Nutrition Ok, specifically nutrition K2, represents a vital phase of the nutrition marketplace. In truth, the worldwide nutrition K2 marketplace dimension was once estimated at $421.1 million in 2023 and is projected to develop at a CAGR of 10.8 % from 2024 to 2030.1 For sure, nutrition K2 as menaquinone-7 (MK-7) has been known for its position in bone well being and cardiovascular well being, and to a lesser extent MK-4 has additionally been known for its position in bone well being. On the other hand, MK-7 has different advantages past bone and cardiovascular well being, and nutrition K1 additionally has significant advantages to supply referring to cardiovascular well being. This newsletter critiques the variations between and the packages for nutrition K1 and K2 as MK-7 and MK-4. Let’s get started with a bit of background.
Background
Came upon in 1929, nutrition Ok was once firstly recognized for its position as a blood-clotting (coagulation) cofactor.2 Within the Seventies, nutrition Ok-dependent proteins (VKDPs) had been came upon, which resulted in a extra complete figuring out of nutrition Ok’s position with recognize to bone and cardiovascular well being.3
Moreover, two kinds of this fat-soluble nutrition exist: nutrition K1 and K2. Vegetation synthesize phylloquinone (aka, nutrition K1), and intestinal microbiota and fermentation of a few meals synthesize a variety of K2 paperwork jointly known as menaquinones (e.g., MK-4 and MK-7).4 The menaquinones have a bunch designation in line with the collection of repeating 5-carbon gadgets in its facet chain. As an example, if there are seven repeating 5-carbon gadgets, the designation can be MK-7.5
The Cardiovascular Advantages of Nutrition K2 as MK-7
In 2016, I wrote an editorial for Nutrition Retailer6 discussing analysis which my co-author and I in the past revealed in a systematic magazine.7 The analysis confirmed that the main means by which nutrition Ok acts to advertise cardiovascular well being is via inhibiting calcification within the arteries, which might another way result in atherosclerosis. In particular, one of the most 17 VKDPs were recognized to this point act as calcification inhibitors. Those come with osteocalcin (OC), sometimes called bone Gla protein (synthesized via osteoblasts), and matrix Gla protein (MGP, present in cartilage, bone and comfortable tissue, together with blood vessel partitions). Those proteins are native inhibitors of calcification within the tissues by which they exert their serve as. Right here’s the way it works.
Carboxylation is a procedure by which a carboxylic acid team is reacted with a substance reminiscent of a protein—and carboxylation is important for the formation of essential VKDPs that experience a good have an effect on on arterial stiffness and bone power. Since 10 to 40 % of VKDPs stay undercarboxylated, analysis was once undertaking appearing that the MK-7 type of nutrition K2 was once efficient in expanding the carboxylation of VKDPs.8
Within the analysis, we additionally mentioned the population-based Rotterdam learn about,9 which integrated 4,807 topics, and which equipped the primary proof for a hyperlink between nutrition Ok and vascular well being. The consequences confirmed the relative possibility of coronary middle illness mortality and calcification of the aorta (an artery within the middle) was once decreased in the ones with top intakes of nutrition K2, in comparison to the ones with a decrease consumption. Every other study10 with 564 post-menopausal additionally confirmed a reduced possibility of coronary calcification with upper intakes of nutrition K2.
Much more significant was once a 3 12 months, double-blind, placebo-controlled trial11 by which 248 postmenopausal girls won 180 mcg/day of MK-7 or a placebo for 3 years to inspect the impact on arterial stiffness (i.e., led to via calcification). The consequences had been that supplementation with MK-7 considerably reduced measures of aortic stiffness and stepped forward undercarboxylated VKDPs via 50 %.
The Bone Well being Advantages of Nutrition K2 as MK-7 & MK-4
In any other 3 12 months, double-blind, placebo-controlled trial,12 244 wholesome postmenopausal girls additionally won 180 mcg/day of MK-7 or a placebo for 3 years, this time to inspect signs of bone well being. The consequences had been that MK-7 reduced age-related decline in bone mineral content material and bone mineral density, and favorably affected bone power and reduced loss in vertebral top. Additionally, postmenopausal girls with osteopenia (bone softening) additionally demonstrated a preservation of bone construction with 375 mcg/day MK-7.13
It is very important needless to say MK-4 additionally has vital analysis to beef up its position in bone well being. In truth, it might be argued that it has extra analysis for this goal than MK-7. It must even be famous that the doses used of MK-4 are upper (despite the fact that protected) than MK-7. As an example, in a single randomized, double-blind, placebo-controlled trial,14 1.5 mg/day of MK-4 for 6-One year in postmenopausal girls stepped forward carboxylation of VKDPs and helped care for bone mineral density. An identical effects had been noticed in any other study15 with 600 mcg/MK-4. When 5 mg/day MK-4 was once used there was once a vital development in carboxylation of VKDPs, and not using a further receive advantages in comparison to 45 m/day MK-4.16
That is specifically significant since there are seven randomized managed trials17-23 demonstrating that 45 mg/day of MK-4 stepped forward carboxylation of VKDPs and bone mineral density and decreased the prevalence of fracture in osteoporosis sufferers. Likewise, there are seven human studies24-30 demonstrating that 45 mg/day of MK-4 stepped forward bone high quality in quite a lot of inhabitants sorts.
Further Advantages for MK-7
Along with its cardiovascular and bone well being advantages, MK-7 has additionally demonstrated advantages for muscle cramps, polycystic ovary syndrome, rheumatoid arthritis and glucose/insulin modulation. • Muscle cramps: A randomized, placebo-controlled scientific trial31 discovered that 360 mcg/day MK-7 decreased the frequency, length and severity of muscle cramps in 39 hemodialysis sufferers.
• Polycystic ovary syndrome: A randomized, double-blind, placebo-controlled scientific trial32 discovered that 90 mcg/day MK-7 considerably reduced serum fasting insulin, insulin resistance, serum triglyceride, dihydrotestosterone ranges, unfastened androgen index, waist circumference and frame fats mass, in addition to considerably expanding skeletal muscle and intercourse hormone binding globulin in polycystic ovary syndrome sufferers. It additionally stepped forward despair standing.33
• Rheumatoid arthritis: A randomized, cross-sectional, scientific study34 discovered that 100 mcg/day MK-7 added to standard healing routine reduced erythrocyte sedimentation fee (which can be higher in RA), illness task ranking assessing 28 joints, C-reactive protein (CRP, an irritation marker), and matrix metalloproteinase (a tissue injury marker) in rheumatoid arthritis sufferers.
• Glucose/insulin modulation: A double-blinded, placebo-controlled, randomized trial35 discovered that 360 mcg/day MK-7 decreased fasting plasma glucose, glycated hemoglobin in sufferers with type-2 diabetes. Cardiovascular Advantages for Nutrition K1
As said initially of this text, nutrition K1 additionally has significant advantages to supply referring to cardiovascular well being—particularly in regards to arterial calcification:
• High blood pressure medicine customers: A study36 of 296 individuals with excessive coronary artery calcium (CAC) development and 561 randomly decided on individuals with out excessive CAC development discovered that high blood pressure medicine customers with low serum nutrition K1 had been much more likely to have excessive CAC development than had been medicine customers with out excessive CAC development.
• Preexisting coronary artery calcification: A double-blind trial of 388 wholesome males and postmenopausal girls with preexisting coronary artery calcification discovered that the ones receiving a multivitamin with 500 mcg/day nutrition K1 had 6 % much less development of CAC than did those that won the multivitamin on my own.37
• Aortic and coronary artery calcification: A double-blind, randomized, placebo-controlled trial38 discovered that 10 mg/day nutrition K1 learn about helped save you the improvement of newly calcifying lesions throughout the aorta and the coronary arteries in diabetic sufferers.
• Decrease possibility of cardiovascular headaches: A inhabitants study39 discovered that middle-aged topics and not using a historical past of atherosclerotic heart problems who had the easiest consumption of nutritional nutrition K1 consumption (162–800 mcg) had a 21 % decrease possibility of CVD-related hospitalization and headaches over 17-22 years when in comparison to the ones with the bottom consumption (73–101 mcg).
To be had Types of Nutrition Ok & Complementary/Synergistic Issues
Nutrition K2 as MK-7 is to be had in artificial shape, in addition to in each natto (soy) and chickpea-derived paperwork for individuals who desire a soy-free possibility (e.g., K2Go via Nutraland USA). Nutrition K2 as MK-4 is most effective to be had in artificial shape. Nutrition K1 is to be had in artificial shape and as a herbal alfalfa-derived shape (from Nutraland USA).
Believe that there are complementary benefits to concurrent use of the quite a lot of kinds of nutrition Ok. As an example, If the function is to beef up cardiovascular well being, a mix of nutrition K1 and nutrition K2 as MK-7 has benefits. If the function is to beef up bone well being, then a mix of nutrition K2 as each MK-7 and MK-4 is a great selection.
As well as, there’s a synergistic dating between nutrition Ok and nutrition D. In a study40 carried out with persistent kidney illness sufferers, artery thickness of the carotid intima-media was once considerably decrease in the ones receiving nutrition K2 as MK-7 and nutrition D3 in comparison to D3 on my own. A 2-year randomized study41 discovered that the mixed management of nutrition D3 and nutrition K2 (as MK-4), was once efficient in expanding the bone mineral density in postmenopausal girls with osteoporosis. Every other study42 in girls with estrogen deficiency discovered that MK-4 mixed with nutrition D3 in part avoided bone loss led to via estrogen deficiency.
Conclusion
3 commercially viable kinds of nutrition Ok come with K1, K2 as MK-7 and K2 as MK-4. Each and every shape has its personal distinct benefits. Analysis has demonstrated the cardiovascular advantages of K1 and K2 as MK-7, whilst different analysis has demonstrated the advantages of MK-7 and MK-4 for bone well being. Moreover, analysis has demonstrated that MK-7 additionally has advantages for muscle cramps, polycystic ovary syndrome, rheumatoid arthritis and glucose/insulin modulation. Those quite a lot of kinds of nutrition Ok is also used in combination and/or together with nutrition D3 to maximise complementary/synergistic results.VR
References
1 Nutrition K2 Marketplace Measurement & Tendencies. Grand View Analysis. Retrieved July 23, 2024, from https://www.grandviewresearch.com/industry-analysis/vitamin-k2-market-report#:~:textual content=Vitaminp.c20K2p.c20Marketp.c20Sizep.c20p.c26p.c20Trends,10.8p.c25p.c20fromp.c202024p.c20top.c202030.
2 Meals and Diet Board, Institute of Drugs: Nutrition Ok, Bankruptcy 5, in Nutritional Reference Intakes for Nutrition A, Nutrition Ok, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Nationwide Academy Press, Washington, District of Columbia, USA (2001).
3 Ferland, G. “The invention of nutrition Ok and its scientific packages,” Ann. Nutr. Metab., 61(3), 213-218 (2012).
4 Shearer, M.J. “Nutrition Ok”, Lancet, 345(8944), 229-234 (1995).
5 Sales space, S.L. “Nutrition Ok: meals composition and nutritional intakes”, Meals Nutr. Res., 56, 5505 (2012).
6 Bruno G. New Analysis on Nutrition K2. Nutrition Store. Might 2016: 38-39.
7 Maresz Ok, Bruno EJ. Nutrition K2: An Very important Protector for Cardiovascular Well being. Agro Meals Ind Hello Tech 2015;26(5):21-24.
8 Bruno G. New Analysis on Nutrition K2. Nutrition Store. Might 2016: 38-39.
9 Geleijnse, J.M., Vermeer, C., Grobbee, D.E., et al. “Nutritional consumption of menaquinone is related to a discounted possibility of coronary middle illness: The Rotterdam Find out about,” J. Nutr., 134, 3100-3105 (2004).
10 Beulens JW, Bots ML, Atsma F, Bartelink ML, Prokop M, Geleijnse JM, Witteman JC, Grobbee DE, van der Schouw YT. “Top nutritional menaquinone consumption is related to decreased coronary calcification,” Atherosclerosis 2009;203(2):489-493.
11 Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in wholesome postmenopausal girls. A double-blind randomised scientific trial. Thromb Haemost. 2015;113(5):1135-1144.
12 Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. 3-year low-dose menaquinone-7 supplementation is helping lower bone loss in wholesome postmenopausal girls. Osteoporos Int. 2013;24(9):2499-2507.
13 Rønn SH, Harsløf T, Pedersen SB, Langdahl BL. Nutrition K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture on the tibia in postmenopausal girls. Eur J Endocrinol. 2016 Dec;175(6):541-549.
14 Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita Ok, Ishimi Y. Low-dose nutrition K2 (MK-4) supplementation for One year improves bone metabolism and stops forearm bone loss in postmenopausal Eastern girls. J Bone Miner Metab. 2014 Mar;32(2):142-50.
15 Nakamura E, Aoki M, Watanabe F, Kamimura A. Low-dose menaquinone-4 improves γ-carboxylation of osteocalcin in younger men: a non-placebo-controlled dose-response learn about. Nutr J. 2014 Aug 27;13:85.
16 Giri TK, Newton D, Chaudhary O, Deych E, Napoli N, Villareal R, Diemer Ok, Milligan PE, Gage FB. Maximal dose-response of vitamin-K2 (menaquinone-4) on undercarboxylated osteocalcin in girls with osteoporosis. Int J Vitam Nutr Res. 2020 Jan;90(1-2):42-48.
17 Iwamoto J. Nutrition K2 Treatment for Postmenopausal Osteoporosis. Vitamins. 2014; 6(5):1971-1980. 18 Su S, He N, Males P, Track C, Zhai S. The efficacy and protection of menatetrenone within the control of osteoporosis: a scientific evaluation and meta-analysis of randomized managed trials. Osteoporos Int. 2019 Jun;30(6):1175-1186.
19 Jiang Y, Zhang ZL, Zhang ZL, Zhu HM, Wu YY, Cheng Q, Wu FL, Xing XP, Liu JL, Yu W, Meng XW. Menatetrenone as opposed to alfacalcidol within the remedy of Chinese language postmenopausal girls with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, certain drug-controlled scientific trial. Clin Interv Ageing. 2014;9:121-7.
20 Purwosunu Y, Muharram, Rachman IA, Reksoprodjo S, Sekizawa A. Nutrition K2 remedy for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res. 2006 Apr;32(2):230-4.
21 Miki T, Nakatsuka Ok, Naka H, Kitatani Ok, Saito S, Masaki H, Tomiyoshi Y, Morii H, Nishizawa Y. Nutrition Ok(2) (menaquinone 4) reduces serum undercarboxylated osteocalcin degree as early as 2 weeks in aged girls with established osteoporosis. J Bone Miner Metab. 2003;21(3):161-5.
22 Shiraki M, Shiraki Y, Aoki C, Miura M. Nutrition K2 (menatetrenone) successfully prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000 Mar;15(3):515-21. 23 Iwamoto J, Takeda T, Ichimura S. Impact of mixed management of nutrition D3 and nutrition K2 on bone mineral density of the lumbar backbone in postmenopausal girls with osteoporosis. J Orthop Sci. 2000;5(6):546-51.
24 Je SH, Joo NS, Choi BH, Kim KM, Kim BT, Park SB, Cho DY, Kim KN, Lee DJ. Nutrition Ok complement along side nutrition D and calcium decreased serum focus of undercarboxylated osteocalcin whilst expanding bone mineral density in Korean postmenopausal girls over sixty-years-old. J Korean Med Sci. 2011 Aug;26(8):1093-8.
25 Ochiai M, Nakashima A, Takasugi N, Kiribayashi Ok, Kawai T, Usui Ok, Shigemoto Ok, Hamaguchi N, Kohno N, Yorioka N. Nutrition K2 alters bone metabolism markers in hemodialysis sufferers with a low serum parathyroid hormone degree. Nephron Clin Pract. 2011;117(1):c15-9.
26 Knapen MH, Schurgers LJ, Vermeer C. Nutrition K2 supplementation improves hip bone geometry and bone power indices in postmenopausal girls. Osteoporos Int. 2007 Jul;18(7):963-72.
27 Bunyaratavej N, Penkitti P, Kittimanon N, Boonsangsom P, Bonjongsat A, Yunoi S. Efficacy and protection of Menatetrenone-4 postmenopausal Thai girls. J Med Assoc Thai. 2001 Oct;84 Suppl 2:S553-9.
28 Plaza SM, Lamson DW. Nutrition K2 in bone metabolism and osteoporosis. A/tern Med Rev 2005;10:24-35.
29 Knapen MH, Schurgers LJ, Vermeer C. Nutrition K2 supplementation improves hip bone geometry and bone power indices in postmenopausal girls. Osteoporos Int 2007;18:963-972.
30 Somekawa Y, Chigughi M, Harada M, Ishibashi T. Use of nutrition K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 within the prevention of bone loss precipitated via leuprolide. J Clin Endocrinol Metab. 1999 Aug;84(8):2700-4.
31 Xu D, Yang A, Ren R, Shan Z, Li YM, Tan J. Nutrition K2 as a possible healing candidate for the prevention of muscle cramps in hemodialysis sufferers: A potential multicenter, randomized, managed, crossover pilot trial. Diet. 2022 Might;97:111608.
32 Tarkesh F, Namavar Jahromi B, Hejazi N, Tabatabaee H. Really useful well being results of Menaquinone-7 on frame composition, glycemic indices, lipid profile, and endocrine markers in polycystic ovary syndrome sufferers. Meals Sci Nutr. 2020 Sep 4;8(10):5612-5621.
33 Tarkesh F, Namavar Jahromi B, Hejazi N, Hoseini G. Impact of nutrition K2 management on despair standing in sufferers with polycystic ovary syndrome: a randomized scientific trial. BMC Womens Well being. 2022 Jul 26;22(1):315.
34 Abdel-Rahman MS, Alkady EA, Ahmed S. Menaquinone-7 as a singular pharmacological remedy within the remedy of rheumatoid arthritis: A scientific learn about. Eur J Pharmacol. 2015 Aug 15;761:273-8.
35 Rahimi Sakak F, Moslehi N, Niroomand M, Mirmiran P. Glycemic keep watch over development in people with form 2 diabetes with nutrition K2 supplementation: a randomized managed trial. Eur J Nutr. 2021 Aug;60(5):2495-2506.
36 Shea MK, Sales space SL, Miller ME, Burke GL, Chen H, Cushman M, Tracy RP, Kritchevsky SB. Affiliation between circulating nutrition K1 and coronary calcium development in community-dwelling adults: the Multi-Ethnic Find out about of Atherosclerosis. Am J Clin Nutr. 2013 Jul;98(1):197-208.
37 Shea MK, O’Donnell CJ, Hoffmann U, et al. Nutrition Ok supplementation and development of coronary artery calcium in older women and men. Am J Clin Nutr 2009;89:1799-807.
38 Bellinge JW, Francis RJ, Lee SC, Bondonno NP, Sim M, Lewis JR, Watts GF, Schultz CJ. The impact of nutrition K1 on arterial calcification task in topics with diabetes mellitus: a publish hoc evaluation of a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2022 Jan 11;115(1):45-52.
39 Bellinge JW, Dalgaard F, Murray Ok, et al. Nutrition Ok consumption and atherosclerotic heart problems within the Danish Nutrition Most cancers and Well being Find out about. J Am Center Assoc. 2021;10(16):e020551.
40 Kurnatowska I., Grzelak P., Masajtis-Zagajewska A., et al. Impact of nutrition K2 on development of atherosclerosis and vascular calcification in nondialyzed sufferers with persistent kidney illness levels 3-5. Polskie Archiwum Medycyny Wewnętrznej. 2015;125:631–640.
41 Iwamoto J, Takeda T, Ichimura S. Impact of mixed management of nutrition D3 and nutrition K2 on bone mineral density of the lumbar backbone in postmenopausal girls with osteoporosis. J Orthop Sci. 2000;5(6):546-51.
42 Somekawa Y, Chigughi M, Harada M, Ishibashi T. Use of nutrition K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 within the prevention of bone loss precipitated via leuprolide. J Clin Endocrinol Metab. 1999 Aug;84(8):2700-4.
Gene Bruno, MS, MHS, Professor Emeritus of Nutra-ceutical Science, is creator, educator and a nutraceutical scientist with greater than 45 years of revel in instructing herbal product outlets and well being care pros and formulating herbal merchandise for dozens of nutritional complement firms. He has written articles on vitamin, natural medication, nutraceuticals and integrative well being problems for industry, shopper magazines and peer-reviewed publications. Bruno additionally hosts “The Nutrition Professor Podcast” dropped at you via VRM Media. He can also be reached at eugenejbruno@gmail.com.