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Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women. Koitaya N, Ezaki J, Nishimuta M, Yamauchi J, Hashizume E, Morishita K, Miyachi M, Sasaki S, Ishimi Y. J Nutr Sci Vitaminol (Tokyo). 2009 Feb;55(1):15-21. PMID: 19352059 It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the gamma-carboxylated OC (GlaOC) and GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma-carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

Effect of low dose vitamin K2 (MK-4) supplementation on bio-indices in postmenopausal Japanese women. Koitaya N, Ezaki J, Nishimuta M, Yamauchi J, Hashizume E, Morishita K, Miyachi M, Sasaki S, Ishimi Y. J Nutr Sci Vitaminol (Tokyo). 2009 Feb;55(1):15-21. PMID: 19352059 These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R. PLoS Med. 2008 Oct 14;5(10):e196. Erratum in: PLoS Med. 2008 Dec;5(12):e247. PMID: 18922041 CONCLUSIONS: Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers. Trial registration: ClinicalTrials.gov (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241)

Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy. Heikkinen AM, Tuppurainen MT, Niskanen L, Komulainen M, Penttilä I, Saarikoski S. Eur J Endocrinol. 1997 Nov;137(5):495-502. PMID: 9405029 CONCLUSIONS: Our results confirm the positive long-term effect of HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations. In addition, the results suggest that vitamin D3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin D3 treatment was associated with increased serum LDL cholesterol. Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D3. However, the relevance of these associations to cardiovascular morbidity remains to be established.

Dose response to vitamin D supplementation among postmenopausal African American women.\nTalwar SA, Aloia JF, Pollack S, Yeh JK.\nAm J Clin Nutr. 2007 Dec;86(6):1657-62.\nPMID: 18065583

Jehle S, Zanetti A, Muser J, Hulter HN, Krapf R. Partial neutralization of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol. 2006 Nov;17(11):3213-22. Epub 2006 Oct 11

Many postmenopausal women are looking for alternatives to hormone therapy, especially in light of research findings in 2003 from the Women's Health Initiative. With major funding from the National Institutes of Health, this initiative studied the risks of combined estrogen and progestin therapy, among other health issues of critical importance to postmenopausal women. Of particular interest are phytoestrogens, which have been gaining popularity because they are marketed as "natural," because of the alleged health benefits they provide, and because they are available in a wide range of foods and supplements. This fact sheet provides an overview of phytoestrogens and discusses their potential role in osteoporosis prevention and treatment.

Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE. J Clin Endocrinol Metab. 2005 Jun;90(6):3215-24. Epub 2005 Mar 29. PMID: 15797954 doi:10.1210/jc.2004-2364 Conclusions: More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population.

Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women's Health Study. Cancer Causes Control. 2007 Sep;18(7):775-82. Epub 2007 Jun 5. PMID: 17549593 [PubMed - in process]

Reginster JY. Prevalence of vitamin D inadequacy in European postmenopausal women. Curr Med Res Opin. 2007 Jul 12; [Epub ahead of print] PMID: 17631697 [PubMed - as supplied by publisher]

Gonzalez G, Alvarado JN, Rojas A, Navarrete C, Velasquez CG, Arteaga E. High prevalence of vitamin D deficiency in Chilean healthy postmenopausal women with normal sun exposure: additional evidence for a worldwide concern. Menopause. 2007 May-Jun;14(3

Role of vitamin K2 in the treatment of postmenopausal osteoporosis. Iwamoto J, Takeda T, Sato Y. Curr Drug Saf. 2006 Jan;1(1):87-97. Review. PMID: 18690918

Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Erkkilä AT, Lichtenstein AH, Mozaffarian D, Herrington DM. Am J Clin Nutr. 2004 Sep;80(3):626-32. PMID: 15321802 Conclusions: Consumption of fish is associated with a significantly reduced progression of coronary artery atherosclerosis in women with coronary artery disease.

Increased intakes of vitamin K2, but not vitamin K1, may decrease the risk of coronary heart disease in postmenopausal women, says a new study.\nFor every 10 microgram increase in the amount of vitamin K2 consumed, researchers from the Netherlands report a 9 per cent reduction in the risk of developing coronary heart disease (CHD).

Sakhaee K, Maalouf NM, Abrams SA, Pak CY. Effects of potassium alkali and calcium supplementation on bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2005 Jun;90(6):3528-33. Epub 2005 Mar 8. PMID: 15755853

Sebastian A, Harris ST, Ottaway JH, Todd KM, Morris RC Jr. Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med. 1994 Jun 23;330(25):1776-81. PMID: 8190153 [PubMed - indexed for MEDL

Frassetto L, Morris RC Jr, Sebastian A. Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women. J Clin Endocrinol Metab. 2005 Feb;90(2):831-4. Epub 2004 Nov 30. PMID: 15572425 [PubMed - indexed for M

Frassetto L, Morris RC Jr, Sebastian A. Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J Clin Endocrinol Metab. 1997 Jan;82(1):254-9. PMID: 8989270 [PubMed - indexed for MEDLINE]

Low dietary potassium intakes and high dietary estimates of net endogenous acid production are associated with low bone mineral density in premenopausal women and increased markers of bone resorption in postmenopausal women. Macdonald HM, New SA, Fraser WD, Campbell MK, Reid DM. Am J Clin Nutr. 2005 Apr;81(4):923-33. PMID: 15817873

Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Freedman DM, Chang SC, Falk RT, Purdue MP, Huang WY, McCarty CA, Hollis BW, Graubard BI, Berg CD, Ziegler RG. Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):889-94. Epub 2008 Apr 1. PMID: 18381472 doi: 10.1158/1055-9965.EPI-07-2594 In this prospective study of postmenopausal women, we did not observe an inverse association between circulating 25(OH)D or 1,25(OH)2D and breast cancer risk, although we cannot exclude an association in younger women or with long-term or earlier exposure