Limoneno (limonene en inglés)
El limoneno es una sustancia natural que se extrae de los cítricos. Es la sustancia que da olor característicos a las naranjas y los limones. Pertenece al grupo de los terpenos.
El limoneno levógiro (-) se extrae de la cáscara de la naranja y le confiere su olor característico.
El limoneno dextrógiro (+) es un líquido aceitoso que puede extraerse fácilmente de la cáscara del limón y es el responsable de su olor.
Pues hay varios artículos en MedLine (PubMed) http://www.ncbi.nlm.nih.gov/pubmed/ sobre diferentes efectos biológicos de limón y cítricos como naranja, especialmente en su cáscara, que es la que tiene mayor contenido de limoneno.
Los resúmenes a continuación son los que se obtienen con términos de búsqueda limonene and cancer and trial and humans
- Life Sci. 2013 Jul 10;92(24-26):1151-6. doi: 10.1016/j.lfs.2013.04.013. Epub 2013 May 7. Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans. d’Alessio PA(1), Ostan R, Bisson JF, Schulzke JD, Ursini MV, Béné MC. Author information: (1)Biopark Cancer Campus, University Paris Sud-11, 94807 Villejuif, France. email@example.com AIMS: To further explore the anti-inflammatory properties of d-Limonene. MAIN METHODS: A rat model was used to compare evolution of TNBS (2,5,6-trinitrobenzene sulfonic acid)-induced colitis after oral feeding with d-Limonene compared to ibuprofen. Peripheral levels of TNF-α (Tumor Necrosis Factor alpha) were assessed in all animals. Cell cultures of fibroblasts and enterocytes were used to test the effect of d-Limonene respectively on TNFα-induced NF-κB (nuclear factor-kappa B) translocation and epithelial resistance. Finally, plasmatic inflammatory markers were examined in an observational study of diet supplementation with d-Limonene-containing orange peel extract (OPE) in humans. KEY FINDINGS: Administered per os at a dose of 10mg/kg p.o., d-Limonene induced a significant reduction of intestinal inflammatory scores, comparable to that induced by ibuprofen. Moreover, d-Limonene-fed rats had significantly lowered serum concentrations of TNF-α compared to untreated TNBS-colitis rats. The anti-inflammatory effect of d-Limonene also involved inhibition of TNFα-induced NF-κB translocation in fibroblast cultures. The application of d-Limonene on colonic HT-29/B6 cell monolayers increased epithelial resistance. Finally, inflammatory markers, especially peripheral IL-6, markedly decreased upon OPE supplementation of elderly healthy subjects submitted or not to 56 days of dietary supplementation with OPE. SIGNIFICANCE: In conclusion, d-Limonene indeed demonstrates significant anti-inflammatory effects both in vivo and in vitro. Protective effects on the epithelial barrier and decreased cytokines are involved, suggesting a beneficial role of d-Limonene as diet supplement in reducing inflammation. Copyright © 2013 Elsevier Inc. All rights reserved. PMID: 23665426 [PubMed – indexed for MEDLINE]
- Cancer Prev Res (Phila). 2013 Jun;6(6):577-84. doi: 10.1158/1940-6207.CAPR-12-0452. Epub 2013 Apr 3. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. Miller JA(1), Lang JE, Ley M, Nagle R, Hsu CH, Thompson PA, Cordova C, Waer A, Chow HH. Author information: (1)The University of Arizona Cancer Center, 1515 N Campbell Ave, Tucson, AZ 85724, USA. firstname.lastname@example.org Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene’s role for breast cancer prevention or treatment. PMCID: PMC3692564 PMID: 23554130 [PubMed – indexed for MEDLINE]
- Altern Med Rev. 2007 Sep;12(3):259-64. D-Limonene: safety and clinical applications. Sun J(1). Author information: (1)Thorne Research, PO Box 25, Dover, ID 83825, USA. email@example.com D-limonene is one of the most common terpenes in nature. It is a major constituent in several citrus oils (orange, lemon, mandarin, lime, and grapefruit). D-limonene is listed in the Code of Federal Regulations as generally recognized as safe (GRAS) for a flavoring agent and can be found in common food items such as fruit juices, soft drinks, baked goods, ice cream, and pudding. D-limonene is considered to have fairly low toxicity. It has been tested for carcinogenicity in mice and rats. Although initial results showed d-limonene increased the incidence of renal tubular tumors in male rats, female rats and mice in both genders showed no evidence of any tumor. Subsequent studies have determined how these tumors occur and established that d-limonene does not pose a mutagenic, carcinogenic, or nephrotoxic risk to humans. In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year. Being a solvent of cholesterol, d-limonene has been used clinically to dissolve cholesterol-containing gallstones. Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer. Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer. PMID: 18072821 [PubMed – indexed for MEDLINE]
- Drug Metab Pharmacokinet. 2004 Aug;19(4):245-63. Cancer prevention by natural compounds. Tsuda H(1), Ohshima Y, Nomoto H, Fujita K, Matsuda E, Iigo M, Takasuka N, Moore MA. Author information: (1)Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, Japan. firstname.lastname@example.org Increasing attention is being paid to the possibility of applying cancer chemopreventive agents for individuals at high risk of neoplastic development. For this purpose by natural compounds have practical advantages with regard to availability, suitability for oral application, regulatory approval and mechanisms of action. Candidate substances such as phytochemicals present in foods and their derivatives have been identified by a combination of epidemiological and experimental studies. Plant constituents include vitamin derivatives, phenolic and flavonoid agents, organic sulfur compounds, isothiocyanates, curcumins, fatty acids and d-limonene. Examples of compounds from animals are unsaturated fatty acids and lactoferrin. Recent studies have indicated that mechanisms underlying chemopreventive potential may be combinations of anti-oxidant, anti-inflammatory, immune-enhancing, and anti-hormone effects, with modification of drug-metabolizing enzymes, influence on the cell cycle and cell differentiation, induction of apoptosis and suppression of proliferation and angiogenesis playing roles in the initiation and secondary modification stages of neoplastic development. Accordingly, natural agents are advantageous for application to humans because of their combined mild mechanism. Here we review naturally occurring compounds useful for cancer chemoprevention based on in vivo studies with reference to their structures, sources and mechanisms of action. PMID: 15499193 [PubMed – indexed for MEDLINE]
- Exp Biol Med (Maywood). 2004 Jul;229(7):567-85. Studies of the isoprenoid-mediated inhibition of mevalonate synthesis applied to cancer chemotherapy and chemoprevention. Mo H(1), Elson CE. Author information: (1)Department of Nutrition and Food Sciences, Texas Woman’s University, Denton, TX 76204, USA. email@example.com Pools of farnesyl diphosphate and other phosphorylated products of the mevalonate pathway are essential to the post-translational processing and physiological function of small G proteins, nuclear lamins, and growth factor receptors. Inhibitors of enzyme activities providing those pools, namely, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and mevalonic acid-pyrophosphate decarboxylase, and of activities requiring substrates from the pools, the prenyl protein transferases, have potential for development as novel chemotherapeutic agents. Their potentials as suggested by the clinical responses recorded in Phase I and II investigations of inhibitors of HMG CoA reductase (the statins), of mevalonic acid-pyrophosphate decarboxylase (sodium phenylacetate and sodium phenylbutyrate), and of farnesyl protein transferase (R115777, SCH66336, BMS-214662, Tipifarnib, L-778,123, and, prematurely, perillyl alcohol) are dimmed by dose-limiting toxicities. These nondiscriminant growth-suppressive agents induce G1 arrest and initiate apoptosis and differentiation, effects attributed to modulation of cell signaling pathways either by modulating gene expression, suppressing the post-translational processing of signaling proteins and growth factor receptors, or altering diacylglycerol signaling. Diverse isoprenoids and the HMG CoA reductase inhibitor, lovastatin, modulate cell growth, induce cell cycle arrest, initiate apoptosis, and suppress cellular signaling activities. Perillyl alcohol, the isoprenoid of greatest clinical interest, initially was considered to inhibit farnesyl protein transferase; follow-up studies revealed that perillyl alcohol suppresses the synthesis of small G proteins and HMG CoA reductase. In sterologenic tissues, sterol feedback control, mediated by sterol regulatory element binding proteins (SREBPs) 1a and 2, exerts the primary regulation on HMG CoA reductase activity at the transcriptional level. Secondary regulation, a nonsterol isoprenoid-mediated fine-tuning of reductase activity, occurs at the levels of reductase translation and degradation. HMG CoA reductase activity in tumors is elevated and resistant to sterol feedback regulation, possibly as a consequence of aberrant SREBP activities. Nonetheless, tumor reductase remains sensitive to isoprenoid-mediated post-transcriptional downregulation. Farnesol, an acyclic sesquiterpene, and farnesyl homologs, gamma-tocotrienol and various farnesyl derivatives, inhibit reductase synthesis and accelerate reductase degradation. Cyclic monoterpenes, d-limonene, menthol and perillyl alcohol and beta-ionone, a carotenoid fragment, lower reductase mass; perillyl alcohol and d-limonene lower reductase mass by modulating translational efficiency. The elevated reductase expression and greater demand for nonsterol products to maintain growth amplify the susceptibility of tumor reductase to isoprenoids, therein rendering tumor cells more responsive than normal cells to isoprenoid-mediated growth suppression. Blends of lovastatin, a potent nondiscriminant inhibitor of HMG CoA reductase, and gamma-tocotrienol, a potent isoprenoid shown to post-transcription-ally attenuate reductase activity with specificity for tumors, synergistically affect the growth of human DU145 and LNCaP prostate carcinoma cells and pending extensive preclinical evaluation, potentially offer a novel chemotherapeutic strategy free of the dose-limiting toxicity associated with high-dose lovastatin and other nondiscriminant mevalonate pathway inhibitors. PMID: 15229351 [PubMed – indexed for MEDLINE]
- Eur J Cancer. 2000 Jun;36(10):1292-7. The state-of-the-art in chemoprevention of skin cancer. Stratton SP(1), Dorr RT, Alberts DS. Author information: (1)Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, AZ 85724, USA. firstname.lastname@example.org The incidence of skin cancer (both melanoma and non-melanoma) continues to grow at an alarming rate. Our chemoprevention strategies include the development of novel agents evaluated by (1) preclinical mechanistic studies in models of ultraviolet (UV) radiation-induced skin carcinogenesis; (2) clinical studies of immunohistochemical surrogate endpoint biomarkers in high-risk patients; and (3) randomised, placebo-controlled phase I, II and III clinical chemoprevention trials. Recent clinical results validate this development model. Molecular targets of chemopreventive strategies for melanoma and non-melanoma skin cancers include the ras and activator protein-1 (AP-1) signal transduction pathways. A transgenic murine melanoma model has been developed for evaluating potential agents in vivo. Agents at various stages of study include the green tea catechin epigallocatechin gallate (EGCG), the limonene derivative perillyl alcohol, the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO), selenium, retinoids and salicylates. New chemopreventive agents that can be used to complement sunscreens may result in decreased incidence, morbidity and mortality of skin cancer. PMID: 10882869 [PubMed – indexed for MEDLINE]
- Cancer Chemother Pharmacol. 1998;42(2):111-7. Phase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee. Vigushin DM(1), Poon GK, Boddy A, English J, Halbert GW, Pagonis C, Jarman M, Coombes RC. Author information: (1)Department of Medical Oncology, Charing Cross Hospital, London, UK. email@example.com PURPOSE: D-Limonene is a natural monoterpene with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. A phase I clinical trial to assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in patients with advanced cancer was followed by a limited phase II evaluation in breast cancer. METHODS: A group of 32 patients with refractory solid tumors completed 99 courses of D-limonene 0.5 to 12 g/m2 per day administered orally in 21-day cycles. Pharmacokinetics were analyzed by liquid chromatography-mass spectrometry. Ten additional breast cancer patients received 15 cycles of D-limonene at 8 g/m2 per day. Intratumoral monoterpene levels were measured in two patients. RESULTS: The MTD was 8 g/m2 per day; nausea, vomiting and diarrhea were dose limiting. One partial response in a breast cancer patient on 8 g/m2 per day was maintained for 11 months; three patients with colorectal carcinoma had prolonged stable disease. There were no responses in the phase II study. Peak plasma concentration (Cmax) for D-limonene ranged from 10.8+/-6.7 to 20.5+/-11.2 microM. Predominant circulating metabolites were perillic acid (Cmax 20.7+/-13.2 to 71+/-29.3 microM), dihydroperillic acid (Cmax 16.6+/-7.9 to 28.1+/-3.1 microM), limonene-1,2-diol (Cmax 10.1+/-8 to 20.7+/-8.6 microM), uroterpenol (Cmax 14.3+/-1.5 to 45.1+/-1.8 microM), and an isomer of perillic acid. Both isomers of perillic acid, and cis and trans isomers of dihydroperillic acid were in urine hydrolysates. Intratumoral levels of D-limonene and uroterpenol exceeded the corresponding plasma levels. Other metabolites were trace constituents in tissue. CONCLUSIONS: D-Limonene is well tolerated in cancer patients at doses which may have clinical activity. The favorable toxicity profile supports further clinical evaluation. PMID: 9654110 [PubMed – indexed for MEDLINE]
- Drug Metab Dispos. 1996 May;24(5):565-71. Identification and characterization of limonene metabolites in patients with advanced cancer by liquid chromatography/mass spectrometry. Poon GK(1), Vigushin D, Griggs LJ, Rowlands MG, Coombes RC, Jarman M. Author information: (1)Cancer Research Campaign Centre for Cancer Therapeutics, Charing Cross Hospital. Limonene is a farnesyl transferase inhibitor that has shown antitumor properties. The drug had been given orally to cancer patients. Plasma and urine samples collected from the patients were examined by reversed-phase HPLC-atmospheric pressure chemical ionization and electrospray ionization MS. The drug underwent rapid conversion to hydroxylated and carboxylated derivatives. Characterization and structural elucidation of the metabolites were achieved by LC/MS and NMR. Five major metabolites were detected in the plasma extracts, namely limonene-1,2-diol, limonene-8,9-diol, perillic acid, an isomer of perillic acid, and dihydroperillic acid. Urinary metabolites comprised the glucuronides of the two isomers of perillic acid, dihydroperillic acid, limonene-8,9-diol, and a monohydroxylated limonene. PMID: 8723738 [PubMed – indexed for MEDLINE]
- JAMA. 1996 May 1;275(17):1349-53. Chemoprevention of breast cancer. O’Shaughnessy JA(1). Author information: (1)Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. PMID: 8614122 [PubMed – indexed for MEDLINE]
- J Cell Biochem Suppl. 1995;22:139-44. Prevention and therapy of mammary cancer by monoterpenes. Gould MN(1). Author information: (1)Department of Human Oncology, University of Wisconsin-Madison 53792, USA. Monoterpenes, found in a wide variety of plants, are a major component of plant essential oils. The unsubstituted monocyclic monoterpene limonene has been shown to prevent carcinogen-induced mammary cancer at both the initiation and the promotion/progression stages. This terpene also causes the complete regression of the majority of advanced rat mammary cancer when added to the diet. Modification of limonene by hydroxylation at various positions increases both its chemopreventive and therapeutic efficacy. For example, the naturally occurring hydroxylated limonene analog perillyl alcohol is 5-10 times more potent than limonene and has a similar therapeutic index. Several cellular, metabolic and molecular activities are associated with terpene exposure. These include induction of phase I and II hepatic detoxification enzymes, selective inhibition of protein isoprenylation, inhibition of CoQ synthesis, and induction of the mannose 6-phosphate/IGFII receptor and TGF beta. Due to the therapeutic efficacy of monoterpenes in experimental model systems, clinical evaluation of this class of compounds has begun in advanced cancer patients. A Phase I trial of limonene is in progress in the UK. Efforts in the US will target perillyl alcohol for Phase I testing. Pre-IND toxicology is currently being completed. Phase I trails are anticipated to begin in the Spring of 1995. We feel that the results of these therapeutic trials, if positive, will facilitate the development of current terpenes and more potent analogs for future chemoprevention trials. PMID: 8538191 [PubMed – indexed for MEDLINE]
- Clin Nutr. 2015 Jul 15. pii: S0261-5614(15)00188-0. doi: 10.1016/j.clnu.2015.06.010. [Epub ahead of print]Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an open-label randomized control trial. Ostan R1, Béné MC2, Spazzafumo L3, Pinto A4, Donini LM4, Pryen F5, Charrouf Z6, Valentini L7, Lochs H8, Bourdel-Marchasson I9, Blanc-Bisson C9, Buccolini F10, Brigidi P11, Franceschi C12, d’Alessio PA13.
BACKGROUND & AIMS:
Eating habits may influence the life span and the quality of ageing process by modulating inflammation. The RISTOMED project was developed to provide a personalized and balanced diet, enriched with or without nutraceutical compounds, to decrease and prevent inflammageing, oxidative stress and gut microbiota alteration in healthy elderly people. This paper focused on the effect on inflammation and metabolism markers after 56 days of RISTOMED diet alone or supplementation with three nutraceutical compounds.
A cohort of 125 healthy elderly subjects was recruited and randomized into 4 arms (Arm A, RISTOMED diet; Arm B, RISTOMED diet plus VSL#3 probiotic blend; Arm C, RISTOMED diet plus AISA d-Limonene; Arm D, RISTOMED diet plus Argan oil). Inflammatory and metabolism parameters as well as the ratio between Clostridium cluster IV and Bifidobacteria (CL/B) were collected before and after 56 days of dietary intervention, and their evolution compared among the arms. Moreover, participants were subdivided according to their baseline inflammatory parameters (erythrocytes sedimentation rate (ESR), C-Reactive Protein, fibrinogen, Tumor Necrosis Factor-alfa (TNF-α), and Interleukin 6) in two clusters with low or medium-high level of inflammation. The evolution of the measured parameters was then examined separately in each cluster.
Overall, RISTOMED diet alone or with each nutraceutical supplementation significantly decreased ESR. RISTOMED diet supplemented with d-Limonene resulted in a decrease in fibrinogen, glucose, insulin levels and HOMA-IR. The most beneficial effects were observed in subjects with a medium-high inflammatory status who received RISTOMED diet with AISA d-Limonene supplementation. Moreover, RISTOMED diet associated with VSL#3 probiotic blend induced a decrease in the CL/B ratio.
Overall, this study emphasizes the beneficial anti-inflammageing effect of RISTOMED diet supplemented with nutraceuticals to control the inflammatory status of elderly individuals.
Ageing; Diet; Inflammation; Nutraceutics; Probiotics; d-Limonene
Entre los años 2006 y 2010 se registraron 326.711 casos incidentes (112.458 y 214.253 tumores malignos y no malignos); el 7% se documentó en menores de 20 años y el resto (93%) en individuos mayores.
El 58% de los tumores se presentó en mujeres, aunque las lesiones malignas fueron más frecuentes entre los hombres (55% versus 45% para las mujeres). El 62% de los tumores tenían un diagnóstico histológico confirmado (rango, 53,3-75,2%).
La tasa de incidencia ajustada por edad fue de 21,0 por 100.000 habitantes, menor para la población pediátrica (5,26 por 100.000 niños entre los 0-19 años y 5,15 por 100.000 niños menores de 15 años) y de 27,38 por 100.000 adultos (mayores de 20 años).
La tasa de incidencia es creciente según el estrato de la edad, siendo superior para los mayores de 75 años (80,99 por 100.000) y más baja entre los niños de 0 a 14 años (5,14 por 100.000). Sin embargo, los patrones de distribución de las diversas histologías difieren sustancialmente según la edad; por ejemplo, las tasas de incidencia del astrocitoma pilocítico, los tumores de células germinales y los embrionarios son mayores entre los más jóvenes y disminuyen con el envejecimiento. En contraste la tasa de incidencia del meningioma aumenta gradualmente con la edad.
Comentario: la incidencia de tumores de SNC viene en aumento. No se menciona si la incidencia viene aumentando de año en año, dato que serìa de utilidad para evaluar alguna variable que influyera en eso. Se hace un tan solo un análisis global, describiendo tipos de tumores, edades en que se presentan, creo que es un tipo de información que se presta para un análisis mucho más rico, teniendo en cuenta que la OMS describe a los celulares como posiblemente carcinògenos, Hay que tener en cuenta que la OMS ha tenido conflicto de intereses, y no los ha declarado, lo cual debe motivar mucho más interés de los usuarios.
En su momento el link original de donde se bajó esta información fue http://www.ehponline.org/members/2005/7561/7561.pdf, el cual ya no muestra el documento.
Y más sobre el tema de conflicto de intereses, a propósito de estudio Repacholi:
Estudio Repacholi en http://www.who.int/peh-emf/meetings/archive/en/keynote4repacholi.pdf, que menciona a la OM S
Conclusión: se necesita bastante cautela con el uso del celular. Qué hacer?
- Mantener lejos de la cabeza al marcar. Dejar unos segundos cuando contesten y luego sí acercar a la oreja. Para evitar el campo de pulso electromagnético, que al llevar bastante energía, calienta tejidos alrededor y causa estrés térmico.
- HABLAR LO MAS CORTO POSIBLE.
- No hablar en ascensores. El equipo automáticamente aumenta la intensidad del campo.
- Usar filtros de ferrita (los de cìrculos concéntricos en el compartimento de la pila)
- Enterarse sobre contaminación electromagnética, electrosmog, contaminación de campos electromagnéticos. La contaminación electromagnètica es silenciosa y mortal: http://www.slideshare.net/guest8dd35a/contaminacin-electromagntica-upload-presentation