The effect of vitamin K2 fortified nutritional intervention on muscle condition and clinical outcomes in elderly patients with muscle wasting syndrome

Start Date19 Mar 2024

Sponsor / Collaborator-

ChiCTR2400081953 / RecruitingPhase 1IIT

A single-arm clinical trial study of the efficacy and safety of vitamin k2 in combination with a second-line standard regimen for the treatment of advanced hepatocellular carcinoma

Start Date18 Mar 2024

Sponsor / Collaborator

The Affiliated Hospital of Qingdao University

NCT05942053 / RecruitingPhase 4IIT

Clinical Study Evaluating the Role of Vitamin K2 as Adjuvant Therapy to Angiotensin Converting Enzyme Inhibitor on Blood Pressure, Proteinuria and Bone Metabolism in Patients With Chronic Kidney Disease

This randomized placebo controlled double blind parallel clinical study will be conducted on 44 non-dialysis chronic kidney disease (CKD) patients (Stages 2-3b).Clinical Study Evaluating the Role of Vitamin K2 as Adjuvant Therapy to Angiotensin Converting Enzyme Inhibitor on Blood Pressure, Proteinuria and Bone Metabolism in Patients with Chronic Kidney Disease. Patients will be recruited from, Internal Medicine Department, Nephrology Unit, Alexandria Main University Hospital, Egypt. Patients with albumin-to-creatinine ratio ≥ 30 mg/g, with serum Potassium < 5 mEq/L and newly diagnosed patients with hypertension. The study duration will be 6 months. The patients will be randomized using stratified random block method into two groups.
Group 1: Control group Non-dialysis chronic kidney disease (CKD) patients (Stages 2-3b). Patients will be treated with ramipril 10 mg/day and a placebo match vitamin K2 capsules once per day.The dose of ramipril may be modified according to blood pressure control.
Group 2: Vitamin K2 (menaquinone-7) Non-dialysis chronic kidney disease (CKD) patients (Stages 2-3b).Patients will be treated with ramipril 10 mg/day and vitamin K2 capsules (menaquinone-7) 90 mcg/day. The dose of ramipril may be modified according to blood pressure control.
Participants will be followed-up by weekly telephone calls and monthly direct meetings to assess their adherence for 6 months.

Start Date15 Jul 2023

Sponsor / Collaborator

Tanta University

100 Clinical Results associated with Menatetrenone

100 Translational Medicine associated with Menatetrenone

100 Patents (Medical) associated with Menatetrenone

1,359

Literatures (Medical) associated with Menatetrenone

01 Jan 2024·Free radical biology & medicine

Menaquinone-4 attenuates ferroptosis by upregulating DHODH through activation of SIRT1 after subarachnoid hemorrhage

Article

Author: Zhang, Jiatong ; Ding, Peng-Fei ; Liu, Yang ; Li, Xiao-Jian ; Zhuang, Zong ; Li, Wei ; Peng, Zheng ; Lu, Yue ; Zhu, Qi ; Hang, Chun-Hua ; Sheng, Bin ; Gao, Sen

BACKGROUND:

Menaquinone-4(MK-4), the isoform of vitamin K2 in the brain, exerts neuroprotective effects against a variety of central nervous system disorders. This study aimed to demonstrate the anti-ferroptosis effects of MK-4 in neurons after SAH.

METHODS:

A subarachnoid hemorrhage (SAH) model was prepared by endovascular perforation in mice. In vitro hemoglobin stimulation of primary cortical neurons mimicked SAH. MK-4, Brequinar (BQR, DHODH inhibitor), and Selisistat (SEL, SIRT1 inhibitor) were administered, respectively. Subsequently, WB, immunofluorescence was used to determine protein expression and localization, and transmission electron microscopy was used to observe neuronal mitochondrial structure while other indicators of ferroptosis were measured.

RESULTS:

MK-4 treatment significantly upregulated the protein levels of DHODH; decreased GSH, PTGS2, NOX1, ROS, and restored mitochondrial membrane potential. Meanwhile, MK-4 upregulated the expression of SIRT1 and promoted its entry into the nucleus. BQR or SEL partially abolished the protective effect of MK-4 on, neurologic function, and ferroptosis.

CONCLUSIONS:

Taken together, our results suggest that MK-4 attenuates ferroptosis after SAH by upregulating DHODH through the activation of SIRT1.

01 Jan 2024·World journal of microbiology & biotechnology

Advances in regulating vitamin K2 production through metabolic engineering strategies

Review

Author: Gao, Xu-Li ; Liu, Yan ; Wang, Jian ; Xue, Zheng-Lian ; Wu, Jing ; Huang, Jun-Bao ; Tao, Wei ; Luo, Ya-Ni ; Huang, Xi-Lin ; Zhao, Ming ; Li, Xiang-Fei ; Chen, Yu ; Liu, Kun

Vitamin K₂ (menaquinone, VK₂, MK) is an essential lipid-soluble vitamin that plays critical roles in inhibiting cell ferroptosis, improving blood clotting, and preventing osteoporosis. The increased global demand for VK₂ has inspired interest in novel production strategies. In this review, various novel metabolic regulation strategies, including static and dynamic metabolic regulation, are summarized and discussed. Furthermore, the advantages and disadvantages of both strategies are analyzed in-depth to highlight the bottlenecks facing microbial VK₂ production on an industrial scale. Finally, advanced metabolic engineering biotechnology for future microbial VK₂ production will also be discussed. In summary, this review provides in-depth information and offers an outlook on metabolic engineering strategies for VK₂ production.

01 Jan 2024·Journal of chromatography. A

Analysis of vitamin K1 and major K2 variants in rat/human serum and lipoprotein fractions by a rapid, simple, and sensitive UHPLC-MS/MS method

Article

Author: Carazo, Alejandro ; Pourová, Jana ; Matysová, Ludmila ; Matoušová, Kateřina ; Krčmová, Lenka Kujovská ; Švec, František ; Mladěnka, Přemysl ; Mrštná, Kristýna

Determination of the various forms of vitamin K, which are involved in coagulation and other physiological processes in humans, is challenging and no standardized method is yet available. Therefore, a reliable and practical method was developed to quantify vitamin K levels in serum and additionally in lipoprotein fractions to clarify its distribution. The LC-MS/MS method for the determination of vitamin K₁ and the three main isoforms of vitamin K₂ (MK-4, MK-7, MK-9) was combined with a gradient ultracentrifugation technique to allow the separation of lipoprotein fractions. The chromatographic separation was carried out on a Kinetex™ C18 column using a mobile phase consisting mainly of methanol. The target analytes were detected by electrospray ionization mass spectrometry. The separation of all four substances was achieved after a simple sample preparation technique based on miniaturized liquid-liquid extraction. Our method of only 8.5 min revealed the levels of the major forms of vitamin K in 59 human and 12 rat sera and confirmed our hypothesis that vitamin K is primarily (about 50 %) found in the high-density lipoprotein fraction. The median concentrations of vitamin K₁, MK-4, MK-7, and MK-9 were found to be 1.19, 2.98, 0.43, and < 0.71 nmol/L in human serum and 1.74, 6.75, less than 0.2, and less than 0.5 nmol/L in rat serum, respectively.

News (Medical) associated with Menatetrenone

04 Jan 2024

·www.globenewswire.com

Healthy Extracts Launches First Anti-Aging Formulation, LONGEVITY

LAS VEGAS, Jan. 04, 2024 (GLOBE NEWSWIRE) -- Healthy Extracts Inc. (OTCQB: HYEX), a platform for acquiring, developing, patenting, marketing, and distributing plant-based nutraceuticals that target select high-growth categories within the multibillion-dollar nutraceuticals market, has launched LONGEVITY Anti-Aging™, a new proprietary formulation designed to support skin vitality, arterial flexibility, and cellular and joint health. LONGEVITY Anti-Aging is available to order today on BergametNA.com. In celebration of the launch, for a limited time you can buy two and get one free. You can also subscribe and save 15% on every order. The formulation is a special blend of the most powerful anti-aging warriors that include trans-resveratrol, quercetin, vitamin D, and vitamin K2. These substances are known to boost blood flow and circulation, reduce the deleterious effects of misplaced calcium in the body, and slow the effects of aging with powerful antioxidants. “LONGEVITY Anti-Aging complements our growing heart health product portfolio which supports a holistic approach to anti-aging like healthy skin,” noted Healthy Extracts president, Duke Pitts. “We anticipate this new product, along with the others we’re planning to launch early this year, will continue drive our growth and market expansion, as they leverage our multiple sales and distribution channels and existing customer base.” LONGEVITY Anti-Aging represents a holistic approach to aging, with a proprietary blend focused on providing the nutrition the body needs for optimal health. It is formulated to help sustain vitality, support heart health, ensure robust bone strength, and contribute to a healthier aging process. The formulation is vegan friendly, non-GMO, gluten-free, and produced and tested by certified U.S. facilities. Key substances and benefits: Trans-resveratrol and quercetin are powerful antioxidants that shield cells from aging and oxidative stress for more youthful function.Vitamin D and K2 are vital for proper calcium absorption and distribution, bolstering bone health and reducing osteoporosis risk.For heart health, ingredients like vitamin K2 and trans-resveratrol are key in maintaining cardiovascular wellness, helping to lower the risk of heart ailments.Vitamin D and quercetin also strengthens immune defense, enhancing protection against infection and disease. LONGEVITY Anti-Aging is your ally for overall longevity, blending ingredients renowned for their anti-aging benefits that support a longer, healthier life. LONGEVITY Anti-Aging introduction follows the recent official launch of BERGAMET SLEEP BREATHING SUPPORT™ , a natural supplement designed to support respiratory function for deeper, more restorative sleep. Given the better than anticipated initial sales of this new product, it is on track to become one of the company’s best sellers in 2024. Healthy Extracts’ full line of natural heart health formulations address the fast-growing, multi-billion dollar heart-health supplement market which is projected to grow at 5.9% CAGR to reach $24.8 billion by 2027, according to ResearchAndMarkets. To learn more about Healthy Extracts’ full line of clinically-backed, natural brain and hearth health products, go to bergametna.com or tryubn.com. About Healthy Extracts “Live Life Young Again” Healthy Extracts Inc. is a platform for acquiring, developing, researching, patenting, marketing, and distributing plant-based nutraceuticals. The company’s subsidiaries, BergametNA™ and Ultimate Brain Nutrients™ (UBN), offer nutraceutical natural heart and brain health supplements. This includes the only heart health supplement distributed in North America containing Citrus Bergamot SuperFruit™. This superfruit has the highest known concentration of polyphenols and flavonoids. UBN’s KETONOMICS® proprietary formulations, which have been designed to enhance brain activity, focus, headache and cognitive behavior, provide many sales and intellectual property licensing opportunities. For more information visit: healthyextractsinc.com, bergametna.com or tryubn.com. Forward-Looking Statements and Safe Harbor Notice All statements other than statements of historical facts included in this press release are "forward-looking statements" (as defined in the Private Securities Litigation Reform Act of 1995). Such forward-looking statements include our expectations and those statements that use forward-looking words such as "projected," "expect," "possibility" and "anticipate." The achievement or success of the matters covered by such forward-looking statements involve significant risks, uncertainties and assumptions. Actual results could differ materially from current projections or implied results. Investors should read the risk factors set forth in the Company's Annual Report on Form 10-K filed with the SEC on March 31, 2023, and future periodic reports filed with the SEC. All of the Company's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The Company cautions that statements and assumptions made in this news release constitute forward-looking statements and make no guarantee of future performance. Forward-looking statements are based on estimates and opinions of management at the time statements are made. The information set forth herein speaks only as of the date hereof. The Company and its management undertake no obligation to revise these statements following the date of this news release. Food & Drug Administration Disclosure The product and formulation featured in this release is not for use by or sale to persons under the age of 12. This product should be used only as directed on the label. Consult with a physician before use if you have a serious medical condition or use prescription medications. A doctor’s advice should be sought before using this and any supplemental dietary product. These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease. BergametNA™, Ultimate Brain Nutrients™, UBN™, Citrus Bergamot SuperFruit™ and F4T® are registered trademarks of Healthy Extracts Inc.™ Company ContactDuke Pitts, PresidentHealthy Extracts Inc.Tel (720) 463-1004Email contact Investor ContactRonald Both CMA Investor RelationsTel (949) 432-7566Email contactMedia Contact:Tim RandallCMA Media RelationsTel (949) 432-7572Email Contact A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/200b922a-c04a-45ab-b819-dba1b9750c42

Drug Approval

07 Mar 2023

·www.prnewswire.com

NUTRISHOP® Launches Comprehensive Heart Formula To Support Cardiovascular Health

Heart Formula by Nu-Tek Nutrition® is now available exclusively at Nutrishop HENDERSON, Nev., March 7, 2023 /PRNewswire/ -- Nutrishop, a leading national retail nutrition franchise specializing in dietary and nutritional supplements, vitamins and wellness, is proud to announce the launch of Heart Formula by Nu-Tek Nutrition®. This product's comprehensive approach to cardiovascular health contains some of the most sought-after, heart-healthy ingredients on the market. And, it is now available exclusively through Nutrishop. Continue Reading "We all have only one heart, and it is never too early to start caring for it." Tweet this Let’s face it, wellness is the new fitness. Introducing Heart Formula by Nu-Tek Nutrition. It’s loaded with heart-healthy ingredients like Olive Leaf Extract, Garlic, Organic Beet Root, Turmeric, CoEnzymeQ10, and more. Let’s be as healthy on the inside as we look on the outside. "We all know the importance of a healthy heart, yet some of us may overlook it in pursuit of a fit physique. However, the importance of a healthy heart cannot be overstated," said Nutrishop Founder and CEO Bryon McLendon. "If the interior of our bodies is not functioning properly, nothing on the exterior matters. Nu-Tek Nutrition's Heart Formula is the perfect solution to support our body's most important muscle." Loaded with heart-healthy ingredients such as Olive Leaf Extract, Garlic Extract, Turmeric Root, Hawthorn Berry, Organic Beet Root, CoEnzymeQ10, Grape Seed Extract, and Vitamin K2, Heart Formula is easy to incorporate into any wellness routine. In addition to maintaining a healthy body weight, regularly engaging in cardio exercise (brisk walking counts!), reducing stress and consuming good-for-your-heart foods, such as salmon, vegetables, whole grains, nuts and seeds, simply take three capsules daily or as directed by your healthcare professional. "We all have only one heart, and it is never too early to start caring for it," McLendon said. "With Heart Formula by Nu-Tek Nutrition combined with a healthy lifestyle, you're definitely stepping in the right direction." To learn more or purchase Heart Formula, visit NutrishopUSA.com or stop by any Nutrishop location nationwide. About Nu-Tek Nutrition ®: For nearly 20 years, Nu-Tek Nutrition has dedicated itself to building the foundation of health and wellness with innovative, complex powders like Supergreens, Superfruits, and Daily Detox and supplements like Gut Formula and Super Multi+. The brand's products are backed by over 25 years of formulating experience to offer the best wellness supplementation and help people live their best lives. About NUTRISHOP ® Since 2003, NUTRISHOP® has helped countless individuals live a fit, healthy, happy lifestyle. Nutrishop stores offer customers a low-price guarantee on a wide array of cutting-edge dietary supplements along with exceptional, individualized customer service, easy-to-follow meal plans, body composition assessment tools, and sound nutritional guidance. The Nutrishop business model focuses primarily on franchisee-owned and operated stores that provide consumers with the tools required to achieve their health and fitness goals. For more information, visit NutrishopUSA.com and follow on Instagram @NutrishopUSA. To learn more about becoming a Nutrishop franchisee, visit NutrishopFranchise.com. SOURCE Nutrishop

03 Aug 2022

·www.worldpharmanews.com

Vitamin K prevents cell death: a new function for a long-known molecule

Vitamin K is well-known for its blood clotting and bone building properties but today a new study published in Nature reports on a novel function for vitamin K. The researchers discovered that the fully reduced form of vitamin K acts as an antioxidant efficiently inhibiting ferroptotic cell death. Ferroptosis is a natural form of cell death in which cellular iron plays an important role and which is characterized by the oxidative destruction of cellular membranes. In addition, the team identified FSP1 as the warfarin-insensitive enzyme reducing vitamin K, the identity of which had been postulated but remained unknown for more than half a century. During the last years, ferroptosis has been implicated as a driver of Alzheimers disease and acute organ injuries among many other diseases. Thus, the present findings put forward the concept that vitamin K treatment might be a new powerful strategy to ameliorate these ferroptosis-related diseases. Vitamin K is a potent ferroptosis suppressor Since ferroptosis prevention is considered a highly promising approach for the therapy of many degenerative diseases, new mechanisms and compounds regulating ferroptosis are extensively being explored. To identify these new molecules, a team of researchers led by Dr. Eikan Mishima and Dr. Marcus Conrad, both from the Institute of Metabolism and Cell Death at Helmholtz Munich, along with collaborators from Tohoku University (Japan), University of Ottawa (Canada) and Technical University of Dresden (Germany), systematically studied a number of naturally occurring vitamins, as well as their derivatives. "Surprisingly, we identified that vitamin K, including phylloquinone (vitamin K1) and menaquinone-4 (vitamin K2), is able to efficiently rescue cells and tissues from undergoing ferroptosis" Dr. Eikan Mishima, first author of the study explained. Unraveling the long sought-after vitamin K reducing enzyme FSP1 In 2019 a team of researchers around Dr. Marcus Conrad already identified an enzyme as a novel and strong inhibitor of ferroptosis: ferroptosis suppressor protein-1, short FSP1. At the time, the team showed that FSP1 reduced coenzyme Q10 to its hydroquinone, which suppressed ferroptosis. The research team now found that the fully reduced form of vitamin K (i.e., vitamin K hydroquinone) is, like the reduced form of coenzyme Q10, a strong lipophilic antioxidant and prevents ferroptosis by trapping oxygen radicals in lipid bilayers. "The reduced forms of Vitamin K and coenzyme Q10 are not very stable, so our finding that FSP1 can maintain them in their active (reduced) state is key to understanding how they are able to function to maintain cell viability." explained Derek A. Pratt, co-author and University Research Chair in Free Radical Chemistry at the University of Ottawa. In addition, they identified that FSP1 is the enzyme that efficiently reduces vitamin K to vitamin K hydroquinone, thereby driving a novel non-canonical vitamin K cycle. Since vitamin K is critically involved in blood clotting processes, the team further showed that FSP1 is responsible for the vitamin K-reduction pathway insensitive against warfarin, one of the most commonly prescribed anticoagulants. Breakthrough in understanding vitamin K metabolism Unraveling the identity of this enzyme solved the last riddle of vitamin K metabolism in blood clotting and elucidated the molecular mechanism of why vitamin K constitutes the antidote for overdosing of warfarin. "Our results therefore link the two worlds of ferroptosis research and vitamin K biology. They will serve as the stepping stone for the development of novel therapeutic strategies for diseases where ferroptosis has been implicated," Dr. Marcus Conrad highlighted. In addition, since ferroptosis most likely constitutes one of the oldest types of cell death, the researchers hypothesize that vitamin K might be one of the most ancient types of naturally occurring antioxidants. "Thus, new aspects of the role of vitamin K throughout the evolution of life are expected to be unveiled," Dr. Marcus Conrad explained. Mishima E, Ito J, Wu Z et al. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature, 2022. 10.1038/s41586-022-05022-3

100 Deals associated with Menatetrenone

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KEGG	Wiki	ATC	Drug Bank
D00100	Menatetrenone	B02BA	DB12148

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Vitamin K Deficiency Bleeding	JP	Sannova KK	25 May 2012
Vitamin K Deficiency Bleeding	JP	Alfresa Pharma Corp.	25 May 2012
Osteoporosis	JP	Eisai Co., Ltd.	30 Jun 1995
Hemorrhage	JP	Eisai Co., Ltd.	29 Jun 1972
Hypoprothrombinemias	JP	Eisai Co., Ltd.	29 Jun 1972

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoporosis, Postmenopausal	Phase 3	CN	Eisai Co., Ltd.	01 May 2005
Hepatocellular Carcinoma	Phase 3	JP	Eisai Co., Ltd.	01 Mar 2004

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AVADEC (ESC2022)	Not Applicable	Coronary Artery Disease	389	Vitamin K2 (720 μg/day) and Vitamin D (25 μg/day)	nhmchjhydn(deejgsboil) = muuyachdvn gevomrxvai (gcptworhwk ) View more	-	28 Aug 2022
				vitamin k2	nhmchjhydn(deejgsboil) = wuumshyeem gevomrxvai (gcptworhwk ) View more
MO789 (ERA2022)	Not Applicable	matrix Gla protein (MGP)	120	Vitamin K1	xwhfgwsvtn(yehlbbvvdo) = mdfmqgvegw msxywwuzxu (rwoiqhmuox )	Positive	03 May 2022
				Vitamin K2	xwhfgwsvtn(yehlbbvvdo) = maggsbsrxq msxywwuzxu (rwoiqhmuox )
Pubmed \| J Am Coll Cardiol	Not Applicable	Aortic Valve, Calcification Of	365	MK-7 plus vitamin D	nyyqgnmned(xtdubocqah) = ypkuybmtwn ndcxoctarm (tquyeshfns, 225 - 326) View more	-	25 Apr 2022
				Vitamin K2 (Placebo)	nyyqgnmned(xtdubocqah) = opgtabomfu ndcxoctarm (tquyeshfns, 246 - 338) View more
FP608 (ERA2019)	Not Applicable	Vascular Calcification uncarboxylated-MGP	102	Vitamin K2 supplementation (200μg/day)	uxjddgiryv(edheavitfy) = eswpvvrxll wigijdugvl (kawphyzdlt ) View more	Negative	13 Jun 2019
				Vitamin K2	uxjddgiryv(edheavitfy) = jsmfppctpy wigijdugvl (kawphyzdlt ) View more
NCT02876354 (Pubmed \| BMC Nephrol)	Phase 4	Hemodialysis complication	50	Vitamin K2 (menaquinone-7)	eewixgqmug(unuegscswt) = pjhbmkugno sxdjrcoanq (vzptkmosci )	-	07 Jun 2017
NCT02876354 (MO021, ERA2017)	Phase 4	Hemodialysis complication dp-ucMGP \| MGP \| vitamin K2	50	Vitamin K2 (menaquinone-7)	mfmvqhigtx(oevsudzdub) = pgpphdujwy ntvsazhzfi (bqaacsnqaj )	Positive	26 May 2017
NCT04247087 \| NCT01101698 (Pubmed)	Phase 4	Chronic Kidney Diseases	42	Vitamin K2 + cholecalciferol (K+D)	dxnjcfyypi(ggfnzbpkuv) = olithessvy gjfghulmaj (ozijasrzgg )	-	01 Jan 2015
				Cholecalciferol (D)	dxnjcfyypi(ggfnzbpkuv) = ifbzitefpn gjfghulmaj (ozijasrzgg )
SP230 (ERA2014)	Not Applicable	dp-ucMGP positive \| MGP positive \| osteocalcin	42	Vitamin K2 (menaquinone-7, MK-7) + cholecalciferol	bwunsfhsze(blkqhivcfx) = djwypxqbzk ffsfbvdjzl (jsudemznrj, 1077.1±507.7) View more	Positive	01 May 2014
				Vitamin D	bwunsfhsze(blkqhivcfx) = rcjroxauls ffsfbvdjzl (jsudemznrj, 793.9±400.3) View more
Pubmed \| Nutr J	Not Applicable	-	-	Menaquinone-4 (MK-4)	ilsiqjbefk(wznzlzhecn) = gryaocgkmv bnpwkmpzrj (eqvtdrlunq )	-	01 Dec 2012
ASN2012	Not Applicable	dp-uc-MGP	200	Vitamin K2 360 µg	fjeopdcazp(tofmxysjak) = 13% of patients suffered from gastro-intestinal side effects, unrelated to the dose. Nausea caused by the unpleasant smell of the uncoated tablets was reported most frequent. bekblnolan (kzaahpsbxv )	Positive	30 Oct 2012
				Vitamin K2 720 µg

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