Vitamins, minerals, dietary supplements for ADHD

As with all drug studies, careful consideration should be given to whether the authors of a study have particular advantages in propagating the particular drugs. Some drugs have a market simply because certain “conventional” drugs are rejected out of a convinced rejection of the “conventional” per se. That this is merely substituting one dogma for another is obvious. It should be noted that on all markets - on the market for “alternative” treatment offers just as on the market for “conventional” treatment offers - there are market participants who have only their economic advantage in mind. Therefore, a solid scientific basis must also be ensured for “alternative” treatment methods.
Strictly speaking, a demonstrably effective “alternative” treatment is a contradiction in terms - if an alternative treatment method were to record a scientifically or empirically demonstrable significant treatment success, it would no longer be alternative, but conventional. Only in the period between the presentation and the establishment of a new treatment method could an alternative treatment method that is effective not yet be established. During this time, it is then not conventional - but Lotto whether it works at all and that no undesirable side effects occur.
By their very nature, manufacturers of established remedies may have no interest in the spread of new, competing forms of treatment. However, they have no influence on whether or not physicians or therapists (who are primarily interested in the success of treatment and hardly in the use of very specific forms of treatment) use a different form of treatment. Rather, it is up to the providers of new (and, until established, thus “alternative”) forms of treatment themselves whether they can demonstrate and communicate the efficacy and safety of the treatments they offer.

However, there is a difference in terms of the marketing budgets of different forms of treatment. The more general and widespread active ingredients are, the more providers there are for them. Studies on the efficacy of active ingredients are expensive. Individual providers of widely used active ingredients usually cannot afford such studies, especially if they are off-patent active ingredients.

Fittingly, there are repeatedly studies that show positive results through massive vitamin or micronutrient administration in double-blind studies. The effect strength of one study was comparatively (not to say suspiciously*) high at 0.46 to 0.67¹ - and yet still well below that which can be achieved with suitable drugs (MPH 1, AMP 1.1). Nevertheless, it would be gratifying to be able to generate this effect additionally.
The doses given in the cited study are in some cases very far above the recommended daily doses.² It cannot be ruled out that such high overdoses of these substances can produce adverse side effects.
Moreover, since this is a branded product, the results should be assessed with particular caution. Study results are only reliable if they can be repeated in different studies by different research teams. Studies of branded products are generally financed by the manufacturer, who in turn only publishes such studies if they are positive. Since studies often have a range of inaccuracies, it often only requires a higher number of studies, among which only the positive ones are published. Des explains why studies financed by manufacturers of active ingredients or even branded products should be viewed with particular caution.

We present in this article many vitamins, minerals and other remedies that have been mentioned by the literature in relation to ADHD.

In principle, the blood levels of thyroid hormones, vitamins and minerals should always be clarified by a blood test as part of an ADHD diagnosis. The administration of vitamins and minerals that are too low can certainly help to alleviate ADHD symptoms (especially

• D3 (especially in the winter months)
• B12
• B6
• B9 (folate)
• Zinc
• Iron
• Magnesium
• Folic acid

The hope, however, that ADHD symptoms can be adequately eliminated solely by means of vitamins, minerals or other remedies discussed in this article is unfortunately only an illusion. Even a vitamin or mineral deficiency that actually exists and is adequately remedied usually only produces an effect size of 0.2 for improving ADHD symptoms, while the standard drugs MPH or AMP show an effect size of 1 to 1.4.

An excess of vitamins and minerals is just as harmful as a deficiency. Therefore applies:

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

• 1. Vitamins for ADHD
  • 1.1. Vitamin D3
    • 1.1.1. Vitamin D3 and dopamine
    • 1.1.2. Vitamin D3 and serotonin
    • 1.1.3. Other effects of vitamin D3
      • 1.1.3.1. Vitamin D3 blood levels
    • 1.1.4. Vitamin D3 and ADHD
      • 1.1.4.1. Vitamin D3 supplementation alongside stimulants
      • 1.1.4.2. Vitamin D3 medication
      • 1.1.4.3. Vitamin D3 receptor levels
    • 1.1.5. Vitamin D3 formation
    • 1.1.6. Dietary intake of vitamin D3
    • 1.1.7. Vitamin D3 substitution
  • 1.2. Vitamin B12
  • 1.3. Vitamin B6
  • 1.4. Vitamin B1 (thiamine, aneurine)
    • 1.4.1. Symptoms of B1 deficiency confusable with ADHD:
    • 1.4.2. Symptoms of B1 deficiency atypical of ADHD:
  • 1.5. Vitamin B9 / B11 (folate / folic acid)
  • 1.6. Vitamin C
  • 1.7. Vitamin A
  • 1.8. Vitamin E
  • 1.9. Vitamin B2 (less frequently)
  • 1.10. Vitamin B5 (pantothenate, less frequently)
• 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
• 3. Unsaturated fatty acids in ADHD
  • 3.1. Monounsaturated fatty acids
  • 3.2. Polyunsaturated fatty acids (PUFAs)
    • 3.2.1. Omega-3 fatty acids
    • 3.2.2. Omega-6 fatty acids
• 4. Other substances for ADHD
  • 4.1. Homocysteine
  • 4.2. Polyphenols
  • 4.3. Phosphatidylserine

1. Vitamins for ADHD¶

1.1. Vitamin D3¶

D3 is a vitamin that is converted into a hormone in the body, i.e. a prohormone. The daily dose recommended by the DGE is 800 i.U., which corresponds to 20 μg (micrograms). Most D3 experts consider this value to be too low.³

Prevalence D3 deficiency:⁴⁵

• 30.2 % inadequately supplied
• 38.4 % Sufficiently supplied
• 31.4 % in need of improvement or oversupplied

According to another source, the prevalence of insufficient vitamin D3 intake in Europe ranges from 33% to 100%.⁵ In Germany, insufficient intake for adults (19 to 64 years) was reported to be 99.9% (women) and 98.9% (men), and for the elderly (65 years and older) 99.1% (women) and 91.4% (men).

At the same time, a vitamin D3 deficiency seems to be very common in ADHD.⁶ A D3 administration especially in autumn / winter is recommended.
D3 requires fat for absorption, i.e. an intake requires that the preparations contain fat or a simultaneous food intake. A glass of milk should already suffice for this purpose.

1.1.1. Vitamin D3 and dopamine¶

Vitamin D3 is associated with changes in dopamine levels in various studies. The primary focus is on vitamin D3 deficiency during pregnancy and after birth, which causes maldevelopment of the brain.^7891011 An extensive long-term study in Spain on vitamin D3 deficiency during pregnancy found no correlation between low blood D3 levels in the mother during pregnancy and ADHD in children aged 5 to 18 years. Now, sunlight intensity in Spain is likely to be high enough to produce abundant D3 for most of the year, whereas in Germany, sunlight intensity is too low during the winter months to exceed the threshold required for D3 formation.¹²
A study of Chinese children with ADHD found decreased D3 blood levels.¹³
A study from less sunny countries showed that depression due to D3 deficiency is strongly tied to the amount of sunshine in the region:¹⁴

• 20% of the population in Alaska, 64th latitude
• 12.5% of the population in New York, 41st latitude
• 2.6% of Florida population, 28th latitude

Other studies examine the dopaminergic links between vitamin D3 deficiency and Parkinson’s disease¹⁵ or schizophrenia.¹⁶
Vitamin D attenuated behavioral deficits induced by severe dopamine deficiency in the striatum, dopamine dysmetabolism, oxidative stress, and neuroinflammation in mice¹⁷ and protected dopaminergic neurons from inflammation and oxidative stress in rats with severe dopamine deficiency in the striatum.¹⁸
A daily administration of 2000 UI D3 increased serum dopamine levels in ADHD sufferers, but not levels of BDNF or serotonin.¹⁹ Since dopamine in the blood cannot cross the blood-brain barrier, the serum dopamine increase has no effect on dopamine deficiency in the brain.
Regular vitamin D treatment can improve anhedonia-like symptoms in rats exposed to chronic mild stress, which causes depression symptoms, similar to the antidepressant fluoxetine. This is thought to occur by means of regulating the action of dopamine-related effects in the nucleus accumbens.²⁰

1.1.2. Vitamin D3 and serotonin¶

D3 increases mood (especially in winter) even in healthy people²¹ by increasing serotonin synthesis.²²²³

A daily administration of 2000 UI D3 increased serum dopamine levels in ADHD sufferers, but not levels of BDNF or serotonin.¹⁹ However, dopamine in the blood is not able to cross the blood-brain barrier, so the serum dopamine increase has no effect in relation to dopamine deficiency in the striatum.

1.1.3. Other effects of vitamin D3¶

Vitamin D3

• Promotes the biosynthesis of neurotrophic factors²⁴
• Promotes biosynthesis of at least one enzyme involved in neurotransmitter synthesis²⁴
• Promotes the biosynthesis of glutathione by supporting the synthesis of
  γ-glutamyltransferase²⁵
• Can inhibit the synthesis of inducible nitric oxide synthase²⁴
• May increase glutathione levels²⁴²⁵ which may counteract Parkinson’s.²⁶
• Promotes detoxification of astrocytes²⁵
• Does not seem to have any influence on oxidative stress.²⁷

1.1.3.1. Vitamin D3 blood levels¶

A frequent D3 deficiency is reported in ADHD. At the same time, according to several studies, D3 administration - also in addition to MPH - seems to reduce ADHD symptoms.^628293031

Reduced vitamin D3 serum levels of the mother in the 30th week of pregnancy correlated significantly with depression of the offspring until the age of 22, but not with ADHD.³² It is an open question whether D3 deficiency has different effects at other weeks of pregnancy, because later mental disorders are related in particular to those brain regions that are undergoing a developmental surge at that particular week of pregnancy. See more at ⇒ Exposure to stress at different stages of brain development In the chapter ⇒ Stress damage - effects of early / prolonged stress.

In the Spontaneous(ly) hypertensive rat (SHR), which is an animal model of ADHD-HI (with hyperactivity) (more specifically, a single, specific genetic variant thereof), one study found, compared with WKY rats (serving as healthy controls):

• Systolic blood pressure increased
• Sympathetic drive increased
• Cardiac hypertrophy and cardiac remodeling

These abnormalities correlated in the paraventricular nucleus of the hypothalamus (PVN) with

• Higher mRNA and protein expression levels of
  • High mobility box 1 (HMGB1)
  • Receptor for advanced glycation end products (RAGE)
  • Toll-like receptor 4 (TLR4)
  • Nuclear factor-kappa B (NF-κB)
  • Proinflammatory associated cytokines
  • NADPH oxidase subunit
• Increased level of reactive oxygen species
• Microglia activation

as well as

• Increased norepinephrine level in the blood plasma

These phenomena were eliminated in one study by an infusion of 40 ng of calcitriol daily (the physiologically active form of vitamin D3).³³

40 ng calcitriol corresponds to 0.04 micrograms vitamin D3. At a weight of approx. 200 g / rat, this should correspond to 0.2 micrograms / kg body weight. At 70 kg, this would correspond to a dose of 14 µg (micrograms). For humans an intake of 5-10 µg (200 - 400 IU) daily is recommended, whereas an intake of up to 50 µg (2000 I.U.) would be harmless for adults.³⁴³⁵

1.1.4. Vitamin D3 and ADHD¶

1.1.4.1. Vitamin D3 supplementation alongside stimulants¶

Randomized double-blind placebo-controlled trials in children found benefits of vitamin D administration in addition to previously taken stimulants in children 5 to 12 years of age with ADHD.³⁶ or at high doses of 50,000 iE/week and combined with magnesium ³⁷
A metastudy of 4 trials with n = 256 subjects of vitamin D supplementation as add-on therapy to methylphenidate for ADHD found small but statistically significant improvements in

• ADHD total scores
• Inattention
• Hyperactivity
• Behavior

No statistically significant improvement in opposition scores was found. No increased side effects were reported.³⁸

1.1.4.2. Vitamin D3 medication¶

A placebo-controlled study in children 2 to 18 years of age found improvements in attention in all D3 recipients with ADHD. In addition, and improvements were also found in hyperactivity and ADHD total score in those ADHD sufferers who had previously shown reduced D3 blood levels.³⁹

1.1.4.3. Vitamin D3 receptor levels¶

In addition to the - independent of the subtype - significantly reduced vitamin D level in the blood, the vitamin D receptors seem to be significantly reduced in ADHD.⁴⁰ Differences in calcium, phosphorus or alkaline phosphates were not found in this study.

Anyone who has symptoms typical of D3 deficiency despite adequate D3 levels should therefore have the D3 receptor examined, which is possible in the laboratory, as is D3 serum level determination.

1.1.5. Vitamin D3 formation¶

In summer, between 10 a.m. and 2 p.m., between 10,000 and 20,000 i.e. D3 is formed within 15 to 30 minutes by full-body sunbathing. Longer tanning does not provide any more benefits. Taking into account individual skin sensitivity, half the time from which redness forms in unprotected sun exposure in the following hours is optimal. However, this should also be perceived unprotected to ensure the D3 supply. When using sunscreen from SPF 14 as well as in winter, no more D3 is formed due to lack of sufficient sun intensity.⁴¹

1.1.6. Dietary intake of vitamin D3¶

The recommended daily dose of 800 i.U. can hardly be absorbed through food. Required would be (alternatively):⁴¹

• 400 g mackerel
• 4 kg pork cutlet
• 16 - 20 eggs
• 20 liters of whole milk
• 10 kg calfskin
• 10 kg Brie (with 45 percent fat content)
• 600 g avocado
• 1 kg shiitake mushrooms

Against this background, it becomes plausible that in Germany an average of 80 to 160 i.U. is absorbed daily through food. Consequently, 60% of Germans are deficient in vitamin D3 between November and April, and people with dark skin color are deficient even in summer.⁴¹ For humans, an intake of 5-10 µg (200 - 400 IU) daily is recommended, with an intake of up to 50 µg (2000 I.U.) being harmless for adults.³⁴³⁵

1.1.7. Vitamin D3 substitution¶

According to our impression, ADHD sufferers are particularly susceptible to winter depression. Therefore, it is recommended (based on the light conditions in Germany) to take additional D3 from mid-October to the end of April.
When taken, D3 requires fat to be absorbed by the body. Therefore, it should be taken with meals. Furthermore, vitamin D3 needs vitamin K2 and magnesium to work optimally.³

On the differences between plant D2 and animal D3 (which is also formed by sunlight), in depth and with quite a few sources: Rotter.⁴²

When D3 is taken (short-term daily doses of 2000 I.U. or more or weekly use of up to 20,000 I.U:), blood serum calcium levels should be checked for excessive levels every 3 to 6 months. Good normal values calcidiol are 80 to 160 nmol/l. Vitamin D-induced hypercalcemia shows serum calcidiol levels above 220 nmol/l.³⁴

In children with ADHD 6-12 years of age, a double-blind placebo-controlled study found that 50,000 IU of D3 per week and 6 mg/kg/day of magnesium significantly improved symptoms in the areas of behavioral disturbance, social behavior, and anxiety, but not psychosomatic symptoms.⁴³

1.2. Vitamin B12¶

How often a B12 deficiency exists in ADHD is controversial. Some sources assume a rare involvement of B12 deficiency in ADHD,^{4445 46} others think that in ADHD there often seems to be a vitamin B12 deficiency.⁴⁷
Prevalence of B12 deficiency⁴⁸⁵

• Young adults 5 to 10
• Older adults 10 - 30

The prevalence of insufficient vitamin B12 intake in Europe is between 0% and 40%.⁵ In Germany, insufficient intake was reported in 7.7% (women) and 8% (men) for adults (19 to 64 years) and 7.4% (women) and 3.6% (men) for the elderly (65 years and older).

A large study of 432 children found significantly lower serum levels of vitamin B12 in children with ADHD.⁴⁹ This correlated with an increased intake of nutrient-poor foods such as high-sugar and high-fat foods and a decreased intake of vegetables, fruits and protein-rich foods than in healthy children.
It is an open question whether the altered diet is the cause, consequence, or vicious cycle of ADHD.

Another study found a correlation between low B12 levels and increased hyperactivity/impulsivity in ADHD and Oppositional Defiant Disorder (ODD).⁵⁰⁵¹ B12 deficiency can increase homocysteine levels in several ways.⁵² B12 deficiency (or the excess homocysteine levels it triggers) may explain up to 13% of the hyperactivity/impulsivity symptoms of ADHD.⁵⁰

1.3. Vitamin B6¶

Vitamin B6 (pyridoxal phosphate) is needed for the synthesis of catecholamines (dopamine, norepinephrine, epinephrine) and the neurotransmitter PEA (phenylethylamine, a co-transmitter of norepinephrine).⁴⁶

In ADHD, there often seems to be a vitamin B6 deficiency = pyridoxine deficiency.⁴⁷⁴⁵

A large study of 432 children found significantly lower serum levels of vitamin B6 in children with ADHD.⁴⁹ This correlated with an increased intake of nutrient-poor foods such as high-sugar and high-fat foods and a decreased intake of vegetables, fruits and protein-rich foods than in healthy children.
It is an open question whether the altered diet is the cause, consequence, or vicious cycle of ADHD.

One study found a correlation between low serum B6 levels and ADHD along with symptom severity in adults.⁵³

A report indicates that the enzymes related to vitamin B6 are in significant imbalance in ADHD. Treatment with pyridoxine (vitamin B6) for several years would correct this imbalance without side effects. The same research team already considers these B6 metabolic enzyme complex imbalances to be the cause of epilepsy.⁵⁴ However, considering the scope of the theory presented, the number of subjects is very limited
For ADHD sufferers, he said

• TRP (tryptophan) tripled
• KYN (kynurenine) more than doubled
• 3-HOKYN (3-hydroxykynurenine) more than doubled
• KA (kynurenic acid) strongly increased
• IND (indoxyl sulfate) reduced
• 4PA (4-pyridoxic acid)/TRP ratio reduced
• IND/TRP ratio reduced
• IND/KYN ratio reduced

3-HOKYN is toxic. The KYN / TRP ratio represents an index of indoleamine 2,3-dioxygenase activity, the enzyme limiting tryptohan degradation. The 3-HOAA / 3-HOKYN ratio is considered an index of kynureninase activity.

MPH, the standard medication for children with ADHD, appears to increase kynurenic acid and decrease quinolinic acid in their plasma.⁵⁵

1.4. Vitamin B1 (thiamine, aneurine)¶

B1 deficiency can cause various symptoms, some of which resemble ADHD.symptoms.⁴⁵ Bieger operates a laboratory and sells dietary supplements. In laboratory analyses, own products were recommended without the conflict of interest being made known.

1.4.1. Symptoms of B1 deficiency confusable with ADHD:¶

• Lack of concentration
• Irritability
• Depression
• Fatigue
• Memory disorders (Korsakow’s syndrome), states of confusion
• Decreased production of antibodies during infections
• Disturbed energy production

1.4.2. Symptoms of B1 deficiency atypical of ADHD:¶

• Disorders of carbohydrate metabolism and nervous system (e.g. polyneuropathy)
• Visual disturbances
• Loss of appetite
• Anaemia (anemia)
• Frequent headaches
• Heart problems
  • Heart failure
  • Tachycardia (rapid heartbeat)
  • Low blood pressure
  • Shortness of breath (dyspnea)
• Edema
• Muscle problems
  • Muscular atrophy
  • Weak muscles (especially calf muscles)
  • Muscle cramps (calf cramps)
• Diseases:
  • Beriberi
  • Wernicke’s encephalopathy
  • Strachan syndrome
  • Alzheimer
    frequently reduced glucose and oxygen utilization in the brain, which is associated with B1 deficiency. It remains to be seen whether B1 deficiency is the cause or consequence of Alzheimer’s disease.

1.5. Vitamin B9 / B11 (folate / folic acid)¶

Folate refers to the sum of folate-active compounds (with a mono- or multiple glutamate residues attached; polyglutamates), folic acid is the form with a monoglutamate residue.
Vitamin B9 is sensitive to heat and light.

The prevalence of insufficient vitamin B9 intake in Europe is between 10% and 45%.⁵ In Germany, insufficient intake was reported in 26.7% (women) and 27.5% (men) for adults (19 to 64 years) and 20.7% (women and men) for the elderly (65 years and older).

Folate deficiency often appears to be present in ADHD.⁴⁷⁴⁵

A large study of 432 children found significantly lower serum levels of folate in children with ADHD.⁴⁹ This correlated with an increased intake of nutrient-poor foods such as high-sugar and high-fat foods and a decreased intake of vegetables, fruits and protein-rich foods than in healthy children.
It is an open question whether the altered diet is the cause, consequence, or vicious cycle of ADHD.

Another study also found decreased folate levels in ADHD.⁵⁰

1.6. Vitamin C¶

Vitamin C is needed for noradrenaline synthesis.⁵⁶ Bieger operates a laboratory and sells dietary supplements. In laboratory analyses, own products were recommended without the conflict of interest being made known.

The prevalence of insufficient vitamin C intake in Europe is reported to be between 5 and 35%.⁵
In Germany, for adults (19 to 64 years), 11% (women) and 19% men) were mentioned, and for the elderly (65 years and older), 11% (women) and 12% (men).

1.7. Vitamin A¶

A study of Chinese children with ADHD found decreased vitamin A blood levels.¹³ Another source comes to similar conclusions.⁴⁵

1.8. Vitamin E¶

Vitamin E is a collective term for certain fat-soluble substances with antioxidant effects. Examples are tocopherols, tocotrienols, tocomonoenols, marine derived tocopherols (MDT).

Source: Bieger.⁴⁵ Bieger operates a laboratory and sells dietary supplements. In laboratory analyses, its own products were recommended without the conflict of interest being made known.

1.9. Vitamin B2 (less frequently)¶

Source: Bieger.⁴⁵ Bieger operates a laboratory and sells dietary supplements. In laboratory analyses, its own products were recommended without the conflict of interest being made known.

1.10. Vitamin B5 (pantothenate, less frequently)¶

Source: Bieger.⁴⁵ Bieger operates a laboratory and sells dietary supplements. In laboratory analyses, its own products were recommended without the conflict of interest being made known.

2. Minerals for ADHD¶

2.1. Zinc¶

2.1.1. Zinc deficiency affects dopamine transporters and melatonin¶

Zinc can increase dopamine levels by decreasing DAT activity.⁵⁷⁵⁸

• Prevalence zinc deficiency:
  * Population-wide
  * Europe: 11 % (0.8 to 28.8 %)⁵
  * In Germany, insufficient uptake was cited here for adults (19 to 64 years) by 9.8% (women) and by 10.3% (men), and for the elderly (65 years and older) by 13.4% (women) and 8% (men).
  * Healthy children from 1 to 3 years:
  * Western Europe: 31.3 %⁵⁹
  * in children under five (Disease Control Priorities in Developing Countries 2006).
  * East Asia/Pazifik: 7%
  * Eastern Europe and Central Asia: 10
  * Latin America and Caribbean: 33 %
  * Middle East and North Africa: 46 %
  * Sub-Saharan Africa: 50
  * South Asia: 79 %
  • Zinc deficiency is manifested, among other things, by a deficiency of T and B lymphocytes
  • Zinc deficiency is often accompanied by vitamin A deficiency

ADHD medications, nicotine and zinc block the dopamine transporters (DAT) (which are too abundant in the brain in ADHD) and thus reduce their overactivity.⁶⁰. Zinc thus acts as a dopamine reuptake inhibitor.

Zinc deficiency can affect the modulation of melatonin. Melatonin regulates dopamine function.⁶¹ Melatonin deficiency can cause sleep disorders.⁶²

Dysregulation of zinc or copper may increase susceptibility to oxidative damage to tissues or oxidative stress to the brain by damaging antioxidant defenses, which may be a possible cause of ADHD.⁶³

2.1.2. Zinc deficiency and ADHD¶

Zinc can potentially supplement and enhance methylphenidate therapy.⁶⁴ However, the dosage of zinc used in the aforementioned study requires medical monitoring to avoid iron or copper deficiency as well as gastrointestinal distress or zinc flu. However, the reported improvements were impressive.
Whether the effect is independent of MPH therapy is unknown. Differentiating Krause.⁶⁵

It is possible that metabolism is altered in ADHD with respect to cobalt, copper, lead, zinc, and vanadium. Reduced cycle stability (determinism), duration (mean diagonal length), and complexity (entropy) of exposure profiles have been noted.⁶⁶

One study found 19% less zinc in the hair of children with ADHD. Low zinc hair levels could at the same time be used as a predictor for ADHD ⁶⁷
In contrast, a comprehensive meta-study of 11 studies on 1,311 subjects could not find any relevant differences in zinc levels in the blood or hair of ADHD sufferers compared to non-affected individuals. The results of the individual studies are very heterogeneous.⁶⁸

One study found average blood serum levels in children with ADHD compared to those not affected:⁶⁹

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

A zinc supplement in ADHD sufferers with zinc deficiency without iron deficiency⁷⁰

• Improved statistically significant
  • Hyperactivity
  • Attention
  • Impulsivity
  • Mood stability
• Remained unchanged
  • Intelligence
  • Cognitive problems
  • Opposition problems

A zinc and iron supplement in ADHD sufferers with zinc deficiency and iron deficiency⁷⁰

• Improved statistically significant
  • Verbal IQ
  • Total IQ
  • Hyperactivity
  • Impulsivity
  • Mood stability
• Remained unchanged
  • Performance IQ
  • Attention
  • Cognitive problems
  • Opposition problems

One study found elevated zinc levels in the blood and hair of children with hyperactivity and comorbid ODD or CD,⁷¹ where the study apparently equated hyperactivity with ADHD. Further, the study found frequent deficiency of magnesium. In the magnesium-deficient children, administration of magnesium also improved ADHD symptoms.

One large study found decreased blood zinc levels in children with ADHD, while levels of magnesium, copper, iron, and lead were unchanged.⁷² Several other studies⁷³⁷⁴ and a metastudy⁷⁵ also reported lower zinc levels in ADHD and an association between zinc levels and ADHD symptom severity,
One meta-study reported that zinc deficiency was primarily associated with ADHD-I.⁷⁶ A randomized double-blind study also found that zinc administration in addition to existing treatment with MPH further improved inattention (only), but not hyperactivity, impulsivity, or ADHD total score.⁷⁷
A meta-study found a positive effect of zinc in ADHD.⁷⁸

In conclusion, it can be stated that zinc levels are not generally altered in ADHD. However, the results of zinc supplementation in individual affected persons indicate that an existing zinc deficiency can contribute to the intensification of ADHD symptoms in some affected persons. Therefore, the zinc level and the functioning of the zinc receptors should be checked individually during diagnosis. If deficits are found here, zinc supplementation should be able to reduce ADHD symptoms in these patients.

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 strength of medication. However, correcting any deficiencies in vitamins or minerals can be helpful in ADHD as a supplement.

2.2. Magnesium¶

Seven studies consistently found decreased magnesium blood levels in ADHD sufferers.⁷⁹⁴⁶

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

• 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 of the anterior palate (46 %)
• Motor slowdown (42%)
• Abnormalities in brain imaging (43%)
• ADHD (35 %)
• Autism spectrum disorders (27%)
• Epilepsy (26 %)
• Schizophrenia / paranoid psychoses (20 %)

It is suspected that magnesium administration may be helpful here.⁸⁰

In children with ADHD, hair magnesium was found to be reduced by 29%. However, low hair magnesium levels could not be used as a diagnostic tool for ADHD.⁶⁷

One study found average blood serum levels in children with ADHD compared to those not affected:⁶⁹

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

In children with ADHD 6 to 12 years of age, a double-blind placebo-controlled study found that 50,000 IU of 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.⁴³³⁷

One study found a frequent deficiency of magnesium in the blood and hair of children with hyperactivity. In the magnesium-deficient children, magnesium administration also improved ADHD symptoms,⁷¹ though the study apparently equated hyperactivity with ADHD.

2.3. Iron, ferritin¶

The prevalence of low iron intake in Europe is between 0% and 20%.⁵ In Germany, the prevalence of low iron intake for adults (19 to 64 years) was reported to be 7.1% (men), and for the elderly (65 years and older) 6.1% (women) and 4.5% (men).

One meta-analysis found an association between ferritin levels as a peripheral marker of iron levels in ADHD and ADHD risk in children.⁸¹ Another meta-study found a beneficial effect of iron in ADHD.⁷⁸ A third meta-study also found a significant association between iron deficiency and ADHD.⁸² Another meta-analysis does not appear to have found a clear correlation for iron with ADHD ⁷⁵
Another meta-analysis concluded that serum ferritin levels were lower in ADHD (10 studies, n = 3,387), whereas there was no correlation between serum iron levels and ADHD (6 studies, n = 986).⁸³
Another meta-analysis found lower serum ferritin levels in children with ADHD and a correlation of iron deficiency to ADHD as well as to more severe ADHD symptoms.⁸⁴

A large study of 432 children found significantly lower serum levels of iron in children with ADHD.⁴⁹ This correlated with an increased intake of nutrient-poor foods such as high-sugar and high-fat foods and a decreased intake of vegetables, fruits and protein-rich foods than in healthy children.
It is an open question whether the altered diet is the cause, consequence, or vicious cycle of ADHD.

In contrast, another study found no correlation between iron deficiency and ADHD.⁸⁵

Another study found significantly decreased brain iron levels in ADHD-affected children in

• Globus pallidus
• Putamen
• Caudate nucleus
• Thalamus
• Nucleus ruber

This iron deficiency in the brain in ADHD is eliminated by stimulant medication. The increase in brain iron correlated with the duration of stimulant administration and was greater in older children than in younger children.⁸⁶ Iron deficiency may therefore be a consequence rather than a cause of ADHD, which is consistent with the very manageable effect size of treating iron deficiency in ADHD on ADHD symptoms

One study found lower iron levels in the bilateral limbic region of the striatum in children with ADHD. Lower tissue iron levels in the bilateral limbic striatum correlated with higher severity of ADHD symptoms, whereas lower tissue iron levels in the left limbic striatum correlated only with severity of anxious, depressive, and affective symptoms.⁸⁷

Iron can cross the blood-brain barrier by means of the transferrin receptor.⁸⁸

One study found that severe iron deficiency could decrease oxytocin, dopamine, irisin, MAO-A, β-endorphin, and α-MSH in the brain and increase synaptophysin.⁸⁹

One review found strong evidence of a correlation of iron deficiency and restless legs sleep problems, as well as possible evidence of correlations with sleep problems in ADHD.⁹⁰

Rodents with iron deficiency develop the major neurochemical dopaminergic changes common in restless legs (RLS), such as decreased striatal D2 receptors. Likewise, they develop hyperarousal⁹¹

Approximately 10% of Europeans suffer from an iron deficiency. Particularly frequently affected are

• Women
  in particular:
  • of childbearing age
  • after menstruation
  • during pregnancy
  • during breastfeeding
• Children
• Teenagers
• Dialysis-required
• for acute inflammations
  • chronic intestinal diseases
  • Gastritis
• Heart failure
• Cancer

Symptoms of iron deficiency may include:

• Brittle, dull, fragile hair
• Hair loss
• Rough, cracked skin
• Chapped corners of the mouth
• Brittle nails
• Hollow nails (nails that bend inward)
• Burning tongue with pain when swallowing
• Abnormal food cravings, for example, for lime, soil, or ice cubes (picacism)
• Impaired (athletic) performance
• Depression
• Headache
• Fatigue
• 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 only fill the deficit

During acute infections, iron administration may be detrimental.⁹²

2.4. Niacin¶

Source: Bieger.⁴⁴⁴⁵ Bieger operates a laboratory and sells dietary supplements. In laboratory analyses, its own products were recommended without the conflict of interest being made known.

2.5. Manganese¶

Manganese may affect the dopaminergic system.⁹³

One meta-analysis found increased levels of manganese in hair but not in blood of children with ADHD.⁹⁴ 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.⁶⁷

Manganese exposure has been discussed as a possible cause of ADHD. One study found that this depended on the genotype of the manganese transporter and that girls were more sensitive to ADHD responses to manganese than boys.⁹⁵ A metastudy also reported an association between manganese exposure and hyperactive behavior.⁷⁶

Another study reported that methylphenidate administration significantly decreased manganese levels.⁹⁶

2.6. Copper¶

It is possible that metabolism is altered in ADHD with respect to cobalt, copper, lead, zinc, and vanadium. Reduced cycle stability (determinism), duration (mean diagonal length), and complexity (entropy) of exposure profiles have been noted.⁶⁶

The prevalence of low iron intake in Europe ranges from 8% to 24%.⁵

Dysregulation of copper or zinc may increase susceptibility to tissue oxidative damage or brain oxidative stress by damaging antioxidant defenses, which may be a possible ADHD cause.⁹⁷

Several enzymes believed to play an essential role in the neurophysiology of ADHD are dependent on copper.⁹⁸

Excess copper can promote oxidation of dopamine and its metabolite salsolinol, leading to degeneration of dopaminergic neurons.⁹⁹

In children with ADHD, 10% less copper was found in the hair. However, low hair copper levels could not be used as a diagnostic tool for ADHD.⁶⁷

One study found average blood serum levels of in children with ADHD compared to unaffected individuals:⁶⁹

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

Another study of children with diabetes 1 and ADHD also found an elevated copper-zinc ratio.¹⁰⁰

One study found decreased levels in plasma, erythrocytes, urine, and hair in children with increased hyperactivity of¹⁰¹

• Magnesium
• Zinc
• Copper
• Iron
• Calcium

One large study found decreased levels of zinc in the blood of children with ADHD, while levels of magnesium, copper, iron and lead were unchanged.⁷²

One study found no change in copper blood levels in children with ADHD. Changes in copper blood levels doer ceruloplasmin blood levels also did not correlate with ADHD symptoms within the group of ADHD subjects.¹⁰²

2.7. Cobalt¶

In children with ADHD, 18% less cobalt was found in the hair. However, low hair cobalt levels could not be used as a diagnostic tool for ADHD.⁶⁷

2.8. Silicon¶

In children with ADHD, 16% less silicon was found in the hair. However, low hair silicon levels could not be used as a diagnostic tool for ADHD.⁶⁷

2.9. Chrome¶

One study found altered blood serum levels in children with ADHD compared to those not affected:⁶⁹

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

Another study found altered levels in the hair of children with ADHD of¹⁰³

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

2.10. Vanadium¶

It is possible that metabolism is altered in ADHD with respect to cobalt, copper, lead, zinc, and vanadium. Reduced cycle stability (determinism), duration (mean diagonal length), and complexity (entropy) of exposure profiles have been noted.⁶⁶

2.11. Bismuth¶

One study found altered levels in the hair of children with ADHD of¹⁰³

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

2.12. Germanium¶

One study found altered levels in the hair of children with ADHD of¹⁰³

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

2.13. Magnesium L-threonate¶

A very small study claims to have found benefits from administration of magnesium L-threonate.¹⁰⁴ Magnesium L-threonate is a compound of magnesium and L-threonic acid. Magnesium L-threonate is a degradation product of vitamin C.

3. Unsaturated fatty acids in ADHD¶

3.1. Monounsaturated fatty acids¶

A large study of 432 children found significantly lower serum levels of monounsaturated fatty acids (PUFAs) in children with ADHD.⁴⁹ This correlated with an increased intake of nutrient-poor foods such as high-sugar and high-fat foods and a decreased intake of vegetables, fruits and protein-rich foods than in healthy children.
It is an open question whether the altered diet is the cause, consequence, or vicious cycle of ADHD.

3.2. Polyunsaturated fatty acids (PUFAs)¶

One review came to the recommendation of a combination of EPA, DHA and GLA in a 9:3:1 ratio for ADHD.¹⁰⁵ The lead author is involved in a company that sells unsaturated fatty acids.

3.2.1. Omega-3 fatty acids¶

Administration of 635 mg eicosapentaenoic acid (EPA) and 195 mg docosahexaenoic acid (DHA) (unsaturated fatty acids) reduced serum CRP and IL-6 levels in children with ADHD and improved ADHD symptoms within 8 weeks in a double-blind placebo study.¹⁰⁶

A combination of the 3-fold unsaturated fatty acids EPA and DHA in rats in stress tests¹⁰⁷

• Prevented or compensated dendritic atrophy in the CA3 region of the hippocampus
• Restored GABA release in the CA1 region of the hippocampus
• Improved spatial memory.

A double-blind, placebo-controlled study found improvements in attention in children with ADHD as well as unaffected children with omega-3 fatty acids.¹⁰⁸

A randomized, double-blind, placebo-controlled study of 160 subjects found no improvement in ADHD-RS retention score or inattention with omega-3/6 supplementation at either 6 or 12 months. Positive responses were 46.3% in the omega-3/6 group and 45.6% in the placebo group. The study used two capsules daily, each containing 279 mg eicosapentaenoic acid [EPA], 87 mg docosahexaenoic acid [DHA], 30 mg gamma-linolenic acid [GLA].¹⁰⁹

Omega-3 fatty acids include:

• Eicosapentaenoic acid (EPA)
  • A Japanese study found significantly decreased EPA blood plasma levels in 24 ADHD sufferers under 20 years of age.¹¹⁰
• Docosahexaenoic acid (DHA)
  • A Japanese study found significantly decreased DHA blood plasma levels in 24 ADHD sufferers under 20 years of age.¹¹⁰
  • A combination of the 3-fold unsaturated fatty acids EPA and DHA in rats in stress tests¹⁰⁷
    • Prevented or compensated dendritic atrophy in the hippocampal CA3 region
    • Restored GABA release in the hippocampal CA1 region
    • Improved spatial memory.
• Roughanic acid
• Alpha-linolenic acid
• Stearidonic acid
• Eicosatetraenoic acid
• Heneicosapentaenoic acid
• Docosapentaenoic acid
• Tetracosapentaenoic acid
  (scoliodonic acid)
• Tetracosahexaenoic acid
  (nisic acid)

3.2.2. Omega-6 fatty acids¶

A randomized, double-blind, placebo-controlled study of 160 subjects found no improvement in ADHD-RS retention score or inattention with omega-3/6 supplementation at either 6 or 12 months. Positive responses were 46.3% in the omega-3/6 group and 45.6% in the placebo group. The study used two capsules daily, each containing 279 mg eicosapentaenoic acid [EPA], 87 mg docosahexaenoic acid [DHA], 30 mg gamma-linolenic acid [GLA].¹⁰⁹

Omega-6 fatty acids include:

• Arachidonic acid (AA)
  • A Japanese study found significantly decreased AA blood plasma levels in 24 ADHD sufferers under 20 years of age.¹¹⁰
• Linoleic acid (LA)
• Gamma-linolenic acid (GLA)
• Dihomo-gamma-linolenic acid (DHGLA)

4. Other substances for ADHD¶

4.1. Homocysteine¶

Homocysteine is not a vitamin, but an amino acid
A deficiency of folic acid, vitamin B2, B6 and/or B12 can cause excess homocysteine.¹¹¹ Elevated homocysteine levels can have a neurotoxic effect.

One study found elevated homocysteine levels in ADHD correlated with increased hyperactivity/impulsivity ¹¹²
In contrast, a smaller study found evidence of homocysteine deficiency in children with ADHD.⁴⁷

4.2. Polyphenols¶

Polyphenols are aromatic compounds with two or more hydroxy groups directly attached to an aromatic ring. Polyphenols form from phenylalanine, which in turn forms from shikimic acid.

Natural polyphenols (of which there are said to be over 8,000) are often present in plants as bioactive substances (colorants, flavorings, tannins), e.g.

• Flavonoids (colorants)
  • Flavonoids appear to have glutamate antagonistic and GABA agonistic effects.¹¹³
• Anthocyanins (colorants)
• Procyanidins
• Benzoic acid derivatives, e.g.
  • Vanillic acid
  • Gallic acid
  • Protocatechuic acid
• Cinnamic acid derivatives, e.g.
  • Caffeic acid
  • Coumaric acid
• Style derivatives, e.g.
  • Resveratrol
    • Red wine ingredient

Certain polyphenols are thought to be able to influence neurophysiological changes caused by early childhood stress,¹¹⁴ e.g.:

• Reduction of depressive symptoms through
  • Xanthohumol
  • Quercetin
  • Phlorotannins
• Reduction of anxiety symptoms through
  • Quercetin
  • Phlorotannins
• Remediation of the BDNF reduction through
  • Xanthohumol
• Failure to reverse early stress-induced dopamine and serotonin level changes in the brainstem
• Reducing the cortisol stress response to acute stress by
  • Xanthohumol

One study found a correlation of increased polyphenol intake with reduced ADHD risk in preschool children.¹¹⁵

4.3. Phosphatidylserine¶

Phosphatidylserine is not a vitamin but a phospholipid.

Source: Bieger.⁴⁵