Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

2002 ◽  
Vol 87 (6) ◽  
pp. 543-553 ◽  
Author(s):  
Robert E. Olson ◽  
Jean Chao ◽  
Donna Graham ◽  
Margaret W. Bates ◽  
Jessica H. Lewis

The aims of this study were to determine the total body phylloquinone and its metabolic turnover in human subjects using a tracer dose of [5-H3]phylloquinone containing 55·5×104MBq/mmol. Seven subjects aged 22 to 49 years were given 0·3 μg isotopic phylloquinone intravenously on a control diet (75 μg phylloquinone/d) and blood, urine and faeces were sampled periodically for 6 d. Five of these subjects were studied a second time after 3–8 weeks on a low-vitamin K diet (8 μg/d). The changes in the radioactivity of plasma phylloquinone with time were analysed by the method of residuals and fitted to a curve composed of two exponential components. The size of the exchangeable body pool was calculated by isotope dilution. Plasma phylloquinone levels fell during vitamin K restriction but the vitamin K-dependent coagulation factors did not change. After injection the first exponential decay curvet1/2was 1·0 (SD 0·47) H IN THE SUBJECTS ON THE CONTROL DIET AND 0·49 (sd 0·27) h after vitamin K restriction. On the control diet, the second exponentialt1/2was 27·6 (sd 124) h that did not change on the low-vitamin K diet (t1/2=25·1 (sd 13·5) h). These results indicate that the turnover time for phylloquinone in human subjects is about 1·5 d. Urinary excretion of3H-metabolites ranged from 30 % of the administered dose on the control diet to 38 % on the restricted diet and had the same turnover rate as the second component of the plasma decay curves. The exchangeable body pool of phylloquinone declined from about 1·0 μg/kg before restriction to lower values after vitamin K restriction. The faecal excretion of phylloquinone and its metabolites fell from 32 % of the administered dose on the control diet to 13 % on the restricted diet.

2002 ◽  
Vol 88 (4) ◽  
pp. 437-437
Author(s):  
R. E. Olson ◽  
J. Chao ◽  
D. Graham ◽  
M. W. Bates ◽  
J. H. Lewis
Keyword(s):  

2002 ◽  
Vol 87 (6) ◽  
pp. 543-553 ◽  
Author(s):  
Olson R.E.* ◽  
J. Chao ◽  
D. Graham ◽  
M.W. Bates ◽  
J.H. Lewis
Keyword(s):  

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 52-59 ◽  
Author(s):  
Sherry A. Tanumihardjo ◽  
Anura V. Kurpad ◽  
Janet R. Hunt

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.


1977 ◽  
Vol 38 (02) ◽  
pp. 0465-0474 ◽  
Author(s):  
M Constantino ◽  
C Merskey ◽  
D. J Kudzma ◽  
M. B Zucker

SummaryLevels of blood coagulation factors, cholesterol and triglyceride were measured in human plasma. Prothrombin was significantly elevated in type Ha hyperlipidaemia; prothrombin and factors VII, IX and X in type lib; and prothrombin and factors VII and IX in type V. Multiple regression analysis showed significant correlation between the levels of these plasma lipids and the vitamin K-dependent clotting factors (prothrombin, factors VII, IX and X). Higher cholesterol levels were associated with higher levels of prothrombin and factor X while higher triglyceride levels were associated with higher levels of these as well as factors VII and IX. Prothrombin showed a significant cholesterol-triglyceride interaction in that higher cholesterol levels were associated with higher prothrombin levels at all levels of triglyceride, with the most marked effects in subjects with higher triglyceride levels. Higher prothrombin levels were noted in subjects with high or moderately elevated (but not low) cholesterol levels. Ultracentrifugation of plasma in a density of 1.21 showed activity for prothrombin and factors VII and X only in the lipoprotein-free subnatant fraction. Thus, a true increase in clotting factor protein was probably present. The significance of the correlation between levels of vitamin K-dependent clotting factors and plasma lipids remains to be determined.


2011 ◽  
Vol 106 (09) ◽  
pp. 563-565 ◽  
Author(s):  
Sara Roshani ◽  
Julie Rutten ◽  
Astrid van Hylckama Vlieg ◽  
Hans Vos ◽  
Frits Rosendaal ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 95
Author(s):  
Imran Ramzan ◽  
Moira Taylor ◽  
Beth Phillips ◽  
Daniel Wilkinson ◽  
Kenneth Smith ◽  
...  

Elevated circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are associated with obesity and type 2 diabetes (T2D). Reducing circulatory BCAAs by dietary restriction was suggested to mitigate these risks in rodent models, but this is a challenging paradigm to deliver in humans. We aimed to design and assess the feasibility of a diet aimed at reducing circulating BCAA concentrations in humans, while maintaining energy balance and overall energy/protein intake. Twelve healthy individuals were assigned to either a 7-day BCAA-restricted diet or a 7-day control diet. Diets were iso-nitrogenous and iso-caloric, with only BCAA levels differing between the two. The BCAA-restricted diet significantly reduced circulating BCAA concentrations by ~50% i.e., baseline 437 ± 60 to 217 ± 40 µmol/L (p < 0.005). Individually, both valine (245 ± 33 to 105 ± 23 µmol/L; p < 0.0001), and leucine (130 ± 20 to 75 ± 13 µmol/L; p < 0.05), decreased significantly in response to the BCAA-restricted diet. The BCAA-restricted diet marginally lowered Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels: baseline 1.5 ± 0.2 to 1.0 ± 0.1; (p = 0.096). We successfully lowered circulating BCAAs by 50% while maintaining iso-nitrogenous, iso-caloric dietary intakes, and while meeting the recommended daily allowances (RDA) for protein requirements. The present pilot study represents a novel dietary means by which to reduce BCAA, and as such, provides a blueprint for a potential dietary therapeutic in obesity/diabetes.


Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3811-3815 ◽  
Author(s):  
Yan-Mei Sun ◽  
Da-Yun Jin ◽  
Rodney M. Camire ◽  
Darrel W. Stafford

Previously we reported that we could increase the fraction of carboxylated factor X by reducing the affinity of the propeptide for its binding site on human gamma glutamyl carboxylase. We attributed this to an increased turnover rate. However, even with the reduced affinity propeptide, when sufficient overproduction of factor X is achieved, there is still a significant fraction of uncarboxylated recombinant factor X. We report here that the factor X of such a cell line was only 52% carboxylated but that the fraction of carboxylated factor X could be increased to 92% by coexpressing the recently identified gene for vitamin K epoxide reductase. Because vitamin K is in excess in both the untransfected and vitamin K epoxide reductase (VKOR)–transfected cells, the simplest explanation for this result is that VKOR catalyzes both the reduction of vitamin K epoxide to vitamin K and the conversion of vitamin K to vitamin K hydroquinone. In addition to its mechanistic relevance, this observation has practical implications for overproducing recombinant vitamin K–dependent proteins for therapeutic use.


2000 ◽  
Vol 71 (1) ◽  
pp. 111-117 ◽  
Author(s):  
M. Marchetti ◽  
M. Tassinari ◽  
S. Marchetti

AbstractWhen compared with other menadione derivatives such as menadione sodium bisulphite (MSB), menadione nicotinamide bisulphite (MNB), an organic salt combining menadione and nicotinamide, shows better stability towards physical and chemical factors once it is added to pre-mixes or foods. The present work evaluates the bioavailability of the two vitamins present in this compound and toxicity in the pig. To assess vitamin bioavailability, pigs were given small amounts of food containing MNB or equivalent amounts of MSB and nicotinamide in the free form. Menadione and nicotinamide concentrations in blood samples drawn at set times after the diets were given did not reveal any significant differences between the two modes of administration. Haematic levels of both vitamins in animals receiving MNB, or MSB and nicotinamide, were after 2, 4, 8 and 12 h higher (P < 0·001) than those of untreated animals. The tolerance level to MNB was evaluated in pigs given diets containing graded amounts of MNB (100, 500, 2500 mg/kg) for 28 days. No significant (P > 0·05) differences were recorded in live weight, food intake and gain/food ratio in pigs given these diets when compared with those given an unsupplemented diet. Haemoglobin and bilirubin levels did not differ between animals given various amounts of MNB and control animals. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in pigs given 100 mg/kg of MNB did not show significant differences when compared with those observed in pigs given an unsupplemented control diet. In pigs on the diets supplemented with 500 and 2500 mg/kg of MNB there was a significant increase in the two enzymatic activities as compared with controls (P < 0·001 and P < 0·01). In the case of ALT this had disappeared by 28 weeks. MNB is a good source of vitamin K for the pig and does not appear to have any adverse effects, even when administered at levels higher than those normally used in pig food supplementation.


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