Nutritional Neuroscience

An International Journal on Nutrition, Diet and Nervous System

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Efficacy of supplemental MCT oil on seizure

reduction of adult drug-resistant epilepsy – a
single-center open-label pilot study

Emmaline Rasmussen, Vimal Patel, Samuel Tideman, Robert Frech, Roberta

Frigerio & Jaishree Narayanan

To cite this article: Emmaline Rasmussen, Vimal Patel, Samuel Tideman, Robert Frech, Roberta
Frigerio & Jaishree Narayanan (2023) Efficacy of supplemental MCT oil on seizure reduction of
adult drug-resistant epilepsy – a single-center open-label pilot study, Nutritional Neuroscience,
26:6, 535-539, DOI: 10.1080/1028415X.2022.2065816

To link to this article: https://doi.org/10.1080/1028415X.2022.2065816

Published online: 26 Apr 2022.

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NUTRITIONAL NEUROSCIENCE
2023, VOL. 26, NO. 6, 535–539
https://doi.org/10.1080/1028415X.2022.2065816

Efficacy of supplemental MCT oil on seizure reduction of adult drug-resistant

epilepsy – a single-center open-label pilot study
Emmaline Rasmussen, Vimal Patel, Samuel Tideman, Robert Frech, Roberta Frigerio and Jaishree Narayanan
NorthShore Neurological Institute, NorthShore University HealthSystem, Evanston, IL, USA

ABSTRACT KEYWORDS
Objective: We set out to determine whether adding medium chain triglyceride (MCT) oil as a Drug resistant epilepsy;
dietary supplement to standard diet in adult subjects with intractable epilepsy in a U.S. ketones; standard of care;
neurology clinical practice was associated with a reduction in number of seizures. We dietary supplements;
seizures; medium chain
secondarily aimed to determine whether subjects experienced any side effects and whether
triglycerides;
there was a presence of urinary ketones while using MCT oil as a dietary supplement. intractable epilepsy; ketosis
Methods: Adult patients with intractable epilepsy were recruited at standard of care clinical visits
with their epileptologist. Once enrolled, subjects were instructed to supplement their diet with
MCT oil as tolerated twice daily for three months (including a 1–2 week titration period,
followed by a 1–2 week tapering off window) while keeping a seizure diary to record total
number of seizures, presence of urinary ketones, and any side effects.
Results: Our data although limited by small sample size, shows that there is an estimated 42%
reduction (p < 0.0001) in the rate of seizures. The MCT oil supplementation was well tolerated
by most subjects except for minor GI side effects like nausea and loose stools. Most subjects
developed ketones in their urine at some point during the trial.
Conclusions: MCT oil supplementation reduced seizure frequency in study participants. The
reported side effects included mild nausea, stomachache, loose stools. A placebo-controlled
study will be more informative.

Introduction but neither study was a randomized controlled trial

(RCT). The classical Ketogenic Diet (CKD) is a general
Epilepsy is a major public health problem that affects term for a set of diets that contain high amounts of fat
0.6–1% of the general population [1]. Most efforts are and low content of carbohydrates originally designed
targeted to the development of increasing numbers of to mimic metabolic changes in the body caused by fast-
anti-epileptic drugs (AEDs) – more than 20 AEDs are ing. In CKD, calories and fluids were generally restricted
used clinically today. However, despite the availability, to 85%–90% of the estimated daily needs [7]; however, it
30–40% of patients do not respond to pharmacotherapy was not widely adopted for seizure control, maybe due
and continue to have ‘uncontrolled’ or ‘intractable’ sei- to the increased availability of newer antiepileptic medi-
zures – a condition termed drug-resistant epilepsy [2]. cations [8]. Subsequently, various modifications to the
Uncontrolled seizures pose a significant risk to quality CKD were developed, including the medium-chain tri-
of life [3]. In addition, uncontrolled seizures are likely glyceride (MCT) ketogenic diet, modified Atkin’s diet,
to be one of the strongest risk factors of sudden death and low glycemic index diet [7]. These modified keto-
in epilepsy [4]. Therefore, it is important not to rely genic diets have an efficacy for seizure control close to
on pharmacological interventions alone when treating that of the CKD [9].
intractable epilepsy and further evidence for comp- RCTs using the CKD, or modifications described
lementary and alternative interventions must be above, have been most performed in children and
developed. young people with drug-resistant epilepsy – in whom
Diets have been used in an attempt to control epi- there has been a great deal of success [10–13]. However,
leptic seizures throughout the centuries. Scientific perhaps due to inability to predict efficacy or the
assessment of dietary manipulation reported by Guelpa unknown mechanism of action only modest evidence
in 1911 [5], and subsequently in Geyelin in 1921 [6], is available regarding the efficacy of these diets in adults
confirmed that seizures may cease on absolute fasting, with refractory epilepsy [14].

CONTACT Jaishree Narayanan [email protected] Department of Neurology, NorthShore University HealthSystem, 2650 Ridge Avenue, Evanston,
IL, 60201, USA
© 2022 Informa UK Limited, trading as Taylor & Francis Group
536 E. RASMUSSEN ET AL.

MCT oil is more ketogenic than longer fatty acids. (if applicable), provided with MCT oil and supplies
The addition of MCT oil into the CKD allowed to (dosing cups, urine collection cups, and urinary ketone
reduce the amount of fat that is required in the diet, test strips), and educated on the MCT oil administration
thereby allowing a larger amount of protein and even schedule and procedure for using urinary ketone test
carbohydrate intake. This version of diet, however, strips. The MTC oil supplement used consisted of 14 g
can cause gastrointestinal distress in patients MCT oil per 15 ml (containing 50% caprylic acid
(stomach cramps and diarrhea) and is used now only (C8), 30% capric acid (C10)). Subjects were also pro-
occasionally [15]. vided a seizure diary and instructed to track their
With respect to MCT-oil given as add-on therapy usage of the MCT oil, presence of any urinary ketones,
alone, evidence is limited, we were able to identify a and any other side effects. They were also asked to
single case report in which add-on MCT oil was used inform the investigator of any anticipated or unantici-
as a dietary supplement in a single patient with nonsur- pated side effects they experienced during the study.
gical partial epilepsy, without any other dietary modifi- Diaries were verified with the subjects or their legally
cations and which showed a significant reduction in authorized representative when they turned them in at
seizure frequency[16]. follow-up visits. In subjects who had a responsive
In this open-label study, we aimed to further assess neuro stimulator (RNS) device implanted, seizures
the effectiveness of supplemental use of MCT oil to were counted by reading the data from the device.
the standard diet in a small group of adults with drug- The MCT oil dosing schedule was created to gradu-
resistant epilepsy. ally increase MCT oil intake, titrating up to full dose
over a 1–2 week period. Titration was started at 15 ml
once a day and increased as tolerated to reach a maxi-
Methods
mum of 60 ml twice a day by day nine which is the tol-
This single-center open-label pilot study conducted erable upper-safety limit for chronic, oral,
with approval from the NorthShore University Health- administration in healthy adults.
System (Northshore) Institutional Review Board. Once at the maximum tolerable dosage was deter-
Adult patients were screened at a single epilepsy clinic. mined based on titration period, the subjects continued
to use the MCT oil twice daily for three months. If they
were unable to reach the target dosage due to inability to
Patients
tolerate the oil at that dosage, one ‘re-challenge’ was per-
The patient population of NorthShore consists primar- mitted per subject. Subjects met with the epileptologist
ily of individuals living in the Northern suburbs of Chi- at baseline and approximately every month per standard
cago. For this study, non-pregnant adult patients of age of care. Subjects met with the research dietitian or other
18–65 with a history of epilepsy who continued to have research personnel at baseline and at the end of the
a minimum of 3 seizures per month despite being on or study, where general nutrition guidance the taper-on
having tried maximum tolerated doses of 3 or more and taper-off schedule was explained to decrease the
standard antiepileptic drugs under medical supervision MCT oil following completion of the study.
were eligible to be enrolled. Patients must have a com-
plete 3-month seizure diary for the 3 months preceding
Statistical analyses
study enrollment. Patients were excluded if they had
Type I diabetes mellitus, currently prescribed to and The monthly seizure rate was calculated for each subject
using insulin, uncontrolled hypothyroidism, B12 for both the pre and post MCT oil periods. A Poisson
deficiency, or clinically sufficient hepatic disease or regression was used to estimate the rate ratio between
insufficiency. Patients were excluded if currently pre- the pre and post MCT oil periods. Individual effect
scribed to and taking valproate, unable to tolerate a terms were added to the Poisson regression to adjust
high fat diet due to contraindications, diagnosed with for the diversity in individual baseline seizure rates.
irritable bowel syndrome or inflammatory bowel disease After adjusting for individual rate effects, a single rate
with regular bouts of diarrhea or constipation that is not ratio was calculated for the whole dataset. These calcu-
well controlled. lations were done in R version 4.0.2.

Design Results
In this simple add-on study, with each subject serving as Nine subjects were enrolled in the study. Six of these
their own control, subjects were screened for pregnancy subjects completed the study; their age, gender,
 NUTRITIONAL NEUROSCIENCE 537

Table 1. Patient details.

Age (years)_ Gender Weight (kg)/BMI Epilepsy type Medications
46 Male 107/36.96 Temporal lobe epilepsy Lacosamide, lamotrigine, briveracetam, clobazam
24 Male 104/32.08 Temporal lobe epilepsy Valproic acid, lacosamide
32 Female 54/19.6 Multifocal epilepsy Phenytoin, lacosamide, clonazepam
47 Female 69/26.95 Generalized epilepsy Valproic acid, levetiracetam
63 Female 66/24.46 Temporal lobe epilepsy Levetiracetam, lacosamide
25 Female 59/27.17 Lennox Gastaut syndrome Valproic acid, lamotrigine, clobazam

weight/BMI, epilepsy type, and medications are shown Discussion

in Table 1. One subject was lost to follow up. Two sub-
Fasting has been used as a treatment for epilepsy since
jects dropped out of the study. One withdrew due to
ancient times. KD has been used since 1921. Dr. Wilder
adverse events (AEs) of severe nausea, abdominal
proposed the use of this diet for epilepsy to avoid the
cramps, and loose stools. The other withdrew due to
malnutrition caused by starvation [17]. The CKD was
AEs of loose stools leading to fecal incontinence. Of
formulated by Dr. Peterman, and it was shown to be
the six subjects who completed the study, there were
very successful in children [18]. 95% of the patients
four females and two males. The ages ranged from 24
had improved seizure control and 60% became seizure
to 63 years. Two subjects were on 60 ml twice a day;
free [19]. The diet has the significant drawback of
one subject on 45 ml twice a day; one subject on
being cumbersome to implement, and is not very pala-
15 ml twice a day; two subjects were on 30 ml in morn-
table, leading to poor compliance. It needs to be fol-
ing and 45 ml in the evening. Two subjects had RNS
lowed strictly for benefit. Modified Atkin’s diet and
implanted, and seizure counts for pre and during
low glycemic index treatment have been used as
MCT oil were obtained by reading the data collected
modified alternatives. KD and its alternatives shift the
by the RNS device. In the other four subjects, seizures
metabolism from a glucose dependent state to use of
were counted from subject- or caregiver-kept seizure
dietary fats for generating energy. The MCT–KD is a
diaries. Table 2 shows 5/6 subjects recorded a reduction
variant in which a proportion of long chain triglycerides
in seizures after adding MCT oil. One subject had the
(LCT) are replaced by medium chain triglycerides
same number of seizures before and after MCT oil
(MCT) comprised of 60% triglycerides of caprylic acid
was added. 5/6 subjects developed urinary ketones at
(CA8) and 40% capric acid (CA10) [19]. Huttenlocher
some point during the trial. The reported AEs among
reported that the MCT are absorbed more efficiently
the six subjects who completed the study, included
[20]. MCT can cross the blood brain barrier and affect
mild nausea, stomachache, and loose stools.
brain metabolism directly [21]. In animal models
Overall seizure rate ratio comparing the pre-MCT oil
CA10 has been shown to have inhibitory role in epilepsy
seizures rates with those observed after subjects began
by selective inhibition of AMPA receptors [22]. MCT-
supplementing their diet with MCT oil (Table 3). A sei-
KD has similar efficacy as CKD but is more palatable,
zure rate ratio of 0.5804 [95% confidence interval
though it is still very complicated to implement [14].
0.4676–0.7203] was observed with a p-value less than
Although, most of these studies are in children there
0.0001. There is an estimated 41.96% reduction in the
is limited data in adults suggesting some benefit [15].
rate of seizures.
Azzam et al. reported significant seizure reduction in
one patient with MCT oil supplementation [16].
Table 2. Numbers of seizures before starting MCT oil and during MCT oil is commercially available, inexpensive diet-
use of MCT oil in subjects who completed the study. ary supplements that can induce ketosis without the
Number of seizures per Number of seizures per month
Subjects month pre-MCT oil while taking MCT oil
need for a traditional ketogenic diet or prolonged
Subject 16 (per RNS) 13 (per RNS)
1
Subject 9 (per RNS) 6 (per RNS) Table 3. Statistical analysis of the outcome data.
2
Subject 84 52 Variable Estimate Exponentiated P Value SE Z Score
3 Rate ratio −0.5441 0.5804 <0.0001 0.1103 −4.9349
Subject 9 9 Subject 1 2.9096 18.3495 <0.0001 0.1901 15.3092
4 Subject 2 −0.6592 9.4915 0.0382 0.318 −2.0728
Subject 77 36 Subject 3 1.5454 86.0562 <0.0001 0.2045 7.5554
5 Subject 4 −0.4769 11.3896 0.112 0.3001 −1.5894
Subject 29 14 Subject 5 1.3601 71.5002 <0.0001 0.2082 6.5337
6 Subject 6 0.3939 27.2077 0.1012 0.2403 1.6393
RNS: responsive neuro stimulator; MCT: medium chain triglycerides. SE: standard error.
538 E. RASMUSSEN ET AL.

fasting [23]. The potential pathophysiological anti-sei- Data availability statement

zure mechanisms include the increase in ketone bodies, The data that support the findings of this study are available
increase in polyunsaturated fatty acids, protection from from the corresponding author, JN, upon reasonable request
apoptosis and cell death and inhibition of pro-apoptotic where this does not violate the protection of human subjects.
factors, change of intestinal microbiota, or change of
proinflammatory and anti-inflammatory mediators pro-
duction [24–27]. Recent preclinical data suggest that the
anti-convulsant effect of the MCT-KD is due to the References
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