Vitamin K and K1

What is vitamin K and what does it do in the body?

Vitamin K is the general name for a family of compounds with a common chemical structure: phylloquinone (K1) and the menaquinones (K2), ranging from MK-4 to MK-13. Phylloquinone is found mainly in green leafy vegetables and is the main dietary form; menaquinones are mostly of bacterial origin, are found in small amounts in fermented and animal foods, and are also produced by gut bacteria. Unlike these, MK-4 can form in the body from phylloquinone without bacterial action. ^[1]

The vitamin is the coenzyme of the K-dependent carboxylase enzyme. This enzyme is required for the synthesis of clotting proteins (including prothrombin, that is, factor II) and of proteins involved in bone metabolism. Matrix Gla protein is found in vascular smooth muscle, bone, and cartilage and is being investigated because it may reduce abnormal calcification; osteocalcin is another K-dependent protein found in bone. Warfarin and some anticoagulants used in Europe work by blocking the action of this vitamin. ^[1]

Unlike other fat-soluble vitamins, vitamin K is metabolized and excreted rapidly; NIH states that only about 30–40% of a physiological oral dose is retained in the body, so blood levels and tissue stores remain low. ^[1] The only clinically meaningful status marker is prothrombin time, and it is monitored routinely only in people taking anticoagulants or with bleeding disorders. ^[1]

Are K1 and K2 the same thing? Which foods contain them?

The two groups belong to the same vitamin family but differ in their sources and absorption. According to NIH, phylloquinone in plant foods is tightly bound to chloroplasts; phylloquinone absorbed from spinach is only 4–17% of that from a tablet. Absorption rises in vegetables eaten with fat, but remains below the amount absorbed from oils or supplements. Data on the food composition of K2 are limited. ^[1]

The table uses US servings and the US Daily Value (DV, 120 µg for adults); a value of 20% and above counts as a “high source.” According to NIH, the most common sources in the US diet are spinach, broccoli, lettuce, and liquid oils such as soybean and canola oil. ^[1] In Türkiye, in the 2008 book by Samur of Hacettepe University published on the HSGM (General Directorate of Public Health) website, the richest sources are listed as spinach and similar green leafy vegetables, liver, dried legumes, and fish. ^[13]

How much is the daily vitamin K reference intake?

Official reference values are not a single number and should be read with the institution stated. The US Food and Nutrition Board, on which NIH relies, could not set an estimated average requirement (EAR) because of insufficient data and defined an adequate intake (AI) for all age groups: 120 µg for men and 90 µg for women over age 19 (90 µg in pregnancy and lactation). ^[1] EFSA (2017), for its part, concluded that an average requirement and population reference intake could not be derived and, on the basis of 1 µg phylloquinone/kg body weight, set the AI for all adults, including pregnant and breastfeeding women, at 70 µg/day, for phylloquinone only; it gave no AI for menaquinones because it found the evidence insufficient. ^[2]

For Türkiye, the 2008 book prepared by Samur of Hacettepe University and published on the HSGM website gives a daily requirement of 80 µg for adult men and 65 µg for women. ^[13] The three values come from different institutions and different years; none is an individual dose. NIH reports mean food-derived intake in the US as 122 µg in adult women and 138 µg in men and points out that the AI is only an estimate of requirement, that the vitamin is also produced in the body, and that deficiency is very rare in adults. ^[1] NIH writes that no upper limit (UL) has been set because no adverse effects have been reported from food or supplements. Menadione (synthetic, “K3”), however, is not used in supplements and fortified foods because it damaged liver cells in laboratory studies. ^[1]

Who develops vitamin K insufficiency?

Clinically significant deficiency is very rare in adults and is generally limited to people with malabsorption and those using drugs that interfere with vitamin K metabolism; NIH states that on a varied diet it is almost impossible to reach an intake low enough to alter clotting tests. The groups at risk: ^[1]

• Newborns: Placental transfer of K is poor, clotting factors are low, and breast milk is low in vitamin K. ^[1]
• People with malabsorption: K status may be low in cystic fibrosis, celiac disease, ulcerative colitis, short bowel syndrome, and after bariatric surgery. ^[1]
• People using medications: Antibiotics can lower K status by reducing gut bacteria (the effect may be more pronounced with cephalosporins); bile acid sequestrants and orlistat can reduce absorption of fat-soluble vitamins. NIH writes that supplementation may be needed if antibiotic use lasts longer than a few weeks and K intake is also poor. ^[1]

The book published on the HSGM website in Türkiye likewise states that the use of vitamin K becomes insufficient in liver and digestive system disorders, especially when bile flow is obstructed, and that prolonged antibiotic treatment may also reduce vitamin K activity by disturbing the gut flora. ^[13]

Why is vitamin K given to newborns?

According to NIH, vitamin K deficiency bleeding (VKDB; formerly classic hemorrhagic disease of the newborn) can occur in newborns in the first weeks; it presents as bleeding from the umbilicus, digestive tract, skin, or nose. VKDB occurring in the first week is called early and that occurring at weeks 2–12 is called late; late VKDB occurs particularly in exclusively breastfed infants or those with absorption problems and can be fatal as sudden intracranial bleeding. NIH reports that the American Academy of Pediatrics recommends a single 0.5–1 mg intramuscular dose of K1 at birth. ^[1]

In the Cochrane review, two randomized trials comparing a single intramuscular dose of vitamin K after birth with placebo or nothing reduced clinical bleeding on days 1–7; 11 trials evaluated oral doses and improved clotting markers, but none measured clinical bleeding. The authors state that a single 1.0 mg intramuscular dose prevents classic hemorrhagic disease, while the effect of oral administration on late disease or clinical bleeding has not been tested in randomized trials. ^[10]

In Türkiye, Circular No. 2021/11, “Vitamin K Administration in Newborns,” of the Turkish Ministry of Health General Directorate of Public Health states that all newborns are to receive administration in the delivery room after birth, that administration is to be generally intramuscular and the dose 1 mg, and that for babies with a birth weight under 1,500 g the dose is 0.5 mg intramuscular. Families are informed; in case of refusal, an additional form is signed, kept in the patient file, and forwarded to the provincial health directorate. The text is addressed to health institutions; the official practice is reported here, and it is not dose information for parents. ^[11] The Ministry’s public-facing page also describes vitamin K as a single dose given shortly after birth and states that the oral route is not a substitute. ^[12]

Does vitamin K strengthen bones?

The biological role is clear; the question is whether extra supplementation prevents fractures. NIH writes that some studies found an association between vitamin K intake and bone density or hip fracture and others did not, that it is uncertain whether supplementation reduces osteoporosis risk, and that in Japan a pharmacological dose of MK-4 is used in osteoporosis treatment. After the 2006 meta-analysis reported by NIH, the systematic review was updated because the integrity of part of the earlier evidence was questioned (below). ^{[1] [3]}

The update (Mott et al., 2019) identified 36 randomized trials evaluating oral vitamin K supplementation in adults. In postmenopausal or osteoporotic people, the odds of clinical fracture were lower than with control (OR 0.72; 95% CI 0.55–0.95); limited to low-risk-of-bias studies, the OR was 0.76 (0.58–1.01). There was no difference in vertebral fracture (OR 0.96; 0.83–1.11). For bone density, the difference at the lumbar spine at year 1 was not significant (mean difference 0.93%; −0.02 to 1.89) and at year 2 was significant (1.63%; 0.10–3.16); when high-risk-of-bias studies were removed, the difference shrank and became nonsignificant. The authors concluded that there is no evidence that vitamin K affects bone density or vertebral fracture in postmenopausal or osteoporotic patients, and that it may reduce clinical fracture but the evidence is not enough to confirm this. ^[3]

In the published correction, estimates were recalculated because of concerns about the integrity of one study (this study had been counted as high risk of bias): OR 0.74 (0.56–0.97) for clinical fracture and OR 0.98 (0.85–1.14) for vertebral fracture; results in the low-risk-of-bias subgroup did not change. The authors state that the overall conclusions and their judgments on bone density and fractures did not change. ^[4] For this reason, the corrected values rather than the figures in the original abstract are used.

NIH also reports a 12-month study in 381 postmenopausal women: in the groups receiving K1 or MK-4, undercarboxylated osteocalcin fell, but there was no difference between groups in lumbar spine or proximal femur bone density. ^[1] NIH reports that EFSA approved the relationship between vitamin K and “maintenance of normal bones” as a nutrition claim; in the US, the FDA has not approved such a health claim. ^[1]

Does vitamin K work for heart and vascular health?

Evidence on markers of vascular calcification is small and variable. Lees et al. examined 13 controlled studies (n=2,162) and 14 longitudinal studies (n=10,726): vitamin K supplementation was associated with a 9.1% reduction in vascular calcification (95% CI −17.7 to −0.5; p=0.04), with no significant improvement in arterial stiffness; the authors noted that the results are limited by a small number of studies and marked heterogeneity. ^[5]

In the most frequently cited single randomized trial (Shea et al.), a multivitamin supplement containing phylloquinone was compared for 3 years with a multivitamin supplement without phylloquinone in 388 healthy men and postmenopausal women aged 60–80. In the intention-to-treat analysis, there was no difference in progression of coronary artery calcification (change in Agatston score 27 and 37). In the subgroup with adherence of at least 85% (n=367), progression was lower (p=0.03); in those with prior calcification, 6% less progression was seen (p=0.04). The authors characterized the data as hypothesis-generating. ^[6]

Observational data answer a different question. In the Rotterdam Study (4,807 people, no history of myocardial infarction at baseline), coronary death RR was 0.43 (95% CI 0.24–0.77) and all-cause death RR 0.74 (0.59–0.92) in the top tertile of menaquinone intake; in the middle tertile, coronary death RR was 0.73 (0.45–1.17) and not significant; phylloquinone intake was unrelated to the outcomes. ^[7] This finding is specific to K2 and, because intake level varies together with other dietary habits in observational studies, does not show causation. Details on K2 are covered in a separate guide.

What should people taking warfarin watch for in vitamin K intake?

NIH states that vitamin K antagonist drugs (warfarin, phenprocoumon, acenocoumarol, tioclomarol) reduce K-dependent clotting factors and that people taking these drugs should keep the vitamin K they get from foods and supplements consistent, because sudden changes can increase or decrease the anticoagulant effect. ^[1]

Evidence on whether food restriction is necessary is disputed. The 2016 systematic review by Violi et al. examined two dietary intervention studies and nine observational studies; it found conflicting evidence on the effect of dietary vitamin K on INR, wrote that an effect could be detected only at high intake (>150 µg/day), that the current evidence does not support a recommendation to change dietary habits when starting treatment, that restricting dietary vitamin K does not appear to be a valid strategy for improving anticoagulation quality, and that avoiding large fluctuations in intake may be more meaningful. ^[9]

In the double-blind, placebo-controlled study by Rombouts et al., 200 patients taking phenprocoumon received daily low-dose vitamin K or placebo for 24 weeks. Time in INR target range was 85.5% in the placebo group and 89.5% in the K group (adjusted difference 3.6%; 95% CI −0.8 to 8.0), that is, the difference in the primary outcome was not significant; the maximum stability relative risk was 1.8 (1.1–2.7). ^[8] This single study cannot be turned into a rule; drug and vitamin K adjustments belong to the physician managing the treatment.

What is vitamin K’s status in Türkiye?

As a supplement, vitamin K falls under the Ministry of Agriculture and Forestry’s Turkish Food Codex Communiqué on Dietary Supplements (2013/49) in Türkiye. According to the current consolidated text with its amendments, the Communiqué requires that only those vitamins and minerals listed in Annex-1 be used, in the forms specified in Annex-2, and that daily maximum limits comply with Annex-3; it prohibits statements on labels and in advertising that claim to prevent, treat, or cure disease, and it prohibits the production and marketing of dietary supplements for infants and young children under 2 years (before the amendment of November 21, 2015, this limit was 4 years); products aimed at the 2–4 age group are evaluated separately by the Ministry. ^[14] Newborn administration, on the other hand, is not a supplement but a preventive procedure performed at a health facility. ^[11]

Evidence table: claim, population, and limits

This guide does not recommend personal doses or drug adjustments; anticoagulant use, bowel disease, newborn care, or a supplement decision is evaluated with the relevant physician.