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Vitamin K1 (Phytomenadione/Phylloquinone/Phytonadione)

Vitamin K was first identified in 1929 as a nutrient essential for blood clotting, a process known scientifically as coagulation (haemostasis). The discovery of this nutrient was published in a German scientific journal, where it was referred to as "Koagulationsvitamin," which is where the "K" in vitamin K comes from. While often associated with its role in blood clotting, Vitamin K actually refers to a group of fat soluble vitamins that have similar chemical structures and offer a range of health benefits. There are various types of Vitamin K, but the two most commonly found in the human diet are:

Vitamin K1 (phytomenadione/phylloquinone): primarily found in plant foods like leafy green vegetables.

Vitamin K2 (menaquinone): primarily of bacterial origin and found in animal foods and fermented foods.

Phytomenadione, also known as vitamin K1, phylloquinone and phytomenadione, is a fat-soluble vitamin that plays a crucial role in the body's blood clotting process (coagulation or haemostasis). It was discovered a century ago through various conditions that involved bleeding in animals on restricted diets. It is an essential cofactor for the synthesis of vitamin K-dependant proteins (VKD/VKDP) involved in blood clotting, such as prothrombin and clotting factors VII, IX, and X. Vitamin K1 is absorbed through the intestinal tract by enterocytes, cells that line the intestine. This process is facilitated by micelles, which are small particles made up of bile and pancreatic salts and enzymes. Micelles help to solubilise, or dissolve, vitamin K1, similar to the way they help dissolve dietary lipids. This allows the vitamin to be absorbed into the body. It is then transported to the lymphatic system and eventually reaches the venous circulation via the thoracic duct. The liver metabolises phytomenadione, which is then excreted in the bile and urine.

The Vitamin K1 found in plant sources is generally more poorly absorbed by the body than in nutritional supplements, with estimates suggesting that only about 10% of the K1 from plants is absorbed. Once absorbed, it is estimated that approximately 60% of vitamin K is excreted from the body. However, adequate intake of vitamin K1 is essential for normal blood clotting (haemostasis) and preventing bleeding disorders (haemorrhaging).

Natural dietary sources of vitamin K1 (phytomenadione)

Vitamin K1, also known as phylloquinone, is the primary form of vitamin K present in plant-based foods such as leafy green vegetables. It is the most prevalent form of vitamin K consumed by humans, comprising of up to 90% of all vitamin K intake. The most abundant sources of vitamin K1 include:

  • Leafy green vegetables: Leafy green vegetables are rich sources of vitamin K1, with a cup of cooked kale, for example, providing about 1 milligram (mg) of vitamin K1.

  • Broccoli: Broccoli is a good source of vitamin K1, with a cup of cooked broccoli providing about 0.9 mg of vitamin K1.

  • Spinach: Spinach is a good source of vitamin K1, with a cup of cooked spinach providing about 0.9mg of vitamin K1.

  • Brussels sprouts: Brussels sprouts are a good source of vitamin K1, with a cup of cooked Brussels sprouts providing about 0.8 mg of vitamin K1.

  • Cabbage: Cabbage is a good source of vitamin K1, with a cup of cooked cabbage providing about 0.5 mg of vitamin K1.

  • Lettuce: Lettuce is a good source of vitamin K1, with a cup of chopped lettuce providing about 0.3 mg of vitamin K1.

It is worth noting that the amount of vitamin K1 you can obtain from food varies based on factors such as the soil in which it was grown, the processing methods used, the form in which it is present, and the presence of other substances that may interfere its absorption.

While dietary intake of vitamin K1 is important for maintaining adequate levels in the body - particularly those individuals taking anticoagulants, the K1 found in plants is poorly absorbed and thus obtaining this essential nutrient may be necessary through vitamin supplements. However, the best way to get the essential nutrients your body needs is to eat a variety of whole, unprocessed, fruits, vegetables, nuts, seeds, and other plant-based foods. These types of food ensure that you are getting a wide range of nutrients, which may include vitamin K1, and should not be replaced by vitamin and mineral supplements alone.

Benefits of phytomenadione for osteoporosis

Vitamin K1 plays a role in bone metabolism by activating proteins involved in bone mineralization. Several observational studies, such as the Nurses' Health Study and the Rotterdam Study, have found that higher intake of dietary vitamin K1 is associated with increased bone density and a lower risk of fractures in both men and women. The Framingham Offspring Study found that higher plasma concentrations of phylloquinone were associated with a lower risk of hand osteoarthritis, but not knee osteoarthritis. In contrast, a longitudinal study of elderly adults found that low plasma concentrations of phylloquinone (≤0.5 nM) at baseline were associated with a 56% increase in the risk of knee osteoarthritis after 30 months, compared to those with higher concentrations.

A more recent study involving older US adults participating in the Health, Aging, and Body Composition Study also found that those with extremely low plasma concentrations of phylloquinone (<0.2 nM) at baseline had increased progression of knee osteoarthritis over three years, as assessed by MRI, while those with higher concentrations did not experience significant progression. These findings suggest that vitamin K1 may play a role in the development and progression of osteoarthritis. These data infer that only those individuals with low vitamin K1 status benefit from vitamin K1 supplementation.

Protective effect of phytomenadione against cardiovascular disease

Vitamin K1 activates the protein matrix Gla protein (MGP) which helps to prevent calcification of arteries. While vitamin K1 can activate MGP, it is less effective than menaquinone-7 (vitamin K2 MK-7) because it is first transported to the liver where it is used to activate blood clotting proteins. Regardless, several studies have shown that adequate intake of vitamin K1 has been linked to a lower risk of arterial calcification and a reduced risk of coronary artery disease. 

While more compelling evidence has found that higher intakes of menaquinone-7 may be associated with lower rates of cardiovascular disease, a prospective study of 56,048 men and women in the Danish Diet, Cancer, and Health cohort found that higher intakes of phylloquinone were associated with lower risks of both cardiovascular disease-related mortality and all-cause mortality. Another study of 388 elderly participants indicated that taking phylloquinone supplements may slow the progression of coronary artery calcification (CAC) in healthy older adults who already have CAC, regardless of its effect on the overall concentration of MGP. These findings suggest that while Menaquinone-7 may have potentially more benefits for cardiovascular health, further research is needed to confirm these associations and to understand the specific roles of different forms of vitamin K in CVD risk.

Anti-inflammatory effects of phytomenadione

There is evidence from some studies, such as the Framingham Offspring Study, suggesting that vitamin K1 may have anti-inflammatory effects in humans. Specifically, these studies have found that vitamin K1 may inhibit the production of pro-inflammatory cytokines, which are signalling molecules that promote inflammation, and increase the production of anti-inflammatory cytokines in human monocytes, a type of immune cell. This change in cytokine production may lead to a reduction in inflammation in the body. Another study published in the journal "Biological and Pharmaceutical Bulletin" found that phylloquinone was able to inhibit the production of pro-inflammatory mediators and reduce inflammation in human fibroblast cells, a type of cell involved in wound healing. 

Vitamin K1 supplements were found to reduce markers of inflammation in postmenopausal women and healthy men in two separate studies. The first study, published in the Journal of Nutrition in 2010, included 84 postmenopausal women who were given either a placebo or a vitamin K1 supplement for 12 weeks. The second study, published in the American Journal of Clinical Nutrition in 2011, included 38 healthy men who were given either a placebo or a vitamin K1 supplement for 8 weeks. In both studies, those who received the vitamin K1 supplement had lower levels of inflammation compared to the placebo group. This may be beneficial in the prevention and management of inflammatory diseases such as asthma and rheumatoid arthritis.

Phytomenadione and cancer prevention

Some observational studies, such as the Japan Public Health Center-Based Prospective Study, have found that higher intake of dietary vitamin K1 is associated with a lower risk of certain types of cancer, such as liver and prostate cancer. However, more research is needed to confirm these findings and to determine the potential mechanisms behind the protective effects of vitamin K1.

What are the symptoms of vitamin K1 deficiency?

Vitamin K1 is an essential nutrient that plays a vital role in blood clotting (haemostasis). A deficiency in vitamin K1 can lead to a variety of health problems including excessive bleeding (haemorrhaging). Symptoms of vitamin K1 deficiency may include:

  • Easy bruising: Vitamin K1 is necessary for blood clotting, so a deficiency can cause easy bruising.

  • Extremely heavy periods: A deficiency in vitamin K1 may cause extremely heavy periods (menstruation) in women.

  • Bleeding gums: A deficiency in vitamin K1 may cause bleeding gums.

  • Nosebleeds: Some people with a deficiency in vitamin K1 may experience frequent nosebleeds.

  • Blood in the urine or stool: A deficiency in vitamin K1 may cause blood in the urine or stool.

  • Bleeding within the skull: In infants, a deficiency in vitamin K1 may result in life-threatening bleeding within the skull (intracranial haemorrhage).

Adults at risk for vitamin K deficiency include those taking vitamin K antagonists and individuals with significant liver damage or disease. If you are experiencing symptoms of vitamin K1 deficiency, it is important to speak with a health professional. They can help diagnose the cause of your symptoms and recommend appropriate treatment.

It is important to note that vitamin K1 deficiency is relatively rare in healthy individuals who follow a balanced diet. Vitamin K1 deficiency is more common in people who have difficulty absorbing fat from the diet or in people with certain medical conditions, such as cystic fibrosis or liver disease.

What are the potential side effects of taking vitamin K1 supplements?

Vitamin K1 supplements are generally well tolerated and have a low risk of side effects when taken in recommended amounts. However, taking excessive amounts of vitamin K1 can cause side effects, including:

  • Nausea: Consuming large amounts of vitamin K1 may cause nausea.

  • Diarrhea: Vitamin K1 supplements may cause diarrhea in some people.

  • Headache: Some people may experience headaches after taking high doses of vitamin K1.

  • Rash: Taking high doses of vitamin K1 may cause a rash to develop on the skin.

  • Fatigue: Large amounts of vitamin K1 may cause weakness and fatigue.

It is important to note that these side effects are typically associated with taking large amounts of vitamin K1, well above the recommended daily intake. It is important to speak with a health professional before taking vitamin K1 supplements to ensure that you are taking the appropriate amount.

Vitamin K1 supplements are generally safe when taken in recommended amounts. However, as with any supplement, it is important to speak with a health professional before starting to ensure that they are safe and appropriate for you.

Can vitamin K1 supplements interact with other medications or supplements?

Yes, vitamin K1 supplements can interact with certain medications and supplements. Some medications and supplements that may interact with vitamin K1 include:

  • Blood thinners: Vitamin K1 is necessary for blood clotting, so taking it with blood thinners, such as warfarin or aspirin, may interfere with their effectiveness.

  • Antibiotics: Some antibiotics, such as ciprofloxacin and norfloxacin, may interfere with the absorption of vitamin K1.

  • Other supplements: Some supplements, such as large doses of vitamin E, may interact with vitamin K1. It is important to speak with a health professional about potential interactions between vitamin K1 and any other supplements you are taking.

It is important to speak with a health professional before taking vitamin K1 supplements to ensure that they are safe and appropriate for you. They can help you understand any potential interactions with other medications or supplements you are taking.

Is it safe to take vitamin K1 supplements if I have a particular health condition?

Vitamin K1 supplements are generally safe and well tolerated when taken in recommended amounts. However, if you have a particular health condition, it is important to speak with a health professional before taking vitamin K1 supplements to ensure that they are safe and appropriate for you. Some conditions that may be affected by vitamin K1 supplements include:

  • Bleeding disorders: Vitamin K1 is necessary for blood clotting, so taking it may interfere with the effectiveness of blood thinners if you have a bleeding disorder.

  • Antibiotic use: Some antibiotics may interfere with the absorption of vitamin K1. It is important to speak with a health professional about the appropriate amount of vitamin K1 to take if you are taking antibiotics.

  • Other medications: Vitamin K1 supplements may interact with certain medications, such as blood thinners. It is important to speak with a health professional about potential interactions between vitamin K1 and any medications you are taking.

It is always important to speak with a health professional before starting any new supplement to ensure that it is safe and appropriate for you. They can help you understand any potential risks or interactions with your specific health condition and any medications or supplements you are taking.

Conclusion

In conclusion, phytomenadione, or vitamin K1, is a vital nutrient with numerous health benefits. Adequate intake of vitamin K1 is necessary for normal blood coagulation and the prevention of bleeding disorders. It also has potential benefits in the prevention of osteoporosis, cardiovascular disease, inflammation, and certain types of cancer. 

It is worth noting that vitamin K1 supplements may interact with certain medications or supplements, and it may have side effects in some people. If you are currently taking any medications or supplements, or if you have any underlying medical conditions, you should speak to your health professional before taking vitamin K1 or any other nutritional supplement. Your health professional can help you determine if vitamin K1 is safe and appropriate for you, based on your individual circumstances and medical history.

References and additional reading

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