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Type 1 diabetes mellitus successfully managed with the paleolithic ketogenic diet

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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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International Journal of Case Reports and Images, Vol. 5 No. 10, October 2014. ISSN – [0976-3198]
Int J Case Rep Images 2014;5(10):699–703.
www.ijcasereportsandimages.com
Tóth et al. 699
CASE REPORT OPEN ACCESS
Type 1 diabetes mellitus successfully managed with the
paleolithic ketogenic diet
Csaba Tóth, Zsófia Clemens
ABSTRACT
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.
Keywords: Type 1 diabetes mellitus, Ketogenic
diet, Paleolithic-ketogenic diet, C-peptide,
Evolutionary medicine
Csaba Tóth1, Zsófia Clemens2
Affiliations: 1MD, Medical Director, Paleomedicina Hungary
Ltd, Evolutionary Medicine Working Group, Hidász u. 3,
H-1026, Budapest, Hungary; 2PhD, Senior Research Fellow,
Department of Neurology, University of Pécs, Rét u. 2,
H-7623, Pécs, Hungary.
Corresponding Author: Zsófia Clemens, Department of
Neurology, University of Pécs, Rét u. 2, H-7623, Pécs, Hungary.
Ph: 003672535900; Email: clemenszsofia@gmail.com
Received: 08 July 2014
Accepted: 31 July 2014
Published: 01 October 2014
How to cite this article
Tóth C, Clemens Z. Type 1 diabetes mellitus
successfully managed with the paleolithic ketogenic
diet. Int J Case Rep Images 2014;5(10):699–703.
doi:10.5348/ijcri-2014124-CR-10435
INTRODUCTION
Diabetic patients are, generally, recommended to
follow a diet that is low in fat and high in carbohydrates
[1]. Clinical studies, conversely, showed metabolic
benefits conferred by carbohydrate-restricted diets
including the ketogenic diet [2, 3] and the paleolithic
diet [4, 5] in type 2 diabetes. Much less data on the use
of low carbohydrate diets in type 1 diabetes (T1DM)
are available. Two studies by Nielsen et al. showed that
a low carbohydrate diet lowers the need for insulin as
well as the number of hypoglycemic episodes in T1DM
[6, 7]. It was also suggested that a low carbohydrate diet
is sustainable on the long-term [6, 7]. Ketogenic diets
have long been used in epilepsy [8]. There are three
cases in literature, where concurrent epilepsy and T1DM
were treated with the classical ketogenic diet and both
conditions improved [9–11]. Recently, we published
a case of childhood absence epilepsy where seizure
freedom was achieved using a modified ketogenic diet we
refer to as the paleolithic-ketogenic diet [12]. Herein, we
present a case of T1DM, where the same diet resulted in
remission of T1DM as assessed by normalization of blood
glucose levels and elevation in C-peptide level allowing
for discontinuation of external insulin replacement.
CASE REPORT
A 19-year-old male complained of increased thirst,
polyuria, itchy skin, malaise, and weight loss. The
symptoms were present for about two weeks prior to
International Journal of Case Reports and Images, Vol. 5 No. 10, October 2014. ISSN – [0976-3198]
Int J Case Rep Images 2014;55(10):699–703.
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Tóth et al. 700
diagnosis. On November 24, 2013 self monitoring of
blood glucose showed 384 mg/dL. Previous medical
history was unremarkable. Anamnestic data included
consuming of muscle boosting protein through a month
prior to symptom onset. Laboratory assessment on
November 25, 2013 (Table 1) showed elevations in glucose
(218 mg/dL) and HbA1c (9.2%). Testing for glutamic acid
decarboxylase (GAD) antibodies showed positivity
(52 U/mL; normal range 0–10 U/mL) and mild positivity
for pancreatic islet cell autoantibodies (ICAs). C-peptide
level was not measured at this time. He was diagnosed
with T1DM. He was put on insulin replacement therapy
(38 IU of insulin) and standard conventional diabetes
diet with six meals containing 240 grams carbohydrate
daily. He followed this regime for 20 days. While on this
regime his glucose levels fluctuated between 68–267
mg/dL (Figure 1).
Carbohydrate he consuming before was less than 240
grams. Since his malaise did not improve the patient
consulted the first author in December 2013. To ascertain
T1DM laboratory examination of C-peptide was carried
out. C-peptide level of 0.6 ng/mL measured on January
08, 2014 indicated subnormal insulin secretion (Figure
2). The patient was suggested to switch to the paleolithic-
ketogenic diet which he initiated on December 21, 2013.
From this time, he was also taking 5,000 IU of vitamin
D3 but nothing else as supplement. His diet consisted
of meat, organ meat, fat and eggs. In his diet, red and
fat meats dominated over lean meats. He was eating
vegetables in insignificant amounts. His diet had a
ketogenic ratio (fat : protein + carbohydrate) of at least
2:1. No oil of plant origin or artificial sweeteners were
allowed. The patient was under our close control and
reported daily food records and blood glucose levels.
Upon shifting toward the paleolithic ketogenic diet
glucose levels returned to normal and no major elevations
were seen postprandially either. Insulin was therefore
discontinued. The tapering of insulin was done promptly:
following the first paleolithic-ketogenic meal glucose level
was only 86 mg/dL thus there was no need for external
insulin. Similar blood glucose levels were measured on
subsequent meals on the diet. Thus, the patient required
no insulin subsequently either. Home glucose monitoring
was carried out preprandially as well as postprandially
and tracked once a day for consecutive meals (that is on
consecutive days measures were taken for breakfast, lunch
and dinner, respectively). Average blood glucose level
while on the standard diabetes diet with insulin was 119
mg/dL while 85 mg/dL on the paleolithic-ketogenic diet
without insulin. Fluctuations in glucose levels decreased
as indicated by a reduction of standard deviation values
from 47 mg/dL on the standard diabetes diet to 9 mg/dL
on the paleolithic-ketogenic diet. Average postprandial
glucose elevation on the standard diabetes diet was 23
mg/dL while only 5.4 mg/dL on the paleolithic-ketogenic
diet (Figure 1).
C-peptide measurement was repeated on the 10th
week of the diet (on March 06, 2014). This indicated
an elevation to a value of 2.2 ng/mL (Figure 2). A
comprehensive laboratory workup carried out on March
14, 2014 indicated normal laboratory parameters with
the exception of total cholesterol and LDL cholesterol
which were slightly elevated. Glucose level was 88 mg/
dL while HbA1c was 5.5% (for all laboratory values see
Table 1). Urinary ketone was positive. On March 21, 2014
antibody testing for ICA showed no change in the mild
Table 1: Laboratory data at the time of diagnosis on a normal diet
(on November 25, 2013) and at 10 weeks after diet initiation,
on the paleolithic-ketogenic diet without insulin (on March 14,
2014). Note the normal level of glucose, HbA1c and low level
of triglyceride while on the paleolithic-ketogenic diet. Dashes
indicate that the given parameter was not measured.
Normal diet Paleolithic-ketogenic diet
WBC 5.9 5.4 G/l
RBC 5.7 5.3 T/l
Hemoglobin 16 15.2 G/dL
Hematocrit 48 45 %
Iron 136.3 98.9 µg/ dL
Thrombocyte 230 150 G/l
Sodium 134 139 mEq/l
Potassium 3.9 3.8 mEq/l
Calcium 9.52 10 mg/dL
Magnesium 2.02 mg/dL
Carbamide 10.6 14.8 mg/dL
Creatinine 0.88 0.97 mg/dL
eGFR >90 >90
Glucose 218 88 mg/dL
Hb1Ac 9.2 5.5 %
Total cholesterol 143 301 mg/dL
HDL cholesterol 54.8 mg/dL
LDL cholesterol 224 mg/dL
Triglyceride 168 111 mg/dL
Uric acid 6.12 mg/dL
GOT 31 19 U/l
GPT 44 18 U/l
GGT 17 16 U/l
Total bilirubin 0.94 mg/dL
TSH 3.53 mIU/l
CRP 1.1 mg/L
Abbreviations: WBC - white blood cell count, RBC - red blood
cell count, eGFR - estimated glomerular filtration rate, HbA1c -
glycated hemoglobin, HDL - high density lipoprotein, LDL - low
density lipoprotein, TSH - thyroid stimulating hormone, CRP
- C-reactive protein
International Journal of Case Reports and Images, Vol. 5 No. 10, October 2014. ISSN – [0976-3198]
Int J Case Rep Images 2014;55(10):699–703.
www.ijcasereportsandimages.com
Tóth et al. 701
positivity measured before and some elevation in GAD
antibodies (86 U/mL). At the time of writing this case
report, the patient is on the paleolithic ketogenic diet for
6.5 months and still exhibit low glucose levels. No side
effects emerged and he is completely free of symptoms.
The patient gave written informed consent for writing
this case study.
DISCUSSION
This is a first report of T1DM being successfully
managed with the paleolithic-ketogenic diet. In literature,
a few studies are available on the use of carbohydrate
restricted diet in the treatment of T1DM [6, 7]. Low
carbohydrate diet in these studies resulted in reduced
number of hypoglycemic episodes and also lowered
the need for insulin. In our case, however, insulin
replacement was not just reduced but could be stopped.
Importantly, insulin discontinuation was paralleled by
a marked increase in C peptide level indicating restored
pancreatic insulin production.
Shortly before diabetes onset our patient consumed
muscle boosting protein which contained bovine milk
protein. Consumption of cow’s milk has repeatedly been
shown to increase risk of T1DM [13, 14]. It is suggested
that bovine milk protein may promote autoimmune
processes giving rise to T1DM [15]. Also in two case
reports from literature, where epilepsy was treated
with the classical ketogenic diet, which contains large
amount of dairy, T1DM developed subsequently [9, 11].
A major difference between the classical ketogenic diet
and the paleolithic ketogenic diet is that milk and dairy
are excluded in the latter. We suggest that the paleolithic
ketogenic diet not only normalize glucose levels but
may also halt autoimmune processes mediated by non-
paleolithic substances including milk protein [16].
While on the paleolithic-ketogenic diet glucose levels
remained low both during preprandially and postprandially.
Follow-up laboratory assessment indicated laboratory
parameters remaining in the normal range except for
elevations in total cholesterol and LDL cholesterol. In fact,
these elevations are expected on a diet rich in animal fat
and cholesterol and were also reported in studies with the
classical ketogenic diet [17] as well as in our previous case
of childhood absence epilepsy treated with the paleolithic
ketogenic diet [12]. Moreover, it is now acknowledged that
neither dietary nor serum cholesterol represent a risk factor
for cardiovascular disease [18]. On follow-up antibody
testing ICA remained mildly positive while GAD antibodies
elevated to some extent. Although these parameters are
frequently associated with T1DM they do not seem to be
specific nor indicate progression of disease [19].
Type 1 diabetes mellitus is considered as a lifelong
metabolic condition due to the exhaustion of insulin-
secretory cells of the pancreas. Therefore, T1DM is
generally believed to be untreatable by any diet. There
are indications, however, that residual pancreatic beta
cell functioning may extend well beyond the time of
diagnosis [20]. Nevertheless C-peptide levels decrease
monotonically through years after diagnosis [20]. We are
not aware of any data from literature indicating elevation
of C-peptide resulting from a dietary intervention. A
recent case study of a child with T1DM reported remission
without insulin on gluten-free diet [21]. However, in that
case C-peptide continued to decline while on the gluten-
free diet.
Figure 1: Blood glucose levels while on the standard diabetes
diet containing 240 g carbohydrate with insulin therapy and
while on the paleolithic-ketogenic diet without insulin. Glucose
was measured preprandially and postprandially once a day for
consecutive meals (that is on consecutive days measures were
taken for breakfast, lunch and dinner, respectively). Note low
glucose levels and the absence of major postprandial elevations
while on the paleolithic ketogenic diet. Due to stable glucose
levels through five months, from May 15, 2014 the patient
switched to self-monitoring his glucose levels only once a week.
Figure 2: C-peptide levels shortly after diet initiation (on the
18th day of the paleolithic ketogenic diet) and two months later.
Note the more than three-fold increase in C-peptide within two
months.
International Journal of Case Reports and Images, Vol. 5 No. 10, October 2014. ISSN – [0976-3198]
Int J Case Rep Images 2014;55(10):699–703.
www.ijcasereportsandimages.com
Tóth et al. 702
In the standard care of T1DM insulin is a cornerstone.
It is important to emphasize that the paleolithic-
ketogenic diet as a standalone therapy may be applied
only in those cases with residual insulin secretion. In
cases with no internal insulin secretion the paleolithic-
ketogenic therapy may be only used as an adjunct to
insulin replacement.
CONCLUSION
We suggest that an intervention with the paleolithic
ketogenic diet in an early stage of the disease with residual
insulin secretion may halt or reverse type 1 diabetes
mellitus (T1DM). Follow-up at sixth month in the case of
our patient is relatively short and the positive results may
appear as a honeymoon effect. However, this term is used
in relation to the beginning of insulin therapy not the end
of it. We believe that with normalized insulin secretion
and a further adherence to the diet the patient may be
managed on the long-term.
*********
Author Contributions
Tóth Csaba – Substantial contributions to conception and
design, Acquisition of data, Analysis and interpretation
of data, Drafting the article, Revising it critically for
important intellectual content, Final approval of the
version to be published
Zsófia Clemens – Substantial contributions to
conception and design, Acquisition of data, Analysis
and interpretation of data, Drafting the article, Revising
it critically for important intellectual content, Final
approval of the version to be published
Guarantor
The corresponding author is the guarantor of submission.
Conflict of Interest
Authors declare no conflict of interest.
Copyright
© 2014 Tóth Csaba et al. This article is distributed
under the terms of Creative Commons Attribution
License which permits unrestricted use, distribution
and reproduction in any medium provided the original
author(s) and original publisher are properly credited.
Please see the copyright policy on the journal website for
more information.
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ABOUT THE AUTHORS
Article citation: Tóth C, Clemens Z. Type 1 diabetes mellitus successfully managed with the paleolithic ketogenic
diet. Int J Case Rep Images 2014;5(10):699–703.
Csaba Tóth is General Practitioner from Hungary with 20 years experience in intensive care medicine,
internal medicine and family medicine. He is using the paleolithic-ketogenic nutrition in the treatment
of chronic medical illnesses including diabetes, cancer, autoimmune diseases and epilepsy for ve
years. He is operating private practice in Budapest and in a few other cities in Hungary. In 2013, he
organized a course on evolutionary medicine in the mandatory training of GPs at the University of
Szeged, Hungary. With an evolutionary medical attitude he strives for the full recovery of his patients.
Email: csaba@paleomedicina.com
Zsóa Clemens is Biologist and clinical researcher specialized in nutrition, nutritional therapy and
brain research. She earned her PhD in electroencephalograpy of sleep and epilepsy from Semmelweis
University, Budapest, Hungary in 2005. Currently, she is Senior Research Fellow at the Neurological
Department, University of Pécs, Hungary and is also afliated with the Evolutionary Medicine Working
Group of Paleomedicina Hungary Ltd. In international academic journals, she has published 29 research
articles with more than 500 citations. Email: clemenszsoa@gmail.com
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... Thus far, we have published several case reports of patients successfully treated with the PKD. These include: type 2 (Tóth and Clemens, 2015a) and type 1 diabetes (Tóth and Clemens, 2014;2015b), Crohn's disease , Gilbert's syndrome (Tóth and Clemens, 2015c), epilepsy (Clemens et al., 2013(Clemens et al., , 2015; complete reversal of cervical intraepithelial neoplasia ; halted progression of soft palate cancer , regression of rectal cancer (Tóth and Clemens, 2017) and unexpectedly long survival with glioblastoma (Tóth et al., 2019). In 2017, we published a study with 50 patients on the PKD with 98% showing magnesium levels in the normal range, which is unexpected for a population with chronic diseases. ...
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C-peptide is used as a measure of endogenous insulin production. Given that insulin and C-peptide are produced in equal amounts, C-peptide is typically used to differentiate between external and endogenously produced insulin in insulin-treated type 1 diabetes mellitus (T1DM). In a clinical setting, a decline in C-peptide is regarded as a loss of beta cell function. However, physiological conditions may also be associated with low C-peptide levels. The authors of this paper use a low-carbohydrate diet, the so-called paleolithic ketogenic diet (PKD), in the treatment of various conditions and observed that C-peptide is typically low on this diet. In order to characterize C-peptide levels on this diet, we designed a study to retrospectively assess C-peptide levels in 100 non-T1DM subjects. We found that 55% of the subjects had a C-peptide level below the standard reference range. C-peptide levels correlated with glucose levels. A significant correlation was found between C-peptide and age, with younger subjects having lower C-peptide levels. Males also showed lower C-peptide levels than females. Given the increasing number of patients using low-carbohydrate diets worldwide, physicians should be aware of laboratory correlates of low-carbohydrate diets, including low C-peptide levels, most importantly to prevent incorrect T1DM diagnosis.
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The exponentially growing frequency of diagnosing diabetes mellitus means that a verification of the previous dietetic approach to treating the disease seems justified. The simultaneous growth of interest in the ketogenic diet and the development of knowledge in this field have contributed to the increasingly frequent application of the ketogenic diet in diabetes treatment. This paper also deals with that issue; its aim includes an extensive analysis of the influence of the ketogenic diet on the prophylaxis and treatment of diabetes. The paper has been prepared based on a wide, meticulous analysis of the available literature on the subject. Among other findings, a favorable effect of that nutrition model has been demonstrated on the values of glycated hemoglobin, glucose, insulin, or other metabolic parameters in diabetes patients. The effect of the ketogenic diet on the pharmacotherapy of type 1 and type 2 diabetes has been presented and compared with the standard nutritional management plan recommended for that disease. Further research is needed in this field, especially studies with a long follow-up period. The discussed articles report interesting therapeutic advantages to the ketogenic diet in comparison with standard diets.
... One study reported a reversal of acidosis in several diabetes patients fed a ketogenic diet (Newburgh and MARSH, 1920). In recent years, there have been several case reports (Chandrasekaran and Rani, 2020;Dressler et al, 2010;Tóth, 2014) and larger studies (Choi et al, 2020;Goday et al, 2016;Westman et al, 2008) in humans highlighting the efficacy and safety of ketogenic diets in diabetic patients. These results are replicated in preclinical models of type I and type II diabetes (Enders et al, 2021;Hussain et al, 2012;Poplawski et al, 2011) and metabolic syndrome (Cooper et al, 2018b). ...
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Significance: Diabetic peripheral neuropathy (DPN), a complication of metabolic syndrome, type I, and type II diabetes, leads to sensory changes that include slow nerve conduction, nerve degeneration, loss of sensation, pain, and gate disturbances. These complications remain largely untreatable, although tight glycemic control can prevent neuropathy progression. Nonpharmacological approaches remain the most impactful to date, but additional advances in treatment approaches are needed. Recent advances: This review highlights several emerging interventions, including a focus on dietary interventions and physical activity that continue to show promise for treating DPN. We provide an overview of our current understanding of how exercise can improve aspects of DPN. We also highlight new studies in which a ketogenic diet has been used as an intervention to prevent and reverse DPN. Critical issues: Both exercise and consuming a ketogenic diet induce systemic and cellular changes that collectively improve complications associated with DPN. Both interventions may involve similar signaling pathways and benefits but also impact DPN through unique mechanisms. Future directions: These lifestyle interventions are critically important as personalized medicine approaches will likely be needed to identify specific subsets of neuropathy symptoms and deficits in patients and determine the most impactful treatment. Overall, these two interventions have the potential to provide meaningful relief for patients with DPN and provide new avenues to identify new therapeutic targets.
... 25,43 However, aminoguanidine failed in a clinical trial for diabetic nephropathy because of poor tolerability, 39 leaving the niche for a well-tolerated MGO-targeting therapy unfilled in diabetic complications. A ketogenic diet is welltolerated in patients with diabetes 10,15,40,42 as well as preclinical models of diabetes. 13,17,28 Moreover, ketogenic diets are showing efficacy in an ever-increasing number of preclinical models of chronic pain related to MGO. 13,17,44 In this study, we demonstrated that a ketogenic diet prevents and reverses MGO-evoked nociception and activation in the spinal dorsal horn. ...
Article
Methylglyoxal is a reactive dicarbonyl byproduct of glycolysis that has been implicated in a growing number of chronic pain conditions, including diabetic peripheral neuropathy (DPN). We previously demonstrated the efficacy of a ketogenic diet in reversing sensory symptoms in a rodent model of DPN. The purpose of this study was to determine whether a ketogenic diet modified methylglyoxal-evoked nociception as a potential mechanism of improving sensory symptoms of DPN. We delivered methylglyoxal to C57Bl/6 mice by intraperitoneal or intraplantar injections. Sensory behaviors were quantified for mechanical thresholds as assessed by von Frey filament testing and spontaneous nonreflexive nociceptive behaviors (shaking, biting, lifting, etc. of the injected paw). Intraperitoneal methylglyoxal injection induced lasting mechanical allodynia in standard chow-fed mice, while ketogenic diet-fed mice were protected. Importantly, ketogenic diet-fed mice exhibited significantly decreased methylglyoxylated-protein concentrations following injection relative to standard, chow-fed mice, and methylglyoxylated-protein concentration correlated negatively with blood ketones. A reaction between the ketone body acetoacetate and methylglyoxal was recently demonstrated in vivo as a potential mechanism of methylglyoxal detoxification, consistent with this observation. To assess whether ketone bodies modified methylglyoxal-evoked nociception by direct methylglyoxal detoxification, we incubated methylglyoxal with either β-hydroxybutyrate or acetoacetate overnight prior to intraplantar injection. Mice receiving an injection of methylglyoxal alone exhibited an increase in spontaneous nociceptive behaviors, whereas coincubation of either acetoacetate or β-hydroxybutyrate reduced these behaviors. In summary, a ketogenic diet prevented the onset of methylglyoxal-evoked mechanical allodynia and increased scavenging of circulating methylglyoxal. Ketone bodies were individually capable of detoxifying methylglyoxal to prevent nociception. These findings provide insight to a potential mechanism by which a ketogenic diet improves DPN in mice and provide a rationale for exploring a ketogenic diet as a therapeutic intervention in other chronic pain conditions associated with elevated methylglyoxal. This work was supported by NIH grants RO1 NS043314 (DEW), the Kansas Institutional Development Award (IDeA) P20 GM103418, Kansas University Training Program in Neurological and Rehabilitation Sciences (NIH T32 award) supported by NIH Award Number T32HD057850, and core support from the Kansas IDDRC P30 HD00228.
... 25,43 However, aminoguanidine failed in a clinical trial for diabetic nephropathy because of poor tolerability, 39 leaving the niche for a well-tolerated MGO-targeting therapy unfilled in diabetic complications. A ketogenic diet is welltolerated in patients with diabetes 10,15,40,42 as well as preclinical models of diabetes. 13,17,28 Moreover, ketogenic diets are showing efficacy in an ever-increasing number of preclinical models of chronic pain related to MGO. 13,17,44 In this study, we demonstrated that a ketogenic diet prevents and reverses MGO-evoked nociception and activation in the spinal dorsal horn. ...
Article
Methylglyoxal (MGO) is a reactive dicarbonyl byproduct of glycolysis implicated in a growing number of neuropathic pain conditions, including chemotherapy-induced peripheral neuropathy, diabetic peripheral neuropathy, and radiculopathy with lumbar disk herniation. Recent studies show success in preclinical models treating these disorders with an interventional ketogenic diet. Here, we tested the hypothesis that a ketogenic diet modifies pathological MGO signaling as a mechanism underlying neuropathy improvement. We found that mice injected with MGO displayed nocifensive behaviors, whereas mice prefed a ketogenic diet were resistant to mechanical allodynia elicited by MGO. In addition, levels of circulating MGO were reduced in ketogenic diet-fed mice and negatively correlated with levels of the ketone body β-hydroxybutyrate (β-HB). Methylglyoxal is normally scavenged by the glyoxalase system, and ketogenic diet-fed mice displayed increased glyoxalase 1 activity compared with chow-fed control mice. Recent studies also suggest that ketone bodies contribute to MGO detoxification, consistent with a negative correlation between β-HB and MGO. To assess whether ketone bodies modified MGO-evoked nociception through direct MGO detoxification, we coincubated either acetoacetate or β-HB with MGO before injection. Mice receiving intraplantar MGO injection exhibit increased nociceptive behavior (lifting, licking, biting, and scratching), which was significantly reduced by coincubation with either acetoacetate or β-HB. Methylglyoxal increased phospho-extracellular signal-regulated kinase-positive cells in the spinal dorsal horn, and this evoked spinal activation was ameliorated by preincubation with acetoacetate or β-HB. These results suggest that a ketogenic diet and ketone bodies ameliorate MGO-evoked nociception, partially through detoxification of MGO, and provide rationale for therapeutic intervention with a ketogenic diet in MGO-driven pathologies.
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To date, treating type I diabetes mellitus (T1D) is a difficult clinical task that is based, from the traditional point of view, exclusively on adjusting an insulin dose and monitoring a daily carbohydrate intake. Dietary changes are not considered a type of treatment in T1D patients yet, although this autoimmune disease is accompanied by disorders of carbohydrate metabolism. The article explores the international experience in the use of a low-carbohydrate diet and the features of disease development when putting patients into ketosis on a ketogenic diet. Article discusses the clinical experience obtained during T1D patient management, including ketogenic diet and mitochondrial support, at the clinic “PlanetaMed”. In addition, the article describes the case reports and case studies. According to the clinical experience of “PlanetaMed” specialists, the use of a ketogenic diet results in a decreasing blood glucose level in almost all cases. The average dose of injected insulin was 22.8 units before the ketogenic diet and 6,625 units during the ketogenic diet. The absolute decrease was 16.205 units, and the relative decrease was 70.9%. At the same time, the concentration level of glucose decreased by 39.2%. The decrease in blood glucose level and the injected insulin dose were connected (correlation coefficient: 0.76). Therefore, the studies have shown a significant positive impact of a ketogenic diet on the treatment of T1D patients.
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Traditional guidelines for type 1 diabetics do not restrict carbohydrates to improve clinical outcomes for patients. This paper highlights the favorable blood glucose control outcomes when a type 1 diabetic focuses on caloric intake from protein and healthy fats instead of the traditional carbohydrate-focused meals. We followed a male type 1 diabetic in his 20s adopting a ketogenic diet through a process of slowly lowering total daily carbohydrate intake. Diabetes-related biomarkers were measured throughout the process. Diabetes-related biomarkers saw massive improvements and ended up in the official non-diabetic range. Total daily insulin requirements dropped by 70%. The patient also experienced great improvements in his quality of life. This study demonstrates the possibility of improving diabetes-related biomarkers through dietary changes, which have positive effects on health outcomes in patients living with this disease. Learning points: The adaptation of a ketogenic diet improved diabetes-related biomarkers in this patient. Diabetes-related biomarkers, such as HbA1c, are the main risk factors for developing complications in diabetics. The ketogenic diet is a feasible approach to minimizing the risk of developing complications in diabetics. Total daily insulin requirements dropped by 67% adapting a ketogenic diet. The patient experienced enormous changes in the quality of life after adapting to the new diet. The safe and physiological state of ketosis might be associated with additional benefits for the patient.
Chapter
As common complication of prediabetes, type I and type II diabetes, diabetic peripheral neuropathy (DPN) includes a series of sensory and motor changes associated with slow nerve conduction, nerve degeneration, gate disturbances, pain, and loss of sensation. Although proper glycemic control can prevent DPN progression, these complications remain difficult to clinically treat. Current pharmacological medications have limited effectiveness, creating the need for additional clinical options. Lifestyle interventions hold great promise as the broad spectrum of improvements derived from certain lifestyle changes appears promising to improve diabetes management and DPN. In this chapter, we highlight research that illustrates the consequences of poor diet on DPN and discuss the benefits of lifestyle changes associated with dietary change and/or exercise. Reversal of dietary changes appears to have positive impact on DPN, and we highlight new studies in which a low-carbohydrate/high-fat diet has been used to prevent and/or reverse DPN. In addition, a growing number of basic and clinical studies are revealing how exercise can improve symptoms of DPN. These interventions affect a broad range of cellular and metabolic changes that can lead to improvements in DPN symptoms. These interventions likely involve overlapping cellular pathways but could also improve DPN through unique mechanisms. As approaches using personalized medicine increase, clinical treatments for DPN will need to determine the most impactful interventions that are relevant to specific symptoms in patients suffering from DPN. Lifestyle and dietary interventions should play an important role in these treatment plans and the convergence of shared mechanisms should be a focus of preclinical and clinical research.KeywordsDiabetesKetogenic dietMediterranean dietExercisePhysical activity
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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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The very-high-fat ketogenic diet can worsen lipid levels in children with pre-existing hyperlipidemia by increasing serum lipoproteins and reducing antiatherogenic high-density lipoproteins. A retrospective chart review of 160 children treated with the ketogenic diet from September 2000 to May 2011 was performed. Twelve children with pre-existing hyperlipidemia were identified. Lipid levels including total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and total cholesterol/high-density lipoprotein were measured pre-diet and at 3, 6, and 12 months of treatment. During treatment, there was a significant reduction in mean total cholesterol, low-density lipoprotein, and total cholesterol/high-density lipoprotein. Total cholesterol and low-density lipoprotein were normalized in 8 and 7 children at 6 months; and 9 and 9 children at 12 months respectively. At 6 and 12 months, tot cholesterol/HDL ratio was normalized in 5 and 7 children respectively. Diet modifications were made to achieve healthy lipid levels. By extrapolating the data, it suggests lipid levels can be controlled in children and adults with ketogenic diet treatment.
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Cow’s milk-based infant formulas and cow’s milk consumption in childhood have been suggested to promote the development of type 1 diabetes mellitus and other immune-mediated or neurological diseases. Epidemiological studies in man have led to the hypothesis that introduction of cow’s milk-based infant formula within the first 3 months of life is associated with increased risk of type 1 diabetes mellitus. Furthermore, in animal models of type 1 diabetes mellitus, cow’s milk proteins have been proven to be ‘diabetogenic’. However, the issue seems far from being resolved. Several epidemiological studies and, more importantly, the first prospective trials did not show an association between early exposure to cow’s milk and type 1 diabetes mellitus. In animal models, cow’s milk proteins are modestly and variably diabetogenic, wheat or soyabean proteins in the diet cause higher rates of autoimmune diabetes. In both man and rodents there is increasing evidence that the gut-associated immune system plays a major role in disease development, probably because of disturbed oral tolerance mechanisms. Oral tolerance depends on immunological homeostasis and normal maturation of the gut. These factors are influenced by growth factors and cytokines from breast milk, normal bacterial colonization, infections and diet. All these factors have been proposed as risk factors for type 1 diabetes mellitus. Hence, cow’s milk proteins may provide mimicry epitopes relevant in autoimmunity, as well as destabilizing oral tolerance mechanisms by biologically active peptides. The concept of dietary regulation of autoimmunity does not apply only to cow’s milk protein, but also to other dietary proteins.
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Dietary cholesterol comes exclusively from animal sources, thus it is naturally present in our diet and tissues. It is an important component of cell membranes and a precursor of bile acids, steroid hormones and vitamin D. Contrary to phytosterols (originated from plants), cholesterol is synthesised in the human body in order to maintain a stable pool when dietary intake is low. Given the necessity for cholesterol, very effective intestinal uptake mechanisms and enterohepatic bile acid and cholesterol reabsorption cycles exist; conversely, phytosterols are poorly absorbed and, indeed, rapidly excreted. Dietary cholesterol content does not significantly influence plasma cholesterol values, which are regulated by different genetic and nutritional factors that influence cholesterol absorption or synthesis. Some subjects are hyper-absorbers and others are hyper-responders, which implies new therapeutic issues. Epidemiological data do not support a link between dietary cholesterol and CVD. Recent biological data concerning the effect of dietary cholesterol on LDL receptor-related protein may explain the complexity of the effect of cholesterol on CVD risk.