Vitamin K2 contributes to bone and cardiovascular health. Therefore, two vitamin K2 homologues, menaquinone-4 (MK-4) and menaquinone-7 (MK-7), have been used as nutrients by the food industry and as nutritional supplements to support bone and cardiovascular health. However, little is known about the bioavailability of nutritional MK-4. To investigate MK-4 and MK-7 bioavailability, nutritional doses were administered to healthy Japanese women.
Findings
Single dose administration of MK-4 (420 ?g; 945 nmol) or MK-7 (420 ?g; 647 nmol) was given in the morning together with standardized breakfast. MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point. Consecutive administration of MK-4 (60 ?g; 135 nmol) or MK-7 (60 ?g; 92 nmol) for 7 days demonstrated that MK-4 supplementation did not increase serum MK-4 levels. However, consecutive administration of MK-7 increased serum MK-7 levels significantly in all subjects.
Conclusions
We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues.
Keywords: Vitamin K2, Menaquinone-4, Menaquinone-7, Bioavailability, Absorption
VITAMIN K ACTS AS A COFACTOR FOR THE ENDOPLASMIC ENZYME ?- GLUTAMYLCARBOXYLASE DURING THE POST-TRANSLATIONAL CONVERSION OF GLUTAMIC ACID RESIDUES OF SPECIFIC PROTEINS TO ?-CARBOXYGLUTAMIC ACID (GLA) TO FORM GLA-CONTAINING PROTEINS. A NUMBER OF BLOOD COAGULATION FACTORS INCLUDING COAGULATION FACTORS II (PROTHROMBIN), VII, IX, AND X ARE WELL-KNOWN EXAMPLES OF GLA-CONTAINING PROTEINS, WHICH ARE SYNTHESIZED IN THE LIVER. OSTEOCALCIN, A BONE-SPECIFIC PROTEIN SYNTHESIZED BY OSTEOBLASTS, AND MATRIX GLA PROTEIN SYNTHESIZED IN BLOOD VESSEL AND BONE ARE GLA-CONTAINING PROTEINS SYNTHESIZED AT EXTRA-HEPATIC SITES.
THERE ARE TWO NATURALLY OCCURRING FORMS OF VITAMIN K: VITAMIN K1 (PHYLLOQUINONE) DERIVED FROM GREEN PLANTS AND VITAMIN K2 (MENAQUINONES, MK-N), WHICH IS A SERIES OF VITAMERS WITH MULTI-ISOPRENE UNITS AT POSITION 3 OF THE COMMON 2-METHYL-1,4-NAPHTHOQUINONE RING STRUCTURE.
IN FOOD, VITAMIN K1 IS BOUND TO THE CHLOROPLAST MEMBRANE OF LEAFY GREEN VEGETABLES. MK-4 IS FOUND IN ANIMAL PRODUCTS SUCH AS EGGS, MEAT, AND LIVER. MK-4 IS DERIVED FROM THE CONVERSION OF MENADIONE (SYNTHETIC ANALOG OF VITAMIN K ONLY CONSISTING OF THE 2-METHYL-1,4-NAPHTHOQUINONE RING STRUCTURE), WHICH IS GIVEN TO THE ANIMALS. LONG CHAIN MENAQUINONES (I.E. MK-7, MK-8, AND MK-9) ARE FOUND IN FERMENTED FOODS SUCH AS CHEESE, CURD, AND SAUERKRAUT. THE JAPANESE FERMENTED FOOD “NATTO” CONTAINS MK-7 AT AN EXCEPTIONALLY HIGH CONCENTRATION.
THE EFFECTS OF LONG CHAIN MK-N SUCH AS MK-7 ON NORMAL BLOOD COAGULATION IS GREATER AND LONGER LASTING THAN VITAMIN K1 AND MK-4. THE EFFECT OF NATTO DERIVED MK-7 WAS ATTRIBUTED TO ITS VERY LONG HALF-LIFE IN SERUM, PROVIDING A BETTER CARBOXYLATION-GRADE OF OSTEOCALCIN COMPARED TO VITAMIN K1.
RECENT STUDIES REVEALED THAT VITAMIN K2 CONTRIBUTES TO BOTH BONE AND CARDIOVASCULAR HEALTH. BOTH MK-4 AND MK-7 HAVE BEEN USED AS NUTRITIONAL INGREDIENTS. IT HAS BEEN SHOWN THAT ALL VITAMIN K HOMOLOGUES CAN BE CONVERTED TO MK-4 IN VIVO. MK-4 IS THOUGHT TO HAVE SPECIFIC FUNCTIONS OTHER THAN ?-CARBOXYLATION OF VITAMIN K-DEPENDENT PROTEINS. HOWEVER, ONLY LITTLE IS KNOWN ABOUT THE BIOAVAILABILITY OF THE NUTRITIONAL DOSE OF MK-4.
THERE ARE TWO MAIN FORMS OF VITAMIN K:
· VITAMIN K1 (PHYLLOQUINONE): FOUND IN PLANT FOODS LIKE LEAFY GREENS.
· VITAMIN K2 (MENAQUINONE): FOUND IN ANIMAL FOODS AND FERMENTED FOODS (2TRUSTED SOURCE ).
VITAMIN K2 CAN BE FURTHER DIVIDED INTO SEVERAL DIFFERENT SUBTYPES, THE MOST IMPORTANT ONES BEING MK-4 AND MK-7.
SUMMARYVITAMIN K WAS INITIALLY DISCOVERED AS A NUTRIENT INVOLVED IN BLOOD CLOTTING. THERE ARE TWO FORMS: K1 (FOUND IN PLANT FOODS) AND K2 (FOUND IN ANIMAL AND FERMENTED FOODS).
HOW DO VITAMINS K1 AND K2 WORK?
VITAMIN K ACTIVATES PROTEINS THAT PLAY A ROLE IN BLOOD CLOTTING, CALCIUM METABOLISM AND HEART HEALTH.
ONE OF ITS MOST IMPORTANT FUNCTIONS IS TO REGULATE CALCIUM DEPOSITION. IN OTHER WORDS, IT PROMOTES THE CALCIFICATION OF BONES AND PREVENTS THE CALCIFICATION OF BLOOD VESSELS AND KIDNEYS (3TRUSTED SOURCE , 4TRUSTED SOURCE ).
SOME SCIENTISTS HAVE SUGGESTED THAT THE ROLES OF VITAMINS K1 AND K2 ARE QUITE DIFFERENT, AND MANY FEEL THAT THEY SHOULD BE CLASSIFIED AS SEPARATE NUTRIENTS ALTOGETHER.
THIS IDEA IS SUPPORTED BY AN ANIMAL STUDY SHOWING THAT VITAMIN K2 (MK-4) REDUCED BLOOD VESSEL CALCIFICATION WHEREAS VITAMIN K1 DID NOT (5TRUSTED SOURCE ).
CONTROLLED STUDIES IN PEOPLE ALSO OBSERVE THAT VITAMIN K2 SUPPLEMENTS GENERALLY IMPROVE BONE AND HEART HEALTH, WHILE VITAMIN K1 HAS NO SIGNIFICANT BENEFITS (6TRUSTED SOURCE ).
HOWEVER, MORE HUMAN STUDIES ARE NEEDED BEFORE THE FUNCTIONAL DIFFERENCES BETWEEN VITAMINS K1 AND K2 CAN BE FULLY UNDERSTOOD.
SUMMARYVITAMIN K PLAYS AN ESSENTIAL ROLE IN BLOOD CLOTTING, HEART HEALTH AND BONE HEALTH.
MAY HELP PREVENT HEART DISEASE
CALCIUM BUILD-UP IN THE ARTERIES AROUND YOUR HEART IS A HUGE RISK FACTOR FOR HEART DISEASE (7TRUSTED SOURCE , 8TRUSTED SOURCE , 9TRUSTED SOURCE ).
THEREFORE, ANYTHING THAT CAN REDUCE THIS CALCIUM ACCUMULATION MAY HELP PREVENT HEART DISEASE.
VITAMIN K IS BELIEVED TO HELP BY PREVENTING CALCIUM FROM BEING DEPOSITED IN YOUR ARTERIES (10TRUSTED SOURCE ).
IN ONE STUDY SPANNING 7-10 YEARS, PEOPLE WITH THE HIGHEST INTAKE OF VITAMIN K2 WERE 52% LESS LIKELY TO DEVELOP ARTERY CALCIFICATION AND HAD A 57% LOWER RISK OF DYING FROM HEART DISEASE (11TRUSTED SOURCE ).
ANOTHER STUDY IN 16,057 WOMEN FOUND THAT PARTICIPANTS WITH THE HIGHEST INTAKE OF VITAMIN K2 HAD A MUCH LOWER RISK OF HEART DISEASE - FOR EVERY 10 MCG OF K2 THEY CONSUMED PER DAY, HEART DISEASE RISK WAS REDUCED BY 9% (12TRUSTED SOURCE ).
ON THE OTHER HAND, VITAMIN K1 HAD NO INFLUENCE IN EITHER OF THOSE STUDIES.
HOWEVER, KEEP IN MIND THAT THE ABOVE STUDIES ARE OBSERVATIONAL STUDIES, WHICH CANNOT PROVE CAUSE AND EFFECT.
THE FEW CONTROLLED STUDIES THAT HAVE BEEN CONDUCTED USED VITAMIN K1, WHICH SEEMS TO BE INEFFECTIVE (13TRUSTED SOURCE ).
LONG-TERM CONTROLLED TRIALS ON VITAMIN K2 AND HEART DISEASE ARE NEEDED.
STILL, THERE IS A HIGHLY PLAUSIBLE BIOLOGICAL MECHANISM FOR ITS EFFECTIVENESS AND STRONG POSITIVE CORRELATIONS WITH HEART HEALTH IN OBSERVATIONAL STUDIES.
SUMMARYA HIGHER INTAKE OF VITAMIN K2 IS STRONGLY ASSOCIATED WITH A REDUCED RISK OF HEART DISEASE. VITAMIN K1 APPEARS TO BE LESS USEFUL OR INEFFECTIVE.
MAY HELP IMPROVE BONE HEALTH AND LOWER YOUR RISK OF OSTEOPOROSIS
OSTEOPOROSIS - WHICH TRANSLATES TO “POROUS BONES” - IS A COMMON PROBLEM IN WESTERN COUNTRIES.
IT PREVAILS ESPECIALLY AMONG OLDER WOMEN AND STRONGLY RAISES THE RISK OF FRACTURES.
AS MENTIONED ABOVE, VITAMIN K2 PLAYS A CENTRAL ROLE IN THE METABOLISM OF CALCIUM - THE MAIN MINERAL FOUND IN YOUR BONES AND TEETH.
VITAMIN K2 ACTIVATES THE CALCIUM-BINDING ACTIONS OF TWO PROTEINS - MATRIX GLA PROTEIN AND OSTEOCALCIN, WHICH HELP TO BUILD AND MAINTAIN BONES (14TRUSTED SOURCE , 15TRUSTED SOURCE ).
INTERESTINGLY, THERE IS ALSO SUBSTANTIAL EVIDENCE FROM CONTROLLED STUDIES THAT K2 MAY PROVIDE MAJOR BENEFITS FOR BONE HEALTH .
A 3-YEAR STUDY IN 244 POSTMENOPAUSAL WOMEN FOUND THAT THOSE TAKING VITAMIN K2 SUPPLEMENTS HAD MUCH SLOWER DECREASES IN AGE-RELATED BONE MINERAL DENSITY (16 ).
LONG-TERM STUDIES IN JAPANESE WOMEN HAVE OBSERVED SIMILAR BENEFITS - THOUGH VERY HIGH DOSES WERE USED IN THESE CASES. OUT OF 13 STUDIES, ONLY ONE FAILED TO SHOW SIGNIFICANT IMPROVEMENT.
SEVEN OF THESE TRIALS, WHICH TOOK FRACTURES INTO CONSIDERATION, FOUND THAT VITAMIN K2 REDUCED SPINAL FRACTURES BY 60%, HIP FRACTURES BY 77% AND ALL NON-SPINAL FRACTURES BY 81% (17TRUSTED SOURCE ).
IN LINE WITH THESE FINDINGS, VITAMIN K SUPPLEMENTS ARE OFFICIALLY RECOMMENDED FOR PREVENTING AND TREATING OSTEOPOROSIS IN JAPAN (18TRUSTED SOURCE ).
HOWEVER, SOME RESEARCHERS ARE NOT CONVINCED - TWO LARGE REVIEW STUDIES CONCLUDED THAT EVIDENCE TO RECOMMEND VITAMIN K SUPPLEMENTS FOR THIS PURPOSE IS INSUFFICIENT (19 , 20 ).
SUMMARYVITAMIN K2 PLAYS AN ESSENTIAL ROLE IN BONE METABOLISM, AND STUDIES SUGGEST THAT IT CAN HELP PREVENT OSTEOPOROSIS AND FRACTURES.
MAY IMPROVE DENTAL HEALTH
RESEARCHERS HAVE SPECULATED THAT VITAMIN K2 MAY AFFECT DENTAL HEALTH.
HOWEVER, NO HUMAN STUDIES HAVE TESTED THIS DIRECTLY.
BASED ON ANIMAL STUDIES AND THE ROLE VITAMIN K2 PLAYS IN BONE METABOLISM, IT'S REASONABLE TO ASSUME THAT THIS NUTRIENT IMPACTS DENTAL HEALTH AS WELL.
ONE OF THE MAIN REGULATING PROTEINS IN DENTAL HEALTH IS OSTEOCALCIN - THE SAME PROTEIN THAT IS CRITICAL TO BONE METABOLISM AND IS ACTIVATED BY VITAMIN K2 (21TRUSTED SOURCE ).
OSTEOCALCIN TRIGGERS A MECHANISM THAT STIMULATES THE GROWTH OF NEW DENTIN, WHICH IS THE CALCIFIED TISSUE UNDERNEATH THE ENAMEL OF YOUR TEETH (22TRUSTED SOURCE , 23TRUSTED SOURCE ).
VITAMINS A AND D ARE ALSO BELIEVED TO PLAY AN IMPORTANT ROLE HERE, WORKING SYNERGISTICALLY WITH VITAMIN K2 (24TRUSTED SOURCE ).
SUMMARYIT'S BELIEVED THAT VITAMIN K2 MAY PLAY A CRITICAL ROLE IN DENTAL HEALTH, BUT HUMAN STUDIES SHOWING THE BENEFITS OF SUPPLEMENTS IN THIS AREA ARE CURRENTLY LACKING.
MAY HELP FIGHT CANCER
CANCER IS A COMMON CAUSE OF DEATH IN WESTERN COUNTRIES.
EVEN THOUGH MODERN MEDICINE HAS FOUND MANY WAYS TO TREAT IT, NEW CANCER CASES ARE STILL ON THE RISE.
THEREFORE, FINDING EFFECTIVE PREVENTION STRATEGIES IS OF UTMOST IMPORTANCE.
INTERESTINGLY, SEVERAL STUDIES HAVE BEEN DONE ON VITAMIN K2 AND CERTAIN TYPES OF CANCER.
TWO CLINICAL STUDIES SUGGEST THAT VITAMIN K2 REDUCES RECURRENCE OF LIVER CANCER AND INCREASES SURVIVAL TIMES (25TRUSTED SOURCE , 26TRUSTED SOURCE ).
ADDITIONALLY, AN OBSERVATIONAL STUDY IN 11,000 MEN FOUND THAT A HIGH VITAMIN K2 INTAKE WAS LINKED TO A 63% LOWER RISK OF ADVANCED PROSTATE CANCER, WHEREAS VITAMIN K1 HAD NO EFFECT (27TRUSTED SOURCE ).
HOWEVER, MORE HIGH-QUALITY STUDIES ARE NEEDED BEFORE ANY STRONG CLAIMS CAN BE MADE.
SUMMARYVITAMIN K2 HAS BEEN FOUND TO IMPROVE SURVIVAL IN PATIENTS WITH LIVER CANCER. MEN WHO CONSUME THE HIGHEST AMOUNTS OF K2 APPEAR TO HAVE A LOWER RISK OF ADVANCED PROSTATE CANCER.
HOW TO GET THE VITAMIN K2 YOU NEED
SEVERAL WIDELY AVAILABLE FOODS ARE RICH SOURCES OF VITAMIN K1, BUT VITAMIN K2 LESS COMMON.
YOUR BODY CAN PARTLY CONVERT VITAMIN K1 TO K2. THIS IS USEFUL, AS THE AMOUNT OF VITAMIN K1 IN A TYPICAL DIET IS TEN TIMES THAT OF VITAMIN K2.
HOWEVER, CURRENT EVIDENCE INDICATES THAT THE CONVERSION PROCESS IS INEFFICIENT. AS A RESULT, YOU MAY BENEFIT MUCH MORE FROM EATING VITAMIN K2 DIRECTLY.
VITAMIN K2 IS ALSO PRODUCED BY GUT BACTERIA IN YOUR LARGE INTESTINE. SOME EVIDENCE SUGGESTS THAT BROAD-SPECTRUM ANTIBIOTICS CONTRIBUTE TO K2 DEFICIENCY (28TRUSTED SOURCE , 29TRUSTED SOURCE ).
STILL, THE AVERAGE INTAKE OF THIS IMPORTANT NUTRIENT IS INCREDIBLY LOW IN THE MODERN DIET.
VITAMIN K2 IS MAINLY FOUND IN CERTAIN ANIMAL AND FERMENTED FOODS, WHICH MOST PEOPLE DON'T EAT MUCH OF.
RICH ANIMAL SOURCES INCLUDE HIGH-FAT DAIRY PRODUCTS FROM GRASS-FED COWS, EGG YOLKS, AS WELL AS LIVER AND OTHER ORGAN MEATS (30TRUSTED SOURCE ).
VITAMIN K IS FAT-SOLUBLE, WHICH MEANS LOW-FAT AND LEAN ANIMAL PRODUCTS DON'T CONTAIN MUCH OF IT.
ANIMAL FOODS CONTAIN THE MK-4 SUBTYPE, WHILE FERMENTED FOODS LIKE SAUERKRAUT , NATTO AND MISO PACK MORE OF THE LONGER SUBTYPES, MK-5 TO MK-14 (31TRUSTED SOURCE ).
IF THESE FOODS ARE INACCESSIBLE TO YOU, TAKING SUPPLEMENTS IS A VALID ALTERNATIVE. AN EXCELLENT SELECTION OF K2 SUPPLEMENTS CAN BE FOUND ON AMAZON .
THE BENEFITS OF SUPPLEMENTING WITH K2 MAY BE ENHANCED EVEN FURTHER WHEN COMBINED WITH A VITAMIN D SUPPLEMENT, AS THESE TWO VITAMINS HAVE SYNERGISTIC EFFECTS (32TRUSTED SOURCE ).
THOUGH THIS NEEDS TO BE STUDIED IN MORE DETAIL, CURRENT RESEARCH ON VITAMIN K2 AND HEALTH IS PROMISING.
IN FACT, IT MAY HAVE LIFE-SAVING IMPLICATIONS FOR MANY PEOPLE.
SUMMARYYOU CAN GET VITAMIN K2 FROM HIGH-FAT DAIRY PRODUCTS, EGG YOLK, LIVER AND FERMENTED FOODS, SUCH AS SAUERKRAUT.
THE BOTTOM LINE
VITAMIN K IS A GROUP OF NUTRIENTS THAT ARE DIVIDED INTO VITAMINS K1 AND K2.
VITAMIN K1 IS INVOLVED IN BLOOD COAGULATION AND VITAMIN K2 BENEFITS BONE AND HEART HEALTH. HOWEVER, MORE STUDIES ON THE ROLES OF VITAMIN K SUBTYPES ARE NEEDED.
SOME SCIENTISTS ARE CONVINCED THAT VITAMIN K2 SUPPLEMENTS SHOULD BE REGULARLY USED BY PEOPLE AT RISK OF HEART DISEASE. OTHERS POINT OUT THAT MORE STUDIES ARE NEEDED BEFORE ANY SOLID RECOMMENDATIONS CAN BE MADE.
HOWEVER, IT'S CLEAR THAT VITAMIN K PLAYS AN ESSENTIAL ROLE IN BODY FUNCTION.
TO MAINTAIN GOOD HEALTH, MAKE SURE TO GET ADEQUATE AMOUNTS OF VITAMINS K1 AND K2 THROUGH YOUR DIET .
VITAMIN K IS A NECESSARY NUTRIENT. IT HELPS BUILD AND MAINTAIN HEALTHY BONES. THE VITAMIN'S BIGGEST CLAIM TO FAME IS ITS ROLE IN HELPING BLOOD CLOTTING, KNOWN AS “COAGULATION.” IN FACT, THE “K” COMES FROM THE GERMAN WORD FOR BLOOD CLOTTING, KOAGULATION.
LEAFY GREEN VEGETABLES CONTAIN THE HIGHEST AMOUNTS OF VITAMIN K, BUT THERE ARE MANY OTHER GOOD SOURCES. ON AVERAGE, ADULT WOMEN NEED 90 MICROGRAMS (MCG) OF VITAMIN K PER DAY AND ADULT MEN NEED 120 MCG.
NOTE: IF YOU TAKE BLOOD THINNERS SUCH AS WARFARIN (COUMADIN), YOUR INTAKE OF THIS NUTRIENT MAY AFFECT THE DOSAGE OF YOUR MEDICATION. CHECK WITH YOUR DOCTOR AND SPEAK WITH A DIETITIAN TO UNDERSTAND THE PROPER DAILY VALUE OF VITAMIN K FOR YOU.
HERE'S THE FULL LIST OF FOODS PACKED WITH VITAMIN K:
· KALE
· COLLARD GREENS
· SPINACH
· TURNIP GREENS
· BRUSSELS SPROUTS
· BROCCOLI
· ASPARAGUS
· LETTUCE
· SAUERKRAUT
· SOYBEANS
· EDAMAME
· PICKLES
· PUMPKIN
· PINE NUTS
· BLUEBERRIES