Neuropathy
Acetyl-L-Carnitine
Taking acetyl-L-carnitine can reduce pain in people with diabetic neuropathy, but does not appear to consistently benefit cases of chemotherapy-induced neuropathy.Dose:
500 to 1,000 mg three times dailyAcetyl-L-CarnitineAcetyl-l-carnitine has been found to reduce diabetic peripheral neuropathy in multiple controlled clinical trials. A meta-analysis included data from four trials: the subjects in three trials had diabetic peripheral neuropathy and those in the fourth trial had peripheral neuropathy due to antiretroviral therapy for HIV. The analysis found a 20.2% greater reduction in pain in people treated with acetyl-l-carnitine compared to placebo.5
Findings from trials examining the use of acetyl-l-carnitine for chemotherapy-induced peripheral neuropathy have been mixed: While several uncontrolled trials have reported decreased nerve pain in cancer patients using various chemotherapy agents, others have noted no effect.5,7 In one placebo-controlled trial that included 239 patients with chemotherapy-induced neuropathy, those who received 3 grams daily of acetyl-l-carnitine were more likely to have pain reduction and nerve function improvement.8 Conversely, another placebo-controlled trial that included 409 breast cancer patients treated with a class of chemotherapy agents called taxanes found treatment with acetyl-l-carnitine increased the severity of chemotherapy-induced neuropathy over 24 weeks and this effect persisted more than 1.5 years after the end of treatment.9
Magnesium
Supplementing with magnesium may reverse poor magnesium status and improve diabetic peripheral neuropathy, but does not appear to be helpful for preventing or treating chemotherapy-induced neuropathy.Dose:
200 to 600 mg dailyMagnesiumPeople with diabetes frequently have low magnesium levels, and low magnesium is correlated with poor blood glucose control and high risk of diabetes complications, including peripheral neuropathy.9,10,11 In a controlled trial that included 97 magnesium-depleted participants with type 1 diabetes, taking 300 mg of magnesium daily for five years improved magnesium status and decreased or stabilized neuropathic symptoms in 88% of subjects; on the other hand, 61% of those not taking magnesium had worsening of neuropathic symptoms.12
Low magnesium intake has also been associated with greater risk and severity of chemotherapy-induced neuropathy, but intravenous magnesium has not been found to be beneficial in cancer patients being treated with platinum-based chemotherapies.13,14
Vitamin B6, Vitamin B12, and Folic Acid
B vitamins, and vitamin B12 in particular, may be helpful in treating various types of neuropathies. People with type 2 diabetes taking metformin should be monitored for B12 deficiency.Dose:
2,000 mcg methylcobalamin (B12); 3,000 mcg methylfolate (B9); and 35 mg pyridoxal 5-phosphate once to twice dailyVitamin B6, Vitamin B12, and Folic AcidVitamin B12 has demonstrated neuroprotective and analgesic effects and has been found to have benefits in treating peripheral neuropathy from various causes.15,16,17,18 Vitamin B12 deficiency is common in people with type 2 diabetes, and a widely used anti-diabetes medication, metformin, has been found to induce vitamin B12 deficiency.19,20,21 Vitamin B12 deficiency has been associated in some, but not all, studies with increased risk of diabetic neuropathy.22,23,24 A possible link between low folate levels and diabetic neuropathy has also been reported.23 Preliminary trials using combinations of active forms of oral vitamin B12, folate, and vitamin B6 found they have a positive effect on diabetic neuropathy symptoms and quality of life.26,27,28 In a comparison trial, vitamin B12 injections were found to be more effective than the pain medication, nortriptyline, for reducing diabetic neuropathy symptoms.29 One meta-analysis of 17 clinical trials found the combination of intramuscular or intravenous vitamin B12 plus intravenous alpha-lipoic acid may be more effective than vitamin B12 alone.30 The possible role of vitamin B12 and other B vitamins in preventing or treating chemotherapy-induced neuropathy is suggested by laboratory and animal research, but findings from human trials have not been conclusive.31,32Vitamin D
Supplementing with vitamin D3 daily or weekly can help reduce symptoms of diabetic neuropathy.Dose:
7,100 IU daily or 50,000 IU weekly of vitamin D3 for eight to twelve weeks, followed by 2,000 to 4,000 IU daily long termVitamin DVitamin D deficiency is strongly correlated with type 2 diabetes and its complications, including neuropathy and related foot disease.32,33,34 One placebo-controlled trial with 112 participants found 50,000 IU per week (equivalent to about 7,100 IU daily) of oral vitamin D3 reduced diabetic neuropathy symptoms, but not disability or nerve dysfunction, after eight weeks of treatment.35 However, using a very high infrequent dose may not be as effective: in a preliminary uncontrolled trial, 143 subjects with diabetic neuropathy were given a single 600,000 IU injection of vitamin D and were monitored for 20 weeks; vitamin D did not relieve neuropathy symptoms but did improve neuropathy-specific quality of life scores.36 A meta-analysis of data from four randomized controlled trials found vitamin D supplementation can improve signs and symptoms of diabetic neuropathy.37 Low vitamin D levels have also been associated with increased risk of chemotherapy-induced neuropathy, but clinical trials investigating the effects of vitamin D supplementation are lacking.38,39