3 september 2018: Bronnen: zie studiereferenties en literatuurlijsten van arts-bioloog drs. Engelbert Valstar.

Het volledige studieverslag van onderstaand besproken studie:

The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment is inmiddels gratis in te zien.

Met opvallende resultaten op overall overleving t.o.v. placebo:

Voor de patiënten die menatetrenone (vitamine K-2) hadden gehad was de overleving 100% op 1 jaar, 96.6% op 2 jaar en 87.0% op 3 jaar; Ter vergelijking waren dit de overall overlevingscijfers voor de patiënten die een placebo hadden gehad: 96.4% op 1 jaar, 80.9%, op 2 jaar en 64.0% op 3 jaar. (P = 0.051).

Ook de kans op een recidief was voor de menatetrenone (K-2) groep beter dan voor de placebogroep:

In het tijdschrift PlaceboNocebo beschrijft Hilda Maris ook wat vitamine K is en in combinatie met vitamine C kan betekenen.

Hier een werkingsmechanisme uit de studie: Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect waaruit Hilde Maris citeert. (zie onder afbeelding waar de tekst verder loopt).

Vitamine K & vitamine C als antikankerduo

Vitamine K is een vetoplosbare vitamine die vooral bekend is van haar rol in de bloedstolling. Vitamine K is ook nodig voor sterke botten, ze remt ontsteking, voorkomt atherosclerose en heeft een antikankerwerking.

Vitamine K is betrokken bij een proces dat oxidatie-reductie (redox) heet. Redox reacties vormen een belangrijk onderdeel van biochemische reacties. Oxidatie-reductie is de overdracht van elektronen van de ene naar de andere molecule. Bij oxidatie wordt een elektron weggenomen, bij reductie wordt een elektron toegevoegd. Een molecule die een elektron van een andere molecule wegneemt is een oxidant. Deze molecule wordt zelf gereduceerd in het proces. Een molecule die een elektron aan een andere molecule afgeeft is een reductor. Deze molecule wordt zelf geoxideerd in het proces.

Vitamine K wordt bijvoorbeeld geoxideerd tijdens de activatie van bloedstollingsfactoren of het regelen van het calciummetabolisme. Ze moet daarna opnieuw gereduceerd worden.

Vitamine K wordt gereduceerd of geregenereerd door vitamine C. Daarbij wordt vitamine C geoxideerd en weer gereduceerd door glutathion. De oxidatie-reductie cyclus van vitamine K en vitamine C zijn onderling verbonden en vormen een krachtig redoxsysteem dat de aanmaak van kankerceldodende zuurstofradicalen stimuleert, de aanmaak van energie in de cellen verhoogt, de werking van de mitochondriën verbetert en ervoor zorgt dat kankercellen weer zuurstof krijgen, zodat ze afsterven.

Een combinatie van vitamine C en vitamine K wordt beschouwd als een krachtig antikankerduo. Het heeft op zichzelf een antikankerwerking en het maakt kankercellen gevoeliger voor chemotherapie, zodat er minder chemo kan gebruikt worden en de bijwerkingen tot een minimum beperkt kunnen worden (Ivanova D, 2018).

Voedingsbronnen van vitamine K

Vitamine K1 zit vooral in groene bladgroenten en koolsoorten, zoals boerenkool, broccoli, bloemkool, spinazie, alfalfa, groene thee, algen, sla en peterselie.

Vitamine K2 zit vooral in gefermenteerde producten zoals yoghurt, kaas en natto (gefermenteerde sojabonen) en in mindere mate in eierdooiers, vis, gevogelte, lever en zuurkool.

Voedingsbronnen van vitamine C

Vitamine C zit vooral in groenten en fruit: acerola, citrusvruchten, aardbeien, frambozen, rode bessen, zwarte bessen, mango, papaja, guave, kiwi, mandarijn, groene bladgroenten, tomaten, waterkers, bloemkool, zoete aardappelen, paprika, Spaanse pepers, peterselie, knoflook, spruiten, broccoli, kool, rozenbottel en aloë vera

(Artikel uit PlaceboNocebo 39)

Referentie

Ivanova D, Zhelev Z, Getsov P, et al. Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect. Redox Biol. 2018 Jun;16:352-358.

Referenties:

En er zijn meer studies die bewijzen dat Vitamine K-2 of K-3 een recidief kan verkomen bij operabele leverkanker.

1288) Sarin SK et al ; J Gastroenterol Hepatol 21:1478-82; 2006 : Vitamine K3 geeft bij vergevorderde primaire leverkanker significant meer regressies dan een placebo. PMID 16911696.

1338)Kakizaki S et al ; J Gastroenetrol Hepatol 22:518-22 ; 2007 : Na RFA - Radio Frequency Ablation of chirurgie wegens een primair levercarcinoom verbetert vitamine K2 de ziektevrije overleving. De overleving sec was met K2 niet aantoonbaar beter ; maar en dat zagen de onderzoekers over het hoofd een trendanalyse, welke gevoeliger is, liet wel een langere overleving zien ; PMID 17376044.

1356)Kakazaki S et al ; J Gastroenterol Hepatol 22(4):518-22 ; 2007 : Vitamine K2 vertraagt recidiveren leverkanker (mede)veroorzaakt door hepatitis C ; 17376044.

1956)Ishizuka M et al; Anticancer Res 2012 Dec;32(12): 5415-20; PMID 23225445 : vitamine K2 vertraagt op z’n minst de relaps-rate na operatie vanwege een HCC - primaire leverkanker. Zie ook 1338.

2237)Hotta N et al; Hepatogastroenterology 2007 Oct-Nov;54(79):2073-7 ;PMID 18251162 : Vitamne K2 liet een trend tot minder recidieven zien. Zie ook 1338, 1356 en 1456 : het belang van K2 bij het HCC - primaire leverkanker is duidelijk.

3488)Mizuta T et al; Cancer 2006 Feb 15;106(4):867-72; PMID 16400650; vitamine K2 vermindert recidiefkans primaire leverkanker - HCC en verlengt op z’n minst het leven.

15 oktober 2011: Onderaan heb ik het abstract van een recentere studie naar effect van menatetrenone ( vitamine K2) bij levertumoren geplaatst. Met zelfde positieve resultaten als uit onderstaande studie blijkt uit maart 2006.

22 maart 2006: Bron: SOURCE: Cancer 2006;106:867-872

Menatetrenone ( = analoog aan vitamine K2) vermindert bij operabele leverkanker de kans op een recidief significant met na 1 jaar 42,7 % en na drie jaar 27,3% en verbetert 3 jaars overleving met 23 %. Wij vertaalden voor u het volledige persbericht van Reuters over deze studie.

Menatetrenone verbetert significant behandelingen van leverkanker

NEW YORK MAT 16, 2006 (Reuters Health) - Voor patiënten die een curatieve - genezende behandeling hebben gekregen voor hun leverkanker (HCC) vermindert menatetrenone (een medicijn analoog aan vitamine K2) recidieven en verbetert significant de overleving, aldus tonen de resultaten uit een gerandomiseerde pilotstudie.

Menatetrenone is een analoog van vitamine K2, welke eerder aantoonde antiproliferatieve effecten te geven tegen leukemie en levercellijnen verklaren de auteurs.

Dr. Toshihiko Mizuta en collega's van de Saga Medical School, Japan, onderzochten de effecten van menatetrenone (analoog aan vitamine K2) op terugkeer van de ziekte en overleving bij 61 patiënten met HCC - primaire leverkanker, welke een operatie of percutane lokale ablatie therapie (TACE en/of RFA) hadden gehad.

Het vervolgens optredende recidief van HCC in de menatetrenone groep was 12.5% na 12 maanden, 39.0% na 24 maanden, en 64.3% na 36 maanden, vergeleken met 55.2%, 83.2%, en 91.6%, respectievelijk, in de placebo groep, aldus de auteurs.

De uiteindelijke overlevingscijfers waren ook beduidend hoger in de menatetrenone groep dan in de placebo groep (100% versus 96.4% na 12 maanden, 96.6% versus 80.9% na 24 maanden, en 87.0% versus 64% na 36 maanden), meldt het studieverslag.

Menatetrenone toediening werd niet geassocieerd met bijwerkingen, rapporteren de onderzoekers in de 15 februari editie van Cancer en geen enkele patiënt is met de studie gestopt tijdens de follow-up studie periode van mediaan 28,9 maanden Menatetrenone was effectief (profijtelijk) voor patiënten onafhankelijk van de basiswaarden van des-gamma-carboxy-prothrombin (een mogelijke marker van agressievere tumoren welke worden onderdrukt door toediening van vitamine K2), tonen de resultaten aan. "De resultaten van deze gerandomiseerde pilot studie wijst uit dat menatetrenone mogelijk het risico op een recidief van HCC - leverkanker vermindert na operatie of lokale ablatieve ingreep," concluderen de auteurs. "Het effect op overleving vergt wel nadere studies; Echter, al bij al, chemopreventie van een recidief van HCC - leverkanker door gebruik van menatetrenone - vit. K2 lijkt een beloftevolle optie".

SOURCE: Cancer 2006;106:867-872.

Menatetrenone Improves Hepatocellular Carcinoma Outcome

NEW YORK MAT 16, 2006 (Reuters Health) - For patients who have received curative treatment for hepatocellular carcinoma (HCC),menatetrenone reduces recurrences and improves survival, the results of a pilot study suggest.

Menatetrenone is an analog of vitamin K2, which has been shown to have antiproliferative effects against leukemia and hepatoma cell lines, the authors explain. Dr. Toshihiko Mizuta and colleagues from Saga Medical School, Japan, investigated the effects of menatetrenone on disease recurrence and survival in 61 patients with HCC after they underwent curative resection or percutaneous local ablation therapy.

The cumulative incidence of HCC recurrence in the menatetrenone group was 12.5% at 12 months, 39.0% at 24 months, and 64.3% at 36 months, the authors report, compared with 55.2%, 83.2%, and 91.6%, respectively, in the placebo group. Survival rates were also higher in the menatetrenone group than in the placebo group (100% versus 96.4% at 12 months, 96.6% versus 80.9% at 24 months, and 87.0% versus 64% at 36 months), the report indicates. Menatetrenone treatment was not associated with any adverse effects, the researchers report in the February 15th issue of Cancer, and no patient was withdrawn from the study during an average 28.9 months of follow-up. Menatetrenone was beneficial in patients regardless of the baseline level of des-gamma-carboxy-prothrombin (a possible marker of more aggressive tumors that is suppressed by vitamin K2 administration), the results indicate. "The results from this randomized, controlled, pilot study revealed that menatetrenone possibly may reduce the risk of HCC recurrence after curative surgical resection or local ablation therapy," the authors conclude. "The effect on survival warrants further research; however, overall, chemoprevention of secondary HCC using menatetrenone appears to be a promising option."

SOURCE: Cancer 2006;106:867-872.

Vitamin analogues in chemoprevention of hepatocellular carcinoma after resection or ablation--a systematic review and meta-analysis

Asian J Surg. 2010 Jul;33(3):120-6.

Vitamin analogues in chemoprevention of hepatocellular carcinoma after resection or ablation--a systematic review and meta-analysis.

Chu KJ, Lai EC, Yao XP, Zhang HW, Lau WY, Fu XH, Lu CD, Shi J, Cheng SQ.

Source

Department of Oncology Comprehensive Treatment, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, China.

Abstract

OBJECTIVE:

While hepatic resection or local ablative therapy may provide a potentially curative treatment for hepatocellular carcinoma (HCC), more than half of these patients develop recurrent HCC within 5 years after treatment. Thus identification of any therapy which can decrease or delay the incidence of recurrence will improve the results of treatment. However, no chemopreventive agent has been approved for HCC.

METHODS:

A MEDLINE database, Embase, Cancerlit (National Cancer Institute), and CBM (Chinese Biomedical Database) search from 1990 to 2009 was performed to identify relevant articles using the keywords "hepatocellular carcinoma," "vitamin analogue," and "chemoprevention." Additional papers were identified by a manual search of the references from the key articles. The fixed effect model was used for a meta-analysis.

RESULTS:

Oral administration of acyclic retinoids (vitamin A analogue), and menatetrenone (vitamin K2 analogue) have been tested as chemopreventive agents after hepatic resection or local ablative therapy for HCC. There were one and four randomised, controlled trials (RCTs) which evaluated the efficacy of polyprenoic acid and menatetrenone, respectively. All studies were conducted in Japan. One RCT showed the preventive effect of polyprenoic acid in lowering the incidence of HCC recurrence after hepatic resection or percutaneous ethanol injection, and this effect lasted up to 199 weeks after randomization (or 151 weeks after completion of retinoid administration). Four RCTs evaluated the preventive efficacy of menatetrenone on HCC recurrence after hepatic resection or local ablative therapy. The results of three studies, as well as the meta-analysis of all four studies, showed significantly better tumour recurrence-free survival. The beneficial effect on the overall survival was less definite.

CONCLUSION:

There is evidence to suggest that chemopreventive therapy after partial hepatectomy or local ablative therapy is beneficial in prolonging disease-free survival, but the evidence is less for an effect on the overall survival. To confirm the beneficial role of vitamin A or K analogues in the chemoprevention of HCC further and larger randomised trials are now required.

PMID:: 21163409; [PubMed - indexed for MEDLINE]

Referentielijst : Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect

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