Epilepsy & ketogenic diet research

Dr. Palmer’s Psychology Today article on the ketogenic diet in epilepsy treatment. 

• Neal EG, Chaffe H, Schwartz RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomized controlled trial. Lancet Neurology 2008; 7:500–506. [Article] [PubMed]
• Freeman JM, Vining EPG, Kossoff EH, et al. A blinded, crossover study of the ketogenic diet. Epilepsia 2009; 50:322–325.
• Martin K, Jackson CF, Levy RG, Cooper PN. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database of Systematic Reviews 2016, Issue 2. Art. No.: CD001903. DOI: 10.1002/14651858.CD001903.pub3.
•  Bough, K. J. and Rho, J. M. (2007), Anticonvulsant Mechanisms of the Ketogenic Diet. Epilepsia, 48: 43-58. doi:10.1111/j.1528-1167.2007.00915.x

Weight loss, type 2 diabetes and ketogenic diet research

Our keto research summary article

• Abbasi J. Interest in the Ketogenic Diet Grows for Weight Loss and Type 2 Diabetes. JAMA. 2018;319(3):215–217
• Bueno, N., De Melo, I., De Oliveira, S., & Da Rocha Ataide, T. (2013). Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: A meta-analysis of randomised controlled trials. British Journal of Nutrition, 110(7), 1178-1187.
• Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, Ludwig DS. Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance. JAMA. 2012;307(24):2627–2634. doi:10.1001/jama.2012.6607 [PubMed]
• Palmer, C. M. (2019). Diets and Disorders: Can Foods or Fasting Be Considered Psychopharmacologic Therapies? The Journal of Clinical Psychiatry, 81(1), 0–0. https://doi.org/10.4088/JCP.19ac12727
• Saslow, L, Daubenmier, J, Moskowitz, J, Kim, S, Murphy, E, Phinney, S, Ploutz-Snyder, R, Goldman, V, Cox, R, Mason, A, Moran, P, Hecht, F. (2017). Twelve-month outcomes of a randomized trial of a moderate-carbohydrate versus very low-carbohydrate diet in overweight adults with type 2 diabetes mellitus or prediabetes. Nutrition & Diabetes. 7. 10.1038/s41387-017-0006-9.
• Snorgaard O, Poulsen GM, Andersen HK, et al. Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes. BMJ Open Diabetes Research and Care. 2017; 5:e000354. doi: 10.1136/bmjdrc-2016-000354 [PubMed]
• Tobias, Deirdre K et al. Effect of low-fat diet interventions versus other diet interventions on long-term weight change in adults: a systematic review and meta-analysis. 2015. The Lancet Diabetes & Endocrinology, Volume 3 , Issue 12 , 968 – 979 [Article]

Schizophrenia and ketogenic diet research

Our keto research summary article

• Sarnyai Z, Kraeuter AK, Palmer CM. Ketogenic diet for schizophrenia: clinical implication. Current Opinion in Psychiatry.  2019 Jun 11. doi: 10.1097/YCO.0000000000000535. Epub ahead of print [PubMed]
• Palmer C, Javier T, Westman C. The ketogenic diet and remission of psychotic symptoms in schizophrenia: Two case studies. Schizophrenia Research 2019; April 6 
• Pacheco et al.  A pilot study of the ketogenic diet in schizophrenia. Am J Psychiatry 1965, 121:1110-1111. [Article] [PubMed] [Google Scholar]
• Kraft and Westman. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutrition & Metabolism 2009, 6:10 [Article] [Google Scholar]
• Gilbert-Jaramillo, J., Vargas-Pico, D., Espinosa-Mendoza, T., Falk, S., Llanos-Fernandez, K., Guerrero-Haro, J., Orellana-Roman, C., Poveda-Loor, C., Valdevila-Figueira, J., & Palmer, C. (2018). The effects of the ketogenic diet on psychiatric symptomatology, weight and metabolic dysfunction in schizophrenia patients. Clinical Nutrition and Metabolism, 1(1). https://doi.org/10.15761/CNM.1000105
• Kraeuter, A.K., Loxton, H., Lima, B.C., Rudd, D., Sarnyai, Z., 2015. Ketogenic diet reverses behavioral abnormalities in an acute NMDA receptor hypofunction model of schizophrenia. Schizophrenia Research. 169, 491-493. [Abstract] [Google Scholar]

Bipolar & ketogenic diet research

Our bipolar &  keto research summary article

• Yaroslovsky et al. Ketogenic Diet in Bipolar Illness. Bipolar Disorders 2002: 4: 75
• Phelps et al.  The ketogenic diet for type II bipolar disorder. Neurocase, 2013;19(5):423-6 [PubMed] [Google Scholar]
• Coello K, Vinberg M, Knop FK, et al. Metabolic profile in patients with newly diagnosed bipolar disorder and their unaffected first‑degree relatives [published online April 2, 2019]. International Journal Bipolar Disorder. doi:10.1186/s40345-019-0142-3

Cardiovascular disease & ketogenic diet research

• Dehghan M, Mente A, Zhang X, et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.  Lancet. 2017 Aug 28 doi: 10.1016/S0140-6736(17)32252-3
• Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. New England Journal of Medicine. (2003) 348(21):2074–81.

Inflammation, longevity and ketogenic diet research

• Dupuis N, Curatolo N, Benoist JF, Auvin S. Ketogenic diet exhibits anti-inflammatory properties. Epilepsia. 2015; 56:e95–e98.
• Roberts MN, Wallace MA, Tomilov AA, et al. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metabolism. 2017 Sep 5;26(3):539-546.e5

Useful overviews of low carb and ketogenic research –

• Diet Doctor: The Science of low carb and keto
• Virta Health: A comprehensive list of low-carb research. 2018, January 31.
• Public Health Collaboration UK: Randomised controlled trials comparing low-carb diets to low-fat diets

The post Bibliography – Medical ketogenic diet for metabolic and mental health research appeared first on Chris Palmer, MD.

The Epilepsy Connection

Many treatments that are approved for the treatment of epilepsy also work for bipolar disorder and other psychiatric disorders, including medications like Depakote (valproic acid), Tegretol (carbamazepine), and Lamictal (lamotrigine). Other anticonvulsant medications are used off label very commonly in the treatment of bipolar disorder. This includes medications such as Neurontin (gabapentin), Topamax (topiramate), and all of the benzodiazepines, such as Klonopin, Ativan, and Xanax. Given the overlap in effective treatments, it is not unreasonable to question if the evidence-based ketogenic diet might play a role in the treatment of bipolar disorder, at least for some people.

Energy Metabolism in Brain Cells

In support of this possibility, recent research suggests that disturbances in energy metabolism play a role in bipolar disorder, meaning the brain or certain parts of the brain may not be getting enough energy, at least from glucose. (1) This is often described as mitochondrial dysfunction. There appears to be a correlation between bipolar disorder and the body’s impaired ability to process glucose/sugar for energy. The ketogenic diet forces the body and brain to begin using ketones for energy instead of glucose, possibly bypassing some of these abnormalities. The ketogenic diet also has numerous other effects on the body and brain, such as changes in neurotransmitter systems and decreased inflammation, that may also play a role in a therapeutic effect.

Is there evidence that the ketogenic diet can work in bipolar disorder?

There are case reports, which should be considered preliminary evidence (definitive evidence would be a blinded, randomized, controlled trial).

In 2013, Phelps et al (2) described two women diagnosed with bipolar disorder, type II, whoeach did the ketogenic diet for over 2 years, were able to get off all of their psychiatric medications, and reportedly did much better on the diet alone than they had ever done on medication. [As a caution… getting off of psychiatric medication is a complicated process that requires slow tapering and medical supervision! Please don’t stop psychiatric medications on your own!]

For those who suffer from a more serious form of bipolar disorder, including those with psychotic symptoms, in 2017, I published two case studies (3) of patients with schizoaffective disorder, bipolar type, that improved dramatically on the ketogenic diet. Improvement occurred in both mood and psychotic symptoms. Although these people were diagnosed with schizoaffective disorder, the medications used to treat bipolar disorder and schizoaffective disorder are often then same. If anything, schizoaffective disorder is more treatment-refractory, so given that the ketogenic diet worked for these two patients, it should at least be considered for those with treatment-resistant bipolar disorder.

I would be remiss to exclude a 2002 report from Israel (4) that described a 49 year old woman with bipolar disorder who reportedly tried the ketogenic diet for one month without any effect on her bipolar disorder symptoms. Of note, however, is that she NEVER had urine ketones and didn’t lose any weight (a common “side effect” early on), which tells me that she was never in ketosis, so was not doing the diet correctly. The authors concluded that she had tried it and it just didn’t work for her, which again speaks to the lack of understanding of the different versions of the ketogenic diet, appropriate monitoring for compliance, and most importantly, appropriate education on how to do this diet. It’s not easy to do. Even when people think they are doing everything correctly, they may not be. The good news is that there is an objective test to tell us if a person is doing everything right, and that is the presence and levels of ketones in urine and blood.

So… should people just try this diet on their own?

As much as I wish it were that simple, it’s not. First of all, the version of the diet that appears to work for serious psychiatric disorders is the strict medical version (2:1 up to a 4:1 ratio diet), the same one used in treating epilepsy. This version of the diet should be medically prescribed and monitored, as it is very difficult to do and has risks, as well as potential benefits. Levels of ketones, glucose, and body weight all impact the effectiveness of the diet. Additionally, medications often need to be adjusted, as new side effects can emerge when people are in ketosis, and some medications can interfere with the effectiveness of the ketogenic diet by increasing blood glucose levels and preventing ketosis, so they may need to be safely reduced or stopped. Adjusting psychiatric medications can sometimes be very dangerous, and should only be done with medication supervision and monitoring. Finally, when starting the ketogenic diet, people can experience hypoglycemia, low blood pressure, weakness,dizziness, and other worrisome symptoms, which all need to be monitored and safely managed by a skilled medical team.

Sources:

1.  Clay, H.B., Sillivan, S., Konradi, C., 2011. Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia. Int. J. Dev. Neurosci. 29, 311–324.
2. Phelps et al, The ketogenic diet for type II bipolar disorder. Neurocase. 2013;19(5):423-6
3. Palmer, CM. Ketogenic diet in the treatment of schizoaffective disorder: Two case studies. Schizophrenia Research, Volume 189 , 208 – 209
4.  Yaroslovsky et al, Ketogenic Diet in Bipolar Illness. Bipolar Disorders 2002: 4: 75

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