ORLANDO — A new review adds to growing evidence that the modified Atkins diet (MAD) significantly reduces seizures in adults with drug-resistant epilepsy.
The results of the small new review and meta-analysis suggest that "the MAD may be an effective adjuvant therapy for older patients who have failed anti-seizure medications," study investigator Aiswarya Raj, MBBS, Aster Malabar Institute of Medical Sciences, Kerala, India, told Medscape Medical News.
The findings (abstract #3.332) were presented on December 4 at the American Epilepsy Society (AES) 2023 Annual Meeting.
Paucity of Adult Data
The MAD is a less restrictive hybrid of the ketogenic diet that limits carbohydrate intake and encourages fat consumption. It does not restrict fluids, calories, or proteins and does not require fats to be weighed or measured.
The diet includes fewer carbohydrates than the traditional Atkins diet and places more emphasis on fat intake. Raj said that the research suggests that the MAD "is a promising therapy in pediatric populations, but there's not a lot of data in adults."
Raj noted that this diet type has not been that popular in patients who clinicians believe might be better treated with drug therapy, possibly because of concern about the cardiac impact of consuming high-fat foods.
After conducting a systematic literature review assessing the efficacy of MAD in adults, the researchers included three randomized controlled trials and four observational studies published from January 2000 to May 2023 in the analysis.
The randomized controlled trials in the review assessed the primary outcome, a greater than 50% seizure reduction, at the end of 2 months, 3 months, and 6 months. In the MAD group, 32.5% of participants had more than a 50% seizure reduction vs 3% in the control group (odds ratio [OR], 12.62; 95% CI, 4.05-39.29; P < .0001).
Four participants who followed the diet achieved complete seizure-freedom compared with no participants in the control group (OR, 16.20; 95% CI, 0.82-318.82; P = .07).
The prospective studies examined this outcome at the end of 1 month or 3 months. In these studies, 41.9% of individuals experienced more than a 50% seizure reduction after 1 month of following the MAD, and 34.2% experienced this reduction after 3 months (OR, 1.41; 95% CI, 0.79-2.52; P = .24), with zero heterogeneity across studies.
It's difficult to interpret the difference in seizure reduction between 1 and 3 months of therapy, Raj noted, because "there's always the issue of compliance when you put a patient on a long-term diet."
Positive results for MAD in adults were shown in another recent systematic review and meta-analysis published in Seizure: European Journal of Epilepsy.
That analysis included six studies with 575 patients who were randomly assigned to MAD or usual diet (UD) plus standard drug therapy. After an average follow-up of 12 weeks, MAD was associated with a higher rate of 50% or greater reduction in seizure frequency (relative risk [RR], 6.28; 95% CI, 3.52-10.50; P < .001), both in adults with drug-resistant epilepsy (RR, 6.14; 95% CI, 1.15-32.66; P = .033) and children (RR, 6.28; 95% CI, 3.43-11.49; P < .001).
MAD was also associated with a higher seizure freedom rate compared with UD (RR, 5.94; 95% CI, 1.93-18.31; P = .002).
Cholesterol Concern
In Raj's analysis, there was an increment in blood total cholesterol level after 3 months of MAD (standard mean difference, -0.82; 95% CI, -1.23 to -0.40; P = .0001).
Concern about elevated blood cholesterol affecting coronary artery disease risk may explain why doctors sometimes shy away from recommending the MAD to their adult patients. "Some may not want to take that risk; you don't want patients to succumb to coronary artery disease," said Raj.
She noted that 3 months "is a very short time period," and studies looking at cholesterol levels at the end of at least 1 year are needed to determine whether levels return to normal.
"We're seeing a lot of literature now that suggests dietary intake does not really have a link with cholesterol levels," she said. If this can be proven, "then this is definitely a great therapy."
The evidence of cardiovascular safety of the MAD includes a study of 37 patients who showed that althoughtotal cholesterol and low-density lipoprotein (LDL) cholesterol increased over the first 3 months of MAD treatment, these values normalized within 1 year of treatment, including in patients treated with MAD for more than 3 years.
Primary Diet Recommendation
Medscape Medical News asked one of the authors of that study, Mackenzie C. Cervenka, MD, professor of neurology and medical director of the Adult Epilepsy Diet Center, Johns Hopkins Hospital, Baltimore, Maryland, to comment on the new research.
She said that she was "thrilled" to see more evidence showing that this diet therapy can be as effective for adults as for children. "This is a really important message to get out there."
At her adult epilepsy diet center, the MAD is the "primary" diet recommended for patients who are resistant to seizure medication, not tube fed, and are keen to try diet therapy, said Cervenka.
In her experience, the likelihood of having a 50% or greater seizure reduction is about 40% among medication-resistant patients, "so very similar to what they reported in that review," she said.
However, she noted that she emphasizes to patients that "diet therapy is not meant to be monotherapy."
Cervenka's team is examining LDL cholesterol levels as well as LDL particle size in adults who have been on the MAD for 2 years. LDL particle size, she noted, is a better predictor of long-term cardiovascular health.
No conflicts of interest were reported.
Comments