Difference between revisions of "Health Risks of the Ketogenic Diet"

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They are many potential benefits to the ketogenic diet, but there are also a number of potentially serious health risks. It appears that most of these health risks can be mitigated with care.
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They are [[Ketogenic Diet as a Treatment| many potential benefits to the ketogenic diet]], but there are also a number of potentially serious health risks. It appears that most of these health risks can be mitigated with care.
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{{Skeleton}}
 
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=Perspective=
 
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All diets have risk;
 
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=Context=
 
=Context=
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My of the data on KD risks come from KD epilepsy, obesity, starvation.
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The list of health risks for the [[Ketogenic Diet]] can be rather intimidating. It's worth remembering that all diets have risks associated with them, and many of these risks are severe. In some ways the health risks of the ketogenic diet are better understood than most diets because the ketogenic diet is typically given under medical supervision, and adverse effects are well documented. It should also be noted that the patients that have been studied on the ketogenic diet are often children with severe epilepsy or adults with morbid obesity. In fact, an important source of information on the ketogenic diet comes from obese subjects undergoing complete fasts. This may increase the relative risk of the ketogenic diet.
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=Health Risks=
 
=Health Risks=
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==Death==
 
==Death==
 
There have been two reported cases of sudden death of children on the Ketogenic Diet, probably due to selenium deficiency causing heart failure<ref name="BankShemie2008"/>. Selenium deficiency can occur rapidly; one child was diagnosed with selenium deficiency and related heart problems before their scheduled 3 month selenium test<ref name="Sirikonda-2012"/>. In addition, a study of 20 children on the Ketogenic Diet found heart rhythm abnormalities and heart enlargement in 3 (15%, diet duration 13 ± 8.4 months), and one had severe dilated cardiomyopathy<ref name="Best-2000"/>. The effected children has normal selenium levels, but there was a significant correlation was found between the heart rhythm abnormality (QTc) and both bicarbonate and blood ketones, suggesting the level of acidosis or ketosis may be important factors.  
 
There have been two reported cases of sudden death of children on the Ketogenic Diet, probably due to selenium deficiency causing heart failure<ref name="BankShemie2008"/>. Selenium deficiency can occur rapidly; one child was diagnosed with selenium deficiency and related heart problems before their scheduled 3 month selenium test<ref name="Sirikonda-2012"/>. In addition, a study of 20 children on the Ketogenic Diet found heart rhythm abnormalities and heart enlargement in 3 (15%, diet duration 13 ± 8.4 months), and one had severe dilated cardiomyopathy<ref name="Best-2000"/>. The effected children has normal selenium levels, but there was a significant correlation was found between the heart rhythm abnormality (QTc) and both bicarbonate and blood ketones, suggesting the level of acidosis or ketosis may be important factors.  
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==Sodium Loss and Hypotension==
 
==Sodium Loss and Hypotension==
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Low carbohydrate diets cause of the kidneys to excrete more sodium. This is known as "natriuresis of starvation", and may be due to low insulin<ref name="Stenvinkel-1995"/>, increased dopamine excretion<ref name="Swaminathan-1983"/>, or elevated Glucagon<ref name="SaudekBoulter1973"/>. If carbohydrate and sodium intakes are both limited, then the body will secrete the hormone aldosterone<ref name="Phinney-2011-p312"/> which will cause the kidneys to excrete potassium and conserve sodium<ref name="Lote2012"/>. This loss of potassium can cause muscle cramps and heart arrhythmias, as well has the loss of muscle tissue.
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Low carbohydrate diets cause of the kidneys to excrete more sodium. This is known as "natriuresis of starvation", and may be due to low insulin<ref name="Stenvinkel-1995"/>, increased dopamine excretion<ref name="Swaminathan-1983"/>, or elevated Glucagon<ref name="SaudekBoulter1973"/>. If carbohydrate and sodium intakes are both limited, then the body will secrete the hormone aldosterone<ref name="Phinney-2011-p312"/> which will cause the kidneys to excrete potassium and conserve sodium<ref name="Lote2012"/>. This loss of potassium can cause [[Cramps| Muscle Cramps]] and heart arrhythmias, as well has the loss of [[Muscle| Muscle Tissue]].
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==Vitamin or mineral deficiency==
 
==Vitamin or mineral deficiency==
 
The ketogenic diet is frequently deficient in vitamins and minerals, so supplementation is required with a carbohydrate free multivitamin/mineral<ref name="Kossoff-2011-p137"/>.  
 
The ketogenic diet is frequently deficient in vitamins and minerals, so supplementation is required with a carbohydrate free multivitamin/mineral<ref name="Kossoff-2011-p137"/>.  
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* Carnitine may also be required, depending on the results of testing.  
 
* Carnitine may also be required, depending on the results of testing.  
 
* There are case reports of scurvy with the ketogenic diet<ref name="Willmott-2008"/>, so additional supplementation with Vitamin C may be appropriate.
 
* There are case reports of scurvy with the ketogenic diet<ref name="Willmott-2008"/>, so additional supplementation with Vitamin C may be appropriate.
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==Constipation==
 
==Constipation==
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Constipation is a common issue as the ketogenic diet is generally low in fiber. Even with supplementary fiber, constipation can still be a problem. This may be partly due to changes in the intestinal flora that occur with the ketogenic diet. There are also indications that some non-fiber carbohydrate parses far enough through the digestive tract to supply fuel to bacteria for fermentation.
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Constipation is a common issue as the ketogenic diet is generally low in fiber. Even with supplementary fiber, constipation can still be a problem. This may be partly due to changes in the intestinal flora that occur with the ketogenic diet. There are also indications that some non-fiber carbohydrate passes far enough through the digestive tract to supply fuel to bacteria for fermentation<ref name="Bergman-1990"/>.
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==Kidney Stones==
 
==Kidney Stones==
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5% of the children on the ketogenic diet for epilepsy suffer from kidney stones<ref name="Sampath-2007"/>. A study showed that oral potassium citrate significantly decreased the occurrence of kidney stones<ref name="McNally-2009"/>. It has been shown that while [http://en.wikipedia.org/wiki/Carbonic_anhydrase_inhibitor carbonic anhydrase inhibitors] are also a risk factor for kidney stones, carbonic anhydrase inhibitors while on the ketogenic diet does not further increase the risk<ref name="Kossoff-2002"/>. (Carbonic anhydrase inhibitors are a type of antiepileptic drug.) Maintaining a good level of hydration is important, and Oral citrates may be appropriate. The urine should be [[Health Checks for the Ketogenic Diet| tested for blood]] at least once a week<ref name="Kossoff-2011-p109"/>.  
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About 5% of the children on the ketogenic diet for epilepsy suffer from kidney stones<ref name="Sampath-2007"/>. A study showed that oral potassium citrate significantly decreased the occurrence of kidney stones<ref name="McNally-2009"/>. It has been shown that while [http://en.wikipedia.org/wiki/Carbonic_anhydrase_inhibitor carbonic anhydrase inhibitors] are also a risk factor for kidney stones, carbonic anhydrase inhibitors while on the ketogenic diet does not further increase the risk<ref name="Kossoff-2002"/>. (Carbonic anhydrase inhibitors are a type of antiepileptic drug.) Maintaining a good level of hydration is important, and Oral citrates may be appropriate. The urine should be [[Health Checks for the Ketogenic Diet| tested for blood]] at least once a week<ref name="Kossoff-2011-p109"/>.  
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==Hypoglycemia==
 
==Hypoglycemia==
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Hypoglycemia (low blood sugar) seems to predominantly a risk if the ketogenic diet is started with a fast, and blood sugar levels should be checked every 6–8 hours during the first few days of the diet. Generally the ketogenic diet helps stabilize, and normalize blood sugar.
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Hypoglycemia (low blood sugar) seems to predominantly a risk if the ketogenic diet is started with a fast, and blood sugar levels should be checked every 6–8 hours during the first few days of the diet<ref name="Kossoff-2011-2452"/>. Generally the ketogenic diet helps stabilize, and normalize blood sugar.
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==Acidosis==
 
==Acidosis==
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Uncontrolled diabetic patients can suffer from diabetic ketoacidosis, a life-threatening condition where very high levels of ketones are produced. In diabetic ketoacidosis not only are their high levels of ketones, but also their blood glucose is high, and there is often potassium depletion and dehydration (citation required.) Acidosis is not a common problem on the ketogenic diet, but it can occur and symptoms are lethargy, nausea, vomiting, and headache<ref name="Kossoff-2011-p318"/>.   
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Uncontrolled diabetic patients can suffer from diabetic ketoacidosis, a life-threatening condition where very high levels of ketones are produced. In diabetic ketoacidosis not only are their high levels of ketones, but also their blood glucose is high, and there is often [[Potassium]] depletion and dehydration<ref name="SolerDixon1972"/>. Acidosis is not a common problem on the ketogenic diet, but it can occur and symptoms are lethargy, [[Nausea]], vomiting, and headache<ref name="Kossoff-2011-p318"/>.   
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==Hyperketosis==
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Excessively high ketone levels can produce symptoms such as rapid panting, irritability, high heart rate, facial flushing, fatigue lethargy, and vomiting<ref name="Kossoff-2011-2680"/>. Taking a couple of tablespoons of orange juice should resolve this, but if a second dose 20 minutes later does not help, seek prompt medical help<ref name="Kossoff-2011-2680"/>.
 
==Elevated cholesterol and blood lipid changes==
 
==Elevated cholesterol and blood lipid changes==
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About 30% of children on the ketogenic diet experience elevated cholesterol levels, but this is normally transient, and the levels return to baseline after 6-12 months<ref name="Kossoff-2011-2512"/>. Broader anecdotal evidence suggests that some people's cholesterol improves, while others cholesterol levels degrade. The health implications of cholesterol while on a [[Ketogenic Diet]] are unclear. If cholesterol levels are a concern, then the [[Ketogenic Ratio]] could be reduced, the percentage of unsaturated fats increased, [[MCT]] can be added, or carnitine can be supplemented<ref name="Kossoff-2011-2522"/>.
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About 30% of children on the ketogenic diet experience elevated cholesterol levels, but this is normally transient, and the levels return to baseline after 6-12 months<ref name="Kossoff-2011-2512"/>. Children on the diet for longer than 6 years mostly have normal levels<ref name="Kossoff-2011-2519"/>. Broader anecdotal evidence suggests that some people's cholesterol improves, while others cholesterol levels degrade. The health implications of cholesterol while on a [[Ketogenic Diet]] are unclear. If cholesterol levels are a concern, then the [[Ketogenic Ratio]] could be reduced, the percentage of unsaturated fats increased, [[MCT]] can be added, or Carnitine can be supplemented<ref name="Kossoff-2011-2522"/>.
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==Bone fractures==
 
==Bone fractures==
 
Children on the ketogenic diet suffer a higher rate of bone fractures, with 20% of children on the diet for 6+ years having fractures<ref name="Kossoff-2011-p271"/>. Children on the ketogenic diet have poorer bone health, lower vitamin D levels, lower intakes of calcium and vitamin D, and lower Bone Mineral Content<ref name="BergqvistSchall2008"/>. However, epilepsy medications are associated with bone loss and calcium metabolism<ref name="Kossoff-2011-p174"/>, so this may also be a contributory factor.  
 
Children on the ketogenic diet suffer a higher rate of bone fractures, with 20% of children on the diet for 6+ years having fractures<ref name="Kossoff-2011-p271"/>. Children on the ketogenic diet have poorer bone health, lower vitamin D levels, lower intakes of calcium and vitamin D, and lower Bone Mineral Content<ref name="BergqvistSchall2008"/>. However, epilepsy medications are associated with bone loss and calcium metabolism<ref name="Kossoff-2011-p174"/>, so this may also be a contributory factor.  
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==Growth reduction==
 
==Growth reduction==
 
Children treated with the ketogenic diet can have growth reduction<ref name="Kossoff-2011-2533"/>. However, early uses of the ketogenic diet for epilepsy included calorie restriction below the recommended level for the child, as partial starvation was believed to be important for reducing seizures.
 
Children treated with the ketogenic diet can have growth reduction<ref name="Kossoff-2011-2533"/>. However, early uses of the ketogenic diet for epilepsy included calorie restriction below the recommended level for the child, as partial starvation was believed to be important for reducing seizures.
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==Fatty Liver==
 
==Fatty Liver==
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There are case reports of children on the [[MCT Diet]] having fatty infiltration of the liver. It's unclear how common this problem is. ("Fatty liver and medium chain triglyceride (MCT) diet.pdf").
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There are case reports of children on the [[MCT Diet]] having fatty infiltration of the liver<ref name="Beverley-1988"/>. However, a study in rats suggests that MCTs may be a treatment for both non-alcoholic fatty liver disease<ref name="Ronis-2013"/> and alcoholic fatty liver<ref name="Theuer-1972"/>.
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==Fat Intake Imbalance==
 
==Fat Intake Imbalance==
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When increasing the geometry fat intake, it is easy to get too much Omega-6. They are anecdotal reports that excessive Omega-6 can cause digestive problems, as well as longer-term health issues. The general recommendation is to avoid too much Omega-6, and aim for saturated or monounsaturated fats.
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With increasing fat intake it is easy to get too much Omega-6. They are anecdotal reports that excessive Omega-6 can cause digestive problems, as well as longer-term health issues. The general recommendation is to avoid too much Omega-6, and aim for saturated or monounsaturated fats, plus some Omega-3.
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==Insulin Resistance ==
 
==Insulin Resistance ==
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While the Ketogenic Diet can be beneficial for those suffering from insulin resistance or diabetes<ref name="Veech-2004"/>, there are also concerns that the Ketogenic Diet may also result in some insulin resistance<ref name="Jornayvaz2011"/>. This would not be expected to be an issue while on a Ketogenic Diet, but it may mean that care should be taken when exiting the Ketogenic Diet.  
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While the Ketogenic Diet can be beneficial for those suffering from [[Insulin Resistance]] or diabetes<ref name="Veech-2004"/>, there are also concerns that the Ketogenic Diet may also result in some insulin resistance<ref name="Jornayvaz2011"/><ref name="Robinson-1980"/>. There is conflicting evidence for the insulin resistance coming from a low carbohydrate<ref name="KanekoWang1998"/> or a high fat intake<ref name="Anderson-1975"/>. This would not be expected to be an issue while on a Ketogenic Diet, but it may mean that care should be taken when exiting the Ketogenic Diet. The Ketogenic Diet may also exacerbate reactive hypoglycemia<ref name="Anderson-1975"/>.
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==Thirst and Hydration==
 
==Thirst and Hydration==
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Ketones may reduce thirst<ref name="Kossoff-2011-2218"/>.
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Ketones may reduce thirst<ref name="Kossoff-2011-2218"/>, which could impair hydration, but the details are unclear.
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==Thyroid ==
 
==Thyroid ==
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Investigate further.  
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The ketogenic diet has been shown to reduce the levels of the thyroid hormone [http://en.wikipedia.org/wiki/Triiodothyronine T3]<ref name="Phinney-1983"/><ref name="Phinney-1980"/><ref name="Fery-1982"/><ref name="Pasquali-1982"/>, and there is some evidence that T3 production is proportional to carbohydrate intake<ref name="Serog-1982"/>. It has been suggested that the ketogenic diet may not be suitable for those with thyroid deficiencies<ref name="Hite-2011"/>.
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==Gout==
 
==Gout==
 
The ketogenic diet can produce an initial rise in the level of uric acid in the blood and the level of uric acid returns to baseline after 4-6 weeks, but some individuals can develop gout<ref name="Phinney-2011-p343"/>.
 
The ketogenic diet can produce an initial rise in the level of uric acid in the blood and the level of uric acid returns to baseline after 4-6 weeks, but some individuals can develop gout<ref name="Phinney-2011-p343"/>.
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==Wound Healing==
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I've found no studies concerning the effect of the ketogenic diet on wound healing. My personal experience is that wounds heal at a similar rate to a high carbohydrate diet. However, I've experienced far more problems on the Ketogenic Diet with my skin condition, [[Epidermolysis Bullosa]], including more dystrophic scaring.
 
=Contraindications=
 
=Contraindications=
 
There are a number of contraindications for the ketogenic diet, including [http://en.wikipedia.org/wiki/Fatty-acid_metabolism_disorder genetic deficiencies in fat metabolism]<ref name="Kossoff-2011-1864"/>. A discussion of these contraindications is outside of the scope of this article.
 
There are a number of contraindications for the ketogenic diet, including [http://en.wikipedia.org/wiki/Fatty-acid_metabolism_disorder genetic deficiencies in fat metabolism]<ref name="Kossoff-2011-1864"/>. A discussion of these contraindications is outside of the scope of this article.
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=See Also=
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{{KetoList}}
 
=References=
 
=References=
 
<references>
 
<references>
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<ref name="SaudekBoulter1973">C. D. Saudek, P. R. Boulter, R. A. Arky, The Natriuretic Effect of Glucagon and Its Role in Starvation, Journal of Clinical Endocrinology & Metabolism, volume 36, issue 4, 1973, pages 761–765, ISSN [http://www.worldcat.org/issn/0021-972X 0021-972X], doi [http://dx.doi.org/10.1210/jcem-36-4-761 10.1210/jcem-36-4-761]</ref>
 
<ref name="SaudekBoulter1973">C. D. Saudek, P. R. Boulter, R. A. Arky, The Natriuretic Effect of Glucagon and Its Role in Starvation, Journal of Clinical Endocrinology & Metabolism, volume 36, issue 4, 1973, pages 761–765, ISSN [http://www.worldcat.org/issn/0021-972X 0021-972X], doi [http://dx.doi.org/10.1210/jcem-36-4-761 10.1210/jcem-36-4-761]</ref>
 
<ref name="Stenvinkel-1995">P. Stenvinkel, A. Ottosson-Seeberger, A. Alvestrand, J. Bolinder, Effect of insulin on renal sodium handling and renal haemodynamics in insulin-dependent (type 1) diabetes mellitus patients., Acta Diabetol, volume 32, issue 4, pages 230-4, Dec 1995, PMID [http://www.ncbi.nlm.nih.gov/pubmed/8750761 8750761]</ref>
 
<ref name="Stenvinkel-1995">P. Stenvinkel, A. Ottosson-Seeberger, A. Alvestrand, J. Bolinder, Effect of insulin on renal sodium handling and renal haemodynamics in insulin-dependent (type 1) diabetes mellitus patients., Acta Diabetol, volume 32, issue 4, pages 230-4, Dec 1995, PMID [http://www.ncbi.nlm.nih.gov/pubmed/8750761 8750761]</ref>
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<ref name="Lote2012">Christopher J. Lote [http://www.amazon.com/Principles-Renal-Physiology-Christopher-Lote/dp/0792360745 http://www.amazon.com/Principles-Renal-Physiology-Christopher-Lote/dp/0792360745] Principles of Renal Physiology], 22 June 2012, Springer, ISBN 978-1-4614-3785-7</ref>
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<ref name="Lote2012">Christopher J. Lote [http://www.amazon.com/Principles-Renal-Physiology-Christopher-Lote/dp/0792360745 http://www.amazon.com/Principles-Renal-Physiology-Christopher-Lote/dp/0792360745] Principles of Renal Physiology, 22 June 2012, Springer, ISBN 978-1-4614-3785-7</ref>
 
<ref name="Willmott-2008"> NS. Willmott, RA. Bryan, Case report: scurvy in an epileptic child on a ketogenic diet with oral complications., Eur Arch Paediatr Dent, volume 9, issue 3, pages 148-52, Sep 2008, PMID [http://www.ncbi.nlm.nih.gov/pubmed/18793598 18793598]</ref>
 
<ref name="Willmott-2008"> NS. Willmott, RA. Bryan, Case report: scurvy in an epileptic child on a ketogenic diet with oral complications., Eur Arch Paediatr Dent, volume 9, issue 3, pages 148-52, Sep 2008, PMID [http://www.ncbi.nlm.nih.gov/pubmed/18793598 18793598]</ref>
 
<ref name="Sampath-2007"> A. Sampath, EH. Kossoff, SL. Furth, PL. Pyzik, EP. Vining, Kidney stones and the ketogenic diet: risk factors and prevention., J Child Neurol, volume 22, issue 4, pages 375-8, Apr 2007, doi [http://dx.doi.org/10.1177/0883073807301926 10.1177/0883073807301926], PMID [http://www.ncbi.nlm.nih.gov/pubmed/17621514 17621514]</ref>
 
<ref name="Sampath-2007"> A. Sampath, EH. Kossoff, SL. Furth, PL. Pyzik, EP. Vining, Kidney stones and the ketogenic diet: risk factors and prevention., J Child Neurol, volume 22, issue 4, pages 375-8, Apr 2007, doi [http://dx.doi.org/10.1177/0883073807301926 10.1177/0883073807301926], PMID [http://www.ncbi.nlm.nih.gov/pubmed/17621514 17621514]</ref>
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<ref name="Sirikonda-2012"> NS. Sirikonda, WD. Patten, JR. Phillips, CJ. Mullett, Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation., Pediatr Cardiol, volume 33, issue 5, pages 834-8, Jun 2012, doi [http://dx.doi.org/10.1007/s00246-012-0219-6 10.1007/s00246-012-0219-6], PMID [http://www.ncbi.nlm.nih.gov/pubmed/22367552 22367552]</ref>
 
<ref name="Sirikonda-2012"> NS. Sirikonda, WD. Patten, JR. Phillips, CJ. Mullett, Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation., Pediatr Cardiol, volume 33, issue 5, pages 834-8, Jun 2012, doi [http://dx.doi.org/10.1007/s00246-012-0219-6 10.1007/s00246-012-0219-6], PMID [http://www.ncbi.nlm.nih.gov/pubmed/22367552 22367552]</ref>
 
<ref name="BergqvistSchall2008">A. C. Bergqvist, J. I Schall, V. A Stallings, B. S Zemel, Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet, American Journal of Clinical Nutrition, volume 88, issue 6, 2008, pages 1678–1684, ISSN [http://www.worldcat.org/issn/0002-9165 0002-9165], doi [http://dx.doi.org/10.3945/ajcn.2008.26099 10.3945/ajcn.2008.26099]</ref>
 
<ref name="BergqvistSchall2008">A. C. Bergqvist, J. I Schall, V. A Stallings, B. S Zemel, Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet, American Journal of Clinical Nutrition, volume 88, issue 6, 2008, pages 1678–1684, ISSN [http://www.worldcat.org/issn/0002-9165 0002-9165], doi [http://dx.doi.org/10.3945/ajcn.2008.26099 10.3945/ajcn.2008.26099]</ref>
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<ref name="Robinson-1980"> AM. Robinson, DH. Williamson, Physiological roles of ketone bodies as substrates and signals in mammalian tissues., Physiol Rev, volume 60, issue 1, pages 143-87, Jan 1980, PMID [http://www.ncbi.nlm.nih.gov/pubmed/6986618 6986618]</ref>
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<ref name="SolerDixon1972">N.G. Soler, K. Dixon, M.A. Bennett, M.G. Fitzgerald, J.M. Malins, POTASSIUM BALANCE DURING TREATMENT OF DIABETIC KETOACIDOSIS WITH SPECIAL REFERENCE TO THE USE OF BICARBONATE, The Lancet, volume 300, issue 7779, 1972, pages 665–667, ISSN [http://www.worldcat.org/issn/01406736 01406736], doi [http://dx.doi.org/10.1016/S0140-6736(72)92083-1 10.1016/S0140-6736(72)92083-1]</ref>
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<ref name="Beverley-1988">D. Beverley, R. Arthur, Fatty liver and medium chain triglyceride (MCT) diet., Arch Dis Child, volume 63, issue 7, pages 840-2, Jul 1988, PMID [http://www.ncbi.nlm.nih.gov/pubmed/3137894 3137894]</ref>
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<ref name="Theuer-1972"> RC. Theuer, WH. Martin, TJ. Friday, BL. Zoumas, HP. Sarett, Regression of alcoholic fatty liver in the rat by medium-chain triglycerides., Am J Clin Nutr, volume 25, issue 2, pages 175-81, Feb 1972, PMID [http://www.ncbi.nlm.nih.gov/pubmed/5009783 5009783]</ref>
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<ref name="Ronis-2013"> MJ. Ronis, JN. Baumgardner, N. Sharma, J. Vantrease, M. Ferguson, Y. Tong, X. Wu, MA. Cleves, TM. Badger, Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease., Exp Biol Med (Maywood), volume 238, issue 2, pages 151-62, Feb 2013, doi [http://dx.doi.org/10.1258/ebm.2012.012303 10.1258/ebm.2012.012303], PMID [http://www.ncbi.nlm.nih.gov/pubmed/23576797 23576797]</ref>
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<ref name="Phinney-1983"> SD. Phinney, BR. Bistrian, WJ. Evans, E. Gervino, GL. Blackburn, The human metabolic response to chronic ketosis without caloric restriction: preservation of submaximal exercise capability with reduced carbohydrate oxidation., Metabolism, volume 32, issue 8, pages 769-76, Aug 1983, PMID [http://www.ncbi.nlm.nih.gov/pubmed/6865776 6865776]</ref>
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<ref name="Hite-2011"> AH. Hite, VG. Berkowitz, K. Berkowitz, Low-carbohydrate diet review: shifting the paradigm., Nutr Clin Pract, volume 26, issue 3, pages 300-8, Jun 2011, doi [http://dx.doi.org/10.1177/0884533611405791 10.1177/0884533611405791], PMID [http://www.ncbi.nlm.nih.gov/pubmed/21586415 21586415]</ref>
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<ref name="Phinney-1980"> SD. Phinney, ES. Horton, EA. Sims, JS. Hanson, E. Danforth, BM. LaGrange, Capacity for moderate exercise in obese subjects after adaptation to a hypocaloric, ketogenic diet., J Clin Invest, volume 66, issue 5, pages 1152-61, Nov 1980, doi [http://dx.doi.org/10.1172/JCI109945 10.1172/JCI109945], PMID [http://www.ncbi.nlm.nih.gov/pubmed/7000826 7000826]</ref>
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<ref name="Fery-1982"> F. Fery, P. Bourdoux, J. Christophe, EO. Balasse, Hormonal and metabolic changes induced by an isocaloric isoproteinic ketogenic diet in healthy subjects., Diabete Metab, volume 8, issue 4, pages 299-305, Dec 1982, PMID [http://www.ncbi.nlm.nih.gov/pubmed/6761185 6761185]</ref>
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<ref name="Pasquali-1982"> R. Pasquali, M. Parenti, L. Mattioli, M. Capelli, G. Cavazzini, G. Baraldi, G. Sorrenti, G. De Benedettis, P. Biso, Effect of dietary carbohydrates during hypocaloric treatment of obesity on peripheral thyroid hormone metabolism., J Endocrinol Invest, volume 5, issue 1, pages 47-52, PMID [http://www.ncbi.nlm.nih.gov/pubmed/7096916 7096916]</ref>
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<ref name="Serog-1982"> P. Serog, M. Apfelbaum, N. Autissier, F. Baigts, L. Brigant, A. Ktorza, Effects of slimming and composition of diets on VO2 and thyroid hormones in healthy subjects., Am J Clin Nutr, volume 35, issue 1, pages 24-35, Jan 1982, PMID [http://www.ncbi.nlm.nih.gov/pubmed/7064875 7064875]</ref>
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<ref name="KanekoWang1998">Takashi Kaneko, Pei-Yu Wang, Masato Tawata, Akio Sato, Low carbohydrate intake and oral glucose-tolerance tests, The Lancet, volume 352, issue 9135, 1998, pages 1224, ISSN [http://www.worldcat.org/issn/01406736 01406736], doi [http://dx.doi.org/10.1016/S0140-6736(05)60565-X 10.1016/S0140-6736(05)60565-X]</ref>
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<ref name="Anderson-1975"> JW. Anderson, RH. Herman, Effects of carbohydrate restriction on glucose tolerance of normal men and reactive hypoglycemic patients., Am J Clin Nutr, volume 28, issue 7, pages 748-55, Jul 1975, PMID [http://www.ncbi.nlm.nih.gov/pubmed/1146728 1146728]</ref>
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<ref name="Bergman-1990">EN. Bergman, Energy contributions of volatile fatty acids from the gastrointestinal tract in various species., Physiol Rev, volume 70, issue 2, pages 567-90, Apr 1990, PMID [http://www.ncbi.nlm.nih.gov/pubmed/2181501 2181501]</ref>
 
<ref name="Kossoff-2011-1864">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 1864</ref>
 
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<ref name="Kossoff-2011-p271">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 271</ref>
 
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<ref name="Kossoff-2011-2512">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2512</ref>
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<ref name="Kossoff-2011-2680">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2680</ref>
 
<ref name="Kossoff-2011-p318">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 318</ref>
 
<ref name="Kossoff-2011-p318">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 318</ref>
 +
<ref name="Kossoff-2011-2452">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2452</ref>
 
<ref name="Kossoff-2011-p109">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 109</ref>
 
<ref name="Kossoff-2011-p109">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 109</ref>
 
<ref name="Kossoff-2011-p137">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 137</ref>
 
<ref name="Kossoff-2011-p137">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 137</ref>

Latest revision as of 12:50, 15 August 2015

They are many potential benefits to the ketogenic diet, but there are also a number of potentially serious health risks. It appears that most of these health risks can be mitigated with care.

1 Context

The list of health risks for the Ketogenic Diet can be rather intimidating. It's worth remembering that all diets have risks associated with them, and many of these risks are severe. In some ways the health risks of the ketogenic diet are better understood than most diets because the ketogenic diet is typically given under medical supervision, and adverse effects are well documented. It should also be noted that the patients that have been studied on the ketogenic diet are often children with severe epilepsy or adults with morbid obesity. In fact, an important source of information on the ketogenic diet comes from obese subjects undergoing complete fasts. This may increase the relative risk of the ketogenic diet.

2 Health Risks

2.1 Death

There have been two reported cases of sudden death of children on the Ketogenic Diet, probably due to selenium deficiency causing heart failure[1]. Selenium deficiency can occur rapidly; one child was diagnosed with selenium deficiency and related heart problems before their scheduled 3 month selenium test[2]. In addition, a study of 20 children on the Ketogenic Diet found heart rhythm abnormalities and heart enlargement in 3 (15%, diet duration 13 ± 8.4 months), and one had severe dilated cardiomyopathy[3]. The effected children has normal selenium levels, but there was a significant correlation was found between the heart rhythm abnormality (QTc) and both bicarbonate and blood ketones, suggesting the level of acidosis or ketosis may be important factors.

2.2 Sodium Loss and Hypotension

Low carbohydrate diets cause of the kidneys to excrete more sodium. This is known as "natriuresis of starvation", and may be due to low insulin[4], increased dopamine excretion[5], or elevated Glucagon[6]. If carbohydrate and sodium intakes are both limited, then the body will secrete the hormone aldosterone[7] which will cause the kidneys to excrete potassium and conserve sodium[8]. This loss of potassium can cause Muscle Cramps and heart arrhythmias, as well has the loss of Muscle Tissue.

2.3 Vitamin or mineral deficiency

The ketogenic diet is frequently deficient in vitamins and minerals, so supplementation is required with a carbohydrate free multivitamin/mineral[9].

  • Separate supplementation of Calcium and Vitamin D is also recommended.
  • Selenium is important to prevent heart problems (see above).
  • Carnitine may also be required, depending on the results of testing.
  • There are case reports of scurvy with the ketogenic diet[10], so additional supplementation with Vitamin C may be appropriate.

2.4 Constipation

Constipation is a common issue as the ketogenic diet is generally low in fiber. Even with supplementary fiber, constipation can still be a problem. This may be partly due to changes in the intestinal flora that occur with the ketogenic diet. There are also indications that some non-fiber carbohydrate passes far enough through the digestive tract to supply fuel to bacteria for fermentation[11].

2.5 Kidney Stones

About 5% of the children on the ketogenic diet for epilepsy suffer from kidney stones[12]. A study showed that oral potassium citrate significantly decreased the occurrence of kidney stones[13]. It has been shown that while carbonic anhydrase inhibitors are also a risk factor for kidney stones, carbonic anhydrase inhibitors while on the ketogenic diet does not further increase the risk[14]. (Carbonic anhydrase inhibitors are a type of antiepileptic drug.) Maintaining a good level of hydration is important, and Oral citrates may be appropriate. The urine should be tested for blood at least once a week[15].

2.6 Hypoglycemia

Hypoglycemia (low blood sugar) seems to predominantly a risk if the ketogenic diet is started with a fast, and blood sugar levels should be checked every 6–8 hours during the first few days of the diet[16]. Generally the ketogenic diet helps stabilize, and normalize blood sugar.

2.7 Acidosis

Uncontrolled diabetic patients can suffer from diabetic ketoacidosis, a life-threatening condition where very high levels of ketones are produced. In diabetic ketoacidosis not only are their high levels of ketones, but also their blood glucose is high, and there is often Potassium depletion and dehydration[17]. Acidosis is not a common problem on the ketogenic diet, but it can occur and symptoms are lethargy, Nausea, vomiting, and headache[18].

2.8 Hyperketosis

Excessively high ketone levels can produce symptoms such as rapid panting, irritability, high heart rate, facial flushing, fatigue lethargy, and vomiting[19]. Taking a couple of tablespoons of orange juice should resolve this, but if a second dose 20 minutes later does not help, seek prompt medical help[19].

2.9 Elevated cholesterol and blood lipid changes

About 30% of children on the ketogenic diet experience elevated cholesterol levels, but this is normally transient, and the levels return to baseline after 6-12 months[20]. Children on the diet for longer than 6 years mostly have normal levels[21]. Broader anecdotal evidence suggests that some people's cholesterol improves, while others cholesterol levels degrade. The health implications of cholesterol while on a Ketogenic Diet are unclear. If cholesterol levels are a concern, then the Ketogenic Ratio could be reduced, the percentage of unsaturated fats increased, MCT can be added, or Carnitine can be supplemented[22].

2.10 Bone fractures

Children on the ketogenic diet suffer a higher rate of bone fractures, with 20% of children on the diet for 6+ years having fractures[23]. Children on the ketogenic diet have poorer bone health, lower vitamin D levels, lower intakes of calcium and vitamin D, and lower Bone Mineral Content[24]. However, epilepsy medications are associated with bone loss and calcium metabolism[25], so this may also be a contributory factor.

2.11 Growth reduction

Children treated with the ketogenic diet can have growth reduction[26]. However, early uses of the ketogenic diet for epilepsy included calorie restriction below the recommended level for the child, as partial starvation was believed to be important for reducing seizures.

2.12 Fatty Liver

There are case reports of children on the MCT Diet having fatty infiltration of the liver[27]. However, a study in rats suggests that MCTs may be a treatment for both non-alcoholic fatty liver disease[28] and alcoholic fatty liver[29].

2.13 Fat Intake Imbalance

With increasing fat intake it is easy to get too much Omega-6. They are anecdotal reports that excessive Omega-6 can cause digestive problems, as well as longer-term health issues. The general recommendation is to avoid too much Omega-6, and aim for saturated or monounsaturated fats, plus some Omega-3.

2.14 Insulin Resistance

While the Ketogenic Diet can be beneficial for those suffering from Insulin Resistance or diabetes[30], there are also concerns that the Ketogenic Diet may also result in some insulin resistance[31][32]. There is conflicting evidence for the insulin resistance coming from a low carbohydrate[33] or a high fat intake[34]. This would not be expected to be an issue while on a Ketogenic Diet, but it may mean that care should be taken when exiting the Ketogenic Diet. The Ketogenic Diet may also exacerbate reactive hypoglycemia[34].

2.15 Thirst and Hydration

Ketones may reduce thirst[35], which could impair hydration, but the details are unclear.

2.16 Thyroid

The ketogenic diet has been shown to reduce the levels of the thyroid hormone T3[36][37][38][39], and there is some evidence that T3 production is proportional to carbohydrate intake[40]. It has been suggested that the ketogenic diet may not be suitable for those with thyroid deficiencies[41].

2.17 Gout

The ketogenic diet can produce an initial rise in the level of uric acid in the blood and the level of uric acid returns to baseline after 4-6 weeks, but some individuals can develop gout[42].

2.18 Wound Healing

I've found no studies concerning the effect of the ketogenic diet on wound healing. My personal experience is that wounds heal at a similar rate to a high carbohydrate diet. However, I've experienced far more problems on the Ketogenic Diet with my skin condition, Epidermolysis Bullosa, including more dystrophic scaring.

3 Contraindications

There are a number of contraindications for the ketogenic diet, including genetic deficiencies in fat metabolism[43]. A discussion of these contraindications is outside of the scope of this article.

4 See Also

5 References

  1. ↑ Ilana M. Bank, Sam D. Shemie, Bernard Rosenblatt, Chantal Bernard, Andrew S. Mackie, Sudden Cardiac Death in Association With the Ketogenic Diet, Pediatric Neurology, volume 39, issue 6, 2008, pages 429–431, ISSN 08878994, doi 10.1016/j.pediatrneurol.2008.08.013
  2. ↑ NS. Sirikonda, WD. Patten, JR. Phillips, CJ. Mullett, Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation., Pediatr Cardiol, volume 33, issue 5, pages 834-8, Jun 2012, doi 10.1007/s00246-012-0219-6, PMID 22367552
  3. ↑ TH. Best, DN. Franz, DL. Gilbert, DP. Nelson, MR. Epstein, Cardiac complications in pediatric patients on the ketogenic diet., Neurology, volume 54, issue 12, pages 2328-30, Jun 2000, PMID 10881264
  4. ↑ P. Stenvinkel, A. Ottosson-Seeberger, A. Alvestrand, J. Bolinder, Effect of insulin on renal sodium handling and renal haemodynamics in insulin-dependent (type 1) diabetes mellitus patients., Acta Diabetol, volume 32, issue 4, pages 230-4, Dec 1995, PMID 8750761
  5. ↑ R. Swaminathan, G. Cope, M. Sheltawy, MR. Lee, JK. Wales, Dopamine excretion during natriuresis of starvation., Int J Obes, volume 7, issue 1, pages 31-5, 1983, PMID 6840964
  6. ↑ C. D. Saudek, P. R. Boulter, R. A. Arky, The Natriuretic Effect of Glucagon and Its Role in Starvation, Journal of Clinical Endocrinology & Metabolism, volume 36, issue 4, 1973, pages 761–765, ISSN 0021-972X, doi 10.1210/jcem-36-4-761
  7. ↑ Phd Stephen D. Phinney MD, Rd Jeff S. Volek Phd, The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable, 2011, publisher Beyond Obesity LLC, isbn 978-0-9834907-0-8, Page 312
  8. ↑ Christopher J. Lote http://www.amazon.com/Principles-Renal-Physiology-Christopher-Lote/dp/0792360745 Principles of Renal Physiology, 22 June 2012, Springer, ISBN 978-1-4614-3785-7
  9. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 137
  10. ↑ NS. Willmott, RA. Bryan, Case report: scurvy in an epileptic child on a ketogenic diet with oral complications., Eur Arch Paediatr Dent, volume 9, issue 3, pages 148-52, Sep 2008, PMID 18793598
  11. ↑ EN. Bergman, Energy contributions of volatile fatty acids from the gastrointestinal tract in various species., Physiol Rev, volume 70, issue 2, pages 567-90, Apr 1990, PMID 2181501
  12. ↑ A. Sampath, EH. Kossoff, SL. Furth, PL. Pyzik, EP. Vining, Kidney stones and the ketogenic diet: risk factors and prevention., J Child Neurol, volume 22, issue 4, pages 375-8, Apr 2007, doi 10.1177/0883073807301926, PMID 17621514
  13. ↑ MA. McNally, PL. Pyzik, JE. Rubenstein, RF. Hamdy, EH. Kossoff, Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet., Pediatrics, volume 124, issue 2, pages e300-4, Aug 2009, doi 10.1542/peds.2009-0217, PMID 19596731
  14. ↑ EH. Kossoff, PL. Pyzik, SL. Furth, HD. Hladky, JM. Freeman, EP. Vining, Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet., Epilepsia, volume 43, issue 10, pages 1168-71, Oct 2002, PMID 12366731
  15. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 109
  16. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2452
  17. ↑ N.G. Soler, K. Dixon, M.A. Bennett, M.G. Fitzgerald, J.M. Malins, POTASSIUM BALANCE DURING TREATMENT OF DIABETIC KETOACIDOSIS WITH SPECIAL REFERENCE TO THE USE OF BICARBONATE, The Lancet, volume 300, issue 7779, 1972, pages 665–667, ISSN 01406736, doi 10.1016/S0140-6736(72)92083-1
  18. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 318
  19. ↑ 19.0 19.1 Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2680
  20. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2512
  21. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2519
  22. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2522
  23. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 271
  24. ↑ A. C. Bergqvist, J. I Schall, V. A Stallings, B. S Zemel, Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet, American Journal of Clinical Nutrition, volume 88, issue 6, 2008, pages 1678–1684, ISSN 0002-9165, doi 10.3945/ajcn.2008.26099
  25. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 174
  26. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2533
  27. ↑ D. Beverley, R. Arthur, Fatty liver and medium chain triglyceride (MCT) diet., Arch Dis Child, volume 63, issue 7, pages 840-2, Jul 1988, PMID 3137894
  28. ↑ MJ. Ronis, JN. Baumgardner, N. Sharma, J. Vantrease, M. Ferguson, Y. Tong, X. Wu, MA. Cleves, TM. Badger, Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease., Exp Biol Med (Maywood), volume 238, issue 2, pages 151-62, Feb 2013, doi 10.1258/ebm.2012.012303, PMID 23576797
  29. ↑ RC. Theuer, WH. Martin, TJ. Friday, BL. Zoumas, HP. Sarett, Regression of alcoholic fatty liver in the rat by medium-chain triglycerides., Am J Clin Nutr, volume 25, issue 2, pages 175-81, Feb 1972, PMID 5009783
  30. ↑ RL. Veech, The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism., Prostaglandins Leukot Essent Fatty Acids, volume 70, issue 3, pages 309-19, Mar 2004, doi 10.1016/j.plefa.2003.09.007, PMID 14769489
  31. ↑ F. R. Jornayvaz, Fibroblast growth factor 21, ketogenic diets, and insulin resistance, American Journal of Clinical Nutrition, volume 94, issue 3, 2011, pages 955–955, ISSN 0002-9165, doi 10.3945/ajcn.111.019646
  32. ↑ AM. Robinson, DH. Williamson, Physiological roles of ketone bodies as substrates and signals in mammalian tissues., Physiol Rev, volume 60, issue 1, pages 143-87, Jan 1980, PMID 6986618
  33. ↑ Takashi Kaneko, Pei-Yu Wang, Masato Tawata, Akio Sato, Low carbohydrate intake and oral glucose-tolerance tests, The Lancet, volume 352, issue 9135, 1998, pages 1224, ISSN 01406736, doi 10.1016/S0140-6736(05)60565-X
  34. ↑ 34.0 34.1 JW. Anderson, RH. Herman, Effects of carbohydrate restriction on glucose tolerance of normal men and reactive hypoglycemic patients., Am J Clin Nutr, volume 28, issue 7, pages 748-55, Jul 1975, PMID 1146728
  35. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2218
  36. ↑ SD. Phinney, BR. Bistrian, WJ. Evans, E. Gervino, GL. Blackburn, The human metabolic response to chronic ketosis without caloric restriction: preservation of submaximal exercise capability with reduced carbohydrate oxidation., Metabolism, volume 32, issue 8, pages 769-76, Aug 1983, PMID 6865776
  37. ↑ SD. Phinney, ES. Horton, EA. Sims, JS. Hanson, E. Danforth, BM. LaGrange, Capacity for moderate exercise in obese subjects after adaptation to a hypocaloric, ketogenic diet., J Clin Invest, volume 66, issue 5, pages 1152-61, Nov 1980, doi 10.1172/JCI109945, PMID 7000826
  38. ↑ F. Fery, P. Bourdoux, J. Christophe, EO. Balasse, Hormonal and metabolic changes induced by an isocaloric isoproteinic ketogenic diet in healthy subjects., Diabete Metab, volume 8, issue 4, pages 299-305, Dec 1982, PMID 6761185
  39. ↑ R. Pasquali, M. Parenti, L. Mattioli, M. Capelli, G. Cavazzini, G. Baraldi, G. Sorrenti, G. De Benedettis, P. Biso, Effect of dietary carbohydrates during hypocaloric treatment of obesity on peripheral thyroid hormone metabolism., J Endocrinol Invest, volume 5, issue 1, pages 47-52, PMID 7096916
  40. ↑ P. Serog, M. Apfelbaum, N. Autissier, F. Baigts, L. Brigant, A. Ktorza, Effects of slimming and composition of diets on VO2 and thyroid hormones in healthy subjects., Am J Clin Nutr, volume 35, issue 1, pages 24-35, Jan 1982, PMID 7064875
  41. ↑ AH. Hite, VG. Berkowitz, K. Berkowitz, Low-carbohydrate diet review: shifting the paradigm., Nutr Clin Pract, volume 26, issue 3, pages 300-8, Jun 2011, doi 10.1177/0884533611405791, PMID 21586415
  42. ↑ Phd Stephen D. Phinney MD, Rd Jeff S. Volek Phd, The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable, 2011, publisher Beyond Obesity LLC, isbn 978-0-9834907-0-8, Page 343
  43. ↑ Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 1864
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