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Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for vitamin K. In this Opinion, the Panel considers vitamin K to comprise both phylloquinone and menaquinones. The Panel considers that none of the biomarkers of vitamin K intake or status is s...
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Context 1
... K represents a family of fat-soluble compounds with the common chemical structure 3- substituted 2-methyl-1,4-napthoquinone (Figure 1). ...
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... the c-glutamyl carboxylation of vitamin K-dependent proteins, the active (reduced) form of vitamin K (hydroquinone) is converted to vitamin K epoxide (Figure 1), the oxidised form of vitamin K, that is subsequently reduced back to hydroquinone (Furie et al., 1999;Tie et al., 2005). This redox cycle, called vitamin K cycle, takes place in different tissues, particularly in the liver and bone. ...
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... side chain is metabolised by an initial x-hydroxylation, followed by a progressive side-chain shortening via the b-oxidation pathway (Shearer and Newman, 2014), until the side chain is shortened to two major metabolites with 7-and 5-carbon side chains. The 5C-metabolite has the structure 2-methyl-3-(3 0 -3 0 -carboxymethylpropyl)-1,4-naphthoquinone and the 7C-metabolite has the structure 2-methyl-3-(5 0 -carboxy-3 0 -methyl-2 0 -pentenyl)-1,4-naphthoquinone ( Figure 1 in Sections 2.1 and 2.4). These two metabolites are conjugated with glucuronic acid and excreted in the bile ( Shearer et al., 1972Shearer et al., , 1974 and the urine ( Shearer et al., 1970aShearer et al., , 1974Shearer and Barkhan, 1973;McBurney et al., 1980) (Section 2.3.6). ...
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... 5C-and 7C-metabolites are common products of the metabolism of phylloquinone and menaquinones ( Figure 1 and Section 2.3.5). The 5C-metabolite was shown as the main urinary vitamin K metabolite in adults either unsupplemented or consuming various doses/intakes of phylloquinone, MK-4 or MK-7 ( Harrington et al., 2005Harrington et al., , 2007) (Section 2.4) and in term infants before or after vitamin K prophylaxis ( Harrington et al., 2010). ...
Citations
... No adverse effects have been reported for individuals consuming high doses of vitamin K, and no tolerable upper intake level has been established by authorities [41]. Nevertheless, concerns have been raised about the safety of vitamin K administration, specifically in COVID-19, due to the pro-thrombotic nature of the disease. ...
Background: In observational studies, high levels of desphospho-uncarboxylated matrix gla protein (dp-ucMGP) that result from vitamin K deficiency were consistently associated with poor clinical outcomes during COVID-19. Vitamin K-activated matrix gla protein (MGP) is required to protect against elastic fibre degradation, and a deficiency may contribute to pathology. However, intervention trials assessing the effects of vitamin K supplementation in COVID-19 are lacking. Methods: This is a single-centre, phase 2, double-blind, randomised, placebo-controlled trial investigating the effects of vitamin K2 supplementation in 40 hospitalised COVID-19 patients requiring supplemental oxygen. Individuals were randomly assigned in a 1:1 ratio to receive 999 mcg of vitamin K2—menaquinone-7 (MK-7)—or a placebo daily until discharge or for a maximum of 14 days. Dp-ucMGP, the rate of elastic fibre degradation quantified by desmosine, and hepatic vitamin K status quantified by PIVKA-II were measured. Grade 3 and 4 adverse events were collected daily. As an exploratory objective, circulating vitamin K2 levels were measured. Results: Vitamin K2 was well tolerated and did not increase the number of adverse events. A linear mixed model analysis showed that dp-ucMGP and PIVKA-II decreased significantly in subjects that received supplementation compared to the controls (p = 0.008 and p = 0.0017, respectively), reflecting improved vitamin K status. The decrease in dp-ucMGP correlated with higher plasma MK-7 levels (p = 0.015). No significant effect on desmosine was found (p = 0.545). Conclusions: These results demonstrate that vitamin K2 supplementation during COVID-19 is safe and decreases dp-ucMGP. However, the current dose of vitamin K2 failed to show a protective effect against elastic fibre degradation.
... The high intake of vitamin K might partly compensate for the effects of the low intake of calcium and vitamin D in vegetarians since the estimated dairy intake was above the recommended amounts [39]. Concerning vitamin A, retinol was almost absent in the vegan diet, but the contribution of carotenes, with known vitamin A activity, could play a protecting role that cannot be underestimated. ...
Sustainable healthy diets are promoted, and consequently vegetarian diets are currently increasing. However, scientific information on their effects on bone health is scarce. A cross-sectional study was performed in adults (66% women) classified into three groups: omnivores (n = 93), lacto-ovo vegetarians (n = 96), and vegans (n = 112). Nutrient intake, body composition, physical activity, vitamin D status (25-hydroxycholecalciferol, 25-OHD), parathormone (PTH), and bone formation (bone alkaline phosphatase, BAP) and resorption (N-telopeptides of type I collagen, NTx) markers were determined. Lacto-ovo vegetarians and especially vegans showed lower protein, fat, calcium, phosphorous, vitamin D, retinol, iodine, and zinc intakes, and higher carbohydrate, fibre, carotenes, magnesium, and vitamin K intakes compared to omnivores. Body composition was similar in the three groups that performed vigorous physical activity regularly. Body bone mass and muscle mass were positively correlated with BAP, and time performing physical activity with 25-OHD. The prevalence of vitamin D deficiency or insufficiency (25-OHD < 75 nmol/L) was 93.7% in the studied population, and vitamin D deficiency (25-OHD < 25 nmol/L) was significantly higher in vegans. Vegetarians of both groups had increased PTH and NTx with vegans showing significantly higher PTH and NTx than omnivores. Conclusion: Adult vegetarians, especially vegans, should reduce the risk of bone loss by appropriate diet planning and vitamin D supplementation.
... Vitamin K is absorbed mainly in the small intestine through the pathway common to most dietary lipids (4). Absorption of phylloquinone is highly variable, with 80% of purified phylloquinone from supplements, but considerably less (3-50% of that absorbed from supplements) from plant foods (3). Absorption is dependent on food matrix and accompanying meal. ...
... Vitamin K is primarily stored in adipose tissue, but the total body pool of vitamin K is relatively low compared to other fat-soluble vitamins. Besides the liver, vitamin K can be detected in other organs such as heart and pancreas (3,6). ...
... There are several biomarkers that reflect vitamin K intake; however, none are considered sufficient to be used alone (10,11). Serum concentration of phylloquinone is a short-term marker of phylloquinone intake, and it is the most frequently used marker for vitamin K status (3,(10)(11)(12). Serum phylloquinone concentration responds to dietary changes. ...
Vitamin K occurs in dietary supply in two major forms: phylloquinone (vitamin K1) and menaquinones (collectively referred as vitamin K2). Phylloquinone is derived from plants. There are at least 10 forms of menaquinones varying in chain length and they are produced by bacteria except menaquinone-4. Menaquinone-4 is formed from phylloquinone or other menaquinone forms. Phylloquinone is considered to be the major contributor and menaquinones are thought to contribute less to vitamin K intake in Western diets. However, less is known about the content of menaquinones than phylloquinones in foods.
Vitamin K is known to function as an enzymatic cofactor in the gamma-carboxylation of vitamin K dependent proteins (VKDPs). Hepatic VKDPs are involved in coagulation. Extrahepatic VKDPs have a role e.g. in bone health and vascular calcification. However, the amount of vitamin K needed for optimal functioning of the different VKDPs is not known.
... More evidence is needed about the effects of VitK supplementation at physiological and pharmacological doses and what the required dose of VitK is to ensure bone and vascular health [68]. In adults, the adequate intake of VitK, in according to EFSA is 70 µg/day (VitK as phylloquinone) [69] (Table 3). The AI is relate to ergocalciferol (VitD2) and cholecalciferol (VitD3). ...
Osteoporosis is considered the most frequent rheumatic pathology in the elderly population. It is often accompanied by sarcopenia, defined as the progressive loss of skeletal muscle mass and strength. Together, these conditions increase the risk of falls, fractures, disability, lower quality of life, and frequent hospitalization. This means increased healthcare costs for all European countries, due to the increase in the average age and elderly population. Multiple pharmacological therapies are available for osteoporosis, but the prevention seems to be an important tool to reduce the risk of fracture and hospitalization of patients. A healthy lifestyle, consisting of the right amount of nutrients and micronutrients and physical exercise can help prevent the development of osteoporosis and sarcopenia in the elderly. This review brings together the information present in the literature on the benefits that nutrients and micronutrients, naturally present in foods, have on the prevention of these pathologies. it is suggested that a correct intake of proteins, calcium, phosphorus, magnesium, vitamin.D, vitamin C and antioxidants, vitamin K and omega 3, associated with constant physical exercise, can help to contain osteoporosis. It also indicates the right physical exercise for older osteoporotic adults. This document drawn up by the CReI-Food study group of the Italian College of Rheumatologists aims to provide, based on the most recent scientific evidence, indications on correct nutrition and lifestyle for the prevention and treatment of osteoporosis in older people.
... The basic difference in the chemical structure of these two forms is the carbon chain. Vitamin K 1 has a carbon chain with one double bond, whereas vitamin K 2 has a variable number of carbons and several double bonds [29]. ...
... Studies have shown an association between vitamin K and calcium deposition in bones, glucose metabolism, energy metabolism, cardiovascular health, and fertility [31]. After absorption from the blood, vitamin K is included in micelles and is present in chylomicrons [29]. According to US dietary guidelines, women and men should consume 90 and 120 μg/day of vitamin K, respectively [32]. ...
Fat-soluble vitamins (FSVs) offer a range of beneficial properties as important nutrients in human nutrition. However, the high susceptibility to environmental conditions such as high temperature, light, and oxygen leads to the degradation of these compounds. This review highlights the different formulations underlying the encapsulation of FSVs in biopolymer (polysaccharide and protein) and lipid-based micro or nanocarriers for potential applications in food and pharmaceutical industries. In particular, the function of these carrier systems in terms of encapsulation efficiency, stability, bioavailability, and bio-accessibility is critically discussed. Recently, tremendous attention has been paid to encapsulating FSVs in commercial applications. According to the chemical nature of the active compound, the vigilant selection of delivery formulation, method of encapsulation, and final application (type of food) are the key important factors to be considered in the encapsulation of FSVs to ensure a high loading capacity, stability, bioavailability, and bio-accessibility. Future studies are recommended on the effect of different vitamin types and micro and nano encapsulate sizes on bioaccessibility and biocompatibility through in vitro/in vivo studies. Moreover, the toxicity and safety evaluation of encapsulated FSVs in human health should be evaluated before commercial application in food and pharmaceuticals.
... While more investigations are needed to fill the knowledge gap between vitamin K synthesis and bioavailability, current evidence [37] suggests that dietary vitamin K is transported by lipoproteins and taken up chemically unchanged into chylomicrons in the intestinal mucosa, secreted into the lymph system and released in the circulation. The chylomicrons then enter the liver via chylomicron remnant particles. ...
... Indeed, the US dietary recommendations do not include menaquinone intake, as the United States Department of Agriculture (USDA) Nutrient Database [67] details only the phylloquinone content of foods and current knowledge about the identification and quantification of dietary sources of menaquinones is still in its infancy. Similarly, the European Food Safety Authority (EFSA) suggests that until more is known about dietary menaquinone content and relative bioavailability, it is premature to set a separate dietary recommendation for menaquinone intake [37]. ...
Vitamin K and vitamin K-dependent proteins have been reported to be associated with a large spectrum of age-related diseases. While most of these associations have been deduced from observational studies, solid evidence for the direct impact of vitamin K on cellular senescence remains to be proven. As vitamin K status reflects the complexity of interactions between dietary intake, gut microbiome activity and health, we will demonstrate the pivotal role of the diet-microbiome-health axis in human ageing and exemplify how vitamin K is implicated therein. We propose that food quality (i.e., food pattern) should be highlighted beyond the quantity of total vitamin K intake. Instead of focusing on a single nutrient, exploring a healthy diet containing vitamin K may be more strategic. As such, healthy eating patterns can be used to make dietary recommendations for the public. Emerging evidence suggests that dietary vitamin K is a modulator of the diet-microbiome-health axis, and this needs to be incorporated into the investigation of the impact of vitamin K on gut microbial composition and metabolic activities, along with host health outcomes. In addition, we highlight several critical caveats that need to be acknowledged regarding the interplay between diet, vitamin K, gut microbiome and host health that is pivotal for elucidating the role of vitamin K in ageing and responding to the urgent call of healthy eating concerning public health.
... The mean prevalence of VL was 2.17% for the year 2017, which increased to 20.37% in persons aged 85 years and older, representing nearly 7.08 million people, 1.08 million of whom have blindness, a 68.7% increase over previous estimates [7]. The cost of VL is significant, with estimates of the yearly US total economic burden of VL in 2017 being USD 134.2 billion-USD Current recommendations with respect to VK intake are framed as Adequate Intake (AI) values for PK and have been set at 120 µg per day for men and 90 µg for women in the USA [47] and at 70 µg/day for both men and women over the age 19 years in the EU [48]. The importance of menaquinones from meat, eggs, and dairy products is being increasingly recognized [36,37], as are fermented foods such as natto and other similar products in Asia [49]. ...
... A total of 768 individuals underwent cataract surgery. Notably, the European Food Safety Authority has set an adequate intake (AI) of 1 µg phylloquinone/kg body weight per day for all age and sex groups [48], and though the PREDIMED study did not report body weights, the average weights for adults in Spain are 82 kg and 66 kg for males and females [126]; the United States and Canada AI-s are 120 and 90 µg/day [127]. Thus, on average, the estimated daily intake of PK in this cohort was 2.75-5.5 times the recommended AIs on the low and high ends respectively, yet a near doubling of the PK intake from 249.4 to 496.7 µg/d was associated with a 29% reduction in the hazard ratio (HR) for cataract surgeries comparing the lowest to highest tertiles. ...
Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic-related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in mice. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with those with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is, therefore, the intention of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and provide some historical context for recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon in the hope of raising awareness and encouraging continued VK-related investigations in this important and highly specialized sensory system.
... Only the deficit reported for some essential nutrients such as choline could be of concern, although it could be easily corrected with crop planning that would allow a greater amount of animal sourced food such as chicken eggs to enter the diet without exceeding protein requirements. The excess of vitamin K in the diet was caused by the overproduction of dark green vegetables that are rich in this type of vitamin [25], although it would be resolved with a correct planning of crops, it is not worrying due to the high tolerance in humans, especially to phylloquinone, with values higher than those provided by the calculated diet [26,27]. ...
Homestead aquaponic production has been proposed as a reasonable alternative for obtaining food within the framework of the circular economy. However, little is known about the ability of homestead aquaponics to contribute to a healthy diet and the savings it represents on the cost of such diets for inhabitants of economically depressed communities. In the present work, based on a case study, the nutritional contribution of vegetables and fish produced in one year has been calculated, with the goal of determining the contribution of aquaponics to the healthy diet of an adult during this study period. The amount of external food products that should be purchased, the nutritional contribution of the complete diet (comparing it with that of a Mediterranean diet), and its cost have also been determined. The results show that achieving a balanced diet in macronutrients, minerals and essential nutrients with aquaponics is feasible, with a real cost of about 3.07 euros per person per day, amounting to a mean savings of 22% compared to the market price of food. The percentage of nutrient contribution of aquaponic foods exceeds in most cases 20%, being especially high for protein, dietary fiber, some minerals such as potassium, and vitamins.
... In addition, in accordance with previous studies, 10,17 we observed a significant reduction in dp-ucMGP in the intervention group, suggesting that our dosage significantly modulated vitamin K deficiency. Currently there are no recommendations about MK-7 intake, but according to the European Food Safety Authority, the average daily recommended dose of phylloquinone (vitamin K1) to adults is 70 µg, 18 and because MK-7 is the most effective cofactor for the carboxylation-and activation-of vitamin K-dependent proteins, 19 our dose seems not to be too low. However, we cannot exclude that patients with low vitamin K status might benefit from further supplementation. ...
Background: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis.
Methods: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 μg MK-7 plus 25 μg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events.
Results: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, -0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P<0.001).
Conclusions: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression.
... Menaquinone-7 (MK-7) is a type of vitamin K 2 composed of a mother ring of menadione and seven isoprene side chains. MK-7 plays a role in respiratory chain transmission, coagulation function, and calcium homeostasis (Turck et al., 2017;Wilkens et al., 2021;Wu et al., 2021). In addition, MK-7 has more and more benefits in promoting bone healing, preventing cerebrovascular and cardiovascular diseases and fighting cancer cells, Alzheimer's disease and Parkinson's disease (Halder et al., 2019;Mahdinia et al., 2019a;Tarkesh et al., 2020). ...
Menaquinone-7 (MK-7) is an important vitamin K2, synthesized from the menaquinone parent ring and seven isoprene side chains. Presently, the synthesis of MK-7 stimulated by environmental stress primarily focuses on oxygen stress, while the effect of alkali stress is rarely studied. Therefore, this study researched the effects of alkali stress on the fermentation performance and gene expression of Bacillus subtilis natto. The organism’s growth characteristics, biomass, sporogenesis, MK-7 biosynthesis, and gene expression were analyzed. After a pH 8.5 stress adaptation treatment for 0.5 h and subsequent fermentation at pH 8.5, which promoted the growth of the strain and inhibited the spore formation rate. In addition, biomass was significantly increased (P < 0.05). The conversion rate of glycerol to MK-7 was 1.68 times higher than that of the control group, and the yield of MK-7 increased to 2.10 times. Transcriptomic analysis showed that the MK-7 high-yielding strain had enhanced carbon source utilization, increased glycerol and pyruvate metabolism, enhanced the Embden-Meyerhof pathway (EMP), tricarboxylic acid (TCA) circulation flux, and terpenoid biosynthesis pathway, and promoted the accumulation of acetyl-CoA, the side-chain precursor of isoprene. At the same time, the up-regulation of transketolase increased the metabolic flux of the pentose phosphate (HMP) pathway, which was conducive to the accumulation of D-erythrose 4-phosphate, the precursor of the menadione parent ring. This study’s results contribute to a better understanding of the effects of environmental stress on MK-7 fermentation by Bacillus subtilis natto and the molecular regulatory mechanism of MK-7 biosynthesis.
