For Medical Practitioners

PROLEEVA™ consists of a patent-pending proprietary formulation of Choline Bitartrate, Turmeric Root Powder, Devil’s Claw Root Powder, 5-Hydroxytryptophan (from Griffonia Simplicifolia Seed Extract), L-Arginine, gamma-Aminobutyric Acid (GABA), Bromelain Complex, Matcha Green Tea Leaf Powder, Asian Ginseng Root, and Caffeine Anhydrous.



All the ingredients above fall into the classification of Generally Recognized as Safe (GRAS) as defined by the Food and Drug Administration (FDA) (Sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act).



Patients with pain disorders may have increased nutritional demand and require certain amino acids in the amount that cannot be obtained from normal diet alone. Complex of amino acids included in PROLEEVA plays crucial role in modulation of pain.  In addition, PROLEEVA contains ingredients of herbal supplements with antinociceptive, anti-inflammatory, and antioxidant properties. For centuries, people used herbal medicine for variety of diseases. Nowadays, with support by clinical trials, herbalism is proving to be effective as adjunctive in a treatment of pain, fatigue, and inflammation.



5-Hydroxytryptophan is a metabolic intermediate in biosynthesis of serotonin from tryptophan. Tryptophan, an essential amino acid, is metabolized to serotonin, a neurotransmitter that controls mood and pain. Tryptophan can also be metabolized to kynurenine via tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in the brain. Kynurenine derivatives contribute to neurotoxicity and, via interaction with glutamate receptors, to pain and depression as well. IDO1 is upregulated in the brain in response to either pain or stress, could account for the link between pain and depression. IDO1 catalyzes the formation of kynurenine from tryptophan, which leaves less tryptophan available for serotonin production. Moreover, proinflammatory cytokines like IL-6 play a role in pain and depression, and some induce IDO1. Human studies demonstrated elevated plasma IL-6 levels in patients with chronic pain and depression. Animal studies report IL-6 boosts IDO1 expression in hippocampus. Therefore, it is important to prevent the interaction between pain and depression in the first place, by normalizing tryptophan metabolic pathway.  PROLEEVA complex includes 5-Hydroxytryptophan and the ingredients implicated in down-regulation of proinflammatory cytokines.



Choline Bitartrate is an essential nutrient, which also known as Lecithin, Choline is precursor of neurotransmitter acetylcholine, a major neurotransmitter in central and peripheral nervous system. Acetylcholine is a neurotransmitter at the neuromuscular junction and in the autonomic ganglia. In the brain cholinergic neurotransmission targets neuronal excitability, modifies presynaptic release of neurotransmitters, and coordinates the firing of groups of neurons. Acetylcholine regulates memory and cognition, due to influence on synaptic plasticity. In the spinal cord Acetylcholine modulates pain via its effects on nicotinic or muscarinic receptors, lessens firing of NMDA-pain receptors, potentiates the release of endogenous opiate peptides in the spinal cord, increases pain threshold. There is evidence that Choline supplementation improves exercise performance among individuals with choline deficiency and it has no effects on healthy individuals. Moreover, higher dietary choline intakes are associated with more favorable body composition (lower body fat and higher lean body mass) and lower insulin resistance.

L-arginine is a semi-essential amino acid that must be supplied in the diet in some pathological conditions, including, chronic pain, trauma, sepsis, and cancer.

L-Arginine is mainly metabolized intracellularly by nitric oxide synthase (NOS) and arginase. nitric oxide synthases and arginases, which are closely integrated with the control of immune response under physiological and pathological conditions. Nitric oxide is a messenger molecule, playing important role in pain modulation, inflammation, and regulation of apoptosis. NO can be generated by three different isoforms of the enzyme NO synthase (NOS): neuronal nNOS, inducible iNOS, and endothelial eNOS. Neuronal NO synthase (nNOS) implicated in modulating physiological functions such as learning, memory, neurogenesis, central blood pressure, and peripheral vascular tone regulation. Inducible NOS (iNOS), when induced in macrophages, produces large amounts of NO, which represent a major cytotoxic principle of those cells. Once induced by any harmful agent (bacteria, cytokine), iNOS is constantly active. iNOS produces large amounts of NO by immune and non-immune, which represent a major cytotoxic principle of those cells. iNOS is implicated in inflammatory and auto-immune processes. Endothelial NOS impede atherogenesis, fibrous plaque formation. Significant oxidative stress may deplete L-arginine, therefore it converts eNOS from an NO-producing enzyme to an enzyme that generates O2 (NOS uncoupling). Moreover, highly expressed Arginase compete with NOS for substrate. Relative L-Arginine deficiency can be improved by L-Arginine supplement. There are some other antioxidant effects of L-Arginine supplementation. Recent study on animals and humans observe L-arginine prevents the increase in the spinal NO level in diabetic group and delays the development of behavioral and histologic changes of diabetic neuropathy. L-arginine can be useful in diabetic patients to prevent diabetic neuropathy.



Gamma-Aminobutyric Acid (GABA) is an amino acid which works as major inhibitory neurotransmitter in brain and gut. GABA down-regulates activity pain receptors-NMDA and  decreases firing of pain neurons, therefore improves  neuropathic pain (such as diabetic neuropathy, postherpetic neuralgia, and central neuropathic pain). Currently, there are no sufficient evidence that GABA supplement alone crosses blood-brain barrier to an adequate degree. One study observes increase of blood-brain barrier permeability to GABA concurrently administered with  L-Arginine.  Some clinical trials indicate  GABA supplement may work through the signaling on gut GABA receptors.



Turmeric (Curcuma longa; an Indian spice) has a long history of safe use as food and it has long been used as in anti-inflammatory treatment in traditional Chinese and Ayurvedic medicine. Turmeric root powder contains a yellow-pigmented fraction that mainly consists of curcuminoids. Studies showed antioxidant and anti-inflammatory properties of Turmeric. Curcumin abate inflammation by inhibiting tumor necrosis factor-alpha, Interleukins, Cyclooxygenase 1 (COX-1) and COX-2, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and 5-lipoxygenase (5-LOX). Therefore, Curcumin improves joint function measured by morning stiffness, movements, and pain in patients with arthritis.



Devil’s Claw (Harpagophytum procumbens), an African plant with high medicinal value, exhibits strong anti-inflammatory characteristics, due to direct inhibitory effect on the COX-2 enzyme and Prostaglandin E2 (PGE2). In animal studies H. procumbens  extract crosses blood-brain barrier, dose-dependently increases superoxide dismutase, catalase and glutathione peroxidase activities in brain and reduces lipid peroxidation activity. H. procumbens extract exhibits its antioxidant effects by reducing the expression of hyperalgesia and allodynia. Devil’s Claw root powder has been used to treat a wide range of pathological conditions, including pain, arthritis and inflammation.



Bromelain complex is naturally derived mixture of proteolytic enzymes obtained from pineapple (Ananas comosus) and possesses notable anti-inflammatory, fibrinolytic effects, antiedematous, and immunomodulatory effects. Proteolytic enzymes  in Bromelain complex downregulate the expression levels of Cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2).  Bromelain complex is characterised by low toxicity compared to non-steroidal anti-inflammatory drugs, and is suitable for treatment of inflammation. In human studies bromelain demonstrated the reduction of IL-1β, IL-6 and TNF-α secretion when immune cells are already stimulated in the condition of inflammation-induced overproduction of cytokines. All of the above make Bromelain effective in treatment of osteo and rheumatoid arthritis.



Matcha Green Tea Leaf Powder is produced from the plant Camellia sinensis. Matcha is a traditional Chinese and Japanese tea.  It contains the highest concentration of amino acid L-theanine than in any other green tea. L-theanine i is a competitive antagonist of glutamate receptors, it binds to NMDA receptors, and acts as antagonist. L-theanine crosses blood-brain barrier and acts as neuroprotector by inhibiting glutamate metabolism and neurotransmission within the central nervous system. Furthermore, L-theanine increases level of dopamine and GABA, and regulates serotonin levels in the brain. L-theanine by itself has anxiolytic properties. Matcha Green Tea Leaf has the highest caffeine content compared with other green teas. Studies showed combination caffeine and green tea increase metabolism and enhance the improvement of fatigue, alertness, and focus. Furthermore, Camellia sinensis plays an effective role in the treatment of osteo and rheumatoid arthritis, due to its antioxidant properties. It modulates levels of antioxidants, and reduces levels of free radicals.



Caffeine Anhydrous is the most popular legal psychoactive substance. It improves fatigue, attention span, alertness, and accuracy of reactions. It increases energy, alertness, wakefulness, the accuracy of reactions, and the ability to concentrate and focus attention and decreases fatigue. Caffeine amplifies dopaminergic transmission via both presynaptic as well as postsynaptic mechanisms. Therefore, supraspinal dopaminergic transmission increases arousal and motivation as well as spontaneous motor activity and prolonged exercise time. Serotonin transmission is enhanced by caffeine at spinal level which causes excitation of alpha motoneuron pool and antinociception. Human studies have revealed an increase in central excitability, endurance, spinal excitability, and self-sustained firing, as well as decreases in force sensation, and muscle pain after oral caffeine administration. Caffeine down-regulates nociception via central blocking of adenosine receptors that influence pain signaling or by blocking of peripheral adenosine receptors on primary afferent nociceptors. Caffeine is gaining a more prominent role in treatment of migraine. It crosses blood-brain barrier, acts as a vasoconstrictor on cranial vessels, and is described as safe and well-tolerated abortive medication for the treatment of acute migraine.



Asian ginseng root (Panax ginseng) has been used in Chinese medicine for thousands of years. Panax ginseng exerts neuroprotective and antioxidant action It lessens neuronal damage by activation of the cytoprotective transcriptional factor Nrf2, which results in decrease in reactive oxygen species. Ginseng is neuroprotective in various chronic neurodegenerative disorders. It promotes neuronal survival, neuronal growth and differentiation. Panax ginseng inhibited neuronal damage and generation of intracellular reactive oxygen species (ROS) induced by excitatory amino acids, such as glutamate and N-methyl-D-aspartate (NMDA). Studies showed Ginseng improves memory and chronic fatigue including cancer related. Moreover, Asian ginger root exert analgesic and anti-inflammatory activities in treatment of autoimmune arthritis, due to its immunomodulatory properties. It is observed, Panax ginseng suppresses the effects of tumor necrosis factor alpha (TNF-a), the major mediator of inflammation.