Age and Dietary Form of Vitamin K Affect Menaquinone-4 Concentrations in Male Fischer 344 Rats3

Booth, Sarah L.; Peterson, James W.; Smith, Donald E.; Shea, M. Kyla; Chamberland, John P.; Crivello, Natalia A.

doi:10.1093/jn/138.3.492

Cited by 28 publications

(21 citation statements)

References 20 publications

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“…According to some, this production is not a main source of vitamin K2 [36,37], but in the opinion of others these bacteria play an important role with regard to vitamin K status [38]. Animal studies have shown that vitamin K1 may be converted to K2 in tissues, making it even more difficult to distinguish between a potential effect of these two nutrients [39]. Thus, the results from the present study must be interpreted with caution.…”

Section: Discussionmentioning

confidence: 71%

Dietary vitamins K1, K2 and bone mineral density: the Hordaland Health Study

et al. 2010

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Associations between bone mineral density (BMD) and dietary vitamins K1 and K2 in 4,461 individuals were studied. For women, odds ratio of low BMD was 1.48 in lowest to highest quartile of K1. A weak positive association was found for K2. Our results do not support dietary vitamins K as being major determinants of BMD.Purpose Some studies suggest a positive association between intake of vitamin K1 (phylloquinone) or vitamin K2 (menaquinone) and BMD. The objective was to examine associations between BMD and dietary vitamins K1 and K2.Methods BMD of the total hip was measured in 2,575 women and 1,886 men, 47-50 and 71-75 years, in the community-based Hordaland Health Study. Dietary vitamins K1 and K2 were assessed by a food frequency questionnaire. Low BMD was defined as the lowest BMDquintile for each age-sex group. Multiple linear, logistic and fractional polynomial regression analyses were applied. Results No significant associations between vitamin K1 or K2 intake and BMD were found in linear regression analyses. Comparing women in the highest to lowest quartile of vitamin K1 intake, an odds ratio of 1.48 (95% confidence interval (CI): 1.08, 2.04) for low BMD was found. This was not found among men or for vitamin K2 intake in either gender. A weak, positive association between log (vitamin K2) intake and BMD was found by fractional polynomial regression analyses in women (beta coefficient: 0.018; 95% CI: 0.009, 0.027; p=0.001), but not in men. Conclusions Although we observed an increased risk of low BMD with low intake of vitamin K1 and a weak positive association between BMD and vitamin K2 intake among women, this study does not support dietary intake of vitamins K1 or K2 as major determinants of BMD. Future studies should investigate possible associations between intake of vitamin K1, K2 and fracture risk.

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Section: Discussionmentioning

confidence: 71%

Dietary vitamins K1, K2 and bone mineral density: the Hordaland Health Study

et al. 2010

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“…Male Fischer 344 rats (8 mo old, n = 15) obtained from National Institute of Aging were acclimated for 2 wk with a vitamin K-deficient diet (TD.09686, Harlan Teklad) in suspended wire caging to minimize coprophagy (9). Rats were weight-matched and placed in individual metabolic cages to enable monitoring of food consumption (including spillage) while minimizing coprophagy.…”

Section: Methodsmentioning

confidence: 99%

Deuterium-Labeled Phylloquinone Has Tissue-Specific Conversion to Menaquinone-4 among Fischer 344 Male Rats,

Rajabi

Booth

Peterson

et al. 2012

The Journal of Nutrition

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Phylloquinone (PK) is converted into menaquinone-4 (MK-4) via side chain removal-addition. Stable isotope use is an effective approach to identify the tissue location of this conversion, which is currently unknown. Following a 14-d PK-deficient diet, male Fischer 344 rats (8 mo; n = 15) were fed 1.6 mg deuterium-labeled PK (L-PK) per kg diet for 0 (control), 1 d (PK-1d), and 7 d (PK-7d). Both L-PK and deuterium-labeled MK-4 (L-MK-4) were detected in tissues in PK-1d and PK-7d, although the results varied. Whereas some tissues had an overall increase in MK-4 in response to L-PK, total brain, testes, and fat MK-4 concentrations did not. In contrast, L-MK-4 concentrations increased in all 3 tissues. The deuterium label was found only on the L-MK-4 naphthoquinone ring, confirming the need for side chain removal for the formation of MK-4. Labeled menadione (MD) was detected in urine and serum in PK-1d and PK-7d, confirming its role as an intermediate. A Caco-2 cell monolayer model was used to study the role of the enterocytes in the conversion process. Neither MK-4 nor MD was detected in Caco-2 cells treated with PK. However, when Caco-2 cells were treated with MD, MK-4 was formed. Similarly, MK-4 was formed in response to MD-treated 293T kidney cells, but not HuH7 liver cells. These data demonstrate that MK-4 is the predominant form of vitamin K in multiple tissues, but there appears to be a tissue-specific regulation for the conversion of PK to MK-4.

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“…Animals were randomly assigned into 6 experimental groups (n = 16/group): Sham group (control animals who surgery to mimic an ovariectomy, but the ovaries are left intact); OVX control group; OVX+bisphosphonate (BP) group [100 μg/mL of saline (100 μg of Fosamax/kg body weight) daily by subcutaneous injection]; OVX+PK group (target: 0.3 mmol/kg diet; 135 mg/kg diet); OVX+MK-4 group (target: 0.3 mmol/kg diet; 133 mg/kg diet); and OVX+MK-7 group (target: 0.3 mmol/kg diet; 195 mg/kg diet). For 6 wk, all 6 groups were fed a low vitamin K diet (PK: 0.14 mg/kg diet, Harlan Teklad, TD.97053) [21] containing 1% calcium and 2.2 IU vitamin D/g, which were supplemented with one of the three different forms of vitamin K. Sham group rats were fed ad libitum . Amount of food offered for all OVX groups were adjusted weekly based on sham rats consumption.…”

Section: Methodsmentioning

confidence: 99%

Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

Moreines

Booth

2012

Nutr Metab (Lond)

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BackgroundDespite plausible biological mechanisms, the differential abilities of phylloquinone (PK) and menaquinones (MKn) to prevent bone loss remain controversial. The objective of the current study was to compare the effects of PK, menaquinone-4 (MK-4) and menaquinone-7 (MK-7) on the rate of bone loss in ovariectomized (OVX) Norway rats. A secondary aim was to compare the effects of vitamin K with those of bisphosphonates (BP) on bone loss.MethodsRats (n = 96) were randomized to 6 dosing groups [n = 16/group; Sham; OVX; OVX + BP (100 μg/kg/100 μg/mL saline sc); OVX + PK; OVX + MK-4; and OVX + MK-7] for 6 wk. Equimolar daily doses of 107 mg PK/kg, 147 mg MK-4/kg, and 201 mg MK-7/kg diet were provided.ResultsBP significantly increased bone strength and bone mineral density (BMD) vs. OVX (P < 0.05). However, PK, MK-4 or MK-7 did not change bone strength or BMD compared to the OVX group. Whereas supplementation of PK, MK-4 and MK-7 increased serum and tibia concentrations of each respective form, PK concentrations were consistently higher despite equimolar intakes.ConclusionPK, MK-4, and MK-7 do not appear to prevent bone loss in OVX rats when administered concurrent with adequate intake of other nutrients.

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Age and Dietary Form of Vitamin K Affect Menaquinone-4 Concentrations in Male Fischer 344 Rats3

Cited by 28 publications

References 20 publications

Dietary vitamins K1, K2 and bone mineral density: the Hordaland Health Study

Dietary vitamins K1, K2 and bone mineral density: the Hordaland Health Study

Deuterium-Labeled Phylloquinone Has Tissue-Specific Conversion to Menaquinone-4 among Fischer 344 Male Rats,

Vitamin K supplementation does not prevent bone loss in ovariectomized Norway rats

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