Ketogenic strategies for Alzheimer’s disease and other memory impairments: History, rationale, and 288 caregiver case reports
Main Article Content
Abstract
Glucose hypometabolism predates Alzheimer’s disease symptoms by at least one to two decades. Ketones are an alternative fuel to glucose and are taken up normally in affected regions of the Alzheimer’s brain and could address certain pathologies that are common in the aging brain and exaggerated in Alzheimer’s disease including insulin resistance, a brain-energy deficit, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Ketones have also been shown to reduce formation of beta-amyloid plaques and neurofibrillary tangles in animal models. Experts have estimated that at least 30 percent of Alzheimer’s and other dementias could be avoided by adopting a healthy diet, increasing physical activity, and correcting other modifiable lifestyle risk factors. Mild to moderate ketosis can be achieved through consumption of a healthy whole food low-carbohydrate ketogenic diet, ketogenic oils containing medium-chain triglycerides, or exogenous ketone supplements as well as intermittent or overnight fasting, and moderately vigorous aerobic exercise. An analysis was performed of 288 anecdotal reports about people with Alzheimer’s, other dementias, Parkinson’s disease with dementia, mild cognitive impairment, and other diagnosed or subjective memory impairments consuming coconut oil and/or medium-chain triglyceride oil. Improvement was reported by 89.2 percent, no improvement by 7.3 percent, and no improvement but stabilization for at least 3 months by 2.4 percent. One or more improvements were reported in the areas of memory/cognition (65.3%), social/behavior/ mood/personality (32.6%), speech/language/conversation (33%), resumption of self-care/other activities (24.7%), physical symptoms (18.4%), sleep (3.5%), appetite (2.4%), vision (1.4%), and improvement that was otherwise unspecified (8%). Certain fatty acids found in medium-chain triglyceride oil and coconut oil are ketogenic but also have other important biological effects which, along with polyphenols and other bioactive substances in virgin coconut oil, could explain these results. Adopting a personalized ketogenic lifestyle plan using one or more ketogenic strategies could address certain pathological processes that occur in the aging brain while potentially improving symptoms in people with Alzheimer’s disease. In addition, this approach could possibly prevent or delay the onset of cognitive impairment during aging, though larger long-term studies would be needed to confirm this.
Keywords:
Alzheimer, memory impairments, review, caregiver case reports, Ketogenic strategies for Alzheimer’s disease
Article Details
How to Cite
NEWPORT, Mary T..
Ketogenic strategies for Alzheimer’s disease and other memory impairments: History, rationale, and 288 caregiver case reports.
Medical Research Archives, [S.l.], v. 12, n. 4, apr. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5316>. Date accessed: 26 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i4.5316.
Section
Case Reports
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Espay AJ, Sturchio A, Schneider LS, Ezzat K. Soluble Amyloid-β Consumption in Alzheimer's Disease. J Alzheimers Dis. 2021;8 2(4):1403-1415. doi: 10.3233/JAD-210415.
2. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One. 2010;5(3):e9505. doi: 10.1371/journal. pone.0009505.
3. Kumar DK, Eimer WA, Tanzi RE, Moir RD. Alzheimer's disease: the potential therapeutic role of the natural antibiotic amyloid-β peptide. Neurodegener Dis Manag. 2016;6(5) :345-8. doi: 10.2217/nmt-2016-0035.
4. Itzhaki RF, Lathe R, Balin BJ, et al. Microbes and Alzheimer's Disease. J Alzheimers Dis. 20 16;51(4):979-84. doi: 10.3233/JAD-160152.
5. Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9): 609-633. doi: 10.1038/s41573-020-0072-x.
6. Palmer CM, Gilbert-Jaramillo J, Westman EC. The ketogenic diet and remission of psychotic symptoms in schizophrenia: Two case studies. Schizophr Res. 2019;208:439-440. doi: 10.1016/j.schres.2019.03.019.
7. Höhn S, Dozières-Puyravel B, Auvin S. History of dietary treatment from Wilder's hypothesis to the first open studies in the 1920s. Epilepsy Behav. 2019;101(Pt A):10658 8. doi: 10.1016/j.yebeh.2019.106588.
8. Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018;3(2):175-192. doi: 10.1002/epi4.12225.
9. Dyńka D, Kowalcze K, Paziewska A. The Role of Ketogenic Diet in the Treatment of Neurological Diseases. Nutrients. 2022;14(23) :5003. doi: 10.3390/nu14235003.
10. Weber DD, Aminzadeh-Gohari S, Tulipan J, Catalano L, Feichtinger RG, Kofler B. Ketogenic diet in the treatment of cancer - Where do we stand? Mol Metab. 2020;33:102 -121. doi: 10.1016/j.molmet.2019.06.026.
11. Dyńka D, Kowalcze K, Charuta A, Paziewska A. The Ketogenic Diet and Cardiovascular Diseases. Nutrients. 2023;15(1 5):3368. doi: 10.3390/nu15153368.
12. Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015;31( 1):1-13. doi: 10.1016/j.nut.2014.06.011.
13. Hallberg SJ, McKenzie AL, Williams PT, et al. 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 Ther. 2018;9(2):583-612. doi: 10.1007/s13300 -018-0373-9.
14. Stoykovich S, Gibas K. APOE ε4, the door to insulin-resistant dyslipidemia and brain fog? A case study. Alzheimers Dement (Amst). 201 9;11:264-269. doi: 10.1016/j.dadm.2019.01.009.
15. Morrill SJ, Gibas KJ. Ketogenic diet rescues cognition in ApoE4+ patient with mild Alzheimer's disease: A case study. Diabetes Metab Syndr. 2019;13(2):1187-1191. doi: 10.1 016/j.dsx.2019.01.035.
16. Evert AB, Dennison M, Gardner CD, et al. Nutrition Therapy for Adults with Diabetes or Prediabetes: A Consensus Report. Diabetes Care. 2019;42(5):731-754. doi: 10.2337/dci19-0014.
17. Lennerz BS, Barton A, Bernstein RK, et al. Management of Type 1 Diabetes with a Very Low-Carbohydrate Diet. Pediatrics. 2018;141( 6):e20173349. doi: 10.1542/peds.2017-3349.
18. Sato K, Kashiwaya Y, Keon CA, Tsuchiya N, King MT, Radda GK, Chance B, Clarke K, Veech RL. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. 1995;9(8):651-8. doi: 10.1096/fasebj.9.8.7768357.
19. Kashiwaya Y, King MT, Veech RL. Substrate signaling by insulin: a ketone bodies ratio mimics insulin action in heart. Am J Cardiol. 1997;80(3A):50A-64A. doi: 10.1016/s 0002-9149(97)00458-x.
20. Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL. D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proc Natl Acad Sci U S A. 2000;97(10):5440-4. doi: 10.1073/pnas.97.10.5440.
21. Costantini LC, Barr LJ, Vogel JL, Henderson ST. Hypometabolism as a therapeutic target in Alzheimer's disease. BMC Neurosci. 2008;9 Suppl 2(Suppl 2):S16. doi: 10.1186/1471-2202-9-S2-S16.
22. Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill GF Jr. Ketone bodies, potential therapeutic uses. IUBMB Life. 2001;51(4):241-7. doi:10.1080/152165401753311780. PMID: 11569918.
23. Cahill GF Jr, Veech RL. Ketoacids? Good medicine? Trans Am Clin Climatol Assoc. 2003;114:149-61; discussion 162-3. https://pubmed.ncbi.nlm.nih.gov/12813917/
24. VanItallie TB, Nufert TH. Ketones: metabolism's ugly duckling. Nutr Rev. 2003;6 1(10):327-41. doi: 10.1301/nr.2003.oct.327-341.
25. Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids. 2004;70(3):309-19. doi: 10.1016/j.plefa.2003.09.007. PMID: 14769489.
26. Kashiwaya Y, Bergman C, Lee JH, 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):1530-9. doi: 10.1016/j.neur obiolaging.2012.11.023.
27. Wu Y, Gong Y, Luan Y, et al. BHBA treatment improves cognitive function by targeting pleiotropic mechanisms in transgenic mouse model of Alzheimer's disease. FASEB J. 2020;34(1):1412-1429. doi: 10.1096/fj.201901984R.
28. Yin JX, Maalouf M, Han P, et al. Ketones block amyloid entry and improve cognition in an Alzheimer's model. Neurobiol Aging. 2016 ;39:25-37. doi: 10.1016/j.neurobiolaging.2015.11.018.
29. Youm YH, Nguyen KY, Grant RW, et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015 Mar;21( 3):263-9. doi: 10.1038/nm.3804.
30. Shippy DC, Wilhelm C, Viharkumar PA, Raife TJ, Ulland TK. β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer's disease pathology. J Neuroinflammation. 2020;17(1):280. doi: 10.1 186/s12974-020-01948-5.
31. Xiao YL, Gong Y, Qi YJ, Shao ZM, Jiang YZ. Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential. Signal Transduct Target Ther. 2024;9(1):59. doi: 10.1038/s41392-024-01771-x.
32. Xu Y, Zheng F, Zhong Q, Zhu Y. Ketogenic diet as a promising non-drug intervention for Alzheimer's disease: Mechanisms and clinical implications. J Alzheimers Dis. 2023;92(4):1173-1198. doi: 10.3233/JAD-230002.
33. Rusek M, Pluta R, Ułamek-Kozioł M, Czuczwar SJ. Ketogenic diet in Alzheimer's disease. Int J Mol Sci. 2019;20(16):3892. doi: 10.3390/ijms20163892.
34. Castro CB, Dias CB, Hillebrandt H, et al. Medium-chain fatty acids for the prevention or treatment of Alzheimer's disease: a systematic review and meta-analysis. Nutr Rev. 2023;81(9 ):1144-1162. doi: 10.1093/nutrit/nuac104.
35. Sun L, Ye KX, Wong HLK, et al. The effects of medium chain triglyceride for Alzheimer's disease related cognitive impairment: A systematic review and meta-analysis. J Alzheimers Dis. 2023;94(2):441-456. doi: 10.3233/JAD-230406.
36. Price S, Ruppar TM. Ketogenic therapies in Parkinson's disease, Alzheimer's disease, and mild cognitive impairment: An integrative review. Appl Nurs Res. 2023;74:151745. doi: 10.1016/j.apnr.2023.151745.
37. Bohnen JLB, Albin RL, Bohnen NI. Ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease: A systematic review and critical appraisal. Front Neurol. 2023 Feb 9;14:11232 90. doi: 10.3389/fneur.2023.1123290.
38. Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely FJS, Lynch CDP. Low-fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial. Mov Disord. 2018 Aug;33(8):1306-1314. doi: 10.1002/mds.2739 0. Epub 2018 Aug 11.
39. Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease. Alzheimers Res Ther. 2021;13(1):51. doi: 10.1 186/s13195-021-00783-x.
40. Castellano CA, Paquet N, Dionne IJ, et al. A 3-month aerobic training program improves brain energy metabolism in mild Alzheimer's disease: Preliminary results from a neuroimaging study. J Alzheimers Dis. 2017;56(4):1459-146 8. doi: 10.3233/JAD-161163.
41. Abe S, Ezaki O, Suzuki M. Medium-chain triglycerides in combination with leucine and vitamin d benefit cognition in frail elderly adults: A randomized controlled trial. J Nutr Sci Vitaminol (Tokyo). 2017;63(2):133-140. doi: 10.3177/jnsv.63.133.
42. Abe S, Ezaki O, Suzuki M. Medium-chain triglycerides in combination with leucine and vitamin d increase muscle strength and function in frail elderly adults in a randomized controlled trial. J Nutr. 2016;146(5):1017-26. doi: 10.3945/jn.115.228965.
43. Abe S, Ezaki O, Suzuki M. Medium-chain triglycerides (8:0 and 10:0) increase Mini-Mental State Examination (MMSE) score in frail elderly adults in a randomized controlled trial. J Nutr. 2020 Sep 1;150(9):2383-2390. doi: 10.1093/jn/nxaa186.
44. Fortier M, Castellano CA, St-Pierre V, et al. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimers Dement. 2021;17(3):5 43-552. doi: 10.1002/alz.12206.
45. Roy M, Rheault F, Croteau E, et al. Fascicle- and glucose-specific deterioration in white matter energy supply in Alzheimer's disease. J Alzheimers Dis. 2020;76(3):863-881. doi: 10.3233/JAD-200213.
46. Roy M, Edde M, Fortier M, et al. A ketogenic intervention improves dorsal attention network functional and structural connectivity in mild cognitive impairment. Neurobiol Aging. 2022;115:77-87. doi:10.101 6/j.neurobiolaging.2022.04.005.
47. Myette-Côté É, St-Pierre V, Beaulieu S, et al. The effect of a 6-month ketogenic medium-chain triglyceride supplement on plasma cardiometabolic and inflammatory markers in mild cognitive impairment. Prostaglandins Leukot Essent Fatty Acids. 2021;169:102236. doi: 10.1016/j.plefa.2020.102236.
48. Fernando MG, Silva R, Fernando WMADB, et al. Effect of virgin coconut oil supplementation on cognition of individuals with mild-to-moderate Alzheimer's disease in Sri Lanka (VCO-AD Study): A randomized placebo-controlled trial. J Alzheimers Dis. 2023;96(3):1195-1206. doi: 10.3233/JAD-230670.
49. St-Pierre V, Vandenberghe C, Lowry CM, Fortier M, Castellano CA, Wagner R, Cunnane SC. Plasma Ketone and Medium Chain Fatty Acid Response in Humans Consuming Different Medium Chain Triglycerides During a Metabolic Study Day. Front Nutr. 2019 Apr 16;6:46. doi: 10.3389/fnut.2019.00046. PMID: 31058159; PMCID: PMC6481320.
50. Likhodii SS, Burnham WM. Ketogenic diet: does acetone stop seizures? Med Sci Monit. 2002;8(8):HY19-24. https://medscimonit.com/abstract/index/idArt/13550. PMID: 12165751.
51. Stonnington CM, Chen Y, Savage CR, et al. Predicting imminent progression to clinically significant memory decline using volumetric MRI and FDG PET. J Alzheimers Dis. 2018;63( 2):603-615. doi: 10.3233/JAD-170852.
52. Reiman EM, Chen K, Alexander GE, et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci U S A. 2004;101( 1):284-9. doi: 10.1073/pnas.2635903100.
53. de la Monte SM, Wands JR. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease. J Alzheimers Dis. 2005;7( 1):45-61. doi: 10.3233/jad-2005-7106.
54. de la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol. 2008;2(6):1101-13. doi: 10.1177/193229680800200619.
55. Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P. Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease. Ann Neurol. 1994;35(5):5 46-51. doi: 10.1002/ana.410350507.
56. Jia D, Wang F, Yu H. Systemic alterations of tricarboxylic acid cycle enzymes in Alzheimer's disease. Front Neurosci. 2023;17: 1206688. doi: 10.3389/fnins.2023.1206688.
57. Castellano CA, Nugent S, Paquet N, et al. Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer's disease dementia. J Alzheimers Dis. 2015;43(4):1343-53. doi: 10.3233/JAD-141074.
58. 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. Alzheimers Dement. 2015;11(1):99-103. doi: 10.1016/j.jalz.2014.01.006.
59. USDA FoodData Central (usda.gov) https://fdc.nal.usda.gov/
60. Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent cognitive impairment, dementia, and Alzheimer disease. Nat Rev Neurol. 2018;14(11):653-666 . doi: 10.1038/s41582-018-0070-3.
61. Norwitz NG, Jaramillo JG, Clarke K, Soto A. Ketotherapeutics for neurodegenerative diseases. Int Rev Neurobiol. 2020;155:141-168. doi: 10.1016/bs.irn.2020.02.003.
62. Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity, and brain health. Nat Rev Neurosci. 2018;19(2):63-80. doi: 10.1038/nrn.2017.156.
63. Watanabe S and Tsujino S. Applications of Medium-Chain Triglycerides in Foods. Front. Nutr. 2022;9:802805. doi: 10.3389/fnut .2022.802805
64. Blackburn GL, Babayan VK. Infant feeding formulas using coconut oil and the medium chain triglycerides. J Am Coll Nutr. 1989;8(3): 253-4. doi: 10.1080/07315724.1989.10720300.
65. Hamosh M, Bitman J, Wood L, Hamosh P, Mehta NR. Lipids in milk and the first steps in their digestion. Pediatrics. 1985;75(1 Pt 2):146-50. PMID: 3880885.
66. Gutiérrez-García AG, Contreras CM, Díaz-Marte C. Myristic acid in amniotic fluid produces appetitive responses in human newborns. Early Hum Dev. 2017;115:32-37. doi: 10.1016/j.earlhumdev.2017.08.009.
67. Cunnane SC, Menard CR, Likhodii SS, Brenna JT, Crawford MA. Carbon recycling into de novo lipogenesis is a major pathway in neonatal metabolism of linoleate and alpha-linolenate. Prostaglandins Leukot Essent Fatty Acids. 1999;60(5-6):387-92. doi: 10.1016/s09 52-3278(99)80018-0.
68. Augustin K, Khabbush A, Williams S, Eaton S, Orford M, Cross JH, Heales SJR, Walker MC, Williams RSB. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. Lancet Neurol. 2018;17(1):84-93. doi: 10.1016/S1474-4422(17)30408-8.
69. Andersen JV, Westi EW, Neal ES, Aldana BI, Borges K. β-Hydroxybutyrate and medium-chain fatty acids are metabolized by different cell types in mouse cerebral cortex slices. Neurochem Res. 2023;48(1):54-61. doi: 10.1007/s11064-022-03726-6.
70. Nonaka Y, Takagi T, Inai M, Nishimura S, Urashima S, Honda K, Aoyama T, Terada S. Lauric acid stimulates ketone body production in the KT-5 astrocyte cell line. J Oleo Sci. 2016;65(8):693-9. doi: 10.5650/jos.ess16069.
71. Itzhaki RF, Lathe R, Balin BJ, et al. Microbes and Alzheimer's Disease. J Alzheimers Dis. 2016;51(4):979-84. doi: 10.3233/JAD-160152.
72. Goc A, Niedzwiecki A, Rath M. In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii. J Appl Microbiol. 2015;119(6):1561-72. doi: 10.1111/jam.12970.
73. Kabara JJ, Swieczkowski DM, Conley AJ, Truant JP. Fatty acids and derivatives as antimicrobial agents. Antimicrob Agents Chemother. 1972 Jul;2(1):23-8. doi: 10.1128/ AAC.2.1.23. PMID: 4670656; PMCID: PMC444260.
74. Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31(1):27-31. doi: 10. 1128/AAC.31.1.27.
75. Dayrit, F.M. The properties of lauric acid and their significance in coconut oil. J Am Oil Chem Soc 2015; 92:1-15 (2015). https://doi.org/10.1007/s11746-014-2562-7 .
76. Dodge JA, Sagher FA. Antiviral and antibacterial lipids in human milk and infant formula. Arch Dis Child. 1991;66(2):272-3. doi: 10.1136/adc.66.2.272-b.
77. Currenti W, Godos J, Alanazi AM, Lanza G, Ferri R, Caraci F, Grosso G, Galvano F, Castellano S. Dietary fats and cognitive status in Italian middle-old adults. Nutrients. 2023;15(6):1429. doi:10.3390/nu15061429.
78. Mett J, Lauer AA, Janitschke D, et al. Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme. Cells. 2021;10(11):2941. doi: 10.3390/cells10112941.
79. Nishimura Y, Moriyama M, Kawabe K, Satoh H, Takano K, Azuma YT, Nakamura Y. Lauric acid alleviates neuroinflammatory responses by activated microglia: Involvement of the GPR40-dependent pathway. Neurochem Res. 2018;43(9):1723-1735. doi: 10.1007/s11064-018-2587-7.
80. Shaheryar ZA, Khan MA, Hameed H, Mushtaq MN, Muhammad S, Shazly GA, Irfan A, Jardan YAB. Natural fatty acid guards against brain endothelial cell death and microvascular pathology following ischemic insult in the presence of acute hyperglycemia. Biomedicines. 2023;11(12):3342. doi:10.3390 /biomedicines11123342.
81. Chatterjee P, Fernando M, Fernando B, et al. Potential of coconut oil and medium chain triglycerides in the prevention and treatment of Alzheimer's disease. Mech Ageing Dev. 2020;186:111209. doi: 10.1016/j.mad.2020.111209.
82. Illam SP, Narayanankutty A, Raghavamenon AC. Polyphenols of virgin coconut oil prevent pro-oxidant mediated cell death. Toxicol Mech Methods. 2017;27(6):442 -450. doi: 10.1080/15376516.2017.1320458.
83. Nafar F, Clarke JP, Mearow KM. Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways. Neurochem Int. 2017;105:6 4-79. doi: 10.1016/j.neuint.2017.01.008.
84. Nafar F, Mearow KM. Coconut oil attenuates the effects of amyloid-β on cortical neurons in vitro. J Alzheimers Dis. 2014;39(2):233-7. doi: 10.3233/JAD-131436.
85. Neelakantan N, Seah JYH, van Dam RM. The effect of coconut oil consumption on cardiovascular risk factors: A systematic review and meta-analysis of clinical trials. Circulation. 2020;141(10):803-814. doi: 10.1161/CIRCULATIONAHA.119.043052.
86. Assunção ML, Ferreira HS, dos Santos AF, Cabral CR Jr, Florêncio TM. Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity. Lipids. 2009;44:593–601. doi:10.1007/s11745-009-3306-6
87. Vijayakumar M, Vasudevan DM, Sundaram KR, Krishnan S, Vaidyanathan K, Nandakumar S, Chandrasekhar R, Mathew N. A randomized study of coconut oil versus sunflower oil on cardiovascular risk factors in patients with stable coronary heart disease. Indian Heart J. 2016;68:498–506. doi:10.1016 /j.ihj.2015.10.384
88. Korrapati D, Jeyakumar SM, Putcha UK, Mendu VR, Ponday LR, Acharya V, Koppala SR, Vajreswari A. Coconut oil consumption improves fat-free mass, plasma HDL-cholesterol and insulin sensitivity in healthy men with normal BMI compared to peanut oil. Clin Nutr. 2019;38:2889– 2899. doi:10.1016/j. clnu.2018.12.026.
89. Reiser R, Probstfield JL, Silvers A, Scott LW, Shorney ML, Wood RD, O’Brien BC, Gotto AM Jr, Insull W Jr. Plasma lipid and lipoprotein response of humans to beef fat, coconut oil and safflower oil. Am J Clin Nutr. 1985;42:190–197. doi:10.1093/ajcn/42.2.190
90. Mendis S, Kumarasunderam R. The effect of daily consumption of coconut fat and soya-bean fat on plasma lipids and lipoproteins of young normolipidaemic men. Br J Nutr. 1990;63:547–552. doi:10.1079/bjn19900141
91. Heber D, Ashley JM, Solares ME, Wang HJ, Alfin-Slater RB. The effects of a palm-oil enriched diet on plasma lipids and lipoproteins in healthy young men. Nutr Res. 1992;12:S53-S59. doi:10.1016/S0271-5317(0 5)80450-6.
92. McKenney JM, Proctor JD, Wright JT Jr, Kolinski RJ, Elswick RK Jr, Coaker JS. The effect of supplemental dietary fat on plasma cholesterol levels in lovastatin-treated hypercholesterolemic patients. Pharmacotherapy. 1995;15:565–572. doi:10.1002/j.1875-9114.1 995.tb02864.
93. Lu Z, Hendrich S, Shen N, White PJ, Cook LR. Low linolenate and commercial soybean oils diminish serum HDL cholesterol in young free-living adult females. J Am Coll Nutr. 1997;16:562–569. PMID: 9430084.
94. Voon PT, Ng TK, Lee VK, Nesaretnam K. Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults. Am J Clin Nutr. 2011;94:1451-1457. doi:10.3945/ajcn.111.020107.
95. Harris M, Hutchins A, Fryda L. The impact of virgin coconut oil and higholeic safflower oil on body composition, lipids, and inflammatory markers in postmenopausal women. J Med Food. 2017;20:345–351. doi: 10.1089/jmf.2016.0114
96. Khaw KT, Sharp SJ, Finikarides L, Afzal I, Lentjes M, Luben R, Forouhi NG. Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women. BMJ Open. 2018;8: e020167. doi:10.1136/bmjopen-2017-020167
97. Oliveira-de-Lira L, Santos EMC, de Souza RF, Matos RJB, Silva MCD, Oliveira LDS, Nascimento TGD, Schemly P, Souza SL. Supplementationdependent effects of vegetable oils with varying fatty acid compositions on anthropometric and biochemical parameters in obese women. Nutrients. 2018;20:E932. doi:10.3390/nu10070932.
98. Maki KC, Hasse W, Dicklin MR, Bell M, Buggia MA, Cassens ME, Eren F. Corn oil lowers plasma cholesterol compared with coconut oil in adults with above-desirable levels of cholesterol in a randomized crossover trial. J Nutr. 2018;148:1556–1563. doi:10.1093/jn/nxy156
99. McKenzie KM, Lee CM, Mijatovic J, Haghighi MM, Skilton MR. Medium-chain triglyceride oil and blood lipids: A systematic review and meta-analysis of randomized trials. J Nutr. 2021;151(10):2949-2956. doi: 10.1093 /jn/nxab220.
2. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One. 2010;5(3):e9505. doi: 10.1371/journal. pone.0009505.
3. Kumar DK, Eimer WA, Tanzi RE, Moir RD. Alzheimer's disease: the potential therapeutic role of the natural antibiotic amyloid-β peptide. Neurodegener Dis Manag. 2016;6(5) :345-8. doi: 10.2217/nmt-2016-0035.
4. Itzhaki RF, Lathe R, Balin BJ, et al. Microbes and Alzheimer's Disease. J Alzheimers Dis. 20 16;51(4):979-84. doi: 10.3233/JAD-160152.
5. Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9): 609-633. doi: 10.1038/s41573-020-0072-x.
6. Palmer CM, Gilbert-Jaramillo J, Westman EC. The ketogenic diet and remission of psychotic symptoms in schizophrenia: Two case studies. Schizophr Res. 2019;208:439-440. doi: 10.1016/j.schres.2019.03.019.
7. Höhn S, Dozières-Puyravel B, Auvin S. History of dietary treatment from Wilder's hypothesis to the first open studies in the 1920s. Epilepsy Behav. 2019;101(Pt A):10658 8. doi: 10.1016/j.yebeh.2019.106588.
8. Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018;3(2):175-192. doi: 10.1002/epi4.12225.
9. Dyńka D, Kowalcze K, Paziewska A. The Role of Ketogenic Diet in the Treatment of Neurological Diseases. Nutrients. 2022;14(23) :5003. doi: 10.3390/nu14235003.
10. Weber DD, Aminzadeh-Gohari S, Tulipan J, Catalano L, Feichtinger RG, Kofler B. Ketogenic diet in the treatment of cancer - Where do we stand? Mol Metab. 2020;33:102 -121. doi: 10.1016/j.molmet.2019.06.026.
11. Dyńka D, Kowalcze K, Charuta A, Paziewska A. The Ketogenic Diet and Cardiovascular Diseases. Nutrients. 2023;15(1 5):3368. doi: 10.3390/nu15153368.
12. Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015;31( 1):1-13. doi: 10.1016/j.nut.2014.06.011.
13. Hallberg SJ, McKenzie AL, Williams PT, et al. 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 Ther. 2018;9(2):583-612. doi: 10.1007/s13300 -018-0373-9.
14. Stoykovich S, Gibas K. APOE ε4, the door to insulin-resistant dyslipidemia and brain fog? A case study. Alzheimers Dement (Amst). 201 9;11:264-269. doi: 10.1016/j.dadm.2019.01.009.
15. Morrill SJ, Gibas KJ. Ketogenic diet rescues cognition in ApoE4+ patient with mild Alzheimer's disease: A case study. Diabetes Metab Syndr. 2019;13(2):1187-1191. doi: 10.1 016/j.dsx.2019.01.035.
16. Evert AB, Dennison M, Gardner CD, et al. Nutrition Therapy for Adults with Diabetes or Prediabetes: A Consensus Report. Diabetes Care. 2019;42(5):731-754. doi: 10.2337/dci19-0014.
17. Lennerz BS, Barton A, Bernstein RK, et al. Management of Type 1 Diabetes with a Very Low-Carbohydrate Diet. Pediatrics. 2018;141( 6):e20173349. doi: 10.1542/peds.2017-3349.
18. Sato K, Kashiwaya Y, Keon CA, Tsuchiya N, King MT, Radda GK, Chance B, Clarke K, Veech RL. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. 1995;9(8):651-8. doi: 10.1096/fasebj.9.8.7768357.
19. Kashiwaya Y, King MT, Veech RL. Substrate signaling by insulin: a ketone bodies ratio mimics insulin action in heart. Am J Cardiol. 1997;80(3A):50A-64A. doi: 10.1016/s 0002-9149(97)00458-x.
20. Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL. D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proc Natl Acad Sci U S A. 2000;97(10):5440-4. doi: 10.1073/pnas.97.10.5440.
21. Costantini LC, Barr LJ, Vogel JL, Henderson ST. Hypometabolism as a therapeutic target in Alzheimer's disease. BMC Neurosci. 2008;9 Suppl 2(Suppl 2):S16. doi: 10.1186/1471-2202-9-S2-S16.
22. Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill GF Jr. Ketone bodies, potential therapeutic uses. IUBMB Life. 2001;51(4):241-7. doi:10.1080/152165401753311780. PMID: 11569918.
23. Cahill GF Jr, Veech RL. Ketoacids? Good medicine? Trans Am Clin Climatol Assoc. 2003;114:149-61; discussion 162-3. https://pubmed.ncbi.nlm.nih.gov/12813917/
24. VanItallie TB, Nufert TH. Ketones: metabolism's ugly duckling. Nutr Rev. 2003;6 1(10):327-41. doi: 10.1301/nr.2003.oct.327-341.
25. Veech RL. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids. 2004;70(3):309-19. doi: 10.1016/j.plefa.2003.09.007. PMID: 14769489.
26. Kashiwaya Y, Bergman C, Lee JH, 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):1530-9. doi: 10.1016/j.neur obiolaging.2012.11.023.
27. Wu Y, Gong Y, Luan Y, et al. BHBA treatment improves cognitive function by targeting pleiotropic mechanisms in transgenic mouse model of Alzheimer's disease. FASEB J. 2020;34(1):1412-1429. doi: 10.1096/fj.201901984R.
28. Yin JX, Maalouf M, Han P, et al. Ketones block amyloid entry and improve cognition in an Alzheimer's model. Neurobiol Aging. 2016 ;39:25-37. doi: 10.1016/j.neurobiolaging.2015.11.018.
29. Youm YH, Nguyen KY, Grant RW, et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015 Mar;21( 3):263-9. doi: 10.1038/nm.3804.
30. Shippy DC, Wilhelm C, Viharkumar PA, Raife TJ, Ulland TK. β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer's disease pathology. J Neuroinflammation. 2020;17(1):280. doi: 10.1 186/s12974-020-01948-5.
31. Xiao YL, Gong Y, Qi YJ, Shao ZM, Jiang YZ. Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential. Signal Transduct Target Ther. 2024;9(1):59. doi: 10.1038/s41392-024-01771-x.
32. Xu Y, Zheng F, Zhong Q, Zhu Y. Ketogenic diet as a promising non-drug intervention for Alzheimer's disease: Mechanisms and clinical implications. J Alzheimers Dis. 2023;92(4):1173-1198. doi: 10.3233/JAD-230002.
33. Rusek M, Pluta R, Ułamek-Kozioł M, Czuczwar SJ. Ketogenic diet in Alzheimer's disease. Int J Mol Sci. 2019;20(16):3892. doi: 10.3390/ijms20163892.
34. Castro CB, Dias CB, Hillebrandt H, et al. Medium-chain fatty acids for the prevention or treatment of Alzheimer's disease: a systematic review and meta-analysis. Nutr Rev. 2023;81(9 ):1144-1162. doi: 10.1093/nutrit/nuac104.
35. Sun L, Ye KX, Wong HLK, et al. The effects of medium chain triglyceride for Alzheimer's disease related cognitive impairment: A systematic review and meta-analysis. J Alzheimers Dis. 2023;94(2):441-456. doi: 10.3233/JAD-230406.
36. Price S, Ruppar TM. Ketogenic therapies in Parkinson's disease, Alzheimer's disease, and mild cognitive impairment: An integrative review. Appl Nurs Res. 2023;74:151745. doi: 10.1016/j.apnr.2023.151745.
37. Bohnen JLB, Albin RL, Bohnen NI. Ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease: A systematic review and critical appraisal. Front Neurol. 2023 Feb 9;14:11232 90. doi: 10.3389/fneur.2023.1123290.
38. Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely FJS, Lynch CDP. Low-fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial. Mov Disord. 2018 Aug;33(8):1306-1314. doi: 10.1002/mds.2739 0. Epub 2018 Aug 11.
39. Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease. Alzheimers Res Ther. 2021;13(1):51. doi: 10.1 186/s13195-021-00783-x.
40. Castellano CA, Paquet N, Dionne IJ, et al. A 3-month aerobic training program improves brain energy metabolism in mild Alzheimer's disease: Preliminary results from a neuroimaging study. J Alzheimers Dis. 2017;56(4):1459-146 8. doi: 10.3233/JAD-161163.
41. Abe S, Ezaki O, Suzuki M. Medium-chain triglycerides in combination with leucine and vitamin d benefit cognition in frail elderly adults: A randomized controlled trial. J Nutr Sci Vitaminol (Tokyo). 2017;63(2):133-140. doi: 10.3177/jnsv.63.133.
42. Abe S, Ezaki O, Suzuki M. Medium-chain triglycerides in combination with leucine and vitamin d increase muscle strength and function in frail elderly adults in a randomized controlled trial. J Nutr. 2016;146(5):1017-26. doi: 10.3945/jn.115.228965.
43. Abe S, Ezaki O, Suzuki M. Medium-chain triglycerides (8:0 and 10:0) increase Mini-Mental State Examination (MMSE) score in frail elderly adults in a randomized controlled trial. J Nutr. 2020 Sep 1;150(9):2383-2390. doi: 10.1093/jn/nxaa186.
44. Fortier M, Castellano CA, St-Pierre V, et al. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimers Dement. 2021;17(3):5 43-552. doi: 10.1002/alz.12206.
45. Roy M, Rheault F, Croteau E, et al. Fascicle- and glucose-specific deterioration in white matter energy supply in Alzheimer's disease. J Alzheimers Dis. 2020;76(3):863-881. doi: 10.3233/JAD-200213.
46. Roy M, Edde M, Fortier M, et al. A ketogenic intervention improves dorsal attention network functional and structural connectivity in mild cognitive impairment. Neurobiol Aging. 2022;115:77-87. doi:10.101 6/j.neurobiolaging.2022.04.005.
47. Myette-Côté É, St-Pierre V, Beaulieu S, et al. The effect of a 6-month ketogenic medium-chain triglyceride supplement on plasma cardiometabolic and inflammatory markers in mild cognitive impairment. Prostaglandins Leukot Essent Fatty Acids. 2021;169:102236. doi: 10.1016/j.plefa.2020.102236.
48. Fernando MG, Silva R, Fernando WMADB, et al. Effect of virgin coconut oil supplementation on cognition of individuals with mild-to-moderate Alzheimer's disease in Sri Lanka (VCO-AD Study): A randomized placebo-controlled trial. J Alzheimers Dis. 2023;96(3):1195-1206. doi: 10.3233/JAD-230670.
49. St-Pierre V, Vandenberghe C, Lowry CM, Fortier M, Castellano CA, Wagner R, Cunnane SC. Plasma Ketone and Medium Chain Fatty Acid Response in Humans Consuming Different Medium Chain Triglycerides During a Metabolic Study Day. Front Nutr. 2019 Apr 16;6:46. doi: 10.3389/fnut.2019.00046. PMID: 31058159; PMCID: PMC6481320.
50. Likhodii SS, Burnham WM. Ketogenic diet: does acetone stop seizures? Med Sci Monit. 2002;8(8):HY19-24. https://medscimonit.com/abstract/index/idArt/13550. PMID: 12165751.
51. Stonnington CM, Chen Y, Savage CR, et al. Predicting imminent progression to clinically significant memory decline using volumetric MRI and FDG PET. J Alzheimers Dis. 2018;63( 2):603-615. doi: 10.3233/JAD-170852.
52. Reiman EM, Chen K, Alexander GE, et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci U S A. 2004;101( 1):284-9. doi: 10.1073/pnas.2635903100.
53. de la Monte SM, Wands JR. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease. J Alzheimers Dis. 2005;7( 1):45-61. doi: 10.3233/jad-2005-7106.
54. de la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol. 2008;2(6):1101-13. doi: 10.1177/193229680800200619.
55. Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P. Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease. Ann Neurol. 1994;35(5):5 46-51. doi: 10.1002/ana.410350507.
56. Jia D, Wang F, Yu H. Systemic alterations of tricarboxylic acid cycle enzymes in Alzheimer's disease. Front Neurosci. 2023;17: 1206688. doi: 10.3389/fnins.2023.1206688.
57. Castellano CA, Nugent S, Paquet N, et al. Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer's disease dementia. J Alzheimers Dis. 2015;43(4):1343-53. doi: 10.3233/JAD-141074.
58. 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. Alzheimers Dement. 2015;11(1):99-103. doi: 10.1016/j.jalz.2014.01.006.
59. USDA FoodData Central (usda.gov) https://fdc.nal.usda.gov/
60. Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent cognitive impairment, dementia, and Alzheimer disease. Nat Rev Neurol. 2018;14(11):653-666 . doi: 10.1038/s41582-018-0070-3.
61. Norwitz NG, Jaramillo JG, Clarke K, Soto A. Ketotherapeutics for neurodegenerative diseases. Int Rev Neurobiol. 2020;155:141-168. doi: 10.1016/bs.irn.2020.02.003.
62. Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity, and brain health. Nat Rev Neurosci. 2018;19(2):63-80. doi: 10.1038/nrn.2017.156.
63. Watanabe S and Tsujino S. Applications of Medium-Chain Triglycerides in Foods. Front. Nutr. 2022;9:802805. doi: 10.3389/fnut .2022.802805
64. Blackburn GL, Babayan VK. Infant feeding formulas using coconut oil and the medium chain triglycerides. J Am Coll Nutr. 1989;8(3): 253-4. doi: 10.1080/07315724.1989.10720300.
65. Hamosh M, Bitman J, Wood L, Hamosh P, Mehta NR. Lipids in milk and the first steps in their digestion. Pediatrics. 1985;75(1 Pt 2):146-50. PMID: 3880885.
66. Gutiérrez-García AG, Contreras CM, Díaz-Marte C. Myristic acid in amniotic fluid produces appetitive responses in human newborns. Early Hum Dev. 2017;115:32-37. doi: 10.1016/j.earlhumdev.2017.08.009.
67. Cunnane SC, Menard CR, Likhodii SS, Brenna JT, Crawford MA. Carbon recycling into de novo lipogenesis is a major pathway in neonatal metabolism of linoleate and alpha-linolenate. Prostaglandins Leukot Essent Fatty Acids. 1999;60(5-6):387-92. doi: 10.1016/s09 52-3278(99)80018-0.
68. Augustin K, Khabbush A, Williams S, Eaton S, Orford M, Cross JH, Heales SJR, Walker MC, Williams RSB. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. Lancet Neurol. 2018;17(1):84-93. doi: 10.1016/S1474-4422(17)30408-8.
69. Andersen JV, Westi EW, Neal ES, Aldana BI, Borges K. β-Hydroxybutyrate and medium-chain fatty acids are metabolized by different cell types in mouse cerebral cortex slices. Neurochem Res. 2023;48(1):54-61. doi: 10.1007/s11064-022-03726-6.
70. Nonaka Y, Takagi T, Inai M, Nishimura S, Urashima S, Honda K, Aoyama T, Terada S. Lauric acid stimulates ketone body production in the KT-5 astrocyte cell line. J Oleo Sci. 2016;65(8):693-9. doi: 10.5650/jos.ess16069.
71. Itzhaki RF, Lathe R, Balin BJ, et al. Microbes and Alzheimer's Disease. J Alzheimers Dis. 2016;51(4):979-84. doi: 10.3233/JAD-160152.
72. Goc A, Niedzwiecki A, Rath M. In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii. J Appl Microbiol. 2015;119(6):1561-72. doi: 10.1111/jam.12970.
73. Kabara JJ, Swieczkowski DM, Conley AJ, Truant JP. Fatty acids and derivatives as antimicrobial agents. Antimicrob Agents Chemother. 1972 Jul;2(1):23-8. doi: 10.1128/ AAC.2.1.23. PMID: 4670656; PMCID: PMC444260.
74. Thormar H, Isaacs CE, Brown HR, Barshatzky MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31(1):27-31. doi: 10. 1128/AAC.31.1.27.
75. Dayrit, F.M. The properties of lauric acid and their significance in coconut oil. J Am Oil Chem Soc 2015; 92:1-15 (2015). https://doi.org/10.1007/s11746-014-2562-7 .
76. Dodge JA, Sagher FA. Antiviral and antibacterial lipids in human milk and infant formula. Arch Dis Child. 1991;66(2):272-3. doi: 10.1136/adc.66.2.272-b.
77. Currenti W, Godos J, Alanazi AM, Lanza G, Ferri R, Caraci F, Grosso G, Galvano F, Castellano S. Dietary fats and cognitive status in Italian middle-old adults. Nutrients. 2023;15(6):1429. doi:10.3390/nu15061429.
78. Mett J, Lauer AA, Janitschke D, et al. Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme. Cells. 2021;10(11):2941. doi: 10.3390/cells10112941.
79. Nishimura Y, Moriyama M, Kawabe K, Satoh H, Takano K, Azuma YT, Nakamura Y. Lauric acid alleviates neuroinflammatory responses by activated microglia: Involvement of the GPR40-dependent pathway. Neurochem Res. 2018;43(9):1723-1735. doi: 10.1007/s11064-018-2587-7.
80. Shaheryar ZA, Khan MA, Hameed H, Mushtaq MN, Muhammad S, Shazly GA, Irfan A, Jardan YAB. Natural fatty acid guards against brain endothelial cell death and microvascular pathology following ischemic insult in the presence of acute hyperglycemia. Biomedicines. 2023;11(12):3342. doi:10.3390 /biomedicines11123342.
81. Chatterjee P, Fernando M, Fernando B, et al. Potential of coconut oil and medium chain triglycerides in the prevention and treatment of Alzheimer's disease. Mech Ageing Dev. 2020;186:111209. doi: 10.1016/j.mad.2020.111209.
82. Illam SP, Narayanankutty A, Raghavamenon AC. Polyphenols of virgin coconut oil prevent pro-oxidant mediated cell death. Toxicol Mech Methods. 2017;27(6):442 -450. doi: 10.1080/15376516.2017.1320458.
83. Nafar F, Clarke JP, Mearow KM. Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways. Neurochem Int. 2017;105:6 4-79. doi: 10.1016/j.neuint.2017.01.008.
84. Nafar F, Mearow KM. Coconut oil attenuates the effects of amyloid-β on cortical neurons in vitro. J Alzheimers Dis. 2014;39(2):233-7. doi: 10.3233/JAD-131436.
85. Neelakantan N, Seah JYH, van Dam RM. The effect of coconut oil consumption on cardiovascular risk factors: A systematic review and meta-analysis of clinical trials. Circulation. 2020;141(10):803-814. doi: 10.1161/CIRCULATIONAHA.119.043052.
86. Assunção ML, Ferreira HS, dos Santos AF, Cabral CR Jr, Florêncio TM. Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity. Lipids. 2009;44:593–601. doi:10.1007/s11745-009-3306-6
87. Vijayakumar M, Vasudevan DM, Sundaram KR, Krishnan S, Vaidyanathan K, Nandakumar S, Chandrasekhar R, Mathew N. A randomized study of coconut oil versus sunflower oil on cardiovascular risk factors in patients with stable coronary heart disease. Indian Heart J. 2016;68:498–506. doi:10.1016 /j.ihj.2015.10.384
88. Korrapati D, Jeyakumar SM, Putcha UK, Mendu VR, Ponday LR, Acharya V, Koppala SR, Vajreswari A. Coconut oil consumption improves fat-free mass, plasma HDL-cholesterol and insulin sensitivity in healthy men with normal BMI compared to peanut oil. Clin Nutr. 2019;38:2889– 2899. doi:10.1016/j. clnu.2018.12.026.
89. Reiser R, Probstfield JL, Silvers A, Scott LW, Shorney ML, Wood RD, O’Brien BC, Gotto AM Jr, Insull W Jr. Plasma lipid and lipoprotein response of humans to beef fat, coconut oil and safflower oil. Am J Clin Nutr. 1985;42:190–197. doi:10.1093/ajcn/42.2.190
90. Mendis S, Kumarasunderam R. The effect of daily consumption of coconut fat and soya-bean fat on plasma lipids and lipoproteins of young normolipidaemic men. Br J Nutr. 1990;63:547–552. doi:10.1079/bjn19900141
91. Heber D, Ashley JM, Solares ME, Wang HJ, Alfin-Slater RB. The effects of a palm-oil enriched diet on plasma lipids and lipoproteins in healthy young men. Nutr Res. 1992;12:S53-S59. doi:10.1016/S0271-5317(0 5)80450-6.
92. McKenney JM, Proctor JD, Wright JT Jr, Kolinski RJ, Elswick RK Jr, Coaker JS. The effect of supplemental dietary fat on plasma cholesterol levels in lovastatin-treated hypercholesterolemic patients. Pharmacotherapy. 1995;15:565–572. doi:10.1002/j.1875-9114.1 995.tb02864.
93. Lu Z, Hendrich S, Shen N, White PJ, Cook LR. Low linolenate and commercial soybean oils diminish serum HDL cholesterol in young free-living adult females. J Am Coll Nutr. 1997;16:562–569. PMID: 9430084.
94. Voon PT, Ng TK, Lee VK, Nesaretnam K. Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults. Am J Clin Nutr. 2011;94:1451-1457. doi:10.3945/ajcn.111.020107.
95. Harris M, Hutchins A, Fryda L. The impact of virgin coconut oil and higholeic safflower oil on body composition, lipids, and inflammatory markers in postmenopausal women. J Med Food. 2017;20:345–351. doi: 10.1089/jmf.2016.0114
96. Khaw KT, Sharp SJ, Finikarides L, Afzal I, Lentjes M, Luben R, Forouhi NG. Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women. BMJ Open. 2018;8: e020167. doi:10.1136/bmjopen-2017-020167
97. Oliveira-de-Lira L, Santos EMC, de Souza RF, Matos RJB, Silva MCD, Oliveira LDS, Nascimento TGD, Schemly P, Souza SL. Supplementationdependent effects of vegetable oils with varying fatty acid compositions on anthropometric and biochemical parameters in obese women. Nutrients. 2018;20:E932. doi:10.3390/nu10070932.
98. Maki KC, Hasse W, Dicklin MR, Bell M, Buggia MA, Cassens ME, Eren F. Corn oil lowers plasma cholesterol compared with coconut oil in adults with above-desirable levels of cholesterol in a randomized crossover trial. J Nutr. 2018;148:1556–1563. doi:10.1093/jn/nxy156
99. McKenzie KM, Lee CM, Mijatovic J, Haghighi MM, Skilton MR. Medium-chain triglyceride oil and blood lipids: A systematic review and meta-analysis of randomized trials. J Nutr. 2021;151(10):2949-2956. doi: 10.1093 /jn/nxab220.