Vitamin K

Vitamin K is an omni vitamin that is important for the health of your body.

Historically, vitamin K1, or phylloquinone, was best known for its role in supporting the coagulation system to ensure that blood clots or coagulates properly, and otherwise, with the non-clotting system, to keep your blood fluid and flowing throughout your body

However, when vitamin K2, or menaquinones, were discovered, it transformed our understanding of the role vitamin K plays in the body.  it became clear that vitamin K had a significant impact well beyond the coagulation systems.

Research has shown that there are vitamin K dependent proteins (VKDP) in tissues and organs throughout the body.  These proteins need enough vitamin K as a cofactor to activate them, converting enzymes in a process known as carboxylation (Azuma et al, 2014). This is a very important transformation, enabling these proteins to bind calcium and function normally (Proudfoot et al, 1998; Kapoor et al, 2021). 

Without the availability of vitamin K, these proteins are not active and don’t function to their full capacity (Shearer & Newman, 2008).  The body then employs less efficient backup systems.  This is referred to as the Triage Theory.

The body operates on the Triage Theory, where functions required for short-term survival are prioritized.  As coagulation is essential for survival, and vitamin K is essential for the coagulation system, then vitamin K intake would be conserved for the coagulation system.  Only after the coagulation system was satiated, and or when intake of vitamin K was generous, would the other, less essential body functions be/receive allocation (McCann & Ames, 2009). 

Some of the VKDP proteins discovered so far include matrix Gla protein (MGP), growth arrest-specific protein 6 (Gas6), osteocalcin (OC), and Gla-rich protein (GRP) (Wen et al, 2018).  Research has steadily discovered more of these proteins and their importance in health.

Through these proteins, vitamin K acts on almost every system in the body, and thus has a tremendous impact on movement and fitness. (Danziger, 2008; Willems et al, 2014; Beulens et al, 2013; Popa et al, 2021).

Exercise involves major systems in the body, including the cardiovascular system, respiration system) lungs, muscles and bones.  Vitamin K supports each of these systems.

Cardiovascular System
Your heart and the many blood vessels in your body make up your cardiovascular system. The purpose of the cardiovascular system is to circulate oxygen and nutrients through your whole body via an intricate network of blood vessels and red blood cells.  This network also removes the things your body doesn’t need, such as carbon dioxide, removed in the lungs, and contaminants removed via the kidneys and toxins neutralized in the liver.  The system also assists with thermoregulation and helps to eliminate heat.

The fitness of the cardiovascular system is defined by the body’s ability to deliver oxygen to your muscles.  The lungs take in oxygen from the air we breathe where it gets perfused into the blood stream, the heart and blood vessels deliver it into the working muscles, and the skeletal muscles utilize that oxygen to execute muscular contractions. 

Exercising and physical activity cause the cardiovascular system to adapt and improve, promoting cardiovascular fitness (Pinckard et al, 2019).

Vitamin K and the Cardiovascular System
Decades of research have shown that vitamin K supports heart health and functioning and could be an important intervention for exercise success. Vitamin K helps prevent calcification, it keeps your vascular system from stiffening via elastin, it is anti-inflammatory, and it helps create maximum heart output (Crintea et al, 2021).

-Vascular calcification 
Vascular calcification is a pathological process and is manifested by deposits of hydroxyapatite, a form of calcium, lining the blood vessel walls (Wasilewski et al, 2019).  Ninety‐nine percent of bodily calcium is stored in bone, with the remaining 1% circulating in the blood, muscle, and other tissues (Weaver, 2012). Calcium storage in the bone occurs with the presence of vitamin K2 and the protein osteocalcin.  Low levels of vitamin K2 can cause disruption in the binding between calcium and osteocalcin, leading to the buildup of calcium to other tissues such as arteries (Maresz, 2015).

It used to be that vascular calcification was viewed as a standard part of the pathological aging process, but is now understood to be an active and regulated process that can be managed and improved with adequate vitamin K intake (Roumeliotis et a, 2019).

Ample evidence from animal and clinical studies has shown that low levels of vitamin K (suggesting low intake) are associated with vascular calcification and an elevated risk of cardiovascular diseases (Mozos et al, 2017; Jaminion et al, 2020; Shioi et al, 2020; Dalmeijer et al, 2013). 

Several studies demonstrated that higher dietary consumption of vitamin K2, significantly reduced the incidence of calcification and coronary heart disease (Geleijnse et al 2004; Gast et al, 2009; Haugsgjerd et al, 2020), and a slowed progression of preexisting coronary artery calcification (CAC), in asymptomatic older men and women (Shea et al, 2009).

Cardiovascular tissues contain several key proteins that are dependent upon vitamin K to be active.  Some of these proteins include, Matrix Gla Protein (MGP), Gla rich protein (GRP), and Growth arrest-specific protein-6 (Gas6).  Matrix Gla protein is the most influential natural inhibitor of all types of calcifications in the body and is closely associated with mortality, and cardiovascular disease (Price et al, 1983; Akbari & Rasouli‐Ghahroudi, 2018). Upon activation, MGP binds calcium, thereby inhibiting the calcification process, removing it from circulation and leading it to the bones (Goiko et al, 2013; Cui et al, 2018; Jaminion et al, 2020).

When not activated by vitamin K, MGP is associated with (peripheral) vascular calcification and carotid femoral/aortic pulse wave velocity, suggesting that it is a risk biomarker associated with mortality and the severity of vascular calcification and cardiac function (Schurgers et al, 2010; Ueland et al, 2010; Schlieper et al, 2011; Dalmeijer et al, 2012; Rennenberg et al, 2010; Dalmeijer et al, 2013; Liu et al, 2015; Griffin et al, 2019; Wei et al, 2016). 

Research shows that levels of activated MGP increase after improved vitamin K intake, in a dose dependent manner, meaning the more vitamin K taken, the higher levels of active MGP are found in the body, available to help reduce calcification (Westenfeld et al, 2012; Caluwe et al, 2014).

Additionally, Vitamin K modulates the Gas6 pathway which also inhibits the vascular calcification process (Jadhav et al, 2022, Jiang et al, 2016). Gas6 has been shown to suppress vascular calcification and reduce coronary heart disease (Beulens et al, 2009; Geleijnse et al, 2004; Vossen et al, 2015; Qiu et al, 2017).

-Arterial Elasticity
Pulse wave velocity (PWV) is the velocity at which the blood pressure pulse propagates through the circulatory system.  It is used as a measure of arterial stiffness and is a predictor of cardiovascular risk.  The stiffer and harder the blood vessel walls, the wider the pulse pressure and the more the heart is working to pump blood into the arteries (Seals et al, 2006).  A study of patients with hypertension found that low intakes of vitamin K led to lower muscle mass and increased large artery stiffness (Vidula et al, 2022).

Vitamin K has been shown to significantly delay the onset of arterial stiffness in postmenopausal women (Braam et al, 2004).  Patients who received MK7 had better pulse wave velocities than those who received placebos (Knapen et al, 2015).  And those with more stiffness have high levels of uncarboxylated MGP, a marker of K deficiency indicating that vitamin K intake leads to better arterial function (Pivin et al, 2015; Roumeliotis et al, 2019; Wei et al, 2019).

-Anti-inflammatory
Vascular calcification is also regarded as a chronic inflammatory state mediated by the NF-кB signaling pathway, which plays a crucial role with inflammation and the immune response.  A high vitamin K status exerts anti-inflammatory effects and prevents calcification through antagonizing NF-кB signaling (Shioi et al, 2020). 

Interleukins are cell proteins that defend the body and ensure that our immune system is responsive.  High levels of interleukin 6 (IL-6) arestrongly associated with chronic inflammation and most pro-inflammatory diseases, including obesity, arthritis, cancers. A lab study showed that all the vitamin K forms K1, MK3, MK4, and MK7 were anti-inflammatory and suppressed IL-6, with MK4 having the most impact (Ohsaki et al, 2010).  

The Multi-Ethnic Study of Atherosclerosis (MESA), showed that blood levels of vitamin K1 were inversely associated with inflammatory markers, namely IL-6 and C-Reactive Protein (Shea et al, 2014). A cohort analysis of 1163 older adults in the Health ABC study, found that those with lower circulating levels of K1 at baseline, also had higher circulating IL-6 levels, further supporting the anti-inflammatory effect of vitamin K at a systemic level (Shea et al, 2017). 

Vitamin K is required for the effective function of a range of proteins (Shearer & Okano, 2018) involved with inflammation and neuromuscular function (Harshman & Shea, 2016; Lees et al, 2019; Paulsen et al, 2012).  For these reasons, a pilot study has begun to determine whether vitamin K2 supplementation can modulate responses to exercise, and accelerate recovery in young and older adults (Lithgow et al, 2022).  

-Maximal Cardiac Output
A recent study showed a powerful effect of MK7 on heart output during exercise in active athletes.  In a recent randomized controlled trial, MK7 was given to subjects during an 8- week period, while they maintained their typical exercise habits.  They found that MK7 intake was associated with a 12% increase in maximal cardiac output, using a graded cycle ergometer test.  This was the first study to report potential of vitamin K in active individuals. 

The major finding was that cardiac output rose by a very significant 12% for the athletes receiving vitamin K2.  Cardiac output was defined as the maximum amount of blood (and therefore oxygen) that the heart can pump around the body each minute.  This increase translates to an increase in the maximum amount of blood and oxygen available to exercising muscles, which should improve endurance.  Research on elite runners and cyclists have confirmed that high cardiac outputs are associated with high levels of endurance performance (McFarlin et al, 2017). 

Respiration System
Lungs are part of the respiration system, a group of organs and tissues that work together to help you breathe.  The respiratory system's main job is to move fresh air into your body while removing carbon dioxide, and it includes the nose, mouth, throat, voice box, windpipe, and lungs.  

The air we breathe contains oxygen and other gases. When we inhale, the air travels to the alveoli in your lungs, where oxygen and carbon dioxide are exchanged.  Once absorbed in the lungs, oxygen is pushed to your heart via red blood cells, which pumps it through your body, supplying oxygen to the body’s cells. Every cell in your body needs oxygen to live. Breathing is the first stage for supplying oxygen to the body’s cells.

At each cell in your body, oxygen is exchanged for a waste gas called carbon dioxide. Carbon dioxide is made in our bodies as the cells do their jobs.  Too much carbon dioxide can result in damage to muscles or other body parts, so it must be removed. Your bloodstream carries this waste gas back to the lungs where it is removed from the bloodstream and then exhaled. Your lungs and respiratory system automatically perform this vital process.

When you exercise and your muscles work harder, your body uses more oxygen and produces more carbon dioxide. To cope with this extra demand, your breathing must increase from a resting rate of about 15 times a minute (12 liters of air) up to about 40–60 times a minute (100 liters of air) to supply the increased amount of energy the muscles need to contract while exercising. Your heart rate and circulation also speed up to take the oxygen to the muscles so that they can keep moving. 

An important tissue in lungs is elastin.  Elastin is a unique protein that provides elasticity and resilience to dynamic tissues, such as arteries and lungs (Davidson, 1992; Mariani et al, 1997; Noakes, 1996; Luo et al, 2018).  The elastin protein is roughly 1,000 times more flexible than the rigid protein, collagen. Elastin confers resilience upon structures that undergo repetitive stress, enabling them to retain their expand and contract functionality and tensile strength (Mercer & Crapo, 1990; Mithieux & Weiss, 2006; Mecham, 2018; Jesperson et al, 2023; Kristensen & Karsdal, 2016; Cocciolone et al, 2018). 

Cardiorespiratory fitness (CRF), is often referred to as (VO₂max). V02 max is defined as the maximum rate of oxygen that can be delivered to and used by the working muscles, aerobic capacity.  The more oxygen your body absorbs per minute, the higher your VO2 Max, and the more fit a person is (Green & Askew, 1985; Poole & Jones, 1985; Burtscher et al, 2019; Valenzuela et al, 2020).  V02 max reflects the entire oxygen transport system – the lungs, cardiovascular, and active muscles- which transport and utilize the oxygen in the blood stream. 

VO2max values can vary greatly between individuals, with untrained individuals typically having a range of 25-45 ml/kg/min while elite endurance athletes have values in the 80s or even 90s.  Males tend to have higher values than females.  After 30 years of age, VO2 max progressively decreases with age at a rate of about 10% per decade  (Jansson & Kaijser, 1987; Levine, 2008; Simon et al, 1986),  while longitudinal studies suggest that VO2max decline may accelerate after ages 40–50 years, though appropriate training can slow the pace of decline (Fleg et al, 2005; McGavock et al, 2009; Haugen et al, 2018; Rønnestad et al, 1985; Weibel & Hoppeler, 2005).

The decline in aerobic capacity is likely related to an increase in the stiffness of the pulmonary vasculature. In principle, stiffer elastin fibers contribute to the increase in vascular stiffness that comes with age. These changes in pulmonary vascular stiffness modify lung capacity in older individuals (Gonza et al, 1974; Harris & Heath, 1965; Hosoda et al, 1984; Mackay et al, 1978; Plank et al, 1980). 

Vitamin K and the Respiration System
Vitamin K supports the lungs in their most basic function – to move – as they expand and contract with every breath.  Vitamin K activates the MGP protein in elastin which maximizes the function of lung tissue and lung vasculature during exercise and movement (Gheduzzi et al, 2007).

Matrix Gla protein (MGP) is a potent inhibitor of elastin calcification (Fraser & Price, 1988; Luo et al, 1997). The presence of calcium in elastin, stimulates MGP synthesis to prevent further calcium build up within the elastin fibers (Price et al, 2001). The ‘Vitamin K deficit and ‘elastolysis theory’ implies that vitamin K supplementation prevents elastin degradation (Schurgers et al, 2013; Piscaer et al, 2019).

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes obstructed airflow from the lungs.  COPD is characterized by accelerated elastic fiber degradation (Vogelmeier et al, 2017; Lee et al, 2007).  High dp-ucMGP levels (representing vitamin K deficiency) were associated with increased elastin degradation rate in two cohorts of COPD patients (Piscaer et al, 2018; Dofferhoff et al, 2021; Piscaer et al, 2017).  A follow up study demonstrated that patients with COPD had a reduced vitamin K status, where the lower status of vitamin K was associated with a greater rate of elastin degradation. The results suggested a potential role of vitamin K in COPD pathogenesis (Piscaer et al, 2019).

Low vitamin K status was associated with lower ventilatory capacity.  The Danish study of Functional Disorders (DanFunD) cohort was a random sample of the general adult population comprising men and women born in Denmark (Dantoft et al, 2017). Participants underwent health examinations. The results showed that lower vitamin K status was associated with a lower ventilatory capacity and a higher risk of self-reported asthma, COPD, and wheezing (Jesperson et al, 2023). 

Bone
Bone is primarily made up of two components, an organic part comprised of collagenous and non-collagenous proteins (30%) and cells, and a mineral component of hydroxyapatite (70%) composed primarily of calcium and phosphate (Boskey, 2013). These components allow bone to act as a scaffold for muscle and other organs, protecting the organs from injury while forming a load-bearing framework that allows physical activity to take place (Russo, 2009). 

Bone also functions as an important mineral reserve.  Hydroxyapatite is mainly composed of calcium, phosphorus, magnesium, and other minerals in lesser amounts (Bronner, 2001; Murshed, 2017; Whyte, 2017).  Calcium is an important element in the body.  Its main job is to build strong bones and teeth, which contain 99% of the body's calcium.  Calcium is also necessary to propagate electrical signals in the nervous system, support clotting factors, and enable muscle contraction, including the beat of your heart, among other vital functions.  The bone mineral reserve also maintains the calcium content in our blood, as well as making good use of ingested calcium (Heaney, 2006).

The organic component of bone includes at least two vitamin K‐dependent Gla proteins; osteocalcin and matrix Gla protein (MGP) (Azuma et al, 2014; Zhou et al, 2021). There are many vitamin K dependent proteins in the bone, including osteocalcin (OC), matrix Gla protein (MGP), gas 6, periostin, and protein S (Fusaro, et al, 2017). When activated by vitamin K, osteocalcin binds calcium to the bone matrix.

Bone constantly destroys and regenerates itself through a process termed remodeling. To fulfil this function, bone hosts two functionally antagonistic cell populations: osteoclasts, which break down bone tissue and resorb mineralized bone matrix; and osteoblasts, which deposit new matrix, building bone that eventually becomes mineralized. (Hadjidakis & Androulakis, 2006; Baron & Kneissel, 2013; Hiam et al, 2021).

Vitamin K and Bone
There is a wealth of research on the importance of vitamin K and bone health.  Physical movement and exercise require your bones to be strong and solid, so they can power movement, and not suffer fractures of any kind. Bone diseases such as osteopenia, osteoporosis and arthritis impact bone function and interfere with exercise.  The research shows that vitamin K helps to preserve bone health in multiple ways.

-Osteocalcin
Osteocalcin is the most abundant non-collagenous protein in the bone matrix. It is synthesized by osteoblasts and helps take calcium from the blood circulation and bind it to the bone matrix, promoting mineralization, which in turn makes the skeleton stronger and less susceptible to fracture (Hoang et al, 2003).  

However, the newly made osteocalcin is inactive, and it needs vitamin K to become fully activated and carboxylated, which is noted as cOC (Hauschka, 1986; Hauschka et al, 1989), making vitamin K a major player in bone health, and subsequently a major player for optimal fitness and physical activity. 

Research shows that a high intake of MK4 daily (45 mg) activated osteocalcin, and bone density increased, indicating a correlation between K2 and bone health (Ozuru et al, 2002).  Lab studies showed increased osteocalcin production after exposure of osteoblasts to Vitamin K2 (Matsunaga et al, 1999; Koshihara et al, 2003) and increased expression of genes that form bone (Akbari & Rasouli‐Ghahroud, 2018).

Exercise is sensed by bone cells.  The mechanical stress on the skeleton initiates strains that are recognized by bone cells, and they start a cascade of events that lead to stronger bone.  Their response can be measured by markers of bone turnover, such as osteocalcin, which increases during exercise (Lanyon, 1984; Banfi et al, 2010; Ferron et al, 2010; Vasikaran et al, 2011; Brotto & Johnson, 2014; Levinger et al, 2016; Smith et al, 2021; Komori, 2022; Hiam et al, 2019; Adami et al, 2008; Rahimi et al, 2020; Chowdhury et al, 2020; Rahimi et al, 2021). 

Osteocalcin is such an important aspect of bone activity that it increases during exercise, as bone responds to the forces and this effect is found in different age groups and by sex (Lin et al, 2012; Kim et al, 2016; Rämson et al, 2012). 

-Strong Bones
Studies of people around the world have shown that vitamin K improves the markers of bone building and bone mineral density (BMD). Without the appropriate nutrition, menopause can negatively impact bone health, making menopausal women a popular subject pool.  A Korean study showed that administering 15 mg of vitamin K2 (MK4) three times daily, for six months to postmenopausal women significantly increased the bone density of the lumbar spine while increasing the level of cOC (Je et al, 2011; Shiraki et al, 2000). A study in the Netherlands of postmenopausal women showed that taking 45 mg/day of MK4 for three years prevented loss of hip bone strength, whereas the group who did not receive MK4 had a significant loss of bone (Knapen et al, 2007). Taking 1.5 milligrams of MK4 daily increased the serum levels of cOC in postmenopausal Norwegian women compared to a group who received a placebo (Emaus et al, 2010).  Post-menopausal Japanese women with osteoporosis taking MK4 for 6-12 months showed significant improvement of vertebral BMD (Koitaya et al, 2014).  Postmenopausal Syrian women, without estrogen replacement therapy, had a positive correlation of their K1 levels with with lumbar spine bone mineral density, indicating that measures of K1 might be a valuable diagnostic tool (Jaghsi et al, 2018).  Another study showed that subjects given 200 micrograms of MK7 had an increase in cOC, indicating better bone quality for postmenopausal women.

Meta-analysis of the research confirms these findings.  Huang (et al, 2015) performed a meta-analysis of 19 clinical trials, which included 6759 participants.  The data supported the role of vitamin K2 in the maintenance and improvement of vertebral BMD and the prevention of fractures in postmenopausal women with osteoporosis. Another review of found that vitamin K2 is osteoprotective (Akbari et al, 2018). Another review involving a total of 6,425 subjects found a significant improvement in lumbar spine bone mineral density when given vitamin K2, and a significant reduction in fracture incidence.  Another meta-analysis showed that vitamin K2 increased the level of cOC, and reduced the fracture incidence (Ma et al, 2022).  Sato and colleagues reviewed the literature on MK7 and conclude its higher bioavailability and longer half-life increase bone mineral density and strength (Sato et al, 2020).

Collagen is an important component for bone that builds strength and flexibility and occupies more than half the volume of bones.  It is responsible for matrix production, the material on which calcium and other minerals accumulate and is critical for bone formation. Research shows that MK-4 increases collagen accumulation (Ichikawa et al, 2006) and MK-7 increased collagen production (Sato, 2012).

Glucocorticoids are often given for inflammation; however, they lead to a decrease in bone density and an increase in fracture risk.  In animal models, even with glucocorticoid damage, K2 still showed an osteoprotective effect on osteoblasts, and promoted bone healing in osteoporotic rat models (Iwamoto et al, 2010; Zhang et al, 2017).

-Vitamin K reduces the risk of fractures
Exercise and physical activity require weight and load to be placed on bones.  Research shows that both vitamin K1 and K2 reduce the risk of fractures and microfractures.

In Australia, women with the lowest intake of vitamin K1 had the highest long-term risk for fractures.  Women were followed over 14.5 years and their intake of vitamin K was measured via osteocalcin blood levels (Sim et al, 2022).

Japanese Shorinji Kempo athletes were given a medical exam showing that 44% of them had experienced a sports-related fracture during practice, 75% had a lower daily vitamin D intake, and 94% had a lower daily vitamin K intake.  The authors indicated that the athletes needed to improve their bone mass, bone metabolism and improve their nutrition, including vitamin K in order to improve their physical function (Sumida et al, 2012).  Improving the intake of vitamin K with an increased intake of green leafy vegetables substantially improved osteocalcin markers of bone health suggesting increased entry of osteocalcin into the bone matrix, improvement of bone quality and lower fracture risk (Sim et al, 2020).  

Large-scale epidemiological studies on the relationship between vitamin K and fracture risk have been conducted. One of the largest studies in this matter is a prospective analysis conducted within the Nurse' Health Study performed with 72,327 women between 38 and 74 years of age, with a 10-year follow-up. In that study, subjects with a vitamin K1 intake more than 109 μg/day presented a 30% lower risk of hip fracture than women with a lower intake (Feskanich et al, 1999).  An epidemiological study conducted in North America revealed low vitamin K intake to be associated with an increased risk of hip fracture (Booth et al, 2000). 

A four-year study was conducted with postmenopausal Canadian women with osteopenia and normal levels of vitamin D who were taking vitamin K1 (phylloquinone) 500 mcg/day.  The women taking vitamin K had fewer clinical fractures than the placebo group of women (Cheung et al, 2008). Another study showed that a low concentration of vitamin K1 in elderly Asian patients was associated with an increased risk of fractures in both sexes (Nakano et al, 2011). Recently, postmenopausal women with osteoporosis were studied, and the results showed that those with fractures had a significantly lower value of vitamin K1 (Yaegashi et al, 2008; Torbergsen et al, 2015; Moore et al, 2020).

Another systematic review analyzed both BMD and fracture risk with K1 or MK-4 supplements. The authors found that all thirteen trials except one showed less bone loss (measured by BMD) in patients supplemented with either type of vitamin K. They also found that MK-4 supplements caused a reduction in all fracture types;  hip fractures showed a 77% reduction, vertebral fractures a 60% reduction and all nonvertebral fractures 81% reduction (Cockayne et al, 2006).

Low plasma concentrations of vitamin K are associated with a high risk of bone fractures in both northern Europeans and Asian populations of both sexes (Yaegashi et al, 2008; Torbergsen et al, 2015).The NOREPOS study (Norwegian Epidemiologic Osteoporosis Study) showed that low serum levels of vitamin K1 were associated with a 50% higher risk for hip fractures (Finnes et al, 2016).  The Perth Longitudinal study of aging Women in Australia showed that women who ate 125 g of dark leafy vegetables or more than 100 micrograms of vitamin K1, were 31% less likely to have any fractures (Sim et al, 2020). Lead author Dr. Marc Sim said the results further solidified vitamin K1 as a factor in fracture risk.

A pilot study indicated that children with low vitamin K2 status may be at greater risk of developing low-energy bone fractures. A low-energy bone fracture is defined as a fracture resulting from a fall that happens from standing height or lower (Popko et al, 2018; Karpinski et al, 2017).

A recent meta-analysis involving a total of 80,982 participants, showed an inverse association between dietary vitamin K1 intake and the risk of fractures.  Those subjects with the highest intake of vitamin K presented a 22% reduction in fracture risk (Hao et al, 2017). The prevalence of VK deficiency was found to be higher in older patients (mean age 80.0) with hip fractures than those without (Bultynck et al, 2020).

Natto is a Japanese delicacy and is made of fermented soybeans, which have the highest concentration of MK7.  A cross-sectional study comparing the serum vitamin K2 levels in Asian and European women found that the presence of natto in the diet of the Japanese population was associated with increased serum levels of MK7, and were associated with a reduced osteoporotic fracture risk compared to the women from the UK (Kaneki et al, 2001; Yaegashi et al, 2008).  Recently, a large prospective cohort study revealed that natto intake is inversely correlated with fracture risk (Kojima et al, 2019).

Stress fractures occur due to repetitive loading of the bones with stress, rather than a single traumatic event. They can occur in all bones of the lower extremity, particularly in people predisposed to repetitive strain, such as athletes. A recent report was published of a 13-year-old basketball player with right foot pain.  After six weeks of standard treatment, his pain had increased.  When testing showed he was low in vitamin K levels, he was told to add green vegetables to his diet.  He returned to the sport in six months and his physician felt that correcting the vitamin K deficiency was an important factor (Bayramoğlu et al, 2017).

In summary, evidence supports the role of Vitamin K2 in maintenance of bone health in numerous ways; increasing bone strength and density, reducing the risk of osteoporosis, increasing bone mineral content, inhibiting bone resorption, decreasing fracture risk, reducing the impact of arthritis, and upregulating cOC and carboxylated‐MGP levels.   Exercise requires strong bones, and vitamin K supports that need in multiple ways. 

While this page is reviewing the role of vitamin K and exercise, it is also important to note that there is significant research on the relationship of magnesium and vitamin D, along with vitamin K in making necessary contributions to bone health.  Everyone who wishes to be physically active should absolutely take all three nutrients to support your bones. 

Muscle
Bone and muscle are linked anatomically, biochemically, and metabolically, and there is crosstalk between the two systems (Battafarano et al, 2020; Kirk et al, 2020; Smith et al, 2021).  While Vitamin K supports bone health, it also has been linked to greater muscle mass, muscle strength, and greater exercise capacity.

The body has about 6000 skeletal muscles, accounting for 40-50% of the total body weight (Schnyder et al, 2015; Janssen et al, 2000; Strasser & Burtscher, 2018).  Men have about 36% more skeletal muscle mass than women. Muscle mass decreases with age in both men and women.

Fat, in the form of triglycerides, is stored as lipid droplets inside muscle fibers (van Loon et al, 2001).  Triglycerides are composed of three fatty acids attached to a molecule of glycerol.    Intramuscular triglycerides (IMCL) are easily available and in close proximity to the muscle mitochondria.  During exercise, the triglycerides are broken down into glycerol and free fatty acids in a process called lipolysis (Ogasawara et al, 2015; Watt & Spriet, 2010; Zechner et al, 2009). The fatty acids are released to the circulation and directed into muscle cells for energy.  Once inside the muscle cell, fatty acids are transported to the mitochondria (i.e., energy factory of the cell) to be broken down to produce ATP as fuel for working muscles (Thompson et al, 2012).

Intramuscular triglyceride generally supplies the fatty acids for up to 2 hours of continuous exercise. Individuals with higher fitness have a greater storage capacity and ability to metabolize intramuscular triglyceride.  Endurance-trained athletes rely more heavily on IMCL to fuel exercise.

During exercise, an important function of the cardiovascular system is to supply oxygen to the active muscles according to the demand.  Just how much oxygen your muscles will use depends on two processes: the blood flow to the muscles and the extraction of oxygen from the blood into the muscle tissue, known as perfusion. (Andersen & Saltin, 1985; Rowell et al, 1986; Wagner, 1996; Koskolou et al, 1997; Delp & Laughlin, 1998; González -Alonso et al, 2022).

Working muscles can take oxygen out of the blood three times better than your resting muscles.  Some believe that maximal oxygen uptake is dependent on the muscle fiber oxidative capacity (van der Zwaand et al, 1985; Wisloff et al, 1998). 

Anything that can affect oxygen intake or blood flow can impact the amount of oxygen delivered to working muscles during exercise, such as restrictions in blood flow. Cardiac function and vascular health can help, or it can limit the ability of the circulatory system the meet the increasing demands of muscle and tissues during whole-body exercise. Lung health or disease can impair the ability of the lungs to exchange oxygen, meaning there is less oxygen to carry in the blood stream to muscles. 

Vitamin K and Muscle
The research shows that vitamin K helps with better physical performance, larger muscle mass, muscle strength, and reduces muscle cramping.

-Better Physical Performance
The first study on the role of vitamin K and physical performance was carried out in 2016, where 1,089 elderly participants of the Health, Ageing and Body Composition Study (Health ABC) had their lower extremity muscle function assessed.  It was found that vitamin K1 was significantly associated with better physical function, and this effect was maintained over 5 years of follow-up (Shea et al, 2016).

The Longitudinal Aging Study Amsterdam (LASA) followed women for 14 years, measuring their biochemical markers of vitamin K along with measures of strength.  They found that higher ucMGP concentrations (indicating low vitamin K intake) were associated with lower handgrip strength and calf circumference and a lower physical performance (van Ballegooijen et al, 2018; Machado-Fraguo et al, 2010). 

Mouse models established that osteocalcin can be considered a bone hormone that can regulate tissue, including muscle (Lee et al, 2007).  Research has been able to show that muscle uptake of glucose and fatty acids was increased upon exposure to osteocalcin in vitro, meaning that osteocalcin signaling supports glucose and fatty acid utilization during exercise (Lin et al, 2017; Tsuka et al, 2015; Pi et al, 2016; Moser & van der Eerden, 2019; Mera et al, 2016; Alonso et al, 2022).  

-Muscle Mass
Observational studies conducted on patients with sarcopenia showed that high levels of vitamin K were associated with muscle strength, large muscle mass and high physical performance.  The beneficial effect of vitamin K on muscle quality was best represented by physical performance scores rather than muscle mass (Azuma & Inoue, 2019).

Vitamin K deficiency is correlated with progressive reductions in muscle mass.  The authors concluded that vitamin K2 moderates skeletal muscle mitochondria, and recommended studies on vitamin K2 supplementation to prevent muscle mass loss (Rønning et al, 2018; Simes et al, 2019). A lab study showed that vitamin K2 increased slow twitch muscle fibers and improved mitochondrial function (Su et al, 2022). 

-Muscle Strength
Handgrip indicates muscle strength and is directly related to lower-extremity strength. Calf circumference indicates skeletal muscle mass and is associated with higher strength (Jakobsen et al, 2010; Rolland et al, 2003). A longitudinal cohort study conducted in community-dwelling adults analyzed the association between vitamin K status and physical functioning over 13 years. Low vitamin K status was associated with lower handgrip strength, smaller calf circumference, and poorer functional performance (Ballegooijena et al, 2018).

-Leg Cramps
Leg cramps are a distressing problem characterized by involuntary, painful, sudden contractions of the skeletal muscles, accompanied by pain or muscle hardening, and are typically found in the lower extremities.  It affects about 30% of people over the age of sixty, and 50% of people over the age of 80 (Naylor et al, 1994; Abdulla et al, 1999).  A study using MK7, at a dose of 100 mcg/day for three months relieved muscle cramps (Mehta et al, 2010).

To further elucidate the effects of MK-7 on cramps, a clinical trial showed that vitamin K2 reduced the frequency and severity of muscle cramps in patients on dialysis.  Those who received 360 ug/day of K2 showed a significant decrease in the frequency of muscle cramps within eight weeks, with a further reduction in the next eight weeks.  The group receiving the placebo had no significant reduction in the frequency of cramps.  The vitamin K benefit was manifested by decreased frequency, shortened duration, and weakened intensity of cramping Furthermore, the improvements went away when vitamin K2 was replaced with the placebo (Xu et al, 2022).

Osteocalcin, exercise capacity and age.
Osteocalcin naturally declines in humans as we age, beginning in women at age 30 and in men at age 50. This decrease in circulating bioactive OCN occurs at the same time as the ability to perform exercise declines (Mera et al, 2016a).  However, during exercise in both mice and humans, the levels of osteocalcin in the blood do increase, depending on age (Levinger et al, 2014; Rahimi et al, 2020; Rahimi et al, 2021).

To investigate whether osteocalcin levels were affecting exercise performance, Karsenty and his colleagues tested mice genetically engineered so osteocalcin could not signal properly in their muscles. Without osteocalcin muscle signaling, the mice ran 20%-30% slower than their healthy counterparts before reaching exhaustion.  It was concluded that the osteocalcin signaling in myofibers favors adaptation to exercise because it promotes the uptake of glucose and fatty acids, a necessary step to create energy (Mera et al, 2016a; Karsenty & Olsen, 2016).

These experiments highlighted the therapeutic potential of OCN to reverse the age-induced decline in exercise capacity and muscle mass observed in mice, and humans. This study not only showed that osteocalcin is necessary and sufficient to increase exercise capacity; but that osteocalcin has anti-geronic properties; that is, it has the ability to ameliorate the consequences of aging (Mera et al, 2016; Diaz-Franco et al, 2019).

Mitochondria
The human body needs energy to function, and food is the fuel source for energy. Foods are made up of nutritional components called fats, carbohydrates, and proteins. Through digestion, foods are deconstructed into their most basic states, called glucose, fatty acids, and amino acids. Once these nutrients are broken down, they are transported through the blood to either be used in a metabolic pathway or stored for later use.  Carbohydrates are generally used for short-term energy needs, while fats are used for long-term energy needs. Proteins can supply energy, but are often used for building muscle, not providing energy (Da Poian et al, 2010; Hargreaves & Spriet, 2018).

Food is converted into an important form of chemical energy, adenosine triphosphate or ATP. Mitochondria mediate this conversion to ATP, the immediately usable form of chemical energy utilized for most cellular functions. Mitochondria are popularly known as the ‘powerhouses of the cell’, as they provide about 80% of the energy for cell life activities.  Only a small amount of ATP is stored within the body, which is not a significant energy reserve.  

In 1967, John Holloszy published the first direct evidence that exercise training promotes mitochondrial biogenesis in skeletal muscle several ways. This seminal study showed that a strenuous program of treadmill running in rats led to significant increases in mitochondrial protein and enzyme activity in recruited skeletal muscles. Later research showed that exercise training increases the synthesis of mitochondrial proteins in human skeletal muscle (Wilkinson et al, 2008; Miller & Hamilton, 2012; Scalzo et al, 2014; Ju, 2017; Oliveira & Hood, 2019).

Mitochondria and Vitamin K
Mitochondrai stay healthy through mitophagy, the mechanism of finding and degrading damaged mitochondria .  Research has shown that vitamin K has an important role of supporting mitophagy (Drake et al, 2015; Ploumi et al, 2017; Anzell et al, 2018]. In normal mitochondria, the PINK1 protein can function as a sensor for damaged mitochondria, mediating the mitophagy that clears out the damage (Gomes et al, 2013; Tang et al, 2022).  When there is mitochondrial damage, PINK1 is not imported into the mitochondria (Jin et al, 2012), resulting in an accumulation of dysfunctional and fragmented mitochondria which can result in the accumulation of ROS in damaged mitochondria, leading to cellular oxidative stress (Geisler et al, 2010; Greene et al, 2012). 

Importantly, research has shown that vitamin K2 (MK4) rescued severe mitochondrial defects caused by mutations in the PINK1 gene. Vitamin K2 served as a mitochondrial electron carrier and rescued mitochondrial dysfunction due to Pink1 protein deficiency (Vos et al, 2012). 

Another recent study found that vitamin K2 treatments promoted mitophagy and alleviated damage to cells.  In labs, SH-SY5Y cells serve as a model for neurodegenerative disorders. In the study, SH-SY5Y cells were stimulated with 6-hydroxydopamine (6-OHDA) (often used in research to induce Parkinson’s disease). In the presence of 6-OHDA, cell viability was reduced, the mitochondrial membrane potential was decreased, reactive oxygen species (ROS) accumulated, and there was abnormal mitochondrial fission and fusion.  However, when MK4 was added to the cells, it significantly suppressed damage from 6-OHDA, enabling the cells to maintain the important balance of mitochondrial fusion and fission (Tang et al, 2022).  These results suggest that vitamin K2 reduces mitochondrial dysfunction and alleviates cell damage by regulating the mitochondrial quality-control system (Su et al, 2021).

Rotenone, a widely used pesticide, can selectively inhibit aspects of the mitochondrial electron transport chain, inducing oxidative stress  and neurodegeneration (Martinez & Greenamyre, 2012; Radad et al, 2006) Research found that MK4 inhibits  rotenone-induced damage, and significantly decreased reactive oxygen species (ROS) production. In addition, MK-4 represses microglial neuronal cell death (Yu et al, 2016].

Summary

There is a wealth of research detailing the role of vitamin K in each of these systems, particularly for the cardiovascular system, and bones.  Research has just begun looking at the relationship of vitamin K to exercise outcomes, and the initial findings are exciting, showing that in just 8 weeks, a person can significantly improve their VO2 max by taking MK7.K serves as the catalyst for these organ systems and is key to fitness and physical activity.  With adequate availability of vitamin K, these organ systems are best prepped for peak training and performance (Crintea et al, 2021; Brancaccio et al, 2022). 

Dose
The term vitamin K refers to a family of fat-soluble vitamins, which the body stores in fat tissue and the liver.  Fat-soluble means the vitamin is transported around the body on lipid or fat cells.  Any intake of vitamin K should be following a meal, or with a fat. 

Per the FDA there are no upper limits for taking vitamin K, as there are no negative side effects.  The only caution is that folks who are taking warfarin, a blood thinner, should consult with their physician. 

 

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