The Initial Discovery of Vitamin K
In the late 1920s, Danish biochemist Carl Peter Henrik Dam began a series of nutritional experiments on chicks. He fed them a fat-free diet to investigate the role of cholesterol but observed a unexpected and puzzling symptom: the chicks developed a severe bleeding disorder due to poor blood coagulation. Adding purified cholesterol didn't help, leading Dam to theorize that another fat-soluble compound, which he termed the 'koagulations vitamin' or vitamin K, was missing from their diet. He correctly concluded that this new vitamin was essential for normal blood clotting.
The Elucidation of Vitamin K1 and K2
Following Dam's discovery, numerous research groups worked to isolate and characterize vitamin K. The American biochemist Edward Adelbert Doisy and his team at Saint Louis University made significant breakthroughs in this area. In 1939, Doisy successfully isolated and determined the chemical structure of two variants: vitamin K1, or phylloquinone, from alfalfa, and vitamin K2, or menaquinones, from fermented fish meal. For their contributions, Dam and Doisy were jointly awarded the Nobel Prize in Physiology or Medicine in 1943.
The Bacterial Origin of Vitamin K2
One of the most important aspects of discovering vitamin K2 was understanding its source. While K1 is synthesized by plants, the various subtypes of K2 (known as MK-4, MK-7, etc.) are primarily produced by bacteria. Early work established that the anti-hemorrhagic factor in dried chick feed was produced by bacteria like Bacillus cereus. Later, it was found that the traditional Japanese fermented soybean food, natto, was a particularly rich source of the long-chain menaquinone MK-7, synthesized by the bacterium Bacillus subtilis natto. This helped solidify the understanding of K2's bacterial origins.
The Unique Function of Vitamin K2
Originally, all vitamin K was associated with blood clotting. However, subsequent research uncovered that vitamin K2 has distinct functions, particularly related to extrahepatic (outside the liver) tissues. It was found to activate proteins involved in bone health (osteocalcin) and vascular health (Matrix Gla Protein, or MGP), guiding calcium to the bones and teeth while preventing its harmful accumulation in soft tissues like arteries. The longer half-life and superior absorption of certain K2 forms, like MK-7, further highlight its unique role compared to K1.
K1 vs. K2: A Comparative Look
| Feature | Vitamin K1 (Phylloquinone) | Vitamin K2 (Menaquinones) |
|---|---|---|
| Primary Source | Plant sources, especially green leafy vegetables like spinach, kale, and broccoli. | Primarily from bacterial synthesis found in fermented foods (natto, some cheeses) and animal products (egg yolks, liver). |
| Absorption | Poorly absorbed from plants; less than 10% absorbed. | Better absorbed, especially from fatty foods. |
| Circulation Half-life | Relatively short, stays in the blood for only a few hours. | Longer, can remain in circulation for days, especially longer-chain forms like MK-7. |
| Primary Function | Cofactor for blood clotting proteins produced in the liver. | Activates extrahepatic proteins for bone mineralization and inhibition of soft-tissue calcification. |
| Distribution | Preferentially stored and utilized by the liver. | Redistributed more effectively to extrahepatic tissues like bones and blood vessels. |
The Rediscovery and Modern Interest
For decades after the Nobel Prize, the distinction between K1 and K2 was largely overlooked by the wider scientific community, with a primary focus on K1's role in coagulation. However, renewed interest in the 1990s and 2000s, driven largely by research in Japan and the Netherlands, began to highlight the distinct benefits of K2 for bone and cardiovascular health. Landmark studies like the Rotterdam Study further demonstrated the inverse relationship between high vitamin K2 intake and reduced risk of heart disease. This modern research has cemented the importance of K2 as a separate and crucial nutrient.
Why the Re-evaluation of Vitamin K?
The shift in focus from a single 'vitamin K' to distinct K1 and K2 compounds was driven by accumulating evidence showing their different roles and bioavailabilities. While the human body can convert some K1 to K2 (specifically MK-4), dietary intake of fermented foods rich in long-chain menaquinones like MK-7 has a more profound effect on extrahepatic vitamin K status. The discovery of vitamin K-dependent proteins outside the liver, such as osteocalcin and MGP, revealed new physiological roles that were not fulfilled by K1 alone.
Conclusion
While the journey began with Henrik Dam's accidental discovery of a coagulation-regulating factor, the true story of vitamin K2’s origin is a tale of scientific progress over many decades. It involves the meticulous isolation work of Edward Doisy, the recognition of its production by bacteria, and subsequent modern research revealing its critical and unique functions beyond blood clotting. The distinction between K1 and K2 represents a significant advancement in nutritional science, with implications for bone health and cardiovascular well-being. It is a testament to how scientific understanding evolves, distinguishing complex nutrients from single, simple compounds. For more detailed information on the chemical and biological responses of vitamin K2, one can consult comprehensive reviews published in scientific journals.
