10/16/12: Integrative mental health: Simple approaches to complex pathways


Integrative mental health: Simple approaches to complex pathways

By Kelly C. Heim, Ph.D. and James Greenblatt, M.D.

The human mind is orchestrated by large networks of neurons. Like any type of network, proper function depends on the coordinated efficiency and accuracy of communication. In the brain, a language of chemical messengers allows high-fidelity neuronal conversations that enable us to think, learn, remember, and experience emotion. Known as neurotransmitters, these compounds are critical for emotional wellness, cognitive performance and behavioral health.

Dopamine and serotonin are neurotransmitters that are critical for overall mental health. Dopamine plays important roles in maintaining alertness, while serotonin facilitates relaxation and appetite regulation. A healthy presence of both compounds is contingent upon an adequate supply of nutrients that serve as precursors and cofactors.1,2 Once synthesized, these neurotransmitters must remain intact to function properly. There are many steps in each pathway that provide multiple opportunities for nutritional support. Specifically, three approaches have been characterized:

  1. Provision of amino acids as building blocks for neurotransmitters1
  2. Adequacy of vitamin and mineral cofactors required by biosynthetic pathways2
  3. Supplementation of phytonutrients that stabilize neurotransmitters and maintain healthy reuptake to maximize activity in the synapse3


Dopamine synthesis begins with the amino acid L-phenylalanine, which is sequentially converted to tyrosine and L-DOPA, its immediate precursor.1,2 This pathway requires activated folate (5-methyltetrahydrofolate; MTHF), activated vitamin B6 (pyridoxal 5′-phosphate; P5P) and zinc.2 Once synthesized and released into the synapse, dopamine binds to receptors on the receiving (postsynaptic) neuron to exert its beneficial effects. However, dopamine is subject to removal from the synapse in a process known as reuptake. In addition, dopamine may be degraded by the enzymes catechol O-methyltransferase (COMT) and monoamine oxidase (MAO) (Figure 1). Nearly a decade of research has indicated that the polyphenols in green tea directly target COMT, supporting dopamine stability.4 Rhodiola rosea and grape seed proanthocyanidins have been reported to promote healthy MAO activity.5,6


Serotonin synthesis begins with the amino acid L-tryptophan, which is hydroxylated to form 5-hydroxytryptophan in a pathway that requires 5-MTHF, vitamin B6 and vitamin C.1,2 Clinical studies have also indicated essential roles of zinc and magnesium.2 Once released into the synapse, serotonin activity depends on healthy reuptake balance, which may be maintained in the presence of taurine.7 Upon binding of serotonin to its receptor, an inositol-dependent signaling pathway ensures effective communication with the postsynaptic neuron (Figure 1).

PureSYNAPSE is comprised of three main products formulated to support overall mental and emotional health. DopaPlus delivers the precursors, cofactors and phytonutrients that support multiple steps in dopamine signaling to promote alertness, cognitive function and positive mood. SeroPlus provides precursors, cofactors and taurine and inositol to help moderate occasional stress, promote relaxation and support healthy eating behavior.

Figure 1. Mechanisms of nutritional support for dopamine and serotonin neurotransmission. Dopamine and serotonin are synthesized in the presynaptic neuron (blue) in pathways requiring amino acids and cofactors. When released into the synapse, they must bind to their receptors on the postsynaptic neuron (green) to relay messages that support various aspects of mental health and emotional wellness.

In many clinical contexts, support for both serotonin and dopamine signaling is indicated. NeuroPure combines serotonin and dopamine precursors and cofactors. This formula provides the polyphenols curcumin and quercetin for healthy MAO activity, which further supports both pathways.8,9 An additional mechanism of these polyphenols is maintaining L-tryptophan availability by moderating the enzyme responsible for its degradation into excitatory metabolites.10 NeuroPure provides comprehensive support for emotional balance and mood stability.

Each product is designed to be used individually with the co-support of magnesium and essential fatty acids. PureSYNAPSE has been developed based on decades of research and clinical experience in integrative psychiatry. Each formula delivers powerful bioactives in combinations that address multiple aspects of neurotransmission to optimally support mental health and emotional well-being.


  1. Fernstrom JD. Large neutral amino acids: dietary effects on brain neurochemistry and function. Amino Acids. 2012; Jun 8.
  2. Kaplan, Bonnie J.; Crawford, et al. Vitamins, minerals, and mood. Psychological Bulletin, Vol 133(5), Sep 2007;747-760.
  3. Dias GP, Cavegn N, Nix A, et al. The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioural effects on depression and anxiety. Oxid Med Cell Longev. 2012;2012:541971.
  4. Lu H, Meng X, Yang CS. Enzymology of methylation of tea catechins and inhibition of catechol-O-methyltransferase by (-)-epigallocatechin gallate. Drug Metab Dispos. 2003;31(5):572-579.
  5. van Diermen D, Marston A, Bravo J, et al. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397-401.
  6. Xu Y, Li S, Chen R, et al. Antidepressant-like effect of low molecular proanthocyanidin in mice: involvement of monoaminergic system. Pharmacol Biochem Behav. 2010;94(3):447-453.
  7. Lakhan SE, Vieira KF. Nutritional therapies for mental disorders. Nutr J. 2008;21;7:2.
  8. Dixon Clarke SE, Ramsay RR. Dietary inhibitors of monoamine oxidase A. J Neural Transm. 2011;118(7):1031-1041.
  9. Kulkarni S, Dhir A, Akula KK. Potentials of curcumin as an antidepressant. Sci World Journal. 2009;9:1233-1241.
  10. Maes M, Leonard BE, Myint AM, et al. The new ‘5-HT’ hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):702-721.
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