New research links vitamin D deficiency and diabetic peripheral neuropathy—but questions still remain

New research published in Diabetes Research and Clinical Practice explored the link between vitamin D deficiency (VDD) and diabetic peripheral neuropathy (DPN) in elderly patients (60 years or older) with type 2 diabetes mellitus (T2DM). The article concluded that VDD is independently associated with a higher risk of DPN. The research also found that VDD may promote the development of DPN due to its impact on large nerve fibers.^[]

Peripheral neuropathy occurs when damage has been done to the peripheral nervous system, resulting in loss of signals, inappropriate signaling, and distorted signal messaging.^[]

The American Diabetes Association says that about 50% of patients with diabetes have some type of nerve damage; it is more common in patients who’ve had diabetes for many years. Symptoms include numbness, tingling, burning feet, and other problems.^[]

“Vitamin D is a complex vitamin that works in multiple body areas. Some even classify this vitamin as a hormone,” says Betul Hatipoglu, MD,  Professor of Medicine at Case Western Reserve University School of Medicine in Cleveland, OH. Hatipoglu says that the vitamin influences the mood, immune system, and cardiovascular system—and that research has shown its relationship to cancer, metabolic disease, heart disease, and autoimmune disorders.

A look at the study

From January 1, 2020, to March 1, 2023, the research team looked at 230 participants (175 with DPN and 55 without DPN) with T2DM. The mean age was 66.87, and most patients had T2DM for an average of 14.72 years. 

The researchers assessed patients’ vitamin D status by measuring circulating 25-hydroxyvitamin D [25(OH)D] levels in the serum. They also set out to determine vitamin D’s impact on nerve fiber lesions.

To validate whether patients had DPN, the researchers screened participants for “ankle reflexes, vibration perception using a 128 Hz tuning fork, pressure perception with a 10 g monofilament, pinprick pain perception, and temperature sensitivity.” They also took note of any pain symptoms and sensory abnormalities. DPN was determined based on two or more positive manifestations of the above. 

“Large-fiber neuropathy in diabetic patients leads to lower limb proprioceptive defects, decreased tactile sensitivity and vibratory sensation, and loss of coordination due to balance abnormalities,” the authors note. The team assessed the participants' large nerve fibers using an electromyogram, noting that less is known about large-fiber neuropathy. They also found that “VDD may increase the prevalence of DPN by affecting large-fiber lesions.” 

On the other hand, small fiber neuropathy is responsible for the burning, prickling, and pain patients may experience. The authors note that the study “did not assess small nerve fiber lesions using the ‘gold-standard’ method of quantifying intraepidermal nerve fiber density by skin biopsy.”^[]

VDD was defined as serum 25(OH)D circulating levels below 20 ng/ml, while vitamin D insufficiency was defined as 25(OH)D levels between 21 and 29 ng/ml. According to the findings, the participants with DPN had lower serum 25(OH)D levels than the non-DPN patients (15.05 ng/ml vs. 18.4 ng/ml). 

The VDD group experienced a higher prevalence of DPN (80.4%) versus the non-VDD group (63.9%). 

Additionally, the group with DPN had higher BMIs, were more likely to have hypertension, tended to smoke, and were mostly female. 

What do the experts think of these findings?

Andrew Tan, PhD, Deputy Director of the Center for Neuroscience and Regeneration Research at Yale School of Medicine, says that it’s important to note that the research only looked at the “risk” of DPN in these patients; it did not find a cause-effect relationship. 

“In the case of neuropathy, low vitamin D may exacerbate or lead to the condition through disrupted regulation of inflammation or nerve function as a result of the metabolic stress of diabetic disease,” Dr. Tan says. 

He says that for individuals who already have vitamin D deficiency, it will take more than daily exposure to sunlight for the body to restore sufficient levels of vitamin D. Physicians, in this case, will want to prescribe vitamin D supplementation to patients. 

That said, Dr. Tan notes that there “still isn’t a clear answer about whether taking supplemental vitamin D will prevent the development of diabetic peripheral neuropathy.”

As the authors conclude, “Future research on the potential connection between VDD and DPN, as well as large/small fiber neuropathy, may provide a potential strategy for the prevention and treatment of DPN in diabetic patients.”

Despite being unable to answer this specific question, Dr. Tan says that the research underscores the idea that monitoring patients for vitamin D deficiency would be useful. This, he says, could potentially help older individuals and patients with prediabetes reduce the risk of developing DPN. 

“We should continue to emphasize the importance of taking vitamin D supplements in areas of the world where we have low sun exposure,” Dr. Hatipoglu adds. “It is also important to remember [that] this vitamin is one of the vitamins that [in] excess can be toxic to the body. More is not always better, and aiming for high levels has damaging consequences. I always recommend that my patients take supplements from October to May in Ohio during winter.”