Diet in the Treatment of Epilepsy: What We Know So Far
Abstract
:1. Introduction
2. Different Dietary Regimens Inducing Ketosis
2.1. Classic Ketogenic Diet (KD)
2.2. Modified Atkins Diet (MAD)
2.3. Low-Glycemic Index Treatment (LGIT)
2.4. Medium-Chain Triglyceride Diet (MCTD)
3. Responders and Non-Responders to the Ketogenic Diet
4. Pathophysiology of Ketogenic Diet and Epilepsy
5. Clinical Efficacy against Epilepsy
5.1. Pediatric Population
5.1.1. Refractory Epilepsy
5.1.2. Other Childhood Epilepsies
5.2. Adult Population
6. Tolerability
6.1. General Comment
6.2. Short Term Adverse Events
6.3. Long Term Adverse Events
6.4. Deaths, Retention Rates, and Reasons for Diet Discontinuation
7. Special Considerations
7.1. Exclusion Criteria of the Ketogenic Diet
7.2. Variation of Ketogenic Diet Regimen per Age Group
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Ketogenic Diets | Macronutrients (% Total Daily Calories) | Ketogenic Ratio | ||
---|---|---|---|---|
Fat | Protein | Carbohydrate | ||
Classic | 80–90 | 6–8 | 2–4 | 4:1 |
MAD | 65 | 25 | 10 | 1:1 |
LGIT | 60 | 20–30 | 10 | 1:0.6 |
MCTD | 30–60 | 10 | 15–19 | 1:1 or 2:1 |
Primary Physiological Alteration | Possible Anti-Seizure Mechanisms |
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References | Type of Study | Participants | KD Ratio | Fasting | Outcomes | Follow-Up | Statistical Significance | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[] | (Months) | ||||||||||||
Number | Age (Years) | KD Group | Control Group | ||||||||||
Number | SFR >50%(n) | SFR >50% | Number | SFR >50%(n) | SFR >50% | ||||||||
Vining EP, et al. 1998 [59] | Observational | 51 | 8–1 years | Classic KD/4:1 | Yes | 45 | 54 | 28 | / | / | / | 3 | p < 0.001 |
35 | 53 | 27 | / | / | / | 6 | NA | ||||||
24 | 40 | 20 | / | / | / | 12 | NA | ||||||
Freeman JM, et al. 1998 [60] | Observational | 150 | 0.3–16 years | Classic KD/3–4:1 | Yes | 125 | 89 | 60 | / | / | / | 3 | NA |
106 | 77 | 51 | / | / | / | 6 | NA | ||||||
83 | 75 | 50 | / | / | / | 12 | NA | ||||||
Freitas A, et al. 2007 [61] | Observational | 54 | 1–12 years | Classic KD/4:1 | Yes | 54 | 47 | 88.9 | / | / | / | 2 | NA |
49 | 44 | 89.4 | / | / | / | 6 | Efficacy for generalized epilepsy p < 0.001 | ||||||
39 | 38 | 97.5 | / | / | / | 12 | NA | ||||||
29 | 29 | 100 | / | / | / | 24 | NA | ||||||
Wu YJ, et al. 2016 [62] | Observational | 87 | 0.5–16 years | Classic KD/4:1 | Yes | 87 | 47 | 41 | / | / | / | 1 | NA |
87 | 51 | 44 | / | / | / | 3 | NA | ||||||
87 | 52 | 45 | / | / | / | 6 | Positive correlation between increased cognition and KD efficacy after 3 months (p = 0.003) | ||||||
Neal EG, et al. 2008 [23] | RCT | 145 | 2–16 years | Classic KD or MCT/2–5:1 or 40−60% | No | 54 | 20 | 38 | 49 | 3 | 6 | 12 | p < 0.0001 |
El-Rashidy OF, et al. 2013 [63] | RCT | 10 | 26 ± 0.9 mon | Classic KD/4:1 | NA | 25 | 12 | 49.41 | 15 | 1 | 8.31 | 6 | p < 0.005 |
Sharma S, et al. 2013 [64] | RCT | 102 | 2–14 years | MAD (carbohydrate 10 g/die) | NA | 50 | 26 | 52 | 52 | 6 | 11.5 | 3 | p < 0.001 |
Sharma S, et al. 2016 [65] | RCT | 81 | 2–14 years | MAD | NA | 41 | 23 | 56.1 | 40 | 3 | 7.5 | 3 | p < 0.0001 |
Lambrechts DAJE, et al. 2017 [66] | RCT | 48 | 1–17 years | prevalent MCT | No | 26 | 13 | 50 | 22 | 4 | 18.2 | 4 | p = 0.024 |
Wijnen BFM, et al. 2017 [67] | RCT | 48 | 1–18 years | Classic KD or MCT | NA | 26 | 9 | 35 | 22 | 4 | 18 | 16 | p = 0.171 |
Sourbron J, et al. 2020 [68] | Review-meta-analysis 5 RCTs | 472 | 35–56.1 | 6–18.2 | p < 0.001 |
References | Type of Study | Participants | KD Ratio | Fasting | Outcomes | Follow-Up | Statistical Significance | |||
---|---|---|---|---|---|---|---|---|---|---|
[] | (Months) | |||||||||
Number | Age | Pt on KD | SFR >50% | SFR >50% | ||||||
(Months) | (n) | (%) | ||||||||
Than KD, et al. 2005 [69] | Retrospective observational | 25 | NA | 3–4:1 | Yes | 25 | NA | NA | NA | NA |
Eun SH, et al. 2006 [70] | Retrospective observational | 43 | 1–14 | 3–4:1 | Yes | 43 | 12 | 27,9 | NA | NA |
35 | 30 | 85,7 | 3 | NA | ||||||
25 | 23 | 92 | 6 | NA | ||||||
Kossoff EH, et al. 2008 [71] | Retrospective observational | 13 | Median (range): 5 (2–10) | 3–4:1 | Yes | 13 | 8 | 62 | 1 | p = 0.06 |
Hong AM, et al. 2010 [72] | Prospective observational | 104 | Median: 4.8 | 3–4:1 | Yes | 86 | 66 | 63 | 3 | NA |
76 | 67 | 64 | 6 | p = 0.84 | ||||||
No | 53 | 76 | 73 | 9 | NA | |||||
47 | 80 | 77 | 12 | NA | ||||||
28 | 80 | 77 | 24 | NA | ||||||
Caraballo R, et al. 2011 [73] | Retrospective observational | 12 | NA | 3–4:1 | NA | 12 | 9 | 75 | NA | NA |
Numis AL, et al. 2011 [74] | Retrospective observational | 26 | Mean ± SD: 19.5 ± 2.2 | 3–4:1 | No | 26 | 12 | 46.2 | 3 | p = 0.02 |
21 | 11 | 52.4 | 6 | p = 0.02 | ||||||
19 | 12 | 63.2 | 12 | p = 0.02 | ||||||
Lee J, et al. 2013 [75] | Retrospective observational | 14 | NA | NA | NA | 14 | 11 | 78,6 | NA | NA |
Li B, et al. 2013 [76] | Prospective observational | 31 | 7–84 | 4:01 | Yes | 31 | 21 | 67,74 | 1 | NA |
22 | 70,97 | 3 | NA | |||||||
Pires ME, et al. 2013 [77] | Prospective observational | 17 | Mean ± SD: 9.4 ± 1.1 | 3–4:1 | No | 17 | 15 | 88.2 | 3 | NA |
16 | 14 | 87.5 | 6 | NA | ||||||
Kayyali HR, et al. 2014 [78] | Prospective observational | 20 | 4–35 | 3–3.5:1 | No | 20 | 14 | 70 | 3 | NA |
20 | 13 | 72.2 | 6 | NA | ||||||
17 | 13 | 76.5 | 12 | NA | ||||||
8 | 8 | 100 | 24 | NA | ||||||
Hirano Y, et al. 2015 [79] | Retrospective observational | 6 | 9–40 | 3–4:1 | NA | 6 | 5 | 83,3 | 3 | NA |
Ville D, et al. 2015 [80] | Retrospective observational | 23 | NA | 4:01 | Yes | 23 | 4 | 17,4 | NA | NA |
Hussain SA, et al. 2016 [81] | Retrospective observational | 22 | 12.5–38.7 | 3–4:1 | No | 22 | 7 | 35 | 3 | NS |
20 | 6 | 35.3 | 6 | NS | ||||||
17 | 2 | 20 | 12 | NS |
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Verrotti, A.; Iapadre, G.; Di Francesco, L.; Zagaroli, L.; Farello, G. Diet in the Treatment of Epilepsy: What We Know So Far. Nutrients 2020, 12, 2645. https://doi.org/10.3390/nu12092645
Verrotti A, Iapadre G, Di Francesco L, Zagaroli L, Farello G. Diet in the Treatment of Epilepsy: What We Know So Far. Nutrients. 2020; 12(9):2645. https://doi.org/10.3390/nu12092645
Chicago/Turabian StyleVerrotti, Alberto, Giulia Iapadre, Ludovica Di Francesco, Luca Zagaroli, and Giovanni Farello. 2020. "Diet in the Treatment of Epilepsy: What We Know So Far" Nutrients 12, no. 9: 2645. https://doi.org/10.3390/nu12092645