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Home > Anti-aging Research > Vitamin K

Vitamin K

Specific Recommendations:

News & Research:

  • Multi-ethnic study suggests vitamin K may offer protective health benefits in older age - Science Daily, 6/15/20 - "The meta-analysis, involving nearly 4,000 Americans aged 54-76, one-third of whom were non-white ... the people with the lowest vitamin K levels had a 19 percent higher risk of death, compared to the those with vitamin K levels that reflected adequate vitamin K intake" - See vitamin k2 at Amazon.com and iHerb.
  • Low vitamin K levels linked to mobility limitation and disability in older adults - Science Daily, 6/13/19 - "The new study examined two biomarkers: circulating levels of vitamin K (phylloquinone) and a functional measure of vitamin K (plasma ucMGP). Using participant data from the Health, Aging, and Body Composition Study (Health ABC), the study found that older adults with low levels of circulating vitamin K were more likely to develop mobility limitation and disability ... Specifically, older adults with low circulating vitamin K levels were nearly 1.5 times more likely to develop mobility limitation and nearly twice as likely to develop mobility disability compared to those with sufficient levels."
  • Aortic Stiffness is Associated with Increased Risk of Incident Dementia in Older Adults - Alzheimers Dis. 2018; 66(1): 297–306 - "The Cardiovascular Health Study Cognition Study followed 532 non-demented older adults with annual cognitive exams from 1998–99 through 2013. CfPWV was measured on 356 (mean age = 78, 59% women) between 1996–2000. Over 15 years, 212 (59.6%) developed dementia (median time from cfPWV measurement = 4 years). In age and sex-adjusted Cox models, cfPWV was significantly associated with increased risk of dementia, but systolic blood pressure, mean arterial pressure and pulse pressure were not. CfPWV (transformed as –1/cfPWV) remained significantly associated with dementia risk when further adjusted for education, race, APOE4, diabetes, body mass index, mean arterial pressure, and anti-hypertensive medication (hazard ratio = 1.60, 95%CI = 1.02, 2.51). Results were similar when further adjusted for baseline global cognition, subclinical brain measures, and coronary artery calcification. Finally, higher cfPWV was related to lower physical activity intensity and higher systolic blood pressure, heart rate, and waist circumference measured 5 years prior. An important unanswered question is whether interventions to slow arterial stiffening can reduce the risk of dementia" - [Nutra USA] - Note: Some studies support vitamin K for aortic stiffness:
    • Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women - Thromb Haemost 2015; 113(05): 1135-1144 - "Indices of local carotid stiffness (intimamedia thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index β significantly decreased in the total group, whereas distension, compliance, distensibility, Young’s Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness" - [Nutra USA] - See MK-7 at Amazon.com.
    • Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus - American Journal of Hypertension, Volume 30, Issue 2, 1 February 2017 - "In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes" - [Nutra USA]
  • Vitamin K2 Steps Into the Spotlight for Bone and Heart Health - Medscape, 10/10/18 - "For example, meat products typically include the MK-4 variants, whereas the traditional Japanese vegetarian dish natto ,made from fermented soybeans, contains MK-7, which provides the highest known vitamin K activity ... Supplemental K2 has been associated with significant reductions (approximately 25%-80%) in fracture risk when used alone or combined with vitamin D and calcium,[7,8] as well as with maintenance of bone density in osteoporotic patients.[9,10] K1 supplementation has shown comparatively less benefit for such outcomes ... K2 activates matrix Gla protein (MGP), which keeps calcium deposits from forming on vessel walls. Research has shown that adequate K2 intake generally frees calcium up for its more beneficial roles, whereas K2 deficiencies will lead to a buildup of calcifications ... Studies comparing relatively lower doses of MK-7 supplementation with placebo in early menopausal[14] and postmenopausal women[15] produced conflicting results, with the former experiencing no differences in bone loss at 1 year but the latter seeing less age-related decline in bone content and density at the femoral neck and lumbar spine at 3 years ... Certain varieties of K2 supplements, such as MK-7, have also been shown to interfere with anticoagulation therapy, whereas others like MK-4 carry no risk for hypercoagulation even at relatively high doses" - See vitamin K at Amazon.com.
  • Low consumption of vitamin K by adolescents associated with unhealthy enlargement of the heart's major pumping chamber - Science Daily, 10/2/17 - "A study of 766 otherwise healthy adolescents showed that those who consumed the least vitamin K1 -- found in spinach, cabbage, iceberg lettuce and olive oil -- were at 3.3 times greater risk for an unhealthy enlargement of the major pumping chamber of their heart ... In the 14-18 year olds who consumed the least vitamin K1, the study found the overall size and wall thickness of the left ventricle were already significantly greater and the amount of blood the heart pumped out significantly lower ... Only 25 percent of the teens in the study met current adequate intake levels" - See vitamin K at Amazon.com.
  • Kids with low vitamin K2 status at greater risk of fracture: new study - Nutraceutical Business Review, 6/13/17 - "Bone fractures are very common in children and their number is growing every year. Vitamin D has a proven role in the prevention of fractures… [but the] past decade has seen increased interest in the role of Vitamin K, especially K2 menaquinone-7, in bone health and prevention of bone fractures" - [Nutra USA] - See MK-7 at Amazon.com.
  • Efficiency of Use of Dietary Supplement Arteroprotect® In Prevention of Cardiovascular Diseases - International Journal of Pharmaceutical Science Invention, Feb. 2017 - "In study group there was a significant reduction in mean values of cholesterol, triglycerides and LDL- cholesterol, as well as an increase in mean values of HDL-cholesterol, whereas in the control group there was a significant decrease in the mean values of all observed laboratory parameters. This indicates a significant impact ARTEROprotect® in terms of sinergistic effect with a statin. In fact, earlier studies have shown that as many as 56,2% of respondents who receive statin do not reach the target value of LDL-cholesterol" - Note:  The Nutra USA article claims that ARTEROprotect® contains 45 mcg of vitamin K2 and and 20 mg of octacosanol which is Policosanol.  See vitamin K2 at Amazon.com and Policosanol at Amazon.com.
  • Is Vitamin K2 the New Vitamin D? - Medscape, 11/18/14 - "Deficiencies of vitamin K2 are now being reported in serious journals to be associated with—get this—all-cause mortality, cardiovascular disease, osteoporosis, diabetes, many forms of cancer, dementia, and chronic inflammation" - See vitamin K at Amazon.com.
  • The Week in Bone Health | Breaking news on natural vitamin K2 MK-7 - betterbones.com, 6/25/12 - "Noted vitamin K expert Dr. Cees Vermeer led the European study which found that natural vitamin K2 as MK-7 (MenaQ 7 ®) significantly increases the strength of both the spine and the hip in postmenopausal women"
  • Vitamin K2: New hope for Parkinson's patients? - Science Daily, 5/11/12 - "Fruit flies (Drosophila) are frequently used in lab experiments because of their short life spans and breeding cycles, among other things ... When the flies were given vitamin K2, the energy production in their mitochondria was restored and the insects' ability to fly improved. The researchers were also able to determine that the energy production was restored because the vitamin K2 had improved electron transport in the mitochondria. This in turn led to improved energy production ... Vitamin K2 plays a role in the energy production of defective mitochondria. Because defective mitochondria are also found in Parkinson's patients with a PINK1 or Parkin mutation, vitamin K2 potentially offers hope for a new treatment for Parkinson's"
  • Vitamin K may cut lymph cancer risk: US study - Nutra USA, 4/21/10
  • Vitamin K may protect against developing non-Hodgkin's lymphoma, say Mayo Clinic researchers - Science Daily, 4/19/10 - "the risk of developing Non-Hodgkin lymphoma was approximately 45 percent lower for participants who had vitamin K intakes in the top quartile of intake in the study (>108 ug/day), compared to participants who had intakes in the bottom quartile (<39 ug/day). This association remained after accounting for other factors such as age, sex, education, obesity, smoking, alcohol use and intake of foods with high amounts of antioxidants"
  • New Vitamin K Analysis Supports The Triage Theory - Science Daily, 9/17/09 - "An important analysis conducted by Children's Hospital Oakland Research Institute scientists suggests the importance of ensuring optimal dietary intakes of vitamin K to prevent age-related conditions such as bone fragility, arterial and kidney calcification, cardiovascular disease, and possibly cancer ... Average intakes of vitamin K in the United States and the United Kingdom are less even than currently recommended intakes, which are primarily based on levels to ensure adequate coagulation. McCann & Ames' analysis supports recommendations by some experts that non-clotting functions requiring vitamin K may need higher intakes than are currently recommended"
  • Study strengthens Vitamin K1's heart benefits - Nutra USA, 5/26/09 - "Subjects receiving a daily vitamin K1 plus multivitamin supplement experienced 6 per cent less progression of coronary artery calcification (CAC), or hardening of the arteries that leads to atherosclerosis and cardiovascular disease" - [Abstract]
  • Review supports vitamin K's fracture reducing power - Nutra USA, 5/20/09 - "The most important findings in this review are that although supplementation with lower doses of vitamin K may be sufficient to reduce serum ucOC levels, supplementation with higher doses may be required for optimal bone health" - [Abstract]
  • Vitamin K and prostate cancer – study supports benefits - Nutra USA, 3/31/09 - "increased intakes of vitamin K2, but not K1, were associated with a 35 per cent reduction in prostate cancer risk. The potential benefits of K2 were more pronounced for advanced prostate cancer ... A higher ratio of undercarboxylated osteocalcin (ucOC) to intact total osteocalcin (iOC) is indicative of poorer vitamin K status ... of ucOC and iOC were analysed from serum samples, and every 0.1 increment in the ratio was associated with a 38 per cent increase in advanced-stage prostate cancer, and a 21 per cent increase in high-grade prostate cancer" - [Abstract] - See vitamin K at Amazon.com.
  • Vitamin K2, but not K1, effective for heart health benefits: Study - Nutra USA, 2/12/09 - "This study confirms our findings in the Rotterdam study, showing that increased vitamin K2 intake strongly reduces the risk of coronary heart disease" - [Abstract]
  • Vitamin K Linked To Insulin Resistance In Older Men - Science Daily, 11/26/08 - "Vitamin K slowed the development of insulin resistance in elderly men in a study of 355 non-diabetic men and women ages 60 to 80 who completed a three-year clinical trial at the Jean Mayer Human Nutrition Research Center on Aging at Tufts University"
  • Vitamin K2 linked to better heart health - Nutra USA, 9/10/08 - "When the intakes of K1 and K2 were divided into four groups from the lowest to highest, no association was found between K1 intakes and calcification. However, high consumption of K2 (about 45 micrograms per day) was associated with 20 per cent decreased coronary calcification, compared with low consumption of K2 (about 18micrograms per day)"
  • Effect of vitamin K supplementation on insulin resistance in older men and women - Diabetes Care. 2008 Aug 12 - "The effect of 36-month vitamin K supplementation on HOMA-IR differed by sex (sex-by-treatment interaction: P = 0.02). HOMA-IR was statistically significantly lower at the 36-month visit among men in the supplement group vs. the men in the control group (P = 0.01) after adjustment for baseline HOMA-IR, BMI, and body weight change. There were no statistically significant differences in outcome measures between intervention groups in women ... Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men"
  • Vitamin K good for young bones, too: study - Nutra USA, 7/17/08 - "These findings suggest that improvement in vitamin K status, and thus in the amount of active osteocalcin, might significantly improve bone health in children, even in those with arthritis"
  • Vitamin K2 linked to lower prostate cancer risk - Nutra USA, 4/9/08 - "While no reduction in the risk of prostate cancer was observed for vitamin K1 (phylloquinone), an increased intake of all menaquinones (vitamin K2) was associated with a 35 per cent reduction in risk"
  • Study gives vitamin K anti-inflammation boost - Nutra USA, 12/3/07 - "Limited in vitro data support the inverse association between vitamin K and interleukin-6, and this may influence the association between vitamin K and other cytokines, such as osteoprotegerin" - [Abstract]
  • Vitamin K shows potential in the fight against wrinkles - Nutra USA, 10/19/07 - [Abstract] - "Recent studies have linked vitamin K to the elasticity of skin in patients suffering from pseudoxanthoma elasticum (PXE), an inherited condition resulting in severe wrinkling of the skin on the face and body"
  • Vitamin K linked to fewer varicose veins, better vascular health - Nutra USA, 8/23/07 - "they suggested that adequate dietary intake of vitamin K may be a necessary prerequisite in preventing the development of varicose veins" - [Abstract]
  • Vitamin K may reverse arterial calcification - Nutra USA, 4/3/07 - "using 10-week old male Wistar Kyoto rats ... high-vitamin K intake (both K1 and K2) not only blocked the progress of further calcium accumulation but also lead to a greater than 37 per cent reduction of previously accumulated arterial calcium precipitates within six weeks"
  • Many Seniors Are Still Not Meeting The Recommended Intake Of Vitamin K - Science Daily, 2/12/07 - "Although older adults seem to consume more vitamin K than younger adults, many seniors are still not meeting the recommended intake of vitamin K ... Research has shown poor vitamin K intake may be associated with conditions such as bone fractures, bone loss, hardening of the arteries, and osteoarthritis"
  • Vitamin K may reverse artery hardening, suggests study - Nutra USA, 12/11/06 - "A high-dose vitamin K supplement reduced calcium precipitates associated with hardening of the arteries by 37 per cent in rats"
  • Study Suggests Vitamin K Deficiency as an Osteoporosis Risk Factor - Doctor's Guide, 9/22/06 - "one of the early effects of declining estrogen is the impairment of vitamin K function in bone even before any bone loss that could be attributed to menopause can be measured ... Our study suggests that the generally accepted level of vitamin K in healthy women is inadequate to maintain bone health just at the onset of menopause"
  • Vitamin K1-rich diet linked to better heart health - Nutra USA, 8/29/06
  • Strong support for vitamin K’s bone health benefits - Nutra USA, 6/27/06 - "Supplementation of vitamin K (MK-4) resulted in reductions in hip fractures of 77 per cent, vertebral fracture of 60 per cent, and all non-vertebral fractures of 81 per cent"
  • More support for vitamin K’s protection from osteoarthritis - Nutra USA, 4/12/06 - "Higher intake of vitamin K, found naturally in cabbage, spinach, cauliflower, and other green leafy vegetables, could reduce the risk of osteoarthritic knee problems by 40 per cent"
  • Vitamin K's Delicate Balancing Act - Life Extension Magazine, 4/06 - "Scientists have discovered that vitamin K regulates several biochemical processes that require exquisite balance to function normally, including blood coagulation, bone mineralization, and vascular health"
  • Vitamin K in the Treatment and Prevention of Osteoporosis - Am J Health-Syst Pharm. 2005;62(15):1574-1581/Medscape, 8/5/05 - "The results of two dose-response studies have indicated that (1) the amount of vitamin K needed for optimal γ-carboxylation of osteocalcin is significantly higher than what is provided by diet alone and (2) there is a need to increase current dosage recommendations to optimize bone mineralization"
  • Vitamin K Builds Strong Bones - New Hope Natural Media, 3/28/03 - "Without adequate vitamin K, osteocalcin cannot be produced, and bone formation becomes impaired ... when women with osteoporosis take supplemental vitamin K, the urinary excretion of calcium falls by about 50%, suggesting that less calcium is being leached from the bones ... Some research, however, suggests that the optimal level of intake may be higher, as much as 400 mcg per day. A typical western diet contains 80 to 150 mcg per day"
  • Vitamin K(1) Absorption Unreliable in Infants with Conjugated Hyperbilirubinaemia - Doctor's Guide, 3/5/03
  • Watch Out for Vitamin K? - Dr. Weil, 11/27/02
  • Low Bone Mineral Density and Quantitative Ultrasound in Men Associated with Low Vitamin K Status - Doctor's Guide, 9/23/02 - "Low vitamin K status is associated with low quantitative ultrasound (QUS) and low bone mineral density (BMD) of the femoral neck and trochanter ... What we did was measure the amount of vitamin K in circulation and use the more sensitive measures of vitamin K status which was % undercarboxylated osteocalcin ... We corrected for triglycerides because vitamin K is transported in the blood by triglyceride-rich lipoproteins ... What we found was that the higher the amounts of vitamin K in the plasma, the higher the BMD" - So does that mean that if your triglycerides are in check you may need extra vitamin K? - Ben
  • Vitamin K Therapy Slows Spread of Liver Cancer - Doctor's Guide, 5/29/02 - "Results show that 59 percent of patients treated with vitamin K-II were alive at two years compared to 29 percent of those who were not given vitamin K-II (p=0.14). Invasion of the cancer into the portal vein occurred in 2 percent of the vitamin K-II treated group at one year and in 13 percent at two years, compared to 21 and 55 percent of controls, respectively" - Also see liver cancer.  Vitamin K3 (menadione sodium bisulfite) is put in animal foods and animal vitamins.
  • Hydrogenated Oils Affect Amount of Vitamin K Available to Bone - Doctor's Guide, 11/30/01 - "Hydrogenation of plant oils decreases the amount of vitamin K available to bone in consumers using food products containing the oils ... available data indicate that more than half of younger US adults do not meet the current guidelines governing adequate intake of the nutrient" - Another reason to stay away from the brands of peanut butter that are hydrogenated. - Ben

Abstracts:

  • Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Covid-19 - Br J Nutr 2020 Oct 7;1-25 - "Coronavirus disease 2019 (Covid-19), caused by SARS-CoV-2, exerts far-reaching effects on public health and socioeconomic welfare. The majority of infected individuals have mild to moderate symptoms but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in activation of both pro- and anticlotting factors in the liver, and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2 induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively" - [Nutra USA] - See vitamin k2 at Amazon.com and iHerb.
  • Association of Dietary Vitamin K and Risk of Coronary Heart Disease in Middle-Age Adults: The Hordaland Health Study Cohort - BMJ 2020 May 21 - "During a median follow-up time of 11 years, we documented 112 incident CHD cases. In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HRQ4vsQ1 = 0.92 (95% CI 0.54 to 1.57), p for trend 0.64), while there was a lower risk of CHD associated with higher intake of energy-adjusted vitamin K2 (HRQ4vsQ1 = 0.52 (0.29 to 0.94), p for trend 0.03). Further adjustment for potential dietary confounders did not materially change the association for K1, while the association for K2 was slightly attenuated (HRQ4vsQ1 = 0.58 (0.28 to 1.19)) ... A higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD" - [Nutra USA]
  • Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19 - pharmacology & toxicology 24 Apr 2020 - "We hypothesized that vitamin K status is reduced in patients with severe COVID-19. Methods: Vitamin K status was assessed by measuring desphospho-uncarboxylated matrix Gla protein (dp-ucMGP; inversely related to vitamin K status) and the rate of elastin degradation by measuring desmosine. We included 123 patients who were admitted with COVID-19 and 184 controls. Results: Dp-ucMGP levels were significantly elevated in COVID-19 patients (1,673Å}1,584 pmol/L) compared to controls (536±291 pmol/L; p<0.0005). Dp-ucMGP levels were significantly higher in COVID-19 patients with unfavorable outcome compared to those with less severe disease. Furthermore, dp-ucMGP and desmosine levels were significantly associated (r=0.65; p<0.0005). Conclusions: Vitamin K status was reduced in patients with COVID-19 and related to poor prognosis. Also, low vitamin K status seems to be associated with accelerated elastin degradation. An intervention trial is now needed to assess whether vitamin K administration improves outcome in patients with COVID-19" -  [Nutra USA] - See vitamin K at Amazon.com and vitamin K at iHerb.com.
  • Early Vascular Ageing in Chronic Kidney Disease: Impact of Inflammation, Vitamin K, Senescence and Genomic Damage - Nephrol Dial Transplant. 2020 Mar 1 - "Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by cardiovascular disease, persistent uraemic inflammation, osteoporosis muscle wasting and frailty. The accelerated early vascular ageing (EVA) process mediated by medial vascular calcification (VC) is a hallmark of senescence as well as a strong predictor of cardiovascular morbidity and mortality in the CKD population ... An accumulating body of evidence indicates that deoxyribonucleic acid (DNA) damage-induced cellular senescence and 'inflammaging' may largely contribute to such pathological conditions characterized by accelerated EVA. Growing evidence shows that nuclear factor erythroid 2-related factor 2 (NRF2) signalling and vitamin K play a crucial role in counteracting oxidative stress, DNA damage, senescence and inflammaging, whereby NRF2 activation and vitamin K supplementation may provide a novel treatment target for EVA. In this review we discuss the link between senescence and EVA in the context of CKD, with a focus on the role of NRF2 and vitamin K in DNA damage signalling, senescence and inflammaging" - [Nutra USA]
  • Central Hemodynamics in Relation to Circulating Desphospho-Uncarboxylated Matrix Gla Protein: A Population Study - J Am Heart Assoc. 2019 Apr 2 - "Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP (Matrix Gla protein), which requires vitamin K-dependent activation, is a potent locally acting inhibitor of arterial calcification ... In people representative for the general population, higher inactive dp-uc MGP was associated with greater PWV , central pulse pressure, forward pulse wave, and backward pulse wave. These observations highlight new avenues for preserving vascular integrity and preventing cardiovascular complications (eg, by improving a person's vitamin K status)" - [Nutra USA]
  • The Bone—Vasculature Axis: Calcium Supplementation and the Role of Vitamin K - Front. Cardiovasc. Med., 05 February 2019 - "Data suggest that supplementing post-menopausal women with high doses of calcium has a detrimental impact on cardiovascular morbidity and mortality. Chronic kidney disease (CKD) patients are prone to vascular calcification in part due to impaired phosphate excretion. Calcium-based phosphate binders further increase risk of vascular calcification progression. In both bone and vascular tissue, vitamin K-dependent processes play an important role in calcium homeostasis and it is tempting to speculate that vitamin K supplementation might protect from the potentially untoward effects of calcium supplementation. This review provides an update on current literature on calcium supplementation among post-menopausal women and CKD patients and discusses underlying molecular mechanisms of vascular calcification. We propose therapeutic strategies with vitamin K2 treatment to prevent or hold progression of vascular calcification as a consequence of excessive calcium intake" - [Nutra USA] - See vitamin K2 at Amazon.com.
  • Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans - Scientific Reportsvolume 8, Article number: 15088 (2018) - "Our observations highlight the possibility that vitamin K supplementation might promote retinal health" - [Nutra USA]
  • Oral Consumption of Vitamin K2 for 8 Weeks Associated With Increased Maximal Cardiac Output During Exercise - Altern Ther Health Med. 2017 Jul;23(4):26-32 - "Vitamin K1 and K2 are not typically common in a Western diet because they are found in a variety of fermented foods. Vitamin K2 in particular has been demonstrated to restore mitochondrial function and has a key role in production of mitochondrial adenosine triphosphate. Thus, it is reasonable to speculate that dietary supplementation with vitamin K2 could increase the function of muscle with high mitochondrial content (ie, skeletal and cardiac muscle) ... Vitamin K2 supplementation was associated with a 12% increase in maximal cardiac output, with P = .031, with a trend toward an increase in heart-rate AUC, with P = .070" - [Nutra USA] - See vitamin K at Amazon.com.
  • Joint Association of Low Vitamin D and Vitamin K Status With Blood Pressure and Hypertension  - Hypertension. 2017 Apr 10 - "The combination of low vitamin D and K status was associated with increased blood pressure and a trend for greater hypertension risk" - See vitamin D at Amazon.com and MK-7 at Amazon.com.
  • Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus - Am J Hypertens. 2016 Dec 7 - "Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes ... In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes" - [Nutra USA] - See MK7 at Amazon.com.  Other article mentioned in the Nutra USA article:
  • Cardiovascular Disease Death Before Age 65 in 168 Countries Correlated Statistically with Biometrics, Socioeconomic Status, Tobacco, Gender, Exercise, Macronutrients, and Vitamin K - Cureus. 2016 Aug 24;8(8):e748 - "The attributable risks of the variables in the CVD early death formula were: too much alcohol (0.38%), too little vitamin K2 (6.95%), tobacco (6.87%), high blood pressure (9.01%), air pollution (9.15%), early childhood death (3.64%), poverty (7.66%), and male gender (6.13%)" - [Nutra USA] - See MK-7 at Amazon.com.
  • Inhibition of TNF-α, IL-1α, and IL-1β by Pretreatment of Human Monocyte-Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro - J Med Food. 2016 May 20 - "Circulatory markers of low-grade inflammation such as tumor necrosis factor-alpha (TNF-α), interleukin-1 alpha (IL-1α), and interleukin-1 beta (IL-1β) positively correlate with endothelial damage, atheroma formation, cardiovascular disease, and aging ... MK-7 is able to modulate immune and inflammatory reactions in the dose-response inhibition of TNF-α, IL-1α, and IL-1β gene expression and protein production by the healthy hMDMs in vitro" - [Nutra USA]
  • Plausible ergogenic effects of vitamin D on athletic performance and recovery - J Int Soc Sports Nutr. 2015 Aug 19 - "The hormonally-active form of vitamin D, 1,25-dihydroxyvitamin D, has been shown to play critical roles in the human body and regulates over 900 gene variants. Based on the literature presented, it is plausible that vitamin D levels above the normal reference range (up to 100 nmol/L) might increase skeletal muscle function, decrease recovery time from training, increase both force and power production, and increase testosterone production, each of which could potentiate athletic performance. Therefore, maintaining higher levels of vitamin D could prove beneficial for athletic performance ... it is possible that dosages exceeding the recommendations for vitamin D (i.e. dosages up to 4000-5000 IU/day), in combination with 50 to 1000 mcg/day of vitamin K1 and K2 could aid athletic performance" - [Nutra USA] - Note:  100 nmol/L equals 40 ng/ml.  I think they usually use ng/ml in the U.S.  At least that's what my blood tests show.  See vitamin D at Amazon.com.
  • High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification - Nutrients. 2015 Aug 18 - "MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures"
  • Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: double-blind randomised clinical trial - Thromb Haemost. 2015 Feb 19 - "Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years ... In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness" - [Nutra USA] - See MK-7 at Amazon.com.
  • Dietary Intake of Vitamin K Is Inversely Associated with Mortality Risk - J Nutr. 2014 Mar 19 - "A prospective cohort analysis was conducted in 7216 participants from the PREDIMED (Prevención con Dieta Mediterránea) study (median follow-up of 4.8 y). Energy and nutrient intakes were evaluated using a validated 137-item food frequency questionnaire. Dietary vitamin K intake was calculated annually using the USDA food composition database and other published sources ... Energy-adjusted baseline dietary phylloquinone intake was inversely associated with a significantly reduced risk of cancer and all-cause mortality after controlling for potential confounders (HR: 0.54; 95% CI: 0.30, 0.96; and HR: 0.64; 95% CI: 0.45, 0.90, respectively). In longitudinal assessments, individuals who increased their intake of phylloquinone or menaquinone during follow-up had a lower risk of cancer (HR: 0.64; 95% CI: 0.43, 0.95; and HR: 0.41; 95% CI: 0.26, 0.64, respectively) and all-cause mortality (HR: 0.57; 95% CI: 0.44, 0.73; and HR: 0.55; 95% CI: 0.42, 0.73, respectively) than individuals who decreased or did not change their intake. Also, individuals who increased their intake of dietary phylloquinone had a lower risk of cardiovascular mortality risk (HR: 0.52; 95% CI: 0.31, 0.86)"
  • Vitamin K1 and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: A case control study - Clin Nutr. 2014 Jan 29 - "Vitamin K1 and 25(OH)D are independently and synergistically associated with the risk of hip fracture when adjusting for confounders" - See vitamin K at Amazon.com.
  • Vitamin K status and cognitive function in healthy older adults - Neurobiol Aging. 2013 Dec;34(12):2777-83 - "Using data from the Québec Longitudinal Study on Nutrition and Successful Aging (NuAge), a cross-sectional analysis was conducted to examine the associations between vitamin K status, measured as serum phylloquinone concentrations, and performance in verbal and non-verbal episodic memory, executive functions, and speed of processing. The sample included 320 men and women aged 70 to 85 years who were free of cognitive impairment. After adjustment for covariates, higher serum phylloquinone concentration (log-transformed) was associated with better verbal episodic memory performances (F = 2.43, p = 0.048); specifically with the scores (Z-transformed) on the second (β = 0.47; 95% confidence interval [CI] = 0.13-0.82), third (β = 0.41; 95% CI = 0.06-0.75), and 20-minute delayed (β = 0.47; 95% CI = 0.12-0.82) free recall trials of the RL/RI-16 Free and Cued Recall Task"
  • Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women - J Bone Miner Metab. 2013 May 24 - "The participants (aged 50-65 years) were randomly assigned to one of two groups according to the MK-4 dose received: the placebo-control group (n = 24) and the 1.5-mg MK-4 group (n = 24). The baseline concentrations of undercarboxylated osteocalcin (ucOC) were high in both groups (>5.1 ng/ml). After 6 and 12 months, the serum ucOC concentrations were significantly lower in the MK-4 group than in the control group. In the control group, there was no significant change in serum pentosidine concentrations. However, in the MK-4 group, the concentration of pentosidine at 6 and 12 months was significantly lower than that at baseline. The forearm BMD was significantly lower after 12 months than at 6 months in the control group. However, there was no significant decrease in BMD in the MK-4 group during the study period. These results suggest that low-dose MK-4 supplementation for 6-12 months improved bone quality in the postmenopausal Japanese women by decreasing the serum ucOC and pentosidine concentrations, without any substantial adverse effects" - See vitamin K at Amazon.com.  See the section in this article "MK4 versus MK7 for Bone Health".
  • Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women - Nutr J. 2012 Nov 12;11(1):93 - "Consecutive administration of MK-4 (60 mug; 135 nmol) or MK-7 (60 mug; 92 nmol) for 7 days demonstrated that MK-4 supplementation did not increase serum MK-4 levels. However, consecutive administration of MK-7 increased serum MK-7 levels significantly in all subjects ... We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues"
  • Dietary phylloquinone intake and risk of type 2 diabetes in elderly subjects at high risk of cardiovascular disease - Am J Clin Nutr. 2012 Oct 3 - "Limited evidence from human and animal studies has suggested that vitamin K has a potentially beneficial role in glucose metabolism and insulin resistance ... Cross-sectional associations were tested in 1925 men and women in the Prevention with the Mediterranean Diet trial ... Dietary intake was collected during each annual visit by using a food-frequency questionnaire, and phylloquinone intake was estimated by using the USDA database ... Dietary phylloquinone at baseline was significantly lower in subjects who developed type 2 diabetes during the study. After adjustment for potential confounders, risk of incident diabetes was 17% lower for each additional intake of 100 μg phylloquinone/d. Moreover, subjects who increased their dietary intake of vitamin K during the follow-up had a 51% reduced risk of incident diabetes compared with subjects who decreased or did not change the amount of phylloquinone intake"
  • Vitamin K, vertebral fractures, vascular calcifications and mortality: Vitamin K Italian (VIKI) dialysis study - J Bone Miner Res. 2012 Jun 12 - "Vitamin K1 deficiency was the strongest predictor of vertebral fractures (OR 2.94 95%CI 1.38-6.26). MK4 deficiency was a predictor of aortic calcification (OR 2.82 95%CI 1.14-7.01), whereas MK5 deficiency actually protected against it (OR 0.38 95%CI 0.15-0.95). MK7 deficiency was a predictor of iliac calcification (OR 1.64 95%CI 1.03-2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR 1.76 95%CI 1.00-3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health"
  • Inhibitory Effect of Vitamin C in Combination With Vitamin K3 on Tumor Growth and Metastasis of Lewis Lung Carcinoma Xenografted in C57BL/6 Mice - Nutr Cancer. 2011 Sep 2 - "Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice ... These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation" - See vitamin C products at Amazon.com and vitamin K at Amazon.com.
  • Dietary phylloquinone and menaquinones intake and risk of type 2 diabetes - Diabetes Care. 2010 Apr 27 - "phylloquinone intake tended to be associated (p=0.08) with a reduced risk of type 2 diabetes with a hazard ratio of 0.81 (95%-CI: 0.66-0.99) for the highest versus the lowest quartile. For menaquinones intake, a linear, inverse association (p=0.038) with risk of type 2 diabetes was observed with a hazard ratio of 0.93 (0.87-1.00) for each 10 mug increment in the multivariate model. Conclusion: This study shows that both phylloquinone and menaquinones intake may be associated with a reduced risk of type 2 diabetes"
  • Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg) - Am J Clin Nutr. 2010 Mar 24 - "Dietary intake of menaquinones was nonsignificantly inversely associated with overall cancer incidence (HR for the highest compared with the lowest quartile: 0.86; 95% CI: 0.73, 1.01; P for trend = 0.08), and the association was stronger for cancer mortality (HR: 0.72; 95% CI: 0.53, 0.98; P for trend = 0.03). Cancer risk reduction with increasing intake of menaquinones was more pronounced in men than in women, mainly driven by significant inverse associations with prostate (P for trend = 0.03) and lung cancer (P for trend = 0.002). We found no association with phylloquinone intake"
  • Vitamin K2 Suppresses Proliferation and Motility of Hepatocellular Carcinoma Cells by Activating Steroid and Xenobiotic Receptor - Endocr J. 2009 Jun 24 - "These results suggest that the activation of SXR could contribute to tumor suppressive effects of vitamin K2 on HCC cells"
  • Combination of vitamin K(2) and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma - J Hepatol. 2009 May 15 - "A 48-month follow-up revealed that the combination treatment with VK and ACE-I markedly inhibited the cumulative recurrence of HCC in association with suppression of the serum level of the vascular endothelial growth factor (VEGF); a central angiogenic factor. The serum level of lectin-reactive alpha-fetoprotein was also suppressed almost in parallel with VEGF. These beneficial effects were not observed with single treatment using VK or ACE-I" - See vitamin K at Amazon.com.
  • High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature - Nutr Res. 2009 Apr;29(4):221-8 - "randomized controlled trials (RCTs) ... The review of the reliable literature confirmed the effect of vitamin K(1) and vitamin K(2) supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover"
  • Vitamin K supplementation and progression of coronary artery calcium in older men and women - Am J Clin Nutr. 2009 Apr 22 - "those who received phylloquinone supplements had 6% less progression than did those who received the multivitamin alone ... Phylloquinone supplementation slows the progression of CAC in healthy older adults with preexisting CAC, independent of its effect on total MGP concentrations"
  • A high menaquinone reduces the incidence of coronary heart disease in women - Nutr Metab Cardiovasc Dis. 2009 Jan 27 - "A high intake of menoquinones, especially MK-7, MK-8 and MK-9, could protect against CHD"
  • Serum undercarboxylated osteocalcin as biomarker of vitamin k intake and risk of prostate cancer: a nested case-control study in the heidelberg cohort of the European prospective investigation into cancer and nutrition - Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):49-56 - "From cell studies, Vitamin K is known to exert anticancer effects on a variety of cancer cell lines, including prostate cancer cells. Recently, we reported an inverse association between dietary intake of menaquinones (vitamin K(2)), but not phylloquinone (vitamin K(1)), and risk of prostate cancer ... There was indication of a lower prostate cancer risk in carriers of the A allele (compared with GG carriers) of the +2255 VKORC1 polymorphism with increasing menaquinone intake (P(interaction) = 0.14) whereas no distinct effect modification was observed for the ucOC/iOC ratio (P(interaction) = 0.37). The increased risks of advanced-stage and high-grade prostate cancer with higher serum ucOC/iOC ratio strengthen the findings for dietary menaquinone intake"
  • Phylloquinone intake, insulin sensitivity, and glycemic status in men and women - Am J Clin Nutr. 2008 Jul;88(1):210-5 - "Limited evidence suggests that vitamin K may have a beneficial role in glucose homeostasis ... Higher phylloquinone intake was associated with greater insulin sensitivity and glycemic status, as measured by 2-h post-OGTT insulin and glucose and ISI(0,120), after adjustment for age, sex, waist circumference, lifestyle characteristics, and diet quality [2-h post-OGTT insulin: lowest and highest quintile, 81.0 and 72.7 microU/mL, respectively (P for trend = 0.003); 2-h post-OGTT glucose: 106.3 and 101.9 mg/dL, respectively"
  • An Attempt to Evaluate the Effect of Vitamin K(3) Using as an Enhancer of Anticancer Agents - Biol Pharm Bull. 2008;31(6):1270-1273 - "These findings suggest that VK(3) induces G(2)/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G(2) phase-dependent drugs in hepatic cancer chemotherapy"
  • A 12 week, open label, phase I/IIa study using apatone for the treatment of prostate cancer patients who have failed standard therapy - Int J Med Sci. 2008 Mar 24;5(2):62-7 - "oral Apatone (Vitamin C and Vitamin K3) administration in the treatment of prostate cancer ... 5,000 mg of VC and 50 mg of VK3 each day ... At the conclusion of the 12 week treatment period, PSAV decreased and PSADT increased in 13 of 17 patients (p < or = 0.05). There were no dose-limiting adverse effects. Of the 15 patients who continued on Apatone after 12 weeks, only 1 death occurred after 14 months of treatment"
  • Vitamin K(2) suppresses malignancy of HuH7 hepatoma cells via inhibition of connexin 43 - Cancer Lett. 2008 Jan 29 - "The anti-cancer potential of vitamin K(2) (VK(2)) in hepatoma has gained considerable attention"
  • Vitamin K and Vitamin D Status: Associations with Inflammatory Markers in the Framingham Offspring Study - Am J Epidemiol. 2007 Nov 15 - "Vitamin K status, measured by plasma phylloquinone concentration and phylloquinone intake, was inversely associated with circulating inflammatory markers as a group and with several individual inflammatory biomarkers" - See vitamin K at Amazon.com.
  • Vitamin K(2) supplementation improves hip bone geometry and bone strength indices in postmenopausal women - Osteoporos Int. 2007 Feb 8 - "Vitamin K(2) helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD"
  • Vitamin K and the Prevention of Fractures: Systematic Review and Meta-analysis of Randomized Controlled Trials - Arch Intern Med. 2006 Jun 26;166(12):1256-61 - "This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss. In the case of the latter, there is a strong effect on incident fractures among Japanese patients"
  • Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women - J Bone Miner Res. 2007 Apr;22(4):509-19 - "women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius"
  • Vitamin K treatment for postmenopausal osteoporosis in Indonesia - J Obstet Gynaecol Res. 2006 Apr;32(2):230-4 - "After 48 weeks of treatment, the mean percentage change of lumbar BMD in the vitamin K(2) group was significantly higher (P < 0.05) than that of the control group"
  • Vitamin K, bone turnover, and bone mass in girls - Am J Clin Nutr. 2004 Oct;80(4):1075-80 - "Better vitamin K status was associated with decreased bone turnover in healthy girls consuming a typical US diet"
  • Bone health. New role for vitamin K? - Can Fam Physician. 2004 Jul;50:993-7 - "Evidence suggests that dietary phylloquinone intake of <100 microg daily might not be optimal for bone health. Low intake of vitamin K could contribute to osteoporosis and subsequent fracture ... Family physicians need to be aware of the importance of encouraging adequate vitamin K intake, particularly among institutionalized elderly people, to prevent increased bone resorption"
  • Role of Vitamin K2 in the Development of Hepatocellular Carcinoma in Women With Viral Cirrhosis of the Liver - JAMA. 2004 Jul 21;292(3):358-61 - "Hepatocellular carcinoma was detected in 2 of the 21 women given vitamin K2 and 9 of the 19 women in the control group ... the risk ratio for the development of hepatocellular carcinoma in patients given vitamin K2 was 0.13" - See vitamin K at Amazon.com.
  • Vitamin K intake and bone mineral density in women and men - Am. J. of Clin. Nutr., 2/03 - "Low dietary vitamin K intake was associated with low BMD in women ... In contrast, there was no association between dietary vitamin K intake and BMD in men"
  • Vitamin K supplementation in cystic fibrosis - Arch Dis Child. 2003 Nov;88(11):974-5 - "a increased vitamin K intake may have significant health benefits for children with CF"