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The Effect of Fatty Acids and Their Dietary Ratio on Attention Deficit/Hyperactivity Disorder

 

 

 

Shih-Chen Liu

9/18/06

 

 

 

Introduction:

            Attention-deficit/hyperactive disorder (ADHD) is one of the most common developmental disorders of childhood and some of the symptoms include inattention, hyperactivity, and impulsivity.  The definition of ADHD also includes impaired attention and over-activity occurring in more that one situation, such as in school or/and at home.  Impaired attention leads to “frequent changes from one activity to another and unfinished activities” and over-activity often results in excessive restlessness. (Richardson A.J., Puri B.K., 2000)  All of these symptoms have social and cultural implications that will not only represent significant burden for those affected, but also for the society as a whole as well.  The prevalence of ADHD and other related childhood developmental disorders has been estimated to vary between 4% and 15% for school-aged children in the United States and the world.  However, lower estimates are obtained when the criteria for diagnosis were more rigorous.  The discrepancies in the prevalence of these disorders demonstrate the difficulty in establishing a clear distinct boundary between normal and abnormal functions.  Furthermore, the multifactorial aetiology of ADHD contributes to the challenge of defining on set guideline for diagnosis in a clinical setting.  Nevertheless, there are various treatment methods in the modern medical field for the disorder.  For instance, physicians often prescribe stimulant medications that improve brain dopaminergic abnormalities and increase the availability of dopamine through inhibiting the removal mechanism in the synapse.  These medications, however, has various side effects including difficulty in sleeping, irritability, nervousness, and other experiences that can lead to other problems in society.

 

The Alternative Treatment:

            Jeannine Virtue, a freelance journalist and mother of an ADHD son, wrote an article advocating an alternative method in the treatment of the disorder.  She stated that “nutrition alone can effective work as an ADHD alternative treatment” and this is the underlying purpose for the article.(Virtue, 2003)  This advertisement for the alternative method also included findings from different research groups that suggest the cause of ADHD are nutritional deficiencies, especially in certain types of essential fatty acids.  For instance, the author stated that “in 1996…researchers have found that boys with low blood levels of Omega-3 fatty acids have a greater frequency of ADHD.”(Virtue, 2003)  These are the supports for her claim about the cause of ADHD.  The author, through reviewing these studies, concluded that although not all ADHD children are “nutritionally deficient in essential fatty acids, studies show that a significant number of ADHD children are.”(Virtue, 2003)  However, she mistakenly made the simple association between fatty acid deficiency and ADHD into a causal relationship and did not provide any support or statistics about the effectiveness of the alternative treatment.  She simply stated that because ADHD is related to fatty acid deficiency, a good balance diet would replace medications and help to treat the disorder.

Although the author did not provide evidence for her claim, she did discuss the rationale behind this alternative method.  Fatty acids are crucial components of the cell membrane and this is important because membrane proteins such as signal receptors and ion channels are embedded in the phospholipids bilayer construct of the membrane.  Fatty acid imbalance can affect the structures of these membrane proteins and thus the associated neurotransmitter functioning and signaling events.  The essential fatty acids that can not be synthesized by the human body and therefore must be provided by diet are the linoeic acid and alpha-linolenic acid; otherwise know as omega-3 and omega-6 family of fatty acids.  The longer chain polyunsaturated fatty acids that came from these precursors are crucial neuronal membrane components and active biological compounds that perform numerous regulatory functions in the brain and throughout the rest of the body.  The problem of fatty acid deficiency is a result of the eating habits of the society.  A typical Western diet is high in foods that contain the omega-6 family of fatty acids, including corn, sunflower and vegetable oil.  However, most Western diets are deficient in Omega-3 fatty acids.  This particular group of compounds is found in flax oil and various types of fish, foods that many children tend to avoid.  The author also introduced different methods of incorporating these foods into kids’ diets and ended her discussion on the importance of a balanced nutrition meal. 

The author of the article attempted to convince the general public to utilize nutritional balance as the main treatment method rather than an adjunct to the current method.  While the author’s description of the alternative method seemed promising, further research into the genetics and biological nature of the fatty acid metabolism process as well as other clinical research and reviews on the importance of fatty acid in treating ADHD proved otherwise.  These research efforts demonstrated that while the Omega-3 class fatty acids seem to alleviate ADHD-related symptoms in at least some children, “larger trials are needed to confirm these findings and establish the treatment effects as well as the optimal formulations and dosage forms.”(Richardson A.J., Puri B.K., 2000)  Furthermore, these studies indicate that fatty acid supplements can not replace the conventional treatment for the disorder; it can only offer a promising complementary approach to standard treatments. 

 

Evaluation of the Treatment: Review Paper

Some of the most important sources of evidence that refute the author’s view on fatty acid diet as the main treatment method for ADHD came from review papers that focused on a question and collected available research data from other studies to answer that question.  Richardson and Puri (2000) reviewed various clinical and biochemical experiments and suggested that a “functional deficiency of certain long chain polyunsaturated fatty acids could contribute to many of the features associated with” ADHD and that such treatment form is relatively safe compare to the existing pharmacological intervention.(Richardson A.J., Puri B.K., 2000)  However, they also stated that further studies are still needed in order to “evaluate fatty acid supplement’s potential efficacy in the management of ADHD symptoms.”(Richardson A.J., Puri B.K., 2000)  In the paper, the authors gave an overview of the theoretical plausibility of fatty acid imbalance as a risk factor for ADHD.  For instance, animal studies has shown that Omega-3 polyunsaturated fatty acid (PUFA) deficiency is associated with decreased level of endogenous dopamine and this also reduced the dopamine storage of brain, causing inadequate release of the during stimulated cognitive processes.  This demonstrated the relevance of fatty acid in ADHD because the studies were able to account for the abnormal dopamine amount in ADHD patients.  The authors furthered the association between fatty acid and the disorder when they examined studies reporting that ADHD children, when compared to normal children, had more somatic complaints such as headaches, stomach-aches, and proneness to infection.  These are some of the problems that are known to results of essential fatty acids (EFA) deficiency because fatty acids and their derivatives play a crucial role in the regulations of immune and digestive functions.  The co-morbidity of ADHD and these somatic illnesses is an example of the association of the mental disorder with fatty acid imbalance. 

Moreover, there are clinical studies that underscore this relationship.  Studies carried out at Purdue University examined the essential metabolism of EFA in boys with ADHD and concluded that relative to 43 normal controls, 53 boys with ADHD were not only more likely to suffer from allergies and other health problems known to be associated with EFA deficiency.  However, they showed no deficiency in the EFA precursors in their diet.  This highlights the possibility that it is the abnormality in fatty acid metabolism that could be a cause for ADHD.  The review provides different kinds of evidence showing the relationship between nutritional balance and ADHD and how studying more into this association could provide a complementary solution to a problem that affects the society. 

While the review article argues for the link between fatty acid deficit and the disorder, the authors also presented several complications which lead to the need for further studies.  The two authors emphasized the importance of fatty acids in brain development; particularly the ways that essential fatty acid metabolism can affect brain activity.  Animals studies has shown that both “neural integrity and functions can be permanently disrupted by deficits of these fatty acids during fetal and neonatal development”, and there are many factors that can contribute to this imbalance even with a nutritional diet.(Richardson A.J, Puri B.K., 2000)  These include genetic problems and deficiency of vitamins and mineral cofactors and other molecules that are necessary for proper enzyme actions in the EFA to PUFA conversion process.  This indicates that even with the availability of EFA precursors in the diet, patients can still end up with a deficiency in the fatty acids that are crucial in brain development.  The consistent findings both in the clinical setting and in blood biochemical work indicate that “supplementation with PUFAs might be helpful in the management of this condition in at least some cases.”(Richardson A.J., Puri B.K., 2000)  However, the article also stated that the future challenge is to determine the portion of the ADHD children that can benefit from such fatty acid supplement and the ways to identify these patients.  The different treatments, procedures and measures used in these experiments as well as poorly-designed experiments also made the comparison between studies difficult, prompting the authors to call for a standardized testing method for the projects.  For instance, one of the early double-bind placebo trials demonstrated while there are modest benefits of fatty acid supplement over placebo, this was less effective than the current stimulant-based medication.  However, this particular study failed to recognize that unlike the drug, fatty acids cannot be expected to change symptoms and behaviors rapidly.  The PUFA levels in the brain may take up to three months to recover from a chronic deficiency state.  This heightens the need for careful considerations of experimental variables in the design of future projects as well as the need for more large scale studies to investigate this issue.  Anecdotal evidence of benefits has convinced a lot of people to try fatty acid supplementation as an alternative to the current medication; however, until no further data are available, no recommendation can be made concerning the effectiveness of this as a treatment for ADHD.  This review article highlights some of the small scale studies that elucidated the relationship between fatty acid and ADHD, but at the same time supports further research to confirm these findings and possible side effects of this supplementation.

Figure 1. The proteins that are involved in the EFA to

PUFA conversion process (Brookes, K.J. etc, 2006)

 

 

Evaluation of the Treatment: Biological Experiment

    Other sources of evidence that refute the author’s view on fatty acid diet as a treatment method for ADHD came from actual clinical studies and biological experiments that aim to solve understand a specific relationship between two variables.  As Figure 1 illustrated, there are various proteins that work on EFAs in the process of turning them into their effective PUFA form and any abnormalities in the proteins involved will result in an inappropriate ratio of fatty acids, particularly the Omega-3 and Omega-6 class of fatty acids.  Such change form the optimal ratio will disrupt normal functioning of the cell membrane.  Other projects mentioned in this paper also suggested that an excess intake of either one of the two fatty acid classes could be problematic due to the fact that excess amount of either one could suppress the conversion of other fatty acid types, exacerbating the imbalance of the dietary ratio.  Previous studies had already isolated three genes that code for different desaturases and this region of the genome has been highlighted in ADHD genome-wide linkage analysis.  This study explored the relationship between the fatty acid desaturase genes with ADHD and investigated “the biological mechanisms that could lead to deficiency of Omega-3 fatty acids observed in ADHD subjects.”(Brookes, K.J. etc, 2006)  They were able to do so through scanning for genetic associations between various single nucleotide polymorphism (SNP) and ADHD.  Previous studies also demonstrated an increased amount of ethane exhaled by ADHD patients but was not able to figure out how this fit into the breakdown of fatty acid in metabolism.

 

 

 

 

 

In the beginning of the experiment, the scientists collected data about their ADHD subjects and determine their eligibility through research interview, questionnaire, and case notes where necessary.  The study comprised of two groups, a control sample consisted of 90 unrelated female and 90 unrelated male individuals with low scores on a composite index of ADHD symptom scores, and a clinical ADHD sample consisted of 180 patients who had a research diagnosis of ADHD following the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria.  They then collected DNA samples from the control and the patients, amplified the samples through PCR, and determined the individual allele/SNP frequency within both populations.  Through the result of the experiment, they were able to identify an increased prevalence of a particular SNP in one of the three desaturases among the ADHD cases.  This finding also provides a possible explanation for the increased in ethane exhaled by ADHD patients.  Assuming that this SNP resulted in a lower desatruase activity, this would lead to a lower incorporation of omega-3 PUFAs into the cell membrane and the result of this would be increased breakdown through the oxidation of Omega-3 PUFAs, which forms ethane.  Although this finding was able to identify a particular biological factor that is prominent in ADHD patients, there are no “functional information for this SNP and thus the association remain speculative at this stage.”(Brookes K.J. etc, 2006)  It is through previous studies before this experiment that the authors set out to investigate the relationship between ADHD and fatty acids, and even though the results were inconclusive, this study was a beginning and could serve as a hypothesis for further investigation of the genes that regulate fatty acid metabolism in relation to ADHD.

Evaluation of the Treatment: Clinical Studies

Another source of evidence that would question the author’s view on fatty acid diet as a treatment method for ADHD came from actual clinical studies that supplemented fatty acid-rich substance to ADHD patients.  In this study, researchers aimed to investigate the effect of flax oil and antioxidant supplementation on the symptoms of ADHD and compare EFA levels in ADHD with normal children.  The study is composed two groups, normal controls and ADHD subjects.  For the ADHD group, there were 30 children who were diagnosed with the disorder by a trained clinical psychologist with the help of DSM-IV criteria.  For the control, there were 30 health children from the general population with hyperactivity scores below 50.  They were also matched for age, gender, lifestyle, and dietary patterns with the ADHD group.  Flax oil was used as the main ingredient in the supplement because it is high in alpha-linolenic acid, a kind of Omega-3 fatty acids.  This flax oil supplement also contained Vitamin C and patients were to take the medicine twice a day for three months.  A placebo group was not designed; rather, the pre- and post-supplementation measures were used to access the change in the psychopathology along with changes in red blood cell (RBC) membrane PUFA content.  During the supplementation, the controls and the patients were asked to visit the pediatrician every 15 days and blood samples were also collected during these visits.  These samples were put through a series of double blind analysis that would determine the fatty acid content in the RBC. 

The result of the RBC analysis demonstrated that flax oil supplementation resulted in significant increase in the level of two kinds of Omega-3 fatty acids while the rest were unaltered.  At the same time, individual scores for inattention, impulsivity, restlessness, and self control reduced significantly post supplementation.  This is the first study where the flax oil based Omega-3 fatty acid precursor in combination with antioxidant is “effective in improving symptoms of ADHD.”(Joshi K. etc, 2006)  Although the result of this study was encouraging, there were no placebo group and this was one of the limitations to the experiment.  Furthermore, the paper concluded that the flax oil-based medication could be a useful adjunct, not a replacement, for effective therapy of ADHD and large numbers with placebo-controlled clinical trials on large numbers of patients with longer duration of supplementation need to be done.  Moreover, the data from the experiment can not lead the researchers to conclude that it is only through fatty acid supplementation that there were reduced symptoms in ADHD patients because the medication in the study also included vitamin C, which could actually function as a cofactor for one of the enzymes to function properly in the pathway in Figure 1.  The limitations of this clinical study demonstrated the need for further investigation and it is still too early to make any recommendation on the potential value of dietary supplements in the management of ADHD.             

Conclusion:

Although through clinical and biological experiments there has been an enormous amount of evidence suggesting that the deficiency in Omega-3 and Omega-6 fatty acid families is related to ADHD, there has not been a definite accurate study that indicates such deficit is the direct cause for the disorder.  Furthermore, most of these review papers and research projects did not take an extreme stance on the effectiveness of the fatty acid supplement as did Virtue and suggested that such methods should not be given to patients unless there is a study on a particular dosage form that directly suppresses ADHD symptoms.  ADHD and related psychological behavior problems are disorders that affect many in the society.  Virtue was not intended to sell a particular product or method; she was simply trying to help to solve a problem.  However, it is irresponsible and ineffective to advocate for an alternative method without a careful evaluations of all the facts and studies associated with the issue.  

 

 

 

 

 

 

 

 

 

 

References

  1. Brookes, K.J., Chen W., Xu X., Taylor E., Asherson P. (2006) Association of Fatty Acid Desaturase Genes with Attention-Deficit/Hyperactivity Disorder.  Biological Psychiatry. 1-9
  2. Joshi K. et al. (2006) Supplementation with Flax Oil and Vitamin C Improves the Outcome of Attention-Deficit Hyperactivity Disorder (ADHD). Elsevier. 17-21
  3. Richardson A.J. (2006) Omega-3 Fatty Acids in ADHD and related Neurodevelopment Disorders. International Review of Psychiatry. 155-172
  4. Richardson A.J., Puri B.K. (2000) The Potential Role of Fatty Acids in Attention-Deficit/Hyperactivity Disorder. Prostaglandins, Leukotrienes and Essential Fatty Acids. 79-87
  5. Richardson A.J., Ross M.A. (2000) Fatty Acid Metabolism in Neurodevelopment Disorder: A New Perspective on Associations between Attention-Deficit/Hyperactivity Disorder, Dyslexia, Dyspraxia and the Autistic Spectrum. Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1-9
  6. Virtue J. (2003) Nutrition as an ADHD Alternative Treatment: Help is as Close as the Kitchen. Retrieved from  

http://www.mental-health-matters.com/articles/article.php?artID=435

 

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