Original research articleRelationship between polyunsaturated fatty acid and eating disorders: Systematic review and meta-analysis
Introduction
Eating disorders are serious illnesses that particularly affect young women and can result in poor nutrition, significant physical conditions, and even suicidality [1], [2], [3], [4]. Development of eating disorders is reportedly influenced by multiple factors, including genetic, biological and psychosocial factors, and individual personality traits. Recently, several human and animal studies have attempted to elucidate a biological basis of eating disorders [5], [6]. In eating disorders, disturbance of the striatal circuit and receptors and transporters of dopamine and serotonin have been reported in neuroimaging studies [7]. Notably, psychological stress leads to abnormal activity of serotonin in the hypothalamus and this influences appetite [8], [9]. Other studies have reported a relationship between eating disorders and reduction of serum brain-derived neurotrophic factor (BDNF) levels [10], genetic abnormalities of BDNF [10], increase of serum and plasma level of pro-inflammatory cytokines [11], and genetic abnormalities relating to inflammation [12].
Polyunsaturated fatty acids (PUFAs) have attracted attention in the field of psychiatry due to their neuroprotective effects, such as increased levels of BDNF [13], enhancement of membrane fluidity [14], and antioxidant [8] and anti-inflammatory effects [15]. Evidence on the relationship between eating disorders and PUFAs has gradually accumulated. Abnormal levels of PUFAs in individuals with an eating disorder have been reported in recent studies [16], [17], as well as abnormal activity of fatty acid desaturase, an enzyme that metabolizes PUFAs [16], [17], [18], [19]. These data highlighted the involvement of PUFAs in the pathology of eating disorders. Consistent results have not yet been reached, however, because subject characteristics, sample sizes, and outcome measures have varied between studies.
The importance of interventions other than pharmacological therapies has recently been discussed in the field of nutritional psychiatry. In individuals with psychiatric disorders, nutritional interventions are particularly expected to provide holistic benefits for both physical and psychiatric symptoms. PUFAs, for example, have been suggested to exert therapeutic effects on eating disorders [20], [21]. Regarding their association with appetite, intake of fish oil reportedly contributed to increased appetite in healthy individuals [22]. In cancer cachexia, administration of omega-3 fatty acids has been associated with improvements in appetite, weight gain, and inhibition of lipolysis and proteolysis [23], [24], [25]. Increased body weight as a result of PUFA administration has been reported in clinical studies on eating disorders [21], [26], and improvement in eating disorder assessment scores in addition to body weight have also been reported [20]. On the other hand, some studies described no effect on psychopathological indicators [26], [27]. A consensus has therefore not yet been reached and most interventional studies on eating disorders have been limited by small sample size and high dropout rate.
From the viewpoint of neurotrophic factors and neuroinflammation, PUFAs may be closely associated with eating disorders. As previous observational or interventional studies have not reached consensus, the present study aims to elucidate a potential relationship between PUFAs and eating disorders and the potential benefit of PUFAs in such diseases by meta-analysis.
Section snippets
Protocol
This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) [28]. (Supplement Fig. 1 and online supplement material). The study protocol followed the requirements of the Tri-Service General Hospital Institutional Review Board (TSGHIRB: B-105-12).
Literature search and screening
Two psychiatrists (K Satogami and PT Tseng) separately performed a systematic search of literature up to June 3rd, 2018 on PubMed, Embase, ProQuest, ClinicalKey, ScienceDirect,
Studies included in each meta-analysis
After the initial screening procedure, a total of thirty articles were considered for a full-text review (Fig. 1). Among them, nineteen were excluded according to the exclusion criteria (Supplement Table S2). Finally, the eleven remaining articles were eligible for inclusion in the current study [17], [19], [20], [26], [27], [44], [45], [46], [47], [48], [49] (Table 1).
Characteristics of the included studies
Among the recruited eleven articles [17], [19], [20], [26], [27], [44], [45], [46], [47], [48], [49], seven described the
Discussion
To our knowledge, this is the first meta-analysis to investigate the roles in peripheral blood levels of PUFAs in patients with eating disorders. Our main findings are that the concentrations of general PUFAs (i.e., plasma omega-3: ALA, EPA, SDA, and total omega-3 fatty acid, omega-6: OBA, omega-7: PA, and omega-9: OA; RBC membrane: omega-7: PA, omega-9: OA) were significantly higher in patients with eating disorders than in controls. Only the omega-6 (i.e., RBC membrane adrenic acid and RBC
Conclusion
The analysis of observational studies demonstrated significantly higher omega-3 PUFA levels and lower omega-6 levels in patients with eating disorders. Furthermore, omega-3 PUFAs supplementation could improve the BW, but not disease severity or mood symptoms. The relationship between PUFAs and eating disorders should be interpreted cautiously considering the specific lipid metabolism under starvation state. Further accumulation of evidence on the pathophysiology between changes of PUFAs and
Declaration of interest
There are no conflicts of interest to declare.
Acknowledgement
We thank Benjamin Phillis from Wakayama Medical University for proofreading and editing the manuscript.
Funding/Support
The authors of this work were supported by the following grants: MOST 106-2314-B-039-027-MY3; 106-2314-B-038-049; 106-2314-B-039-031; 106-2314-B-039-035; 104-2314-B-039-022-MY2, 104-2314-B-039-050-MY3, 103-2320-B-039-036, and 104-2314-B039-050-MY3 from the Ministry of Science and Technology, Taiwan; NHRI-EX105-10528NI from the National Health Research Institutes, Taiwan; and CRS-106-063, DMR-107-202, DMR-107-204 and Chinese Medicine Research Center from the China Medical University, Taiwan. All
Authors' contributions
Kazumi Satogami and Ping-Tao Tseng all contributed equally as first authors and took the responsibility of completion of current manuscript
Shun Takahashi, Satoshi Ukai, Yutaka J. Matsuoka, Dian-Jeng Li, Tien-Yu Chen, Pao-Yen Lin, and Yen-Wen Chen, all contributed in study design and concept formation.
Kuan-Pin Su, the corresponding author, took the responsibility of collecting all the information/data from the other authors and submitted this manuscript.
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Kazumi Satogami and Ping-Tao Tseng should be considered joint first author.