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Markus Bock MD1,2,3; Andreas Michalsen MD4; Friedemann Paul MD1,2
Ketogenic diet and prolonged fasting improve health-related quality of life and
lipid profiles in multiple sclerosis – A randomized controlled trial
Methods
RCT and parallel-group 6-month pilot study after ethical committee
approval (NCT 01538355). 60 RRMS patients were recruited from July
2011 to August 2012. The patients received disease modifying therapy
or no immunomodulatory treatment. Ketonuria-/aemia was monitored.
One group received a usual diet, another group enhanced their diet
with an initial 7-day fasting episode. A third group received KD from
the outset. We used MS-54 self-assessment questionnaires and
measured the blood lipid profiles.
1Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Berlin, Germany.
2NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.
3Integrative Proteomics and Metabolomics, Berlin Institute of Health (BIH), Berlin, Berlin, Germany
4Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medicine Berlin, Berlin, Germany.
Conclusions
PF and KD are feasible in RRMS patients. QOL and lipid profile improve
with KD and PF. KD has a sustainable, specific effect on LDL/HDL ratio and
triglycerides, which may be associated with disease progression. KD and PF
could favorably influence RRMS outcomes when coupled with conventional
treatments.
Background
Ketone bodies may mediate neuroprotection. Ketone oxidation is
compensated by equal reduction in glucose oxidation in the brain
under prolonged fasting (PF) or ketogenic diet (KD) conditions. KD and
prolonged effectively fasting modulate the immune system in
experimental autoimmune encephalomyelitis. We show that PF or KD
ameliorate health-related quality of life (QOL) measures in relapsing
remitting multiple sclerosis (RRMS).
Data are mean + SD, or median with inter quartile range or number (percent); baseline
data were available for 48 patients deviations are given in brackets; *Kruskal Wallis
test for comparison between the three groups was performed.
Hypothesis
KD and PF improve the Multiple Sclerosis Quality of Life-54 (MS-54)
scale in RRMS patients.
Corresponding Author: markus.bock@charite.de
Results
Mean quality of life score
PHCS
MHCS
SXF
HD
OQL
CF
PF
HP
E/F
RP
P
SoF
EW
RE
0
10
20
30
40
50
60
70
80 Patients with MS present study Patients with MS US-study1
Month
Mean Change from Baseline
Physical Health Composite (MS-54)
1
3
6
0
5
10
15
Month
Mean Change from Baseline
Mental Health Composite (MS-54)
1
3
6
-5
0
5
10
15
Control Diet Prolonged Fasting Ketogenic Diet
Month
Mean Change from Baseline
Bodily Pain (MS-54)
1
3
6
-10
0
10
20
30
Month
Mean Change from Baseline
LDL/HDL Cholesterol Ratio
0
1
3
6
-0.6
-0.4
-0.2
0.0
0.2 Control Diet Prolonged Fasting Ketogenic Diet
Month
Mean Change from Baseline
Triglycerides (mg/dl)
0
1
3
6
-40
-30
-20
-10
0
10
Fig. 2 a-d Longitudinal MS-54 changes
a
b
c d
Fig. 3 a+b
In comparison
to control
group the LDL
/ HDL ratio and
triglycerides
decreased
significantly in
the KD group
only. *p<0.05,
**p<0.01 Mann
–Whitney-U
test was
performed to
compare the
mean change
from baseline
between the
control group
and the PF or
KD groups.
Fig. 1 Representative baseline values on MS-54
Comparison of the mean MS-54 scores of patients from the present study to US MS
patients1. Abbreviations: PHCS= physical health composite, MHCS= mental health
composite, SXF= sexual function, HD= health distress, OQL= overall quality of life,
CF=cognitive function, PF=physical function, HP= health perception, E/F= energy / fatigue,
RP= role limitations physical, P= bodily pain, SoF= social function, EW= emotional well-
being. RE= role limitations emotional. 1 Vickrey et al. (1995)
Fig. 2 a-d
PF and KD improve
summary (a+b) and
single (b+c) MS-54
scores in MS Patients.
MS-54 data are
mean+SEM. Dotted line
represents threshold
which is thought to be a
clinically meaningful gain
(>5 points) in MS-54
outcome. *p<0.05,
**<0.01 Mann-Whitney-U
test was performed to
compare the mean
change from baseline
between the control
group and the PF or KD
groups. In PF a
maximum effect size was
found at month 3 (0.8)
and in KD at month 6
(0.7).
Fig. 3 a+b Longitudinal blood lipid changes
a
b
Tab. 1 Patients baseline
characteristics Total
(n=48) SD
IQR Control
(n=12) SD
IQR Fasting
(n=18) SD
IQR Ketogenic
(n=18) SD
IQR *p-
value
Age in years 44.8 10.4 50.5 10.4 44.4 11.1 41.3 8.2 ns
Gender F/M 38/10
(79/21)
9/3
(75/25) 15/3
(83/17) 14/4
(78/22) ns
Expanded disability status score 3.0 2,0-4 2.5 1,5-4 4.0 2,4-4 3.0 2,4-3,5
ns
Disease Duration in years 8.9 7.3 9.9 9.2 11.0 7.7 6.3 4.3 ns
Relapse rate 12 months prior
study outset 0.4 0.5 0.3 0.7 0.4 0.5 0.4 0.5 ns
No immunomodulatory treatment 11 (23)
3 (35) 2 (11) 6 (33) ns
Glatirameracetate 15 (31)
7 (58) 6 (33) 2 (11) <0.05
Interferon beta 1a 9 (19) 1 (8) 6 (33) 2 (11) ns
Interferon beta 1b 3 (6) 0.0 1 (6) 2 (11) ns
Fingolimod 4 (8) 0.0 1 (6) 3 (17) ns
Natalizumab 4 (8) 1 (8) 1 (6) 2 (11) ns
Intravenous immuneglobulin 2 (4) 0.0 1 (6) 1 (6) ns
BMI 26.7 5.5 27.3 6.9 26.0 4.8 26.9 5.3 ns
Percent Body Fat 36.6 10.4 38.0 10.6 35.7 9.9 36.5 11.3 ns
Physical Health Composite;
(n=12,13,13) 67.4 15.2 73.1 8.8 59.6 15.6 69.9 15.2 ns
Mental Health Composite;
(n=12,17,15) 71.1 16.8 75.4 13.6 64.2 19.1 75.5 14.7 ns
Total Cholesterol, mg/dl 203.5 32.1 220.8 28.7 209.7 27.0 198.6 41.4 ns
Low Density Lipoprotein, mg/dl 124.3 32.1 129.8 31.1 126.3 25.5 119.7 36.7 ns
High Density Lipoprotein, mg/dl 68.1 17.8 69.9 17.1 62.9 17.9 62.1 18.1 ns
LDL/HDL ratio 2.0 0.8 2.0 0.9 2.2 0.8 2.1 0.8 ns
Triglycerides, mg/dl 89.3 42.9 105.1 43.2 111.1 48.2 87.2 36.4 ns
Month
Mean Change from Baseline
Physical Function (MS-54)
1
3
6
-15
-10
-5
0
5
10
15
