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Foto: werkingsmechanisme van natuurlijke aanmaak van melatonine

16 juni 2016: Ik heb aan onderstaande meta analyse verschillende andere studies over effecten van melatonine toegevoegd. Het IGZ - Inspectie voor de Gezondheidszorg heeft ook informatie over melatonine maar nog geen update gemaakt van de beslissing van de Hoge Raad dat melatonine in dosering tot 5 mg. gewoon mag worden verkocht als voedingssupplement en niet hoeft te voldoen aan de eisen die aan een medicijn worden gesteld. Klik hier voor de uitspraak d.d. 1 juni 2016

Voedingssupplementen met melatonine behouden voor consument

PERSBERICHT, Amersfoort, 2 juni 2016

Melatoninesupplementen mogen vanaf een bepaalde dosering niet zomaar als medicijn worden bestempeld. De Inspectie voor de Gezondheidszorg (IGZ) moet in de beoordeling of een product een geneesmiddel is, van geval tot geval, alle kenmerken van het product meenemen zoals de manier waarop het door de consument wordt gebruikt; om de gezondheid te bevorderen of om ziekte of een tekort op te heffen.

De Haagse rechter heeft deze uitspraak gisterenmiddag gedaan in de bodemprocedure die NPN heeft aangespannen tegen IGZ. Nederlanders gebruiken de lichaamseigen stof melatonine om jetlag te bestrijden of om beter in slaap te vallen. ”De uitspraak betekent een bescherming van het aanbod voedingssupplementen voor de consument.”, reageert Saskia Geurts, directeur van brancheorganisatie NPN. Lees verder>>>>>>>>>>

Onderstaande studies bewijzen dat melatonine wel degelijk werkzaam is als medicijn bij kanker. De abstracten en lange referentielijst (166 studies) staan onderaan dit artikel.

De volgende studie is uit 2015 en geeft gemiddeld genomen een voordeel van 28 procent versus 52 procent op 1-jaars overleving wanneer melatonine wordt gegeven naast chemo met ook een groot verschil in bijwerkingen. Let wel dit is een optelsom van een aantal gerandomiseerde studies die dus de overleving op 1 jaar bijna verdubbelen bij verschillende vormen van kanker. Hier een artikel over die studie: Melatonin could be an overlooked treatment for cancer

en als u klikt op de volgende PDF-link kunt u het studierapport lezen en of uitprinten: Melatonin and the influence on immune system and cancer

Een andere studie laat de meerwaarde zien van melatonine bij zowel chemo als bestraling ook dit is een reviewstudie: The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials.

En deze reviewstudie bij longkanker geeft uitstekende informatie over de werking van melatonine bij met name longkanker en longziektes in het studierapport: Melatonin as a potential anticarcinogen for non-small-cell lung cancer

Zie hieronder een plaatje uit de studie bij longkanker en longziektes en hoe melatonine het schadelijke effecten van bv. roken herstelt of voorkomt:

Figure 2: Effect of melatonin on the prevention of lung carcinogenesis. Melatonin inhibits urethane-induced lung carcinogenesis in mice. Moreover, melatonin attenuates cigarette smoke-induced lung tissue damage, inflammation, and oxidative stress. Melatonin may reduce the incidence of lung cancer and lung diseases (such as COPD, a key risk factor for lung cancer). TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; MPO, myeloperoxidase; MMP-9, matrix metalloproteinase-9; GSH, glutathione; SOD, superoxide dismutase; ROS, reactive oxygen species; LPO, lipid peroxidation; COPD, chronic obstructive pulmonary diseases.

14 februari 2012: Bron: Cancer Chemother Pharmacol. 2012 Jan 24. [Epub ahead of print]

Een nieuwe meta analyse van tientallen gerandomiseerde studies bevestigt de meerwaarde van melatonine bij vele verschillende vormen van kanker, al of niet als aanvulling op chemo en bestraling - radiotherapie. Zo blijkt bv. dat de bijwerkingen van chemo en bestraling dramatisch minder zijn als daarbij 20 mg. melatonine per dag wordt gebruikt. Waaronder trombocytopenie (19,7 versus 2,2%; RR = 0,13, 95% CI, 0.06-0.28, P <0,00001), neurotoxiciteit (15,2 versus 2,5%; RR = 0,19, 95% CI, 0.09-0.40, P <0,0001) , en vermoeidheid (49,1 vs 17,2%; RR = 0,37, 95% CI, 0.28-0.48, P <0,00001). Maar ook de gedeeltelijke en volledige remissiecijfers verdubbelden (16,5 vs 32,6%; RR = 1,95, 95% CI, 1.49-2.54, P <0,00001) en ook de mediane 1-jaars overleving verbeterde significant (28,4 vs 52,2%; RR = 1,90; 95% CI, 1.28-2.83, P = 0,001). En deze meta analsye werd gedaan bij alle vormen van kanker dus niet 1 specifieke vorm. Klik hier voor adressen van goed gekwalificeerde orthomoleculaire artsen, die melatonine kunnen voorschrijven.

Hier het abstract van de studie. Als u hier klikt kunt u tegen betaling het volledige studirapport inzien.

Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission, 1-year survival, and alleviation of radiochemotherapy-related side effects.

Cancer Chemother Pharmacol. 2012 Jan 24. [Epub ahead of print]

The efficacy and safety of melatonin in concurrent chemotherapy or radiotherapy for solid tumors: a meta-analysis of randomized controlled trials.

Wang YM, Jin BZ, Ai F, Duan CH, Lu YZ, Dong TF, Fu QL.

Source

Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, 88 Jiankang Road, The City of Weihui, Xinxiang, Henan Province, China.

Abstract

BACKGROUND:

Recently, melatonin has been associated with cancer both in vitro and in vivo. However, the value of melatonin in the treatment of cancer remains disputable. Hence, we performed a systematic review of randomized controlled trials (RCTs) of melatonin in solid tumor cancer patients and observed its effect on tumor remission, 1-year survival, and side effects due to radiochemotherapy.

METHODS:

An electronic search was conducted using the databases Pubmed, Medline, EMBASE, Cochrane library, and CNKI, from inception to November 2011. Trials using melatonin as adjunct treatment concurrent with chemotherapy or radiotherapy for cancer were included. Pooled relative risk (RR) for the tumor remission, 1-year survival, and radiochemotherapy-related side effects were calculated using the software Revman 5.0.

RESULTS:

The search strategy identified 8 eligible RCTs (n = 761), all of which studied solid tumor cancers. The dosage of melatonin used in the 8 included RCTs was 20 mg orally, once a day. Melatonin significantly improved the complete and partial remission (16.5 vs. 32.6%; RR = 1.95, 95% CI, 1.49-2.54; P < 0.00001) as well as 1-year survival rate (28.4 vs. 52.2%; RR = 1.90; 95% CI, 1.28-2.83; P = 0.001), and dramatically decreased radiochemotherapy-related side effects including thrombocytopenia (19.7 vs. 2.2%; RR = 0.13; 95% CI, 0.06-0.28; P < 0.00001), neurotoxicity (15.2 vs. 2.5%; RR = 0.19; 95% CI, 0.09-0.40; P < 0.0001), and fatigue (49.1 vs. 17.2%; RR = 0.37; 95% CI, 0.28-0.48; P < 0.00001). Effects were consistent across different types of cancer. No severe adverse events were reported.

CONCLUSIONS:

Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission, 1-year survival, and alleviation of radiochemotherapy-related side effects.

PMID:

22271210

[PubMed - as supplied by publisher]

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

DOI: 10.18632/oncotarget.8776

Zhiqiang Ma1,*, Yang Yang2,3*, Chongxi Fan1,*, Jing Han4, Dongjin Wang2, Shouyin Di1, Wei Hu2, Dong Liu5, Xiaofei Li1, Russel J. Reiter6 and Xiaolong Yan1

1 Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China

2 Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China

3 Department of Biomedical Engineering, The Fourth Military Medical University, Xi’an, China

4 Department of Ophthalmology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China

5 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

6 Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA

* These authors have contributed equally to this work.

Correspondence to:

Xiaolong Yan, email: xiaolongyanfmmu@126.com

Russel J. Reiter, email: reiter@uthscsa.edu

Xiaofei Li, email: xiaofeilitangdu@126.com

Keywords: melatonin; non-small-cell lung cancer; oncostatic effects; drug synergy; potential directions

Received: December 08, 2015 Accepted: March 31, 2016 Published: April 18, 2016

Table 2:The drug synergy of melatonin in NSCLC

Cancer categories	Number of patients	Drugs and dose	Outcome	References
Experimental studies
SK-LU-1 NSCLC cell line	None	Melatonin (1, 2 mM) + cisplatin (10-200 μM) (48 h in culture)	In the drug combination, 1 and 2 mM melatonin reduced IC50 concentration of cisplatin alone from 50 μM to 11 and 4 μM. Thus, melatonin enhances cisplatin-induced cytotoxicity and apoptosis in SK-LU-1 cells and induces cell cycle arrest in the S phase in contrast to cisplatin alone group	Plaimee et al. [5]
A549 cells and healthy human lymphocytes	None	Melatonin (50 μM) + irinotecan (7.5, 15, 30, and 60 μM)	The combination treatment resulted in an increase in the amount of DNA damage in A549 cells, but was not effective in inducing DNA damage in healthy human lymphocytes	Kontek et al. [122]
A549 cells	None	Melatonin (0.1, 1 mM) + doxorubicin (0.1, 1 microg/ml)	Melatonin intensified cytotoxicity of doxorubicin in all cell lines, significantly decreasing cell numbers and promoting apoptosis	Fic et al. [124]
Female C57B/6 mice with subcutaneous propagation of Lewis lung carcinoma	None	Melatonin (1 mg/kg) + cyclophosphamide (40, 160 mg/kg) + etoposide (20, 40 mg/kg)	Melatonin can rescue myeloid progenitor cells from chemotherapy-induced apoptosis via a mechanism involving the endogenous production of GM-CSF by T cells	Maestroni et al. [114]
H1299 and A549 cells	None	Melatonin (1 mM) + berberine (20μM to 200 μM)	Melatonin sensitized NSCLC cells to berberine and enhanced the growth inhibitory effect of berberine by activating caspase/Cyto C and inhibiting AP-2β/hTERT, NF-κB/COX-2 and Akt/ERK signaling pathways	Lu et al. [125]
Clinical trials
Untreatable metastatic NSCLC or GI cancers	846	Melatonin (20 mg/day) + IL-2 (3 million IU/day, 5 days/week, 4 weeks) + supportive care	The combination treatment provided a further improvement in the percentage of tumor regressions and of 3-year survival with respect to melatonin or supportive care alone	Lissoni et al. [127]
Advanced lung adenocarcinoma	23	Melatonin (20 mg/day) + somatostatin (1-3 mg/day) + Retinoids (5 ml) + Vitamin D (0.3 mg/day) + bromocriptine (2.5 mg/day) + cyclophosphamide (150 mg/day)	Patients with combination treatment had a median overall survival of 95 days, with very modest toxic effects and an improvement in both respiratory and general symptoms associated with length of survival	Norsa et al. [123]
Untreated metastatic NSCLC	147	Melatonin (20 mg/day) + cisplatin plus etoposide or gemcitabine	The 2-year survival rate and the overall tumor regression rate achieved in patients concomitantly treated with melatonin was significantly higher than that found in those treated with chemotherapy alone	Lissoni et al. [33]
Untreated metastatic NSCLC	100	Melatonin (20 mg/day) + cisplatin (20 mg/m2/day) + etoposide (100 mg/m2/day)	Overall tumor regression rate and the 5-year survival results (49%) were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years	Lissoni et al. [8]
Advanced NSCLC	70	Melatonin (20 mg/day) + cisplatin (20 mg/m2/day) + etoposide (100 mg/m2/day)	The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone (15/34 vs. 7/36, P <0.05)	Lissoni et al. [129]

GM-CSF, granulocyte-macrophage colony-stimulating factor; Cyto C, cytochrome C; AP-2β, activator protein 2β; hTERT, telomerase reverses transcriptase; NF-κB, nuclear factor κB; COX-2, cyclooxygenase 2; ERK, extracellular signal-regulated kinase

Abstract

Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an idoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC.

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