**10. Bone health, menaquinones, and fermented dairy products**

to use biomarkers. Biomarkers for menaquinones are undercarboxylated vitamin K‐depend‐ ent proteins in the circulatory system. However, in addition to vitamin K availability, these biomarkers depend on the total amount of protein. To be sure that protein status does not confound vitamin K status, the measurements must be corrected for the total amount of the

These limitations, together with the scarce and widely varying data on concentrations of different menaquinones in food items, show how fragmentary our knowledge of the supply

Although the forms of vitamin K are classified as fat‐soluble nutrients, the lipophilicity of the different forms changes with side‐chain length. Whereas menadione is water soluble, phylloquinone and MK‐4 are mildly lipophilic. Long‐chain menaquinones are strongly lipo‐ philic and soluble only in apolar organic solvents [36]. This lipophilicity also influences the absorption of vitamin K, which varies greatly depending on the food matrix. As long‐chain menaquinones are found mainly in the fat fraction of dairy products, the absorption of these menaquinones is almost 100% in contrast to PK, where the poor uptake of only 5–10% from cooked vegetables can be improved only slightly by concomitant fat intake [6]. As a conse‐ quence, even the dietary intake of phylloquinone is much higher, menaquinones are equally important for vitamin K status, because of their better intestinal absorption. Independently of their form and origin, all K vitamins are transported to the liver, incorporated in triglycer‐ ide‐rich lipoproteins. Unlike phylloquinone, which mostly remains in the liver to be used for clotting factor synthesis, menaquinones are released to the bloodstream incorporated in low‐density lipoproteins and transported to the target tissue such as bone and arteries for Gla‐protein carboxylation. Absorbability is further supported by a longer half‐life, up to several days for long‐chain menaquinones compared to phylloquinone, which normally dis‐ appears from the bloodstream after 8 hours. This longer postprandial presence in the blood‐ stream leads to a more constant circulating level of vitamin K2 and, as a consequence, longer availability of these long‐chain menaquinones for uptake by extrahepatic tissues [36, 53]. Although there is some evidence that menaquinones with medium‐chain length like MK‐7 are better absorbed than short‐ (MK‐4) or long‐chain menaquinones (MK‐8 and MK‐9) [6], human data on the bioavailability, absorption, and kinetics of K2 vitamins from food are limited to MK‐7 and MK‐9 and have not been systematically tested for all menaquinones

As researchers have found that MKs play an important role in health aspects beyond coagu‐ lation, the cooperation with other nutrients in vitamin K‐rich food such as fermented dairy products may lead to a better understanding of the effect of different food items on health

aspects, for example, bone health or cardiovascular health.

protein under study [52].

74 Vitamin K2 - Vital for Health and Wellbeing

thus far [36, 49].

of vitamin K2 in the general population remains.

**9. Pharmacokinetics of menaquinones**

One of the most important research fields in the past and present is the study of the factors that influence the formation and conservation of strong bones. Osteopenia, including osteo‐ porosis, is one of the most prevalent diseases in elderly individuals and is a large social, medical, and economic burden throughout the world. One out of three women and one out of five men older than 50 years are at risk of experiencing an osteoporotic fracture [54]. Low bone mineral mass is the main factor that causes osteoporotic fractures. Bone mass in later life is the result of the peak bone mass achieved during growth and the rate of age‐related bone loss. Consequently, a high peak bone mass at maturity and a low bone loss during aging are the most promising factors in the prevention of osteoporosis and fractures. In addition to factors that influence bone health such as gender, age, body size, genetics, and ethnicity that are not changeable, other factors, especially lifestyle factors such as physical activity, smoking, alcohol consumption, and dietary patterns, can be modified [55]. Different dietary factors are known to positively influence bone health. They range from minerals (e.g., calcium, magnesium, phosphorus, potassium, and various trace elements) and vitamins (A, D, E, K, C, and certain B vitamins) to macronutrients such as proteins and fatty acids and finally to bioactive food components (e.g., peptides) that in recent years have been proposed to be beneficial for bone health [55]. All these elements are involved in bone metabolism. Currently, researchers are trying to identify and understand the mechanisms and interactions of these factors in relation to bone health [56].

Most studies that have investigated the relationship between dairy and bone health have shown a beneficial effect of dairy consumption, even if the reason for this link is still unclear [56, 57]. After many years of focusing on calcium as the beneficial element for bone health in dairy, recent evidence suggests that other macro‐ and micronutrients, as well as food compo‐ nents such as bioactive peptides, milk fat globule membrane, prebiotics, and probiotics present in milk and dairy products, play an important role in this health outcome [56]. Many of these nutrients support the bioavailability (phosphorus, vitamin D, magnesium, zinc, potassium), absorption (casein phosphopeptides, phosphorus, lactose, protein) and homeostasis (magne‐ sium, potassium, vitamin D) of calcium and contribute to bone‐building properties (phospho‐ rus, magnesium, potassium, zinc, vitamin D, vitamin B12, and vitamin K) [56–58].

Most of these components are not or are positively affected by fermentation. That means their concentration remains the same in the fermented product compared with milk or even increases either by processing (i.e., fat‐soluble vitamins in cheese) or by the activity of micro‐ organisms (i.e., bioactive peptides, vitamin B12, or vitamin K2).

The role of vitamin K2 in bone health is strongly bound to osteocalcin (OC), a key regulator of calcium usage. This small Ca2+‐binding protein is involved in the mineralization of bones and teeth, and its potential to bind calcium is dependent on carboxylation with vitamin K2.

Only the fully carboxylated OC is able to strongly bind calcium and to consolidate calcification of the hydroxyapatite crystal lattice that requires a sufficient supply with vitamin K2 and other nutrients, such as retinoic acid and vitamin D, all involved in the regulation of osteocalcin production [59].

Fermented dairy products are vital for bone health because of their unique combination of various nutrients and microorganisms that support and maintain positive bone metabolism [57, 60]. Additionally, dairy matrix and nutrient composition may affect the delivery of menaquinones and improve vitamin K status [61].

**Author details**

Barbara Walther\*

**References**

and Magali Chollet

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\*Address all correspondence to: barbara.walther@agroscope.admin.ch

Federal Department of Economic Affairs, Education and Research EAER Agroscope, Institute

Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet

http://dx.doi.org/ 10.5772/63712

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