Neuropathy Not Caused By Diabetes

This article is titled for sensationalism, but may be a breakthrough to jolt researchers out of their lethargy. I say this because I feel that another study needs to be done to prove the conclusion. If it turns out to be true, then this is a great conclusion. Yes, I know that vitamin B12 deficiency causes neuropathy, but other deficiencies also contribute to neuropathy, vitamin D being one of them.

This article also talks about other medications that can cause neuropathy. The two medications are often prescribed for treatment of GERD (gastroesophageal reflux disease). The two are histamine H2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs).

First, this is a brief discussion of the relationship of metformin and vitamin B12. People who have been on metformin have shown a malabsorption of vitamin B-12. People with diabetes being treated with metformin tend to have a lower vitamin B-12 level and worse diabetic neuropathy than patients on other oral therapies. The proposed mechanisms of metformin-induced vitamin B-12 deficiency include a decrease in bile acid secretion resulting in bacterial overgrown that decreases intestinal absorption, decreased intrinsic factor secretion, and decreased absorption due to metformin's antagonism of cell surface receptors in the ileum. Supplementation of vitamin B-12, cessation of metformin therapy, administration of doxycycline, and oral calcium supplement, have all been shown to improve vitamin B-12 levels.

Now, this is a brief discussion of the prescriptions for GERD. H2RAs and PPIs have been documented to interfere with vitamin B-12 absorption, showing a 53% drop in protein-bound vitamin B-12 absorption with H2RA. In one study with ranitidine, the decrease in absorption was shown to be 89%. It should be noted that unbound vitamin B-12 (i.e. vitamin B-12 supplements) can be absorbed with H2RAs, but protein-bound vitamin B-12 found from food sources are not fully absorbed. The mechanism of interference has been attributed to the decrease in gastric acid, pepsin, and intrinsic factor output; however, improvement in vitamin B-12 levels can be obtained with vitamin B-12 supplementation and cessation of H2RAs and PPIs therapy.

Vitamin B-12 has several important roles in the human body, and the signs and symptoms of vitamin B-12 deficiency can easily be mistaken for diabetic neuropathy. These signs and symptoms include: paresthesias (an abnormal sensation, as prickling, itching, etc.); diminished sensation, proprioception (awareness of the position of one's body) and nerve conduction; loss of cutaneous sensation; muscle weakness; abnormal reflexes; incontinence; loss of vision; and axonal degeneration. Several studies have shown that vitamin B-12 supplementation, alone or concomitant with other agents, has improve multiple aspects of diabetic neuropathy, such as cutaneous sensitivity, pain, paresthesia, nerve conduction, and autonomic symptoms.

Metformin, H2RA, and PPI are known independently to result in a B-12 deficiency. When combined together, it has an additive effect; therefore, it is important to recognize the potential of neuropathy due to the combination of these drug therapies. Patients and doctors should be aware of this polypharmacy-induced vitamin B-12 deficiency and its potential for neuropathy, especially in the type 2 diabetes patient population with GERD. Patients and healthcare providers should also be aware of the strategies to correct this deficiency.

I contacted Allen and Barry and we did a survey of the group and only two of the group were taking metformin and a PPI and outside of a few of us that were aware of metformin causing problems, no one was aware of the GERD medications also being causes of neuropathy. This eased our minds, but we know we needed more information