Could ADHD be iron deficiency anemia?

Too many mothers think their children suffer from ADHD (attention deficit hyperactivity disorder). Some decide to medicate their children with amphetamine or other stimulants. As a mother, I lived through the slashing feedback of various experienced teachers. They thought my kids, too, had to be evaluated for ADHD and I felt vulnerable in making my decisions.

KidsOptimizedWitnessing a child growing, is like observing a universe under a microscope: you notice every detail and constantly wonder what some insignificant detail means and whether it’s “normal” or not. Maybe not all parents are the same, but this is how I was raising my first son. While with my youngest I got the “been there, done that” worry-less attitude, for my first born I sterilized every item that came in contact with him and kept everything germ-free. I’m laughing now at how stupid the sterilizing was – of course, I didn’t repeat that with his brother! I recall analyzing the time-to-event for each and every little milestone. Did he grow too slow? Did he crawl straight? Did he talk too late? How long did he focus on playing, listening, sneezing, pooping… etc.

lego-blocks-2458575_1280Well, by all the measures and official reports, NOTHING happened as expected! My oldest son was either above the curve or below, regardless of what we were measuring. As a toddler he enjoyed throwing cars, demolishing Lego blocks, and pulling every tablecloth with full glasses on it. He lost interest in anything that lacked a blasting moment of some sort. It had to “boom”, “splash”, “crash” or anything along these lines; otherwise, he wouldn’t waste more than 30 seconds on it. In a way, this preference for “the memorable” reminded me of the comments of my Ph.D. coordinator after reading my first thesis draft. She looked at me over her glasses, tilted her chin down, and told me: “Alice, dear, you are too bombastic! You really have to re-write everything properly”. I wasn’t sure how someone could approach “bombastic” writing when talking about human polymorphism and DNA fingerprinting, but I knew already that I was quite unusual, hence the premises were set… in a way. So, looking at my son, he was very much the-kid-of-his-mother: everything he enjoyed had to have a… bombastic end! But – holy crap! – was this normal?! Were these ADHD symptoms? Did he need treatment??

As a pharmacist, I was very familiar with the extent of ADHD over-diagnosis and amphetamine/stimulant overprescribing. Looking at the trends, it seemed that documented symptoms during childhood were linked with an amphetamine or another stimulant prescribed to enhance learning performance in college. A ton of teens took amphetamines for enhanced learning performance, but several colleagues of mine (and myself) thought that most users weren’t actual ADHD patients. As you guess, if true, such use was inappropriate. That’s what determined the FDA to look very carefully into the ADHD prescribing practices (Kornfield et al) and things became more regulated after 2010. However, at the time when my first-born was still a toddler, the ADHD prescribing practice was booming. The scientific opinion was quite liberal, see below.

“In mid-1995, at least 1.5 million US children were receiving methylphenidate or dexamphetamine. However, in other countries these agents are not used as widely. Specific stimulant-induced benefits for children with ADHD include: improved school grades, more completed classroom work, fewer reprimands for disruptive behaviour, improved handwriting, and improved behaviour at home and in social situtions. Stimulants benefit at least 75% of children with ADHD and are remarkably well tolerated, having few (for the most part minor and temporary) adverse effects.” – Safer DJ, 1997.

Reading this, made sense that teachers were beyond excited to have these medicated kids in their classes. Here comes another:

“Both medications (i.e.methylphenidate and Adderall) appear to improve teachers’ and parents’ ratings of behavior. Single-dose treatments of Adderall appear to be as effective as 2 daily doses of MPH and therefore increase the possibility of managing treatment without involving the school in medication administration. In addition, youths who have previously been unsuccessfully treated with MPH because of adverse side effects or poor response may be successfully treated with Adderall.” – Manos MJ et al, 1999.

As I was reading these articles, many parents in the U.S. were already well informed and ready to give amphetamines a try. The amphetamine option seemed to be the shortest cut toward hearing some school-related praise about their pupil. Soon after, however, the abuse concern became real and tricyclic antidepressants and monoamine oxidase inhibitors came into the ADHD treatment spotlight (Spencer et al, 2002). Nevertheless, stimulants continued to rule the game until 2010. The time window covered exactly my oldest son’s kindergarten and elementary school age. Teachers’ feedback was, I thought, somehow aggressive about a possible ADHD diagnosis. Nothing seemed wrong to me… No worries, I thought, if he doesn’t pay attention in your class, I can tutor him in quite every discipline you have on the schedule – and so it was!

teachingkidoptimizedMy son still remembers our first month of two-hours-daily math. “Is he failing to focus, or the teaching method he was exposed to just didn’t work for him? I want to see him losing focus with me!”. We started from ground ZERO and I pushed an insane amount of repetition. Was this about to get him bored, frustrated, or make him faster? According to the premises of my study, if you get faster at performing a repeated task, then you surely couldn’t have lost focus. Now, let’s be on the same page here: this was math, not dish-washing. Repeating the same type of math exercise keeps the task similar while soliciting your brain to solve the problem. The differences between exercises were designed ever so slightly off to require attention and prevent default rationale. Are you asking who wrote the exercises? Thank you! Yes, myself. Did you expect that I would leave this to anyone else?

forge-411923__480The first week, he kept screaming and telling me that he will never be able to do this. The second week he laughed every time it worked. The third week he was 5 times as fast as he was the week before and, by the end of the month, he was as fast as I was! Now, for clarification: this wasn’t mathematical analysis. This was basic arithmetic, so no big deal. However, it proved a point: he didn’t lose focus if he understood how things worked. He also never became preoccupied with other stuff while I was teaching him. I wasn’t fun, I didn’t play with him, so that wasn’t the key factor in him getting better. It was the motivation that, if he gets it right once, then he can do it again. Interestingly though, my mini-study revealed something else that solved my puzzle: he was more tired than he should have. I could easily figure more than one instance where the teachers’ feedback got biased and this one was one of them. “There is more than one way of combing a cat”, I thought. Why would I first think about the need for amphetamine to stimulate brain oxygenation, when I could instead ensure that he has enough red blood cells to carry the oxygen there? This was how my first anemia suspicion occurred.

iron-man-933709__480Back then, same as today, iron-deficiency anemia (IDA) was more prevalent than we were ready to accept. Was I the only crazy pharmacist that thought of this? Seriously? And one day… there it was in its full splendor: a clinical trial that looked at the iron deficiency in children with ADHD! The study was showing that the vast majority of the children with ADHD were iron deficient, comparing to only just under 20% in the rest of the children (Konofal et al). I dared to ask myself: “after iron replacement, would kids have ADHD symptoms any longer?!” Of course, that wasn’t done in that study, but it made plenty of sense to me to keep looking further. Like in any science, in parenting the most important part is to ask the right questions. I will fly to the moon and back before giving a kid any stimulant. I’m not sure if that’s just me, but that was how I felt about it. For me, a giving a stimulant to a child could have had implications much further away than the foreseeable future. Nope, not rushing into that. That’s when you keep searching and looking and asking and… you find another article. In 2002, Yager and Hartfield published that “ADHD symptoms improved when iron-deficient children with ADHD took an iron supplement”. Woooooow! Did that mean that we failed to feed properly a generation of kids and then we proceeded to explore a whole class of drugs to get rid of the consequences of our wrong diet and lifestyle? Damn!

analysis-2030261__480Little is clarified to-date and at least one study reports exactly the opposite. However, a recent meta-analysis of many studies shows a clear link between lack of iron and ADHD symptoms (Wang et al). Clearly, the matter is very sensitive, so the jury is still out on this and there is no [apparent time] pressure to rule over it. Today we know that the prevalence of ADHD (please read ADHD symptoms) among adult women with IDA is higher than in the women without IDA. Unfortunately, nobody could run that explicit study to clarify if giving iron would prevent ADHD symptoms and diagnosis because such study was unethical to design. That would mean enrolling say 1,000 individuals diagnosed with ADHD based on their symptoms, then randomize them to receive either the established FDA approved treatment (amphetamine/stimulants/other) OR receive iron replacement alone (an unestablished, unconfirmed treatment). Let this go for 3 to 6 months and then check if they still have ADHD symptoms – I mean whether anyone will still confirm ADHD diagnosis. But that would be unethical by each and every institutional review board rule!! Would we ever be able to run such study? Maybe. If in 20 years we see dramatic negative consequences associated with past use of amphetamines or stimulants for ADHD treatment, then it will be fair to give the iron a chance! Until then, unlikely.

spinach broccoliIs it just me that sees something totally off about this? I would rather try iron supplementation, spinach, and broccoli before attempting stimulant treatment and I would do this despite the lack of a clinical trial to support the hypothesis. After all, I can run a lab for it, I know the safety of the drug, it only takes a few months, and I know what to expect from it on a long-term!! Certainly, do this under clinical supervision, as iron may be toxic if given too much. This is quite easy to plan, though. Check the hemoglobin, red blood cells number and size and see if iron is warranted. Remember, IDA is one of the most prevalent clinical conditions globally and it is known to impair a child’s cognitive ability. A considerable proportion of humans on Earth are iron-malnourished and the consequences are unbelievable! Stay tuned for my next coming post where I will tell you more about iron deficiency and anemia and how to prevent it or treat it.

book-1421097__480What happened with my son? The day I understood that IDA could be the cause, I made an appointment with his pediatrician. We rarely disagreed, but my theory was quite crazy this time. So, I made it there, presented full details of the situation, and compared my anemia hypothesis with the teachers’ fixation on the ADHD treatment. We discussed in detail every pro and con. To be fair, both of us knew that IDA was impossible to diagnose early. That was the main reason the condition was so prevalent! Low iron (ferritin) was only noticeable in advanced stages of IDA which was unlikely to be my son’s case. If we were to suspect IDA, we had to rely on the borderline low hemoglobin value as the sole indicator (and on mom’s gut feeling). We decided to start him on vitamin B12, folate, and iron supplementation. After three months he was perfectly fine. Today he averages over 90% GPA and loves math. We never attempted ADHD treatment.

Is ADHD a misdiagnosis? I don’t know. I surely hope that there is more than lack of iron in the ADHD. In any case, if for a patient the only cause for ADHD-like symptoms is the lack of iron, then, by all means, give iron first and re-consider whether or not there is any ADHD symptom after that. Hope this makes sense. Send me your questions, if any, and share what you learned. Save a life!

Stay healthy until next time, my friends!

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References

Kornfield R, Sydeaka W, Higashi AS et al. Effects of FDA Advisories on the Pharmacologic Treatment of ADHD, 2004–2008. Psychiatr Serv. 2013;64(4):339-346.
McCarthy S, Wilton L, Murray ML, et al. The epidemiology of pharmacologically treated attention deficit hyperactivity disorder (ADHD) in children, adolescents and adults in UK primary care. BMC Pediatr. 2012;12:78.
Duong S, Chung K, Wigal SB. Metabolic, toxicological, and safety considerations for drugs used to treat ADHD. Expert Opin Drug Metab Toxicol. 2012;8(5):543-52.
Safer DJ. Central stimulant treatment of childhood attention deficit hyperactivity disorder: issues and recommendations from a US perspective. CNS Drugs. 1997;7(4):264-72.
Manos MJ, Short EJ, Findlig RL. Differential effectiveness of methylphenidate and Adderall in school-age youths with ADHD. J Am Acad Child Adolesc Psychiatry.1999;38(7):813-9.
Spencer TJ, Biederman J, Wilens TE, Faraone SV. Novel treatments for ADHD in children. J Clin Psychiatry. 2002;63 Suppl 12:16-22.
Konofal E, Lecendreux M, Arnulf I, Mouren MC. Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med. 2004;158(12):1113-5.
Yager JI, Hartfield DS. Neurologic manifestations of iron deficiency in childhood. Pediatr Neurol. 2002;27(2):85-92.
Percinel I, Yazici KU, Ustundag B. Iron deficiency parameters in children and adolescents with attention-deficit/hyperactivity disorder. Child Psychiatry Hum Dev. 2016;47(2):259-69.
Wang Y, Huang L, Zhang L, et al. Iron status in ADHD: a systematic review and meta-analysis. PLOS One.2017;12(1):e0169145.
Demirici K, Yildirim BF, Arslan B, et al. The investigation of symptoms and diagnoses of adult ADHD in women with iron deficiency anemia. Noro Psikiyatr Ars. 2-17;54(1):72-77.

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Dr. Alice

I teach people how drugs work, when they are needed, and why. My expertise as a pharmacist and researcher allows me to determine whether taking or not taking a drug will pose any risk given all current circumstances that apply at this moment. Many times we don't know unless we try, but other many times walking the extra mile pays off giving in return more wonderful moments and more to give to others.

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