What Metabolites Tell Us About ADHD — And What This Means for Diet and Treatment

A relatively new area of ADHD research has been examining the association between ADHD and eating disorders (i.e., anorexia nervosa, bulimia nervosa, and binge-eating disorder). Nazar and colleagues conducted a systematic review and meta-analysis of extant studies.  

They found only twelve studies that assessed the presence of eating disorders among people with ADHD and five that examined the prevalence of ADHD among patients with eating disorders. Although there were few studies, the total number of people studied was large, with 4,013 ADHD cases and 29,404 controls for the first set of studies and 1,044 eating disorder cases and 11,292 controls for the second set of studies.  The meta-analyses of these data found that ADHD people had a 3.8-fold increased risk for an eating disorder compared with non-ADHD controls.  The level of risk was similar for each of the eating disorders.  Consistent with this, their second meta-analysis found that people with eating disorders had a 2.6-fold increased risk for ADHD compared with controls who did not have an eating disorder. The risk for ADHD was highest for those with binge-eating disorder (5.8-fold increased risk compared with controls).  

This bidirectional association between ADHD and eating disorders provides converging evidence that this association is real and, given its magnitude, clinically significant. The results were similar for males and females and pediatric and adult populations.

We cannot tell from these data why ADHD is associated with eating disorders. Nazar et al. note that other work implicates both impulsivity and inattention in promoting bulimic symptoms, whereas inattention and hyperactivity are associated with craving. The association may also be due to the neurocognitive deficits of ADHD, which could lead to a distorted sense of self-awareness and body image.

Given that ADHD is also associated with obesity, some obese ADHD patients may have an underlying eating disorder, such as binge-eating, which has been associated with obesity in prospective studies. Also, lisdexamfetamine is FDA-approved for treating both binge eating and ADHD, which suggests the possibility that the two conditions share an underlying etiology involving the dopamine system. We do not know if treating ADHD would reduce the risk for eating disorders, as that hypothesis has not yet been tested. But such an effect would seem likely if ADHD behaviors mediate the association between the two disorders.

If we are to read what we believe on the Internet, dieting can cure many of the ills faced by humans. Much of what is written is true. Changes in dieting can be good for heart disease, diabetes, high blood pressure, and kidney stones to name just a few examples. But what about ADHD? Food elimination diets have been extensively studied for their ability to treat ADHD. They are based on the very reasonable idea that allergies or toxic reactions to foods can have effects on the brain and could lead to ADHD symptoms.

Although the idea is reasonable, it is not such an easy task to figure out what foods might cause allergic reactions that could lead to ADHD symptoms. Some proponents of elimination diets have proposed eliminating a single food, others include multiple foods, and some go as far as to allow only a few foods to be eaten to avoid all potential allergies. Most readers will wonder if such restrictive diets, even if they did work, are feasible. That is certainly a concern for very restrictive diets.

Perhaps the most well-known ADHD diet is the Feingold diet(named after its creator). This diet eliminates artificial food colorings and preservatives that have become so common in the western diet. Some have claimed that the increasing use of colorings and preservatives explains why the prevalence of ADHD is greater in Western countries and has been increasing over time. But those people have it wrong. The prevalence of ADHD is similar around the world and has not been increasing over time. That has been well documented but details must wait for another blog.

The Feingold and other elimination diets have been studied by meta-analysis. This means that someone analyzed several well-controlled trials published by other people. Passing the test of meta-analysis is the strongest test of any treatment effect. When this test is applied to the best studies available, there is evidence that the exclusion of fool colorings helps reduce ADHD symptoms. But more restrictive diets are not effective. So removing artificial food colors seems like a good idea that will help reduce ADHD symptoms. But although such diets ‘work’, they do network very well. On a scale of one to 10where 10 is the best effect, drug therapy scores 9 to 10 but eliminating food colorings scores only 3 or 4. Some patients or parents of patients might want this diet change first in the hopes that it will work well for them. That is a possibility, but if that is your choice, you should not delay the more effective drug treatments for too long in the likely event that eliminating food colorings is not sufficient. You can learn more about elimination diets from Nigg, J. T., and K.Holton (2014). "Restriction and elimination diets in ADHD treatment."Child Adolesc Psychiatr Clin N Am 23(4): 937-953.

Keep in mind that the treatment guidelines from professional organizations point to ADHD drugs as the first-line treatment for ADHD. The only exception is for preschool children where medication is only the first-line treatment for severe ADHD; the guidelines recommend that other preschoolers with ADHD be treated with non-pharmacologic treatments, when available. You can learn more about non-pharmacologic treatments for ADHD from a book I recently edited: Faraone, S. V. &Antshel, K. M. (2014). ADHD: Non-Pharmacologic Interventions. Child AdolescPsychiatr Clin N Am 23, xiii-xiv.

A Swedish-Danish-Dutch team used the Swedish Medical Birth Register to identify the almost 1.7 million individuals born in the country between 1980 and 1995. Then, using the Multi-Generation Register, they identified 341,066 pairs of full siblings and 46,142 pairs of maternal half-siblings, totaling 774,416 individuals.

The team used the National Patient Register to identify diagnoses of ADHD, as well as neurodevelopmental disorders (autism spectrum disorder, developmental disorders, intellectual disability, motor disorders), externalizing psychiatric disorders (oppositional defiant and related disorders, alcohol misuse, drug misuse), and internalizing psychiatric disorders (depression, anxiety disorder, phobias, stress disorders, obsessive-compulsive disorder).

The team found that ADHD was strongly correlated with general psychopathology overall (r =0.67), as well as with the neurodevelopmental (r = 0.75), externalizing (r =0.67), and internalizing (r = 0.67) sub factors.

To tease out the effects of heredity, shared environment, and non-shared environment, a multivariate correlation model was used. Genetic variables were estimated by fixing them to correlate between siblings at their expected average gene sharing (0.5for full siblings, 0.25 for half-siblings). Non-genetic environmental components shared by siblings (such as growing up in the same family) were estimated by fixing them to correlate at 1 across full and half-siblings. Finally, non-shared environmental variables were estimated by fixing them to correlate at zero across all siblings.

This model estimated the heritability of the general psychopathology factor at 49%, with the contribution of the shared environment at 7 percent and the non-shared environment at 44%. After adjusting for the general psychopathology factor, ADHD showed a significant and moderately strong phenotypic correlation with the neurodevelopmental-specific factor (r = 0.43), and a significantly smaller correlation with the externalizing-specific factor (r = 0.25).

For phenotypic correlation between ADHD and the general psychopathology factor, genetics explained 52% of the total correlation, the non-shared environment 39%, and the shared familial environment only 9%. For the phenotypic correlation between ADHD and the neurodevelopmental-specific factor, genetics explained the entire correlation because the other two factors had competing effects that canceled each other out. For the phenotypic correlation between ADHD and the externalizing-specific factor, genetics explained 23% of the correlation, shared environment 22%, and non-shared environment 55%.

The authors concluded that "ADHD is more phenotypically and genetically linked to neurodevelopmental disorders than to externalizing and internalizing disorders, after accounting for a general psychopathology factor. ... After accounting for the general psychopathology factor, the correlation between ADHD and the neurodevelopmental-specific factor remained moderately strong, and was largely genetic in origin, suggesting substantial unique sharing of biological mechanisms among disorders. In contrast, the correlation between ADHD and the externalizing-specific factor was much smaller and was largely explained by-shared environmental effects. Lastly, the correlation between ADHD and the internalizing subfactor was almost entirely explained by the general psychopathology factor. This finding suggests that the comorbidity of ADHD and internalizing disorders are largely due to shared genetic effects and non-shared environmental influences that have effects on general psychopathology."