Ketogenic Diet as a Treatment

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The Ketogenic Diet may have benefits for a number of medical conditions, many of them serious or life threatening. The research for the use of the Ketogenic Diet in epilepsy is well established, but for other illnesses it is still emerging. However, the Ketogenic Diet is believed to have a number of benefits, especially in cancer[1] and neurological diseases like Alzheimer's and Parkinson's[2]. There are indications that the Ketogenic Diet might also help with Heart Disease, ALS, Autism, Hyperactivity, Schizophrenia, Depression and Bipolar disorder. However, these benefits must be balanced against the Health Risks of the Ketogenic Diet.

1 Epilepsy

Main article: Ketogenic Diets for Epilepsy

The use of the Ketogenic Diets for Epilepsy is well established. Generally, around of 50% of patients have a 50% reduction in seizures, 25% have 90% reduction in seizures, and around 10% become seizure free.

2 Cancer

Main article: Ketogenic Diets for Cancer

The Ketogenic Diet may help with the treatment of cancer, including brain tumors[1]. Currently most of the available research is based on animal studies, with just a few human case studies. However, the research to date looks promising.

3 Hypoxia, including Stroke

There are a number of medical conditions that reduce the supply of oxygen (hypoxia), and the Ketogenic Diet may reduce the damage that occurs as a result.

  • Head trauma. Head trauma often results in a rapid increase in cerebral glucose metabolism, followed by a prolonged decrease. Administering glucose to patients tends to result in hyperglycemia (high blood sugar) that worsens the outcome. In animal studies, fasting or a ketogenic diet improves tissue preservation, but further research is needed[3].
  • Stroke. Because a stroke involves the reduction of blood flow to areas of the brain, the Ketogenic diet may help reduce the resulting damage[4]. Animal studies have looked at the ketogenic diet, ketone administration, and calorie restriction, which all raise ketone levels, and all have shown to be beneficial in animal stroke models[4].
The analysis of 19 animal (rodent) studies on the changes in outcome following cerebral ischemia with the ketogenic state. Pathological outcomes included lesion volume, brain water content, and neuronal counts, whereas functional outcomes included all measures of behavior.
  • Altitude Sickness. It is possible that the ketogenic diet may help with altitude sickness (Acute Mountain Sickness), but I've found not studies to support this.

4 Heart disease

There are some concerns that the ketogenic diet raises blood lipids, and this in turn may increase the risk for heart disease. One study of children using the Ketogenic Diet for Epilepsy showed a deterioration of blood lipid profiles, and only one in six were in the commonly accepted levels for a pediatric population[5]. Another study of adults on the Ketogenic Diet for Epilepsy also showed a worsening of blood lipids[6]. It's also been reported that around 30% of children on the ketogenic diet have elevated cholesterol, but it's also noted that this is normally transient, and the levels return to baseline after 6-12 months[7]. However, other studies have shown that the ketogenic diet has no adverse effects on the lipid profiles[8][9][10] or actually improves the markers[11][12][13][14][15]. (A study of children on the MCT Diet did not indicate any adverse blood lipid changes[16].) It seems possible that the structure of the Ketogenic Diet when it's used for epilepsy is in some way different, causing this split in results.

5 Alzheimer's disease (AD)

AD is a degenerative neurological condition characterized by memory loss and there is currently no treatment. Models of Alzheimer's disease (and Parkinson's) suggest that 4 mmol/L of BOHB can protect neurons and may play a therapeutic role[17].There is some evidence that a ketogenic diet may not only improve the symptoms of AD[18], but may also modify the disease activity itself. These benefits may also apply to other neurological conditions involving neuron death. There is evidence that raising Ketone levels through MCT supplementation without carbohydrate restriction may also improve memory function in AD sufferers[19]. In a study of 152 subjects with mild to moderate AD, half were given an MCT based treatment over a period of 90 days and had significantly improved cognitive scores compared with the placebo control group[20]. A drug called Axona was introduced in 2009 as an FDA approved "medical food" and it consists of an MCT oil (caprylic acid). There is also some evidence that a higher carbohydrate intake is associated with poorer memory, and increased aberrant motor behavior in subjects with probable AD[21].

6 Parkinson's disease

Parkinson's disease appears to generally result from an acquired defect in the mitochondria rather than genetic causes[22]. Animal studies and anecdotal reports suggest that the ketogenic diet may reverse the symptoms of Parkinson's disease, but there are no published human studies. It is possible to treat Parkinson's disease for a time with dopamine , but free radical damage lessens the effectiveness of this therapy over time[23]. Models of Parkinson's disease (and Alzheimer's) suggest that 4 mmol/L of BOHB can protect neurons and may play a therapeutic role[17]. A 28 day study of five Parkinson's patients on the Ketogenic Diet with blood BOHB levels averaging 6.6 mmol/L (range 4.8 to 8.9) had an average decrease in Unified Parkinson's Disease Rating Scale (UPDRS) scores of 43.4% (range 21% to 81%), but the study had too few subjects and no controls, so conclusions could be drawn about effectiveness[23].

7 Amyotropic Lateral Sclerosis (ALS)

Like Parkinson's disease, the evidence to support the use of the Ketogenic Diet for ALS is extremely limited[24], but human studies are under way. One study showed that the Ketogenic Diet alters the progression of ALS in a mouse model, but it did not extend the survival time[25]. However, other studies of high fat (non-ketogenic) diets in animal models did show an improved survival time[26][27].

8 Type 1 diabetes

At one time, type 1 diabetes (previously called childhood diabetes) was expected to be fatal within a year. The first approach was a starvation diet of 450 calories per day, which lead Fredrick M Allen to use a 70% fat, 8% carbohydrate diet that was the standard treatment before the discovery of insulin.

9 Autism

There are early reports from a Greek study in Crete indicating that the ketogenic diet may produce some improvement in some children. There are also anecdotal reports of epileptic children treated with the ketogenic diet also having improvements in their autism.

10 Migraine

While a 1930's textbook talks of the possibility of the ketogenic diet helping with migraines, a study of 8 teenagers with severe migraines at John Hopkins showed the ketogenic diet was ineffective.

11 Severe hyperactivity

There are initial reports that the ketogenic diet improves hyperactivity in animal reports, and some anecdotal reports of the benefit in humans. As with Autism, there are also reports of epileptic children treated with the ketogenic diet also having improvements in their hyperactivity.

12 Schizophrenia

There is a case report of a radical improvement in schizophrenia with the ketogenic diet[28]. However, this may be due to a removal of the gluten from the diet rather than the overall dietary changes[29].

13 Depression and bipolar disorder

There are a number of cases that have been reported where the ketogenic diet helps normalize the Mood State of those with bipolar disorder[30]. One report indicated that over 2-3 years the mood stabilization exceeded that achieved with medication[31].

14 Obesity

A recent analysis of 13 trials comparing the Ketogenic Diet (KD) with a Low Fat Diet (LFD) showed that the KD resulted in greater weight loss (an extra 0.9Kg/2 pounds), reduced triglycerides and blood pressure, but increased cholesterol[32]. However, while the extra weight loss was statistically significant, the loss of an additional 0.9Kg/2 pounds has limited real world value when the Health Risks of the Ketogenic Diet are considered[32].

15 See Also

16 References

  1. ↑ 1.0 1.1 TN. Seyfried, MA. Kiebish, J. Marsh, LM. Shelton, LC. Huysentruyt, P. Mukherjee, Metabolic management of brain cancer., Biochim Biophys Acta, volume 1807, issue 6, pages 577-94, Jun 2011, doi 10.1016/j.bbabio.2010.08.009, PMID 20804725
  2. ↑ M. Gasior, MA. Rogawski, AL. Hartman, Neuroprotective and disease-modifying effects of the ketogenic diet., Behav Pharmacol, volume 17, issue 5-6, pages 431-9, Sep 2006, PMID 16940764
  3. ↑ Mayumi L Prins, Cerebral metabolic adaptation and ketone metabolism after brain injury, Journal of Cerebral Blood Flow & Metabolism, volume 28, issue 1, 2007, pages 1–16, ISSN 0271-678X, doi 10.1038/sj.jcbfm.9600543
  4. ↑ 4.0 4.1 Claire L. Gibson, Anne N. Murphy, Sean P. Murphy, Stroke outcome in the ketogenic state - a systematic review of the animal data, Journal of Neurochemistry, volume 123, 2012, pages 52–57, ISSN 00223042, doi 10.1111/j.1471-4159.2012.07943.x
  5. ↑ Peter O. Kwiterovich, Jr, Effect of a High-Fat Ketogenic Diet on Plasma Levels of Lipids, Lipoproteins, and Apolipoproteins in Children, JAMA, volume 290, issue 7, 2003, pages 912, ISSN 0098-7484, doi 10.1001/jama.290.7.912
  6. ↑ Joseph Sirven, Barbara Whedon, Deborah Caplan, Joyce Liporace, David Glosser, Joyce O'Dwyer, Michael R. Sperling, The Ketogenic Diet for Intractable Epilepsy in Adults: Preliminary Results, Epilepsia, volume 40, issue 12, 1999, pages 1721–1726, ISSN 0013-9580, doi 10.1111/j.1528-1157.1999.tb01589.x
  7. ↑ 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
  8. ↑ B. J. Brehm, A Randomized Trial Comparing a Very Low Carbohydrate Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women, Journal of Clinical Endocrinology & Metabolism, volume 88, issue 4, 2003, pages 1617–1623, ISSN 0021972X, doi 10.1210/jc.2002-021480
  9. ↑ SB. Sondike, N. Copperman, MS. Jacobson, Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents., J Pediatr, volume 142, issue 3, pages 253-8, Mar 2003, doi 10.1067/mpd.2003.4, PMID 12640371
  10. ↑ James H. Hays, Angela DiSabatino, Robert T. Gorman, Simi Vincent, Michael E. Stillabower, Effect of a High Saturated Fat and No-Starch Diet on Serum Lipid Subfractions in Patients With Documented Atherosclerotic Cardiovascular Disease, Mayo Clinic Proceedings, volume 78, issue 11, 2003, pages 1331–1336, ISSN 00256196, doi 10.4065/78.11.1331
  11. ↑ EC. Westman, WS. Yancy, MK. Olsen, T. Dudley, JR. Guyton, Effect of a low-carbohydrate, ketogenic diet program compared to a low-fat diet on fasting lipoprotein subclasses., Int J Cardiol, volume 110, issue 2, pages 212-6, Jun 2006, doi 10.1016/j.ijcard.2005.08.034, PMID 16297472
  12. ↑ HM. Dashti, NS. Al-Zaid, TC. Mathew, M. Al-Mousawi, H. Talib, SK. Asfar, AI. Behbahani, Long term effects of ketogenic diet in obese subjects with high cholesterol level., Mol Cell Biochem, volume 286, issue 1-2, pages 1-9, Jun 2006, doi 10.1007/s11010-005-9001-x, PMID 16652223
  13. ↑ William S. Yancy, A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia, Annals of Internal Medicine, volume 140, issue 10, 2004, pages 769, ISSN 0003-4819, doi 10.7326/0003-4819-140-10-200405180-00006
  14. ↑ HM. Dashti, TC. Mathew, M. Khadada, M. Al-Mousawi, H. Talib, SK. Asfar, AI. Behbahani, NS. Al-Zaid, Beneficial effects of ketogenic diet in obese diabetic subjects., Mol Cell Biochem, volume 302, issue 1-2, pages 249-56, Aug 2007, doi 10.1007/s11010-007-9448-z, PMID 17447017
  15. ↑ MJ. Sharman, WJ. Kraemer, DM. Love, NG. Avery, AL. Gómez, TP. Scheett, JS. Volek, A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men., J Nutr, volume 132, issue 7, pages 1879-85, Jul 2002, PMID 12097663
  16. ↑ Peter R Huttenlocher, Ketonemia and Seizures: Metabolic and Anticonvulsant Effects of Two Ketogenic Diets in Childhood Epilepsy, Pediatric Research, volume 10, issue 5, 1976, pages 536–540, ISSN 0031-3998, doi 10.1203/00006450-197605000-00006
  17. ↑ 17.0 17.1 Y. Kashiwaya, T. Takeshima, N. Mori, K. Nakashima, K. Clarke, RL. Veech, D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease., Proc Natl Acad Sci U S A, volume 97, issue 10, pages 5440-4, May 2000, PMID 10805800
  18. ↑ Robert Krikorian, Marcelle D. Shidler, Krista Dangelo, Sarah C. Couch, Stephen C. Benoit, Deborah J. Clegg, Dietary ketosis enhances memory in mild cognitive impairment, Neurobiology of Aging, volume 33, issue 2, 2012, pages 425.e19–425.e27, ISSN 01974580, doi 10.1016/j.neurobiolaging.2010.10.006
  19. ↑ Mark A. Reger, Samuel T. Henderson, Cathy Hale, Brenna Cholerton, Laura D. Baker, G.S. Watson, Karen Hyde, Darla Chapman, Suzanne Craft, Effects of β-hydroxybutyrate on cognition in memory-impaired adults, Neurobiology of Aging, volume 25, issue 3, 2004, pages 311–314, ISSN 01974580, doi 10.1016/S0197-4580(03)00087-3
  20. ↑ Samuel T Henderson, Janet L Vogel, Linda J Barr, Fiona Garvin, Julie J Jones, Lauren C Costantini, Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial, Nutrition & Metabolism, volume 6, issue 1, 2009, pages 31, ISSN 1743-7075, doi 10.1186/1743-7075-6-31
  21. ↑ KW. Young, CE. Greenwood, R. van Reekum, MA. Binns, A randomized, crossover trial of high-carbohydrate foods in nursing home residents with Alzheimer's disease: associations among intervention response, body mass index, and behavioral and cognitive function., J Gerontol A Biol Sci Med Sci, volume 60, issue 8, pages 1039-45, Aug 2005, PMID 16127110
  22. ↑ GA. Veech, J. Dennis, PM. Keeney, CP. Fall, RH. Swerdlow, WD. Parker, JP. Bennett, Disrupted mitochondrial electron transport function increases expression of anti-apoptotic bcl-2 and bcl-X(L) proteins in SH-SY5Y neuroblastoma and in Parkinson disease cybrid cells through oxidative stress., J Neurosci Res, volume 61, issue 6, pages 693-700, Sep 2000, PMID 10972966
  23. ↑ 23.0 23.1 TB. Vanitallie, C. Nonas, A. Di Rocco, K. Boyar, K. Hyams, SB. Heymsfield, Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study., Neurology, volume 64, issue 4, pages 728-30, Feb 2005, doi 10.1212/01.WNL.0000152046.11390.45, PMID 15728303
  24. ↑ S. Paganoni, AM. Wills, High-fat and ketogenic diets in amyotrophic lateral sclerosis., J Child Neurol, volume 28, issue 8, pages 989-92, Aug 2013, doi 10.1177/0883073813488669, PMID 23666040
  25. ↑ Z. Zhao, DJ. Lange, A. Voustianiouk, D. MacGrogan, L. Ho, J. Suh, N. Humala, M. Thiyagarajan, J. Wang, A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis., BMC Neurosci, volume 7, pages 29, 2006, doi 10.1186/1471-2202-7-29, PMID 16584562
  26. ↑ MP. Mattson, RG. Cutler, S. Camandola, Energy intake and amyotrophic lateral sclerosis., Neuromolecular Med, volume 9, issue 1, pages 17-20, 2007, PMID 17114821
  27. ↑ L. Dupuis, H. Oudart, F. Rene, J.-L. G. de Aguilar, J.-P. Loeffler, Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: Benefit of a high-energy diet in a transgenic mouse model, Proceedings of the National Academy of Sciences, volume 101, issue 30, 2004, pages 11159–11164, ISSN 0027-8424, doi 10.1073/pnas.0402026101
  28. ↑ Bryan D Kraft, Eric C Westman, Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature, Nutrition & Metabolism, volume 6, issue 1, 2009, pages 10, ISSN 1743-7075, doi 10.1186/1743-7075-6-10
  29. ↑ M. Hadjivassiliou, A. Gibson, GA. Davies-Jones, AJ. Lobo, TJ. Stephenson, A. Milford-Ward, Does cryptic gluten sensitivity play a part in neurological illness?, Lancet, volume 347, issue 8998, pages 369-71, Feb 1996, PMID 8598704
  30. ↑ R.S. El-Mallakh, M.E. Paskitti, The ketogenic diet may have mood-stabilizing properties, Medical Hypotheses, volume 57, issue 6, 2001, pages 724–726, ISSN 03069877, doi 10.1054/mehy.2001.1446
  31. ↑ JR. Phelps, SV. Siemers, RS. El-Mallakh, The ketogenic diet for type II bipolar disorder., Neurocase, volume 19, issue 5, pages 423-6, 2013, doi 10.1080/13554794.2012.690421, PMID 23030231
  32. ↑ 32.0 32.1 NB. Bueno, IS. de Melo, SL. de Oliveira, T. da Rocha Ataide, Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials., Br J Nutr, volume 110, issue 7, pages 1178-87, Oct 2013, doi 10.1017/S0007114513000548, PMID 23651522
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