The heart is one of the hardest-working organs in the body. It contracts and relaxes a little more than once per second, providing the blood flow on which every other organ in your body relies. That requires a steady supply of energy, and to perform at optimal function, your heart needs to derive that energy from its fuel (primarily fatty acids and glucose) efficiently and with little waste. This is where coenzyme-Q10 (CoQ10) comes into play.

Meanwhile, for the heart to operate optimally, the blood vessels and arteries must be healthy and flexible. But as we age, calcium in the bloodstream can accumulate and deposit in the artery walls, causing them to stiffen. This can result in reduced blood flow, which increases blood pressure and the formation of microfractures that can give way and even fissure. Enter vitamin K2.

Vitamin K2 and CoQ10 provide similar support to the heart and blood vessels, but a staple of traditional medical treatment for cardiovascular health actually works against both of these vital nutrients.

Vitamin K2
Effect on heart health. The body produces matrix Gla protein (MGP), a K-dependent protein that is the most potent natural inhibitor of calcification known today (1). But to perform this function, MGP must be activated. When the body has adequate amounts of vitamin K2 (specifically as menaquinone-7, or MK-7, it is said to be the most biologically active and available form of vitamin K2), MGP stops calcium from depositing in the arteries and blood vessels, returning it to the bloodstream so it can be used for other purposes such as building strong, dense bones.

A three-year study (using a specific brand of vitamin K2 as MK-7) on 244 healthy postmenopausal women provided a breakthrough demonstration of vitamin K2’s effect on heart health. The group was randomly assigned to take a nutritional dose (180 mcg) of vitamin K2 as MK-7 daily or placebo for three years. After three years of supplementation, the Stiffness Index ß in the MK-7 group had decreased significantly compared to the slight increase in the placebo group. Results confirmed that vitamin K2 as MK-7 not only inhibited age-related stiffening of the artery walls, but also made a statistically significant improvement of vascular elasticity.

This study is the first intervention trial in which the results confirm the association made by previous population-based studies: vitamin K2 intake is linked to positive changes in cardiovascular risk factors. According to the researchers, the data demonstrated that a nutritional dose of vitamin K2 promotes cardiovascular health (2).

Mechanism of action. Vitamin K is not a single compound. It consists of a group of fat-soluble vitamins that are essential for the body to have normal coagulation activity and to utilize calcium for healthy bones, arteries and soft tissues. The vitamin K family is divided into vitamin K1 (i.e., one molecule, or “phylloquinone”) and vitamin K2 (i.e., a group of molecules, or menaquinones).Gelita

While both vitamins K1 and K2 are responsible for blood clotting, only vitamin K2 is available and can be utilized by soft tissues and systems beyond the liver due to its molecular structure.

K vitamins play an essential role as cofactor for the enzyme γ-glutamyl carboxylase, which is involved in the carboxylation of the vitamin K-dependent proteins, specifically the conversion of
peptide-bound glutamic acid (Glu) to γ-carboxy glutamic acid (Gla).

Carboxylation, or activation, of vitamin K-dependent proteins (called Gla-proteins) serves as a recycling pathway to recover vitamin K from its epoxide metabolite (KO) for reuse in carboxylation. Several human Gla-containing proteins synthesized in many different types of tissues have been discovered. But specific to cardiovascular health, MGP is a calcification-inhibitory protein found in numerous body tissues. Its role is most pronounced in cartilage and in arterial vessel walls.

Vitamin K2 activates clotting factors, MGP and osteocalcin—proteins produced in the liver, bone and vasculature that coagulate blood, “clean up” calcium deposits stored in the arteries and bind them to the surface of bone. The activation occurs via a carboxylation reaction, in which vitamin K acts as a cofactor for gammaglutamyl carboxylase, an enzyme that transforms proteins’ Glu residues into Gla, which gives them the ability to bind calcium ions. Then, vitamin K2 is recycled, which allows the body to reuse it.

Heart-health benefit. By helping the arteries and blood vessels to remain healthy and flexible, vitamin K2 supports cardiovascular health, thus improving endothelial function (i.e., the vasculatures’ ability to relax and contract) and protecting against atherosclerosis (i.e., a disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls).

Vitamin K2: An Essential Bone Builder… for Young and Old
By Hogne Vik, M.D., Ph.D., MBA

Evidence continues to grow confirming the importance of vitamin K2 for bone health and our need to address this aspect of health as early as possible.

Understanding Vitamin K2
Vitamin K2 is part of the vitamin K family. Vitamin K1 is better known due to its essential role in blood clotting. Vitamin K2, specifically as the menaquinone-7 (MK-7) form, also contributes to blood clotting to a minor degree. However, because K2 is the most bioavailable of the K vitamins (1), it is able to extend beyond the liver to activate K-dependent proteins in other systems, such as the bones and vasculature.

With respect to bone health, vitamin K2 activates a protein produced by bone cells called osteocalcin, which binds calcium ions to the bone mineral matrix, thus strengthening the skeleton. But without adequate K2, osteocalcin remains inactive and calcium is not directed to create stronger bones.

A three-year study of vitamin K2 as MK-7 and 244 healthy postmenopausal women, published in Osteoporosis International, offered the clearest validation of its impact on bone health, showing the first clinically statistically significant protection of the vertebrae and the hip (femoral neck) against bone loss. This was achieved with a nutritional dose of 180 mcg daily of K2 (MenaQ7 from NattoPharma). MK-7 significantly increased the circulating active osteocalcin (cOC), while the decreasing inactive osteocalcin (ucOC) as compared to the placebo. After three years of supplementation, maintenance in both bone mineral content and bone mineral density were statistically significant in the MK-7 group. Moreover, bone strength was statistically improved, demonstrating therapeutic benefits for the MK-7 group (2).

In addition, a study published last year in the Journal of Nutritional Science (3) further highlighted MK-7’s positive effect on both bone and cardiovascular health. Researchers examined an MK-7-fortified yogurt drink (28 μg MenaQ7 PURE yogurt drink) for its effect on vitamin K status as well as markers of vascular health. Healthy men (n = 32) and postmenopausal women (n = 28) with a mean age of 56 years (SD 5) received either a basic or fortified yogurt drink twice per day for 12 weeks. MK-7 was efficiently absorbed from the fortified yogurt drink and K status was improved, as measured by significant decreases in inactive osteocalcin and matrix Gla protein (MGP), a K-dependent protein that is the strongest inhibitor of vascular calcification.vitamin K2

Addressing Bone Health Early
The probability of developing a bone disease later in life is closely related to the amount of bone mass one accumulates before age 30, so it is essential to adopt good bone-building habits early. Up to 90% of peak bone mass is acquired by age 18 in girls and by age 20 in boys. Just a 10% increase in bone mass is estimated to reduce the risk of osteoporotic fracture in adult life by 50% (4).

Not only has it been revealed that 97% of Western populations are deficient in vitamin K2 (5), but a 2014 study published in Food & Function revealed that healthy children have the largest tissue-specific vitamin K deficiency—eight to 10 times more inactive osteocalcin than adults (6). Further, a 2009 study published in the British Journal of Nutrition demonstrated in healthy prepubertal children that modest supplementation with MenaQ7 vitamin K2 as MK-7 (45 mcg/day for eight weeks) increased osteocalcin activation, creating stronger, denser bones (7).

In conclusion, we need sufficient vitamin K2 to secure healthy skeletal foundation during childhood; we need K2 to support our bones during our adult life; and we need K2 to inhibit loss of bone mass and strength during our senior years. As most are deficient in this vital nutrient, supplementation presents a viable alternative, for young and old. WF

Hogne Vik, M.D., Ph.D., MBA, is the chief medical officer with Nattopharma.

1. H.C. Buitenhuis et al., “Comparison of the Vitamins K1, K2 and K3 as Cofactors for the Hepatic Vitamin K-Dependent Carboxylase,” Biochim. Biophys. Acta. 1034 (2), 170–175 (1990).
2. M.H.J.  Knapen et al., “Three-Year Low-Dose Menaquinone-7 Supplementation Helps Decrease Bone Loss In Healthy Postmenopausal Women,” Osteoporos. Int. 24 (9), 2499–2507 (2013).
3. M.H.J. Knapen et al., “Yogurt Drink Fortified with Menaquinone-7 Improves Vitamin K Status in a Healthy Population,” J. Nutr. Sci. 4: e35 (2015). Published online 2015 Oct 16.
4. S.R. Cummings et al., “Bone Density at Various Sites for Prediction of Hip Fractures. The Study of Osteoporotic Fractures Research Group,” Lancet 341 (8837), 72–75 (1993).
5. M.K. Shea et al., “Circulating Uncarboxylated Matrix Gla Protein Is Associated With Vitamin K Nutritional Status, But Not Coronary Artery Calcium, in Older Adults,” J. Nutr. 141 (8), 1529–1534 (2011).
6. E. Theuwissen et al., “Vitamin K Status in Healthy Volunteers,” Food Funct. 5 (2), 229–234 (2014).
7. M.J. van Summeren et al., “The Effect of Menaquinone-7 (Vitamin K2) Supplementation on Osteocalcin Carboxylation in Healthy Prepubertal Children,” Br. J. Nutr. 102 (8), 1171–1178 (2009).

Effect on heart health. CoQ10 is essential for the heart to maintain sufficient energy management (3, 4). When CoQ10 levels decline, tissues burn fuel inefficiently, eventually producing oxidative damage and ultimately losing their function. When the heart muscle loses its fuel efficiency, heart failure may occur (3, 4).

Studies show that CoQ10 supplementation at 300 mg/day not only restores normal CoQ10 levels, but also prevents the progression of heart failure and, in fact, can reverse that progression and extend survival and improve quality of life.

Similar beneficial effects have now been shown in patients with endothelial dysfunction, hypertension and coronary artery disease, the precursors of heart attacks and, ultimately, heart failure.

IlhwaMechanism of action. CoQ10 is a fat-soluble, vitamin-like compound that is naturally found in most tissue of the human body. The highest concentrations are found in the heart, liver, kidney and pancreas. The human body produces CoQ10, yet we can replenish it from dietary sources. Within cells, CoQ10 is mostly present in the mitochondria (40–50%). It is the electron acceptor for the mitochondrial electron transport chain. It is also a cofactor used in processes of aerobic respiration, aerobic metabolism, oxidative metabolism and cell respiration.

CoQ10’s primary function is as an antioxidant, a membrane stabilizer and a producer of adenosine triphosphate (ATP) in the oxidative respiration process. As an antioxidant and in its role in ATP production, CoQ10 offers many therapeutic benefits. Also, CoQ10 has been shown to help preserve myocardial sodium-potassium ATPase activity and stabilize myocardial calcium-dependent ion channels.

Heart health benefit. Chronic oxidative stress is one main factor that reduces the functioning of the endothelium, the thin layer of cells lining arteries that controls blood flow and pressure. Endothelial dysfunction is a major precursor to hypertension, coronary heart disease and strokes. As a unique antioxidant, CoQ10 reduces blood vessel stiffness, which is a consequence of endothelial dysfunction.

In patients with known coronary artery disease, who are at high risk for heart attack and who need every bit of functioning endothelium, supplementation with 300 mg of CoQ10 per day significantly improved their natural endothelial antioxidant levels, improved their arterial relaxation and improved their oxygen utilization (5).

Further, oxidative stress and endothelial dysfunction are major causes of elevated blood pressure. CoQ10 supplementation is showing promise in balancing blood pressure in hypertensive patients, without producing dangerous abrupt drops in pressure.

Connection Between CoQ10 and Vitamin K2: Endothelial Function and Statins
Both vitamin K2 and CoQ10 have been shown to improve endothelial function, but that is not the only connection tethering these vital nutrients.

Statins are a common recommendation for lowering LDL-C levels (cholesterol), and their use has been on the rise over the last few decades, even though it is commonly known that statins deplete CoQ10 levels in the body. In response, it is recommended to patients on statins to offset the side effect by taking supplemental CoQ10.

However, a paper recently published in Expert Review Clinical Pharmacology suggests statins may act as “mitochondrial toxins” with negative effects on the heart and blood vessels not only via CoQ10 depletion, but also by inhibiting “the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification” (6).

This new paper speaks directly to statins interrupting the mechanism of action by which vitamin K2 inhibits calcification. Yet while CoQ10 and vitamin K2 are both affected by statins, no recommendation currently exists for supplemental vitamin K2 to be given to statin patients. That is something that the medical community needs to consider. WF

1. L.J. Schurgers, E.C.M. Cranenburg and C. Vermeer, “Matrix Gla Protein: The Calcification Inhibitor in Need of Vitamin K,” Thromb. Haemost. 100 (4) 593-603 (2008).
2. M.J.J. Knapen, “Menaquinone-7 Supplementation Improves Arterial Stiffness in Healthy Postmenopausal Women: Double-Blind Randomised Clinical Trial,” Thromb. Haemost. 1135–1144 (2015).
3. E. Fosslien, “Review: Mitochondrial Medicine—Cardiomyopathy Caused By Defective Oxidative Phosphorylation,” Ann. Clin. Lab. Sci. 33 (4), 371–395 (2003).
4. S.A. Mortensen et al., “Coenzyme Q10: Clinical Benefits With Biochemical Correlates Suggesting A Scientific Breakthrough in the Management of Chronic Heart Failure,” Int. J. Tissue React. 12 (3), 155–162 (1990).
5. L. Tiano et al., “Effect of Coenzyme Q10 Administration On Endothelial Function And Extracellular Superoxide Dismutase in Patients With Ischaemic Heart Disease: A Double-Blind, Randomized Controlled Study,” Eur. Heart J. 28 (18), 2249–2255 (2007).
6. H. Okuyama et al., “Statins Stimulate Atherosclerosis and Heart Failure: Pharmacological Mechanisms,” Expert Rev. Clin. Pharmacol. 8 (2), 189-199 (2015).

Katarzyna Maresz, Ph.D., is the president of the International Science and Health Foundation, a not-for-profit research consortium that launched in 2014 in an effort to highlight the substantial research supporting the benefit of vitamin K2 for human health.

Published in WholeFoods Magazine April 2016