Background: Subclinical vitamin K insufficiency, manifested by under-␥-carboxylation of the bone matrix protein osteocalcin, may be common. Objective: Our objective was to delineate the prevalence of submaximal ␥-carboxylation as assessed by response to phylloquinone supplementation and to evaluate the effect of this intervention on skeletal turnover in healthy North American adults. Design: Healthy subjects (n = 219), approximately equally distributed by sex and age (18-30 y and ≥ 65 y), received daily phylloquinone (1000 g) or placebo for 2 wk. Serum undercarboxylated osteocalcin (ucOC) and total osteocalcin, N-telopeptides of type I collagen (NTx), bone-specific alkaline phosphatase (BSAP), and phylloquinone concentrations were measured at baseline and after weeks 1 and 2. Results: At baseline, the mean serum phylloquinone concentration was lower in the young than in the old group; there was no effect of sex. Concomitantly, baseline %ucOC was highest in the young and lowest in the old men (P < 0.0001) but did not differ significantly by age in women. After supplementation, serum phylloquinone concentration increased Ϸ10-fold (P < 0.0001) at week 1 (from 0.93 ± 0.08 to 8.86 ± 0.70 nmol/L, x -± SEM); this was sustained through week 2. Among all supplemented groups, mean %ucOC decreased from 7.6% to 3.4% without significant differences by age or sex; 102 of 112 subjects had a > 1% decrease.

The ability of male rats to accumulate menaquinone-4 (MK-4) in tissues when fed a vitamin K-deficient diet supplemented with intraperitoneal phylloquinone (K) as the sole source of vitamin K for 14 d was assessed. In both conventionally housed controls and gnotobiotic rats, supplementation with the equivalent of 1500 microg vitamin K/kg diet increased (P < 0.001) tissue MK-4 concentrations above those of controls fed a vitamin K-deficient diet. MK-4 concentrations were approximately 5 ng/g (11 pmol/g) in liver, 14 ng/g in heart, 17 ng/g in kidney, 50 ng/g in brain and 250 ng/g in mandibular salivary glands of gnotobiotic rats. MK-4 concentrations in conventionally housed rats were higher than in gnotobiotic rats in heart (P < 0.01), brain (P < 0.01) and kidney (P < 0.05) but lower in salivary gland (P < 0.05). Cultures of a kidney-derived cell line (293) converted K to the expoxide of MK-4 in a manner that was dependent on both time of incubation and concentration of vitamin K in the media. A liver-derived cell line (H-35) was less active in carrying out this conversion. These data offer conclusive proof that the tissue-specific formation of MK-4 from K is a metabolic transformation that does not require bacterial transformation to menadione as an intermediate in the process.

In exclusively breastfed infants who receive intramuscular phylloquinone at birth, the vitamin K status as measured by plasma phylloquinone and des-gamma-carboxy-prothrombin concentrations is improved by maternal oral supplements of 5 mg/d phylloquinone through the first 12 weeks of life.

Vitamin K is required to convert specific glutamyl residues in a limited number of proteins to gamma-carboxyglutamyl residues. The response of various measures of vitamin K insufficiency to the administration of 1 mg/d of the vitamin K antagonist warfarin was studied in two groups of nine older (55-75 y) or younger (20-28 y) subjects. The most consistent and extensive alteration was an increase in the concentration of serum under-gamma-carboxylated osteocalcin followed by increased immunochemical detection of plasma under-gamma-carboxylated prothrombin (PIVKA-II), and by a decreased urinary excretion of gamma-carboxyglutamic acid. Plasma concentrations of prothrombin were altered by this treatment but prothrombin times, factor VII activity, prothrombin F-1 x 2 concentrations, and a less sensitive assay for under-gamma-carboxylated prothrombine were not. The concentration of serum under-gamma-carboxylated osteocalcin was lower when subjects consumed 1 mg vitamin K/d than when they consumed their normal diet.

Objective-To compare serum total protein (sTP) and serum IgG (sIgG) concentrations in neonatal calves administered colostrum or a bovine serum-based colostrum replacement (CR) product followed by a bovine serum-based colostrum supplement (CS) product. Design-Randomized controlled clinical trial. Animals-18 Jersey and 269 Holstein neonatal heifer calves.Procedures-141 calves were given 4 L of colostrum in 1 or 2 feedings (first or only feeding was provided ≤ 2 hours after birth; when applicable, a second feeding was provided between 2 and 12 hours after birth). Other calves (n = 146) were fed 2 L of a CR product ≤ 2 hours after birth and then 2 L of a CS product between 2 and 12 hours after birth. Concentrations of sTP and sIgG were measured 1 to 7 days after birth. Data from cohorts on individual farms and for all farms were analyzed.Results-Mean sTP and sIgG concentrations differed significantly between feeding groups. In calves fed colostrum and calves fed CR and CS products, mean ± SD sTP concentration was 5.58 ± 0.67 g/dL and 5.26 ± 0.54 g/dL, respectively, and mean sIgG concentration was 1,868 ± 854 mg/ dL and 1,320 ± 620 mg/dL, respectively. The percentage of calves that had failure of passive transfer of immunity (ie, sIgG concentrations < 1,000 mg/dL) was not significantly different between groups.Conclusions and Clinical Relevance-Results suggested that sequential feeding of bovine serum-based CR and CS products to neonatal calves is an alternative to feeding colostrum for achieving passive transfer of immunity.Consumption of an adequate quantity of good-quality colostrum within the first 24-hour period after birth is important for the health and future productivity of dairy calves. 1-3 When the formation, ingestion, or absorption of colostral-derived immunologic factors is inadequate, calves have FPT of immunity. Failure of passive transfer of immunity in calves causes substantial economic losses to stakeholders in the dairy industry because of increases in morbidity and mortality rates. The increased awareness of the importance of confirming successful passive transfer of immunity in neonatal calves has led to the development of several assays that provide quantitative or semiquantitative evidence for determining whether a calf has an adequate concentration of serum immunoglobulins. 4 Several products have been marketed as a CS, complete CR, or both to provide adequate nutrition and immunoglobulin mass for neonatal calves born on farms with colostrum supply shortages. Although CS products have been used to increase the fed volume of colostrum or increase the quality of colostrum, IgG concentrations in these products are low. Furthermore, the immunoglobulins provided in these products are poorly absorbed after ingestion, and the products are considered inadequate when used as a colostrum substitute. 18-21 A CR product that contains 125 g of bovine immunoglobulins concentrated from processed bovine serum is available for use in neonatal calves born on farms during a colostrum supply shortage [2...