Gilbert's Syndrome Successfully Treated with the Paleolithic Ketogenic Diet

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DOI: 10.12691/ajmcr-3-4-9
Cite this publication
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.
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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
DOI:10.12691/ajmcr-3-4-9
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: clemenszsofia@gmail.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:
10.12691/ajmcr-3-4-9.
1. Introduction
Gilbert’s syndrome (GS) is a hereditary
hyperbilirubinaemia syndrome affecting 5-10% of the
population [1]. 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 [2] and a positive
feedback of bilirubin through its mild haemolytic effect
[3].
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 [3].
Nevertheless GS is also known to be associated with a set
of unfavorable symptoms including fatigue, itching,
gastrointestinal symptoms [2], increased risk for
gallstones [6] 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 [7], type 1 diabetes [8]
and metabolic syndrome [9] 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 [10].
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 [11]. 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
Jul 2012.
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.
3. Discussion
GS is regarded as a lifelong condition of altered
bilirubin metabolism [11]. 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 [7], type 1 diabetes [8] and
metabolic syndrome [9] 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
[14]. 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 [15]. However
there is growing evidence that the recommendation on
high carbohydrate/low fat diet may not be supported with
sufficient evidence [16] while carbohydrate-restricted
ketogenic diets have been shown to confer several health
benefits [17]. 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 [18]
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 [22] 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
Normal diet
Popular paleolithic diet
Paleolithic ketogenic diet
26 Apr 2006
09 Nov 2011
04 Dec 2012
18 Jul 2013
11 Feb 2014
12 Feb 2015
Total bilirubin
31
21.6
17.4
20.5
20.5
17.7
µmol/l
Direct bilirubin
9.16
< 5
-
-
3
3
µmol/l
WBC
8.6
6.3
6.06
6.1
6.4
6.4
G/l
RBC
5.07
4.78
4.44
4.82
4.8
4.6
T/l
Hgb
143
139
136
141
144
136
g/l
Ht
45
43
41
42
0.44
0.42
%
Thrombocyte
277
285
284
249
253
252
G/l
Natrium
136.3
138
132
133
136
138
mmol/l
Kalium
3.8
4.3
4.1
4.4
4.2
4.1
mmol/l
Glucose
4.7
5.1
5.1
5.5
5.4
4.7
mmol/l
GGT
10
13
16
19
14
13
U/l
GOT
19
16
12
15
20
22
U/l
GPT
26
26
23
33
15
12
U/l
ALP
70
70
62
66
-
-
U/l
Total cholesterol
4.03
4.8
5.8
5
7.7
6.8
mmol/l
HDL cholesterol
1.95
2.25
2.23
2.36
-
2.21
mmol/l
LDL cholesterol
1.81
2.39
-
-
-
4.49
mmol/l
Triglycerides
0.59
0.35
0.48
0.24
0.71
0.99
mmol/l
Uric acid
189
-
188
175
201
266
µmol/l
Total protein
79.3
70
72
71
73
72
g/l
Albumin
50
49
40
40
47.8
48.2
g/l
Carbamide
3.8
4.1
5
4.7
5.7
5.7
mmol/l
Creatinine
72
68
58
79
63
75
µmol/l
CRP
<3
1
1
<3
0.27
0.28
mg/l
ESR
-
3
7
3
3
4
mm/h
Iron
8.2
17.6
14.9
24.9
22.1
19.7
µmol/l
Magnesium
-
-
-
0.64
0.87
0.84
mmol/l
Vitamin B12
-
-
-
-
371.6
429
pmol/l
Folic acid
-
-
-
-
51.2
31.8
nmol/l
25(OH)D
-
-
-
-
163
124.1
nmol/l
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
sedimantation rate.
Funding
None
Statement of Competing Interests
The authors have no competing interests.
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  • ... Geijer and Ekelund. I am using a low carbohydrate diet, we refer to as the paleolithic ketogenic diet, in the treatment of diverse chronic diseases already for six years [1][2][3][4][5][6]. I have to say that in my practice I did never see a single case where ketoacidosis or metabolic acidosis developed while on the paleolithic ketogenic diet, even though I am familiar with the diagnosis and treatment of these conditions given my 5-years experience in ICU. ...
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    I became curious when I read the title of the case report by drs. Geijer and Ekelund. I am using a low carbohydrate diet, we refer to as the paleolithic ketogenic diet, in the treatment of diverse chronic diseases already for six years [16]. I have to say that in my practice I did never see a single case where ketoacidosis or metabolic acidosis developed while on the paleolithic ketogenic diet, even though I am familiar with the diagnosis and treatment of these conditions given my 5 years experience in ICU. reflected in this report. First, lactation itself does not predispose to ketosis. Whether ketosis develops in a healthy lactating woman only depends on the type of the nutrition. In newborn infants, however, ketosis is achieved within a few hours after birth and they remain so while breastfeeding. There is ample evidence showing that the state of ketosis is not abnormal but physiological at any age. For example, indigenous people of the Arctic following a traditional fatmeat based diet containing little or no carbohydrate are in ketosis through their entire lifespan. Our experience with patients also indicates that even a prolonged full fatmeat diet does neither predispose to ketosis or metabolic acidosis. Given these facts the explanation for the phenomenon described in the report of drs. Geijer and Ekelund lies elsewhere.
  • ... Geijer and Ekelund. I am using a low carbohydrate diet, we refer to as the paleolithic ketogenic diet, in the treatment of diverse chronic diseases already for six years [1][2][3][4][5][6]. I have to say that in my practice I did never see a single case where ketoacidosis or metabolic acidosis developed while on the paleolithic ketogenic diet, even though I am familiar with the diagnosis and treatment of these conditions given my 5-years experience in ICU. ...
    Article
    Full-text available
    I became curious when I read the title of the case report by drs. Geijer and Ekelund. I am using a low carbohydrate diet, we refer to as the paleolithic ketogenic diet, in the treatment of diverse chronic diseases already for six years [16]. I have to say that in my practice I did never see a single case where ketoacidosis or metabolic acidosis developed while on the paleolithic ketogenic diet, even though I am familiar with the diagnosis and treatment of these conditions given my 5years experience in ICU. In my reply I would like to comment on the case presented and to clarify some common misunderstandings related to ketosis whi ch are also reflected in this report. First, lactation itself does not predispose to ketosis. Whether ketosis develops in a healthy lactating woman only depends on the type of the nutrition. In newborn infants, however, ketosis is achieved within a few hours after birth and they remain so while breastfeeding. There is ample evidence showing that the state of ketosis is not abnormal but physiological at any age. For example, indigenous people of the Arctic following a traditional fat-meat based diet containing little or no carbohydrate are in ketosis through their entire lifespan. Our experience with patients also indicates that even a prolonged full fat-meat diet does neither predispose to ketosis or metabolic acidosis. Given these facts the explanation for the phenomenon described in the report of drs. Geijer and Ekelund lies elsewhere. It is important to emphasize that low carbohydrate diets can only be maintained on the long term when the diet is high in fat... report it is not detailed how the authors ascertained whether the diet was indeed high in fat and what exactly the patient was eating. Other important details were not mentioned either such as the weight or BMI of the patient. This is an important issue given that loss of 4 kg within 10 days in a thin patient should be regarded as starvation. In an obese patient, however, such a weight loss simply reflects loss of retained water but not starvation. It is also not mentioned whether breath acetone was detectable or not, an important characteristic of ketoacidosis. In the following I put forward those possible scenarios which alone or in combination may explain the development of the condition described in the patient.
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    Background: Many concepts try to explain the current rise in the chronic non-communicable diseases. Within the framework of evolutionary medicine there is a common explanation for these diseases in the form of an insufficient adaption to the modern lifestyle, which also reflects in the word “diseases of civilization”. Nutrition plays a key role within this framework. Accordingly, the terms “Paleolithic diet”, “Stone Age diet” or simply “Paleo diet” have been introduced to refer to a diet that tries to mimic human dietary behaviors during the Old Stone Age (Paleolithic) era, which chronologically spans the majority of human existence. Because the Paleo diet is not only becoming more popular among consumers, but also receives increased attention from the international scientific community, the goal of this review is to comprehensively summarize the background, principles and scientific evaluation of the Paleo diet for the German-speaking part. Materials and Methods: Based on anthropological and ethnographic studies, supplemented with physiological insights, a short overview of the evolution of the human diet during the Old Stone Age is given. From these insights the principles of a modern Paleo diet are derived. All clinical studies published to date using a Paleo diet as an intervention have been shortly described and evaluated. Finally, the Paleo diet is discussed within the broader context of a modern evolutionary medicine that primarily aims at preventing the chronic non-communicable diseases. Results: Although only studies with small sample sizes and methodological shortcomings have been published, they nevertheless have consistently shown that a Paleolithic diet is superior to other diets, also those regarded as wholesome. The largest evidence supports a beneficial effect on coronary risk factors, while beneficial effects on autoimmune diseases seem probable. Conclusion: A Paleolithic diet appears suitable for the treatment of coronary diseases, and probably also autoimmune disorders. Compliance to the diet is facilitated by its intuitive analogy to a “species-appropriate” diet.
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    Objectives: National dietary guidelines were introduced in 1977 and 1983, by the US and UK governments, respectively, with the ambition of reducing coronary heart disease (CHD) by reducing fat intake. To date, no analysis of the evidence base for these recommendations has been undertaken. The present study examines the evidence from randomised controlled trials (RCTs) available to the US and UK regulatory committees at their respective points of implementation. Methods: A systematic review and meta-analysis were undertaken of RCTs, published prior to 1983, which examined the relationship between dietary fat, serum cholesterol and the development of CHD. Results: 2467 males participated in six dietary trials: five secondary prevention studies and one including healthy participants. There were 370 deaths from allcause mortality in the intervention and control groups. The risk ratio (RR) from meta-analysis was 0.996 (95% CI 0.865 to 1.147). There were 207 and 216 deaths from CHD in the intervention and control groups, respectively. The RR was 0.989 (95% CI 0.784 to 1.247). There were no differences in all-cause mortality and non-significant differences in CHD mortality, resulting from the dietary interventions. The reductions in mean serum cholesterol levels were significantly higher in the intervention groups; this did not result in significant differences in CHD or all-cause mortality. Government dietary fat recommendations were untested in any trial prior to being introduced. Conclusions: Dietary recommendations were introduced for 220 million US and 56 million UK citizens by 1983, in the absence of supporting evidence from RCTs.
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    Introduction: Metabolic syndrome is a major public health problem affecting at least 20% of the world’s adult population. Components of the metabolic syndrome include obesity, impaired glucose metabolism, hypertension and altered lipid profile. Currently, medical treatment relies on drugs. A major problem is that patients with long-standing disease are excessively medicated because of an increase in the number of symptoms over time. A few clinical studies indicate that low-carbohydrate diets, including the paleolithic as well as the ketogenic diet, may be beneficial in the treatment of conditions associated with the metabolic syndrome. Case Report: Herein, we present a case of patient with metabolic syndrome successfully treated with the paleolithic ketogenic diet. While on the diet the patient was able to discontinue eight medicines, lost weight, showed a continuous improvement in glucose parameters and her blood pressure normalized. Currently, the patient is on the paleolithic ketogenic diet for 22 months, free of symptoms and side effects. Conclusion: We conclude that the paleolithic ketogenic diet was safe, feasible and effective in the treatment of this patient with metabolic syndrome.
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    Objectives: National dietary guidelines were introduced in 1977 and 1983, by the US and UK governments, respectively, with the ambition of reducing coronary heart disease (CHD) by reducing fat intake. To date, no analysis of the evidence base for these recommendations has been undertaken. The present study examines the evidence from randomized controlled trials (RCTs) available to the US and UK regulatory committees at their respective points of implementation. Methods: A systematic review and meta-analysis were undertaken of RCTs, published prior to 1983, which examined the relationship between dietary fat, serum cholesterol and the development of CHD. Results: 2467 males participated in six dietary trials: five secondary prevention studies and one including healthy participants. There were 370 deaths from all-cause mortality in the intervention and control groups. The risk ratio (RR) from meta-analysis was 0.996 (95% CI 0.865 to 1.147). There were 207 and 216 deaths from CHD in the intervention and control groups, respectively. The RR was 0.989 (95% CI 0.784to 1.247). There were no differences in all-cause mortality and non-significant differences in CHD mortality, resulting from the dietary interventions. The reductions in mean serum cholesterol levels were significantly higher in the intervention groups; this did not result in significant differences in CHD or all-cause mortality. Government dietary fat recommendations were untested in any trial prior to being introduced. Conclusions: Dietary recommendations were introduced for 220 million US and 56 million UK citizens by 1983, in the absence of supporting evidence from RCTs.
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    Introduction: Type 1 diabetes mellitus (T1DM) patients are usually instructed to follow a low fat/high carbohydrate diet. A few studies in literature, however, reported metabolic benefits and sustainability of carbohydrate restricted diets. Case Report: Herein, we present a case of a 19-year-old male with newly diagnosed T1DM. The patient was first put on an insulin regime. Twenty days later, he shifted towards the paleolithic ketogenic diet and was able to discontinue insulin. Strict adherence to the diet resulted in normal glucose levels and a more than three-fold elevation of C-peptide level indicating restored insulin production. Currently, the patient is on the paleolithic ketogenic diet for 6.5 months. He is free of complaints, and no side effects emerged. Conclusion: We conclude that the paleolithic ketogenic diet was effective and safe in the management of this case of newly diagnosed T1DM. Marked increase in C peptide level within two months indicates that the paleolithic ketogenic diet may halt or reverse autoimmune processes destructing pancreatic beta cell function in T1DM.
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    Introduction Childhood absence epilepsy is an epilepsy syndrome responding relatively well to the ketogenic diet with one-third of patients becoming seizure-free. Less restrictive variants of the classical ketogenic diet, however, have been shown to confer similar benefits. Beneficial effects of high fat, low-carbohydrate diets are often explained in evolutionary terms. However, the paleolithic diet itself which advocates a return to the human evolutionary diet has not yet been studied in epilepsy. Results Here, we present a case of a 7-year-old child with absence epilepsy successfully treated with the paleolithic ketogenic diet alone. In addition to seizure freedom achieved within 6 weeks, developmental and behavioral improvements were noted. The child remained seizure-free when subsequently shifted toward a paleolithic diet. Conclusion It is concluded that the paleolithic ketogenic diet was effective, safe and feasible in the treatment of this case of childhood absence epilepsy.
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    Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.European Journal of Clinical Nutrition advance online publication, 26 June 2013; doi:10.1038/ejcn.2013.116.