Low mood with low self-esteem and a loss of interest in activities and experiences affects hundreds of millions of people worldwide. This pervasive condition affects the quality of life through emotional, cognitive, behavioral, and physical symptoms. Thus, practitioners and patients alike may search for solutions. The underlying idea of targeting serotonin and the communication system of neurotransmitters by natural means may offer an alternative or complementary option.
Serotonin is an inhibitory neurotransmitter synthesized from tryptophan, an amino acid. It is found in the central nervous system (CNS), blood platelets, and most abundantly in the gut. Serotonin is involved in many body functions, including mood, sleep (as the precursor to melatonin), pain perception, hormone secretion, food intake, and cognitive function. This inhibitory neurotransmitter helps to promote calm, relaxation, and a sense of wellbeing. Serotonin also acts as a neuromodulator, able to reduce the release of glutamate, the main excitatory neurotransmitter, as well as stimulate the release of the main inhibitory neurotransmitter GABA. 
If the level or function in the body is insufficient, serotonin will not be able to work optimally in regulating excitation or stimulating GABA. Without serotonin’s modulation and inhibitory effects, excitatory neurotransmission (glutamate, dopamine, norepinephrine, epinephrine) may be in excess, causing over-excitation that could result in anxiousness, irritability, poor memory, lack of focus, and poor sleep. People with low serotonin levels may experience increases in mood issues, as well as anxiousness, aches and discomfort, carbohydrate cravings, and sleep difficulties due to the low serotonin and GABA activity. Sufficient levels of serotonin in the body may help maintain balance between excitation/energy and inhibition/relaxation. 
Individuals with mood issues and low serotonin may benefit from supplementation to support serotonin. 5-HTP is a popular supplement for this use, as it is the direct precursor to serotonin in the serotonin biosynthetic pathway. Supplemental 5-HTP readily crosses the blood-brain barrier and increases CNS synthesis of serotonin. 5-HTP supplementation has been shown to be effective in reducing anxiousness, increasing calmness, and promoting a sense of well-being. 
Additionally, some individuals may benefit from a supplement containing myo-inositol. Inositol is an isomer of glucose that we consume naturally in our diets. In the body, inositol is found in cell membranes. Inositol helps with the maintenance and effectiveness of cell signaling as part of the second messenger system. [5, 8] Inositol’s functions in cell communication is important because this second messenger system is associated with neurotransmitter pathways and receptors, including serotonin. Inositol may modulate the interaction between neurotransmitters, drugs, receptors, and signaling proteins. [2, 5] Inositol may also reverse desensitization of serotonin receptors.  Research has shown that inositol may be beneficial for people with mood imbalances, as well as anxiousness, compulsion and urges, and other mood concerns. [3, 5, 8, 10]
St. John’s wort is an herb commonly used for mood issues. St. John’s wort inhibits the reuptake of neurotransmitters such as serotonin, GABA, and dopamine, leaving more of these neurotransmitters available for potential use. This herb can also increase neurotransmitter sensitivity. Better neurotransmission means that there could be more potential for the mood regulation and calming effects of serotonin and GABA. 
Individuals with mood issues may also consider a supplement containing vitamin B6. Vitamin B6 has a variety of positive health effects due to its involvement with neurotransmitters. In the active form of pyridoxal-5-phosphate, vitamin B6 is a cofactor in the serotonergic pathway. B6 supplementation can increase serotonin and dopamine, thus increasing the calming and pleasurable effects of these neurotransmitters.  Vitamin B6 has been found to decrease mood concerns, as well as anxiousness, headaches, and discomfort. [4, 11] Additionally, vitamin B6 may be even more effective in combination with calcium or magnesium supplementation. [4, 9]
Overall, serotonin plays a major role in maintaining balance within the body and regulating a variety of functions associated with mood. It is important to test serotonin and other neurotransmitters to determine if low serotonin is present and how much support is needed. After introducing an appropriate intervention, such as 5-HTP supplementation, allowing adequate time for levels to replenish, it is important to retest neurotransmitter levels to determine the effectiveness of the intervention in increasing serotonin and improving mood, and making any necessary adjustments to the individual’s therapy.
Following this model of testing and retesting, along with safe, effective therapies, may help people with mood concerns understand underlying imbalances related to their experience, and offer evidence-based therapies that may be effective in managing depression and improving their quality of life.
- Alramadhan, E., Hanna, M. S., Hanna, M. S., Goldstein, T. G., Avila, S. M., & Weeks, B. S. (2012). Dietary and botanical anxiolytics. Medical Science Monitor, 18(4), RA40-RA48.
- Chengappa, K. R., Levine, J., Gershon, S., Mallinger, A. G., Hardan, A., Vagnucci, A., … & Kupfer, D. J. (2000). Inositol as an add‐on treatment for bipolar depression. Bipolar disorders, 2(1), 47-55.
- Ciranna, Á. (2006). Serotonin as a modulator of glutamate-and GABA-mediated neurotransmission: implications in physiological functions and in pathology. Current neuropharmacology, 4(2), 101-114.
- Ebrahimi, E., Khayati Motlagh, S., Nemati, S., & Tavakoli, Z. (2012). Effects of magnesium and vitamin B6 on the severity of premenstrual syndrome symptoms. J Caring Sci, 1(4), 183-9.
- Harvey, B. H., Brink, C. B., Seedat, S., & Stein, D. J. (2002). Defining the neuromolecular action of myo-inositol: application to obsessive–compulsive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry,26(1), 21-32.
- Jenkins, T. A., Nguyen, J. C., Polglaze, K. E., & Bertrand, P. P. (2016). Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis. Nutrients, 8(1), 56.
- Kennedy, D. O., & Wightman, E. L. (2011). Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Advances in Nutrition: An International Review Journal, 2(1), 32-50.
- Levine, J. (1997). Controlled trials of inositol in psychiatry. European neuropsychopharmacology, 7(2), 147-155.
- Masoumi, S. Z., Ataollahi, M., & Oshvandi, K. (2016). Effect of Combined Use of Calcium and Vitamin B6 on Premenstrual Syndrome Symptoms: A Randomized Clinical Trial. Journal of caring sciences, 5(1), 67.
- Mukai, T., Kishi, T., Matsuda, Y., & Iwata, N. (2014). A meta‐analysis of inositol for depression and anxiety disorders. Human Psychopharmacology: Clinical and Experimental, 29(1), 55-63.
- Wyatt, K. M., Dimmock, P. W., Jones, P. W., & O’Brien, P. S. (1999). Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. Bmj, 318(7195), 1375-1381.
Clinical Support Specialist at Sanesco International, Inc.
Emily Harrill is our newest Clinical Support Specialist, and a graduate of UNC Asheville with a Bachelor of Science in Health and Wellness Promotion. Improving quality of life for others is her ultimate goal. She enjoys being a part of the team at Sanesco, exploring wellness through the HPA-T Axis and encouraging others to use holistic, integrative means to achieve balanced health. She loves participating in challenging, empowering, and fun activities – especially Olympic weightlifting and belly dance.