curcumin and Vitamin-B-Deficiency

Complementary and alternative treatment modalities are commonly utilized by patients for neuropathy and neuropathic pain due to perceived lack of benefit from conventional medical treatment. As the association between metabolic syndrome and neuropathy is increasingly recognized, diet and lifestyle interventions are becoming important components in the management of neuropathy. Progress in the understanding of the gut-immune interaction highlights the role the gut microbiome and inflammation plays in the modulation of neuropathy and neuropathic pain. Evidence for nutritional interventions, exercise, supplements, acupuncture, and mindfulness-based practices in the treatment of neuropathic pain is encouraging. This article reviews the available evidence to support the safe use of complementary and alternative treatments for commonly encountered conditions associated with neuropathy and neuropathic pain. Muscle Nerve 60: 124-136, 2019.

Topics: Acetylcarnitine; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diet; Diet Therapy; Dietary Supplements; Dysbiosis; Exercise; Exercise Therapy; Fatty Acids, Omega-3; Folic Acid; Gastrointestinal Microbiome; Humans; Integrative Medicine; Life Style; Metabolic Syndrome; Neuralgia; Peripheral Nervous System Diseases; Pyridoxal Phosphate; Thioctic Acid; Vitamin B 12; Vitamin B Complex; Vitamin B Deficiency; Vitamin D

Primary carnitine deficiency is a recessive disorder caused by heterogeneous mutations in the SLC22A5 gene encoding the OCTN2 carnitine transporter. Here we extend mutational analysis to eight new families with this disorder. To determine the mechanism by which missense mutations impaired carnitine transport, the OCTN2 transporter was tagged with the green fluorescent protein and expressed in CHO cells. Analysis by confocal microscopy indicated that several missense mutants (M1I, R169W, T232 M, G242 V, S280F, R282Q, W283R, A301D, W351R, R399Q, T440 M, E452 K, and T468R) matured normally to the plasma membrane. By contrast, other mutations (including R19P, DeltaF22, R83L, S280F, P398L, Y447C, and A142S/R488 H) caused significant retention of the mutant OCTN2 transporter in the cytoplasm. Failed maturation to the plasma membrane is a common mechanism in disorders affecting membrane transporters/ion channels, including cystic fibrosis. To correct this defect, we tested whether drugs reducing the efficiency of protein degradation in the endoplasmic reticulum (ER) (phenylbutyrate, curcumin) or capable of binding the OCTN2 carnitine transporter (verapamil, quinidine) could improve carnitine transport. Prolonged incubation with phenylbutyrate, quinidine, and verapamil partially stimulated carnitine transport, while curcumin was ineffective. These results indicate that OCTN2 mutations can affect carnitine transport by impairing maturation of transporters to the plasma membrane. Pharmacological therapy can be effective in partially restoring activity of mutant transporters.

Topics: Adult; Animals; Biological Transport; Carnitine; Child, Preschool; CHO Cells; Cricetinae; Cricetulus; Curcumin; DNA Mutational Analysis; DNA, Complementary; Endoplasmic Reticulum; Enzyme Inhibitors; Female; Humans; Infant; Male; Mutation, Missense; Organic Cation Transport Proteins; Phenylbutyrates; Quinidine; Solute Carrier Family 22 Member 5; Verapamil; Vitamin B Deficiency