Attention Deficit Hyperactivity Disorder

Orthomolecular Interventions

Orthomolecular interventions are substances that have roles in promoting or addressing attention deficit hyperactivity disorder, depending on individual biological requirements and the amount present in the body.

Vitamin B6 (pyridoxine)

Vitamin B6 and mental health

Vitamin B6 is required for:

  • conversion of the amino acid tryptophan into serotonin – Low levels of serotonin are associated with ADHD
  • the synthesis of monoamine neurotransmitters, such as serotonin, dopamine, and γ-aminobutyrate. PLP, the active form of vitamin B6, is a cofactor in this synthesis process (Food and Nutrition Board, Institute of Medicine, 1998; Skarupski et al., 2010)

Vitamin B6 and ADHD

Deficiency of vitamin B6 can be identified by:

  • the absence of dreams, or the inability to remember dreams
  • having disturbing dreams or nightmares

Causes of vitamin B6 deficiencies

  • inadequate dietary intake
  • medications, including anti-tuberculosis drugs, anti-parkinsonians, nonsteroidal anti-inflammatory drugs, and oral contraceptives, may interfere with vitamin B6 metabolism. (Vitamin B6, 2014)
  • alcoholism – due to low intake and impaired metabolism of vitamin B6

Top sources of vitamin B6 based on serving size

  • salmon
  • potato
  • turkey
  • avocado

Comprehensive food list:

Table 2. Some Food Sources of vitamin B6 (Vitamin B6, 2014)

Referenced Dietary Intakes

RDAs for vitamin B6 (mg/day)

Adolescents (14-18 years): 1.3 (M) 1.2 (F)

Adults (19-50 years): 1.3 (M) 1.3 (F)

Adults (51 years and older): 1.7 (M) 1.5 (F)

Tolerable Upper Intake: 100 mg/day

(Office of dietary supplements, 2020)

Vitamin B6 Supplementation

  • Amounts of vitamin B6 used in practice and research range from 20–6000 mg/day in divided doses (Office of Dietary Supplements, 2020).
  • “In women with laboratory evidence of vitamin B6 deficiency, apparently as a result of taking oral contraceptives, supplementation with 40 mg/day of vitamin B6 relieved anxiety and depression” (Bermond, 1982).


  • Doses above 100 mg/day may, in some people, cause side effects that include nausea, vomiting, stomach pain, diarrhea, headache, tingling, and sleepiness. The risk of negative effects can be reduced by supplementing magnesium 6.6–8.8 mg /kg in addition to a B-complex vitamin (Prousky, 2015).


  • High doses of vitamin B6 have been found to decrease the efficacy of phenobarbital, phenytoin, and L-Dopa (Vitamin B6, 2014).

Vitamin C

Vitamin C

Vitamin C is required for the synthesis of many compounds important for good mental health. Some of these are:

  • tyrosine
  • thyroxine
  • norepinephrine
  • epinephrine
  • serotonin
  • carnitine
  • corticosteroids.

Vitamin C has been show in research to (Meister, 1994):

  • reduce psychological stress
  • decrease blood pressure
  • lower cortisol levels

Functions of vitamin C in the brain (Smythies, 1996):

  • Prevents oxidation of dopamine into toxic derivatives (Baez, Segura-Aguilar, Widerslen, Johansson, & Mannervik, 1997)
  • Protects NMDA receptors from glutamate toxicity
  • Counteracts the effects of amphetamines
  • Enhances the effects of older antipsychotic medications like haloperidol

Vitamin C and mental health

  • 3 g/day of vitamin C supplementation in healthy volunteers significantly decreased monoamine oxidase activity (MOA). MOA is responsible for metabolizing serotonin, norepinephrine, and dopamine. (Gaby)

Vitamin C and ADHD

Vitamin C (Greenblatt, 2018):

  • Combats oxidative stress
  • Acts as an antihistamine
  • Regulates dopamine and norepinephrine release
  • Promotes nerve cell integrity

Even a small negative change in vitamin C in the brain can cause a significant increase in oxidative damage, showing that vitamin C is extremely important. Vitamin C acts as the primary molecule for protecting the central nervous system from oxidative stress damage (Moghadas et al, 2019).

Causes of vitamin C deficiency

  • restrictive diets
  • diet lacking in sources of vitamin C especially fresh fruit and vegetables
  • digestive tract disorders, e.g. diarrhea, Crohn’s and colitis
  • smoking
  • alcoholism
  • chronic inflammatory conditions

Signs of vitamin C deficiency

  • bleeding or swollen gums
  • frequent nosebleeds
  • dry hair, split ends
  • easy bruising
  • slow wound healing
  • fatigue
  • moodiness
  • depression and cognitive impairment (Plevin & Galletly, 2020)

Top sources of vitamin C based on serving size

  • grapefruit and orange juice
  • strawberries
  • kiwifruit
  • orange
  • sweet pepper
  • broccoli

Comprehensive food list:

Table 3. Some Food Sources of vitamin C (Vitamin C, 2014)

Referenced Dietary Intakes

RDAs for vitamin C (mg/day)

Adolescents (14-18 years): 75 (M) 65 (F)

Adults (19-50 years): 90 (M) 75 (F)

Smokers: 125 (M) 110 (F)

Tolerable Upper Intake: 2000 mg /day

(Office of Dietary Supplements – Vitamin C, n.d.)

Vitamin C supplementation

  • Amounts of vitamin C used in practice and research range from 500–6000 mg/day in divided doses.


  • Vitamin C has low toxicity and is not believed to cause serious adverse effects at high intakes (Office of Dietary Supplements – Vitamin C, n.d.).
  • Vitamin C at higher doses can, in some people, cause side effects such as nausea, abdominal cramps, and other digestive tract disturbances

Vitamin C and medications

  • Vitamin C has been shown beneficial and safe when used in conjunction with depression medications.

Vitamin D

Vitamin D

Vitamin D, which is made from cholesterol in the skin and UVB radiation, is a neurosteroid hormone that has roles in brain development and normal brain function.

Vitamin D and mental health

  • Vitamin D regulates the transcription of genes involved in pathways for synaptic plasticity, neuronal development and protection against oxidative stress (Graham et al., 2015).
  • Vitamin D-deficient cells produce higher levels of the inflammatory cytokines TNF-α and IL-6, while cells treated with vitamin D release significantly less.
  • In the adrenal glands, vitamin D regulates tyrosine hydroxylase, which is the rate-limiting enzyme for the synthesis of dopamine, epinephrine, and norepinephrine.
  • In the brain, vitamin D regulates the synthesis, release, and function of serotonin. Serotonin modulates executive function, sensory gating, social behaviour, and impulsivity (Patrick & Ames, 2015).

Vitamin D and ADHD

  • Roles of vitamin D in ADHD include reduction of pro-inflammatory cytokines and oxidative stress, and neurotransmitter synthesis and regulation in the brain and gut.

It has been shown that Vitamin D deficiency is more common in children with ADHD than in healthy children (Hemamy et al 2020).

Vitamin D supplementation caused a significant improvement in ADHD evening symptoms (Hemamy et al 2020).

Causes of vitamin D deficiency

  • limited sun exposure
  • strict vegan diet (most sources of vitamin D are animal-based)
  • darker skin (the pigment melanin reduces the vitamin D production by the skin)
  • digestive tract and kidney issues
  • obesity (vitamin D is sequestered by fat cells)

Measuring vitamin D

The best indicator of vitamin D status is serum 25(OH)D, also known as 25-hydroxyvitamin D. 25(OH)D reflects the amount of vitamin D in the body that is produced by the skin and obtained from food and supplements.

Vitamin D levels and health status

Institute of Medicine, Food and Nutrition Board. (2010)

Serum (ng/ml)  and Health status

<20  deficient

20–39  generally considered adequate

40–50  adequate

>50–60   proposed optimum health level

>200  potentially toxic

Top sources of vitamin D based on serving size (Office of Dietary Supplements – Vitamin D, 2020)

  • cod liver oil
  • trout
  • pink salmon
  • sardines
  • fortified cereal, milk, and orange juice
  • fortified almond, soy, and oat milks
  • egg yolk

Comprehensive food list

Table 3: Vitamin D Content of Selected Foods

Referenced Dietary Intakes

RDAs for vitamin D (IU/day)

Adolescents (14-18 years): 600 (M) 600 (F)

Adults (19-50 years): 600 (M) 600 (F)

Adults (51 years and older): 800 (M) 800 (F)

Tolerable Upper Intake: 4000 IU/day

(Office of Dietary Supplements, 2020)

Vitamin D supplementation

  • Amounts of vitamin D used in practice and research range from 400-14 000 IU/day. (Vitamin D, 2014)

SAFETY, SIDE EFFECTS (Vitamin D, 2014)

  • “Research suggests that vitamin D toxicity is very unlikely in healthy people at intake levels lower than 10,000 IU/day”
  • Vitamin D can increase risk of hypercalcemia with calcium-related medical conditions – including primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma
  • Certain medical conditions can increase the risk of hypercalcemia in response to vitamin D, including primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma

Some drugs that affect vitamin D absorption or metabolism include (Vitamin D, 2014):

  • cholestyramine
  • colestipol
  • orlistat
  • mineral oil
  • phenytoin
  • fosphenytoin
  • phenobarbital
  • carbamazepine
  • rifampin
  • cimetidine
  • ketoconazole
  • glucocorticoids
  • HIV treatment drugs


Iron and Mental Health

Iron is required for the synthesis of serotonin and norepinephrine (Gaby).

Iron Deficiency in Children with ADHD

  • Average iron levels in children with ADHD were significantly lower than controls (6.04 ng/mL vs. 48.96 ng/mL) (Juneja 2010).
  • Ferritin (Iron) levels were low (<12 ng/mL) in the majority of cases with ADHD, and in 0% of controls (Juneja 2010, Calarge 2010).
  • Low Iron levels are correlated with inattention, hyperactivity/ impulsivity, difficulty concentrating, and higher total ADHD symptom scores (Calarge 2010, Juneja 2010, Gaby 2011). In many cases, these were improved with iron supplementation (Gaby 2011).
  • Individuals with lower iron levels have been found to require higher doses of amphetamine to reach optimal response than those with regular iron levels (Calarge 2010, Juneja 2010).

Causes of deficiencies (Iron, 2014)

Chronic blood losses due to:

  • parasitic infestations
  • frequent blood donation
  • regular intense exercise

Decreased iron absorption due to:

  • celiac disease
  • gastritis
  • Helicobacter pylori infection
  • inflammatory bowel diseases (IBD)
  • gastric bypass surgery

Other causes of iron deficiency include:

  • vegetarian diet with inadequate sources of iron
  • chronic kidney disease
  • pregnancy (due to increased need)
  • chronic inflammation

Deficiency of iron can be identified by (10 Signs and Symptoms of Iron Deficiency, 2020):

  • unusual tiredness
  • pale skin, inner eyelids, gums, or nails
  • cracks at the corners of the mouth
  • mouth ulcers
  • swollen, pale or smooth tongue
  • shortness of breath
  • headaches
  • dizziness, lightheadedness
  • heart palpitations
  • dry or damaged skin or hair

Top sources of iron based on typical serving size

  • beef, beef liver
  • chicken liver
  • oysters, clams
  • tuna
  • raisins
  • prunes

Comprehensive food list:

Table 2: some food sources of iron (Iron, 2014)

Referenced Dietary Intakes

RDAs for iron (mg/day)

Adolescents (14-18 years): 11 (M) 15 (F)

Adults (19 years and older): 8 (M) 18 (F)

Tolerable upper intake: 45 mg/day

(Office of Dietary Supplements – Iron, n.d.)

Supplementing iron

  • Amounts of iron used in practice and research range from 12–120 mg/day (Stoltzfus & Dreyfuss, 1999).


  • Supplementation  with more than 20 mg/kg can cause gastric upset, constipation, nausea, abdominal pain, vomiting, and faintness
  • Doses of 60 mg/kg can lead to multisystem failure, convulsions, coma, and death (Office of Dietary Supplements – Iron, n.d.)

Iron and Medications

  • Iron can reduce the absorption of levothyroxine; Levodopa, carbidopa, methyldopa; proton pump inhibitors such as lansoprazole (Prevacid) and omeprazole (Prilosec); cholestyramine and colestipol; penicillamine; quinolones; tetracyclines; and bisphosphonates. These medications should be taken two hours away from iron supplements (Iron, 2014).


Magnesium and Mental Health

Magnesium in the context of mental health (Kirkland, Sarlo, & Holton, 2018):

  • calms neurotransmission by regulating glutamate and GABA
  • modulates the HPA axis
  • has roles in the synthesis of serotonin and dopamine
  • regulates cortisol levels
  • increases brain-derived neurotrophic factor (BDNF)
  • is required for enzyme systems that use thiamine (vitamin B1) and pyridoxine (vitamin B6) – these vitamins are cofactors in the production of serotonin, GABA, and melatonin (Kanofsky, & Sandyk, 1991)
  • decreases activation of the NMDA receptor which in turn, decreases excitatory neurotransmission (Bartlik, Bijlani, & Music, 2014)

Magnesium and ADHD

Several observational studies showed that serum magnesium levels are lower in children with ADHD than in controls (Hemamy et al., 2020).

  • Magnesium deficiency was found in 95% of hyperactive children with ADHD (Kozielec & Starobrat-Hermelin 1997)
  • Adolescents with the highest intake of dietary magnesium were the least likely to show behaviors like hyperactivity, aggression, and delinquency (Black 2015)
  • Low magnesium levels of children with ADHD correlated with more hyperactivity and lower IQ (Greenblatt, 2018)

Causes of magnesium deficiencies include:

  • loss of soil magnesium due to farming practices
  • following the standard American diet pattern, as it is high in processed and nutrient-deficient foods,
  • decreased magnesium levels in foods, especially cereal grains (Guo, Nazim, Liang, & Yang, 2016)
  • low dietary protein (needed for magnesium absorption)
  • gastrointestinal disorders (e.g. Crohn’s disease, malabsorption syndromes, and prolonged diarrhea)
  • stress, which causes magnesium to be lost through urine (Deans, 2011), and
  • chronically elevated cortisol, which depletes magnesium (Cuciureanu, & Vink, 2011).
  • high doses of supplemental zinc (competes for absorption)
  • alcoholism
  • certain diuretic medications
  • Elderly adults tend to have lower dietary intake, absorption, and increased loss of magnesium.

Top sources of magnesium based on serving size

  • Brazil nuts
  • oat bran
  • brown rice (whole grain)
  • mackerel

Comprehensive food list:

Table 2. Some Food Sources of Magnesium (Magnesium, 2014)

Referenced Dietary Intakes

RDAs for magnesium (mg/day)

Adolescents (14-18 years): 410 (M) 360 (F)

Adults (19-30 years): 400 (M) 310 (F)

Adults (31 years and older): 420 (M) 320 (F)

Supplementing Magnesium

  • Amounts of magnesium used in practice and research range from 100–750 mg a day in divided doses (elemental magnesium dose).
  • Correction of magnesium deficiency with magnesium supplementation has resulted in significant improvement in psychiatric symptoms (Kanofsky & Sandyk, 1991).

Magnesium supplementation – beneficial forms and dosing (Greenblatt, 2018)

  • Magnesium glycinate supplementation of 120-240 mg per meal and at bedtime has been shown to benefit mood
  • Magnesium glycinate or citrate supplementation of 240-360 mg before bed supports sleep onset and sleeping through the night
  • Some beneficial forms of magnesium include magnesium aspartate, magnesium glycinate, magnesium threonate
  • The magnesium oxide form is less beneficial
  • Magnesium treatment (200 mg/day for 6 months) significantly decreased scores of hyperactivity across all scales in hyperactive children with ADHD (Starobrat-Hermelin & Kozielec 1997)
  • 200 mg/day of magnesium also was found to result in (Baza 2016)
    • 90% less hyperactivity
    • • 66% less inattention
    • • 33% less oppositional behavior
    • • 40% better executive function (such as: keeping track of time,finishing work on time, problem solving, using memory for everyday tasks)

Magnesium and Vitamin B6

Supplementation of 48 mg magnesium lactate + 5 mg Vitamin B6 three times daily for 30 days showed (Neuroscience and Behavioral Physiology, 2007):

  • less hyperactivity
  • improved attention
  • less anxiety
  • improvements in task performance
  • increased rate of work


  • Side effects of magnesium supplementation are rare, but can include a laxative effect, dizziness or faintness, sluggishness, cognitive impairment, and depression.
  • An effective strategy for dosing magnesium is to gradually increase the amount to bowel tolerance, then reduce slightly.
  • Magnesium is best taken in divided doses throughout the day. Caution is required for high doses of magnesium with existing kidney disease.


Zinc and mental health

Roles of zinc in the central nervous system (Prasad 1995) include:

  • maintaining protein structures
  • promoting enzymatic activity
  • maintaining neurotransmitter activity
  • supporting structural function in the hippocampus

Zinc and ADHD

Serum zinc concentration has been found to be significantly lower in children with ADHD than in healthy individuals (Gaby, 2011).

Zinc Deficiency in ADHD

  • Zinc levels in red blood cells, hair, and urine have been found to be lower in children with ADHD
  • When testing children for their zinc levels, 30.2% of children with ADHD had severe serum zinc deficiency (levels below 8.3 μmol/L), while no healthy controls showed these levels (Toren 1996)
  • Zinc level has been found to be inversely correlated with the severity of ADHD symptoms and parent/teacher rating scales of ADHD (Arnold 2005)
  • Hair zinc levels have been correlated to inattention, hyperactivity and impulsivity (Elbaz 2016)
  • Zinc levels of ADHD children were in the lowest 30% of the zinc level reference range (Arnold 2005)
  • 70% of children with ADHD were deficient in zinc (Elbaz 2016)

Zinc Supplementation

  • Zinc monotherapy (150 mg/day) for 12 weeks significantly reduced hyperactivity, impulsivity, and impaired socialization in some children with ADHD (Bilici et al 2004).
  • Supplementing with Zinc Sulfate (55 mg/ day) for 6 weeks significantly lowered ADHD ratings at each 2-week evaluation.
  • Supplementing with Zinc Glycinate (30mg/day) reduced optimal amphetamine dose needed in children with ADHD (Greenblatt 2018).

Top sources of zinc based on serving size

  • oyster, cooked
  • beef, chuck, blade roast, cooked
  • beef, ground, 90% lean meat, cooked
  • crab, Dungeness, cooked
  • fortified, whole-grain toasted oat cereal

Comprehensive food list:

Table 2. Some Food Sources of Zinc

Referenced Dietary Intakes

RDAs for zinc (mg/day)

Adolescents (14-18 years): 11 (M) 9 (F)

Adults (19 years and older): 11 (M) 8 (F)

Supplementing zinc

  • Amounts of zinc used in practice and research range from 10–200 mg/day in divided doses (Zinc, 2014).
  • “Long-term zinc supplementation should be accompanied by a copper supplement (1–4 mg/day, depending on the zinc dose), in order to prevent zinc-induced copper deficiency” (Gaby)


  • High zinc intakes can inhibit copper absorption, sometimes producing copper deficiency and associated anemia (Office of Dietary Supplements, 2014).
  • Intakes of zinc should not exceed the UL (40 mg/day for adults) in order to limit the risk of copper deficiency in particular
  • Milder gastrointestinal distress has been reported at doses of 50 to 150 mg/day of supplemental zinc (Zinc, 2014).

Essential fatty acids

Essential fatty acids and mental health

  • Polyunsaturated fatty acids (PUFAs) (omega 3 and 6 fatty acids) are necessary for normal development and function of the brain.

Essential fatty acids and ADHD

  • Omega 3 fatty acids and their metabolites help regulate inflammation, neuroinflammation, and neurotransmission (Larrieu, & Layé, 2018).
  • The concentrations of certain omega-3 and omega-6 fatty acids were significantly lower in children with ADHD than in healthy controls (Gaby, 2011).
  • Children with ADHD have lower blood levels of long-chain omega-3 fatty acids than control children (Antalis et al. 2006).

Lower DHA concentrations in children were found to be associated with (Montgomery 2013):

  • Reduced working memory performance
  • More oppositional behavior and emotional lability
  • Poorer reading ability


  • Children with ADHD are 60% more likely to have a Single Nucleotide Polymorphism (SNP, a change in one nucleotide in DNA) for fatty acid desaturase 2 (FADS2) gene (Brookes 2006).
  • This SNP results in less omega-3’s being incorporated into the cell membrane, which potentially explains why low omega-3 concentrations have been seen in ADHD subjects who do not lack dietary omega-3 intake (Brookes 2006).

EPA, DHA, and Omega 6 and ADHD

  • The ratio of omega 3 to omega 6 fatty acids is important in ensuring proper function of the body. Too much omega 6 compared to omega 3 has been shown to negatively affect health. However, too little omega 6 is also a problem.
  • Adolescents with ADHD had lower total omega-3 fatty acids, lower DHA levels, higher linoleic acid levels, and a lower omega-3:omega-6 ratio than controls. This ratio still was seen despite no difference in consumption of fatty acids (Colter et al 2008).
  • Higher Omega-6 levels predicted poorer reading, vocabulary, spelling, and attention in children with ADHD (Milte 2011).
  • Higher levels of EPA, DHA, and total Omega-3s were associated with better reading skills (Milte 2011).
  • A potential block in converting linoleic acid to gamma-linolenic acid (GLA) by the enzyme delta-6-desaturase was seen in boys with ADHD, suggesting a possible mechanism (Gaby, 2011).

Reasons for EFA deficiencies

  • Inadequate dietary intake
  • Poor absorption
  • Deficiencies of nutrients required for EFA metabolism
  • Issues with metabolism that cause decreased incorporation of, or increased removal of, fatty acids from cell membranes

Top EPA and DHA (omega 3) food sources by serving size

  • herring, pacific
  • salmon, chinook
  • sardines, pacific
  • salmon, atlantic
  • oysters, pacific

Comprehensive food list:

Table 4. Food Sources of EPA (20:5n-3) and DHA (22:6n-3) (Office of Dietary Supplements, n.d.)

Top α-Linolenic Acid (omega 3) food sources by serving size

  • flax seed oil
  • chia seeds
  • walnuts
  • flax seeds ground

Comprehensive food list:

Table 3. Food Sources of α-Linolenic Acid (18:3n-3) (Office of Dietary Supplements, n.d.)

Top Linoleic Acid (omega-6) sources by serving size

  • safflower oil
  • sunflower seeds
  • pine nuts
  • sunflower oil

Comprehensive food list: Table 2. Food Sources of Linoleic Acid (18:2n-6)

(Office of Dietary Supplements, n.d.)

Commonly suggested amounts for dietary fatty acid consumption:

  • cold water fish – 2 to 3 times a week, or
  • flaxseed oil – 2 to 6 tbsp daily, or
  • ground flax seed – 2 tbsp daily

Flaxseed oil may have negative effects in about 3% people, including: hypomania, mania, behaviour changes. (Prousky, 2015)

Referenced Dietary Intakes

Adequate Intakes for Alpha linolenic acid (Omega 3) (g/day) (Institute of Medicine, 2002)

Adolescents (14–18 years): 1.6 (M) 1.1 (F)

Adults (19 years and older):  1.6 (M) 1.1 (F)

Recommendations for long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (mg/day) (European Food Safety Authority, 2009)

Adults: 250 mg/day (M+F)

Supplementing omega 3 fatty acids

  • Supplementation of omega 3 fatty acids seems beneficial for addressing depression (Bruinsma & Taren, 2000).
  • Amounts of omega 3 fatty acids used in practice and research range from 1–4 g/day of combined EPA and DHA, in divided doses.
  • Fish oil and E-EPA are generally well tolerated, but may cause gastrointestinal side effects in some individuals (Gaby)
  • Long-term supplementation with EPA and DHA should be accompanied by a vitamin E supplement (Gaby), as polyunsaturated fatty acids increase vitamin E requirements in the body.

EPA and DHA supplementation and ADHD

  • 7.5-10g/day of omega-3 fatty acids showed significant positive impact in the treatment of ADHD (Sorgi et al 2007; Germano et al 2007).
  • Treatment with 650mg DHA + 650mg EPA improved attention in both ADHD children and healthy controls (Bos 2015).
  • Significant improvements in inattention, hyperactivity, oppositional/defiant behavior, and conduct disorder were seen when children with ADHD received 10.8 grams EPA and 5.4 grams DHA daily for 8 weeks (Sorgi 2007).
  • Reduction in Omega-6:Omega-3 ratio (AA:EPA) positively correlated with severity of illness (Sorgi 2007).
  • Supplementation with DHA has also been shown to increase attention and reduce symptom severity in ADHD (McNamara 2009).

EPA, DHA, and Omega 6 Supplementation in ADHD

  • Children with ADHD symptoms were given 558 mg EPA + 174 mg DHA, + 60 mg gamma linoleic acid (GLA) daily for 3 months. Significant improvements were seen in reading, spelling, and behaviour, that maintained or improved in progress with continued treatment (Richardson & Montgomery 2005).

Omega-3 & Omega-6 Treatment Reduce Medication Dose

  • Fatty acid supplements may permit lower doses of medications (Barragan et al 2014):
    • Greater change of total and hyperactivity- impulsivity scores
    • Less frequent side effects

For patients who do not respond to omega-3 fatty acids, a trial of evening primrose oil (omega 6) could be considered (Gaby, 2011)

It can take over 10 weeks to recover unsaturated fatty acid levels in chronically deficient individuals (Bourre et al 1993)


  • Common side effects of high dose EPA and DHA supplementation include heartburn, nausea, gastrointestinal discomfort, diarrhea, headache, and odoriferous sweat
  • The European Food Safety Authority considers long-term consumption of EPA and DHA supplements at combined doses of up to about 5 g/day appears to be safe.
  • The FDA recommends not exceeding 3 g/day EPA and DHA combined, with up to 2 g/day from dietary supplements (Office of Dietary Supplements, n.d.).


  • Use caution when supplementing omega 3 fatty acids while taking blood-thinning medications, or blood-sugar issues (Essential fatty acids, 2014).


Amino Acids and ADHD

  • ADHD is potentially linked to abnormal absorption or transport of amino acids (Bornstein 1990).
  • Children with ADHD had lower phenylalanine, tyrosine, and tryptophan levels (Gaby 2011).
  • Lower levels of amino acids were associated with more ADHD symptoms on the Conners Parent Rating Scale for behaviour (Bornstein 1990).

Tyrosine and mental health

Tyrosine is a dietary amino acid that also functions as a neurotransmitter. The body can also make tyrosine from the amino acid phenylalanine.

Tyrosine is a precursor molecule for the neurotransmitters dopamine, noepinephrine, and epinephrine, and is also required for the production of thyroid hormones.

Causes of deficiencies of tyrosine

  • a low-protein diet

Top sources of tyrosine based on serving size (Top Foods High in Tyrosine, n.d.)

  • sesame seeds
  • cheese
  • soybeans
  • meat and Poultry
  • fish

Supplementing tyrosine

  • Amounts of tyrosine used in practice and research range from 100–1000 mg/day in divided doses (Mahoney et al., 2007).
  • Tyrosine seems to be safe when used in doses up to 150 mg/kg per day for up to 3 months”  (Tyrosine, n.d.) (Gaby).
  • Since L-tyrosine may act as a mild stimulant, Tyrosine should not be taken near bedtime. L-tyrosine is likely most effective when it is taken with carbohydrates on an empty stomach (Gaby).

Tyrosine and 5-HTP supplementation and ADHD

  • Supplementation of L-tyrosine and 5-HTP and (precursors of dopamine and serotonin) for 8-10 weeks showed (Hinz 2011):
    • Improvement in behavioral symptoms on ADHD Rating Scale
    • complete relief of symptoms in some patients


  • Some people may experience side effects such as nausea, headache, fatigue, heartburn, and joint pain (Tyrosine, n.d.)
  • People who have migraine headaches may need to avoid tyrosine, as it can trigger migraine headaches
  • People with hyperthyroidism or Graves disease may need to avoid supplementing tyrosine as it may promote increased thyroid hormone production


  • Tyrosine may decrease how much levodopa the body absorbs (Tyrosine, n.d.)
  • Tyrosine may increase how much thyroid hormone the body produces


Amino Acids and ADHD

  • ADHD is potentially linked to abnormal absorption or transport of amino acids (Bornstein 1990).
  • Children with ADHD had lower phenylalanine, tyrosine, and tryptophan levels (Gaby 2011).
  • Lower levels of amino acids were associated with more ADHD symptoms on the Conners Parent Rating Scale for behaviour (Bornstein 1990).

Tryptophan and 5-HTP and mental health

  • Serotonin, regarded as the happy, feel good neurotransmitter, is synthesized from the amino acid tryptophan. Tryptophan is converted in the body to 5-HTP , which is then converted into the neurotransmitter serotonin.
  •  Tryptophan depletion can lead to (Mette 2013):
    • decreased attention
    • increased impulsivity
  • Tryptophan depletion in adults with ADHD decreased reaction times.

Food sources of tryptophan

Common sources of tryptophan (Richard et al. 2009):

  • turkey
  • chicken
  • tuna
  • oats
  • peanuts

Referenced Dietary Intakes

The recommended daily allowance for tryptophan for adults is estimated to be between 250 mg/day and 425 mg/day (Richard et al. 2009).

  1. Supplementing tryptophan
  • Children given 500 mg oral tryptophan showed (Nantel-Vivier, 2011):
    • less impulsiveness
    • higher accuracy in distinguishing emotion through facial expressions
    • more helpfulness and proactivity
  • Amounts of tryptophan used in practice and research range from 50–6000 mg/day in divided doses.
  • Carbohydrate consumption increases the amount of TRP that crosses the Blood Brain Barrier (BBB) (Richard et al., 2009). Therefore tryptophan is best taken away from meals, but with a small amount of carbohydrate to facilitate absorption. 5-HTP transport across the Blood-Brain Barrier (BBB) is not affected by dietary protein consumption and can be taken with meals (Werbach, 1997).
  • The optimal dose of tryptophan has been found in practice to be 2 g/day, taken with vitamin B6 (Prousky, 2015).
  • L-tryptophan increases serotonin levels, suggesting that it is most likely to be effective in serotonin-deficient patients. This includes patients with a history of a positive response to SSRIs or other serotonergic drugs (Gaby).
  • A dosage of 6 g/day or less  is recommended when L-tryptophan is used by itself,  and 4 g/day or less is recommended when given in combination with 2 g/day of niacinamide. These should be given in two separate doses per day to minimize fluctuation of tryptophan concentration (Chouinard et al., 1977) (Chouinard et al., n.d.).
  • The dose required can be reduced by administering L-tryptophan and niacinamide on an empty stomach along with carbohydrates. (Gaby)
  • L-tryptophan may cause fatigue. When this is experienced, the addition of 500 mg of L-tyrosine twice a day in addition to the L-tryptophan dose can prevent the fatigue and potentially increase the antidepressant effect of L-tryptophan. (Gaby)
  • For tryptophan-deficent individuals, L-tryptophan supplementation can provide a larger range of benefits than supplementation with 5-HTP.


  • Side effects of L-tryptophan supplementation can include heartburn, stomach pain, belching and gas, nausea, vomiting, diarrhea, and loss of appetite, headache, lightheadedness, drowsiness, dry mouth, visual blurring, muscle weakness, and sexual problems in some people (L-Tryptophan: Uses, Side Effects, n.d.).
  • High doses of tryptophan can promote bronchial asthma aggravation and nausea.
  • Tryptophan should not be used during pregnancy, with lupus, or with adrenal insufficiency (Prousky, 2015).
  • Co-administering L-tryptophan and antidepressants that increase serotonergic activity (SSRIs, amitriptyline, monoamine oxidase inhibitors) may increase the efficacy and toxicity of the drugs (Gaby).


  • Supplementing tryptophan or 5-HTP while on SSRI or MAOI medications is not generally recommended as it may promote an excessive buildup of serotonin  (Birdsall, 1998).
  • Do not supplement tryptophan if taking morphine (Prousky, 2015).
  • Avoid taking tryptophan or 5-HTP (or limit to very low doses) if receiving electroconvulsive therapy (Gaby, 2011).
  1. Supplementing 5-HTP

Referenced Dietary Intakes

RDAs/Upper intakes for 5-HTP

None established.

  • Amounts of 5-HTP used in practice and research range from 100–900 mg/day in divided doses (Prousky, 2015; Rakel, 2012).
  • 5-HTP can be taken with meals, as opposed to tryptophan, which needs to be taken away from meals.
  • Common amounts of 5-HTP used for addressing anxiety range from 100 to 900 mg daily in divided doses  (Prousky, 2015; Rakel, 2012).


  • Side effects of 5-HTP supplementation are typically minimal and can include heartburn, flatulence, rumbling sensations, feeling of fullness, mild, nausea, vomiting, and hypomania (Werbach 1999: Murray & Pizzorno, 1998, p. 391-93).
  • Other possible side effects include, stomach pain, diarrhea, drowsiness, sexual problems, and muscle problems (5-Htp: Uses, Side Effects, n.d.).
  • High-dose supplementation – from 6-10 grams daily – have been linked to severe stomach problems and muscle spasms (5-HTP: Uses, Side Effects, n.d.).


  • Supplementing tryptophan or 5-HTP while on SSRI or MAOI medications is not generally recommended as it may cause an excessive buildup of serotonin (Birdsall, 1998).
  • Avoid taking tryptophan or 5-HTP (or limit to very low doses) if receiving electroconvulsive therapy (Gaby, 2011).

Oligomeric proanthocyanidins (OPCs)


  • Oligomeric Proanthocyanidins (OPCs) are plant chemicals called polyphenols and are produced by plants to protect themselves from environmental harm.
  • OPCs help address ADHD symptoms by several mechanisms.


Roles of OPCs in the body include (Greenblatt, 2018):

  • decreasing theta waves, and improve theta:beta ratio
  • supporting antioxidant activity (e.g. GSH)
  • moderating catecholamine levels
  • helping to maintain blood brain barrier
  • decreasing copper levels
  • acting as antihistamines

Pycnogenol was found to reduce oxidative damage to DNA, normalize TAS, and improve attention in children with ADHD (Moghadas et al, 2019).

OPC’s and allergies

OPCs act as antihistamines by inhibiting histidine decarboxylase from binding to collagen microfibrils. This moderates the production and release of immune-activating molecules which would cause an allergic reaction.


An individual’s theta/beta ratio is predictive of ADHD, as it shows abnormal cortical activity patterns at all ages (Bresnahan 1999). These patterns include:

  • increased slow-wave (theta) activity, which may be due to hyperactivity in individuals with ADHD
  • decreased fast-wave (beta) activity (beta activity expresses concentration, suggesting that low beta activity may be due to hyperactivity)
  • high theta/beta ratio

Neurofeedback vs. Stimulants

  • Theta/beta training sessions and methylphenidate treatment (1 mg/kg/d) in children with ADHD led to reductions in primary symptoms and functional impairment. The neurofeedback group also improved significantly in academic performance (Meisel 2013).
  • Improvements from neurofeedback remained at 2-month and 6-month follow-ups (Meisel 2013).

Sources of OPCs

OPCs are often plant pigments:

  • Blue pigment in blueberries
  • Red pigment in grapes, red wine
  • Green pigment in green tea
  • Dark brown pigment in dark chocolate
  • plums
  • Ginkgo biloba (Maidenhair Tree)

Foods high in OPCs (Gu et al., 2004)

  • Blueberries
  • Cranberries
  • Black currant
  • Strawberries
  • Plums
  • Small red beans
  • Kidney beans
  • Hazelnuts, pecans, pistachios, almonds
  • Dark chocolate
  • Red wine
  • Ground cinnamon

Supplement sources of OPCs

  • Grape seed extract
  • Pine bark extract
  • Ginkgo biloba
  • Green tea extract
  • Resveratrol


B-complex vitamins and mental health

  • Symptoms including stress, illness, poor diet and nutrient absorption, as well as certain medications can increase needs for B-vitamins.
  • A good quality B-complex can address the minimum nutrient requirements for the important B-vitamins including vitamins B1, B3, B6, B12, and folate.

“A trial of B-complex supplement seems advisable, especially in older persons and in persons taking medications that may deplete this vitamin” (Rakel, 2012).

Multivitamin/multimineral complex

Multivitamins and Mental Health

  • Conditions including stress, illness, poor diet and nutrient absorption, as well as certain medications can increase needs for many different vitamins and minerals.
  • A good quality multivitamin/mineral formula can address the minimum nutrient requirements for the important vitamins and minerals.

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