Neuropathy is a common condition estimated to affect between 25-30% of Americans at some point in their lives. Neuropathy can significantly impact day-to-day living and is often characterized as tingling, burning, numbness, or sharp, shooting pains in a generalized area of the body, mostly the hands and feet. Some who live with chronic neuropathy and the pain associated with it also experience coinciding depression and anxiety, trouble sleeping, difficulty performing daily activities, and even disability due to gait disturbance or amputation.
What is Neuropathy?
Neuropathy is caused by damage or dysfunction of one or more nerves that can result in numbness, tingling, muscle weakness, and pain. Our nervous system is separated into two separate classifications. Our central nervous system includes the brain and spinal cord. Think of the central nervous system like the central station or the control hub. Then there is our peripheral nervous system, the network of nerves outside the brain and spinal cord that innervate all other parts of the body.
The peripheral nervous system allows you to feel the sand between your toes, recognize and respond to a hot surface with your fingertip, and feel the sensation of a kiss from a loved one. The two systems work together. All tracks (peripheral nervous system) stem from and return to the central station (central nervous system).
The most common form of neuropathy is peripheral neuropathy (PN), which refers specifically to a problem with the peripheral nervous system. PN does not look or feel the same for everyone, and it can be caused by various conditions.
- Diabetes: 60-70% of diabetic patients will experience neuropathy, with 50% experiencing varying degrees of pain, which may result in decreased quality of life.
- Trauma: falls, car accidents, etc., can lead to neuropathy.
- Autoimmune disorders or infections: Lupus, rheumatoid arthritis, HIV, and other inflammatory conditions can lead to neuropathy.
- Medications: cancer treatments, among others, can lead to neuropathy.
- Vascular disorders: neuropathy can occur when blood flow is restricted and deprives nerves of oxygen.
- Abnormal vitamin levels: specific vitamins, such as B vitamins, are essential for healthy nerve function.
Is There an Association Between Low Vitamin D and Neuropathy?
As we have already touched on, there are many different types of neuropathies. While there is no evidence (at this time) that vitamin D is associated with all kinds of neuropathies, there is substantial evidence that it is associated with one type: Diabetic Peripheral Neuropathy (DPN). While not every study has found an association between vitamin D levels and diabetic neuropathic pain, a great majority have.
A study conducted in 2012 evaluated the incidence and associations of vitamin D deficiency in 210 patients with type 2 diabetes with and without DPN, and their findings were noteworthy. They found that diabetic patients with peripheral neuropathy had significantly lower mean vitamin D levels than those without peripheral neuropathy and concluded that vitamin D deficiency is an independent risk factor for DPN.
The association between low vitamin D status and diabetic neuropathy has been confirmed in several other studies since then, including the NHANES survey, a 2017 study from the Shanghai Clinical Medical Centre of Diabetes, a 2019 study from the Diabetes Research Unit in Sheffield, UK, and a 2020 study from the University of Liverpool, UK.
Furthermore, a 2017 systematic review concluded that vitamin D deficiency is associated with the generation and development of DPN. Lastly, a 2021 meta-analysis found that among more than 6,000 participants, diabetic patients with DPN showed significantly lower serum vitamin D levels compared with patients without diabetic neuropathy.
The association between DPN and vitamin D status appears clear. But what does vitamin D have to do with diabetic neuropathy? In March of 2021, a study was published exploring the mechanisms behind some of the painful neuropathic symptoms and how vitamin D might play a role.
How Does Vitamin D Deficiency Lead to Diabetic Peripheral Neuropathy?
The primary proposed mechanism behind the development of neuropathy in the diabetic population is due to chronic hyperglycemia (high blood sugar). Uncontrolled blood sugar can lead to an excess of free radical production and oxidative stress. Prolonged oxidative stress can cause damage to microvasculature leading to peripheral nerve hypoxia. Nerves that no longer receive adequate blood and oxygen supply (due to the microvasculature damage) can become impaired (neuropathy), leading to nerve pain, nerve malfunction, or nerve death.
Research suggests that vitamin D may play a role in DPN through its maintenance actions on inflammation. Studies have found a significant negative correlation between vitamin D and inflammatory cytokines such as IL-6 and TNF alpha. This correlation has been confirmed on multiple occasions in the diabetic population.
Tiwari et al. found a significant positive correlation between severe vitamin D deficiency and high cytokine levels. Laird et al. reported significantly higher concentrations of IL-6 and CRP in individuals with vitamin D <10 ng/mL compared to those whose status was >30 ng/mL. Xiaohua et al. also found that inflammatory cytokines such as IL-2, IL-6, and CRP were significantly higher in diabetic patients with neuropathy than those without. Adequate levels of Vitamin D may protect the structure and integrity of neurons through enhancing antioxidant pathways and tempering inflammation.
Additionally, animal studies have shown that vitamin D deficiency is associated with low neurotrophin levels (proteins that regulate many aspects of neuronal function). In rats, the production of nerve growth factor, which is required for the development and survival of neurons, decreases with vitamin D deficiency. Furthermore, vitamin D deficient diabetic rats experience improvements in nerve growth factor production with vitamin D correction. Animal studies have also identified that vitamin D bolsters axon regeneration.
Lastly, it’s important to note that some scientists have suggested that vitamin D may improve function in those with neuropathy simply by increasing the pain threshold. While the research on vitamin D and pain tolerance is mixed, there is some evidence that vitamin D influences pain manifestation through anatomical, hormonal, neurological, and immunological effects. Therefore, vitamin D may support symptom relief in patients with diabetic neuropathy by increasing pain tolerance alone or in conjunction with other mechanisms listed above.
It seems that vitamin D’s influence on nerve health is complex and includes roles such as reducing oxidative stress, improving pain threshold, and producing higher levels of neurotrophins. It’s important to note that one study identified pretreatment, but not co-administration, of vitamin D protected neurons against cytotoxicity in a concentration – and time-dependent manner. This suggests that having adequate vitamin D levels BEFORE oxidative stress and neural damage occurs could be protective against neural damage from the start. But does vitamin D help if neuropathy already exists?
Does Vitamin D Replacement Therapy Improve Diabetic Peripheral Neuropathy?
Many studies say… yes. In a randomized, placebo-controlled study of patients with low vitamin D levels and DPN, Sari et al. examined the effect of vitamin D replacement therapy on neuropathic symptoms and balance. They found that a one-time injection of 300,000 IU vitamin D led to significant improvements in neuropathic pain (DN4 questionnaire), balance (the Berg balance test), and perception of electric shock and burning sensations 12 weeks after administration compared to the placebo group. The study’s authors attributed the improvement in scores to axonal regeneration.
A prospective observational study of type 2 diabetic subjects showed a 50% decrease in pain scores related to diabetic neuropathy with vitamin D repletion. In this study, mean vitamin D levels of 30 ng/mL were associated with improved symptom scores. Moreover, another study that included 33 diabetic subjects with DPN and 29 controls concluded that vitamin D has an independent and inverse association with both diabetic neuropathy presence and severity. They found that each 1 ng/mL increase in serum vitamin D was correlated with a 2.2% decrease in the presence and a 3.4% decrease in the severity of nerve conduction velocity impairment.
Another recent study found that high-dose vitamin D supplementation of 40,000 IU/week for 24 weeks was associated with improved clinical manifestations, cutaneous microcirculation, and inflammatory markers in patients with type 2 diabetes and DPN.
Basit et al. conducted a clinical trial to assess the effect of high-dose vitamin D in patients with painful diabetic neuropathy. They found a single intramuscular dose of 600,000 IU of vitamin D brought mean vitamin D levels up from 31.7 ng/mL to 46 ng/mL and significantly decreased several pain scores.
Finally, a 2020 systemic review investigating whether supplementation of vitamin D would improve pain among those with diabetes and DPN concluded that vitamin D supplementation could provide added value in a treatment care plan.
These results suggest that vitamin D can improve subjective and objective pain scores in those with painful DPN and vitamin D deficiency. Although the high doses of vitamin D seen in some of these studies should only be utilized under medical supervision, the results indicate that vitamin D can still improve outcomes after neuropathy has begun.
How Much Vitamin D is Enough?
Instead of identifying how much vitamin D a person should take to reduce the risk of developing neuropathy and the pain associated with it, it would be wiser to identify protective serum vitamin D levels. The reality is no one dose is suitable for everyone. Around the nation, everyone’s baseline serum vitamin D levels will likely look very different. A person from Florida who spends regular time in the sun and eats an abundance of fresh seafood is likely to have higher baseline vitamin D levels than, say, a person from the Upper Peninsula of Michigan who eats a vegan diet. It’s expected that those two individuals would need different amounts of supplemental vitamin D in their diet to reach optimal serum levels. So, what serum levels are best to reduce risk and decrease the severity of DPN?
The NHANES survey identified that vitamin D levels below 30 ng/mL in adult diabetics were associated with symptoms of DPN, including numbness, pain, loss of feeling, and tingling of the hands and/or feet. He et al. found that vitamin D levels <16.01 ng/mL predict more than a two-fold risk of the presence of DPN. Furthermore, Basit et al. demonstrated that elevating mean vitamin D levels from 31.7 ng/mL to 46.2 ng/mL resulted in significant improvements in symptoms of painful diabetic neuropathy. Based on the reported studies, achieving serum vitamin D levels above 30 ng/mL seems to be the minimum level to be protective in incidence and severity of DPN, while levels above 40 ng/mL may be optimal.
While research in this area continues to grow, it’s clear that vitamin D plays a complex role in health and wellness and may influence a broad range of systems, including the nervous system. While vitamin D’s role in neuropathy is not yet conclusive, it’s safe to say that attaining optimal vitamin D levels (at minimum >30 ng/mL) will support those who have or are at risk for DPN.
The best way to know if additional vitamin D intake may support your health outcomes is to test your vitamin D status. Then plug your current levels into this vitamin D calculator to get individualized dosing suggestions. If you think you may have neuropathy, be sure to see your healthcare provider.