Study Adds Weight to Link Between Calcium Supplements and Heart Problems

Research: Calcium supplements with or without vitamin D and risk of cardiovascular events: Reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis

Research published in BMJ (British Medical Journal) in April 2011 adds to mounting evidence that calcium supplements increase the risk of cardiovascular events, particularly heart attacks, in older women. The findings suggest that their use in managing osteoporosis should be re-assessed.

Calcium supplements are often prescribed to older (postmenopausal) women to maintain bone health. Sometimes they are combined with vitamin D, but it’s still unclear whether taking calcium supplements, with or without vitamin D, can affect the heart.

The Women’s Health Initiative (WHI) study – a seven-year trial of over 36,000 women – found no cardiovascular effect of taking combined calcium and vitamin D supplements, but the majority of participants were already taking personal calcium supplements, which may have obscured any adverse effects.

So a team of researchers, led by Professor Ian Reid at the University of Auckland, re-analysed the WHI results to provide the best current estimate of the effects of calcium supplements, with or without vitamin D, on the risk of cardiovascular events.

They analysed data from 16,718 women who were not taking personal calcium supplements at the start of the trial and found that those allocated to combined calcium and vitamin D supplements were at an increased risk of cardiovascular events, especially heart attack.

By contrast, in women who were taking personal calcium supplements at the start of the trial, combined calcium and vitamin D supplements did not alter their cardiovascular risk.

The authors suspect that the abrupt change in blood calcium levels after taking a supplement causes the adverse effect, rather than it being related to the total amount of calcium consumed. High blood calcium levels are linked to calcification (hardening) of the arteries, which may also help to explain these results.

Further analyses – adding data from 13 other trials, involving 29,000 people altogether – also found consistent increases in the risk of heart attack and stroke associated with taking calcium supplements, with or without vitamin D, leading the authors to conclude that these data justify a reassessment of the use of calcium supplements in older people.

But in an accompanying editorial, Professors Bo Abrahamsen and Opinder Sahota argue that there is insufficient evidence available to support or refute the association.

Because of study limitations, they say “it is not possible to provide reassurance that calcium supplements given with vitamin D do not cause adverse cardiovascular events or to link them with certainty to increased cardiovascular risk. Clearly further studies are needed and the debate remains ongoing.”


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Medical News: Calcium Builds Bones But May Weaken Heart – in Cardiovascular, Myocardial Infarction from MedPage TodayThe findings suggest the use of these supplements in managing osteoporosis should be re-assessed, researchers reported online today in the BMJ. In the new study, researchers analyzed data from 16,718 women who were not taking personal calcium supplements at the start of the trial and found that those allocated to combined calcium and vitamin D supplements were at an increased risk of cardiovascular events, especially MI.

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“Anticonvulsant Action” of Vitamin D in Epileptic Patients? A Controlled Pilot Study

This pilot study by Christiansen, Rødbro, and Sjö was published in 1974 in the British Medical Journal. The frequency of epileptic seizures was observed in a controlled therapeutic trial on 23 epileptic inpatients before and after treatment with vitamin D2 or placebo in addition to anticonvulsant drugs. The number of seizures was reduced during treatment with vitamin D2 but not with placebo. The effect was unrelated to changes in serum calcium or magnesium. The results may support the concept that epileptics should be treated prophylactically with vitamin D (Br Med J 1974; 2 (5913): 258-9).

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Vitamin D Deficiency Common in Cancer Patients

Predicts advanced disease

More than three-quarters of cancer patients have insufficient levels of vitamin D (25-hydroxy-vitamin D) and the lowest levels are associated with more advanced cancer, according to a study presented on October 2, 2011, at the 53rd Annual Meeting of the American Society for Radiation Oncology (ASTRO).

“Until recently, studies have not investigated whether vitamin D has an impact on the prognosis or course of cancer. Researchers are just starting to examine how vitamin D may impact specific features of cancer, such as the stage or extent of tumor spread, prognosis, recurrence or relapse of disease, and even sub-types of cancer,” Thomas Churilla, lead author of the study and a medical student at the Commonwealth Medical College, Scranton, Pa., said.

Researchers sought to determine the vitamin D levels of patients at Northeast Radiation Oncology Center in Dunmore, Pa., a community oncology practice, and to see if vitamin D levels were related to any specific aspects of cancer. The study involved 160 patients with a median age of 64 years and a 1:1 ratio of men to women. The five most common primary diagnoses were breast, prostate, lung, thyroid and colorectal cancer. A total of 77 percent of patients had vitamin D concentrations either deficient (less than 20 ng/mL) or sub-optimal (20-30 ng/mL). The median serum vitamin D level was 23.5 ng/mL. Regardless of the age or sex of the patient, levels of vitamin D were below the median predicted for advanced stage disease in the patient group.

Patients who were found to be vitamin D deficient were administered replacement therapy, increasing serum D levels by an average of 14.9 ng/mL. Investigators will be analyzing if vitamin D supplementation had an impact on aspects of treatment or survival in the long-term.

“The benefits of vitamin D outside of improving bone health are controversial, yet there are various levels of evidence to support that vitamin D has a role in either the prevention or the prediction of outcome of cancer,” Churilla said. “Further study is needed to continue to understand the relationship between vitamin D and cancer.”


Vitamin D Deficiency Linked With Airway Changes In Children With Severe Asthma

Children with severe therapy-resistant asthma (STRA) may have poorer lung function and worse symptoms compared to children with moderate asthma, due to lower levels of vitamin D in their blood, according to researchers in London. Lower levels of vitamin D may cause structural changes in the airway muscles of children with STRA, making breathing more difficult. The study provides important new evidence for possible treatments for the condition.

The findings were published online ahead of the print edition of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

“This study clearly demonstrates that low levels of vitamin D are associated with poorer lung function, increased use of medication, worse symptoms and an increase in the mass of airway smooth muscle in children with STRA,” said Atul Gupta, MRCPCH, M.D., a researcher from Royal Brompton Hospital and the National Heart and Lung Institute (NHLI) at Imperial College and King’s College London. “It is therefore plausible that the link between airway smooth muscle mass and lung function in severe asthma may be partly explained by low levels of vitamin D.”

While most children with asthma can be successfully treated with low doses of corticosteroids, about 5 to 10 percent of asthmatic children do not respond to standard treatment. These children have severe therapy-resistant asthma, or STRA, experience more asthma episodes and asthma-related illnesses, and require more healthcare services, than their treatment-receptive peers.

Although previous studies of children with asthma have linked increases in airway smooth muscle mass with poorer lung function and in vitro studies have established a connection between levels of vitamin D and the proliferation of airway smooth muscle, this is the first study to evaluate the relationship between vitamin D and the pathophysiology of children with STRA.

“Little is known about vitamin D status and its effect on asthma pathophysiology in these patients,” Dr. Gupta noted. “For our study, we hypothesized that children with STRA would have lower levels of vitamin D than moderate asthmatics, and that lower levels of vitamin D would be associated with worse lung function and changes in the airway muscle tissue.”

The researchers enrolled 86 children in the study, including 36 children with STRA, 26 with moderate asthma and 24 non-asthmatic controls, and measured the relationships between vitamin D levels and lung function, medication usage and symptom exacerbations.The researchers also examined tissue samples from the airways of the STRA group to evaluate structural changes in the airway’s smooth muscle.

At the conclusion of the study the researchers found children with STRA had significantly lower levels of vitamin D, as well as greater numbers of exacerbations, increased use of asthma medications and poorer lung function compared to children with moderate asthma and non-asthmatic children. Airway muscle tissue mass was also increased in the STRA group.

“The results of this study suggest that lower levels of vitamin D in children with STRA contribute to an increase in airway smooth muscle mass, which could make breathing more difficult and cause a worsening of asthma symptoms,” Dr. Gupta said.

The findings suggest new treatment strategies for children suffering from difficult-to-treat asthma, he added.

“Our results suggest that detecting vitamin D deficiency in children with STRA, and then treating that deficiency, may help prevent or reduce the structural changes that occur in the airway smooth muscle, which in turn may help reduce asthma-related symptoms and improve overall lung function,” Dr. Gupta said.

Before any widespread treatment recommendations can be made, however, larger studies will

“The determination of the exact mechanism between low vitamin D and airway changes that occur in STRA will require intervention studies,” Dr. Gupta said. “Hopefully, the results of this and future studies will help determine a new course of therapy that will be effective in treating these children.”



Gupta A, Sjoukes A, Richards D, Banya W, Hawrylowicz C, Bush A, Saglani S. Relationship Between Serum Vitamin D, Disease Severity and Airway Remodeling in Children with Asthma. Am J Respir Crit Care Med. 2011 Sep 15. [Epub ahead of print]


Increased Vitamin D in Blood Adds Years To Life

Low blood levels of vitamin D represent a significant health concern. New research published in the European Journal of Clinical Nutrition demonstrates that small increases in vitamin D can add precious years to life. The vast majorities of adults (and many children) are grossly deficient in circulating blood levels of vitamin D.  

Eur J Clin Nutr


W B Grant

An estimate of the global reduction in mortality rates through doubling vitamin D levels
European Journal of Clinical Nutrition 2011; 65: 1016-1026


The goal of this work is to estimate the reduction in mortality rates for six geopolitical regions of the world under the assumption that serum 25-hydroxyvitamin D (25(OH)D) levels increase from 54 to 110 nmol/l.

This study is based on interpretation of the journal literature relating to the effects of solar ultraviolet-B (UVB) and vitamin D in reducing the risk of disease and estimates of the serum 25(OH)D level–disease risk relations for cancer, cardiovascular disease (CVD) and respiratory infections. The vitamin D-sensitive diseases that account for more than half of global mortality rates are CVD, cancer, respiratory infections, respiratory diseases, tuberculosis and diabetes mellitus. Additional vitamin D-sensitive diseases and conditions that account for 2 to 3% of global mortality rates are Alzheimer’s disease, falls, meningitis, Parkinson’s disease, maternal sepsis, maternal hypertension (pre-eclampsia) and multiple sclerosis. Increasing serum 25(OH)D levels from 54 to 110 nmol/l would reduce the vitamin D-sensitive disease mortality rate by an estimated 20%.

The reduction in all-cause mortality rates range from 7.6% for African females to 17.3% for European females. Reductions for males average 0.6% lower than for females. The estimated increase in life expectancy is 2 years for all six regions.

Increasing serum 25(OH)D levels is the most cost-effective way to reduce global mortality rates, as the cost of vitamin D is very low and there are few adverse effects from oral intake and/or frequent moderate UVB irradiance with sufficient body surface area exposed.


Why You Need More Vitamin D. A Lot More

by William B. Grant, Ph.D. 

Vitamin D has emerged as the nutrient of the decade. Numerous studies have found benefits for nearly 100 types of health conditions. These health benefits include reduced risk of bone diseases, many types of cancer, cardiovascular disease (CVD), diabetes mellitus, bacterial and viral infectious diseases, and autoimmune diseases such as multiple sclerosis,[1] neurological conditions such as cognitive dysfunction,[2] and improved athletic and physical performance.[3]

Sunshine, Skin, Sunburn, and Sunscreen

The primary source of vitamin D for most people is solar ultraviolet-B (UVB) light. Skin pigmentation has adapted to where a population lives for a thousand years or more as those with skin too dark or light do not survive as well as those with the appropriate skin pigmentation.[4]Dark skin protects against the harmful effects of UV, but also blocks the UVB from penetrating deeply enough into the skin to produce vitamin D from 7-dehydrocholesterol. Those with lighter skin can produce vitamin D more rapidly, but are more prone to melanoma and other skin cancer. Sunscreens block UVB and thus limit vitamin D production. While sunscreens are useful in reducing risk of sunburning, they do not block the long wave UV (UVA) as well as UVB. UVA is linked to risk of melanoma. Wearing sunscreen when there is no danger of burning can actually increase the risk of melanoma.[5]

Understanding Vitamin D Research

Since vitamin D production is the primary source of vitamin D, ecological and observational studies have been very useful in teasing out the effects of vitamin D on health. There are two types of ecological studies, based on geographical and temporal (over time) variations. In geographical studies, populations are defined geographically and both health outcome and risk-modifying factors are averaged for each geographical unit. Statistical analyses are then used to determine the relative importance of each factor. The first paper linking UVB and vitamin D to reduced risk of colon cancer was published in 1980.[6] This link has now been extended to about 15 types of cancer in the United States with respect to average noontime solar UVB doses in July.[7] Solar UVB doses in July are highest in the Southwest and lowest in the Northeast.[8]Mortality rates are generally lowest in the Southwest and highest in the Northeast.[9] Similar results have been found in Australia, China, France, Japan, Russia, and Spain, and the entire world.[10]

In temporal studies, seasonal variations in health outcomes are sought. A good example of a seasonal effect linked to solar UVB doses and vitamin D is influenza, which peaks in winter.[11]

Observational studies are generally of three types: case-control, cohort, and cross-sectional. In case-control studies, those diagnosed with a disease have serum 25-hydroxyvitamin D [25(OH)D] level or oral vitamin D intake determined at that time and are compared statistically with others with similar characteristics but without that disease. In cohort studies, people are enrolled in the study and the vitamin D index determined at that time. The cohort is followed for a number of years and those who develop a specific disease are compared statistically with matched controls who did not. The main problem with cohort studies is that the single value of the vitamin D index may not relate to the time in the individual’s life when vitamin D had the most impact on the disease outcome. Cross-sectional studies are essentially snapshots of a population and look at various factors in relation to the prevalence of health conditions. As biochemistry can be affected by health status, such studies provide less reliable information on the role of UVB and vitamin D on health outcome.

The role of vitamin D in CVD and diabetes mellitus type 2 have largely been studied using cohort studies. Significantly reduced risk of CVD and diabetes mellitus incidence have been reported in a number of studies in the past three years.[12]

Health policy officials like to see randomized controlled trials (RCTs) reporting health benefits with limited adverse effects. RCTs are certainly appropriate for pharmaceutical drugs which, by definition, are artificial substances that the human body has no experience with. RCTs with vitamin D are problematic for a number of reasons. For one, many RCTs used only 400 IU/day vitamin D3, which is much lower than the 10,000 IU/day that can be produced with whole-body exposure to the midday sun in summer, or 1500 IU/day from casual sunlight exposure in summer.[13] For another, there are both oral and UVB sources of vitamin D, so the amount taken in the study will compete with the other sources. There is considerable individual variation in serum 25(OH)D for a given oral vitamin D intake.[14] Unfortunately, serum 25(OH)D levels are generally not measured in oral vitamin D RCTs.

Nonetheless, there have been several vitamin D RCTs that found significant health benefits beyond preventing falls and fractures.[15] These include ones for cancer,[16],[17] influenza and colds,[18] type A influenza,[19] and pneumonia.[20]

Important Benefits of Vitamin D

The evidence of beneficial roles of UVB and vitamin D for a large number of health conditions have recently been posted at the Vitamin D Council’s website.

In addition to an overview of the literature, the website also includes a feature to pull up a large number of titles on each condition from .

Sufficient information is currently available from observational studies with support from ecological studies and RCTs to determine relationships between serum 25(OH)D levels and incidence rates for breast and colorectal cancer,[21] CVD,[22] and influenza.[23] Risk decreases rapidly for small increases in 25(OH)D for those with initial values below 10 ng/ml (25 nmol/L), then decrease at a slower rate to levels above 40 ng/ml (100 nmol/L). These relations have been used to estimate the change in mortality rates and life expectancy if population mean serum 25(OH)D levels were raised from current levels of 20-25 ng/ml (50-63 nmol/L) to 45 ng/ml (113 nmol/L). For the U.S., it was estimated that 400,000 deaths/year could be delayed,[24] which is about 15% of all deaths/year. For the entire world, it was estimated that the reduction in all-cause mortality rates would correspond to an increased life expectancy of two years.[22]

The mechanisms whereby vitamin D reduces the risk of disease are largely understood. For cancer, they include effects on cellular differentiation and proliferation, angiogenesis and metastasis.[25] For infectious diseases, they include induction of cathelicidin and defensins [26]and shifting cytokine production from proinflammatory T-helper 1 (Th1) cytokines to Th2 cytokines.[27] For CVD, they may include reducing blood pressure and keeping calcium in the bones and teeth and out of the vascular tissues.[28] For diabetes mellitus type 2, they may include improving insulin sensitivity.[29]

Current Government-Sponsored Recommendations are Too Low

In spite of the large and expanding body of scientific evidence that vitamin D has many health benefits, the US Institute of Medicine issued a report in November 2010 claiming that the evidence was strong only for effects on bones.[30],[31] The reason given was lack of convincing randomized controlled trials on other health conditions. The one on cancer showing a 77% reduced risk of all-cancer incidence between the ends of the first and fourth years involved 1100 IU/day vitamin D plus 1450 mg/day calcium.[16] However, the IOM Committee relied on the findings from the start of the study, which was not statistically significant. In addition, the IOM Committee pointed to observational studies reporting a U-shaped serum 25(OH)D-disease incidence relation as a reason to be concerned about higher doses of vitamin D. However, these studies used a single serum 25(OH)D value from the time of enrollment followed by follow-up times as long as 17 years. Two studies reported that the sign of the correlation between disease outcome and serum 25(OH)D level changes from negative to positive after seven-to-15 years.[32],[33] Thus, the U-shaped relations are not reliable and should not be used as the basis for policy decisions, especially since the Committee refused to consider the largely beneficial findings from observational studies.

How Much Vitamin D Do We REALLY Need?

The IOM committee set the recommended vitamin D intake at 600 IU/day for those under the age of 70 years and 800 IU/day for those over 70, and stated that 20 ng/ml (50 nmol/L) was an adequate level. The scientific consensus is that oral intake should be 1000-5000 IU/day vitamin D with a goal of 30-40 ng/ml (75-100 nmol/L).[34] The vitamin D research community has responded to the IOM report on vitamin D with over 60 letters and articles in peer-reviewed journals pointing out the absurdity and illogic of the IOM report.[35] The Endocrine Society published a paper recommending 1500-2000 IU/day and 30 ng/ml.[36] Meanwhile, members of the IOM Committee have been publishing articles in mainstream journals promoting their report.

(William Grant, PhD, is the director of the Sunlight, Nutrition, and Health Research Center (SUNARC)in San Francisco, California. The author receives funding from the UV Foundation, the Sunlight Research Forum, Bio-Tech-Pharmacal, the Vitamin D Council, and the Vitamin D Society of Canada.) 

(Orthomolecular Medicine News Service, September 16, 2011)



1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81.

2. Llewellyn DJ, Lang IA, Langa KM, Melzer D. Vitamin D and cognitive impairment in the elderly U.S. population. J Gerontol A Biol Sci Med Sci. 2011;66(1):59-65.

3. Cannell JJ, Hollis BW, Sorenson MB, Taft TN, Anderson JJ. Athletic performance and vitamin D. Med Sci Sports Exerc. 2009;41(5):1102-10.

4. Jablonski NG, Chaplin G. Colloquium paper: human skin pigmentation as an adaptation to UV radiation. Proc Natl Acad Sci U S A. 2010;107 Suppl 2:8962-8.

5. Gorham ED, Mohr SB, Garland CF, Chaplin G, Garland FC. Do sunscreens increase risk of melanoma in populations residing at higher latitudes? Ann Epidemiol. 2007;17(12):956-63.

6. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9(3):227-31.

7. Grant WB, Garland CF. The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res. 2006;26(4A):2687-99.

8. Leffell DJ and Brash DE: Sunlight and skin cancer. Sci Am. 275(1): 52-53, 56-59, 1996. (accessed March 9, 2011).

9. Devesa SS, Grauman DJ, Blot WJ, Pennello GA, Hoover RN, Fraumeni JF Jr: Atlas of Cancer Mortality in the United States, 1950-1994. NIH Publication No. 99-4564, 1999.

10. Grant WB, Mohr SB. Ecological studies of ultraviolet B, vitamin D and cancer since 2000. Ann Epidemiol. 2009;19(7):446-54.

11. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiol Infect. 2006;134(6):1129-40.

12. Parker J, Hashmi O, Dutton D, Mavrodaris A, Stranges S, Kandala NB, Clarke A, Franco OH. Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas. 2010;65(3):225-36.

13. Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007;85(3):860-8.

14. Garland CF, French CB, Baggerly LL, Heaney RP. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res 2011:31:617-22.

15. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169(6):551-61.

16. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85(6):1586-91.

17. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set. Am J Clin Nutr. 2011 Aug 31. [Epub ahead of print]

18. Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin D. Epidemiol Infect. 2007;135(7):1095-6; author reply 1097-8.

19. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010;91(5):1255-60.

20. Manaseki-Holland S, Qader G, Isaq Masher M, Bruce J, Zulf Mughal M, Chandramohan D, Walraven G. Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Trop Med Int Health. 2010;15(10):1148-55.

21. Grant WB. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B, 2010;101:130-136.

22. Grant WB. An estimate of the global reduction in mortality rates through doubling vitamin D levels. Eur J Clin Nutr, 2011;65:1016-1026.

23. Sabetta JR, DePetrillo P, Cipriani RJ, Smardin J, Burns LA, Landry ML. Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PLoS One. 2010;5(6):e11088.

24. Grant WB. In defense of the sun: An estimate of changes in mortality rates in the United States if mean serum 25-hydroxyvitamin D levels were raised to 45 ng/mL by solar ultraviolet-B irradiance. Dermato-Endocrinology, 2009;1(4):207-14.

25. Krishnan AV, Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol. 2011;51:311-36.

26. Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007;179(4):2060-3.

27. Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood). 2004;229(11):1136-42.

28. Zagura M, Serg M, Kampus P, Zilmer M, Eha J, Unt E, Lieberg J, Cockcroft JR, Kals J. Aortic stiffness and vitamin D are independent markers of aortic calcification in patients with peripheral arterial disease and in healthy subjects. Eur J Vasc Endovasc Surg. 2011 Aug 24. [Epub ahead of print]

29. Alvarez JA, Ashraf AP, Hunter GR, Gower BA. Serum 25-hydroxyvitamin D and parathyroid hormone are independent determinants of whole-body insulin sensitivity in women and may contribute to lower insulin sensitivity in African Americans. Am J Clin Nutr. 2010;92(6):1344-9.

30. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011.

31. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-8.

32. Lim U, Freedman DM, Hollis BW, Horst RL, Purdue MP, Chatterjee N, Weinstein SJ, Morton LM, Schatzkin A, Virtamo J, Linet MS, Hartge P, Albanes D. A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. Int J Cancer. 2009;124(4):979-86.

33. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control. 2007;18(7):775-82.

34. Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, Bischoff-Ferrari HA, Cavalier E, Ebeling PR, Fardellone P, Gandini S, Gruson D, Guérin AP, Heickendorff L, Hollis BW, Ish-Shalom S, Jean G, von Landenberg P, Largura A, Olsson T, Pierrot-Deseilligny C, Pilz S, Tincani A, Valcour A, Zittermann A. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev 2010;9:709-15.

35. Heaney RP, Grant WB, Holick MF, Amling M. The IOM Report on Vitamin D misleads. J Clin Endocrinol Metab. eLetter. (4 March 2011)

36. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2011;96(7):1911-30.


For More Information:

For additional information on vitamin D, the reader is directed to PubMed to search “vitamin D” along with any keyword of interest. Some representative papers found there, with free access, are listed below. Papers published in the Journal of Orthomolecular Medicine are (still) not listed on PubMed. All J Orthomolecular Med papers may all be accessed at the Journal’s free archive.

Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010 Feb;95(2):471-8. Review.

Bikle DD. Vitamin D: newly discovered actions require reconsideration of physiologic requirements. Trends Endocrinol Metab. 2010 Jun;21(6):375-84. Epub 2010 Feb 10. Review.

Herr C, Greulich T, Koczulla RA, Meyer S, Zakharkina T, Branscheidt M, Eschmann R, Bals R. The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer. Respir Res. 2011 Mar 18;12:31. Review.

Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am. 2010 Jun;39(2):365-79, table of contents. Review.

Raman M, Milestone AN, Walters JR, Hart AL, Ghosh S. Vitamin D and gastrointestinal diseases: inflammatory bowel disease and colorectal cancer. Therap Adv Gastroenterol. 2011 Jan;4(1):49-62.

Zhang R, Naughton DP. Vitamin D in health and disease: current perspectives. Nutr J. 2010 Dec 8;9:65. Review.


Vitamin D And Cancer Campaign Launched

SAN LUIS OBISPO, CA – The Vitamin D Council, a nonprofit educational corporation based in California, launches their “Vitamin D and Cancer” campaign today, presenting 20 detailed summaries of the evidence on the role of vitamin D in preventing cancer. Epidemiologist Dr. William Grant prepared the evidence-based summaries. He is the founder of the nonprofit organization, Sunlight, Nutrition and Health Research Center (SUNARC) and serves as the Science Director for the Vitamin D Council.

Some researchers believe the link between vitamin D sufficiency and a decreased risk in cancer is promising. A randomized controlled trial found a 77% reduction in all-cancer incidence when the study group supplemented with 1100 IU/day of vitamin D plus 1450 mg/day calcium. Says Dr. Grant, “Based on various studies of UVB, vitamin D and cancer to date, it appears that global cancer burden can be reduced by 15-25% if everyone had vitamin D blood levels above 40 ng/ml.”

The summaries can be found under the “Health conditions” tab on the Vitamin D Council website, or more specifically at The Vitamin D Council hopes the campaign will spread more awareness about the importance of vitamin D sufficiency and the dangers of vitamin D deficiency.

Top ten facts about vitamin D and cancer (presented in the summaries)

  1. Many studies have found solar ultraviolet-B (UVB) and vitamin D associated with reduced risk of breast, colon, and rectal cancer.
  2. randomized controlled trial with 1100 IU/day vitamin D3 plus 1450 mg/day calcium found a 77% reduction in all-cancer incidence.
  3. Geographical studies have found reduced risk in mortality rates for 20 types of cancer in regions of higher solar UVB doses.
  4. Observational studies have found that the risk of breast, colon, and rectal cancer fall as vitamin D blood levels rise at least up to 40 ng/mL (100 nmol/L).
  5. Mechanisms have been proposed to explain how vitamin D acts to reduce the risk of cancer from starting, growing, and spreading.
  6. Those who develop nonmelanoma skin cancer may have produced enough vitamin D to reduce their risk of internal cancers.
  7. Those with higher vitamin D blood levels at time of cancer diagnosis had nearly twice the survival rate of those with the lowest levels.
  8. African-Americans have an increased risk of cancer in part due to lower vitamin D blood levels because of darker skin.
  9. Higher UVB exposure early in life has been found associated with reduced risk of breast and prostate cancer.
  10. Those diagnosed with breast, colon and prostate cancer in summer in Norway had higher survival rates than those diagnosed in winter.

Confirmation That Vitamin D Acts As A Protective Agent Against The Advance Of Colon Cancer

A study conducted by VHIO researchers confirms that a lack of vitamin D increases the aggressiveness of colon cancer.

Héctor G. Palmer. Photo: Katherin Wermke.

The indication that vitamin D and its derivatives have a protective effect against various types of cancer is not new. In the field of colon cancer, numerous experimental and epidemiological studies show that vitamin D3 (or cholecalciferol) and some of its derivatives inhibit the growth of cancerous cells.

Researchers at the Vall d’Hebron Institute of Oncology (VHIO), in collaboration with the Alberto Sols Institute of Biomedical Research (CSIC-UAB), have confirmed the pivotal role of vitamin D, specifically its receptor (VDR), in slowing down the action of a key protein in the carcinogenic transformation process of colon cancer cells. These results have been in the journal PLoS One.

This protein, known as beta-catenin, which is normally found in intestinal epithelial cells where it facilitates their cohesion, builds up in large quantities in other areas of the cells when the tumour transformation begins. As a result of these changes, the protein is retained in the cell nucleus, where it facilitate the carcinogenic process, and this is the point at which vitamin D intervenes, or rather, the vitamin D receptor (VDR).

“Our study has confirmed the pivotal role of the VDR in controlling the anomalous signal that sparks off the growth and uncontrolled proliferation of colon cells which, in the final instance, ends up causing a tumour to emerge”, says Héctor Palmer, the coordinator of this study and head of the VHIO’s Stem Cells and Cancer laboratory. He continues, “The stimulation of this receptor suppresses the action of the beta-catenin protein, intercepting the series of events that change the intestinal cell into a malignant tumour cell”.

The study was conducted on mice and human colon cancer cells. The mice were used as a model to replicate the initial phases of colon cancer. “These findings show that mice of this kind, which also lack the VDR and hence do not respond to vitamin D, present larger and more aggressive tumours than mice with the VDR”, explains Dr. Palmer, and concludes: ”The number of tumours is not influenced by the absence of VDR, which would indicate that this factor does not protect against the appearance of the tumour but does intervene in its growth phase, reducing its aggressiveness”.

The researchers then analysed the effect of the VDR on human colon cancer cell cultures and observed that the concentration of the altered protein, beta-catenin, increased in cells without the VDR. These findings were repeated in the three types of colon cancer cells studied, and confirmed the results observed in the mice.

In two-thirds of advanced colon cancer tumours there was a lack of VDR in the cancer cells, and this circumstance leads us to believe that this loss may contribute to speeding up the growth of the tumour. The findings of this study confirm this supposition.

Vitamin D: essential in the initial phases of colon cancer

In light of these findings, chronic vitamin D deficiency represents a risk factor in the development of more aggressive colon tumours. Patients in the initial stages of colon cancer, the time when the VDR still has a substantial presence in the cells, could benefit from being treated with vitamin D3. However, this would not be useful in the advanced stages of the disease when the presence of the VDR is very much reduced.

The study data support the development of anti-tumour medicines based on the structure of vitamin D, although their use in patients will require further research in the next few years.

The body not only obtains vitamin D from food, especially milk and fish oils, but also manufactures it from exposure to sunlight. Prolonged exposure is not necessary; just 10 minutes in the sun every day when it is not at its peak is sufficient to stimulate its production. During the summer, when we are more likely to sunbathe, it is important to use the appropriate protective measures against sunburn to avoid future sun damage. Use high-factor solar protection products and do not expose the skin to the sun in the middle of the day to protect against skin cancers.


Vitamin D Relieves Joint, Muscle Pain For Breast Cancer Patients

Assistant Professor Antonella Luisa Rastelli, M.D.

Washington University doctors have found that high-dose vitamin D helps relieve joint and muscle pain in breast cancer patients taking estrogen-lowering drugs. Known as aromatase inhibitors, the drugs are prescribed to treat breast tumors fueled by the hormone estrogen. They are less toxic than chemotherapy, but many patients experience severe musculoskeletal discomfort, including pain and stiffness in the hands, knees, hips, lower back, shoulders and feet.



Antonella L. Rastelli, Marie E. Taylor, Feng Ga, Roeina Armamento-Villareal, Shohreh Jamalabadi-Majidi, Nicola Napoli and Matthew J. Ellis
Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial
Breast Cancer Res Treat 2011; 129 (1): 107-16.


A double-blind placebo-controlled randomized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation (HDD) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletalsymptoms (AIMSS) and bone loss. Patients with early breast cancer and AIMSS were stratified according to their baseline 25-hydroxy vitamin D (25OHD) level. Stratum A (20-29 ng/ml) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo. Stratum B (10-19 ng/ml) received either HDD for 16 weeks and then monthly for 2 months, or placebo. AIMSS was assessed by the Brief Pain Inventory-Short Form (BPI-SF), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline, 2, 4, and 6 months. Bone Mineral Density (BMD) was measured at baseline and at 6 months. The primary endpoint of the study was the change-from-baselinemusculoskeletal pain. The secondary endpoint was the percent change in BMD at 6 months. Sixty women were enrolled. Baseline characteristics were comparable between the groups. At 2 months, FIQ pain (P = 0.0045), BPI worst-pain (P = 0.04), BPI average-pain (P = 0.0067), BPI pain-severity (P = 0.04), and BPI interference (P = 0.034) scores were better in the HDD than placebo group. The positive effect of HDD on AIMSS was stronger across all time points in Stratum B than Stratum A (FIQ pain, P = 0.04; BPI average, P = 0.03; BPI severity, P = 0.03; BPI interference, P = 0.04). BMD at the femoral neck decreased in the placebo and did not change in the HDD group (P = 0.06). Weekly HDD improves AIMSS and may have a positive effect on bone health. Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated.


Advances In Research Into Alzheimer’s Disease

Transporter proteins at the blood CSF barrier and vitamin D may help prevent amyloid beta build-up in the brain.

Advancing age is a major risk factor for Alzheimer’s disease and is associated with build- up of the peptide amyloid β in the brain. New research published in BioMed Central’s open access journal Fluids and Barriers of the CNS shows that removal of amyloid β from the brain depends on vitamin D and also on an age-related alteration in the production of transporter proteins which move amyloid β in and out of the brain.

Low levels of vitamin D are thought to be involved in age-related decline in memory and cognition and are also associated with Alzheimer’s disease. Researchers from Tohoku University, Japan, looked at the mechanism behind this and found that vitamin D injections improved the removal of amyloid β from the brain of mice.

Prof Tetsuya Terasaki said, “Vitamin D appears increase transport of amyloid β across the blood brain barrier (BBB) by regulating protein expression, via the vitamin D receptor, and also by regulating cell signaling via the MEK pathway. These results lead the way towards new therapeutic targets in the search for prevention of Alzheimer’s disease.”

The transport of amyloid β across the BBB is known to be orchestrated by transporter proteins such as LRP-1 and P-gp, which move amyloid β out of the brain, and RAGE, which controls influx. Looking at the transport of amyloid β from blood to cerebrospinal fluid (CSF), and from CSF to blood, researchers from Rhode Island Hospital and The Warren Alpert Medical School, found that LRP-1 and P-gp at the blood-cerebrospinal fluid barrier (BCSFB), increased with age so increasing removal of amyloid β from the CSF and brain.

Prof Gerald Silverberg said, “While increased production of transporter proteins at the blood CSF barrier may help amyloid β removal from the older brain, production of these proteins eventually fails. This failure may be an important event in brain function as we age and for people with Alzheimer’s disease.”


1. Ito S, Ohtsuki S, Nezu Y, Koitabashi Y, Murata S, Tetsuya Terasaki T. 1α,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-β peptide(1-40) from mouse brain across the blood-brain barrier.  Fluids and Barriers of the CNS 2011, 8:20 (8 July 2011).

2. Pascale CL, Miller MC, Chiu C, Boylan M, Caralopoulos IN, Gonzalez L, Johanson CE and Silverberg GD. Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent. Fluids and Barriers of the CNS 2011, 8:21 (8 July 2011).