Vitamin K is a less discussed fat-soluble vitamin (other vitamin A, vitamin E, vitamin D), first discovered in the 1939s, named from the Danish word koagulation, which means blood clotting, is a key nutrient to maintain blood clotting function
What is the effect of vitamin K in empirical medicine? Are there any side effects? See text analysis for details
What is Vitamin K?
Vitamin K is a class of structurally similar compounds, and in the physiological mechanism of the human body, vitamin K is a molecule necessary for the synthesis of the gamma-carboxyglutamate/Gla-protein family, and these processes are also known as the vitamin K cycle.
This group of Gla-protein produced by vitamin K is not only related to four coagulation factors, but also plays a key role in maintaining bone strength, inhibiting vascular wall calcification, holding endothelial integrity, participating in tissue renewal, regulating cell growth, etc., which is no less important than other nutrients, so it is also known as the forgotten vitamin.
What are the types of vitamin K and food sources?
There are two forms of vitamin K in our diet: vitamin K1 and K2.
Vitamin K1 (phylloquinone) is mainly found in green leafy vegetables or algae foods.
Vitamin K2 (menaquinones) is the most bioactive form, longer than vitamin K1 half-life, mainly found in foods of animal origin, such as liver or fermented foods, such as yogurt, natto or can be produced directly by human intestinal bacteria, and can be subdivided into MK-1 to MK-10 according to the number of isoprene units, and MK-7 and MK-4 are the most common.
MK-7 is often derived from natto, a popular Japanese food made from fermented soybeans. Compared with vitamin K1, long-term intake of MK-7 is not only more stable in the blood, but also has higher concentrations (up to 7 to 8 times) and is significantly better distributed in various tissues.
MK-4 is found in animal tissues or, to a lesser extent, in meat and egg yolks.
What are the proven benefits of vitamin K?
Maintain bone health
Osteoporosis is an age-related disease characterized by loss of bone mass, leading to weak bones and an increased risk of fractures.
The causes of osteoporosis may be related to abnormal endocrine, parathyroid hormone and calcitonin secretion, inadequate vitamin D and calcium intake, postmenopausal hormonal status, pregnancy, nutritional disorders, and drug use.
A meta-analysis (17 prospective randomized controlled studies) suggested that vitamin K supplementation (especially Vitamin K2) helped increase lumbar spine, but had no significant effect on femoral neck bone density. Note 1
Another meta-analysis (19 randomized controlled trials, 6759 participants) pointed out that for postmenopausal women with osteoporosis, additional vitamin K2 supplementation can help maintain and improve spinal bone density and reduce the incidence of fractures. Note 2
A recent meta-analysis (5 studies, 1114 fracture cases, 80,982 participants) suggests that higher dietary vitamin K intake (mainly vitamin K1) can modestly reduce the risk of fracture. Note 3
*Conclusion: Moderate intake of vitamin K can positively help bone health and reduce the incidence of fractures
Good for diabetes
Diabetes mellitus is a group of metabolic disorders characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both.
Due to dietary refinement and lifestyle changes, the global prevalence of diabetes has doubled in 30 years, reaching 1.8% of the total population (about 5 million people)
Common complications of type 2 diabetes include: cardiovascular disease, kidney failure, vision loss, nerve damage, etc
A meta-analysis (8 RCTs, 1,077 participants) noted that vitamin K supplementation (either K1 or K2) did not affect insulin sensitivity (measured by insulin resistance, fasting blood glucose, fasting plasma insulin, C-reactive protein, adiponectin, leptin, interleukin 6). Note 4
Another meta-analysis (5 clinical studies, 533 participants) pointed out that vitamin K supplementation had no significant effect on glycemic control in people without diabetes (measures including fasting blood glucose, 2-hour oral glucose tolerance test, fasting insulin, insulin resistance). Note 5
*Conclusion: For healthy people, additional vitamin K supplementation did not bring significant improvement in blood sugar control, and more studies are needed to confirm the effect on pre-diabetes and pre-existing diseases
Improve coagulation function (for patients using anticoagulants)
Warfarin is an anticoagulant (also known as a vitamin K antagonist) commonly used for thromboembolism prophylaxis, particularly in patients with atrial fibrillation, a history of venous thromboembolism, and prosthetic valve replacement.
However, long-term use of oral anticoagulation with vitamin K antagonists may be associated with a risk of bleeding or thromboembolic complications.
Therefore, coagulation function is clinically tested regularly at an international normalized ratio (INR), followed by drug dose adjustments.
INR is based on the ratio of the patient’s thrombin time to normal mean thrombin time, when between 2 and 3 is most beneficial for preventing stroke, major bleeding, and reducing mortality.
A systematic literature review and meta-analysis (4 studies, 678 participants) noted that there was insufficient evidence to support the need for routine vitamin K supplementation to achieve INR stabilization in patients on chronic anticoagulation. Note 6
However, vitamin K supplementation may be a viable option to improve INR in patients with unstable INR without proper attribution.
Good for arteriosclerosis
Arterial stiffness is characterized by thickening of the inner and middle layers of blood vessels, accompanied by an increase in the lumen of the central artery, endothelial dysfunction, hyperplasia of vascular smooth muscle cells, increased collagen, degradation of elastin.
Carotid-femoral pulse wave velocity (CFPWV) is the current reference standard for measuring aortic sclerosis, and numerical abnormalities are associated with cardiovascular diseases, including coronary heart disease, stroke and cardiovascular mortality.
In addition, elevated vascular calcification index: stromal gla protein (dp-ucMGP) is also associated with aortic stiffness. Note 8
A double-blind, placebo-controlled trial (3-year study of 244 healthy postmenopausal women) showed that long-term use of MK-7 supplements (vitamin K2) helped improve arteriosclerosis, particularly in those with high levels of arteriosclerosis (as measured by beta stiffness index, femoral pulse wave conduction velocity (CFPWV), and matrix gla protein (dp-ucMGP)). Note 7
*Conclusion: For healthy postmenopausal women, taking MK-7 (vitamin K2) may improve aortic stiffness
Good for chronic kidney disease
Chronic kidney disease is defined as impairment of kidney function and presents with abnormal albumin excretion or renal insufficiency, with measured or estimated glomerular filtration rate (GFR) as the diagnostic criterion and lasting more than three months.
Progression of chronic kidney disease is associated with many serious complications, including cardiovascular disease, hyperlipidemia, anemia, and metabolic bone disease.
End-stage renal disease and subsequent dialysis or transplantation often account for a large total medical cost and place a heavy burden on the patient.
An observational study (13.3 years, 3401 participants) found that adequate vitamin K intake in patients with chronic kidney disease was associated with lower all-cause and cardiovascular mortality. Note 9
*Conclusion: Adequate dietary vitamin K intake may have a positive effect on chronic kidney disease, but further validation in randomized controlled trials is still needed
Are there any side effects of vitamin K supplementation?
For most healthy adults, vitamin K1 and vitamin K2 generally have few side effects when used in appropriate doses, but it is best to consult a local pharmacist or physician before using any supplement to ensure safety
Vitamin K3 (menadione) is extremely rare in the market, is a synthetic form, and is generally not recommended because it inhibits the action of antioxidants (glutathione), resulting in oxidative damage. In addition, intravenous administration has been associated with hepatotoxicity, jaundice, and haemolytic anaemia
Safety precautions (7 point use taboo)
- Pregnant women, breastfeeding mothers, and those with poor liver and kidney function should confirm with their doctor before use (the relevant risks are unknown)
- Rare metabolic disease: do not use for patients with fava bean disease (Glucose-6-Phosphate Dehydrogenase deficiency/G6PD)
- Vitamin K1 may have the effect of lowering blood sugar, diabetic patients or those taking hypoglycemic drugs, please pay special attention
- Do not use together with anticoagulants, such as Warfarin (due to the effect of vitamin K to help blood clotting, it may offset the effects of drugs)
- Taking related drugs that interfere with fat absorption, such as: antiepileptic drugs (Dilantin), antibiotics, cholesterol-lowering drugs (Cholestyramine/cholic acid binding resin), weight loss drugs (Orlistat/Roche fresh), will affect the absorption of fat-soluble vitamins, including vitamins K
- Large doses of vitamin A seem to interfere with the absorption of vitamin K, while large doses of vitamin E may inhibit vitamin K-dependent carboxylase activity and interfere with the coagulation mechanism
- Long-term use of broad-effective antibiotics, such as cephalosporins and salicylates, may interfere with the synthesis of vitamin K in the intestines
What are the possible symptoms of vitamin K deficiency?
Vitamin K deficiency is uncommon in healthy adults for the following reasons: widespread presence in food, vitamin K circulating to preserve vitamin K, and bacteria in the large intestine synthesizing menaquinones (vitamin K2)
Symptoms of vitamin K deficiency include easy bruising and bleeding, which may manifest as nosebleeds, bleeding gums, small blood clots under the nails, hematuria, bloody stools, or excessive menstrual bleeding.
Who are the groups that are prone to vitamin K deficiency?
The poor efficiency of vitamin K through the placenta and the relatively low amount of vitamin K in breast milk increases the risk of newborns deficiencies in this nutrient.
In the first weeks of life, vitamin K deficiency can lead to vitamin K deficiency bleeding (VKDB), also known as “typical bleeding disorders in newborns.”
This type of bleeding often occurs in the umbilical, gastrointestinal, skin, nose, or other sites, especially advanced VKDB (occurring at 2 to 12 weeks’ age), and can also present as sudden intracranial haemorrhage with a high mortality rate.
To prevent VKDB, the American Academy of Pediatrics recommends a single intramuscular dose of 0.5 to 1 mg of vitamin K1 at birth
Patients with malabsorption disorders:
People with malabsorption syndrome and other gastrointestinal disorders (due to fat malabsorption) such as cystic fibrosis, celiac disease, ulcerative colitis, and short bowel syndrome may not be able to absorb vitamin K smoothly.
Subjects who take vitamin K antagonists (anticoagulants) for a long time
Patients with long-term dialysis