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January Newsletter

  • Writer: Admin
    Admin
  • Jan 5, 2024
  • 4 min read

Does the Ketogenic Ratio Matter When Using Ketogenic Diet Therapy in Pediatric Epilepsy?

Sharma S, et al. Does the ketogenic ratio matter when using ketogenic diet therapy in pediatric epilepsy? Epilepsia. 2023 Feb;64(2):284-291. doi: 10.1111/epi.17476. Epub 2022 Dec 15. PMID: 36471628.

 

Key Points:

  • Ketone bodies constitute one of several mechanisms contributing to the anti-seizure effects of ketogenic diet (KD) therapy.


  • Blood and urine ketone measurements may not consistently correlate with seizure control, but aid in monitoring dietary compliance.


  • Modified Atkins diet (MAD), lower ratio KD, and low glycemic index treatment (LGIT) offer effective seizure control with improved tolerability.


  • Choosing a dietary therapy requires considering individual clinical, sociocultural, and economic factors for tailored and successful implementation

 



INTRODUCTION: 


The ketogenic diet (KD), is a well-established therapeutic option for epilepsy and metabolic conditions, and involves a high-fat, low-carb intake. Despite its effectiveness, certain aspects, like its mechanism and pathophysiology, remain unclear. The diet induces ketone bodies through fat metabolism in low-carb conditions. Traditional KD has a high fat-to-carb/protein ratio, but lower ratios like modified Atkins (MAD) version of the KD show comparable efficacy with improved tolerability. The importance of ketosis in achieving seizure control is not fully understood, and blood ketone levels don't always correlate. This review explores the role of ketosis and ketogenic ratios in KD efficacy, emphasizing individualized macronutrient selection and non-ketosis-based benefits for children with epilepsy.


TYPES OF THE KETOGENIC DIET:


The classic ketogenic diet (KD) is composed of long-chain triglyceride fats and strict restriction of carbs. Lower ketogenic ratios, like 1:1 to <3:1, allow for more carb intake, improving acceptability. The medium-chain triglyceride (MCT) diet, a KD variation, yields more ketones per energy unit, enabling lower fat intake and more carb and protein intake. The modified MCT diet combines MCT and long-chain fatty acids. The modified Atkins diet (MAD) is a high-fat, low-carb therapy with a 1:1–2:1 ratio, allowing more liberal protein, fluid, and calorie intake. The liberal MAD variation which is typically started in a slow manner outpatient can be effective for certain conditions. The low glycemic index treatment (LGIT) allows ~40–60 g/day carbs with a <1:1 ratio, emphasizing low-glycemic-index carbs.


BLOOD KETONES AND URINE KETONES:

Several clinical studies have investigated the relationship between blood β-OHB levels and seizure control in individuals on the ketogenic diet (KD). Gilbert et al. found that children with blood β-OHB levels above 4mmol/L were significantly more likely to experience seizure reduction compared to those with levels below 4mmol/L. Similarly, van Delft et al. observed a correlation between blood β-OHB levels and seizure reduction at 3 and 6 months on the KD, while urine ketones did not show a consistent correlation. Buchhalter et al. noted a positive correlation between seizure frequency and blood β-OHB levels, though not statistically significant. Lowe et al. found similar seizure outcomes between patients on the medium-chain triglyceride (MCT) KD and classic KD, despite lower urine ketones in the MCT group.


While some studies support a positive correlation between ketone levels and seizure control, this relationship is not universal. Obtaining blood ketone samples can be challenging in children, and measuring urine ketones at home is more practical. However, the correlation between blood and urine ketones is not well-defined, varying based on factors like hydration, acid–base balance, and renal function. In infants, serum β-hydroxybutyrate levels are considered a more reliable marker of ketosis than urine ketones. The 2018 international ketogenic diet consensus guidelines do not specify a preference for blood or urine ketone monitoring.


Proposed mechanisms of the ketogenic diet


• Production of ketone bodies with antiseizure effects (although ketone levels do not necessarily correlate with seizure control) 

• Modulation of mitochondrial metabolism 

• Alteration of reactive oxygen species production 

• Opening of K(ATP) channels 

• Promotion of γ-aminobutyric acid (GABA)ergic inhibition 

• Histone acetylation and transcriptional activation 

• Increased polyunsaturated acid levels with activation of peroxisome proliferator-activated receptors and neuronal hyperpolarization 

• Alteration of the gut microbiome 

• Anti-inflammatory effects


KETOGENIC RATIO AND SEIZURE REDUCTION CORRELATION:


Kim et al. (n=104 children) found that the classic KD group showed a lower mean percentage of baseline seizures at 3 and 6 months compared to the modified Atkins diet (MAD) group, but the difference was not statistically significant. For young children (1–2 years old), seizure reduction was more favorable on the classic KD. However, the MAD was better tolerated overall, and blood β-OHB levels did not correlate with seizure control in either group.

Sondhi et al. compared classic KD, MAD, and low glycemic index treatment (LGIT) in a trial with 158 children. At 24 weeks, median reduction in seizure frequency was similar across all groups, and adverse effects were significantly reduced in the LGIT group. The change in seizure frequency did not correlate with urinary ketones in any group.


In another study by Raju et al., 38 children with drug-resistant epilepsy were randomized to receive either a classic 4:1 or a 2.5:1 KD. Seizure efficacy, defined by a 50% reduction, was similar in both groups at 3 months (58% in 4:1 and 63% in 2.5:1; p = 0.78).


CHOOSING THE RIGHT DIET: 


Choosing the appropriate form of dietary therapy for epilepsy involves considering various factors, such as individual patient needs, contraindications, and psychosocial aspects. While the classic ketogenic diet (KD) ratios may be challenging for those accustomed to high-carbohydrate diets and vegetarians, MAD and LGIT offer more accessible alternatives, especially in resource-constrained settings. The classic KD remains the standard therapy for specific conditions like infants with drug-resistant epilepsy and certain genetic or metabolic disorders. The ketogenic ratio and type of diet can be modified based on patient response and tolerability, 


CONCLUSION:


Recent studies comparing classic KD to other dietary therapies suggest similar reductions in seizure frequency among all diets, with greater tolerability in more liberalized forms. The level of ketosis (in blood and urine) doesn't consistently correlate with seizure control. Reports on lower ratio classic KD initiation and gradual advancement based on seizure control and tolerability suggest that slower titration may achieve good seizure control even at lower ratios, challenging the notion that higher ratios are always necessary.


Please feel free to reach out with any topics you would like me to explore related to the ketogenic diet 



 
 
 

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