Modulation of colon cancer by nutmeg.

Colon cancer is the most common cancer and the third leading cause of cancer mortality in humans. Using mass spectrometry-based metabolomics, the current study revealed the accumulation of four uremic toxins (cresol sulfate, cresol glucuronide, indoxyl sulfate, and phenyl sulfate) in the serum of mice harboring adenomatous polyposis coli (APC) gene mutation-induced colon cancer. These uremic toxins, likely generated from the gut microbiota, were associated with an increase in the expression of the proinflammatory cytokine IL-6 and a disorder of lipid metabolism. Nutmeg, which exhibits antimicrobial activity, attenuated the levels of uremic toxins and decreased intestinal tumorigenesis in Apc(min/+) mice. Nutmeg-treated Apc(min/+) mice had decreased IL-6 levels and normalized dysregulated lipid metabolism, suggesting that uremic toxins are responsible, in part, for the metabolic disorders that occur during tumorigenesis. These studies demonstrate a potential biochemical link among gut microbial metabolism, inflammation, and metabolic disorders and suggest that modulation of gut microbiota and lipid metabolism using dietary intervention or drugs may be effective in colon cancer chemoprevention strategies.

Serum nutrients and habitual dietary intake in colectomized FAP patients in Norway.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) are colectomized in young age in order to avoid development of colorectal cancer. Because colectomy radically changes gastrointestinal physiology, and food avoidance may be present, colectomized patients may be at risk for nutritional deficiency. AIM OF THE STUDY: to evaluate: (1) serum biochemical levels as compared to reference; (2) dietary intake as compared to the recommendations. METHODS: Blood samples, interviews and food frequency questionnaire were collected from 38 colectomized FAP patients with duodenal adenomas (mean age 40 years, range: 24-70). They were recruited from the Norwegian database on FAP. RESULTS: Serum albumin was significantly higher (P < or = 0.0001), and Mg (P = 0.02), ferritin (P < or = 0.001), and cholesterol (P = 0.03) significantly lower, than reference levels. Compared to recommendations, a low intake was seen for folate and fiber (<50%), iron, thiamin, riboflavin (< 25%), and omega-3 fatty acids (8%). Sugar intake exceeded the recommendation, mainly due to a high intake of soft drinks. Food avoidance was reported by 53%. CONCLUSIONS: We would suggest that the nutrient intake among FAP patients should at least meet the recommendations for healthy subjects. Their risk of metachronous cancers should also cause special attention to dietary factors that may prevent nutritional deficiency and carcinogenesis.

Responses of biomarkers of folate and riboflavin status to folate and riboflavin supplementation in healthy and colorectal polyp patients (the FAB2 Study).

Epidemiologic data suggest that increasing folate intake may protect against colorectal cancer. Riboflavin may interact with folate to modulate the effect. A double-blind randomized placebo-controlled intervention study (the FAB2 Study) was carried out in healthy controls and patients with colorectal polyps (adenomatous and hyperplastic) to examine effects of folic acid and riboflavin supplements on biomarkers of nutrient status and on putative biomarkers of colorectal cancer risk (DNA methylation and DNA damage; to be reported elsewhere). Ninety-eight healthy controls and 106 patients with colorectal polyps were stratified for the thermolabile variant of methylene tetrahydrofolate reductase, MTHFR C677T, and were randomized to receive 400 microg of folic acid, 1,200 microg of folic acid, or 400 microg of folic acid plus 5 mg of riboflavin or placebo for 6 to 8 weeks. Blood samples and colon biopsy samples were collected for the measurement of biomarkers of folate and riboflavin status. Supplementation with folic acid elicited a significant increase in mucosal 5-methyl tetrahydrofolate, and a marked increase in RBC and plasma, with a dose-response. Measures of riboflavin status improved in response to riboflavin supplementation. Riboflavin supplement enhanced the response to low-dose folate in people carrying at least one T allele and having polyps. The magnitude of the response in mucosal folate was positively related to the increase in plasma 5-methyl tetrahydrofolate but was not different between the healthy group and polyp patients. Colorectal mucosal folate concentration responds to folic acid supplementation to an extent comparable to that seen in plasma, but with a suggestion of an upper limit.

Assessment of dietary intake and trace element status in patients with ileal pouch-anal anastomosis.

PURPOSE: Panproctocolectomy and ileal pouch-anal anastomosis is the operation of choice for patients with ulcerative colitis and familial polyposis. The long-term nutritional consequences after pouch surgery are unknown. We have assessed the nutritional status of the essential trace elements-zinc, copper, manganese, and selenium-in patients several years (median, 10 (range, 2-15) years) after surgery. METHODS: Fifty-five patients with uncomplicated ileal pouch-anal anastomosis and 46 healthy control subjects were studied. A dietary assessment of trace element intake was undertaken by using a semiquantitative food frequency questionnaire. The patients' trace elements status for zinc, copper, manganese, and selenium was assessed by measuring their concentrations in blood. RESULTS: The dietary intake of individual trace elements was similar in both groups (all P values > 0.4). There was no significant difference in the concentrations of plasma copper, zinc, and selenium between patients and healthy control subjects (all P values > 0.07). The concentration of whole blood manganese was significantly higher (P = 0.004) in patients (median, 178.5 nmol/l; range, 59-478 nmol/l) compared with healthy control subjects (median, 140 nmol/l; range, 53-267 nmol/l). Four (7 percent) patients had manganese concentrations more than three standard deviations of the mean of control group (>255 nmol/l). CONCLUSIONS: This study shows that patients who have had uncomplicated pouch surgery have a normal dietary intake of trace elements and do not develop deficiencies in copper, zinc, manganese, and selenium. However, these patients may be at increased risk of manganese toxicity.

Selenoprotein levels in patients with colorectal adenomas and cancer.

OBJECTIVES: Selenium is a trace mineral that, as a constituent of certain selenoproteins, acts as an antioxidant. Results of studies addressing a cancer protective effect of selenium have been controversial. The present study measured selenoprotein-P, extracellular glutathione peroxidase, and plasma selenium in patients with colon cancer and adenomatous colon polyps to determine whether patients who develop colorectal adenomas or cancer are selenium deficient. METHODS: Patients who presented to an endoscopy center for colonoscopy or who were referred to our institution with a newly diagnosed colorectal cancer were offered enrollment in the trial. Each patient underwent phlebotomy, usually immediately after colonoscopy. In all, 103 patients were enrolled in the study. Of these, 33 patients were found to have colorectal cancer, 35 adenomatous colon polyps, and 17 normal examinations. A total of 18 patients had other diagnoses and were not included in the study group. RESULTS: The mean age for the colorectal cancer group was 69 yr, for the adenomatous colon polyp group 62 yr, and for the normal group was 56 yr. The adenomatous colon polyp and normal groups were predominantly female. Based on one way analysis of variance tests, there was no significant difference in selenoprotein-P or plasma selenium levels or extracellular glutathione peroxidase activity among the three groups (p = 0.28, 0.098, and 0.35 respectively). CONCLUSIONS: The present data suggest that patients with adenomatous colon polyps and those with colorectal cancer are not selenium deficient.

Plasma (carotenoids, retinol, alpha-tocopherol) and tissue (carotenoids) levels after supplementation with beta-carotene in subjects with precancerous and cancerous lesions of sigmoid colon.

OBJECTIVES: (1) To compare tissue and plasma carotenoids status of healthy subjects and subjects with pre-cancer and cancer lesions; (2) to evaluate the effect of beta-carotene supplementation on the concentrations of other carotenoids in tissue (luteine + zeaxanthin, cryptoxanthin, lycopene, alpha-carotene) and in plasma and also retinol and alpha-tocopherol levels. DESIGN: Eighteen subjects were divided into three groups on the basis of colonoscopy and histological analytical findings: four healthy subjects (control group A); seven subjects affected by adenomatous polyps (group B with pre-cancer lesions); seven subjects suffering from colonic cancer (group C). Blood and colonic biopsy samples were taken (of colon and rectal mucosa) before and after beta-carotene supplementation in all subjects. Groups A and B received a daily dose of beta-carotene (30 mg/die) for 43 d. Group C's supplementation was terminated at the time which was performed, usually within 15 d. The tissue and plasma concentration of carotenoids, retinol and alpha-tocopherol were determined by high-performance liquid chromatography. RESULTS: The tissue concentrations of each carotenoid were similar in all the intestinal sites examined as regards groups A and B, although there was a high degree of intra individual variability within each group. Only beta-carotene made significant increases (P < 0.001) after supplementation. The subjects with cancer show tissue levels for each carotenoid lower than those of healthy subjects or subjects with polypous. The plasma levels of alpha-tocopherol did not change after supplementation while significant increases were noted of retinol, alpha-carotene (P < 0.01) and of beta-carotene (P < 0.001). CONCLUSIONS: The patients with colonic cancer seemed to undergo a significant reduction in their antioxidant reserves with respect to the normal subjects and or polyps. We can confirm that oral B-carotene supplementation induces also an increase in plasma alpha-carotene in all groups.

[Differences in serum selenium concentration in probands and patients with colorectal neoplasms in Zagreb, Croatia]. / Unterschiede in den Selenkonzentrationen im Serum bei Gesunden und bei Patienten mit kolorektaler Neoplasie in Zagreb, Kroatien.

Serum selenium concentration (scSe) (microgram/l) was comparatively measured in healthy persons (n = 202), patients with colorectal adenoma(s) (n = 44) and colorectal carcinoma (n = 48). In patients with adenoma(s) scSe (59.05 +/- 15) was significantly lower (p < 0.001) compared with scSe in the control group (66.8 +/- 14.43). Hyposelenemia was more pronounced in patients with multiple polyps (n = 11) than in patients with single adenoma (n = 33) (p < 0.05). Patients with colorectal carcinoma had also significant decrease in scSe (50.93 +/- 13.81) compared with the control group (p < 0.001 and with the adenoma patients (p < 0.001). According to the analysis of variance, highly significant differences were found among the cancer patients stratified in Dukes' stages A to D (p < 0.001), indicating a strong negative correlation between extension of cancer and hyposelenemia. Furthermore, hyposelenemia seemed to be more pronounced in the mucinous type of carcinoma than in adenocarcinoma (p = 0.056). This results indicate that hyposelenemia is strongly associated with colorectal neoplasia (including extension and severity of the disease) and that it may not only be a result but also one of tumorogenic factors. That means that selenium supplementation could be important in prevention or even adjuvant therapy of colorectal cancer.