Vitamin D, Migraine, and Health - Medical Complications: Optimize Therapy!

 

Vitamin D, Migraine, and Health - Medical Complications: Optimize Therapy!
Steve D. Wheeler, MD; Barclay R. Gang, MS; Frederick R. Taylor, MD

 
Key Points:
  1. Vitamin D deficiency occurs in 30-100% of various populations, particularly the ill, elderly, highly pigmented ethic groups, obese, postmenopausal, pregnant and lactating women, children, young adults and those who avoid sun exposure—all populations, including migraineurs, are at risk.
  2. Vitamin D is not a vitamin but a non-sex hormone.
  3. Vitamin D deficiency is associated with many diseases including multiple cancers and inflammatory disorders including cardiovascular disease and severe arthritic conditions.
  4. Vitamin D has anti-inflammatory and analgesic activities. Deficiency may play a role in mechanisms responsible for migraine and other pain syndromes.
  5. Vitamin D deficiency is diagnosed by a simple, inexpensive blood test, a 25-hydroxyvitamin D level, and is easy and inexpensive to treat.
  6. To obtain optimum levels for health, typically an average of 1000 international units (IU) vitamin D3 per 25-30 pounds of body weight daily is required. This is not a toxic dose.
We make vitamin D from sunlight at certain times of the year dependent on where we live. We get small amounts of vitamin D from our diets, like oily fish, and fortified foods, particularly milk, and supplements.  Vitamin D deficiency is a worldwide problem. You may be surprised to learn that recent studies show vitamin D deficiency occurs in 32% of healthy students, physicians, and hospital residents, 73% of pregnant women, and 40-100% of community dwelling elderly. Studies on the ill show that 93% of people admitted to hospital emergency departments with muscle aches, bone pain, and a variety of diagnoses, including fibromyalgia, chronic fatigue syndrome, and depression, are vitamin D deficient.   Low back pain is associated with vitamin D deficiency and reports show that improved vitamin D levels result in pain relief.  Furthermore, breast cancer survivors who experience Femara® (letrozole) associated joint or muscular pains improve dramatically with vitamin D supplements.
 
What is vitamin D deficiency?                                                                                                   
The 25-hydroxyvitamin D blood level defines vitamin D deficiency and is the best marker for deficiency in all populations except those with chronic kidney failure where 1, 25-dihydroxyvitamin D is the best test.  
           
25-hydroxyvitamin D blood levels:
                        < 20 ng/ml                                          Vitamin D Deficiency
                        20-30 ng/ml                                        Vitamin D Insufficiency
                        > 30 ng/ml                                          Vitamin D Sufficiency
                        >40/50-80 ng/ml                                 Vitamin D Optimized
                        >150 ng/ml                                         Vitamin D Toxicity
                       
Laboratories report reference ranges for 25-hydroxyvitamin D levels to vary between 20-32 ng/ml and 100 ng/ml.  The concepts of adequate (sufficient) and optimized vitamin D are not well understood!  It is clear that blood levels considerably higher than 30 ng/ml are required for any health advantage.  Generally, to obtain a health benefit the target 25-hydroxyvitamin D level has been suggested to be 40-60 ng/ml by grassrootshealth.net and 50-80 ng/ml by vitamindcouncil.com.  Hints about what a truly optimal 25-hydroxyvitamin D level ought to be can be derived from the observations that women reduce the risk of breast cancer by 50% when the vitamin D level is greater than 52 ng/ml and Femara® (letrozole) associated joint and muscle pain resolves when intake results in levels greater than 66 ng/ml.  Although many are concerned about vitamin D toxicity, it is uncommon, and studies show that vitamin D levels less than 300 ng/ml are safe and tolerable, but for even greater safety levels less than 150 ng/ml are desired. 
 
General Information on vitamin D                                                                         
Vitamin D is not actually a vitamin—a vitamin is an essential nutrient that must be obtained from food.  Instead, vitamin D is a hormone that our bodies make from a type of cholesterol in our skin after it is exposed to ultraviolet B radiation from the sun.   The active form of vitamin D is 1, 25-dihydroxyvitamin D, but it is not a good measure of vitamin D status.  1, 25-dihydroxyvitamin D stimulates vitamin D receptors and regulates the function of at least 200 human genes, although some estimate that up to 1000 to 2000 genes are regulated by vitamin D. 
 
Vitamin D supplements are available as D2 and D3. Vitamin D2, known as ergocalciferol, is plant derived, kosher, and synthetic. Your liver makes it into by-products your body doesn’t generally contain. One of these by-products may block the action of vitamin D. We prefer D3, known as cholecalciferol, and also called human vitamin D. It is animal derived, but identical to human vitamin D and has metabolites identical to what our body makes from proper sunlight exposure. Vitamin D3 is available as 400, 1000, 2000, 2500, 5000 and 50,000 IU doses via the Internet.  The three lowest doses are available in retail stores and most pharmacies. With some frustration you may be able to get your pharmacy to carry 5,000 IU capsules. Expect to pay $15.00 to $20.00 per year for optimum replacement. If you are paying more, look for a better price. Typically, the higher the strength capsule the better the price per week of optimum vitamin D.
 
What is the Role of vitamin D?
Given vitamin D gene activity, a multitude of diverse and widespread body functions depend on vitamin D gene regulation. Deficiency may be associated with a wide range of illnesses.   
 
Most of us recognize that vitamin D plays a role in bone metabolism by making the oral absorption of calcium possible.  Calcium is involved in many other physiological processes that may suffer without sufficient vitamin D and calcium.  As calcium needs increase in the setting of vitamin D deficiency, skeletal calcium stores are depleted. This eventually leads to osteopenia, osteoporosis, or osteomalacia in adults and rickets in children.  Recent decades have led to advances in the diagnosis and treatment of these conditions, including increased access to bone density scans, fortifying foods with vitamin D and the development and marketing of bisphosphonates (e.g., Actonel® (risedronate), Boniva® (ibandronate), Fosamax® (alendronate), and Reclast® (zoledronic acid)).  In fact, such advances may have blunted our understanding of vitamin D, particularly its impact on overall health and disease.
 
Most providers think incorrectly that vitamin D’s role is minor compared to calcium and the bisphosphonates for the treatment of osteopenia, osteoporosis or osteomalacia. Over the last several years we have noted that approximately 70% of the women in our clinic have osteopenia or osteoporosis that is usually stable, rarely improved, and occasionally deteriorates despite calcium and bisphosphonates.  Even though rheumatologists, endocrinologists and other specialists treat these women, many are not taking vitamin D and rarely have any ever had a 25-hydroxyvitamin D level. 
 
What else does vitamin D do?                                                       
Recently vitamin D has been implicated in reducing the risk of many chronic illnesses including cancers, immune system dysfunction, infectious diseases, diabetes, hypertension, and both heart and brain related vascular diseases.  Vitamin D has been shown to reduce the growth of both normal and cancerous cells. This may help account for the association of vitamin D deficiency with 17 cancers.  The most common vitamin D deficiency associated cancers include breast, colon, prostate, ovarian, and malignant melanoma.  Further, brain, prostrate, breast, colon and immune cells, among others, have vitamin D receptors and respond to the active form of vitamin D.  Recent reports show poorer long-term outcomes when vitamin D deficiency existed at the time of initial cancer diagnosis.  Moreover, vitamin D deficiency is associated with multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjogrens, and inflammatory bowel disease, perhaps produced by an inability to restrain overactive immune cells.  Additionally, vitamin D deficiency is associated with increased birth defects, caesarian sections, muscle weakness, chronic pain, depression, propensity to falls and mortality.  It plays a causative role in hypertension and diabetes mediated by renin and pancreatic ƒÒ cells mechanisms, respectively.  Even the common cold and influenza seem to be associated with deficiency in vitamin D due to reduced antimicrobial effect influenced by the naturally occurring peptide, cathelicidin. Vitamin D controls this peptide's production, which may explain why these conditions are associated with season changes.
 
Does vitamin D play a role in migraine or pain?                                                  
In 2008 we reported an observational study that was conducted to determine whether vitamin D deficiency occurred in patients with chronic or frequent migraine.  54 patients had chronic and one had frequent migraine (48 females, 7 males).  In the sunshine state 41.8% of these patients had vitamin D deficiency or insufficiency, a trend toward earlier onset of migraine, and greater risks for hypertension and type 2 diabetes.  Although our observational study gave no insight into whether migraine headache responds to vitamin D, Thys-Jacobs in 1994 reported four vitamin D deficient women with migraine who improved with vitamin D replacement.  In 2009 Prakash and Shah reported eight vitamin D deficient patients (4 men and 4 women) with chronic tension-type headache who responded to vitamin D replacement.
 
Fibromyalgia has been associated with vitamin D deficiency, however this is controversial.  As mentioned earlier, low back pain and the Femara® (letrozole) associated pain syndromes respond to vitamin D supplementation, thus suggesting a mechanistic connection.  Additionally, Lee and Chen in 2008 reported an observational study in patients with type 2 diabetes, neuropathic pain and vitamin D deficiency who had significant pain reduction with vitamin D repletion, suggesting a possible analgesic effect.
 
Possible vitamin D mechanisms in migraine and pain:
1.    Anti-inflammatory effects mediated through reductions in matrix metalloproteinases, C-reactive protein, tumor necrosis factor-alpha and other inflammatory mediators
2.    Analgesic effects
3.    Nitric oxide reduction
4.    Magnesium absorption increased
 
How much vitamin D do we need?                                                                        
Many people believe they can get adequate amounts of vitamin D from casual sunlight exposure or from diet, but this typically is not true.  If your skin is aged, pigmented, obese, covered by clothing or sunscreen (>15 SPF) or behind glass, it is very unlikely that you will get adequate ultraviolet B rays from sunshine.  Ultraviolet B waves are delicate and have little ability to penetrate these cover-ups.  For those fair-skinned folks among us, getting 10-20 minutes of sun 2-3 times weekly to bare arms and legs, just enough to avoid redness, may be sufficient, but optimal levels are unlikely.
 
The American Academy of Dermatology recommends that you avoid sun exposure and get your vitamin D from food or supplements.  The Institute of Medicine currently recommends 400-600 units of vitamin D daily for adults, although this is an inappropriately low dose and is to be reevaluated in 2010, most people do not get this much.  Multiple protocols using various doses of vitamin D have been suggested and no single treatment fits all.  For the timid 1000-2000 units of vitamin D daily are safe and tolerable, may not be sufficient, but is likely better than nothing.  However, the Council for Responsible Nutrition has published in a peer-reviewed journal that 10,000 IU vitamin D per day is absolutely safe.
 
Typically to obtain 25-hydroxyvitamin D levels between 40-80 ng/ml the average individual between the months of September through May will need to consume 1000 IU vitamin D3 for every 25-30 pounds of body weight. For the vast majority of people that means between 5,000 to 10,000 IU daily.  In cases where severe deficiency exists, your physician may prescribe what seems like gigantic doses, possibly up to 50,000 units every week.  However, as detailed previously most of us need around 35,000 to easily 50,000 IU weekly to ever reach optimum levels. If 10,000 per day is safe, this equals 70,000 IU per week. You will not need such doses in the summer with sun exposure as outlined above or with body weight below 200 pounds. Since the only side effect in large studies is an overall improved sense of well being the only way to know what you need lifelong is to know your level and decide between sufficient and optimum. To increase your level you will need to add about 1000 IU for every 10 ng/ml increase desired in your level. Doses of vitamin D larger than 2000 IU per day should not be taken without your physician’s knowledge and permission.  Smaller doses are necessary for those less than 50 pounds in weight. Perhaps needless to say, sometimes a new provider is necessary when they completely disagree with your vitamin D goals.  However, first you may wish to share this article with your provider. 
 
Vitamin D Tests
Everyone should know their 25-hydroxyvitamin D level!  Some controversy may exist as to when to test. Do you test at the start or only after replacement? Some practitioners hold the strong opinion that testing need not be obtained until you take the steps to optimize your levels. If you agree that you want optimum treatment levels you need either sunlight or about 1000 IU per 25-30 pounds of weight. So you can be sure you are not optimum without regular sunlight exposure in the right climate or you take about 5,000 IU per day or more on average for most. If you test before these steps you and your physician should not be surprised to find that your vitamin D level is appallingly low or at most sufficient but certainly not optimum.  Dr. Cannell of the Vitamin D Council does not support testing before starting treatment. Exceptions might be if there is a question about your degree of “tan” or result desired on your current vitamin D replacement. However, many physicians and patients require an initial vitamin D level since they do not recognize the pandemic nature or health consequences of vitamin D deficiency and are fearful of toxicity. 
 
Since vitamin D intake needs to be a lifetime habit, some question whether anyone needs to know where the vitamin D level started out. Everyone agrees all need to know where it ends up! Once you take a replacement dose and your level is tested your doctor will have a better idea about changes in your dose. Obtain your level, initially 3 months after treatment starts or changes, and then annually to make certain that it is maintained in an optimal range.  Be advised, your provider may not be aware of vitamin D information such as sufficient versus optimum levels and doses required to reach optimum.
 
In August 2009 the Dark Report reported that 25-hydroxyvitamin D levels can vary by the laboratory which runs the test. Since the result is important to whether you are just sufficient or optimal the actual laboratory running the test must be known. Most physicians and clinics send the test out to a major laboratory. A few do “in-house” testing. The method used matters with the gold standard referred to as the Diasorin test. Research has shown that ARUP, LabCorp and Clinical Pathology Labs are highly reliable, while historically Quest and Mayo Lab results have run artificially high, by as much as 30%. Running multiple tests on one blood sample also assessed variability of test results. The Quest Lab results showed the most significant variability. Not all lab print outs list the testing lab. Your provider can get that information when not known. Know your 25-hydroxyvitamin D level and name of the testing lab.
 
Summary
The high frequency of vitamin D deficiency with its concomitant risk of cardiovascular disease, malignancy, and other illnesses, suggests that it may be an important, unrecognized, however treatable cause of disease, morbidity and mortality in migraine.  While current research to further clarify the role of vitamin D is ongoing, certainly a strong case already exists for optimally treating vitamin D deficiency.  After all is said and done the long-term goal is a healthy life. None of the recommendations listed here will lead to toxic results or injury in those without kidney, parathyroid or calcium problems, so optimize your therapy!
 
Steve D. Wheeler, MD, FAAN, FAHS, and Barclay R. Gang, MS, Ryan Wheeler Headache Treatment Center, Miami, FL; and Frederick R. Taylor, MD, FAHS, Park Nicollet Headache Clinic and Research Center, Minneapolis, MN.
 
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