American Journal of Medical Case Reports, 2015, Vol. 3, No. 4, 117-120
Available online at http://pubs.sciepub.com/ajmcr/3/4/9
© Science and Education Publishing
Gilbert’s Syndrome Successfully Treated with the
Paleolithic Ketogenic Diet
Csaba Tóth1, Zsófia Clemens1,2,*
1Paleomedicina Hungary Ltd., Evolutionary Medicine Working Group, Budapest, H-1026 Hidász u. 3/A, Hungary
2Neurological Department, University of Pécs, Pécs, H-7623, Rét u. 2, Hungary
*Corresponding author: email@example.com
Received March 17, 2015; Revised April 03, 2015; Accepted April 12, 2015
Abstract Gilbert’s syndrome (GS) is a common hyperbilirubinaemia syndrome caused by reduced conjugation of
serum bilirubin by the liver. Although it is considered as a common and harmless condition not requiring treatment
symptoms associated with GS may be unfavorable. Here we present a case of GS where high level of total and direct
bilirubin, yellowish discoloration of the sclera as well as associated symptoms including migraine, fatigue and
granulomatosus dermatitis were reversed following a shift toward the popular paleolithic and then toward the
paleolithic ketogenic diet.
Keywords: Gilbert’s syndrome, Paleolithic ketogenic diet, hyperbilirubinaemia, liver function
Cite This Article: Csaba Tóth, and Zsófia Clemens, “Gilbert’s Syndrome Successfully Treated with the
Paleolithic Ketogenic Diet.” American Journal of Medical Case Reports, vol. 3, no. 4 (2015): 117-120. doi:
Gilbert’s syndrome (GS) is a hereditary
hyperbilirubinaemia syndrome affecting 5-10% of the
population . It is primarily attributed to impaired
conjugation of bilirubin in the liver due to decreased
bilirubin glucuronyltransferase activity. Impaired activity
of this enzyme is attributed to mutations of the UGT1A1
gene. Beside this failure other alterations of the hepatic
bilirubin metabolism have been suggested in GS including
impaired hepatic uptake of bilirubin  and a positive
feedback of bilirubin through its mild haemolytic effect
GS is regarded as a common and harmless condition. In
population studies GS is associated with decreased
cardiovascular risk and all-cause mortality [4,5] which
may also be due to to the low BMI of those with GS .
Nevertheless GS is also known to be associated with a set
of unfavorable symptoms including fatigue, itching,
gastrointestinal symptoms , increased risk for
gallstones  as well as several unspecific symptoms
including neurologic ones.
Given that GS is regarded as a chronic condition not
requiring treatment symptoms are persisting life-long after
onset of the disease. Herein we present a case of a patient
with GS in whom both laboratory parameters and
associated symptoms have been reversed following a shift
toward the popular paleolithic and then toward the
paleolithic ketogenic diet. Previously we have published
successful treatment of epilepsy , type 1 diabetes 
and metabolic syndrome  with the paleolithic ketogenic
diet. This diet is close to the meat-fat based diet originally
proposed by gastroenterologist Voegtlin as being the
evolutionary adapted diet in humans .
2. Case Report
In 2006 GS was accidentally discovered in the female
patient aged 30 due to a routine laboratory test. This
showed elevations in both serum total bilirubin (31 µmol/l)
and directbilirubin (9.16 µmol) levels. Liver function tests
as well as other laboratory parameters were normal except
for low serum iron concentration (Table 1). Sclera of the
eyes showed persistent yellowish discolouration but no
signs of liver disease were present. Based on the
proportion of direct bilirubin to total bilirubin and clinical
features the hyperbilirubinaemia was classified as
Gilberts’s syndrome . At this time the patient had a
10-year history of migrain episodes with an average
frequency of ~3/month. Her additional symptoms included
fatigue, constipation and unclassified granulomatosus
dermatitison both legs. Dermatitis was present for 10
years. No biopsy was taken to specify histology. She had
not been taking any medicines, vitamins or other
supplements. She reported no smoking and alcohol
abstinence. She was weak with a BMI of 17,9 (weight: 50
kg, height: 167 cm).
2.1. Popular Paleolithic Diet
On 09 November 2010 the patient decided to initiate
the paleolithic diet. Laboratory blood test performed at
diet onset showed a further eleveation in total bilirubin but
other laboratory parameters were normal (Figure 1 and
Table 1). Direct bilirubin was not tested at this time. The
popular form of the paleolithic diet she initiated restricted
118 American Journal of Medical Case Reports
milk, dairy, refined carbohydrates, cereals, legumes,
maize, rice and most vegetable oils. Thus the diet was
based on vegetables, fruits, meat, eggs but also contained
oilseeds, coconut oil, sugar alcohols and coconut. This
diet was however low in animal fat, red meats and offal.
Amount of fat, protein and carbohydrates were not
predefined in the popular paleolithic diet. She had been
following the diet for 20 months between Nov 2010 and
A laboratory test on 09 Nov 2011, a year after diet
onset, indicated a decrease in the level of both total and
direct bilirubin. Iron level was now in the normal range
and other parameters were normal too (Table 1).
Yellowish decoloration of the sclera disappeared. There
was a decrease in the number of migraine episodes (~6
episodes/year) and constipation resolved too. However
there was no change in feeling fatigue and in the presence
of granulomatosus dermatitis. Another concern was
weight loss. While on the popular paleolithic diet she lost
5 kilograms and so her BMI at this time was only 16.1.
2.2. Paleolithic Ketogenic Diet
In July 2012 we adviced a shift toward the paleolithic
ketogenic diet. This diet is based on animal fat, meat, eggs
and offal and to a lesser extent (less than 30%) vegetables
and fruits. Fat to protein ratio was at least 2:1 (in gram).
Fat and red meats derived from pork and cattle were
encouraged over lean meats from poultry. She consumed
offal from pork and cattle (predominantly liver, brain and
marrow) at least two times a week. She was avoiding
foods with additives including nitrites and/or nitrates.
Foods that are allowed or even encouraged in the popular
paleolithic diet such as artificial sweeteners, coconut oil,
oilseeds, oilseed flours and cocoa were excluded. She used
small amounts of honey. Ketosis was checked regularly by
urinary keton strips which showed sustained ketosis. The
four laboratory tests taken five months, 12 months, 19
months and 31 months after the onset of the paleolithic
ketogenic diet showed total bilirubin and direct bilirubin
levels below the upper reference limit (Figure 1). In these
measurements cholesterol and LDL cholesterol were
elevated but other laboratory measures were normal.
Testing for folic acid, vitamin B12 and vitamin D
(25(OH)D) in years 2014 and 2015 showed adequate
levels of these vitamins (Table 1).
Figure 1. Time course of total bilirubin levels through the normal, the
popular paleolithic and the paleolithic ketogenic diet. Note that with a
shift toward the popular paleolithic and then toward the paleolithic
ketogenic diet bilirubin levels fall below the upper reference limit
While on the paleolithic ketogenic diet her fatigue
disappeared and she experienced increased fittness both
physically and mentally. Her migraine episodes further
decreased (to ~2/year). Granulomatosus dermatitis
disappeared on both legs. Her weight was increased by 4
kilograms. Currently her BMI is 17.6. She reports no side
effects of the diet.
GS is regarded as a lifelong condition of altered
bilirubin metabolism . In our patient, however, clinical
features designating this condition have been reversed by
shifting first toward the paleolithic then toward the
paleolithic ketogenic diet. During this time serum level of
both total and directbilirubin declined below the upper
limit of the normal range. Although bilirubin levels
decreased and yellowish decoloration of the sclera
disappeared while on the popular paleolithic diet,
weakness, fatigue, migraine and granulomatosus
dermatitis improved considerably only after the shift
toward the paleolithic ketogenic diet.
While on the paleolithic ketogenic diet a laboratory
assessement indicated low level of inflammatory markers
(CRP, fibrinogen), normal level of triglicerides, uric acid,
glucose, ions, normal liver and kidney function. Total
cholesterol as well as LDL cholesterol were elevated.
Such a laboratory profile corresponds to that seen in our
previous patients with epilepsy , type 1 diabetes  and
metabolic syndrome  on the paleolithic ketogenic diet.
Supplementing vitamins on the classical ketogenic diet is
generally recommended. In the present case, however,
despite the absence of supplementing, vitamin D, folic
acid and vitamin B12, as assessed by laboratory
measurements in 2014 and 2015, were in the normal range.
Physicians generally opine that a metabolic condition
with a perceived genetic predisposition such as the GS
cannot be influenced by diet. We are not aware of studies
using dietary intervention is GS. However fasting and
glucose administration both orally and intravenously are
known to elevate bilirubin levels in GS patients [12,13].
Interestingly in a study carried out 40 years ago both
phenomena could be reversed by the addition of lipids
. Then it was concluded that both phenomena are due
to the withdrawal of lipids.
Current dietary guidelines recommend the reduction of
fat and especially saturated fat in the diet . However
there is growing evidence that the recommendation on
high carbohydrate/low fat diet may not be supported with
sufficient evidence  while carbohydrate-restricted
ketogenic diets have been shown to confer several health
benefits . This was also the case in our patient with
GS and in the three other cases on the paleolithic
ketogenic diet [7,8,9].
It is of important to emphasize that unlike the classical
ketogenic diet which is known to be associated with
several adverse effects the paleolithic ketogenic diet does
not have any side effects as also examplified our present
and previous patients [7,8,9]. A second important point is
that although in this case there were some improvements
onthe popular paleolithic diet, the remaining symptoms
were only resolved with the paleolithic ketogenic diet.
American Journal of Medical Case Reports 119
We believe that the beneficial effects of the paleolithic
ketogenic effect are due tothe shift from carbohydrate-
based to fat-based metabolism, adequate intake and
bioavailability of vitamins and minerals as well as the
restriction of ”antinutrients” found in non-paleolithic 
and in the popular paleolithic foods.
In the literature there are a few short-term studies
[19,20,21] and a long-term intervention study  with
the paleolithic diet in healthy people and in patients with
metabolic syndrome. The present case strenghtens our
experience that the paleolithic diet in its widely used
popular form is limited in effectiveness in diseases with
components other than glucose metabolism alterations.
The paleolithic ketogenic diet, however, may be remedial
in these cases [7,8,9,23].
Table 1. Laboratory data while on the normal, the popular paleolithic and the paleolithic ketogenic diet. Dashes indicate that the given
parameter was not measured
Popular paleolithic diet
Paleolithic ketogenic diet
26 Apr 2006
09 Nov 2010
09 Nov 2011
04 Dec 2012
18 Jul 2013
11 Feb 2014
12 Feb 2015
Abbreviations: WBC – white blood cell, RBC – red blood cell, Hgb – hemoglobin, Ht – hematocrit, GOT – glutamate-oxaloacetate transaminase, GPT –
glutamate-pyruvate transaminase, GGT – gamma-glutamyl transferase, ALP – alkaline phosphatase, CRP – C reactive protein, ESR – erythrocyte
Statement of Competing Interests
The authors have no competing interests.
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