Orthomolecular Interventions
Orthomolecular interventions include substances that have roles in promoting or addressing anxiety, depending on individual metabolic requirements and the amount present in the body.
Vitamin B1 (thiamine)
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
Vitamin B3 (niacin)
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
Vitamin B6 (pyridoxine)
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
Vitamin B12 (cobalamin)
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)
Folate/Folic acid
- 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)
Inositol
- 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).
Magnesium
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.
Chromium
- 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)
Zinc
- 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).
Essential fatty acids
- 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
Glycine
- Glycine is an inhibitory neurotransmitter in the brainstem and spinal cord (Kawai et al., 2015)
GABA (gamma-aminobutyric acid)
- GABA is the most important calming neurotransmitter in the body. Low levels of GABA are associated with anxiety (Lydiard 2003: Braverman 2003)
L-theanine
- Theanine is a calming amino acid. The L- 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).
Tryptophan/5-HTP
- 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).
B-complex
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
Multivitamin/multimineral complex
- 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
