Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention
Leo Baggerly , Christine French, Cedric F Garland
Robert P Heaney
Author affiliations (2)
Stacie Nguyen, Leo Baggerly, and Christine French are with GrassrootsHealth, Encinitas, CA. Robert P. Heaney is with Creighton University, Osteoporosis Research Center, Omaha, NE. Edward D. Gorham ...
Studies indicate that intake of vitamin D in the range from 1,100 to 4,000 IU/d and a serum 25-hydroxyvitamin D concentration [25(OH)D] from 60-80 ng/ml may be needed to reduce cancer risk. Few community-based studies allow estimation of the dose-response relationship between oral intake of vitamin D and corresponding serum 25(OH)D in the range above 1,000 IU/d.
Materials and Methods
A descriptive study of serum 25(OH)D concentration and self-reported vitamin D intake in a community-based cohort (n = 3,667, mean age 51.3 ± 13.4 y).
Results
Serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion, with no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml). Unsupplemented all-source input was estimated at 3,300 IU/d. The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d.
Conclusion
Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.
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PMID 21378345 21378345
Cite this article
Garland, C. F., French, C. B., Baggerly, L. L., & Heaney, R. P. (2011). Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Research, 31(2), 607-611.
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(2):607-611.
Garland, C. F., et al. "Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention." Anticancer research, vol. 31, no. 2, 2011, pp. 607-611.
Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).
Contraception/ComparisonBreast Cancer RiskCancer OnsetCancer Risk Reduction
Breast cancer is the most frequent cancer in women in western countries. A number of risk factors are now known, but the etiology of the disease is not fully understood. The aim of this study was to determine the effects of reproductive, anthropometric and environmental factors on cancer onset. 934 women who developed a non-hereditary breast cancer were recruited from different hospitals in the Auvergne region (France) and completed a questionnaire. The use of oral contraceptives (OC) increased the risk of early cancer development (odds ratio = 1.84, 95% confidence interval = 1.38-2.44). The age at first OC use appeared to be a major factor since the risk decreased when OC use was after the age of 23 years (odds ratio = 0.52, 95% confidence interval = 0.34-0.79). A duration of breast-feeding greater than 26 weeks decreased the risk of early cancer development (odds ratio = 0.62, 95% confidence interval = 0.39-0.97). No overall association was found with anthropometric or lifestyle factors and early age at breast cancer onset. OC use, age at first OC use and lactation were significantly associated with an early age at breast cancer onset. Thus, a number of "risk factors" could be considered as "early onset risk factors".
PCOSBreast Cancer RiskBreast Cancer AssociationHyperandrogenism and Anovulation
Two long and broad streams of medical literature, from the 1950's to date, have established the existence of two unrelated abnormalities of androgen production in women with breast cancer. One is the genetically determined presence of subnormal production of adrenal androgens (i.e. DHEA and DHEAS) in women with premenopausal breast cancer and their sisters, who are at increased risk for breast cancer. The other is excessive production of testosterone, of ovarian origin, in subsets of women with either premenopausal or postmenopausal breast cancer and women with atypical breast-duct hyperplasia, who are at increased risk for breast cancer; along with the hypertestosteronism, there is frequently chronic anovulation in the premenopausal patients. The combination of ovarian hypertestosteronism and chronic anovulation is characteristic of the polycystic ovary syndrome and is also frequently seen in women with abdominal ("android") obesity; both PCOS and abdominal obesity are known to be characterized by high risk for postmenopausal cancer. The elevated testosterone levels and the increased levels of insulin, IGF-I, and IGF-II that are seen in PCOS and abdominal obesity could favor the development of breast cancer in several ways, all of which have been binding of testosterone to cancer cells bearing testosterone receptors, with direct stimulation; intratissular aromatization of testosterone to estradiol, with stimulation of estrogen-sensitive cells; stimulation of the production of epithelial growth factor (EGF) by testosterone, with direct mitogenic effect of EGF on cancer cells; stimulation of aromatase by insulin and IGF-I; direct mitogenic stimulation of cancer cells by insulin, IGF-I, and IGF-II; and stimulation by IGF-I and IGF-II of the intratissular reduction of estrone to estradiol. Since PCOS is probably largely genetically determined, and abdominal obesity may also be, the hypertestosteronism of these conditions may represent a second genetically determined hormonal risk factor for breast cancer.