Vitamin D and the influence on chronic pain

Vitamin D could save the country about €37.5 billion in health care costs for pain, according to a new review  of professor A. Zittermann.

Vitamin D and the influence on chronic pain INPVitamin D through its receptor modulates neuronal differentiation as well as neuronal growth and function. In rats, the production of nerve growth factor which is required for the development and survival of both sympathetic and sensory neurons decreases in the presence of vitamin D deficiency.

In fact, in vitamin D deficient diabetic animals correction of vitamin D deficiency resulted in an improvement in nerve growth factor production. Decrease in neurotrophins and defective calcium homeostasis leaves the nerve vulnerable to toxins including hyperglycemia. As a result, a deficiency of vitamin D impairs nociceptor function, worsens nerve damage, and lowers the pain threshold.

Patient experienced pain relief

In another study vitamin D levels were not only inversely proportional to a neuropathy symptoms score but also showed a statistically significant (OR 3.47 95% CI 1.04–11.56 P = 0.04) association with slower nerve conduction velocities after correction for duration of diabetes and levels of HbA1c, LDL, and urinary albumin. 

Two quotes from a recent report were a patiënt suffering from severe neuropathic diabetic pain, refractory to analgesics, experienced pain relief after the correction of the vitamin D deficiency. 

Vitamin D receptors are expressed in many other tissues beyond the musculoskeletal system, and vitamin D plays protective physiologic roles against several chronic diseases such as cancer, osteoarthritis, diabetes, and cardiovascular conditions. There is clear evidence for an association between low vitamin D status and pain in the general population.

The chronic pain syndromes included chronic back pain, chronic musculoskeletal pain or widespread pain, and polymyalgia and in all these cases vitamin D was suggested as the cause of such nonspecific pain.

Prospectively, a non randomized study of 51 type 1 diabetic subjects with painful diabetic neuropathy showed a 50% decrease in pain scores with vitamin D repletion. In addition, in humans topical vitamin D application to the areas affected by neuropathy has been reported to relieve neuropathic symptoms.

The author described the following:

Vitamin D deficiency has been shown to be more common in diabetic patients who have symptoms of distal symmetrical polyneuropathy. In addition, vitamin D deficiency has been associated with a lower pain threshold which increases when vitamin D deficiency is corrected.

Herein, I describe a type 1 diabetic patiënt with neuropathic symptoms so severe that he could not work and for which he needed narcotics for pain management and whose symptoms improved dramatically with correction of the vitamin D deficiency.  [1] See also [2]

Vitamin D deficiency is an independent risk factor for diabetic peripheral neuropathy, based on a study in 210 patients.[3]



Low levels of vitamin D in Sjögren’s syndrome

Low levels of vitamin D correlated with the presence of peripheral neuropathy and lymphoma among Sjögren’s syndrome patients. The link between vitamin D and neuropathy or lymphoma was reported in other conditions, and may support a role for vitamin D in the pathogenesis of these processes. Plausible beneficial effect for vitamin D supplementation may thus be suggested.  [4]

Low levels of vitamin D in Spinal Stenosis

Vitamin D deficiency was highly prevalent in LSS patients (74.3%), and severe pain was associated with higher prevalence of vitamin D deficiency and osteoporosis which could be potential risk factors or a fall and fracture.  [5] This explanation was suggested by the authors:


In our clinic we often found very low levels in patients suffering from neuropathic pain. As vitamin D has no side effect risk in a great dose-range, we advise all chronic neuropathic pain patients to supplement up to a level of at least 80nmol/l.

April 2013, Jan M. Keppel Hesselink
‘Vitamin D and the influence on chronic pain’


Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health*



Health status



Associated with vitamin D deficiency, leading to rickets in infants and children and osteomalacia in adults



Generally considered inadequate for bone and overall health in healthy individuals



Generally considered adequate for bone and overall health in healthy individuals (conservative estimation)



Emerging evidence links potential adverse effects to such high levels, particularly >150 nmol/L (>60 ng/mL)

* Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL).
** 1 nmol/L = 0.4 ng/mL

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[1] Bell DS. | Reversal of the Symptoms of Diabetic Neuropathy through Correction of Vitamin D Deficiency in a Type 1 Diabetic Patient. | Case Rep Endocrinol. | 2012;2012:165056. doi: 10.1155/2012/165056. Epub 2012 Dec 12.

[2] Skalli S, Muller M, Pradines S, Halimi S, Wion-Barbot N. | Vitamin D deficiency and peripheral diabetic neuropathy. | Eur J Intern Med. | 2012 Mar;23(2):e67-8. doi: 10.1016/j.ejim.2011.11.008. Epub 2011 Dec 10.

[3] Shehab D, Al-Jarallah K, Mojiminiyi OA, Al Mohamedy H, Abdella NA. | Does Vitamin D deficiency play a role in peripheral neuropathy in Type 2 diabetes? | Diabet Med. | 2012 Jan;29(1):43-9. doi: 10.1111/j.1464-5491.2011.03510.x.

[4] Agmon-Levin N, Kivity S, Tzioufas AG, López Hoyos M, Rozman B, Efes I, Shapira Y, Shamis A, Amital H, Youinou P, Shoenfeld Y. | Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sjögren's syndrome. | J Autoimmun. | 2012 Jul 24. [Epub ahead of print]

[5] Kim TH, Lee BH, Lee HM, Lee SH, Park JO, Kim HS, Kim SW, Moon SH. | Prevalence of vitamin d deficiency in patients with lumbar spinal stenosis and its relationship with pain. | Pain Physician. | 2013 Mar;16(2):165-76.

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