Summary
Insufficient calcium consumption can result in decreased bone mineral density, which may enhance the danger of bone fractures. Supplemental calcium promotes bone mineral density and energy and might forestall osteoporosis (ie, porous bones), notably in older adults and postmenopausal ladies.1,2 Nonetheless, current scientific proof means that elevated consumption of calcium dietary supplements can increase the danger for coronary heart illness and may be related to accelerated deposit of calcium in blood vessel partitions and comfortable tissues.3–8
In distinction, vitamin K2 is related to the inhibition of arterial calcification and arterial stiffening,9,10 which implies that elevated vitamin K2 consumption could possibly be a way of decreasing calcium-associated well being dangers. Nonetheless, since 1950, the consumption of vitamin K has decreased progressively,11 and even a well-balanced weight loss program won’t present vitamin K in quantities adequate for satisfying the physique’s wants.
Additional, because of trendy manufacturing processes, the vitamin K content material, notably the vitamin K2 content material, of the meals provide as we speak has considerably dropped, making vitamin K2 dietary supplements a extra dependable option to safe satisfactory consumption.12 By hanging the proper steadiness in consumption of calcium and K2, it might be doable to battle osteoporosis and concurrently forestall the calcification and stiffening of the arteries. A brand new medical examine with vitamin K2 supplementation confirmed an enchancment in arterial elasticity and regression in age-related arterial stiffening (information pending publication). Most necessary, by its activation of K–dependent proteins, vitamin K2 can optimize calcium use within the physique, stopping any potential adverse well being impacts related to elevated calcium consumption.
Vitamin K2: Important Function
Bone consists of a tough outer shell and a spongy matrix of interior tissues and is a dwelling substance. The complete skeleton is changed each 7 to 10 years. Throughout the skeleton’s transforming, the physique releases calcium from the bone into the bloodstream to satisfy a person’s metabolic wants, permitting the bone to change dimension and form because it grows or repairs from accidents.13 This transforming is regulated by osteoblasts—cells that construct up the skeleton—and osteoclasts—cells that break down the skeleton. So long as the bone-forming exercise (ie, absorption) is larger than the breakdown of bone (ie, resorption), the method of sustaining a wholesome bone construction is maintained.
Osteoblasts produce osteocalcin, which helps take calcium from the blood circulation and bind it to the bone matrix. Partly, osteocalcin influences bone mineralization by its potential to bind to the mineral part of bone, hydroxyapatite,14 which in flip makes the skeleton stronger and fewer prone to fracture. The newly made osteocalcin, nevertheless, is inactive, and it wants vitamin K2 to turn out to be absolutely activated and bind calcium.15
That requirement alone makes vitamin K2 a serious participant in bone well being, however its significance doesn’t cease there. Vitamin K2 additionally retains calcium from accumulating within the partitions of blood vessels. The vitamin K–dependent protein, matrix GLA protein (MGP), is a central calcification inhibitor produced by the cells of vascular clean muscular tissues and regulates the doubtless deadly accumulation of calcium.16
Calcium: Blended Messages
Calcium serves many necessary roles within the human physique, together with (1) offering construction and hardness to bones and enamel, (2) permitting muscular tissues to contract and nerves to ship alerts, (3) making blood vessels broaden and contract, (4) serving to blood to clot, and (5) supporting protein perform and hormone regulation.17 Despite the fact that dairy merchandise symbolize a wealthy supply of calcium, roughly 43% of the US inhabitants and 70% of older ladies often take calcium dietary supplements.18 Calcium supplementation is supported by a number of research that again its advantages for bone well being and osteoporosis prevention in addition to for total well being.
Calcium’s potential to decrease blood pressure19 and decrease ranges of blood cholesterol20–22 contributes to coronary heart well being. Certainly, a potential cohort examine of postmenopausal ladies from Iowa related increased calcium consumption to decrease threat of demise because of coronary heart illness by the managed provide of calcium within the blood.23 However most not too long ago, a number of research have forged doubt on the notion that “more is better” in relation to calcium consumption and prevention of heart problems.24
A examine printed by Xiao et al8 mentioned the end result of the Nationwide Institutes of Well being (NIH) AARP Food plan and Well being Examine, which evaluated the position of supplemental calcium on cardiovascular well being. This potential examine concerned a big group, 219 059 males and 169 170 ladies, whose well being was tracked for 12 years. The researchers discovered that males, however not ladies, taking greater than 1000 mg/day of calcium dietary supplements had a threat of complete cardiovascular demise that was 20% increased than that of contributors taking no calcium dietary supplements.
Different printed research have discovered a detrimental influence for calcium supplementation on ladies’s cardiovascular well being, too. Knowledge from the Ladies’s Well being Initiative confirmed that these ladies taking 1000 mg/day within the type of calcium dietary supplements, with or with out the addition of 400 IU/day of vitamin D, elevated their threat of cardiovascular occasions by 15% to 22%, notably ladies who originally of examine didn’t take calcium dietary supplements.4 Furthermore, the danger for coronary coronary heart illness elevated by 24% in a bunch of 10 555 Finnish ladies who used calcium dietary supplements, with or with out vitamin D.7
Additional, a examine by the European Potential Investigation into Most cancers and Diet (EPIC-Heidelberg) with 23 980 contributors concluded that contributors often taking a calcium complement had an threat for coronary heart assault that was 86% increased than that for contributors not taking a complement.5 The impact was much more pronounced when no dietary supplements aside from calcium had been taken; the danger of coronary heart assault greater than doubled in these instances.
In sufferers with kidney failure, supplemental calcium has additionally been linked to elevated hardening of the arteries by calcification in addition to to increased mortality.25,26 A meta-analysis combining and analyzing the outcomes from completely different randomized, managed trials of kidney illness additionally linked calcium supplementation with a 22% enhance within the threat of demise from cardiovascular points.27
A doable rationalization for the adverse results of high-dose (1000 mcg day by day), long-term consumption of calcium on cardiovascular well being is that it renders the traditional homeostatic management of calcium concentrations within the blood ineffective.6 Substantial epidemiological proof has proven that ranges of serum calcium within the higher a part of the traditional vary are a threat issue for vascular illness and that calcium dietary supplements acutely elevate serum calcium. This mixture of findings lends plausibility to the concept supplementation can will increase vascular threat.28 In different phrases, elevated ranges of blood calcium have been correlated with elevated blood clotting and calcium deposition in blood vessels, which ends up in arterial hardening. Each of those results enhance the danger of coronary heart illness.4,8,29,30
Vitamin K: Kind and Construction – “k2 calcium”
Eighty-four years in the past, whereas investigating the consequences of a low-fat weight loss program fed to chickens, Danish scientist Henrik Dam found vitamin K. He discovered that the bleeding tendencies discovered within the chickens on that weight loss program could possibly be prevented when a weight loss program with regular ranges of fats was restored and vitamin K was added to their diets. From that time ahead, vitamin K turned referred to as the coagulation vitamin, the “K” coming from the German phrase koagulation.31
Later, it was discovered that the fat-soluble compound wanted for blood clotting existed in 2 kinds: phylloquinone (vitamin K1) and menaquinone (vitamin K2).32 Vitamin K1 is made in crops and algae; inexperienced leafy greens are a very wealthy supply. Then again, micro organism generate vitamin K2, which may also be present in meat, dairy, eggs, and fermented meals, reminiscent of cheese, yogurt, and natto—a Japanese dish of fermented soybeans.33,34
Despite the fact that the aspect chains of isoprenoid models of vitamin K differ in size, usually from 4 to 13 repeats (MK-4 to MK-13), they’re all utilized by the enzyme γ-glutamate carboxylase to activate a particular set of proteins, together with proteins concerned in blood coagulation, bone formation, and inhibition of soppy tissue calcification. Each types of vitamin K, K1 and K2, are important in sustaining blood hemostasis and optimum bone and coronary heart well being by the position they play in inducing calcium use by proteins. Vitamin K, notably vitamin K2, is important for calcium use, serving to construct sturdy bones and inhibiting arterial calcification.35
Vitamin K is a cofactor for 1 enzyme, γ-glutamylcarboxylase, which γ-carboxylates sure glutamic-acid residues posttranslationally in a variety of vitamin K–dependent (VKD) proteins. This γ-carboxylation permits VKD proteins to bind calcium. Vitamin K is required for the exercise of coagulation and anticoagulation factors36 and for the binding of osteocalcin to hydroxyapatite in bone37; it’s usually thought of to be required for the perform of MGP.38
Vitamin K shouldn’t be a single entity however, slightly, a household of structurally associated molecules derived from completely different sources. Main molecular kinds, their main dietary sources, and their relative contributions to vitamin K exercise are proven in Desk.35,37,39–44 All molecules listed in Desk 1 share the identical nucleus—methylated naphthoquinone (menadione)—however have aspect chains of differing composition and size, which leads to completely different potencies and absorption efficiencies.44
Kind positively issues. The truth is, research on natto assist the significance of vitamin K2 within the type of menaquinone with 7 isoprene residues (MK-7). Kaneki and colleagues have proven that elevated consumption of MK-7 results in extra activated osteocalcin, which is linked to elevated bone-matrix formation and bone mineral density and, due to this fact, a decrease threat of hip fracture.45,46 These outcomes had been confirmed in a 3-year examine with 944 ladies aged 20 to 79 years, which confirmed that consumption of MK-7-rich natto was related to the preservation of bone mineral density.47
Coronary heart Well being: Supreme State
Enough consumption of vitamin K2 has been proven to decrease the danger of vascular harm as a result of it prompts MGP, which inhibits calcium from depositing within the vessel partitions. Therefore, calcium is out there for a number of different roles within the physique, leaving the arteries wholesome and versatile.46
Nonetheless, vitamin K deficiency leads to insufficient activation of MGP, which enormously impairs the method of calcium removing and will increase the danger of calcification of the blood vessels.48–52 As a result of that calcification happens within the vessel partitions, it results in thickening of the wall through calcified plaques (ie, to the everyday development of atherosclerosis), which is related to the next threat of cardiovascular occasions.
The population-based Rotterdam examine studied 4807 wholesome women and men older than age 55 years, evaluating the connection between dietary consumption of vitamin K and aortic calcification, coronary heart illness, and all-cause mortality.10 The examine revealed that top dietary consumption of vitamin K2—no less than 32 mcg per day, with no consumption of vitamin K1, was related to a 50% discount in demise from cardiovascular points associated to arterial calcification and a 25% discount in all-cause mortality.
These findings had been supported by one other population-based examine with 16 000 wholesome ladies aged 49 to 70 years that was drawn from EPIC’s cohort inhabitants.53 After 8 years, the information confirmed {that a} excessive consumption of pure vitamin K2 (ie, not artificial K2, however not of vitamin K1) was related to safety towards cardiovascular occasions. For each 10 mcg of dietary vitamin K2 consumed within the types of menaquinone 7 (MK-7), menaquinone 8 (MK-8), and menaquinone 9 (MK-9), the danger of coronary coronary heart illness was decreased by 9%. A examine on 564 postmenopausal ladies additionally revealed that consumption of vitamin K2 was related to decreased coronary calcification, whereas consumption of vitamin K1 was not.9
One current, double-blind, randomized medical trial investigated the consequences of supplemental MK-7, MenaQ7 (NattoPharma ASA, Hovik, Norway), inside a 3-year interval for a bunch of 244 postmenopausal Dutch ladies.54 The researchers discovered {that a} day by day dose of 180 mcg was sufficient to enhance bone mineral density, bone energy, and cardiovascular well being. In addition they confirmed that reaching a clinically related enchancment required no less than 2 years of supplementation.
A examine pending publication of 244 postmenopausal ladies who took dietary supplements with 180 mcg of vitamin K2, as MK-7, for 3 years day by day really confirmed a big enchancment in cardiovascular well being as measured by ultrasound and pulse-wave velocity, that are acknowledged as customary measurements for cardiovascular well being.55–57 In that trial, carotid artery distensibility was considerably improved for a 3-year interval as in contrast with that of a placebo group. Additionally, pulse-wave velocity confirmed a statistically considerably lower after 3 years for the vitamin K2 (MK-7) group, however not for the placebo group, demonstrating a rise within the elasticity and discount in age-related arterial stiffening.
Calcium Issues: Vitamin K2
Research illustrate that top calcium consumption helps strengthen the skeleton however, on the identical time, might enhance the danger of coronary heart illness because of arterial calcification.3–8,22 Inactive proteins regulating calcium, reminiscent of MGP, correlate with the event of arterial calcification. Though vitamin K1 can activate MGP, it’s a lot much less environment friendly as a result of it’s transported to the liver first to activate coagulation proteins.35 To render the proteins regulating calcium energetic, a adequate quantity of vitamin K2 needs to be current within the physique.58
If no less than 32 mcg of vitamin K2 is current within the weight loss program, then the dangers for blood-vessel calcification and coronary heart issues are considerably lowered,10 and the elasticity of the vessel wall is elevated.59 Furthermore, the useful results of nutritional vitamins D and K on the elastic properties of the vessel wall in postmenopausal ladies has been seen in medical trials.59 If much less vitamin K2 is current within the weight loss program, then cardiovascular issues might come up.
Normally, the everyday Western weight loss program accommodates inadequate quantities of vitamin K2 to activate MGP adequately, which implies that roughly 30% of the proteins that may be activated by vitamin K2 stay inactive. The proportion of K deficiency will increase with age.12
Vitamin K, notably as vitamin K2, is almost nonexistent in junk meals, with little being consumed even in a wholesome Western weight loss program. Though vitamin K1 is current in inexperienced leafy greens, solely 10% of the entire quantity is absorbed from that supply within the diets of individuals in industrialized international locations.60–61 The one exception appears to be the Japanese weight loss program, notably for the portion of the inhabitants consuming excessive portions of meals wealthy in vitamin K2, reminiscent of natto.
It seems that suboptimal ranges of vitamin K2 within the physique might drawback the activation of particular proteins which can be depending on vitamin K2.35 If these proteins can’t carry out their perform in protecting calcium within the bones and stopping calcium deposits in comfortable tissues (eg, in arterial partitions) throughout conditions of elevated calcium consumption, then normal well being, and—particularly—cardiovascular well being, might undergo because of an inefficient and misdirected use of calcium within the physique.