Orthomolecular Interventions

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

Vitamin B1 (thiamine)

Vitamin B1 and alcohol addiction

    • Thiamin deficiency is a common effect of alcoholism (Dastur et al., 1976; Morgan, 1982).
    • Thiamin deficiency can ( Zimatkin & Zimatkina, 1996):
      • promote increased alcohol consumption
      • result from excessive alcohol consumption
    • Alcohol decreases thiamin availability in the body by (Jeynes & Gibson, 2017):
      • decreasing its absorption by intestinal cells
      • decreasing production of the enzyme that converts thiamin to the metabolically important coenzyme thiamin pyrophosphate (TPP)

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)

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)

Vitamin B1 supplementation and alcoholism

  • Thiamin supplementation during alcohol detoxification helps prevent complications associated with the withdrawal symptom delirium tremens (DTs) (Smith, 2021).
  • Thiamin (with magnesium and folate) may help prevent the serious neurological condition called Wernicke’s encephalopathy. (“Best Vitamin And Mineral Supplements For Alcohol Detox.”)

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).

Thiamin is not known to interact with any medications (Thiamin, 2014).

Vitamin B3 (niacin)

There are two main forms of nicotinic acid known medically as Niacin and Nicotinamide.

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 mental health:

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

Vitamin B3 and alcohol addiction

  • People with alcoholism have been shown to be deficient in vitamin B3 (Badawy, 2014).
  • Niacin is depleted by (Petralli, “The HPA Axis: The ‘Home’ of Alcoholism.”):
    • excessive metabolism of carbohydrates (alcoholics typically consume high-sugar, high-carbohydrate diets)
    • chronic stress (promoted by alcohol consumption)
  • Nicotinamide adenine dinucleotide (NAD) is a molecule required for energy production in all cells, is created from niacin.
    • Low cell energy causes issues with physical and mental health
    • Chronic heavy alcohol consumption reduces body capacity to synthesize NAD (Zelfand, 2021)
  • In the context of low vitamin B3, the amino acid tryptophan is converted to vitamin B3 instead of serotonin. Low serotonin is associated with (Petralli, “The HPA Axis: The ‘Home’ of Alcoholism.”):
    • carbohydrate and alcohol cravings
    • compulsive/addictive behaviour

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)

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).

Vitamin B3 supplementation and alcohol addiction

  • The beneficial effects of vitamin B3 in alcoholism appear to be due to increased production of NAD (Maclean, 2013).
  • Beneficial manifestations of niacin supplementation in the context of alcoholism include (Smith, 1974):
    • stabilization of mood
    • decreased insomnia
    • increased social and emotional function
    • reduction of need for other forms of medication
    • decreased drinking recidivism
    • Typical dosing of niacin for addressing alcohol cravings is 500-3000 mg/day (Zelfland, 2021)

The niacin flush

Niacin causes capillaries to dilate which results in increased blood flow to the skin. This effect is known as the “niacin flush”. It is harmless, but can be uncomfortable.

About the niacin flush:

  • Causes a“prickly heat” sensation
  • Causes the skin to feel warm and become red
  • The flush begins in the forehead and works its way down the body, rarely affecting the toes
  • The flush usually begins a few minutes after taking the niacin supplement
  • The flush may last for several hours
  • Each time that niacin is taken, the degree of flushing decreases
  • Most people will flush with 100 mg of niacin, some people will flush with less than 100 mg
  • The higher the initial niacin dose, the greater the initial flush
  • If the niacin supplementation is interrupted for several days, the flushing will resume as if starting for the first time, but not as strong as the original flush

Reducing the niacin flush

In a guide for patients, updated in 2018 by his long-time assistant Frances Fuller, Dr. Hoffer explained ways to mitigate the niacin flush. 

Actions to take to reduce the niacin flush include:

  • Taking 2 to 4 g of vitamin C at the beginning of a meal, and then taking niacin at the end of the meal. (Vitamin C decreases the flush by neutralizing histamine in the blood)
  • Taking the niacin with a cold beverage
  • Avoiding hot showers or baths immediately after taking niacin
  • Starting with a lower amount of niacin and gradually increasing the daily dose—for example starting with 125 mg, then doubling the amount every 4-5 days (flushing should stop shortly after reaching 1,000 mg per day)

Chronic exposure to allergens, either food-based or environmental, can stimulate continuous production of histamine. This ongoing supply of histamine can be a reason why some people continue to flush, even after long-term niacin supplementation.


  • 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).
  • Although rare, serum aminotransferase levels should periodically be tested to monitor possible hepatotoxicity in patients who take large doses of vitamin B3 (Gaby, 2011).

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).


  • 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).

Vitamin B12 (cobalamin)

Vitamin B12 and mental health

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 brain:

  • 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

Vitamin B12 and addiction

  • Supplementation with vitamin B12 during recovery may support healing of the brain and affected areas of the nervous system.  (“These Are the 4 Best Vitamins for Opiate Withdrawal.”)

Vitamin B12 deficiency

40% of Americans have low levels of vitamin B12, and 20% of elderly people have severe vitamin B12 deficiencies. This is due to a decreased ability to absorb B12 with older age (Wolters et al., 2004) (Andrès et al., 2004) (Greenblatt & Brogan, 2016).

People with depression 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)

Vitamin B12 and vegetarians

When comparing omnivores and vegetarians, it was found that vegetarians had (Kapoor et al., 2017):

• significantly lower Serum B12 levels

• significantly higher Methylmalonic Acid (MMA) levels

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
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)

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).
  • Daily 5 mg B12 injections for two weeks in men and women with normal serum B12 were found to improve appetite, mood, energy, and sleep to the 4-week follow-up (Ellis & Nasser, 1973).


  • 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).

Vitamin C

Vitamin C is required for the synthesis of many compounds important for good mental health. Some of these are:

  • tyrosine
  • thyroxine
  • norepinephrine
  • epinephrine
  • serotonin
  • carnitine
  • corticosteroids.

Vitamin C has been shown in research to (Meister, 1994):

  • reduce psychological stress
  • decrease blood pressure
  • lower cortisol levels

Functions of vitamin C in the brain (Smythies, 1996):

  • Prevents oxidation of dopamine into toxic derivatives (Baez, Segura-Aguilar, Widerslen, Johansson, & Mannervik, 1997)
  • Protects NMDA receptors from glutamate toxicity
  • Counteracts the effects of amphetamines
  • Enhances the effects of older antipsychotic medications like haloperidol

Vitamin C and mental health

  • 3 g/day of vitamin C supplementation in healthy volunteers significantly decreased monoamine oxidase activity (MAO). MAO is responsible for metabolizing serotonin, norepinephrine, and dopamine. (Gaby, 2011)
  • Vitamin C exerts a powerful antioxidant and anti-inflammatory effect in the body. It plays a role in brain health by supporting the production of serotonin, and the regulation of dopamine and glutamate. (Zelfand, “Vitamin C, Pain and Opioid Use Disorder.”)

Vitamin C and addiction

Vitamin C deficiency and vulnerability to addiction

  • Chronic stress significantly depletes vitamin C.
  • Vitamin C plays an essential role in the body’s response to stress by helping to regulate cortisol.
  • Deficiency of vitamin C may result in higher levels of cortisol and an impaired stress response, which may increase vulnerability to addiction (Zelfand, 2020).

Opioid addiction and vitamin C depletion:

  • Chronic use of opioids can deplete vitamin C resulting in a greater level of oxidative stress damage in the body (Zelfand, 2020).

Vitamin C and opioid withdrawal

  • Through its interruption of the brain chemistry associated with opioid addiction vitamin C has been found to help reduce withdrawal symptoms. (Zelfand, 2020).
  • Vitamin C also plays a role in the recycling of glutathione, an important antioxidant in the body that is depleted by opioid addiction (Zelfand, 2020).
  • By preserving concentrations of glutathione in red blood cells and liver cells, vitamin C can help to address glutathione depletion, Low levels of glutathione can contribute to the perseverance of addiction (Zelfand, 2020).

Vitamin C and smoking

  • Smoking increases the body’s requirements for vitamin C while at the same time decreasing the body’s absorption of it (Healthfully, n.d.).  
  • Vitamin C deficiency in smokers is evidenced by lower levels in the bloodstream Schectman et al., 1989).

Causes of vitamin C deficiency

  • restrictive diets
  • diet lacking in sources of vitamin C, especially fresh fruit and vegetables
  • digestive tract disorders, e.g. diarrhea, Crohn’s and colitis
  • smoking
  • alcoholism
  • chronic inflammatory conditions

Signs of vitamin C deficiency

  • bleeding or swollen gums
  • frequent nosebleeds
  • dry hair, split ends
  • easy bruising
  • slow wound healing
  • fatigue
  • moodiness
  • depression and cognitive impairment (Plevin & Galletly, 2020)

Top sources of vitamin C based on serving size

  • grapefruit and orange juice
  • strawberries
  • kiwifruit
  • orange
  • sweet pepper
  • broccoli

Comprehensive food list:

Table 3. Some Food Sources of vitamin C (Vitamin C, 2014)

Referenced Dietary Intakes

RDAs for vitamin C (mg/day)

Adolescents (14-18 years): 75 (M) 65 (F)

Adults (19-50 years): 90 (M) 75 (F)

Smokers: 125 (M) 110 (F)

Tolerable Upper Intake: 2000 mg /day

(Office of Dietary Supplements – Vitamin C, n.d.)

Vitamin C supplementation

  • Amounts of vitamin C used in practice and research range from 500–6000 mg/day in divided doses.

Vitamin C Supplementation and opiod addiction

  • Several studies have demonstrated the effectiveness of vitamin C in helping to reduce symptoms associated with withdrawal from opioids (Opiate Withdrawal Vitamins, 2018).
  • The availability and affordability of vitamin C, along with its tolerability and overall safety make it a viable option in supporting withdrawal from opioids (Zelfand, 2020). 
  • A suggested dose for vitamin C in the form of sodium ascorbate is anywhere from 25 to 85 grams per day in divided doses up to bowel tolerance for those withdrawing completely at the outset. (Zefland)
  • Taking 2 grams of sodium ascorbate every two waking hours over a period of three days has found to be effective in those withdrawing incrementally.  The dose can then be increased as needed to help offset withdrawal symptoms (Millar, T. (2020).
  • Individuals undergoing treatment with methadone have also found relief from relevant side effects and symptoms through supplementation of up to 5 grams of vitamin C per day (Scher, 1976).

Vitamin C and smoking

  • Increasing the intake of vitamin C through supplementation can help to prevent deficiency in smokers (Schectman et al., 1989).


  • Vitamin C has low toxicity and is not believed to cause serious adverse effects at high intakes (Office of Dietary Supplements – Vitamin C, n.d.).
  • Vitamin C at higher doses can, in some people, cause side effects such as nausea, abdominal cramps, and other digestive tract disturbances

Vitamin C and medications

  • Vitamin C has been shown beneficial and safe when used in conjunction with depression medications.

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 addiction

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

Causes of vitamin D deficiency

  • limited sun exposure
  • strict vegan diet (most sources of vitamin D are animal-based)
  • darker skin (the pigment melanin reduces the vitamin D production by the skin)
  • digestive tract and kidney issues
  • obesity (vitamin D is sequestered by fat cells)

Measuring vitamin D

The best indicator of vitamin D status is serum 25(OH)D, also known as 25-hydroxyvitamin D. 25(OH)D reflects the amount of vitamin D in the body that is produced by the skin and obtained from food and supplements.

Vitamin D levels and health status

Institute of Medicine, Food and Nutrition Board. (2010)

Serum (ng/ml)  and Health status

<20  deficient 20–39  generally considered adequate 40–50  adequate >50–60   proposed optimum health level

>200  potentially toxic

Top sources of vitamin D based on serving size (Office of Dietary Supplements – Vitamin D, 2020)

  • cod liver oil
  • trout
  • pink salmon
  • sardines
  • fortified cereal, milk, and orange juice
  • fortified almond, soy, and oat milks
  • egg yolk

Comprehensive food list

Table 3: Vitamin D Content of Selected Foods

Referenced Dietary Intakes

RDAs for vitamin D (IU/day)

Adolescents (14-18 years): 600 (M) 600 (F)

Adults (19-50 years): 600 (M) 600 (F)

Adults (51 years and older): 800 (M) 800 (F)

Tolerable Upper Intake: 4000 IU/day

(Office of dietary supplements, 2020)

Vitamin D supplementation

  • Amounts of vitamin D used in practice and research range from 400-14,000 IU/day. (Vitamin D, 2014)

SAFETY, SIDE EFFECTS (Vitamin D, 2014)

  • “Research suggests that vitamin D toxicity is very unlikely in healthy people at intake levels lower than 10,000 IU/day”
  • Vitamin D can increase risk of hypercalcemia with calcium-related medical conditions – including primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma
  • Certain medical conditions can increase the risk of hypercalcemia in response to vitamin D, including primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma

Some drugs that affect vitamin D absorption or metabolism include (Vitamin D, 2014):

  • cholestyramine
  • colestipol
  • orlistat
  • mineral oil
  • phenytoin
  • fosphenytoin
  • phenobarbital
  • carbamazepine
  • rifampin
  • cimetidine
  • ketoconazole
  • glucocorticoids
  • HIV treatment drugs


Magnesium and mental health

Magnesium in the context of mental health (Kirkland, Sarlo, & Holton, 2018):

  • calms neurotransmission by regulating glutamate and GABA
  • modulates the HPA axis
  • has roles in the synthesis of serotonin and dopamine
  • regulates cortisol levels
  • increases brain-derived neurotrophic factor (BDNF)
  • is required for enzyme systems that use thiamine (vitamin B1) and pyridoxine (vitamin B6) – these vitamins are cofactors in the production of serotonin, GABA, and melatonin (Kanofsky, & Sandyk, 1991)
  • decreases activation of the NMDA receptor which in turn, decreases excitatory neurotransmission (Bartlik, Bijlani, & Music, 2014)

Magnesium and alcohol addiction

Magnesium in the context of alcohol addiction (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)
  • deficiency promotes anxiety and decreases stress tolerance (Henrotte, 1986).

Magnesium deficiency and alcohol addiction

  • Alcohol consumption depletes magnesium (McLean and Manchip, 1999)
  • Magnesium deficiency in alcoholics is common, with a prevalence of between 13–50 percent. (Dingwall et al., 2015) (Wilkens Knudsen et al., 2014).

Magnesium and opioid withdrawal:

  • Magnesium deficiency can contribute to the pain, and nervous system and muscular issues, experienced by individuals withdrawing from opioids (Nabipour et al., 2014).
  • Magnesium exerts a calming effect, helping the body to relax both mentally and physically during withdrawal (Miller-Reiter et al., 1995).

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)

Referenced Dietary Intakes

RDAs for magnesium (mg/day)

Adolescents (14-18 years): 410 (M) 360 (F)

Adults (19-30 years): 400 (M) 310 (F)

Adults (31 years and older): 420 (M) 320 (F)

Supplementing magnesium

  • Amounts of magnesium used in practice and research range from 100–750 mg a day in divided doses (elemental magnesium dose).
  • Correction of magnesium deficiency with magnesium supplementation has resulted in significant improvement in psychiatric symptoms (Kanofsky & Sandyk, 1991).

Magnesium supplementation – beneficial forms and dosing (Greenblatt, 2018)

  • Magnesium glycinate supplementation of 120-240 mg per meal and at bedtime has been shown to benefit mood
  • Magnesium glycinate or citrate supplementation of 240-360 mg before bed supports sleep onset and sleeping through the night
  • Administration of 732 mg per day of magnesium L-aspartate hydrochloride for 12 weeks in individuals undergoing methadone treatment was found to reduce illicit opioid use (Gaby, 2017; Miller-Reiter et al., 1995).
  • 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.


Zinc and mental health

  • Zinc regulates the storage and release of neurotransmitters (Zinc Regulates, 2017)
  • Zinc has critical roles in axonal and synaptic transmission development and brain cell growth and metabolism (Pfeiffer & Braverman, 1982).
  • Zinc is required for the production of the enzyme, superoxide dismutase, and therefore helps to provide antioxidant support in the body.  (Preston, “Cigarette Smoking-Nutritional Implications.”)
  • 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).

Zinc and alcohol addiction

  • Alcohol consumption frequently promotes zinc deficiency and altered zinc metabolism (Barve et al., 2017).

Causes of low zinc with alcohol consumption:

  • decreased intake and increased urinary excretion (Jeynes & Gibson, 2017).
  • negative effects on zinc transporters (Skalny et al., 2018)

Effects of low zinc in the context of alcoholism:

  • Impediments to neurotransmission
  • leaky gut with a corresponding increase in gut toxins in the blood and brain  (Skalny et al., 2018)
  • increased inflammatory signaling
  • increased oxidative stress

Zinc and smoking addiction

  • tobacco smoke is high in cadmium. Cadmium competes with zinc for body enzyme binding sites, altering enzyme function in a negative way. Increasing body levels of zinc can help mitigate the effects of cadmium.
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

Referenced Dietary Intakes

RDAs for zinc (mg/day)

Adolescents (14-18 years): 11 (M) 9 (F)

Adults (19 years and older): 11 (M) 8 (F)

Supplementing zinc

  • Amounts of zinc used in practice and research range from 10–200 mg/day in divided doses (Zinc, 2014).
  • “Long-term zinc supplementation should be accompanied by a copper supplement (1–4 mg/day, depending on the zinc dose), in order to prevent zinc-induced copper deficiency” (Gaby)
  • Typical dosing of zinc to treat alcohol-induced organ injury is 50 mg of elemental zinc  (Barve et al., “Development, Prevention, and Treatment of Alcohol-Induced Organ Injury.”)
  • Zinc is best taken with food to prevent nausea.


  • 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).

Essential fatty acids

Essential fatty acids and mental health

  • Polyunsaturated fatty acids (PUFAs) (omega 3 and 6 fatty acids) are necessary for normal development and function of the brain.
  • Omega 3 fatty acids and their metabolites have roles in regulating inflammation, neuroinflammation, and neurotransmission (Larrieu, & Layé, 2018).

Essential fatty acids and addiction

EFAs and alcohol addiction

  • Addictive behaviours are associated with neuroinflammation.
  • Studies show that alcohol-induced neuronal inflammation and damage can be offset by essential fatty acids (Barve et al., 2017).
  • Fish oil has been shown to alleviate withdrawal symptoms (Shi et al., 2019).
  • Omega 3 fatty acid intake supports healthy brain function while recovering from chronic alcohol use (Smith, 2021).

Omega 3 fatty acids and opioid withdrawal

  • Low omega 3 fatty acid status has been linked to decreased levels of dopamine. (“These Are the 4 Best Vitamins for Opiate Withdrawal.”)
  • Supplementation with omega 3 fatty acids may help to reduce drug-seeking behaviours during opioid maintenance and withdrawal as a result of the protective role they may play in mitigating composition of the gut microbiome (Hakimian et al., 2019).
  • Preclinical data suggests that a diet enriched with omega 3 fatty acids may also help to alleviate anxiety and associated behaviours that accompany withdrawal (Hakimian et al., 2019).

Omega 3 fatty acids and opiod relapse prevention

  • Supplementation with omega 3 fatty acids may help to facilitate a positive shift in the composition of the gut microbiome.
  • This may help to reduce anxiety, which is often a contributing factor in relapse (Hakimian et al., 2019).

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.


  • 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.).


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

GABA (gamma-aminobutyric acid)

GABA and mental health

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


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

  • upset stomach
  • headache
  • sleepiness
  • muscle weakness


  • 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.).


Roles of glutamine in mental health:

  • is a precursor molecule for the production of the neurotransmitters glutamate and GABA. 
  • provides fuel for the brain and stimulates many brain functions  (Treatment Protocol for Alcoholism, n.d.)
  • supports brain detoxification by supporting glutathione production (Yu et al., 1999) 
  • protects digestive tract cells from damage.

Glutamine and addiction

  • Glutamine decreases physiological cravings in general (Addiction, n.d.), and especially for alcohol
  • Glutamine is made in the body by the kidneys and liver and certain brain cells. Chronic alcohol consumption damages the liver and kidneys which reduces their production of glutamine. (Treatment Protocol for Alcoholism, n.d.)
  • Glutamine can be converted into glucose in the brain without raising insulin levels. Elevated insulin promotes alcohol cravings.
Referenced Dietary Intakes

RDAs/Upper intakes for glutamine: Not established.

Supplementing glutamine

  • Amounts of glutamine used in practice and research range from 5–30 g/day in divided doses (Glutamine Uses, Side Effects & Warnings, n.d.).
  • Starting at the low end of the dosing range is recommended for seniors. (
  • A recommended dose in children is up to 0.7 g/kg of body weight daily. (WebMD)


·       In general, glutamine is well tolerated by most people.

·       Side of effects of glutamine are generally mild and could include (Glutamine Uses, Side Effects & Warnings, n.d.):

o   heartburn, stomach pain, or bloating

o   nausea

o   swelling in hands or feet

o   muscle or joint pain, back pain

o   dizziness

o   headache, fatigue

o   mild skin rash or itching

o   dry mouth

o   runny nose

o   cough

o   increased sweating

  • Avoid supplementing with glutamine with acute liver or kidney failure, or with cirrhosis, chronic kidney problems, Reye’s Syndrome, or any disorder that results in the accumulation of ammonia in the blood
  • Individuals with impaired liver function should not take large doses of glutamine.  A conservative dose of 1-2 g per day may be possible in some individuals with alcoholic liver disease to help reduce cravings (Gaby, 2017).
  • Consult a practitioner before taking glutamine if you are pregnant or breastfeeding (Glutamine, n.d.).
  • Avoid glutamine if you are at risk of seizures (Glutamine, n.d.)
  • In very rare cases, mania or hypomania has been noted with doses of 2-4 g per day.  Symptoms resolved with cessation of glutamine supplementation (Gaby, 2017).
  • Individuals with MSG sensitivity may also be sensitive to glutamine (Glutamine, n.d.).
  • Supplementation with glutamine may exacerbate Crohn’s disease symptoms (Gaby, 2017)


·    The effectiveness of anticonvulsant medications used in the prevention of seizures may be reduced with glutamine supplementation (WebMD)

·    The effectiveness of Lactulose may be decreased with glutamine supplementation (

·    Large doses of glutamine have been found to reduce the severity of side effects associated with certain chemotherapies, without obviously interfering with the effectiveness of the chemo treatment. (Gaby, 2011)

NAC (n-acetylcysteine)

  • N-acetylcysteine, more commonly known as NAC, is a derivative of the amino acid cysteine.

NAC in the context of mental health:

  • has roles in inflammation regulation and antioxidant production, and is required for the production of glutathione
  • modulates neurotransmitters including glutamate and dopamine, and provides neurotrophic support (Dean, Giorlando, & Berk, 2011)
  • regulates inflammation
  • supports mitochondrial energy production
  • supports neurotransmitter metabolism
Food sources of NAC

  • NAC is not found in food, but can be made by the body from the amino acid cysteine.

Food sources high in cysteine include (Foods Highest in Cystine, n.d.):

  • beef, lamb, pork
  • poultry
  • fish
Supplementing NAC in the context of addiction

  • Amounts of NAC used in practice and research range from 600 to 3600 mg a day in divided doses.
  • NAC needs to be taken away from food for maximum therapeutic effect.
  • NAC supplementation has been shown to increase blood glutathione levels (Lavoie et al., 2007), and regulate metabolism of glutamate and GABA (Dean, Giorlando, & Berk, 2011).


  • NAC can be safely combined with atypical antipsychotic medication and can be combined with all classes of psychiatric medication. 

Side effects of NAC can include:

  • mild nausea
  • upset stomach and indigestion
  • diarrhea
  • tiredness or weakness
  • sweating
  • skin rash


Phenylalanine is an essential amino acid. It can be found in 3 forms: L-phenylalanine , D-phenylalanine and DL-phenylalanine, a combination of both (Phenylketonuria, n.d.).

Phenylalanine and mental health

  • People have reported mood improvement after taking phenylalanine. This may be because phenylalanine increases production of chemicals in the brain such as dopamine and norepinephrine (PHENYLALANINE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews, n.d.)
  • Phenylalanine also appears to protect endorphins from routine destruction. Supplementation of phenylalanine therefore increases endorphins levels and can improve depressed moods” (Greenblatt & Brogan, 2016) Page 139.

Causes of Phenylalanine deficiencies

  • A low-protein diet
  • phenylketonuria (PKU, genetic condition)
Top food sources of phenylalanine (Metcalf & MPH, n.d.):

  • Meat
  • Egg
  • Fish
  • Cheese
Phenylalanine Supplementation

  • Amounts of phenylalanine used in practice and research range from 75–5,000 mg/day in divided doses (Metcalf & MPH, n.d.).
  • D-phenylalanine is more effective than L-phenylalanine at raising phenylethylamine levels (Borison et al., 1978) (Gaby).

DL-phenylalanine and Withdrawal:

  • DL-phenylalanine contains two forms of the amino acid phenylalanine. Used in combination, they may help with the depression, anxiety, and fatigue that can accompany withdrawal from opioids.
  • Over the longer term, supplementation with DL-phenylalanine may also help to increase dopamine and endorphins in the brain (Opiate Withdrawal Vitamins, 2018).


  • Side effects are often mild, and primarily include (Gaby):
    • Anxiety
    • Sleep disturbances
    • Gastrointestinal symptoms
    • Transient headaches or vertigo
  • Phenylalanine can trigger allergic reactions in some individuals. Symptoms of allergic reactions include (Metcalf, n.d.):
    • Itching
    • Swelling of the face or hands
    • Trouble breathing
    • Tingling feeling in the mouth
  • Phenylalanine  should be avoided in people with phenylketonuria and schizophrenia (Metcalf, n.d.).
  • Phenylalanine should be used with caution in those with high blood pressure, anxiety, sleep issues, or current antidepressant use (Metcalf, n.d.).


Theanine and mental health

  • 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.


  • 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.


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


Tryptophan and 5-HTP and mental health

  • Serotonin, regarded as the happy, feel good neurotransmitter, is synthesized from the amino acid tryptophan. Tryptophan is converted in the body to 5-HTP , which is then converted into the neurotransmitter serotonin.
  • Serotonin is depleted by substance abuse. Tryptophan and 5-HTP help maintain proper serotonin levels

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

  • turkey
  • chicken
  • tuna
  • oats
  • peanuts

Referenced Dietary Intakes for Tryptophan

The recommended daily allowance for tryptophan for adults is estimated to be between 250 mg/day and 425 mg/day (Richard et al. 2009).

RDAs/Upper intakes for 5-HTP

None established.

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.
  • Supplementation with 5-HTP may help to promote relaxation and sleep and help to regulate mood (Opiate Withdrawal Vitamins, 2018). 


  • 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)

Supplementing 5-HTP

  • 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)


Tyrosine is a dietary amino acid that also functions as a neurotransmitter.

The body can also make tyrosine from the amino acid phenylalanine

Tyrosine and mental health

Tyrosine is a precursor molecule for the neurotransmitters dopamine, noepinephrine, and epinephrine, and is also required for the production of thyroid hormones.

Tyrosine and opioid WIthdrawal:

  • Tyrosine may help to mitigate symptoms of depression, anxiety, and fatigue that accompany opioid withdrawal (Opiate Withdrawal Vitamins, 2018).

Causes of deficiencies

  • a low-protein diet

Top sources of tyrosine based on serving size (Top Foods High in Tyrosine, n.d.)

  • sesame seeds
  • cheese
  • soybeans
  • meat and poultry
  • fish

Supplementing tyrosine

  • Amounts of tyrosine used in practice and research range from 100–1000 mg/day in divided doses (Mahoney et al., 2007).
  • Tyrosine seems to be safe when used in doses up to 150 mg/kg per day for up to 3 months”  (Tyrosine, n.d.) (Gaby).
  • Since L-tyrosine may act as a mild stimulant, Tyrosine should not be taken near bedtime. L-tyrosine is likely most effective when it is taken with carbohydrates on an empty stomach (Gaby).


  • Some people may experience side effects such as nausea, headache, fatigue, heartburn, and joint pain (Tyrosine, n.d.)
  • People who have migraine headaches may need to avoid tyrosine, as it can trigger migraine headaches
  • People with hyperthyroidism or Graves disease may need to avoid supplementing tyrosine as it may promote increased thyroid hormone production


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

3 Amazing Benefits of GABA. (n.d.). Psychology Today. Retrieved October 29, 2020, from

5-HTP: Uses, Side Effects, Interactions, Dosage, and Warning. (n.d.). Retrieved October 29, 2020, from

Addiction. (n.d.). Integrative Psychiatry. Retrieved December 21, 2021, from

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.

Andrès, E., Loukili, N. H., Noel, E., Kaltenbach, G., Abdelgheni, M. B., Perrin, A. E., Noblet-Dick, M., Maloisel, F., Schlienger, J.-L., & Blicklé, J.-F. (2004). Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ: Canadian Medical Association Journal = Journal de l’Association Medicale Canadienne, 171(3), 251–259.

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.

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).

Badawy, A. A.-B. (2014). Pellagra and Alcoholism: A Biochemical Perspective. Alcohol and Alcoholism, 49(3), 238–250.

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

Bartlik, B., Bijlani, V., & Music, D. (2014, July 22). Magnesium: An essential supplement for psychiatric patients—Psychiatry Advisor. Psychiatry Advisor.

Barve, S., Chen, S.-Y., Kirpich, I., Watson, W. H., & McClain, C. (2017). Development, Prevention, and Treatment of Alcohol-Induced Organ Injury: The Role of Nutrition. Alcohol Research: Current Reviews, 38(2), 289–302.

Berk, M., Copolov, D., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., … & Ording-Jespersen, S. (2008). N-acetyl cysteine as a glutathione precursor for schizophrenia—a double-blind, randomized, placebo-controlled trial. Biological Psychiatry, 64(5), 361-368.

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

Borison, R. L., Maple, P. J., Havdala, H. S., & Diamond, B. I. (1978).

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.

Bruinsma, K. A., & Taren, D. L. (2000). Dieting, Essential Fatty Acid Intake, and Depression. Nutrition Reviews, 58(4), 98–108.

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

Chouinard, G., Young, S. N., Annable, L., & Sourkes, T. L. (1977). Tryptophan-nicotinamide combination in depression. Lancet (London, England), 1(8005), 249.

Chouinard, G., Young, S. N., Annable, L., & Sourkes, T. L. (n.d.). Tryptophan-nicotinamide, imipramine and their combination in depression. Acta Psychiatrica Scandinavica, 59(4), 395–414. Retrieved August 26, 2021, from

Cuciureanu, M. D., & Vink, R. (2011). Magnesium and stress. In R. Vink & M. Nechifor (Eds.), Magnesium in the Central Nervous System. University of Adelaide Press.

Dastur, D. K., Santhadevi, N., Quadros, E. V., Avari, F. C. R., Wadia, N. H., Desai, M. M., & Bharucha, E. P. (1976). The B-vitamins in malnutrition with alcoholism: A model of intervitamin relationships*. British Journal of Nutrition, 36(2), 143–159.

Dean, O., Giorlando, F., & Berk, M. (2011). N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. Journal of Psychiatry and Neuroscience, 36(2), 78.

Deans, E. (2011, June 12). Magnesium and the brain: The original chill pill. Psychology Today. http:/www.psychol-

Dingwall, K. M., Delima, J. F., Gent, D., & Batey, R. G. (2015). Hypomagnesaemia and its potential impact on thiamine utilisation in patients with alcohol misuse at the Alice Springs Hospital. Drug and Alcohol Review, 34(3), 323–328.

Dommisse, J. (1991). Subtle vitamin-B12 deficiency and psychiatry: A largely unnoticed but devastating relationship? Medical Hypotheses, 34(2), 131–140.

Ellis, F. R., & Nasser, S. (1973). A pilot study of vitamin B12 in the treatment of tiredness. British Journal of Nutrition, 30(2), 277–283.

Essential Fatty Acids. (2014, April 28). Linus Pauling Institute.

European Food Safety Authority. Labelling reference intake values for n-3 and n-6 polyunsaturated fatty acids. (2009, July 10).

Foods highest in Cystine. (n.d.). Retrieved December 8, 2020, from

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

Gaby, A. R. (2017). Nutritional Medicine—Second Edition (Second). Fritz Perlberg Publishing.

Gamma Aminobutyric Acid: Uses and Side Effects of GABA Supplement. (n.d.). Retrieved October 29, 2020, from

Gedye, A. (2001). Hypothesized treatment for migraines using low doses of tryptophan, niacin, calcium, caffeine, and acetylsalicylic acid. Medical Hypotheses, 56(1), 91–94.

Glutamine (n.d.). Retrieved December 20, 2020, from

Glutamine: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews. (n.d.). WebMD. Retrieved December 22, 2021, from

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

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

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

Guo, W., Nazim, H., Liang, Z., & Yang, D. (2016). Magnesium deficiency in plants: An urgent problem. The Crop Journal, 4(2), 83–91.

Hakimian, J. K., Dong, T. S., Barahona, J. A., Lagishetty, V., Tiwari, S., Azani, D., Barrera, M., Lee, S., Severino, A. L., Mittal, N., Cahill, C. M., Jacobs, J. P., & Walwyn, W. M. (2019). Dietary Supplementation with Omega-3

Healthfully. (n.d.). Healthfully. Retrieved December 1, 2021, from

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

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

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

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

Institute of Medicine. (2002). Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids.

Jeynes, K. D., & Gibson, E. L. (2017). The importance of nutrition in aiding recovery from substance use disorders: A review. Drug and Alcohol Dependence, 179, 229–239.

Kanofsky, J. D., & Sandyk, R. (1991). Magnesium Deficiency in Chronic Schizophrenia. International Journal of Neuroscience, 61(1–2), 87–90.

Kirkland, A. E., Sarlo, G. L., & Holton, K. F. (2018). The Role of Magnesium in Neurological Disorders. Nutrients, 10(6).

L-Glutamine (n.d.). Medlineplus. Retrieved December 20, 2020, from

L-Theanine Uses, Benefits & Herbal Database. (n.d.). Drugs.Com. Retrieved October 29, 2020, from

L-Tryptophan: Uses, Side Effects, Interactions, Dosage, and Warning. (n.d.). Retrieved October 29, 2020, from

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

Lavoie, S., Murray, M. M., Deppen, P., Knyazeva, M. G., Berk, M., Boulat, O., . . . Do, K. Q. (2007). Glutathione pre- cursor, N-Acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology, 33(9), 2187-2199.

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.

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

Maclean, M. (2013). The Genetics and Neurochemistry of Schizophrenia and Addiction: Enhanced Options for Treatment Using Nicotinic Acid (Vitamin B3). 28(2), 6.

Magnesium. (2014, April 23). Linus Pauling Institute.

Mahoney, C. R., Castellani, J., Kramer, F. M., Young, A., & Lieberman, H. R. (2007). Tyrosine supplementation mitigates working memory decrements during cold exposure.

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

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

Metabolism of an amino acid with antidepressant properties. Research Communications in Chemical Pathology and Pharmacology, 21(2), 363–366.

Metcalf, E. (n.d.). Phenylalanine: Uses and Risks. WebMD. Retrieved December 22, 2021, from

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

Millar, T. (2020) Personal communication to Zefland.

Miller-Reiter, E., Fodor, G., Presslich, O., & Kasper, S. (1995). P-10-8 The use of magnesium in opioid detoxification and withdrawal. European Neuropsychopharmacology, 5(3), 395.

Morgan, M. Y. (1982). Alcohol and Nutrition. British Medical Bulletin, 38(1), 21–30.

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

Nabipour, S., Ayu Said, M., & Hussain Habil, M. (2014). Burden and Nutritional Deficiencies in Opiate Addiction- Systematic Review Article. Iranian Journal of Public Health, 43(8), 1022–1032.

Niacin. (2014, April 22). Linus Pauling Institute.

Office of Dietary Supplements—Omega-3 Fatty Acids. (n.d.). Retrieved October 29, 2020, from

Office of Dietary Supplements—Vitamin C. (n.d.). Retrieved December 4, 2020, from

Office of Dietary Supplements—Vitamin D. (2020).

Office of Dietary Supplements—Zinc. (n.d.). Retrieved October 29, 2020, from

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

Opiate Withdrawal Vitamins: Top 12 Vitamins THAT WORK. (2018, February 28). Opiate Addiction Support.

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

Petralli, G. (2008). The HPA Axis: The “Home” of Alcoholism. 23(4), 4.

Pfeiffer, C. C., & Braverman, E. R. (1982). Zinc, the brain and behavior. Biological Psychiatry, 17(4), 513–532.

Physiology & Behavior, 92(4), 575–582.

Plevin, D., & Galletly, C. (2020). The neuropsychiatric effects of vitamin C deficiency: A systematic review. BMC Psychiatry, 20(1), 315.

Polyunsaturated Fatty Acids Reduces Opioid-Seeking Behaviors and Alters the Gut Microbiome. Nutrients, 11(8), E1900.

Preston, A. M. (1991). Cigarette smoking-nutritional implications. Progress in Food & Nutrition Science, 15(4), 183–217.

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

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

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.

Schectman, G., Byrd, J. C., & Gruchow, H. W. (1989). The influence of smoking on vitamin C status in adults. American Journal of Public Health, 79(2), 158–162.

Scher, J. (1976). Massive Vitamin C as an Adjunct in Methadone Maintenance and Detoxification. Orthomolecular Psychiatry, 5(3), 8.

Shi, Z., Xie, Y., Ren, H., He, B., Wang, M., Wan, J.-B., Yuan, T.-F., Yao, X., & Su, H. (2019). Fish oil treatment reduces chronic alcohol exposure induced synaptic changes. Addiction Biology, 24(4), 577–589.

Skalny, A. V., Skalnaya, M. G., Grabeklis, A. R., Skalnaya, A. A., & Tinkov, A. A. (2018). Zinc deficiency as a mediator of toxic effects of alcohol abuse. European Journal of Nutrition, 57(7), 2313–2322.

Smith, J. (2021, October 4). Best Vitamin And Mineral Supplements For Alcohol Detox. Addiction Resource.

Smith, R. F. (1974). A Five-Year Field Trial of Massive Nicotinic Acid Therapy of Alcoholics in Michigan. ORTHOMOLECULAR PSYCHIATRY, 3(4), 5.

Smythies, J. (1996). Oxidative reactions and schizophrenia: A review-discussion. Schizophrenia Research, 24(3), 357–364.

Theanine: Uses, Side Effects, Interactions, Dosage, and Warning. (n.d.). Retrieved October 29, 2020, from

These Are the 4 Best Vitamins for Opiate Withdrawal. (2019, March 23). The Health Supplement Review.

Thiamin. (2014, April 22). Linus Pauling Institute.

Top Foods High in Tyrosine. (n.d.). WebMD. Retrieved August 15, 2021, from

Treatment Protocol for Alcoholism. (n.d.). Retrieved December 21, 2021, from

Tyrosine: Health Benefits, Side Effects, Uses, Dose & Precautions. (n.d.). RxList. Retrieved August 15, 2021, from

Valizadeh, M., & Valizadeh, N. (2011). Obsessive Compulsive Disorder as Early Manifestation of B12 Deficiency. Indian Journal of Psychological Medicine, 33(2), 203–204.

Vitamin B12. (2014, April 22). Linus Pauling Institute.

Vitamin C. (2014, April 22). Linus Pauling Institute.

Vitamin D. (2014, April 22). Linus Pauling Institute.

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

Wilkens Knudsen, A., Jensen, J.-E. B., Nordgaard-Lassen, I., Almdal, T., Kondrup, J., & Becker, U. (2014). Nutritional intake and status in persons with alcohol dependency: Data from an outpatient treatment programme. European Journal of Nutrition, 53(7), 1483–1492.

Wolters, M., Ströhle, A., & Hahn, A. (2004). Cobalamin: A critical vitamin in the elderly. Preventive Medicine, 39(6), 1256–1266.

Zelfand, E. (2021, July 15). How Niacin May Help Treat Alcoholism.

Zelfland, E. (2021, July 27). Niacin for Alcoholism. Nutrition In Focus.

Zimatkin, S. M., & Zimatkina, T. I. (1996). Thiamine Deficiency As Predisposition To, And Consequence Of, Increased Alcohol Consumption. Alcohol and Alcoholism, 31(4), 421–427.

Zinc. (2014, April 23). Linus Pauling Institute.