Bell, C. C. A comparison of daily consumption of artificial dye-containing foods by American children and adults, Eastern Michigan University Master’s Theses. 2013.

Counting number of exposures to food dye rather than actual amounts of dye consumed, she found that children encounter at least twice the number of exposures to food dyes as adults, and also that fruit and vegetable consumption was inversely correlated to the number of dye exposures per day in the children, who were found to “habitually consume more brightly colored foods with additives in lieu of nutrient dense foods.“It appears we are training a generation of future adults to consume little more than easily-available and highly-advertised processed foods.

Doguc et al., Effects of maternally exposed colouring food additives on cognitive performance in rats, Toxicology and Industrial Health, 2013 Aug;29(7):616-23. doi: 10.1177/0748233712436638

” ” Artificial food colourings and additives (AFCAs) have long been suggested to adversely affect the learning and behaviour in children. In this study, we aimed to provide additional data to clarify the possible side effects of colouring additives on behaviour and memory. We administered acceptable daily intake values of AFCAs as a mixture (Eritrosin, Ponceau 4R, Allura Red AC, Sunset Yellow FCF, Tartrazin, Amaranth, Brilliant Blue, Azorubin and Indigotin) to female rats before and during gestation and then tested their effects on behaviour and on spatial working memory in their offspring. … Our results showed that commonly used artificial food colourings have no adverse effects on spatial working memory and did not create a depressive behaviour in offspring. But they showed a few significant effects on locomotor activity as AFCAs increased some parameters of locomotor activity. 

Eagle, K. ADHD impacted by sulfotransferase (SULT1A) inhibition from artificial food colors and plant-based foods  Physiology & Behavior, 135 (2014), 174-179.

” SULT1A inhibitors in foods, including natural substances and artificial food colors, have a role in ADHD that can both worsen or improve symptoms. … SULT1A inhibition can influence brain catecholamines through the intermediary of plasma tyrosine levels, which are influenced by dopamine inhibition of intestinal tyrosine hydroxylase.”Note: SULT1A is the same enzyme group elsewhere called PST. This is a complicated study for those not well versed in organic chemistry, but it basically gives a clue why some children appear to get worse when first put on the diet.

Gray et al., Salicylate elimination diets in children: Is food restriction supported by the evidence?

Gray was treating patients who had previously been on the low-salicylate diet (or FAILSAFE diet) used in Australia, which is far more restrictive than the Feingold diet. He reported adverse effects in almost half the children, including weight loss, failure to thrive, nutritional deficiencies, food aversion, and hair loss. He did not, presumably, ever see those children who had been successfully treated via the FAILSAFE diet, and his conclusions provoked some interesting responses from other researchers

Hoekstra PJ.   Is there potential for the treatment of children with ADHD beyond psychostimulants?  European Child & Adolescent Psychiatry 2011, 20 (9), 431-2.  doi: 10.1007/s00787-011-0212-2.

 … What promise may alternative treatments offer for children with ADHD? Food-based interventions may be one option. In 2009, this Journal had published promising effects of a restricted elimination diet in reducing symptoms of ADHD versus a waiting list control group.  Result

Husarova V, & Ostatnikova D. Monosodium glutamate toxic effects and their implications for human intake: A review, JMED Research, Vol. 2013 (2013), doi: 10.5171/2013.60876

This is a review of the “studies about MSG effects and its potential pathological influence on different systems in humans.”Effects of injected MSG into rats included neuron damage, and prefrontal cerebral cortex changes, but such tests cannot be done on humans, who are not injected with MSG anyway (except in some vaccines which were not discussed in this article). Rats given MSG mixed with their food, however, also showed degenerative changes and inflammation in various brain areas.

Mice born to mothers fed MSG had impaired maze learning although no neuronal damage was visible. Also, lower doses given orally to young rats led to learning problems in adulthood, indicating that “early-life MSG exposure could lead to subtle behavioral aberrations in adulthood.” More research on doses approximating those used by humans are needed.

The Potential Health Hazard of Tartrazine and Levels of Hyperactivity, Anxiety-Like Symptoms, Depression and Anti-social behaviour in Rats. (Scroll down to #183), Kamel MM, El-lethey HS, Journal of American Science, 2011;7(6)

” The current research aimed to determine the influence of different doses of exposure to tartrazine [Yellow 5] on levels of hyperactivity, anxiety, depression and anti-social behaviours in rats. . . Tartrazine-treated rats showed hyperactivity in open field test presented by increased horizontal locomotion. . . Furthermore, tartrazine intake significantly promoted depression as expressed by prolonged immobilization during forced swim test. Impairment in social interaction test was also detected . . . This study provides sufficient scientific evidence that a causal link truly exists between tartrazine and inflection of hyperactivity, anxiety and depression-

The role of diet in the behavior of children has been controversial, but the association of several nutritional factors with childhood behavioral disorders has been continually suggested. We conducted a case-control study to identify dietary patterns associated with attention deficit hyperactivity disorder (ADHD). The study included 192 elementary school students aged seven to 12 years. Three non-consecutive 24-h recall (HR) interviews were employed to assess dietary intake, and 32 predefined food groups were considered in a principal components analysis (PCA). PCA identified four major dietary patterns: the “traditional” pattern, the “seaweed-egg” pattern, the “traditional-healthy” pattern, and the “snack” pattern. The traditional-healthy pattern is characterized by a diet low in fat and high in carbohydrates as well as high intakes of fatty acids and minerals. The multivariate-adjusted odds ratio (OR) of ADHD for the highest tertile of the traditional-healthy pattern in comparison with the lowest tertile was 0.31 (95% CI: 0.12-0.79). The score of the snack pattern was positively associated with the risk of ADHD, but a significant association was observed only in the second tertile. A significant association between ADHD and the dietary pattern score was not found for the other two dietary patterns. In conclusion, the traditional-healthy dietary pattern was associated with lower odds having ADHD.

Malakar, S & Bhattacharya, S. (2014). Minding the greens: Role of dietary salicylates in common behavioural health conditions. Acta Alimentaria, 43(2), 344-359.

“The role of artificial food additives and food chemicals in abetting certain behavioural conditions has been the subject of behavioural nutrition research over several decades. However, a few studies have also raised questions regarding a similar role possibly played by naturally occurring phytochemicals in general and salicylates in particular. … The gap in the extant literature is even more prominent for salicylates present naturally in a number of fruits, vegetables, and plant-sourced food items – the common core ingredients of what one would likely consider to be a healthy diet. Given that it is now well-known that autistic patients tend to be PST-deficient, causal link between a low-salicylate diet and the mitigation of symptom- severity seems a rather plausible hypothesis. However, while the literature is replete with dietary intervention studies that look at artificial food additives, peer-reviewed studies focusing exclusively on the role of a diet low in salicylates in general and natural salicylates in particular in treating autism spectrum disorders are conspicuously absent…. It is quite apparent from the above discussions that Feingold hypothesis is still the central theoretical edifice when it comes to explaining the possible role of salicylates in several behavioural disorders.

… However, studies that have specifically tried to isolate the effect of salicylates (which is only one of the several elimination items in a typical Feingold diet) are few, and in those the effect of naturally occurring salicylates in common food items has not been studied. ”

Millichap JG & Yee MM. The diet factor in attention-deficit/hyperactivity disorder.Pediatrics, 2012 Feb;129(2):330-7. doi: 10.1542/peds.2011-2199.

” This article is intended to provide a comprehensive overview of the role of dietary methods for treatment of children with attention-deficit/hyperactivity disorder (ADHD) when pharmacotherapy has proven unsatisfactory or unacceptable. Results of recent research and controlled studies, based on a PubMed search, are emphasized and compared with earlier reports… In practice, additive-free and oligoantigenic/elimination diets are time-consuming and disruptive to the household; they are indicated only in selected patients. … “Note: He left out most of the studies on diet and behavior done over the past 20 years, in spite of his promise in his abstract (above) – but he had no problem claiming it would cause “household disruption” in spite of not one single study ever done on that.

Effects of food on physical and sleep complaints in children with ADHD: a randomised controlled pilot study.,Pelsser LM, Frankena K, Buitelaar JK, Rommelse NN. European Journal of Pediatrics, 2010 Apr 17. [Epub ahead of print]

“… Dietary intervention studies have shown convincing evidence of efficacy in reducing ADHD symptoms in children. In this pilot study, we investigated the effects of an elimination diet on physical and sleep complaints in children with ADHD. . . The number of physical and sleep complaints was significantly decreased in the diet group compared to the control group . . . headaches or bellyaches, unusual thirst or unusual perspiration, and sleep complaints. . . An elimination diet may be an effective instrument to reduce physical complaints in children with ADHD“

Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial., Pelsser LM, Frankena K, Toorman J, Savelkoul HF, Dubois AE, Pereira RR, Haagen TA, Rommelse NN, Buitelaar JK. Lancet. 2011 Feb 5;377(9764):494-503

“… 100 children were enrolled and randomly assigned to the control group (n=50) or the diet group (n=50). Between baseline and the end of the first phase, the difference between the diet group and the control group in the mean ARS [ADHD Rating Scale] total score was 23·7 according to the masked ratings. … In the challenge phase, after challenges with either high-IgG or low-IgG foods, relapse of ADHD symptoms occurred in 19 of 30 (63%) children, independent of the IgG blood levels…INTERPRETATION: A strictly supervised restricted elimination diet is a valuable instrument to assess whether ADHD is induced by food. The prescription of diets on the basis of IgG blood tests should be discouraged.”

Saab, L., The effect of diet supplementation on children with ADHD, Lebanese American University, Masters Thesis 2012

A case study was conducted on a 9 year old boy attending in a private school in Beirut who was diagnosed with ADHD. The participant had food additives, refined sugars, casein, gluten, and foods with salicylates removed from his diet and an increased intake of essential fatty acids (omega 3 and omega 6). The study that lasted 5 weeks aimed to observe the effects of this special diet on the boy’s hyperactivity, impulsivity and inattention. The diet proved effective in that diet modification played an effective role in the management of ADHD and hence should be recommended to students with similar conditions.

Sonuga-Barke et al., Nonpharmacological Interventions for ADHD: Systematic Review and Meta-Analyses of Randomized Controlled Trials of Dietary and Psychological Treatments, American Journal of Psychiatry, 2013 Mar;170(3):275-89. doi: 10.1176/appi.ajp.2012.12070991.

“Free fatty acid supplementation and artificial food color exclusions appear to have beneficial effects on ADHD symptoms, although the effect of the former are small and those of the latter may be limited to ADHD patients with food sensitivities.”

Dietary sensitivities and ADHD symptoms: thirty-five years of research., Stevens LJ, Kuczek T, Burgess JR, Hurt E, Arnold LE., Clin Pediatr (Phila). 2011 Apr;50(4):279-93. Epub 2010 Dec 2.

” . . .accumulated evidence suggests that a subgroup shows significant symptom improvement when consuming an AFC-free diet and reacts with ADHD-type symptoms on challenge with AFCs [artificial food colors]. Of children with suspected sensitivities, 65% to 89% reacted when challenged with at least 100 mg of AFC. . . . A trial elimination diet is appropriate for children who have not responded satisfactorily to conventional treatment or whose parents wish to pursue a dietary investigation. ”

Stevens LJ, et al. Mechanisms of behavioral, atopic, and other reactions to artificial food colors in children. Nutrition Review, 2013 May;71(5):268-81. doi: 10.1111/nure.12023

” This review examines the research on mechanisms by which artificial food colors (AFCs) and common foods may cause behavioral changes in children with and without attention-deficit/hyperactivity disorder (ADHD). . . Studies have shown that a subgroup of children (with or without ADHD) react adversely to challenges with AFCs. . . Three types of potential mechanisms are explored: toxicological, antinutritional, and hypersensitivity. Suggestions for future studies in animals and/or children include dose studies as well as studies to determine the effects of AFCs on the immune system, the intestinal mucosa, and nutrient absorption. Given the potential negative behavioral effects of AFCs, it is important to determine why some children may be more sensitive to AFCs than others and to identify the tolerable upper limits of exposure for children in general and for children at high risk. ”

Stevens, L.J. et al., Amounts of artificial food dyes and added sugars in foods and sweets commonly consumed by children, Clinical Pediatrics, 2014 Apr 24, 1-13.

“Artificial food colors (AFCs) are used to color many beverages, foods, and sweets in the United States and throughout the world. … Amounts of AFCs reported here along with the beverage data show that many children could be consuming far more dyes than previously thought. ”

Stevens, L.J. et al., Amounts of artificial food colors in commonly consumed beverages and potential behavioral implications for consumption in children,Clinical Pediatrics, 2014 Feb;53(2):133-40. doi: 10.1177/0009922813502849.

” Artificial food colors (AFCs) are widely used to color foods and beverages. The amount of AFCs the Food and Drug Administration has certified over the years has increased more than 5-fold since 1950 (12 mg/capita/day) to 2012 (68 mg/capita/day). In the past 38 years, there have been studies of adverse behavioral reactions such as hyperactivity in children to double-blind challenges with AFCs. Studies that used 50 mg or more of AFCs as the challenge showed a greater negative effect on more children than those which used less. The study reported here is the first to quantify the amounts of AFCs in foods (specifically in beverages) commonly consumed by children in the United States. … “Winners in each category with the most dye in a single cup (8 ounces or 240 ml) were:

• 34 mg – Faygo Redpop (a carbonated beverage)
• 52.3 mg – Kool-Aid Burst Cherry (a fruit-flavored beverage)
• 22.1 (Powerade Orange (a sports beverage)
• 18.8 mg (Full Throttle Red Berry (an energy drink)

Stevenson et al, Research review: the role of diet in the treatment of attention-deficit/hyperactivity disorder–an appraisal of the evidence on efficacy and recommendations on the design of future studies. Journal of Child Psychology & Psychiatry, 2014 May;55(5):416-27. doi: 10.1111/jcpp.12215

“The efficacy of three dietary treatments for ADHD has been repeatedly tested in randomized controlled trials (RCTs). These interventions are restricted elimination diets (RED), artificial food colour elimination (AFCE) and supplementation with free fatty acids (SFFA). . . The aim of this review is to critically appraise the studies on the dietary treatments of ADHD, to compare the various meta-analyses of their efficacy that have been published and to identify where the design of such RCTs could be improved and where further investigations are needed. … The methodology of many of the trials on which the meta-analyses are based is weak. Nevertheless, there is evidence from well-conducted studies for a small effect of SFFA. Restricted elimination diets may be beneficial, but large-scale studies are needed on unselected children, using blind assessment and including assessment of long-term outcome. Artificial food colour elimination is a potentially valuable treatment but its effect size remains uncertain, as does the type of child for whom it is likely to be efficacious. There are additional dietary supplements that have been used with children with ADHD. A systematic search identified 11 RCTs that investigated the effects of these food supplements. Despite positive results for some individual trials, more studies are required before conclusions can be reached on the value in reducing ADHD symptoms of any of these additional supplements. ”

Tomova et al., Gastrointestinal microbiota in children with autism in Slovakia.Physiology & Behavior 2015 Jan;138:179-87. doi: 10.1016/j.physbeh.2014.10.033

” Development of Autism Spectrum Disorders (ASD), including autism, is based on a combination of genetic predisposition and environmental factors. … The fecal microflora of 10 children with autism, 9 siblings and 10 healthy children was investigated by real-time PCR. The fecal microbiota of autistic children showed a significant decrease of the Bacteroidetes/Firmicutes ratio and elevation of the amount of Lactobacillus spp. … The participants in our study demonstrated strong positive correlation of autism severity with the severity of GI dysfunction. Probiotic diet supplementation normalized the Bacteroidetes/Firmicutes ratio, Desulfovibrio spp. and the amount of Bifidobacterium spp. in feces of autistic children. … This pilot study suggests the role of gut microbiota in autism as a part of the “gut-brain” axis and it is a basis for further investigation 

Verlaet AAJ, Noriega DB, Hermans N, & Savelkoul HFJ. Nutrition, immunological mechanisms and dietary immunomodulation in ADHD. European Child & Adolescent Psychiatry, 2014 Jul;23(7):519-29. doi: 10.1007/s00787-014-0522-2

” Attention-deficit hyperactivity disorder (ADHD) etiology is not completely understood, but common comorbid dysfunction of the gastrointestinal and immune system suggests that these systems may be affected by a common genetic background and molecular mechanisms. For example, increased levels of specific cytokines were observed in ADHD. Moreover, ADHD has a high comorbidity with both Th1- and Th2-mediated disorders like ear infections, eczema and asthma. A common pathophysiological mechanism was suggested to underlie both asthma and ADHD, while several genes that are linked to ADHD have immune functions.Furthermore, immunological recognition of food provoking ADHD-like behavior was suggested. An immune imbalance, probably requiring a predisposing genetic background, is therefore suggested to contribute to ADHD etiology, with immune dysregulation being more likely than a single subcellular defect. However, next to allergic mechanisms, also pharmacological mechanisms (especially in case of food additives) might be involved. . . . As a result, chronic inflammation and oxidative stress could develop, which can lead to ADHD symptoms, for example by chronic T-cell-mediated neuroinflammation. If immune pathways contribute to ADHD, both its diagnosis and treatment should be reconsidered.Modulation of immune system activity might have potential in ADHD treatment, for example by nutritional approaches providing safe and low-cost ADHD therapy, but further research in these fields is implicated. ”

Vojdani & Vojdani, Immune reactivity to food coloring. Alternative Therapies in Health and Medicine, 2015;21 Suppl 1:52-62

“Artificial food dyes are made from petroleum and have been approved by the US Food and Drug Administration (FDA) for the enhancement of the color of processed foods. …. However, since the use of artificial food coloring has become widespread, many allergic and other immune reactive disorders have increasingly been reported. During the past 50 y, the amount of synthetic dye used in foods has increased by 500%. Simultaneously, an alarming rise has occurred in behavioral problems in children, such as aggression, attention deficit disorder (ADD), and attention-deficit/hyperactivity disorder (ADHD). The ingestion of food delivers the greatest foreign antigenic load that challenges the immune system. Artificial colors can also be absorbed via the skin through cosmetic and pharmaceutical products. The molecules of synthetic colorants are small, and the immune system finds it difficult to defend the body against them. They can also bond to food or body proteins and, thus, are able to act in stealth mode to circumvent and disrupt the immune system. The consumption of synthetic food colors, and their ability to bind with body proteins, can have significant immunological consequences.This consumption can activate the inflammatory cascade, can result in the induction of intestinal permeability to large antigenic molecules, and could lead to cross-reactivities, autoimmunities, and even neurobehavioral disorders. The Centers for Disease Control (CDC) recently found a 41% increase in diagnoses of ADHD in boys of high-school age during the past decade. More shocking is the legal amount of artificial colorants allowed by the FDA in the foods, drugs, and cosmetics that we consume and use every day. The consuming public is largely unaware of the perilous truth behind the deceptive allure of artificial color.

Weiss, B. Synthetic Food Colors and Neurobehavioral Hazards: The View from Environmental Health Research.

Dr. Weiss examines ” the basis of the FDA’s position, the elements of the review that led to its decision and that of the Food Advisory Committee, and the reasons that this is an environmental health issueDISCUSSION: The FDA review confined itself, in essence, to the clinical diagnosis of hyperactivity, as did the charge to the committee, rather than asking the broader environmental question of behavioral effects in the general population; it failed to recognize the significance of vulnerable subpopulations; and it misinterpreted the meaning of effect size as a criterion of risk. The FDA’s response would have benefited from adopting the viewpoints and perspectives common to environmental health research. At the same time, the food color debate offers a lesson to environmental health researchers; namely, too narrow a focus on a single outcome or criterion can be misleading.”

Vojdani & Vojdani, Immune reactivity to food coloring. Alternative Therapies in Health and Medicine, 2015;21 Suppl 1:52-62

“Artificial food dyes are made from petroleum and have been approved by the US Food and Drug Administration (FDA) for the enhancement of the color of processed foods. …. However, since the use of artificial food coloring has become widespread, many allergic and other immune reactive disorders have increasingly been reported. During the past 50 y, the amount of synthetic dye used in foods has increased by 500%. Simultaneously, an alarming rise has occurred in behavioral problems in children, such as aggression, attention deficit disorder (ADD), and attention-deficit/hyperactivity disorder (ADHD). The ingestion of food delivers the greatest foreign antigenic load that challenges the immune system. Artificial colors can also be absorbed via the skin through cosmetic and pharmaceutical products. The molecules of synthetic colorants are small, and the immune system finds it difficult to defend the body against them. They can also bond to food or body proteins and, thus, are able to act in stealth mode to circumvent and disrupt the immune system. The consumption of synthetic food colors, and their ability to bind with body proteins, can have significant immunological consequences.This consumption can activate the inflammatory cascade, can result in the induction of intestinal permeability to large antigenic molecules, and could lead to cross-reactivities, autoimmunities, and even neurobehavioral disorders. The Centers for Disease Control (CDC) recently found a 41% increase in diagnoses of ADHD in boys of high-school age during the past decade. More shocking is the legal amount of artificial colorants allowed by the FDA in the foods, drugs, and cosmetics that we consume and use every day. The consuming public is largely unaware of the perilous truth behind the deceptive allure of artificial color.

Whiteley et al., Gluten- and casein-free dietary intervention for autism spectrum conditions, Frontiers in Human Neuroscience, 2013 Jan 4;6:344. doi: 10.3389/fnhum.2012.00344. eCollection 201

” … We examine evidence suggestive that a gluten-free (GF), casein-free (CF), or gluten- and casein-free diet (GFCF) can ameliorate core and peripheral symptoms and improve developmental outcome in some cases of autism spectrum conditions. Although not wholly affirmative, the majority of published studies indicate statistically significant positive changes to symptom presentation following dietary intervention. In particular, changes to areas of communication, attention, and hyperactivity are detailed, despite the presence of various methodological shortcomings. … the appearance of a possible diet-related autism phenotype seems to be emerging supportive of a positive dietary effect in some cases. Further debate on whether such dietary intervention should form part of best practice guidelines for autism spectrum conditions (ASCs) and onward representative of an autism dietary-sensitive enteropathy is warranted. ”