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Medical Hypotheses: Adam W Łodarczyk, Mariusz S. Wiglusz, Wies Ław Jerzy Cubała
Medical Hypotheses: Adam W Łodarczyk, Mariusz S. Wiglusz, Wies Ław Jerzy Cubała
Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy
A R T I C LE I N FO A B S T R A C T
Keywords: Schizophrenia is a mental disorder that mostly appears in the second or third decade of life with no consistent
Schizophrenia appearance. The first-line pharmacological treatment are antipsychotic drugs, which mainly act by suppressing
Ketogenic diet the activity of dopamine. Unfortunately many of schizophrenic patients suffer from persistent positive or ne-
Dietary intervention gative symptoms that cannot be fully treated with available medication. With exploration on the possible causes
GABA-ergic activity
of the disease there is evidence on dopaminergic transmission defects, there is a need to find more holistic way in
treating the disease and a diet regimen could be one of them. Ketogenic diet, which is a popular diet regimen that
consists in low-carbohydrate (about 30–50 g/day), medium-protein (up to 1 g/kg daily) and high-fat intake
(around 80% of daily calories) mainly known for its helpful role in weight-loss. The key mechanism is to gen-
erate ketosis. A state in which ketones bodies in the blood provides energy part of the body's energy comes from
ketone bodies in the blood. Possible hypothesis can be that ketogenic diet changes the ratio of GABA:glutamate
in favor of GABA, by suppressing the catabolism and increasing the synthesis of GABA as well as glutamate
metabolism, which could help to compensate the disrupted GABA levels in schizophrenic brain, leading to
possible better outcome of the disease regarding symptomatology and preventing the weight-gain regarding
some medications used and the correlating diseases responsible for weight gain.
Overview mostly preferring bad quality nutrients, fried, processed food [8]. Thus,
often literature mostly focuses on proper vitamin B, antioxidants, mi-
Schizophrenia is a mental disorder that mostly appears in the nerals intake with a linkage to less comorbidities and improving the
second or third decade of life and does not have a consistent appearance quality of life [5,9,10,11]. There are also other potential nutritional
but the origin of it keeps unclear [1]. The sufferer experiences changes interventions that showed validity supporting the inflammation status
in his thinking and feeling, in the sensation and in the perception of his in schizophrenic patients, which are gluten-free diet and probiotic
environment [2]. Still there are many unmet needs in trying to control therapy showing their impact regulation of immune system [12,13]
the symptoms and relapses of the disease. The first-line pharmacolo- with certain effect on life quality through bowel difficulty [14]. Inter-
gical treatment is antipsychotic drugs, which mainly act by suppressing estingly, there are some papers showing improvement in the outcome of
the activity of dopamine [3]. Unfortunately, many of schizophrenic schizophrenia when increasing intake of essential polyunsaturated fatty
patients suffer from persistent positive or negative symptoms that acids (EPUFAs), omega-3 fatty acids. Studies mainly focused on adding
cannot be fully treated with nowadays medication [4]. only some portion (0.3–1.4 g) of fatty acids, which did not change
With exploration on the possible causes of the disease there is evi- significantly daily fat percentage intake [5,15], nevertheless reduction
dence on dopaminergic transmission defects, there is a need to find in scores for positive and negative syndrome scale (PANSS) in positive,
more holistic way in treating the disease and a diet regimen could be negative and general subscales, the Montgomery Asberg Depression
one of them [5]. Regarding depression, for example, consumption of Rating Scale (MADRS), and the Global Assessment of Functioning were
more processed foods such as fried foods, refined sugars is associated observed [15]. Furthermore, American Psychiatric Association supports
with depression, while eating Mediterranean-style diet associated with the American Heart Association’s guidelines regarding fish consump-
prevention or reduced depression intensity [6,7]. Unfortunately, there tion, and further recommends that patients with mood, impulse control,
is a low number of strong value literature on ‘schizophrenia diet’. or psychotic disorders consume ≥1 g/d of combined long-chain omega-
Studies shown that about ¾ of the schizophrenic patients are obese, 3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid
⁎
Corresponding author at: Department of Psychiatry Faculty of Medicine, Medical University of Gdańsk, Dębinki St. 7 Build. 25, 80-952 Gdańsk, Poland.
E-mail address: aswlodarczyk@gmail.com (A. Włodarczyk).
https://doi.org/10.1016/j.mehy.2018.06.022
Received 28 April 2018; Accepted 19 June 2018
0306-9877/ © 2018 Elsevier Ltd. All rights reserved.
A. Włodarczyk et al. Medical Hypotheses 118 (2018) 74–77
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A. Włodarczyk et al. Medical Hypotheses 118 (2018) 74–77
Fig. 1. The interplay of Dopamine, Glutamate and GABA in the human brain.
body, which could happen regarding schizophrenic patients. As studies present and future. Schizophr Res 1997. PMID: 9468346.
show, even ¾ of the patients discontinues assigned treatment [39]. [3] Wlodarczyk A, Szarmach J, Cubala WJ, Wiglusz MS. Benzodiazepines in combina-
tion with antipsychotic drugs for schizophrenia: gaba-ergic targeted therapy.
There is a chance that in some patients the diet could have negative Psychiatr Danub 2017;29(Suppl. 3):345–8. PubMed: 28953788.
impact on lipidogram, as mentioned before [21,22], also in rare occa- [4] Möller HJ, Czobor P. Pharmacological treatment of negative symptoms in schizo-
sions the ketoacidosis can be an adverse event of maintaining low- phrenia. Eur Arch Psychiatry Clin Neurosci 2015. http://dx.doi.org/10.1007/
s00406-015-0596-y.
carbohydrate diet regimen [26]. [5] Arroll MA, Wilder L, Neil J. Nutritional interventions for the adjunctive treatment of
schizophrenia: a brief review. Nutr J 2014. http://dx.doi.org/10.1186/1475-2891-
Summary 13-91.
[6] Sanchez-Villegas A, Martínez-González MA. Diet, a new target to prevent depres-
sion? BMC Med 2013. http://dx.doi.org/10.1186/1741-7015-11-3.
We propose that ketogenic diet may facilitate the therapeutic re- [7] Opie RS, O'Neil A, Jacka FN, Pizzinga J, Itsiopoulos C. A modified Mediterranean
sponse to antipsychotics in schizophrenic subjects. A proof of concept dietary intervention for adults with major depression: dietary protocol and feasi-
bility data from the SMILES trial. Nutr. Neurosci. 2017. http://dx.doi.org/10.1080/
study of a high fat-low carbohydrate-load, “liberal ketogenic diet”
1028415X.2017.1312841.
should be performed with several patients with schizophrenia who are [8] McCreadie RG, Scottish Schizophrenia Lifestyle Group. Diet, smoking and cardio-
not responding to usual treatment in order to test the hypothesis. vascular risk in people with schizophrenia: descriptive study. Br J Psychiatry 2003.
PMID: 14645025.
[9] Hoffer A. Nutrition and schizophrenia. Can Fam Physician 1975. PMCID:
Conflict of interest PMC2274561.
[10] Strassnig M, Brar JS, Ganguli R. Dietary intake of patients with schizophrenia.
No other potential conflict of interest was reported by the authors. Psychiatry (Edgmont) 2005. PMID: 21179633.
[11] Arroll MA, Wilder L, Neil J. Nutritional interventions for the adjunctive treatment
of schizophrenia: a brief review. Nutr J 2014. http://dx.doi.org/10.1186/1475-
Authors’ Contribution 2891-13-91.
[12] Deanna K, Demyanovich H, Rodriguez K, Cihakova D, Talor M, Gold J, et al. T191.
Randomized double-blind feasibility study of a gluten-free diet in people with
Adam Włodarczyk: Study conception and design, Acquisition of schizophrenia and elevated antigliadin antibodies (AGA IgG). Schizophr Bull 2018.
data, Analysis and interpretation of data, Drafting of manuscript. http://dx.doi.org/10.1093/schbul/sby016.467.
Mariusz S. Wiglusz: Critical revision. [13] Tomasik J, Yolken RH, Bahn S, Dickerson FB. Immunomodulatory effects of pro-
biotic supplementation in schizophrenia patients: a randomized, placebo-controlled
Wiesław Jerzy Cubała: Drafting of manuscript, Critical revision. trial. Biomarker Insights 2015. http://dx.doi.org/10.4137/BMI.S22007.
[14] Dickerson FB, Stallings C, Origoni A, Katsafanas E, Savage CLG, Schweinfurth LAB,
Acknowledgement Goga J, Khushalani S, Yolken RH. Effect of probiotic supplementation on schizo-
phrenia symptoms and association with gastrointestinal functioning: a randomized,
placebo-controlled trial. Prim Care Companion CNS Disord 2014. http://dx.doi.
This work is supported by the Medical University of Gdańsk, Poland org/10.4088/PCC.13m01579.
(Grant No. ST-02-0039/07/221). [15] Amminger GP, Schäfer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM,
et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic dis-
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