Management of chronic back pain is a challenge for physicians. Although standard treatments exert a modest effect, they are associated with narcotic addiction and serious side effects from nonsteroidal antiinflammatory agents. Moreover, neurotransmitter depletion from both the pain syndrome and therapy may contribute to a poor treatment outcome. Neurotransmitter deficiency may be related both to increased turnover rate and inadequate neurotransmitter precursors from the diet, particularly for essential and semi-essential amino acids. Theramine, an amino acid blend 68405-1 (AAB), is a physician-prescribed only medical food. It contains neurotransmitter precursors and systems for increasing production and preventing attenuation of neurotransmitters. A double-blind controlled study of AAB, low-dose ibuprofen, and the coadministration of the 2 agents were performed. The primary end points included the Roland Morris index and Oswestry disability scale. The cohort included 122 patients aged between 18 and 75 years. The patients were randomized to 1 of 3 groups: AAB alone, ibuprofen alone, and the coadministration of the 2 agents. In addition, C-reactive protein, interleukin 6, and plasma amino acid concentrations were measured at baseline and 28 days time points. After treatment, the Oswestry Disability Index worsened by 4.52% in the ibuprofen group, improved 41.91% in the AAB group, and improved 62.15% in the combination group. The Roland Morris Index worsened by 0.73% in the ibuprofen group, improved by 50.3% in the AAB group, and improved 63.1% in the combination group. C-reactive protein in the ibuprofen group increased by 60.1%, decreased by 47.1% in the AAB group, and decreased by 36% in the combination group. Similar changes were seen in interleukin 6. Arginine, serine, histidine, and tryptophan levels were substantially reduced before treatment in the chronic pain syndrome and increased toward normal during treatment. There was a direct correlation between improvement in amino acid concentration and treatment response. Treatment with amino acid precursors was associated with substantial improvement in chronic back pain, reduction in inflammation, and improvement in back pain correlated with increased amino acid precursors to neurotransmitters in blood.

Selenium prevents cancer in some cases but fails to do so in others. Selenium's failure in this respect may be due to the development of resistance to its chemopreventive actions. Selenocompounds induce a variety of cancer-preventive actions in tumor cells, but these actions may be limited by the low concentrations of free selenocompounds able to reach cells from the plasma. Therefore, we have sought to identify the chemopreventive action requiring the lowest concentration of the redox-active form of selenium, methylseleninic acid (MSA). At submicromolar concentrations, MSA inhibited the malignant transformation of RWPE-1 prostate epithelial cells. In contrast, in already transformed prostate cancer cells, selenium in the micromolar range was required to inhibit cell growth and invasion and to induce apoptosis. The role of protein kinase C (PKC) in these cellular processes, especially the moderately selenium-sensitive PKCepsilon, was demonstrated using PKC-specific inhibitors and small interfering RNA. PKCepsilon levels inversely correlated with cellular sensitivity to MSA. An over-expression of PKCepsilon minimized MSA-induced inhibition of RWPE-1 cell transformation and induction of apoptosis. Thioredoxin reductase (TR), a selenoprotein, reversed the MSA-induced inactivation of PKC isoenzymes. High TR expression in advanced prostate cancer cells correlated with resistance to MSA. Furthermore, inhibition of TR by its specific inhibitor, auranofin, resulted in increased sensitivity of prostate cancer cells to MSA. Collectively, these results suggest that the cancer-preventive actions of selenium may be negated both by an over-expression of PKCepsilon, which is a redox-sensitive target for MSA, and by the selenoprotein TR, which reverses PKC sulfhydryl redox modification.