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Supplements, Herbs, Vitamins, and Actual Evidence: Managing Anxiety, Depression, and Insomnia

Below is an outline of various natural herbs, supplements, and vitamins that have been shown to be effective in significantly impacting mood, sleep, and cognition in clinical trials. The recommended doses are an estimate based on clinical trials and not a guideline. This outline is not meant to be a prescription for anyone, but simply an outline to inform anyone interested of the many natural supplements that have been shown to be beneficial in supporting a healthy mind and body. Any addition of supplements, herbs, or vitamins from the list below should first be discussed with your doctor or psychiatrist should you be taking any prescribed medications.

Improve Sleep (Insomnia)

Melatonin (Start at 1mg and go as high as 5mg, max is 10mg)

o Melatonin is a hormone the body naturally produces from the pineal gland and regulates the sleep-wake cycle (Ye et al., 2019)

GABA (800-1500mg)

o Natural intake of GABA has been shown to clearly enhance sleep, however intake of supplements is less conclusive (Hepsomali et al., 2020)

o Supplemental GABA intake has been shown to possibly restrain wakefulness (Yu et al., 2019) rather than promote sedation or sleep

o Activates calming neurotransmitters and has been shown to decrease time to get to sleep as well as length of sleep (Kim et al., 2019)

L-theanine (100-200mg 2-3x daily)

o Amino acid that increases alpha wave activity which promotes relaxation (Gilbert, 2019)

o Shown to improve response to environmental stressors and reduce cortisol levels (White et al., 2016), which impacts ability to fall asleep and sleep quality

Chamomile (1-2 cups of tea or follow guidelines on pill, powder, or tincture supplement)

o Shown in many studies to decrease symptoms of anxiety, one reason being it contains the compound apigenin which has similar effects as benzodiazepines; a common anti-anxiety medication (Karetnick & Cassetty, 2020)

o Shown to improve sleep quality, especially among older adults (Adib-Hajbaghery & Seyedeh, 2017)

Magnesium (400-500mg)

o Shown to improve sleep quality and sleep duration in a recent longitudinal study (Zhang et al., 2021)

Valerian Root (300-900mg, cycle of after 28 days for a week)

o One of the most studied plant extracts and shows evidence of supporting better sleep quality due to anxiolytic effects, however the research is mixed and more needs to be known (Guadagna et al., 2020; Cassidy, 2021)

Improve Mood (Depression)

Vitamin B12 (2.4mcg-3mcg)

o Shown to increase efficacy of depression medication in decreasing depression symptoms (Syed et al., 2013)

o Low levels of B12 have been shown to possibly contribute to postpartum depression (Dhiman et al., 2021) and other forms of depression (Esnafoglu et al., 2020)

Vitamin B6 (50-100mg)

o Vitamin B6 has been shown to be linked to symptoms of depression, with 100mg per day supplementation showing significant improvement in depression symptoms in women taking oral contraceptives (Johnston & Curtin, 2020), among older women (Odai et al., 2020), and in the general population

5-HTP (100mg-300mg; taking 100mg at a time up to 3x daily)

o Helps to replenish serotonin after 5-HTP goes through decarboxylation and results in 5-HT (serotonin), which helps regulate mood and decreases as we age (Maffei, 2020)

o Tryptophan is converted into 5-HTP, but this is an extra step, therefore it is more efficient to supplement 5-HTP directly to increase serotonin production

Magnesium (300-450mg)

o This is necessary in creating serotonin due to needing both 5-HTP and P5P (pyridoxyl-5-phosphate) for the process to produce adequate levels of 5-HTP (serotonin) (Fredricks, n.d.)

Niacin (B3) (50mg taken at once or 25mg x2 daily if experience flushing or tingling)

o This is necessary to convert tryptophan into 5-HTP, sufficient levels of 5-HTP are needed to produce serotonin (5-HT), which regulates mood

o Some research has shown levels as high as 1000mg-3000mg per day is beneficial

Vitamin D (800IU)

o Shown to improve symptoms of both unipolar and bipolar depression (Berridge, 2017) and a meta-analysis showed clear significant impact of Vitamin D in managing symptoms of depression (Spedding, 2014)

o Deficiency has been linked to poorer mental health outcomes and associated with increase in depression symptoms (Boulkrane et al., 2020)

GABA (800-1500mg)

o A decline in GABA levels is identified in individuals experiencing depression (Duman et al., 2019)

Probiotics (Target as many strains as possible)

o Many studies have shown that probiotic supplementation results in anti-inflammatory effects which may mediate depression symptoms (Park et al., 2018)

o Probiotics have been shown to have antidepressant effects, especially in regulating 5-HT receptors (Li et al., 2019), which are responsible for replenishing/processing serotonin for mood and regulating hormones

Saffron (15-20mg 2x daily)

o Saffron has been shown to reduce depression symptoms in men and women at many age levels (Mazdi et al., 2016; Gholamali et al., 2018; Shafiee et al., 2018) and has been shown to improve depression symptoms specifically in individuals who are overweight (Akhondzadeh et al., 2019)

o Saffron was shown to be as effective as Setraline in reducing symptoms of depression, especially in the older population (Ahmadpanah et al., 2019)

Rhodiola (Start at 100-200mg per day and work up to 400-600mg daily)

o Shown to help decrease symptoms of depression (Amsterdam & Panossian, 2016), especially when combined with Saffron (Bangratz et al., 2018), which has been shown to also be effective on its own (Shafiee et al., 2018)

Decrease Stress (Anxiety)

B12 (2.4mcg-3mcg)

o Contains anxiolytic effects and has been shown to mediate hyperhomocysteinemia, which is associated with 3-6x increase in anxiety and/or depression (Saraswathy et al., 2019), however research is mixed in this finding

5-HTP (>100mg)

o Helps to replenish serotonin after 5-HTP goes through decarboxylation and results in 5-HT (serotonin), and 5-HT has been shown to decrease symptoms of anxiety (Kahn & Westenberg, 1985), especially agoraphobia and panic disorder ( Kahn et al., 1987)

Magnesium (300-400mg)

o Magnesium has been shown to be effective in managing stress, especially when combined with B6 (Pouteau et al., 2018)

Ashwagandha (300-500mg)

o Found to be useful in clinical trials at reducing stress and anxiety due to adaptogenic and anxiolytic effects (Jaysing et al., 2019)

GABA (800-1500mg)

o Activates calming neurotransmitters (Kim et al., 2019)

o Stress-reducing effects have been well established in the research (Hepsomali et al., 2020)

L-theanine (100-200mg 2-3x daily)

o Best source is green tea, which has other benefits due to catechins (Zdravic, 2018).

o Shown to reduce feeling of stress and decrease anxiety (White et al., 2016; Phing & Chee, 2019)

Rhodiola (Start at 100-200mg per day and work up to 400-600mg daily)

o Shown to be helpful in managing anxiety and chronic stress (Anghelescu et al., 2018)

Passion Flower (>500mg or 1-3 cups of tea per day)

o Helps to increase GABA

o Shown to help reduce symptoms or triggers of anxiety, especially in relationship to public speaking (Avelino da Silva et al., 2017)

o Shown to increase benefits of Setraline (common medication for anxiety) when used in conjunction (Nojoumi et al., 2016)

Chamomile (1-2 cups of tea or follow guidelins on pill, powder, or tincture supplement)

o Shown in many studies to decrease symptoms of anxiety , one reason being it contains the compound apigenin which has similar effects as benzodiazepines; a common anti-anxiety medication (Karetnick & Cassetty, 2020).

Milky Oat Tops

o Avena Sativa (oat extract to include milky oats) has been shown to benefit cognitive function and modulate the physiological response to a stressor (Kennedy et al., 2020)


Adib-Hajbaghery, M., & Seyedeh, N. M. (2017). The effects of chamomile extract on sleep quality among elderly people: A clinical trial. Complementary Therapies in Medicine, 35, 109-114.

Ahmadpanah, M., Ramezanshams, F., Ghaleiha, A., Akhondzadeh, S., Sadeghi Bahmani, D., & Brand, S. (2019). Crocus sativus L. (saffron) versus sertraline on symptoms of depression among older people with major depressive disorders–a double-blind, randomized intervention study. Psychiatry Research, 282, 112613.

Akhondzadeh, S., Mostafavi, S., Keshavarz, S. A., Mohammadi, M. R., Hosseini, S., & Eshraghian, M. R. (2020). A placebo controlled randomized clinical trial of Crocus sativus L. (saffron) on depression and food craving among overweight women with mild to moderate depression. Journal of Clinical Pharmacy & Therapeutics, 45(1), 134–143.

Amsterdam, J. D., & Panossian, A. G. (2016). Rhodiola rosea L. as a putative Botanical antidepressant. Phytomedicine, 23(7), 770–783.

Anghelescu, I.-G., Edwards, D., Seifritz, E., & Kasper, S. (2018). Stress management and the role of Rhodiola rosea: a review. International Journal of Psychiatry in Clinical Practice, 22(4), 242– 252.

Artukoglu, B. B., & Bloch, M. H. (2018). Editorial: Can omega‐3 fatty acids improve executive functioning? Will this reduce ADHD and depression? Journal of Child Psychology & Psychiatry, 59(6), 615–617.

Avelino da Silva, J., De Carvalho da Costa, Maria José, Rodrigues da Alves, Maria da Conceição, Fernandes da Braga, João Euclides, Bezerra Luna da Lima, Caliandra Maria, & De Morais da Pordeus, Liana Clébia. (2017). Effects of the single supplementation and multiple doses of passiflora incarnata L. on human anxiety: A clinical trial, double-blind, placebo-controlled, randomized. International Archives of Medicine, 10

Bangratz, M., Samira, A. A., Berlin, A., Blondeau, C., Guilbot, A., Dubourdeaux, M., & Lemoine, P. (2018). A preliminary assessment of a combination of rhodiola and saffron in the management of mild–moderate depression. Neuropsychiatric Disease and Treatment, 14, 1821-1829.

Berridge, M. J. (2017). Vitamin d and depression: Cellular and regulatory mechanisms. Pharmacological Reviews, 69(2), 80–92.

Boulkrane, M. S., Fedotova, J., Kolodyaznaya, V., Micale, V., Drago, F., van den Tol, A., & Baranenko, D. (2020). Vitamin D and Depression in Women: A Mini-review. Current neuropharmacology, 18(4), 288–300.

Cassady, B. (2021). Spotlight on Supplements: Valerian. Environmental Nutrition, 44(5), 3.

Dhiman, P., Raji, R. P., Anand, B. W., Premkumar, N., Bharadwaj, B., Ranjan, V. P., & Rajendiran, S. (2021). Cross-sectional association between vitamin B12 status and probable postpartum depression in Indian women. BMC Pregnancy and Childbirth, 21, 1-11.

Duman, R. S., Sanacora, G., & Krystal, J. H. (2019). Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron, 102(1), 75-90.

Esnafoglu, E., & Ozturan, D. D. (2020). The relationship of severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents. Child and Adolescent Mental Health,

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Guadagna, S., Barattini, D. F., Rosu, S., & Ferini-Strambi, L. (2020). Plant Extracts for Sleep Disturbances: A Systematic Review. Evidence - Based Complementary and Alternative Medicine, 2020, 9.

Hepsomali, P., Groeger, J. A., Nishihira, J., & Scholey, A. (2020). Effects of Oral Gamma- Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Frontiers in Neuroscience.

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Jelodar, G., Javid, Z., Sahraian, A., & Jelodar, S. (2018). Saffron improved depression and reduced homocysteine level in patients with major depression: A Randomized, double-blind study. Avicenna journal of phytomedicine, 8(1), 43–50.

Johnston, C., & Curtin, A. (2020). Vitamin B6 supplementation reduces depression in college women taking Oral CONTRACEPTIVES: A randomized, Double-Blind Cross-Over Trial. Current Developments in Nutrition, 4(Supplement_2), 1813–1813.

Jaysing, S., Sucheta, P., Khokan, D., & Deepak, L. (2019). Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus, 11(12)

Kahn, R., & Westenberg, H. G. (1985). L-5-Hydroxytryptophan in the treatment of anxiety disorders. Journal of affective disorders, 8(2), 197-200.

Kahn, R. S., Westenberg, H. G., Verhoeven, W. M., Wied, G. D., Christien, C., & Kamerbeek, W. D. (1987). Effect of a serotonin precursor and uptake inhibitor in anxiety disorders: a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. International Clinical Psychopharmacology.

Kennedy, D. O., Bonnländer, B., Lang, S. C., Pischel, I., Forster, J., Khan, J., Jackson, P. A., & Wightman, E. L. (2020). Acute and chronic effects of Green OAT (Avena sativa) extract on cognitive function and mood during a LABORATORY stressor in HEALTHY Adults: A Randomised, double-blind, placebo-controlled study in healthy humans. Nutrients, 12(6), 1598.

Kim, S., Jo, K., Hong, K., Han, S. H., & Suh, H. J. (2019). GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharmaceutical Biology, 57(1), 64-72.

Li, H., Wang, P., Huang, L., Li, P., & Zhang, D. (2019). Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model. Neurogastroenterology & Motility, 31(10), N.PAG.

Lv, T., Ye, M., Luo, F., Hu, B., Wang, A., Chen, J., Yan, J., He, Z., Chen, F., Qian, C., Zhang, J., Liu, Z., & Ding, Z. (2021). Probiotics treatment improves cognitive impairment in patients and animals: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 120,159-172. https://

Maffei, M. E. (2020). 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, BIOSYNTHESIS, Biotechnology, physiology and toxicology. International Journal of Molecular Sciences, 22(1), 181.

Nojoumi, M., Ghaeli, P., Salimi, S., Sharifi, A., & Raisi, F. (2016). Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients ‎with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study. Iranian journal of psychiatry, 11(3), 191–197.

Odai, T., Terauchi, M., Suzuki, R., Kato, K., Hirose, A., & Miyasaka, N. (2020). Depressive symptoms in middle-aged and elderly women are associated with a low intake of vitamin b6: A cross-sectional study. Nutrients, 12(11), 3437.

Park, C., Brietzke, E., Rosenblat, J. D., Musial, N., Zuckerman, H., Ragguett, R., Pan, Z., Rong, C., Fus, D., & McIntyre, R. S. (2018). Probiotics for the treatment of depressive symptoms: An anti-inflammatory mechanism? Brain, Behavior, and Immunity, 73, 115-124. https://

Phing, C. H., & Chee, O. Y. (2019). effects of alpha-s1-casein tryptic hydrolysate and l-theanine on sleep disorder and psychological components: A randomized, double-blind, placebo-controlled study. Malaysian Journal of Public Health Medicine, 19(1), 47-55.

Pouteau, E., ⨯ Marmar Kabir-Ahmadi, Noah, L., Mazur, A., Dye, L., Hellhammer, J., Pickering, G., & Dubray, C. (2018). Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PLoS One, 13(12)

Saraswathy, K. N., Ansari, S. N., Kaur, G., Joshi, P. C., & Chandel, S. (2019). Association of vitamin B12 mediated hyperhomocysteinemia with depression and anxiety disorder: A cross-sectional study among bhil indigenous population of India. Clinical Nutrition ESPEN, 30, 199-203. https://

Shafiee, M., Arekhi, S., Omranzadeh, A., & Sahebkar, A. (2018). Saffron in the treatment of depression, anxiety and other mental disorders: Current evidence and potential mechanisms of action. Journal of Affective Disorders, 227, 330–337.

Spedding, S. (2014). Vitamin D and Depression: A Systematic Review and Meta-Analysis Comparing Studies with and without Biological Flaws. Nutrients, 6(4), 1501-1518.

Syed, E. U., Wasay, M., & Awan, S. (2013). Vitamin B12 supplementation in treating major depressive disorder: a randomized controlled trial. The open neurology journal, 7, 44–48.

White, D., de Klerk, S., Woods, W., Gondalia, S., Noonan, C., & Scholey, A. (2016). Anti-Stress, behavioural And Magnetoencephalography effects of AN L-theanine-based nutrient Drink: A Randomised, double-blind, Placebo-Controlled, crossover trial. Nutrients, 8(1), 53.

Ye, T., Yin, X., Yu, L., Zheng, S. J., Cai, W. J., Wu, Y., & Feng, Y. Q. (2019). Metabolic analysis of the melatonin biosynthesis pathway using chemical labeling coupled with liquid chromatography‐mass spectrometry. Journal of pineal research, 66(1), e12531.

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