KETOJENİK BESLENME VE SAĞLIK

Yıl 2022, Cilt: 5 Sayı: 2, 317 - 345, 30.09.2022

Ceren Filiz , Elif Yıldız , Ozan Gürbüz

https://doi.org/10.52538/iduhes.1093564

Cited By: 1

Öz

Ketojenik diyet (KD), keton cisimlerinin üretimini teşvik etmek amacıyla açlık durumunun metabolizmasını taklit eden yüksek yağlı, yeterli proteinli ve çok düşük karbonhidratlı bir diyet rejimidir. KD, epilepsi tedavisi için uzun süredir oldukça başarılı bir diyet yaklaşımı olarak öne çıkmaktadır. Son verilere göre KD’nin teröpotik etkisi, epilepsinin yanısıra kanser, diyabet, obezite gibi birçok hastalık için umut vadedici görünmektedir. Hatta kilo vermeye ihtiyacı olmayan bireyler arasında bile bu diyetin popüler olarak uygulanması göz önüne alındığında, nüfusun geniş kesimleri tarafından bu diyetin geniş bir şekilde benimsenmesinin potansiyel uzun vadeli sonuçlarıyla ilgili bazı endişeler oluşmaktadır. Bu derlemede, KD ve KD ile ilgili olarak öne çıkan kavramlara yer verilmiş olup, farklı hastalıklarda KD'nin etkililiği ve güvenilirliğine ilişkin deneysel ve/veya klinik veriler özetlenmiştir. KD'nin hücresel ve moleküler düzeydeki anlaşılan etkilerinin olası mekanizmaları tartışılarak, daha fazla açıklığa kavuşturulması gereken çoklu mekanizmaların olabileceği vurgulanmıştır. KD’nin terapötik etkileri ve etki mekanizmalarına dair bilimsel veriler yetersiz olup, KD'nin klinik uygulamasının yaygınlaştırılabilmesi için daha fazla çalışmaya ihtiyaç duyulmaktadır.

Anahtar Kelimeler

ketojenik diyet, yağ, karbonhidrat, keton

Destekleyen Kurum

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Proje Numarası

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Teşekkür

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Ketogenic Nutrition and Health

Öz

The ketogenic diet (KD) is a high-fat, adequate-protein and very low-carb diet regimen that simulates/mimics the metabolism of the fasting state to stimulate the production of ketone bodies. KD has long stood out as a highly successful dietary approach for the treatment of epilepsy. According to the latest data, the therapeutic effect of KD seems promising for many diseases such as cancer, diabetes, obesity as well as epilepsy. Given the widespread practice of this diet, even among individuals who do not need to lose weight, there is some concern about the potential long-term consequences of widespread adoption of this diet by large sections of the population. In this review, prominent concepts related to KD and the KD are expressed, and experimental and/or clinical data on the efficacy and safety of KD in different diseases are summarized. The possible mechanisms of the understood effects of KD at the cellular and molecular level were discussed, emphasizing that there may be multiple mechanisms that need further clarification. Scientific data on the therapeutic effects and mechanisms of action of KD are insufficient, and more studies are required in order to expand the clinical application of KD.

Anahtar Kelimeler

ketogenic diet, fat, carbs, ketone

Proje Numarası

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Kaynakça

• Abbasi, J. (2018). Interest in the ketogenic diet grows for weight loss and type 2 diabetes. JAMA, 319(3), 215-217.
• Al-Khalifa, A., Mathew, T. C., Al-Zaid, N. S., Mathew, E., & Dashti, H. M. (2009). Therapeutic role of low-carbohydrate ketogenic diet in diabetes. Nutrition, 25(11-12), 1177-1185.
• American Diabetes Association. (2017). 2. Classification and diagnosis of diabetes. Diabetes Care, 40(Suppl. 1), S11-S24.
• Annalisa, N., Alessio, T., Claudette, T. D., Erald, V., Antonino, D. L., Nicola, D. D. (2014). Gut microbioma population: an indicator really sensible to any change in age, diet, metabolic syndrome, and life-style. Mediators of Inflammation, Article ID 901308, 1-11.
• Augustin, K., Khabbush, A., Williams, S., Eaton, S., Orford, M., Cross, J. H., ve ark. (2018). Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. The Lancet Neurology, 17(1), 84-93.
• Boison, D. (2017). New insights into the mechanisms of the ketogenic diet. Current Opinion in Neurology, 30(2), 187.
• Brinkworth, G. D., Noakes, M., Clifton, P. M., & Bird, A. R. (2009). Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations. British Journal of Nutrition, 101(10), 1493-1502.
• Brouns, F. (2018). Overweight and diabetes prevention: is a low-carbohydrate-high-fat diet recommendable? European Journal of Nutrition, 57(4), 1301-1312.
• Cervenka, M. C., Henry, B. J., Felton, E. A., Patton, K., & Kossoff, E. H. (2016). Establishing an adult epilepsy diet center: experience, efficacy and challenges. Epilepsy & Behavior, 58, 61-68.
• Choi, H. R., Kim, J., Lim, H. & Park, Y. K. (2018). Two-week exclusive supplementation of modified ketogenic nutrition drink reserves lean body mass and improves blood lipid profile in obese adults: a randomized clinical trial. Nutrients, 10(12), 1895.
• Choragiewicz, T., Zarnowska, I., Gasior, M., & Zarnowski, T. (2010). Anticonvulsant and neuroprotective effects of the ketogenic diet. Przeglad Lekarski, 67(3), 205-212.
• Cohen, C. W., Fontaine, K. R., Arend, R. C., Alvarez, R. D., Leath III, C. A., Huh, W. K., Bevis, K. S., Kim, K. H., Straughn, J. M. & Gower, B. A. (2018a). A ketogenic diet reduces central obesity and serum insulin in women with ovarian or endometrial cancer. The Journal of Nutrition, 148(8), 1253-1260.
• Cohen, C. W., Fontaine, K. R., Arend, R. C., Soleymani, T. & Gower, B. A. (2018b). Favorable effects of a ketogenic diet on physical function, perceived energy, and food cravings in women with ovarian or endometrial cancer: a randomized, controlled trial. Nutrients, 10(9), 1187.
• D’Andrea Meira, I., Romão, T. T., Pires do Prado, H. J., Krüger, L. T., Pires, M. E. P. & da Conceição, P. O. (2019). Ketogenic diet and epilepsy: what we know so far. Frontiers in Neuroscience, 13, 5.
• Dashti, H. M., Mathew, T. C., Hussein, T., Asfar, S. K., Behbahani, A., Khoursheed, M. A., ve ark. (2004). Long-term effects of a ketogenic diet in obese patients. Experimental & Clinical Cardiology, 9(3), 200.
• Dashti, H. M., Mathew, T. C., Khadada, M., Al-Mousawi, M., Talib, H., Asfar, S. K., ve ark. (2007). Beneficial effects of ketogenic diet in obese diabetic subjects. Molecular and Cellular Biochemistry, 302(1), 249-256.
• De Git, K. C. G., & Adan, R. A. H. (2015). Leptin resistance in diet‐induced obesity: the role of hypothalamic inflammation. Obesity Reviews, 16(3), 207-224.
• Drabińska, N., Wiczkowski, W., & Piskuła, M. K. (2021). Recent advances in the application of a ketogenic diet for obesity management. Trends in Food Science & Technology. 110, 28-38.
• El‐Rashidy, O. F., Nassar, M. F., Abdel‐Hamid, I. A., Shatla, R. H., Abdel‐Hamid, M. H., Gabr, S. S. ve ark. (2013). Modified Atkins diet vs classic ketogenic formula in intractable epilepsy. Acta Neurologica Scandinavica, 128(6), 402-408.
• EUFIC, The European Food Information Council (2012). New Insights into Nutrition Labelling in Europe. http://www.eufic.org/article/en/artid/ New-insights-into-nutrition-labelling-in-Europe/.
• Fine, E. J., Segal-Isaacson, C. J., Feinman, R. D., Herszkopf, S., Romano, M. C., Tomuta, N. ve ark. (2012). Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition, 28(10), 1028-1035.
• Fraser, D. A., Thoen, J., Bondhus, S., Haugen, M., Reseland, J. E., Dioseland, O. ve ark. (2000). Reduction in serum leptin and IGF-1 but preserved T-lymphocyte numbers and activation after a ketogenic diet in rheumatoid arthritis patients. Clinical and Experimental Rheumatology, 18(2), 209-214.
• Freeman, J. M., & Kossoff, E. H. (2010). Ketosis and the ketogenic diet, 2010: advances in treating epilepsy and other disorders. Advances in Pediatrics, 57(1), 315-329.
• Furukawa, K., Shigematus, K., Iwase, Y., Mikami, W., Hoshi, H., Nishiyama, T. ve ark. (2018). Clinical effects of one year of chemotherapy with a modified medium-chain triglyceride ketogenic diet on the recurrence of stage IV colon cancer. Journal of Clinical Oncology, 36(Suppl. 15), e15709-e15709.
• Gardner, C. D., Trepanowski, J. F., Del Gobbo, L. C., Hauser, M. E., Rigdon, J., Ioannidis, J. P. ve ark. (2018). Effect of low-fat vs low-carbohydrate diet on 12-month weight loss in overweight adults and the association with genotype pattern or insulin secretion: the DIETFITS randomized clinical trial. JAMA, 319(7), 667-679.
• Gershuni, V. M., Yan, S. L., & Medici, V. (2018). Nutritional ketosis for weight management and reversal of metabolic syndrome. Current Nutrition Reports, 7(3), 97-106.
• Gudzune, K. A., Doshi, R. S., Mehta, A. K., Chaudhry, Z. W., Jacobs, D. K., Vakil, R. M., ve ark. (2015). Efficacy of commercial weight-loss programs: an updated systematic review. Annals of Internal Medicine, 162(7), 501-512.
• Hall, K. D., Chen, K. Y., Guo, J., Lam, Y. Y., Leibel, R. L., Mayer, L. E. ve ark. (2016). Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men. The American Journal of Clinical Nutrition, 104(2), 324-333.
• Hall, K. D., Guo, J., Courville, A. B., Boring, J., Brychta, R., Chen, K. Y. ve ark. (2021). Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake. Nature Medicine, 27(2), 344-353.
• Hallberg, S. J., McKenzie, A. L., Williams, P. T., Bhanpuri, N. H., Peters, A. L., Campbell, W. W. ve ark. (2018). Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study. Diabetes Therapy, 9(2), 583-612.
• Holt, S. H., Miller, J. C., & Petocz, P. (1997). An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods. The American Journal of Clinical Nutrition, 66(5), 1264-1276.
• Hopkins, B. D., Pauli, C., Du, X., Wang, D. G., Li, X., Wu, D., ve ark. (2018). Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature, 560(7719), 499-503.
• Hussain, T. A., Mathew, T. C., Dashti, A. A., Asfar, S., Al-Zaid, N., & Dashti, H. M. (2012). Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition, 28(10), 1016-1021.
• Jin, R., Hao, J., Yi, Y., Yin, D., Hua, Y., Li, X. ve ark. (2021). Dietary Fats High in Linoleic Acids Impair Antitumor T-cell Responses by Inducing E-FABP–Mediated Mitochondrial Dysfunction. Cancer Research, 81(20), 5296-5310.
• Joshi, S., Ostfeld, R. J., & McMacken, M. (2019). The ketogenic diet for obesity and diabetes-enthusiasm outpaces evidence. JAMA Internal Medicine, 179(9), 1163-1164.
• Kenig, S., Petelin, A., Vatovec, T. P., Mohorko, N., & Jenko-Pražnikar, Z. (2019). Assessment of micronutrients in a 12-wk ketogenic diet in obese adults. Nutrition, 67, 110522, 67–68.
• Khodabakhshi, A., Akbari, M. E., Mirzaei, H. R., Seyfried, T. N., Kalamian, M., & Davoodi, S. H. (2021). Effects of Ketogenic metabolic therapy on patients with breast cancer: A randomized controlled clinical trial. Clinical Nutrition, 40(3), 751-758.
• Kinzig, K. P., Honors, M. A., Hargrave, S. L., Davenport, B. M., Strader, A. D., & Wendt, D. (2010). Sensitivity to the anorectic effects of leptin is retained in rats maintained on a ketogenic diet despite increased adiposity. Neuroendocrinology, 92(2), 100-111.
• Klement, R. J. (2017). Beneficial effects of ketogenic diets for cancer patients: a realist review with focus on evidence and confirmation. Medical Oncology, 34(8), 1-15.
• Kong, C., Yan, X., Liu, Y., Huang, L., Zhu, Y., He, J., ve ark. (2021). Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome. Signal Transduction and Targeted Therapy, 6(1), 1-12. Kossoff, E. H., & Dorward, J. L. (2008). The modified Atkins diet. Epilepsia, 49, 37-41.
• Kossoff, E. H., Zupec‐Kania, B. A., Amark, P. E., Ballaban‐Gil, K. R., Christina Bergqvist, A. G., Blackford, R., ve ark. (2009a). Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia, 50(2), 304-317.
• Kossoff, E. H., Zupec-Kania, B. A., & Rho, J. M. (2009b). Ketogenic diets: an update for child neurologists. Journal of Child Neurology, 24(8), 979-988.
• Kossoff, E. H., & Hartman, A. L. (2012). Ketogenic diets: new advances for metabolism-based therapies. Current Opinion in Neurology, 25(2), 173.
• Krikorian, R., Shidler, M. D., Dangelo, K., Couch, S. C., Benoit, S. C., & Clegg, D. J. (2012). Dietary ketosis enhances memory in mild cognitive impairment. Neurobiology of Aging, 33(2), 425-e19-425.e27.
• Linkner, E., Humphreys, C. (2018). Chapter 32 - insulin resistance and the metabolic syndrome David Rakel (Ed.), Integrative Medicine (4th ed.), Elsevier, pp. 320-333.e5 ISBN: 9780323358682
• Liśkiewicz, A., Jędrzejowska-Szypułka, H., & Lewin-Kowalik, J. (2012). Characteristics of ketogenic diet and its therapeutic properties in central nervous system disorders. In Annales Academiae Medicae Silesiensis (Vol. 6, No. 66, pp. 66-76).
• Liu, Y. M., & Wang, H. S. (2013). Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets. Biomedical Journal, 36(1), 9-15.
• Longo, R., Peri, C., Cricrì, D., Coppi, L., Caruso, D., Mitro, N., ve ark. (2019). Ketogenic diet: a new light shining on old but gold biochemistry. Nutrients, 11(10), 2497.
• Ludwig, D. S. (2020). The ketogenic diet: evidence for optimism but high-quality research needed. The Journal of Nutrition, 150(6), 1354-1359.
• Magee, B. A., Potezny, N., Rofe, A. M., & Conyers, R. A. (1979). The inhibition of malignant cell growth by ketone bodies. Australian Journal of Experimental Biology and Medical Science, 57(5), 529-539.
• Mansoor, N., Vinknes, K. J., Veierød, M. B., & Retterstøl, K. (2016). Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. British Journal of Nutrition, 115(3), 466-479.
• Ministrini, S., Calzini, L., Nulli Migliola, E., Ricci, M. A., Roscini, A. R., Siepi, D., ve ark. (2019). Lysosomal acid lipase as a molecular target of the very low carbohydrate ketogenic diet in morbidly obese patients: the potential effects on liver steatosis and cardiovascular risk factors. Journal of Clinical Medicine, 8(5), 621
• Miranda, M. J., Turner, Z. & Magrath, G. (2012). Alternative diets to the classical ketogenic diet-Can we be more liberal?. Epilepsy Research, 100(3), 278-285.
• Morscher, R. J., Aminzadeh-Gohari, S., Feichtinger, R. G., Mayr, J. A., Lang, R., Neureiter, D., ve ark. (2015). Inhibition of neuroblastoma tumor growth by ketogenic diet and/or calorie restriction in a CD1-Nu mouse model. PloS One, 10(6), e0129802, 1-19.
• Morscher, R. J., Aminzadeh-Gohari, S., Hauser-Kronberger, C., Feichtinger, R. G., Sperl, W., & Kofler, B. (2016). Combination of metronomic cyclophosphamide and dietary intervention inhibits neuroblastoma growth in a CD1-nu mouse model. Oncotarget, 7(13), 17060-17073.
• Olson, C. A., Iñiguez, A. J., Yang, G. E., Fang, P., Pronovost, G. N., Jameson, K. G., ve ark. (2021). Alterations in the gut microbiota contribute to cognitive impairment induced by the ketogenic diet and hypoxia. Cell Host & Microbe, 29(9), 1378-1392.
• Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018). The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell, 173(7), 1728-1741.
• Paoli, A. (2014). Ketogenic diet for obesity: friend or foe? International Journal of Environmental Research and Public Health, 11(2), 2092-2107.
• Paoli, A., Rubini, A., Volek, J. S., & Grimaldi, K. A. (2013). Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition, 67(8), 789-796.
• Phillips, M. C., Deprez, L. M., Mortimer, G., Murtagh, D. K., McCoy, S., Mylchreest, R., ve ark. (2021). Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer's Research & Therapy, 13(1), 1-12.
• Poff, A. M., Ari, C., Seyfried, T. N., & D’Agostino, D. P. (2013). The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer. PloS One, 8(6), e65522.
• Poff, A. M., Ward, N., Seyfried, T. N., Arnold, P., & D’Agostino, D. P. (2015). Non-toxic metabolic management of metastatic cancer in VM mice: novel combination of ketogenic diet, ketone supplementation, and hyperbaric oxygen therapy. PloS One, 10(6), e0127407.
• Prasoppokakorn, T., Jirasakuldej, S. & Lakananurak, N. (2019). Medium-chain triglyceride ketogenic diet is effective for treatment of an adult with super-refractory status epilepticus: a case report and literature review. European Journal of Clinical Nutrition, 73(12), 1594-1597.
• Rafiullah, M., Musambil, M., & David, S. K. (2022). Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: a meta-analysis. Nutrition Reviews, 80(3), 488-502.
• Rezaei, S., Harsini, S., Kavoosi, M., Badv, R. S., & Mahmoudi, M. (2018). Efficacy of low glycemic index treatment in epileptic patients: a systematic review. Acta Neurologica Belgica, 118(3), 339-349.
• Ristic, B., Bhutia, Y. D., & Ganapathy, V. (2017). Cell-surface G-protein-coupled receptors for tumor-associated metabolites: A direct link to mitochondrial dysfunction in cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1868(1), 246-257.
• Roberts, M. N., Wallace, M. A., Tomilov, A. A., Zhou, Z., Marcotte, G. R., Tran, D., ve ark. (2017). A ketogenic diet extends longevity and healthspan in adult mice. Cell Metabolism, 26(3), 539-546.
• Rusek, M., Pluta, R., Ułamek-Kozioł, M., & Czuczwar, S. J. (2019). Ketogenic diet in Alzheimer’s disease. International Journal of Molecular Sciences, 20(16), 3892
• Santos, J. G., Da Cruz, W. M. S., Schönthal, A. H., Salazar, M., Fontes, C. A. P., Quirico‑Santos, T., & Da Fonseca, C. O. (2018). Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma. Oncology Letters, 15(1), 1263-1270.
• Seyfried, T. N., Sanderson, T. M., El-Abbadi, M. M., McGowan, R., & Mukherjee, P. (2003). Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. British Journal of Cancer, 89(7), 1375-1382.
• Shang, S., Wang, L., Zhang, Y., Lu, H., & Lu, X. (2018). The beta-hydroxybutyrate suppresses the migration of glioma cells by inhibition of NLRP3 inflammasome. Cellular and Molecular Neurobiology, 38(8), 1479-1489.
• Sharman, M. J., Kraemer, W. J., Love, D. M., Avery, N. G., Gómez, A. L., Scheett, T. P., & Volek, J. S. (2002). A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. The Journal of Nutrition, 132(7), 1879-1885.
• Singh, A., & Trevick, S. (2016). The epidemiology of global epilepsy. Neurologic Clinics, 34(4), 837-847. Stemmer, K., Zani, F., Habegger, K. M., Neff, C., Kotzbeck, P., Bauer, M., ve ark. (2015). FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice. Diabetologia, 58(10), 2414-2423.
• Sumithran, P., & Proietto, J. (2008). Ketogenic diets for weight loss: a review of their principles, safety and efficacy. Obesity Research & Clinical Practice, 2(1), 1-13.
• Sumithran, P., Prendergast, L. A., Delbridge, E., Purcell, K., Shulkes, A., Kriketos, A., & Proietto, J. (2013). Ketosis and appetite-mediating nutrients and hormones after weight loss. European Journal of Clinical Nutrition, 67(7), 759-764.
• Taylor, M. K., Sullivan, D. K., Mahnken, J. D., Burns, J. M., & Swerdlow, R. H. (2018). Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 4, 28-36.
• VanItallie, T. B., & Nufert, T. H. (2003). Ketones: metabolism's ugly duckling. Nutrition Reviews, 61(10), 327-341.
• Weber, D. D., Aminzadeh-Gohari, S., Tulipan, J., Catalano, L., Feichtinger, R. G., & Kofler, B. (2020). Ketogenic diet in the treatment of cancer–where do we stand?. Molecular Metabolism, 33, 102-121.
• Wilder, R. M. (1921). The effects of ketonemia on the course of epilepsy. In Mayo Clinic Proceedings (Vol. 2, pp. 307-308).
• Xie, G., Zhou, Q., Qiu, C. Z., Dai, W. K., Wang, H. P., Li, Y. H., ve ark. (2017). Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy. World Journal of Gastroenterology, 23(33), 6164.
• Yuan, X., Wang, J., Yang, S., Gao, M., Cao, L., Li, X., ve ark. (2020). Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis. Nutrition & Diabetes, 10(1), 1-8.
• Zare, M., Okhovat, A. A., Esmaillzadeh, A., Mehvari, J., Najafi, M. R., & Saadatnia, M. (2017). Modified Atkins diet in adult with refractory epilepsy: a controlled randomized clinical trial. Iranian Journal of Neurology, 16(2), 72.
• Zhang, Y., Zhou, S., Zhou, Y., Yu, L., Zhang, L., & Wang, Y. (2018). Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Research, 145, 163-168.
• Zhou, W., Mukherjee, P., Kiebish, M. A., Markis, W. T., Mantis, J. G., & Seyfried, T. N. (2007). The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutrition & Metabolism, 4(1), 1-15.
• Zhu, H., Bi, D., Zhang, Y., Kong, C., Du, J., Wu, X., ve ark. (2022). Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations. Signal Transduction and Targeted Therapy, 7(1), 1-21.