Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?

Chronic Kidney Disease (CKD) patients are at high risk of presenting with arterial calcification or stiffness, which confers increased cardiovascular mortality and morbidity. In recent years, it has become evident that VC is an active process regulated by various molecules that may act as inhibitors of vessel mineralization. Matrix Gla Protein (MGP), one the most powerful naturally occurring inhibitors of arterial calcification, requires vitamin K as a co-factor in order to undergo post-translational γ-carboxylation and phosphrorylation and become biologically active. The inactive form of MGP (dephosphorylated, uncarboxylated dp-ucMGP) reflects vitamin K deficiency and has been repeatedly associated with surrogate markers of VC, stiffness, and cardiovascular outcomes in CKD populations. As CKD is a state of progressive vitamin K depletion and VC, research has focused on clinical trials aiming to investigate the possible beneficial effects of vitamin K in CKD and dialysis patients. In this study, we aim to review the current evidence regarding vitamin K supplementation in uremic patients.     

Hepatic and Vascular Vitamin K Status in Patients with High Cardiovascular Risk

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r² ≤ 0.26) and distinct distribution pattern in renal and non-renal patients. In conclusion, VKA use exacerbated vitamin K deficiency across all etiologies, while vitamin K supplementation resulted in a vascular VKDP status better than that of the general population. Weak correlation of vitamin K biomarkers calls for thoughtful selection lead by the research question. Vitamin K status in non-renal deficient patients was not anomalous and may question the role of vitamin K deficiency in the pathogenesis of VC in these patients.     

Vitamin K status and vascular calcification: evidence from observational and clinical studies

Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality. A preventive role for vitamin K in vascular calcification has been proposed based on its role in activating matrix Gla protein (MGP), a calcification inhibitor that is expressed in vascular tissue. Although animal and in vitro data support this role of vitamin K, overall data from human studies are inconsistent. The majority of population-based studies have relied on vitamin K intake to measure status. Phylloquinone is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone, but not phylloquinone, to be associated with less calcification. Vascular calcification is highly prevalent in certain patient populations, especially in those with chronic kidney disease (CKD), and it is plausible vitamin K may contribute to reducing vascular calcification in patients at higher risk. Subclinical vitamin K deficiency has been reported in CKD patients, but studies linking vitamin K status to calcification outcomes in CKD are needed to clarify whether or not improving vitamin K status is associated with improved vascular health in CKD. This review summarizes the available evidence of vitamin K and vascular calcification in population-based studies and clinic-based studies, with a specific focus on CKD patients.     

The role of vitamin K in soft-tissue calcification

Seventeen vitamin K-dependent proteins have been identified to date of which several are involved in regulating soft-tissue calcification. Osteocalcin, matrix Gla protein (MGP), and possibly Gla-rich protein are all inhibitors of soft-tissue calcification and need vitamin K-dependent carboxylation for activity. A common characteristic is their low molecular weight, and it has been postulated that their small size is essential for calcification inhibition within tissues. MGP is synthesized by vascular smooth muscle cells and is the most important inhibitor of arterial mineralization currently known. Remarkably, the extrahepatic Gla proteins mentioned are only partly carboxylated in the healthy adult population, suggesting vitamin K insufficiency. Because carboxylation of the most essential Gla proteins is localized in the liver and that of the less essential Gla proteins in the extrahepatic tissues, a transport system has evolved ensuring preferential distribution of dietary vitamin K to the liver when vitamin K is limiting. This is why the first signs of vitamin K insufficiency are seen as undercarboxylation of the extrahepatic Gla proteins. New conformation-specific assays for circulating uncarboxylated MGP were developed; an assay for desphospho-uncarboxylated matrix Gla protein and another assay for total uncarboxylated matrix Gla protein. Circulating desphospho-uncarboxylated matrix Gla protein was found to be predictive of cardiovascular risk and mortality, whereas circulating total uncarboxylated matrix Gla protein was associated with the extent of prevalent arterial calcification. Vitamin K intervention studies have shown that MGP carboxylation can be increased dose dependently, but thus far only 1 study with clinical endpoints has been completed. This study showed maintenance of vascular elasticity during a 3-y supplementation period, with a parallel 12% loss of elasticity in the placebo group. More studies, both in healthy subjects and in patients at risk of vascular calcification, are required before conclusions can be drawn.     

High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.     

Bioavailable dietary phosphate,a mediator of cardiovascular disease,may be decreased with plant-based diets,phosphate binders,niacin, and avoidance of phosphate additives

Increased fasting serum phosphate within the normal physiological range has been linked to increased cardiovascular risk in prospective epidemiology; increased production of fibroblast growth factor 23, and direct vascular effects of phosphate, may mediate this risk. Although dietary phosphate intake does not clearly influence fasting serum phosphate in individuals with normal renal function, increased phosphate intake can provoke a rise in fibroblast growth factor 23, and in diurnal phosphate levels, and hence may adversely influence vascular health. Dietary phosphate absorption can be moderated by emphasizing plant-based dietary choices (which provide phosphate in less bioavailable forms); avoidance of processed foods containing inorganic phosphate food additives; and by ingestion of phosphate-binder drugs, magnesium supplements, or niacin, which precipitate phosphate or suppress its gastrointestinal absorption. The propensity of dietary phosphate to promote vascular calcification may be opposed by optimal intakes of magnesium, vitamin K, and vitamin D; the latter should also counter the tendency of phosphate to elevate parathyroid hormone.     

Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.     

Selected Mineral Intakes of Adult African-Americans in the Washington, DC Area

The objective of this study was to assess daily self-selected mineral intake of free-living African-American adults using the duplicate portion collection technique coupled with direct chemical analysis. A duplicate sample of every food and beverage consumed was collected by each subject. The collection period was for 3 days (Sunday, Tuesday, and Thursday) of 1 week in 1986. The chemical analysis included calcium, phosphorus, magnesium, sodium, potassium, manganese, iron, copper, zinc, and phytate. Forty adult African-Americans (20 females and 20 males) living in the Washington, DC area volunteered to participate. They were apparently healthy, ranging in age from 21 to 65 years, with a median age of 38.5 years. The analytical data from the daily food and beverage intake were compared with the Recommended Dietary Allowances (RDA)/ Estimated Safe and Adequate Daily Dietary Intakes (ESADDI). The results were also compared with data from the National Health and Nutrition Examination Survey (NHANES) III and USDA's Continuing Survey of Food Intakes by Individuals(USDA-CSFII 1989–91). Compared with the RDA/ESADDI, for women, the median intakes of less than two-thirds the recommendations were : calcium (54%), magnesium (65%), iron (61%), copper(60%), zinc (61%), and potassium (50%) as determined by chemical analysis. For the men, applying the same criteria, the minerals and percentages are: calcium (64%), magnesium (56%), copper (60%), zinc (61%), and potassium (58%). The phytate:zinc and phytate × Ca:Zn molar ratios suggested no general inhibition of zinc bioavailability despite some higher than suggested limiting molar ratios found in a few individual daily diets. Although limited in scope, these results suggest that African-American adults are selecting diets that are frequently low in specific minerals. Some of these essential nutrients have been implicated in chronic health problems prevalent in this ethnic group; e.g., hypertension and cardiovascular diseases. Therefore, nutritionists and other health professionals should emphasize the need for a wider selection of foods to prevent specific mineral deficits. These foods might include acceptable dairy products, meats/seafood, and mineral-fortified cereals/breads and juices.     

GLV supplements increased plasma β–carotene, vitamin C, zinc and hemoglobin in young healthy adults

Summary Background Green leafy vegetables (GLV) are rich sources of β–carotene, iron and other micronutrients. Our in vitro studies have demonstrated good antioxidant potential in GLV. Moreover linkages of GLV intakes with plasma retinol and ascorbic acid were seen in apparently healthy Indians. Aim of the study To investigate the effect of GLV as a natural fortificant of multiple micronutrients through a prospective human trial. Methods Short–term (0–4 h) response (AUC) of single dose of 7.9 mg β–carotene and 130 mg ascorbic acid through a spinach–carrot meal against the standard meal without GLV plus10 mg β–carotene and 150 mg ascorbic acid tablets was studied in two groups of 4 young volunteers each. In the second trial of 3 weeks' supplementation, 5 groups of young adults (n = 40) were given either 100 g GLV/day alone or with tablets of vitamin E (100 mg/day), or C (100 mg/day) or more oil (5 g/day) or non–GLV meal with tablet of β–carotene (10 mg/day). Hemoglobin (Hb), plasma β–carotene, zinc, vitamin C, glucose, and triglycerides were measured. Results In a postprandial response, AUC were comparable in both GLV and standard meals for β–carotene and ascorbic acid. In case of triglycerides and glucose AUC the GLV meal showed a better recovery to the baseline value after 4 hours than the standard meal. Three weeks' supplementation of GLV with more oil resulted in significant increase of plasma β–carotene (51%) and Hb (9%). GLV with vitamin E showed a significant increase in plasma β–carotene (40%), Hb (8%) and plasma vitamin C (6%). Supplementing β–carotene without GLV significantly increased Hb (11%), plasma zinc (14%) in addition to β–carotene. Multiple regression analyses weighted for energy intake indicated a significant association of percent increase in Hb with intakes of iron, riboflavin, folic acid, β–carotene, copper, phytate and fiber (p < 0.01), percent change in plasma zinc with intakes of zinc, β–carotene, vitamin C, riboflavin, copper, iron, and thiamin (p < 0.01), percent change in vitamin C with intakes of vitamin C, vitamin E, niacin, riboflavin, thiamin, β–carotene, zinc, phytate and fiber (p < 0.05) and percent change in plasma β–carotene with intakes of β–carotene, thiamin, folic acid, zinc, phytate and tannins (p < 0.05). Conclusion Using 100 g GLV/day with 10 g oil could be a single moderate strategy for supplementation of iron, β–carotene, ascorbic acid and zinc.     

Combined zinc and iron compared with iron supplementation of diets of 6- to 12-year old village schoolchildren in southern Iran.

The effects of supplementation of the diets of 6- to 12-year-old children in a village near Shiraz in Iran with zinc plus iron or iron alone, together with the indispensable amino acids in the form of egg white protein, vitamins, minerals, and corn oil have been evaluated. Initially 48 of 59 children had zinc concentrations below the minimum found in well-nourished persons. Eight months of supplementation with zinc plus iron (20 mg daily of elemental zinc as carbonate and 20 mg ferrous iron as fumarate) failed to stimulate growth or bone development or to bring about an increase in plasma zinc concentrations. However, supplementation with iron in the above amount was associated with an acceleration of growth in height and weight. The persistence of low concentrations of zinc in plasma and the failure of supplemental zinc to stimulate growth are attributed to the poor availability of both dietary and supplemental zinc resulting from sequestering action of fiber and phytate present in large amounts in the unleavened whole meal bread consumed by villagers. In addition, the results suggest that simultaneous administration of iron and zinc supplements may impair utilization of the metals.     

临产孕妇血清与新生儿脐血血清微量元素的研究

目的:探讨临产孕妇血清与新生儿脐血血清中微量元素钙、镁、锌、铁、铜的含量及其临床意义。方法:采用日立7 600型自动生化分析仪及罗氏自动生化分析仪测定210例孕妇血清及新生儿脐血血清的钙、镁、锌、铁、铜含量,并进行对照研究。结果:新生儿脐血血清中铁、钙、锌含量高于孕妇血清(P0.05);临产孕妇血清铜含量高于新生儿脐血血清(P0.05);新生儿脐血血清与临产孕妇血清中镁的含量比较无统计学差异(P0.05);维吾尔族孕妇血清及新生儿脐血血清与汉族孕妇血清及新生儿脐血血清钙、镁、铜、锌、铁含量无统计学差异(P0.05)。结论:①血清微量元素铁、钙、锌、镁的减少,铜的升高可能导致妊娠期疾病的发生。②无论孕妇机体在正常状态下还是在病理状态下,均需首先保证胎儿对锌、铜、铁、钙、镁的需要。③孕期应定期监测微量元素,合理补充微量元素钙、锌、铁,从而减少妊娠期疾病的患病率,保证孕妇身体健康和胎儿的正常生长发育。     

Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers

BACKGROUND: The coexistence of multiple micronutrient deficiencies is a widespread public health problem in many regions of the world. Interactions between zinc deficiency and vitamin A metabolism have been reported but no longitudinal studies have evaluated the effect of iron deficiency on vitamin A. OBJECTIVE: The objective of this study was to investigate the effect of supplementation with iron, zinc, or both on vitamin A and its metabolically related proteins retinol binding protein (RBP) and transthyretin. DESIGN: The study was a longitudinal, double-blind, placebo-controlled trial in which 219 rural Mexican children aged 18-36 mo were randomly assigned to receive 20 mg Zn/d, 20 mg Fe/d, 20 mg Zn/d plus 20 mg Fe/d, or placebo. RESULTS: Six months after supplementation, plasma retinol increased in all supplemented groups. Compared with placebo, zinc supplementation was associated with significantly higher plasma retinol and transthyretin but the increase in RBP was not significant. Iron supplementation significantly increased plasma retinol, RBP, and transthyretin. Supplementation with zinc plus iron significantly increased plasma retinol but not RBP or transthyretin. Children deficient in zinc, iron, or vitamin A (as indicated by nutrient plasma concentration) at the beginning of the study had a significantly greater increase in retinol than did children with adequate nutrient status. CONCLUSIONS: Supplementation with zinc, iron, or both improved indicators of vitamin A status. The results of this study agree with previous observations of a metabolic interaction between zinc and vitamin A and suggest an interaction between iron and vitamin A metabolism.     

Redistribution of vitamin A after iron supplementation in Indonesian infants

BACKGROUND: Deficiencies of iron and vitamin A are prevalent worldwide. Single-micronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients. OBJECTIVE: This study investigated interactions among 3 important micronutrients--iron, vitamin A, and zinc--when they are given as supplements. DESIGN: In a randomized, double-blind, placebo-controlled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg beta-carotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg beta-carotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study. RESULTS: Iron-supplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration <0.70 micromol/L, than did the non-supplemented infants. In contrast, the modified relative dose response of the iron-supplemented infants indicated greater liver stores of vitamin A. Iron supplementation improved iron status, and zinc supplementation improved zinc status, but beta-carotene supplementation did not significantly improve vitamin A status. CONCLUSIONS: In this study, iron supplementation in infants with marginal vitamin A status led to lower plasma vitamin A concentrations and simultaneously to greater vitamin A liver stores. This implies a redistribution of retinol after iron supplementation, which might induce vitamin A deficiency. Therefore, iron supplementation in infants should be accompanied by measures to improve vitamin A status.     

锌、镁、铁和维生素D缺乏与儿童注意缺陷多动障碍关系的研究进展

注意缺陷多动障碍(ADHD)是一种神经发育障碍性疾病, 发病率呈逐年上升趋势, 病因和发病机制尚不明确。虽然支持营养补充剂治疗ADHD的证据有限, 但大量研究表明ADHD患儿的锌、镁、铁和维生素D水平显著低于健康儿童。这些营养素在神经功能中均具有重要作用。因此, 本文综述了锌、镁、铁和维生素D缺乏与ADHD关系的研究进展, 鼓励医务工作者通过回顾患儿的饮食历史, 采取适当的筛查和预防性治疗措施。     

Nutrition evaluation of published weight-reducing diets

The objective of this study was to determine the nutritional adequacy of some of the popular published diet plans. Diet analyses were made using the University of Massachusetts Nutrient Data Bank. Not one of the 11 diets evaluated provided 100% of the U.S. Recommended Daily Allowances for the 13 vitamins and minerals studied. The nutrients most often below recommended levels were thiamin, vitamin B-6, vitamin B-12, calcium, iron, zinc, and magnesium. Vitamin and mineral supplementation may be warranted for individuals following some diet plans.     

Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal

BACKGROUND: We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15%. OBJECTIVE: We examined the effect of daily maternal micronutrient supplementation on fetal loss and infant mortality. DESIGN: The study was a double-blind, cluster-randomized, controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal. In addition to vitamin A (1000 microg retinol equivalents), the intervention groups received either folic acid (FA; 400 microg), FA + iron (60 mg), FA + iron + zinc (30 mg), or multiple micronutrients (MNs; the foregoing plus 10 microg vitamin D, 10 mg vitamin E, 1.6 mg thiamine, 1.8 mg riboflavin, 2.2 mg vitamin B-6, 2.6 microg vitamin B-12, 100 mg vitamin C, 64 microg vitamin K, 20 mg niacin, 2 mg Cu, and 100 mg Mg). The control group received vitamin A only. RESULTS: None of the supplements reduced fetal loss. Compared with control infants, infants whose mothers received FA alone or with iron or iron + zinc had a consistent pattern of 15-20% lower 3-mo mortality; this pattern was not observed with MNs. The effect on mortality was restricted to preterm infants, among whom the relative risks (RRs) were 0.36 (95% CI: 0.18, 0.75) for FA, 0.53 (0.30, 0.92) for FA + iron, 0.77 (0.45, 1.32) for FA + iron + zinc, and 0.70 (0.41, 1.17) for MNs. Among term infants, the RR for mortality was close to 1 for all supplements except MNs (RR: 1.74; 95% CI: 1.00, 3.04). CONCLUSIONS: Maternal micronutrient supplementation failed to reduce overall fetal loss or early infant mortality. Among preterm infants, FA alone or with iron reduced mortality in the first 3 mo of life. MNs may increase mortality risk among term infants, but this effect needs further evaluation.     

肝硬化病人维生素A、E及某些矿物质营养状况探讨

本文观察了24例肝硬化病人维生素A、E及铁、锌、铜、锰、钙和镁的营养状况。结果显示,肝硬化(代偿期)病人除维生素E外,上述各种营养素的摄入量均显著低于健康对照组;肝腹水病人的摄入量更低。肝硬化(代偿期)病人血清维生素A、E、铁、锌、铜和锰的含量显著低于健康对照组;肝腹水病人血清铜、镁的含量未见明显变化,但血清钙的含量显著下降,其他各项指标的值更低。上述结果提示,肝硬化病人有维生素A、E、铁、锌、锰和钙的不足或缺乏。     

Influence of mineral intake and use of oral contraceptives before pregnancy on the mineral content of human colostrum and of more mature milk

The effects of mineral intake and long-term oral contraceptive use before pregnancy on the mineral content of milk of healthy lactating women were evaluated in a study of 52 volunteers ages 18-31. Subjects reporting previous oral contraceptive use had significantly lower levels of copper in serum, perhaps reflecting reduced copper stores resulting from prolonged estrogen exposure, but concomitant changes in copper levels in their milk were not noted. Serum calcium and magnesium levels were not significantly affected by prior pill use. Pill use had no significant effect on concentrations of calcium, magnesium, zinc, copper, or iron in colostrum at day 3 or more mature milk at day 14 of lactation, while mean manganese levels were significantly lower at both times for previous oral contraceptive users (but still exceeded manganese levels recommended for infants). Mineral and vitamin supplementation significantly improved the levels of zinc and iron intake, but did not appreciably alter the mineral content of milk. Higher levels of zinc were found in colostrum compared to day 14 milk, while manganese concentrations increased significantly during the 1st 2 weeks of lactation. Calcium, magnesium, iron and copper levels did not change significantly as lactation progressed. Levels of calcium, magnesium, zinc, copper, and manganese in colostrum were significantly positively correlated with the mineral concentration on day 14. No significant diurnal or daily variation was observed in the levels of calcium, magnesium, or zinc content in milk during 2 24-hour periods.     

Phytate intake and molar ratios of phytate to zinc, iron and calcium in the diets of people in China

OBJECTIVE: To assess the phytate intake and molar ratios of phytate to calcium, iron and zinc in the diets of people in China. DESIGN: 2002 China Nationwide Nutrition and Health Survey is a cross-sectional nationwide representative survey on nutrition and health. The information on dietary intakes was collected using consecutive 3 days 24 h recall by trained interviewers. SUBJECTS: The data of 68 962 residents aged 2-101 years old from 132 counties were analyzed. RESULTS: The median daily dietary intake of phytate, calcium, iron and zinc were 1186, 338.1, 21.2 and 10.6 mg, respectively. Urban residents consumed less phytate (781 vs 1342 mg/day), more calcium (374.5 vs 324.1 mg/day) and comparable amounts of iron (21.1 vs 21.2 mg/day) and zinc (10.6 vs 10.6 mg/day) than their rural counterparts. A wide variation in phytate intake among residents from six areas was found, ranging from 648 to 1433 mg/day. The median molar ratios of phytate to calcium, iron, zinc and phytate x calcium/zinc were 0.22, 4.88, 11.1 and 89.0, respectively, with a large variation between urban and rural areas. The phytate:zinc molar ratios ranged from 6.2 to 14.2, whereas the phytate x calcium/zinc molar ratios were from 63.7 to 107.2. The proportion of subjects with ratios above the critical values of phytate to iron, phytate to calcium, phytate to zinc and phytate x calcium/zinc were 95.4, 43.7, 23.1 and 8.7%, respectively. All the phytate/mineral ratios of rural residents were higher than that of their urban counterparts. CONCLUSIONS: The dietary phytate intake of people in China was higher than those in Western developed countries and lower than those in developing countries. Phytate may impair the bioavailability of iron, calcium and zinc in the diets of people in China.     

Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.