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Dawson-Hughes B, Konieczynski EM, Ceglia L. Obesity may extend the time required to reach a steady-state 25(OH)D level after initiating vitamin D supplementation. JBMR Plus 2025; 9:ziaf030. [PMID: 40124405 PMCID: PMC11929376 DOI: 10.1093/jbmrpl/ziaf030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 02/04/2025] [Accepted: 02/05/2025] [Indexed: 03/25/2025] Open
Abstract
Obesity is known to influence the circulating 25(OH)D level but less is known about whether it influences the time required to reach a stable 25(OH)D level after initiating vitamin D supplementation. This observational study was done to investigate whether BMI modified the time required to reach a steady-state 25(OH)D level in response to vitamin D supplementation. Participants in the Boston STOP IT study who were treated for 12 mo with 700 IU of vitamin D3 and 500 mg of calcium daily and had 25(OH)D measures at 0, 6, and 12 mo, were included. We assessed the trajectory of 25(OH)D levels by baseline BMI category (normal weight, BMI 18.5-24.9 kg/m2, n = 62; overweight and obese, BMI ≥ 25 kg/m2, n = 105). Baseline 25(OH)D levels were 78 ± 31.3 nmol/L (normal weight) and 74.7 ± 36.5 nmol/L (overweight and obese). In a linear mixed model examining the influence of time and baseline BMI category on change in the mean 25(OH)D level, there was a significant time x BMI group interaction (p = .024. The normal weight participants had reached steady-state 25(OH)D levels by 6 mo whereas 25(OH)D levels continued to rise between 6 and 12 mo in the overweight and obese participants. This analysis suggests that the time required to reach a steady-state 25(OH)D level after initiating vitamin D supplementation in overweight and obese adults is greater than the usual 3-mo time point commonly used in clinical practice. A more refined definition of the time course of circulating 25(OH)D response to supplementation is needed in overweight and obese individuals in order to optimize clinical monitoring of vitamin D status.
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Affiliation(s)
- Bess Dawson-Hughes
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, United States
| | - Elsa M Konieczynski
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, United States
| | - Lisa Ceglia
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, United States
- Tufts Medical Center, Boston, MA 02111, United States
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McCourt AF, Mulrooney SL, O'Neill GJ, O'Riordan ED, O'Sullivan AM. Postprandial 25-hydroxyvitamin D response varies according to the lipid composition of a vitamin D3 fortified dairy drink. Int J Food Sci Nutr 2021; 73:396-406. [PMID: 34615419 DOI: 10.1080/09637486.2021.1984400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
In-vitro evidence suggests that the lipid component of foods alters vitamin D absorption. This single-blinded, cross-over postprandial study examined the effect of changing the lipid component of a 20 µg vitamin D3 fortified dairy drink on postprandial 25(OH)D concentrations. Participants consumed one dairy drink per visit: a non-lipid, a pre-formed oleic acid micelle, an olive oil and a fish oil dairy drink. There was a significant time*drink*baseline status effect on 25(OH)D concentrations (p = 0.039). There were no time*drink, time or drink effects on 25(OH)D in vitamin D sufficient participants (>50nmol/L). However, there was an effect of time on changes in 25(OH)D concentrations after the olive oil dairy drink (p = 0.034) in vitamin D insufficient participants (<50nmol/L). There were no effects after the other diary drinks. Olive oil may improve vitamin D absorption from fortified foods. Further research is needed to examine the practical implications of changing the lipid component of fortified foods.
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Affiliation(s)
- Aislinn F McCourt
- UCD Institute of Food and Health, UCD School of Agriculture and Food Science, University College Dublin (UCD), Dublin, Ireland
| | - Steven L Mulrooney
- UCD Institute of Food and Health, UCD School of Agriculture and Food Science, University College Dublin (UCD), Dublin, Ireland
| | - Graham J O'Neill
- TUD School of Food Science and Environmental Health, Technological University Dublin (TUD), Dublin, Ireland
| | - E Dolores O'Riordan
- UCD Institute of Food and Health, UCD School of Agriculture and Food Science, University College Dublin (UCD), Dublin, Ireland
| | - Aifric M O'Sullivan
- UCD Institute of Food and Health, UCD School of Agriculture and Food Science, University College Dublin (UCD), Dublin, Ireland
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Abstract
Vitamin D is essential for bone health and is known to be involved in immunomodulation and cell proliferation. Vitamin D status remains a significant health issue worldwide. However, there has been no clear consensus on vitamin D deficiency and its measurement in serum, and clinical practice of vitamin D deficiency treatment remains inconsistent. The major circulating metabolite of vitamin D, 25-hydroxyvitamin D (25(OH)D), is widely used as a biomarker of vitamin D status. Other metabolic pathways are recognised as important to vitamin D function and measurement of other metabolites may become important in the future. The utility of free 25(OH)D rather than total 25(OH)D needs further assessment. Data used to estimate the vitamin D intake required to achieve a serum 25(OH)D concentration were drawn from individual studies which reported dose-response data. The studies differ in their choice of subjects, dose of vitamin D, frequency of dosing regimen and methods used for the measurement of 25(OH)D concentration. Baseline 25(OH)D, body mass index, ethnicity, type of vitamin D (D2 or D3) and genetics affect the response of serum 25(OH)D to vitamin D supplementation. The diversity of opinions that exist on this topic are reflected in the guidelines. Government and scientific societies have published their recommendations for vitamin D intake which vary from 400-1000 IU/d (10-25 μg/d) for an average adult. It was not possible to establish a range of serum 25(OH)D concentrations associated with selected non-musculoskeletal health outcomes. To recommend treatment targets, future studies need to be on infants, children, pregnant and lactating women.
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Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation. Nutrients 2015; 7:5111-42. [PMID: 26121531 PMCID: PMC4516990 DOI: 10.3390/nu7075111] [Citation(s) in RCA: 142] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Revised: 06/05/2015] [Accepted: 06/12/2015] [Indexed: 12/27/2022] Open
Abstract
Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.
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Luong KVQ, Nguyen LTH. Beneficial role of vitamin D3 in the prevention of certain respiratory diseases. Ther Adv Respir Dis 2013; 7:327-50. [PMID: 24056290 DOI: 10.1177/1753465813503029] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
There is evidence of aberrations in the vitamin D-endocrine system in subjects with respiratory diseases. Vitamin D deficiency is highly prevalent in patients with respiratory diseases, and patients who receive vitamin D have significantly larger improvements in inspiratory muscle strength and maximal oxygen uptake. Studies have provided an opportunity to determine which proteins link vitamin D to respiratory pathology, including the major histocompatibility complex class II molecules, vitamin D receptor, vitamin D-binding protein, chromosome P450, Toll-like receptors, poly(ADP-ribose) polymerase-1, and the reduced form of nicotinamide adenine dinucleotide phosphate. Vitamin D also exerts its effect on respiratory diseases through cell signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the Wnt/β-catenin signaling pathway, prostaglandins, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D plays a significant role in respiratory diseases. The best form of vitamin D for use in the treatment of respiratory diseases is calcitriol because it is the active metabolite of vitamin D3 and modulates inflammatory cytokine expression. Further investigation of calcitriol in respiratory diseases is needed.
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Affiliation(s)
- Khanh Vinh Quoc Luong
- Vietnamese American Medical Research Foundation, 14971 Brookhurst Street, Westminster, CA 92683, USA
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vinh quốc Lu'o'ng K, Nguyễn LTH. The beneficial role of vitamin D in obesity: possible genetic and cell signaling mechanisms. Nutr J 2013; 12:89. [PMID: 23800102 PMCID: PMC3702462 DOI: 10.1186/1475-2891-12-89] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2013] [Accepted: 06/21/2013] [Indexed: 02/06/2023] Open
Abstract
The prevalence rates of overweight and obesity are considered an important public issue in the United States, and both of these conditions are increasing among both children and adults. There is evidence of aberrations in the vitamin D-endocrine system in obese subjects. Vitamin D deficiency is highly prevalent in patients with obesity, and many studies have demonstrated the significant effect of calcitriol on adipocytes. Genetic studies have provided an opportunity to determine which proteins link vitamin D to obesity pathology, including the vitamin D receptor, toll-like receptors, the renin-angiotensin system, apolipoprotein E, vascular endothelial growth factor, and poly (ADP-ribose) polymerase-1. Vitamin D also exerts its effect on obesity through cell-signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the reduced form of nicotinamide adenine dinucleotide phosphate, prostaglandins, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D may have a role in obesity. The best form of vitamin D for use in the obese individuals is calcitriol because it is the active form of the vitamin D3 metabolite, its receptors are present in adipocytes, and modulates inflammatory cytokine expression.
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Affiliation(s)
- Khanh vinh quốc Lu'o'ng
- Vietnamese American Medical Research Foundation, 14971 Brookhurst Street, Westminster, CA 92683, USA.
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Lương KVQ, Nguyễn LTH. Theoretical basis of a beneficial role for vitamin D in viral hepatitis. World J Gastroenterol 2012; 18:5338-50. [PMID: 23082050 PMCID: PMC3471102 DOI: 10.3748/wjg.v18.i38.5338] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2011] [Revised: 03/22/2012] [Accepted: 05/06/2012] [Indexed: 02/06/2023] Open
Abstract
Abnormal bone metabolism and dysfunction of the calcium-parathyroid hormone-vitamin D axis have been reported in patients with viral hepatitis. Some studies suggested a relationship between vitamin D and viral hepatitis. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to the pathology of viral hepatitis (i.e., the major histocompatibility complex class II molecules, the vitamin D receptor, cytochrome P450, the renin-angiotensin system, apolipoprotein E, liver X receptor, toll-like receptor, and the proteins regulated by the Sp1 promoter gene). Vitamin D also exerts its effects on viral hepatitis via non-genomic factors, i.e., matrix metalloproteinase, endothelial vascular growth factor, prostaglandins, cyclooxygenase-2, and oxidative stress. In conclusion, vitamin D could have a beneficial role in viral hepatitis. Calcitriol is best used for viral hepatitis because it is the active form of the vitamin D3 metabolite.
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Goussous R, Song L, Dallal GE, Dawson-Hughes B. Lack of effect of calcium intake on the 25-hydroxyvitamin d response to oral vitamin D3. J Clin Endocrinol Metab 2005; 90:707-11. [PMID: 15562015 DOI: 10.1210/jc.2004-1380] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
This study was conducted to examine the effect of calcium intake on the rise in serum 25-hydroxyvitamin D [25(OH)D] levels in response to supplemental vitamin D(3). Fifty-two healthy older men and women were randomly assigned to take calcium (500 mg twice daily with meals) or placebo tablets for 90 d between October 1 and the end of March. All participants were placed on 800 IU/d (20 microg/d) vitamin D(3). Serum 25(OH)D measurements were made at baseline and on d 30, 60, and 90. The mean baseline 25(OH)D values were 19.2 +/- 6.4 ng/ml (47.9 +/- 15.9 nmol/liter) in the calcium group and 19.6 +/- 6.7 ng/ml (49.1 +/- 16.7 nmol/liter) in the control group (P = 0.808). The difference in pattern of change in 25(OH)D was not statistically significant (group by time interaction, P = 0.651); the calcium group increased 6.5 +/- 5.9 ng/ml (16.2 +/- 14.8 nmol/liter; P < 0.001), and the control group increased 6.6 +/- 7.0 ng/ml (16.6 +/- 17.4 nmol/liter; P < 0.001). The 95% confidence interval for difference in mean increase, calcium vs. control, was -3.8 +/- 3.5 ng/ml (-9.6, 8.7) nmol/liter. In older men and women, the level of calcium intake, within the range of 500-1500 mg/d, does not have an important effect on the rise in serum 25(OH)D that occurs in response to 800 IU (20 microg)/d vitamin D(3).
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Affiliation(s)
- Rula Goussous
- Division of Endocrinology, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA
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Fraser DR. Effect of calcium deficiency on vitamin D metabolism. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 1994; 352:237-41. [PMID: 7832053 DOI: 10.1007/978-1-4899-2575-6_21] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- D R Fraser
- Department of Animal Science, University of Sydney, New South Wales, Australia
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Love RR, Mazess RB, Barden HS, Epstein S, Newcomb PA, Jordan VC, Carbone PP, DeMets DL. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992; 326:852-6. [PMID: 1542321 DOI: 10.1056/nejm199203263261302] [Citation(s) in RCA: 720] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND METHODS Tamoxifen, a synthetic antiestrogen, increases disease-free and overall survival when used as adjuvant therapy for primary breast cancer. Because it is given for long periods, it is important to know whether tamoxifen affects the skeleton, particularly since it is used extensively in postmenopausal women who are at risk for osteoporosis. Using photon absorptiometry, we studied the effects of tamoxifen on the bone mineral density of the lumbar spine and radius and on biochemical measures of bone metabolism in 140 postmenopausal women with axillary-node-negative breast cancer, in a two-year randomized, double-blind, placebo-controlled trial. RESULTS In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 0.61 percent per year, whereas in those given placebo it decreased by 1.00 percent per year (P less than 0.001). Radial bone mineral density decreased to the same extent in both groups. In a subgroup randomly selected from each group, serum osteocalcin and alkaline phosphatase concentrations decreased significantly in women given tamoxifen (P less than 0.001 for each variable), whereas serum parathyroid hormone and 1,25-dihydroxyvitamin D concentrations did not change significantly in either group. CONCLUSIONS In postmenopausal women, treatment with tamoxifen is associated with preservation of the bone mineral density of the lumbar spine. Whether this favorable effect on bone mineral density is accompanied by a decrease in the risk of fractures remains to be determined.
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Affiliation(s)
- R R Love
- Department of Human Oncology, University of Wisconsin-Madison
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Scharla SH, Minne HW, Oswald C, Lempert UG, Schmidt-Gayk H, Ziegler R. The hypercalcemic Walker carcinosarcoma 256 of the rat causes an increase in serum 1,25-dihydroxyvitamin D3. BONE AND MINERAL 1989; 6:155-64. [PMID: 2765706 DOI: 10.1016/0169-6009(89)90047-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
We have studied vitamin D metabolism in rats with the transplantable hypercalcemic Walker carcinosarcoma 256, which is a well characterized animal model for humoral hypercalcemia of malignancy. 25-Hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) concentrations were determined in blood samples obtained from parathyroidectomized (PTX) female rats at different time intervals after intramuscular tumor cell inoculation. We observed a dramatic increase in serum 1,25(OH)2D3 (280 +/- 184 vs. 98 +/- 31 pmol/l) 6 days after tumor cell injection and 4 days after the initial rise of serum calcium, whereas 25(OH)D3 tended to decrease. In a separate control experiment we compared this to the effect of exogenous parathyroid hormone in PTX rats and found similar results. In contrast, rats exhibited no change in vitamin D metabolite blood concentration after inoculation of the normocalcemic Yoshida sarcoma, which obviously does not interfere with vitamin D metabolism. We conclude that the humoral bone-resorbing agent produced by the Walker tumor cells causes elevation of serum 1,25(OH)2D3 concentration by this fulfilling an additional criterion of PTH-like activity.
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Affiliation(s)
- S H Scharla
- Department of Internal Medicine 1 (Endocrinology and Metabolism), University of Heidelberg, FRG
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Benbrahim N, Dubé C, Vallieres S, Gascon-Barré M. The calcium ionophore A23187 is a potent stimulator of the vitamin D3-25 hydroxylase in hepatocytes isolated from normocalcaemic vitamin D-depleted rats. Biochem J 1988; 255:91-7. [PMID: 2848514 PMCID: PMC1135194 DOI: 10.1042/bj2550091] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The role played by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and/or by calcium on the C-25 hydroxylation of vitamin D3 (D3) was studied in hepatocytes isolated from D-depleted rats which were divided into four treatment groups: Group 1 served as controls, Group 2 received calcium gluconate, Groups 3 and 4 were infused with 1,25(OH)2D3 at 7 and 65 pmol/24 h x 7 days respectively. The treatments normalized serum calcium in all but the controls which remained hypocalcaemic, while serum 1,25(OH)2D3 remained low in Groups 1 and 2 but increased to physiologic and supraphysiologic levels in Groups 3 and 4. The data show that basal D3-25 hydroxylase activities were not significantly affected by any of the treatments. Addition of CaCl2, EGTA, or Quin-2 in vitro revealed that relative to basal values, EGTA strongly inhibited the enzyme activity in all groups (P less than 0.0001), except in G 1; Quin-2 and CaCl2 had no significant effect on the activity of the enzyme in any of the groups. Addition of 1,25(OH)2D3 or A23187 in vitro in the presence of CaCl2 revealed that 1,25(OH)2D3 did not significantly affect enzyme activity, while A23187 was found to stimulate its activity in vitamin D-depleted animals, but most specifically in Group 2 (P less than 0.001); low serum calcium (Group 1) dampened (P less than 0.01), and 1,25(OH)2D3 treatment in vivo totally blunted (P less than 0.001) the response to A23187. The data suggest that 1,25(OH)2D3 supplementation in vivo has per se little or no effect on the basal D3-25 hydroxylase activity. The data show, however, that the magnitude of the response to various challenges in vitro is greatly influenced by the conditioning in vivo of the animals. They also show that A23187 can be a potent stimulator of the enzyme activity, which allowed us to demonstrate a significant reserve for the C-25 hydroxylation of D3 which is well expressed in hepatocytes obtained from D-depleted calcium-supplemented rats.
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Affiliation(s)
- N Benbrahim
- Centre de Recherche Clinique André-Viallet, Hôpital Saint-Luc, Montreal, Quebec, Canada
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