Attention Deficit/Hyperactivity Disorder (ADHD)

Attention Deficit/Hyperactivity Disorder (ADHD)

Last Section Update: 04/2022

Contributor(s): Carrie Decker, ND, MS; Stephen Tapanes, PhD

1 Overview

Summary and Quick Facts for Attention Deficit/Hyperactivity Disorder (ADHD)

  • ADHD is a neuropsychiatric disorder that can manifest as inattentiveness, impulsivity, and hyperactivity. There are three major types of ADHD: predominantly hyperactive, predominantly inattentive, and a combination of both.
  • Upon reading this protocol you will acquire a basic understanding of ADHD and its treatment. Several innovative and emerging ADHD management strategies, such as neurofeedback therapy, as well as nutrients that may benefit those with ADHD will be presented.
  • Nutrients such as omega-3 fatty acids, vitamin B6, and magnesium, as well as undergoing neurofeedback therapy, have benefited those affected by ADHD.

Nutrients

  • Multivitamin/Multi-nutrient formula: Nutritional supplements containing various micronutrients have been shown to benefit both children and adults with ADHD.
  • Omega-3 fatty acids (eg, fish oil): A UK-based study on school children found that omega-3 fatty acid insufficiency was very common and associated with ADHD-related symptoms.
  • Phosphatidylserine: Phosphatidylserine supplements in children diagnosed with ADHD contributed to significant improvement in ADHD symptoms, including inattention, impulsivity, and short-term memory.
  • Acetyl-L-carnitine: In a randomized double-blind trial, acetyl-L-carnitine had a beneficial effect on hyperactivity and social behavior in individuals with ADHD.
  • Vitamin B6 and magnesium: A study on children with ADHD found that supplementation with magnesium and vitamin B6 led to improvements in hyperactivity and school attention.
  • Zinc: Children with ADHD treated with Ritalin plus zinc supplements for six weeks received better behavioral ratings from teachers and parents than children who received Ritalin plus placebo.

ADHD Causes and Risk Factors

No single factor has been identified as a definitive cause of ADHD; instead, it is more likely due to several variables:

  • Genetics
  • Environmental factors
  • Brain injury
  • Diet/nutritional deficiencies
  • Sleep disorders, which may also be a cause of ADHD-like symptoms

Dietary and Lifestyle Considerations for ADHD

  • A growing body of research indicates dietary changes can substantially improve ADHD symptoms:
    • Avoid foods high in sugar as doing so may help limit reactive low blood sugar symptoms, which may mimic ADHD symptoms.
    • Eat a nutritious breakfast.
  • Exercise may have a positive impact on ADHD symptoms in both adults and children.
  • In one study on children and adolescents, neurofeedback was as effective as methylphenidate in treating attention and hyperactivity symptoms.

Signs and Symptoms of ADHD

ADHD is characterized by behaviors that can include persistent impulsivity, hyperactivity, and inattention.

Symptoms of impulsivity include:

  • blurting out an answer before a question is finished
  • difficulty waiting one’s turn
  • interrupting or intruding on others during conversations

Symptoms of hyperactivity include:

  • fidgeting with hands or feet
  • leaving one’s seat inappropriately, like during a meeting
  • difficulty working quietly

Symptoms of inattention include:

  • displaying poor listening skills
  • difficulty staying focused during work
  • difficulty organizing tasks and activities

Diagnosis of ADHD

There is no single diagnostic test for ADHD; instead, diagnosis is a process that rules out factors such as learning disabilities and anxiety, which may cause similar symptoms.

ADHD Treatment

  • The most widely used drugs to treat ADHD are brain stimulants, including methylphenidate (available in many forms, including Ritalin).
  • Amphetamine-based drugs including dextroamphetamine

Novel and Emerging Strategies for ADHD

  • Neuropsychiatric EEG-Based Assessment Aid monitors brain waves to aid ADHD diagnosis.

2 Introduction

The concept of treating aberrant childhood behavior as a medical disorder dates as far back as the 1700s and has always been fraught with controversy regarding what constitutes a “disorder” as opposed to typical, albeit difficult, childhood behavior.1 The diagnosis and treatment of attention deficit/hyperactivity disorder (ADHD), especially among children, continues to remain a hotly debated topic today as many aspects of the condition are subjective and different systems to classify the disorder are often used by physicians from different countries.2

Using Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria, ADHD is characterized as a neuropsychiatric disorder that can include inattentiveness, impulsivity, and hyperactivity. An individual does not need to demonstrate all these characteristics for diagnosis and may be predominantly inattentive or impulsive/hyperactive. Prevalence varies depending on reporting criteria (and whom it is reported by, such as physicians versus teachers or parents), with studies finding that between 5–15% of school-aged children may be diagnosable with ADHD.3,4 Although commonly diagnosed in childhood, adults can also be diagnosed with ADHD. Prevalence of ADHD in adults is lower than children, and large multinational studies estimate it to be less than 4.5%, with higher rates in high-income countries.5,6 Up to 60% of school-age children with ADHD may continue to experience symptoms into adulthood.7-12 In adults, the diagnosis of ADHD commonly coexists with other psychiatric diagnoses including mood disorders and substance use disorder.6

Changes introduced in the fifth edition of the DSM (DSM-5) include broadening the definition of ADHD by including more examples of diagnostic behaviors and increasing the maximum age of symptom onset from 7 to 12 years, leading to concerns that normal developmental processes (eg, pubertal restlessness and distractibility) could be misdiagnosed as ADHD. In addition, diagnostic criteria for adults with ADHD are present for the first time.13 These, along with other changes incorporated into the DSM-5, are predicted to increase the prevalence of ADHD in the years to come, mostly in adults and adolescents, but possibly also in children.14,15

The pathogenesis of ADHD likely involves both biological and environmental factors.16 Genetics are thought to play an important role as children born to parents with ADHD have an increased risk of developing the condition.17,18 There is also some evidence that brain structure and/or function is perturbed in ADHD.19-23 For instance, alterations in brain networks that govern attention and emotion have been observed in patients with ADHD.16,24-26

Mainstream medicine relies heavily upon powerful stimulant drugs from the amphetamine drug class (eg, Adderall) and methylphenidate (eg, Ritalin) to treat ADHD symptoms. This is not ideal for several reasons, including the fact that methylphenidate may induce lipid damage in certain brain regions27,28 and may cause abnormalities in the developing brain.29 Stimulant ADHD drugs may cause other side effects as well, such as growth suppression, sleep problems, loss of appetite, and increased blood pressure and heart rate.11 There are also questions about if their use may contribute to the development of substance use disorders.30,31

The good news is that several integrative interventions have been evaluated and show promise in helping maintain focus and attention. For example, supplementation with fish oil and omega-3 fatty acids and magnesium as well as undergoing neurofeedback therapy have been shown to offer considerable benefit to those affected by ADHD.32-36 Certain nutritional tools like zinc and vitamin D have also been shown to improve outcomes when used alongside pharmaceutical treatment.37,38

Upon reading this protocol you will acquire a basic understanding of ADHD. You will also learn how conventional medications work to treat ADHD and about their troublesome side effects. In addition, several novel and emerging ADHD management strategies and scientifically-studied integrative interventions will be presented.

3 Nutrients

Vitamins and Minerals

Multivitamin/multi-nutrient formulas. A comprehensive nutritional supplement containing vitamins, minerals, and amino acids, may help improve symptoms of ADHD. In a fully blinded controlled trial of 93 children (ages 7‒12) with ADHD not taking any medication, subjects were randomized to receive a nutritional supplement providing micronutrients (13 vitamins, 17 minerals, and 4 amino acids) or placebo for 10 weeks. Most of the nutrients in the formula were at doses between the recommended daily allowance (RDA) and the traditionally tolerable upper intake level (UL). There was a significant improvement on the Clinical Global Impression-Improvement (CGI-I) scale, a measure of a clinician’s view of the patient’s global function, in which 47% of those given the micronutrients were identified as improved versus 28% given placebo. Furthermore, 32% of subjects on micronutrients versus only 9% on placebo showed clinically meaningful improvements in attention. Clinician, parent, and teacher reports also identified that those on micronutrients showed greater improvements in emotional regulation, aggression, and general function compared with placebo.39 In a 1-year follow up of this trial, children who benefitted from micronutrients in the short-term maintained these improvements at follow up without side effects. Eighty-four percent of participants who remained on micronutrients were identified as having improved overall functioning relative to baseline, compared to 50% of participants who switched to psychiatric mediations and 21% who discontinued treatment, strongly supporting a role for micronutrient supplementation in improving ADHD symptoms.40

The effect of nutritional supplements containing micronutrients on ADHD has also been evaluated in adults. In a double-blind controlled trial in 80 adults randomized to a broad-spectrum multivitamin/mineral and botanical formula or placebo for eight weeks, those taking micronutrients showed improvements in ADHD symptoms compared with placebo. The micronutrient group showed greater overall improvement as measured by the Global Assessment of Functioning (GAF) scale, and 64.3% of participants in the micronutrient group showed a ≥30% drop on at least one subscale of the Conners Adult ADHD Rating Scale (CAARS), a measure to assess various symptoms of ADHD such as inattention, memory issues, and hyperactivity, compared with 36.8% in the placebo group. More participants in the micronutrient group were also rated as improved on the CGI-I scale compared with placebo.41 A 1-year follow up on 72 of these subjects found that those who stayed on micronutrients still had significant improvement over the initial baseline and performed better than those who had switched to psychiatric medications or discontinued micronutrient treatment.42

B vitamins. B vitamins are a family of water-soluble nutrients that play a vital role in metabolism and maintaining homeostasis. Levels of B vitamins, namely vitamin B6 (pyridoxine) and B9 (folate), have been found to be reduced in children and adults with ADHD; additionally, vitamin B12 (cobalamin) levels in children with ADHD were found to be significantly lower than controls.43,44 Deficiency of B vitamins may contribute to disease pathology because of their essential role in production of serotonin, catecholamines, and other monoamines.

B vitamins are also of interest for their ability to lower blood homocysteine levels, as high levels of homocysteine have been observed in a variety of diseases, including ADHD, and may contribute to oxidative stress.45-47 Further studies are required to clarify the relationship between B vitamins and homocysteine in the pathology of ADHD.

Vitamin B6 and magnesium. Vitamin B6 (pyridoxine) is involved in the production of serotonin. Early research found that B6 supplementation increased serotonin levels and improved hyperactivity in ADHD.48 In a nutritional survey comparing 100 people with ADHD to 150 healthy individuals, vitamin B6 intake levels were significantly lower in those with ADHD. Studies have also shown that magnesium deficiency is common among individuals with ADHD.49,50 In a placebo-controlled trial, supplemental magnesium at a dose of about 200 mg per day for six months showed a significant decrease of hyperactivity in 7–12 year old children with ADHD.51

An 8-week study on 40 children with ADHD found that supplementation with magnesium (6 mg/kg/day) and vitamin B6 (0.6 mg/kg/day) led to improvements in hyperactivity and school attention. Interestingly, when the treatment regimen was discontinued, the children’s symptoms reappeared in a few weeks.32 A similar regimen of vitamin B6 and magnesium supplements improved hyperexcitability symptoms in a previous study by the same researchers. In this study, the magnesium-B6 supplement combination was given to 52 hyperexcitable children for six months; symptoms such as physical aggressiveness and attention in school improved in all subjects during treatment.52

Zinc. Zinc is involved in dopaminergic signaling and has been shown to be a common nutrient deficiency in individuals with ADHD.53,54 Children with ADHD treated with Ritalin for six weeks received better behavioral ratings from teachers and parents when they also took zinc supplements (55 mg zinc sulfate per day, providing 15 mg of elemental zinc) than children who received Ritalin and a placebo.37 As a monotherapy, 150 mg zinc sulfate daily for 12 weeks was shown to significantly improve hyperactive, impulsive, and impaired socialization symptoms versus placebo in a large study of 400 children with ADHD.

Iron. Iron is an essential trace element in the body that is important for growth, development, oxygen transport by red blood cells, and dopamine signaling.55 Iron is stored in the body by the protein ferritin, which can subsequently release iron in a controlled fashion as required by the body.56 Low ferritin levels have been observed in patients with ADHD, suggesting an important role of ferritin in ADHD pathology.57,58 Many children with ADHD are iron deficient, and the severity of iron deficiency correlates with symptom severity.59 Low iron levels have also been observed in children who have ADHD plus sleep disorders (eg, restless leg syndrome).57,58

A randomized placebo-controlled study in 23 children (aged 5–8 years) with ADHD as well as iron deficiency (defined by ferritin levels less than 30 ng/mL) showed that 80 mg of ferrous sulfate supplementation daily (providing 16 mg of elemental iron) for 12 weeks resulted in a significant decrease in symptoms.60 Another trial with 14 subjects (7–11 years old) showed that 5mg/kg (about 2.3 mg per pound of bodyweight) iron per day for 30 days significantly reduced parent ratings of ADHD symptoms.61 In a trial of 52 iron-deficient children on methylphenidate randomized to receive iron supplementation (ferrous sulfate 300 mg capsule containing 80 mg of elemental iron) or placebo for 12 weeks, parents reported significant improvement in ADHD symptoms for those receiving iron but not for those receiving placebo.62

Importantly, high doses of iron (such as those used in these trials) exceeding the RDA should only be used under the guidance of a healthcare practitioner, as accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6 years of age.

Vitamin D. Vitamin D is a fat-soluble vitamin obtained through the diet and synthesized by the body in response to sun exposure. Vitamin D deficiency has been suggested as a possible contributor to several neuropsychiatric disorders and may be a risk factor for ADHD. A meta-analysis of eight studies totaling 11,324 children (2,655 with ADHD) found that vitamin D serum levels were significantly lower in patients diagnosed with ADHD compared with healthy controls.63 In a separate meta-analysis of five studies, lower vitamin D status was significantly associated with a higher risk of developing ADHD.64 Vitamin D deficiency may also contribute to mood disorders, which commonly coexist with ADHD.65

Vitamin D supplementation has been examined in various clinical trials as a therapy to ameliorate ADHD symptoms. A double-blind trial randomized 54 children (5‒12 years) to receive 2,000 IU (50 mcg) vitamin D or placebo for eight weeks as adjunctive therapy to methylphenidate. While ADHD symptoms decreased significantly in both groups, evening symptoms as observed by the Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) standardized assessment were improved at four and eight weeks with vitamin D.66 In a separate trial including 96 children with ADHD randomized to receive 50,000 IU (1,250 mcg) vitamin D weekly or placebo for six weeks (along with a stable daily dose of methylphenidate), the vitamin D group saw an improvement in ADHD symptoms with a particular effect on symptoms of inattention.67 Further, a systematic review and meta-analysis of four randomized controlled trials including 256 children found that vitamin D supplementation demonstrated a small but statistically significant improvement in ADHD total scores, inattention scores, hyperactivity scores, and behavior scores.38

Study: Multi-nutrient Formula for ADHD Management

The multifactorial origins of ADHD suggest that an intervention targeting multiple specific underlying contributing factors might be beneficial. To test this hypothesis, researchers at McLean Hospital in Massachusetts divided 20 children with ADHD into two groups. One group of 10 children received 5–15 mg of Ritalin 2–3 times daily and the other received a comprehensive multi-nutrient formula designed to target several factors that possibly play a role in ADHD development.68

The multi-nutrient formula used in this study included probiotics, amino acids (eg, tyrosine, histidine, glutamine, glycine, methionine, and cysteine), essential fatty acids and phospholipids (eg, EPA, DHA, and phosphatidylcholine), and vitamins and minerals.

Impressively, ADHD symptoms among children who took the multi-nutrient formula improved in standardized ADHD assessments at four weeks just as much as those who received Ritalin. Upon concluding their study, the researchers noted “Improvements … were … found to be significant and essentially identical in both groups…

Theanine

L-theanine, a naturally occurring compound found in tea, has been shown to help ease anxiety, reduce stress, and improve focus and attention.69,70 L-theanine is structurally similar to L-glutamate and its effects are attributed to its ability to bind glutamate receptors, inhibit glutamate and glutamine reuptake, and elevate levels of the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA).71 Sleep disorders, a common comorbidity in ADHD that also can be a factor in its etiology, have been shown to be improved with L-theanine. In boys (aged 8‒12 years) diagnosed with ADHD, 400 mg L-theanine daily was shown to improve sleep.72

Conversely, studies suggest L-theanine alone and in combination with caffeine, another compound naturally found in tea, can also improve attention and focus in patients with ADHD.73 A study including five male children (ages 8‒17) administered L-theanine (2.5 mg/kg), caffeine (2 mg/kg), L-theanine plus caffeine, or placebo found L-theanine and the combination improved cognitive function and decreased mind-wandering activity during functional magnetic resonance imaging (fMRI).74 These results were corroborated in a separate small trial involving five boys (age 8‒15 years) with ADHD; administration of a drink containing L-theanine and caffeine (2.5 mg/kg and 2 mg/kg, respectively) improved cognitive function, inhibitory control, and reduced mind-wandering (“daydreaming”) compared with placebo, whereas L-theanine alone only improved cognition.75

Omega-3 & Omega-6 Fatty Acids

Children with ADHD may have lower levels of omega-3 fatty acids in their blood.76 While the typical Western diet often contains excessive levels of certain omega-6 fatty acids, it is lacking in omega-3 fatty acids, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).77,78 Considering that dopamine-producing nerve endings are composed of up to 80% of the omega-3 fatty acid DHA,79 these molecules have an important role in the central nervous system and its functions. In children, the severity of ADHD symptoms is linked to lower levels of omega-3 and higher levels of omega-6 fatty acids. Hyperactivity and inattention in general are also linked to omega-3 fatty acid deficiency, thus indicating this may be a risk factor for ADHD.33 A UK-based study in 493 school children aged 7–9 years found omega-3 fatty acid insufficiency was very common and associated with ADHD-related symptoms (eg, oppositional behavior and emotional instability). Research from another group found that low blood levels of omega-3 fatty acids correlated with callous-unemotional behavior, antisocial traits, and impaired emotional processing.26,80

Swedish scientists studied the effects of fish oil supplements containing polyunsaturated omega-3 fatty acids (558 mg EPA, 174 mg DHA daily) and the beneficial omega-6 fatty acid gamma linolenic acid (GLA) (60 mg daily) in 75 children and adolescents with ADHD over a six-month period. They found that after six months, nearly half of subjects responded to the omega-3 and omega-6 supplements with a reduction in ADHD symptoms.81 In a subsequent analysis of these study data, the same researchers found that subjects with at least a 25% reduction in symptoms exhibited a significantly greater decrease in the ratio of omega-6’s to omega-3’s in their blood at three and six months.82 A comprehensive review conducted by researchers at Yale University examined evidence from 10 trials involving 699 children with ADHD. It was found that supplementation with omega-3 fatty acids modestly improved ADHD symptoms among study participants. In their concluding remarks, the researchers noted “…it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacological interventions…83 An analysis of several published studies also found that supplementation with free fatty acids and exclusion of artificial food coloring from the diet had statistically significant effects on reducing ADHD symptoms.84

Flax oil, which provides high levels of the omega-3 fatty acid alpha-linolenic acid (ALA), a precursor to EPA and DHA, also may be of benefit. A study examining the benefit of supplementation with an emulsion of flax oil (providing 200 mg ALA) and vitamin C (25 mg) given twice daily to children with ADHD found a significant improvement in symptoms of ADHD, including impulsivity, restlessness, inattention and self-control, as reflected by a reduction in total hyperactivity scores.85

Fish oil is a good source of polyunsaturated omega-3 fatty acids. The balance of fatty acid levels can be measured with blood tests, and people taking fatty acid supplements can have repeat blood tests to measure their effect.

Phosphatidylserine

Phosphatidylserine (PS) is a major component of cell membranes and is considered one of the most important brain nutrients. PS has a variety of functions within the brain including supporting cell membrane fluidity and beneficially influencing neurotransmitter systems (eg, acetylcholine, dopamine, and serotonin). Researchers, patients, and their caregivers have long been interested in the potential of PS supplements for ADHD. A 2021 meta-analysis found that at a dose of 200–300 mg daily, PS had a significant effect on symptoms of inattention compared with placebo.86

In a 2013 randomized controlled trial, 36 children diagnosed with ADHD were given either 200 mg PS daily or placebo for two months. PS supplementation resulted in significant improvement in ADHD symptoms including inattention, impulsivity, and short-term memory. No adverse effects were reported and the supplement was well tolerated.87 Another randomized controlled trial of 15 weeks duration studied the effects of PS combined with omega-3 fatty acids. In this study, 200 children with ADHD were given either 300 mg PS plus 120 mg EPA and DHA or placebo. The treatment resulted in significant improvement in ADHD symptoms. A subgroup analysis revealed this treatment may be especially effective in children with ADHD with more pronounced hyperactive and impulsive behavior. In a 15-week open label continuation, the treatment showed continued efficacy as well as improvement in children who switched over from placebo.88

Acetyl-L-carnitine

Acetyl-L-carnitine (ALC), a natural derivative of L-carnitine, serves a key role in the metabolism of fatty acids and cellular energy production and is a precursor to acetylcholine which plays a role in memory.89 Evidence from both animal and human studies suggests it may help alleviate ADHD symptoms. In an animal model of ADHD, long-term administration of ALC to rats consistently decreased impulsivity. This study also found that impulsive animals had altered levels of certain neurotransmitter metabolites, and ALC helped improve this imbalance.90 In a placebo-controlled trial in 112 subjects, 500–1,500 mg ALC twice daily (based on weight) improved symptoms in children with the inattentive ADHD subtype.91 In a separate randomized double-blind trial, ALC had a beneficial effect on hyperactivity and social behavior in 51 young boys with fragile X syndrome and ADHD.89 However, a 2011 study of boys and girls with ADHD found that 500–1,500 mg ALC daily did not have an effect when combined with methylphenidate.92

Ginkgo biloba and Ginseng

Ginkgo biloba contains compounds called terpene trilactones (eg, ginkgolides and bilobalide) that have various effects on the central nervous system.93 Ginkgo (80–120 mg daily in 25 children with ADHD for six weeks) was shown in a clinical trial to improve subjective teacher and parent ratings; however, it did not outperform methylphenidate (20–30 mg daily). Side effects of decreased appetite, headache, and insomnia were seen more frequently in the methylphenidate group.94 In an 8-week trial, 18 children (6–14 years old) received a 1,000 mg dose of Korean red ginseng twice daily; at the end of the trial a significant reduction in inattentiveness, ADHD rating scale scores, and level of anxiety was observed.95 In a pilot study, the daily combination of 200 mg American ginseng extract and 50 mg ginkgo biloba also improved a range of symptoms from social problems to impulsivity in children being treated for ADHD.96

Pine Bark Extract (Pycnogenol)

Pycnogenol, an extract from the bark of French maritime pine (Pinus pinaster), has antioxidant and vasodilatory properties and has been shown to benefit cognitive function in multiple human studies.97 A double-blind randomized trial in 61 children receiving 1 mg/kg Pycnogenol or placebo daily for four weeks showed a significant decrease in hyperactivity, improvement in attention, and increase in visual and motor coordination in the Pycnogenol group.98 Another double-blind, randomized, placebo-controlled trial showed Pycnogenol decreased hyperactivity and oxidative stress in children with ADHD.99

4 Dietary and Lifestyle Considerations for ADHD

Dietary Considerations

A growing body of research indicates that dietary changes can substantially improve ADHD symptoms, either alone or as a complement to medical therapies.100

Food colorings and food sensitivities. Artificial food coloring has not been established as a cause of ADHD. Nevertheless, inconsistent evidence suggests some children may experience neurobehavioral changes in response to some food colorings.

A 2007 trial from Southampton University assessed the effects of several food colorings (ie, tartrazine [E103], quinoline yellow [E104], sunset yellow [E110], carmoisine [E122], ponceau 4R [E124], and allura red [E129]) on 3-year-old (153 total) and 8–9-year-old (144 total) children.101 The researchers found these artificial colorings resulted in increased hyperactivity in these populations when added to their diet. A small pilot study found artificial food colorings did affect brainwave patterns in individuals with ADHD when exposed after a period of avoidance; changes were not seen in college students who did not have ADHD.102 A marginal, non-significant increase in ADHD symptoms was also observed after artificial food coloring exposure. Genetics associated with histamine breakdown may play a role in the adverse effects seen with food coloring and additive exposure and could explain some of the inconsistencies seen in this research.103

An analysis of several published studies using various dietary interventions found that exclusion of artificial food coloring from the diet led to statistically significant reductions in some ADHD symptoms, particularly in children with food sensitivities.84 However, a major challenge with interpreting studies in which artificial colorings are eliminated from kids’ diets is that removal of colorings may also reduce the amount of processed foods the kids consume overall. It may be the case that changes in children’s behavior observed in some of these elimination diet studies were the result of generally improved diet quality.104 The literature on human studies over the past decade does not offer a strong explanation of the impact of the dietary presence or elimination of artificial food coloring on ADHD symptoms and development.105 Moreover, the clinical guidelines and practice parameters from the American Academy of Pediatrics and the United Kingdom's National Institute for Health and Care Excellence do not routinely recommend elimination of artificial food coloring from diets for the treatment of ADHD.106-108

Some children who exhibit sensitivity to food colorings may also be sensitive to some foods such as milk, eggs, wheat, and soy.109 Caregivers of children who tend to exhibit behavioral changes in response to certain foods should explore food sensitivity testing for the children. In fact, a clinical study including 16 children with ADHD found that reintroduction of food sensitivities after four weeks of elimination led to an increase in reported ADHD symptoms, suggesting that eliminating certain foods may help reduce ADHD symptoms.110

Sugar. Although the majority of research does not support a causative role of sugar intake in ADHD development, many parents anecdotally report that foods high in sugar can make their child’s ADHD hyperactivity symptoms more pronounced. However, children are more vulnerable to the effects of reactive hypoglycemia (ie, low blood sugar following the rise in blood sugar from a high carbohydrate meal) on cognitive function. Avoiding foods high in sugar may help limit reactive hypoglycemia symptoms, which may mimic some aspects of ADHD symptoms, in sensitive children.100

Overall diet quality. Studies indicate children who eat a balanced breakfast containing protein, vitamins, and minerals, such as found in whole grains, have less deterioration in attention levels during morning hours at school.33 An emphasis should be placed on general healthy eating patterns such as the Mediterranean diet. In fact, a clinical trial totaling 120 children and adolescents showed that lower adherence to a Mediterranean diet was associated with ADHD diagnosis. There was also an association with ADHD diagnosis and lower frequency of consuming vegetables, fruit, pasta, and rice; higher frequency of skipping breakfast; and higher frequency of eating at fast-food restaurants.111

Lifestyle Considerations

Physical activity. Exercise may have a positive impact on ADHD symptoms in both adults and children.112 Thirty adults with ADHD were enrolled in a study comparing frequent aerobic exercise with infrequent activity. The exercise group showed a significant decrease in impulsive symptoms and anxiety.113 Another study showed that cognitive symptoms in children with ADHD were improved after just 20 minutes of moderate exercise.114 A meta-analysis conducted on research through March 2020 found that exercise significantly improved overall executive function of children and adolescents with ADHD, and had a moderate-to-large effect on inhibitory control and cognitive flexibility.115

Yoga may also help reduce ADHD symptoms.116 A small-scale study in nine children demonstrated a significant improvement in ADHD symptoms as a result of learning and practicing yoga.36

5 ADHD Causes and Risk Factors

No single factor has been identified as a definitive cause of ADHD. Instead, most scientists believe that several variables influence ADHD risk and severity. For example, genetics, exposure to stressors during pregnancy or infancy, early social interactions, nutritional deficiencies, and environmental toxins all appear to affect ADHD risk.17

Genetics

A considerable portion of ADHD cases are thought to be attributable to genetics and heritability.117 A number of specific genetic variations are associated with ADHD. These are predominantly related to the regulation of dopamine (ie, a chemical messenger used by brain cells).17,18,118 The importance of dopamine in ADHD is highlighted by the fact that methylphenidate is thought to treat ADHD symptoms in part by increasing dopamine signaling in the brain.119

Environmental Factors

Environmental toxins such as polychlorinated biphenyls, some pesticides, and lead have been linked to ADHD development, but no studies have proven that they directly cause the disorder.17 Other external factors, such as negative child-parent interactions and poor or lacking early social contact, have been found to contribute to ADHD onset.17,120 Some variables in utero (in the womb), including maternal smoking during pregnancy, premature birth and/or low birth weight, and/or maternal stress, are seen as risk factors but not causative links to ADHD.17

Brain Changes

Technological advances in neuroimaging techniques have allowed scientists to observe the brains of children diagnosed with ADHD and compare them to those of adolescents without the condition. Several studies have identified subtle differences in brain structure or function among children with ADHD. For example, fMRI showed that the brain networks in children with ADHD activate in different patterns compared with healthy children’s brains.121 Other studies suggest brains of children with ADHD display variations in volume or density of various brain regions compared with non-ADHD kids.122-124

Traumatic brain injury (TBI) has been linked to behaviors similar to those observed in ADHD.125 Approximately 20–50% of children who suffer a TBI develop a form of clinically relevant attention disorder termed secondary ADHD.122-124 It is uncertain if mild TBI, which is commonly experienced by children, increases the risk of ADHD-type behaviors developing.126

Evidence suggests several aspects of the variation in brain function observed in ADHD are attenuated by psychostimulant drugs such as methylphenidate. This has led some researchers to speculate that reversion of brain network structure and activity to normal may underlie the therapeutic benefits of psychostimulant drugs.22,127

Diet

There is some evidence that deficiencies in certain nutrients, such as zinc, magnesium, iodine, vitamin D, and polyunsaturated fatty acids, may be linked to ADHD.17 As discussed earlier in this protocol, studies have found evidence for insufficiency or imbalance of omega-3 and omega-6 fatty acids in people with ADHD.76 Zinc and magnesium intake have been found to be reduced in those with ADHD, while iron and vitamin D deficiency also may increase risk of ADHD.128,59,64 Iodine is particularly important for thyroid function and the developing brain, and has been shown to often be deficient in children with ADHD.129 Additionally, limited evidence suggests high intake of certain food additives, such as artificial colorings, may contribute to hyperactivity in those with ADHD.130

Excessive sugar intake has often been linked to ADHD as well, although the majority of research has largely debunked this as unsubstantiated; definitive evidence for a causal relationship is currently lacking.131 Higher intake of sugar, candy, and soft drinks has been shown to be associated with a higher prevalence of ADHD in children and adolescents with a new ADHD diagnosis.111

Sleep Disorders and ADHD

Several lines of evidence suggest a relationship between ADHD and sleep disorders such as sleep apnea. It has been reported that up to 95% of obstructive sleep apnea sufferers experience attentional deficits, and obstructive sleep apnea has been observed in up to 30% of individuals with ADHD. Moreover, successfully treating obstructive sleep apnea appears to relieve ADHD symptoms in some individuals.132 Overall, sleep disorders have been observed in up to 30% of children and 80% of adults with ADHD.133 Various brain parameters related to sleep have been shown to be altered in children and adolescents with ADHD.134

It is important for physicians to realize that symptoms of sleep disorders (eg, sleep apnea or restless leg syndrome) can resemble those of ADHD in both children and adults. Otherwise, a person may be misdiagnosed with ADHD when their symptoms are actually the consequence of a sleep disorder.135,136

Despite intensive study and an active body of research, it is not entirely clear whether sleep disorders directly cause ADHD or vise-versa, or if the conditions have a high rate of concurrence yet remain distinct entities.133,137

Sleep and ADHD must also be contemporaneously considered since stimulant medications like methylphenidate, which are used to treat ADHD, may contribute to impaired sleep patterns. In a study on 93 children with ADHD, methylphenidate treatment was shown to considerably delay bedtimes and lead to reduced total sleep duration.138 On the other hand, some studies have found that methylphenidate treatment does not disrupt sleep habits and may lead to better sleep quality in certain populations.139,140 Since the impact of methylphenidate on sleep patterns appears not to be uniform in all individuals, a reasonable approach is to carefully monitor sleep habits following treatment initiation. If signs of diminished sleep duration or quality emerge, consult a healthcare provider about dose-adjustment or pursuing a different treatment option.

6 Signs and Symptoms of ADHD

ADHD is defined primarily by persistent symptoms of impulsivity, hyperactivity, and/or inattention that can severely affect a person’s quality of life. Some people present mostly with symptoms related to inattention, others present mostly symptoms related to hyperactivity and impulsivity, while others have all three types of symptoms in combination.141,142

Symptoms of inattention include141,142:

  • failing to provide close attention to detail and making careless mistakes
  • difficulty staying focused during work or play
  • difficulty paying attention/listening when spoken to
  • difficulty organizing tasks and activities
  • difficulty following tasks through to completion
  • aversion to tasks that require continued mental engagement
  • often losing toys, books, or tools used for activities
  • being easily distracted
  • forgetfulness during daily activities and tasks

Symptoms of hyperactivity include141,142:

  • excessive fidgeting
  • leaving one’s seat when it is expected to remain seated
  • running/climbing in inappropriate situations and feelings of restlessness
  • difficulty working/playing quietly
  • often being "on the go"
  • talking excessively

Symptoms of impulsivity include141,142:

  • blurting out an answer before a question is finished
  • difficulty awaiting one’s turn
  • interrupting or intruding on others during conversations/play

Many children with ADHD struggle academically and in social situations. Also, symptoms are frequently accompanied by other problems, including depression, anxiety, sleep disturbances, and substance abuse.143-146

7 Diagnosis of ADHD

There is no single diagnostic test for ADHD; instead, diagnosis is a stepwise process that also has to take into consideration several other conditions, such as anxiety, learning disabilities, and sleep disorders, which may cause similar symptoms.147

The first national survey that asked parents about ADHD was completed in 1997. Since then, there has been an increase in the number of parentally reported ADHD diagnoses as well as in prescribing rates. However, it is difficult to tell whether this represents an increase in the number of children diagnosed or an increased number of children who developed this condition.13,148

It is thought that some important contributors to the increasing rate of diagnosis are the lack of consistent criteria to objectively assess the severity of symptoms and the shift observed over the years in ADHD diagnostic criteria.13,148

Diagnostic criteria describe three types of ADHD: predominantly inattentive, predominantly hyperactive/impulsive, or a combination of both. Symptoms must be present for at least six months, occur frequently, and impair aspects of function in academic, social, or occupational activities.149 The DSM-5 criteria for ADHD diagnosis can be seen in Table 1.

Type of ADHD
Age Predominantly inattentive Predominantly hyperactive/impulsive Combined Presentation
≤ 17 years old ≥ 6 symptoms of inattention ≥ 6 symptoms of hyperactivity and impulsivity ≥ 6 symptoms from both dimensions
≥ 18 years old ≥ 5 symptoms of inattention ≥ 5 symptoms of hyperactivity and impulsivity ≥ 5 symptoms from both dimensions

Table 1. DSM-5 criteria for ADHD diagnosis149

To assist in the diagnosis of ADHD, the Food and Drug Administration (FDA) approved the use in July 2013 of Neuropsychiatric EEG-Based Assessment Aid (NEBA), a new brain-wave-monitoring system, to assist physicians in diagnosing ADHD in children and adolescents aged 6–17 years. The non-invasive test takes about 15–20 minutes and involves placement of sensors on the scalp of the individual to monitor their brainwaves. Individuals with ADHD typically have a significantly higher theta/beta brainwave ratio, and the NEBA system can identify this phenomenon.150,151

8 ADHD Treatment

The treatment of ADHD often involves drug therapy, cognitive behavioral therapy, or both.152,153 The best choice of initial therapy will depend on each person’s unique personal history and clinical situation. Several drugs may be tried sequentially until the one that provides the best results for a given patient is selected. Among adults, the average duration of medication treatment is about 230 days. Children tend to take medications for a shorter period, about 136 days.153 Additionally, a clinical trial including 88 adults with ADHD suggests drug therapy may enhance the effect of cognitive behavioral therapy to produce a synergistic effect.154

Stimulants

The most widely used drugs to treat ADHD are brain stimulants.155 Stimulants are divided into methylphenidates and amphetamines. These drugs enhance signaling through certain neurotransmitter pathways (eg, norepinephrine and dopamine).156 Stimulant drugs are effective in approximately 70% of patients with ADHD.157

Side effects, including trouble sleeping, worsening of anxiety (which can exacerbate inattention), possible cardiovascular events in adults, and risk of misuse, are often a problem with stimulants.158 Trial and error can help people with ADHD and their doctors determine which medication most effectively balances benefits and side effects for each person.

Amphetamines. Amphetamine drugs, including dextroamphetamine (Dexedrine) and Adderall (a combination of amphetamine and dextroamphetamine), are commonly used in the treatment of ADHD.155 In fact, a systematic review and meta-analysis of 133 clinical trials conducted in 2018 suggests amphetamines as the preferred first pharmacological choice for short-term treatment of adult ADHD.159

Another FDA-approved stimulant, lisdexamfetamine dimesylate (Vyvanse), is a "prodrug" (ie, an inactive precursor converted to the active form of the drug after ingestion). This property increases the duration of action, which is up to 14 hours in adults per observations in some clinical trials.160,161

Side Effects of Stimulant ADHD Medications

The side effects of stimulant-based drugs include headache, insomnia, decreased appetite, rapid heart rate, abdominal pain, anxiety, and growth suppression (with long-term use).162,163 Stimulants should not be used by people with high blood pressure, heart or vascular disease, hyperthyroidism, glaucoma, psychosis, or those taking monoamine oxidase inhibitors (MAOIs).

Because of their potential for abuse and effects on addiction-related pathways in the brain (through dopamine), stimulants are also not suitable for people with substance abuse disorders.

Stimulants, particularly amphetamines, can also induce mania or psychosis in some people who have not previously shown signs of bipolar disorder or schizophrenia.157,164 A clinical study in the New England Journal of Medicine involving over 330,000 individuals with ADHD found that amphetamine use was associated with a greater risk of psychosis than methylphenidate, where approximately 0.21% of amphetamine users experienced an episode of psychosis compared with 0.10% of methylphenidate users.165

Methylphenidate. Methylphenidate is the most common stimulant medication used to treat ADHD. Many different forms of methylphenidate are available, including Ritalin, Methylin, Metadate, Concerta, and Daytrana, which vary in dosage, delivery system (capsule, tablet, or patch), and rate of drug delivery. A systematic review and meta-analysis of 64 trials conducted in 2020 found that there were few differences in efficacy among individual methylphenidate medications.164,166-168

Methylphenidate Drugs Induce Oxidative Stress

Aside from known side effects such as heart problems and growth suppression, methylphenidate also causes oxidative stress (ie, the metabolic process by which reactive molecules damage cells and tissues). Oxidative stress is implicated as a contributing factor in several diseases and the aging process.169,170

Animal studies have shown that methylphenidate treatment leads to an increase in the production of tissue-damaging reactive oxygen species in certain brain regions.28 One animal experiment showed that brains of young animals were especially prone to the increased oxidative stress caused by methylphenidate, suggesting children may be more susceptible to this phenomenon than adults.171

Ironically, although methylphenidate is used as a treatment for ADHD, some evidence suggests oxidative stress contributes to the development and progression of several psychiatric disorders, including ADHD.172-174

This is concerning, especially considering that evidence shows methylphenidate exposure during development likely has lasting neurological consequences that may affect brain health in later life. The long-term developmental effects of methylphenidate-based drug use in children requires more study.29,175

Non-stimulant Medications

Non-stimulant medications are an effective alternative to stimulant-based medications for some people with ADHD. There are only a few non-stimulant ADHD drugs approved by the FDA.

Atomoxetine. Atomoxetine (Strattera), which inhibits reuptake of the neurotransmitter norepinephrine, is the most commonly used non-stimulant medication for ADHD. Others include extended-release clonidine (Kapvay) and guanfacine (Tenex, Intuniv), which agonize postsynaptic alpha-2 adrenergic receptors in the brain to modulate neuronal activity and improve attention.176-180

Use of atomoxetine avoids some of the complications associated with stimulants, notably tics and sleep disturbances, but there is an increased risk of suicidal thinking in children and adolescents given the drug, so people in these age groups should be carefully monitored for the first few months after beginning treatment or changing dosage.181,182

Viloxazine. The FDA approved extended-release viloxazine (Qelbree), a nonstimulant medication for the treatment of ADHD, in April 2021. Viloxazine was found to inhibit the reuptake of norepinephrine like atomoxetine. Additionally, viloxazine was found to modulate serotonin receptors and increase extracellular serotonin levels in the prefrontal cortex, an area of the brain implicated in ADHD.183 Viloxazine was shown in phase II and III clinical trials to significantly reduce ADHD symptoms.184,185 It is a selective norepinephrine reuptake inhibitor (SNRI) and is not a controlled substance. Viloxazine has previously been used in the treatment of depression and is well tolerated by patients.186

Antidepressants. Although not FDA approved for the treatment of ADHD, antidepressants, including venlafaxine (Effexor) and the tricyclic antidepressant bupropion (Wellbutrin), have also shown some promise in treating ADHD.164,187 In one double-blind randomized trial, bupropion was found to be comparable in effect to methylphenidate.188 This was further corroborated in a systematic review of six clinical trials conducted in 2017.189

Modafinil. Modafinil (Provigil), a wakefulness- and cognition-promoting drug used for the treatment of conditions such as narcolepsy, has also been used to treat ADHD and has shown promise in clinical trials on both children and adults with ADHD.164,190 It is not FDA approved for ADHD treatment as of March 2022.191

Psychotherapy

Psychotherapy, also known as talk therapy (individually or in a group), has been shown to be an effective treatment for ADHD when used as an adjunct to traditional medication.158 Group-based therapy has the added benefits of providing social support and being more cost-effective.

Cognitive behavioral therapy. Cognitive behavioral therapy (CBT) is based on the idea that thoughts and behaviors influence feelings, and by extension that changing the way one thinks can help improve ADHD symptoms. CBT sessions last approximately 30–60 minutes and may occur for up to 20 weeks. CBT begins with patients identifying and monitoring their negative thoughts, emotions, and triggers and finding positive replacement thoughts with the assistance of a therapist. The therapist creates a plan to have the patient practice incorporating these replacement thoughts in daily life to reinforce positive thinking. Patient cooperation and compliance are paramount to achieving success with CBT.192

A 2020 meta-analysis of 18 studies found that CBT was effective at reducing inattentive symptoms and enhancing cognitive function in college students with ADHD. Furthermore, evidence suggests that, in individuals taking medication for adult ADHD, CBT improves outcomes for at least 12 months.154

9 Novel and Emerging Strategies for ADHD

Neurofeedback

Neurofeedback, a technique introduced in the 1960s, helps people regulate their own mental states by viewing an EEG (electroencephalogram) recording of their brain activity in real time. Neurofeedback utilizes sensors placed on the scalp that detect brainwaves and then graphs them on a computer screen that the test subject can visualize. This allows the subject to recognize ways of thinking that favorably alter their neurological function and can help them gain better control over their brain activity.193,194 Neurofeedback has few adverse effects but usually requires 20–40 sessions and may be expensive for the patient.

Neurofeedback aims to change the threshold that triggers brain activity in the cortex, which appears to be impaired in ADHD. Many clinical studies have been conducted on school-age children and adolescents, but more studies are needed to determine the efficacy in adults. Nevertheless, the majority of clinical studies conducted to date have reported promising, long-lasting results. In fact, a 2019 meta-analysis of 19 studies found that neurofeedback appears to have treatment effects that last for at least six months following treatment.193,195

Multiple clinical trials have found neurofeedback to be as effective as methylphenidate in reducing inattention and hyperactivity symptoms in children and adolescents.195-197 In a meta-analysis examining seven meta-analyses and 17 studies, neurofeedback was found to significantly improve symptoms of inattention.198 Several other studies examining the efficacy of neurofeedback for ADHD management concluded that it confers robust benefits for impulsivity and modest benefits for hyperactivity.34,194,197

Repurposed Pharmaceuticals

Certain drugs are being examined for their ability to be repurposed for ADHD. Vortioxetine (Trintellix, Brintellix) is an antidepressant that inhibits the reuptake of serotonin and is being tested as a treatment for adult ADHD. A clinical study including 227 participants taking vortioxetine (10 or 20 mg/day) found no difference in improvement of symptoms compared with placebo. However, there was an overall functional improvement among those taking vortioxetine.199

Solriamfetol (Sunosi) is a medication used for the treatment of narcolepsy and sleep apnea. As of early 2022, it was being examined in a clinical trial for its ability to improve symptoms in adults with ADHD.200

Digital Health Interventions

In June of 2020, the FDA approved EndeavorRx, the first game-based digital therapeutic device, to improve symptoms of ADHD in children aged 8–12 years old. EndeavorRx is indicated to improve attention as measured by computer-based testing and is the first digital therapeutic intended to improve symptoms associated with ADHD.201 The STARS-ADHD clinical trial, which examined the efficacy of EndeavorRx on reducing ADHD symptoms, enrolled 857 patients aged 8–12 with ADHD and found that digital intervention significantly improved attention compared with a placebo intervention.202 In a separate clinical trial, EndeavorRx improved symptoms of ADHD in children when used both with and without stimulant medication.203 The device is affordable, covered by health insurance, and displays very few adverse effects. However, it is intended for use as part of a holistic therapeutic program and not as a stand-alone or replacement for medication. Other digital health interventions, such as smartphone apps and wearable technologies, are being investigated for their ability to improve ADHD symptoms.204

2022

  • Apr: Comprehensive update & review

2014

  • Jan: Comprehensive update & review

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

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