비타민K2+D3

Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized Controlled Trial.

1. Nutrients. 2025 Jan 16;17(2):304. doi: 10.3390/nu17020304. Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized Controlled Trial. Atieh O(1), Daher J(1), Durieux JC(2), Abboud M(3), Labbato D(2), Baissary J(1), Koberssy Z(1), Ailstock K(4), Cummings M(4),

Effects of vitamin K2 and D3 supplementation on epicardial adipose tissue and systemic inflammation: A substudy of the AVADEC trial.

1. Atherosclerosis. 2025 Nov;410:120540. doi: 10.1016/j.atherosclerosis.2025.120540. Epub 2025 Oct 12. Effects of vitamin K2 and D3 supplementation on epicardial adipose tissue and systemic inflammation: A substudy of the AVADEC trial. Hasific S(1), Ravn EJ(2), Rasmussen LM(3), Mejldal A(4), Dey D(5), Frandsen NE(2), Lindholt JS(6), Auscher S(7), Lambrechtsen J(7), Hosbond S(8), Alan D(8), Urbonaviciene G(9), Becker S(9), Øvrehus KA(2), Diederichsen A(2). Author information: (1)University Hospital, Department of Cardiology, Odense, Denmark. Electronic address: selmahasific@outlook.com. (2)University Hospital, Department of Cardiology, Odense, Denmark. (3)Odense University Hospital, Department of Clinical Biochemistry, Odense, Denmark. (4)OPEN - Open Patient data Explorative Network, Odense University Hospital, Denmark. (5)Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, United States of America. (6)Odense University Hospital, Department of Cardiothoracic and Vascular Surgery, Odense, Denmark. (7)OUH Svendborg Hospital, Department of Cardiology, Svendborg, Denmark. (8)Lillebaelt Hospital, Department of Cardiology, Vejle, Denmark. (9)Aarhus University Hospital, Department of Cardiology, Aarhus, Denmark. BACKGROUND AND AIMS: Vitamins K2 and D3 may improve cardiovascular health by modulating inflammation and vascular calcification. Inflammation contributes to atherosclerosis and can be assessed through imaging and systemic biomarkers. This study investigated whether vitamin K2 and D3 supplementation reduces inflammation in epicardial adipose tissue (EAT), including pericoronary adipose tissue (PCAT), and systemic inflammation in elderly men at cardiovascular risk. METHODS: In the Aortic Valve DECalcification (AVADEC) trial, 388 men aged 65-74 received daily vitamin K2 (720 μg) and D3 (25 μg) or placebo for 24 months. EAT inflammation was assessed using non-contrast CT [EAT volume and attenuation] and contrast-enhanced CT [PCAT attenuation]. Systemic inflammation was evaluated via hs-CRP, IL-6, TNF-α, Fetuin-A, and osteopontin (OPN). Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), the inactive form of MGP, served as a proxy for vitamin K2 status. RESULTS: After 24 months, EAT volume increased in the placebo group (Δ5.66 cm3,95% CI 1.35; 9.98) and non-significantly in the vitamin group (Δ3.44 cm3, 95% CI -0.44; 7.33), with an intergroup difference of -2.22 cm3 (95% CI -8.01; 3.57). EAT attenuation declined similarly (intergroup difference: 0.32 HU, 95% CI -0.23; 0.87). PCAT attenuation remained unchanged. No significant changes were seen in systemic markers, though OPN increased modestly in the vitamin group (Δ25.72 pg/mL, 95% CI 2.40; 49.05). dp-ucMGP decreased significantly with supplementation (intergroup difference: 255.31 pmol/L, 95% CI -289.56; -221.05). CONCLUSIONS: Despite reduction in dp-ucMGP, high-dose vitamin K2 and D3 supplementation did not affect EAT, PCAT or systemic inflammation over 24 months. Alternative strategies may be needed to target inflammatory pathways in cardiovascular disease prevention. Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.atherosclerosis.2025.120540 PMID: 41100911 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial.

2. BMJ Open. 2023 Sep 22;13(9):e073761. doi: 10.1136/bmjopen-2023-073761. Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial. Seely D(1)(2)(3), Legacy M(4)(2), Conte E(4), Keates C(4), Psihogios A(4), Ramsay T(2)(5), Fergusson DA(2)(5), Kanji S(2)(6), Simmons JG(2)(7), Wilson K(2)(7)(8). Author information: (1)Patterson Institute for Integrative Oncology Research, Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada dseely@thechi.ca. (2)Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. (3)School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada. (4)Patterson Institute for Integrative Oncology Research, Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada. (5)School of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada. (6)Department of Pharmacy, Ottawa Hospital, Ottawa, Ontario, Canada. (7)Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. (8)Bruyère Research Institute, Ottawa, Ontario, Canada. BACKGROUND: COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D3, vitamin K2 and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19. METHODS: Participants were randomised to receive either vitamin C (6 g), vitamin D3 (1000 units), vitamin K2 (240 μg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D3 (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality. RESULTS: 90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control-treatment) in cumulative overall health was -37.4 (95% CI -157.2 to 82.3), p=0.53 on a scale of 0-2100. No clinically or statistically significant differences were seen in any secondary outcomes. INTERPRETATION: In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D3, vitamin K2 and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility. TRIAL REGISTRATION NUMBER: NCT04780061. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. DOI: 10.1136/bmjopen-2023-073761 PMCID: PMC10533655 PMID: 37739466 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: None declared.

Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial.

3. BMJ Open. 2023 Jul 14;13(7):e073233. doi: 10.1136/bmjopen-2023-073233. Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial. Hasific S(1), Øvrehus KA(1), Hosbond S(2), Lambrechtsen J(3), Kumarathurai P(1), Mejldal A(4)(5), Ravn EJ(1), Rasmussen LM(6)(7), Gerke O(8), Mickley H(1), Diederichsen A(9). Author information: (1)Department of Cardiology, Odense University Hospital, Odense, Denmark. (2)Department of Cardiology, Sygehus Lillebalt, Vejle, Syddanmark, Denmark. (3)Department of Cardiology, Svendborg Hospital, Svendborg, Denmark. (4)Department of Clinical Research, University of Southern Denmark, Odense, Denmark. (5)Open Patient Data Explorative Network, Odense University, Odense, Denmark. (6)Department of Clinical Biochemistry and Pharmacology, Odense Universitetshospital, Odense, Denmark. (7)Centre for Individualised Medicine in Arterial Diseases, Odense Universitetshospital, Odense, Denmark. (8)Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. (9)Department of Cardiology, Odense University Hospital, Odense, Denmark axel.diederichsen@rsyd.dk. INTRODUCTION: Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process. METHOD AND ANALYSIS: In this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses. ETHICS AND DISSEMINATION: There are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported. TRIAL REGISTRATION NUMBER: NCT05500443. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. DOI: 10.1136/bmjopen-2023-073233 PMCID: PMC10351276 PMID: 37451735 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: None declared.

Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial.

4. Nutrients. 2021 Dec 20;13(12):4554. doi: 10.3390/nu13124554. Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial. Nowak JK(1), Sobkowiak P(2), Drzymała-Czyż S(1)(3), Krzyżanowska-Jankowska P(1), Sapiejka E(4), Skorupa W(5), Pogorzelski A(6), Nowicka A(7), Wojsyk-Banaszak I(2), Kurek S(1), Zielińska-Psuja B(8), Lisowska A(1), Walkowiak J(1). Author information: (1)Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland. (2)Department of Pneumonology, Allergology and Clinical Immunology, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland. (3)Department of Bromatology, Poznan University of Medical Sciences, Marcelinska 42, 60-354 Poznan, Poland. (4)The Specialist Centre for Medical Care of Mother and Child, Polanki 119, 80-308 Gdańsk, Poland. (5)Department of Lung Diseases, Institute for Tuberculosis and Lung Diseases, Plocka 26, 01-138 Warsaw, Poland. (6)Department of Pneumology and Cystic Fibrosis, Institute of Tuberculosis and Lung Diseases, Rudnika 3, 34-700 Rabka-Zdroj, Poland. (7)Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569 Poznan, Poland. (8)Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30, 60-631 Poznan, Poland. Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of β-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma). DOI: 10.3390/nu13124554 PMCID: PMC8706805 PMID: 34960106 [Indexed for MEDLINE] Conflict of interest statement: J.K.N. reports personal fees from Norsa Pharma within an EU-funded project and grant support from Biocodex. S.D.-C., P.K.-J. and A.L. report personal fees from Norsa Pharma within an EU-funded project. J.W. reports personal fees and grant support from Norsa Pharma within an EU-funded project, as well as personal fees and non-financial support from Biocodex, BGP Products, Chiesi, Hipp, Humana, Mead Johnson Nutrition, Merck Sharp & Dohme, Nestle, Nutricia, Roche, Sequoia Pharmaceuticals, and Vitis Pharma, alongside, outside the submitted work, grants, personal fees, and non-financial support from Nutricia Research Foundation Poland.

Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial.

5. Diabetol Metab Syndr. 2020 Aug 18;12:73. doi: 10.1186/s13098-020-00580-w. eCollection 2020. Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial. Aguayo-Ruiz JI(1), García-Cobián TA(2), Pascoe-González S(2), Sánchez-Enríquez S(3), Llamas-Covarrubias IM(4), García-Iglesias T(2), López-Quintero A(4), Llamas-Covarrubias MA(4), Trujillo-Quiroz J(2), Rivera-Leon EA(4). Author information: (1)Pharmacology, Health Sciences University Center (CUCS), Universidad de Guadalajara (UdeG), 44350 Guadalajara, Jalisco Mexico. (2)Department of Physiology, Health Sciences University Center (CUCS), Universidad de Guadalajara (UdeG), 44350 Guadalajara, Jalisco Mexico. (3)Department of Clinics, Altos University Center (CuAltos), Universidad de Guadalajara (UdeG), 47620 Tepatitlán de Morelos, Jalisco Mexico. (4)Department of Molecular Biology and Genomics, Health Sciences University Center (CUCS), Universidad de Guadalajara (UdeG), 44350 Guadalajara, Jalisco Mexico. BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are characterized by chronic hyperglycemia as a consequence of decreased insulin sensitivity, which contributes to bone demineralization and could also be related to changes in serum levels of osteocalcin and insulin, particularly when coupled with a deficiency in the daily consumption of vitamins D3 and K2. The objective of this study was to evaluate the effect of vitamin D3 and vitamin K2 supplements alone or in combination on osteocalcin levels and metabolic parameters in patients with T2DM. METHODS: A double-blind, randomized clinical trial was carried out in 40 patients aged between 30 and 70 years old for 3 months. Clinical and laboratory assessment was carried out at the beginning and at the end of the treatment. The patients were divided into three groups: (a) 1000 IU vitamin D3 + a calcinated magnesium placebo (n = 16), (b) 100 µg of Vitamin K2 + a calcinated magnesium placebo (n = 12), and (c) 1000 IU vitamin D3 + 100 µg vitamin K2 (n = 12). RESULTS: After treatment in the total studied population, a significant decrease in glycemia (p = 0.001), HOMA-IR (Homeostatic model assessment-insulin resistance) (p = 0.040), percentage of pancreatic beta cells (p < 0.001), uOC/cOC index and diastolic blood pressure (p = 0.030) were observed; in vitamin D3 group, differences in serum undercarboxylated osteocalcin (p = 0.026), undercarboxylated to carboxylated osteocalcin index (uOC/cOC) (p = 0.039) glucose (p < 0.001) and  % of functional pancreatic beta cells (p < 0.001) were demonstrated. In vitamin K2 group a significant decrease in glycemia (p = 0.002), HOMA-IR (p = 0.041), percentage of pancreatic beta cells (p = 0.002), and in cOC (p = 0.041) were observed, conversely cOC concentration was found high. Finally, in the vitamins D3 + K2 a significant decrease in glycemia (p = 0.002), percentage of pancreatic beta cells (p = 0.004), and in the uOC/cOC index (p = 0.023) were observed. CONCLUSION: Individual or combined supplementation with vitamins D3 and K2 significantly decreases the glucose levels and  % of functional pancreatic beta cells, while D3 and D3 + K2 treatments also induced a reduction in the uOC/cOC index. Only in the group with vitamin D3 supplementation, it was observed a reduction in undercarboxylated osteocalcin while vitamin K2 increased the carboxylated osteocalcin levels.Trial registration NCT04041492. © The Author(s) 2020. DOI: 10.1186/s13098-020-00580-w PMCID: PMC7436967 PMID: 32831908 Conflict of interest statement: Competing interestsThere are no conflicts of interest between the authors.

Effect of Low-Dose Vitamin K2 Supplementation on Bone Mineral Density in Middle-Aged and Elderly Chinese: A Randomized Controlled Study.

6. Calcif Tissue Int. 2020 May;106(5):476-485. doi: 10.1007/s00223-020-00669-4. Epub 2020 Feb 14. Effect of Low-Dose Vitamin K2 Supplementation on Bone Mineral Density in Middle-Aged and Elderly Chinese: A Randomized Controlled Study. Zhang Y(1), Liu Z(1), Duan L(2), Ji Y(2), Yang S(1), Zhang Y(1), Li H(1), Wang Y(1), Wang P(1), Chen J(3), Li Y(4). Author information: (1)Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China. (2)Vitamin K2 Research Center, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110015, People's Republic of China. (3)Vitamin K2 Research Center, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110015, People's Republic of China. stcjp888@163.com. (4)Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150086, People's Republic of China. liying_helen@163.com. Previous studies indicated a positive effect of vitamin K2 (VK2) supplementation on bone turnover biomarkers and bone mineral density (BMD), but the doses varied, and few studies have focused on the difference between VK2 supplementation alone and in combination with calcium and vitamin D3. The aim of this study was to explore a low and effective dose of VK2 for improving BMD, and to examine whether the co-supplementation of VK2, calcium and vitamin D3 would bring greater effects. In this trial, a total of 311 community-dwelling men and postmenopausal women aged 50 and 75 years were randomly assigned to four groups, receiving placebo, 50 µg/day, 90 µg/day or co-supplementation with calcium (500 mg/day) and vitamin D3 (10 µg/day) for 1 year. At the endpoint, the bone loss of femoral neck was significantly lower in postmenopausal women in the two 90 µg groups (treatment × time, p = 0.006) compared with placebo, but no effects in men. Serum biomarkers cOC/ucOC ratio increased in the intervention groups (treatment × time, p < 0.001). VK2 supplementation in dose of 90 µg/day performed a significant effect on reducing bone loss in postmenopausal women, but in combination with calcium and vitamin D3 brought no additional effects.Trial registration This trial was registered at http://www.chictr.org.cn as chiCTR1800019240. DOI: 10.1007/s00223-020-00669-4 PMID: 32060566 [Indexed for MEDLINE]

Steady-state vitamin K2 (menaquinone-7) plasma concentrations after intake of dairy products and soft gel capsules.

7. Eur J Clin Nutr. 2016 Jul;70(7):831-6. doi: 10.1038/ejcn.2016.3. Epub 2016 Feb 24. Steady-state vitamin K2 (menaquinone-7) plasma concentrations after intake of dairy products and soft gel capsules. Knapen MH(1), Braam LA(1), Teunissen KJ(1), Van't Hoofd CM(1), Zwijsen RM(2), van den Heuvel EG(2), Vermeer C(1). Author information: (1)R&D Group VitaK, Biopartner Center Maastricht, Maastricht University, Maastricht, The Netherlands. (2)FrieslandCampina, Amersfoort, The Netherlands. BACKGROUND: In a previous human intervention study, we observed an improved vitamin K status after 8 weeks of intake of a yogurt that was fortified with vitamin K2 (as menaquinone-7, MK-7) and enriched with vitamins C and D3, magnesium and polyunsaturated fatty acids. It was hypothesized that the added nutrients contributed to this improvement. Here we report on a study in which we compared the fasting plasma concentrations of MK-7 from (a) yogurt enriched with MK-7, vitamins D3 and C, magnesium, n-3 poly unsaturated fatty acids (n-3 PUFA) and fish oil (yogurt Kplus), (b) yogurt fortified with MK-7 only (yogurt K) and (c) soft gel capsules containing only MK-7. SUBJECTS/METHODS: For 42 days, healthy men and postmenopausal women between 45 and 65 years of age daily consumed either yogurt K, yogurt Kplus or capsules. Circulating MK-7, 25-hydroxy vitamin D (25(OH)D) and markers for vitamin K status (uncarboxylated osteocalcin (ucOC) and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP)) were assessed. Plasma MK-7 was also measured during the washout period of 2 weeks. MK-7 and dp-ucMGP were measured in citrated plasma, and 25(OH)D3 and ucOC were measured in the serum. RESULTS: The increase in plasma MK-7 with the yogurt Kplus product was more pronounced than the increase in MK-7 with the capsules. Circulating dp-ucMGP and ucOC were significantly lowered after consumption of the yogurt products and the MK-7 capsules, reflecting vitamin K status improvement. No significant differences in fasting plasma concentrations of various biomarkers between the yogurts were found. CONCLUSIONS: Dairy matrix and nutrient composition may affect MK-7 delivery and improvement of vitamin K status. Yogurt fortified with MK-7 is a suitable matrix to improve the nutritional status of the fat-soluble vitamins. DOI: 10.1038/ejcn.2016.3 PMID: 26908424 [Indexed for MEDLINE]

A comparative effectiveness study of bone density changes in women over 40 following three bone health plans containing variations of the same novel plant-sourced calcium.

8. Int J Med Sci. 2011 Mar 2;8(3):180-91. doi: 10.7150/ijms.8.180. A comparative effectiveness study of bone density changes in women over 40 following three bone health plans containing variations of the same novel plant-sourced calcium. Kaats GR(1), Preuss HG, Croft HA, Keith SC, Keith PL. Author information: (1)Integrative Health Technologies, Inc, 4940 Broadway, San Antonio, Texas 78209, USA. grk@ihtglobal.com Erratum in Int J Med Sci. 2013;10(9):1135. BACKGROUND: The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans incorporating components of (1) improved nutrition, (2) increased health literacy, and (3) increased physical activity. OBJECTIVE: To conduct a Comparative Effectiveness Research (CER) study comparing changes in bone mineral density in healthy women over-40 with above-average compliance when following one of three bone health Plans incorporating the SG's three components. METHODS: Using an open-label sequential design, 414 females over 40 years of age were tested, 176 of whom agreed to participate and follow one of three different bone-health programs. One Plan contained a bone-health supplement with 1,000 IUs of vitamin D(3 )and 750 mg of a plant-sourced form of calcium for one year. The other two Plans contained the same plant form of calcium, but with differing amounts of vitamin D(3) and other added bone health ingredients along with components designed to increase physical activity and health literacy. Each group completed the same baseline and ending DXA bone density scans, 43-chemistry blood test panels, and 84-item Quality of Life Inventory (QOL). Changes for all subjects were annualized as percent change in BMD from baseline. Using self-reports of adherence, subjects were rank-ordered and dichotomized as "compliant" or "partially compliant" based on the median rating. Comparisons were also made between the treatment groups and two theoretical age-adjusted expected groups: a non-intervention group and a group derived from a review of previously published studies on non-plant sources of calcium. RESULTS: There were no significant differences in baseline BMD between those who volunteered versus those who did not and between those who completed per protocol (PP) and those who were lost to attrition. Among subjects completing per protocol, there were no significant differences between the three groups on baseline measurements of BMD, weight, age, body fat and fat-free mass suggesting that the treatment groups were statistically similar at baseline. In all three treatment groups subjects with above average compliance had significantly greater increases in BMD as compared to the two expected-change reference groups. The group following the most nutritionally comprehensive Plan outperformed the other two groups. For all three groups, there were no statistically significant differences between baseline and ending blood chemistry tests or the QOL self-reports. CONCLUSIONS: The increases in BMD found in all three treatment groups in this CER stand in marked contrast to previous studies reporting that interventions with calcium and vitamin D(3) reduce age-related losses of BMD, but do not increase BMD. Increased compliance resulted in increased BMD levels. No adverse effects were found in the blood chemistry tests, self-reported quality of life and daily tracking reports. The Plans tested suggest a significant improvement over the traditional calcium and vitamin D(3) standard of care. DOI: 10.7150/ijms.8.180 PMCID: PMC3053489 PMID: 21448303 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest: The authors have declared that no conflict of interest exists.

Fat-Soluble Vitamins in Standard vs. Liposomal Form Enriched with Vitamin K2 in Cystic Fibrosis: A Randomized Multi-Center Trial.

9. J Clin Med. 2022 Jan 17;11(2):462. doi: 10.3390/jcm11020462. Fat-Soluble Vitamins in Standard vs. Liposomal Form Enriched with Vitamin K2 in Cystic Fibrosis: A Randomized Multi-Center Trial. Nowak JK(1), Krzyżanowska-Jankowska P(1), Drzymała-Czyż S(1)(2), Goździk-Spychalska J(3), Wojsyk-Banaszak I(4), Skorupa W(5), Sapiejka E(6), Miśkiewicz-Chotnicka A(1), Brylak J(1), Zielińska-Psuja B(7), Lisowska A(1), Walkowiak J(1). Author information: (1)Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland. (2)Department of Bromatology, Poznan University of Medical Sciences, Marcelinska 42, 60-354 Poznan, Poland. (3)Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569 Poznan, Poland. (4)Department of Pediatric Pneumonology, Allergology and Clinical Immunology, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland. (5)Department of Lung Diseases, Institute for Tuberculosis and Lung Diseases, Plocka 26, 01-138 Warsaw, Poland. (6)The Specialist Centre for Medical Care of Mother and Child, Polanki 119, 80-308 Gdańsk, Poland. (7)Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30, 60-631 Poznan, Poland. BACKGROUND: We aimed to assess a liposomal fat-soluble vitamin formulation containing vitamin K2 with standard treatment in cystic fibrosis (CF). METHODS: A multi-center randomized controlled trial was carried out in 100 pancreatic-insufficient patients with CF. The liposomal formulation contained vitamin A as retinyl palmitate (2667 IU daily) and beta-carotene (1333 IU), D3 (4000 IU), E (150 IU), K1 (2 mg), and K2 as menaquinone-7 (400 µg). It was compared with the standard vitamin preparations in the closest possible doses (2500 IU, 1428 IU, 4000 IU, 150 IU, 2.14 mg, respectively; no vitamin K2) over 3 months. RESULTS: Forty-two patients finished the trial in the liposomal and 49 in the control group (overall 91 pts: 22.6 ± 7.6 years, 62.6% female, BMI 19.9 ± 2.8 kg/m2, FEV1% 70% ± 30%). The main outcome was the change of vitamin status in the serum during the study (liposomal vs. standard): all-trans-retinol (+1.48 ± 95.9 vs. -43.1 ± 121.4 ng/mL, p = 0.054), 25-hydroxyvitamin D3 (+9.7 ± 13.4 vs. +2.0 ± 9.8 ng/mL, p = 0.004), α-tocopherol (+1.5 ± 2.5 vs. -0.2 ± 1.6 µg/mL, p < 0.001), %undercarboxylated osteocalcin (-17.2 ± 24.8% vs. -8.3 ± 18.5%, p = 0.061). The secondary outcome was the vitamin status at the trial end: all-trans-retinol (370.0 ± 116.5 vs. 323.1 ± 100.6 ng/mL, p = 0.045), 25-hydroxyvitamin D3 (43.2 ± 16.6 vs. 32.7 ± 11.5 ng/mL, p < 0.001), α-tocopherol (9.0 ± 3.1 vs. 7.7 ± 3.0 µg/mL, p = 0.037), %undercarboxylated osteocalcin (13.0 ± 11.2% vs. 22.7 ± 22.0%, p = 0.008). CONCLUSION: The liposomal fat-soluble vitamin supplement containing vitamin K2 was superior to the standard form in delivering vitamin D3 and E in pancreatic-insufficient patients with CF. The supplement was also more effective in strengthening vitamin K-dependent carboxylation, and could improve vitamin A status. DOI: 10.3390/jcm11020462 PMCID: PMC8777794 PMID: 35054157 Conflict of interest statement: J.K.N. reports personal fees from Norsa Pharma within an EU-funded project and grant support from Biocodex. P.K.-J., S.D.-C. and A.L. report personal fees from Norsa Pharma within an EU-funded project. J.W. reports personal fees and grant support from Norsa Pharma within an EU-funded project, personal fees and non-financial support from Biocodex, BGP Products, Chiesi, Hipp, Humana, Mead Johnson Nutrition, Merck Sharp & Dohme, Nestle, Nutricia, Roche, Sequoia Pharmaceuticals, and Vitis Pharma, outside the submitted work, grants, personal fees and non-financial support from Nutricia Research Foundation Poland, also outside the submitted work. The remaining authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study.

10. J Pediatr Endocrinol Metab. 2021 Feb 25;34(4):441-447. doi: 10.1515/jpem-2020-0637. Print 2021 Apr 27. Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study. Solmaz I(1)(2), Ozdemir MA(1), Unal E(1), Abdurrezzak U(3), Muhtaroglu S(4), Karakukcu M(1). Author information: (1)Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Erciyes University, Kayseri, Turkey. (2)Department of Pediatric Neurology, Hacettepe University, Ankara, Turkey. (3)Department of Nuclear Medicine, Faculty of Medicine, Erciyes University, Kayseri, Turkey. (4)Department of Biochemistry, Faculty of Medicine, Erciyes University, Kayseri, Turkey. OBJECTIVES: Current treatment protocols in acute lymphoblastic leukemia (ALL) are associated with high remission rates and long life expectancy, enhancing the importance of quality of life and prevention of treatment-related complications in patient care. As osteoporosis is a frequent complication in patients under chemotherapy, we investigated the effect of vitamin K2 (100 mcg menaquinone-7) and vitamin D3 (10 mcg calcitriol) on bone metabolism in children with ALL. METHODS: Twenty-nine consecutive patients recently diagnosed with B precursor ALL (B-ALL) and treated according to the Turkish Acute Lymphoblastic Leukemia Berlin Frankfurt Münster 2000 protocol were randomly assigned into study and control groups. The study group (n=15, M/F: 8/7, age 1-14.5 years, mean 6.5 years) received vitamin K2 and vitamin D3 with their chemotherapy, while the control group (n=14, M/F 9/5, age 2-17 years, mean 7.1 years) received chemotherapy only. Serum calcium, phosphorus, magnesium, alkaline phosphatase, bone-specific alkaline phosphatase, uncarboxylated osteocalcin (ucOC), tartrate resistant acid phosphatase 5b, carboxyl terminal procollagen propeptide (PICP), osteoprotegerin (OPG), and receptor activator nuclear kappa B ligand (RANKL) were measured and bone mineral density (BMD) was determined at baseline and first, second, third and sixth months. RESULTS: The study group had higher serum OPG/RANKL ratio and lower ucOC levels compared to the control group at the first month; PICP levels were higher in the study group at second and third months. CONCLUSIONS: These results suggest an early beneficial effect of the combination of vitamin K2 and vitamin D3 on BMD in ALL patients especially during the period of intensive steroid therapy in the first months. © 2021 Walter de Gruyter GmbH, Berlin/Boston. DOI: 10.1515/jpem-2020-0637 PMID: 33639045 [Indexed for MEDLINE]

The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial.

11. Osteoporos Int. 2021 Jan;32(1):185-191. doi: 10.1007/s00198-020-05638-z. Epub 2020 Oct 8. The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. Rønn SH(1), Harsløf T(1), Oei L(1)(2), Pedersen SB(1), Langdahl BL(3). Author information: (1)Aarhus University Hospital, Palle Juul-Jensen Boulevard 99, 8200, Aarhus N, Denmark. (2)Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. (3)Aarhus University Hospital, Palle Juul-Jensen Boulevard 99, 8200, Aarhus N, Denmark. bente.langdahl@aarhus.rm.dk. We conducted a randomized placebo-controlled double-blinded clinical trial of MK-7 or placebo daily for 3 years in postmenopausal women with osteopenia. BMD decreased at all sites without differences between the MK-7 and placebo-treated women. Changes in bone turnover markers and microstructure were similar between the two groups. INTRODUCTION: Vitamin K is a cofactor in the carboxylation of osteocalcin (OC) and carboxylated OC promotes mineralization of bone. Clinical studies suggest that vitamin K2 prevents bone loss. The aim of the study was to investigate the effect of vitamin K2 as an add-on to calcium and vitamin D supplementation on osteocalcin, bone mass, and microarchitecture in postmenopausal women. METHODS: We conducted a randomized placebo-controlled double-blinded clinical trial, including 142 postmenopausal women with osteopenia who received vitamin K2 (375 μg MK-7) or placebo daily for 3 years. Both groups received vitamin D3 (38 μg/day) and calcium (800 mg/day). We measured bone turnover markers in serum and bone mineral density and microarchitecture by DXA and HRpQCT. RESULTS: Undercarboxylated osteocalcin decreased in the MK-7-group (- 65.2 ± 23.5%) (mean ± SD) compared with the placebo group (- 0.03 ± 38.5%), p < 0.01 after 1 year. After 3 years, aBMD decreased at all sites without differences between the MK-7 and placebo-treated women (p > 0.09). aBMD decreased at the total hip by 1.5 ± 2.5% and 2.4 ± 2.7% in the MK-7 and the placebo groups, respectively, at the femoral neck by 1.5 ± 3.5% and 1.0 ± 5.0% in the MK-7 and the placebo groups, respectively, and at the lumbar spine by 1.8 ± 3.9% and 1.1 ± 3.1% in the MK-7 and the placebo groups, respectively. Changes in bone turnover markers were also similar between the two groups.We have previously reported improved microarchitecture with MK-7 after 1 year. However, changes in microstructure over 3 years were similar between the two groups, as assessed by both HRpQCT and DXA trabecular bone score. CONCLUSION: Treatment with MK-7 375 μg daily as an add-on to calcium and vitamin D increased carboxylation of osteocalcin. However, treatment of postmenopausal women with osteopenia for 3 years did not affect biochemical markers of bone turnover, bone mineral density, or bone microarchitecture. TRIAL REGISTRATION: The study was registered at Clinicaltrial.gov : NCT01922804 . DOI: 10.1007/s00198-020-05638-z PMID: 33030563 [Indexed for MEDLINE]

Effects of macro- and micronutrients on exercise-induced hepcidin response in highly trained endurance athletes.

12. Appl Physiol Nutr Metab. 2017 Oct;42(10):1036-1043. doi: 10.1139/apnm-2017-0207. Epub 2017 Jun 12. Effects of macro- and micronutrients on exercise-induced hepcidin response in highly trained endurance athletes. Dahlquist DT(1)(2), Stellingwerff T(1)(2), Dieter BP(3), McKenzie DC(1)(4), Koehle MS(1)(4). Author information: (1)a UBC Environmental Physiology Laboratory, School of Kinesiology, University of British Columbia, Vancouver, BC V6T 1Z1, Canada. (2)b Canadian Sport Institute - Pacific, Victoria, BC V9E 2C5, Canada. (3)c Providence Health Care, Providence Sacred Heart Medical Center and Children's Hospital, Spokane, WA 99204, USA. (4)d Division of Sports Medicine, University of British Columbia, Vancouver, BC V6T 1Z1, Canada. Iron deficiency has ergolytic effects on athletic performance. Exercise-induced inflammation impedes iron absorption in the digestive tract by upregulating the expression of the iron regulatory protein, hepcidin. Limited research indicates the potential of specific macro- and micronutrients on blunting exercise-induced hepcidin. Therefore, we investigated the effects of postexercise supplementation with protein and carbohydrate (CHO) and vitamins D3 and K2 on the postexercise hepcidin response. Ten highly trained male cyclists (age: 26.9 ± 6.4 years; maximal oxygen uptake: 67.4 ± 4.4 mL·kg-1·min-1 completed 4 cycling sessions in a randomized, placebo-controlled, single-blinded, triple-crossover study. Experimental days consisted of an 8-min warm-up at 50% power output at maximal oxygen uptake, followed by 8 × 3-min intervals at 85% power output at maximal oxygen uptake with 1.5 min at 60% power output at maximal oxygen uptake between each interval. Blood samples were collected pre- and postexercise, and at 3 h postexercise. Three different drinks consisting of CHO (75 g) and protein (25 g) with (VPRO) or without (PRO) vitamins D3 (5000 IU) and K2 (1000 μg), or a zero-calorie control drink (PLA) were consumed immediately after the postexercise blood sample. Results showed that the postexercise drinks had no significant (p ≥ 0.05) effect on any biomarker measured. There was a significant (p < 0.05) increase in hepcidin and interleukin-6 following intense cycling intervals in the participants. Hepcidin increased significantly (p < 0.05) from baseline (nmol·L-1: 9.94 ± 8.93, 14.18 ± 14.90, 10.44 ± 14.62) to 3 h postexercise (nmol·L-1: 22.27 ± 13.41, 25.44 ± 11.91, 22.57 ± 15.57) in VPRO, PRO, and PLA, respectively. Contrary to our hypothesis, the drink compositions used did not blunt the postexercise hepcidin response in highly trained athletes. DOI: 10.1139/apnm-2017-0207 PMID: 28605609 [Indexed for MEDLINE]

Possible site-specific effect of an intervention combining nutrition and lifestyle counselling with consumption of fortified dairy products on bone mass: the Postmenopausal Health Study II.

13. J Bone Miner Metab. 2011 Jul;29(4):501-6. doi: 10.1007/s00774-010-0256-2. Epub 2011 Apr 1. Possible site-specific effect of an intervention combining nutrition and lifestyle counselling with consumption of fortified dairy products on bone mass: the Postmenopausal Health Study II. Moschonis G(1), Kanellakis S, Papaioannou N, Schaafsma A, Manios Y. Author information: (1)Department of Nutrition and Dietetics, Harokopio University of Athens, 70, El.Venizelou Ave, Kallithea, 176 71 Athens, Greece. gmoschi@hua.gr The aim of the present study was to examine whether a holistic approach combining nutrition and lifestyle counselling with the consumption of milk and yoghurt enriched with calcium, vitamin D(3) and phylloquinone (vitamin K(1)) or menaquinone (vitamin K(2)) would have any additional benefit on bone mineral density (BMD) indices measured at various skeletal sites using two different techniques, dual energy X-ray absorptiometry and quantitative ultrasonography (QUS). A sample of 115 postmenopausal women were randomized to three intervention groups, receiving daily via fortified milk and yoghurt and for 12 months, 800 mg calcium and 10 μg vitamin D(3) (CaD group, n = 26); 800 mg calcium, 10 μg vitamin D(3) and 100 μg vitamin K(1) (CaDK1 group, n = 26); 800 mg calcium, 10 μg vitamin D(3) and 100 μg vitamin K(2) (CaDK2 group, n = 24); and a control group (CO group, n = 39) following their usual diet. All three intervention groups attended biweekly nutrition and lifestyle counselling sessions. Total BMD significantly increased in all three intervention groups and these changes were significantly higher compared to the CO (P < 0.001). Furthermore, the significant increases observed for L2-L4 BMD in the CaDK1 and CaDK2 groups were found to be significantly higher compared to the decrease observed in the CO (P = 0.001). No significant differences were observed for QUS parameters. The combined approach used in the current study led to favourable changes for all three intervention groups in total body BMD, while an additional benefit was observed for L2-L4 BMD in CaDK1 and CaDK2 groups. No significant differences were observed among groups in any of the QUS parameters. DOI: 10.1007/s00774-010-0256-2 PMID: 21455716 [Indexed for MEDLINE]

[A-TOP research group/JOINT program].

14. Nihon Rinsho. 2009 May;67(5):1017-21. [A-TOP research group/JOINT program]. [Article in Japanese] Kuroda T(1), Miyakawa N, Miyazaki T, Shiraki M. Author information: (1)Comprehensive Support Project for A-TOP, Public Health Research Foundation. A-TOP research consortium has been authorized at 2000 by the Japanese Society of Osteoporosis and assisted by Public Health Research Foundation in order to obtain the clinical evidences regarding osteoporosis treatment. Each clinical trial program was named as JOINT (Japanese Osteoporosis Intervention Trial), which was multi-center randomized open label trial and was registered into clinical trial registry. JOINT-02 was started at 2003 to confirm the effect of combination treatment of active vitamin D3 and alendronate in the prevention of osteoporotic bone fracture occurrence. This trial will be terminated at 2009 and the subsequent third clinical trial to obtain the evidence regarding the combination effects of risedronate and vitamin K2 as JOINT-03 project has been started from 2008. Each trial included around 2,000 participants mainly from practitioner and the registration of the cases in JOINT-02 has been finished within 3 years, suggesting that the participated practitioner would have sympathy with the research aims. The A-TOP research group would have carried out epidemiological studies regarding establishment of osteoporosis database (JOB study), which will contribute the additional knowledge of Japanese osteoporosis. PMID: 19432126 [Indexed for MEDLINE]

[Concurrent treatment of osteoporosis including vitamin K].

15. Clin Calcium. 2007 Nov;17(11):1731-7. [Concurrent treatment of osteoporosis including vitamin K]. [Article in Japanese] Kobayashi S(1), Shiraki M, Takaoka K. Author information: (1)Shinshu University School of Medicine, Department of Orthopaedic Surgery. The 2006 version of the guideline for prophylaxis and treatment of osteoporosis recommends vitamin K(VK)supplementation in the state of its deficiency. As VK(2) gained grade B in all aspects in the guideline, single use of the drug is limited. VK(2) may be used concurrently with other drugs in the treatment of osteoporosis. In this paper, the results of our concurrent use of two of vitamin D(3), VK(2), and EHDP are summarized, and the combined therapy including VK(2) will be reviewed. PMID: 17982194 [Indexed for MEDLINE]

Comparative studies on effect of risedronate and alfacalcidol against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients.

16. Yakugaku Zasshi. 2007 Sep;127(9):1491-6. doi: 10.1248/yakushi.127.1491. Comparative studies on effect of risedronate and alfacalcidol against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients. Yamada S(1), Takagi H, Tsuchiya H, Nakajima T, Ochiai H, Ichimura A, Iwata H, Toriyama T. Author information: (1)Department of Pharmacy, Kaikokai Nagoya Kyoritsu Hospital, Hokke, Nagoya, Japan. syamada@kaikou.or.jp Osteoporosis is a common adverse reaction induced by glucocorticoid treatment. Bisphosphonate, vitamin D(3) (VD(3)) or vitamin K(2) (VK(2)) is recommended as first or second choice of drug for treatment of glucocorticoid-induced osteoporosis. In the present study, the treatment effect of risedronate against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients was compared with that of alfacalcidol. Twelve patients were randomized to receive either risedronate (2.5 mg) or alfacalcidol (0.5 microg) daily for 48 weeks. Each patient also received 800 mg of calcium supplementation (800 mg/day) daily. Bone mineral density (BMD) and the biochemical markers of bone turnover were measured before (baseline) and 12, 24, and 48 weeks after treatment with risedronate or alfacalcidol, and the percentage changes in these parameters from baseline were compared. The BMD values 12, 24 and 48 weeks after treatment with risedronate increased by 3.9%, 4.1% and 5.2%, respectively, which were significantly higher than those after treatment with alfacalcidol (2.8%, 2.1% and 2.5%, respectively). Urinary excretion of N-telopeptides of type I collagen and deoxypyridinoline after risedronate treatment were more significantly decreased than that after alfacalcidol treatment. The present findings at least suggest that risedronate is more useful for the prevention and treatment of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis than alfacalcidol, although the number of patients studied was small. DOI: 10.1248/yakushi.127.1491 PMID: 17827929 [Indexed for MEDLINE]