Food for thought: Dietary changes in essential fatty acid ratios and the increase in autism spectrum disorders

Elst, Kim van; Bruining, Hilgo; Birtoli, Barbara; Terreaux, Christian; Buitelaar, Jan K.; Kas, Martien

doi:10.1016/j.neubiorev.2014.07.004

Cited by 57 publications

(41 citation statements)

References 160 publications

(240 reference statements)

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“…To date, one systematic review [110] about the efficacy of HUFAs in the treatment of autism spectrum disorders is available. The conclusions showed that the omega-6/omega-3 fatty acid ratio’s alteration during early life can affect major processes in brain development and induces aberrant behavior.…”

Section: Methodsmentioning

confidence: 99%

Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data

Bozzatello

Brignolo

Borghi

et al. 2016

JCM

149

109

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A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day.

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Section: Methodsmentioning

confidence: 99%

Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data

Bozzatello

Brignolo

Borghi

et al. 2016

JCM

149

109

View full text Add to dashboard Cite

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“…Over the past 100-150 years, the ratio of omega-6 to omega-3 fatty acids in our modern Western diets has shown a steep increase from~1-2:1 to~20-30:1. Although alternative explanations have also been suggested (Dehue 2008;Bracke et al 2016), this may have contributed to a suggested parallel rise in burden of disease due to psychiatric disorders (Simopoulos 1999;Muskiet 2010;Hidaka 2012;Grosso et al 2014;van Elst et al 2014). Similar observations in more recently modernizing countries could suggest that history repeats itself (Sun and Ryder 2016).…”

Section: Historical Epidemiological Perspectivementioning

confidence: 97%

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Mocking

Assies

Ruhé

et al. 2018

J of Inher Metab Disea

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Continuous research into the pathophysiology of psychiatric disorders, such as major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and schizophrenia, suggests an important role for metabolism. This narrative review will provide an upto-date summary of how metabolism is thought to be involved in the pathophysiology of these psychiatric disorders. We will focus on (I) the important role of fatty acids in these metabolic alterations, (II) whether fatty acid alterations represent epiphenomena or risk factors, and (III) similarities and dissociations in fatty acid alterations between different psychiatric disorders. (Historical) epidemiological evidence links fatty acid intake to psychiatric disorder prevalence, corroborated by altered fatty acid concentrations measured in psychiatric patients. These fatty acid alterations are connected with other concomitant pathophysiological mechanisms, including biological stress (hypothalamic-pituitary-adrenal (HPA)-axis and oxidative stress), inflammation, and brain network structure and function. Metabolomics and lipidomics studies are underway to more deeply investigate this complex network of associated neurometabolic alterations. Supplementation of fatty acids as disease-modifying nutraceuticals has clinical potential, particularly add-on eicosapentaenoic acid (EPA) in depressed patients with markers of increased inflammation. However, by interpreting the observed fatty acid alterations as partly (mal)adaptive phenomena, we attempt to nuance translational expectations and provide new clinical applications for these novel neurometabolic insights, e.g., to predict treatment response or depression recurrence. In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease.

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“…Furthermore, it appears to reduce neuronal apoptosis after induced hypoxic injury (Zhang et al, 2010) through increasing anti-apoptotic proteins (Bcl-xl, Bcl-2, Bfl-1), while decreasing pro-apoptotic proteins (Bax, Bik) (Lukiw et al, 2005). It is also important to note that increased Ω-6, or a low ratio of Ω3:Ω6, is also associated with impaired cognition and behavior in animal and human studies (Loef and Walach, 2013; Van Elst et al, 2014), although few studies have looked at this to date.…”

Section: Introductionmentioning

confidence: 99%

Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-Î± expression in 7 month old unchallenged mice

Grundy

Toben

Jaehne

et al. 2014

Front. Cell. Neurosci.

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Dietary polyunsaturated fatty acid (PUFA) manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD). Animal studies suggest that high omega (Ω)-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS) inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium, and high Ω-3:Ω-6 dietary ratio, given from the age of 3–7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX) was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay aging effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α.

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Food for thought: Dietary changes in essential fatty acid ratios and the increase in autism spectrum disorders

Cited by 57 publications

References 160 publications

Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data

Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-Î± expression in 7 month old unchallenged mice

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