Table 1.
Characteristics of the included studies.
| First Author, Year, Country | Study Population & Type of Chronic Disease | Age; %Male | Duration | Intervention: Features of KD | Control | Isocaloric Diets (arms) | Co-intervention | Assessment of Ketosis | Assessment of QOL |
|---|---|---|---|---|---|---|---|---|---|
| Cancer | |||||||||
| Augustus, 2021, Trinidad and Tobago (Trinidad) [36] | Stages 2 and 3 cancer patients, receiving chemotherapy or radiation, nonvegetarian, on a CHO-based diet (>40%) I: n = 20; 16 completers C: n = 20; 20 completers |
Age: mean (SD): I: 49.80 ± 6.72 C: 51.80 ± 4.18 %Male: NR |
16 weeks | MKD: 7-day cyclic altered KD (≈10% CHO (50 g), 15% Protein (75 g), 75% Fat (167 g); 2000 Kcal); main source of Fat: MCT | Standard traditional diet | Not specified by study protocol | None | Urinary ketones: dip stick test and urine analyzer | EORTC QLQ-C30 |
| Cohen, 2018, Birmingham (USA) [42] | Women with ovarian or endometrial cancer, BMI ≥ 18.5 kg/m2 I: n = 37; 25 completers C: n = 36; 20 completers |
Age: mean (SD): I: 61.5 ± 8.5 C: 58.6 ± 11.7 %Male: 0% |
12 weeks | KD: 5% CHO (≤20 g); 25% Protein (≤100 g); 70% Fat (≤125 g) | ACS diet | Neither group was instructed to alter total energy intake | None | Serum BHB: SIRRUS analyzer Urinary ketones: strips |
SF-12 (PCS and MCS) |
| Khodabakhshi, 2020, Tehran (Iran) [40] | 80 women with locally advanced or metastatic breast cancer receiving chemotherapy for ≥12 weeks I: n = 40; 30 completers C: n = 40; 30 completers |
Age Range: 18–70 I: 44.8 ± 8.4 C: 45.2 ± 15.0 %Male: 0% |
12 weeks | 6% CHO, 19% Protein, 20% MCT, 55% Fat | 55% CHO, 15% Protein, 30% Fat | Both diets calculated to be eucaloric | None | Blood BHB: home kit | EORTC QLQ-C30 and EORTC QLQ-BR23 |
| Martin-McGill, 2020, United Kingdom [39] | 12 patients with glioblastoma planning to go temozolomide chemotherapy and radiotherapy MKD: n = 6; 1 completed 12 weeks; 1 completed 12 months MCTKD: n = 6; 3 completed 12 weeks; 2 completed 12 months |
Age Median: 57; Range: 44–66 %Male: 66.60% |
12 weeks 12 months |
I1: MKD: 5% CHO, 80% Fat, 15% Protein I2: MCTKD: 10% CHO, 75% Fat (30% from MCT nutrition product), 15% Protein |
None | Not specified by study protocol | None | Urinary ketones: dip stick test Blood ketones: home kit |
EORTC QLQ C30 and BN20 |
| Neurological disorders | |||||||||
| Lee, 2020, Iowa (USA) [43] | 15 patients with relapsing remitting multiple sclerosis or progressive relapsing-remitting multiple sclerosis (expanded disability status ≥ 4.5) KD: n = 5; 4 analyzed (1: insufficient data) MPD: n = 6 Usual diet: n = 4 |
Age Total: Range: 36–63 Mean (SD): 51.9 ± 9.5 KD: 51.8 ± 11.8 MPD: 50.3 ± 9.5 C: 54.5 ± 11.8 %Male: 50% |
12 weeks | MCT-based KD: ketogenic version of the modified Paleolithic diet with supplemental MCTs to achieve a daily goal of 70% of total Kcal from fat) | Modified Paleolithic diet C: Usual diet |
Not specified by study protocol | Pre-study vitamins, supplements, and/or medications | Plasma BHB: NR | Multiple Sclerosis Quality of Life-54 |
| Philips, 2021, Hamilton (New Zealand) [41] | 26 patients with Alzheimer diseases BMI > 18.5 kg/m2
Phase 1 KD: n = 13; 11 completers Usual diet: n = 13; 13 completers Phase 2 KD: n = 13; 10 completers Usual diet: n = 13; 13 completers |
Age Total: Range: 57–79 Mean (SD): 69.8 ± 6.0 KD > Usual diet: Range: 57–77 Mean(SD): 68.0 ± 5.4 Usual diet > KD: Range: 61–79 Mean(SD): 71.7 ± 6.2 %Male: Total: 62% KD > Usual diet: 77% Usual diet > KD: 46% |
12 weeks: I or C 10 weeks: washout |
58% Fat (26% SFA, 32% non-saturated), 29% Protein, 7% Fiber, 6% net CHO by weight | Usual diet 11% Fat (3% SFA, 8% non-saturated), 19% Protein, 8% Fiber, 62% net CHO by weight | Not specified by study protocol | Daily multivitamin | Serum BHB: ketone blood monitor | QOL-AD |
| Obesity and T2DM | |||||||||
| Brinkworth, 2016, Adelaide (Australia) [37] | Adults with T2DM (HbA1c ≥ 7.0% or taking a diabetes medication), overweight and obese (BMI: 26–45 kg/m2) I: n = 58; 41 completers C: n = 57; 37 completers |
Age Range: 35–68 Mean (SD) I: 58 ± 72 C: 58 ± 7 %Male: I: 64% C: 51% |
12 months | Very-low CHO, high-fat diet: 14% CHO (<50 g); 28% Protein, 58% Fat (35% MUFA, 13% PUFA, <10% SFA) | High-CHO, low-fat diet: 53% CHO; 17% Protein; <30% Fat (15% MUFA, 9% PUFA, <10% SFA) | For I and C: ∼30% energy restriction (500–1000 Kcal/day) | 60-min, moderate-intensity, exercise: 3 days/week | Plasma BHB: D-3 Hydroxybutyrate kit | Diabetes-39 |
| Durrer, 2021, Southern British Columbia (Canada) [38] | Adults with T2DM, using glucose-lowering medication, obese (BMI ≥ 30 kg/m2) I: n = 98; 78 completers (98 ITT) C: n = 90; 60 completers (90 ITT) |
Age: mean (SD): I: 58 ± 11 C: 59 ± 8 %Male: I: 44% C: 43% |
12 weeks | Low-CHO energy-restricted commercial weight loss plan supplemented with whole foods (<50 g CHO; 35–45 g Fat, 110–120 g Protein; 850–1100 Kcal) | Information conforming with 2013 Diabetes Canada Clinical Practice Guidelines | Not specified by study protocol | None | Capillary blood ketones: NR | SF-20 |
| Knee Osteoarthritis | |||||||||
| Strath, 2020, Birmingham (USA) [44] | 21 adults with knee osteoarthritis LCD: n = 8 LFD: n = 6 C: n = 7 |
Age Range: 65–75 Mean (SD) LCD: 71.00 ± 3.12 LFD: 72.33 ± 1.97 C: 68.71 ± 7.11 %Male: LCD: 60%; LFD: 75%; C: 80% (Completers: LCD: 60%; LFD: 100%; C: 75%) |
12 weeks | Kcal: unlimited; Fat: unlimited; CHO: 20 g; Proteins: 100 g | LFD: Kcal: 800–1200; Fat: 50–67 g; CHO: unlimited; Proteins: 100 g C: Kcal, Fat, CHO, Proteins: unlimited |
No | None | Not measured | Knee Injury and Osteoarthritis Outcome Score quality of life |
ACS: American Cancer Society; BHB: B-Hydroxybutyrate; BMI: Body mass index; C: Control; CHO: Carbohydrate; EORTC QLQ-C30: European Organization for Research and Treatment of Cancer current core; GHS: Global Health Status; HbA1c: Glycated hemoglobin; I: Intervention; ITT: Intention to treat; KD: Ketogenic diet; LCD: Low-carbohydrate diet; LFD: Low fat diet; MCS: Mental component summary; MCT: Medium chain triglycerides; MCTKD: Medium chain triglyceride ketogenic diet; MKD: Modified ketogenic diet; MPD: Modified Paleolithic diet; MUFA: Monounsaturated fatty acids; NR: Not reported; PCS: Physical component summary; PUFA: Polyunsaturated fatty acids; QOL: Quality of life; QOL-AD: Quality of Life in Alzheimer’s Disease; SD: Standard deviation; SF-12: Medical Outcomes Study Short Form-12 Health Survey; SF-20: Medical Outcomes Study Short Form-20 Health Survey; SFA: Saturated fatty acids; T2DM: Type 2 diabetes mellitus; WHO: World Health Organization.