.
Introduction

Welcome to the ISOM webpage for Attention Deficit Hyperactivity Disorder (ADHD). The purpose of this resource is to provide information on potential causes and promoters of ADHD that are related to nutrition, micronutrients, and metabolism. Understanding these factors can be an important and productive part of both addressing and recovering from ADHD.

The information provided is not intended to be a substitute for medical advice from a licensed physician or other qualified healthcare professional.

.

Back to Main Page

Page Contents

What is ADHD?

Attention-deficit/hyperactivity disorder, or ADHD, is a common neurodevelopmental disorder, which is usually diagnosed in childhood. Individuals with ADHD often have symptoms of inattention, hyperactivity, and/or impulsivity.

Symptoms of ADHD include:

  • Avoids or dislikes tasks needing sustained mental effort
  • Difficulty staying focused on tasks or activities
  • Does not pay close attention to details
  • Is easily distracted
  • Forgets daily tasks or loses items
  • Squirming or fidgeting

There are two classifications of ADHD: Predominantly Inattentive type and Predominantly Hyperactive-Impulsive type. Those who present as predominantly inattentive often find it hard to finish tasks, pay attention, follow instructions, or continue conversation. Those who are predominantly hyperactive-impulsive will fidget, may interrupt others, find it hard to sit, and act very impulsively. Some individuals with ADHD may have combined presentations of both types.

Further information

American Psychiatric Association webpage: https://www.psychiatry.org/patients-families/adhd/what-is-adhd

CDC.gov – “Attention-Deficit/Hyperactivity Disorder (ADHD)” https://www.cdc.gov/ncbddd/adhd/facts.html


References

Gaby AR. (2011) Nutritional Medicine. Alan R. Gaby, VitalBook file.

The standard medical approach typically does not consider, or address, dietary, nutrient, and environmental contributors to ADHD.

Conventional treatment for ADHD involves a combination of behavioral therapy and medication.

Medications commonly taken for ADHD include:

  • Stimulants (Methylphenidate, Amphetamines)
  • Non-stimulants (Atomoxetine, Guanfacine)

Stimulant medications work by increasing activities in areas of the brain that control behavior and attention/concentration. Non-stimulant medications may be used when stimulants are not working.  Atomoxetine is an SNRI which increases noradrenaline, which then can help with concentration and impulse control. Guanfacine is an alpha agonist that lowers hyperactivity and impulsivity.

 


References

American Psychiatric Association webpage. https://www.psychiatry.org/patients-families/adhd/what-is-adhd

NHS UK – “Attention deficit hyperactivity disorder”. https://www.nhs.uk/conditions/attention-deficit-hyperactivity-disorder-adhd/

ADHD has numerous biological causes and contributors that have been identified through nutritional research and clinical practice. Each individual may experience ADHD symptoms for different reasons.

An orthomolecular approach:

  • Identifies the drivers and causes of ADHD and focuses on understanding them
  • Works WITH the body to restore balance and normal function, and considers the person with the ADHD vs. just the ADHD
  • Addresses nutrient depletions that promote ADHD whereas medications do not
  • Can be done SAFELY in conjunction with most medical interventions

Diet, environment, and genetics play roles in the causation or promotion of ADHD. These factors can cause brain-related deficits and interruptions in neurotransmitter pathways, which then can affect attention, focus, and reward (Greenblatt 2018)

Contributing factors for ADHD

Contributing factors are substances, contexts or conditions that have roles in the causation or promotion of ADHD.

Food, food components, and food additives

Diet and Mental Health 

Diet is commonly considered the most important mediator of health and disease. 

Patients with psychiatric disorders often have poor food patterns, either from a reduced appetite, skipping meals, consuming fast or processed foods, or a general lack of interest in food altogether. (Greenblatt & Brogan, 2016).

Diet and ADHD

ADHD is associated with a “Western-style” diet, which is high in refined sugars and fats (Millichap & Yee, 2012).

Nutritional imbalances from poor diet in early childhood can cause behavioral issues in late childhood (Wiles 2009).

    • Consuming lots of junk food (high-fat, processed foods, burgers, fried chicken, snack foods high in fat and/or sugar, chips, chocolate) at age 4 was later connected to increased hyperactivity (age 7) (Wiles 2009).

Sugar-restricted, additive-free, and preservative-free diets that are supplemented with Omega-3s can reduce ADHD symptoms (Millichap & Yee, 2012). See the Mediterranean diet below:

Mediterranean diet and anxiety

  • The Mediterranean diet is considered a good model for a healthy diet. It includes foods that are beneficial and reduces or elimates foods that promote mental health issues.
  • General components of the Mediterranean diet include:
    • plenty of vegetables and fruit
    • healthy fats including olive oil
    • regular consumption of seafood
    • poultry, beans, and small amounts of red meat
    • small amounts of dairy such as yogurt and cheeses.
    • whole grains instead of refined grains

Elimination Diets and ADHD

Comprehensive elimination diets:

  • Typical elimination diets for ADHD simultaneously exclude refined sugar, food additives, common food allergens, salicylates, and amines. This can be a difficult diet to follow.
  • Substantial improvement can be achieved in many cases [of ADHD] after eliminating just the refined sugar, food additives, and common food allergens (Gaby, 2011).

Oligoantigenic diets (restricted elimination diet, hypoallergenic diet):

  • Eliminate highly allergenic foods such as cow’s milk, cheese, egg, chocolate, and nuts. Oligoantigenic diets can vary in their strictness (Ly et al., 2017).

The oligoantigenic diet often involves an elimination phase (usually two to five weeks). During this phase, all of the food items are completely removed. (Ly et al 2017). The elimination phase could consist of only a few hypoallergenic foods such as rice, turkey, lettuce, pears, and water (Ly et al., 2017).

The oligoantigenic diet promotes the reduction of ADHD symptoms (Ly et al., 2017). After the elimination period, foods are reintroduced slowly to identify ‘problem’ foods. Re-introduction of problematic foods often causes reappearance of ADHD symptoms (Ly et al 2017)

Fiengold Diet and ADHD

The Feingold Diet is a type of elimination diet that eliminates certain food chemicals and  salicylates. The Feingold Diet has been shown to be effective in addressing ADHD symptoms. See more in the Food Additives section.

Additional information

Mediterranean diet for heart health
Mayo clinic

https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801


References

Gaby, A. R. (2011). Nutritional Medicine. Alan R. Gaby, VitalBook file. 

Mediterranean diet for heart health. (n.d.). Mayo Clinic. Retrieved September 27, 2020, from https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801

Ly, V., Bottelier, M., Hoekstra, P. J., Arias Vasquez, A., Buitelaar, J. K., & Rommelse, N. N. (2017). Elimination diets’ efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. European Child & Adolescent Psychiatry, 26(9), 1067–1079. https://doi.org/10.1007/s00787-017-0959-1

Millichap JG, Yee MM. The diet factor in attention-deficit/hyperactivity disorder. Pediatrics. 2012;129(2):330-337. https://doi.org/10.1542/peds.2011-2199

Wiles, N., Northstone, K., Emmett, P. et al. ‘Junk food’ diet and childhood behavioural problems: results from the ALSPAC cohort. Eur J Clin Nutr 63, 491–498 (2009). https://doi.org/10.1038/sj.ejcn.1602967

Sugar and Mental Health

Refined sugars are sources of carbohydrates, but lack the nutrients required for their metabolism (breakdown in the body). As a result, the body’s reserves of nutrients are used instead. With chronic sugar consumption, the body becomes depleted in nutrients – especially those that are important for mental health.

Elevated consumption of sugar can promote:

  • damage to neurons by promoting oxidative stress and inflammation in the brain (Meng et al., 2014)
  • cognitive impairments and neurodegenerative disorders (Jacques et al., 2019)
  • insulin resistance, which in turn, can promote neurodegenerative disorders (Cetinkalp et al., 2014)

Sugar and ADHD

Refined sugar is one of the most common foods that induces ADHD symptoms in children (Gaby, 2011).

  • “Glucose and insulin metabolism issues can promote neuropsychiatric symptoms through several different mechanisms” (Gaby, 2011)

The relationship between ADHD and refined sugar has been shown through clinical observation and research (Gaby, 2011)

  • A strong positive association between soft drink consumption and odds of mental health issues was found, particularly in teens consuming 4+ soft drinks/day. Levels of hyperactivity directly connected to the number of soft drinks consumed (Lien et al 2006)

References

Cetinkalp, S., Simsir, I. Y., & Ertek, S. (2014). Insulin resistance in brain and possible therapeutic approaches. Current Vascular Pharmacology, 12(4), 553–564. https://doi.org/10.2174/1570161112999140206130426

Meng, X.-F., Wang, X.-L., Tian, X.-J., Yang, Z.-H., Chu, G.-P., Zhang, J., Li, M., Shi, J., & Zhang, C. (2014). Nod-like receptor protein 1 inflammasome mediates neuron injury under high glucose. Molecular Neurobiology, 49(2), 673–684. https://doi.org/10.1007/s12035-013-8551-2

Jacques, A., Chaaya, N., Beecher, K., Ali, S. A., Belmer, A., & Bartlett, S. (2019). The impact of sugar consumption on stress driven, emotional and addictive behaviors. Neuroscience & Biobehavioral Reviews, 103, 178–199. https://doi.org/10.1016/j.neubiorev.2019.05.021

Lien L, Lien N, Heyerdahl S, Thoresen M, Bjertness E. Consumption of soft drinks and hyperactivity, mental distress, and conduct problems among adolescents in Oslo, Norway. Am J Public Health. 2006;96(10):1815-1820. https://doi.org/10.2105/AJPH.2004.059477

Gluten and ADHD

Gluten is a general name for proteins found in wheat and related grains. Although many people are not affected by gluten, for a variety of reasons for others it can cause problems..

  • Gluten can damage the digestive tract, resulting in decreased nutrient absorption, and increased inflammation
  • The gliadin component of gluten can be improperly converted into gluteomorphins – which are addictive. Withdrawal symptoms include anxiety, depression (Scott, 2011)
  • Gluten sensitivity can decrease serotonin (Pynnönen 2005). Low serotonin is a risk factor for several mental health conditions.

Celiac disease and gluten

  • Celiac disease is an autoimmune condition triggered by consumption of gluten.  Not all symptoms of celiac disease manifest in the digestive system (Naidoo, 2020; Anderson, n.d.; Jackson et al., 2011). 
  • The neurological and psychiatric symptoms associated with celiac disease may mimic those of ADHD.  (Medicine.net, 2017; Ertürk et al., 2020). Ruling out celiac
    disease may be helpful to the formal diagnosis of ADHD (Medicine.net, 2017).
  • Studies have found that symptoms indicative of ADHD are more prevalent in individuals with celiac disease than in the general population (Niederhofer & Pittschieler, 2006; Anderson, n.d.; Jackson et al., 2011).  These symptoms may improve with strict adherence to a gluten-free approach to eating (Niederhofer & Pittschieler, 2006; Anderson, n.d.; Jackson et al., 2011; Ertürk et al., 2020; Medicine.net, 2017). 

Non-celiac gluten sensitivity and ADHD

  • Individuals with a non-celiac sensitivity to gluten may also experience psychiatric and neurologic symptoms associated with ADHD (Jackson et al., 2011).  
  • Consumption of foods containing gluten may worsen symptoms experienced by individuals with ADHD, especially if they have a non-celiac gluten sensitivity (Naidoo, 2020; Anderson, n.d.). 
  • Absorption of nutrients supportive of balanced brain chemistry may also improve with removal of gluten from the diet (Gore, n.d.). 

Some sources of gluten (Sources of Gluten, n.d.)
• wheat, rye, barley, triticale, malt, brewer’s yeast, wheat starch, pastas, noodles, bread, crackers, baked goods, cereals, sauces and gravy, beer


References

Anderson, J. (n.d.). Celiac Disease or Gluten Sensitivity With ADHD. Verywell Mind. https://www.verywellmind.com/gluten-and-adhd-562627

Jackson, J. R., Eaton, W. W., Cascella, N. G., Fasano, A., & Kelly, D. L. (2012). Neurologic and Psychiatric Manifestations of Celiac Disease and Gluten Sensitivity. Psychiatric Quarterly, 83(1), 91–102. https://doi.org/10.1007/s11126-011-9186-y

Naidoo, U. (2020). This is your brain on food: An indispensable guide to the surprising foods that fight depression, anxiety, PTSD, OCD, ADHD, and more (First edition.). Little, Brown Spark.

Potocki P & Hozyasz K. (2002)  Psychiatric symptoms and coeliac disease. Psychiatria Polska,
36(4), 567–578.

Pynnönen PA, Isometsä ET, Aronen ET, Verkasalo MA, Savilahti E & Aalberg VA. (2004).
Mental disorders in adolescents with celiac disease. Psychosomatics, 45(4), 325–335.
https://doi.org/10.1176/appi.psy.45.4.325

Scott T. (2011). The Antianxiety Food Solution: How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood, and End Cravings (Illustrated edition). New Harbinger Publications.

Sources of Gluten. (n.d.). Celiac Disease Foundation. Retrieved September 27, 2020, from https://celiac.org/gluten-free-living/what-is-gluten/sources-of-gluten/

Food Additives

Food additives are substances that get added to food to improve safety, taste, appearance, etc. Food additives can cause ADHD symptoms either through pharmacological effects or because of non-allergic (pseudoallergic) reactions (Gaby, 2011). Pseudoallergic reactions are generally not revealed by typical allergy tests (IgE, IgG RAST) (Gaby, 2011).

Food Additives and Hyperactivity

Artificial colours and sodium benzoate preservatives (in combination or separately) increase hyperactivity in children (McCann 2007).

Artificial Food Colours and ADHD
  • “An estimated 8% of children with ADHD may have symptoms related to synthetic food colors.” (Nigg 2012)
  • When artificial colours and flavours, chocolate, MSG, preservatives, and caffeine were removed from the diet for 10 weeks, more than half of the children showed improvement in behavior, and reduced sleep problems (Kaplan 1989).

Salicylates and ADHD

Salicylates are natural substances found in some fruits and vegetables as well as aspirin and other pain medication. It has been reported that 30–50% of children with ADHD showed marked improvement in ADHD symptoms after avoiding salicylates with results usually apparent within 3 to 21 days (Gaby, 2011).

Feingold Diet and ADHD

The Feingold Diet is a form of elimination diet that removes certain harmful food additives as well as the aspirin-like chemical salicylate. Salicylates have been found to promote symptoms of ADHD (Ly et al., 2017). The benefits of the Feingold Diet approach have been confirmed by clinical observations, uncontrolled and double-blind trials (Gaby, 2011).

Chemicals removed in the Feingold diet (FAQ | Feingold Association, n.d.):

  • artificial (synthetic) food dyes
  • artificial (synthetic) flavorings & fragrances
  • artificial sweeteners
  • three specific food preservatives

Also removed from the diet:

  • Foods and non-foods containing salicylates
  • Aspirin and medicine containing aspirin

References

Ly, V., Bottelier, M., Hoekstra, P. J., Arias Vasquez, A., Buitelaar, J. K., & Rommelse, N. N. (2017). Elimination diets’ efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. European Child & Adolescent Psychiatry, 26(9), 1067–1079. https://doi.org/10.1007/s00787-017-0959-1

FAQ | Feingold Association. (n.d.). Retrieved October 18, 2021, from https://www.feingold.org/faq/
Kaplan, B.J., McNicol, J., Conte, R.A. et al. Overall nutrient intake of preschool hyperactive and normal boys. J Abnorm Child Psychol 17, 127–132 (1989). https://doi.org/10.1007/BF00913788
McCann D, Barrett A, Cooper A, et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial [published correction appears in Lancet. 2007 Nov 3;370(9598):1542]. Lancet.
Nigg, J. T., Lewis, K., Edinger, T., & Falk, M. (2012). Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives. Journal of the American Academy of Child and Adolescent Psychiatry51(1), 86–97.e8. https://doi.org/10.1016/j.jaac.2011.10.015

Environmental factors

Lead and Mental Health

Toxic levels of lead are associated with (Pataracchia, 2008): 

  • psychosis
  • behavioural issues
  • mood disorders
  • learning disabilities
  • insomnia
  • compromised immunity
  • brain damage
  • delayed infant development
  • disruption of thyroid hormone transport

Lead is involved in several processes, including:

  • Blocking N-methyl- D-aspartate (NMDA) glutamate receptors, which affects brain plasticity and organization.
  • Replacing calcium and altering cellular function (Brochin et al 2008)
  • Free radical production
  • Neurotransmitter generation (Verlaet et al., 2018)
  • Midbrain dopamine circuitry

Low-level lead exposure remains a potential influence on ADHD, due to its abundance internationally, and it’s role in disrupting midbrain dopamine circuitry, as it is the same circuitry involved in ADHD (Nigg et al., 2008)

Lead and ADHD

Children with ADHD or learning disabilities have significantly higher levels of lead than healthy children. (Gaby, 2011). These higher levels are associated with increased hyperactivity symptoms and higher ratings of attention-deficit behaviour.

The current population average of lead blood levels in children in the US  is 1–2 μg/dL (Nigg et al., 2008). Blood lead levels of up to 10 μg/dL are associated with:

  • lower child intelligence scores
  • weaker executive cognitive abilities
  • behavioural symptoms of ADHD (inattentiveness, hyperactivity
  • diagnosis of ADHD

Lead & ADHD symptoms

  • Children with high lead levels had almost 3x the odds of inattentive and hyperactive symptoms. Children with low lead levels showed risk of ADHD symptoms (Kim 2010)

Removing lead improves symptoms. When treated with a chelating agent (EDTA or penicillamine) to reduce high lead levels, ADHD patients showed clinical improvement, which sometimes was after an initial worsening of behaviour (Gaby, 2011).

Sources of Lead Exposure

Lead exposure via water, soil, and other sources remains a worldwide health concern (Nigg et al., 2008).

Common sources of lead exposure (Common Sources of Lead, n.d., Campbell, 1995):

  • lead-based paint
  • children’s toys and jewelry
  • mini blinds
  • imported candy
  • lead water pipes
  • drinking water
  • newsprint
  • organ meats
  • tobacco
  • cosmetics
  • workplace and hobby hazards
  • traditional home remedies and cosmetics
  • lead-glazed ceramic ware, pottery and leaded crystal
  • contaminated soil
  • car batteries
  • leaded gas (which may persist in the environment still) (Eschner, 2016)

Addressing Lead Toxicity

Environmental and dietary sources of toxic metal exposures need to be removed as much as possible.

Many patients will improve with a basic protocol of a healthy diet, supplementation of essential nutrients, exercise, and rest. Sweating from exercise or sauna can also help remove toxic metals (Sears, 2018).

Detoxification of toxic metals must be properly supported with a protocol tailored to the patient’s unique situation and toxic load, in order to minimize the risk of releasing, then depositing the metals back into tissues. The best approach for brain detoxification is conservatively, “with repeated, modest treatments, using multiple agents” (Sears, 2018).


References

Campbell, D. (1995). Minerals and disease. Journal of Orthomolecular Medicine, 10(3 & 4).

Eschner, K. (2016). Leaded gas was a known poison the day it was invented. Smithsonian Magazine. Retrieved May 4, 2020, from https://www.smithsonianmag.com/smart-news/leaded-gas-poison-invented-180961368/

Pataracchia, R. J. (2008). Orthomolecular treatment for schizophrenia: A review (Part Two). Journal of Ortho- molecular Medicine, 23(2), 95–105.

Sears M. E. (2013). Chelation: harnessing and enhanc- ing heavy metal detoxi cation – a review. The Scienti c World Journal, 2013, 219840. https://doi.org/10.1155/ 2013/219840.


Metabolic conditions

Nutrient DEFICIENCY:

  • When the minimum amounts of nutrients needed for normal body function are not met by diet.
  • A nutrient deficiency results in depletion of nutrients in body tissues, and changes to mental and physical functioning.

Nutrient DEPENDENCY:

  • The metabolic need for a nutrient exceeds what can be supplied by diet and results in impaired biochemical processes and functions.
  • A nutrient dependency results from long-term environmental and genetic stressors.

Food allergies and sensitivities

Food allergies and sensitivities that affect the brain can be referred to as “cerebral allergies”. Cerebral allergies include more than just antibody-antigen reactions.

Cerebral allergies are mediated by:

  1. Direct biochemical effects of substances found in food or drink, for example caffeine, alcohol, and sugar
  2. Hidden or delayed allergic reactions to food or drink, for example wheat, milk, corn, and egg

Foods commonly associated with allergies (Prousky, 2015):

  • dairy products
  • wheat, rye, barley
  • eggs
  • pork, beef, seafood
  • soy
  • corn, tomato
  • citrus fruits
  • nuts, peanuts
  • chocolate
  • coffee, tea
  • sugar
  • yeast

Food Allergies and ADHD

Studies have shown that children with ADHD have a higher risk of developing allergies and that food allergies are a common cause of ADHD (Ly et al., 2017). “Children with ADHD are 7x more likely to have food allergies” (Bellanti 2001; Greenblatt, 2018).

Adverse food reactions associated with ADHD are often surrounding wheat and dairy. Both dairy and wheat show reaction types including (Greenblatt, 2018):

  • IgG Food Allergy
  • IgE Food Allergy
  • Suboptimal DPP IV 
  • Autoimmune

​​IgG food allergy symptoms include (Rapp 1991):

  • hyperactive, uncontrollably wild, unrestrained
  • nonstop talk, repetition, loud talk, stuttering
  • inattentive, disruptive, impulsive
  • short attention span and inability to concentrate
  • nervous, irritable, upset, short-tempered, moody
  • high-strung, excitable, agitated

Eliminating Food Allergies 

The most frequent symptom-evoking foods have been found to be (starting with most common):

  • sugar
  • colours (especially red), additives, and flavours
  • milk/dairy
  • corn
  • chocolate
  • egg
  • wheat
  • oats
  • soy
  • citrus
  • pork

Less frequent symptom-evoking foods were beef, apple, chicken, grape, peanut, onion, pineapple, tomato, carrot, oats, rice, and lettuce (Gaby, 2011).


References

Gaby, A. R. (2011). Nutritional Medicine. Alan R. Gaby, VitalBook file. 

Greenblatt, J. (2018). Orthomolecular Applications in Integrative Psychiatry, Depression [Pdf].

Rapp, D. J. (1991). Is this your child?: Discovering and treating unrecognized allergies in children and adults. New York: William Morrow Paperbacks.

The Microbiome

  • The human microbiome is made up of 10-100 trillion microbial cells consisting of bacteria, fungi, and viruses, among many others.
  • The microbiome also includes the genes contained by these cells (Ursell et al., 2012).
  • The composition of the microbiome is influenced by changes in diet and health (Quigley, 2013).

The microbiome is affected by:

  • antibiotics
  • infections
  • dietary sucrose (sugar and starch consumption)
  • dietary chemicals – including pesticides, additives and preservatives
  • medications – NSAIDs, Prednisone, oral contraceptives
  • food intolerances 
  • location of birth
  • the birthing process 
  • formula feeding

The Gut-Brain Axis and Mental Health

  • The gut-brain axis includes the brain, spinal cord, autonomic nervous system (sympathetic, parasympathetic and enteric nervous systems), and the hypothalamic-pituitary–adrenal (HPA) axis (Dinan et al., 2015).
  • Mental health conditions affected by the gut-brain axis include anxiety, depression, autism, obsessive compulsive disorder, and schizophrenia. 

The Microbiome and ADHD

  • Evidence has shown that the microbiome plays a large role in the development and progression of many psychiatric and behavioural disorders such as Attention Deficit/Hyperactivity Disorder (ADHD). (Understanding Gut Microbial Link with ADHD – an Update, n.d.)
  • The gut microbiome of ADHD individuals is different than the average healthy individual. It has been suggested that gut microbial imbalance can alter the gut and brain barriers, which leads to chronic inflammation and neurotransmitter dysfunction, which then can contribute to the development of ADHD. (Understanding Gut Microbial Link with ADHD – an Update, n.d.)

Probiotics and ADHD

  • Children with ADHD have been found to have significantly fewer probiotic species at early age (Pärtty, 2015).
  • Mothers taking Probiotic Lactobacillus rhamnosus GG for 4 weeks before delivery and for 6 months after delivery resulted in:
    • No children treated with the probiotic were diagnosed with ADHD or ASD, compared to 17% of untreated children (Greenblatt 2018).
    • Supplementation with Lactobacillus acidophilus and bifidus showed similar effects on ADHD symptoms (attention, self control) as 5-15 mg Ritalin 2-3 times daily for four weeks (Harding 2003; Greenblatt 2018).

References

Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015;63:1-9. https://doi.org/10.1016/j.jpsychires.2015.02.021

Harding. Altern Med Rev. 2003 Aug;8(3):319-30.

Understanding Gut Microbial Link with ADHD – an Update, n.d

Quigley EM. Gut bacteria in health and disease. Gastroenterol Hepatol (N Y). 2013;9(9):560-569.

Oxidative Stress

Oxidative Stress is a biological condition that results in excess accumulation of oxidants as a result of (Moghadas et al, 2019):

  • production of excessive amounts of oxidants
  • decreased level of antioxidants
  • a combination of both events

People are constantly exposed to free radicals, which are unstable atoms that can damage other cells. Exposure to free radicals in the environment can be from (Moghadas et al, 2019):

  •  Electromagnetic radiation from the man-made environment (pollutants, cigarette smoke)
  • Natural resources (radon, cosmic radiation, cellular metabolisms)

Oxidative Stress and ADHD

  • Excessive amounts of free-radicals and/or an ineffective anti-oxidant system can cause changes in proteins, and damage to membranes and DNA structure. Therefore, there is some evidence suggesting a correlation between ADHD and oxidative stress levels (Moghadas et al, 2019).
  • It has been suggested that oxidants can inhibit the uptake of enzymes and/or neurotransmitters. Since these are a part of the physiological functioning of cells, they could be seen as a predisposing factor for ADHD (Moghadas et al, 2019).
  • Changes in oxidative metabolism have been reported as a major factor in the cause of ADHD (Moghadas et al, 2019). 

ADHD Patients have been found to have (Ceylan et al 2010):

  • significantly higher markers of reactive oxygen molecules (known as reactive oxygen species) and lipid peroxidation (nitric oxide and MDA)
  • inhibited antioxidant activity (such as low glutathione peroxidase activity)
  • oxidative damage to neurons

References

Ceylan, M. & Akca, Ö. (2013). Secondary attention deficit/hyperactivity disorder due to right basal ganglia injury: A case report . Journal of Experimental and Clinical Medicine , 30 (2) , 189-191 . https://doi.org/10.5835/jecm.omu.30.02.022

Moghadas M, Essa MM, Ba-Omar T, et al. Antioxidant therapies in attention deficit hyperactivity disorder. Front Biosci (Landmark Ed). 2019;24:313-333. Published 2019 Jan 1. https://doi.org/10.2741/4720

Orthomolecular interventions for ADHD

Orthomolecular interventions are substances like vitamins and minerals that have roles in promoting or addressing ADHD, depending on the amount present in the body.

Vitamins

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)

https://lpi.oregonstate.edu/mic/vitamins/vitamin-B6

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).

SAFETY, SIDE EFFECTS

  • 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).

VITAMIN B6 AND MEDICATIONS

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

References

Bermond P. (1982). Therapy of side effects of oral contraceptive agents with vitamin B6. Acta Vitaminologica et Enzymologica, 4(1-2), 45–54.

McCarty M. F. (2000). High-dose pyridoxine as an ‘anti-stress’ strategy. Medical hypotheses, 54(5), 803–807. https://doi.org/10.1054/mehy.1999.0955

Office of Dietary Supplements—Vitamin B6. (n.d.). Retrieved October 28, 2020, from https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/

Prousky J, (2015) Anxiety: Orthomolecular diagnosis and treatment, Kindle Edition. CCNM Press.

Vitamin B6. (2014, April 22). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/vitamins/vitamin-B6

Werbach, M. R. (1997). Adverse effects of nutritional supplements. Foundations of Nutritional Medicine. Tarzanna, CA: Third Line Press, Inc,.

Greenblatt, J. M., & Brogan, K. (Eds.). (2016). Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention (1st edition). CRC Press.

Food and Nutrition Board, Institute of Medicine. (1998). Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. National Academy Press, 196–305.

Skarupski KA, Tangney C, Li H, Ouyang B, Evans DA, Morris MC. Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Am J Clin Nutr. 2010;92(2):330-335. doi:10.3945/ajcn.2010.29413

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)

https://lpi.oregonstate.edu/mic/vitamins/vitamin-C

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.

SAFETY, SIDE EFFECTS

  • 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.

References

Baez, S., Segura-Aguilar, J., Widersten, M., Johansson, A. S., & Mannervik, B. (1997). Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes. Biochemical Journal, 324(Pt 1), 25–28.

Meister, A. (1994). Glutathione, ascorbate, and cellular protection. Cancer Research, 54(7 Supplement), 1969s–1975s

Office of Dietary Supplements—Vitamin C. (n.d.). Retrieved December 4, 2020, from https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/

Plevin, D., & Galletly, C. (2020). The neuropsychiatric effects of vitamin C deficiency: A systematic review. BMC Psychiatry, 20(1), 315. https://doi.org/10.1186/s12888-020-02730-w

Rv, B., Np, R., & G, V. (2010). Biological investigations in Indian psychiatry. Indian Journal of Psychiatry, 52(Suppl 1), S136-8. https://doi.org/10.4103/0019-5545.69225

Smythies, J. (1996). Oxidative reactions and schizophrenia: A review-discussion. Schizophrenia Research, 24(3), 357–364. https://www.academia.edu/24021570/Oxidative_reactions_and_schizophrenia_A_review_discussion

Vitamin C. (2014, April 22). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/vitamins/vitamin-C

Schleicher, R. L., Carroll, M. D., Ford, E. S., & Lacher, D. A. (2009). Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). The American Journal of Clinical Nutrition, 90(5), 1252–1263. https://doi.org/10.3945/ajcn.2008.27016

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 https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

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

References

Graham, K. A., Keefe, R. S., Lieberman, J. A., Calikoglu, A. S., Lansing, K. M., & Perkins, D. O. (2015). Relationship of low vitamin D status with positive, negative and cognitive symptom domains in people with first‐episode schizophrenia. Early Intervention in Psychiatry, 9(5), 397-405.

Institute of Medicine, Food and Nutrition Board. (2010). Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academy Press.

Office of Dietary Supplements—Vitamin D. (2020). https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

Patrick, R. P., & Ames, B. N. (2015). Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. The FASEB Journal, 29(6), 2207- 2222.

Vitamin D. (2014, April 22). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/vitamins/vitamin-D

Umhau, J., George, D., Heaney, R., Lewis, M., Ursano, R., Heilig, M., Hibbeln, J., & Schwandt, M. (2013). Low Vitamin D Status and Suicide: A Case-Control Study of Active Duty Military Service Members. PloS One, 8, e51543. https://doi.org/10.1371/journal.pone.0051543

Minerals

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) 

https://lpi.oregonstate.edu/mic/minerals/iron

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).

SAFETY, SIDE EFFECTS

  • 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).

References

Calarge. J Child Adolesc Psychopharmacol. 2010 Dec;20(6):495-502.

Juneja. Indian Pediatr. 2010 Nov;47(11):955-8

https://lpi.oregonstate.edu/mic/minerals/iron

Murray, M. T. (1996). Encyclopedia of Nutritional Supplements: The Essential Guide for Improving Your Health Naturally (1st edition). Harmony.

Office of Dietary Supplements—Iron. (n.d.). Retrieved August 14, 2021, from https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

Stoltzfus, R. J., & Dreyfuss, M. L. (1999). Guidelines for the use of iron supplements to prevent and treat iron deficiency anemia. ILSI Pr.

Ballin, A., Berar, M., Rubinstein, U., Kleter, Y., Hershkovitz, A., & Meytes, D. (1992). Iron State in Female Adolescents. American Journal of Diseases of Children, 146(7), 803–805. https://doi.org/10.1001/archpedi.1992.02160190035015

10 Signs and Symptoms of Iron Deficiency. (2020, October 26). Healthline. https://www.healthline.com/nutrition/iron-deficiency-signs-symptoms

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)

https://lpi.oregonstate.edu/mic/minerals/magnesium

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

SAFETY, SIDE EFFECTS

  • 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.

References

Baza. Egypt. J. Med. Hum. Genet. 2016;17(1):63-70.

Starobrat-Hermelin & Kozielec. Magnes Res. 1997 Jun;10(2):149-56.

Bartlik, B., Bijlani, V., & Music, D. (2014, July 22). Magnesium: An essential supplement for psychiatric patients—Psychiatry Advisor. Psychiatry Advisor. https://www.psychiatryadvisor.com/home/therapies/magnesium-an-essential-supplement-for-psychiatric-patients/

Cuciureanu, M. D., & Vink, R. (2011). Magnesium and stress. In R. Vink & M. Nechifor (Eds.), Magnesium in the Central Nervous System. University of Adelaide Press. http://www.ncbi.nlm.nih.gov/books/NBK507250/

Deans, E. (2011, June 12). Magnesium and the brain: The original chill pill. Psychology Today. http://www.psychologytoday.com/blog/evolutionary-psychiatry/201106/magnesium-and-the-brain-the-original-chill-pill

Gaby, A. R. (2011). Nutritional Medicine. Alan R. Gaby, VitalBook file. 

Greenblatt, J. (2018). Orthomolecular Applications in Integrative Psychiatry, Depression [Pdf].

Jung, K. I., Ock, S. M., Chung, J. H., & Song, C. H. (2010). Associations of serum Ca and Mg levels with mental health in adult women without psychiatric disorders. Biological Trace Element Research, 133(2), 153–161. https://doi.org/10.1007/s12011-009-8421-y

Guo, W., Nazim, H., Liang, Z., & Yang, D. (2016). Magnesium deficiency in plants: An urgent problem. The Crop Journal, 4(2), 83–91. https://doi.org/10.1016/j.cj.2015.11.003

Kanofsky, J. D., & Sandyk, R. (1991). Magnesium Deficiency in Chronic Schizophrenia. International Journal of Neuroscience, 61(1–2), 87–90. https://doi.org/10.3109/00207459108986275

Kirkland, A. E., Sarlo, G. L., & Holton, K. F. (2018). The Role of Magnesium in Neurological Disorders. Nutrients, 10(6). https://doi.org/10.3390/nu10060730

Magnesium. (2014, April 23). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/minerals/magnesium

Vidal Freyre, A., & Flichman, J. C. (1970). Spasmophilia Caused by Magnesium Deficit. Psychosomatics, 11(5), 500–501. https://doi.org/10.1016/S0033-3182(70)71617-4

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

https://lpi.oregonstate.edu/mic/minerals/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) 

SAFETY, SIDE EFFECTS

  • 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).

References

Akhondzadeh. BMC Psychiatry. 2004 Apr 8;4:9.

Arnold. J Child Adolesc Psychopharmacol. 2005 Aug;15(4):628-36.

Bilici M, et al Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:181-90.

effects of gestational zinc deficiency. Medical Hypotheses, 31(2), 141-153.

Elbaz. Egypt J Med Hum Genet. 2016;18(2):153-163. Zinc Supplements for ADHD

Institute of Medicine. (2006). Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. https://doi.org/10.17226/11537

Joshi, M., Akhtar, M., Najmi, A. K., Khuroo, A. H., & Goswami, D. (2012). Effect of zinc in animal models of anxiety, depression and psychosis. Human & Experimental Toxicology, 31(12), 1237-1243.

Office of Dietary Supplements—Zinc. (n.d.). Retrieved October 29, 2020, from https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

Zinc. (2014, April 23). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/minerals/zinc

Aggett, P. J., & Harries, J. T. (1979). Current status of zinc in health and disease states. Archives of Disease in Childhood, 54(12), 909–917. https://doi.org/10.1136/adc.54.12.909

Kay, R. G., Tasman-Jones, C., Pybus, J., Whiting, R., & Black, H. (1976). A syndrome of acute zinc deficiency during total parenteral alimentation in man. Annals of Surgery, 183(4), 331–340. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1344200/

Swardfager, W., Herrmann, N., Mazereeuw, G., Goldberger, K., Harimoto, T., & Lanctôt, K. L. (2013). Zinc in depression: A meta-analysis. Biological Psychiatry, 74(12), 872–878. https://doi.org/10.1016/j.biopsych.2013.05.008

Irmisch, G., Schlaefke, D., & Richter, J. (2010). Zinc and fatty acids in depression. Neurochemical Research, 35(9), 1376–1383. https://doi.org/10.1007/s11064-010-0194-3

McLoughlin, I. J., & Hodge, J. S. (1990). Zinc in depressive disorder. Acta Psychiatrica Scandinavica, 82(6), 451–453. https://doi.org/10.1111/j.1600-0447.1990.tb03077.x

Nowak, G., Siwek, M., Dudek, D., Zieba, A., & Pilc, A. (2003). Effect of zinc supplementation on antidepressant therapy in unipolar depression: A preliminary placebo-controlled study. Polish Journal of Pharmacology, 55(6), 1143–1147.

Warner-Schmidt, J. L., & Duman, R. S. (2006). Hippocampal neurogenesis: Opposing effects of stress and antidepressant treatment. Hippocampus, 16(3), 239–249. https://doi.org/10.1002/hipo.20156

Fatty acids and lipids

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

ADHD and SNPs

  • 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.)

https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids

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.)

https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids

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.)

https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids

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)

SAFETY, SIDE EFFECTS

  • 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.).

OMEGA 3 FATTY ACIDS AND MEDICATIONS

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

References

Bruinsma, K. A., & Taren, D. L. (2000). Dieting, Essential Fatty Acid Intake, and Depression. Nutrition Reviews, 58(4), 98–108. https://doi.org/10.1111/j.1753-4887.2000.tb07539.x

Essential Fatty Acids. (2014, April 28). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids

European Food Safety Authority. Labelling reference intake values for n-3 and n-6 polyunsaturated fatty acids. (2009, July 10). https://www.efsa.europa.eu/en/efsajournal/pub/1176

Institute of Medicine. (2002). Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. https://doi.org/10.17226/10490

Larrieu, T., & Layé, S. (2018). Food for Mood: Relevance of Nutritional Omega-3 Fatty Acids for Depression and Anxiety. Frontiers in Physiology, 9. https://doi.org/10.3389/fphys.2018.01047

Office of Dietary Supplements—Omega-3 Fatty Acids. (n.d.). Retrieved October 29, 2020, from https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/

Prousky J, (2015) Anxiety: Orthomolecular diagnosis and treatment, Kindle Edition. CCNM Press.

Bloch, M. H., & Qawasmi, A. (2011). Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: Systematic review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 50(10), 991–1000. https://doi.org/10.1016/j.jaac.2011.06.008 

Bos. Neuropsychopharmacology. 2015 Sep;40(10):2298-306. Omega-3 + Omega-6 Treatment

Barragán, Breuer, & Döpfner. J Atten Disord. 2014 Jan 24. [Greenblatt, 2018]

Bourre, et al. Prostaglandins Leukot Essent Fatty Acids 1993.

Germano M et al. Nutr Neurosci 10: 1-9 (2007) [ADHD, n.d]

McNamara. J Psychiatr Res. 2009 Mar;43(6):656-63. Implications of Low DHA

Richardson & Montgomery. Pediatrics. 2005 May;115(5):1360-6.

Sorgi, P. J., Hallowell, E. M., Hutchins, H. L., & Sears, B. (2007). Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder. Nutrition Journal, 6, 16. https://doi.org/10.1186/1475-2891-6-16

Amino acids

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

SAFETY, SIDE EFFECTS

  • 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 AND MEDICATIONS

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

References

Gaby, A. R. (2011). Nutritional Medicine. Alan R. Gaby, VitalBook file.

Hinz M, Stein A, Neff R, Weinberg R, Uncini T. Treatment of attention deficit hyperactivity disorder with monoamine amino acid precursors and organic cation transporter assay interpretation [retracted in: Neuropsychiatr Dis Treat. 2020 Dec 16;16:3131]. Neuropsychiatr Dis Treat. 2011;7:31-38. Published 2011 Jan 26. https://doi.org/10.2147/NDT.S16270

Mahoney CR, Castellani J, Kramer FM, Young A, Lieberman HR. Tyrosine supplementation mitigates working memory decrements during cold exposure. Physiol Behav. 2007;92(4):575-582. doi:10.1016/j.physbeh.2007.05.003

Top Foods High in Tyrosine, n.d. https://www.myfooddata.com/articles/high-tyrosine-foods.php

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.

SAFETY, SIDE EFFECTS – Tryptophan

  • 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).

TRYPTOPHAN AND MEDICATIONS

  • 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).

SAFETY, SIDE EFFECTS – 5-HTP

  • 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.).

5-HTP AND MEDICATIONS

  • 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).

References

Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.

Gaby, A. R. (2011). Nutritional Medicine. Alan R. Gaby, VitalBook file. 

Murray & Pizzorno. The Encyclopedia of Natural Medicine Third Edition. 2014

Nantel-Vivier, A., Pihl, R. O., Young, S. N., Parent, S., Bélanger, S. A., Sutton, R., Dubois, M.-E., Tremblay, R. E., & Séguin, J. R. (2011). Serotonergic contribution to boys’ behavioral regulation. PLoS ONE, 6(6), Article e20304. https://doi.org/10.1371/journal.pone.0020304

Werbach & Moss. Textbook of Nutritional Medicine, 1999.

Prousky, Jonathan. (2015). A Transdiagnostic Approach to the Orthomolecular Treatment of Emotional Disorders: Preliminary Ideas for Intervention and Suggestions for Future Research. 30.

Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009;2:45-60. https://doi.org/10.4137/ijtr.s2129

Rakel D. Integrative Medicine, 3rd edition, Saunders, 2012.

Other Nutrients

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.

OPCs and ADHD

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.

ADHD EEGs

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

References

Bresnahan SM, Anderson JW, Barry RJ. Age-related changes in quantitative EEG in attention-deficit/hyperactivity disorder. Biol Psychiatry. 1999;46(12):1690-1697. https://doi.org/10.1016/s0006-3223(99)00042-6

Greenblatt, J. M., & Brogan, K. (Eds.). (2016). Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention (1st edition). CRC Press.

Gu L, Kelm MA, Hammerstone JF, et al. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J Nutr. 2004;134(3):613-617. https://doi.org/10.1093/jn/134.3.613

Meisel V, Servera M, Garcia-Banda G, Cardo E, Moreno I. Neurofeedback and standard pharmacological intervention in ADHD: a randomized controlled trial with six-month follow-up. Biol Psychol. 2013;94(1):12-21. https://doi.org/10.1016/j.biopsycho.2013.04.015

Moghadas M, Essa MM, Ba-Omar T, et al. Antioxidant therapies in attention deficit hyperactivity disorder. Front Biosci (Landmark Ed). 2019;24:313-333. Published 2019 Jan 1. https://doi.org/10.2741/4720

Multinutrient formulas

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).


References

Gaby, A. R. (2011). Nutritional Medicine. Alan R. Gaby, VitalBook file.

Rakel, D., (2012). Integrative Medicine (3rd ed.). Elsiver.

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.

Resources

This section contains useful information and tools for getting started as well as exploring further the orthomolecular approach to addressing ADHD.

Diet:

  • follow a Mediterranean-type diet with adequate protein and good fat to stabilize blood sugar
  • avoid processed foods
  • avoid sources of refined sugar
  • avoid sources of food additives
  • avoid any suspected allergic foods or foods you may be sensitive to

Nutrients to supplement daily:

  • multivitamin/mineral or B-complex
  • vitamin C
  • vitamin D
  • magnesium
  • zinc
  • fish oils

Further steps:

  • consider identifying potential food allergies and avoiding suspect foods
  • follow the Fiengold diet (See ADHD and Diet section)
  • test for iron deficiency
  • consider hair testing for lead and other heavy metals

Additional nutrients to consider supplementing:
(see each nutient for food sources and dosing information)

  • OPC formulas or nutrients (See OPCs) as single nutrients or formulas
  • B-complex (If not already taking)

If taking medications:

  • ask your doctor if they may be inducing your ADHD symptoms, and what can be done about it
  • research any associated nutrient depletions and consider supplementing those nutrients
  • do not discontinue taking medications without consulting with your doctor

Seek qualified guidance

  • Consider working with someone trained in Orthomolecular practice or Orthomolecular Psychiatry

Exercise

Exercise has been shown to influence brain serotonin (Dunn, & Dishman, 1991) and may promote increased release of endorphins.

Exercise increased concentration scores in children with ADHD. These score increases were similar to two common ADHD medications (“Children with ADHD Concentrate Better after Walking in a Park,” n.d.). https://doi.org/10.1177/1087054708323000


References

Dunn, A. L., & Dishman, R. K. (1991). Exercise and the neurobiology of depression. Exercise and sport sciences reviews, 19, 41–98.

Martinsen, E. W., Hoffart, A., & Solberg, Ø. Y. (1989). Aerobic and non-aerobic forms of exercise in the treatment of anxiety disorders. Stress Medicine, 5(2), 115–120. https://doi.org/10.1002/smi.2460050209

Moses, J., Steptoe, A., Mathews, A., & Edwards, S. (1989). The effects of exercise training on mental well-being in the normal population: a controlled trial. Journal of psychosomatic research, 33(1), 47–61. https://doi.org/10.1016/0022-3999(89)90105-0

Paluska, S. A., & Schwenk, T. L. (2000). Physical activity and mental health: current concepts. Sports medicine (Auckland, N.Z.), 29(3), 167–180. https://doi.org/10.2165/00007256-200029030-00003

Petruzzello, S. J., Landers, D. M., Hatfield, B. D., Kubitz, K. A., & Salazar, W. (1991). A meta-analysis on the anxiety-reducing effects of acute and chronic exercise. Outcomes and mechanisms. Sports Medicine (Auckland, N.Z.), 11(3), 143–182. https://doi.org/10.2165/00007256-199111030-00002

Rakel, D., (2012). Integrative Medicine (3rd ed.). Elsiver.

Mindfulness

Mindfulness meditation involves paying attention to the current moment, focusing on the breath, and bringing one’s awareness to the body. 

Mindfulness training showed reductions in problem behaviors in adolescents with ADHD, and improvements in executive functioning (van de Weijer-Bergsma, 2012). Parents reported reduced parental stress and overreactive parenting after mindfulness training  (van de Weijer-Bergsma, 2012).


References

van de Weijer-Bergsma E, Formsma AR, de Bruin EI, Bögels SM. The Effectiveness of Mindfulness Training on Behavioral Problems and Attentional Functioning in Adolescents with ADHD. J Child Fam Stud. 2012;21(5):775-787. https://doi.org/10.1007/s10826-011-9531-7