TABLE 1.
Overview of studies evaluating a ketogenic diet in patients with MS: study design and execution1
| Author (year) | Study design | Dietary interventions | Supervision or coaching | Study participants | Age of study subjects, y | Other notes or comments |
|---|---|---|---|---|---|---|
| Choi et al. (2016) (17) | Randomized, parallel-group, 3-arm trial | Experimental groups: KD for 6 mo, or a single cycle of a modified FMD for 7 d followed by a Mediterranean diet for 6 mo. Comparator group: control diet | Nutritional coach during group-based workshops on 3 weekends | 60 RRMS (20 for each group; 18/18/12 in KD/FMD/control group completed study, respectively) | Adults, mean 41.3 ± 8.2 | clinicaltrials.gov identifier: NCT01538355 |
| Swidsinski et al. (2017) (24) | Interventional study (focusing on microbiome study) | KD for 6 mo | Nutritional coach during group-based workshops on 3 weekends | 10 RRMS, 14 HC | Adults, details not reported | Longitudinal evaluation of colonic microbiome change under KD, without evaluation of clinical effects; HC group was not treated with KD, so the effects of KD on MS vs. HC could not be compared |
| Bock et al. (2018) (22) | Randomized, 3-arm trial | Experimental groups: adapted (by Dr Bock) KD for 6 mo, or FMD (7-d fasting followed by usual diet). Comparator group: control diet | Nutritional coach | 24 RRMS (11 on adapted KD, 5 on FMD, 8 controls) | Adults, mean 43.1 ± 8.8 | Adapted KD and CR groups were pooled for analysis due to small sample size (because of patients' dropout and loss of blood samples) |
| Nathan et al. (2019) (25) | Single case study | KD plus CR (75%). Ketogenic ratio 2.2 | Diet diary, daily urine ketones | 1 SPMS | 60 | KD as monotherapy for SPMS |
| Benlloch et al. (2019) (27) | Prospective, mixed and quasi-experimental pilot study | Isocaloric, MCT-rich diet for 4 mo | Weekly telephone calls in which patients were asked about any problems in following the diet | 20 RRMS, 6 SPMS, 1 PPMS | Adults, mean 44.56 ± 11.27 | Not genuinely ketogenic (see text for details) |
| Brenton et al. (2019) (3) | Single-arm, open-label pilot study | Modified Atkins diet for 6 mo | The study dietitian provided a personalized educational session on initiation and maintenance of MAD, and provided contact information so that subjects could use her as a resource outside of study visits | 20 RRMS | 15–50 | Study subjects largely overweight or obese; no comparator group |
| Lee et al. (2021) (21) | Randomized, waitlist controlled, open-label study | Experimental groups: MCT-based KD for 12 wk, or modified Paleolithic diet. Comparator group: usual diet. Ketogenic ratio 0.99 ± 0.47 | Participants were taught the study diet by RD, who answered all diet-related questions throughout the study. RD made nutrition counseling calls to participants 2–3 d after visit 1, then weekly for 3 wk | 10 SPMS, 2 PPMS, 1 PRMS, 1 RRMS; 5 on MCT-based KD, 6 on modified Paleolithic diet, 4 on usual diet | 36–63 | clinicaltrials.gov identifier: NCT01915433 |
| Bock et al. (2022) (23) | Retrospective evaluation of a randomized, 3-arm trial | As described in the study of Bock et al. (2018) (22) (see above) | As described in the study of Bock et al. (2018) (22) (see above) | 40 RRMS (17 on adapted KD, 14 on FMD, 9 controls) | Adults, mean 43.06 ± 9.7 |
1
CR, calorie restriction; FMD, fasting mimicking diet; HC, healthy controls; KD, ketogenic diet; MAD, modified Atkins diet; MCT, medium-chain triglyceride; MS, multiple sclerosis; PPMS, primary progressive multiple sclerosis; PRMS, progressive relapsing multiple sclerosis; RD, registered dietitian; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.