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, 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

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

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)

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

• 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).