|March 24th, 2019||#1|
Join Date: Dec 2018
ADHD and Food Dyes
Of course, we all know one of the earliest proponents admitted near his death that it was somewhat of a misnomer at best, and a fraud at the worst, the notion of such a disorder. However, "hyperkinetic" children was a known description of children who learned fast and became bored during school, even as far back as the 1800's, and surely far before.
I wrote this for a psychology course and hope it will be of use to some.
ADHD and Food dyes:
The use of colorful substances to augment the appearance, taste, and stability of food is quite an old practice. According to Dr. Sheldon Margen, a professor of public health at UC Berkeley, historians date some of the earliest practices to Egyptian candy makers, who used natural extracts of colorful plants and wines in their products to improve their appearance (LA Times.) The famous Greek poet Homer noted the use of saffron in his epic The Iliad. These practices had eventually made their way to greater Europe, who sought out various colorful spices such as saffron, marigold, and parsley, spinach, indigo and such. Wars were even fought for their control. The medicinal system most prominent during Middle Age Europe was similar to the long standing doctrine of signatures, which states that plants that resemble parts of the body, were to be used to treat said parts of the body.
This included ascribing certain medicinal properties to even the colors of food and medicines. Indeed, colorants may also reduce the appearance of spoilage and some colorants additionally have highly sought preservative effects. Some other natural pigments include flavonoids, betalains, carotenoids, chlorophyll, myoglobin, caramel, and annatto (Göğüş F. Ch12)
Not all of these food colorings were benign, however. Even as early as the 13th century, unscrupulous bakers would add chalk or ground up bones to their flour to improve the white appearance of their product, and people became ill. This lead to one of the first laws upon the use of food coloring additives, according to the Encyclopedia Britannica from 1911 on page 638 of the first volume: "If any default shall be found in the bread of a baker in the city, the ﬁrst time, let him be drawn upon a hurdle from the Guildhall to his own house through the great street where there be most people assembled, and through the streets which are most dirty, with the faulty loaf hanging from his neck."
Later, towards the Victorian age, food colorings strayed from plant-derived ingredients and became more likely to be based off of elemental dyes. Copper compounds were used to make preserved vegetables appear greener, iron oxide was used to bring out red sauces’ hue, for example. As trade with China developed, they noticed that they could grade their most profitable item, tea, at higher prices the more green it was. Thus, toxic materials such as Prussian blue and yellow gypsum were added to increase the value of the tea. Candy, and other so-called junk food, were some of the worst offenders, as they very may well be today. Bright yellow and pink were achieved by the use of various lead compounds, copper and arsenic for blue and green. The toxicity of these elements were well-known, even to the time of the Romans (Flora G.)
Medical doctors by the Victorian era were aware of their potentially deleterious effects. The use of overtly toxic dyes and adulterants did not phase out until the introduction of the cheaper coal-derived dyes, which are used to this day, from drinks, candy, to even fruit and main foodstuffs. Thanks to the timely coincidence of the Pure Food and Drug Act of 1906, these dyes and additives had to meet far more rigorous standards in relation to toxicity and health. It must be noted that natural does not necessarily mean healthy, as many “natural” plants and compounds may be profoundly toxic.
We shall review some modern reevaluations of some of the food coloring additives used, and address some concerns about some of these additives correlations to hyperactivity. In the 1950’s, it was noticed that children were becoming ill after eating Halloween candy heavily laden with Orange 1, Orange 2, and Red 32. Tests were conducted and the researchers concluded that these three dyes had caused health problems in lab animals, and subsequently were banned (Janseen.) This sparked a renewed interest in ensuring the safety of food additives.
The correlation of some food coloring additives to the symptomology of hyperactivity (now known as Attention Deficit Hyperactivity Disorder, or ADHD) was brought to attention by controversial studies published by pediatrician Benjamin Feingold during the 1970s. It became controversial as his findings evolved into an elimination fad diet that even included excluded various fruits that may have had colorants added to improve their appearance, and a 1983 meta-analysis found the research and diets promoted in the 1970s to be of poor quality and control (Forness, S. Kavale K.)
However, researchers and even the FDA have conceded that those with a genetic predisposition (Millichap JG, Yee MM,) or diagnosis of ADHD may have their symptoms exacerbated by the presence of certain substances in food, including, but not limited to, synthetic color additives (FDA/CFSAN March 30-31, 2011 Food Advisory Committee.) Thus, it is in the best interest to identify exactly which compounds may worsen hyperactivity in susceptible children, rather than to demonize all additives as unquestionably toxic. Indeed, there have been food coloring additives and preservatives that have been phased out of food products due to the concern for toxicity, as suggested by animal studies that may hold relevance in humans.
One theory is that certain additives may interfere with the absorption of nutrients, and those children whom are hyperactive may suffer the most immediate deleterious effects. Another theory is that the compounds themselves are stimulating and may possess a pharmacological effect in humans. Yet another is that certain combinations of these food additives may be the culprit. We shall review some of the evidence in support of these claims.
First, we must review the evidence concerning the existence of nutrient deficiencies in those who have been diagnosed with hyperactivity or attention disorders. Starobrat-Hermelin assessed the levels of magnesium, copper, zinc, calcium, and iron in a group of 116 hyperactive children and found a higher rate of deficiencies amongst them relative to control. Kozielec T, along with the aforementioned researchers, focused on magnesium in particular and found that 95% of the children tested were determined to be deficient in magnesium. Additional research in the study “Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders” (Mousain-Bosc M) supports this assertion. It should be noted that both studies were published in a journal named “Magnesium Research” and the authors did not disclose any conflict of interest, which may raise criticism. However, a larger body of studies have investigated the effect of fatty acid, vitamin and trace element supplementation concerning the mitigation of the symptoms of hyperactivity and have found favorable results (Rucklidge JJ, Huss M, Volp A, et al.) Most of these studies included supplementation as an adjunct to pharmaceuticals.
A recurring theme among reviews of the body of literature concerning the effect of food dyes upon children and hyperactivity is that these substances may be more apt to effect those who are genetically predisposed to sensitivity. One further correlation concerning those diagnosed with ADHD is that researchers (Bener A, El-Layel MS, Kamal M) have found significantly lower levels of serum 25-hydroxyvitamin D in ADHD children relative to control. This is relevant to explaining the mechanism by which why some children may react more profoundly to certain food dyes present in the diet. According to the study “Interplay between Vitamin D and the drug Metabolizing Enzyme CYP3a4,” humans who had additional vitamin D supplementation showed an increased clearance of a substrate of CYP3a4 (Schuetz EG et al.) One food dye class that has been used in prior toxicity studies is the basic xanthene category, which includes erythrosine, which was found to inhibit the CYP3a4 enzyme and additionally, the P-glycoprotein transporter, which regulates the flow of substances across the blood brain barrier (Mizutani T.)
This may help to explain the compounded toxicity encountered in studies of combinations of food dye consumption. Erythrosine is a very common additive. Another colorant that may be consumed with erythrosine may be inert without being able to pass through the BBB. CYP3a4 enzyme inhibition and P-glycoprotein inhibition are well-known mechanisms in which some substances may achieve higher plasma levels in the body, or cross the BBB, and thus, have a higher risk of enhanced toxicity. It also may help explain why levels of vitamin D are relevant when assessing the presence and severity of the symptoms of hyperactivity. One is reminded of the biochemical aspect of cofactors, which are chemicals that are required for the proper function of enzymes. Some cofactors can be recycled, like ATP into ADP and vice versa, however some may need to be continuously consumed by an organism in order to ensure proper function.
Also important to consider is the chelating activity of some of these food dyes. Tartrazine, commonly used in “orange” beverages, is well known to be a chelator of zinc, and according to preliminary research, lower levels of serum zinc were found in hyperactive boys compared to control (Ward et al.) Additionally, they found that tartrazine produced a reduction in serum zinc and increase in urinary zinc when administered to a total of twenty participants, ten of whom were hyperactive and ten of whom were age-matched controls. Zinc has been investigated as an adjunct to psychostimulants which are commonly prescribed for the treatment of hyperactivity, with favorable results.
Additionally, zinc is a coenzyme of the enzyme delta-6 desaturase, which is important to maintain neuronal membranes via the metabolism of fatty acids and oleic acid in the human body. Abnormal neuron membrane activity and the progression of ADHD has been researched (Kitagishi Y et al.) More importantly, delta-6 desaturase polymorphism has been found in individuals with hyperactivity (Brookes KJ, Chen W, Xu W, et al.) As aforementioned, researchers have studied augmentation of omega-6 fatty acids to pharmacological intervention with varying results, mostly positive. Fatty acids and other lipids are critical to proper cellular metabolism and thus, cognitive function (Göğüş F. Ch8)
Finally, some food coloring additives have been found to have a direct psychostimulatory effect in lab animals. This was assessed by giving some rats tartrazine, aka FD&C Yellow 5, and measuring against control (non-dosed rats), the amount of times the rats crossed black lines laid across an open wooden arena, quantifying hyperactivity. The highest treated rats were found to cross nearly 30 more squares on average relative to control (El-Lethey H, Kamel M.) A direct pharmacological mechanism still has not been elucidated.
The evidence establishing a link between certain food additives and the symptoms of hyperactivity in those who may be predisposed to experience an enhanced detrimental response is still being developed, controversial, and yet to be elucidated. It is best that both sides of the conflict, that being the “naturalists” and the food industry, can come to an agreement in that certain substances may not be safely combined in food products for some individuals, or should be included in the amounts they may be. It is good that consumers have product labels and a valuable resource such as the internet in order to make sure that the product’s ingredients may not exacerbate their or their children’s health conditions. From personal, admittedly anecdotal evidence, the author has observed marked hyperactivity in younger siblings after they consumed foods heavy in food dyes, something that sugar alone does not replicate.
Not all food coloring additives are bad. One, Brilliant Blue G, was found to help prevent inflammation and reduce the healing time associated with paralysis after spinal cord injury in rodents (Goldman S, Nedergaard M, et al.) As many papers conclude, more research is needed ($.)
Margen, Sheldon and Ogar, Dale. "Food Coloring's Come a Long Way." LA Times Website. Los Angeles Times, 18 Jan. 1999. Web. 11 Apr. 2016. <http://articles.latimes.com/1999/jan/18/health/he-64868>.
Göğüş, Fahrettin, and Sibel Fadıloğlu. Food Chemistry. Ankara: Ada Kitabevi. Web. 11 Apr. 2016. <https://csn.instructure.com/courses/1247006/modules>.
Chisholm, Hugh. The Encyclopaedia Britannica : A Dictionary of Arts, Sciences, Literature and General Information. Vol. 1. New York: Encyclopaedia Britannica, 1911. Web. 11 Apr. 2016. <https://archive.org/details/encyclopaediabri01chisrich>.
Flora G, Gupta D, Archana T. "Toxicity of Lead: A Review with Recent Updates." Interdisciplinary Toxicology. Slovak Toxicology Society SETOX. Web. 11 Apr. 2016. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485653/>.
Damon, E, Janseen, W. ”Additives For Eye Appeal”, FDA Consumer, Jul. and Aug., 1973.
Forness S, Kavale K. “Hyperactivity and Diet Treatment: A Meta-Analysis of the Feingold Hypothesis.” J Learn Disabil June/July 1983 16: 324-330. Web. 11 Apr. 2016. <http://ldx.sagepub.com/content/16/6/324.abstract>.
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. EPub 2012 Jan 9. Web 11 Apr. 2016 < http://www.ncbi.nlm.nih.gov/pubmed/22232312>.
"U.S. Food and Drug Administration." Quick Minutes: Food Advisory Committee Meeting March 30-31, 2011. Web. 12 Apr. 2016. < http://www.fda.gov/…/Co…/FoodAdvisoryCommittee/ucm250901.htm>.
Kozielec T, Starobrat-Hermelin B. “Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD).” Magnesium Research. 1997 Jun;10(2):143-8. Web. 11 Apr. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/9368235>.
Bali JP, Mousain-Bosc M, Polge A, Pradal-Prat D, Rapin J, Roche M. "Improvement of Neurobehavioral Disorders in Children Supplemented with Magnesium-vitamin B6. I. Attention Deficit Hyperactivity Disorders." Europe PMC. Magnesium Research, 19 Mar. 2006. Web. 11 Apr. 2016. <http://europepmc.org/abstract/med/16846100>.
Rucklidge JJ et al. “Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial.” The British Journal of Psychiatry Apr 2014, 204 (4) 306-315; DOI: 10.1192/bjp.bp.113.132126. Web. 11 Apr. 2016. < http://bjp.rcpsych.org/content/204/4/306>.
Huss M, Stauss-Grabo M, Völp A. “Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems - an observational cohort study.” Lipids Health Dis. 2010 Sep 24;9:105. doi: 10.1186/1476-511X-9-105. Web. 11 Apr. 2016. < http://www.ncbi.nlm.nih.gov/pubmed/20868469>.
Schuetz EG, Thummel KE, Wang Z, Xu Y. “Interplay between vitamin D and the drug metabolizing enzyme CYP3A4.” J Steroid Biochem Mol Biol. 2013 Jul;136:54-8. doi: 10.1016/j.jsbmb.2012.09.012. Epub 2012 Sep 15. Web. 11 Apr. 2016. < http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549031/>.
Mizutani T. “Toxicity of Xanthene Food Dyes by Inhibition of Human Drug-Metabolizing Enzymes in a Noncompetitive Manner.” J Environ Public Health. 2009; 2009: 953952. Published online 2009 Aug 23. doi: 10.1155/2009/953952. Web. 11 Apr. 2016. < http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778353/>.
Ward NI. “Assessment of chemical factors in relation to child hyperactivity.” J Nutr Environ Med (Abingdon) 1997;7:333–342. Web. 11 Apr. 2016. < http://www.feingold.org/Research/PDFstudies/Ward97.pdf>. (Only place I could find the full article online, sorry.)
Kitagishi Y, Minami A, Matsuda S, Nakanishi A, Ogura Y. “Neuron membrane trafficking and protein kinases involved in autism and ADHD.” Int J Mol Sci. 2015 Jan 30;16(2):3095-115. doi: 10.3390/ijms16023095. Web. 11 Apr. 2016. < http://www.ncbi.nlm.nih.gov/pubmed/25647412>.
Asherson P, Brookes KJ, Chen W, Taylor E, Xu X. “Association of fatty acid desaturase genes with attention-deficit/hyperactivity disorder.” Biol Psychiatry. 2006 Nov 15;60(10):1053-61. Epub 2006 Aug 7. Web. 11 Apr. 2016. < http://www.ncbi.nlm.nih.gov/pubmed/16893529>.
El-Lethey H, Kamel, M. “The Potential Health Hazard of Tartrazine and Levels of Hyperactivity, Anxiety-Like Symptoms, Depression and Anti-social behaviour in Rats.” Journal of American Science 2011;7(6):1211-1218].(ISSN: 1545-1003). Web. 11 Apr. 2016. < http://www.jofamericanscience.org/…/183_6181am0706_1211_121…>.
Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L, Takano T, Tian GF, Goldman SA, Nedergaard M. “Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury.” Proc Natl Acad Sci U S A. 106, 12489-93. 2009 Jul 28. Web. 11 Apr. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/19666625>.