Ketogenic
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Misconceptions abound when it comes to ketogenic diets. Some people swear by them, others shun them, and the rest of us are confused. Before we can decide whether ketogenic diets are good for us or not, let’s first discuss what a ketogenic diet is, and what a ketogenic diet does.
Essentially, a ketogenic diet is any high-fat, adequate-protein, very low-carbohydrate diet that forces the body to burn fats, rather than carbohydrates, as its main energy source; the liver converts excess fats into ketones, molecules that can provide energy for most cells in the body (1). Depending on the particular fat to carbohydrate ratio of a person’s ketogenic diet, their blood ketone (beta-hydroxybutyrate) level will lie within the range of 0.5 to 8 mmol/L; this is the range of "physiological ketosis."
The over-arching aim of a person on a ketogenic diet is to be in sustained physiological ketosis, but the range of physiological ketosis is quite broad and that person's goals will determine where they want to be on it. If weight loss is the goal, a low level of ketosis (around 1 mmol/L) may be ideal. However, if a person is using the diet to combat drug-resistant epilepsy or cancer, a high level of ketosis (around 4 mmol/L) may be desired.
A sustained state of physiological ketosis simply indicates that a person's body metabolism is altered to simulate a multiday fasted state; mimicking this state is the true aim of the diet. Unlike fasting, the diet can be followed indefinitely; Angus Barbieri holds the world record for the longest recorded fast at 382 days, functioning normally while living on tea, coffee, soda water, and vitamins the entire time, but eventually even he had to eat. |
Angus Barbieri fasted for 382 days, losing 276 pounds. |
Potential Pros
What could be so special about altering one's metabolism to be in sustained physiological ketosis, to mimicking a fasted state? Well, there are several potential pros to such a state.
One potential pro has to do with the ketones themselves. Glucose is the usual primary body fuel, but ketones are probably a more energy-efficient and "cleaner" (produce fewer free radicals) kind of fuel (1). Ketones promote anaplerosis (the replenishing of depleted metabolic cycle intermediates), which ultimately increases cell metabolism and enhances energy production (2). Thus, ketones not only serve as an alternative energy source to glucose, they also serve as a superior energy source to glucose, a fuel that can be used by many body organs, particularly brain and muscle.
Fascinating as this concept may be, there is much, much more to ketogenic diets and fasting than the mere production of massive quantities of ketones; physiological ketosis is not the goal, it is a marker of the goal. The goal of ketogenic diet therapies (and therapeutic fasting) is to produce an altered metabolic state. By "flipping" the body from a state of anabolism (body growth) to the opposite state, catabolism (maintenance and repair), ketogenic diets decrease the activity of master anabolic hormones and enzymes such as insulin and mTOR, which enhance cell growth and proliferation and are upregulated in obesity, type 2 diabetes, and most cancers (3). It it likely that ketogenic diets also increase the activity of master catabolic enzymes like AMPK which replenishes cell energy reserves and anti-oxidant defences, and promotes autophagy (recycling of worn-out cell parts) (3).
Entering sustained physiological ketosis and a metabolic state of catabolism to promote weight loss and lowered insulin levels is probably a positive thing for people in developed nations facing epic rates of obesity and type 2 diabetes. Yet the potential benefits of ketogenic diets go further still, beyond weight loss and diabetes control. The ability to enhance body energy metabolism as well as activate maintenance and repair processes extends their potential applications into other medical conditions, such as debilitating neurological diseases.
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There are three ketone types: acetone (top), acetoacetate (middle), and beta-hydroxybutyrate (bottom). |
For nearly a century, ketogenic diets have been used to treat the one-third of epilepsy patients with drug-resistant epilepsy (people who continue to suffer from seizures no matter how many anti-epileptic drugs they try, with surgery not a realistic option) (4, 5). Ketogenic diets improve seizure control by an impressive 50% or more in nearly half of these most difficult epilepsy cases; this includes both children and adults (4, 5).
Ketogenic diets are also being studied in some of our most challenging neurodegenerative disorders, namely Parkinson’s disease and Alzheimer’s disease.
In 2018, a randomized controlled study showed that a ketogenic diet substantially improved many of the most disabling, least medication-responsive symptoms of Parkinson’s disease (6). You can hear more about it here:
In 2019, we hope to see another randomized controlled study examining whether dietary therapy can help people with mild Alzheimer’s disease, a crippling condition that lacks any effective medical treatment.
Neurological disorders such as drug-resistant epilepsy, Parkinson’s disease, and Alzheimer’s disease are some of the most pervasive and troublesome conditions of our time, yet medications cannot cure them; as a rule, medications temporarily mask symptoms; they do not slow down or stop a disease process. We need better treatments for these conditions, and dietary therapy may be a superior option.
Potential Cons
Unfortunately, numerous misconceptions about the potential cons of ketogenic diets continue to hinder their potential applications in health and disease (I only have space to talk about a few, otherwise this article would be too long).
Ketogenic diets are criticized as restrictive, with those of the 100-year old "classic" ketogenic diet usually mentioned (7, 8). However, the restrictions of the classic ketogenic diet do not apply to newer diets (just as the limitations of a 100-year old automobile do not apply to modern cars). Ketogenic diets can be purely vegetarian or purely carnivorous, and everything in-between; they may be adapted to most ethnic cuisines. Moreover, fiber does not need to be restricted, nor should it be since our gut bacteria metabolize fiber to create short-chain fatty acids necessary for gut health. Most fleshy fruits are off the table (these are not as "natural" as is often thought, for example, watermelons now are 1,680 times larger than they were 3,000 years ago, a massive size increase in a relatively short time thanks to human cultivation) (9). Berries are excepted; these may be eaten daily.
Ketogenic diets are also frequently criticized for having potentially serious adverse effects (7, 8); again, critics tend to focus on the classic ketogenic diet in children, about half of whom experience at least one of nausea, abdominal pain, and constipation. However, these adverse effects are rare in adults, in whom the most prevalent adverse effects are raised cholesterol levels and weight loss (10). Yet cholesterol levels usually normalize within a year (11), and the cholesterol increase is due to increased cholesterol particle size rather than particle number, which appears to be associated with a lower risk of atherosclerosis (12). Moreover, since weight loss is often the goal, in most people this is not really an "adverse" effect. There are also benefits that tend to be glossed over; adults on a ketogenic diet often report improved cognition, mood, and quality of life scores (13).
Lastly, most diet studies are observational studies, a type of design that detects associations between variables. Yet these studies cannot detect if a thing caused another to occur. For example, a recently-published observational study of 25,000 people showed an association between low-carb (not ketogenic) diets and increased mortality (14), concluding that "low-carb diets cause increased mortality." Yet observational studies also show that smokers are 30% less likely to develop Parkinson’s disease compared to people who never smoked (15); this does not necessarily mean that "smoking protects against Parkinson’s disease."
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In epidemiology, there is a massive difference between what randomized controlled studies and observational studies are able to tell us. |
Observational studies often lead people to infer that a causal relationship exists where it does not. Unfortunately, this is very common (especially in media releases, where the main aim may not be to spread truth so much as to get attention). However, only randomized controlled studies can definitively tease out any causative links that may exist between variables. Since well-designed, randomized controlled dietary studies are (very) difficult to conduct, they are quite rare, but these are the studies we really need more of.
Until then, we should not be too quick to pass judgement as to whether ketogenic diets are good for us or not. Given their potential pros, it is reasonable for a person experiencing subjective benefit to continue with their diet. Medications are good at modifying single targets - an enzyme here, a receptor there. In contrast, ketogenic diets can substantially alter a person’s metabolic state, modifying multiple targets; theoretically, this makes them much more powerful, especially when assaulting a complex disease.
Thus, rather than blindly swear by or ruthlessly shun ketogenic diets, maybe it's best to keep an open mind, conduct the correct studies rather than leaping to unsupported conclusions based on observational studies, and discover whether these diets really can help people suffering from the most devastating disorders in existence.
Solace.
References
(1) Rho. 2017. How does the ketogenic diet induce anti-seizure effects? Neurosci Lett 637, 4-10.
(2) Simeone et al. 2018. Do ketone bodies mediate the anti-seizure effects of the ketogenic diet? Neuropharmacology 133, 233-241.
(3) O'Flanagan et al. 2017. When less may be more: calorie restriction and response to cancer therapy. BMC Medicine 15(106), 1-9.
(4) Kossoff et al. 2018. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open 3(2), 175-192.
(5) Schoeler and Cross. 2016. Ketogenic dietary therapies in adults with epilepsy: a practical guide. Pract Neurol 16, 208-214.
(6) Phillips et al. 2018. Low-fat versus ketogenic diet in Parkinson's disease: a pilot randomized controlled trial. Mov Disord 33(8), 1306-1314.
(7) https://www.noted.co.nz/health/nutrition/keto-weight-loss-diet-long-term-risks/.
(8) https://www.healthline.com/health-news/keto-diet-is-gaining-popularity-but-is-it-safe-121914#7.
(9) https://jameskennedymonash.wordpress.com/2014/07/14/artificial-vs-natural-watermelon-sweetcorn/.
(10) Cervenka et al. 2016. Establishing an adult epilepsy diet center: experience, efficacy and challenges. Epilepsy Behav 58, 61-68.
(11) Cervenka et al. 2014. The impact of the modified Atkins diet on lipid profiles in adults with epilepsy. Nutr Neurosci 19(3), 131-137.
(12) Song et al. 2015. Low-density lipoprotein particle size predicts a poor outcome in patients with atherothrombotic stroke. J Clin Neurol 11(1), 80-96.
(13) Lambrechts et al. 2012. The ketogenic diet as a treatment option in adults with chronic refractory epilepsy: efficacy and tolerability in clinical practice. Epilepsy Behav 23, 310-314.
(14) https://ipccs.org/2018/09/04/increased-risk-of-mortality-in-adults-with-low-carbohydrate-diets/
(15) Bellou et al. 2016. Environmental risk factors and Parkinson’s disease: An umbrella review of meta-analyses. Parkinsonism and Related Disorders 23, 1-9.
