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As the ketogenic diet becomes more popular, it is important to have a balanced discussion about the benefits of this diet and who can benefit from it. Let me stress at the outset that ketogenic diets have a significant therapeutic potential for certain clinical pathologies. However, it is also a regime with inherent risks, as evidenced by the long list of adverse reactions that have occurred very frequently in the scientific literature.
Every anecdotal story of someone who has regained health through a ketogenic diet is a counterpoint that tells the story of a person who derailed his health with an identical diet. But do not talk about anecdotes. Instead, let's look at the huge collection of scientific articles – including the results of clinical trials, case studies and mechanistic studies – that reveal a dark side of the ketogenic diet. And everyone needs to be aware of this dark side while doing its own cost-benefit analysis to decide if this food strategy is worth the risk involved.
A brief history of ketogenic diets
The origins of the ketogenic diet were the observations of Hippocrates in 500 BC. AD that fasting could reduce and even cure epileptic seizures (fasting is also a ketogenic state). However, it was not until 1911 that the first scientific study on starvation as a treatment for epilepsy was published. Fasting is a very important obstacle to widespread clinical use: it is not sustainable. You can not starve for the rest of your life and expect it to last a very long time.
In 1921, Drs. Stanley Cobb and WG Lennox were the first to find that the control of seizures by fasting occurs through a change in body metabolism that can be induced either by the lack of food or by a very low carbohydrate intake. And this observation led to the birth of a form of nutritional starvation, the ketogenic diet, a term coined by Dr. Russell Wilder, who developed the diet as an alternative to fasting and demonstrated comparable efficacy in terms of diet. ;epilepsy. Dr. Wilder observed that the diet produced high levels of ketones in the blood and hypothesized that a diet high in fats and carbohydrates would mimic the anticonvulsant effects of fasting, as limited glucose intake would fat to be metabolized to ketones, which could then occur. used as alternative fuel by the brain (this hypothesis has taken decades to prove, and more detailed mechanisms remain to be elucidated). In 1925, Dr. Mynie Peterman calculated the exact formula for nutritional ketosis, a daily diet comprising: 10-15 grams of carbohydrate, 1 gram per kilogram of protein body weight and the rest of the fat (a formula based on macronutrients narrow range used in variations of the ketogenic diet today).
Research on ketogenic diets has had its ups and downs in the decades that followed. Whenever a new anticonvulsant drug for the treatment of epilepsy was developed, interest in ketogenic diets disappeared, assuming that it was easier and more tolerable to take a pill every day than a severely restrictive diet. which caused many intolerable side effects. Interest in the recognition of the profession and the public as a result of the popularity of the Atkins diet revolution; a Dateline report of a 2-year-old Charlie Abrahams, whose epileptic seizures were successfully halted following a ketogenic diet; the creation of the Charlie Foundation, which distributes informative videos on the ketogenic diet to doctors and dieticians; and the movie Do not hurt. Since the late 1990s, research on ketogenic diets has developed, including a series of long-term studies on ketogenic diets for refractory epilepsy (epilepsy that does not not respond to anticonvulsant drugs) and the study of various other applications.
Undesirable effects of ketogenic diets
As the list of health problems that could be at least partially relieved by ketogenic diets (and which currently includes epilepsy, Alzheimer's disease, Parkinson's disease, autism, traumatic brain injury, bipolar disease, multiple sclerosis, PCOS, cancer, obesity and diabetes), the same goes for a whole literature highlighting common side effects and potential adverse effects.
An adverse reaction is an undesirable / unexpected and dangerous reaction to a therapeutic agent (as opposed to a side effect that is simply an unpleasant side effect). Adverse reactions to a ketogenic diet have been reported in the scientific literature. Yes, even with well-designed clinical trials done and published very recently. In fact, intolerance of side effects and adverse reactions is the main reason for trial participants to discontinue clinical trials of a ketogenic diet (the other reasons for discontinuing trials include the inefficiency of food and a diet too difficult to follow). .
Documented side effects reported in long-term ketogenic studies (any study allowing a keto-adaptation, which lasts up to one month) include:
- Gastrointestinal disorders (diarrhea, vomiting, nausea, constipation, GER)
- Risk of inflammation
- Sepsis, infection, proliferation of bacteria
- Acute pancreatitis
- L & # 39; hypothyroidism
- Thinning hair / hair loss
- Menstrual irregularities and amenorrhea
- L & # 39; hypoglycemia
- Increased cortisol
- Decreased testosterone
- Low number of platelets
- Increased bruising
- Kidney stones
- Renal tubular acidosis
- High liver enzymes
- Muscle cramps or weakness
- Concentration / Cognition Disorder
- Altered mood
- Nutrient deficiency (including vitamin D, calcium, selenium, iron, potassium, phosphorus, vitamin C, magnesium and copper)
- Disordered mineral metabolism
- Low growth in children
- Skeletal fracture
- Osteopenia / osteoporosis
- Transition to atherogenic lipid profiles (including hypercholesterolemia and hypertriglyceridemia)
- Long QT intervals
- Cardiac arrythmia
- Myocardial infarction
The studies report a frequency of adverse reactions ranging from 10% to 100%, which may reflect variations in the severity of the statement in addition to the actual incidence in different populations. The long list of documented adverse reactions indicates that the positive effects of a ketogenic diet on health have a cost that may not be acceptable to many.
Mechanisms behind adverse reactions
The ketogenic diet is designed to mimic the biochemical changes that occur during starvation while reaching a nutritional threshold to avoid starvation. It is therefore not surprising that the list of adverse reactions above substantially overlaps the effects of starvation. Anorexia Nervosa causes so-called starvation ketosis, whose adverse effects include: abnormal blood counts, increased liver enzyme levels, fatigue, dizziness or fainting, seizures, brittle nails, hair loss, hair loss, amenorrhea, constipation, loss of appetite, hair loss, dry skin, cardiac arrhythmia, osteoporosis, atherogenic lipid profile, cold intolerance, hypercortisolemia, low blood pressure, dehydration, nutrient deficiency (including anemia, electrolyte imbalances and deficiency diseases such as scurvy), hypothyroidism, osteoporosis, bone fracture, renal failure, edema, fatigue and lethargy, poor growth of children, and death. It's a very similar list! So what are the biological pathways that cause these side effects, whether because of actual starvation or nutritional starvation?
It is common for people who follow a long-term ketogenic diet to fail the challenge of oral glucose, and studies on animal ketogenic diets provide an explanation for this: insulin resistance induced by fatty acids. Proponents of ketogenic diets say it does not matter if you are insulin resistant if you do not eat carbohydrates. But this ignores the many physiological roles of insulin that go beyond glucose homeostasis. In fact, it is increasingly evident that very low carbohydrate diets, such as ketogenic diets, have negative effects on our health, often analogous to insulin resistance, brought about by the combination of insulin resistance induced by fatty acids and insufficient secretion of insulin. for normal signage. See also The case of more carbohydrates: The non-metabolic roles of insulin in the human body, 3 ways to regulate an insulin that has nothing to do with food and how many carbohydrates should we eat?
Insulin activates an essential enzyme (type 2 deiodinase) that converts thyroid prohormone T4 into active hormone T3. In a recent study of patients with pediatric epilepsy following a ketogenic diet for seizure control, participants exhibited an overall decrease in free T3 and a concomitant increase in TSH. A whopping 1/6 participants developed hypothyroidism requiring treatment with L-thyroxine during the first 6 months of the study! Of course, weight loss in general can reduce T3, but studies that have examined the effect of weight loss through caloric restriction on thyroid function have not shown an increased risk of hypothyroidism ( T3 and TSH remain within normal limits).
Insulin increases the transport rate of important amino acids in muscle tissue and increases muscle protein synthesis, while simultaneously reducing the breakdown of muscle proteins. While all fast weight loss diets cause lean body mass loss in addition to body fat, when a ketogenic diet was opposed to a non-ketogenic diet with calories and a protein intake , the loss of protein was less important, while the total weight loss was equivalent between the two groups. The authors identified greater protein synthesis in the non-ketogenic diet group as the mechanism to preserve proteins. Maintaining lean mass through weight loss is highly desirable and the body of evidence in favor of higher protein intake, associated with physical activity, is the best way to achieve this goal .
Insulin regulates bone remodeling by stimulating the activity of osteoblasts, the type of cell responsible for bone mineralization. A recent study on epileptic children showed a significant loss of bone mineral density (whole body and lumbar spine), two children having suffered a fracture during the period of the study. These results confirm a previous study in which the loss of bone mineral density was even higher, due to the fact that half of the children in this study had started with a lower than average bone mineral content. Only one study in adults measured bone mineral density and no significant decline was observed over 5 years. However, the effects of ketogenic diets on bone health are more readily observed in pediatric populations, as bone turnover and growth rates are higher in children. See also Paleo diet for skeletal health
Insulin acts in the hippocampus to promote learning and memory, and to promote synaptic plasticity. It also reduces the cellular activity of microglia (resident immune cells in the brain). In a study of cognitive performance in young, healthy men on a short-term ketogenic diet, participants showed reduced focal concentration, memory recovery speed, and speed of treatment. visual information significantly. In another study of overweight women with long-term ketogenic diets, participants scored significantly lower than a neuropsychological test requiring higher mental processing and flexibility (called a trail-building task). Rodent studies have also shown that ketogenic diets are detrimental to cognition, thereby impairing the learning of memory and visual space.
Insulin regulates sex hormone levels by removing globulin binding sex hormones and increasing the production of estrogen and testosterone. It also interacts with cortisol, growth hormone, glucagon and hormonal neurotransmitters such as dopamine, serotonin and melatonin. In male athletes, some studies have shown a decrease in testosterone, while others have increased. and in women with PCOS, ketogenic diets improved symptoms by decreasing testosterone. However, a significant percentage of young women on a long-term ketogenic epilepsy diet report amenorrhea (loss of menstruation). In addition, ketogenic diets suppress sex hormones in animal studies, including the metabolites of progesterone and testosterone. Whether ketogenic diets are beneficial or harmful to hormonal systems probably depends a lot on the situation. See also How chronic stress causes hormonal imbalance
Insulin regulates the development and activity of many immune cells, usually improving the effectiveness of the immune system while playing the role of essential immune regulator. This is why insulin resistance is associated with generalized inflammation; allergic, inflammatory and autoimmune diseases; and a reduced ability to fight the infection. A recent study showed an increase in C-reactive protein (a marker of blood-borne inflammation) during weight loss with a low carbohydrate diet, high in fat but not high. Another study in patients with rheumatoid arthritis has shown no benefit for the number of IL-6 cytokines nor for T cell number nor for activation with a ketogenic diet. And, in an animal study on malignant glioma, a ketogenic diet increased the number and activation of effector cells (especially Th1) while decreasing the regulatory cell population. Long-term studies of ketogenic diets in children and adolescents with epilepsy show a tendency to reduce white blood cell counts, while indicating increased susceptibility to serious infections, affecting 10 to 15% of participants at the study. See also the autoimmune protocol
Scientists have discovered other mechanisms explaining adverse reactions. For example, carriers of ApoE4 are genetically predisposed to higher elevation of cholesterol during a high fat diet due to greater intestinal resorption of cholesterol and lower blood cholesterol. a faster hepatic clearance of dietary fat than non-ApoE4 carriers. About 25% of the population owns at least one copy of ApoE4; this may explain the large variation in lipid profile changes among ketogenic diet studies. (The carriers of ApoE4 also present a higher risk of heart disease, Alzheimer's disease and severe malaria.) Interestingly, ApoE4 carriers do not see any improvement in symptoms. Alzeimer on a ketogenic diet.) A loss of bone mineral density can also be attributed to children on a ketogenic diet. to acidosis. The nutritional deficiency inherent in ketogenic diets explains many undesirable effects. for example, heart complications can be caused by a severe deficiency of selenium. See also the genes to know: ApoE
Finally, significant and problematic changes in the intestinal microbiome are observed after a ketogenic diet, probably due to a very inadequate intake of fiber and starch and a high intake of saturated fats. In particular, ketogenic diets cause: a decrease in microbial diversity (diversity in the most important aspect of a healthy intestinal microbiome); greatly reduced (by 3 to 16 times less) the levels of key probiotic bacteria (Bifidobacterium and Roseburia species, and Rectal Eubacterium) and increased growth of Escherichia coli as good as Desulfovibrio species, a bacterial genus known to exacerbate the inflammatory state of the intestinal mucosa. An adverse intestinal microbiome has been associated with conditions as diverse as cancer, obesity, and other metabolic problems, diabetes, heart disease, anxiety, depression, and other conditions. autism, autoimmunity, ulcers, IBD, liver disease, systemic infections, etc. See also How the ketogenic diet has devastating effects on your gut
Who should not do Keto:
Due to the ability of ketogenic diets to significantly worsen certain conditions, it is not recommended to:
- Women planning to become pregnant (with the possible exception of those with PCOS): ketogenic diets may cause amenorrhea and loss of fertility
- People with hypothyroidism: Ketogenic diets suppress thyroid function
- People with autoimmune diseases (with the possible exception of multiple sclerosis and other autoimmune diseases affecting the central nervous system): the immune system changes induced by ketogenic diets are in contrast to which is desirable for the management of autoimmune diseases
- Anyone with risk factors for kidney stones: note that potassium citrate supplementation prevents a proportion of kidney stones due to a ketogenic diet
- People without healthy livers: ketogenic diets exert additional stress on the liver and are known to increase markers of liver lesions
- People with one or two copies of the ApoE4 gene: you are much more likely to face a skyrocketing triglyceride and LDL cholesterol with a ketogenic diet, and also less likely to take advantage of it
- People with risk factors for cardiovascular diseaseIf you do not have the ApoE4 gene, discuss with your doctor the close monitoring of lipid profiles with a ketogenic diet, as triglycerides and LDL cholesterol can still skyrocket.
- People with osteopenia or osteoporosis: a ketogenic diet may increase bone mineral density loss
- People with choline deficiency: It increases the risk of non-alcoholic fatty liver condition as a result of a ketogenic diet
- People with selenium deficiency: It increases the risk of serious heart complications
- People with high cortisol levels, unmanaged stress, malfunction of HPA axis: ketogenic diets increase the secretion of cortisol, which can aggravate the symptoms of stress
- People with intestinal dysbiosis: Ketogenic diets can exacerbate an already unbalanced intestinal microbiome
- People who can not keep up with it: because following a long-term ketogenic diet causes insulin resistance, one of the worst things is the "almost keto."
And for all those who choose to follow a ketogenic diet for therapeutic purposes, close medical supervision is highly recommended!
Death due to ketogenic diets
Five scientific articles have reported deaths from long-term ketogenic diets. Two of these articles are case studies, and the other three are articles from two separate clinical trials, all of which focus on children and adolescents with epilepsy. Some of these deaths may be attributed to additional complications due to secondary conditions or accidents to the child during the clinical trial; However, other deaths – due to a serious infection or heart disease – can be directly attributed to long-term ketosis.
Warning: The following summaries of deaths attributable to ketogenic diets may disturb some readers.
Stewart WA, Gordon K., Camfield P. Acute pancreatitis causing death in a child with a ketogenic diet. J Neurol child. September 2001; 16 (9): 682.
In this case report, a 9-year-old girl who was on a ketogenic diet for Glut1 deficiency syndrome was presented to the emergency room in a coma with "a decrease in respiratory effort and shock, requiring a resuscitation". She went into cardiac arrest and died. The post mortem examination revealed hemorrhagic pancreatitis, which the author attributes to hypertriglyceridemia attributable to his ketogenic diet.
Kang HC, Chung DE, Kim DW, Kim HD. Early and late complications of the ketogenic diet for persistent epilepsy. L & # 39; epilepsy. September 2004; 45 (9): 1116-23.
This study followed 129 patients with epilepsy in children and adolescents on a ketogenic diet for 6 years on average. During the study, 4 patients died, three of infection and one of cardiomyopathy. However, the four patients had additional health problems. The patient died of cardiomyopathy had a deficiency of pyruvate dehydrogenase (PDHD); the patient who died from lipoid pneumonia had a history of prenatal hypoxic cerebral palsy; and the two patients who died from sepsis had meconium aspiration syndrome and anterior encephalitis.
Kang HC, Kim YJ, Kim DW, Kim HD. Efficacy and safety of the ketogenic diet for endurable epilepsy in children: Korean multicentric experience. L & # 39; epilepsy. February 2005; 46 (2): 272-9.
The dataset presented in this paper overlaps with the above study, including 199 children using ketogenic diets for the management of epilepsy for one year. Another child died, this time for unknown reasons. The authors recommended an autopsy but the parents refused.
IM Bank, Shemie SD, Rosenblatt B, Bernard C, Mackie AS. Sudden death of cardiac origin in association with the ketogenic diet. Pediatr Neurol. 2008 Dec; 39 (6): 429-31. doi: 10.1016 / j.pediatrneurol.2008.08.013.
This case study describes two boys who died after following a ketogenic diet for about three years. The first, aged 11, died of complications related to torsade de pointes (a dangerous tachyarrhythmia), with documented prolongation of QT. He had normal QT intervals before starting the ketogenic diet and no congenital heart defects. His first-degree relatives were examined and had normal electrocardiograms. The second, age 7, also had a normal electrocardiogram before starting a ketogenic diet, but follow-up revealed prolonged QT interval intervals and selenium deficiency. He received a supplement of selenium but died suddenly at home a month later.
Suo C, Liao J, Lu X, Fang K, Hu Y, L Chen, Cao D, Li Huang, Li B, Li C. Efficacy and safety of the ketogenic diet in Chinese children. Entering. 2013 April; 22 (3): 174-8
This study followed 317 children followed by a ketogenic diet for epilepsy for one year. During the study, 10 children died, although 3 of them withdrew from the study before their death and 1 died after a fall in height. Of the remaining children, 2 died of epileptic status, 2 of pneumonia and the cause of death was not revealed for the last 2 cases.
Are these deaths relevant to the average person seeking to improve their health with a ketogenic diet approach? Given that the overwhelming majority of long-term studies on the ketogenic diet have been conducted so far in the context of epilepsy, this is the area of research that has the most reported d & # 39; Adverse effects. Admittedly, these children belong to a more sensitive population, but that does not mean that these reports do not provide extremely useful information, nor a warning that deserves to be taken into account. After all, it is usually not the robust, healthy man who experiences ketogenic diets to improve his health. Although death is probably very unlikely, the possible damage to other systems of the body (cardiovascular, immune, endocrine, digestive) remain. Close medical supervision while following a ketogenic diet is clearly indicated.
Some scientific studies reporting adverse effects
The high frequency of adverse reactions is often overlooked in media reports and website articles, which focus on the effectiveness of the ketogenic diet (which this article does not dispute). To give you an idea of the frequency and severity of adverse effects of long-term ketogenic diets, as well as the relevance to the population, here is a sample of clinical trials reporting adverse effects. Note that the severity of adverse reaction reporting varies considerably from study to study.
Sirven, et al., 1999: "The ketogenic diet for intractable epilepsy in adults: preliminary results"
duration: 8 months and over
Population: 11 adults (9 females and 2 males) aged 19-45, treated with a 4: 1 fat / non-fat ketogenic diet; no change of medication during the plan
- 100% of participants had gastrointestinal problems such as constipation and bloating
- 100% of patients had menstrual irregularities (missed or irregular cycles)
- 73% said they were hungry
- 18% had an impaired concentration
- Effets lipidiques sanguins défavorables: les triglycérides et le cholestérol LDL ont tous deux augmenté chez presque tous les patients. Le rapport cholestérol / HDL est passé de 3,8 à 5,02 (plus athérogène).
- Un patient dont les crises répondaient mal au régime après cinq mois et un autre cinq mois après la fin du traitement avait eu un infarctus du myocarde (le rapport cholestérol / HDL avait augmenté chez ce patient).
Coppola, et al., 2002: «Le régime cétogène chez les enfants, les adolescents et les jeunes adultes atteints d'épilepsie réfractaire: une expérience italienne multicentrique»
Durée: 1 à 18 mois
Population: 56 jeunes patients âgés de 1 à 23 ans atteints d'épilepsie résistante aux médicaments; placé sur un régime cétogène 4: 1 avec des calories ajustées pour éviter la perte ou le gain de poids
Effets indésirables: Effets indésirables chez 57% des patients
- 18% avaient une constipation grave
- 16% avaient une irritabilité
- 16% avaient de la somnolence
- Hyperlipidémie chez 14% des patients
- 11% ont eu des épisodes de vomissements
- 7% ont eu des épisodes d'hypoglycémie
- 6% avaient des douleurs abdominales récurrentes
- 5% avaient une diarrhée épisodique aiguë
- 4% avaient une candidose orale
- 4% souffraient d'hyporexie
- 2% avaient une acidose sévère et une cétonémie
Kwiterovich, et al., 2003: «Effet d'un régime cétogène riche en graisse sur les taux plasmatiques de lipides, de lipoprotéines et d'apolipoprotéines chez les enfants»
Durée: 6 mois, étude de cohorte prospective
Population: 141 enfants et jeunes adultes de 4 mois à 20 ans soumis à un régime cétogène pour le contrôle des crises
- En moyenne, le cholestérol total, les LDL, les VLDL, les non-HDL, les triglycérides et l'apoB total ont tous augmenté de manière significative. Le cholestérol HDL moyen a diminué de manière significative.
- Après s'être mis au régime, seulement 1 sur 6 avait un taux de cholestérol ou de triglycérides compris dans l'intervalle acceptable pour son groupe d'âge
Mady et al., 2003: «Le régime cétogène: les adolescents peuvent aussi le faire»
Durée: 6 mois; durée moyenne de l'alimentation 1,2 ans
Population: 45 épileptiques âgés de 12 à 19 ans
- 45% des participantes ont signalé des problèmes menstruels
- 67% ont eu une aménorrhée
- 33% ont connu une puberté retardée
- 11% ont eu une ménorragie après l'arrêt du régime
- 89% des règles sont revenues à la normale après l'arrêt du régime
- 4% avaient une ecchymose ou un saignement accru
- 4% avaient signalé une perte de cheveux et / ou une perte de cheveux
Yancy, et al., 2004: «Un régime cétogène à faible teneur en glucides par rapport à un régime faible en gras pour traiter l'obésité et l'hyperlipidémie: un essai contrôlé randomisé»
Durée: 24 semaines
Population: 120 adultes hyperlipidémiques en surpoids suivis d'un régime cétogène ou pauvre en graisse et en cholestérol
- 2 personnes ont abandonné en raison d'un taux élevé de C-LDL (augmentation de 184 à 283 mg / dL à 3 mois et de 182 à 219 mg / dL à 1 mois)
- 30% avaient un taux de C-LDL élevé d'au moins 10%
- 68% avaient la constipation
- 60% ont eu des maux de tête
- 38% ont eu la mauvaise haleine
- 35% avaient des crampes musculaires
- 23% avaient la diarrhée
- 25% se sont plaints d'une faiblesse générale
Kang et al., 2004: «Complications précoces et tardives du régime cétogène pour épilepsie persistante»
Durée: Au moins 1 an; Moyenne sur 6 ans
Population: 129 patients au centre d'épilepsie (nourrissons, enfants et adolescents); régime cétogène supplémenté en multivitamines, calcium (30 mg par kg de poids corporel par jour), vitamine D (40 UI par kg de poids corporel par jour), L-Carnitine (66 mg par kg de poids corporel par jour)
Effets indésirables à long terme (au-delà de 4 semaines): 17% des patients ont arrêté leur régime en raison de complications graves
- 28% avaient un malaise gastro-intestinal tardif
- 20% avaient une hypertriglycéridémie
- 19% d'hypercholestérolémie
- 15% souffraient d'ostéopénie
- 11% avaient une hypomagnésémie
- 8% avaient une hyperuricémie
- 5% avaient l'hépatite
- 5% avaient une pneumonie par aspiration lipoïde
- 4% avaient une hypoprotéinémie
- 3% avaient des calculs rénaux
- Une hypocarnitinémie secondaire, une anémie ferriprive, de faibles concentrations de HDL, une hypoglycémie symptomatique et une cardiomyopathie ont également été rapportés.
- 1 patient a interrompu son régime en raison d'une hypertriglycéridémie persistante et incontrôlable supérieure à 1 000 mg / dL; 12 patients ont persisté malgré des triglycérides supérieurs à 500 mg / dL
- 4 patients sont décédés
Johnston, et al., 2006: «Les régimes cétogènes à faible teneur en glucides ne présentent aucun avantage métabolique par rapport aux régimes non cétogènes à faible teneur en glucides»
Durée: 6 weeks
Population: 20 adultes assignés soit à un régime cétogène (5% de glucides), soit à un régime non cétogène; Prises 24 heures strictement contrôlées
- Le risque inflammatoire (rapport entre l'acide arachidonique et l'acide eicosapentaénoïque dans les phospholipides plasmatiques) est plus affecté par le régime cétogène que par le régime non cétogène
- Le cholestérol HDL a chuté de 9% en moyenne
- «Perceptions de vigueur» plus faibles avec un régime cétogène
- Un participant au régime cétogène a développé des arythmies cardiaques au cours de la première semaine de régime et a abandonné
- 9% de la variation du cholestérol LDL étaient directement liés aux concentrations de cétone dans le sang et plusieurs participants suivant le régime cétogène ont présenté une augmentation marquée du cholestérol LDL
Sampath et al., 2007: «Calculs rénaux et régime cétogène: facteurs de risque et prévention»
Durée: Étude de cohorte rétrospective de tous les enfants en clinique de 2000 à 2005; plusieurs années + pour chaque enfant
Population: 197 enfants
- 7% ont développé des calculs rénaux après une médiane de 7 mois
- La thérapie au citrate de potassium était préventive: 3,2% des enfants qui en prenaient avaient des calculs rénaux contre 10% de ceux qui n'en avaient pas.
- Global: La prévalence de calculs rénaux varie de 3 à 10% des personnes à la diète cétogènes, contre 1 sur plusieurs milliers dans la population en général
Mosek et al., 2009: «Traitement par le régime cétogène chez l'adulte atteint d'épilepsie réfractaire: une étude pilote prospective»
Durée: Suivi de 1 à 12 semaines; seuls deux patients ont terminé toutes les 12 semaines
Population: 9 patients adultes inscrits (âgés de 18 à 45 ans) soumis à un régime cétogène à 90% de matières grasses
- 78% ont abandonné leurs études en raison de sentiments de faim, de manque d'efficacité ou de diarrhée
- Changements lipidiques sanguins:
- Augmentation de 26% du cholestérol total après 4 à 7 semaines et de 33% après 11 à 12 semaines (trois personnes)
- LDL a augmenté de 32% et 54% dans ces mêmes délais, sans changement de HDL
- Les triglycérides d’un patient ont atteint 834 mg / dL et il a par la suite mis fin au régime
Goday A, et al., 2016. “Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.”
Duration: 4 months
Population: 45 adults assigned to low-calorie ketogenic diet (c.f. 44 participants assigned to standard low calorie diet)
- 18% had constipation
- 13% had orthostatic hypotension
- 7% had nausea
- 4% had headaches
- 4% had hair loss
- Other reported reactions were asthenia, vomiting, myalgia and edema
Lin A, et al., 2017: “Complications During Ketogenic Diet Initiation: Prevalence, Treatment, and Influence on Seizure Outcomes.”
Duration: 3 months
Population: 158 children, mean age 4.6 years
- 80% reported adverse effects of any kind
- 42% reported gastrointestinal upset
- 28% experienced hypoglycemia to levels <40 mg/dL
- 16% had documented repeated hypoglycemia to <40 mg/dL
- 10% had hypoglycemia to <30 mg/dL
- Other reported reactions included constipation, acidosis, sinusitis, fussiness or mood change, and over-ketosis
Urbain P, et al., 2017: “Impact of a 6-week non-energy-restricted ketogenic diet on physical fitness, body composition and biochemical parameters in healthy adults.”
Duration: 6 weeks
Population: 42 healthy adults
- Total cholesterol increased by 4.7%
- LDL cholesterol increased by 10.7%
- Two participants were unable to continue the diet due to persistent side effects (gastrointestinal complaints and headache)
Di Lorenzo C, et al., 2018: “Efficacy of Modified Atkins Ketogenic Diet in Chronic Cluster Headache: An Open-Label, Single-Arm, Clinical Trial.”
Duration: 12 weeks
Population: 18 drug-resistant chronic cluster headache patients, age 25 to 55
- 6% reported hair loss
- 6% reported abdominal bloating
Baby N, et al., 2018: “A pragmatic study on efficacy, tolerability and long term acceptance of ketogenic diet therapy in 74 South Indian children with pharmacoresistant epilepsy.”
Duration: Median of 10.43 months
Population: 74 children with epilepsy, aged 0-18 years
- 5% had to discontinue the diet due to major adverse events
- 3% had severe diarrhea
- 3% had lipoid pneumonia, resulting in prolonged ICU care and discontinuation of the diet
- 4% had hypoglycemia
- Other reported adverse reactions included persistent hyperammonemia, diarrhea and vomiting, renal calculi, constipation, and aspiration pneumonia
No, the Inuit Are Not Ketogenic Hunter-Gatherers
This seems like a good opportunity to clear up a common myth about the Inuit: no, they are no hunter-gatherer cultures that live in sustained ketosis due to their very low carbohydrate intake, and no, they do not provide evidence that long-term ketosis is safe for humans.
The Inuit have a gene mutation that prevents them from entering ketosis (instead, they’re able to burn long-chain fatty acids for energy, which may help increase their body temperature in their notoriously cold climate). The mutation occurs on the CPT1A gene (it’s the P479L variant), which encodes a major rate-limiting enzyme for long-chain fatty acid oxidation. Interestingly, this mutation evolved in multiple unrelated populations, the common denominator being cold climate and low access to carbohydrate, implying that it is advantageous to survival. The vast majority of the Inuit population carry the CPT1A, P479L variant: approximately 70% of Inuit are homozygous for the gene variant, 24% are heterozygous, and only about 6% do not carry the gene.
The CPT1A, P479L variant makes it so that any situation that would require relying on ketones (such as fasting) becomes virtually lethal to the Inuit. Because the mutation is linked to failure to generate ketones in infancy, it may be responsible for the statistically higher rate of infant mortality in Inuit population. It also solves the previous mysteries as to why no elevated ketone levels have been found among the Inuit, and why they have normal glucose tolerance on their traditional diet (something not seen during ketosis, due to the physiological insulin resistance that occurs).
What’s more, even if the Inuit didn’t possess their unique gene mutation, their diet still wouldn’t be ketogenic due to its super high protein content (averaging 280 grams per day), since protein can be converted to glucose through the process of gluconeogenesis (and thus curtail ketosis) and due to some unique sources of dietary carbohydrates (up to 20% of total calories) like the glycogen in whale blubber. In reality, we have no evidence of any hunter-gatherer society surviving on a ketogenic diet—even among the handful living in environments where it would theoretically be possible!
The Inuit (on their traditional diet) definitely had a huge intake of high-fat animal foods, but they also went to great lengths to gather amazingly nutrient-dense plants whenever they were available (as well as preserve them for year-round use). Those included kelp, algae, and other seaweeds (which are super high in chlorophyll), plankton from whales’ stomachs, fireweed, sorrel grass, flower blossoms preserved in seal oil, mosses, a variety of berries, ground nuts, lichens, willow leaves, sourdock, scurvygrass, roseroot, numerous other weeds and greens, tubers, starchy corms (which the Inuit collected from caches made by tundra mice and voles), and the partially digested stomach contents of caribou and other land animals (considered a delicacy, and usually consisting of a variety of lichens, blueberry leaves and shoots, horsetails, grasses, birch, willow, and other plants the animals had grazed on).
That said, while there aren’t any true ketogenic hunter-gatherer societies, there certainly are plenty of hunter-gatherers who consume fewer carbohydrates (and more fat) than recommended by the USDA and other official health organizations—and who remain enviably free from obesity and chronic disease. The Nukak, Onge, Anbarra, Ache, Hiwi, Arnhem, and !Kung tribes are all examples of such hunter-gatherer groups thriving on a higher fat intake without suffering our modern plague of diseases.
Although long-term ketogenic diets don’t have any historical precedent (at least among entire populations), there are certainly examples of a higher fat intake (compared to what’s considered normal in industrialized nations) sustaining indigenous groups and protecting against disease. In other words, consuming a higher-fat diet of high quality, nutrient-dense foods can definitely be compatible with human health!
Cost Benefit Analysis
When you read reports expounding on the benefits of a ketogenic diet, purporting that there is no risk involved or at least no risk for most of us, the origin of this dogma is either a selective reading of the science or a bias-motivated dismissal of any scientific studies to the contrary of this narrative. For example, you may see adverse reactions described as “minor” and “transient” or attributable in some way to “people doing keto wrong”, statements that are not actually substantiated by the scientific literature (although, those might be fair appraisals of side effects reported in short-term studies).
The ketogenic diet is different from other diets because it’s designed to emulate starvation, taking advantage of the biochemical benefits of starvation for certain body systems (mainly neurological, but this is also why weight loss is a common result of a ketogenic diet) while tolerating the detriments to other body systems (such as endocrine and immune systems). In this regard, the ketogenic diet more closely resembles a drug than a diet (in fact, many of the same pathways activated by a ketogenic diet are manipulated by anticonvulsant drugs), which should not be a deterrent in itself, but rather a caution to read the fine print and talk to your doctor before embarking on this course—especially if going “off-label” and using a ketogenic diet for purposes that have not yet been well studied.
Certainly some of the adverse reactions can be prevented with careful choice of foods and/or targeted supplementation. It’s also important to emphasize that the documented adverse events point to a long list of tests that should be performed regularly by a supervising health professional to monitor for any potential detriment in the event that there are compelling reasons to undertake a ketogenic diet.
It is important to be fully aware of the potential for adverse reactions when weighing a ketogenic diet versus other diets or therapeutic options. See also Modifying Paleo to Meet Your Goals
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