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Biomedical subjects

Loki Natarajan

Publications and source records attributed to Loki Natarajan.

At least 19 recordsLinked to original sources

The association between fatigue and inflammatory marker levels in cancer patients: a quantitative review.

Increased cytokine and neopterin levels may be responsible for cancer-related fatigue, the most common complaint among cancer patients. We quantitatively reviewed empirical findings on this topic, focusing on studies not using immunotherapy. PubMed, PsychINFO and BIOSIS were searched for articles published until July 2006. Studies remained unweighted or were weighted according to study quality and sample size. The correlation coefficient r was used for statistical analyses. Heterogeneity among the studies was examined using the I(2) index. Eighteen studies (1037 participants) of moderately high methodological quality were located and statistically analyzed. Most studies measured more than one inflammatory marker, resulting in a total of 58 correlation estimates. In 31 of these, we had to input a null correlation because results had been simply reported as nonsignificant and no further statistical information was available. General analyses based on weighting according to sample size showed a significantly positive correlation between fatigue and circulating levels of inflammatory markers (r=0.11, p<0.0001). Analyses of individual inflammatory markers revealed significantly positive correlations between fatigue and IL-6 (r=0.12, p=0.004), fatigue and IL-1 ra (r=0.24, p=0.0005), and fatigue and neopterin (r=0.22, p=0.0001). Fatigue did not correlate significantly with IL-1 beta (r=0.05, p=0.42) or TNF-alpha (r=0.04, p=0.34). Given its preliminary nature due to the limited available data, this quantitative review showed a positive association between cancer-related fatigue and circulating levels of IL-6, IL-1 ra and neopterin. Future studies examining the relationship between cancer related fatigue and inflammation would benefit from multiple rather than single blood sampling and from repeated daily ratings of the multidimensional nature of fatigue.

Biomarkers↗

Weight gain and recovery of pre-cancer weight after breast cancer treatments: evidence from the women's healthy eating and living (WHEL) study.

PURPOSE: To examine predictors of weight gain following breast cancer diagnosis and subsequent return to pre-cancer weight. OBJECTIVES: To determine (1) the associations of anti-neoplastic chemotherapy and/or, Tamoxifen((R)) therapy on weight change following breast cancer diagnosis, (2) whether chemotherapy modified the effect of specific demographic and tumor characteristics on weight gain, (3) the proportion and characteristics of women who gained significant weight on chemotherapy and returned to their pre-cancer weight during follow-up. SUBJECTS AND METHODS: Participants were 3088 breast cancer survivors, aged 27-74 years. Weight was measured at baseline and years 1 through 6; pre-cancer weight was self-reported. Cancer stage and treatment modalities were obtained by medical record review; demographic and physical activity data were obtained from questionnaires. Weight gain of >/=5% body weight following cancer diagnosis was considered significant. RESULTS: Chemotherapy was significantly associated with weight gain (OR = 1.65, 95% CI = 1.12, 2.43) and Tamoxifen((R)) was not (OR = 1.03, 95% CI = 0.71, 1.51). Tamoxifen((R)) did not modify the effect of either chemotherapy or its different regimens on weight gain. Both types (anthracycline: OR = 1.63, p-value = 0.01, non-anthracycline: OR = 1.79, p = 0.003) and all regimens of chemotherapy (AC: OR = 1.55, p-value = 0.01, CAF: OR = 1.83, p = 0.003, CMF: OR = 1.76, p = 0.004) were associated with weight gain but the associations were not different from one another. Only 10% of participants returned to their pre-cancer diagnosis weight at the follow-up visits; the degree of initial gain (p for trend <0.0001) predicted that return. CONCLUSION: Chemotherapy was associated with clinically meaningful weight gain, and a return to initial weight following weight gain was unlikely.

Adult↗

Correlates of physical activity level in breast cancer survivors participating in the Women's Healthy Eating and Living (WHEL) Study.

BACKGROUND: Physical activity levels among breast cancer survivors are typically low, and knowledge of the correlates of increased physical activity among cancer survivors is limited. The purpose of this study was to examine factors that are associated with physical activity or inactivity among breast cancer survivors. METHODS: Data from 3088 women participating in the Women's Healthy Eating and Living (WHEL) Study, collected prior to randomization, were the focus of the current analyses. Self-reports of physical activity levels, quality of life, depression, and dietary intakes were collected. Pearson correlation analyses were employed to examine the associations among these variables, and multiple regression analyses were performed to examine the relationship between selected health behaviors and physical activity levels, after controlling for demographic, breast cancer-related, and psychosocial variables. RESULTS: Demographic and psychosocial variables were related to physical activity levels (P < 0.001 for all). Cancer treatment type and cancer stage were correlated with survivors' physical activity levels (P < 0.01), but the associations were no longer significant after controlling for demographic variables. Physical activity levels were strongly associated with other health behaviors, especially dietary intakes (P < 0.001), even after controlling for demographic, cancer-related, and psychosocial factors. CONCLUSION: Low physical activity levels in breast cancer survivors are associated with specific behavioral and other factors, which can be considered as indicators of women at higher risk. Findings of significant differences in physical activity levels based on demographic characteristics suggest the importance of promoting physical activity particularly among breast cancer survivors of ethnic minority or lower education levels.

Breast Neoplasms↗

Objective cancer-related variables are not associated with depressive symptoms in women treated for early-stage breast cancer.

PURPOSE: Women with breast cancer are thought to be vulnerable to depression for reasons associated with impact of diagnosis, treatment, and metabolic/endocrine changes. While the literature shows that most of these women do not become clinically depressed, 15% to 30% report elevated depressive symptoms that may be clinically important. The purpose was to identify and determine the relative importance of predictors of depressive symptoms in women treated for early-stage breast cancer. PATIENTS AND METHODS: A total of 2,595 women (< or = 4 years following completion of initial treatment for early-stage breast cancer) provided data on cancer-related variables, personal characteristics, health behaviors, physical functioning/symptoms, and psychosocial variables. Participants were divided into high or low depressive groups using the Center for Epidemiologic Studies Depression Scale screening form. RESULTS: Results of the binary logistic regression analysis were significant (overall R2 = 32.4%). Before entry of psychosocial variables, younger age, being unmarried, poorer physical functioning, and more vasomotor and gastrointestinal symptoms were significant risk factors for elevated depressive symptoms (R2 = 16.1%), but objective cancer-related variables were not. After inclusion of psychosocial variables in the model (DeltaR2 = 16.3%), none of the preceding variables remained significant. Greater risk for depressive symptoms was associated with stressful life events, less optimism, ambivalence over expressing negative emotions, sleep disturbance, and poorer social functioning. CONCLUSION: Depressive symptoms in women treated for early-stage breast cancer are not associated with objective cancer-related factors. Rather, they are most strongly linked with many subjective psychosocial variables.

Adult↗

Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer.

PURPOSE: To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence. PATIENT AND METHODS: Patients included 3215 women diagnosed with early stage breast cancer (Stage I >1 cm., II, and IIIA) who were enrolled either in an observational cohort of breast cancer survivors or were part of the comparison group of a dietary intervention trial to prevent breast cancer recurrence. We computed weight change from 1 year prior to diagnosis to study enrollment. Delayed entry Cox proportional hazards models were used to evaluate associations of categories of weight change with time to recurrence, controlling for known prognostic factors. RESULTS: Neither moderate (5-10%) nor large (> 10%) weight gain (HR 0.8, 95% CI, 0.6-1.1; HR 0.9, 95% CI, 0.7-1.2, respectively) after breast cancer diagnosis was associated with an increased risk of breast cancer recurrence in the early years post-diagnosis (median time of 73.7 months from diagnosis). CONCLUSION: Our research provides evidence that weight gain commonly seen in the first several years following a breast cancer diagnosis does not increase a woman's risk for breast cancer recurrence in the first 5-7 years post-diagnosis. However, this research does not address the effects of weight gain on overall survival or on the risk of other new cancers, other prognostic outcomes of concern to the breast cancer survivor.

Adolescent↗

Validity and systematic error in measuring carotenoid consumption with dietary self-report instruments.

Vegetables and fruits are rich in carotenoids, a group of compounds thought to protect against cancer. Studies of diet-disease associations need valid and reliable instruments for measuring dietary intake. The authors present a measurement error model to estimate the validity (defined as correlation between self-reported intake and "true" intake), systematic error, and reliability of two self-report dietary assessment methods. Carotenoid exposure is measured by repeated 24-hour recalls, a food frequency questionnaire (FFQ), and a plasma marker. The model is applied to 1,013 participants assigned between 1995 and 2000 to the nonintervention arm of the Women's Healthy Eating and Living Study, a randomized trial assessing the impact of a low-fat, high-vegetable/fruit/fiber diet on preventing new breast cancer events. Diagnostics including graphs are used to assess the goodness of fit. The validity of the instruments was 0.44 for the 24-hour recalls and 0.39 for the FFQ. Systematic error accounted for over 22% and 50% of measurement error variance for the 24-hour recalls and FFQ, respectively. The use of either self-report method alone in diet-disease studies could lead to substantial bias and error. Multiple methods of dietary assessment may provide more accurate estimates of true dietary intake.

Adult↗

A prospective study of the effects of female and male marijuana use on in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) outcomes.

OBJECTIVE: This study was undertaken to examine whether marijuana use affects in vitro fertilization and gamete intrafallopian transfer (IVF/GIFT). STUDY DESIGN: Prospective study of 221 IVF/GIFT couples. RESULTS: Amount of lifetime heavy marijuana use adversely affected IVF/GIFT. Women smoking more than 90 times in their lifetime had 27% fewer oocytes retrieved (P = .03) and 1 fewer embryo transferred (P < .05). Women smoking marijuana more than 10 times in their lifetime had infants 17% (P = .01) smaller at birth. If men smoked marijuana 11 to 90 times in their lifetime, there was a 15% decrease in infant birth weight (P = .03); if this increased to more than 90 times, there was a 23% decrease (P = .01). Timing also played a role. Women smoking marijuana 1 year before IVF/GIFT had 25% fewer oocytes retrieved (P = .03), whereas couples had 28% (P = .04) fewer oocytes fertilized. Women and men who smoked in the past 15 years, had 12% (P = .04) and 16% (P = .03) smaller infants, respectively. CONCLUSION: Both timing and amount of marijuana use negatively affected IVF/GIFT.

Adult↗

Increases in plasma carotenoid concentrations in response to a major dietary change in the women's healthy eating and living study.

BACKGROUND: Cohort studies suggest that higher circulating carotenoid concentrations through food sources may reduce breast cancer events. Other intervention studies have not achieved the level of change in circulating carotenoids required to properly test this hypothesis. METHODS: In a randomized trial of 2,922 breast cancer survivors, we examined blood and self-reported diet at baseline and 1 year. Intensive telephone counseling encouraged a plant-based diet in the intervention group. Diet was measured via 24-hour recalls, and a panel of plasma carotenoid concentrations was assessed at both time points. RESULTS: The study intervention was associated with a 51% increase in total carotenoid concentration, from 2.272 +/- 1.294 to 3.440 +/- 2.320 micromol/L, achieved mainly by marked increases in targeted carotenoids: alpha-carotene, beta-carotene, and lutein. For each of these targeted carotenoids, the proportion of the intervention sample remaining below the cutpoint for the lowest baseline quartile decreased by one third to one half. After 1 year of study, half of the intervention group was in the highest baseline quartile. No change in distribution was observed in comparison group. Intervention participants achieved this change by both dietary pattern and vegetable juice consumption. Participants who chose to change dietary pattern without consuming significant quantities of vegetable juice achieved 75% of the level of change observed in other intervention participants. CONCLUSIONS: Innovative telephone counseling intervention and dietary targets in the Women's Healthy Eating and Living study were associated with the level of change in circulating carotenoid concentration necessary to test the diet and breast cancer hypothesis suggested by cohort studies.

Adolescent↗

The effect of sleep-disordered breathing on stages of sleep in patients with Alzheimer's disease.

Patients with Alzheimer's disease (AD) commonly have poor sleep and a high reported incidence of sleep-disordered breathing (SDB). This study examined how the presence of SDB affected sleep stages in AD patients. Sixty-six volunteers with mild - moderate AD underwent home polysomnography. Results showed that patients with SDB spent less of the night in REM sleep than those with no SDB, but there were no differences in other sleep stages. The findings suggest that the decreased amount of REM sleep may be due to the presence of AD and SDB. Treating these patients' SDB may increase their amount of REM sleep, which may result in improved daytime functioning. Controlled trials of SDB treatment in AD are needed to answer this question.

Aged↗

Plasma carotenoids and recurrence-free survival in women with a history of breast cancer.

PURPOSE: Previous studies suggest that diet may affect recurrence or survival rates in women who have been diagnosed with breast cancer. The purpose of this study was to examine the relationship between plasma carotenoid concentration, as a biomarker of vegetable and fruit intake, and risk for a new breast cancer event in a cohort of women with a history of early-stage breast cancer. METHODS: Participants were 1,551 women previously treated for breast cancer who were randomly assigned to the control arm of a diet intervention trial between March 1995 and November 2000. Outcome events were probed during semiannual interviews and verified by medical record review. During the period under study, 205 women had a recurrence or new primary breast cancer. Plasma carotenoid concentrations were measured in baseline blood samples. Hazard ratios (HR) and 95% CIs by quartiles of plasma carotenoids were computed, controlling for tumor stage, grade, and hormone receptor status; chemotherapy and tamoxifen therapy; clinical site; age at diagnosis; body mass index; and plasma cholesterol concentration. RESULTS: Women in the highest quartile of plasma total carotenoid concentration had significantly reduced risk for a new breast cancer event (HR, 0.57; 95% CI, 0.37 to 0.89), controlled for covariates influencing breast cancer prognosis. CONCLUSION: Plasma carotenoids are a biologic marker of intake of vegetables and fruit, so this observation supports findings from previous studies that have linked increased vegetable and fruit intake with greater likelihood of recurrence-free survival in women who have been diagnosed with early-stage breast cancer.

Adult↗

Mesalazine improves replication fidelity in cultured colorectal cells.

Epidemiologic studies indicate that mesalazine has chemopreventive effects in inflammatory bowel disease-associated colorectal cancer. Most of our general understanding of chemoprevention in colorectal cancer is, however, derived from aspirin, which is structurally similar to mesalazine. Herein we determined the influence of aspirin and mesalazine on replication fidelity in cultured colorectal cells. Flow cytometry was used for quantitation of mutation rates at a (CA)13 microsatellite in HCT116 cells (mismatch repair deficient) and HCT116+chr3 cells (mismatch repair proficient) that had been stably transfected with pIREShyg2-EGFP/CA13, an enhanced green fluorescence protein-based plasmid, and cultured in the absence or presence of various concentrations of aspirin or mesalazine. Aspirin at doses above 1.25 mmol/L markedly reduced cell growth. Mesalazine doses up to 5.0 mmol/L had no such effect. The mutation rate in mismatch repair-deficient HCT116 cells was 6.8 x 10(-4) +/- 9.0 x 10(-5). In aspirin-treated cultures the mutation rate was 8.2 x 10(-4) +/- 1.3 x 10(-4) (121% of control). Instead, mesalazine lowered the mutation rate in a dose-dependent fashion (5.5 x 10(-4) +/- 1.1 x 10(-4); 81% of control). The effects of mesalazine were most significant in the M1 fraction (P < 0.0001), which represents a mutant population immediate after the polymerase error and were confirmed in mismatch repair-proficient HCT116+chr3 cells. Our data indicate that mesalazine reduces frameshift mutations at a (CA)13 microsatellite in cultured colorectal cells independent of mismatch repair proficiency. This finding suggests that mesalazine improves replication fidelity, an effect that may be active in reducing mutations independent of its anti-inflammatory properties.

Aspirin↗

Quantifying estrogen and progesterone receptor expression in breast cancer by digital imaging.

Developments in digital imaging and fluorescent microscopy provide a new method and opportunities for quantification of protein expression in human tissue. Archived collections of paraffin-embedded tumors can be used to study the relationship between quantitative differences in protein expression in tumors and patient outcome. In this report we describe the use of a DeltaVision Restoration deconvolution microscope, combined with fluorescent immunohistochemistry, to obtain reproducible and quantitative estimates of protein expression in a formalin-fixed paraffin-embedded tissue. As proof of principle, we used antibodies to the estrogen and progesterone receptors in a hormone receptor-positive breast cancer specimen. We provide guidelines for control of day-to-day variability in camera and microscope performance to ensure that image acquisition leads to reproducible quantitative estimates of protein expression. We show that background autofluorescence related to formalin fixation can be controlled and that for proteins that are expressed in nearly every cell, multiplexing two primary antibodies on the same slide does not significantly affect the results obtained. We demonstrate that for proteins whose expression varies markedly from cell to cell, data reproducibility, as assessed by imaging successive tissue sections, is more difficult to determine.

Breast Neoplasms↗

Effects of a high-fiber, low-fat diet intervention on serum concentrations of reproductive steroid hormones in women with a history of breast cancer.

PURPOSE: Diet intervention trials are testing whether postdiagnosis dietary modification can influence breast cancer recurrence and survival. One possible mechanism is an effect on reproductive steroid hormones. PARTICIPANTS AND METHODS: Serum reproductive steroid hormones were measured at enrollment and 1 year in 291 women with a history of breast cancer who were enrolled onto a randomized, controlled diet intervention trial. Dietary goals for the intervention group were increased fiber, vegetable, and fruit intakes and reduced fat intake. Estradiol, bioavailable estradiol, estrone, estrone sulfate, androstenedione, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and sex hormone-binding globulin were measured. RESULTS: The intervention (but not the comparison) group reported a significantly lower intake of energy from fat (21% v 28%), and higher intake of fiber (29 g/d v 22 g/d), at 1-year follow-up (P <.001). Significant weight loss did not occur in either group. A significant difference in the change in bioavailable estradiol concentration from baseline to 1 year in the intervention (-13 pmol/L) versus the comparison (+3 pmol/L) group was observed (P <.05). Change in fiber (but not fat) intake was significantly and independently related to change in serum bioavailable estradiol (P <.01) and total estradiol (P <.05) concentrations. CONCLUSION: Results from this study indicate that a high-fiber, low-fat diet intervention is associated with reduced serum bioavailable estradiol concentration in women diagnosed with breast cancer, the majority of whom did not exhibit weight loss. Increased fiber intake was independently related to the reduction in serum estradiol concentration.

Breast Neoplasms↗

The effect of advancing paternal age on pregnancy and live birth rates in couples undergoing in vitro fertilization or gamete intrafallopian transfer.

OBJECTIVE: This study was undertaken to determine effects of male aging on sperm parameters, fertilization, pregnancy, and live birth rates among in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) couples. The impact of female age was also investigated. STUDY DESIGN: Prospective study was made up of 221 IVF and GIFT couples. RESULTS: Pregnancy rates declined as the male subjects aged. Each additional year of paternal age was associated with 11% increased odds (P=.007) of not achieving a pregnancy, and 12% odds (P=.01) of not having a successful live birth. For first-time IVF/GIFT recipients, each additional year of paternal age was associated with a 5% increased odds of not achieving a pregnancy, whereas for repeaters it was 40% (P=.01). Advancing maternal age was associated with decreased numbers of oocytes retrieved or fertilized. Women 40 years or older compared with younger than 35 years had greater than 4-fold risk of not becoming pregnant, and greater than 20-fold risk of not achieving a live birth. CONCLUSION: Advancing paternal (and maternal) age had a deleterious effect on IVF and GIFT outcomes.

Adult↗

The concerns during assisted reproductive technologies (CART) scale and pregnancy outcomes.

OBJECTIVE: To determine whether concerns specific to IVF/GIFT (i.e., side effects, surgery, anesthesia, not enough information, pain, recovery, finances, missing work, and live birth delivery) that were measured by the previously validated Concerns During Assisted Reproductive Technologies (CART) instrument are negatively associated with reproductive endpoints. DESIGN: Prospective study. SETTING: Seven centers in Southern California between July 1993 and June 1998. PATIENT(S): One hundred fifty-one women completed two questionnaires at baseline and at the time of the procedure. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of oocytes aspirated and fertilized, number of embryos transferred, pregnancy rates, and live birth delivery rates. RESULT(S): At baseline, women who were concerned about the medical aspects (i.e., side effects, surgery, anesthesia, not enough information, pain, and recovery) of the procedure had 20% fewer oocytes retrieved and 19% fewer oocytes fertilized, while simultaneously adjusting for female age, race, education, smoking status, parity, type of assisted reproductive technologies (ART) procedure (IVF or GIFT), type of infertility, and number of previous attempts. Women who were very concerned about missing work had 30% fewer ooyctes fertilized. For women who were moderately concerned about missing work, the odds ratio was 2.83 for not achieving a pregnancy. Women who were extremely concerned about the finances associated with the procedure had a very high risk (odds ratio [OR] = 11.62) of not achieving a successful live birth delivery. CONCLUSION(S): The CART scale identified two areas of concerns for women undergoing IVF or GIFT: "missing work/finances" and "medical aspects of the procedure."

Absenteeism↗

Plasma triacylglycerol and HDL cholesterol concentrations confirm self-reported changes in carbohydrate and fat intakes in women in a diet intervention trial.

Diet intervention trials are currently testing whether reduced fat intake can reduce the risk and progression of breast cancer. Energy from dietary fat is generally replaced by energy from carbohydrate in these studies, and altering the proportion of energy from dietary carbohydrate and fat has been shown to affect plasma lipid concentrations in controlled feeding studies. The purpose of this study was to examine the effect of increased carbohydrate and reduced fat intakes on plasma lipids in a randomized, controlled trial that is testing the effect of diet modification on risk for recurrence and survival in women previously treated for breast cancer. Plasma concentrations of lipids and related factors were measured at enrollment and 1-y follow-up in 393 women enrolled in the trial. Dietary goals for the intervention group focused on an increase in vegetable, fruit and fiber intakes, and reduced fat intake. Women assigned to the intervention group significantly reduced fat intake (from 28.1 to 21.0% of energy), and significantly increased intakes of carbohydrate (from 56.9 to 65.3% of energy) and fiber (from 21.0 to 29.6 g/d) (P < 0.05). Body weight did not change significantly in either study group. A small but significant increase in fasting plasma triacylglycerol concentration, and decreases in HDL cholesterol and apoprotein-A1 concentrations, were observed in the intervention group (P < 0.05) but not in the comparison group. Changes in total cholesterol, LDL cholesterol, apoprotein-B, lipoprotein (a), and insulin concentrations, and in the LDL cholesterol/HDL cholesterol ratio, were not observed in either group. The lipid responses that were observed in this study provide biological evidence that validates the self-reported change in dietary intakes of fat and carbohydrate in response to the intervention efforts. The degree of change in these lipid concentrations was small and does not suggest increased cardiovascular disease risk.

Anticarcinogenic Agents↗

Telephone counseling intervention increases intakes of micronutrient- and phytochemical-rich vegetables, fruit and fiber in breast cancer survivors.

Although a large body of evidence suggests that diet may play an important role in cancer prevention, randomized controlled trials reported to date have not achieved sufficient increases in protective micronutrients and phytochemicals to adequately test the hypothesis that diet can reduce cancer risk. The Women's Healthy Eating and Living (WHEL) Study, a randomized controlled trial of the role diet modification may play in future breast cancer events, introduced an innovative theory-based telephone counseling intervention to teach participants to consume a high fiber, low fat diet emphasizing vegetables and fruits rich in carotenoids and other potentially protective phytochemicals. This report examines the baseline to 12-mo changes in dietary intakes of 2970 participants, assessed through 24-h recalls and validated with plasma carotenoid concentrations. At 12 mo, the intervention group reported a significantly increased daily vegetable intake (+vegetable juice) of 7.1 servings (+82%) and fruit intake of 3.9 servings (+18%). Fiber intake increased from 3.04 to 4.16 g/(MJ. d), whereas energy from fat decreased significantly from 28.6 to 23.7%. Plasma carotenoid concentrations increased significantly, i.e., alpha-carotene (+223%); beta-carotene (+87%); lutein (+29%); and lycopene (+17%). In the comparison group, dietary intake and plasma carotenoid concentrations were essentially identical to those of the intervention group at baseline and were unchanged at 12 mo. The WHEL Study showed that a telephone counseling intervention can achieve major increases in micronutrient- and phytochemical-rich vegetables, fruit and fiber intakes, enabling an investigation of the potential cancer preventive effects of these food components.

Adult↗