Dietary sesame seeds elevate alpha- and gamma-tocotrienol concentrations in skin and adipose tissue of rats fed the tocotrienol-rich fraction extracted from palm oil.

The metabolism of tocotrienol remains unclear. We studied the distribution of tocotrienol in rats fed the tocotrienol-rich fraction extracted from palm oil. We have previously shown that dietary sesame seeds markedly elevate the tocopherol concentration in rats. In this study, we also examined the effect of dietary sesame seeds on the tocotrienol concentration. In experiment 1, rats (4-wk-old) were fed the diet with alpha-tocopherol alone or with alpha- and gamma-tocotrienols. In experiment 2, the effect of dietary sesame seeds on tocopherol and tocotrienol concentrations in rats fed the diet with tocopherol and tocotrienol was studied. The rats were fed the experimental diet for 8 wk in both experiments. alpha- and gamma-Tocotrienols accumulated in the adipose tissue and skin, but not in plasma or other tissues, of the rats fed tocotrienols. Dietary sesame seeds elevated (P < 0.05) tocotrienol concentrations in the adipose tissue and skin, but did not affect their concentrations in other tissues or in plasma. The gamma-tocopherol concentration in all tissues and plasma of rats fed gamma-tocopherol was extremely low but was elevated (P < 0.05) in many tissues by feeding sesame seeds. These data suggest that the transport and tissue uptake of vitamin E isoforms are different. Dietary sesame seeds elevate the concentrations of both tocopherols and tocotrienols.     

Validation of a food frequency questionnaire measurement of selected nutrients using biological markers in African-American men

OBJECTIVE: To validate selected nutrients assessed by the food frequency questionnaire (FFQ) used in the Harvard cohort studies in an African-American group. DESIGN: Blood aliquots were pooled for each decile of intake of two carotenoids and alpha tocopherol as measured by FFQ. These pooled samples were analyzed for nutrient content, and the resultant blood levels were plotted against the median for each decile of intake. In addition, adipose tissue samples taken from each man were analyzed for content of specific fatty acids. We calculated the Spearman correlations comparing intakes of specific fatty acids as percent of total fat intake, adjusted for energy intake, as measured by FFQ, with the percentage of the corresponding fatty acid in adipose tissue. SUBJECTS AND SETTINGS: African-American men (N=104) with prostate cancer were recruited from a Detroit physician's practice and completed a detailed FFQ. RESULTS: Comparing decile 10 with decile 1 intake of nutrients as measured by FFQ, there was a 32% higher blood level of lycopene, a 288% higher blood level of beta carotene and a 100% higher blood level of alpha tocopherol. The Spearman correlation coefficients between intakes of linoleic acid, alpha linolenic acid, long-chain n-3 fatty acids and trans fatty acid measured by FFQ and the corresponding adipose tissue levels were between 0.10 and 0.47. CONCLUSION: The FFQ was able to distinguish meaningful differences in biochemical measurements of selected nutrients and presumably corresponding differences in the extremes of intake in African-American men with prostate cancer who were likely to be motivated to report accurately. However, the results found are similar to those found in other populations.     

Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer

Animal studies suggest that dietary polyunsaturated fatty acids (PUFAs) of the n-6 class, found in corn and safflower oils, may be precursors of intermediates involved in the development of mammary tumors, whereas long-chain (LC) n-3 PUFAs, found in fish oil, can inhibit these effects. This case-control study was designed to examine the relationship between the PUFA composition of breast adipose tissue and the risk of breast cancer. Using fatty acid levels in breast adipose tissue as a biomarker of past qualitative dietary intake of fatty acids, we examined the hypothesis that breast cancer risk is negatively associated with specific LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) and positively associated with n-6 PUFAs (linoleic acid and arachidonic acid). Breast adipose tissue was collected from 73 breast cancer patients and 74 controls with macromastia. The fatty acid levels were determined by gas-liquid chromatography. A logistic regression model was used to obtain odds ratio estimates while adjusting for age. The age-adjusted n-6 PUFA (linoleic acid and arachidonic acid) content was significantly higher in cases than in controls (P = 0.02). There was a trend in the age-adjusted data suggesting that, at a given level of n-6 PUFA, LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) may have a protective effect (P = 0.06). A similar inverse relationship was observed with LC n-3-to-n-6 ratio when the data were adjusted for age (P = 0.09). We conclude that total n-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that LC n-3 PUFAs, derived from fish oils, may have a protective effect.     

不同膳食脂肪酸对大鼠乳腺癌组织脂肪酸组成和脂代谢基因表达的影响

目的探讨不同膳食脂肪酸组成影响大鼠乳腺癌发生、发展的可能分子机制。方法用8种不同膳食脂肪酸组成(SFA、MUFA、n-6PUFA、n-3PUFA、1∶1n-6/n-3、5∶1n-6/n-3、10∶1n-6/n-3、1∶2∶1S/M/P其中n-6/n-31∶1)喂养SD雌性大鼠,并在大鼠乳腺癌模型的基础上,用气相色谱内标法观察大鼠乳腺组织脂肪酸组成改变,RT-PCR分析组织脂代谢调控基因(FAS、COX-2和5-LOX)的表达。结果在不同膳食脂肪酸构成中,只有1∶1n-6/n-3能有效抑制大鼠乳腺癌的发生。不同膳食脂肪酸构成可导致大鼠乳腺组织脂肪酸组成发生相应变化,且各组间的脂肪酸含量有显著差异。高乳腺癌诱发的SFA、MUFA、n-6PUFA、5∶1n-6/n-3、10∶1n-6/n-3和1∶2∶1S/M/P喂养组乳腺组织含有较多的C18∶1、C18∶2和C20∶4,而EPA和DHA含量极少。无或低乳腺癌诱发的n-3PUFA和1∶1n-6/n-3喂养组乳腺组织EPA和DHA明显增多,C20∶4含量显著减少。RT-PCR结果显示1∶1n-6/n-3低诱癌组较相应对喂组上调FAS、COX-2和5-LOXmRNA表达力度明显弱于其它高乳腺癌诱发组。结论不同膳食脂肪酸组成能明显改变大鼠乳腺组织脂肪酸组成,进而影响脂代谢基因FAS、COX-2和5-LOX表达,可能是大鼠乳腺癌发生的分子机制之一。     

Dietary predictors of concentrations of polychlorinated biphenyls in breast adipose tissue of women living in Ontario,Canada

The authors evaluated dietary predictors of concentrations of 11 polychlorinated biphenyls (PCBs) in breast adipose tissue from 190 women with benign breast disease who live in Ontario, Canada. Consumption of fish was positively correlated with, and the most consistent dietary predictor of, breast tissue PCB levels. Dietary predictors accounted for < 8% of the variation in breast adipose tissue PCB levels. Age was positively and most strongly associated with tissue PCB levels, perhaps representing long-term dietary intake and the complex interplay of absorption, metabolism, distribution, and excretion.     

Retinoids,Carotenoids, and Tocopherols in Breast Adipose Tissue and Serum of Benign Breast Disease and Breast Cancer Patients

Various retinoic acid (RA) isomers (all-trans, 13-cis, 11-cis, and 9-cis) as well as retinol, carotenoids, and tocopherol concentrations were determined in both serum and breast adipose tissue of 22 benign breast disease patients and 52 breast cancer patients categorized into 4 stages by malignancy. Serum RA isomers were analyzed by a newly developed sensitive method combining a high-performance liquid chromatography and a gas chromatography-mass spectrometry, and retinol, carotenoid, and tocopherol concentrations using a high-performance liquid chromatography system. The breast cancer patients showed significantly lower serum retinol, whereas significantly higher breast adipose tissue retinol concentration than those of benign breast disease patients. Although breast cancer patients showed significantly higher serum all-trans and 13-cis RA concentrations, 11-cis RA in breast adipose tissue was significantly lower in the breast cancer patients than those of benign breast disease patients and it was associated with the stage of malignancy. The current study indicates that the retinol and RA isomers in the target tissue of breast tumor patients are not reflecting their concentrations in circulation. The mechanisms of tissue specific uptake of RA isomers and their functions warrant further studies.     

Adipose tissue biomarkers of fatty acid intake

BACKGROUND: Biomarkers can provide a more accurate measure of long-term intake than can dietary questionnaires. OBJECTIVE: The objective was to identify which adipose tissue fatty acids are suitable biomarkers of intake as assessed with a validated food-frequency questionnaire. DESIGN: Costa Rican men with a mean (+/- SD) age of 56 +/- 11 y (n = 367) and women aged 60 +/- 10 y (n = 136) completed a 135-item food-frequency questionnaire and provided an adipose tissue sample. Fifty fatty acids were identified by capillary gas chromatography. Correlation coefficients were calculated after adjustment for age, sex, body mass index, and smoking status. RESULTS: The best adipose tissue marker for total intake of saturated fatty acids was 15:0 + 17:0 (r = 0.18). Both 15:0 and 17:0 were also the best correlates of dairy product intake (r = 0.31 for each). The diet-adipose tissue correlations for n-3 fatty acids were r = 0.34 for 18:3, r = 0.15 for 20:5, and r = 0.18 for 22:6. Fish intake correlated significantly with these adipose tissue n-3 fatty acids. Dietary and adipose tissue n-6 fatty acids were highly correlated: 18:2 (r = 0.58) and 18:3 (r = 0.24). The best indicators of total trans fatty acid intake were ct18:2n-6 and tc18:2n-6 (r = 0.58 for each); total 18:1 trans fatty acid (r = 0.45) and 16:1 trans fatty acid (r = 0.16) were the next best indicators. CONCLUSIONS: Adipose tissue is a suitable biomarker of dietary fatty acid intake, particularly for n-3 and n-6 cis polyunsaturated fatty acids and trans fatty acids. Ideally, adipose tissue and dietary questionnaires should complement, rather than substitute for, each other in epidemiologic studies.     

Conjugated linoleic acid content in breast adipose tissue of breast cancer patients and the risk of metastasis

The association between the level of conjugated linoleic acid (CLA) in breast adipose tissue at the time of diagnosis and the subsequent development of metastasis was examined in a cohort of 209 patients presenting with an initially localized breast cancer. CLA level in breast adipose tissue was used as a qualitative biomarker of its past dietary intake. Biopsies of adipose tissue were obtained at the time of initial surgery. A CLA-enriched fraction was prepared by high performance liquid chromatography and CLA measured as a percentage of total fatty acids, using capillary gas chromatography. Mean CLA level was low (0.44% of total fatty acids) and the range between patients was narrow (0.19-0.85). With a median follow-up time of 7.5 yr, 45 patients developed metastases. A Cox proportional hazard regression model was used to identify prognostic factors. We did not find any significant association between CLA level in adipose fat and either the prognostic factor (tumor size, nodal status, histoprognostic grade, mitotic index, and estrogen or progesterone receptors) or the risk of metastasis or death. We concluded that CLA are unlikely to be involved in survivorship. However, the hypothesis that a higher intake of CLA might have a protective effect on the risk of metastasis cannot be ruled out from these data, since the level of CLA in breast cancer patients' adipose tissue is likely to be too low and the range of CLA distribution too narrow for any protection to be detectable.     

Adipose tissue fatty acid composition and its relations to diet and plasma lipid concentrations in hemodialysis patients

Adipose tissue fatty acid composition, serum lipid profile, and dietary intake of 37 patients on maintenance hemodialysis were studied. In August 1982, 1984, and 1986, analyses were carried out in 15 normotriglyceridemic (NTG) and 22 hypertriglyceridemic (HTG; type IV hyperlipidemia) patients. No correlations were found between dietary intake of polyunsaturated fatty acids (PUFAs), ratio of polyunsaturated to saturated fatty acids (P-S ratio), and carbohydrate content on the one hand and serum lipid concentrations on the other in the two groups. Adipose tissue linolenic acid correlated negatively with serum cholesterol in both groups. Strong correlations were found between dietary intake of PUFAs and adipose tissue linoleic acid content, between PUFAs and the double-bond index, between P-S ratio and adipose tissue linoleic acid content, and between P-S ratio and the double-bond index. No significant differences in dietary intake or adipose tissue fatty acid composition were observed between NTG and HTG patients. Thus, no evidence was found for exogenous dietary influences on serum lipid concentrations. The adipose tissue linoleic acid content did reflect the dietary intake of PUFAs.     

Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer.

The etiology of human breast cancer is unknown; accepted risk factors, e.g., menstrual, reproductive, and family histories, are implicated in less than half of all cases. Various halogenated hydrocarbons--acting as either co-carcinogens or promoting agents--which are derived from the environment and are concentrated in human fatty stores, may also play a role in breast cancer risk. A pilot study was undertaken to measure and compare levels of chemical residues in mammary adipose tissue from women with malignant and nonmalignant breast disease. Elevated levels of polychlorinated biphenyls, bis (4-chlorophenyl)-1,1 dichloroethene, and bis(4-chlorophenyl)-1,1,1 trichloroethane were found in fat samples from women with cancer, compared with those who had benign breast disease. These results, although preliminary, suggest a role for environmentally derived suspect carcinogens in the genesis of mammary carcinoma.     

Effect of sampling site on fatty acid composition of human breast adipose tissue

The effect of sampling site and proximity of malignant tumor on the relative fatty acid composition of human breast adipose tissue was studied in 10 cases of breast cancer. The four anatomic quadrants of breast did not statistically significantly differ from each other in relation to any of the 30 fatty acids studied. Proximity of the malignant tumor did not affect the relative fatty acid composition of fat when compared with more distant sampling sites. Representative samples of breast adipose tissue for fatty acid composition analysis can be obtained from tissue adjacent to the tumor.     

Effect of sampling site on fatty acid composition of human breast adipose tissue

The effect of sampling site and proximity of malignant tumor on the relative fatty acid composition of human breast adipose tissue was studied in 10 cases of breast cancer. The four anatomic quadrants of breast did not statistically significantly differ from each other in relation to any of the 30 fatty acids studied. Proximity of the malignant tumor did not affect the relative fatty acid composition of fat when compared with more distant sampling sites. Representative samples of breast adipose tissue for fatty acid composition analysis can be obtained from tissue adjacent to the tumor.     

Dietary Associations with a Breast Cancer Risk Biomarker Depend on Menopause Status

We investigated how timing influences the role of diet in breast cancer risk with a cross-sectional study of pre-malignant change in breast tissue. Women with an elevated risk of developing breast cancer (33 premenopausal and 32 postmenopausal) completed the National Cancer Institute's food frequency questionnaire and underwent random periareolar fine-needle aspiration for evaluation of cytologic atypia, an established risk biomarker. Fatty acid composition of breast adipose was measured in 32 (49%) subjects. We found that premenopausal and postmenopausal women had similar diets, but the associations between atypia and intake of total n-3 polyunsaturated fatty acids (PUFA) and soy differed by menopause status (both P _interaction < 0.001). Total n-3 PUFA intake was inversely associated with atypia among premenopausal women (P < 0.0001), but not among postmenopausal women (P = 0.91); associations were similar for soy (P = 0.0003 and P = 0.48, respectively). This pattern of dietary interaction with menopause was mirrored in tissue fatty acids (P _interaction < 0.05), wherein 1) higher levels of linolelaidic acid (an industrially-produced trans fat) and 2) lower levels of docosahexaenoic acid (the predominant long-chain n-3 PUFA) in breast adipose were associated with atypia in premenopausal (both P < 0.05) but not postmenopausal women (both P > 0.37). Dietary associations with breast cancer risk are stronger prior to menopause.     

Relationship of diet to the fatty acid composition of human adipose tissue structural and stored lipids

The habitual intake of 20 healthy free-living subjects was determined by two 7-day food records. Documented fatty acid intakes were utilized to examine the influence of fatty acid intake on fatty acid composition of stored and structural lipids in subcutaneous adipose tissue. Subjects with higher intakes of saturated fatty acids exhibited increased levels of total saturated fatty acids and decreased polyunsaturated fatty acids in adipose tissue triglycerides (p less than 0.01). The dietary P/S ratio was significantly related to the saturated and polyunsaturated content of stored lipids. In the phospholipid fraction, relationships were found between dietary C18:2(6) and the P/S ratio of phosphatidylcholine (p less than 0.05). The essential fatty acid content of the two phospholipids studied was related to the dietary fats consumed. Relationships were identified between major fatty acids in the triglyceride and phospholipid fraction. Although diet was found to relate to fatty acid composition, the structural lipids in human adipose tissue appear more resistant to compositional change than stored triglycerides.     

Influence of dietary intake of energy and carbohydrate on the proportion of saturated and monounsaturated fatty acids in adipose tissue of middle aged men

The fatty acid composition of subcutaneous tissue has been determined in a population sample of apparently healthy middle aged men from Southern Italy. Dietary appraisal has been carried out by evaluating the usual pattern of food consumption during the year preceding the interview. The whole population sample was subdivided into three tertiles on the basis of the energy intake by the different individuals. The proportion of adipose tissue polyunsaturated fatty acids was relatively low in the high energy tertile III and high in the low energy tertile reflecting parallel differences in the intake of polyunsaturated fatty acids. The percentage of monounsaturated fatty acids (mainly oleic acid) was relatively high (p less than 0.01) and that of saturated fatty acids (mainly palmitic acid) relatively low (p less than 0.05) in the high energy tertile (III) as compared to the low energy tertile (I); these differences were independent of the amount and type of dietary fatty acids. Total energy was positively correlated (r = .87, p less than 0.01) to carbohydrate intake (g/day). Dietary carbohydrates (g/day) were inversely related to adipose tissue saturated fatty acids (r = -.40, p less than 0.001) and directly correlated to adipose tissue monounsaturated fatty acids (p = .40, p less than 0.001). Carbohydrate intake was related to adipose tissue monounsaturated and saturated fatty acids independently of daily energy intake. On the other hand when the influence of dietary carbohydrates was eliminated, no correlation was detectable any longer between energy intake and adipose tissue fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review

The role of dietary fatty acids on cancer is still controversial. To examine the current literature on the protective role of conjugated linoleic acid (CLA) and marine long-chain fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and the risk of breast and prostate cancer, data from 41 case-control and cohort studies and relevant in vitro and animal experiments were included in this 2000-2010 revision. Epidemiological studies on CLA intake or its tissue concentration related to breast and prostate tumorigenesis are not conclusive; EPA and DHA intake have shown important inverse associations just in some studies. Additional research on the analysed association is required.     

Organochlorine compounds in human breast fat from deceased with and without breast cancer and in a biopsy material from newly diagnosed patients undergoing breast surgery

Epidemiological studies have related the incidence of mammary cancer to the dietary intake of fat and/or meat. Since organochlorine compounds (e.g., polychlorinated biphenyls (PCB) and DDT (and its metabolite DDE] are accumulated in the adipose tissue it was tempting to suggest a relationship between levels of PCB and "DDT" (i.e., DDT + DDE) in breast fat tissue and the occurrence of mammary cancer. To elucidate this theory, the organochlorine levels of 14 breast fat tissue samples from breast cancer patients and similar samples from 18 deceased mammary cancer patients were compared to that of 21 similar samples from noncancer patients and finally to adipose tissue samples from 35 non-cancer autopsy specimens. No significant differences were traced. Thus it seems that the accumulation of PCB and DDT measured in breast fat tissue do not relate to the occurrence of mammary cancer.     

Assessment of individual fatty acid intake

Dietary assessment of individual fatty acid intake is difficult due to a number of limitations. Information regarding the type, quantity and brand-name of fat used in cooking and at the table is required. In addition, margarine manufacturers may change the component oils used for reasons of cost, which changes the fatty acid composition of their products from season-to-season. Independent markers of fatty acid intake are required, therefore, to compensate for these limitations. Adipose tissue concentrations have been used as a measure of habitual intake of fatty acid groups and individual fatty acids in numerous studies. Saturated (SFA) and monounsaturated fatty acids (MUFA) are generally poorly correlated with adipose tissue concentrations, which can be explained partly by endogenous synthesis. In general, adipose tissue concentrations of exogenously-produced fatty acids (n-3 and n-6 polyunsaturated fatty acids (PUFA)) are well correlated with estimates of habitual intake. Correlations between dietary trans unsaturated fatty acids (TUFA) and adipose tissue concentrations vary between countries, which may be due to differences in dietary sources. Correlations may be affected by differences in bioavailability or selective retention of fatty acids in certain tissue lipids.     

Soy Consumption and Histopathologic Markers in Breast Tissue Using Tissue Microarrays

This study examined the relation of soy intake with hormonal and proliferation markers in benign and malignant breast tissue using tissue microarrays (TMAs). TMAs with up to 4 malignant and 4 benign tissue samples for 268 breast cancer cases were constructed. Soy intake in early life and in adulthood was assessed by questionnaire. The TMAs were stained for estrogen receptor (ER) α, ERβ, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), proliferating cell nuclear antigen (PCNA), and Ki-67 using standard immunohistochemical methods. Logistic regression was applied for statistical analysis. A higher percentage of women showed positive marker expression in malignant than in benign tissue. With one exception, HER2/neu, no significant associations between soy intake and pathologic markers were observed. Early life soy intake was associated with lower HER2/neu and PCNA staining of malignant tissue. In benign tissue, early life soy intake showed higher ER and PR expression, but no difference in proliferation markers. The results of this investigation provide some assurance that soy intake does not adversely affect markers of proliferation. TMAs were shown to be a useful tool for epidemiologic research.     

Identification of a dietary pattern characterized by high-fat food choices associated with increased risk of breast cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

Epidemiological studies conducted thus far have mainly used a single-nutrient approach which may not be sufficient in detecting diet-cancer relationships. The aim of the study was to examine the association of a food pattern based on explained variations in fatty acid intake by means of reduced rank regression with breast cancer risk. Study participants were female subjects (n 15,351) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study free of cancer at baseline and with complete dietary and outcome information followed for an average of 6.0 years. Among those, 137 incident cases of invasive breast cancer were identified. We identified a food pattern characterized by low consumption of bread, and fruit juices, and high consumption of processed meat, fish, butter and other animal fats, and margarine explaining >42 % of total variation in fatty acid intake (SFA, MUFA, n-3 PUFA, n-6 PUFA). Intake of all four fatty acid fractions was positively associated with the pattern score. Adherence to this food pattern adjusted for covariates was associated with a two-fold risk (hazard ratio 2.00; 95 % CI 1.30, 3.09) of breast cancer comparing extreme tertiles of the pattern score. There was no evidence of effect modification by menopausal status, overweight status and use of hormone replacement therapy, respectively. In conclusion, a food pattern characterized by high-fat food choices was significantly associated with increased risk of breast cancer. Given that the food pattern was high in all fatty acid fractions, we found evidence for total dietary fat rather than for specific fatty acids to be associated with breast cancer risk.