.
Introduction

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

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

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What is anxiety?

Anxiety is a condition(s) of excessive and persistent nervousness, worrying, fear, irritability, and sleep disturbances. It is often accompanied by sweating, palpitations, chest pain, fatigue, headaches, shortness of breath, and muscle tension. (Gaby, 2011)

What are anxiety disorders?

American Psychiatric Association
https://www.psychiatry.org/patients-families/anxiety-disorders/what-are-anxiety-disorders

Different types of anxiety disorders: How are they classified?

https://www.talkspace.com/blog/different-types-anxiety-disorders-classifiedx
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REFERENCES

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

The medical approach for anxiety involves psychological and pharmacological treatments. This approach does not consider or address nutritional and environmental contributors to anxiety.

Medical standard of care for anxiety (Katzman et al., 2014):

  • screen for anxiety and related symptoms
  • conduct differential diagnosis (consider severity, impairment, and comorbidity)
  • identify specific anxiety or related disorder
  • provide psychological and/or pharmacological treatment
  • perform follow-up

Typical medications used to treat anxiety include benzodiazepines and antidepressant selective serotonin reuptake inhibitors (SSRIs). (Melinda 2020)

Medications for anxiety

https://www.helpguide.org/articles/anxiety/anxiety-medication.htm

https://www.drugs.com/condition/anxiety.html

Anxiety disorders and treatments

National Institute of Mental Health
https://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml  (09.26.2020)
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REFERENCES

Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M & the Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/ Association Canadienne des troubles anxieux and McGill University. (2014) Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive- compulsive disorders. BMC Psychiatry, 14(1), S1. https://doi.org/10.1186/1471-244X-14-S1-S1

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

An orthomolecular approach:

  • identifies the drivers and causes of anxiety and focuses on understanding them
  • works WITH the body to restore balance and normal function, and considers the person with the condition vs. just the condition
  • addresses nutrient depletions that promote anxiety whereas medications do not
  • can be done SAFELY in conjunction with most medical interventions

Contributing factors for anxiety

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

Food, food components, and food additives

Diet and anxiety

Diet is commonly considered the most important mediator of health and disease. Healthy diets can help prevent anxiety while poor diets can promote and sustain anxiety. Research shows that (Davison & Kaplan, 2012):

  • People with anxiety and depression tend to have poorer diet quality than those who do not experience these conditions
  • More chronic or severe the anxiety symptoms correlated with worse quality of diet

Mediterranean diet and anxiety

  • The mediterranean diet is considered a good model for a healthy diet. It includes foods that are beneficial, and also reduces or eliminates 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 as yogurt and cheeses.
    • whole grains instead of refined grains

Following a Mediterranean-type diet decreases risk of anxiety and depression. (Sadeghi et al., 2019)

Mediterranean diet for heart health

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

Davison KM & Kaplan BJ. (2012) Food intake and blood cholesterol levels of community based adults with mood disorders. BMC Psychiatry, 12, 10. https://doi.org/10.1186/1471-244X-12-10

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

Sadeghi et al. (2019) Adherence to Mediterranean dietary pattern is inversely associated with depression, anxiety and psychological distress. Nutritional Neuroscience, 1–12. https://doi.org/10.1080/1028415X.2019.1620425

Sugar and anxiety

  • 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 have roles in preventing anxiety.
  • Sugar may also increase blood lactate levels. Increased blood lactate increases risk of anxiety.
  • Symptoms of hypoglycemia can be confused with, or trigger anxiety. (See hypoglycemia section)

Gluten and anxiety

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

  • With anxiety patients, the foods most often involved with symptoms contain gluten (Scott, 2011)
  • 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 and depression (Scott, 2011)
  • Gluten sensitivity can decrease serotonin (Pynnönen, 2005). Low serotonin is a risk factor for anxiety.
  • Removing gluten from the diet can help resolve anxiety – especially in people who do not benefit from anti-anxiety medications (Potocki, & Hozyasz, 2002)

Sources of Gluten

  • grains: wheat, rye, barley, triticale
  • grain byproducts: brewer’s yeast, malt, starch
  • pastas, noodles
  • baked goods: bread, cakes, cookies, crackers
  • sauces and gravy (starch)
  • beer

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REFERENCES

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

Pynnönen et al. (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/

Artificial sweeteners/aspartame and anxiety

Artificial sweeteners are widely used in processed foods. They are synthetic molecules which have variety of affects on metabolism, including brain function. Artificial sweeteners include:

  • acesulfame K,
  • aspartame
  • neotame
  • saccharin
  • sucralose

Anxiety is a reported side effect of aspartame consumption (Roberts 2013). Aspartame has been shown to worsen nervousness and depression, and cause headaches, insomnia, and dizziness (Bradstock et al., 1986; Humphries, Pretorius, & Naudé, 2008)

Monosodium glutamate (MSG) and anxiety

Monosodium glutamate, the sodium salt of glutamic acid (glutamate), is one of the most commonly used food additives in commercially prepared foods. It is a flavour enhancer that has the taste sensation of “savoury”.

Common food sources of MSG include (Kubala, 2020):

  • fast foods and snack foods
  • seasoning blends and condiments
  • frozen meals
  • soups and instant noodle products
  • processed meats
Glutamate and anxiety

Glutamate is an amino acid that excites the brain and is involved in the pathophysiology of severe and chronic psychiatric conditions, including anxiety and depression disorders. (Kraal et al.,  2020)

Glutamate has been shown to promote elevated psychological and physiological arousal processes that may relate to anxiety (American Psychiatric Association, 2013)

Animal and human studies have shown that even minimal amounts of MSG have toxic effects on the body. Some of the toxic effects of MSG may be lessened by vitamins A, C, D, and E (Niaz, Zaplatic, & Spoor, 2018)
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REFERENCES

American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). American Psychiatric Association. https://doi.org/10.1176/appi.books.9780890425596

Bradstock et al. (1986) Evaluation of reactions to food additives: The aspartame experience. The American Journal of Clinical Nutrition, 43(3), 464–469. https://doi.org/10.1093/ajcn/43.3.464

Humphries P, Pretorius E & Naudé H (2008) Direct and indirect cellular effects of aspartame on the brain. European Journal of Clinical Nutrition, 62(4), 451–462. https://doi.org/10.1038/sj.ejcn.1602866

Kubala J (2020) 8 Foods That Contain MSG. EcoWatch. https://www.ecowatch.com/foods-that-contain-msg-2645159724.html?rebelltitem=9#rebelltitem9?rebelltitem=9

Niaz K, Zaplatic E & Spoor J (2018) Extensive use of monosodium glutamate: A threat to public health?. EXCLI journal, 17, 273–278. https://doi.org/10.17179/excli2018-1092
Roberts HJ (2013) Reactions attributed to aspartame-containing products: 551 cases. Journal of Applied Nutrition. 40(2):85–94.
Kraal et al. (2020) Could dietary glutamate play a role in psychiatric distress? Neuropsychobiology, 79(1), 13–19. https://doi.org/10.1159/000496294

Substances

Alcohol and anxiety

Alcohol has been shown to increase feelings of anxiety (Montiero, Schuckit, & Irwin, 1990) This may be due to the fact that alcohol depletes several essential nutrients required for preventing anxiety, such as vitamins B1, B6 and folate, vitamin C, magnesium, zinc, and fatty acids (Pizzorno & Murray, 2000).

Alcohol has also been shown to promote hypoglycemia and decrease serotonin (see hypoglycemia and anxiety section)

People with anxiety may react to ingredients in alcohol including wheat, rye, barley, corn, and added sulfites.

Alcohol inhibits gluconeogenesis from lactate.This inhibition increases the lactate to pyruvate ratio. People who are sensitive to lactate can then be more prone to anxiety attacks.
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REFERENCES

Monteiro MG, Schuckit MA & Irwin M (1990) Subjective feelings of anxiety in young men after ethanol and diazepam infusions. The Journal of Clinical Psychiatry, 51(1), 12–16.

Pizzorno JE & Murray MT (2000) Textbook of Natural Medicine. London: Harcourt

Caffeine and anxiety

  • Caffeine can cause anxiety in normal individuals, but can be especially provoking in pre-existing anxiety disorders (Broderick & Benjamin, 2004)
  • A single cup of coffee, or even a few sips of a caffeinated beverage can be problematic in patients with anxiety disorders (Boulenger et al., 1984; Clemenz & Dailey, 1988)
  • Chronic or heavy use of caffeine can increase anxiety (Clemenz & Dailey, 1988)
  • Long-term caffeine consumption is linked to anxiety and depression (Bruce & Lader, 1989)
  • People with panic disorders and/or social anxiety are more sensitive to the anxiety effects of caffeine (Lara, 2010)

Effects of caffeine on anxiety

  • Effects of excessive caffeine consumption can be indistinguishable from anxiety symptoms. These effects include nervousness, irritability, palpitations, insomnia. Caffeine withdrawal can also mimic anxiety (Greden, 1974)
  • Other known effects of caffeine associated with anxiety include: increased heart rate, body temperature, blood flow, blood sugar levels, and the promotion of insomnia

Roles of caffeine in anxiety

  • Caffeine depletes B vitamins, vitamin C, potassium, magnesium, calcium, zinc (Scott, 2011)
  • Caffeine increases lactate in blood. This results in people who are sensitive to lactate being more prone to anxiety attack (Pizzorno & Murray, 2000)
  • Caffeine increases adrenal production of epinephrine and norepinephrine, which over time, can weaken the adrenal glands (Levi, 1967)
  • Excess caffeine makes the way the body responds to hypoglycemia worse (See Hypoglycemia and Anxiety section)

People with anxiety may metabolize caffeine slower than average person, resulting in higher peak concentration, or increased sensitivity to caffeine (Gaby, 2011)
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REFERENCES

Boulenger et al. (1984) Increased sensitivity to caffeine in patients with panic disorders. Preliminary evidence. Archives of General Psychiatry, 41(11), 1067–1071. https://doi.org/10.1001/archpsyc.1983.01790220057009

Bruce MS & Lader M (1989) Caffeine abstention in the management of anxiety disorders. Psychological Medicine, 19(1), 211–214. https://doi.org/10.1017/s003329170001117x

Broderick P & Benjamin AB (2004) Caffeine and psychiatric symptoms: A review. The Journal of the Oklahoma State Medical Association, 97(12), 538–542.

Clementz GL & Dailey JW (1988) Psychotropic effects of caffeine. American Family Physician, 37(5), 167–172.

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

Greden JF (1974) Anxiety or caffeinism: A diagnostic dilemma. American Journal of Psychiatry, 131(10), 1089–1092. https://doi.org/10.1176/ajp.131.10.1089

Lara DR (2010) Caffeine, mental health, and psychiatric disorders. Journal of Alzheimer’s Disease: JAD, 20 Suppl 1, S239-248. https://doi.org/10.3233/JAD-2010-1378

Levi L (1967) The effect of coffee on the function of the sympatho-adrenomedullary system in man. Acta Medica Scandinavica, 181(4), 431–438. https://doi.org/10.1111/j.0954-6820.1967.tb07260.x

Pizzorno JE & Murray MT (2000) Textbook of Natural Medicine. London: Harcourt

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.

Nicotine and anxiety

  • Nicotine is a stimulant compound found in tobacco and it has been shown to increase heart rate and blood pressure.
  • Smoking increases the risk of panic attacks and panic disorder (Goodwin, Lewinsohn, & Seeley, 2005)
  • Although smoking can temporarily relieve immediate anxiety symptoms, chronic smoking can increase chronic nervousness and agitation.
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REFERENCES

Goodwin RD, Lewinsohn PM & Seeley JR (2005) Cigarette smoking and panic attacks among young adults in the community: The role of parental smoking and anxiety disorders. Biological Psychiatry, 58(9), 686–693. https://doi.org/10.1016/j.biopsych.2005.04.042

Environmental factors

Heavy metals and anxiety

  • Heavy metals like mercury, lead, and cadmium are prevalent in the environment we live in.  Accumulation of heavy metals in the body and brain affect mental health.
  • The brain is especially susceptible to accumulation and storage of fat-soluble toxic metals due to its high fatty-acid composition (Orisakwe, 2014).
  • Mercury accumulation from environmental exposures, consuming mercury-containing fish and having dental fillings have been shown to promote anxiety and agitation (O’Carroll, Masterton, Dougall, Ebmeier, & Goodwin, 1995: Kidd, 2000)
  • Lead accumulation may be implicated in anxiety and panic attacks (Bouchard et al., 2009)
  • Attention, psychomotor activity, and memory are negatively affected by cadmium, and exposure during prenatal and neonatal periods has been shown to cause anxiety, mood disorders, and schizophrenia later in life. (Orisakwe, 2014).
  • Excess copper increases the conversion of dopamine to norepinephrine and epinephrine in the body. This conversion can promote feelings of anxiety, panic, and agitation (Tsafrir, 2017).

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

It is important to work with a practitioner that is trained in detoxification when addressing excessive or chronic heavy metal exposure or accumulation.


References

Bouchard M, Bellinger DC, Weuve J, Matthews-Bellinger J, Gilman SE, Wright RO, Schwartz J & Weisskopf MG. (2009) Blood lead levels and major depressive disorder, panic disorder, and generalized anxiety disorder in U.S. young adults. Archives of General Psychiatry, 66(12), 1313–1319. https://doi.org/10.1001/archgenpsychiatry.2009.164

Kidd RF. (2000) Results of dental amalgam removal and mercury detoxification using DMPS and neural therapy. Alternative Therapies in Health and Medicine, 6(4), 49–55.

O’Carroll R, Masterton G, Dougall N, Ebmeier K & Goodwin G. (1995) The neuropsychiatric sequelae of mercury poisoning: The mad hatter’s disease revisited. British Journal of Psychiatry, 167(1), 95-98. https://doi.org/10.1192/bjp.167.1.95

Orisakwe, O. E. (2014). The role of lead and cadmium in psychiatry. North American Journal of Medical Sciences, 6(8), 370. https://doi.org/10.4103/1947-2714.139283.

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

Tsafrir, J. (n.d.). Copper toxicity: A common cause of psychiatric symptoms. Psychology Today. Retrieved April 30, 2020, from https://www.psychologytoday.com/ blog/holistic-psychiatry/201709/copper-toxicity- common-cause-psychiatric-symptoms.

Medications

Medications and anxiety

  • Some medications promote anxiety by causing symptoms that include restlessness, nervousness, insomnia. Some implicated medications include decongestants, steroids, and respiratory medications.
  • Antidepressant medications can promote anxiety, depression, addiction, suicidal tendencies, tremors or involuntary muscle spasms, and senility (Murphy, 2009).
  • Benzodiazepines are associated with numerous unwanted side effects, including poor sleep, seizures, mania, depression, suicide, ringing in the ears, amnesia, dizziness, anxiety, disorientation, low blood pressure, nausea, fluid retention, tremors, sexual dysfunction (decreased desire and performance), weakness, somnolence (prolonged drowsiness or a trancelike condition that may continue for a number of days), and headaches (Murphy, 2009).

Resources

Tools for understanding the effects of medications and what you need to know to safely taper off them:

https://benzo.org.uk/

https://benzo.org.uk/manual/index.htm


References

Murphy RH. (2009). Treating and Beating Anxiety and Depression with Ortomolecular Therapy. Townsend Letter for Doctors & Patients. Retrieved from https://www.townsendletter.com/Dec2009/ortho1209.html

Medication-induced nutrient deficiencies and anxiety

Many types of medications deplete essential nutrients that have roles in preventing anxiety. Research has shown that:

  • Oral contraceptives, antidepressants, and decongestants deplete vitamin B6 (Pelton, LaValle, & Hawkins, 2001)
  • Corticosteroids, ACE inhibitors and oral contraceptives deplete zinc.  (Scott, 2011)
  • Lead may promote anxiety, panic attacks, and depression (Bouchard et al., 2009)

Further information

An in-depth examination of common medications and nutrient depletions. (Mohn et al. 2018)

https://doi.org/10.3390/pharmaceutics10010036


References

Bouchard, M., Bellinger, D. C., Weuve, J., Matthews-Bellinger, J., Gilman, S. E., Wright, R. O., Schwartz, J., & Weisskopf, M. G. (2009). Blood lead levels and major depressive disorder, panic disorder, and generalized anxiety disorder in U.S. young adults. Archives of General Psychiatry, 66(12), 1313–1319. https://doi.org/10.1001/archgenpsychiatry.2009.164

Mohn ES, Kern HJ, Saltzman E, Mitmesser SH & McKay DL. (2018) Evidence of drug–nutrient interactions with chronic use of commonly prescribed medications: An update. Pharmaceutics, 10(1). https://doi.org/10.3390/pharmaceutics10010036

Pelton, R., LaValle, J. B., & Hawkins, E. B. (2001). Drug-Induced Nutrient Depletion Handbook. Hudson OH. Lexi-Comp.

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.

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 from diet, medications.

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 and anxiety

  • Food sensitivities can cause imbalances in key brain chemicals and can cause anxiety, phobias, depression, irritability, mood swings (Pfeiffer 1987: Rippere & Phil, 1984)
  • “Adults and children suffering from food allergy show impaired quality of life and a higher level of stress and anxiety” (Teufel et al., 2007).

Food allergies and sensitivities

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

Cerebral allergies are mediated by:

  1. direct biochemial 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

References

Pfeiffer C. (1987) Nutrition and Mental Illness. Rochester, VT: Healing Arts Press.

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

Rippere V & Phil M. (1984) Some varieties of food intolerance in psychiatric patients: An overview. Nutrition and Health. https://agris.fao.org/agris-search/search.do?recordID=US201301437620

Hypoglycemia and anxiety

  • Symptoms of hypoglycemia can be confused with, or trigger anxiety.
  • Hypoglycemia a common contributing factor or main cause for anxiety (Rippere & Phil, 1984): Salzer, 1966).
  • Fatigue, irritability (Eaton & Konner, 1985) and nervousness, sudden mood changes, rapid heartbeat (Nall, 2012), are common physiological symptoms of hypoglycemia

How hypoglycemia promotes anxiety

  • Consuming a high-carbohydrate meal or drink causes a rapid rise in blood glucose. The high glucose causes the pancreas to release an abnormally high amount of insulin into the blood, which cause an abrupt drop in blood glucose.
  • The excessive drop in blood sugar triggers the release of the hormones epinephrine and norepinephrine, which in turn, trigger the fight or flight response.
  • The fight or flight response shows up as hunger, irritability, sweating, palpitations, and anxiety.

Identifying hypoglycemia:

  • People with hypoglycemia tend to crave sweets.
  • Consuming sugar or refined starches temporarily reduces the anxiety symptoms.
  • Symptoms worsen in the late morning or late afternoon.
  • Mental and anxiety symptoms occur after fasting, late at night, or first thing in the morning (Eaton & Konner, 1985).
  • Typical medical tests to assess blood-sugar metabolim are fasting glucose, HbA1c, but can also include insulin, cortisol, ketone bodies, lactic acid, free fatty acids, and thyroid hormone (Mandal, 2019).

References

Eaton SB & Konner M. (1985) Paleolithic nutrition. New England Journal of Medicine, 312(5), 283–289. https://doi.org/10.1056/NEJM198501313120505

Mandal D. (2019) Hypoglycemia diagnosis. Retrieved September 25, 2020, from https://www.news-medical.net/health/Hypoglycemia-Diagnosis.aspx

Nall R. (2012). Low blood sugar (hypoglycemia): Symptoms, complications, causes. Retrieved September 25, 2020, from https://www.healthline.com/health/hypoglycemia

Rippere V & Phil M. (1984) Some varieties of food intolerance in psychiatric patients: An overview. Nutrition and Health. 3:125–136

Salzer HM. (1966) Relative hypoglycemia as a cause of neuropsychiatric illness. Journal of the National Medical Association, 58(1), 12–17.

Pyroluria and anxiety
  • Pyrroles are a by-product of hemoglobin production and normally excreted in the urine.
  • Pyroluria is a condition of overproduction of pyrroles (McGinnis 2008a, 2008b). Excess pyrroles bind vitamin B6 (pyridoxine) and zinc, removing them from the bloodstream.
The mental symptoms of pyroluria are largely related to zinc and vitamin B6 deficiencies. Symptoms of these deficiencies include:
  • anxiety and depression
  • mood swings
  • poor stress control
  • severe inner tension
  • episodic anger
  • nervousness
  • poor short-term memory
Pyroluria can be objectively diagnosed by elevated levels of HPL, as measured by the kryptopyrrole quantitative urine test. The amount of kryptopyrrole can fluctuate dramatically. Stress, illness, and injury increase levels, so for optimal test results, the urine should be collected during a period of increased stress.

Supplementation support for pyroluria (Greenblatt, 2018)

  • 200-800 mg of vitamin B6 in the pyridoxal-5-phosphate form
  • 25–100 mg of zinc

Dr. Jonathan Prousky (2006) stated, “Although I could test for this compound [HPL], I choose not to, since these nutrients are inexpensive and have minimal side effects. The daily dosages I routinely start with are 250 mg of pyridoxine and 50 mg of zinc”.


References
Greenblatt J. (2018, May 24) Integrative therapies for schizophrenia and psychosis, Module 1 [Webinar]. Retrieved from: https://isom.ca/schizophrenia-psychosis/
McGinnis WR, Audhya T, Walsh WJ, Jackson JA, McLaren-Howard J, Lewis A & Ho er A. (2008a) Discerning the mauve factor, Part 1. Alternative Therapies in Health and Medicine, 14(2), 40–50.
McGinnis WR, Audhya T, Walsh WJ, Jackson JA, McLaren-Howard J, Lewis A & Ho er A. (2008b) Discerning the mauve factor, Part 2. Alternative Therapies in Health and Medicine, 14(3), 56–62.
Prousky J. (2006) The orthomolecular treatment of schizophrenia. Naturopathic Doctor News and Review. https://ndnr.com/neurology/the-orthomolecular-treatment-of-schizophrenia/

Orthomolecular interventions for anxiety

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

Vitamins

Vitamin B1 (Thiamin) and anxiety

Chronic borderline thiamin deficiency may be associated with increased anxiety (Heseker, Kübler, Pudel & Westenhöffer, 1992).

Thiamin and the lactate to pyruvate ratio

Thiamin is a cofactor for the enzyme lactate dehydrogenase – which reduces the amount of lactate in the blood (Donnino, n.d.). Thiamin deficiency can be lead to elevated lactate in the blood. Elevated levels of lactate increases the ratio of lactate to pyruvate, which is associated with increased anxiety.

Causes of thiamin deficiencies:

  • inadequate intake and excessive consumption of refined grains and sugars
  • poor nutrient absorption
  • excessive alcohol consumption

Top food sources of thiamin based on typical serving size:

  • pork, lean
  • green peas
  • long-grain, brown rice
  • pecans
  • lentils

Comprehensive food list:
Table 2. Some Food Sources of Thiamin (Thiamin, 2014)
https://lpi.oregonstate.edu/mic/vitamins/thiamin

Referenced Dietary Intakes
RDAs for Thiamin (mg/day)
Children (9-13 years): 0.9 (M) 0.9 (F)
Adolescents (14-18 years): 1.2 (M) 1.0 (F)
Adults (19 years and older): 1.2 (M) 1.1 (F)

Vitamin B1 Supplementation

Amounts of thiamin used in practice and research range from 50–1000 mg/day in divided doses.
(Thiamin, 2014)

SAFETY, SIDE EFFECTS
There are no well-established toxic effects from consumption of excess thiamin in food or through long-term, oral supplementation (up to 200 mg/day) (Thiamin, 2014).

VITAMIN B1 AND MEDICATIONS
Thiamin is not known to interact with any medications (Thiamin, n.d.).


References

Donnino, M. (n.d.). Effect of Thiamine on Pyruvate Dehydrogenase Activity in Septic Shock. Retrieved September 26, 2020, from https://grantome.com/grant/NIH/K02-HL107447-01A1

Heseker, H., Kübler, W., Pudel, V., & Westenhöffer, J. (1992). Psychological Disorders as Early Symptoms of a Mild-to-Moderate Vitamin Deficiencya. Annals of the New York Academy of Sciences, 669(1), 352–357. https://doi.org/10.1111/j.1749-6632.1992.tb17121.x

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

Thiamin. (2014, April 22). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/vitamins/thiamin

Vitamin B3 (Niacin) and anxiety

Vitamin B3 deficiency is known as pellagra. Dr. Abram Hoffer reported that the earliest symptoms of subclinical pellagra appear as anxiety, depression, and fatigue (Prousky, 2015.)

Actions of vitamin B3 in regards to anxiety: 

  • helps correct subclinical pellagra
  • increases serotonin production by diverting more tryptophan conversion to serotonin (Gedye, 2001)
  • helps improve the lactate to pyruvate ratio by modifying lactate metabolism
  • has sedative, benzodiazepine effects (Hoffer, 1962)
  • can increase the effectiveness of some sedatives, tranquilizers, and anticonvulsants (Hoffer, 1962, 24-31)

Causes of vitamin B3 deficiencies (Niacin, 2014):

  • inadequate oral intake
  • poor bioavailability from grain sources
  • issues with absorption of tryptophan
  • some metabolic disorders, and the long-term chemotherapy treatments

Top food sources of vitamin B3 based on serving size:

  • chicken
  • tuna
  • turkey
  • salmon
  • beef

Comprehensive food list:
Table 2. Some Food Sources of Niacin (Niacin, 2014)
https://lpi.oregonstate.edu/mic/vitamins/niacin

Referenced Dietary Intakes

Tolerable Upper Intake Level (UL) for Niacin and niacinamide (mg/day)
Children (9-13 years): 20
Adolescents (14-18 years): 30
Adults (19 years and older): 35

The Food and Nutrition Board set the tolerable upper intake level (UL) for niacin (nicotinic acid and nicotinamide) at 35 mg/day in adults to avoid the adverse effect of flushing. (Niacin, 2014)

1. Vitamin B3 (niacin) Supplementation

  • Amounts of niacin/nicotinic acid used in practice and research range from 100–3000 mg/day in divided doses (Niacin, 2014).

SAFETY, SIDE EFFECTS

  • People who may be more susceptible to the effects of excess niacin intake include those with: abnormal liver function or liver disease, diabetes, active peptic ulcer disease, gout, cardiac arrhythmias, inflammatory bowel disease, migraine headaches, or alcoholism (Niacin, 2014).
  • Extended-release niacin has been associated with increased risk of serious adverse events (Anderson et al. 2014).

2. Vitamin B3 (nicotinamide) Supplementation

  • Amounts of nicotinamide used in practice and research range from 300–3000 mg/day in divided doses (Niacin, 2014).
  • Dr. Abram Hoffer recommended 1500–6000 mg of niacinamide for all patients with psychiatric syndromes (Hoffer, 1995).
  • Most people need a minimum of  2000–4500 mg/day of niacinamide, and relief of symptoms can be seen within one month (Prousky, 2015)

SAFETY, SIDE EFFECTS

  • Niacinamide supplementation doses of 1500-6000 mg have been used for extended amounts of time in children and adolescents without side effects or complications (Hoffer, 1971: Hoffer 1999).
  • Niacinamide does not generally cause flushing. The most common side effect of niacinamide supplementation is sedation (Werbach, 1997, p133-60).
  • At very high doses (≥10 g/day), nausea, vomiting, and signs of liver toxicity (elevated liver enzymes, jaundice) have been observed (Niacin, 2014).

References

Anderson, T. J., Boden, W. E., Desvigne-Nickens, P., Fleg, J. L., Kashyap, M. L., McBride, R., & Probstfield, J. L. (2014). Safety Profile of Extended-Release Niacin in the AIM-HIGH Trial. New England Journal of Medicine, 371(3), 288–290. https://doi.org/10.1056/NEJMc1311039

Buist, R. A. (1985). Anxiety neurosis: The lactate connection. International Clinical Nutrition Review. 5:1-4. 

Gedye, A. (2001). Hypothesized treatment for migraines using low doses of tryptophan, niacin, calcium, caffeine, and acetylsalicylic acid. Medical Hypotheses, 56(1), 91–94. https://doi.org/10.1054/mehy.2000.1117

Hoffer A. (1962). Nicotinic acid and niacinamide as sedatives. Niacin Therapy in Psychiatry. Springfield, IL: C.C. Thomas.

Hoffer, A.(1995). Vitamin B-3: Niacin and its amide. Townsend Letter for Doctors & Patients 147:30-39.

Hoffer, A. (1971). Vitamin B3 dependent child. Schizophrenia 3:107-13.

Hoffer. A. (1999). Dr. Hoffer’s ABC of Natural Nutrition for Children. CCNM Press.

Niacin. (2014, April 22). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/vitamins/niacin

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

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

Vitamin B6 and anxiety

Vitamin B6 is required for:

  • Conversion of the amino acid tryptophan into serotonin – Low levels of serotonin are associated with anxiety
  • Conversion of glutamate into GABA – Glutamate is a stimulatory neurotransmitter and elevated levels of it can promote anxiety. 
  • Reduction of lactate – Excess lactate can increase anxiety. Vitamin B6 helps decrease lactate by directing it to the Krebs cycle for use in energy production
  • Reduction of homocysteine – Elevated homocysteine has been implicated in anxiety symptoms.

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 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,.

Vitamin B12 and anxiety

A deficiency of vitamin B12 can affect mood, emotions, sleep, and can result in psychiatric disorders. (Valizadeh & Valizadeh, 2011)

Roles of vitamin B12 in the context of anxiety: 

  • Required for the synthesis of neurotransmitters including serotonin and dopamine
  • Required for the preservation of protective myelin sheath around neurons
  • Important for homocysteine metabolism

Psychiatric manifestations of vitamin B12 deficiency include (Oh & Brown, 2003: Dommisse, 1991):

  • agitation, restlessness, irritability
  • dementia
  • depression, fatigue
  • mild memory impairment
  • negativism
  • panic/phobic disorders
  • personality changes
  • psychosis

The most common causes of vitamin B12 deficiency:

  • vitamin B12-deficient diet
  • vegetarianism or veganism
  • decreased stomach acid production
  • bacterial overgrowth in the small intestine

People with anxiety may have higher needs due to decreased vitamin B12 transport across the blood-brain barrier (Arora, Sequeira, Hernández, Alarcon, & Quadros, 2017), or because of increased breakdown of vitamin B12 in brain tissue (Gaby, 2011)

Vitamin B12 levels can be normal in blood tests but be deficient in the cerebral spinal fluid. (Prousky, 2015)

Top food sources of vitamin B12 by serving size:

  • clams, mussels
  • mackerel
  • crab
  • beef

Comprehensive food list:
Table 2. Some Food Sources of vitamin B12 (Vitamin B12, 2014)
https://lpi.oregonstate.edu/mic/vitamins/vitamin-B12

Referenced Dietary Intakes

RDAs for vitamin B12 (mcg/day)
Adolescents (14-18 years): 2.4 (M) 2.4 (F)
Adults (19-50 years): 2.4 (M) 2.4 (F)
Adults (51 years and older): 2.4 (M) 2.4 (F)

Tolerable Upper Intake
Not established due to low potential for toxicity.

1. Vitamin B12 Supplementation

  • Amounts of vitamin B12 used in practice and research range from 1000–5000 IU/day in divided doses.
  • The preferred form of vitamin B12 is methylcobalamin, due to its greater tissue retention (“Methylcobalamin”, 1998)
  • Vitamin B12 is best absorbed in sublingual form.
  • “Those strict vegetarians who eat no animal products (vegans) need supplemental vitamin B12 to meet their requirements” (Vitamin B12, 2014)
  • Vitamin B12 supplementation may have the best clinical response when used in the context of anxiety and fatigue or depression (Prousky, 2015)

2. Vitamin B12 injections

  • A typical injection regimen is 1000 mcg every 2 weeks.
  • Patients who respond to vitamin B12 injections typically need ongoing injections to maintain symptom improvement (Gaby, 2011).
  • Many anxiety patients benefit from B12 injections even though they have no clinical evidence of deficiency (Prousky, 2015).

SAFETY, SIDE EFFECTS

  • The Institute of Medicine states that “no adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals” (Vitamin B12, 2014).

References

Arora, K., Sequeira, J. M., Hernández, A. I., Alarcon, J. M., & Quadros, E. V. (2017). Behavioral alterations are associated with vitamin B12 deficiency in the transcobalamin receptor/CD320 KO mouse. PLoS ONE, 12(5). https://doi.org/10.1371/journal.pone.0177156

Dommisse, J. (1991). Subtle vitamin-B12 deficiency and psychiatry: A largely unnoticed but devastating relationship? Medical Hypotheses, 34(2), 131–140. https://doi.org/10.1016/0306-9877(91)90181-w

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

Methylcobalamin. (1998). Alternative Medicine Review: A Journal of Clinical Therapeutic, 3(6), 461–463.

Oh, R., & Brown, D. L. (2003). Vitamin B12 deficiency. American Family Physician, 67(5), 979–986.

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

Valizadeh, M., & Valizadeh, N. (2011). Obsessive Compulsive Disorder as Early Manifestation of B12 Deficiency. Indian Journal of Psychological Medicine, 33(2), 203–204. https://doi.org/10.4103/0253-7176.92051

Vitamin B12. (2014, April 22). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/vitamins/vitamin-B12

Folate and anxiety

  • Folate is essential for brain development and function
  • Folate deficiency is associated with increased homocysteine
  • Anxiety is a symptom of folate deficiency (Howard, 1975, 112-115)
  • A marginal folate deficiency may aggravate anxiety caused by other factors (Gaby, 2011)

Causes of folate deficiencies

  • low dietary intake
  • poor absorption
  • gastrointestinal issues
  • chronic alcoholism
  • smoking
  • oral contraceptives (Gaby, 2011)
  • drug interactions (Folate, 2014)
  • genetic variations in folate metabolism, for example variations the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene  (“Folate”, 2014)

Top food sources of folate by serving size:

  • lentils
  • chickpeas
  • asparagus
  • spinach

Comprehensive food list:
Table 2. Some Food Sources of folate and folic acid (Folate, 2014)
https://lpi.oregonstate.edu/mic/vitamins/folate

Referenced Dietary Intakes

RDAs for vitamin B12 (mcg/day)
Adolescents (14-18 years): 2.4 (M) 2.4 (F)
Adults (19-50 years): 2.4 (M) 2.4 (F)
Adults (51 years and older): 2.4 (M) 2.4 (F)

Tolerable Upper Intake:
Not established due to low potential for toxicity.

The Food and Nutrition Board of the US Institute of Medicine recommends a maximum intake of 1000 mcg of the folic acid form of folate – from supplements and fortified food.

Supplementing folate

  • Amounts of folate/folic acid used in practice and research range from 100–5000 mcg/day in divided doses (Office of Dietary Supplements, n.d.).
  • A good quality multivitamin/mineral supplement typically contains 400 mcg folate.

SAFETY, SIDE EFFECTS

  • Folate supplementation may mask an underlying vitamin B12 deficiency.
  • In order to be very sure of preventing irreversible neurological damage in vitamin B12-deficient individuals, the Food and Nutrition Board of the US Institute of Medicine advises that all adults limit their intake of folic acid (supplements and fortification) to 1,000 μg (1 mg) per day (Folate, 2014).

References

Folate. (2014, April 22). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/vitamins/folate

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

Howard, J. S. III. (1975). Folate deficiency in psychiatric practice. Psychosomatics, 16.

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

Inositol and anxiety

  • Inositol has important roles in the function of norepinephrine, GABA and serotonin receptors (Benjamin, Agam, Levine, Bersudsky, Kofman, & Belmaker, 1995) and may decrease anxiety symptoms (Supplement sampler, 2020).

Causes of deficiencies

  • An inositol-deficient diet
  • High amounts of dietary glucose – which decreases myo-inositol synthesis and absorption, and increases its degradation rate (Dinicola, Minini, Unfer, Verna, Cucina, & Bizzarri, 2017).

Good sources of inositol (Clements & Darnell, 1980)

  • meat and eggs
  • oranges, grapefruit, lime 
  • peaches, pears
  • whole grains
  • beans and legumes
  • rutabaga

Referenced Dietary Intakes

RDAs/Upper intakes for Inositol
Not established.

Inositol Supplementation

  • Inositol supplementation can increase inositol levels in the brain (Benjamin et al., 1995).
  • Amounts of inositol used in practice and research range from 12–18 g/day in divided doses (Supplement sampler, 2020).
  • The dose should be increased gradually over several weeks. Inositol powder can be added to juice.

SAFETY, SIDE EFFECTS

  • Inositol can cause nausea, fatigue, dizziness, and headaches.
  • Use of inositol has not been associated with and substantial side effects (Benjamin et al., 1995)

INOSITOL AND MEDICATIONS

  • There are no known adverse reactions with other medications and supplements (Supplement sampler, 2020).

References

Benjamin, J., Agam, G., Levine, J., Bersudsky, Y., Kofman, O., & Belmaker, R. H. (1995). Inositol treatment in psychiatry. Psychopharmacology Bulletin, 31(1), 167–175.

Benjamin, J., Levine, J., Fux, M., Aviv, A., Levy, D., & Belmaker, R. H. (1995). Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. The American Journal of Psychiatry, 152(7), 1084–1086. https://doi.org/10.1176/ajp.152.7.1084

Clements, R. S., & Darnell, B. (1980). Myo-inositol content of common foods: Development of a high-myo-inositol diet. The American Journal of Clinical Nutrition, 33(9), 1954–1967. https://doi.org/10.1093/ajcn/33.9.1954

Dinicola, S., Minini, M., Unfer, V., Verna, R., Cucina, A., & Bizzarri, M. (2017). Nutritional and Acquired Deficiencies in Inositol Bioavailability. Correlations with Metabolic Disorders. International Journal of Molecular Sciences, 18(10). https://doi.org/10.3390/ijms18102187

“Supplement Sampler, Inositol”. University of Wisconsin Integrative Medicine. Retreived October 28, 2020, from https://www.fammed.wisc.edu/files/webfm-uploads/documents/outreach/im/ss_inositol.pdf

Minerals

Magnesium and anxiety

Magnesium in the context of anxiety (Kirkland, Sarlo, & Holton, 2018)

  • Calms neurotransmission by regulating glutamate and GABA
  • Modulates the hypothalamic–pituitary–adrenal (HPA) axis
  • Has roles in the synthesis of serotonin and dopamine
  • Regulates cortisol levels
  • Increases brain-derived neurotrophic factor (BDNF)
  • Magnesium supplementation has been shown to decrease the lactate to pyruvate ratio (Fishbein, 1982)

Magnesium deficiency promotes anxiety and decreases stress tolerance (Henrotte, 1986).

Reasons for magnesium deficiencies:

  • Increased stress (causes magnesium depletion) which in turn increases anxiety
  • Low dietary protein (needed for magnesium absorption)
  • Gastrointestinal disorders (e.g. Crohn’s disease, malabsorption syndromes, and prolonged diarrhea)
  • High doses of supplemental zinc (competes for absorption)
  • Certain diuretic medications
  • Alcoholism

Elderly adults tend to have lower dietary intake, absorption, and increased loss of magnesium.

Top food sources of magnesium by serving size

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

Comprehensive 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/day in divided doses (elemental magnesium dose).

SAFETY, SIDE EFFECTS

  • Side effects of magnesium supplementation are rare, but can include a laxative effect, dizziness or faintness, sluggishness, cognitive impairment, and depression.

References

Fishbein, D. (1982) The contribution of refined carbohydrate consumption to maladaptive behaviors. Journal of Orthomolecular Psychiatry, 11:17–25.

Henrotte J. G. (1986) Type A behavior and magnesium metabolism. Magnesium, 5(3-4):201-210.

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

Chromium and anxiety

  • Chromium supplementation has been shown effective for addressing hypoglycemia (Anderson, 1986). Hypoglycemia is a  common contributing factor for anxiety. (See Hypoglycemia and Anxiety for more information)

Top sources of chromium based on serving size

  • broccoli
  • green beans
  • potatoes (mashed) 
  • beef
  • turkey breast

Comprehensive food list:
Table 2. Some Food Sources of Chromium (Chromium, 2014)
https://lpi.oregonstate.edu/mic/minerals/chromium

Referenced Dietary Intakes

Adequate Intakes for chromium (mcg/day)
Adolescents (14-18 years): 35 (M) 24 (F)
Adults (19-50 years): 35 (M) 25 (F)
Adults (51 years and older): 30 (M) 20 (F)

Supplementing chromium

  • Amounts of chromium used in practice and research range from 100–1000 mcg/day in divided doses (Office of Dietary Supplements, n.d.).

SAFETY, SIDE EFFECTS

  • The Food and Nutrition Board concluded that no adverse effects have been linked to high intakes of chromium from food or supplements, so it did not establish a UL for chromium (Office of Dietary Supplements, n.d.).

CHROMIUM AND MEDICATIONS

Chromium can interact with medication interactions including (Office of Dietary Supplements, n.d):

  • insulin
  • metformin and other anti-diabetes medications
  • levothyroxine

Anderson, R. A. (1986). Chromium metabolism and its role in disease processes in man. Clinical Physiology and Biochemistry, 4(1), 31–41.

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

Zinc and anxiety

  • Zinc has anti-anxiety and antidepressant effects, and is critical for regulating excitatory glutamate and NMDA receptor activity in the brain. (Andrews, 1990; Joshi, Akhtar, Najmi, Khuroo, & Goswami, 2012).

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).

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

Andrews, R. R. (1990). Unification of the  findings in schizophrenia by reference to the effects of gestational zinc deficiency. Medical Hypotheses, 31(2), 141-153.

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

Fatty acids and lipids

Essential fatty acids and anxiety

  • Polyunsaturated fatty acids (PUFAs) (omega 3 and 6 fatty acids) are necessary for normal development and function of the brain.
  • Omega 3 fatty acids and their metabolites have roles in regulating inflammation, neuroinflammation, and neurotransmission (Larrieu, & Layé, 2018) – all of which are factors in anxiety.
  • Higher consumption of DHA, a form of EFA, has been shown to be protective against anxiety (Jacka et al.).
  • Deficiency of essential fatty acids, or an imbalanced ratio of omega 6 to omega 3 fatty acids has been shown to correlate with anxiety and depression. (Rakel, 2012).

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)

Supplementating omega 3 fatty acids

  • Supplementation of omega 3 fatty acids seems beneficial for addressing anxiety (Bruinsma & Taren, 2000).
  • Fish oils, which are sources of EPA and DHA are considered preferable for addressing anxiety,  have been shown to have a wide range of neurobehavioural effects (Logan, 2003)
  • Successful addressing of anxiety has been demostrated with a daily dose of 1 gram of EPA. (Logan, 2003) 
  • 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.

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

Jacka, F. N., Pasco, J. A., Williams, L. J., Meyer, B. J., Digger, R., & Berk, M. (2013). Dietary intake of fish and PUFA, and clinical depressive and anxiety disorders in women. The British Journal of Nutrition, 109(11), 2059–2066. https://doi.org/10.1017/S0007114512004102

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

Logan, A. C. (2003). Neurobehavioral aspects of omega-3 fatty acids: Possible mechanisms and therapeutic value in major depression. Alternative Medicine Review: A Journal of Clinical Therapeutic, 8(4), 410–425.

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

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.

Amino acids

Glycine and anxiety

  • Glycine is an inhibitory neurotransmitter in the brainstem and spinal cord (Kawai et al., 2015)

Top sources of glycine based on serving size

  • gelatin
  • pork skins, hocks
  • beef
  • chicken breast

Comprehensive food list: Foods highest in Glycine (Foods highest in Glycine, n.d.)
https://nutritiondata.self.com/foods-000094000000000000000.html

Referenced Dietary Intakes

RDAs/Upper intakes for glycine
Not established.

Supplementing glycine

  • Amounts of glycine used in practice and research range from 3–60 g/day in divided doses.
  • Glycine is usually started at 4 grams daily and increased by 4 grams per day until the effective dose is reached (Glycine: Uses, Side Effects, n.d.).
  • Taking glycine sublingually is considered the most effective method of dosing.
  • 2 to 10 grams of glycine taken sublingually has been shown in practice to stop panic attacks.

SAFETY, SIDE EFFECTS

  • There have been rare reports of nausea and vomiting from glycine supplementation (Glycine: Uses and Risks, n.d.).

GLYCINE AND MEDICATIONS

  • Supplementing glycine along with clozapine (Clozaril) may decrease the effectiveness of the medication (Glycine: Uses, Side Effects, n.d.).

References

Foods highest in Glycine. (n.d.). Retrieved October 29, 2020, from https://nutritiondata.self.com/foods-000094000000000000000.html

Glycine: Uses and Risks. (n.d.). Retrieved October 29, 2020, from https://www.webmd.com/vitamins-and-supplements/glycine-uses-and-risks#2-4

Glycine: Uses, Side Effects, Interactions, Dosage, and Warning. (n.d.). Retrieved October 29, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-1072/glycine

Kawai, N., Sakai, N., Okuro, M., Karakawa, S., Tsuneyoshi, Y., Kawasaki, N., Takeda, T., Bannai, M., & Nishino, S. (2015). The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus. Neuropsychopharmacology, 40(6), 1405–1416. https://doi.org/10.1038/npp.2014.326

GABA and anxiety

  • GABA is the most important calming neurotransmitter in the body. Low levels of GABA are associated with anxiety (Lydiard 2003: Braverman 2003)

Food sources of GABA

There are no food sources of GABA.

Referenced Dietary Intakes

RDAs/Upper intakes GABA
Not established.

Supplementing GABA

  • Amounts of GABA used in practice and research range from 25–3000 mg/day in divided doses.
  • It has been proposed that GABA taken orally does not cross the blood-brain barrier in amounts sufficient for an effect. However, many people do see results from oral supplementation.
  • GABA is best taken away from meals.
  • 125 mg of GABA taken sublingually has been shown to promote mental and physical relaxation.
  • One or two 250–500 mg doses of GABA can be taken at bedtime or during times of stress.
  • Supplementing 2 to 3 g/day of GABA has been shown to help with sleep, promote relaxation, and control symptoms of anxiety (Braverman, 2010)

SAFETY, SIDE EFFECTS

Commonly reported side effects include (Gamma Aminobutyric Acid, n.d.):

  •  upset stomach
  •  headache
  •  sleepiness
  •  muscle weakness

GABA AND MEDICATIONS

  • Supplementing GABA while taking blood pressure medications may cause blood pressure to drop too low.
  • Consult medical advice before supplementing GABA with antidepressant medications (3 Amazing Benefits of GABA, n.d.).

References

3 Amazing Benefits of GABA. (n.d.). Psychology Today. Retrieved October 29, 2020, from https://www.psychologytoday.com/blog/sleep-newzzz/201901/3-amazing-benefits-gaba

Braverman, E. R. (2003). The healing nutrients within. Laguna Beach, CA: Basic Health Publications.

Braverman, E. R. (2012). The Healing Nutrients Within: Facts, Findings, and New Research on Amino Acids (3rd ed. Edition). Basic Health Publications, Inc.

Gamma Aminobutyric Acid: Uses and Side Effects of GABA Supplement. (n.d.). Retrieved October 29, 2020, from https://www.healthline.com/health/gamma-aminobutyric-acid#takeaway

Lydiard, R. B. (2001). Irritable bowel syndrome, anxiety, and depression: What are the links? The Journal of Clinical Psychiatry, 62(Suppl8), 38–45.

Theanine and anxiety

  • Theanine is a calming amino acid. The L-theanine form of theanine is extracted from green tea.
  • L-theanine helps reduce anxiety by enhancing alpha brain wave activity and increasing GABA synthesis. Increased GABA levels promote feelings of calm and well-being by raising brain serotonin and dopamine levels (Mason, 2001).

Referenced Dietary Intakes

RDAs/Upper intakes for theanine
Not established.

Supplementing theanine

  • Amounts of theanine used in practice and research range from 100–400 mg/day in divided doses (L-Theanine Uses, Benefits, n.d.).
  • L-theanine dosing (Lopes Sakamoto, F., Metzker Pereira Ribeiro, R., Amador Bueno, A., & Oliveira Santos, 2019):
  • Daily supplementation of L-theanine of 200 to 400 mg for up to 8 weeks has been shown in published research to decrease anxiety symptoms and decrease stress, with both acute and chronic anxiety. 
  • A 50 to 200 mg dose of L-theanine usually results in a calming effect within 30 to 40 minutes.
  • Supplementing 200 mg of L-theanine once or twice a day can help address moderate anxiety symptoms.
  • For severe anxiety, supplementing up to 800 mg daily, in 100 to 200 mg doses, spread throughout the day, has been shown to be effective.

SAFETY, SIDE EFFECTS

  • Side effects of high-dose theanine supplementation may include headache or sleepiness (Theanine: Uses, Side Effects, n.d.).
  • Taking L-theanine does not increase drowsiness, reduce the ability to concentrate, or lead to the development of tolerance or dependence.

L-THEANINE AND MEDICATIONS

  • Taking theanine along with medications for high blood pressure may cause blood pressure to go too low  (Theanine: Uses, Side Effects, n.d.).

References

L-Theanine Uses, Benefits & Dosage—Drugs.com Herbal Database. (n.d.). Drugs.Com. Retrieved October 29, 2020, from https://www.drugs.com/npp/l-theanine.html

Lopes Sakamoto F, Metzker Pereira Ribeiro R, Amador Bueno A & Oliveira Santos H. (2019) Psychotropic effects of L-theanine and its clinical properties: From the management of anxiety and stress to a potential use in schizophrenia. Pharmacological Research, 147, 104395. https://doi.org/10.1016/j.phrs.2019.104395

Mason R. (2001) 200 mg of zen: L-Theanine boosts alpha waves, promotes alert relaxation. Alternative and Complementary Therapies, 7(2), 91–95. https://doi.org/10.1089/10762800151125092

Theanine: Uses, Side Effects, Interactions, Dosage, and Warning. (n.d.). Retrieved October 29, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-1053/theanine

Tryptophan and 5-HTP and anxiety

  • 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.
  • Evidence shows that serotonin deficiency is involved with anxiety (Birdsall, 1998).

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

  • Amounts of tryptophan used in practice and research range from 50–2000 mg/day in divided doses (Prousky, 2015).
  • 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).

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).

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)

2. 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.
  • Supplementing 5-HTP has been shown to help address panic attacks (Maron, Tõru, Vasar, & Shlik, 2004): Lake, 2007) and generalized anxiety (Lake 2007)
  • 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).

References

5-Htp: Uses, Side Effects, Interactions, Dosage, and Warning. (n.d.). Retrieved October 29, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-794/5-htp https://www.webmd.com/vitamins/ai/ingredientmono-794/5-htp

Birdsall, T. C. (1998). 5-Hydroxytryptophan: A clinically-effective serotonin precursor. Alternative Medicine Review: A Journal of Clinical Therapeutic, 3(4), 271–280.

Jones, R. S. (1982). Tryptamine: A neuromodulator or neurotransmitter in mammalian brain? Progress in Neurobiology, 19(1–2), 117–139. https://doi.org/10.1016/0301-0082(82)90023-5

L-Tryptophan: Uses, Side Effects, Interactions, Dosage, and Warning. (n.d.). Retrieved October 29, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-326/l-tryptophan

Lake, J. (2007). Textbook of Integrative Mental Health. New York: Thieme Medical.

Maron, E., Tõru, I., Vasar, V., & Shlik, J. (2004). The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in healthy volunteers. Journal of Psychopharmacology (Oxford, England), 18(2), 194–199. https://doi.org/10.1177/0269881104042619

Murray, M., & Pizzorno J. (1998). Encyclopedia of Natural Medicine. Revised 2nd ed. Rocklin, CA: Prima Publishing.

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

Richard, D. M., Dawes, M. A., Mathias, C. W., Acheson, A., Hill-Kapturczak, N., & Dougherty, D. M. (2009). L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. International Journal of Tryptophan Research : IJTR, 2, 45–60.

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

Multinutrient formulas

B-complex vitamins and anxiety

  • A number of studies show efficacy of B-vitamin supplementation in addressing anxiety.
  • Conditions 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).

“In my experience, supplementation with a high-potency B-complex vitamin sometimes improves chronic anxiety in patients who have no clinical evidence of B-vitamin deficiency” (Gaby, 2011).

Further reading

Lewis, J. E., Tiozzo, E., Melillo, A. B., Leonard, S., Chen, L., Mendez, A., Woolger, J. M., & Konefal, J. (2013). The effect of methylated vitamin B complex on depressive and anxiety symptoms and quality of life in adults with depression. ISRN Psychiatry, 2013, 621453. https://doi.org/10.1155/2013/621453


References

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

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

Multivitamins and anxiety

  • 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.

Some studies on the effect of multivitamin/multimineral supplementation on anxiety symptoms:

Long, S.-J., & Benton, D. (2013). Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: A meta-analysis. Psychosomatic Medicine, 75(2), 144–153. https://doi.org/10.1097/PSY.0b013e31827d5fbd 

Blampied, M., Bell, C., Gilbert, C., Boden, J., Nicholls, R., & Rucklidge, J. J. (2018). Study Protocol for a Randomized Double Blind, Placebo Controlled Trial Exploring the Effectiveness of a Micronutrient Formula in Improving Symptoms of Anxiety and Depression. Medicines, 5(2). https://doi.org/10.3390/medicines5020056

Rucklidge, J. J., Blampied, N., Gorman, B., Gordon, H. A., & Sole, E. (2014). Psychological functioning 1 year after a brief intervention using micronutrients to treat stress and anxiety related to the 2011 Christchurch earthquakes: A naturalistic follow-up. Human Psychopharmacology, 29(3), 230–243. https://doi.org/10.1002/hup.2392

Resources

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

First steps

Diet

  • Follow a Mediterranean-type diet with adequate protein and good fat to stabilize blood sugar
  • Reduce or remove refined sugar and starches [link]
  • Reduce or remove foods that contain additives [link]
  • Consider as a trial, removing gluten and dairy for 4 to 10 days

Substances

  • Incrementally reduce alcohol, caffeine, and nicotine
  • An appropriate approach is to reduce and eliminate only one substance at a time

Nutrients to supplement daily

  • multivitamin/mineral or B-complex
  • vitamin C
  • magnesium

Further steps

  • Look at identifying potential food allergies and avoiding suspect foods
  • If you suspect blood-sugar issues, it may be tied to your anxiety. Refer to Hypoglycemia and Anxiety section

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

  • niacinamide 
  • vitamin B6
  • vitamin B12
  • zinc
  • inositol

If you are taking medications

  • Ask your doctor if they may be inducing your anxiety 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

If you suspect pyroluria 

  • refer to Pyroluria section for supplementing information

Seek qualified guidance

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

Exercise

  • Moderate exercise helps relieve anxiety symptoms (Petruzzello, Landers, Hatfield, Kubitz, & Salazar, 1991) and has been shown to influence brain serotonin (Dunn, & Dishman, 1991) and may promote increased release of endorphins .
  • Evidence shows that aerobic exercise is more effective than stretching or weight training regimens (Rakel, 2012) for improving anxiety symptoms (Paluska, & Schwenk, 2000: Martinsen, Hoffart, & Solberg, 1989).
  • Benefits of exercise on anxiety are dependent on the length of individual exercise sessions, and how long one continues with the sessions.
  • Research shows that, for beneficial effect, exercise sessions need to be at least 12 minutes long (Moses, Steptoe, Mathews, & Edwards, 1989), with maximum benefit at 40 minutes per session (Paluska, & Schwenk, 2000)

Further reading

DeBoer, L. B., Powers, M. B., Utschig, A. C., Otto, M. W., & Smits, J. A. (2012). Exploring exercise as an avenue for the treatment of anxiety disorders. Expert Review of Neurotherapeutics, 12(8), 1011–1022. https://doi.org/10.1586/ern.12.73


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.

Relaxation techniques

  • Relaxation techniques can help address anxiety, especially when use in conjunction with other anxiety treatment approaches.
  • Some techniques that can help address anxiety include mindfulness meditation (Hoge et al., 2013), yoga (Saeed, Cunningham,  & Bloch, 2019), massage, sound therapy, guided meditations, and hypnotherapy. 

References

Hoge, E. A., Bui, E., Marques, L., Metcalf, C. A., Morris, L. K., Robinaugh, D. J., Worthington, J. J., Pollack, M. H., & Simon, N. M. (2013). Randomized Controlled Trial of Mindfulness Meditation for Generalized Anxiety Disorder: Effects on Anxiety and Stress Reactivity. The Journal of Clinical Psychiatry, 74(8), 786–792. https://doi.org/10.4088/JCP.12m08083

Saeed, S. A., Cunningham, K., & Bloch, R. M. (2019). Depression and Anxiety Disorders: Benefits of Exercise, Yoga, and Meditation. American Family Physician, 99(10), 620–627.

Mindfullness

  • Mindfulness meditation involves paying attention to the current moment, focusing on the breath, and bringing one’s awareness to the body. 
  • Many studies show benefits of mindfullness and reduction of anxiety, for example:

Further reading

Hoge, E. A., Bui, E., Marques, L., Metcalf, C. A., Morris, L. K., Robinaugh, D. J., Worthington, J. J., Pollack, M. H., & Simon, N. M. (2013). Randomized Controlled Trial of Mindfulness Meditation for Generalized Anxiety Disorder: Effects on Anxiety and Stress Reactivity. The Journal of Clinical Psychiatry, 74(8), 786–792. https://doi.org/10.4088/JCP.12m08083

Saeed, S. A., Cunningham, K., & Bloch, R. M. (2019). Depression and Anxiety Disorders: Benefits of Exercise, Yoga, and Meditation. American Family Physician, 99(10), 620–627.

How to Meditate with Anxiety. (2019, June 12). Mindful. https://www.mindful.org/mindfulness-meditation-anxiety/

Answers to Anxiety: An Orthomolecular Approach
Webinar presented by James Greenblatt, MD, on September 9, 2021

Feed Your Head
Full length documentary produced by ISOM, 2010

The Antianxiety Food Solution
Author: Trudy Scott, CN – New Harbinger Publications, July 2011

Anxiety: Orthomolecular Diagnosis and Treatment
Author: Jonathan Prousky, ND – CCNM Press, February 2015

Hoffer & Prousky on Anxiety Book and DVD Interview (Grand Rounds)
Author: Jonathan Prousky, ND – CCNM Press, August 2010

Journal of Orthomolecular Medicine (Full text search of archives)

Answers to Anxiety: An Orthomolecular Approach