DPN is nerve damage induced by diabetes and chronically high blood sugar, and affects 26% to 53% of diabetes patients worldwide; 21% to 53% of DPN sufferers experience ongoing neuropathic pain, which decreases their quality of life and has been reported to cost them 4.2 times more in medical expenditure than for those without neuropathic pain.
Tocotrienols, which are different forms of vitamin E, have been known to modulate the neuropathic pathway and are therefore thought to be able to alleviate neuropathic symptoms via their anti-inflammatory and anti-oxidative properties.
Assessment of pain
Based on this, the Vitamin E in Neuroprotection Study (VENUS), a parallel, double-blind, placebo-controlled trial, was conducted from 30 January 2011 to 7 December 2014 — after which there was a 12-month follow-up period — to assess the efficacy of oral supplementation with mixed tocotrienols on DPN patients.
The trial screened 14,289 diabetes patients from five public hospitals in Malaysia, and 391 patients, who had reported neuropathic symptoms, were further examined using the Neuropathy Impairment Score (NIS) and Total Symptom Score (TSS).
After this, 300 patients aged 20 and above, with an NIS of 2 or higher and a TSS of 3 or higher, were then recruited for the intervention. They were randomised to each receive either 200mg of mixed tocotrienols or a matching placebo twice a day for 12 months.
In both groups, those with hyperhomocysteinemia each received 5mg of folic acid once daily, and 500μg of methylcobalamin thrice daily.
More similarities than differences
The researchers then reported that only 229 of the participants completed the trial; among them, the TSS changes between the treatment and control groups after 12 months were comparable.
In addition, there were no significant difference in NIS and sensory nerve conduction test assessments between the two groups.
In fact, while serious adverse events in both groups were similar, the treatment group experienced more infections.
It was reported, however, that tocotrienol supplementation did reduce lancinating, or short-term 'stabbing' pain in patients with haemoglobin levels above 8% and normohomocysteinemia, but these were preliminary observations that required further investigation.
The paper concluded: "Oral supplementation of 400 mg/d of mixed tocotrienols for one year did not reduce overall neuropathic symptoms of DPN.
"Tocotrienols were relatively well tolerated and had a safety profile comparable to that of placebo. The preliminary observations of the effect of tocotrienols on lancinating pain among subsets of patients generate new hypotheses and need further evaluation.
"We propose future trials on the effects of longer-term mixed tocotrienols on DPN progression and patient quality of life."
Source: JAMA Neurology
"Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy"
Authors: Kah Hay Yuen, et al.