Table 1.
Characteristics of Included studies
| Study | Country | Study Design | Number and type of patients | Diagnostic criteria for inclusion | Study groups | Intervention dose | Duration of intervention | Plasma beta-hydroxybutyrate measurement method | Cognitive measures |
|---|---|---|---|---|---|---|---|---|---|
| Fortier 2019 | Canada | RCT | 52 with MCI | Subjective memory complaint, MoCA, MMSE | MCTs (C8:C10 ≈ 3:2) vs Placebo | 30gr/d | 6 months | colorimetric assay using an automated clinical chemistry analyzer (Dimension XPand Plus, Dade Behring Inc., Newark, DE) | MMSE, MoCA, 16 item free and cued word learning and recall, Trail Making Test, Stroop Test, Verbal Fluency, Digit Symbol Substitut ion, Boston Naming Test |
| Ota part A (2019) | Japan | RCT | 20 with mild/moderate AD | NINCDS-ADRDA | MCTs (C8:C10 ≈ 3:1) vs Placebo | 20gr/d | 2 days | enzymatic method at SRL Corp. (Tokyo) | WAIS III, WMS-R, Stroop test, Trail Making Test |
| Chan (2017) | Malaysia | RCT | 41 with mild/moderate/ severe AD | MMSE | Coconut oil (C8:C10 NR) vs Placebo | 60 ml/d* | 6 months | NA | MMSE, Clock drawing test |
| Rebello (2015) | USA | RCT | 6 with MCI | National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. | MCTS (C 8:C10 ≈ 5:4) vs Placebo | 56gr/day | 6 months | NR | ADAS-Cog, Trail Making Test Digit Symbol Test |
| Yang (2015) | Spain | RCT | 44 with AD | Institutionalized AD patients (unclear diagnostic criteria) | Coconut oil (C8:C10 ≈ 5:1) vs placebo | 40 ml/d | 3 weeks | NA | MMSE (Spanish version) |
| Henderson (2009) | USA | RCT | 152 with mild/moderate AD | NINCDS-ADRDA and DSM-IV criterial | MCTs (C8) vs Placebo | 20 gr/d | 3 months | method Allied Research International (formerly SFBC) of Miami, FL using the BHB Liquicolor diagnostic kit supplied by Stanbio Laboratories (Boenre, TX)] | MMSE, ADAS-Cog |
| Reger (2006) | USA | RCT | 20 with probable AD or amnestic MCI | NINCDS-ADRDA criteria | MCTs vs (C8) Placebo | 40 ml | 2 days | enzymatically, using procedure 310-UV (Sigma Diagnostics, Inc.) | MMSE, ADAS-cog, Stroop Test, Paragraph recall |
| Ota part B* (2019) | Japan | 1 arm trial | 19 with mild/moderate AD | NINCDS-ADRDA criteria | MCTs (C8:C10 ≈ 3:1) | 20gr/d | 3 months | enzymatic method at SRL Corp. (Tokyo) | WAIS III, WMS-R, Stroop test, Trail Making Test |
| Taylor (2017) | USA | 1 arm trial | 10 with very mild/mild/moderate AD | National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. | MCTs + low carb/high fat diet (C8:C10 ≈ 5:3) | 22.5 - 45 ml/d | 3 months | NR | MMSE ADAS-Cog |
| Ohnuma (2016) | Japan | 1 arm trial | 20 with moderate/ severe AD | NINCDS-ADRDA | MCTs (C8 = 50%; C10 % NR) | 20gr/d | 3 months | ELISA using buffer solution and reaction reagent for total ketone bodies (Kainos Laboratories Inc, Tokyo, Japan). The procedure was performed according to the manufacturer’s protocol using the BioMajesty™ system (JCA-BM8000; JEOL, Tokyo, Japan) at SRL Inc (Tokyo, Japan) | MMSE, ADAS-Cog |
| Maynart (2013) | USA | Case series | 55 with probable mild/moderate AD | MMSE | MCTs (C8) | 20 gr/d | 18.8 ± 9.2 months | NA | MMSE |
| Newport (2015) | USA | Case report | Young-onset sporadic AD | Clinical diagnosis, MMSE scores, MRI, Apoe4 carriage | MCTs + coconut oil (4:3 ratio); C8:C9 NR | 165 ml/d | 2.5 months | Precision Xtra Glucose and Ketone Monitoring System* (Abbott) | MMSE, ADAS-Cog |
| Farah (2014) | USA | Case report | Probable AD | MMSE, MoCA, FDG PET | MCTs (C8) | 20 gr/dl | ~ 3 months | NA | MMSE, MoCA |
MCI, Mild Cognitive Impairment; AD, Alzheimer’s Disease; MCTs, Medium Chain Triglycerides; WAIS, Wechsler Adult Intelligence Scale; WMS-R, Wechsler Memory Scale-Revised; MMSE, Mini Mental State Examination; ADAS-Cog, Alzheimer’s Dis. Assessment Scale-cognitive subscale; MoCA, Montreal Cognitive Assessment Scale. NINCDS-ADRDA, National Institute of Neurological and Communicative Disease and Stroke and the Alzheimer’s Disease and Related Disorder Association; NA, Not Applicable; NR, Not Reported; FDG PET, fluorodeoxyglucose (18F) positron emission tomography; C8, caprylic acid; C10, capric acid