Vitamin D and Vitamin K intervention trials - many studies

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10,600 Vitamin K plus D trials in Google Scholar as of Sept 2022

("vitamin K" OR "Vitamin K2") (trial OR RCT) "vitamin d"

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The impact of vitamin K2 and native vitamin D supplementation on vascular calcification in pediatric patients on regular hemodialysis. A randomized controlled trial - June 2022

European J. of Clinical Nutrition Vol 76, pages 848–854 (2022) https://doi.org/10.1038/s41430-021-01050-w
Radwa El Borolossy & Mohamed Samy El-Farsy

Background and aim
Vascular calcification is one of the most prevalent disorders in pediatric hemodialysis patients that eventually lead to cardiovascular morbidity. Vitamin K2 was investigated in adults in previous studies and showed favorable effects on calcification markers. Our aim in this study was to evaluate the efficacy and safety of vitamin K2 and cholecalciferol on the calcification regulators in pediatric patients.

Methods
A prospective, randomized and controlled trial was conducted on sixty hemodialysis pediatric patients who were divided to four groups; Group 1: administered 100 µg of vitamin K2 (MK-7); Group 2: administered 10 µg of native vitamin D; Group 3: administered 100 µg of vitamin K2 (MK-7) in addition 10 µg of native vitamin D, and Group 4: administered the standard therapy only. The duration of supplementation was 4 months. In addition to a group of healthy normal control of age and sex-matched.

Results
At the end of the study period, serum levels of FGF23, dp-uc-MGP, and uc-OC were measured. It was found that serum levels of dp-uc-MGP, uc-OC, and FGF23 were significantly higher (p < 0.05) in the hemodialysis patients as compared to the healthy normal control. After 4 months, group 3 revealed the most significant decrease in dp-uc-MGP, uc-OC as compared to the other groups. However, there was no change in FGF23.

Conclusion
Vitamin K2 and native vitamin D showed a beneficial effect on calcification regulators in pediatric hemodialysis patients.

Trial registration: clinical trial.gov (NCT04145492).

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The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials - March 2020

Food and Function https://doi.org/10.1039/C9FO03063H
Xiaotong Kuang, ORCID logo a Chunxiao Liu,a Xiaofei Guo, ORCID logo a Kelei Li,a Qingxue Denga and Duo Li ORCID logo *a

Background: Previous studies did not draw a consistent conclusion about the effects of vitamin K combined with vitamin D on human skeletal quality.

Method and findings: A comprehensive search on Web of Science, PubMed, Embase and the Cochrane Library (from 1950 to February 2020) and bibliographies of relevant articles was undertaken, with the meta-analysis of eight randomized controlled trials (RCTs) including a total of 971 subjects. Vitamin K combined with vitamin D significantly increased the total bone mineral density (BMD): the pooled effect size was 0.316 [95% CI (confidence interval), 0.031 to 0.601]. A significant decrease in undercarboxylated osteocalcin (−0.945, −1.113 to −0.778) can be observed with the combination of vitamin K and D. Simultaneously, subgroup analysis showed that K2 or vitamin K (not specified) supplement was less than 500 μg d−1, which when combined with vitamin D can significantly increase the total BMD compared with the control group fed a normal diet or the group with no treatment (0.479, 0.101 to 0.858 and 0.570, 0.196 to 0.945).

Conclusions: The combination of vitamin K and D can significantly increase the total BMD and significantly decrease undercarboxylated osteocalcin, and a more favorable effect is expected when vitamin K2 is used.

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Vitamin D–vitamin K interaction: effect of vitamin D supplementation on serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, in Danish girls - May 2010

British Journal of Nutrition Volume 104 Issue 8
Eibhlís O'Connor. Christian Mølgaard. Kim F. Michaelsen Jette Jakobsen Kevin D. Cashman

There is some evidence for a nutritional interaction between vitamin D and vitamin K status. We have recently reported that serum percentage undercarboxylated osteocalcin (%ucOC; a marker of vitamin K status) was inversely correlated with serum 25-hydroxyvitamin D (25(OH)D) concentration (reflective of vitamin D status) in healthy Danish girls (aged 11–12 years), in line with a similar relationship reported in elderly women. While the causal nature of the relationship between vitamin D status and serum %ucOC has been tested in studies of elderly women, it has not been investigated in children. The objective of the present study was to test the hypothesis that improving vitamin D status significantly lowers serum %ucOC. Serum samples from sixty-seven healthy Danish girls (aged 11–12 years), who participated in a 12-month double-blind, placebo-controlled, vitamin D3 intervention trial were used for the present study. These girls were a subset of subjects which began and finished the intervention during wintertime, thus avoiding the influence of seasonality on vitamin D status. A total of thirty-three and thirty-four of the girls had been randomised to treatment with 10 μg vitamin D3 per d and placebo, respectively, for 12 months. Total osteocalcin and the fraction of ucOC in serum (via enzyme-immunoassay) as well as serum 25(OH)D (via HPLC) were assessed at baseline and end-point. Vitamin D3 supplementation significantly increased serum 25(OH)D (21·6 %; P < 0·002) but had no effect on serum %ucOC (P>0·8). In conclusion, the findings of the present intervention study in young girls suggest that vitamin D supplementation does not affect serum %ucOC, a marker of vitamin K status.
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Calcium, vitamin D, vitamin K2, and magnesium supplementation and skeletal health - Oct 2020

Maturitas Volume 140, October 2020, Pages 55-63, https://doi.org/10.1016/j.maturitas.2020.05.020

Supplementation with calcium (Ca) and/or vitamin D (vitD) is key to the management of osteoporosis. Other supplements like vitamin K2 (VitK2) and magnesium (Mg) could contribute to the maintenance of skeletal health. This narrative review summarizes the most recent data on Ca, vitD, vitK2 and Mg supplementation and age-related bone and muscle loss. Ca supplementation alone is not recommended for fracture prevention in the general postmenopausal population. Patients at risk of fracture with insufficient dietary intake and absorption could benefit from calcium supplementation, but it needs to be customized, taking into account possible side-effects and degree of adherence. VitD supplementation is essential in patients at risk of fracture and/or vitD deficiency. VitK2 and Mg both appear to be involved in bone metabolism. Data suggest that VitK2 supplementation might improve bone quality and reduce fracture risk in osteoporotic patients, potentially enhancing the efficacy of Ca ± vitD. Mg deficiency could negatively influence bone and muscle health. However, data regarding the efficacy of vitK2 and Mg supplementation on bone are inconclusive.
 PDF of clips, references, and citations Sept 2022

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Joint Association of Low Vitamin D and Vitamin K Status With Blood Pressure and Hypertension - April 2017

HypertensionVol. 69, No. 6J 2017;69:1165–1172 https://doi.org/10.1161/HYPERTENSIONAHA.116

Low vitamin D and K status are both associated with an increased cardiovascular risk. New evidence from experimental studies on bone health suggest an interaction between vitamin D and K; however, a joint association with vascular health outcomes is largely unknown. To prospectively investigate whether the combination of low vitamin D and K status is associated with higher systolic and diastolic blood pressure in 402 participants and with incident hypertension in 231 participants free of hypertension at baseline. We used data from a subsample of the Longitudinal Aging Study Amsterdam, a population-based cohort of Dutch participants aged 55 to 65 years. Vitamin D and K status were assessed by 25-hydroxyvitamin D and dp-ucMGP (dephosphorylated uncarboxylated matrix gla protein) concentrations (high dp-ucMGP is indicative for low vitamin K status) in stored samples from 2002 to 2003. Vitamin D and K status were categorized into 25-hydroxyvitamin D <50/≥50 mmol/L and median dp-ucMGP <323/≥323 pmol/L. During a median follow-up of 6.4 years, 62% of the participants (n=143) developed hypertension. The combination of low vitamin D and K status was associated with increased systolic 4.8 mm Hg (95% confidence interval, 0.1–9.5) and diastolic 3.1 mm Hg (95% confidence interval, 0.5–5.7) blood pressure compared with high vitamin D and K status (P for interaction =0.013 for systolic blood pressure and 0.068 for diastolic blood pressure). A similar trend was seen for incident hypertension: hazard ratio=1.62 (95% confidence interval, 0.96–2.73) for the low vitamin D and K group. The combination of low vitamin D and K status was associated with increased blood pressure and a trend for greater hypertension risk.
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