A 10-ingredient supplement shows promise in reducing pain and improving nerve function in diabetic neuropathy

Aims: To evaluate whether the combination of palmitoylethanolamide (PEA, 300 mg), superoxide dismutase (SOD, 70 UI), alpha lipoic acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) can alleviate pain and improve nerve function measures in people with diabetic polyneuropathy (DPN) experiencing mild or moderate neuropathic pain.

Methods: This single-center placebo-controlled randomized study included 73 individuals with type 2 diabetes (T2D) who had been diagnosed with painful DPN not on analgesic treatment. Participants randomly assigned to the active arm (n=36) were given a 10-element combination tablet twice daily for 6 months; the remainder (n=37) received placebo. Diabetic neuropathy (DN) was assessed at baseline and after 6 months by means of the Michigan neuropathy screening instrument questionnaire and examination (MNSIQ and MNSIE), vibration perception threshold (VPT), cardiovascular autonomic reflex tests (CARTs), sural nerve conduction velocity (SNCV) and amplitude (SNCA), and electrochemical skin conductance in hands (ESCH) and feet (ESCF). Pain score (PS) and quality of life (QoL) were measured with the Pain DETECT and the Diabetes Quality of Life questionnaires, respectively.

Results: A significant improvement in PS (from 20.9 to 13.9, p <0.001), vitamin B12 levels (from 222.1 to 576.3 pg/mL, p<0.001), SNCV (from 28.8 to 30.4 m/s, p=0.001), VPT (from 32.1 to 26.7 V, p=0.001), ESCF (from 72.2 to 74.8 μS, p<0.001), QoL (from 38.3 to 35.6, p<0.001), and MNSIQ (from 6.1 to 5.9, p=0.017) was observed in the active group over the 6-month period. In the placebo group, MNSIE worsened (from 2.9 to 3.4, p<0.001), while PS and the other parameters did not show significant variations. Overall, the changes from baseline to follow-up were different between the active and placebo groups for vitamin B12 (p<0.001), PS (p<0.001), and VPT (p=0.025).

Conclusions: A 10-element supplement taken twice daily for 6 months improved vitamin B12 levels, pain, and VPT in individuals with T2D and painful DPN.

Comments: This study documents the efficacy and safety of a 10-ingredient supplement for pain relief and improvement of some nerve function indices in people with painful DPN. While the contribution of each component, with previously documented different-degree effects on neuropathic symptoms, could not be evaluated, the authors propose possible synergistic effects among them. Moreover, based on their previous combination studies and the proven efficacy of PEA on diabetic neuropathic pain in a few studies (Pickering E et al Inflammopharmacology 2022;30:2063–207), they attribute a significant proportion of the observed pain reduction (-33%) to PEA.

However, research on combinations of pathogenetic treatments remains limited, and the findings of this work deserve to be confirmed in larger studies involving people with well-characterized painful diabetic neuropathy and greater pain severity. Given their safety, pathogenetic treatments could be a valuable option for a wide range of patients, and efforts to define the place in therapy of these agents are welcome.

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Reference: Didangelos T, Karlafti E, Kotzakioulafi E, Giannoulaki P, Kontoninas Z, Kontana A, Evripidou P, Savopoulos C, Birkenfeld AL, Kantartzis K. Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy. Nutrients. 2024 Sep 10;16(18):3045. doi: 10.3390/nu16183045. PMID: 39339645; PMCID: PMC11434759.

🔗 https://www.mdpi.com/2072-6643/16/18/3045