In addition to its many life-saving benefits …

Vitamin D Reverses
Low Back Pain

And may be helpful for inflammatory
and lifestyle-related chronic disorders

By Will Block

Vitamin D plays a significant role in bone metabolism and neuromuscular function.1 Reversing vitamin D deficiency (hypovitaminosis D) can improve chronic musculo-skeletal pain—a type of pain that affects the muscles, ligaments, tendons, and bones—including chronic low back pain.

In fact, recent data show that vitamin D plays an important preventive role in inflammatory and lifestyle-related chronic disorders like diabetes, cardiovascular diseases, auto-immune disorders, depression, and some cancers.

Vitamin D Helps Prevent Cancer

We recently learned from a meta-analysis that high intakes of vitamin D reduce the risk of most cancers.2 Another meta-analysis, published in 2011, emphasized that vitamin D3 reduces mortality in adults, but other forms of vitamin D such as vitamin D2 do not.3 Of the two types of vitamin D, D2 (known as ergocalciferol) is not as important as D3 (cholecalciferol), which is the most biologically active form in humans and animals.

Pandemic in Many Countries

Hypovitaminosis D is now recognized as epidemic in the US or even pandemic in many other countries. This is due in part to the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. But it is also due to the paucity of vitamin D found naturally in foods. Furthermore, foods that are fortified with vitamin D are often inadequate to satisfy either a child’s or an adult’s vitamin D requirement. It is also due to the obesity epidemic here in the US.

Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. It is worth stating again that hypovitaminosisi D is associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases.


A circulating level of 25-
hydroxyvitamin D of >75 nmol/L is
required to maximize vitamin D’s
beneficial effects for health.


Vitamin D deficiency is typically diagnosed by measuring the concentration of the prehormone calcidiol (1,25-dihydroxyvitamin D) in the blood. which is a precursor to the active form 1,25-dihydroxyvitamin D (calcitriol). A circulating level of 25-hydroxyvitamin D of >75 nmol/L is required to maximize vitamin D’s beneficial effects for health.

In the absence of adequate sun exposure, at least 2,000 IUs and as high as 10,000 IUs of vitamin D3/day are needed to achieve the highest vitamin D benefits, according to Dr. Jonathan V. Wright’s colleague Dr. Alan R. Gaby (see his Nutritional Medicine textbook available at www.doctorgaby.com). The Gaby range may be needed to achieve what is considered to be optimal blood levels (>75 nmol/L) levels in adults.


(NHANES) suggests a dose of 95
mcg/day (3800 IU) for those above a
25(OH)D threshold of 55 nmol/L and
a dose of 125 mcg/day (5000 IU) for
those below that threshold.


Threshold Dose

Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey (NHANES) suggests a dose of 95 mcg/day (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 mcg/day (5000 IU) for those below that threshold.4

Prevalence of Hypovitaminosis D

To follow up on the correspondence of vitamin D levels to chronic low back pain (CLBP), Indian researchers set out to determine the prevalence of hypovitaminosis D and its contribution to chronic low back pain.5 Patients with a diagnosis of CLBP with or without leg pain were recruited from an outpatient pain clinic of a tertiary care hospital.

Measuring Low Back Pain Intensity

A visual analogue scale was used to measure low back pain intensity, and the Modified Oswestry disability questionnaire was used to measure functional ability. The Oswestry Disability Index is currently considered by many as the gold standard for measuring degree of disability and estimating quality of life in a person with low back pain.

Plasma 25-OHD levels of all patients were measured and the prevalence of hypovitaminosis D was calculated. 328 patients were included in the study. Mean age of the study population was 43.8 years. Two hundred eighty-two of the subjects (86%) [men 153/172 (89%), women 129/156 [83%)] had below normal plasma vitamin D levels.

Among these, 217 (66%) (126 men and 91 women) were found to be deficient and 65 (20%) (27 men and 38 women) had insufficient levels.


Two hundred eighty-two of the
subjects (86%) [men 153/172 (89%),
women 129/156 [83%)] had below
normal plasma vitamin D levels.


Definition of Vitamin D Levels

According to the level of 25-OHD, vitamin D deficiency was defined as a 25-OHD level of ≤ 50 nmol/L and vitamin D insufficiency as 52 to 73 nmol/L, and normal level as above 75 nmol/mL. Furthermore, severity of vitamin D deficiency was grouped as follows: ≤ 10 nmol/L profound deficiency; 12.5 – 20 nmol/L severe deficiency; 22.5 – 30 nmol/L moderately severe deficiency; 32.5 – 40 nmol/L moderate deficiency; and 42 – 50 nmol/L marginal deficiency. Of course, these ranges were created to encompass the subjects recruited. The researchers did not look for an ideal level.

Multivariate regression analysis found that men were significantly more prone to have deficiency as compared to women. The researchers also found a significantly positive relationship between vitamin D deficiency and increased functional disability.


Multivariate regression analysis
found that men were significantly
more prone to have Vitamin D
deficiency as compared to women.


The result of this study provides a message about the high prevalence of hypovitaminosis D in the Indian CLBP population, especially given that the distribution did not cover sufficient levels. Clinical guidelines for managing CLBP should include assessment of vitamin D status, together with advice on appropriate vitamin D supplementation in those found to be deficient.

Theoretically, there are 2 possible links between hypovitaminosis D and low back pain:

1) In patients with low back pain, the diffuse pain in bones and muscles, weakness, and paraesthesia (a sensation of tingling, tickling, pricking, or burning of a person’s skin with no apparent physical cause) may be caused by hypovitaminosis D.

2) Hypovitaminosis D could play a role in the development of signal changes in the vertebral body marrow adjacent to the end plates (modic changes) via the increased susceptibility to inflammation in the vertebral end plates.

In a recently published Danish study of 152 patients with nonspecific low back pain, a significant correlation was found between vitamin D deficiency and modic changes. 6

At the end of this study, it was found that the majority of the study population belonged to the age group 39 – 58 years and the prevalence of vitamin D deficiency was found to be maximum in this age group (70%). The researchers also found that the deficiency was more prevalent in the overweight population (68%) and in men (73%).

It was also found that men were significantly more prone to be deficient as compared to women and there was a significant relationship between vitamin D deficiency and higher functional disability.


Patients on the vitamin D group (n =
59) had higher pain relief than the
control group.


However, no relationship was found with pain severity, presence of other co-morbidities, and educational level. As well, the researchers tried to assess the impact of seasonal variation (depending upon sunlight) on vitamin D deficiency.

The mean levels during all the seasons, i.e., spring 41, summer 52, fall 46, and winter 49 were comparable. However, they found a significantly lower prevalence of vitamin D deficiency in summers 57% (54/94) and winters 51% (27/53) as compared to spring 76% (108/142) and fall 72% (28/39).

Inflammatory Diseases

Figure 1 Healthy spine, inflamed spine, and fused spine (Ankylosing spondylitis).
LEM1611spinechart274.jpg
(click on thumbnail for full sized image)

Spondyloarthritis is an umbrella term for inflammatory diseases that involve both the joints and the entheses (the sites where the ligaments and tendons attach to the bones). The most common of these diseases is ankylosing spondylitis, an inflammatory disease that can cause some of the vertebrae in the spine to fuse together (see Fig. 1).

In a recent French/Moroccan study, researchers assessed the vitamin D status in patients presenting inflammatory back pain suggestive of axial spondyloarthritis and to assess the relationship between vitamin D status and disease activity and severity.7 Also measured were comorbidities at baseline and during the first two years of follow-up.

This study was a prospective, multicenter, observational study. Vitamin D deficiency was defined as <50 nmol/L and severe deficiency less than 25 nmol/L. Clinical variables were collected at each six-month interval visit during the two-year follow-up.


The result of this study provides a
message about the high prevalence of
hypovitaminosis D in the
Indian CLBP population.


A total of 700 patients were analyzed. The mean vitamin D was 54.2±28.7 nmol/L. Severe deficiency was observed in 11.7% versus 5% in the study’s cohort versus the French population respectively.

In the cohort, after adjusting for season and ethnicity, vitamin D deficiency remained significantly associated with presence of radiological sacroiliitis—an inflammation of one or both sacroiliac joints — situated where the lower spine and pelvis connect—higher ASDAS score and elevated BASDAI. Such association was also found between vitamin D deficiency and the mean value of disease activity/severity parameters during the two-year follow-up.

Severe Vitamin D Deficiency

In the key messages of the paper, the researchers found:

1) A higher percentage of patients with severe vitamin D deficiency in early axial spondyloarthritis.

2) Vitamin D deficiency was associated with higher disease activity and severity and presence of metabolic syndrome.

Vitamin D and Rheumatoid Arthritis

The active form of vitamin D, 1,25 dihydroxy vitamin D3, has immunomodulatory functions in rheumatoid arthritis (RA), and is an anti-osteoporotic agent. However, prior to 2011 no studies existed to assess its pain-relieving action in RA.8

An open-labeled randomized trial comparing triple disease-modifying anti-rheumatic drug (DMARD) therapy and 500 IUs 1,25 dihydroxy vitamin D3 + calcium combination versus triple DMARD and calcium alone was conducted.

The primary outcome was the time to pain relief by patients’ visual analogue scale (VAS). Changes in VAS after first achievement of pain relief and after 3 months were noted. 25 hydroxy-vitamin D levels were correlated with disease activity score (DAS-28), adjusting for sun exposure. Comparisons between the groups were done by the Mann-Whitney test (a statistical analysis) and independent samples test.


Supplementation of 500 IUs results in
a significantly higher pain relief
at the end of 3 months.


Patients on the vitamin D group (n = 59) had higher pain relief than the control group. There was no significant difference in the time taken for initial pain relief between the two groups. Occurrence of hypovitaminosis D in RA patients (68.1%) is comparable to published normal Indian prevalence. There was no correlation between 25 hydroxy vitamin D levels and disease activity.

Supplementation of 500 IU of 1,25 dihydroxy vitamin D3 daily to previously DMARD-naïve patients with early RA along with triple DMARD therapy results in a significantly higher pain relief at the end of 3 months. The number needed to treat for this additional pain relief was 5. The prevalence of vitamin D deficiency in the study population was 68.1%.

What Are the Other Benefits of Vitamin D?

Articles on the following subjects can be found by using the search engine on Life Enhancement’s Home Page (www.life-enhancement.com).

  • High Levels of Vitamin D Decrease Dementia (including Alzheimer’s disease)
  • Vitamin D May Improve Mood and Cognition in the Elderly
  • Vitamin D in Prostate Cancer Patients with Increasing PSA Levels after Treatment
  • Vitamin D3 Rejuvenation of Aging Eyes in Elderly Mice by Reducing Inflammation and Clearing Amyloid-Beta
  • Increased Phagocytosis (removal of cellular garbage) by Retinal Macrophages in Response to Vitamin D3
  • Longer Leukocyte Telomere Lengths with Higher Serum Vitamin D Concentrations in Women
  • Potential Antiaging Effects of Vitamin D3 Protection Against Neurotoxic Agents
  • Vitamin D Might Prolong Your Life
  • Vitamin D and Calcium Combat Cancer
  • Vitamin D has recently been found to stimulate the production of other immune system peptides that play a crucial role in maintaining healthy immune activity
  • Vitamin D’s suppresses killer cytokine storms
  • Vitamin D Bolsters Muscle Strength
  • Vitamin D Induces Increased Levels of Cystatin D, a Candidate Tumor Suppressor Gene in Colon Cancer


Replacement of vitamin D
had favorable effects on
endothelial function.


Is there a Predominant Mechanism?

Vitamin D receptors are present in many tissues. Hypovitaminosis D is a risk factor for atherosclerosis. A study conducted in 2009 explored the effects of vitamin D replacement on insulin sensitivity, endothelial function, inflammation, oxidative stress, and leptin in vitamin D-deficient subjects.9

Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/L were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter. The vitamin D-deficient group received 300,000 IU intramuscularly monthly for 3 months (that’s about 10,000 IU per day).

The following parameters were evaluated before and after treatment: vitamin D metabolites, leptin, endothelial function by brachial artery flow mediated dilatation (FMD), insulin sensitivity index based on oral glucose tolerance test, and lipid peroxidation as measures of thiobarbituric acid reactive substances (TBARS).


Vitamin D deficiency is an
independent risk factor of
atherosclerosis.


FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls and improved after replacement therapy. Posttreatment values of TBARS were significantly lower than pretreatment levels.

A positive correlation between FMD and 25(OH)D and a negative correlation between FMD and TBARS were observed. There was a significant increase in leptin levels after therapy, and the leptin levels were positively correlated with 25(OH)D levels.

This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D had favorable effects on endothelial function.

Vitamin D deficiency is an independent risk factor of atherosclerosis. Combined with recent evidence that Vitamin D deficiency is associated with chronic back pain, and given its safety, what do you have to lose?

References

  1. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S.
  2. Li M, Chen P, Li J, Chu R, Xie D, Wang H. Review: the impacts of circulating 25-hydroxyvitamin d levels on cancer patient outcomes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014 Jul;99(7):2327-36.
  3. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD007470.
  4. Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr. 2008 Jun;87(6):1952-8.
  5. Ghai B, Bansal D, Kapil G, Kanukula R, Lavudiya S, Sachdeva N. High Prevalence of Hypovitaminosis D in Indian Chronic Low Back Patients. Pain Physician. 2015 Sep-Oct;18(5):E853-62.
  6. Johansen JV, Mannichel C, Kjaer P. Vitamin D levels appear to be normal in Danish patients attending secondary care for low back pain and a weak positive correlation between serum level Vitamin D and Modic changes was demonstrated: A cross-sectional cohort study of consecutive patients with nonspecific low back pain. BMC Musculoskeletal Disorders. 2013; 14:78-87.
  7. Hmamouchi I, Paternotte S, Molto A, Etcheto A, Borderie D, Combe B, Dougados M. Vitamin D, disease activity and comorbidities in early spondyloarthritis. Clin Exp Rheumatol. 2016 May-Jun;34(3):396-403. Epub 2016 Apr 5.
  8. Gopinath K, Danda D. Supplementation of 1,25 dihydroxy vitamin D3 in patients with treatment naive early rheumatoid arthritis: a randomised controlled trial. Int J Rheum Dis. 2011 Oct;14(4):332-9. doi: 10.1111/j.1756-185X.2011.01684.x.
  9. Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab. 2009 Oct;94(10):4023-30.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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