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Dr. Peter Brukner OAM6 min read

Show me the evidence: Low carb and Alzheimer's

Three clinical trials have been published looking at the relationship between Alzheimers Disease and low carb or ketogenic diet.

A single arm study examined the impact of a 12-week ketogenic diet in 15 AD patients The 11 completers improved their cognitive scores, but the lack of a control group meant that additional contributing factors could not be ruled out.

Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimers Dement (N Y). 2017;4:28-36. doi:10.1016/j.trci.2017.11.002 A second ongoing randomized controlled trial has provided preliminary data on the impact of a 12-week Modified Atkins diet versus a recommended diet in 14 patients with mild cognitive impairment or AD. The most adherent patients improved their memory scores, but overall adherence was only fair, and function did not improve.

Brandt J, Buchholz A, Henry-Barron B, Vizthum D, Avramopoulos D, Cervenka M. Preliminary report on the feasibility and efficacy of the modified Atkins diet for treatment of mild cognitive impairment and early Alzheimer’s disease. J Alzheimers Dis. 2019;68:969–81.

The most recent and best designed trial was a single-phase, assessor-blinded, two-period randomized crossover trial conducted at Waikato Hospital, a tertiary hospital in Hamilton, New Zealand. 26 patients were randomized to a modified ketogenic diet (intervention diet) or their usual diet supplemented with low-fat healthy-eating guidelines and optional recipes (control diet). The crossover design specified two 12-week treatment periods separated by a 10-week washout period during which patients resumed their usual diet. For each treatment period, assessments were made at baseline, week 6, and week 12. Subjects showed non-significant improvement n cognition, and clinically significant improvements in daily function and quality of life. Adherence to the diet was very good and there were minimal side-effects from the diet.

Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer’s Research & Therapy. 2021;13(1):51. doi:10.1186/s13195-021-00783-x

There have also been a number of other papers published on this topic.

Reviews, Perspectives and Mechanisms

  1. Lilamand M, Porte B, Cognat E, Hugon J, Mouton-Liger F, Paquet C. Are ketogenic diets promising for Alzheimer’s disease? A translational review. Alzheimer’s Research & Therapy. 2020;12(1):42. doi:10.1186/s13195-020-00615-4
  2. Rusek M, Pluta R, Ułamek-Kozioł M, Czuczwar SJ. Ketogenic Diet in Alzheimer’s Disease. International Journal of Molecular Sciences. 2019;20(16):3892. doi:10.3390/ijms20163892
  3. Pinto A, Bonucci A, Maggi E, Corsi M, Businaro R. Anti-Oxidant and Anti-Inflammatory Activity of Ketogenic Diet: New Perspectives for Neuroprotection in Alzheimer’s Disease. Antioxidants (Basel). 2018;7(5). doi:10.3390/antiox7050063
  4. Cunnane SC, Courchesne-Loyer A, Vandenberghe C, et al. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease. Front Mol Neurosci. 2016;9:53. doi:10.3389/fnmol.2016.00053
  5. Więckowska-Gacek A, Mietelska-Porowska A, Wydrych M, Wojda U. Western diet as a trigger of Alzheimer’s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration. Ageing Research Reviews. Published online June 30, 2021:101397. doi:10.1016/j.arr.2021.101397
  6. Taylor MK, Swerdlow RH, Sullivan DK. Dietary Neuroketotherapeutics for Alzheimer’s Disease: An Evidence Update and the Potential Role for Diet Quality. Nutrients. 2019;11(8):1910. doi:10.3390/nu11081910
  7. Norwitz NG, Saif N, Ariza IE, Isaacson RS. Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers. Nutrients. 2021;13(4). doi:10.3390/nu13041362
  8. Rhea EM, Raber J, Banks WA. ApoE and cerebral insulin: Trafficking, receptors, and resistance. Neurobiology of Disease. 2020;137:104755. doi:10.1016/j.nbd.2020.104755
  9. Berlanga-Acosta J, Guillén-Nieto G, Rodríguez-Rodríguez N, et al. Insulin Resistance at the Crossroad of Alzheimer Disease Pathology: A Review. Front Endocrinol. 2020;11. doi:10.3389/fendo.2020.560375

Trials/Case Studies

  1. Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer’s Research & Therapy. 2021;13(1):51. doi:10.1186/s13195-021-00783-x
  2. 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
  3. Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimers Dement (N Y). 2017;4:28-36. doi:10.1016/j.trci.2017.11.002
  4. Toups K, Hathaway A, Gordon D, et al. Precision Medicine Approach to Alzheimer’s Disease: Successful Proof-of-Concept Trial. medRxiv. Published online May 11, 2021:2021.05.10.21256982. doi:10.1101/2021.05.10.21256982
  5. Taylor MK, Swerdlow RH, Burns JM, Sullivan DK. An Experimental Ketogenic Diet for Alzheimer Disease Was Nutritionally Dense and Rich in Vegetables and Avocado. Curr Dev Nutr. 2019;3(4):nzz003. doi:10.1093/cdn/nzz003
  6. Krikorian R, Shidler MD, Dangelo K, Couch SC, Benoit SC, Clegg DJ. Dietary ketosis enhances memory in mild cognitive impairment. Neurobiol Aging. 2012;33(2):425.e19-425.e27. doi:10.1016/j.neurobiolaging.2010.10.006 PDF
  7. Stoykovich S, Gibas K. APOE ε4, the door to insulin-resistant dyslipidemia and brain fog? A case study. Alzheimers Dement (Amst). 2019;11:264-269. doi:10.1016/j.dadm.2019.01.009
  8. Horner S, Berger L, Gibas K. Nutritional Ketosis and photobiomodulation remediate mitochondria warding off Alzheimer’s disease in a diabetic, ApoE4+ patient with mild cognitive impairment: A case report. Photodiagnosis Photodyn Ther. Published online April 16, 2020:101777. doi:10.1016/j.pdpdt.2020.101777
  9. Newport MT, VanItallie TB, Kashiwaya Y, King MT, Veech RL. A new way to produce hyperketonemia: Use of ketone ester in a case of Alzheimer’s disease. Alzheimer’s & Dementia. 2015;11(1):99-103. doi:10.1016/j.jalz.2014.01.006 PDF
  10. Brandt J, Buchholz A, Henry-Barron B, Vizthum D, Avramopoulos D, Cervenka M. Preliminary report on the feasibility and efficacy of the modified Atkins diet for treatment of mild cognitive impairment and early Alzheimer’s disease. J Alzheimers Dis. 2019;68:969–81.

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