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Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):717-25.

Heme and chlorophyll intake and risk of colorectal cancer in the Netherlands cohort study.

Balder HFVogel JJansen MCWeijenberg MPvan den Brandt PAWestenbrink Svan der Meer RGoldbohm RA.

Department Food and Chemical Risk Analysis, TNO Quality of Life, Zeist, the Netherlands. balder@voeding.tno.nl

 

BACKGROUND: The evidence for red meat as a determinant of colorectal cancer remains equivocal, which might be explained by differences in heme content. Heme is the pro-oxidant, iron-containing porphyrin pigment of meat and its content depends on the type of meat. Chlorophyll from green vegetables might modify this association.

METHODS: The Netherlands Cohort Study was initiated in 1986 when a self-administered questionnaire on risk factors for cancer was completed by 120,852 subjects ages 55 to 69 years.

After 9.3 years of follow-up through the Cancer Registry, 1,535 incident colorectal cancer cases (869 men and 666 women) were available. Nineteen of the 150 items in the validated dietary questionnaire related to consumption of specific types of fresh and processed meat.

Heme iron content was calculated as a type-specific percentage of the total iron content and chlorophyll content of vegetables was derived from the literature.

RESULTS: Multivariate rate ratios for quintiles of heme iron intake and colon cancer were 1.00, 0.98, 1.04, 1.13, and 1.29 (P(trend) = 0.10) among men and 1.00, 1.31, 1.44, 1.18, and 1.20 (P(trend) = 0.56) among women, respectively.

No consistent associations were observed for rectal cancer.

Rate ratios for colon cancer increased across successive quintiles of the ratio of heme/chlorophyll among men only (1.00, 1.08, 1.01, 1.32, and 1.43; P(trend) = 0.01).

No associations were observed between fresh meat and colorectal cancer.


CONCLUSION: Our data suggest an elevated risk of colon cancer in men with increasing intake of heme iron and decreasing intake of chlorophyll. Further research is needed to confirm these results.


PMID: 16614114 [PubMed - indexed for MEDLINE]

 

J Nutr. 2005 Aug;135(8):1995-2000.

Natural chlorophyll but not chlorophyllin prevents heme-induced cytotoxic and hyperproliferative effects in rat colon.

de Vogel JJonker-Termont DSKatan MBvan der Meer R.

Wageningen Centre for Food Sciences (WCFS), Nutrition and Health Programme, The Netherlands.

Diets high in red meat and low in green vegetables are associated with an increased risk of colon cancer.

In rats, dietary heme, mimicking red meat, increases colonic cytotoxicity and proliferation of the colonocytes, whereas addition of chlorophyll from green vegetables inhibits these heme-induced effects.

Chlorophyllin is a water-soluble hydrolysis product of chlorophyll that inhibits the toxicity of many planar aromatic compounds.

The present study investigated whether chlorophyllins could inhibit the heme-induced luminal cytotoxicity and colonic hyperproliferation as natural chlorophyll does.

Rats were fed a purified control diet, the control diet supplemented with heme, or a heme diet with 1.2 mmol/kg diet of chlorophyllin, copper chlorophyllin, or natural chlorophyll for 14 d (n = 8/group).

The cytotoxicity of fecal water was determined with an erythrocyte bioassay and colonic epithelial cell proliferation was quantified in vivo by [methyl-(3)H]thymidine incorporation into newly synthesized DNA.

Exfoliation of colonocytes was measured as the amount of rat DNA in feces using quantitative PCR analysis. Heme caused a >50-fold increase in the cytotoxicity of the fecal water, a nearly 100% increase in proliferation, and almost total inhibition of exfoliation of the colonocytes.

Furthermore, the addition of heme increased TBARS in fecal water.

Chlorophyll, but not the chlorophyllins, completely prevented these heme-induced effects.

 

In conclusion, inhibition of the heme-induced colonic cytotoxicity and epithelial cell turnover is specific for natural chlorophyll and cannot be mimicked by water-soluble chlorophyllins.

 

PMID: 16046728 [PubMed - indexed for MEDLINE]


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