Vitamin D Updates

Vitamin D deficiency is a substantial and growing health problem in almost all countries or cities located more than 30 degrees from the equator.

The biochemical mechanism of how vitamin D might prevent breast cancer is as follows:

 

Vitamin D metabolites inhibit cell growth mainly by up regulating synthesis of compounds that cause epithelial cells to strongly adhere to their neighboring cells. This causes contact inhibition, preventing excessive cell division. As a result, the process leading to cancer does not begin.  If cancer does begin, vitamin D metabolites prevent tumor angiogenesis, depriving the tumor mass of oxygen and glucose. These metabolites also stimulate differentiation and apoptosis of cancer cells leading to their acquiring milder features or their loss from the tissue, rather than uncontrolled proliferation

Serum 25(OH)D levels between 70-85 ng/ml are the target range as adequate to significantly reduce the risk of breast cancer. This will require at least 2000 IU/dayof vitamin D3, and a few minutes (5-15 minutes) in the sun around noon when season allows. Duration of exposure depends on skin type, but more than 15 minutes is rarely needed. Forty percent of the skin area should be exposed.


**A hat with a broad brim should always be worn when spending more than a few minutes in the sun.

 

Sun screens prevent photosynthesis of vitamin D and should be avoided during the first 5-15 minutes of exposure. Patients who do not tan easily, have a personal or family history of skin cancer, are taking photosensitizing medications, or who have a photosensitivity disease should not use solar or other UVB exposure as a means of vitamin D synthesis.

**Vitamin D2 may be is 1/4 to 1/3 as effective for many vitamin D outcomes as vitamin D3.**

In a paper published in the August issue of the American Journal of Clinical Nutrition, Dr. Anthony Norman identifies vitamin D's potential for contributions to good health in the adaptive and innate immune systems, the secretion and regulation of insulin by the pancreas, the heart and blood pressure regulation, muscle strength and brain activity. In addition, access to adequate amounts of vitamin D is believed to be beneficial towards reducing the risk of cancer.

Norman also lists 36 organ tissues in the body whose cells respond biologically to vitamin D. The list includes bone marrow, breast, colon, intestine, kidney, lung, prostate, retina, skin, stomach and the uterus.

According to Norman, deficiency of vitamin D can impact all 36 organs.  Already, vitamin D deficiency is associated with muscle strength decrease, high risk for falls, and increased risk for colorectal, prostate and breast as well as other major cancers.

"It is becoming increasingly clear to researchers in the field that vitamin D is strongly linked to several diseases," said Norman, a distinguished professor emeritus of biochemistry and of biomedical sciences who has worked on vitamin D for more than 45 years. "Its biological sphere of influence is much broader than we originally thought. The nutritional guidelines for vitamin D intake must be carefully reevaluated to determine the adequate intake, balancing sunlight exposure with dietary intake, to achieve good health by involving all 36 target organs."

Vitamin D is synthesized in the body in a series of steps. First, sunlight's ultraviolet rays act on a precursor compound in skin. When skin is exposed to sunlight, a sterol present in dermal tissue is converted to vitamin D, which, in turn, is metabolized in the liver and kidneys to form a hormone. It was Norman's laboratory that discovered, in 1967, that vitamin D is converted into a steroid hormone by the body.

The recommended daily intake of vitamin D is 200 international units (IU) for people up to 50 years old. The recommended daily intake of vitamin D is 400 IU for people 51 to 70 years old and 600 IU for people over 70 years old. Norman's recommendation for all adults is to have an average daily intake of at least 2000 IU.

"To optimize good health you must have enough vitamin D," he said. "Vitamin D deficiency is also especially of concern in third world countries that have poor nutritional practices and religious customs that require the body to be covered from head to toe. Ideally, to achieve the widest frequency of good health by population, we need to have 90 percent of the people with adequate amounts of vitamin D."

About half of the elderly in North America and two-thirds of the rest of the world are not getting enough vitamin D to maintain healthy bone density, lower their risks for fracture and improve tooth attachment.

"There needs to be a sea change by various governmental agencies in terms of the advice they present to citizens about how much vitamin D should be taken," Norman said. "The tendencies of people to live in cities where tall buildings block adequate sunlight from reaching the ground, to spend most of their time indoors, to use synthetic sunscreens that block ultraviolet rays, and to live in geographical regions of the world that do not receive adequate sunlight all contribute to the inability of the skin to biosynthesize sufficient amounts of vitamin D."

Found in minute amounts in food, vitamins are organic substances that higher forms of animals need to grow and sustain normal health. Vitamins, however, are not synthesized in sufficient amounts to meet bodily needs. Therefore, the body must acquire them through diet or in the form of supplements.

Because it is found in very few foods naturally, milk and other foods (often orange juice) are fortified with vitamin D.

While deficiency of vitamin D impacts health negatively, ingestion of extremely high doses of vitamin D can cause hypercalcemia, a condition in which the blood's calcium level is above normal. The highest daily 'safe' dose of vitamin D3 is 10,000 IU.

Source: Anthony Norman is a distinguished professor emeritus of biochemistry and of biomedical sciences at UC Riverside. He also holds the title of Presidential Chair in Biochemistry-Emeritus.

 

 

Various journal articles are summarized and referenced below.

Summary: In a study involving data from a population-based, case-control study involving 289 premenopausal women with breast cancer and 595 matched controls, a significant inverse association was found between risk of breast cancer and plasma 25(OH)D concentrations (an overall indicator of vitamin D status), with a stronger concentration
found in progesterone receptor negative tumors. Compared to women with the lowest levels of plasma 25(OH)D (< 30 nmol/L), the odds ratios for women with higher levels of plasma 25(OH)D were: 0.68 (30-45 nmol/L), 0.59 (45-60 nmol/L), and 0.45 (>/=60 nmol/L). The authors conclude, "Our findings support a protective effect of vitamin D for premenopausal breast cancer."

Reference: "Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study," Abbas S, Chang-Claude J, Linseisen J, Int J Cancer, 2008 Oct 6; [Epub ahead of print]. (Address: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. E-mail: Jenny Chang-Claude, j.chang-claude@dkfz.de ).

Summary: In a case-control study involving 759 women with breast cancer and 1,135 controls, increasing intake of vitamin D (both from sun exposure as well as from diet) was found to be associated with a reduced risk of breast cancer, irrespective of ER/PR status of the tumor. While the most consistent significant association was found for ER+/PR+ tumors (OR=0.76), comparable non-significant associations were found for ER-/PR- tumors (OR=0.74), and mixed (ER+/PR-) tumors (OR=0.79). The authors conclude, "This study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of ER/PR status of the tumor."

Reference: "Vitamin D From Dietary Intake and Sunlight Exposure and the Risk of Hormone-Receptor-Defined Breast Cancer," Blackmore KM, Lesosky M, et al, Am J Epidemiol, 2008 August 27; [Epub ahead of print]. (Address: Kristina M. Blackmore, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Box 18, Toronto, Ontario, Canada M5T 3L9. E-mail: blackmore@mshri.on.ca ).


Summary: In a cross-sectional study involving 790 breast cancer survivors, the prevalence of insufficient vitamin D levels was high (76%). The authors point out that vitamin D has an influence on pathways that relate to carcinogenesis. After adjusting for various potential confounders, stage of disease was found to independently predict serum 25(OH)D level. The mean serum 25(OH)D for the whole group was 24.8 ng/mL. For African-Americans, the mean serum 25(OH)D was 18.1 ng/mL, and for Hispanics, the mean serum 25(OH)D was 22.1 ng/mL. Lower serum 25(OH)D levels were also found in women with localized or regional breast cancer, as compared to women with in situ disease. These results point to the prevalence of insufficient vitamin D status in survivors of breast cancer. The authors conclude, "Clinicians might consider monitoring vitamin D status in breast cancer patients, together with appropriate treatments, if necessary."

Reference: "Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors," Neuhouser ML, Sorensen B, et al, Am J Clin Nutr, 2008; 88(1): 133-9. (Address: ML Neuhouser, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, PO Box 19024, Seattle, WA 98109-1024, USA. E-mail: mneuhous@fhcrc.org ).


Summary: In a study involving a pooled analysis of data from two nested case-control studies involving men and women 40-74 years of age who were free of diabetes at baseline, high vitamin D status was found to protect against type 2 diabetes in men. Over the course of a 22 year follow-up period, 412 cases of diabetes were identified, and 986 matched controls were selected. Results found that compared to men in the lowest quartile of serum 25(OH)D level, those in the highest had a 0.28 relative odds of diabetes, after adjusting for smoking, BMI, physical activity, and education. In women, the relative odds were 1.14. Overall, men had higher vitamin D status than women. These results suggest that optimal vitamin D status may reduce the odds of diabetes in men.

Reference: "Serum vitamin D and subsequent occurrence of type 2 diabetes," Knekt P, Laaksonen M, et al, Epidemiol, 2008; 19(5): 666-71. (Address: National Public Health Institute, Department of Health and Functional Capacity, Mannerheimintie 166, 00300 Helsinki, Finland. E-mail: paul.knekt@ktl.fi ).

In a study involving 6,514 subjects, low levels of vitamin D were found to be predictive for fatal stroke. Levels of 25(OH)D were measured in 3,299 subjects and levels of 1,25(OH)2D were measured in 3,315 subjects. Over the course of a 7.75 year follow-up, 769 patients died, out of which 42 died of fatal strokes (ischemic and hemorrhagic). Results found that the odds ratio for fatal stroke were 0.58 per z value of 25(OH)D and 0.62 per z value of 1,25(OH)2D - the results remained significant even after adjusting for potential confounders. Amongst patients with a history of cerebrovascular disease (n=274), Z values of 25(OH)D and 1,25(OH)2D were also reduced. Given the prevalence of low vitamin D status among the elderly, these results are significant. The authors conclude, "Low levels of 25(OH)D and 1,25(OH)2D are independently predictive for fatal strokes, suggesting that vitamin D supplementation is a promising approach in the prevention of strokes."

 

Reference: "Low vitamin d levels predict stroke in patients referred to coronary angiography," Pilz S, Dobnig H, et al, Stroke, 2008; 39(9): 2611-3. (Address: Winfried März, Synlab Center of Laboratory Diagnostics, Heidelberg, PO Box 10470, D-69037 Heidelberg, Germany. E-mail maerz@synlab.de ).

 

Summary: In a cross-sectional study involving 790 breast cancer survivors, the prevalence of insufficient vitamin D levels was high (76%). The authors point out that vitamin D has an influence on pathways that relate to carcinogenesis. After adjusting for various potential confounders, stage of disease was found to independently predict serum 25(OH)D level. The mean serum 25(OH)D for the whole group was 24.8 ng/mL. For African-Americans, the mean serum 25(OH)D was 18.1 ng/mL, and for Hispanics, the mean serum 25(OH)D was 22.1 ng/mL. Lower serum 25(OH)D levels were also found in women with localized or regional breast cancer, as compared to women with in situ disease. These results point to the prevalence of insufficient vitamin D status in survivors of breast cancer. The authors conclude, "Clinicians might consider monitoring vitamin D status in breast cancer patients, together with appropriate treatments, if necessary."

Reference: "Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors," Neuhouser ML, Sorensen B, et al, Am J Clin Nutr, 2008; 88(1): 133-9. (Address: ML Neuhouser, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, PO Box 19024, Seattle, WA 98109-1024, USA. E-mail: mneuhous@fhcrc.org ).

Summary: In a nested, case-control study involving 400 patients with incident hip fracture and 400 controls who were followed for an average of 7 years, serum 25(OH)D levels were lower among cases (55.95 nmol/L) than controls (59.60 nmol/L). Moreover, lower serum 25(OH)D concentrations increased the risk of hip fracture. Each 25-nmol/L decrease was associated with a 1.33 adjusted odds ratio of hip fracture. Women with the lowest concentrations of 25(OH)D (47.5 nmol/L or lower) had a significantly higher risk of fracture compared to those with the highest concentrations (70.7 nmol/L or higher), with an adjusted odds ratio of 1.71. These results suggest that insufficient vitamin D status may increase the risk of hip fractures.

Reference: "Serum 25-hydroxyvitamin D concentrations and risk for hip fractures," Cauley JA, Lacroix AZ, et al, Ann Intern Med, 2008; 149(4): 242-50. (Address: University of Pittsburgh, Department of Epidemiology, 130 DeSoto Street, Crabtree A524, Pittsburgh, PA 15261, USA. E-mail: jcauley@edc.pitt.edu ).