Does zinc moderate essential fatty acid and amphetamine treatment of attention-deficit/hyperactivity disorder?
Zinc is an important co-factor for metabolism relevant to neurotransmitters, fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine metabolism, believed intimately involved in attention-deficit/hyperactivity disorder (ADHD). To explore the relationship of zinc nutrition to essential fatty acid supplement and stimulant effects in treatment of ADHD, we re-analyzed data from an 18-subject double-blind, placebo-controlled crossover treatment comparison of d-amphetamine and Efamol (evening primrose oil, rich in gamma-linolenic acid). Subjects were categorized as zinc-adequate (n = 5), borderline zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell, and urine zinc levels; for each category, placebo-active difference means were calculated on teachers' ratings. Placebo-controlled d-amphetamine response appeared linear with zinc nutrition, but the relationship of Efamol response to zinc appeared U-shaped; Efamol benefit was evident only with borderline zinc. Placebo-controlled effect size (Cohen's d) for both treatments ranged up to 1.5 for borderline zinc and dropped to 0.3-0.7 with mild zinc deficiency. If upheld by prospective research, this post-hoc exploration suggests that zinc nutrition may be important for treatment of ADHD even by pharmacotherapy, and if Efamol benefits ADHD, it likely does so by improving or compensating for borderline zinc nutrition.
Department of Psychiatry, Ohio State University, Columbus, USA. Arnold.6@osu.edu
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Arnold
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Pinkham
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Votolato
D000975:Antioxidants / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005228:Fatty Acids, Essential / Q000627:therapeutic use*; D006801:Humans; D008041:Linoleic Acids; D008297:Male; D009752:Nutritional Status; D031665:Oenothera biennis; D010938:Plant Oils; D015032:Zinc / Q000172:deficiency / Q000502:physiology*; D017965:gamma-Linolenic Acid
D000975:Antioxidants; D000697:Central Nervous System Stimulants; D005228:Fatty Acids, Essential; D008041:Linoleic Acids; D010938:Plant Oils; C028498:evening primrose oil; D017965:gamma-Linolenic Acid; D015032:Zinc; D003913:Dextroamphetamine