Vitamin B-12 for Diabetic Neuropathy and Metformin Users

Vitamin B-12 for Diabetic Neuropathy and Metformin Users

One of the most common and disheartening complications of diabetes mellitus (DM) is diabetic neuropathy (DN), often underdiagnosed in everyday clinical practice.

Certain forms of DN are “major risk factors for foot ulcers, amputation, and cardiovascular dysfunction.” Other forms lead to about 30% of patients developing nerve pain, and symptoms such as burning, needles, cold, or heat cramps, weakness, and allodynia (pain from non-painful stimuli).

There are four main types of diabetic neuropathy, and diabetics can have one or more of these.

Symptoms depend on what forms of DN the patient has, and thus on which nerves are affected. Unfortunately, these symptoms usually develop gradually, often not becoming apparent until much nerve damage has occurred.

Peripheral neuropathy

This is the most common type of diabetic neuropathy, first affecting the feet and legs, then the hands and arms. Peripheral neuropathy symptoms are often worse at night, and may include:

  • Numbness or reduced ability to feel pain or temperature changes

  • Tingling or burning sensation

  • Sharp pains or cramps

  • Increased sensitivity to touch — even the weight of a bedsheet can be painful

  • Serious foot problems, such as ulcers, infections, and bone and joint pain

Autonomic neuropathy

The autonomic nervous system controls the bladder, eyes, heart, intestines, sex organs, and stomach. Autonomic neuropathy symptoms may include:

  • A lack of awareness that blood sugar levels are low

  • Bladder or bowel problems

  • Slow stomach emptying causing nausea, vomiting and loss of appetite

  • Changes in the way the eyes adjust from light to dark

  • Decreased sexual response

Proximal neuropathy

This type of neuropathy often affects nerves in the abdomen, buttocks, legs, hips, or thighs, with symptoms usually occurring on one side of the body (though they can spread to the other side as well, eventually). Proximal neuropathy symptoms may include:

  • Severe pain in a hip and thigh or buttock

  • Eventual weak and shrinking thigh muscles

  • Difficulty rising from a sitting position

  • Severe stomach pain


The term mononeuropathy refers to damage to a specific nerve. There are two types of mononeuropathy — cranial and peripheral. Mononeuropathy symptoms may include:

  • Difficulty focusing or double vision

  • Aching behind one eye

  • Paralysis on one side of your face (Bell’s palsy)

  • Numbness or tingling in your hand or fingers, except your little finger

  • Weakness in your hand leading you to drop things (Source)

It is known that strict control of blood sugar can delay the progression of DN in some patients, however “strict glycemic control must be maintained for 3–5 years for clinical benefit.”

Severe blood sugar imbalance, over a long period, causes metabolic alterations which leads to neuropathy. Such metabolic malfunctions include “accumulation of advanced glycation end products, oxidative stress, and lipid disorders.” Worsening the damage to our smallest blood vessels, and thus ultimately to the nerves, are the addition of cardiovascular risk factors (hyperlipidemia, smoking, hypertension, and obesity).

As you can well imagine, DN has a strong negative effect on quality of life, due to the painful symptoms and possible resulting disabilities. This issue is not easily treated by modern medicine, as “no single drug proved to be effective enough for DN treatment”, and several drugs have been tried in combination, but without much success.

A New Approach

So, a group of scientists decided to make a cocktail of super nutrients that could tackle a number of the mechanisms involved in the development of diabetic neuropathy.

They included two powerful antioxidants, Superoxide Dismutase (SOD) and A-Lipoic acid (ALA). SOD prevents the formation of free radicals, and ALA removes those free radicals already formed. The formula also contained N-acetyl-carnitine (ALC), which is “believed to have a neurotrophic action” (influencing the nerves). And, they included vitamin B-12, since B12 levels are often low in DN patients, due to metformin treatment (B12 levels also being unnaturally low in those who use proton pump inhibitors).

The scientists hypothesized that “by acting at different metabolic key points these four elements could work synergistically and thereby be more effective in treating DN”.

These four elements included SOD 10mg, ALA 570 mg, ALC 300mg, and B12 250mcg, contained in one tablet, given daily to patients with diabetic neuropathy (who have received metformin for at least four years).

Metformin and B-12

Let’s have a closer look at that bit about metformin reducing vitamin B12 levels.

Metformin has been prescribed in North America for approximately fifteen years, as a way of controlling blood sugar in those who are prediabetic.

In particular, metformin is associated with a low concentration of B12 and a higher risk of B12 deficiency, but the exact mechanism remains elusive.”

Vitamin B12 deficiency has been repeatedly associated with metformin use, and “chronic metformin use results in vitamin B12 deficiency in about 30% of patients”.

In fact, B12 deficiency in extreme can manifest as peripheral neuropathy, and is often misdiagnosed as diabetic neuropathy. “Failure to diagnose the cause of the neuropathy will result in progression of central and/or peripheral neuronal damage which can be arrested but not reversed with vitamin B12 replacement.” (Source)

Thus, it is important that any nerve pain that may be due to B12 deficiency be addressed as soon as possible, as the above statement implies that once the nerves are damaged we can only stop further damage by taking B12, but not reverse the existing damage.

Here I would like to refer readers to a previous newsletter of mine called “Fibromyalgia and Insulin Resistance”, which points out that the herbal extract berberine is a clinically proven effective alternative to the use of Metformin (and won’t cause B12 deficiency).


Now, I dug as deeply as possible into the study we are looking at but could not find a definition of the type of B12 that was used in their mix of supplements.

I would guess/hope that it was methylcobalamin, as this is the form of B12 that is most effective at repairing nerve damage, and promoting myelination (rebuilding of the nerve “sheath”).

And, a variety of studies have been done using methylcobalamin to treat diabetic-induced nerve damage, with positive results. Here are two examples:

  • At the end, untreated diabetic animals developed significant delay of nerve conduction velocity (NCV), and MC (methylcobalamin) treatment normalized the NCV.” (Source)

  • As a vitamin, MeCbl may be a potential candidate for treating peripheral neuropathy with good safety. (Source)

(Here I will point out that NutriStart has an easily absorbed, sublingual methylcobalamin product called Quick B12.)


So, how did our study on the combination of four nutritional supplements work for treating DN?

Well, pretty good, which was not a total surprise to the researchers since “each of the four elements that we used in the present study has been used as monotherapy in clinical studies to treat DN”.

They gave subjects this formula for 12 months, and at the end of it were able to conclude the treatment resulted in “an improvement in all indices of peripheral neuropathy including neurophysiological parameters, pain, and quality of life”. (Study)

For those concerned with this issue I suggest also reading my newsletter on Vitamin D and Diabetic Neuropathy.

Those of us in the danger zone, given blood sugar issues, or simply advancing in age, would be well advised to ensure we supplement with B12 (methylcobalamin) and vitamin D. And those of us with actual full blown DN (or any form of neuropathy or nerve damage), should put together our own version of the formula used above (SOD, ALA, ALC, and MC), perhaps even in higher amounts than they used, and see if that gets the situation under control. At least when we self-prescribe with nutritional supplements we stand very little chance of doing any harm, and a good chance of correcting the problem.

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