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11 januari 2018: Ik heb deze reactie gestuurd aan Medisch Contact die mij hebben beloofd dat deze zal worden geplaatst:

Terneuzen, 10 januari 2018-01-10

Met  het artikel: “Curcumine kan geen geneesmiddel zijn” in Medisch Contact van 14 december 2017 pleit  Henk Timmerman emeritus hoogleraar farmachemie ervoor om een wereldwijd  veel gebruikt plantenextract als kurkuma uit het wetenschappelijk onderzoek te halen,  omdat hij er zelf geen heil meer inziet;  “Het adagium ’genoeg is genoeg’ zou ook door de aanhangers van alternatieve middelen geaccepteerd moeten worden. Altijd geldt immers dat patiënten niet willens en wetens aan ineffectieve onderworpen mogen worden. Goede reden om de hype te stoppen.“ Aldus Timmerman in zijn artikel, en passant de ‘alternatieven’ een sneer meegevend.

Het is maar goed dat Henk Timmerman zelf geen wetenschappelijk onderzoek meer doet, want zijn artikel bewijst dat hij niet meer goed kan onderscheiden waaraan een wetenschappelijke studie moet voldoen.  

Alleen al in de titel en intro van het artikel haalt Timmerman het stofje curcumine en het kruid kurkuma door elkaar heen in 2 zinnen. Boven de titel “Curcumine kan geen geneesmiddel zijn” schrijft hij DE GENEESKRACHTIGE WERKING VAN KURKUMA IS NON EXISTENT.  
En in het artikel zelf gebruikt Timmerman  het kruid kurkuma en het stofje curcumine ook enkele malen bewust door elkaar heen, alsof curcumine en kurkuma hetzelfde zouden zijn.  Weet Timmerman niet dat curcumine een geïsoleerde stof is uit kurkuma? En dat onderzoek naar een geïsoleerd stofje niets zegt over het hele kruid kurkuma? En dat er heel veel studies zijn gedaan en worden gedaan naar kurkuma en  turmeric? Dat alles weet een emeritus hoogleraar farmachemo van de Vrije Universiteit  niet? 

Het klopt dat het heel lastig is om het stofje curcumine te onderzoeken  (ref. 1.) maar het is niet onmogelijk.  Dat oncoloog Casper van Eyck (die door Timmerman als niet competente goed gelovige ‘kwakzalversupporter’ wordt neergezet) zo enthousiast is over curcumine en kurkuma zou wellicht  kunnen komen omdat Casper van Eyck op de hoogte is van  de fase II studie (ref. 2. ) bij zwaar voorbehandelde patiënten met uitgezaaide alvleesklierkanker, waarin curcumine tegenover placebo veelbelovende resultaten liet zien. Zonder de gebruikelijke bijwerkingen van chemo.   

Ik ben geen wetenschapper noch arts, maar als webmaster van kanker-actueel.nl  weet ik wel hoe te zoeken in pubmed. Binnen een half uur kwam ik op een aantal interessante studies met curcumin of kurkuma  / turmeric.  Die Timmerman blijkbaar niet kon vinden? Naast de genoemde studie bij  alvleesklierkanker patiënten vond ik ook een gerandomiseerde placebo gecontroleerde  studie bij patiënten met ernstige depressie (ref  7 en 8), bij atritis (ref 9), bij kanker in het algemeen (ref 3 en 4) en bij prostaatkanker (ref 5) en longkanker  (ref 6) in het bijzonder.

Hieronder de verwijzingen naar deze studies. Wie de referentielijsten van genoemde studies bekijkt (allemaal geven ze een meerwaarde aan van curcumine respectievelijk  kurkuma)  ziet dat er wereldwijd veel onderzoek is en wordt gedaan  naar het stofje curcumine en naar het kruid kurkuma.

Het zou Henk Timmerman sieren als hij in de volgende  Medisch Contact zijn artikel zou corrigeren om daarmee de onrust weg te nemen bij die patiënten die kurkuma gebruiken. 

Kees Braam

Webmaster van www.kanker-actueel.nl
Patient advocate bij www.Inspire2live.org  

 

 

Referenties:

  1. The Essential  Medicinal Chemistry of Curcumin: zie https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346970/
  2. Phase II trial of curcumin in patients with advanced pancreatic cancer Zie http://clincancerres.aacrjournals.org/content/14/14/4491 
  3. Dietary turmeric potentially reduces the risk of cancer. zie: http://journal.waocp.org/article_26033_1b27ce1966fc5c5d034c7ea0d22f2363.pdf  
  4. The Multifaceted Role of Curcumin in Cancer Prevention and Treatment. Zie: http://www.mdpi.com/1420-3049/20/2/2728/htm  
  5. A Placebo-Controlled Double Blinded Randomized Pilot Study of Combination Phytotherapy in Biochemically Recurrent Prostate Cancer. : Zie: https://www.ncbi.nlm.nih.gov/pubmed/28181675
  6. Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer. Zie: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388225
  7. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Zie: https://www.ncbi.nlm.nih.gov/pubmed/23832433 . 
  8. Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study. Zie: https://www.ncbi.nlm.nih.gov/pubmed/27723543 
  9. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials zie   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003001/

 

 

5 januari 2018:

Op dit artikel kreeg ik de volgende reactie en ben ik het wel mee eens. Curcumine is het stofje uit het kruid turmeric / kurkuma en met het hele kruid kurkuma / turmeric zijn wel studies gedaan met goede resultaten. (zie ook in gerelateerde artikelen). Overigens zegt Henk Timmerman dat curcumine geen geneesmiddel kan zijn maar hij zegt dat niet over het hele kruid kurkuma / turmeric, al suggereert hij dat wel met zijn inleidinng en verderop in het artikel nog een keer. Ik denk dat Henk Timmerman, ooit adviserend lid en misschien nog steeds lid van de VtdK - Vereniging tegen de Kwakzalverij dit heel bewust zo heeft gedaan. Als leek maak ik ook de fout als ik het heb over curcumine dat ik dat dan ook wel kurkuma noem. Maar in feite is curcumine een stofje uit het kruid kurkuma. Het kruid zelf is zoals Hugo ook opmerkt niet te patenteren en dus voor de farmaceutische industrie niet interessant om daar onderzoek naar te doen. In dit verband is het goed om het interview met prof. dr. Casper van Eijck te lezen in de Volkskrant. Een goed opgezette gebruikersstudie zou wel interessant zijn maar ja wie betaalt dat? (zie gerelateerde artikelen voor studies met kurkuma en ook met curcumine trouwens, dus het kan wel bljikbaar.

Maar lees deze reactie van Hugo:

Beste Kees,

Dat zijn voor zover ik dat goed begrijp studies naar de Curcumine en geen onderzoeken met het gehele kruid.
Curcumin is the active ingredient of turmeric, and is also found in limited amounts in ginger. It is an anti-inflammatory molecule, and similar to fish oil, it seems to be a metabolic syndrome band-aid.
It has poor bioavailability and black pepper greatly enhances absorption.

Dat wordt ook duidelijk als inleiding van de door jou genoemde bron Pains? Solid Gold op jouw website (de 164 studies) 
Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive
investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro
and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the
essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

Dit onderbouwd zelfs mogelijk wat ik in mijn stukken ook steeds aan jou heb geschreven. 
Onderzoek naar of het gebruik van curcumine zou inderdaad wel eens kunnen eindigen in een fiasco.
Maar dat mag niet een op een leiden tot de uitspraak dat dus het gebruik van kurkuma als kruid onzinnig is.
Valstar verwijst naar het gebruik van de kurkuma als zodanig. Dat doe ik ook steeds. Literatuur daaromtrent is voorradig en eveneens promising.
Praktijkervaringen zijn er voldoende (o.a. dr. Van Eijck). Het kruid is echter niet te patenteren. Wel de verschillende manieren om bepaalde bestanddelen versneld op te nemen en of in te kapselen. Daar
is dus geld mee te verdienen. De vraag is echter of deze oplossingen effectiever zijn als het hoog gedoseerde basisextract. Het antwoord zou weleens ondubbelzinnig nee kunnen zijn.

Mijn verontwaardiging over het artikel zit dus vnl. In het feit dat de heer Timmermans curcumine bestanddeel en kurkuma als kruid met elkaar verwisseld en verward, hetgeen niet juist is, en in het feit
dat hij en passant de gehele alternatieve behandelingsopties weer even door het slijk haalt zonder daarbij aan te geven waarover hij het nu eigenlijk heeft. Fytotherapie, homeopathie en acupunctuur zijn
bijvoorbeeld uitstekend onderbouwde alternatieve behandelopties die een dergelijke schoffering niet verdienen.

Met hartelijke groet, Hugo

4 januari 2018: Bron: Journal of Medicinal Chemistry en Medisch Contact

Curcumine kan geen geneesmiddel zijn is de titel van een artikel uit Medisch
Contact geschreven door Henk Timmerman, emeritus hoogleraar farmachemie, Vrije Universiteit Amsterdam.

Zelfs gerenommeerde wetenschappers geven nu hoog op van de genezende kracht van kurkuma - en de daaruit geïsoleerde stof curcumine. Tijd voor een tegengeluid: farmacologisch onderzoek toont aan dat de stof onbruikbaar is in de geneeskunde.

curcumine grafiek samenstelling

Zo begint het artikel in Medisch Contact d.d. 14 december 2018. 

Van dit artikel is echter alleen de eerste zin te lezen. Alleen voor artsen en abonnees op Medisch Contact is het volledige artikel te lezen. Ik heb nog geprobeerd om via de redactie van Medisch Contact het volledige artikel te mogen lezen maar krijg daarvoor geen toestemming. Ik heb ook nog verwezen naar deze studiepublicatie: Regulation of Polyamine Metabolism by Curcumin for Cancer Prevention and Therapy maar ook deze studie is geen studie bij mensen noch placebo gecontroleerd en juist dat is het probleem, curcumine is een interessant stofje in laboratoriumonderzoek en bij dieren maar bij de mens is tot nu toe geen manier gevonden om de curcumine langdurend opneembaar te maken. 6 weken na publicering zal het volledige artikel in Medisch Contact te lezen zijn, dus rond 1 februari 2018. Wij hebben het artikel in PDF en kunnen u dit digitaal toesturen. U kunt het artikel ook opvragen bij Henk Timmerman, wij hebben zijn adresgegevens. (redactie@kanker-actueel.nl )

Maar eigenwijs als ik ben heb ik verder gezocht heb ik via via het artikel toch gekregen. En ook is het studierapport waarop Henk Timmerman dit artikel mede op heeft gebaseerd (en ook op zijn eigen ervaringen in het verleden met onderzoek naar curcumine) vrij te lezen: The Essential Medicinal Chemistry of Curcumin is een reviewstudie van 164 wetenscahappeljike publicaties. En ook in dit studierapport schrijven de auteurs als laatste zin van hun conclusie: van curcumine is door de instabiliteit en de slechte opneembaarheid van het middel geen werkend geneesmiddel te maken ("curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead"). Wat mij dan wel verbaasd omdat, zie gerelateerde artikelen, er toch studies zijn gepubliceerd die de meerwaarde van curcumine aantonen. Maar ik kan als leek niet beoordelen of er met de resultaten enz publicaties. is gerommeld. 

Maar de boodschap, curcumine kan geen geneesmiddel zijn, lijkt dus de doodsteek voor verder onderzoek naar curcumine als geneesmiddel bij kanker.

Timmerman schrijft ook letterlijk in zijn artikel en ik citeer: " De uitspraak van Heger dat hij 'erin blijft geloven', is dus tegen beter weten in.Omdat curcumine zeer slecht oplosbaar is in water, verpakken sommigen (waaronder Heger) curcumine in nanodeeltjes om de problemen van slechte opname te ondervangen. Het probleem van de snelle afbraak - bij fysiologische pH een haflwaarde tijd van 5 minuten - blijft evenwel onveranderd. De auteurs van het JMC-artikel: ".......curcumin will ultimaterly degrade upon release into physiologic media". Deze benadering kan dus ook niets opleveren.

In de reviewstudie The Essential Medicinal Chemistry of Curcumin en lees aub het volledige studierapport als u hierin bent geinteresseerd, wordt gedetailleeerd beschreven en met tallozxe vorobeelden onderbouwd waarom ziuj weinig heil zien in verder wetenschappelijk onderzoek naar curcumine. Zij geven wel een aantal aanbevelingen voor verder onderzoek maar afgaande op wat Henk Tiummerman schrijft en ook de auteurs van deze studie lijken ook die weinig houvast te bieden om ooit van curcumine een werkend geneesmiddel te maken. Helaas zou ik zeggen, maar deze studie is te goed onderbouwd om hun conclusies te negeren.

Uit: The Essential Medicinal Chemistry of Curcumin

The observations of this Miniperspective offer several key points that can help identify potentially problematic research approaches and/or interpretation of outcomes in publications or preliminary data involving curcumin bioactivity. Notably, many of these strategies have been articulated previously:122,161

  • 1.
    Look for evidence of compound stability in assay buffer/media, including when molecular models are invoked as supporting evidence of target engagement.
  • 2.
    Look for the presence of detergent and thiol-scavenging reagents in biochemical assays to mitigate the impact of chemical aggregation and nonspecific thiol reactivity. Are/were any additional counterscreens performed to rule out these phenomena?
  • 3.
    Examine the selectivity data. What are the magnitudes of any observed selectivity? Are these significant? Can any selectivity be explained by differential target susceptibilities to nonspecific interference modalities like thiol reactivity? Can any apparent selectivity be explained by the assay conditions, such as target or total protein concentration?
  • 4.
    Examine the potency of the compound. At those concentrations, would there be any expected aggregation or off-target effects? And if so, can one make meaningful conclusions about specific pathways and target engagement? Does the stoichiometry make sense?
  • 5.
    Evaluate the methods to confirm target engagement. Look for biophysical orthogonal methods for support of target engagement (e.g., SPR, ITC, CETSA), not solely phenotypic assays.
  • 6.
    Carefully examine the detection method for determining the concentration of 1 present in an assay. What biophysical method is/was used for detection? Can likely degradation products or metabolites have a similar response and/or explain the data/hypothesis?

With respect to curcumin/curcuminoids and in vivo studies and clinical trials, we believe there is rather “much ado about nothing”

Hier het korte abstract van de reviewstudie: The Essential Medicinal Chemistry of Curcumin Daaronder de referentielijst

An external file that holds a picture, illustration, etc.
Object name is jm-2016-009757_0004.jpg

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

J Med Chem. 2017 Mar 9; 60(5): 1620–1637.
Published online 2017 Jan 11. doi:  10.1021/acs.jmedchem.6b00975
PMCID: PMC5346970

The Essential Medicinal Chemistry of Curcumin

Miniperspective

Abstract

An external file that holds a picture, illustration, etc.
Object name is jm-2016-009757_0004.jpg

Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

Acknowledgments

J.L.D., J.B., J.G., and G.F.P. acknowledge Dr. Brian Shoichet for helpful discussions. J.B. and G.F.P. acknowledge funding from NCCIH and ODS/NIH through Grant U41AT008706. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The opinions or assertions contained herein belong to the authors and are not necessarily the official views of the funders.

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