Archive for the 'Vitamin D3' Category

Jun 16 2008

Vitamin D3 – Osteoporosis

Published by under Osteoporosis,Vitamin D3

Vitamin D3:
Higher Doses Reduce Risk of Common Health Concerns
By Chris D. Meletis, ND

Vitamin D3 is one of the most useful nutritional tools we have at our disposal for improving overall health. This vitamin is unique because cholecalciferol (Vitamin D3) is a vitamin derived from 7-dehyrocholesterol; however, Vitamin D3 acquires hormone-like actions when cholecalciferol (Vitamin D3) is converted to 1,25-dihydroxy Vitamin D3 (Calcitriol) by the liver and kidneys. As a hormone, Calcitriol controls phosphorus, calcium, and bone metabolism and neuromuscular function. Vitamin D3 is the only vitamin the body can manufacture from sunlight (UVB). Yet, with today’s indoor living and the extensive use of sunscreens due to concern about skin cancer, we are now a society with millions of individuals deficient in life-sustaining bone building and immune modulating 1,25-dihydroxy Vitamin D3.

For more than a century, scientists have recognized that Vitamin D3 is involved in bone health. Research has continued to accumulate, documenting Calcitriol’s role in the reduction of the risk of fractures to a significant degree. The latest research, however, shows that 1,25-dihyroxy Vitamin D3 deficiency is linked to a surprising number of other health conditions such as depression, back pain, cancer, both insulin resistance and pre-eclampsia during pregnancy, impaired immunity and macular degeneration.

As it becomes clear that Vitamin D3 plays a wide role in overall health, it’s becoming equally clear that a large percentage of individuals are deficient in this important nutrient, which has hormone-like activity. The fear of skin cancer has stopped many individuals from obtaining beneficial amounts of sunlight. The skin uses the energy of UVB to convert 7-dehydrocholesterol into Vitamin D3. Even individuals, who venture out into the sun often and use suntan lotion, may be deficient in Vitamin D3. Furthermore, as we age, we are less equipped to produce sufficient quantities of this vital nutrient. One study found that age-related declines in kidney function may require older people to ingest more Vitamin D3 to maintain the same blood levels as younger people.1

The Recommended Daily Intake (RDI) of Vitamin D3 is set so low those mature individuals who consume this small amount (400 to 600 International Unites (I.U.’s)) are still likely to be deficient if they live north of the Tropic of Cancer or south of the Tropic of Capricorn. In fact, researchers have discovered that the RDI, which was considered adequate to prevent osteomalacia (a painful bone disease) or rickets, is not high enough to protect against the majority of diseases linked to 1,25-dihyroxy Vitamin D3 deficiency. For example, an analysis of the medical literature found that at least 1,000 to 2,000 IU of Vitamin D3 per day is necessary to reduce the risk of colorectal cancer and that lower doses of Vitamin D3 did not have the same protective effect.2

Researchers Call for Higher Doses

In an editorial in the March 2007 edition of the American Journal of Clinical Nutrition, a prominent group of researchers from leading institutions such as the University of Toronto, Brigham and Women’s Hospital, Tufts University and University Hospital in Zurich, Switzerland, lashed out at the conventional media for its inaccurate reporting of Vitamin D supplementation.3

The researchers wrote, “Almost every time the public media report that Vitamin D nutrition status is too low, or that higher Vitamin D intakes may improve measures of health, the advice that accompanies the report is outdated and thus misleading. Media reports to the public are typically accompanied by a paragraph that approximates the following: ‘Current recommendations from the Institute of Medicine call for 200 IU/day from birth through age 50 years, 400 IU for those aged 51–70 years, and 600 IU for those aged >70 years. Some experts say that optimal amounts are closer to 1,000 IU daily. Until more is known, it is wise not to overdo it.’ The only conclusion that the public can draw from this is to do nothing different from what they have done in the past.”

The researchers point out that supplemental intake of 400 IU per day barely raises blood concentrations of 25(OH)D, which is the circulating Vitamin D metabolite that serves as the most frequently measured indicator of Vitamin D status. To raise 25(OH)D from 50 to 80 nmol/L requires an additional intake of 1,700 IU Vitamin D per day.

The researchers went on to write that, “The balance of the evidence leads to the conclusion that the public health is best served by a recommendation of higher daily intakes of Vitamin D. Relatively simple and low-cost changes, such as increased food fortification or increasing the amount of Vitamin D in Vitamin supplement products, may very well bring about rapid and important reductions in the morbidity associated with low Vitamin D status.”

One of the challenges is the outdated acceptable upper limit for Vitamin D3 consumption, which was set at 2,000 IU. However, researchers point out that more recent studies have shown that 10,000 IU is the safe upper limit.4

Dr. R. Vieth, one of the foremost authorities on Vitamin D3 supplementation, has extensively studied Vitamin D, and lamented the low requirements for Vitamin D3 in a recent issue of the Journal of Nutrition: “Inappropriately low UL [upper limit] values, or guidance values, for Vitamin D have hindered objective clinical research on Vitamin D nutrition; they have hindered our understanding of its role in disease prevention, and restricted the amount of Vitamin D in multivitamins and foods to doses (that are) too low to benefit public health.”5

When examining the medical literature, it becomes clear that Vitamin D3 affects human health in an astonishing number of ways and that not obtaining enough of this important nutrient can leave the door open to developing a number of health conditions.


Vitamin D3 deficiency is common in older adults and has been implicated in psychiatric and neurologic disorders. For example, in one study of 80 older adults (40 with mild Alzheimer’s disease and 40 nondemented persons), Vitamin D3 deficiency was associated with low mood and with impairment on two of four measures of cognitive performance.6

Back Pain

Musculoskeletal disorders have been linked to Vitamin D3 deficiency in a number of studies. One of the newest studies explored the role that low Vitamin D3 levels play in the development of chronic low back pain in women. Sixty female patients in Egypt complaining of low back pain lasting more than three months were studied. Researchers measured levels of Vitamin D3 in the women with low back pain and compared those levels to those of 20 matched healthy controls.

The study revealed that patients with low back pain had significantly lower Vitamin D3 levels than controls. Low Vitamin D3 levels (25 OHD < 40 ng/ml) were found in 49/60 patients (81 percent) and 12/20 (60 percent) of controls.7

Bone Health

One of the best known and long-established benefits of Vitamin D3 is its ability to improve bone health and the health of the musculoskeletal system. It is well documented that Vitamin D3 deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes a painful bone disease known as osteomalacia, and exacerbates muscle weakness, which increases the risk of falls and fractures. Vitamin D3 insufficiency may alter the regulatory mechanisms of parathyroid hormone (PTH) and cause a secondary hyperparathyroidism that increases the risk of osteoporosis and fractures.8

Cognitive Enhancement

Scientists are developing a greater appreciation for Vitamin D3’s ability to improve cognition. In a recent study, Vitamin D3 deficient subjects scored worse on mental function tests compared to individuals who had higher levels of the Vitamin.9 The researchers wrote, “In conclusion, the positive, significant correlation between serum 25(OH)D concentration and MMSE [mental state examination scores] in these patients suggests a potential role for Vitamin D in cognitive function of older adults.”


One researcher first noted the connection between Vitamin D3 and protection from cancer in the 1940s, when he discovered that individuals at sunny latitudes had a reduced rate of deaths from cancer. He suggested that sunlight provided “a relative cancer immunity.”
Since then, a number of studies have strongly suggested that Vitamin D3 deficiency is associated with an increased risk of developing many forms of cancer including breast, ovarian, prostate and colon cancer.10 In one recent clinical trial, researchers studied 1,179 healthy, postmenopausal women (all 55 years or older and free of known cancers for at least 10 years prior to entering the study) who were taking large amounts of Vitamin D3 with calcium. The subjects were randomly assigned to take daily dosages of: (1) 1,400-1,500 mg supplemental calcium, (2) 1,400-1,500 mg supplemental calcium plus 1,100 IU of Vitamin D3, or (3) placebos. Over the four-year trial, women in the calcium/Vitamin D3 group experienced a 60 percent or greater reduced risk of cancer than their peers in the placebo group, who were not consuming these supplements.

Because there was the chance that some women may have had undiagnosed cancers at the study’s start, the researchers threw out the first-year results and then analyzed the results from the last three years of the trial. These later years resulted in even more dramatic decrease, with the calcium/Vitamin D3 group experiencing a 77 percent reduction in cancer risk.

There was no statistically significant difference in cancer incidence between the participants taking placebos and subjects consuming only calcium supplements.11

Another interesting study demonstrated that in vitro Vitamin D3 may cause tumor cells to be more sensitive to chemotherapy drugs, increasing the efficacy of the cancer treatment.12


Scientists have linked various aspects of immune health to a Vitamin D3 deficiency. Vitamin D3 regulates T cells, which are important to the functioning of a strong immune system. Vitamin D3 acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the killing efficiency of macrophages. In addition, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in immune system cells such as neutrophils, monocytes, natural killer cells, and in cells lining the respiratory tract. These Vitamin-D3-stimulated peptides play a major role in protecting the lung from infection.13

In addition, Vitamin D3 deficiency may influence development and progression of various autoimmune diseases.14

Multi-Talented Nutrient

Vitamin D3 deficiency has been linked to a host of other conditions such as high blood pressure, fibromyalgia, diabetes, multiple sclerosis, rheumatoid arthritis, and an increased risk of pre-eclampsia and insulin resistance during pregnancy.11,15-16 Most recently, low Vitamin D3 levels have been linked to an increased prevalence of early age-related macular degeneration.17

Proper Dosage

In many of my patients, even after consuming 2,000 to 4,000 IU of Vitamin D3 per day, their test results indicate that their Vitamin D3 levels have not increased. These patients needed to consume 8,000 IU of Vitamin D3 per day to achieve proper blood levels of the Vitamin. Patients should, therefore, have their physicians test their serum 1,25-dihyroxy D3 levels to determine the proper level of supplementation required. Testing is very important due to the fact that, in a small number of patients, Vitamin D3 supplementation can raise calcium levels to an excessively high level. I have found this to be especially true in African American patients. Testing for 1,25-dihyroxy Vitamin D3, PTH and calcium blood levels should therefore become a part of every woman’s regular blood work.


A growing number of researchers who have widely studied Vitamin D3 are almost begging the general public to consume more of this important nutrient. Due to Vitamin D3’s high safety profile in doses up to 10,000 IU per day and because of the wide role it plays in our health, consuming 2,000 to 4,000 IU per day of this nutrient at times of the year when sunlight is scarce is a prudent way to improve overall health.


1. Vieth R, Ladak Y, Walfish PG. Age-related changes in the 25-hydroxyVitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more Vitamin D. J Clin Endocrinol Metab. 2003 Jan;88(1):185-91.
2. Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M, Holick MF. Optimal Vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 2007 Mar;32(3):210-6.
3. Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, Holick MF, Hollis BW, Lamberg-Allardt C, McGrath JJ, Norman AW, Scragg R, Whiting SJ, Willett WC, Zittermann A. The urgent need to recommend an intake of Vitamin D that is effective. American Journal of Clinical Nutrition. March 2007;85(3):649-650.
4. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for Vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18.
5. Vieth R. Critique of the considerations for establishing the tolerable upper intake level for Vitamin D: critical need for revision upwards. J Nutr. 2006 Apr;136(4):1117-22.
6. Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006 Dec;14(12):1032-40.
7. Lotfi A, Abdel-Nasser AM, Hamdy A, Omran AA, El-Rehany MA. HypoVitaminosis D in female patients with chronic low back pain. Clin Rheumatol. 2007 Mar 22; [Epub ahead of print].
8. Pérez-López FR. Vitamin D and its implications for musculoskeletal health in women: An update. Maturitas. 2007 Jun 28; [Epub ahead of print].
9. Przybelski RJ, Binkley NC. Is Vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyVitamin D concentration with cognitive function. Arch Biochem Biophys. 2007 Apr 15;460(2):202-5.
10. Grant WB. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002 Mar 15;94(6):1867-75.
11. Lappe J, Travers-Gustafson D, Davies K, Recker R, Heaney R. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. American Journal of Clinical Nutrition. June 8;85(6):1586-1591.
12. Ma Y, et al. Study presented at the 2007 centennial meeting of the American Association for Cancer Research (AACR), April 14 to 18, 2007, Los Angeles.
13. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and Vitamin D. Epidemiol Infect. 2006 Dec;134(6):1129-40.
14. Kuryłowicz A, Bednarczuk T, Nauman J. [The influence of Vitamin D deficiency on cancers and autoimmune diseases development.] [Article in Polish] Endokrynol Pol. 2007;58(2):140-152.
15. Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal Vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 May 29; [Epub ahead of print].
16. Maghbooli Z, Hossein-Nezhad A, Karimi F, Shafaei AR, Larijani B. Correlation between Vitamin D(3) deficiency and insulin resistance in pregnancy. Diabetes Metab Res Rev. 2007 Jul 2; [Epub ahead of print].
17. Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association Between Vitamin D and Age-Related Macular Degeneration in the Third National Health and Nutrition Examination Survey, 1988 Through 1994. Arch Ophthalmol. May 2007;125: 661-669.

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May 21 2008

Vitamin D3 Important for Male and Female Health

Published by under Vitamin D3

Two recent studies indicate higher levels of vitamin D are associated with a reduced risk of breast and prostate cancer.

In the newest of the two studies, researchers investigated the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels (a measurement of vitamin D3 levels in the body) and the incidence rates of breast cancer in 107 countries. The researchers also looked at the number of breast cancer cases that occurred at varying latitudes since past studies have found lower breast cancer rates in areas that receive higher amounts of sunlight. The lower breast cancer rate in these areas is thought to be attributable to the fact that the skin makes vitamin D from sunlight. Continue Reading »

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Jan 24 2008

Vitamin D3 Deficiency Linked to Increased Risk of Heart Disease and Stroke

Published by under Vitamin D3

Low levels of vitamin D3 may increase the risk of heart disease and stroke by as much as 62 percent, scientists reported in a new study. 

A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system. Vitamin D3 receptors have a broad tissue distribution in areas related to cardiovascular health, including vascular smooth muscle, endothelium, and cardiomyocytes (cells in the heart). Continue Reading »

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Nov 08 2007

Analysis finds inverse relationship between serum vitamin D levels and breast cancer risk

Published by under Vitamin D3

The results of a pooled analysis of 1,760 women confirmed that having higher levels of the vitamin D metabolite serum 25-hydroxyvitamin D is associated with a lower risk of breast cancer. The finding was reported at the 97th Annual Meeting of the American Association for Cancer Research held April 1-5, 2006 in Washington DC.

Cedric Garland, Dr PH, and Edward Gorham, PhD, of the University of California, San Diego, and their colleagues evaluated data from cancer studies conducted by Elizabeth R. Bertone-Johnson and colleagues at Harvard, and L.C. Lowe and associates at Saint George’s Hospital Medical School in London to arrive at their conclusion. “There is a strong inverse dose-response relationship between the serum concentration of 25-hydroxyvitamin D and the risk of breast cancer,” Dr Garland stated. “It’s a close fit to a linear model.”

The research team found that having a serum vitamin D level of 52 nanograms per milliliter was associated with a 50 percent reduction in breast cancer risk. To attain this level of the vitamin, it would be necessary to consume at least 1,000 international units (IU) of vitamin D per day–more than three times as much as most Americans receive. Although the National Academy of Sciences has established 2,400 IU per day as the upper limit for vitamin D intake, there have been no toxic effects associated with up to 3,800 IU per day. “There is no substantial downside to a serum level of 52 nanograms per milliliter of Vitamin D,” Dr Gorham noted. “Such levels are common in sunny climates. There is no known adverse effect of serum levels below 160 nanograms per milliliter.”

The researchers recommend that at least 1,000 IU per day vitamin D3 be consumed until further studies are conducted.

Alvin Yee M.D. recommends up to 5,000 IU per day for patients concerned or have a familial history of breast cancer. See link below

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Nov 08 2007

Vitamin D3: New Studies on Weight Management, Colon and Prenatal Health

Published by under Vitamin D3

Three new studies have emphasized the role vitamin D3 may play in an effective weight management program, reduction of colorectal cancer risk and helping in healthy pregnancies.In the first study, researchers determined the effects of daily vitamin D combined with calcium during a weight-loss intervention program. The researchers set out to determine whether the vitamin D plus calcium affected blood pressure, plasma lipid and lipoprotein concentrations, and glucose and insulin concentrations in people who are low calcium consumers.

The study included 63 healthy, overweight or obese women with a daily calcium intake of greater than 800 mg per day. The subjects were randomly assigned in a double-blind manner to 1 of 2 groups: one group consumed 2 tablets per day of a calcium plus vitamin D supplement (600 mg elemental calcium and 200 IU vitamin D3 per tablet) while another group consumed a placebo. Both groups observed 700 kcal/day energy restriction. The subjects then completed a 15-week weight-loss intervention.

After the 15-week intervention, significantly greater decreases in low-density lipoprotein cholesterol (LDL, or “bad” cholesterol) were observed in the calcium plus vitamin D group than in the placebo group. In addition, the LDL:HDL ratio also decreased substantially in the calcium plus vitamin D group. The differences were independent of changes in fat mass and waist circumference. A tendency for more beneficial changes in high-density lipoprotein (HDL “good” cholesterol), triglycerides, and total cholesterol was also observed in the calcium plus vitamin D group.

According to the study authors, “Consumption of calcium + D during a weight-loss intervention enhanced the beneficial effect of body weight loss on the lipid and lipoprotein profile in overweight or obese women with usual low daily calcium intake.”

In the second new study on vitamin D, scientists reviewed the medical literature to determine the vitamin’s effects on colon health. The reviewers identified five studies that investigated the relationship between serum vitamin D in association with colorectal cancer risk. The researchers then compared the study subjects with the lowest vitamin D levels to those with the highest.

The studies included in the review involved follow-up periods that ranged from two to 25 years. During the follow-up period of 1,448 total participants, there were 535 cases of colorectal cancer and 913 controls.
After analyzing the data, the reviewers concluded that there was a 50 percent lower risk of colorectal cancer when serum vitamin D levels were greater than or equal to 33 ng/mL, compared to less than or equal to 12 ng/mL.

The results of the data was so compelling that the researchers concluded, “The evidence to date suggests that daily intake of 1,000–2,000 IU/day of vitamin D3 could reduce the incidence of colorectal cancer with minimal risk.”

In the third study, University of Pittsburgh researchers determined that pregnant women in America are not receiving enough vitamin D and that the amount contained in prenatal multivitamins is not enough to completely meet their needs. In the study of 200 black women and 200 white women, randomly selected between 1997 and 2001, 92.4 percent of African-American newborns and 66.1 percent of white babies had deficient or insufficient vitamin D levels at birth. These results occurred even though more than 90 percent of the subjects used prenatal vitamins during pregnancy, indicating that pregnant women should consider supplementing with additional vitamin D beyond what’s in a standard prenatal multivitamin.

Additional vitamin D is especially recommended if the prenatal period occurs during the winter or spring, when individuals are not receiving much vitamin D from exposure to sunlight, or if sunlight exposure in the summer is restricted. In both groups in the current study, vitamin D concentrations were highest in summer and lowest in winter and spring. But differences were smaller between seasons for African-American mothers and babies, whose vitamin D deficiency remained more constant no matter what the season.

The study authors concluded, “Higher-dose supplementation is needed to improve maternal and neonatal vitamin D nutriture.”

Past studies have shown that in utero or early-life vitamin D deficiency is associated with skeletal problems, type 1 diabetes, and schizophrenia. Results of previous studies also have led researchers to suggest that anyone who is not receiving regular sun exposure in winter should consume 1,000 to 2,000 IU of vitamin D3 per day.

Griffin Medical Group recommends a minimum of a minimum of 1000 IU and up to 5000 IU of pharmaceutical vitamin D3 per day. See the link below:
Major GC, Alarie F, Dore J, Phouttama S, Tremblay A. Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations. Am J Clin Nutr. 2007 Jan;85(1):54-9.

Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M, Holick MF. Optimal Vitamin D Status for Colorectal Cancer Prevention: A Quantitative Meta Analysis. Am J Prev Med. March 2007; 32(3):210-16.

Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr. 2007 Feb;137(2):447-52.

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Nov 08 2007

New Research on Vitamin D Benefits

Published by under Vitamin D3

Bone Health
A recent meta-analysis of twelve double blind, randomized controlled trials indicates that vitamin D3 promotes bone strength. The study involved almost 20,000 people supplementing with 400 to 800 i.u. cholecalciferol, vitamin D3. Results indicate that 700-800 i.u. cholecalciferol promoted hip and nonvertebral bone health, however 400 i.u. did not have the same effect. In another 3-year randomized controlled study, cholecalciferol and calcium supplementation lessened the risk of falling in women aged 65 or older.*

Emotional Health
A recent trial selected a cross-sectional group of 80 elderly individuals from a longitudinal study researching cognitive function. The trial indicated that higher serum 25-hydroxyvitamin D levels were associated with positive mood and cognitive performance.*

Nerve Health
A prospective, nested case-control study involving more than 7 million U.S. military personnel indicates that vitamin D may promote nerve health. The study reveals that high circulating levels of 25-hydroxyvitamin D were associated with nerve and myelin health. Another cohort study involving women from the Nurses’ Health Study and Nurses’ Health Study II indicates that supplemental vitamin D greater or equal to 400 i.u. per day promotes nerve health.*

Cellular Health of the Colon, Breast and Prostate
A review of 63 observational studies reveals the importance of healthy vitamin D serum levels for supporting normal cellular health of the prostate, colon and breast. A recent cohort study involving 1,095 men indicates that higher serum levels of vitamin D are associated with cellular health, particularly for the gastrointestinal tract. Additionally, a meta-analysis involving 5 trials suggests that a daily intake of 1,000-2,000 i.u. per day of vitamin D3 promotes colon cell health. A case-control study from within the Nurses Health Study indicates that healthy 25-hydroxyvitamin D plasma levels are associated with breast cell health. Furthermore, healthy plasma levels of 1,25 dihydroxyvitamin D, the most active vitamin D metabolite, may also be associated with healthy breast cell function.*

1. Bischoff-Ferrari HA, Willett WC, Wong JB, et al Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005 May 11;293(18):2257-64
2. Bischoff-Ferrari HA, Orav EJ, Dawson-Hughes B. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Arch Intern Med. 2006 Feb 27;166(4):424-30.
3. Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006 Dec;14(12):1032-40.
4. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8.
5. Munger KL, Zhang SM, O’Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004 Jan 13;62(1):60-5.
6. Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006 Feb;96(2):252-61.
7. Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006 Apr 5;98(7):451-9.
8. Gorham ED, Garland CF, Garland FC, et al. Optimal vitamin d status for colorectal cancer prevention a quantitative meta analysis. Am J Prev Med. 2007 Mar;32(3):210-6.
9. Bertone-Johnson ER, Chen WY, Holick MF, et al. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1991-7.
10. Pendas-Franco N, Gonzalez-Sancho JM, Suarez Y, et al. Vitamin D regulates the phenotype of human breast cancer cells. Differentiation. 2006 Dec. 


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Nov 08 2007

Guarding Against the Dangers of Vitamin D Deficiency

Published by under Vitamin D3


The long, dark days of another winter have come and gone. Tens of millions of Americans would be surprised to learn that winter has left them deficient in vitamin D. Your chances of being one of them are probably much greater than you imagine.

Vitamin D is synthesized in the skin in response to sunlight exposure, but few people achieve optimal levels this way, in part due to the limited ultraviolet light available during the winter months. This seasonal deficit is compounded by the fact that many people avoid sun exposure during the spring and summer months because of concern about premature skin aging and cancers like melanoma. Alarming new research suggests that these factors are contributing to a year-round epidemic of vitamin D deficiency, particularly in elderly adults.

Vitamin D does far more than promote healthy teeth and bones. Its role in supporting immunity, modulating inflammation, and preventing cancer make the consequences of vitamin D deficiency potentially devastating. A growing number of scientists who study vitamin D levels in human populations now recommend annual blood tests to check vitamin D status.

In this article, we examine the factors that contribute to the widespread prevalence of vitamin D deficiency, the latest studies supporting vitamin D’s critical role in preventing disease, and how much supplemental vitamin D you need to achieve optimal blood levels.

Vitamin D Deficiency: An Overlooked Epidemic

Vitamin D is a fat-soluble prohormone—that is, it has no hormone activity itself, but is converted to a molecule that does, through a tightly regulated synthesis mechanism. Its two major forms are vitamin D2 (or ergocalciferol) and vitamin D3 (or cholecalciferol). Vitamin D also refers to metabolites and other analogues of these substances. Vitamin D3 is produced in skin exposed to sunlight, specifically ultraviolet B radiation.

While vitamin D is best known for promoting calcium absorption and bone health, researchers have recently discovered important new roles for this versatile vitamin.1 As an active hormone,2 vitamin D is now seen as playing a central role in controlling immunity and inflammation,1,3,4 two vital processes that are tied to a host of age-related disease conditions.5-10

Just as scientists are discovering critical new roles for vitamin D, they are also finding that shockingly few people have blood levels of vitamin D adequate to support their daily needs.5,6 One leading researcher has referred to this deficit as a “vitamin D epidemic.”7 Estimates of the percentage of US adolescents and adults who are vitamin D deficient range from 21% to 58%,11 while as many as 54% of homebound older adults are believed to be vitamin D deficient.12

Because vitamin D3 is obtained in humans primarily as a result of exposure to sunlight,8 this puts people living outside the tropics at particular risk for vitamin D deficiency, especially from late fall to early spring.9 Further compounding the problem, many public health officials are concerned that their warnings about avoiding the sun because of skin cancer risk may in fact be causing people to limit their sun exposure to an unhealthy extent.10,13

Because sun exposure does pose significant health risks, and most Americans live outside of the regions where they can get adequate sun in winter, perhaps the best way to address this dilemma is by paying close attention to your blood levels of vitamin D and optimizing them through appropriate supplementation. To meet all of the body’s needs for proper vitamin D activity, many scientists now advocate supplementing with doses that are considerably higher than the minimums currently recommended by the Institute of Medicine.14 While vitamin D can be obtained through a few dietary sources such as fish, eggs, and dairy products, these foods fail to provide the daily levels required by most individuals, thus necessitating vitamin D supplementation.

How Vitamin D Controls Cell Functions
Vitamin D’s applications in promoting optimal health stem from its ability to control production of vital proteins by switching genes on and off, and thus helping to determine the fate of cells. Cells affected by the active form of vitamin D, known as calcitriol,15-17 stop growing and reproducing, and rapidly mature into their final forms.3,4,17,18These effects help prevent the proliferation (uncontrolled growth) of potentially cancerous cells,19-24 while stimulating cells to differentiate (mature) so that they can carry out their mature functions, such as stimulating immune system activity.3,4,25-27

Since uncontrolled reproduction of immature cells is the defining feature of cancers, vitamin D may have important cancer-preventive effects. Because of its unique ability to switch cell functions on and off, vitamin D has a dual effect that can modulate immune function3 by both boosting deficient immune function and quieting overactive autoimmunity.28

Vitamin D may further help to reduce the excessive inflammation and oxidative damage implicated in conditions such as osteoarthritis,29,30 chronic obstructive pulmonary disease (such as emphysema),31-33 cardiovascular disease,34,35 and metabolic syndrome.36,37 Low vitamin D levels are linked to increased risk for all these conditions,38-46 highlighting the importance of regular vitamin D blood tests to detect and correct deficiencies before they contribute to the onset of disease.

Applications for Preventing and Treating Cancer

Strong epidemiological data now implicate low vitamin D levels in at least 16 different malignancies.47 Powerful clinical evidence indicates that vitamin D may be useful in preventing and even treating colon and prostate cancers, while suggestive evidence points to its effects in countering lung, breast, skin, and other cancers.16,47

Colon Cancer

Twenty-five years of research suggests that detecting and correcting vitamin D deficiency may be especially important in averting colon cancer, a disease that claims approximately 56,000 lives each year in the United States.48

An early study of 1,954 men found that those with the lowest vitamin D intake had more than double the risk of colon cancer compared to men with the highest intake.49 Colon cells reproduce very quickly, placing them at risk for becoming malignant. When active vitamin D was applied to colon cells in culture, reproduction rates fell by 57% in normal colon tissue and by 52% in patients with familial adenomatous polyposis, an inherited syndrome characterized by many pre-cancerous polyps.50 In a laboratory study, pretreatment with vitamin D made colon cancer cells easier to kill with hydrogen peroxide and other natural oxidants present in the bowel.51

A large randomized trial from 2003 helped to establish a clinical role for vitamin D in preventing colon cancer.52 Eight hundred three subjects with previous colorectal adenomas (which can lead to cancer if they recur) were given calcium supplements or placebo, and their rates of adenoma recurrence were measured. Calcium supplements reduced the risk of adenoma recurrence by 29% in subjects with normal D levels. This study demonstrated that both calcium and adequate vitamin D levels are needed to reduce colon cancer risk.

In a 2006 study,53 researchers surgically divided individual adenomatous (potentially precancerous) polyps, removing approximately 50% from 19 patients. They marked the remnants of the polyps in the intestine so they could identify them later, and studied cell proliferation in the polyp tissue before and after six months of treatment with oral vitamin D3 (400 IU) and calcium carbonate (1500 mg, three times daily) or placebo. Adenomas from patients treated with calcium and vitamin D3 showed marked declines in cell proliferation and other signs of cancerous change, while there was no change in tissue taken from the control patients.

Cancer prevention specialists at the University of California recently conducted an extensive review of scientific papers published worldwide between 1966 and 2004. Their analysis suggested that taking 1000 international units (IU) of vitamin D3 daily lowers an individual’s risk of developing colorectal cancer by 50%. The researchers recommended increased intake of vitamin D3 as an inexpensive, non-toxic preventive therapy for colon cancer. Specifically, they hope to see the federal government officially recommend intake of 1000 IU per day of vitamin D3 for cancer prevention.48

Prostate Cancer

Optimal levels of vitamin D may also help protect prostate health.19,54

Aware that low vitamin D levels are a major risk factor for prostate cancer,40,55,56 researchers examined the vitamin’s preventive effect in a cancer-prone mutant strain of mice.57 Mutant and control mice were given vitamin D for four months either before or after developing the first signs of cancer. Vitamin D substantially reduced the occurrence of early cancerous changes in tissue, yet appeared to have no effect on the androgen (male hormone) system. This is crucial, because many conventional prostate cancer drugs impair androgen function. Human prostate cancer cells in culture show similar reductions in cancerous changes and proliferation when treated with vitamin D3 and a synthetic retinoid (a vitamin A-like compound).58

A 1998 study demonstrated that vitamin D can reduce prostate cancer growth in human subjects. Seven men with recurrent prostate cancer following surgery or radiation (as measured by increasing levels of prostate-specific antigen, or PSA) were given a prescription form of vitamin D called calcitriol (Rocaltrol®) at increasing doses from 0.5 to 2.5 mcg (20-100 IU) per day. The rate of PSA increase (an indicator of disease progression) during treatment fell significantly compared to the rate before treatment in six of the subjects, suggesting a slowing of prostate cancer progression.59 In a related study, weekly dosing with calcitriol (at 20 IU per kilogram of body weight) increased median PSA doubling time in men who had been treated for prostate cancer.60,61 An increased PSA doubling time means that it takes longer for the PSA cancer marker to elevate (double), which is a favorable sign.

Treatment of existing prostate cancers with vitamin D also shows promise. In a 2006 Phase II clinical trial,62 researchers administered calcitriol three times weekly (at up to 12 mcg [480 IU] per dose) with the potent steroid dexamethasone. Thirty-seven men with androgen-independent prostate cancer were treated for at least one month. Eight patients had notable decreases in levels of PSA, a marker for tumor size. The researchers concluded that because there was minimal toxicity from this combination, it is a safe and feasible anti-tumor treatment.

Vitamin D: What You Need to Know
  • Low dietary intake and limited sun exposure have led to an epidemic of vitamin D deficiency. Health experts now advise adults to regularly check their blood levels of vitamin D and to address deficiencies with supplemental vitamin D.

  • Vitamin D plays many essential roles throughout the body—enhancing calcium absorption, contributing to healthy bone mass, supporting immune function, quelling inflammation, and helping to fight cancer.
  • Clinical studies support vitamin D’s role in preventing and treating colon and prostate cancers, and emerging studies suggest vitamin D may help avert cancers of the breast, ovaries, head, and neck, among others.
  • Vitamin D quells inflammation that may exacerbate chronic heart failure, and in combination with other nutrients, benefits people with chronic heart failure. Vitamin D also shows promise in preventing both type I and type II diabetes, and offers important support for immune health. Vitamin D may help prevent wound infections and flu, support the body’s defense against tuberculosis, and boost immune function in patients with kidney failure.
  • Vitamin D likewise may help to alleviate seasonal affective disorder (SAD), a type of depression experienced during the winter months due to decreased sunlight.

Breast and Other Cancers

Abundant laboratory research demonstrates that vitamin D prevents human breast cancer cell proliferation and enhances the differentiation of cells into normal, healthy tissue.18,21-23,63,64 Powerful evidence also indicates that rates of breast cancer, like those of many other cancers, are lower in populations with greater exposure to sunlight or greater dietary intake of vitamin D.65-67

Similarly, enticing (though not yet clinically proven) evidence suggests a role for vitamin D supplementation in preventing or treating other cancers, including ovarian cancer, non-Hodgkin’s lymphoma, and cancers of the head and neck.20,47,68-70 Many cancer specialists advise checking vitamin D levels at least once a year, and supplementing with vitamin D if a deficiency is detected.6,40

Vitamin D Helps Alleviate Heart Failure

Heart failure—the heart’s inability to pump enough blood to meet the body’s requirements—is a leading cause of death in industrialized nations.71 Scientists believe that elevated levels of circulating pro-inflammatory cytokines may contribute to heart failure, and that vitamin D may offer heart-protective benefits by quelling these inflammatory mediators.72

Scanning electron micrograph of prostatic cancer cell.

In a recent double-blind clinical trial, 123 patients with congestive heart failure were randomly assigned to receive either vitamin D3 (50 mcg [2000 IU] per day) plus 500 mg of calcium or placebo plus 500 mg of calcium.72 Over the nine months of the study, patients who supplemented with vitamin D had greatly increased levels of the anti-inflammatory cytokine interleukin-10 and lower levels of the pro-inflammatory cytokine tumor necrosis factor-alpha. Scientists believe that by reducing the inflammatory environment in congestive heart failure patients, vitamin D3 holds promise as an anti-inflammatory therapeutic for people suffering from heart failure.

A 2005 study reported on the use of vitamin D and other nutrients in chronic heart failure.71 In a randomized trial, 28 chronic heart failure patients supplemented with 200 IU of vitamin D, 150 mg of coenzyme Q10, minerals, antioxidants, and B vitamins or placebo for nine months. The supplemented patients had an impressive 17% decrease in the heart’s left ventricular volume, which typically is increased in chronic heart failure and adds to the work required of the already-fatigued heart muscle. By contrast, left ventricular volume increased 10% in the placebo group. Supplemented patients also had a modest increase in quality-of-life scores. These findings indicate that vitamin D supplementation, in combination with coenzyme Q10, vitamins, and minerals, can offer important support for people with chronic heart failure.

Ensuring Optimal Vitamin D Levels
Health experts urge all adults to have regular (at least annual) checks of vitamin D levels in their blood. There is a good chance that you will be deficient for at least part of the year if you live in North America, according to those experts. Once a deficiency is identified, supplementation can safely restore levels to the normal range. Checking vitamin D status again after a few months of supplementation is also advised.While the federal government’s recommended dietary allowance (RDA) of vitamin D is 400 IU (10 mcg) daily, many health experts now advise daily doses of at least 800 IU (20 mcg) of vitamin D. Dr. Yee recommends that healthy adults supplement each day with at least 1000 IU of vitamin D. Elderly adults may benefit from higher doses such as 2000 IU daily, and even up to 5000 IU daily. Research published over the last decade suggests that vitamin D toxicity is unlikely at daily intake levels of less than 10,000 IU (250 mcg).

Comprehensive research reviews conducted by a leading authority on vitamin D, Dr. Michael Holick, suggest that a healthy serum level of vitamin D (25-hydroxyvitamin D) is 75-125 nmol/L. Serum levels within this range have been associated with improved bone health and muscle strength, as well as protection against numerous cancers.

As with many supplements, an appropriate dosage is critical for efficacy and safety. Long-term supplementation with very high doses of vitamin D can cause dangerous elevations in blood calcium levels. Too much calcium in the blood can rapidly cause poor muscle and nerve function, and long-term elevations increase the risk of kidney stones. Anyone taking extremely high doses of vitamin D should be monitored for signs and symptoms of vitamin D toxicity, which include nausea, vomiting, poor appetite, constipation, weakness, heart arrhythmias, kidney stones, and elevated blood levels of cholesterol, calcium, or liver enzymes. Vitamin D is contraindicated in individuals with hypercalcemia (high blood calcium levels). People with kidney disease and those who use digoxin or other cardiac glycoside drugs should consult a physician before using supplemental vitamin D.

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Nov 08 2007

Vitamin D May Help Prevent Diabetes

Published by under Vitamin D3

Exciting research also indicates a possible therapeutic role for vitamin D in preventing diabetes.

Vitamin D supplementation may reduce susceptibility to type II diabetes by slowing the loss of insulin sensitivity in people who show early signs of the disease.  Researchers studied 314 adults without diabetes and gave them either 700 IU of vitamin D and 500 mg of calcium daily or a placebo for three years.73 Among subjects who had impaired (slightly elevated) fasting glucose levels at the study’s onset, those taking the active supplement had a smaller rise in glucose levels over three years than did the controls, as well as a smaller increase in insulin resistance. The researchers concluded that for older adults with impaired glucose levels, supplementing with vitamin D and calcium may help avert metabolic syndrome and type II diabetes.

Type I (insulin-dependent) diabetes is an autoimmune condition, in which the body’s immune system attacks its own insulin-producing pancreatic beta cells. Low vitamin D levels are associated with the development of autoimmune conditions,40,74,75 including type I diabetes,38 and scientists have proposed that vitamin D supplementation may help prevent the disease.76

A very large population-based study in Europe demonstrated the powerful effect of vitamin D supplementation in protecting children against the development of type I diabetes.77 Data from 820 diabetics and 2,335 non-diabetic controls showed that children who received vitamin D supplements in infancy reduced their risk of developing type I diabetes by approximately 33%. The researchers believe that activated vitamin D may protect growing children from autoimmune attack on insulin-producing cells of the pancreas.

Vitamin D May Help Alleviate Depression

It is well established that for people with major depression, symptoms tend to worsen in winter, and also that some people without baseline depression develop depressive symptoms in winter (so-called seasonal affective disorder, or SAD).94,95 Light therapy has been found to be useful for treating wintertime depressive symptoms,96 and it seems likely that at least some of the benefit of light therapy is related to increased activation of vitamin D.

To test this idea, researchers conducted a randomized trial in 15 people with SAD.95 Eight received a single dose of 100,000 IU of vitamin D, and seven received one month of light therapy.  All of the supplemented patients—and none of the light-treated patients—had major improvement in depression scores.  Interestingly, similar studies using much lower doses of 400-800 IU per day did not yield improvements in SAD symptoms,94,97 again suggesting that we simply need more vitamin D than has been thought.

Vitamin D’s benefits for mental health may not be limited to depression. A 2004 study from Finland98 showed that the risk of developing schizophrenia in adult men was greatly increased in those who had never had vitamin D supplementation as infants, compared to those who had had at least some supplementation. Another recent paper proposes that prenatal vitamin D deficiency could be linked to adult schizophrenia.99 Finally, a laboratory study showed that prenatal vitamin D deprivation was associated with certain behaviors in adult rats that are typical of schizophrenia in humans.100

Vitamin D Provides Essential Immune Support

Vitamin D appears to be essential in maintaining healthy white blood cells and a robust immune system.75

A recent paper presented persuasive evidence that seasonal infections such as influenza may actually be the result of decreased vitamin D levels,26 not of increased wintertime viral activity, which has been the longstanding conventional wisdom.78 This makes sense, because vitamin D receptors are present on many of the immune system cells responsible for killing viruses and deadly bacteria, and the vitamin—which is less environmentally available in the winter—appears to be a requirement for proper activation of these cells.79,80

A randomized, double-blind study published in 2006 found that vitamin D may support recovery from tuberculosis, a common and deadly infection that most commonly affects the lungs. When patients with moderately advanced tuberculosis supplemented with 0.25 mg (10,000 IU) per day of vitamin D for one week, they had significantly higher rates of improvement than patients who received a placebo.81

Kidney dialysis patients often demonstrate decreased vitamin D levels as well as impaired cellular immune response. Dialysis patients with decreased vitamin D levels and impaired function of anti-viral and anti-cancer natural killer cells experienced substantial increases in natural-killer-cell activity after just one month of supplementation with prescription vitamin D (calcitriol) at 0.5 mcg (20 IU) per day.27 In the laboratory, the same researchers demonstrated that vitamin D treatment of “generalized” white blood cells called monocytes caused them to mature into active natural killer cells within 24 hours.

Further evidence of vitamin D’s ability to bolster protective immune function comes from a laboratory study published earlier this year.82 Researchers discovered that skin cells responding to injury require vitamin D3 to “switch on” vital proteins involved in recognizing and responding to the microbes that cause wound infections. This finding has tremendous implications for preventing and treating wound infections.


Even in people who take vitamin D supplements, the percentage of those with sub-optimal levels remains surprisingly high. Humans cannot arbitrarily consume massive doses of vitamin D (unlike water-soluble nutrients such as vitamin C). For this nutrient, individualized dosing is of particular importance, and the only way to accomplish this is through vitamin D blood testing. With deficiencies likely to be most pronounced following the long winter months, spring is an excellent time to investigate your own vitamin D status.

Detecting deficient levels allows you and your physician to implement vitamin D supplementation to help avert illnesses associated with inadequate vitamin D levels. Optimizing your vitamin D intake may be a safe, low-cost way to protect against cancer, cardiovascular disease, diabetes, immune disorders, and depression, among other serious health conditions.

Vitamin D Basics
Vitamin D occurs in nature in two main forms: vitamin D2, or ergocalciferol, and vitamin D3, or cholecalciferol. While vitamin D2 is obtained from plant sources, vitamin D3 can be either obtained through animal sources, supplements, or synthesized in the skin when its precursor molecule absorbs light energy from ultraviolet B rays.83

In the liver, both vitamin D2 and vitamin D3 are converted into 25-hydroxy-vitamin D, the primary circulating form of vitamin D. Conversion into its active form, 1,25-dihydroxyvitamin D, occurs in the kidney. Pharmaceutical drug forms of activated vitamin D include calcitriol, doxercalciferol, and calcipotriene.83

Supplemental vitamin D is available as vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol). Vitamin D2 is only about 20-40% as effective as D3 in maintaining serum concentrations of 25-hydroxyvitamin D, since it is more rapidly broken down in the body. For this reason, vitamin D3 (cholecalciferol) supplements are considered more beneficial than vitamin D2 (ergocalciferol) supplements.7

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Nov 08 2007

Greater vitamin D levels associated with protection from cardiovascular risk factors

Published by under Vitamin D3

A report published in the June 11, 2007 issue of the journal Archives of Internal Medicine concluded that having higher serum levels of 25-hydroxyvitamin D is associated with a lower risk of hypertension, diabetes, obesity, and elevated triglyceride levels, all risk factors for cardiovascular disease.

Researchers at Charles R. Drew University of Medicine and Science in Los Angeles and colleagues at the University of California, Los Angeles, and Harvard examined data obtained from 7,186 men and 7,902 women enrolled in the Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 through 1994. Blood samples were tested for serum vitamin D, cholesterol, triglycerides, fasting blood glucose and other factors, and height, weight, body mass index, and blood pressure were determined. Interviews with the subjects confirmed pre-existing diabetes and hypertension.

Mean serum vitamin D levels, particularly in women, people aged 60 and older, and minorities, were well below the recommended national goal. The team found significant relationships between lower vitamin D levels and the presence of cardiovascular disease risk factors. Participants whose vitamin D levels were in the lowest one-fourth of the study population had a 30 percent greater risk of hypertension, a 98 percent higher risk of diabetes, more than double the risk of obesity, and a 47 percent greater risk of having high serum triglyceride levels than subjects whose vitamin D levels were in the top 25 percent.

The study is the first, to the authors’ knowledge, to show a significant association between reduced vitamin D levels and risk factors for cardiovascular disease risk factors in a nationally representative sample. They conclude that “Prospective studies to assess a direct benefit of cholecalciferol (vitamin D) supplementation on cardiovascular disease risk factors are warranted.”

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