November 7, 2004
Subject: Low levels of vitamin D are linked with a variety of other conditions. Supplementation may be very useful in treating depression, migraines, PCOS and musculoskeletal pain.
The more I read about vitamin D, the more interesting the things I find out. I've already written articles several articles about vitamin D. Here are links to them:
In this letter I will cover some miscellaneous uses of vitamin D. There are three more vitamin D articles that I need to write after this one. One will be about cancer prevention and treatment. Testing and treating vitamin D deficiency isn't simple and that will require a separate article. Then a summary article so I can make sense of all of these various effects and uses.
Seasonal Affective Disorder:
Around this time of year people start complaining of increasing levels of melancholia that only worsens during the winter. If this gets really bad it'll get diagnosed as Seasonal Affective Disorder (SAD). Typical therapy is to stick these people under sun lamps, maybe give them vitamin B-12 and melatonin. When sun exposure decreases, so does vitamin D levels. This has prompted several researchers to question whether vitamin D might help these SAD patients. An Australian study split a group of 44 SAD sufferers and either gave them 400 iu, 800 iu or no Vitamin D for five days during late winter. The more Vitamin D they got the better they felt. [i] Another study tried a dose of 100,000 iu of Vitamin D on 8 of 15 subjects suffering from SAD. The remaining sufferers were treated with light therapy. Subjects were evaluated a month later. The light therapy had no benefit while the vitamin D improved all 8 subjects. [ii]
Calcium levels regulate the tone of blood vessels and how thick the blood is. Calcium levels are regulated by vitamin D. Both blood calcium and blood coagulation are way off in people who get migraine headaches. There have been several case reports published of menstrual timed migraine headaches improving over time with vitamin D and calcium supplementation. [iii] [iv]
Polycystic Ovary Syndrome (PCOS)
Polycystic ovary syndrome is a disease seen only in humans and is classically characterized by polycystic ovaries, amenorrhea, hirsutism, insulin resistance, and obesity. Vitamin D deficiency was highly prevalent among 13 women with PCOS and supplementation with 1500 mg of Calcium a day and 50,000 iu of Vitamin D2 every week normalized menses and fertility in all the women in the study in three months of treatment. [v] In recent years the focus of treating PCOS is to target the insulin resistance and prescribe the drug Metformin. You may recall that this drug is commonly used to treat Type II diabetes. You may also recall that Vitamin D appears to be more effective and reducing insulin resistance than Metformin.
Patients who have persistent musculoskeletal pain without any history of trauma have a very high frequency of vitamin D deficiency. [vi] Plotnikoff and Quigley at the Mayo clinic reported that 130 out of 150 patients evaluated for chronic musculoskeletal pain were vitamin D deficient. [vii] A 2003 study in Spine looked at data from Saudi Arabia . Of 360 people with low back pain, 83% or 299 had low levels of vitamin D. Vitamin D supplements improved all of the people who started out with low levels plus a few people who had normal levels; 93% of the study participants improved with vitamin D. [viii]
Is this not interesting? That last study was done in Saudi Arabia . Saudis tend to cover themselves from the sun and this may account for what seems like a high incidence of vitamin D deficiency. An Israeli study, and keep in mind these are people who tend to live in shorts and sandals, also showed surprisingly high occurrence of D deficiency; of people hospitalized, 57% had low vitamin D levels. [ix] My days of thinking that because we live in Denver we need not be concerned about low vitamin D are over.
[i] Psychopharmacology (Berl). 1998 Feb;135(4):319-23.
Vitamin D3 enhances mood in healthy subjects during winter .
Lansdowne AT, Provost SC.
Department of Psychology, The University of Newcastle , Callaghan NSW, Australia .
Mood changes synchronised to the seasons exist on a continuum between individuals, with anxiety and depression increasing during the winter months. An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder (SAD) with carbohydrate craving, hypersomnia, lethargy, and changes in circadian rhythms also evident. It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3, the hormone of sunlight, leading to changes in brain serotonin. Forty-four healthy subjects were given 400 IU, 800 IU, or no vitamin D3 for 5 days during late winter in a random double-blind study . Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect. Results are discussed in terms of their implications for seasonality, SAD, serotonin, food preference, sleep, and circadian rhythms.
Randomized Controlled Trial
PMID: 9539254 [PubMed - indexed for MEDLINE]
[ii] J Nutr Health Aging. 1999;3(1):5-7.
Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder.
Gloth FM 3rd, Alam W, Hollis B.
The Department of Medicine, The Union Memorial Hospital , Baltimore , Maryland 21218-2895 , USA .
Seasonal Affective Disorder (SAD) is prevalent when vitamin D stores are typically low. Broad-spectrum light therapy includes wavelengths between 280-320 nm which allow the skin to produce vitamin D. This study was designed to test the hypothesis that vitamin D deficiency might play a role in SAD. A prospective, randomized controlled trial was conducted in a group of 15 subjects with SAD. Eight subjects received 100,000 I.U. of vitamin D and seven subjects received phototherapy . At the onset of treatment and after 1 month of therapy subjects were administered the Hamilton Depression scale, the SIGH-SAD, and the SAD-8 depression scale. All subjects also had serum levels of 25-hydroxyvitamin D (25-OH D) measured before and 1 week after intervention therapy. All subjects receiving vitamin D improved in all outcome measures. The phototherapy group showed no significant change in depression scale measures. Vitamin D status improved in both groups (74% vitamin D group, p < 0.005 and 36% phototherapy group, p < 0.01). Improvement in 25-OH D was significantly associated with improvement in depression scale scores (r2=0.26; p=0.05). Vitamin D may be an important treatment for SAD. Further studies will be necessary to confirm these findings.
Randomized Controlled Trial
PMID: 10888476 [PubMed - indexed for MEDLINE]
[iii] Headache. 1994 Oct;34(9):544-6.
Vitamin D and calcium in menstrual migraine.
Two premenopausal women with a history of menstrually-related migraines and premenstrual syndrome were treated with a combination of vitamin D and elemental calcium for late luteal phase symptoms. Both cited a major reduction in their headache attacks as well as premenstrual symptomatology within 2 months of therapy. These observations suggest that vitamin D and calcium therapy should be considered in the treatment of migraine headaches.
PMID: 8002332 [PubMed - indexed for MEDLINE]
[iv] Headache. 1994 Nov-Dec;34(10):590-2.
Alleviation of migraines with therapeutic vitamin D and calcium.
Department of Medicine, Mount Sinai Hospital , New York , NY 10029.
Two postmenopausal migraineurs who developed frequent and excruciating migraine headaches (one following estrogen replacement therapy and the other following a stroke) were treated with combination vitamin D and calcium. Therapeutic replacement with vitamin D and calcium resulted in a dramatic reduction in the frequency and duration of their migraine headaches.
PMID: 7843955 [PubMed - indexed for MEDLINE]
[v] Steroids. 1999 Jun;64(6):430-5.
Vitamin D and calcium dysregulation in the polycystic ovarian syndrome.
Thys-Jacobs S, Donovan D, Papadopoulos A, Sarrel P, Bilezikian JP.
Department of Medicine, St. Lukes-Roosevelt Hospital Center, Columbia University, College of Physicians & Surgeons, New York, NY 10019, USA.
Over the past 30 years, numerous studies in invertebrates and vertebrates have established a role of calcium in oocyte maturation as well as in the resumption and progression of follicular development. Polycystic ovarian syndrome (PCO) is characterized by hyperandrogenic chronic anovulation, theca cell hyperplasia, and arrested follicular development. The aim of this observational study was to determine whether vitamin D and calcium dysregulation contribute to the development of follicular arrest in women with PCO, resulting in reproductive and menstrual dysfunction. Thirteen premenopausal women (mean age 31 +/- 7.9 years) with documented chronic anovulation and hyperandrogenism were evaluated. Four women were amenorrheic and nine had a history oligomenorrhea, two of whom had dysfunctional bleeding. Nine had abnormal pelvic sonograms with multiple ovarian follicular cysts. All were hirsute, two had alopecia, and five had acanthosis nigricans. The mean 25 hydrovitamin D was 11.2 +/- 6.9 ng/ml [normal (nl): 9-52], and the mean 1,25 dihydroxyvitamin D was 45.8 +/- 18 pg/ml. with one woman with a 1,25 dihydroxyvitamin D <5 pg/ml (nl: 15-60). The mean intact parathyroid hormone level was 47 +/- 19 pg/ml (nl: 10-65), with five women with abnormally elevated parathyroid hormone levels. All were normocalcemic (9.3 +/- 0.4 mg/dl). Vitamin D repletion with calcium therapy resulted in normalized menstrual cycles within 2 months for seven women, with two experiencing resolution of their dysfunctional bleeding. Two became pregnant, and the other four patients maintained normal menstrual cycles. These data suggest that abnormalities in calcium homeostasis may be responsible, in part, for the arrested follicular development in women with PCO and may contribute to the pathogenesis of PCO.
PMID: 10433180 [PubMed - indexed for MEDLINE]
[vi] Nutr Rev. 2004 Sep;62(9):354-9.
Hypovitaminosis D-induced pain.
Mascarenhas R, Mobarhan S.
Department of Internal Medicine, Loyola University Medical Center , Maywood , IL 60153 , USA .
Vitamin D deficiency is a problem of considerable magnitude that has reemerged as a major public health issue in the United States and several other developed countries. Vitamin D plays a crucial role in calcium homeostasis in the body. Hypovitaminosis D leads to osteomalacia and increased risk of fractures, especially in the elderly. Preliminary research suggests that vitamin D can prevent certain types of cancer and autoimmune diseases. A recent large study has shown the association between severe hypovitaminosis D and persistent, non-specific musculoskeletal pain, further suggesting that patients with no apparent cause of pain should be assessed and possibly treated for vitamin D deficiency.
PMID: 15497769 [PubMed - in process]
[vii] Mayo Clin Proc. 2003 Dec;78(12):1463-70.
Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain.
Plotnikoff GA , Quigley JM.
Department of Internal Medicine, University of Minnesota Medical School , Minneapolis , Minn , USA . firstname.lastname@example.org
OBJECTIVE: To determine the prevalence of hypovitaminosis D in primary care outpatients with persistent, nonspecific musculoskeletal pain syndromes refractory to standard therapies. PATIENTS AND METHODS: In this cross-sectional study, 150 patients presented consecutively between February 2000 and June 2002 with persistent, nonspecific musculoskeletal pain t o the Community University Health Care Center, a university-affiliated inner city primary care clinic in Minneapolis , Minn (45 degrees north). Immigrant (n = 83) and nonimmigrant (n = 67) persons of both sexes, aged 10 to 65 years, from 6 broad ethnic groups were screened for vitamin D status. Serum 25-hydroxyvitamin D levels were determined by radioimmunoassay. RESULTS: Of the African American, East African, Hispanic, and American Indian patients, 100% had deficient levels of vitamin D (< or = 20 ng/mL). Of all patients, 93% (140/ 150) had deficient levels of vitamin D (mean, 12.08 ng/mL; 95% confidence interval, 11.18-12.99 ng/mL). Nonimmigrants had vitamin D levels as deficient as immigrants (P = .48). Levels of vitamin D in men were as deficient as in women (P = .42). Of all patients, 28% (42/150) had severely deficient vitamin D levels (< or = 8 ng/mL), including 55% of whom were younger than 30 years. Five patients, 4 of whom were aged 35 years or younger, had vitamin D serum levels below the level of detection. The severity of deficiency was disproportionate by age for young women (P < .001), by sex for East African patients (P < .001), and by race for African American patients (P = .006). Season was not a significant factor in determining vitamin D serum levels (P = .06). CONCLUSION: All patients with persistent, nonspecific musculoskeletal pain are at high risk for the consequences of unrecognized and untreated severe hypovitaminosis D. This risk extends to those considered at low risk for vitamin D deficiency: nonelderly, nonhousebound, or nonimmigrant persons of either sex. Nonimmigrant women of childbearing age with such pain appear to be at greatest risk for misdiagnosis or delayed diagnosis. Because osteomalacia is a known cause of persistent, nonspecific musculoskeletal pain, screening all outpatients with such pain for hypovitaminosis D should be standard practice in clinical care.
PMID: 14661675 [PubMed - indexed for MEDLINE]
[viii] Spine. 2003 Jan 15;28(2):177-9.
Vitamin D deficiency and chronic low back pain in Saudi Arabia .
Al Faraj S, Al Mutairi K.
Department of Medicine, Riyadh Armed Forces Hospital , Riyadh , Saudi Arabia . email@example.com
STUDY DESIGN: Initial assessment involved 360 patients (90% women and 10% men) attending spinal and internal medicine clinics over a 6-year period who had experienced low back pain that had no obvious cause for more than 6 months. The patients ranged in age from 15 to 52 years.
OBJECTIVES: To investigate the contribution of vitamin D deficiency as a cause for idiopathic chronic low back pain, to find a simple and sensitive test for screening patients with low back pain for vitamin D deficiency, and to determine the correlation between the vitamin deficiency and pain.
METHODS: A biochemical assay of serum calcium, phosphate, alkaline phosphatase, and 25-hydroxy vitamin D level was performed before and after treatment with vitamin D supplements.
RESULTS: Findings showed that 83% of the study patients (n = 299) had an abnormally low level of vitamin D before treatment with vitamin D supplements . After treatment, clinical improvement in symptoms was seen in all the groups that had a low level of vitamin D, and in 95% of all the patients (n = 341). CONCLUSIONS: Vitamin D deficiency is a major contributor to chronic low back pain in areas where vitamin D deficiency is endemic. Screening for vitamin D deficiency and treatment with supplements should be mandatory in this setting. Measurement of serum 25-OH cholecalciferol is sensitive and specific for detection of vitamin D deficiency, and hence for presumed osteomalacia in patients with chronic low back pain.
PMID: 12544936 [PubMed - indexed for MEDLINE]
[ix] Isr Med Assoc J. 2004 Feb;6(2):82-7.
Hypovitaminosis D among inpatients in a sunny country.
Hochwald O, Harman-Boehm I, Castel H.
Department of Pediatrics, Bnei Zion Medical Center , Haifa , Israel . firstname.lastname@example.org
BACKGROUND: Hypovitaminosis D is an important risk factor for osteoporosis and its complications. Previous studies found that the incidence of hypovitaminosis D among patients in an internal medicine ward reached up to 57%. OBJECTIVE: To determine the prevalence and determinants of hypovitaminosis D among patients in internal medicine wards in a sunny country. METHODS: We measured 25-hydroxyvitamin D, parathyroid hormone and various other laboratory parameters, and assessed the amount of sun exposure, dietary vitamin D intake and other risk factors for hypovitaminosis D in 296 internal medicine inpatients admitted consecutively to the Soroka University Medical Center , which is situated in a sunny region of Israel . RESULTS: We found hypovitaminosis D (serum 25-HO-D < 15 ng/ml) in 77 inpatients (26.27%). The amount of sunlight exposure, serum albumin concentration, being housebound or resident of a nursing home, vitamin D intake, ethnic group, cerebrovascular accident and glucocorticoid therapy were all significantly associated with hypovitaminosis D. Multivariate analysis showed a significant association between hypovitaminosis D and Bedouin origin, sun exposure, vitamin D intake, and stroke. Hypovitaminosis D was also found among inpatients who reported consuming more than the recommended daily amount of vitamin D. Parathyroid hormone levels were significantly higher in patients with 25-OH-D levels below 15 ng/ml. In a subgroup of 74 inpatients under 65 years old with no known risk factors for hypovitaminosis D, we found 20.3% with hypovitaminosis D. CONCLUSIONS: Hypovitaminosis D is common in patients hospitalized in internal medicine wards in our region, including patients with no known risk factors for this condition. Based on our findings, we recommend vitamin D supplementation during hospitalization and upon discharge from general internal medicine wards as a primary or secondary preventive measure.
PMID: 14986463 [PubMed - indexed for MEDLINE]