Fatty Acids in Autism


Polyunsaturated fatty acids: levels in blood

Although there is argument about the level of fatty acid in the blood of autistic patients, with 1 group finding normal levels, another finding a modified range of fatty acids, and a further one found lower levels but a generally modified ratio of some polyunsaturated fatty acids to others.  They have an anti-oxidant action to some degree. 

 

Treatment: including reviews

Attempts have been used to try treatment of autistics with PUFAs in the diet have shown various results see review. 

 

Discussion

PUFAs are needed by the body for energy, formation of cell walls, absorption of further compounds, and particularly the formation of inflammatory compounds. 

 

Don’t forget that PUFAs change the cholesterol in the  blood and that Low Density Lipoprotein (LDL) is known to be altered in autism.

 

 

Common Omega 6-PUFAs

 

 


 

Fatty Acids (Polyunsaturated Fatty Acids – PUFAs)

 

Bu B, Ashwood P, Harvey D, King IB, Water JV, Jin LW. Fatty acid compositions of red blood cell phospholipids in children with autism. Prostaglandins Leukot Essent Fatty Acids. 2006 Apr;74(4):215-21.  (no useful differences were found between autistic and control blood)

 

Bell JG, Sargent JR, Tocher DR, Dick JR. Red blood cell fatty acid compositions in a patient with autistic spectrum disorder: a characteristic abnormality in neurodevelopmental disorders? Prostaglandins Leukot Essent Fatty Acids. 2000 Jul-Aug;63(1-2):21-5 (they found an excess in highly unsaturated fatty acids in the red cells of autistics and suggested that more research is needed).  Also see: Bell et al. (2002) Abnormal fatty acid metabolism in autism and Asperger’s syndrome. In: Phospholipid Spectrum Disorder in Psychiatry and Neurology (2nd edition).

Phospholipid Spectrum Disorder in Psychiatry and Neurology (2nd edition).

 

Sliwinski S, Croonenberghs J, Christophe A, Deboutte D, Maes M. Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism? Neuro Endocrinol Lett. 2006 Aug;27(4):465-71. (showed a difference in levels between the blood of autistics and controls) In autism there was a significant increase in the fraction of C22:6-3 (docosahexaenoic acid, DHA) and an increase in the total 3/6 ratio. DISCUSSION: The results of this study suggest that an increase of the plasma phospholipid 3 PUFAs, in particular DHA, and of the total 3/6 ratio may take part in the pathophysiology of autism.

 

Vancassel S, Durand G, Barthélémy C, Lejeune B, Martineau J, Guilloteau D, Andrès C, Chalon S. Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids. 2001 Jul;65(1):1-7. (showed a difference between the blood of autistics and controls and particularly in higher unsaturates)  Low Derivative Omega-6 RBC Membrane Levels 50 of 50 autistics assayed through Kennedy Krieger had GLA and DGLA below mean. Low Omega-3 less common (may even be elevated) (J Orthomolecular Medicine Vol 12, No. 4, 1997) (I could not find this article)

 

Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC. Increased excretion of a lipid peroxidation biomarker in autism.  Prostaglandins Leukot Essent Fatty Acids. 2005 Nov;73(5):379-84. (They looked at the urinary excretion of some fatty acids and compounds that would be expected if the body was under oxidative stress.  One of them appeared as an excess – isoprostane – but this was in an odd double peaked format.  This needs to be repeated).

Fatty acids and oxidative stress in psychiatric disorders.  Tsaluchidu S, Cocchi M, Tonello L, Puri BK. BMC Psychiatry. 2008 Apr 17;8 Suppl 1:S5.  This is a simple review in which autism is a minor part.

Novel plasma phospholipid biomarkers of autism: Mitochondrial dysfunction as a putative causative mechanism. Pastural E, Ritchie S, Lu Y, Jin W, Kavianpour A, Khine Su-Myat K, Heath D, Wood PL, Fisk M, Goodenowe DB. Prostaglandins Leukot Essent Fatty Acids. 2009 Jul 14.

Using a longitudinal trial design in which three plasma samples were collected from 15 autistic and 12 non-autistic age-matched controls over the course of 1 year, universal and unambiguous alterations in lipid metabolism were observed. Biomarkers of fatty acid elongation and desaturation (poly-unsaturated long chain fatty acids (PUFA) and/or saturated very long chain fatty acids (VLCFA)-containing ethanolamine phospholipids) were statistically elevated in all autistic subjects.  Glutamate stress also resulted in in vitro decreased levels of reduced glutathione (GSH), methionine and cysteine, in a similar way to the decreases we observed in autism plasma. Impaired mitochondrial fatty acid oxidation, elevated plasma VLCFAs, and glutamate toxicity as putative causal factors in the biochemistry, neuropathology, and gender bias in autism are discussed.   In other words they explain the change in the phospholipids to be due to the oxidative stress that seems to be involved in other chemical changes that are seen.

Plasma fatty acid profiles in autism: a case-control study.  Wiest MM, German JB, Harvey DJ, Watkins SM, Hertz-Picciotto I. Prostaglandins Leukot Essent Fatty Acids. 2009 Apr;80(4):221-7.  In order to definitely determine whether fatty acid concentrations were associated with autism, we quantitatively measured 30 fatty acids from seven lipid classes in plasma from a large subset of subjects enrolled in the Childhood Autism Risk from Genetics and the Environment (CHARGE) study. The CHARGE study is a large, population-based case-control study on children aged 2-5 born in California. Our subset consisted of 153 children with autism and 97 developmentally normal controls. Results showed that docosahexaenoic acid (DHA, 22:6n-3) was significantly decreased in phosphatidylethanolamine. Dimethyl acetals were significantly decreased in phosphatidylethanolamine and phosphatidylcholine as well. These results are consistent with the only other study to measure dimethyl acetals in children with autism, and suggest that the function of peroxisomes and the enzymes of the peroxisome involved with fatty acid metabolism may be affected in autism.

 


PUFA used as a treatment

Always remember that there is quite a large literature of the use of fatty acids in the treatment of other inflammatory bowel diseases. 

 

Richardson AJ. Clinical trials of fatty acid treatment in ADHD, dyslexia, dyspraxia and the autistic spectrum. Prostaglandins Leukot Essent Fatty Acids. 2004 Apr;70(4):383-90. (reviews the various changes in different conditions) refers to Richardson’s own work: At baseline, the groups did not differ, but after 12 weeks mean scores for cognitive problems and general behaviour problems were significantly lower for the group treated with HUFA than for the placebo group; there were significant improvements from baseline on 7 out of 14 scales for active treatment, compared with none for placebo. Group differences in change scores all favoured HUFA, reaching conventional significance levels for 3 out of 14 scales.

 

Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int Rev Psychiatry. 2006 Apr;18(2):155-72. (Results from controlled treatment trials are mixed, but the few studies in this area have involved different populations and treatment formulations. Dietary supplementation with fish oils (providing EPA and DHA) appears to alleviate ADHD-related symptoms in at least some children, and one study of DCD children also found benefits for academic achievement.)

 

Kidd PM. Omega-3 DHA and EPA for cognition, behaviour, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. Altern Med Rev. 2007 Sep;12(3):207-27. (this simply explains to most people why fatty acids may be helpful).

 

Ross BM, Seguin J, Sieswerda LE. Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids Health Dis. 2007 Sep 18;6:21.  (They had a look at a lot of mental illnesses including autism and did meta analyses.  They could not show advantage for autism.)

 

Calder PC. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases.  Mol Nutr Food Res. 2008 May 26. (Fish oil has been shown to decrease colonic damage and inflammation, weight loss and mortality in animal models of colitis and they say that this makes sense concerning the production of inflammatory PUFAs by some forms)

One open study by Audhya et al. (I cant find this) was a 9-month treatment study. They found little improvement by 6 months, but substantial improvements by 9 months. The largest improvement was in gut function (verified by pre and post endoscopies in many cases), but also improvements in other areas.

 

Patrick L and Salik R, The Effect of Essential Fatty Acid Supplementation on Language Development and Learning Skills in Autism and Asperger’s syndrome. Autism/Asperger’s Digest: Research Article – Jan/Feb 2005.  They found that there was an improvement.

 

Amminger GP, Berger GE, Schäfer MR, Klier C, Friedrich MH, Feucht M Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study. Biol Psychiatry. 2006 Aug 22. CONCLUSIONS: The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism

One study by Adams et al. (I feel that this is presented at meetings rather than published) found that 2 months supplementation of fish oil (rich in DHA) led to significant improvements in sociability and other areas, especially in children and adults who consumed 0-1 servings of fish/month.  Little advantage was seen in patients already receiving fish.

 

Young GS, Conquer JA, Thomas R. Effect of randomized supplementation with high dose olive, flax or fish oil on serum phospholipid fatty acid levels in adults with attention deficit hyperactivity disorder. Reprod Nutr Dev. 2005 Sep-Oct;45(5):549-58. (seemed to cause a clinical improvement but they felt that this justified further research and more measurement of FA levels in ADHD children)

 

Young G, Conquer J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev. 2005 Jan-Feb;45(1):1-28. (this is a review and although it is not directed to autism, it goes through many conditions and their association with FA changes in blood and diet).

 

Meguid NA, Atta HM, Gouda AS, Khalil RO. Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem. 2008 Jun 12. Before taking Efalex, linolenic acid showed a significant reduction (71%), followed by docosahexaenoic acid (65%) and arachidonic acid (45%), while linoleic acid was the least affected PUFA (32%). After taking Efalex, 66% of autistic children showed clinical and biochemical improvement, linolenic acid and docosahexaenoic acid showed the highest levels after Efalex supplementation. CONCLUSION: PUFA supplementation may play an important role in ameliorating the autistic behavior.  

Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A. Eur J Pediatr. 2009 Aug 12.  Long-chain PUFAs (LC-PUFAs) such as eicosapentaenoic acid (EPA, C20:5omega-3), docosahexaenoic acid (DHA, C22:6omega-3) and arachidonic acid (AA, C20:4omega-6), in particular, are involved in numerous neuronal processes, ranging from effects on membrane fluidity to gene expression regulation.  Numerous observational studies have shown a link between childhood developmental disorders and omega-6:omega-3 fatty acid imbalances. For instance, neurocognitive disorders such as attention-deficit hyperactivity disorder (ADHD), dyslexia, dyspraxia and autism spectrum disorders are often associated with a relative lack of omega-3 fatty acids.   He then reviews the treatments.

 

 


 

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