(a) The number of subjects are stratified by age and/or sex (b) Total diet study (c) Recommended Dietary Allowance |
Dietary intakes in older infants, children, and adults and their adequacy
The only comprehensive national survey of phylloquinone intakes across all age groups (except infants aged 0–6 months) is that of the US Food and Drug Administration Total Diet Study, which was based on the 1987–88 Nationwide Food Consumption Survey. For infants and children from the age of 6 months to 16 years, average phylloquinone intakes were above the current US recommended dietary allowance (RDA) values for their respective age groups, more so for children up to 10 years than from 10 to 16 years. There have been no studies of intakes in children in relation to functional markers of vitamin K sufficiency in children.
Intakes for adults in The Total Diet Study were also close to or slightly higher than the current US RDA values of 80 μg for men and 65 μg for women, although intakes were slightly lower than the RDA in the 25–30 years age group. There is some evidence from an evaluation of all the US studies that older adults have higher dietary intakes of phylloquinone than do younger adults.
The US results are very comparable with a detailed, seasonality study in the United Kingdom in which mean intakes in men and women (aged 22–54 years) were 72 and 64 μg/day, respectively; no significant sex or seasonal variations were found. Another UK study suggested that intakes were lower in manual workers and in smokers, reflecting their lower intakes of green vegetables and high-quality vegetable oil.
Several dietary restriction and repletion studies have attempted to assess the adequacy of vitamin K intakes in adults. It is clear from these studies that volunteers consuming less than 10 μg/day of phylloquinone do not show any changes in conventional coagulation tests even after several weeks unless other measures to reduce the efficiency of absorption are introduced.
However, a diet containing only 2–5 μg/day of phylloquinone fed for 2 weeks did result in an increase of PIVKA-II and a 70 percent decrease in plasma phylloquinone. Similar evidence of a sub-clinical vitamin K deficiency together with an increased urinary excretion of Gla was found when dietary intakes of phylloquinone were reduced from about 80 to about 40 μg/day for 21 days. A repletion phase in this study was consistent with a human dietary vitamin K requirement (for its coagulation role) of about 1 μg/kg body weight/day.
The most detailed and controlled dietary restriction and repletion study in healthy human subjects is that by Ferland et al. In this study 32 healthy subjects in two age groups (20–40 and 60–80 years) were fed a mixed diet containing about 80 μg/day of phylloquinone, which is the RDA for adult males in the United States. After 4 days on this baseline diet there was a 13-day depletion period during which the subjects were fed a diet containing about 10 μg/day.
After this depletion phase the subjects entered a 16-day repletion period during which, over 4-day intervals, they were sequentially repleted with 5, 15, 25, and 45 μg phylloquinone. The depletion protocol had no effect on conventional coagulation and specific factor assays but did induce a significant increase in PIVKA-II in both age groups. The most dramatic change was in plasma levels of phylloquinone, which fell to about 15 percent of the values on day 1.
The drop in plasma phylloquinone also suggested that the average dietary intake of these particular individuals before they entered the study had been greater than the baseline diet of 80 μg/day. The repletion protocol failed to bring the plasma phylloquinone levels of the young subjects back above the lower limit of the normal range (previously established in healthy, free-living adults) whereas the plasma levels in the elderly group only rose slightly above this lower limit in the last 4 days. Another indication of a reduced vitamin K status in the young group was the fall in urinary output of Gla (90 percent of baseline) that was not seen in the elderly group; this suggested that younger subjects are more susceptible to the effects of an acute deficiency than are older subjects.
One important dietary intervention study measured the carboxylation status of the bone vitamin K-dependent protein, osteocalcin, in response to altered dietary intakes of
phylloquinone. This was a crossover study, which evaluated the effect in young adults of increasing the dietary intake of phylloquinone to 420 μg/day for 5 days from a baseline intake of 100 μg/day. Although total concentrations of osteocalcin were not affected by either of the dietary treatments, ucOC fell dramatically in response to the 420 μg diet and by the end of the 5-day supplementation period was 41 percent lower than the baseline value.
After the return to the mixed diet, the ucOC percent rose significantly but after 5 days had not returned to pre-supplementation values. This study suggested that the carboxylation of osteocalcin in bone may require higher dietary intakes of vitamin K than those needed to sustain its haemostatic function.
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