Promising Perspectives of Low Carbohydrate Diet in Cancer Adjuvant Therapy
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Journal of Nutritional Oncology, May 15, 2020, Volume 5, Number 2 DOI: 10.34175/jno202002001 · 50 ·
Promising Perspectives of Low Carbohydrate Diet in Cancer Adjuvant
Therapy
Istvan G Télessy
Department of Pharmaceutics, University of Pécs, Pécs 7624, Hungary
Abstract: Low carbohydrate diet (LCD) and nutrition is a very popular topic in the nutritional scientific literature.
Main reason is that it is an old established therapy in intractable epilepsy and there are plenty of positive preclinical and
sporadic clinical results in other disorders, including certain cancers. The problem is that a) the metabolic background
of this therapy is not elucidated enough, b) animal studies and human experiences are sometimes divergent, c) there
are negative human results and d) the clinical studies are not comparable because of the wide variety of study design
and conclusion regarding the indication, the composition of diet and duration of treatment can not be drawn. This
publication reviews the current situation and gives some hints to the solution.
Key words: Low carb diet; Ketogenic; Cancer; Nutrition
Introduction KEN (100 g/day), mmol/L brain starts to utilize ketone bodies in a significant
including the ketogenic diet (KD)/ ketogenic enteral manner. This change results in modified control of energy
nutrition (KEN). Ketogenic diet is represented by the serum homeostasis [2]. Transient ketosis is in the range of normal
levels of ketogenic compounds, characteristically by the physiological conditions and also called as “physiological
concentration of beta-hydroxybutyrate. In a recent study ketosis”. If natural sources of glucose production (sugars,
different isocaloric ketogenic diets with 5%, 15% and starches and other carbohydrates) are missing, glucose
25% carbohydrate content were compared in 77 healthy reserves gradually exhaust and the necessary glucose is
adult participants. During the 3 weeks’ test period beta- made from aminoacids (glucogenic AAs) and from glycerol
hydroxybutyrate (BHB) serum concentrations measured originates from fat decomposition. This is the situation after
upon awakening rose with an overall value from baseline consumption of ketogenic diet as well. The liver produces
by 0.62, 0.38 and 0.27 mmol/L, respectively [1]. This ketone bodies, mainly acetoacetate that convert to acetone
demonstrate that all kind of low carb diets exert ketogenic and BHB. The former one is volatile therefore it is exhaled
effect with different efficiency. To date strong KD and but BHB can turn back with help of BHB dehydrogenase
to acetoacetate and further on to two molecules of acetyl-
CoA (Figure 1). This compound is precursor for the Krebs-
Corresponding author: István G Télessy, PharmD, PhD, Department
of Pharmaceutics, University of Pécs, Pécs 7624, Honvéd u. 3. and cycle (citric acid cycle) in order to make energy via oxydative
MedBioFit Lpt. Gödöllő, 2100, Fácán sor 25, Hungary; Tel: +363 0491 phosphorylation. If this latter pathway is blocked due to lack
8192; Email: telessyist@vnet.hu of carbohydrates or it is overloaded with acetyl-CoA as result
· 51 · Journal of Nutritional Oncology, May 15, 2020, Volume 5, Number 2
of hyperutilization of fats, the liver switch to ketogenetic types of epilepsy, especially certain drug-therapy resistant
pathway. This is an economical switch as 100g acetoacetate epilepsies and the status epilepticus can favorably be
and 100g BHB may generate 9,400 and 10,500 g of ATP, treated by this intervention. In case of the genetic defect
respectively. In contrary 100g glucose produces just 8,700g glucose transporter 1 (GLUT1) deficiency induced epileptic
ATP. Thus energy need of the body for synthetic processes, seizures the mechanism of action is obvious but the exact
other cellular functions and cell division is ensured. BHB mechanism in other cases is even today not really known.
is not just an energetic metabolite but also a signaling There are several suggestions, eg. Elamin M suggested
molecule that integrates the metabolic status of the cell [3]. that increased NAD during the ketolytic metabolism may
But energy is not the only requirement of cell proliferation. be the primary mechanism behind the beneficial effects
When pyruvate to acetyl-CoA transformation fails in a variety of brain disorders [5]. General safety of this
exogenous glutamate via alpha-ketoglutarate may serve type of nutritional treatment is, however, not a query and
as lipid-synthesis supporter as well as energy and nitrogen numerous artificial nutrition products have been developed
source [4]. Nitrogen is badly needed to expansion of tumor by manufacturers in order to make this nutrient efficient and
cell mass. The pentose-phosphate pathway also generates palatable. After therapeutic success with ketogenic diet in
building blocks for the proliferation. As demonstrated, there epilepsy attempts have been made to cure patients suffering
are several alternative pathways to tumor-cell propagation. from various forms of cancer diseases, too. Ketogenic diet
has also been tested as treatment option in several other
Theoretical Consideration about Ketogenic Diet illnesses in the past: patients with obesity, NAFLD/NASH,
Therapy heart failure, neurological and neurodegenerative diseases,
In the group of special diets LCD and its extreme inborn errors of metabolism and exercise performance were
form, the classical ketogenic diet plays a specific role. the main subjects of clinical trials with LCD [6]. Even today
The selective capacity of neurons in utilization of ketone ketogenic diet and other LCDs are being used in further
bodies makes this type of food and enteral nutrition able health conditions like cardiovascular diseases, obesity
to support antiseizure therapy. In the oncology impact of (metabolic syndrome) therapy, etc. as well. Main features of
KBs was highlighted by the discovery of Warburg effect these therapies are as follows.
in cancer cell metabolism. KD and KEN usually contains
less than 20% (or 20 g/day) carbohydrate and more than Non-epileptic and Non-cancer Disorders
50% fat counted in energy density. During the past 60~80 The most obvious way of obesity-treatment is
years this type of aggressive therapeutic intervention restriction in calories. As carbohydrates set out majority
regularly rose as preferred or dispreferred choice of of western diet, carbohydrate-restriction together with
treatment beside the members of continuously developing calory restriction is one of the leading form of obesity
pharmacotherapy. The oldest efforts were registered in the management. Human studies generally demonstrate a slow
field of neurological disorders, inclusive epilepsy, where loss of both fat mass and lean mass during low calory low
low carb diet and the extreme low carb diet (classical carb diet. Some authors suggest that reduced energy intake
ketogenic diet) is still accepted therapeutic modality. Some that often accompanied with low carb, high fat (LCHF)
Fat Acetyl-coA Acetyl-coA
Amino acid Acetyl-coA Acetoacetyl-coA HMG-coA
Glucose Acetyl-coA
Circulation Beta-hydroxybutyrate Acetoacetate
Acetone
Figure 1 The ketone body formation. Ketone body formation starts when serum
glucose frastically decreases and the acetyl-CoA production from proteins and
mainly from fat increases. The process runs in the liver but kidney is also able
to produce small amounts of ketone bodies. Final products enter the systemic
circulation. HMG-CoA, hydroxy-methylglutaryl-CoA
Journal of Nutritional Oncology, May 15, 2020, Volume 5, Number 2 · 52 ·
diet, is responsible for weight loss and related metabolic “the Warburg hypothesis” or “Warburg effect” that firstly
and functional improvements [7]. Effect of LCD including intended to explain specific cancer cell energy metabolism.
KD in non-alcoholic fatty liver disease, which is present in He stated based on his research activites in sarcoma cells
90% of obese, is after all, controversial. In contrast type 2 that cancer cells use a specific glucose-utilization pathway
diabetes mellitus (T2DM) patients profit from low carb diet called aerobic glycolysis, in presence of sufficient oxygen,
because of the better control of glucose homeostasis and to support their proliferation (Figure 2a).
reduction in antidiabetic medication [8]. The low carb diet To elucidate details of the metabolic pathways of
seems to be beneficial also to kidney function. Juraschek cancer cells intensive research activity was initiated and
SP et al. published a randomized controlled study (RCT) maintained during the past 100 years but the mechanism
study with 163 overweight/obese patients having diabetes is still not fully understood. The point of the hypothesis is
or kidney disease and learned that reducing percentage of that due to the metabolic switch recognized in all tumor
carbohydrate by increasing proportion of protein and fat in cell cultures, glucose and glutamine metabolism changes
diet increased glomerular filtration rate of the patients [9]. consistently in these cells and their glucose consumption
Low carbohydrate diet in human beings exerts an effective is many fold of that in normal cells. It means theoretically
anti-hyperlipidemic effect as well. Authors report reduction by carbohydrate restriction ATP-production as well as the
in total cholesterol, triglyceride and LDL-cholesterol levels synthesis of building bricks for cancer cell proliferation can
whereas the HDL-cholesterol improves during and after be (temporarily?) limited. But in fact, some cancer cells, eg.
introduction of low carb diet. Heart failure patients also MCF-7 breast cancer cells get 80% of ATPs from oxidative
may benefit from low carb ketogenic diet due to the ketone and only 20% from glycolytic reactions [12]. Glucose
bodies which are good fuels for the heart muscle [10]. dependent cancer cells use the aerobic glycolysis that
provides much less energy but 10-100x quicker in contrast
Ketogenic Diets and Cancer to cell respiration thus energy production per time-unit is
As most conventional cancer therapies (chemotherapy, nearly the same or more [13]. According to the Warburg
radiation therapy and immunotherapy) are usually hypothesis the glycolytic pathway in cancer cells is - due to
associated with several adverse effects alternatives or the increased ATP-demand - upregulated even under normal
additional treatment methods are badly desired. Mounting oxygen tension and before pyruvates reach mitochondria,
individual experiences underpin that dietary restrictions, majority of energy-carrier substrates disappeared in other
particularly the restriction of carbohydrates, can exert pathways like PPP and lactate production (Figure 2b). As
benefit for cancer patients [11]. Thus nutritional therapies a consequence, upregulation in GLUT transporters and
may belong to these efforts and offer positive solution. increase of enzymes of glucose utilization is to be detected.
About 100 years ago, Otto H. Warburg revealed a Due to the pre-mitochondrial leakage of energy substrates
specific phenomenon of cancer cells, later referred to as ATP-output in oxidative phosphorylation pathway does
2a 2b 2c
● Oxidative phosph (healthy cell) ● Aerob glycolysis (cancer cell) ● Aerob glycolysis mix (CAF cell)
Glucose Glucose PPP Glucose
cytosol
cytosol
cytosol
85%
5% secretion
Pyruvate Lactate Pyruvate Lactate Pyruvate Lactate
Fat
Acetyl-CoA
Acetyl-CoA Acetyl-CoA
ondrion
drion
cyte
Cori-cycle
ondrion
cyte
Krebs-cycle
cyte
hepato
Cori-cycle
on
Cori-cycle
hepato
hepato
mitoch
mitoch
mitoch
Krebs-cycle Krebs-cycle
Krebs-cycle
Glucose Glucose CC- Glucose
CO2 + ATP cells
CO2 + ATP CO2 + ATP
Figure 2 The “Warburg-shift”. According to the Warburg effect of cancer cells ferment pyruvate originating from aerobic glycolysis
to lactate. Besides, the pentose phosphate pathway is activated which produce carbon equivalents for macromolecular synthesis of the
tumor biomass. PPP, pentose phosphate pathway; CO2, carbon dioxide; ATP, Adenosine triphosphate; CAFs, cancer cell associated
fibroblast cells; CC-cells, cancer cells· 53 · Journal of Nutritional Oncology, May 15, 2020, Volume 5, Number 2
not increase but the lactate fermentation via lactate to the versatility of tumor cells their survival is still good
dehydrogenase and the aerobic glycolysis. The leaking enough [19]. On a whole, there are a lot of alternative
of lactic acid in the surrounding of cancer cells make pathways embedded in a complex metabolic network (Figure
local environment proliferation-friendly. Some cancer- 3). All these processes can explain the diverse results seen
cell line adapt to the changed metabolic circumstances in various preclinical studies made with LCDs. The real
or have genetically determined enzyme deficiency and driver of the switches is not discovered yet.
remain proliferative even under glucose-poor conditions.
As learned from a recent study eg. low expression of the Preclinical Studies in Cancer Models
ketolytic enzymes 3-hydroxybutyrate dehydrogenase and Beneficial effects of LCD, inclusive ketogenic diet
succinyl-CoA:3-oxoacid CoA transferase in certain cancer in preclinical studies have been demonstrated several
cells might be in the background of the resistance [14]. We years ago in various health disorders. Tumor cell culture
know that tumor cells are able to develop resistance toward experiments as well as animal models were developed for
anticancer interventions as tumor-aspecific attribution. test the effect of LCD to tumor metabolism for decades.
We observe a very similar result in this situation: a part Much more studies were published with use of extreme
of tumors are glycotropic, other part of that cell-lines are low carbohydrate content (ie. classical KD) than with
non-glycotropic thus certain cancer cells exhibit flexible the moderate carbohydrate consumption presumably due
metabolic phenotype. Genetic alterations in the cancer cells to the more definitive ketonemia and the good results
result in metabolic deviations eg. in BRAF gene mutations in epilepsy. In 2014 evaluation of nine studies with KD
detectable in melanoma, colorectal cancer and multiple treated animals was published. Eight out of 9 studies with
myeloma and hairy cell leukemia. HMGCL which converts various tumors resulted in tumor reduction [20]. Three
HMG-CoA to Acetyl-CoA and acetoacetate is upregulated years later results of preclinical studies published till the
in BRAF-V600E-expressing melanoma cells [15,16]. end of 2017 were summarized by Weber DD et al. They
This alteration reorganize metabolism and signaling of the reviewed 13 animal studies with various cancer types and
cancer cell selectively promoting their proliferation. Or, for demonstrated that some of them respond not at all (eg.
instance, acetate originating from glutamate, can also be medulloblastoma, melanoma, kidney, etc.), some respond
utilized by cancer cells for proliferation [4,17,18]. Moreover, partly (eg. glioblastoma, medulloblastoma, prostate cancer,
cancer cells are able to let produce energy carriers by pancreas, etc.) and others respond well (eg. colon tumor,
adjacent healthy cells. This is the reverse “Warburg effect” neuroblastoma, lung- and breast cancer) to ketogenic
where cancer cells induce (mainly oxidative) stress situation nutritional interventions, in summary majority of studies
in neighboring healthy cells (stroma cells) and trigger these resulted in positive effect [21]. However, in another study
cells to produce surplus high energy substrates (ATP, fatty glioblastoma responded well to low carb diet in animal
acids and lactate) which via upregulated monocarboxylate studies [22]. Other animal studies with neuroblastoma
transporters turn back to the cancer cells (Figure 2c). Due demonstrated synergistic effect of KD with chemotherapy
Glucose Healthy Glucose Tumor
Pyruvate PPP Pyruvate PPP
OxPhos Lactate OxPhos Lactate ribose-5P
Prot, lipid & nucleotide Prot, lipid & nucleotide
biosynthesis biosynthesis
Exogenous substrates Exogenous substrates (GLUT)
Figure 3 Metabolic summary. Cancer cells, in contrast to healthy cells, support protein synthesis
more intensively and efficiently via several "abnormal" metabolic pathways inclusive the consumption
of exogenous aminoacids, mainly glutamate and pentose phosphate pathway product ribose-5-
phosphate. PPP, pentose phosphate pathway; OxPhos, oxidative phosphorylation; GLUT, glutamate;
ribose-5P, ribose-5-phosphateJournal of Nutritional Oncology, May 15, 2020, Volume 5, Number 2 · 54 ·
(cyclophosphamide) in xenografted mice [23]. The [32]. In a review of 10 articles including data of 214 patients
peritoneal dissemination of tumor cells was decreased in were analyzed in order to conclude effectiveness and safety
carbohydrate-restricted animals and the KD-fed mice had of KD in humans [33]. This analysis found improvement
longer survival time, smaller ascites-production, improved of body weight while tumor-progression markers reduced.
behavior and also blood cell count, hematocrite and The QoL did not change in the average. Overall judgement
hemoglobin improved [24]. These and many other positive was, however, moderately positive due to the inconsistent
results indicate the use of LCD in cancer therapy. Natheless results. Tolerability of the classical ketogenic diet is often
it seems not only composition of diet or nutrition and the poor [34] in contrast to the low carb diet [35]. In the latter
type of cancer but genetic predisposition plays a key factor study, 16 patients with metastatic cancer received low carb
as well. In case of melanomas it was demonstrated that diet (less than 70g catbohydrate per day) for 3 months, and
even different melanoma cell-lines react differently to the the majority of them completed the trial moreover their
same nutritional intervention. Moreover, a recent study quality of life improved. More studies performed in patients
revealed the signaling basis of high lipid nutrition and with epilepsy clarified that in this disease, effectiveness
the potential pathogenic role of dietary fat related ketone of moderately ketogenic diet (modified Atkins diet) was
body acetoacetate in certain types of mutant melanoma inferior to classical ketogenic diet [36]. Despite of that
cells [25]. In some cases, ketogenic diet may aggravate due to the better adherence, this type of treatment can
neurodegeneration via mitochondrial damage, too [26]. be preferred from therapeutic point of view. Moreover,
Based on this finding the question arise maybe precision the very artificial classical ketogenic diets may initiate
diet based on individual genetic background could prevent pathophysiologic changes that could compensate beneficial
or attenuate cancer risk and/or the cancer progression in effect of this type of nutrition therapy [37]. A very recent
patients? Other negative effects were also demonstrated. publication reported about a randomized controlled study
Huang and coworkers demonstrated that hepatocellular in gynecological patients treated with moderately ketogenic
cancer cell culture could utilize ketone bodies and the diet (70% fat, 25% protein and 5% carbohydratep) [38].
increased ketolysis enhanced tumor growth [27]. Certain Their statement is that adherence of KD and standard diet
kidney tumor models in rats react also with increased tumor patients ranged from 57% to 80% respectively after 12
growth after high fat containing ketogenic diet [28]. These weeks and there were no changes in blood lipid values
and other negative results encourage scientists to search for between the test-meal and control meal groups. In another
the reason of controversial effects. group of patients (ovarian and endometrial cancer), 67%
In the course of evaluation of preclinical studies, one and 56% were the adherence rate in the same sequence, it
important aspect should also be considered: noteworthy that means more KD nourished patients were adherent to the
results of rodent and human studies often do not correlate. special diet after 12 weeks than in the control group [39].
Kosinski pointed out that the cardiovascular parameters Case reports of two pediatric patients with astrocytoma
basically differ, eg. total cholesterol (TC), LDL and HDL displayed 50% success after 12 months of KD [40]. In
cholesterol and triglyceride (TG) levels move just opposite another report one patient with glioblastoma verified by
in the two species ie. KD increases TC, LDL-C and TG contrast-enhanced MRI and histology received standard
in rodents but decreases in humans and HDL is decreased combination therapy of radiotherapy + chemotherapy
in rodents but increases in humans after ketogenic diet + LCD and after 2 months of treatment course, her
[29]. Moreover, some changes in organ functions and malignant lesio disappeared but after termination of KD
pathogenesis are to be observed in rodents, but never tumor recurrence was detected [41]. Gliomas are highly
detected in human beings, eg. 6 days of KD induced heterogenous metabolically active tumors, therefore the
impairment in glucose tolerance and insulin sensitivity, ketogenic diet is very interesting research target within the
but in human studies, this is not relevant even after long neuro-oncologists [42]. Glioma, especially glioblastoma,
term use of KD. Preclinical studies supported so far to is a highly aggressive tumor with poor survival of just one
make sense of organizing clinical trials in order to evaluate or two years. As glioma cells consume mainly glucose,
capacity of dietary interventions to synergize with treatment the low carb diet seems to be advantageous for patients
modalities in oncology [30]. suffering from this type of tumor. Results in a group of
glioma patients on standard chemoradiation receiving
Clinical Experiences adjuvant LCD were positive even if the QoL, neurological
Low carb diet exert beneficial effect in various diease functioning and impairment did not change over time [43].
models as described above. Already more than 10 years Glucose restriction - eg. the extreme of low carbo-
ago various industrially manufactured clinical nutrition hydrate load as strongly ketogenic compositions usually
products supported the human use of ketogenic nutrition contain less than 10% carbohydrate in energy density -
[31]. According to Shi HP and Miao MY, tens of thousands support the Warburg hypothesis and can stop or inhibit
of patients with advanced cancer having tried a ketogenic tumor-cell proliferation in selected tumors. It seems that
diet for the treatment of their disease by themselve in China we have a progression in nutritional recommendations.· 55 · Journal of Nutritional Oncology, May 15, 2020, Volume 5, Number 2
The extreme low carbohydrate is not good for certain do not need to be discontinued for most adverse effects.
cancer types but low carb diet, containing caloric ratio Gastrointestinal complaints are often the most common, but
of 20%~50% carbohydrate-origin energy source maybe can be mostly remedied.”
better [22]. Recently, positive therapeutic effect (overall The first safety concern of LCD for cancer patients
survival) was reported in an RCT involving 40 breast cancer is weight loss. KD is often reported as successful form
patients taking KD and 40 controls under conventional of slimming diets and this assumes a dangerous weight
chemotherapy [44]. In this homogenous cancer group, reduction in frailty population, accidentally in cancer
patients received MCT-fortified ketogenic diet of 75% fat, cachexia. Indeed, in this patient group, increase of body
19% protein and 6% carbohydrate and overall survival were weight (BW) would be advantageous, but in the course of
better after 12 week MCT-KD-nutrition therapy than those anticancer treatment preservation of body weight would
in controls. Another study from 2014 also confirmed the also be acceptable. In cancer cachexia, LCD cannot
better tolerability of the moderate LCD, the more displayed increase body weight especially not the fat free mass but
a positive interaction with bevacizumab therapy [45]. in a randomized controlled study of gynecological tumor
Recent clinical experiences demonstrate further synergic patients’ maintenance of BW was observed [39]. Concerns
effect of LCD with conventional cancer-therapeutic about the weight loss induction of LCD/KD in cancer
modalities [46]. A metabolically supported chemotherapy patients were not affirmed by a recent systematic scoping
treatment (MSCT) is artificially induced hypoglycemic review [52]. In patients with normal or pre-cachectic phase,
condition during the chemotheraputic treatment. This was LCD does not accelerate weight loss. Animal studies
successfully tested in feasibility study (44 patients with supported the hypothesis that ketone bodies reaching
metastatic non-small cell lung cancer) with additional the brain stimulate food intake [2]. The main problem is
ketogenic diet, hyperthermia and hyperbaric oxygen therapy that majority of LCDs, especially KD is not a tasty food,
[47]. The combination of KD and other glucose restrictive therefore the adherence to these diets is relatively low.
modalities with antioxidant therapy (eg. N-acetylcystein) Alternative solutions are being intensively searched (see
significantly reduced anaplastic thyroid tumor growth in later).
vitro as well as in vivo [48]. The systematic review of the Earlier, there was an obscurity whether KD represents
published results, however does not support that LCD or an increased risk for hypoglycemia in patients, especially
other dietary interventions could significantly mitigate having instable carbohydrate metabolism like diabetes.
recurrence or mortality of breast cancer [49]. To sum up, the Recently, Loew ZZX and colleagues published a study
results of clinical data, we can set out that conclusions of the with T1DM patients taking less than 55 g carbohydrate
many divergent trials and case reports are not comparable. per day for several years (mean 2.6 years). The study
Patients, diseases, nutritional interventions and endpoints resulted in positive outcome from safety point of view
are divergent, therefore neither predictivity nor reliability is as HbA1c levels of the patients decreased and time on
not on the expected level. euglycemic state increased while a moderate increase in
episodes of hypoglycemia was observed [53]. Despite the
Safety positive effects, a lot of patients discontinuous KD therapy
Research of safety data on low carb diet and its because of the unpalatability of this food [54]. This can
extreme form the ketogenic diet goes back to 100 years be ameliorated with various kitchen-techniques, but more
ago. Ketogenic diet was first applied as treatment attempt successful attempts have been made with ketone esters or
in epileptic patients and since that it became an accepted, balanced ketone electrolyte formulations [55,56]. Today
relatively safe and effective therapeutic modality in the new approaches appeared in the market eg. in form of
treatment of therapy-resistant epilepsy. However, KD may ketogenic drinks [57]. The drinks reported in the publication
be too drastic metabolic intervention in other disorders, contain ketogenic salt (Na+ or K+ salt of BHB), or ketone
therefore some scholars suggest to use “light low carb diet” ester (3-hydroxybutyl-3-hydroxybutyrate). Both drinks
(eg. modified Atkins diet) instead. According to Rezaei resulted in effective serum ketone body levels. It should
S et al, its efficacy seems to be similar to KD in epileptic be, however, mentioned that effects of ketogenic diet show
children [50]. In case of nutritional treatment, similarly to high inter-individual differences. Therefore, in certain cases
medical treatments, contraindications should be taken into (eg. epilepsy) the measurement of ketotic state may be
account: LCD is not recommended for patients having necessary. For this reason, several tests were developed,
uncontrolled diabetes, pancreatitis, liver failure, dysfunction best of all seems to be the measurement of exhaled acetone
of fat-metabolism, carnitine deficiency. And there are that is in good correlation with the serum ketone levels [58].
side effects as well. Kossoff EH recently summarized the Further, longer lasting KD therapy usually accompanied
side effects of KD in epileptic patient in the frame of a with significant and negative changes in arterial morphology
Consensus Statement [51]. He concluded that “Like all and lipid metabolism resulting in dyslipidemia, according to
medical therapies KDTs have potential adverse effects. the experience in epileptic children [59]. These symptoms
Overall, the risk of serious adverse events is low; KDTs are mostly reversible if the diet is stopped after 1-2 yearsJournal of Nutritional Oncology, May 15, 2020, Volume 5, Number 2 · 56 ·
[60]. In contrast, obese patients on shorter course of low low carb diets are very heterogenous and are not suitable
carb diet present improvement (decrease) in se-cholesteric to draw conclusions. All these facts put us on start clinical
levels. Interestingly, the lipid profile differs between studies with patients having same type of cancer, taking
rodents and humans as KD in rodent models associate with the same type of nutrition and get the same conventional
worsening of serum-lipid parameters [29]. therapy. Only in this case shall we be able to find evidence
and offer the clinicians evidence-based additional nutrition
Discussion that support the treatment of tumor patients. In short, LCD
Low carb diets, used on the Warburg effect concept, still being a promising safe adjuvant therapy, but the real
are effective adjuvants in certain tumors according to their indication is not yet clear.
glucose consumption. Majority of brain tumors are like this.
The results of recent studies show that effectiveness of this Conflict of interests
kind of nutritional intervention depends on several factors, The author declare no conflict of interests.
inclusive mutations, normal metabolic program of the tissue-
of-origin or the enzyme-defects [61]. Preclinical studies
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