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Alzheimer Hastalığında Ketojenik Diyet Tedavisi

Year 2021, Volume , Issue 15, 630 - 638, 31.12.2021
https://doi.org/10.38079/igusabder.1007739

Abstract

Alzheimer, bellek kaybı ve bilişsel fonksiyonlardaki azalma ile karakterize progresif bir nörodejeneratif hastalıktır. Patogenezinde yer alan glikoz hipometabolizmasının yıkıcı sonuçlarını engellemek, artmış oksidatif stresi ve inflamatuar yanıtı azaltmak ve mitokondriyal işlevleri geliştirmek amacıyla çeşitli diyet müdahaleleri kullanılmıştır. Bunlardan biri ketojenik diyet olmuştur. Ketojenik diyet, yüksek yağlı, düşük karbonhidratlı bir diyettir ve vücut enerjisinin yağlardan karşılanmasını sağlamaktadır. Alzheimer gibi nörodejeneratif hastalıklarda tedavi yöntemi olarak kullanılabileceği öne sürülmüştür. Bunun en önemli nedenlerinden birisi beyinin glikoza bağımlılığını azaltacak alternatif bir enerji kaynağı oluşturabilmesidir. Yağların mitokondride β-oksidasyonu sonucu keton cisimcikleri oluşmaktadır. Bu keton cisimcikleri beynin temel enerji kaynağı olan glikozun yokluğunda alternatif enerji kaynağı olarak kullanılmaktadır. Sonuç olarak glikoz metabolizması düzeltmekte, mitokondriyal fonksiyonlar gelişmekte, oksidatif stres azalarak sistemik inflamatuar azalmaktadır. Ketojenik diyetin β-Amiloid plak birikimi ve nörofibril yumak oluşumuna etkisi ise hala tartışmalıdır. Yapılan bazı hayvan modelli çalışmalarda β-Amiloid plak birikimini azalttığı sonucuna varılmıştır. Ancak bunun tersi sonuçlara sahip araştırmalar da mevcuttur. Dolayısıyla diyetin etkisini açıklayabilmek için daha çok çalışmalara ihtiyaç duyulmaktadır. Bu derlemede ketojenik diyetin Alzheimer üzerine etkisini değerlendirmek amaçlanmıştır. 

References

  • Eratne D, Farrand S, Kelso W, et al. Alzheimer’s disease paper 1: Clinical update on epidemiology, pathophysiology and diagnosis. Australasian Psychiatry. 2018;26(4):347-357. doi:10.1177/1039856218762308.
  • Pavon S, Lazaro E, Martinez O, et al. Ketogenic diet and cognition in neurological diseases: A systematic review. Nutrition in Clinical Care. 2021;79(7):802-813. doi: 10.1093/nutrit/nuaa113.
  • Rusek M, Czuczwar J, Koziol M, Pluta R. Ketogenic diet in Alzheimer’s disease. International Journal of Molecular Sciences. 2020;20(16):3892. doi:10.3390/ijms20163892.
  • Lange K, Lange K, Gertruda E, Kanaya S, et al. Ketogenic diets and Alzheimer’s disease. Food Science and Human Wellness. 2017;6(1):1-9. doi:10.1016/j.fshw.2016.10.003.
  • Batch J, Adkins A, Lamsal S, Sultan S, Ramirez M. Advantages and disadvantages of the ketogenic diet: A review article. Crues. 2020;12(8):1-8. doi:10.7759/cureus.9639.
  • Barzegar M, Afghan M, Behtari M, Khamaneh S, Raeisi S. Ketogenic diet: Overview, types, and possible anti-seizure mechanisms. An International Journal on Nutrition, Diet and Nervous System. 2019;24(4):1-10. doi:10.1080/1028415X.2019.1627769.
  • Uyar G, Şanlıer N. Çocukluk çağı dirençli epilepsilerinde ketojenik diyet uygulamalarının etkisi. Turk J Neurology. 2018;24:216-225. doi:10.4274/tnd.71473.
  • Barry D, Ellul S, Watters L, et al. The ketogenic diet in disease and development. J. Developmental Neuroscience. 2018;68(1):53-58. doi:10.1016/j.ijdevneu.2018.04.005.
  • Türk E. Ketojenik Diyet Kullanan Hastalarda Tedavi Etkinliğinin Değerlendirilmesi. [tıpta uzmanlık tezi]. Ankara, Türkiye: Ankara Çocuk Sağlığı ve Hastalıkları Hematoloji Onkoloji Sağlık Uygulama ve Araştırma Merkezi, Tıp Fakültesi; 2018.
  • Ilgaz F, Ardıçlı D, Günbey C, Topçu M, Yalnızoğlu D. Dirençli epilepside düşük glisemik indeksli diyet tedavisi: Olgu sunumu. Beslenme ve Diyet Dergisi. 2019;47(2):108-113. doi:10.33076/2019.BDD.1262.
  • Dhamija R, Eckert S, Wirrell E. Ketogenic diet. Canadian Journal of Neurology Sciences. 2013;40(2):158-167. doi:10.1017/S0317167100013676.
  • Koh S, Auvin S, Dupuis N. Ketogenic diet and neuroinflammation. Epilepsy Research. 2020;167:1-8. doi:10.1016/j.eplepsyres.2020.106454.
  • McDonald T, Cervenka M. The expanding role of ketogenic diets in adult neurological disorders. Brain Sciences. 2018;8(8):148. doi:10.3390/brainsci8080148.
  • McDonald T, Cervenka M. Ketogenic diets for adult neurological disorders. The American Society for Experimental NeuroTherapeutics. 2018;15:1018–1031. doi:10.1007/s13311-018-0666-8.
  • Morril S, Gibas K. Ketogenic diet rescues cognition in ApoE4þ patient with mild Alzheimer's disease: A case study. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019;13(2):1187-1191. doi:10.1016/j.dsx.2019.01.035.
  • Pinto A, Bonucci A, Businaro R, Corsi M, Maggi E. Anti-oxidant and anti-inflammatory activity of ketogenic diet: New perspectives for neuroprotection in Alzheimer’s disease. Journal of Antioxidants. 2018;7(5):63. doi:10.3390/antiox7050063.
  • Vinciguerra F, Graziano M, Frittitta L, Hagnas M, Tumminia A. Influence of the mediterranean and ketogenic diets on cognitive status and decline: A narrative review. Nutrients. 2020;12(4):1019-1042. doi:10.3390/nu12041019.
  • Koziol M, Pluta R. To treat or not to treat Alzheimer's disease by the ketogenic diet? That is the question. Neural Regeneration Research. 2020;15(5):857-858. doi:10.4103/1673-5374.268900.
  • Ohnuma T, Arai H, Higashiyama R. Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer’s disease: A prospective, open-label pilot study. Clinical Interventions in Aging. 2016;8(11): 29-36. doi: 10.2147/CIA.S95362.
  • Henderson S, Constantin L, Garvin F, Jones J, Vogel J. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: A randomized, double-blind, placebo-controlled, multicenter trial. Nutrition&Metabolism. 2009;10(6):31. doi:10.1186/1743-7075-6-31.
  • Rebello C, Greenway F, Johnson W, Keller J, Liu A. Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled trial. BBA Clinical. 2015;3:123-125. doi:10.1016/j.bbacli.2015.01.001.
  • Reger M, Hale C, Henderson S, et al. Effects of β-hydroxybutyrate on cognition in memory-impaired adults. Neurobiology of Aging. 2004;25(3):311-314. doi:10.1016/S0197-4580(03)00087-3.
  • Taylor M, Burns J, Mahnken J, Sullivan D, Swerdlow R. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. 2018;4:28-36. doi:10.1016/j.trci.2017.11.002.
  • Xu Q, Zhang Y, Zhang X et al. Medium-chain triglycerides improved cognition and lipid metabolomics in mild to moderate Alzheimer’s disease patients with APOE4-/-: A double-blind, randomized, placebo-controlled crossover trial. Clinical Nutrition. 2020;39(7):2092-2105. doi:10.1016/j.clnu.2019.10.017.
  • Ota M, Matsuo J, Ishida I et al. Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer’s disease. Neuroscience Letters. 2019;690:232-236. doi: 10.1016/j.neulet.2018.10.048.
  • Phillips M, Deprez L, Mortimer G, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer’s Research&Therapy. 2021;13(51):1-12. doi: 10.1186/s13195-021-00783-x.
  • Fortier M, Castellano C, St-Pierre V et al. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimer’s& Dementia. 2021;17(3):543-552. doi:10.1002/alz.12206.
  • Kashıwaya Y, Bergman C, Clarke K, et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2013;34(6):1530–1539. doi:10.1016/j.neurobiolaging.2012.11.023.
  • Davis J, Ellison J, Fournakis N. Ketogenic diet for the treatment and prevention of dementia: A review. Journal of Geriatric Psychiatry and Neurology. 2020;34(1):3-10. doi:10.1177/0891988720901785.
  • McDonald T, Cervenka M. Ketogenic diets for adult neurological disorders. The American Society for Experimental NeuroTherapeutics. 2018;15:1018–1031. doi:10.1007/s13311-018-0666-8.
  • Wlodarek D. Role of ketogenic diets in neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). Nutrients. 2019;11(1):169. doi:10.3390/nu11010169.
  • Dashti H, Mathew T, Al-Zaid N. Efficacy of low-carbohydrate ketogenic diet in the treatment of type 2 diabetes. Medical Principles and Practice. 2021;30:223-235. doi:10.1159/000512142.
  • Özdemir A, Demirel Z. Beslenme ve mikrobiyota ilişkisi. Journal of Biotechnol and Strategic Health Research. 2017;1:25-33.

Ketogenic Diet Treatment in Alzheimer’s Disease

Year 2021, Volume , Issue 15, 630 - 638, 31.12.2021
https://doi.org/10.38079/igusabder.1007739

Abstract

Alzheimer's is a progressive neurodegenerative disease characterized by memory loss and decreased cognitive function. Various dietary interventions have been used to prevent the devastating consequences of glucose hypometabolism in its pathogenesis, to reduce increased oxidative stress and inflammatory response, and to improve mitochondrial functions. One of them has been the ketogenic diet. The ketogenic diet is a high-fat, low-carb diet that provides the body's energy from fat. It has been suggested that it can be used as a treatment method in neurodegenerative diseases such as Alzheimer's. One of the most important reasons for this is that it can create an alternative energy source that will reduce the brain's dependence on glucose. Ketone bodies are formed as a result of β-oxidation of fats in mitochondria. These ketone bodies are used as an alternative energy source in the absence of glucose, the main energy source of the brain. As a result, glucose metabolism is corrected, mitochondrial functions develop, oxidative stress decreases and systemic inflammation decreases. The effect of the ketogenic diet on β-Amyloid plaque accumulation and neurofibrillary tangle formation is still controversial. In some animal model studies, it has been concluded that it reduces the accumulation of β-Amyloid plaque. However, there are also studies with opposite results. Therefore, more studies are needed to explain the effect of diet. In this review, it was aimed to evaluate the effect of the ketogenic diet on Alzheimer's.

References

  • Eratne D, Farrand S, Kelso W, et al. Alzheimer’s disease paper 1: Clinical update on epidemiology, pathophysiology and diagnosis. Australasian Psychiatry. 2018;26(4):347-357. doi:10.1177/1039856218762308.
  • Pavon S, Lazaro E, Martinez O, et al. Ketogenic diet and cognition in neurological diseases: A systematic review. Nutrition in Clinical Care. 2021;79(7):802-813. doi: 10.1093/nutrit/nuaa113.
  • Rusek M, Czuczwar J, Koziol M, Pluta R. Ketogenic diet in Alzheimer’s disease. International Journal of Molecular Sciences. 2020;20(16):3892. doi:10.3390/ijms20163892.
  • Lange K, Lange K, Gertruda E, Kanaya S, et al. Ketogenic diets and Alzheimer’s disease. Food Science and Human Wellness. 2017;6(1):1-9. doi:10.1016/j.fshw.2016.10.003.
  • Batch J, Adkins A, Lamsal S, Sultan S, Ramirez M. Advantages and disadvantages of the ketogenic diet: A review article. Crues. 2020;12(8):1-8. doi:10.7759/cureus.9639.
  • Barzegar M, Afghan M, Behtari M, Khamaneh S, Raeisi S. Ketogenic diet: Overview, types, and possible anti-seizure mechanisms. An International Journal on Nutrition, Diet and Nervous System. 2019;24(4):1-10. doi:10.1080/1028415X.2019.1627769.
  • Uyar G, Şanlıer N. Çocukluk çağı dirençli epilepsilerinde ketojenik diyet uygulamalarının etkisi. Turk J Neurology. 2018;24:216-225. doi:10.4274/tnd.71473.
  • Barry D, Ellul S, Watters L, et al. The ketogenic diet in disease and development. J. Developmental Neuroscience. 2018;68(1):53-58. doi:10.1016/j.ijdevneu.2018.04.005.
  • Türk E. Ketojenik Diyet Kullanan Hastalarda Tedavi Etkinliğinin Değerlendirilmesi. [tıpta uzmanlık tezi]. Ankara, Türkiye: Ankara Çocuk Sağlığı ve Hastalıkları Hematoloji Onkoloji Sağlık Uygulama ve Araştırma Merkezi, Tıp Fakültesi; 2018.
  • Ilgaz F, Ardıçlı D, Günbey C, Topçu M, Yalnızoğlu D. Dirençli epilepside düşük glisemik indeksli diyet tedavisi: Olgu sunumu. Beslenme ve Diyet Dergisi. 2019;47(2):108-113. doi:10.33076/2019.BDD.1262.
  • Dhamija R, Eckert S, Wirrell E. Ketogenic diet. Canadian Journal of Neurology Sciences. 2013;40(2):158-167. doi:10.1017/S0317167100013676.
  • Koh S, Auvin S, Dupuis N. Ketogenic diet and neuroinflammation. Epilepsy Research. 2020;167:1-8. doi:10.1016/j.eplepsyres.2020.106454.
  • McDonald T, Cervenka M. The expanding role of ketogenic diets in adult neurological disorders. Brain Sciences. 2018;8(8):148. doi:10.3390/brainsci8080148.
  • McDonald T, Cervenka M. Ketogenic diets for adult neurological disorders. The American Society for Experimental NeuroTherapeutics. 2018;15:1018–1031. doi:10.1007/s13311-018-0666-8.
  • Morril S, Gibas K. Ketogenic diet rescues cognition in ApoE4þ patient with mild Alzheimer's disease: A case study. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019;13(2):1187-1191. doi:10.1016/j.dsx.2019.01.035.
  • Pinto A, Bonucci A, Businaro R, Corsi M, Maggi E. Anti-oxidant and anti-inflammatory activity of ketogenic diet: New perspectives for neuroprotection in Alzheimer’s disease. Journal of Antioxidants. 2018;7(5):63. doi:10.3390/antiox7050063.
  • Vinciguerra F, Graziano M, Frittitta L, Hagnas M, Tumminia A. Influence of the mediterranean and ketogenic diets on cognitive status and decline: A narrative review. Nutrients. 2020;12(4):1019-1042. doi:10.3390/nu12041019.
  • Koziol M, Pluta R. To treat or not to treat Alzheimer's disease by the ketogenic diet? That is the question. Neural Regeneration Research. 2020;15(5):857-858. doi:10.4103/1673-5374.268900.
  • Ohnuma T, Arai H, Higashiyama R. Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer’s disease: A prospective, open-label pilot study. Clinical Interventions in Aging. 2016;8(11): 29-36. doi: 10.2147/CIA.S95362.
  • Henderson S, Constantin L, Garvin F, Jones J, Vogel J. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: A randomized, double-blind, placebo-controlled, multicenter trial. Nutrition&Metabolism. 2009;10(6):31. doi:10.1186/1743-7075-6-31.
  • Rebello C, Greenway F, Johnson W, Keller J, Liu A. Pilot feasibility and safety study examining the effect of medium chain triglyceride supplementation in subjects with mild cognitive impairment: A randomized controlled trial. BBA Clinical. 2015;3:123-125. doi:10.1016/j.bbacli.2015.01.001.
  • Reger M, Hale C, Henderson S, et al. Effects of β-hydroxybutyrate on cognition in memory-impaired adults. Neurobiology of Aging. 2004;25(3):311-314. doi:10.1016/S0197-4580(03)00087-3.
  • Taylor M, Burns J, Mahnken J, Sullivan D, Swerdlow R. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. 2018;4:28-36. doi:10.1016/j.trci.2017.11.002.
  • Xu Q, Zhang Y, Zhang X et al. Medium-chain triglycerides improved cognition and lipid metabolomics in mild to moderate Alzheimer’s disease patients with APOE4-/-: A double-blind, randomized, placebo-controlled crossover trial. Clinical Nutrition. 2020;39(7):2092-2105. doi:10.1016/j.clnu.2019.10.017.
  • Ota M, Matsuo J, Ishida I et al. Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer’s disease. Neuroscience Letters. 2019;690:232-236. doi: 10.1016/j.neulet.2018.10.048.
  • Phillips M, Deprez L, Mortimer G, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer’s Research&Therapy. 2021;13(51):1-12. doi: 10.1186/s13195-021-00783-x.
  • Fortier M, Castellano C, St-Pierre V et al. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimer’s& Dementia. 2021;17(3):543-552. doi:10.1002/alz.12206.
  • Kashıwaya Y, Bergman C, Clarke K, et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2013;34(6):1530–1539. doi:10.1016/j.neurobiolaging.2012.11.023.
  • Davis J, Ellison J, Fournakis N. Ketogenic diet for the treatment and prevention of dementia: A review. Journal of Geriatric Psychiatry and Neurology. 2020;34(1):3-10. doi:10.1177/0891988720901785.
  • McDonald T, Cervenka M. Ketogenic diets for adult neurological disorders. The American Society for Experimental NeuroTherapeutics. 2018;15:1018–1031. doi:10.1007/s13311-018-0666-8.
  • Wlodarek D. Role of ketogenic diets in neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). Nutrients. 2019;11(1):169. doi:10.3390/nu11010169.
  • Dashti H, Mathew T, Al-Zaid N. Efficacy of low-carbohydrate ketogenic diet in the treatment of type 2 diabetes. Medical Principles and Practice. 2021;30:223-235. doi:10.1159/000512142.
  • Özdemir A, Demirel Z. Beslenme ve mikrobiyota ilişkisi. Journal of Biotechnol and Strategic Health Research. 2017;1:25-33.

Details

Primary Language Turkish
Subjects Medicine
Journal Section Articles
Authors

Gülsüm KARA (Primary Author)
ANKARA ÜNİVERSİTESİ, SAĞLIK BİLİMLERİ FAKÜLTESİ
0000-0002-8994-3851
Türkiye


Gül Eda KILINÇ
ANKARA ÜNİVERSİTESİ, SAĞLIK BİLİMLERİ FAKÜLTESİ
0000-0002-9068-3081
Türkiye

Publication Date December 31, 2021
Published in Issue Year 2021, Volume , Issue 15

Cite

Bibtex @review { igusabder1007739, journal = {İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi}, issn = {2536-4499}, eissn = {2602-2605}, address = {İstanbul Gelişim Üniversitesi Sağlık Bilimleri Yüksekokulu - Cihangir Mah. Şehit Jandarma Komando Er Hakan Öner Sk. No: 1 Avcılar / İstanbul / Türkiye}, publisher = {İstanbul Gelisim University}, year = {2021}, volume = {}, pages = {630 - 638}, doi = {10.38079/igusabder.1007739}, title = {Alzheimer Hastalığında Ketojenik Diyet Tedavisi}, key = {cite}, author = {Kara, Gülsüm and Kılınç, Gül Eda} }
APA Kara, G. & Kılınç, G. E. (2021). Alzheimer Hastalığında Ketojenik Diyet Tedavisi . İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi , (15) , 630-638 . DOI: 10.38079/igusabder.1007739
MLA Kara, G. , Kılınç, G. E. "Alzheimer Hastalığında Ketojenik Diyet Tedavisi" . İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi (2021 ): 630-638 <https://dergipark.org.tr/en/pub/igusabder/issue/66537/1007739>
Chicago Kara, G. , Kılınç, G. E. "Alzheimer Hastalığında Ketojenik Diyet Tedavisi". İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi (2021 ): 630-638
RIS TY - JOUR T1 - Alzheimer Hastalığında Ketojenik Diyet Tedavisi AU - Gülsüm Kara , Gül Eda Kılınç Y1 - 2021 PY - 2021 N1 - doi: 10.38079/igusabder.1007739 DO - 10.38079/igusabder.1007739 T2 - İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi JF - Journal JO - JOR SP - 630 EP - 638 VL - IS - 15 SN - 2536-4499-2602-2605 M3 - doi: 10.38079/igusabder.1007739 UR - https://doi.org/10.38079/igusabder.1007739 Y2 - 2021 ER -
EndNote %0 Istanbul Gelisim University Journal of Health Sciences Alzheimer Hastalığında Ketojenik Diyet Tedavisi %A Gülsüm Kara , Gül Eda Kılınç %T Alzheimer Hastalığında Ketojenik Diyet Tedavisi %D 2021 %J İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi %P 2536-4499-2602-2605 %V %N 15 %R doi: 10.38079/igusabder.1007739 %U 10.38079/igusabder.1007739
ISNAD Kara, Gülsüm , Kılınç, Gül Eda . "Alzheimer Hastalığında Ketojenik Diyet Tedavisi". İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi / 15 (December 2021): 630-638 . https://doi.org/10.38079/igusabder.1007739
AMA Kara G. , Kılınç G. E. Alzheimer Hastalığında Ketojenik Diyet Tedavisi. IGUSABDER. 2021; (15): 630-638.
Vancouver Kara G. , Kılınç G. E. Alzheimer Hastalığında Ketojenik Diyet Tedavisi. İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi. 2021; (15): 630-638.
IEEE G. Kara and G. E. Kılınç , "Alzheimer Hastalığında Ketojenik Diyet Tedavisi", İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi, no. 15, pp. 630-638, Dec. 2021, doi:10.38079/igusabder.1007739

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