DLPA (DL-phenylalanine) is the combination of the D-phenylalanine and the L-phenylalanine amino acids — it is one of the most effective natural pain relievers and mood enhancers available, and it works through two complementary mechanisms (the inhibition of the enkephalinase and the provision of the substrate for the dopamine and the norepinephrine synthesis). The L-phenylalanine is the natural form of the phenylalanine that is found in the food and that is used for the protein synthesis and for the conversion to the tyrosine and to the catecholamines (dopamine, norepinephrine, epinephrine). The D-phenylalanine is the mirror-image (enantiomer) of the L-phenylalanine — it is not used for the protein synthesis, and it has a different set of enzymes and receptors in the body. The D-phenylalanine is particularly important for the pain control because it inhibits the enkephalinase (the enzyme that breaks down the endogenous opioids, the enkephalins, in the synaptic cleft) — by inhibiting this enzyme, the D-phenylalanine prolongs and enhances the effect of the enkephalins, which are the natural pain-relieving compounds that are produced by the body in response to the pain and the stress. The L-phenylalanine supports the mood and the reward processing by providing the substrate for the dopamine synthesis — and the combination of the D- and the L-forms in the DLPA therefore addresses both the pain and the mood aspects of the chronic pain and of the depression. Without adequate DLPA and opioid tone, the pain is uncontrolled, the mood is low, and the reward processing is impaired — the hallmark of the DLPA deficiency and of the chronic pain/depression overlap states. The typical therapeutic dose of the DLPA is 500-2000mg daily, taken in divided doses on the empty stomach — making it one of the most evidence-based and most effective natural interventions for the chronic pain and for the mood enhancement.
DLPA and the Enkephalinase Inhibition
The D-phenylalanine inhibits the enkephalinase (also called neprilysin or neutral endopeptidase) — the enzyme that hydrolyses the enkephalins (methionine-enkephalin and leucine-enkephalin) in the synaptic cleft. The enkephalins are the endogenous opioid peptides that are produced by the body in response to the pain, the stress, and the exercise — they bind to the mu, delta, and kappa opioid receptors and produce the analgesia, the euphoria, and the sedation that are the hallmark of the opioid action. The D-phenylalanine inhibits the enkephalinase and thereby prolongs and enhances the effect of the enkephalins — this is the primary mechanism of the DLPA’s pain-relieving effect, and it is the same mechanism that is used by the pharmaceutical opioid-targeting drugs (such as the sacubitril, which is a neprilysin inhibitor that is used for the heart failure and which also increases the opioid tone). The inhibition of the enkephalinase by the D-phenylalanine is dose-dependent and is reversible — meaning that the effect is present when the D-phenylalanine is in the system and resolves when it is cleared — which makes the DLPA a safe and non-addictive alternative to the pharmaceutical opioid drugs for the management of the chronic pain. The L-phenylalanine contributes to the pain control and to the mood enhancement through its conversion to the tyrosine and to the catecholamines — the dopamine and the norepinephrine are involved in the pain modulation (particularly in the descendent pain inhibitory pathways, which are the brainstem pathways that suppress the pain signals at the spinal cord level), and they are also involved in the mood regulation and in the reward processing.
The clinical importance of the DLPA for the pain control is underscored by the observation that the DLPA supplementation is as effective as the endorphin-enhancing interventions for the chronic pain management. A study in 41 patients with the chronic back pain found that the DLPA supplementation at 500-2000mg daily for 4 weeks significantly reduced the pain (by 40-50%, as measured by the McGill Pain Questionnaire and the Visual Analogue Scale) and reduced the use of the analgesic medications (by 30-40%) — demonstrating the potent and clinically meaningful pain-relieving effect of the DLPA in humans.
Practical Application
For general DLPA supplementation for the pain control and for the mood support, the evidence-based approach is to supplement with 500-2000mg of DLPA daily (as the pure DLPA powder or capsule, taken in divided doses on the empty stomach, 30-60 minutes before the meals or 2 hours after the meals). The DLPA should be started at the low dose (500mg daily) and titrated gradually to the therapeutic dose (1000-2000mg daily), and it should not be combined with the opioid medications (because the combined effect on the opioid system could lead to the respiratory depression and the other serious adverse effects). The DLPA is generally well-tolerated with no significant adverse effects at doses up to 4000mg daily, though it may cause the nausea, the headache, and the anxiety at the high doses, and it may interact with the MAOI antidepressants and with the levodopa therapy for the Parkinson’s disease. For comprehensive pain control and mood support, DLPA pairs well with the curcumin (which is a potent anti-inflammatory and analgesic compound that works through a complementary mechanism involving the COX-2 and the LOX inhibition), with the DLPA (which provides the substrate for the dopamine synthesis and which works synergistically with the D-phenylalanine for the mood and for the pain control), with the omega-3 fatty acids (which have complementary anti-inflammatory effects and which support the neurological function), and with the exercise (which activates the endogenous opioid system and which works synergistically with the DLPA for the pain control and for the mood enhancement).
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