TABLE 2.
Overview of studies evaluating a ketogenic diet in patients with MS: the results1
| Author (year) | EDSS score | Quality of life | Fatigue | Depression | Anthropometric measures | Biomarkers | Other findings or comments |
|---|---|---|---|---|---|---|---|
| Choi et al. (2016) (17) | Mildly yet significantly improved at 3 and 6 mo | Clinically meaningful improvement in MSQOL-54 at 3 mo | Not reported (assessed using MFIS)2 | Not reported (assessed using BDI)2 | Not reported2 | Slight reduction in lymphocyte and WBC counts | ▪ High compliance rate (90%)▪ Adverse events (KD/FMD/control group): respiratory tract infection (n = 12/7/9), diarrhea (n = 3/0/3), headache (n = 2/2/0), nausea (n = 2/0/0), ureteric colic (n = 1/0/0), urinary tract infection (n = 1/2/1)▪ One relapse in KD group during 6-mo study period (4 in control diet group, 3 in FMD group) |
| Swidsinski et al. (2017) (24) | Not reported | Not reported | Not reported | Not reported | Not reported | Dynamic changes in colonic microbiome | The effects of KD on colonic microbiome were biphasic. Bacterial concentrations and diversity were further reduced from baseline initially, then they started to recover at week 12 |
| Bock et al. (2018) (22) | Expression of all target genes showed statistically nonsignificant trend for positive correlation with the EDSS score | ALOX5 and COX1 expression were inversely correlated with MSQOL-54 at 6 mo | Not reported | Not reported | Improved BMI (P = 0.008) | No significant effects on fasting blood sugar and insulin | ▪ Target genes in this study were those coding for biosynthetic enzymes for proinflammatory (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids▪ Significant increase in serum BHB (mean 1.44 mmol/L) |
| Nathan et al. (2019) (25) | EDSS score deterioration (6.0 → 7.5) after stopping KD, and improving after resumption of KD | No formal assessment was reported | Not reported | Not reported | BW decreased from 67.1 to 65 kg and maintained (= his ideal BW) | CSF-specific OCBs remained positive | Disease activity (EDSS) apparently correlated with use/discontinuation/resumption of KD |
| Benlloch et al. (2019) (27) | Not reported | Not reported | Not reported | Not reported | Significant increase in lean mass and decrease in fat mass | ▪ Ghrelin: no significant change▪ Paraoxonase 1 (an antioxidant marker): significant increase | ▪ Significant satiating effect (decreased hunger perception)▪ Significant yet modest increase in serum BHB (mean 0.10 mmol/L after the 4-mo intervention) |
| Brenton et al. (2019) (3) | Significant decrease in EDSS score at 6 mo | Not reported | Patient-reported fatigue (MFIS) improved (P = 0.002) | Patient-reported depression scores (BDI) improved (P = 0.003) | Reductions in BMI and total fat mass (P < 0.0001) | ▪ Leptin: significantly lower at 3 mo (P < 0.0001)▪ Adiponectin: no significant change▪ Insulin and hemoglobin A1c: significantly decreased | ▪ Adherence rate: 95% at 3 mo and 75% at 6 mo▪ Reported side effects included intermittent constipation (n = 5, 25%), menstrual irregularities (n = 4, 20%), and diarrhea (n = 3, 15%)▪ No new lesion on brain MRI at 6 mo |
| Lee et al. (2021) (21) | No clinically significant change | No significant change in MSQOL-54 | No significant change in perceived fatigue (MFIS) | Not reported | Not reported2 | Reduction in fasting blood sugar and insulin | Maximal mean plasma BHB was 1.48 ± 1.10 mmol/L (at 4 wk); ketosis was maintained (>0.5 mmol/L) at 8 and 12 wk |
| Bock et al. (2022) (23) | Not reported2 | Not reported | Not reported | Not reported | Not reported2 | Significant reduction in sNfL at 6 mo | ▪ One relapse in KD group during study period (3 in control diet group, 2 in FMD group)▪ A single cycle of FMD (7-d fasting) did not affect sNfL |
1
ALOX, arachidonate lipoxygenase; BDI, Beck Depression Inventory; BHB, β-hydroxybutyrate; BW, body weight; COX, cyclooxygenase; CSF, cerebrospinal fluid; EDSS, Expanded Disability Status Scale; FMD, fasting mimicking diet; KD, ketogenic diet; MFIS, Modified Fatigue Impact Scale; MSQOL-54, Multiple Sclerosis Quality of Life-54 questionnaire; OCB, oligoclonal band; sNfL, serum neurofilament light chain; WBC, white blood cell.
2
Only baseline data were reported.