Abstract
Despite advances in clinical and translational research, an effective therapeutic option for diabetic sensorimotor polyneuropathy (DSP) has remained elusive. The pathomechanisms of DSP are diverse, and along with hyperglycemia, the roles of inflammatory mediators and lipotoxicity in the development of microangiopathy have been well elucidated. Omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential fatty acids with a vital role in a number of physiological processes, including neural health, membrane structure integrity, anti-inflammatory processes, and lipid metabolism. Identification of n-3 PUFA derived specialised proresolving mediators (SPM), namely resolvins, neuroprotectin, and maresins which also favour nerve regeneration, have positioned n-3 PUFA as potential treatment options in DSP. Studies in n-3 PUFA treated animal models of DSP showed positive nerve benefits in functional, electrophysiological, and pathological indices. Clinical trials in humans are limited, but recent proof-of-concept evidence suggests n-3 PUFA has a positive effect on small nerve fibre regeneration with an increase in the small nerve fiber measure of corneal nerve fibre length (CNFL). Further randomized control trials with a longer duration of treatment, higher n-3 PUFA doses, and more rigorous neuropathy measures are needed to provide a definitive understanding of the benefits of n-3 PUFA supplementation in DSP.
Keywords: Omega-3, omega-3 polyunsaturated fatty acid, diabetes, diabetic neuropathy, diabetes complication, nutrition therapy.
[http://dx.doi.org/10.1517/14656566.2015.1067680] [PMID: 26161591]
[http://dx.doi.org/10.1038/s41572-019-0092-1] [PMID: 31197153]
[http://dx.doi.org/10.1503/cmaj.190134] [PMID: 31481423]
[http://dx.doi.org/10.1503/cmaj.191064] [PMID: 32392480]
[http://dx.doi.org/10.1001/jama.284.17.2215] [PMID: 11056593]
[http://dx.doi.org/10.1212/WNL.53.3.580] [PMID: 10449124]
[http://dx.doi.org/10.2337/dc08-2110] [PMID: 19366965]
[http://dx.doi.org/10.2337/dc15-2068] [PMID: 26884473]
[http://dx.doi.org/10.1152/jn.00224.2015] [PMID: 25925322]
[http://dx.doi.org/10.4172/2155-9562.1000453] [PMID: 29423332]
[http://dx.doi.org/10.1155/2016/5905891] [PMID: 27774316]
[http://dx.doi.org/10.1212/WNL.0000000000004033] [PMID: 28515269]
[http://dx.doi.org/10.2147/DMSO.S187268] [PMID: 30662277]
[http://dx.doi.org/10.1159/000012775] [PMID: 10436310]
[http://dx.doi.org/10.3945/jn.113.186346] [PMID: 24647395]
[http://dx.doi.org/10.1007/s12035-010-8162-0] [PMID: 21279554]
[http://dx.doi.org/10.1079/NRR2005113] [PMID: 19079874]
[http://dx.doi.org/10.3389/fphar.2011.00069] [PMID: 22125537]
[http://dx.doi.org/10.1080/10408398.2011.596292] [PMID: 24261532]
[http://dx.doi.org/10.1016/S0021-9258(18)76213-3]
[http://dx.doi.org/10.1038/nrn3820] [PMID: 25387473]
[http://dx.doi.org/10.1523/JNEUROSCI.0605-15.2015] [PMID: 26377463]
[http://dx.doi.org/10.2337/db17-0249] [PMID: 28592408]
[http://dx.doi.org/10.3810/pgm.2009.11.2083] [PMID: 19940425]
[http://dx.doi.org/10.7205/MILMED-D-14-00147] [PMID: 25373090]
[http://dx.doi.org/10.1016/j.jacc.2011.06.063] [PMID: 22051327]
[http://dx.doi.org/10.1136/bmj.g2272] [PMID: 24736206]
[http://dx.doi.org/10.1016/j.plipres.2016.05.001] [PMID: 27216485]
[http://dx.doi.org/10.1111/j.2040-1124.2010.00070.x] [PMID: 24843457]
[http://dx.doi.org/10.1016/j.neuron.2017.02.005] [PMID: 28334605]
[http://dx.doi.org/10.1002/ana.410190504] [PMID: 3717907]
[http://dx.doi.org/10.1002/mus.20785] [PMID: 17469109]
[http://dx.doi.org/10.1002/ana.410420509] [PMID: 9392572]
[http://dx.doi.org/10.1186/s40200-016-0235-9] [PMID: 27123439]
[http://dx.doi.org/10.1007/s11892-016-0727-5] [PMID: 26897744]
[http://dx.doi.org/10.1016/j.plipres.2017.01.002] [PMID: 28104532]
[http://dx.doi.org/10.1136/bmj.l4697] [PMID: 31434641]
[http://dx.doi.org/10.4239/wjd.v6.i2.245] [PMID: 25789106]
[http://dx.doi.org/10.1167/iovs.09-3388] [PMID: 19357361]
[http://dx.doi.org/10.1016/S0022-2275(20)37132-7] [PMID: 9374124]
[http://dx.doi.org/10.1111/j.1476-5381.2009.00290.x] [PMID: 19594757]
[http://dx.doi.org/10.3389/fphar.2019.01022] [PMID: 31607902]
[http://dx.doi.org/10.1016/j.prostaglandins.2012.01.005] [PMID: 22326554]
[http://dx.doi.org/10.1007/s11892-018-1046-9] [PMID: 30145729]
[http://dx.doi.org/10.1167/iovs.09-3641] [PMID: 19797230]
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.05.027] [PMID: 18620782]
[http://dx.doi.org/10.1155/2018/2380319] [PMID: 29674943]
[http://dx.doi.org/10.2337/db10-0054] [PMID: 20841610]
[http://dx.doi.org/10.3390/ijms20205028] [PMID: 31614433]
[http://dx.doi.org/10.3945/jn.111.155259] [PMID: 22279140]
[http://dx.doi.org/10.3390/nu2030355] [PMID: 22254027]
[http://dx.doi.org/10.1080/00325481.2019.1607414] [PMID: 31063407]
[http://dx.doi.org/10.3733/ca.v065n03p106] [PMID: 24860193]
[http://dx.doi.org/10.1097/RHU.0000000000000563] [PMID: 28816722]
[http://dx.doi.org/10.4103/2231-4040.90879] [PMID: 22247890]
[http://dx.doi.org/10.1016/S0891-6632(88)80006-0] [PMID: 2853165]
[http://dx.doi.org/10.1007/BF00274252] [PMID: 2477293]
[http://dx.doi.org/10.1093/jn/129.1.207] [PMID: 9915901]
[http://dx.doi.org/10.1242/dmm.028530] [PMID: 28381495]
[http://dx.doi.org/10.3389/fphar.2017.00723] [PMID: 29089890]
[http://dx.doi.org/10.1111/jphp.13213] [PMID: 31876957]
[http://dx.doi.org/10.1111/j.1750-3639.2005.tb00513.x] [PMID: 15912889]
[http://dx.doi.org/10.1016/1056-8727(95)00081-X] [PMID: 8887017]
[http://dx.doi.org/10.1016/j.clinph.2004.08.011] [PMID: 15661104]
[http://dx.doi.org/10.1093/nutrit/nuz054] [PMID: 31532492]
[http://dx.doi.org/10.4093/dmj.2019.0099] [PMID: 31701699]
[http://dx.doi.org/10.1111/dme.13083] [PMID: 26822889]
[PMID: 24429949]
[http://dx.doi.org/10.2337/dc13-2005] [PMID: 24574353]
[http://dx.doi.org/10.1111/j.1529-8027.2012.00420.x] [PMID: 22971096]
[http://dx.doi.org/10.1016/j.jdiacomp.2017.06.010] [PMID: 28716357]
[http://dx.doi.org/10.1111/j.1464-5491.2009.02667.x] [PMID: 19317818]
[http://dx.doi.org/10.2337/dc19-0951] [PMID: 32139385]
[http://dx.doi.org/10.1080/14656566.2020.1812578] [PMID: 32866410]
[http://dx.doi.org/10.2337/db12-0574] [PMID: 23002037]
[http://dx.doi.org/10.1002/14651858.CD006320.pub4] [PMID: 24585498]
[http://dx.doi.org/10.1007/BF01401666] [PMID: 6837347]
[http://dx.doi.org/10.1023/A:1008852127668] [PMID: 10767122]
[http://dx.doi.org/10.1016/S0002-9149(97)89130-8] [PMID: 8540453]
[http://dx.doi.org/10.1001/jama.285.3.304] [PMID: 11176840]
[http://dx.doi.org/10.1016/j.amjcard.2006.11.020] [PMID: 17368277]
[http://dx.doi.org/10.12688/f1000research.17118.1] [PMID: 30828432]
[http://dx.doi.org/10.1016/j.clinthera.2018.04.001] [PMID: 29709457]
[http://dx.doi.org/10.1016/bs.irn.2016.03.008] [PMID: 27133154]