2. Minerals for ADHD

• 2.1. Zinc
  • 2.1.1. Zinc deficiency affects dopamine transporters and melatonin
  • 2.1.2. Zinc deficiency and ADHD
• 2.2. Magnesium
• 2.3. Iron, ferritin
• 2.4. Niacin
• 2.5. Manganese
• 2.6. Copper
• 2.7. Cobalt
• 2.8. Silicon
• 2.9. Chrome
• 2.10. Vanadium
• 2.11. Bismuth
• 2.12. Germanium
• 2.13. Magnesium L-threonate

2.1. Zinc¶

2.1.1. Zinc deficiency affects dopamine transporters and melatonin¶

Zinc can increase dopamine levels by reducing the activity of the DAT.¹²

• Prevalence of zinc deficiency:
  • Population-wide
    • Europe: 11 % (0.8 to 28.8 %)³
    • In Germany, 9.8 % (women) and 10.3 % (men) of adults (aged 19 to 64) and 13.4 % (women) and 8 % (men) of older people (aged 65 and over) stated that their intake was too low.
  • Healthy children from 1 to 3 years:
    • Western Europe: 31.3 %⁴
  • in children under five years of age (Disease Control Priorities in Developing Countries 2006).
    • East Asia/Pacific: 7 %
    • Eastern Europe and Central Asia: 10%
    • Latin America and the Caribbean: 33 %
    • Middle East and North Africa: 46 %
    • Sub-Saharan Africa: 50 %
    • South Asia: 79 %
  • Zinc deficiency manifests itself in a lack of T and B lymphocytes, among other things
  • Zinc deficiency often goes hand in hand with vitamin A deficiency

ADHD medication, nicotine and zinc block the dopamine transporters (DAT) (too frequently present in the brain in ADHD) and thus reduce their overactivity.⁵ Zinc therefore acts as a dopamine reuptake inhibitor.

Zinc deficiency can influence the modulation of melatonin. Melatonin regulates dopamine function.⁶ Melatonin deficiency can cause sleep disorders.⁷

Dysregulation of zinc or copper can increase susceptibility to oxidative damage to tissues or oxidative stress to the brain by damaging antioxidant defenses, which may be a possible ADHD cause.⁸

2.1.2. Zinc deficiency and ADHD¶

Zinc can possibly supplement and improve methylphenidate therapy.¹⁰ However, the dosage of zinc used in the aforementioned study requires medical supervision to avoid iron or copper deficiency as well as gastrointestinal complaints or zinc flu. However, the reported improvements were impressive.
Whether the effect exists independently of MPH therapy is unknown. Differentiating Krause.¹¹

It is possible that the metabolism of cobalt, copper, lead, zinc and vanadium is altered in ADHD. Reduced cycle stability (determinism), duration (mean diagonal length) and complexity (entropy) of the exposure profiles were found.¹²

METASTUDY (3: zinc reduced, 1: zinc unchanged):

• A meta-analysis reported lower zinc levels in ADHD and a correlation between zinc levels and the severity of ADHD symptoms.¹³
• A Chinese meta-analysis of k = 17 studies with n = 5,077 children found decreased serum zinc levels in children with ADHD (SMD: 1.33).¹⁴
• A meta-analysis reports that zinc deficiency is primarily associated with ADHD-I.¹⁵
• A comprehensive meta-analysis of k = 11 studies on n = 1,311 subjects was unable to find any relevant differences in the zinc levels in the blood or hair of people with ADHD compared to those without. The results of the individual studies were very heterogeneous.¹⁶

Individual studies:

Various studies have found reduced zinc levels in ADHD:

• in the blood serum of children with ADHD:¹⁷
  • Zinc: 7 % lower
  • Chromium: 21 % reduced
  • Magnesium: 4 % reduced
  • Copper-zinc ratio: 11 % increased
• in hair in children with ADHD¹⁸
  • Zinc: 19 % reduced. Low zinc hair levels could also be used as a predictor for ADHD.
• in the blood of children with ADHD (large study)¹⁹
  • reduced zinc levels
  • Magnesium, copper, iron and lead unchanged
• Zinc reduces²⁰
• Zinc reduces²¹
• Zinc deficiency in 60 % of the test subjects (Egyptian children)²²

One study found elevated zinc levels in ADHD:

• increased zinc levels in the blood and hair of children with hyperactivity and comorbid ODD or CD,²³ whereby the study apparently equated hyperactivity with ADHD. The study also found a frequent deficiency of magnesium. In the children with magnesium deficiency, the administration of magnesium also improved ADHD symptoms.

Zinc administration for ADHD;

METASTUDY:
A meta-analysis found a positive effect of zinc on ADHD.²⁴

Individual studies:
Zinc supplementation for people with ADHD with zinc deficiency without iron deficiency²⁵

• Improved statistically significantly
  • Hyperactivity
  • Attention
  • Impulsiveness
  • Mood stability
• Remained unchanged
  • Intelligence
  • Cognitive problems
  • Oppositional problems

Zinc and iron supplementation for people with ADHD with zinc deficiency and iron deficiency²⁵

• Improved statistically significantly
  • Verbal IQ
  • Total IQ
  • Hyperactivity
  • Impulsiveness
  • Mood stability
• Remained unchanged
  • Performance IQ
  • Attention
  • Cognitive problems
  • Oppositional problems

A randomized double-blind study found that zinc administration in addition to existing treatment with MPH (only) further improved inattention, but not hyperactivity, impulsivity or the ADHD total score.²⁶

As a result, it can be concluded that zinc levels are not generally altered in ADHD. However, the results of zinc supplementation in individual people with ADHD indicate that an existing zinc deficiency can contribute to the intensification of ADHD symptoms in some persons with ADHD. Therefore, the zinc level and the functionality of the zinc receptors should be checked individually during diagnostics. If deficits are found here, zinc supplementation should be able to reduce ADHD symptoms in these people with ADHD.

Even in the case of an existing deficiency, the administration of zinc or other vitamins or minerals should not be expected to achieve anywhere near the Effect size of medication. However, correcting any deficiencies in vitamins or minerals can be helpful for ADHD.

2.2. Magnesium¶

Seven studies consistently found reduced magnesium blood levels in people with ADHD.²⁷²⁸
A review of k = 45 meta-analyses found an increased risk of ADHD due to reduced magnesium blood levels.²⁹

In 15q11.2 BP1-BP2 microdeletion syndrome (Burnside-Butler syndrome), the following symptoms were found among 200 people with ADHD:

• Developmental disorders (73%)
• Speech disorders (67 %)
• Memory difficulties (60 %)
• Writing problems (60 %)
• Reading problems (57%)
• Verbal IQ below 76 (50 %)
• Behavioral problems (55 %)
• Dysmorphic ears (46 %)
• Anomalies on the front palate (46 %)
• Motor slowdown (42 %)
• Abnormalities in brain imaging (43%)
• ADHD (35 %)
• Autism spectrum disorders (27%)
• Epilepsy (26 %)
• Schizophrenia / paranoid psychoses (20 %)

It is assumed that magnesium administration can be helpful here.³⁰

In children with ADHD, magnesium was found to be 29% lower in the hair. However, low hair magnesium levels could not be used as a diagnostic tool for ADHD.¹⁸

One study found average blood serum levels in children with ADHD compared to those not affected:¹⁷

• Zinc: 7 % lower
• Chromium: 21 % reduced
• Magnesium: 4 % reduced
• Copper-zinc ratio: 11 % increased

In children with ADHD aged 6 to 12 years, a double-blind placebo-controlled study found that 50,000 IU D3 per week and 6 mg/kg/day of magnesium significantly improved symptoms in the areas of conduct disorder, social behavior and anxiety, but not psychosomatic symptoms.³¹³²

One study found a frequent lack of magnesium in the blood and hair of children with hyperactivity. In the children with magnesium deficiency, magnesium administration also improved ADHD symptoms,²³ although the study apparently equated hyperactivity with ADHD.
A study of Egyptian children found a magnesium deficiency in 65% of them²²

2.3. Iron, ferritin¶

Iron is an essential trace element and is required in particular for the formation of the red blood pigment (haemoglobin). Ferritin is a protein that stores the amount of iron present in the body. A low ferritin level is an indicator of reduced iron stores in the body.
Iron can cross the blood-brain barrier via the transferrin receptor.³³ Severe iron deficiency can reduce dopamine, oxytocin, irisin, MAO-A, β-endorphin and α-MSH in the brain and increase synaptophysin.³⁴ Rodents with iron deficiency show typical neuronal dopaminergic changes that are common in restless legs (RLS), such as reduced striatal D2 receptors. They also develop hyperarousal³⁵

In ADHD, 10 (meta-)studies on iron found evidence of decreased iron levels in ADHD, 5 (meta-)studies found no correlation, and one study found evidence of increased brain iron levels in adults with ADHD.

Evidence of decreased peripheral iron levels in ADHD (10 sources):

• significantly lower serum iron levels in children with ADHD³⁶ This correlated with an increased intake of nutrient-poor foods such as high-sugar and high-fat foods and a reduced intake of vegetables, fruit and protein-rich foods than in healthy children.
  It remains to be seen whether the change in diet is the cause, consequence or vicious circle of ADHD.

• a correlation of iron deficiency to ADHD and more severe ADHD symptoms (METASTUDY, k = 17, n = 6,251)³⁷

• significantly reduced iron levels in the brains of children with ADHD in

  • Globus pallidus³⁸
  • Putamen³⁸
  • Caudate nucleus³⁸
  • Thalamus³⁸
  • Nucleus ruber³⁸
  • Bilateral limbic region of the striatum³⁹
    • Which correlated with higher severity of ADHD symptoms, while lower tissue iron levels in the left limbic striatum correlated only with the severity of anxious, depressive and affective symptoms.

• Brain iron deficiency in ADHD is eliminated by stimulant medication. The increase in iron in the brain correlated with the duration of stimulant administration and was greater in older children than in younger children.³⁸ Iron deficiency may therefore be a consequence and not a cause of ADHD, which is consistent with the very manageable Effect size of treatment of iron deficiency in ADHD on ADHD symptoms

• a correlation between iron deficiency and ADHD⁴⁰

• a correlation with sleep problems in ADHD.⁴¹

  • Iron deficiency also correlated with restless legs sleep problems.⁴¹

• positive effect of iron on ADHD (meta-analysis)⁴² (meta-analysis)⁴³

No clear correlation found between serum iron levels and ADHD 5 sources: (meta-analysis)⁴⁴ (meta-analysis, k = 6, n = 986)^45464748

Evidence of excessive brain iron levels in adults with ADHD found 1 Source:

• especially in the right precentral cortex⁴⁹

In ADHD, 2 meta-analyses found decreased serum ferritin levels:

• Serum ferritin levels reduced in ADHD (meta-analysis, k = 10 , n = 3,387)⁵⁰ (METASTUDY, k = 17, n = 6,251)³⁷
• an association between ferritin levels as a peripheral marker of iron levels in ADHD and the risk of ADHD in children (meta-analysis, k = 5, n = 258)⁵¹

The prevalence of insufficient iron intake was stated as

• 20 % of pre-school children⁴¹
• between 0 % and 20 % in Europe ³
• for adults in Germany
  • 7.1 % (men aged 19 to 64)
  • 4.5 % (men aged 65 and over)
  • 6.1 % (women aged 65 and over)
• about 10% of Europeans. Particularly frequently affected are
  • Women
    in particular:
    • of childbearing age
    • after menstruation
      • heavy menstrual bleeding in women correlated with ADHD symptoms⁵²
    • during pregnancy
    • during breastfeeding
  • Children
  • Teenagers
  • Dialysis patients
  • for acute inflammation
    • chronic intestinal diseases
    • Gastritis
  • Heart failure
  • Cancer diseases

Symptoms of iron deficiency can be

• Brittle, dull, fragile hair
• Hair loss
• Rough, cracked skin
• Cracked corners of the mouth
• Brittle nails
• Hollow nails (nails that bend inwards)
• Burning tongue with pain when swallowing
• Abnormal cravings, for example for lime, soil or ice cubes (picacism)
• Impaired (athletic) performance
• Depression
• Headache
• Tiredness
• Concentration problems
• Restless legs (restless legs)
• Sleep disorders

Excess iron is just as harmful as iron deficiency. As with all vitamins and minerals:

1. measure first (repeat annually)
2. then just fill the deficit

During acute infections, iron supplementation can be detrimental.⁵³

2.4. Niacin¶

Source: Bieger.⁵⁴⁵⁵ Bieger operates a laboratory and sells food supplements. Its own products were recommended in laboratory analyses without the conflict of interest being disclosed.

2.5. Manganese¶

Manganese is an essential mineral and is absorbed with food. Important sources of manganese are tea, juices, cereals, rice, nuts, seafood, chocolate, fruit, vegetables, seeds and spices.
Manganese acts as a coenzyme. It is involved in and relevant for:⁵⁶⁵⁷

• Bone formation
• Macronutrient metabolism
• Defense against free radicals
  • Manganese is a component of manganese superoxide dismutase (MnSOD), a primary antioxidant that eliminates reactive oxygen species during oxidative stress in the mitochondria
• Brain function and development⁵⁸
• Activator of antioxidants
• required for insulin synthesis and secretion

Manganese deficiency can cause{Visternicu M, Rarinca V, Burlui V, Halitchi G, Ciobică A, Singeap AM, Dobrin R, Mavroudis I, Trifan A (2024): Investigating the Impact of Nutrition and Oxidative Stress on Attention Deficit Hyperactivity Disorder. Nutrients. 2024 Sep 15;16(18):3113. doi: 10.3390/nu16183113. PMID: 39339712; PMCID: PMC11435085. REVIEW}}

• Disorder of the carbohydrate metabolism
• Brain dysfunctions of the brain

Excess manganese can trigger:⁵⁹

• cognitive deficits⁶⁰
• Attention and learning problems⁶⁰⁶¹
• Executive problems⁶²
• Hyperactivity (meta-analysis)¹⁵
• emotional problem⁶⁰
• One study found that this depends on the genotype of the manganese transporter and that girls are more sensitive to ADHD reactions to manganese than boys⁶³

Manganese can affect the dopaminergic system.⁶⁴⁵⁹⁶¹

A meta-analysis found increased manganese levels in the hair but not in the blood of children with ADHD.⁶⁵ Another study found 27% less manganese in the hair of children with ADHD. However, low hair manganese levels could not be used as a diagnostic tool for ADHD.¹⁸

Another study reported that the administration of methylphenidate significantly reduced manganese levels.⁶⁶

2.6. Copper¶

It is possible that the metabolism of cobalt, copper, lead, zinc and vanadium is altered in ADHD. Reduced cycle stability (determinism), duration (mean diagonal length) and complexity (entropy) of the exposure profiles were found.¹²

The prevalence of insufficient iron intake in Europe is between 8% and 24%.³

Dysregulation of copper or zinc can increase susceptibility to oxidative damage to tissues or oxidative stress to the brain by damaging antioxidant defenses, which may be a possible ADHD cause.⁶⁷

Several enzymes thought to play an essential role in the neurophysiology of ADHD are copper-dependent.⁶⁸

Excess copper can promote the oxidation of dopamine and its metabolite salsolinol, which leads to the degeneration of dopaminergic neurons.⁶⁹

Children with ADHD were found to have 10% less copper in their hair. However, low hair copper levels could not be used as a diagnostic tool for ADHD.¹⁸

One study found average blood serum levels of in children with ADHD compared to those not affected:¹⁷

• Zinc: 7 % lower
• Chromium: 21 % reduced
• Magnesium: 4 % reduced
• Copper-zinc ratio: 11 % increased
  • Copper therefore increases

Another study on children with diabetes 1 and ADHD also found an increased copper-to-zinc ratio.⁷⁰

One study found reduced levels in plasma, erythrocytes, urine and hair in children with increased hyperactivity of⁷¹

• Magnesium
• Zinc
• Copper
• Iron
• Calcium

One study found no change in copper blood levels in children with ADHD. Changes in copper blood levels or ceruloplasmin blood levels also did not correlate with ADHD symptoms within the group of ADHD subjects.⁷²
One study found slight evidence of a role for copper in ADHD. No evidence of a connection was found for other micronutrients.⁷³
A study of Egyptian children found a copper deficiency in 70% of them²²

A large study found decreased levels of zinc in the blood of children with ADHD, while levels of magnesium, copper, iron and lead were unchanged.¹⁹

2.7. Cobalt¶

Children with ADHD were found to have 18% less cobalt in their hair. However, low hair cobalt levels could not be used as a diagnostic tool for ADHD.¹⁸

2.8. Silicon¶

Children with ADHD were found to have 16% less silicon in their hair. However, low hair silicon levels could not be used as a diagnostic tool for ADHD.¹⁸

2.9. Chrome¶

One study found altered blood serum levels in children with ADHD compared to those not affected:¹⁷

• Zinc: 7 % lower
• Chromium: 21 % reduced
• Magnesium: 4 % reduced
• Copper-zinc ratio: 11 % increased

Another study found altered levels in the hair of children with ADHD of⁷⁴

• Bismuth: 8-fold increased
• Chromium: 15 % reduced (and strongest predictor of ADHD symptoms)
• Germanium: 11 % reduced

2.10. Vanadium¶

It is possible that the metabolism of cobalt, copper, lead, zinc and vanadium is altered in ADHD. Reduced cycle stability (determinism), duration (mean diagonal length) and complexity (entropy) of the exposure profiles were found.¹²

2.11. Bismuth¶

One study found altered levels in the hair of children with ADHD of⁷⁴

• Bismuth: 8-fold increased
• Chromium: 15 % reduced (and strongest predictor of ADHD symptoms)
• Germanium: 11 % reduced

2.12. Germanium¶

One study found altered levels in the hair of children with ADHD of⁷⁴

• Bismuth: 8-fold increased
• Chromium: 15 % reduced (and strongest predictor of ADHD symptoms)
• Germanium: 11 % reduced

2.13. Magnesium L-threonate¶

A very small study claims to have found benefits from the administration of magnesium L-threonate.⁷⁵ Magnesium L-threonate is a compound of magnesium and L-threonic acid. Magnesium L-threonate is a degradation product of vitamin C.