Absorption of dietary vitamin K

Phylloquinone, the major form of vitamin K in the
diet, is absorbed in the jejunum, and less effi ciently
in the ileum, in a process that is dependent on the
normal fl ow of bile and pancreatic juice (Shearer
et al., 1974). Both long- and short-chain menaquinones
are readily absorbed by rats after oral ingestion
(Groenen-van Dooren et al., 1995) and therefore dietary
menaquinones are likely to be incorporated into
mixed micelles through the action of bile salts and
absorbed along with phylloquinone.
The effi ciency of vitamin K absorption varies
widely depending on the source of the vitamin and
the amount of fat in the meal. Pure phylloquinone
is absorbed with an effi ciency of 80% (Shearer et al.,
1974). The phylloquinone present in cooked spinach
was only 4% as bioavailable as that from a commercial
detergent suspension of phylloquinone. Adding butter
to the spinach increased this to 13% (Gijsbers et
al., 1996). The absorption of phylloquinone was six
times higher after the ingestion of a 500-μg phylloquinone
tablet than after the ingestion of 150 g of raw
spinach containing 495 μg phylloquinone (Garber et
al., 1999). The phylloquinone from a phylloquinonefortifi
ed oil was absorbed better than that from an
equivalent amount from cooked broccoli, regardless
of adjustment to triglyceride concentrations (Booth
et al., 2002). The tight binding of phylloquinone to
the thylakoid membranes of chloroplasts explains the
poor bioavailability of the vitamin in green plants.
The free phylloquinone in vegetable oils, margarines
and dairy products is well absorbed owing to the
stimulating effect of fat.
10.4.2 Bacterially synthesized
menaquinones as a possible endogenous
source of vitamin K
The large intestine of healthy adult humans contains
a microfl ora of bacteria, many species of which synthesize
menaquinones ranging mainly from MK-6 to
MK-12. The menaquinones are incorporated into the
bacterium’s cytoplasmic membrane where they function
under reduced (anaerobic) conditions as redox
Vitamin K 259
compounds in bacterial respiration. The most prevalent
menaquinone-producing bacteria in the intestine
are Bacteroides species which synthesize MK-10,
MK-11 and MK-12. Among other prevalent species,
Escherichia coli synthesizes mainly MK-8 (Ramotar
et al., 1984).
Conly & Stein (1992a) reported quantitative and
qualitative measurements of phylloquinone and menaquinones
at different sites within the human intestinal
tract. Overall, long-chain menaquinones (MK-
9, -10 and -11) predominated. Menaquinones were
found mostly in the distal colon (10 faecal samples)
and totalled 19.85 ± 0.36 μg per g dry weight. Menaquinones
in two samples of terminal ileal contents
taken during appendectomy totalled 8.85 μg per g dry
weight. Little menaquinone was found in samples of
proximal jejunal contents collected by means of a nasojejunal
tube (total, 0.03 μg per g dry weight).
The menaquinones incorporated into membranes
of viable bacteria are not available for absorption.
However, Conly & Stein (1992b) described in vitro
experiments showing that signifi cant amounts of
biologically active menaquinones can be secreted or
liberated from bacteria. For example, when a dialysis
bag containing Staphylococcus aureus (a known producer
of menaquinones) was immersed into 100 mL
of media, 0.18% of total menaquinone was recovered
from the surrounding media, representing a concentration
of 0.6 nmol L–1. Inoculation of the media with
Bacteroides levii (a vitamin K-requiring organism)
before dialysis resulted in a luxurious growth of this
organism, but not in controls containing no Staphylococcus
aureus.
Being strongly lipophilic, the bacterially synthesized
menaquinones require the presence of bile salts
and the formation of mixed micelles for absorption
to take place. Because bile salts are reabsorbed in
the distal ileum and the amounts remaining are degraded
by colonic bacteria, there is no opportunity
for absorption of menaquinones to take place in the
colon. Indeed, colonic absorption of MK-9 in rats is
extremely poor (Ichihashi et al., 1992; Groenen-van
Dooren et al., 1995). However, bearing in mind the
appreciable amounts of menaquinones found in the
terminal ileum of two subjects (Conly & Stein, 1992a),
and considering the possibility that contents from the
caecum (where large amounts of bacteria reside) may
backwash past the ileocaecal valve into the ileum,
one can envisage some degree of bile salt-mediated
absorption taking place in this region. In addition,
Hollander et al. (1977) demonstrated ileal absorption
of MK-9 in the conscious rat and showed that
the absorption rate increased with increasing bile salt
concentration.
Direct evidence to support absorption of menaquinones
from the distal human intestinal tract,
where intestinal microfl ora are most prevalent, is
lacking. Indirect evidence that enteric menaquinones
are absorbed is the fact that about 90% of liver
stores of vitamin K is in the form of menaquinones
(Shearer, 1992) despite phylloquinone predominating
in the diet. Moreover, the various menaquinones
found in liver are remarkably consistent with the
menaquinone profi le of human intestinal content.
However, it has not been possible to prove that the hepatic
menaquinones do not originate from the diet.
Studies performed on human volunteers placed on
a vitamin K-defi cient diet have consistently failed to
demonstrate any signifi cant changes in prothrombin
time. However, bleeding episodes associated with a
prolonged prothrombin time have been reported in
vitamin K-deprived volunteers receiving broad-spectrum
antibiotics (Allison et al., 1987). The data from
the latter study did not support the hypothesis discussed
by Lipsky (1988) that N-methylthiotetrazolecontaining
antibiotics suppress vitamin K-dependent
clotting factor biosynthesis. Collectively, these
data imply that enteric menaquinones are absorbed
and utilized to some extent.
Conly et al. (1994) demonstrated that menaquinones
can be absorbed directly from the human
ileum and be functionally active. Their study consisted
of an experimental phase followed by a control
phase, using the same four volunteers. The volunteers
were started on a vitamin K-defi cient diet and then
given adjusted doses of warfarin to maintain a stable
elevated prothrombin time. A 1.5-mg dose of mixed
menaquinones (MK-4 to MK-9) extracted from harvested
Staphylococcus aureus was then placed directly
into the ileum by means of a nasoileal tube after an
overnight fast. Within 24 hours of menaquinone administration,
the prothrombin time decreased signifi -
cantly and the factor VII level increased signifi cantly,
indicating that the menaquinones had been absorbed
and utilized. The results of this study provide an explanation
as to why starvation or a complete lack of
dietary intake of vitamin K alone cannot induce a
clinically manifest vitamin K defi ciency.
260 Vitamins: their role in the human body
In conclusion, a report by Ferland et al. (1993) that
subclinical vitamin K defi ciency can be induced in
healthy adults by dietary deprivation of the vitamin
suggests that absorption of bacterially synthesized
menaquinones may not be suffi cient to sustain adequate
vitamin K status.