Suicidal Ideation

Orthomolecular interventions

Orthomolecular interventions include substances that have roles in promoting or addressing suicidal ideation, depending on individual metabolic requirements and the amount present in the body.

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 prevention of suicidal ideation

  • Roles of vitamin D in prevention of suicidal ideation include reduction of pro-inflammatory cytokines and oxidative stress, and neurotransmitter synthesis ans regulation in the brain and gut.

Vitamin D deficiency is common

  • 70% of adults and 67% of children in the United States have inadequate vitamin D levels, even when supplementation is taken into consideration (Patrick & Ames, 2015)

Vitamin D, inflammation, and suicide risk

  • Inflammation is a risk factor for suicide.
  • Vitamin D-deficient cells have increased levels of the the pro-inflammatory compounds
    TNF-a and IL-6 CRP (Greenblatt, 2018).
  • A study of vitamin D levels and inflammation in people who had attempted suicide found that 58% of the suicide attempters were vitamin D deficient. The study authors proposed that “routine clinical testing of vitamin D levels could be beneficial in patients with suicidal symptoms, with subsequent supplementation in patients found to be deficient” (Grudet et al., 2014).

Vitamin D and serotonin

  • Two enzymes that are key for serotonin production are tryptophan hydroxylase 1 and 2 (TPH1 and TPH2):
    • TPH1 produces most of the serotonin found in the body
    • TPH2 produces all of the serotonin in the brain
  • Deficiency of vitamin D suppresses TPH2 and activates TPH1 which results in reduced serotonin synthesis and increased inflammation in the body
  • Low serotonin is associated with increased anxiety, depression, and affective dysregulation (Greenblatt, 2018)

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 levels and health status (ng/ml):

<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

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


Lithium (Greenblatt, 2018):

  • protects neurons from damage
  • stimulates growth of new neurons
  • has anti-inflammatory properties
  • inhibits glutamate synthesis and release
  • modulates dopamine by decreasing its release
  • stimulates production of GABA and GABA receptors
  • increases levels of brain serotonin

Lithium and suicide

  • Higher amounts of lithium in drinking water are related to lower amounts of suicide (Ohgami et al., 2009; Schrauzer & Shrestha, 1990).
  • An examination of 31 studies with patients with major affective disorders showed lithium treatment was associated with an 80% decreased risk of completed or attempted suicide (Baldessarini et al., 2006).

Nutritional lithium

Lithium orotate (Kling et al., 1978):

  • has been used to treat stress, manic depression, alcoholism, ADD, ADHD, PTSD, and Alzhiemer’s disease
  • can be used at much lower doses than medical lithium
  • has fewer side effects

Nutritional lithium supplementation

  • Medical lithium is a mood stabilizer used in the context of manic episode of bipolar disorder. Medical dosing for lithium prescriptions is typically between 900 and 1800 mg a day (Lithium, n.d.).
  • Nutritional lithium as lithium orotate and lithium aspartate have been shown to be beneficial. Dosing ranges from 2–30 mg a day. (Greenblatt, 2015)

Important: medical lithium should not be reduced or eliminated without the supervision of a medical health professional.


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 suicide risk

Magnesium deficiency is associated with major and suicidal depression (Eby & Eby, 2006).

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
  • lower dietary intake, absorption, and increased loss of magnesium (common in the elderly)

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)

Reference Dietary Intakes 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


  • 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.


Cholesterol is a lipid molecule. Approximately 80% made by the body and the rest comes from food.

Cholesterol (Greenblatt, 2018):

  • is required for the production of bile, vitamin D, and all steroid hormones
  • activates serotonin and oxytocin receptors
  • is an important component of brain-cell membranes

Low Cholesterol is associated with (Greenblatt, 2018).

  • increased incidence of stroke
  • increased violent behavior and aggression
  • increased difficulty recovering from drug addiction
  • anxiety, depression, and suicide

Cholesterol and Serotonin

Low cholesterol levels decrease serotonin affect the function of serotonin receptors. Serotonin receptors regulate (Chattopadhyay et al., 2007):

  • sleep
  • aggression
  • anxiety
  • eating behavior

Cholesterol and suicide

  • A 15-year study of over 4000 American veterans found (Boscarino et al., 2009):
    • men with low total cholesterol and depression were seven times more likely to die from suicide and accidents
    • with major depressive disorder, there was a significant correlation between low plasma cholesterol and suicidal behaviour
  • In a study of males with PTSD, higher serum total cholesterol was associated with decreased risk of suicidal ideation (Vilibić et al., 2014).
  • Over 500 inpatient records showed that patients who had attempted suicide had significantly lower serum cholesterol than non-suicidal patients (Modai et al., 1994).

Causes of low cholesterol

Risk factors for low cholesterol include (Elmehdawi, 2008):

  • malabsorption
  • chronic inflammation
  • acute or chronic infection
  • hyperthyroid
  • chronic liver disease
  • statin medications


  • 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).

Omega 3 and 6 fatty acids and suicide risk

Deficiencies in omega-3s can result in a 50% reduction of serotonin and dopamine in the frontal cortex and nucleus accumbens of animal brains (Brunner et al., 2002)

A study of depressed people who were medication free for 2 years found that low amounts of the omega 3 fatty acid DHA, and a high amounts omega 6 to 3 fatty acids predicted suicide attempts (Sublette et al., 2006).

Deficiency of Omega-3 fatty acids have been correlated with (Hibbeln & Gow, 2014):

  • a 25 percent increased risk of suicide
  • 2.6 times increased risk of depression
  • 1.5 times increased risk of suicidal ideations

Deficiency of essential fatty acids is associated with (Greenblatt, 2018)

• digestive tract problems

• inflammation

• anxiety

• depression

• aggression

• distorted perceptions

• increased risk of suicide

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.)

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.)

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.)

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.
  • In a study patients who took omega 3 supplements with antidepressant medication, 44% patients achieved full remission versus 18% of the placebo group (Gertsik et al., 2012).
  • It takes at least 10 weeks to restore brain levels of EPA and DHA after chronic deficiency (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 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).


  • 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.

Serotonin and suicide

  • low levels of serotonin can contribute to general lack of sensitivity to consequences which can trigger risky, impulsive and aggressive behaviours, that may culminate in suicide (Rao et al., 2008).

Top food sources of tryptophan

Common sources of tryptophan (Richard et al. 2009):

  • turkey
  • chicken
  • tuna
  • oats
  • peanuts

Reference 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 50–6000 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.


  • 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).


  • 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)

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.
  • Common amounts of 5-HTP used for addressing anxiety range from 100 to 900 mg daily in divided doses  (Prousky, 2015; Rakel, 2012).


  • 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.).


  • 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)

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