L (15). Conversely, type I diabetic patients who forego their insulin put themselves at risk of entering a pathological metabolic state called diabetic ketoacidosis in which the blood BHB concentration may exceed 25 mmol/L followed by a drop in the blood pH and eventual death (15). Yet between these two extremes there is a "sweet spot" called physiological ketosis in which the blood BHB concentration is 0.3-8 mmol/L - in this range, ketones provide energy yet do not disrupt the blood pH (12). There is no danger of the blood BHB concentration exceeding 8 mmol/L in a person without a metabolic disorder such as type I diabetes, for as it approaches this concentration the brain ramps up its ketone consumption such that the blood BHB concentration cannot go any higher (15).
When glucose stores become low enough for long enough, the human body enters a catabolic state whereupon fat is burned and the liver (and possibly brain cells known as astrocytes) (10,11) begin converting fat into ketones, molecules that may be consumed for energy by the body and brain. There are three different types of ketones - acetone, acetoacetate, and beta-hydroxybutyrate (BHB) (12). The last one, BHB, is the primary circulating ketone in the blood (12). The heart, skeletal muscles, and brain consume large quantities of ketones; the human brain must have at least some glucose, but up to 75% of its total energy needs can be supplied by ketones (13,14). The only major organ that cannot utilize ketones for energy is the one that generates them - the liver.
The blood BHB concentration in humans can range from negligible to downright toxic. In a person eating a typical modern western diet, the blood BHB concentration remains below 0.3 mmol/L (15). Conversely, type I diabetic patients who forego their insulin put themselves at risk of entering a pathological metabolic state called diabetic ketoacidosis in which the blood BHB concentration may exceed 25 mmol/L followed by a drop in the blood pH and eventual death (15). Yet between these two extremes there is a "sweet spot" called physiological ketosis in which the blood BHB concentration is 0.3-8 mmol/L - in this range, ketones provide energy yet do not disrupt the blood pH (12). There is no danger of the blood BHB concentration exceeding 8 mmol/L in a person without a metabolic disorder such as type I diabetes, for as it approaches this concentration the brain ramps up its ketone consumption such that the blood BHB concentration cannot go any higher (15).
Table 1. The range of blood BHB concentrations in ketosis (15,16).
Achieving Physiological Ketosis
Physiological ketosis occurs when the body is primarily burning fat for energy (17). When most people think of fat burning and weight loss, caloric restriction and exercise often come to mind yet in reality this combination has a 99% failure rate in the literature (3,14). This been shown time and time again but perhaps most poignantly by the Women's Health Initiative Dietary Modification Trial, the most ambitious diet and exercise randomized controlled trial ever completed (18). This study examined 48,835 post-menopausal women over seven and a half years, randomizing 40% of them into an intervention group (encouraged to reduce their fat intake and exercise more) and the other 60% into a control group (instructed to eat and exercise as they normally did). Despite the intervention group reducing their caloric intake from 1788 to 1446 calories a day and increasing exercise by 14% over the duration of the study, there was no significant difference in weight between the two groups by the end of the seven and a half years - dismally, weight loss in the intervention group did not even amount to one kilogram! This is not to say that caloric restriction and exercise are always failures at fat burning and weight loss - they do work in extreme cases where caloric restriction is excessive (19) or exercise is prolonged and vigorous (20) - but even then, the results are mediocre considering the enormous effort invested by the study subjects. Bottom line, it is extremely difficult to burn fat or lose weight - and thus achieve physiological ketosis - using any strategy that focuses solely on caloric restriction and exercise.
There are several better ways to burn fat and achieve physiological ketosis.
(1) Fasting.
In its purest form, fasting involves the elimination of all food or beverage intake except water for a specified length of time (3). This may be done on a short time scale as in time restricted feeding where food intake is limited to a 4-8 hour "time window" with a 16-20 hour fast every day, or on a long time scale as in intermittent energy restriction where the fast lasts for one or more days (3). In most people, a 12 hour fast raises the blood BHB concentration to 0.1 mmol/L (21). Three days of fasting bumps the blood BHB concentration up to 1 mmol/L (22). After a full week of fasting, the blood BHB concentration reaches the truly sweet spot of 4-8 mmol/L (22). Fasting is clearly effective at reaching physiological ketosis, but the downside is that it takes about a week to get there.
(2) Ketogenic diets.
In general terms a ketogenic diet is any diet that promotes ketone production by the liver (16). This is usually accomplished by reducing carbohydrate intake to less than 50 g per day (although the exact amount varies from person to person) and increasing the proportion of protein and fat - especially fat (23). By keeping the carbohydrates low and the fats high, ketogenic diets simulate fasting. The original ketogenic diet developed in the 1920s contained only 10-15 g of carbohydrate per day, with very high amounts of fat (24). Nowadays, the typical ketogenic diet is defined as 80% fat by weight, with the remaining 20% largely made up of protein (25). Ketogenic diets can raise the blood BHB concentration to 4-6 mmol/L (16). The downside is that most people find it difficult to adhere to the low carbohydrate, high fat nature of these diets over a long period of time.
(3) Pure cream.
Pure cream, a dairy product composed of the high butterfat layer that is skimmed from the top of milk before homogenization, contains some MCTs which the liver can convert into ketones, particularly caproic acid, a 6-carbon fatty acid (26). It may be surprising to hear that a 2013 review of 16 observational studies demonstrated that the consumption of high fat dairy foods such as pure cream, butter, and cheese tends to be associated with a lower risk of obesity (27). The downside with pure cream is that it is a rather weak source of MCTs.
(4) Coconut oil.
Extracted from the meat of mature coconuts, coconut oil is a powerful source of MCTs (28). Once ingested, the liver promptly converts the MCTs in the oil into ketones, with the blood BHB concentration peaking at three hours and remaining elevated for up to eight hours (28). Roughly 50% of the fatty acids in coconut oil consist of lauric acid, a 12-carbon fatty acid that not only suppresses inflammation but also displays considerable antiviral, antibacterial, and antiprotozoal properties (29) that may well protect the human brain from a variety of inflammatory and infectious insults (28). The downsides of coconut oil are that nausea and diarrhea can occur if too much is ingested in one sitting, and the taste can be difficult for some people to handle.
(5) MCT oil.
MCT oil is also a rich source of MCTs that the liver can convert into ketones. MCT oil is processed from natural oils - it contains more MCTs per unit volume than coconut oil but during processing the lauric acid is removed (28). MCT oil has been shown to elevate the blood BHB concentration to 1 mmol/L after 90 minutes (30). The blood BHB concentration returns to normal after three hours. Therefore MCT oil spikes the blood BHB concentration more quickly than coconut oil, but it fizzles out much more quickly too. There are two other downsides to MCT oil - since it lacks lauric acid it does not possess antimicrobial activity, and there is a slight increase in nausea and diarrhea compared to coconut oil (28).
(6) Ketone ester.
The most direct path to achieving physiological ketosis is by ingesting ketone ester, processed formulations containing mineral salts and BHB. It has been speculated that ketone ester can raise the blood BHB concentration to 2 mmol/L or higher (10) but large trials are lacking, although the self-experimenter Peter Attia raised his blood BHB concentration from 0.6 mmol/L or so to 2.6 mmol/L one hour after ingesting ketone ester (31).
There are several better ways to burn fat and achieve physiological ketosis.
(1) Fasting.
In its purest form, fasting involves the elimination of all food or beverage intake except water for a specified length of time (3). This may be done on a short time scale as in time restricted feeding where food intake is limited to a 4-8 hour "time window" with a 16-20 hour fast every day, or on a long time scale as in intermittent energy restriction where the fast lasts for one or more days (3). In most people, a 12 hour fast raises the blood BHB concentration to 0.1 mmol/L (21). Three days of fasting bumps the blood BHB concentration up to 1 mmol/L (22). After a full week of fasting, the blood BHB concentration reaches the truly sweet spot of 4-8 mmol/L (22). Fasting is clearly effective at reaching physiological ketosis, but the downside is that it takes about a week to get there.
(2) Ketogenic diets.
In general terms a ketogenic diet is any diet that promotes ketone production by the liver (16). This is usually accomplished by reducing carbohydrate intake to less than 50 g per day (although the exact amount varies from person to person) and increasing the proportion of protein and fat - especially fat (23). By keeping the carbohydrates low and the fats high, ketogenic diets simulate fasting. The original ketogenic diet developed in the 1920s contained only 10-15 g of carbohydrate per day, with very high amounts of fat (24). Nowadays, the typical ketogenic diet is defined as 80% fat by weight, with the remaining 20% largely made up of protein (25). Ketogenic diets can raise the blood BHB concentration to 4-6 mmol/L (16). The downside is that most people find it difficult to adhere to the low carbohydrate, high fat nature of these diets over a long period of time.
(3) Pure cream.
Pure cream, a dairy product composed of the high butterfat layer that is skimmed from the top of milk before homogenization, contains some MCTs which the liver can convert into ketones, particularly caproic acid, a 6-carbon fatty acid (26). It may be surprising to hear that a 2013 review of 16 observational studies demonstrated that the consumption of high fat dairy foods such as pure cream, butter, and cheese tends to be associated with a lower risk of obesity (27). The downside with pure cream is that it is a rather weak source of MCTs.
(4) Coconut oil.
Extracted from the meat of mature coconuts, coconut oil is a powerful source of MCTs (28). Once ingested, the liver promptly converts the MCTs in the oil into ketones, with the blood BHB concentration peaking at three hours and remaining elevated for up to eight hours (28). Roughly 50% of the fatty acids in coconut oil consist of lauric acid, a 12-carbon fatty acid that not only suppresses inflammation but also displays considerable antiviral, antibacterial, and antiprotozoal properties (29) that may well protect the human brain from a variety of inflammatory and infectious insults (28). The downsides of coconut oil are that nausea and diarrhea can occur if too much is ingested in one sitting, and the taste can be difficult for some people to handle.
(5) MCT oil.
MCT oil is also a rich source of MCTs that the liver can convert into ketones. MCT oil is processed from natural oils - it contains more MCTs per unit volume than coconut oil but during processing the lauric acid is removed (28). MCT oil has been shown to elevate the blood BHB concentration to 1 mmol/L after 90 minutes (30). The blood BHB concentration returns to normal after three hours. Therefore MCT oil spikes the blood BHB concentration more quickly than coconut oil, but it fizzles out much more quickly too. There are two other downsides to MCT oil - since it lacks lauric acid it does not possess antimicrobial activity, and there is a slight increase in nausea and diarrhea compared to coconut oil (28).
(6) Ketone ester.
The most direct path to achieving physiological ketosis is by ingesting ketone ester, processed formulations containing mineral salts and BHB. It has been speculated that ketone ester can raise the blood BHB concentration to 2 mmol/L or higher (10) but large trials are lacking, although the self-experimenter Peter Attia raised his blood BHB concentration from 0.6 mmol/L or so to 2.6 mmol/L one hour after ingesting ketone ester (31).
Physiological Ketosis - Advantages
The majority of health professionals have preconceived ideas about ketones resulting in unnecessary barriers to their therapeutic use (32). However, the scientific literature is riddled with studies substantiating the many beneficial effects of physiological ketosis on human health.
Ketones produce more energy and less oxidative damage than glucose. Regarding energy production, ketones produce more cellular energy than glucose as a result of increases in Gibbs free energy (23) such that the levels of adenosine triphosphate (ATP), the cell's "energy currency," remain elevated for longer (33,34). Regarding oxidative damage, it has been demonstrated that ketones generate fewer reactive oxygen species or "free radicals" in neurological tissues than glucose (32,33) which is important since these reactive oxygen species are heavily implicated in cell damage and aging in general. Clearly, ketones ought to be most beneficial for those cells with the highest energy demands and the lowest tolerance for oxidative damage, cells that live a long time and cannot be easily replaced – neurons – and indeed, several lines of research show that ketones protect neurons from multiple types of injury and disease (34).
Methods such as fasting and ketogenic diets that produce physiological ketosis have been shown to produce a wide array of beneficial effects on the majority of common human diseases (3,12,32). With respect to the human body, there is ample evidence that fasting and ketogenic diets can stall or reverse the metabolic syndrome, a scourge upon mankind that consists of most or all of obesity, type II diabetes, hypertension, and dyslipidemia, conditions that collectively encompass the greatest risk factors for heart attacks and strokes. With respect to the human brain, physiological ketosis has been shown to improve some of the most common chronic neurological conditions including epilepsy, Alzheimer's disease, and Parkinson's disease.
Let's sift through the evidence with regards to these specific conditions.
(1) Obesity.
A person is said to be obese when they have a body-mass index (BMI) of 30 or greater. Fasting is particularly effective at eliminating obesity (14). In a recent 2015 systematic review of six different randomized controlled trials all of which included overweight or obese patients, fasting for one or more days of the week resulted in a mean weight loss of 6.4% by three months and 8.9% by six months (35). In a 2016 systematic review of eight studies examining 390 patients from five weeks to one year, all of the studies reported a significant mean weight loss of 0.2 to 0.8 kg per week (36). Regarding high fat diets, a nicely designed 2008 study randomized 322 moderately obese patients to one of three diets - calorie restricted low fat, calorie restricted Mediterranean (high in vegetables, cheese, oils, fish, poultry, and red wine), and non-calorie restricted high fat - for a period of two years (37). By the end of the study, mean weight loss in the calorie restricted low fat group was only 2.9 kg whereas in the calorie restricted Mediterranean group mean weight loss was 4.4 kg, just behind the non-calorie restricted high fat group which won the race with a mean weight loss of 4.7 kg. Notably, calories were restricted in the low fat and Mediterranean groups but not in the high fat group, and yet the high fat group still lost the most weight.
(2) Type II diabetes.
The core defect in type II diabetes is insulin resistance (14) and when it comes to curing type II diabetes by reversing insulin resistance, fasting and high fat diets produce results that are nothing short of remarkable (32). A 2013 study subjected 115 overweight women to a 25% energy restriction, with some women randomized to daily caloric restriction and others to fasting for two days a week, and found that both groups showed significant reductions in body fat and improvements in insulin sensitivity by the end of three months (38). However, the reductions in body fat and improvements in insulin sensitivity were significantly greater in the fasting group - thus, even though both groups had the same overall 25% energy restriction placed upon them, fasting conferred additional metabolic benefits over daily caloric restriction. Fasting has actually been known to be the ultimate diabetes cure since the 1960s, with these studies documenting the complete discontinuation of insulin in all of their type II diabetic patients after a mere one to two weeks of fasting (39,40). Even fasting regimes where the intent was not explicitly to improve metabolic health have noted improvements in type II diabetes - for example, an observational study involving 1,301 Muslim diabetic patients showed that blood glucose and HbA1C (a marker of long-term glucose control) significantly improved during the fasting month of Ramadan (41). Regarding high fat diets, a 2014 study randomized 34 overweight or obese patients with prediabetes or diabetes to either a calorie restricted low fat diet or a non-calorie restricted high fat diet for three months and showed that while the low fat group ate only 1,381 calories per day and lost 2.6 kg on average with 11% stopping their diabetes medications, the high fat group ate more at 1,694 calories per day yet still lost 5.5 kg on average with a whopping 44% stopping their diabetes medications (42). So again, in comparing a calorie restricted low fat diet to an unrestricted eat-all-you-want high fat diet, it is the latter that results in more weight loss and greater improvements in insulin sensitivity.
(3) Hypertension.
Hypertension is commonly defined as a blood pressure of 140/90 mmHg or greater. Several studies have shown that fasting reduces both systolic and diastolic blood pressure. In one such study involving 174 hypertensive patients, just 10-11 days of fasting eradicated the hypertension in almost 90% of the patients; the average reduction in blood pressure was an impressive 37/13 mmHg (43). In another study involving 68 patients with borderline hypertension, two weeks of fasting reduced blood pressure by an average of 20/7 mmHg (44).
(4) Dyslipidemia.
Dyslipidemia refers to an abnormal blood lipid profile including high levels of total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides as well as abnormally low levels of high density lipoprotein (HDL) cholesterol. It is known that fasting improves the blood lipid profile (45). The majority of studies this century demonstrate that high fat diets also lead to significant benefits in the blood lipid profile (37,46,47) – while the results are mixed with regards to total and LDL cholesterol, a debate we will address below, there is strong evidence that high fat diets reduce triglycerides and increase HDL cholesterol (48). The diets highest in fat may have the most beneficial effects - in one study involving 66 obese patients (half of whom had normal blood lipid profiles and half of whom had dyslipidemia) fed a ketogenic diet over 56 weeks, the blood lipid profile improved in all of the patients; in the normal group the average total cholesterol fell by 6%, LDL cholesterol fell by 21%, triglycerides fell by 45%, and HDL cholesterol rose by 37% whereas in the dyslipidemia group the average total cholesterol fell by 29%, LDL cholesterol fell by 34%, triglycerides fell by a mighty 70%, and HDL rose by a mighty 64% (49).
(5) Epilepsy.
Roughly 70 million people (1% of the world) are affected by epilepsy (50), a neurological condition characterized by the recurrence of unprovoked seizures. Fasting was the first effective treatment for epilepsy in medical history (51) but the first "official" study may have been in 1911 when two French physicians documented the beneficial effects of fasting on epilepsy control (52). Ketogenic diets were created to simulate fasting in the 1920s (53) and have been used to treat epilepsy ever since, especially in tough cases where anti-epileptic drugs have failed. Several randomized controlled trials attest to the fact that at least half of all patients on a ketogenic diet experience a 50% or greater reduction in seizure frequency (51), even in the "worst of the worst" cases involving patients with multiple daily seizures (54). These improvements occur even at relatively low blood BHB concentrations in the range of 0.3-1.6 mmol/L (55,56).
(6) Alzheimer's disease.
Alzheimer’s disease, the most common chronic neurodegenerative disorder in the world, is characterized by progressive memory deficits and personality changes; 26.6 million people (0.4% of the world) were affected in 2006, a number expected to quadruple to 100 million people (over 1% of the world) by 2050 (57). It is well known that caloric restriction, endurance exercise, and resistance exercise improve cognitive function in people at risk for Alzheimer’s disease (58,59). Looking beyond caloric restriction and exercise, recent studies have shown that being in physiological ketosis also improves this condition. A 2004 study randomized 20 patients with Alzheimer’s disease or mild cognitive impairment to either a cream plus MCT combination or placebo and found significant improvements in cognitive scores in the former compared to the latter that were correlated to the blood BHB concentration, which was in the low range of 0.4-1 mmol/L (30). Moreover, a 2009 study involving 152 patients with mild to moderate Alzheimer’s disease randomized them to receive daily MCTs or placebo over 90 days and demonstrated that the MCT group had significantly improved cognitive scores compared to the placebo group that were correlated to the blood BHB concentration, even though the mean blood BHB concentration achieved by the end of the study was only 0.4 mmol/L (21). Furthermore, a 2012 study randomized 23 patients with mild cognitive impairment to either a high carbohydrate (50% of calories) or low carbohydrate (5-10% of calories) diet over six weeks and found significantly improved verbal memory in the low carbohydrate group that was correlated to urine ketone levels (60). These studies all prove that even low levels of physiological ketosis improve cognition in patients with mild cognitive impairment or Alzheimer’s disease.
(7) Parkinson's disease.
Parkinson’s disease, the second most common chronic neurodegenerative disorder, is characterized by progressive difficulties with movement, cognition, and mood and has a worldwide prevalence of around 0.1-0.2% (61). To date, there is only one published study that has specifically examined the effects of physiological ketosis on this condition, a small 2005 study which unfortunately lacked a control group in which the investigators observed the effects of a “hyperketogenic” diet (90% fat) in five patients with Parkinson’s disease over one month (62). The study showed improvements in resting tremor, freezing, balance, gait, mood, and energy in these five patients as measured by a 43% decrease (improvement) in the Unified Parkinson’s Disease Rating Scale; the mean blood BHB concentration was an impressive 6.6 mmol/L in the three most compliant subjects.
Ketones produce more energy and less oxidative damage than glucose. Regarding energy production, ketones produce more cellular energy than glucose as a result of increases in Gibbs free energy (23) such that the levels of adenosine triphosphate (ATP), the cell's "energy currency," remain elevated for longer (33,34). Regarding oxidative damage, it has been demonstrated that ketones generate fewer reactive oxygen species or "free radicals" in neurological tissues than glucose (32,33) which is important since these reactive oxygen species are heavily implicated in cell damage and aging in general. Clearly, ketones ought to be most beneficial for those cells with the highest energy demands and the lowest tolerance for oxidative damage, cells that live a long time and cannot be easily replaced – neurons – and indeed, several lines of research show that ketones protect neurons from multiple types of injury and disease (34).
Methods such as fasting and ketogenic diets that produce physiological ketosis have been shown to produce a wide array of beneficial effects on the majority of common human diseases (3,12,32). With respect to the human body, there is ample evidence that fasting and ketogenic diets can stall or reverse the metabolic syndrome, a scourge upon mankind that consists of most or all of obesity, type II diabetes, hypertension, and dyslipidemia, conditions that collectively encompass the greatest risk factors for heart attacks and strokes. With respect to the human brain, physiological ketosis has been shown to improve some of the most common chronic neurological conditions including epilepsy, Alzheimer's disease, and Parkinson's disease.
Let's sift through the evidence with regards to these specific conditions.
(1) Obesity.
A person is said to be obese when they have a body-mass index (BMI) of 30 or greater. Fasting is particularly effective at eliminating obesity (14). In a recent 2015 systematic review of six different randomized controlled trials all of which included overweight or obese patients, fasting for one or more days of the week resulted in a mean weight loss of 6.4% by three months and 8.9% by six months (35). In a 2016 systematic review of eight studies examining 390 patients from five weeks to one year, all of the studies reported a significant mean weight loss of 0.2 to 0.8 kg per week (36). Regarding high fat diets, a nicely designed 2008 study randomized 322 moderately obese patients to one of three diets - calorie restricted low fat, calorie restricted Mediterranean (high in vegetables, cheese, oils, fish, poultry, and red wine), and non-calorie restricted high fat - for a period of two years (37). By the end of the study, mean weight loss in the calorie restricted low fat group was only 2.9 kg whereas in the calorie restricted Mediterranean group mean weight loss was 4.4 kg, just behind the non-calorie restricted high fat group which won the race with a mean weight loss of 4.7 kg. Notably, calories were restricted in the low fat and Mediterranean groups but not in the high fat group, and yet the high fat group still lost the most weight.
(2) Type II diabetes.
The core defect in type II diabetes is insulin resistance (14) and when it comes to curing type II diabetes by reversing insulin resistance, fasting and high fat diets produce results that are nothing short of remarkable (32). A 2013 study subjected 115 overweight women to a 25% energy restriction, with some women randomized to daily caloric restriction and others to fasting for two days a week, and found that both groups showed significant reductions in body fat and improvements in insulin sensitivity by the end of three months (38). However, the reductions in body fat and improvements in insulin sensitivity were significantly greater in the fasting group - thus, even though both groups had the same overall 25% energy restriction placed upon them, fasting conferred additional metabolic benefits over daily caloric restriction. Fasting has actually been known to be the ultimate diabetes cure since the 1960s, with these studies documenting the complete discontinuation of insulin in all of their type II diabetic patients after a mere one to two weeks of fasting (39,40). Even fasting regimes where the intent was not explicitly to improve metabolic health have noted improvements in type II diabetes - for example, an observational study involving 1,301 Muslim diabetic patients showed that blood glucose and HbA1C (a marker of long-term glucose control) significantly improved during the fasting month of Ramadan (41). Regarding high fat diets, a 2014 study randomized 34 overweight or obese patients with prediabetes or diabetes to either a calorie restricted low fat diet or a non-calorie restricted high fat diet for three months and showed that while the low fat group ate only 1,381 calories per day and lost 2.6 kg on average with 11% stopping their diabetes medications, the high fat group ate more at 1,694 calories per day yet still lost 5.5 kg on average with a whopping 44% stopping their diabetes medications (42). So again, in comparing a calorie restricted low fat diet to an unrestricted eat-all-you-want high fat diet, it is the latter that results in more weight loss and greater improvements in insulin sensitivity.
(3) Hypertension.
Hypertension is commonly defined as a blood pressure of 140/90 mmHg or greater. Several studies have shown that fasting reduces both systolic and diastolic blood pressure. In one such study involving 174 hypertensive patients, just 10-11 days of fasting eradicated the hypertension in almost 90% of the patients; the average reduction in blood pressure was an impressive 37/13 mmHg (43). In another study involving 68 patients with borderline hypertension, two weeks of fasting reduced blood pressure by an average of 20/7 mmHg (44).
(4) Dyslipidemia.
Dyslipidemia refers to an abnormal blood lipid profile including high levels of total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides as well as abnormally low levels of high density lipoprotein (HDL) cholesterol. It is known that fasting improves the blood lipid profile (45). The majority of studies this century demonstrate that high fat diets also lead to significant benefits in the blood lipid profile (37,46,47) – while the results are mixed with regards to total and LDL cholesterol, a debate we will address below, there is strong evidence that high fat diets reduce triglycerides and increase HDL cholesterol (48). The diets highest in fat may have the most beneficial effects - in one study involving 66 obese patients (half of whom had normal blood lipid profiles and half of whom had dyslipidemia) fed a ketogenic diet over 56 weeks, the blood lipid profile improved in all of the patients; in the normal group the average total cholesterol fell by 6%, LDL cholesterol fell by 21%, triglycerides fell by 45%, and HDL cholesterol rose by 37% whereas in the dyslipidemia group the average total cholesterol fell by 29%, LDL cholesterol fell by 34%, triglycerides fell by a mighty 70%, and HDL rose by a mighty 64% (49).
(5) Epilepsy.
Roughly 70 million people (1% of the world) are affected by epilepsy (50), a neurological condition characterized by the recurrence of unprovoked seizures. Fasting was the first effective treatment for epilepsy in medical history (51) but the first "official" study may have been in 1911 when two French physicians documented the beneficial effects of fasting on epilepsy control (52). Ketogenic diets were created to simulate fasting in the 1920s (53) and have been used to treat epilepsy ever since, especially in tough cases where anti-epileptic drugs have failed. Several randomized controlled trials attest to the fact that at least half of all patients on a ketogenic diet experience a 50% or greater reduction in seizure frequency (51), even in the "worst of the worst" cases involving patients with multiple daily seizures (54). These improvements occur even at relatively low blood BHB concentrations in the range of 0.3-1.6 mmol/L (55,56).
(6) Alzheimer's disease.
Alzheimer’s disease, the most common chronic neurodegenerative disorder in the world, is characterized by progressive memory deficits and personality changes; 26.6 million people (0.4% of the world) were affected in 2006, a number expected to quadruple to 100 million people (over 1% of the world) by 2050 (57). It is well known that caloric restriction, endurance exercise, and resistance exercise improve cognitive function in people at risk for Alzheimer’s disease (58,59). Looking beyond caloric restriction and exercise, recent studies have shown that being in physiological ketosis also improves this condition. A 2004 study randomized 20 patients with Alzheimer’s disease or mild cognitive impairment to either a cream plus MCT combination or placebo and found significant improvements in cognitive scores in the former compared to the latter that were correlated to the blood BHB concentration, which was in the low range of 0.4-1 mmol/L (30). Moreover, a 2009 study involving 152 patients with mild to moderate Alzheimer’s disease randomized them to receive daily MCTs or placebo over 90 days and demonstrated that the MCT group had significantly improved cognitive scores compared to the placebo group that were correlated to the blood BHB concentration, even though the mean blood BHB concentration achieved by the end of the study was only 0.4 mmol/L (21). Furthermore, a 2012 study randomized 23 patients with mild cognitive impairment to either a high carbohydrate (50% of calories) or low carbohydrate (5-10% of calories) diet over six weeks and found significantly improved verbal memory in the low carbohydrate group that was correlated to urine ketone levels (60). These studies all prove that even low levels of physiological ketosis improve cognition in patients with mild cognitive impairment or Alzheimer’s disease.
(7) Parkinson's disease.
Parkinson’s disease, the second most common chronic neurodegenerative disorder, is characterized by progressive difficulties with movement, cognition, and mood and has a worldwide prevalence of around 0.1-0.2% (61). To date, there is only one published study that has specifically examined the effects of physiological ketosis on this condition, a small 2005 study which unfortunately lacked a control group in which the investigators observed the effects of a “hyperketogenic” diet (90% fat) in five patients with Parkinson’s disease over one month (62). The study showed improvements in resting tremor, freezing, balance, gait, mood, and energy in these five patients as measured by a 43% decrease (improvement) in the Unified Parkinson’s Disease Rating Scale; the mean blood BHB concentration was an impressive 6.6 mmol/L in the three most compliant subjects.
Physiological Ketosis - Criticisms
Most of the disadvantages attributed to fasting and ketogenic diets are misinformed. Let's look at the most common criticisms.
(1) Criticism one - fasting is dangerous.
Fasting is difficult the first time around for some people but like anything, the more it’s done the easier it gets. Numerous side-effects such as hunger, headache, and fatigue may occur during fasts of 16 hours or greater if a person is not accustomed to going without food for this amount of time. These effects diminish and disappear after several weeks or months of repeated fasting; in fact, the fasted state may even become desirable with time as ketones are appetite suppressants. The main risks of fasting are probably dehydration and low salt levels, both of which can result in hypotension, loss of consciousness, and falls with a risk of damage to the head (63). Therefore fasting for one or more days should be done under medical supervision for people with chronic hypotension. This is also a good idea for people with rare systemic or metabolic disorders.
(2) Criticism two - high fat intake increases heart disease and stroke.
Fat, especially saturated fat, has been publicly demonized the last half-century and yet the largest studies to date now clearly show that high fat intake is actually not associated with heart disease or stroke. A colossal 2014 systematic review and meta-analysis involving 530,525 patients from 32 observational studies and 103,052 patients from 27 randomized controlled trials showed that fat intake (including saturated fats) had no association with heart disease (64). Another gigantic 2010 meta-analysis of 347,747 patients over 5-23 years of follow-up showed no evidence that dietary saturated fat had any association with heart disease or stroke; in fact, there was an inverse relationship between saturated fat and stroke (65). Indeed, an inverse relationship between saturated fat intake and stroke has been shown in many studies, each involving thousands of patients (66,67), one such example being a 2010 study following 58,000 Japanese patients over 14 years that documented an inverse association between saturated fat intake and both hemorrhagic and ischemic stroke (67).
(3) Criticism three - elevated cholesterol increases heart disease and stroke.
Many studies show that ketogenic diets lower total and LDL cholesterol while others show the reverse, however the issue is somewhat irrelevant as the link between cholesterol and disease is tenuous anyways - like saturated fat, elevated total and LDL cholesterol levels continue to be dogmatically labelled as etiological predecessors to heart disease and stroke even in the face of strong evidence to the contrary. Perhaps the best example of this is a massive 2009 analysis that examined 136,905 patients admitted with heart disease to 541 US hospitals over a six year period (68). In this study in which every single patient had heart disease serious enough to warrant a hospital admission, the mean LDL cholesterol was found to be only 104.9 mg/dL (2.7 mmol/L) with roughly half of the values below 100 mg/dL (2.6 mmol/L), a range considered "optimal" for preventing heart disease (69). Given these results, a rational person might wonder if a low LDL cholesterol was perhaps not optimal for preventing heart disease, yet the unbelievable, dogmatic conclusion made by the authors of this paper was that the LDL cholesterol levels should have been reduced even further! This conclusion is unreasonable at best, hallucinatory at worst. There are other studies involving thousands of patients that have demonstrated in patients aged 65 years and older that higher total and LDL cholesterol levels are associated with reduced all-cause mortality (70,71). Moreover, it has been clearly documented that patients with higher total and LDL cholesterol are less likely to be afflicted by neurodegenerative disease (72,73,74). These studies should make any well-meaning health professional stop and think before reflexively prescribing a cholesterol-lowering medication merely for the sake of doing so. The undeniable protective effects of statins in reducing heart attacks and ischemic strokes are often quoted as incontrovertible evidence that lowering cholesterol is beneficial, however the beneficial effects of statins are unrelated to their ability to directly lower cholesterol since it has been shown that lowering cholesterol through any means other than a statin has no effect on survival - in a meta-analysis involving 24,847 men over 119,000 person years, lowering total cholesterol through diet or non-statin medications had no effect on mortality, although it did increase the number of accidental patient deaths (75), a finding expanded upon by a later Swedish study involving over 54,385 men and women that demonstrated an association between low total cholesterol levels and increased rates of suicide (76).
(4) Criticism four - sticking to fasting and ketogenic diets is difficult.
In my opinion this is the only truly valid disadvantage in using fasting or ketogenic diets to achieve physiological ketosis. The initial difficulty is mental – it takes a bit of courage to expunge the conventional “wisdom" regarding three meals a day plus snacks and low fat diets that has been drilled into humanity over the past half-century. The next difficulty is physical – it takes several weeks or months for the body to become comfortable with multi-day fasting and ketogenic diets containing 80% fat by weight. The final difficulty is social – sitting down to a meal often occurs in the setting of friends and family and if a person is either fasting or chooses not to eat certain foods for fear of breaking physiological ketosis, it can be socially isolating.
(1) Criticism one - fasting is dangerous.
Fasting is difficult the first time around for some people but like anything, the more it’s done the easier it gets. Numerous side-effects such as hunger, headache, and fatigue may occur during fasts of 16 hours or greater if a person is not accustomed to going without food for this amount of time. These effects diminish and disappear after several weeks or months of repeated fasting; in fact, the fasted state may even become desirable with time as ketones are appetite suppressants. The main risks of fasting are probably dehydration and low salt levels, both of which can result in hypotension, loss of consciousness, and falls with a risk of damage to the head (63). Therefore fasting for one or more days should be done under medical supervision for people with chronic hypotension. This is also a good idea for people with rare systemic or metabolic disorders.
(2) Criticism two - high fat intake increases heart disease and stroke.
Fat, especially saturated fat, has been publicly demonized the last half-century and yet the largest studies to date now clearly show that high fat intake is actually not associated with heart disease or stroke. A colossal 2014 systematic review and meta-analysis involving 530,525 patients from 32 observational studies and 103,052 patients from 27 randomized controlled trials showed that fat intake (including saturated fats) had no association with heart disease (64). Another gigantic 2010 meta-analysis of 347,747 patients over 5-23 years of follow-up showed no evidence that dietary saturated fat had any association with heart disease or stroke; in fact, there was an inverse relationship between saturated fat and stroke (65). Indeed, an inverse relationship between saturated fat intake and stroke has been shown in many studies, each involving thousands of patients (66,67), one such example being a 2010 study following 58,000 Japanese patients over 14 years that documented an inverse association between saturated fat intake and both hemorrhagic and ischemic stroke (67).
(3) Criticism three - elevated cholesterol increases heart disease and stroke.
Many studies show that ketogenic diets lower total and LDL cholesterol while others show the reverse, however the issue is somewhat irrelevant as the link between cholesterol and disease is tenuous anyways - like saturated fat, elevated total and LDL cholesterol levels continue to be dogmatically labelled as etiological predecessors to heart disease and stroke even in the face of strong evidence to the contrary. Perhaps the best example of this is a massive 2009 analysis that examined 136,905 patients admitted with heart disease to 541 US hospitals over a six year period (68). In this study in which every single patient had heart disease serious enough to warrant a hospital admission, the mean LDL cholesterol was found to be only 104.9 mg/dL (2.7 mmol/L) with roughly half of the values below 100 mg/dL (2.6 mmol/L), a range considered "optimal" for preventing heart disease (69). Given these results, a rational person might wonder if a low LDL cholesterol was perhaps not optimal for preventing heart disease, yet the unbelievable, dogmatic conclusion made by the authors of this paper was that the LDL cholesterol levels should have been reduced even further! This conclusion is unreasonable at best, hallucinatory at worst. There are other studies involving thousands of patients that have demonstrated in patients aged 65 years and older that higher total and LDL cholesterol levels are associated with reduced all-cause mortality (70,71). Moreover, it has been clearly documented that patients with higher total and LDL cholesterol are less likely to be afflicted by neurodegenerative disease (72,73,74). These studies should make any well-meaning health professional stop and think before reflexively prescribing a cholesterol-lowering medication merely for the sake of doing so. The undeniable protective effects of statins in reducing heart attacks and ischemic strokes are often quoted as incontrovertible evidence that lowering cholesterol is beneficial, however the beneficial effects of statins are unrelated to their ability to directly lower cholesterol since it has been shown that lowering cholesterol through any means other than a statin has no effect on survival - in a meta-analysis involving 24,847 men over 119,000 person years, lowering total cholesterol through diet or non-statin medications had no effect on mortality, although it did increase the number of accidental patient deaths (75), a finding expanded upon by a later Swedish study involving over 54,385 men and women that demonstrated an association between low total cholesterol levels and increased rates of suicide (76).
(4) Criticism four - sticking to fasting and ketogenic diets is difficult.
In my opinion this is the only truly valid disadvantage in using fasting or ketogenic diets to achieve physiological ketosis. The initial difficulty is mental – it takes a bit of courage to expunge the conventional “wisdom" regarding three meals a day plus snacks and low fat diets that has been drilled into humanity over the past half-century. The next difficulty is physical – it takes several weeks or months for the body to become comfortable with multi-day fasting and ketogenic diets containing 80% fat by weight. The final difficulty is social – sitting down to a meal often occurs in the setting of friends and family and if a person is either fasting or chooses not to eat certain foods for fear of breaking physiological ketosis, it can be socially isolating.
Summary
Hopefully you are perhaps a little interested in ketosis by now. Take-home points from this chapter are as follows.
(1) From an evolutionary point of view, eating three meals a day (plus snacking) and low fat (plus processed carbohydrates) is abnormal.
(2) Humans are mostly adapted to the hunter-gatherer diet - alternating periods of fasting and feasting in which energy needs are largely supplied by body fat or dietary fat, respectively.
(3) Humans evolved to be in physiological ketosis (blood BHB concentration 0.3-8 mmol/L) for much of their lives, yet it is rarely or never experienced by most people today.
(4) Sustained physiological ketosis is best achieved by fasting and ketogenic diets; it may be modestly enhanced by products such as pure cream, coconut oil, MCT oil, and ketone esters.
(5) Physiological ketosis induced by fasting, ketogenic diets, or a ketogenic product stalls or reverses the metabolic syndrome (obesity, type II diabetes, hypertension, and dyslipidemia) thus reducing the risk of heart disease and stroke, and improves common chronic neurological conditions (epilepsy, Alzheimer's disease, and Parkinson's disease).
(6) Most disadvantages attributed to fasting and ketogenic diets are not valid - fasting gets easier and desirable with time, high fat intake (including saturated fat) is not associated with an increased risk of heart disease and stroke, and while the debate rages on as to whether ketogenic diets raise or lower total and LDL cholesterol it is not relevant since low total and LDL cholesterol levels are not protective in any way, in fact they may be harmful.
(7) The last disadvantage is the only valid one - that switching to fasting and ketogenic diets may require mental courage, may be physically difficult to initiate, and may be socially isolating.
During the next couple of months I shall perform experiments in an attempt to find a "best method" for achieving physiological ketosis, a method that is simple to follow, effective at achieving at achieving physiological ketosis, and enhancing to the body and brain with an emphasis on tackling that last disadvantage - mental, physical, and social - at every level.
(1) From an evolutionary point of view, eating three meals a day (plus snacking) and low fat (plus processed carbohydrates) is abnormal.
(2) Humans are mostly adapted to the hunter-gatherer diet - alternating periods of fasting and feasting in which energy needs are largely supplied by body fat or dietary fat, respectively.
(3) Humans evolved to be in physiological ketosis (blood BHB concentration 0.3-8 mmol/L) for much of their lives, yet it is rarely or never experienced by most people today.
(4) Sustained physiological ketosis is best achieved by fasting and ketogenic diets; it may be modestly enhanced by products such as pure cream, coconut oil, MCT oil, and ketone esters.
(5) Physiological ketosis induced by fasting, ketogenic diets, or a ketogenic product stalls or reverses the metabolic syndrome (obesity, type II diabetes, hypertension, and dyslipidemia) thus reducing the risk of heart disease and stroke, and improves common chronic neurological conditions (epilepsy, Alzheimer's disease, and Parkinson's disease).
(6) Most disadvantages attributed to fasting and ketogenic diets are not valid - fasting gets easier and desirable with time, high fat intake (including saturated fat) is not associated with an increased risk of heart disease and stroke, and while the debate rages on as to whether ketogenic diets raise or lower total and LDL cholesterol it is not relevant since low total and LDL cholesterol levels are not protective in any way, in fact they may be harmful.
(7) The last disadvantage is the only valid one - that switching to fasting and ketogenic diets may require mental courage, may be physically difficult to initiate, and may be socially isolating.
During the next couple of months I shall perform experiments in an attempt to find a "best method" for achieving physiological ketosis, a method that is simple to follow, effective at achieving at achieving physiological ketosis, and enhancing to the body and brain with an emphasis on tackling that last disadvantage - mental, physical, and social - at every level.
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