Mental Health Information – Addiction

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)

https://lpi.oregonstate.edu/mic/minerals/magnesium

Referenced Dietary Intakes

RDAs for magnesium (mg/day)

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

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

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

Supplementing magnesium

• Amounts of magnesium used in practice and research range from 100–750 mg 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

SAFETY, SIDE EFFECTS

• 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.

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References

Bartlik, B., Bijlani, V., & Music, D. (2014, July 22). Magnesium: An essential supplement for psychiatric patients—Psychiatry Advisor. Psychiatry Advisor. https://www.psychiatryadvisor.com/home/therapies/magnesium-an-essential-supplement-for-psychiatric-patients/

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. http://www.ncbi.nlm.nih.gov/books/NBK507250/

Deans, E. (2011, June 12). Magnesium and the brain: The original chill pill. Psychology Today. http:/www.psychol- ogytoday.com/blog/evolutionary-psychiatry/201106/magnesium-and-the-brain-the-original-chill-pill

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. https://doi.org/10.1111/dar.12237

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

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

Guo, W., Nazim, H., Liang, Z., & Yang, D. (2016). Magnesium deficiency in plants: An urgent problem. The Crop Journal, 4(2), 83–91. https://doi.org/10.1016/j.cj.2015.11.003

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

Kanofsky, J. D., & Sandyk, R. (1991). Magnesium Deficiency in Chronic Schizophrenia. International Journal of Neuroscience, 61(1–2), 87–90. https://doi.org/10.3109/00207459108986275

Kirkland, A. E., Sarlo, G. L., & Holton, K. F. (2018). The Role of Magnesium in Neurological Disorders. Nutrients, 10(6). https://doi.org/10.3390/nu10060730

Magnesium. (2014, April 23). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/minerals/magnesium

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. https://doi.org/10.1016/0924-977X(95)90727-U

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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411899/

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. https://doi.org/10.1007/s00394-014-0651-x

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

https://lpi.oregonstate.edu/mic/minerals/zinc

Referenced Dietary Intakes

RDAs for zinc (mg/day)

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

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

Supplementing zinc

• Amounts of zinc used in practice and research range from 10–200 mg/day in divided doses (Zinc, 2014).
• “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.

SAFETY, SIDE EFFECTS

• High zinc intakes can inhibit copper absorption, sometimes producing copper deficiency and associated anemia (Office of Dietary Supplements, 2014).
• Intakes of zinc should not exceed the UL (40 mg/day for adults) in order to limit the risk of copper deficiency in particular
• Milder gastrointestinal distress has been reported at doses of 50 to 150 mg/day of supplemental zinc (Zinc, 2014).

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References

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

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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513692/

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

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. https://doi.org/10.1016/j.drugalcdep.2017.07.006

Office of Dietary Supplements—Zinc. (n.d.). Retrieved October 29, 2020, from https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

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

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

Zinc. (2014, April 23). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/minerals/zinc

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. https://doi.org/10.1007/s00394-017-1584-y

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.)

https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids

Top α-Linolenic Acid (omega 3) food sources by serving size

• flax seed oil
• chia seeds
• walnuts
• flax seeds ground

Comprehensive food list:

Table 3. Food Sources of α-Linolenic Acid (18:3n-3) (Office of Dietary Supplements, n.d.)

https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids

Top Linoleic Acid (omega-6) sources by serving size

• safflower oil
• sunflower seeds
• pine nuts
• sunflower oil

Comprehensive food list: Table 2. Food Sources of Linoleic Acid (18:2n-6)

(Office of Dietary Supplements, n.d.)

https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids

Commonly suggested amounts for dietary fatty acid consumption:

• cold water fish – 2 to 3 times a week, or
• flaxseed oil – 2 to 6 tbsp daily, or
• ground flax seed – 2 tbsp daily

Flaxseed oil may have negative effects in about 3% people, including: hypomania, mania, behaviour changes. (Prousky, 2015)

Referenced Dietary Intakes

Adequate Intakes for Alpha linolenic acid (Omega 3) (g/day) (Institute of Medicine, 2002)

Adolescents (14–18 years): 1.6 (M) 1.1 (F)

Adults (19 years and older):  1.6 (M) 1.1 (F)

Recommendations for long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (mg/day) (European Food Safety Authority, 2009)

Adults: 250 mg/day (M+F)

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.

SAFETY, SIDE EFFECTS

• Common side effects of high dose EPA and DHA supplementation include heartburn, nausea, gastrointestinal discomfort, diarrhea, headache, and odoriferous sweat
• The European Food Safety Authority considers long-term consumption of EPA and DHA supplements at combined doses of up to about 5 g/day appears to be safe.
• The FDA recommends not exceeding 3 g/day EPA and DHA combined, with up to 2 g/day from dietary supplements (Office of Dietary Supplements, n.d.).

OMEGA 3 FATTY ACIDS AND MEDICATIONS

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

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References

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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513692/

Bruinsma, K. A., & Taren, D. L. (2000). Dieting, Essential Fatty Acid Intake, and Depression. Nutrition Reviews, 58(4), 98–108. https://doi.org/10.1111/j.1753-4887.2000.tb07539.x

Essential Fatty Acids. (2014, April 28). Linus Pauling Institute. https://lpi.oregonstate.edu/mic/other-nutrients/essential-fatty-acids

European Food Safety Authority. Labelling reference intake values for n-3 and n-6 polyunsaturated fatty acids. (2009, July 10). https://www.efsa.europa.eu/en/efsajournal/pub/1176

Institute of Medicine. (2002). Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. https://doi.org/10.17226/10490

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

Larrieu, T., & Layé, S. (2018). Food for Mood: Relevance of Nutritional Omega-3 Fatty Acids for Depression and Anxiety. Frontiers in Physiology, 9. https://doi.org/10.3389/fphys.2018.01047

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 Polyunsaturated Fatty Acids Reduces Opioid-Seeking Behaviors and Alters the Gut Microbiome. Nutrients, 11(8), E1900. https://doi.org/10.3390/nu11081900

Office of Dietary Supplements—Omega-3 Fatty Acids. (n.d.). Retrieved October 29, 2020, from https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/

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

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. https://doi.org/10.1111/adb.12623

Smith, J. (2021, October 4). Best Vitamin And Mineral Supplements For Alcohol Detox. Addiction Resource. https://www.addictionresource.net/treatment/detox/alcohol/nutrition/supplements/

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)

SAFETY, SIDE EFFECTS

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

• upset stomach
• headache
• sleepiness
• muscle weakness

GABA AND MEDICATIONS

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

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References

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

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

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

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

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

• 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).

SAFETY, SIDE EFFECTS

• 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

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References

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.

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.

Foods highest in Cystine. (n.d.). Retrieved December 8, 2020, from https://nutritiondata.self.com/foods-000085000000000000000-10.html?

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.

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).

SAFETY, SIDE EFFECTS

• 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.).

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References

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

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

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

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

Metcalf, E. (n.d.). Phenylalanine: Uses and Risks. WebMD. Retrieved December 22, 2021, from https://www.webmd.com/vitamins-and-supplements/phenylalanine-uses-and-risks

Opiate Withdrawal Vitamins: Top 12 Vitamins THAT WORK. (2018, February 28). Opiate Addiction Support. https://opiateaddictionsupport.com/opiate-withdrawal-vitamins/

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.

SAFETY, SIDE EFFECTS

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

L-THEANINE AND MEDICATIONS

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

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References

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

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

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

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

Tryptophan and 5-HTP and 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

Food sources of tryptophan

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

• turkey
• chicken
• tuna
• oats
• peanuts

Referenced Dietary Intakes

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

1. Supplementing tryptophan

• Amounts of tryptophan used in practice and research range from 50–6000 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). 

SAFETY, SIDE EFFECTS – Tryptophan

• Side effects of L-tryptophan supplementation can include heartburn, stomach pain, belching and gas, nausea, vomiting, diarrhea, and loss of appetite, headache, lightheadedness, drowsiness, dry mouth, visual blurring, muscle weakness, and sexual problems in some people (L-Tryptophan: Uses, Side Effects, n.d.).
• High doses of tryptophan can promote bronchial asthma aggravation and nausea.
• Tryptophan should not be used during pregnancy, with lupus, or with adrenal insufficiency (Prousky, 2015).
• 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).

TRYPTOPHAN AND MEDICATIONS

• Supplementing tryptophan or 5-HTP while on SSRI or MAOI medications is not generally recommended as it may promote an excessive buildup of serotonin  (Birdsall, 1998).
• Do not supplement tryptophan if taking morphine (Prousky, 2015)
• 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).

• SAFETY, SIDE EFFECTS – 5-HTP

• Side effects of 5-HTP supplementation are typically minimal and can include heartburn, flatulence, rumbling sensations, feeling of fullness, mild, nausea, vomiting, and hypomania (Werbach 1999: Murray & Pizzorno, 1998, p. 391-93)
• Other possible side effects include, stomach pain, diarrhea, drowsiness, sexual problems, and muscle problems (5-Htp: Uses, Side Effects, n.d.).
• High-dose supplementation – from 6-10 grams daily – have been linked to severe stomach problems and muscle spasms (5-HTP: Uses, Side Effects, n.d.).

5-HTP AND MEDICATIONS

• Supplementing tryptophan or 5-HTP while on SSRI or MAOI medications is not generally recommended as it may cause an excessive buildup of serotonin (Birdsall, 1998).
• Avoid taking tryptophan or 5-HTP (or limit to very low doses) if receiving electroconvulsive therapy (Gaby)

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References

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

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

Chouinard, G., Young, S. N., Annable, L., & Sourkes, T. L. (1977). Tryptophan-nicotinamide combination in depression. Lancet (London, England), 1(8005), 249. https://doi.org/10.1016/s0140-6736(77)91036-4

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 https://www.academia.edu/24627244/Tryptophan_nicotinamide_imipramine_and_their_combination_in_depression

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

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

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

Opiate Withdrawal Vitamins: Top 12 Vitamins THAT WORK. (2018, February 28). Opiate Addiction Support. https://opiateaddictionsupport.com/opiate-withdrawal-vitamins/

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.

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

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).

SAFETY, SIDE EFFECTS

• 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 AND MEDICATIONS

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

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References

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

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

Opiate Withdrawal Vitamins: Top 12 Vitamins THAT WORK. (2018, February 28). Opiate Addiction Support. https://opiateaddictionsupport.com/opiate-withdrawal-vitamins/

Physiology & Behavior, 92(4), 575–582. https://doi.org/10.1016/j.physbeh.2007.05.003

Top Foods High in Tyrosine. (n.d.). WebMD. Retrieved August 15, 2021, from https://www.webmd.com/diet/foods-high-in-tyrosine

Tyrosine: Health Benefits, Side Effects, Uses, Dose & Precautions. (n.d.). RxList. Retrieved August 15, 2021, from https://www.rxlist.com/tyrosine/supplements.htm

B-complex vitamins and Mental health

• Conditions including stress, illness, poor diet and nutrient absorption, as well as certain medications can increase needs for B-vitamins.
• A good quality B-complex can address the minimum nutrient requirements for the important B-vitamins including vitamins B1, B3, B6, B12, and folate.

“A trial of B-complex supplement seems advisable, especially in older persons and in persons taking medications that may deplete this vitamin” (Rakel, 2012).

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

Further reading

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

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References

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

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

Multivitamins and mental health

• Conditions including stress, illness, poor diet and nutrient absorption, as well as certain medications can increase needs for many different vitamins and minerals.
• A good quality multivitamin/mineral formula can address the minimum nutrient requirements for the important vitamins and minerals.

Use of multiple nutrients at the same time may play a role in helping to reduce toxicity in individuals recovering from opioid addiction.  (Libby et al., “Methodology: Use of Orthomolecular Techniques for Alcohol and Drug Abuse, in a Post-Detox Setting.”)

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References

Libby, A. F., Smart, W., McLeod, C., Wauchope, J. J., & Gutierrez, H. (1982). Methodology: Use of Orthomolecular Techniques for Alcohol and Drug Abuse, in a Post-Detox Setting. ORTHOMOLECULAR PSYCHIATRY, 11(4), 12.