Abstract
Reported associations between vitamin K1 and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52–60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K1 (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87–192 µg/d) intake of vitamin K1 was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K1 intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K1 may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.
Highlights
Vitamin K, a group of fat-soluble vitamins, is important for blood clotting, as well as bone and vascular health and other physiological functions [1]
Five databases were linked to the cohort on the individual level: (1) The Civil Registration System which includes data on age, sex and vital status; (2) The Integrated Database for Labour Market Research [18] which provides information on annual income and employment status; (3) The Danish Register of Causes of Death contains information on the cause of death since 1994 by International Classification of Diseases (ICD) codes; (4) The Danish National Prescription Registry containing information on all filled prescriptions since 1994; (5) The Danish National Patient Register (DNPR) provides data on all hospital admissions in Denmark since 1978 with all diagnoses defined by ICD codes
Compared to participants in the lowest quintile of vitamin K1 intake, a greater percentage of participants in the highest quintile were male, more physically active, had a higher level of education, had a higher income, had never smoked, and had a higher energy intake and a higher intake of alcohol, fish, red meat, wholegrains, fruits and vegetables. They had a higher prevalence of diabetes, but a lower prevalence of hypertension, chronic obstructive pulmonary disease (COPD), ischemic heart disease (IHD), peripheral artery disease (PAD), stroke, and heart failure
Summary
Vitamin K, a group of fat-soluble vitamins, is important for blood clotting, as well as bone and vascular health and other physiological functions [1]. Studies on vitamin K absorption are lacking, but from the limited data available, the bioavailability of vitamin K 1 from vegetables appears to be low (5–10%), with higher absorption observed from oilbased sources [3]. It is not currently possible to accurately estimate dietary intakes of vitamin K2, making it difficult to draw conclusions regarding its association with health outcomes in observational studies. Evidence from observational studies is limited and provides conflicting reports as to the association between vitamin K1 and both all-cause [11,12,13,14] and cause-specific mortality, including CVD- [11, 13, 14] and cancer-related mortality [11, 13, 15, 16]. Our secondary aim was to identify subpopulations that may benefit the most from higher vitamin K1 intakes
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