D-phenylalanine (DPA) is sometimes used as a dietary supplement with claims that it supports the dopamine system. The rationale is that DPA, as an isomer of the amino acid phenylalanine, may indirectly influence dopamine levels by inhibiting certain enzymes involved in the breakdown of endorphins and enkephalins, which modulate dopamine pathways. Some small studies and biochemical evidence suggest that DPA inhibits the enzyme enkephalinase, thereby increasing the levels of endorphins and enkephalins, which are neuropeptides involved in mood regulation and the reward system associated with dopamine signaling. However, direct evidence that DPA supplementation substantially increases dopamine levels in humans or leads to meaningful clinical improvements in dopamine-related conditions (such as depression or Parkinson's disease) is weak and limited.

The majority of research supporting DPA's effects on mood or pain is preliminary, often based on animal studies or small, uncontrolled human trials. Systematic reviews and large randomized controlled trials are lacking. Most peer-reviewed literature focuses on L-phenylalanine (the natural isomer and direct dopamine precursor) rather than DPA. Thus, while there is a plausible biochemical mechanism and some limited scientific support for DPA's use related to dopamine modulation, the overall evidence is modest, and its clinical utility remains unproven.