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Comparison of Metabolic Responses to Daily-Dose or Single-Dose Vitamin D Supplementation Regimens a,b
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![FIGURE 2. 25-Hydroxyvitamin D (25[OH]D) concentrations in breast-fed...](profile/John-Pettifor/publication/259107681/figure/fig2/AS:340647446892548@1458228088317/25-Hydroxyvitamin-D-25OHD-concentrations-in-breast-fed-infants-in-response-to-2_Q320.jpg)
To determine whether a single monthly supplement is as effective as a daily maternal supplement in increasing breast milk vitamin D to achieve vitamin D sufficiency in their infants.
Forty mothers with exclusively breast-fed infants were randomized to receive oral cholecalciferol (vitamin D3) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum...
Contexts in source publication
Context 1
... baseline breast milk cholecalciferol concentrations were below the limit of quantitation of 7 ng/mL. Therefore, mean breast milk cholecalciferol values below the limit of quantitation have been designated as less than 7 ng/mL in Table 2. Baseline breast milk cholecalciferol was related to serum chole- calciferol (r¼0.38; ...
Context 2
... serum 25(OH)D values increased in both groups from baseline to day 28 (Table 2). The single-dose group had significantly greater maternal 25(OH)D concentrations than did the daily-dose group on days 1, 3, and 7 but not on days 14 and 28 ( Figure 1, A); the incremental change in 25(OH)D concentration was signifi- cantly greater in the single-dose group on days 1, 3, 7, and 14 but not on day 28. ...
Similar publications
The impact of vitamin D supplementation on 25-hydroxyvitamin D (25OHD) levels, metabolic status, and pregnancy outcomes in pregnant women with overweight and obesity (OW/OB) is uncertain. This study aimed to examine whether administrating 800 IU of vitamin D3 orally would improve maternal serum 25OHD levels, lipid profile, and pregnancy outcomes co...
Citations
... The American Academy of Pediatrics calls for supplementation with vitamin D at 400 IU/d beginning soon after birth in breastfed infants [10]. Maternal supplementation with vitamin D to enrich breast milk for infants is another method that has been studied to help meet infants' vitamin D requirements [11]. Calcium consumption in an infant depends on the mother's diet in breastfed infants; thus, calcium supplementation should also be considered on a case-by-case basis depending on how much calcium the mother of the infant consumes in her daily diet [12]. ...
... One manuscript focused on sulphated vitamin D metabolites in serum and HM and was not considered further (32). In addition, a study that reported serum 24,25(OH) 2 D 3 concentration and HM vitamin D 3 after supplementation (33) was not included since the HM data was the same as that published previously (34). Consequently, 15 manuscripts were reviewed in detail. ...
... Three manuscripts described methods and provided data on a small number of convenience or commercial HM samples (31, 36, 37). Four reports provided only brief method details and data from randomized controlled trials of maternal vitamin D supplementation (34,38,39). The remaining manuscripts gave either full or partial descriptions of an analytical method that was applied to observational studies across different population groups at different stages postpartum and in different countries with sample sizes ranging from a few to around 100 individuals. ...
... Similarly, a wide range of solvents, alone in or combination were used for LLE, partly reflecting optimisation of procedures for different vitamin D metabolites and their different polarities. These have included hexane (39,48,53), heptane (42), isopropanol (34), methanol (55), dichloromethane (38) or a mix of hexane:ethyl acetate (9:1) (36, 41, 43). ...
Vitamin D is essential for optimal bone health, and vitamin D deficiency has been associated with an increased risk of adverse pregnancy, growth and developmental outcomes. In early life, and in the absence of endogenous vitamin D production from UVB light, infants are reliant on vitamin D stores established in utero and the vitamin D supply from human milk (HM). However, comprehensive data on vitamin D in HM is lacking. Thus, in this review we explore the application of liquid-chromatography tandem mass spectrometry (LC–MS/MS) to the assessment of vitamin D in HM. We discuss the challenges of extracting and measuring multiple vitamin D metabolites from HM including the frequent requirement for a large sample volume, and inappropriate poor sensitivity. Shortcomings in the reporting of experimental procedures and data analysis further hinder advances in the field. Data collated from all studies that have applied LC–MS/MS reveal that, in general, cholecalciferol concentration is greater and more variable than 25-hydroxyvitamin D concentration, and that the vitamin D content of HM is low and less than the currently recommended dietary requirement of infants, although maternal supplementation can increase the vitamin D content of HM. Improvements in analytical methods and their validation and larger, more representative studies are required to better characterize HM milk vitamin D metabolite concentrations and their relationship with maternal status. These data are essential to understand relationships with infant health and to inform public health policies around vitamin D fortification and supplementation.
... The different forms of vitamin D contributed to total ARA in the following decreasing order: 25OHD3, vitamin D3, 25OHD2 and vitamin D2. Fifteen studies reported undetectable levels of vitamin D in all [23][24][25] or some of the breast milk samples [26][27][28][29][30][31][32][33][34][35][36][37]. Several studies had extremely low or high values, however none of the studies were found to be both highly outlying and influential. ...
... An analysis of the studies who specifically looked into the relationship between vitamin D supplementation and vitamin D concentration in breast milk was conducted. A total of 10 trials [26,27,31,32,35,37,[40][41][42][43] investigated the effect of vitamin D supplementation on breast milk concentration. All studies, except one [40], concluded that vitamin D supplementation could significantly increase vitamin D concentration in breast milk. ...
Background
Global estimates of calcium, zinc and vitamin D content in breastmilk are lacking. The objective of this systematic review was to determine the calcium, zinc, and vitamin D content in breast milk.
Methods
A systematic search of the online databases Embase, MEDLINE, and CENTRAL was conducted in November 2022 and complemented by searches of the African Journals Online database and the LILACS database, and reference lists. Studies reporting the calcium, zinc and vitamin D content in breast milk of apparently healthy mothers and infants were included. Random effects meta-analyses were conducted. The effect of influencing factors were investigated with sub-group analyses and meta-regressions.
Results
A total of 154 studies reporting on breast milk calcium were identified, with a mean calcium concentration in breast milk of 261 mg/L (95% CI: 238, 284). Calcium concentration was influenced by maternal health and decreased linearly over the duration of lactation. Calcium concentration at a specific time during lactation could be estimated with the equation: calcium concentration [mg/L] = 282 – 0.2331 ✕ number of days since birth. A total of 242 studies reporting on breast milk zinc were identified, with a mean zinc concentration of 2.57 mg/L (95% CI: 2.50, 2.65). Zinc concentration was influenced by several factors, such as maternal age, gestational age, and maternal diet. Zinc concentration started high in the first weeks post-partum followed by a rapid decrease over the first months. Zinc concentration at a specific time during lactation could be estimated with the equation: zinc concentration [mg/L] = 6 + 0.0005 ✕ days – 2.0266 ✕ log(days). A total of 43 studies reporting on breast milk vitamin D were identified, with a mean total antirachitic activity of breast milk of 58 IU/L (95% CI: 45, 70), which consisted mostly of 25OHD3, and smaller amounts of vitamin D3, 25OHD2 and vitamin D2. Vitamin D concentration showed wide variations between studies and was influenced by vitamin D supplementation, continent and season.
Conclusions
This review provides global estimates of calcium, zinc and vitamin D content in breast milk, as well as indications on changes over time and depending on influencing factors.
... Our results indicate that 4-week vitamin D3 supplementation resulted in an enhanced aerobic capacity and CD4 + /CD8 + ratio as well as lowered IL-6, CK, and LDH levels through performed strenuous endurance exercises. This result is consistent with those of studies indicating that 4-week vitamin D3 supplementation (at 5000 IU/day) can effectively enhance blood 25(OH)D levels-ranging from insufficient (21.89 ng/mL) to sufficient (44.67 ng/mL; Figure 2) [46,47]. ...
... Our results indicate that 4-week vitamin D 3 supplementation resulted in an enhanced aerobic capacity and CD4 + /CD8 + ratio as well as lowered IL-6, CK, and LDH levels through performed strenuous endurance exercises. This result is consistent with those of studies indicating that 4-week vitamin D 3 supplementation (at 5000 IU/day) can effectively enhance blood 25(OH)D levels-ranging from insufficient (21.89 ng/mL) to sufficient (44.67 ng/mL; Figure 2) [46,47]. ...
Reportedly, strenuous endurance exercise can depress the immune system and induce inflammation and muscle damage. Therefore, this double-blinded, matched-pair study aimed to investigate the impact of vitamin D3 supplementation on immune response (leukocyte, neutrophil, lymphocyte, CD4+, CD8+, CD19+, and CD56+ counts), inflammatory profile (TNF-α and IL-6), muscle damage (CK and LDH levels), as well as aerobic capacity after strenuous endurance exercise in 18 healthy men taking 5000 IU of vitamin D3 (n = 9) or placebo (n = 9) daily for 4 weeks. Total and differential blood leukocyte counts, levels of cytokines, and muscle damage biomarkers were determined before, immediately after, and 2, 4, and 24 h after exercise. The IL-6, CK, and LDH levels were significantly lower in vitamin D3 group at 2, 4, and 24 h post exercise (p < 0.05). Maximal and average heart rates during exercise were also significantly lower (p < 0.05). In the vitamin D3 group, the CD4+/CD8+ ratio after 4 weeks of supplementation was only significantly lower at post-0 than at baseline and significantly higher at post-2 than at baseline and post-0 (all p < 0.05). Taken together, 5000 IU of daily vitamin D3 supplementation for 4 weeks exhibited positive effects in terms of increased blood 25(OH)D levels, CD4+/CD8+ ratio (immune response), and aerobic capacity while inhibiting inflammatory cytokines and CK and LDH (muscle damage) in people performing strenuous endurance exercise.
... Therefore, vitamin D supplementation is recommended for infants in the US and globally. 12,13 Infants can receive supplementation directly with oral vitamin D drops or indirectly through breast milk from women who receive daily (4000 to 6400 IU/day [100 to 160 mcg/day]) or monthly (120,000 to 150,000 IU/month [3000 to 3750 mcg/ month]) high-dose vitamin D. 11,[14][15][16][17] Due to continued cases of nutritional rickets and inadequate sunlight exposure, the American Academy of Pediatrics (AAP) revised its guideline on infant vitamin D supplementation in 2008. The guideline recommended increasing supplementation of vitamin D from 200 to 400 IU per day starting in the first few days of life for all infants less than 1 year of age who are exclusively or partially breastfed and nonbreastfed infants who consume less than 1000 mL of formula per day. ...
Introduction:
Rates of infant vitamin D supplementation fall short of guideline recommendations. We explored this discrepancy from the clinician perspective as they advise and affect this important intervention to prevent rickets. We compared infant and high-dose maternal vitamin D supplementation prescribing attitudes and practices between infant-only clinicians (IC) and clinicians who care for mothers and infants (MIC).
Methods:
We surveyed clinicians in departments of family medicine, obstetrics/gynecology, primary care pediatrics, neonatology, newborn nursery, and members of vitamin D and rickets working groups and a social media group for lactation medicine providers about their perspectives and practices regarding vitamin D supplementation.
Results:
360 clinician survey responses were analyzed. In current practice, IC were more likely than MIC to recommend vitamin D supplementation to exclusively (P < .001) and partially breastfed infants (P = .005). MIC were more likely than IC to discuss infant and high-dose maternal supplementation options and let the parents/caregivers choose (34.7%, 22.0%, P = .009). If supplementing the mother with high-dose vitamin D or the infant directly each provided adequate vitamin D in the infant, MIC were more likely than IC to think that supplementation of the mother would be preferred by parents/caregivers (63.0%, 45.2%, P = .003), improve adherence (66.5%, 49.4%, P = .006), and promote breastfeeding (54.7%, 36.5%, P = .001); they were also more likely to recommend supplementation of the mother (17.7%, 8.9%, P = .04).
Conclusions:
MIC are more likely than IC to embrace high-dose maternal vitamin D supplementation to provide adequate vitamin D for infants. This highlights an opportunity for further education of clinicians about this option.
... Thus, the high doses of VD (e. g., 100,000 IU) administered in several of the aforementioned trials [49,[51][52][53] may actually promote vascular calcification, thereby counteracting any of its beneficial antihypertensive effects. Furthermore, while two studies demonstrated that large bolus doses of VD resulted in serum 25[OH]D levels that were similar to those reported in response to daily doses of VD, the levels obtained in response to the large bolus doses dropped significantly at the completion of the trials [70,71]. Given that (1) vascular tissue cells can synthesize calcitriol and (2) circulating 25[OH]D levels do not reflect the full extent of VD activity in target tissues [72,73], serum VD levels have been considered more important than serum 25[OH] D for the evaluation of VD activity in target tissues [55,56]. ...
Purpose of the Review
Results from epidemiological studies suggest that vitamin D (VD) deficiency (VDD) may be a cause of hypertension (HTN). However, the results of randomized clinical trials (RCTs) designed to address the impact of VD supplementation on reducing blood pressure (BP) remain equivocal. To determine whether VD might serve as a beneficial treatment option for a specific subset of hypertensive patients, we performed a stratified analysis of RCT data and addressed problems associated with some methodological issues.
Recent Findings
HTN is caused by multiple factors. VDD may be one of the factors contributing to the development of this disorder. There are more than 70 RCTs that examined the impact of VD supplementation on BP. These RCTs can be classified into four groups based on their respective study populations, including participants who are (1) VD-sufficient and normotensive, (2) VD-deficient and normotensive, (3) VD-sufficient and hypertensive, and (4) VD-deficient and hypertensive.
Summary
Our evaluation of these studies demonstrates that VD supplementation is ineffective when used to reduce BP in VD-sufficient normotensive subjects. VD supplementation for five years or more may reduce the risk of developing HTN specifically among those with VDD. Interestingly, findings from 12 RCTs indicate that daily or weekly supplementation, as opposed to large bolus dosing, results in the reduction of BP in VD-deficient hypertensive patients. Our ongoing research focused on elucidating the mechanisms of VDD-induced HTN will ultimately provide evidence to support the development of etiology-specific prevention and treatment strategies focused on HTN in the VD-deficient population.
... Seven studies focused on the exclusive maternal supplementation of VD and included a total of 652 mothers (Table 2; [38][39][40][41][42][43][44]). In four trials, mothers were provided with a daily dose of VD [39,40,43,44], while three studies evaluated the efficacy of a monthly VD administration [38,41,42]. ...
... Seven studies focused on the exclusive maternal supplementation of VD and included a total of 652 mothers (Table 2; [38][39][40][41][42][43][44]). In four trials, mothers were provided with a daily dose of VD [39,40,43,44], while three studies evaluated the efficacy of a monthly VD administration [38,41,42]. One study compared a single high dose administration given to mothers at delivery to an equivalent dose split over 28 days and found no differences in VD sufficiency neither in mothers nor infants at one month of life [44]. ...
... In four trials, mothers were provided with a daily dose of VD [39,40,43,44], while three studies evaluated the efficacy of a monthly VD administration [38,41,42]. One study compared a single high dose administration given to mothers at delivery to an equivalent dose split over 28 days and found no differences in VD sufficiency neither in mothers nor infants at one month of life [44]. ...
Vitamin D (VD) is an essential micronutrient with multiple functions for human growth, and adequate intake should be guaranteed throughout life. However, VD insufficiency is observed in infants all over the world. Low VD concentration in the breast milk of non-supplemented mothers and low compliance to VD daily supplementation are the main causes of VD insufficiency, especially in the long term. Furthermore, VD supplementation dosages are still debated and differ by country. We conducted a systematic review to compare the most recent evidence on different postnatal VD supplementation strategies, determining whether supplementation given to the mother is as effective as that administered directly to the child, and whether different dosages and administration schedules differ significantly in terms of efficacy and safety. We identified 18 randomized controlled trials (RCTs) addressing the role of infant (n = 961), maternal (n = 652) or combined infant and maternal VD supplementation (n = 260 pairs). In all studies, similar outcomes emerged in terms of efficacy and safety. According to our findings, alternative approaches of VD supplementation may be adopted, especially in cases where the adherence to daily supplementation strategies is poor. This review shows that different dosages and supplementation strategies result in similar VD sufficiency rates. Therefore, international guidelines may be revised in the future to offer multiple and different options of supplementation for specific settings and ages.
... This study showed that 120,000 IU monthly provided sufficient vitamin D in most but not all infants. Another study of 150,000 IU resulted in sufficiency for all infants after one month [7]. Thus, the optimal monthly maternal dose for lactating mothers is likely between 120,000 and 150,000 IU. ...
... Daily maternal supplementation with vitamin D 5000-6400 IU safely achieves sufficient serum 25(OH)D concen trations in breastfed infants [7][8][9]. Maternal supplemen-tation was preferred over infant supplementation by mothers in Minnesota, USA: 88.4% of the surveyed mothers preferred to supplement themselves rather than their infants [10]. Among family medicine clinicians, 87.5% would recommend either maternal supplementation (37.5%) or allow parents to choose between maternal or infant supplementation (50%) [11]. ...
... Supplementation of vitamin D in daily dose is more physiological; however, the bolus dose (weekly or monthly) is equally effective in terms of improving vitamin D status with a higher adherence rate [23]. Comparison of daily vs bolus dose of vitamin D supplementation in lactating mothers showed equal efficacy [24]. We used bolus doses of vitamin D for supplementation, which gave us a very high compliance rate with minimal dropouts (<5% in both groups). ...
Background:
There is a high prevalence of vitamin D deficiency (VDD) in exclusively breast-fed infants in the absence of appropriate vitamin D supplementation.
Objective:
To evaluate the efficacy of two doses of maternal vitamin D supplementation on vitamin D levels of mother-infant pairs and to assess its effect on growth parameters(weight, length and head circumference) and bone mass of infants.
Study design:
Randomized controlled trial.
Participants:
Lactating mother-infant pairs (n=220).
Intervention:
Maternal oral vitamin D supplementation in two doses (group 1: 120 000 IU/month and group 2: 12000 IU/month for 12 months.
Main-outcomes:
Maternal and infant serum 25OHD levels, and infant's growth and bone mass.
Results:
There was high prevalence of VDD at baseline in mothers (94%) as well as infants (98.5%) which was reduced to 43.1% in (mothers) and 46.5% in infants after 12 months. Significantly higher median (IQR) serum 25OHD levels (ng/mL) were observed among mothers in group 1 compared to group 2 [46 (17-159) vs 18 (6-64); P<0.01] and in infants [36.5 (15-160) vs 17 (7-32); P<0.01]. No significant association was observed between growth parameters or bone mass and serum 25OHD levels of mother or infant between the two groups. Four mothers (3.6%) and two infants (1.8%) in group I had serum 25OHD>100 ng/mL, but without hypercalciuria or hypercalcemia.
Conclusion:
Bolus vitamin D supplementation in the dose of 1,20,000IU/month was more efficacious in improving maternal and infant vitamin D status at 12 months, as compared to 12,000 IU/month.
... 11 Maternal vitamin D status determines the vitamin D levels of breastfeeding infants. 12,13 Vitamin D deficient mothers are more likely to have infants with vitamin D deficiency, affecting their immunity and protection against infection. The impact of vitamin D3 concentration in milk from lactating women and their incidence of COVID-19 infection have not been investigated. ...
... 12,28 Circulating vitamin D is transferred into human milk but circulating 25-hydroxyvitamin D does not. 13,29 The parent compound cholecalciferol (vitamin D3) is the major vitamin D metabolite that crosses from maternal serum into human milk. 13 The active vitamin D3 [1,25(OH)D 3 ] can bind to the vitamin D receptor, which potentially regulates the expression of genes involved in innate and adaptive immunity. ...
... 13,29 The parent compound cholecalciferol (vitamin D3) is the major vitamin D metabolite that crosses from maternal serum into human milk. 13 The active vitamin D3 [1,25(OH)D 3 ] can bind to the vitamin D receptor, which potentially regulates the expression of genes involved in innate and adaptive immunity. 30 Whether vitamin D3 in human milk influences the incidence of maternal COVID-19 infection remains unknown. ...
Background: Vitamin D deficiency was associated with an increased risk of coronavirus disease 2019 (COVID-19) infection. Vitamin D deficient mothers are more likely to have infants with vitamin D deficiency, affecting their immunity and protection against infection. This study aimed at comparing the concentrations of vitamin D3 and T cell-related cytokines in milk between mothers with confirmed COVID-19 polymerase chain reaction (PCR) test, mothers with viral infections suggestive of COVID-19, and mothers without infection.
Materials and Methods: Concentrations of vitamin D3 and T cell-related cytokines in milk samples were determined by ELISA from 10 mothers who had a positive COVID-19 PCR test, 10 mothers with viral symptoms suggestive of COVID-19, and 20 mothers without infection.
Results: Vitamin D3 concentration in human milk was higher in women without infection than in women with viral symptoms or COVID-19 PCR. Interleukin-2 level in milk was higher in the no-infection group than the COVID-19 PCR group but it did not differ with the viral symptoms group. Vitamin D3 did not correlate with any cytokines in human milk. Prenatal vitamin intake did not affect the vitamin D3 in human milk. The percentage of milk from mothers with <20 ng/mL of vitamin D3 was 50% in the COVID-19 PCR group, 60% in the viral symptoms group, and 5% in the no-infection group.
Conclusions: Vitamin D3 level in breast milk may influence maternal immunity against COVID-19 infection. A larger study is needed to evaluate the relationship between vitamin D3 concentration in breast milk, maternal immune response, and the incidence of COVID-19 infection in lactating mothers.
