Vitamin D is important not only for bone health but also in the management of pain. Of particular significance is that Vitamin D deficiency has reached epidemic proportions in the U.S. and dietary intervention alone is not likely to be sufficient to maintain optimal blood levels.
The past decade, particularly the last few years, witnessed a marked increase in interest in Vitamin D, mostly due to new research from the National Health and Nutrition Examination Survey (NHANES). The newest statistics show that more than 90% of the pigmented population of the United States (Blacks, Hispanics, and Asians) now suffer from vitamin D insufficiency (25-hydroxyvitamin D <30 ng/ml), with nearly three fourths of the white population in this country also being vitamin D insufficient. This represents a near doubling of the prevalence of vitamin D insufficiency seen just 10 yr ago in the same population. For this reason, it is important to educate the public about Vitamin D, especially those with chronic pain due to the fact that Vitamin D deficiency appears to be related to chronic pain.
Vitamin D – the Basics
Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Vitamin D obtained from sun exposure, food, and supplements is biologically inactive and must undergo two chemical changes in the body for activation. The first occurs in the liver and converts vitamin D to 25- hydroxyvitamin D, also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D (also known as calcitriol).
Vitamin D promotes calcium absorption in the gut and maintains adequate blood levels of calcium and phosphate concentrations to enable normal mineralization of bone. It is needed for bone growth and healthy bones. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. In children, Vitamin D prevents rickets and osteomalacia (softening of bones, susceptible to deformity and fracture) and together with calcium, vitamin D also helps protect older adults from osteoporosis.
Optimal Levels of Vitamin D
Over recent years we have come to learn that Vitamin D has other roles in the body, including cell growth, nerve, muscle and immune function, and reduction of inflammation. Vitamin D is also thought to play a role in chronic pain as well. Due to these additional roles of Vitamin D it is difficult to establish what the optimal blood level of Vitamin D should be and there is no true consensus among physicians as to what the optimal level should be. Relative to protecting against osteoporosis and increased risk for fracture, the Vitamin D levels need to be 30 nmol/L or above. But many physicians believe that much higher blood levels are required to achieve additional benefits from Vitamin D, especially related to chronic pain.
Many vitamin D scientists advise that the minimum Vitamin D blood levels should be 75 nmol/L. Most experts now define frank vitamin D deficiency as a blood Vitamin D level of less than 50 nmol/L. Blood levels between 50 and 75 nmol/L are considered to represent vitamin D insufficiency.
The most recent guidelines (published in 2011) of the Endocrine Society’s Clinical Task Force recommends using the serum 25-hydroxyvitamin D [25(OH)D] level to evaluate vitamin D status in patients who are at risk for vitamin D deficiency. Vitamin D deficiency is defined as a 25(OH)D below 20 ng/ml (50 nmol/liter) and vitamin D insufficiency as a 25(OH) D of 21–29 ng/ml (52.5–72.5 nmol/liter).
Most clinical studies in a variety of health areas recommend a blood level of vitamin D that is between 90 to 100 nmol/L, or 35 to 40 ng/ml, for preventive health. There appears to be a recent trend arguing for even higher levels for optimal Vitamin D, up to 50-70 although this appears to be controversial, but still considered safe. Toxicity does not appear to be likely unless blood levels exceed 90-115 ng/ml.
Potential Vitamin D Benefits for Pain
Vitamin D has been shown to help with chronic pain, including headaches, low back pain, diabetic peripheral neuropathy and fibromyalgia.
For more information regarding the role of Vitamin D in chronic pain, see Vitamin D and Pain.
Conditions associated with increased risk for Vitamin D deficiency:
- Strict vegetarian diet
- Milk allergy, lactose intolerance
- People with limited sun exposure
- People with dark skin
- People who are obese or who have undergone gastric bypass surgery
- People with inflammatory bowel disease and other conditions associated with fat malabsorption. Fat malabsorption is associated with a variety of medical conditions, including some forms of liver disease, cystic fibrosis, celiac disease, and Crohn’s disease, as well as ulcerative colitis when the terminal ileum is inflamed.
- Older adults are at increased risk of developing Vitamin D insufficiency in part because, as they age, skin cannot synthesize Vitamin D as efficiently. They are also likely to spend more time indoors, and they may have inadequate dietary intake of the vitamin. As many as half of older adults in the United States with hip fractures have Vitamin D insufficiency.
- People taking statin-type medications for reducing cholesterol are at greater risk of low Vit D.
Symptoms of Vitamin D Deficiency
Symptoms of Vitamin D deficiency may include weak bones prone to breaking. Symptoms of bone pain and muscle weakness can indicate inadequate Vitamin D levels, but such symptoms can be subtle and go undetected in the initial stages of deficiency.
Vitamin D Requirements
RDAs (Recommended Dietary Allowance: average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy people.) for vitamin D are listed in both International Units (IUs) and micrograms (mcg); the biological activity of 40 IU is equal to 1 mcg. Even though sunlight may be a major source of vitamin D for some, the vitamin D RDAs are set on the basis of minimal sun exposure: for age 1-70 y/o; 600 IU (15mcg); for >70 y/o: 800 IU (20mcg).
Testing for Vitamin D Deficiency:
Based on review of current research, a committee of the Institute of Medicine concluded that persons are at risk of vitamin D deficiency at serum 25(OH)D concentrations <30 nmol/L (<12 ng/mL). Some are potentially at risk for inadequacy at levels ranging from 30–50 nmol/L (12–20 ng/mL). Practically all people are sufficient at levels ≥50 nmol/L (≥20 ng/mL); the committee stated that 50 nmol/L is the serum 25(OH)D level that covers the needs of 97.5% of the population.
Many pain experts recommend maintaining levels of 60-80 due to the pain benefits associated with Vitamin D. Serum concentrations >125 nmol/L (>50 ng/mL) are associated with potential adverse effects.
Sources of Vitamin D
It is estimated that 47% of vitamin D source come from food supplements because very few foods in nature contain vitamin D. The flesh of fatty fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources. Small amounts of vitamin D are found in beef liver, cheese, and egg yolks. Vitamin D in these foods is primarily in the form of vitamin D3 and its metabolite 25(OH)D3. Fortified foods provide most of the vitamin D in the American diet. For example, almost all of the U.S. milk supply is fortified with 100 IU/cup (4 cups = 1 quart).
Wild salmon contains as much as 3 times the amount of vitamin D compared to farmed salmon. Patients inquire regularly about the differences and similarities between farmed and wild fish. Both are equally high in omega-3 fatty acids, which are heart-healthy, and both tend to have a low level of mercury and other contaminants.
Vitamin D Supplements
In supplements and fortified foods, vitamin D is available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol). It appears that at nutritional doses vitamins D2 and D3 are equivalent, but at high doses vitamin D2 is less potent. While symptoms of toxicity are unlikely at daily intakes below 10,000 IU/day, usual recommendations are 4000-6000 IU (100-150 mcg)/day unless treating deficiency. Clinical research studies have shown that supplementary doses less than 1000 IU per day of Vitamin D results in only modest increases in serum levels of 25(OH)D that may be inadequate for achieving optimal serum levels of 75 nmol/L. Dosing frequency can be daily or weekly (50,000-120,000 IU/week), though in some cases even longer dosing intervals with higher doses have been used.
Sun exposure as a source of vitamin D
Most people meet at least some of their vitamin D needs through exposure to sunlight. Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3. Season, time of day, length of day, cloud cover, smog, skin melanin content, and sunscreen are among the factors that affect UV radiation exposure and vitamin D synthesis. Complete cloud cover reduces UV energy, but only by 50%; shade (including that produced by seve
re pollution) reduces it by 60%. UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce Vitamin D. Sunscreens with a sun protection factor (SPF) of 8 or more appear to block vitamin D-producing UV rays, although in practice people generally do not apply sufficient amounts, cover all sun-exposed skin, or reapply sunscreen regularly. Therefore, skin likely synthesizes some Vitamin D even when it is protected by sunscreen as typically applied.
The factors that affect UV radiation exposure and research to date on the amount of sun exposure needed to maintain adequate Vitamin D levels make it difficult to provide general guidelines. It has been suggested by some Vitamin D researchers, for example, that approximately 5–30 minutes of sun exposure between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back without sunscreen usually lead to sufficient vitamin D synthesis. Or, the moderate use of commercial tanning beds that emit 2%–6% UVB radiation is also effective. Individuals with limited sun exposure need to include good sources of vitamin D in their diet or take a supplement to achieve recommended levels of intake.
However, people with naturally dark skin tone appear to require at least three to five times longer sun exposure to make the same amount of vitamin D as a person with a white skin tone. A 21-year-old caucasian man or women exposed to summer UVB light generates 10,000 IU (the equivalent of 250 mcg, 25 multivitamin pills of vitamin D, or 100 glasses of milk) of vitamin D in 15 to 20 minutes. However, longer exposure does not produce more vitamin D.
Despite the importance of the sun for Vitamin D synthesis, it is prudent to limit exposure of skin to sunlight and UV radiation from tanning beds. UV radiation is a carcinogen responsible for most of the estimated 1.5 million skin cancers and the 8,000 deaths due to metastatic melanoma that occur annually in the United States. Lifetime cumulative UV damage to skin is also largely responsible for some age-associated skin dryness and other cosmetic changes. The American Academy of Dermatology advises that protective measures be taken, including the use of sunscreens, whenever one is exposed to the sun. Assessment of Vitamin D requirements cannot address the level of sun exposure because of these public health concerns about skin cancer, and there are no studies to determine whether UVB-induced synthesis of vitamin D can occur without increased risk of skin cancer.
Health Risks from Vitamin D Deficiency:
Vitamin D has immunomodulatory properties and deficient levels of vitamin D may cause dysregulation of the immune system. Although the specifics of how Vitamin D impacts the immune system, Vitamin D influences the immune system via the vitamin D receptor and its activating enzyme 1-α-hydroxylase (CYP27B1) which are present in immune response cells including activated lymphocytes and macrophages and also dendritic cells (a type of sentinel cell that detects foreign invaders). When a dendritic cell detects invasive organisms, they “show” these organisms to B-cells ( to stimulate the production of antibodies) and T-cells (cells of the adaptive immune system). Vitamin D is an essential factor that influences the level of the thymic hormone, thymosin β4 (Tβ4). Tβ4 is important for repairing and remodeling of skin, nerves and heart tissues following injury. It assists in the the development of B cells for production of antibodies and it is implicated in lymphocyte maturation and differentiation.
Recent research strongly suggests that Vitamin D may play an important role in the immune response to COVID-19. It is evident that the role of Vitamin D supplementation in antiviral immunity against respiratory infections is likely to depend on the vitamin D status of the individual. It has been shown that people who are deficient in Vitamin D appear to be at greater risk for dying if they become infected with the COVID-19 virus, SARS CoV-2. For this reason it is strongly advised during this time of pandemic that people maintain good levels of Vitamin D. (See COVID-19 CAM Treatment).
Osteoporosis is most often associated with inadequate calcium intakes, but insufficient vitamin D contributes to osteoporosis by reducing calcium absorption. Although rickets and osteomalacia (weak bones) are extreme examples of the effects of vitamin D deficiency, osteoporosis is an example of a long-term effect of calcium and vitamin D insufficiency. Adequate storage levels of vitamin D maintain bone strength and might help prevent osteoporosis in older adults, non-ambulatory individuals who have difficulty exercising, postmenopausal women, and individuals on chronic steroid therapy.
Laboratory and animal evidence suggest that vitamin D status could affect cancer risk and indicates that vitamin D plays a role in the prevention of colon, prostate, and breast cancers.
Health Risks from Excessive Vitamin D:
Vitamin D toxicity can cause non-specific symptoms such as loss of appetite, weight loss, frequent urination, and heart arrhythmias. More seriously, it can also raise blood levels of calcium which leads to vascular and tissue calcification, with subsequent damage to the heart, blood vessels, and kidneys. A serum 25(OH)D concentration consistently >500 nmol/L (>120 ng/mL) is considered to be potentially toxic.
Vitamin D and Kidney Stones
Studies are mixed in determining whether supplementing with Vitamin D presents an increased risk for forming kidney stone. In one study, the use of supplements of both calcium (1,000 mg/day) and vitamin D (400 IU) by postmenopausal women was associated with a 17% incr
ease in the risk of kidney stones. However, a recent study published in 2017 found “Vitamin D intake in typical amounts was not statistically associated with risk of kidney stone formation, though higher risk with high doses cannot be excluded.”
In contrast, additional studies indicate that laving a low Vitamin D level is associated with increased risk of forming kidney stones. Based on the somewhat conflicting information available, it would appear prudent for someone with a history of kidney stones to maintain “normal” levels of Vitamin D (no less than 30 ng/ml) and supplement cautiously to achieve otherwise more optimal levels (50-80ng/ml) depending on their other medical conditions. Cautiously in this case would mean frequent small dose supplements rather than infrequent large doses and to maintain good hydration.
Interactions with Medications:
Vitamin D supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss vitamin D intakes with their healthcare providers.
Corticosteroid medications such as prednisone, often prescribed to reduce inflammation, can reduce calcium absorption and impair vitamin D metabolism. These effects can further contribute to the loss of bone and the development of osteoporosis associated with their long-term use.
Medications that Lower Vitamin D:
Both the weight-loss drug orlistat (brand names Xenical® and alliTM) and the cholesterol-lowering drug cholestyramine (brand names Questran®, LoCholest®, and Prevalite®) can reduce the absorption of vitamin D and other fat-soluble vitamins. Phenobarbital and phenytoin (Dilantin), used to control epileptic seizures, increase the liver metabolism of vitamin D to inactive compounds and they reduce calcium absorption.
Vitamin D – Overview
- Vitamin D – Summary handout
- Vitamin D – NIH
- Vitamin D – NHS.UK
- Vitamin D status and ill health: a systematic review – The Lancet Diabetes & Endocrinology
- Update in Vitamin D – 2010
- Evaluation, treatment, and prevention of vitamin D deficiency – an Endocrine Society clinical practice guideline – 2011
Vitamin D – Cardiovascular Disease
- Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers – 2009
- The role of vitamin D in cardiovascular disease
- New Meta-Analysis Suggests ‘Threshold’ Effect for Vitamin D and CVD
Vitamin D – Chronic Pain
- Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities – 2015
- Vitamin D Deficiency and Pain – Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States – 2015
- Vitamin D for Chronic Pain
- Vitamin D status in patients with musculoskeletal pain, fatigue and headache – A cross-sectional descriptive study in a multi-ethnic general practice in Norway – 2010
- Vitamin D and Central Hypersensitivity in Patients with Chronic Pain – 2014
- Vitamin D for the treatment of painful diabetic neuropathy – 2016
- Meta-analysis of pain and function placebo responses in pharmacological osteoarthritis trials – 2019
- 25 Hydroxyvitamin D levels, quality of life, and disability in long-standing patients of somatization – 2018
- Is there a role for vitamin D in the treatment of chronic pain? – 2017
- Vitamin D and Its Potential Interplay With Pain Signaling Pathways- 2020
- Vitamin D Benefits Diabetic Neuropathy Pain, Mood – 2022
Vitamin D – COVID-19
- Vitamin D – NHS.UK
- Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19) – 2020
- The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients – 2020
- LARGE, SINGLE-DOSE, ORAL VITAMIN D SUPPLEMENTATION IN ADULT POPULATIONS – A SYSTEMATIC REVIEW – 2014
- Vitamin D supplementation to prevent acute respiratory tract infections – systematic review and meta-analysis of individual participant data – 2016
- The Hidden Function of Vitamin D – 2016
- Vitamin D contributes to mast cell stabilization – 2017
Vitamin D – Depression
Vitamin D – Fibromyalgia
- Is Serum Hypovitaminosis D Associated with Chronic Widespread Pain Including Fibromyalgia?
Vitamin D – Headaches
- Interrelationships between chronic tension-type headache, musculoskeletal pain, and vitamin D deficiency: Is osteomalacia responsible for both headache and musculoskeletal pain?
- Vit D levels in pain and headache patients
Vitamin D – Low Back Pain
- High Prevalence of Hypovitaminosis D in Indian Chronic Low Back Patients – 2015
- Improvement of Chronic Back Pain or Failed Back Surgery with Vitamin D Repletion – 2009
- Vitamin D May Be Linked to Spine Disease – in Ophthalmology, Ophthalmology from MedPage Today
Vitamin D – Inflammation
- Lowering Inflammation Through Diet, Exercise, and Vitamin D – 2015
- The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients – 2020
- Vitamin D contributes to mast cell stabilization – 2017
Vitamin D – Insulin Resistance
- Influence of vitamin D treatment on transcriptional regulation of insulin-sensitive genes. – PubMed – NCBI
- Rising serum 25-hydroxy-vitamin D levels after weight loss in obese women correlate with improvement in insulin resistance. – PubMed – NCBI
- Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults – study protocol for a randomized controlled trial – 2015
Vitamin D – Kidney Disease
- Vitamin D in Health and Disease
- Expanding role for
vitamin D in chronic kidney disease: importance of blood 25-OH-D levels and extra-renal 1alpha-hydr
oxylase in the classical and … – PubMed – NCBI
- Vitamin D and Chronic Kidney Disease – 2009
Vitamin D – Kidney Stones
- Idiopathic Calcium Nephrolithiasis and Hypovitaminosis D: A Case-control Study. – PubMed – NCBI
- Analysis of vitamin D deficiency in calcium stone-forming patients. – PubMed – NCBI
- Vitamin D Intake and the Risk of Incident Kidney Stones – 2017
Vitamin D – Mast Cell Stabilization
Vitamin D – Obesity
- Vitamin status in morbidly obese patients – a cross-sectional study – 2008
- Decreased bioavailability of vitamin D in obesity – 2000
- Obesity and vitamin D 2004
- The Longitudinal Association of Vitamin D Serum Concentrations & Adiposity Phenotype – 2013
Vitamin D – Optimal Levels
Vitamin D – Preventing Pain Related to Surgery
- The Preoperative Supplementation With Vitamin D Attenuated Pain Intensity and Reduced the Level of Pro-inflammatory Markers in Patients After Posterior Lumbar Interbody Fusion – 2019
Emphasis on Education
Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.
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