A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy
Abstract
:1. Introduction
2. Complications of a Ketogenic Diet by System
2.1. Gastrointestinal Complications
2.2. Cardiac Complications
2.3. Vascular Complications
2.4. Renal Complications
2.5. Hematological Complications
2.6. Neurological Complications
2.7. Dermatological Complications
2.8. Bone Density and KD
2.9. Antiseizure Medications and KD Interaction
2.10. Surgical Considerations
2.11. COVID/Respiratory
2.12. Growth and Nutrition
2.13. Metabolic and Endocrine Complications
2.14. KD Complications in Infants
Author | Different Types of Ketogenic Diet * | Side Effects/ Complication of Ketogenic Diet besides Renal Stones |
---|---|---|
Holler A et al. [118] | Classical KD and MAD | Constipation, increased bromine level (3.2%) |
Attar H et al. [119] | MAD | NR |
Felix et al. [120] | MAD | Weight loss, hyperlipidemia |
Mak et al. [121] | KD – Protein + carb (<19%) of caloric requirementsMCT 60–70% of caloric requirements | Weight loss (46%), diarrhea (38%), bad temper (7.6%), abdominal cramps (15%), nausea (15%), bad body smell (7.6%) |
Rios et al. [122] | KD 4:1 (1.5:1 to 4.5:1) | Nausea and vomiting (26.3%), hypercholesterolemia (64.7%), anorexia (31.8%), constipation (40.9%), symptomatic acidosis (9.09%), carnitine deficiency (9.09%) |
Sharma et al. [123] | Classical KD 3:1 or 4:1 | Vomiting (75%), asymptomatic hypocalcemia, constipation (75%), weight loss, hypoalbuminemia |
Kang et al. [30] | Classical KD 4:1 | Dehydration, GI discomfort, hyperlipidemia, hyperuricemia, symptomatic hypoglycemia, lipoid aspiration pneumonia, hypoproteinemia, hypomagnesemia, repeated hyponatremia |
Wibisono et al. [124] | Classical KD, MCT, MAD | Constipation, hypertriglyceridemia, hypercholesterolemia, diarrhea, lethargy, iron deficiency, GERD, vomiting, hypoglycemia |
Simm et al. [77] | KD 2:1 to 4:1 | Osteopenia, fracture |
Guzel et al. [125] | KD 2.5:1 and 4:1 | Hyperlipidemia (50.8%), selenium deficiency (26.9%), constipation (26.2%), sleep disturbances (20%), hyperuricemia (3%), hepatic effects (2.6%), hypoproteinemia (2.6%), hypoglycemia(1.5%) |
Hassan et al. [40] | Classic 4:1 KD or MCT diet | Constipation (85%), gall bladder stone (1.9%), hyponatremia (1.9%) |
Takeoka et al. [126] | KD not specified | Nausea/vomiting (7%), irritability (7%), lethargy (21%), sedation (14%) |
Kossoff et al. [56] | KD 3:1 to 4:1 | NR |
Kossoff et al. [127] | KD 3:1 to 4:1 | Sedation (27%), rash, irritability |
Kossoff et al. [128] | KD 3:1 to 4:1 | Severe GERD (13%), hip dislocation (0.4%) |
Kang et al. [129] | Dehydration, GI discomfort, hyperlipidemia, hyperuricemia, hypoglycemia | |
Mackay et al. [130] | Classical KGD 3:1 to 4.2:1 | Asymptomatic hypoglycemia (24%), poor linear growth (20%), hyperlipidemia (16%), vomiting (12%), hypocarnitinemia (8%), hypercalciuria (8%), constipation (8%), osteopenia (4%), pancreatitis (4%), diarrhea (4%) |
Groesbeck et al. [131] | 60.7% on classical KD7% MAD, 32% other KD | Fractures (21.4%), hyperlipidemia (7%), constipation (53%) |
Sampath et al. [57] | KGD 3:1 (56%) or 4:1 | NR |
Caraballo et al. [132] | KD | GI side effects (30.5%), hyperlipidemia (9.7%), weight gain (2.3%), hypocarnitinemia (3.7%), hypercalciuria (6.9%), hypoglycemia (5.5%), dehydration (6.4%) |
Dressler et al. [61] | KD 3:1,4:1 or 2.5:1 | Carnitine deficiency (13%), growth deficit (5.2%), weight gain (1.7%), hypertriglyceridemia (29.5%), hypercholesterolemia (10.4%) |
Hallbook et al. [133] | KD 3:1 or 4:1 ratio | Hyperlipidemia (6%), bone fractures (0.9%) |
Lim et al. [134] | NR | GI side effects (nausea, vomiting, and constipation), inadequate weight gain or significant weight loss, ketoacidosis, hepatotoxicity, renal dysfunction, sinus tachycardia, osteoporosis |
McNally et al. [60] | KGD unspecified | NR |
Park et al. [135] | KD 4:1 (87.5%), KD 3:1 (12.5%) | Regurgitation, constipation, aspiration, hypertriglyceridemia, hypoproteinemia, nausea, vomiting |
Draaisma et al. [136] | Classic KD (67.6%), MCT diet (2.9%)MAD (19.1%), LGID (7.4%), others (1.5%) | Decrease in BMD 0.22 Z-score/year |
Roehl et al. [137] | Modified ketogenic diet−15 gm carb vs 50 gm carb diet | Constipation 9% |
Lambrechts et al. [138] | KD | GI side effects (30%) |
3. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Potential Complication | High Risk Patient Population | Clinical and Investigational Monitoring | Possible Intervention to Reduce Complication |
---|---|---|---|
Nausea, vomiting, worsening of reflux disease | Young infants, Multiple AED, GERD, Hypotonia |
|
|
Constipation | Prior h/o constipation, Autism, Hypotonia and GDDYoung infants |
|
|
Weight loss | Low BMI before KD initiation, Genetic epilepsy, GDD, Use of ASM such as Topiramate |
|
|
Osteopenia | Poor bone density, Low Vit D, Prior h/o fractures, h/o genetic condition such as Osteogenic imperfecta |
|
|
Persistently Low ASM levels | Use of Multiple ASM, including enzyme-inducing ASM |
|
|
Hypoglycemia | Infants, Low BMI, High KD ratio H/o vomiting and poor feeding tolerance, Surgical procedures |
|
|
Carnitine deficiency | Prior low carnitine levels, Use of High KD ratio, Use of ASM such as Valproic acid |
|
|
Hyperlipidemia | Family h/o hyperlipidemias, High BMI, Type II DM, High KD ratio |
|
|
Renal stones | Infants, H/o prematurity, H/o renal malformation, High KD ratio, Concurrent use of ASM such as Topiramate, Family h/o renal stones |
|
|
Acidosis | Infants, High KD ratio, Concurrent use of ASM such as Topiramate |
|
|
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Newmaster, K.; Zhu, Z.; Bolt, E.; Chang, R.J.; Day, C.; Mhanna, A.; Paudel, S.; Farooq, O.; Swaminathan, A.; Acharya, P.; et al. A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy. Children 2022, 9, 1372. https://doi.org/10.3390/children9091372
Newmaster K, Zhu Z, Bolt E, Chang RJ, Day C, Mhanna A, Paudel S, Farooq O, Swaminathan A, Acharya P, et al. A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy. Children. 2022; 9(9):1372. https://doi.org/10.3390/children9091372
Chicago/Turabian StyleNewmaster, Kyra, Zahra Zhu, Elizabeth Bolt, Ryan J. Chang, Christopher Day, Asmaa Mhanna, Sita Paudel, Osman Farooq, Arun Swaminathan, Prakrati Acharya, and et al. 2022. "A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy" Children 9, no. 9: 1372. https://doi.org/10.3390/children9091372