Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer

BACKGROUND: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding proteins (IGFBPs). OBJECTIVE: The objective of our study was to investigate the effect of an 8-wk supplementation with tomato-derived lycopene (30 mg/d) on serum concentrations of total IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3. DESIGN: We conducted a randomized, placebo-controlled, double-blinded crossover study in 40 men and 31 postmenopausal women with a family history of colorectal cancer, a personal history of colorectal adenoma, or both. RESULTS: Lycopene supplementation significantly (P = 0.01) increased serum IGFBP-1 concentrations in women (median relative difference between serum IGFBP-1 concentrations after lycopene supplementation and after placebo, 21.7%). Serum IGFBP-2 concentrations were higher in both men and women after lycopene supplementation than after placebo, but to a lesser extent (mean relative difference 8.2%; 95% CI: 0.7%, 15.6% in men and 7.8%; 95% CI: -5.0%, 20.6% in women). Total IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly altered by lycopene supplementation. CONCLUSIONS: This is the first study known to show that lycopene supplementation may increase circulating IGFBP-1 and IGFBP-2 concentrations. Because of high interindividual variations in IGFBP-1 and IGFBP-2 effects, these results should be confirmed in larger randomized intervention studies.     

Isolated isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk

Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conducted a randomized, placebo-controlled, double-blind crossover study to investigate the effect of an 8-wk isolated isoflavone supplementation (84 mg/d) on serum concentrations of total IGF-I, free IGF-I, total IGF-II, IGF binding protein (BP)-1, IGFBP-2, and IGFBP-3. Additionally, we investigated whether IGF-system component differences were related to concentrations of the more potent estrogenic isoflavone metabolite, equol. Our study population consisted of 37 men with a family history of colorectal cancer or a personal history of colorectal adenomas. Isoflavone supplementation did not significantly affect serum total IGF-I concentrations (relative difference between serum total IGF-I concentrations after isoflavone supplementation and after placebo: -1.3%, 95% CI -8.6 to 6.0%). Neither free IGF-I, nor total IGF-II, IGFBP-1, IGFBP-2, or IGFBP-3 concentrations were significantly altered. Interestingly, the change in serum IGF-I concentrations after isoflavone supplementation was negatively associated with serum equol concentrations (r=-0.49, P=0.002). In conclusion, isolated isoflavones did not affect the circulating IGF-system in a male high-risk population for colorectal cancer. However, to our knowledge, this is the first study that suggests isoflavones might have an IGF-I lowering effect in equol producers only. This underlines the importance of taking into account equol status in future isoflavone intervention studies.     

Effect of a tomato drink intervention on insulin-like growth factor (IGF)-1 serum levels in healthy subjects

There is concern that dietary factors can modulate the insulin-like growth factor (IGF) system. The aim of this work was to evaluate the effect of a tomato drink intervention providing small amounts of lycopene and other carotenoids on serum levels of IGF-1. Twenty healthy young subjects participated in a repeated measure double-blind, cross-over design. Subjects consumed 250 ml of a tomato drink or a placebo drink for 26 days separated by 26 days wash-out. The tomato drink intake increased plasma lycopene, phytoene, phytofluene, and beta-carotene concentrations by 0.22, 0.12, 0.13, and 0.18 micromol/L, respectively (P < 0.05). No significant effect of the tomato drink intake on IGF-1 levels was observed. However, changes in lycopene before and after each experimental period were inversely and significantly correlated with those of IGF-1 (r = -0.33, P < 0.05, N = 20). No correlation was found with the other carotenoids. A significant reduction of IGF-1 serum level (-5.7%) was observed in subjects (n = 11) with the highest plasma lycopene response but also IGF-1 levels following the tomato drink intake (P < 0.05). No effect was evident after the placebo treatment. The results suggest that further exploration of the role of tomato lycopene on IGF-1 modulation both on healthy and on subjects at risk is necessary.     

Soy isoflavones do not modulate circulating insulin-like growth factor concentrations in an older population in an intervention trial

Insulin-like growth factors (IGF) are essential for normal growth and maintenance of lean muscle mass; however, high insulin-like growth factor-I (IGF-I) and low IGF binding protein-3 (IGFBP-3) levels are also associated with several cancers. To test the hypothesis that long-term soy isoflavone supplementation decreases circulating IGF-I concentrations, we conducted a controlled, parallel-arm, double-blind intervention study with 150 participants (85% men), 50-80 y old. Participants were randomly assigned to consume a soy beverage powder daily for 12 mo. The active treatment group (+ISO) received soy protein containing 83 mg isoflavones, whereas the comparison group (-ISO) received soy protein containing 3 mg isoflavones. Serum IGF-I and IGFBP-3 were measured by ELISA. Mean change in serum IGF-I concentrations was similar in the two groups (+1.4 nmol/L in +ISO, +1.2 nmol/L in -ISO; P = 0.74, 95% confidence interval -1.1, +1.5 nmol/L for the 0.21 nmol/L difference between groups), indicating no effect of the isoflavone intervention. Similarly, the changes in IGFBP-3 and the IGF-I/IGFBP-3 ratio were similar in both groups, again showing no effect of +ISO treatment. A 12 mo, 83 mg/d soy isoflavone intervention did not modulate serum IGF in an older, mostly male population.     

Insulin-like growth factor-1 and binding protein-3 in a 2-year soya intervention among premenopausal women

Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.     

Lycopene status is not associated with insulin-like growth factor-1 concentration in a healthy male population

OBJECTIVE: The aim of this study was to assess the relationship between lycopene and insulin-like growth factor-1 levels in a healthy male population. DESIGN: Insulin-like growth factor-1 status was assessed in healthy men aged 30-49 years (n = 104) with either high or low lycopene concentrations. RESULTS: There was no significant difference between insulin-like growth factor-1 levels in the high- and low-lycopene groups; high lycopene group; 8.21 (2.73) nmol/L; low lycopene group; 7.65 (2.14) nmol/L, p = 0.46 (Mean (SD)). CONCLUSIONS: In this small observational study, no association was found between lycopene concentration and insulin-like growth factor-1 concentration.     

Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study

BACKGROUND: Isoflavones are estrogen-like plant compounds that may protect against cardiovascular disease and endocrine-responsive cancer. Isoflavones may, because of their ability to act as selective estrogen receptor modulators, alter insulin-like growth factor (IGF) status. OBJECTIVE: The aim of this study was to assess the effect of 1-month isoflavone supplementation (86 mg/day red clover-derived isoflavones) on IGF status. DESIGN AND SUBJECTS: Healthy pre- (n=16) and postmenopausal (n=7) women were invited to take part in a randomised, placebo-controlled crossover study with a minimum 2-month washout period. RESULTS:: For premenopausal subjects, the change in IGF-1, IGF-BP1 and IGF-BP3 assessed at different points of the menstrual cycle did not differ between isoflavone and placebo phase. However, the change in IGF-1, when examined pre- and post-supplementation, was nonsignificantly reduced (P=0.06) on the isoflavone supplement compared to placebo. For postmenopausal subjects, the change in IGF-1, IGF-BP1 and IGFBP-3 concentrations over the supplementation period did not differ between isoflavone or placebo phase. Isoflavones increased HDL in postmenopausal women compared to placebo (P=0.02) but did not alter either cholesterol or triacylglycerol concentrations, and had no effect on antioxidant status. CONCLUSIONS: This study shows that 1-month supplementation with red clover isoflavones has a positive effect on HDL cholesterol, but at most a small effect on IGF status in premenopausal and no effect in postmenopausal subjects. Further studies are required to ascertain the role these dietary compounds may have to play in breast cancer prevention.     

Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Japanese women

Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).     

Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk

Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases serum levels of total IGF-I in premenopausal women with 1) a history of breast cancer (n=24) or 2) a high familial breast cancer risk (n=36). Also, IGF binding protein (IGFBP) increasing effects were evaluated. Lycopene supplementation did not significantly alter serum total IGF-I and other IGF system components in the 2 study populations combined. However, statistically significant discordant results were observed between the 2 study populations (i.e., P<0.05 for total IGF-I, free IGF-I, and IGFBP-3). Total IGF-I and IGFBP-3 were increased in the breast cancer survivor population [total IGF-I=7.0%, 95% confidence interval (CI)= -0.2 to 14.3%; IGFBP-3=3.3%, 95% CI=0.7-6.0%), and free IGF-I was decreased in the family history population (-7.6%, 95% CI= -14.6 to -0.6%). This randomized controlled trial shows that 2 mo of lycopene supplementation has no effect on serum total IGF-I in the overall study population. However, lycopene effects were discordant between the 2 study populations showing beneficial effects in high-risk healthy women but not in breast cancer survivors.     

Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women

The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in healthy individuals are not well defined. Three test diets—high-fat diet (40% energy as fat), low-fat diet (LF; 20% energy as fat), and a diet with low fat and high omega-3 fatty acid (LFn3; 23% energy as fat)—were tested in a randomized crossover designed controlled feeding trial in healthy postmenopausal women. Plasma IGF-I, IGF binding protein-3 (IGFBP-3), insulin, glucose, and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets. Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I, insulin, and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets. Eight weeks of the LFn3 diet increased circulating IGF-I (P < .001) and IGFBP-3 (P = .01) and the LF diet increased IGFBP-3 (P = .04), resulting in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet (P = .13 for both comparisons). No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1, IGFBP-3, or the ratio of IGF-1/IGFBP-3. Insulin, glucose, and the homeostatic model assessment of insulin resistance were not altered by the interventions. Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals.     

Supplementation with alpha-tocopherol or beta-carotene reduces serum concentrations of vascular endothelial growth factor-D, but Not -A or -C, in male smokers

Evidence from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study suggests that vitamin E and β-carotene supplement use may influence the risk of several cancers. Vascular endothelial growth factors (VEGF) are proteins involved in angiogenesis, an important requirement for tumor growth and metastasis. Thus, vitamin E and β-carotene may influence cancer risk through one or more VEGF. The ATBC Study was a randomized, double-blind, placebo-controlled, primary cancer prevention trial in which participants were assigned to 1 of 4 supplementation groups based on a 2 × 2 factorial design: 1) α-tocopherol (vitamin E); 2) β-carotene; 3) both; or 4) placebo. For the present study, 100 cancer-free participants with follow-up serum available were randomly selected from each intervention group. VEGF-A, -C, and -D concentrations were measured by ELISA in serum obtained at baseline and after at least 2 y of supplementation. Differences in change in VEGF levels from baseline to follow-up between intervention groups were assessed using the ANOVA test. Change in VEGF-A and VEGF-C concentrations between baseline and follow-up did not differ by intervention group (P = 0.45 and 0.29, respectively). The decrease in the serum VEGF-D concentration was greater in the men supplemented with α-tocopherol (-9.7 ± 2.5%) or β-carotene (-8.5 ± 2.7%) and tended to be greater in those supplemented with both (-6.8 ± 2.4%) compared to the placebo group, in which there was no change (-0.4 ± 3.0%) (P = 0.03). In this population of male smokers, supplementation with α-tocopherol or β-carotene was associated with a decrease in VEGF-D levels over time. Although the mechanism through which these supplements affect cancer etiolog remains unclear, our results support the hypothesis that vitamin E and β-carotene may influence cancer progression through VEGF-mediated lymphangiogenesis.     

Relation of insulin-like growth factor (IGF) I and IGF-binding protein 3 concentrations with intakes of fruit, vegetables, and antioxidants

BACKGROUND: Fruit, vegetable, and antioxidant intakes may reduce the risk of several insulin-like growth factor (IGF)-related chronic diseases, such as certain types of cancers and cardiovascular diseases. OBJECTIVE: This study investigated whether intakes of fruit, vegetables, and antioxidants (beta-carotene, lycopene, and vitamin C) are associated with plasma IGF-I and IGF-binding protein 3 (IGFBP-3) concentrations. DESIGN: Plasma IGF-I and IGFBP-3 concentrations were measured in 1542 healthy women by enzyme-linked immunosorbent assay. A self-administered semiquantitative food-frequency questionnaire was used to estimate mean daily dietary intakes of fruit, vegetables, and antioxidants over the year preceding blood sampling. Multivariate analyses were performed by using generalized linear models to evaluate the association of quintiles of daily intakes with concentrations of growth factors. RESULTS: A higher intake of citrus fruit was associated with higher concentrations of IGF-I (215 ng/mL for quintile 5 compared with 205 ng/mL for quintile 1; P for trend = 0.04) and with lower concentrations of IGFBP-3 (4803 ng/mL for quintile 5 compared with 4960 ng/mL for quintile 1; P for trend = 0.04). Higher dietary vitamin C intake was associated with higher concentrations of IGF-I (214 ng/mL for quintile 5 compared with 204 ng/mL for quintile 1; P for trend = 0.02) and lower concentrations of IGFBP-3 (4813 ng/mL for quintile 5 compared with 4953 ng/mL for quintile 1; P for trend = 0.03). Total intake of fruit and vegetables and intakes of other botanical fruit and vegetable subgroups, beta-carotene, and lycopene were not related to either IGF-I or IGFBP-3 concentrations. CONCLUSION: Women with higher intakes of citrus fruit or dietary vitamin C tend to have higher plasma concentrations of IGF-I and lower plasma concentrations of IGFBP-3.     

Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency

BACKGROUND: Ascorbate and glutathione play central roles in the defense against free radicals and oxidants that are implicated in chronic diseases. OBJECTIVE: The objective was to determine the ability of vitamin C supplements to modulate the concentration of glutathione in human lymphocytes. DESIGN: The effect of vitamin C supplements was determined in a sequential study with time points before supplementation, after 13 wk of vitamin C supplements (500 or 1000 mg/d), and after 13 wk of matching placebo. The supplementation group was selected on the basis of low plasma ascorbate (<33 mmol/L) and consisted of 48 healthy men and women, smokers and nonsmokers, aged 25-64 y. Ascorbate and glutathione were measured in purified lymphocytes. RESULTS: At baseline, the mean (+/-SD) concentration of plasma ascorbate was 19.5 +/- 7.2 micro mol/L, 22.5 micro mol/L below the median of normal distribution. The ascorbate concentration in plasma was linearly associated with that in lymphocytes (r = 0.53, P < 0.001). On supplementation with vitamin C, lymphocyte ascorbate increased by 51% (from 16.7 +/- 4.9 to 25.3 +/- 6.9 nmol/mg protein; P < 0.001) and was accompanied by an increase of lymphocyte glutathione by 18% (from 22.5 +/- 4.5 to 26.6 +/- 6.5 nmol/mg protein; P < 0.001). After placebo, the ascorbate and glutathione concentrations fell to near baseline concentrations (17.1 +/- 5.4 and 23.5 +/- 6.4 nmol/mg protein, respectively). No significant interaction was observed for sex and smoking status. Finally, the changes in lymphocyte ascorbate after supplementation were strongly associated with changes in lymphocyte glutathione (r = 0.71, P < 0.001). The association suggests that every 1-mol change in ascorbate is accompanied by a change of approximately 0.5 mol in glutathione. CONCLUSION: Vitamin C supplements increase glutathione in human lymphocytes.     

Insulin-like growth factor 1, insulin-like growth factor-binding protein 3, and testicular germ-cell tumor risk

Studies have consistently shown that taller men are at increased risk of testicular germ-cell tumors. Thus, it is plausible that factors associated with height may also influence risk of these tumors. The authors examined associations between testicular germ-cell tumor risk and circulating concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) among 517 cases and 790 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study (2002-2005). Odds ratios and 95% confidence intervals were estimated using logistic regression models, adjusting for age, race/ethnicity, height, and body mass index. All tests of significance were two-sided. Overall, there were no associations between IGF-1 or IGFBP-3 concentrations and risk of testicular germ-cell tumors (p > 0.05). However, when cases were separated by histologic type, there was a suggestion of a reduction in seminoma risk associated with the highest concentrations of IGF-1 as compared with the lowest concentrations (odds ratio = 0.66, 95% confidence interval: 0.40, 1.09). Although there were no overall associations with insulin-like growth factor, contrary to expectation, there was a suggestion that IGF-1 concentrations may be inversely associated with risk of seminoma.     

胰岛素样生长因子及其结合蛋白与妊娠期高血压疾病的相关性研究

目的:研究妊娠期高血压疾病患者血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-1(IGFBP-1)的水平与病情程度及新生儿出生体重之间的关系。方法:采用放射免疫方法测定并比较38例妊娠期高血压疾病患者与38例正常血压妊娠妇女的血清IGF-1、IGFBP-1的水平。结果:子痫前期组IGF-1显著低于妊娠期高血压组和正常组,而IGFBP-1水平显著高于妊娠期高血压组和正常组;妊娠期高血压组与正常组间IGF-1、IGFBP-1的水平比较,差异均无统计学意义。IGF-1水平与收缩压、舒张压及平均动脉压呈显著负相关,与新生儿出生体重呈显著正相关,而IGFBP-1与收缩压、舒张压及平均动脉压呈显著正相关,与新生儿出生体重呈显著负相关。结论:妊娠期高血压疾病患者的发病及严重程度与IGF-1、IGFBP-1有明显的关系,IGF-1、IGFBP-1与胎儿的发育及新生儿出生体重有明显的相关性。     

Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults

OBJECTIVE: To assess the vitamin D status of healthy young people living in Northern Ireland and the effect of vitamin D supplementation on vitamin D status and bone turnover. DESIGN: Double-blinded randomised controlled intervention study. SETTING: University of Ulster, Coleraine, Northern Ireland. SUBJECTS: In total, 30 apparently healthy students (15 male and 15 female subjects), aged 18-27 years, were recruited from the university, with 27 completing the intervention. INTERVENTIONS: Subjects were randomly assigned, to receive either 15 microg (600 IU) vitamin D(3) and 1,500 mg calcium/day (vitamin D group), or 1,500 mg calcium/day (control group) for 8 weeks between January and March. Vitamin D status, bone turnover markers, serum calcium and parathyroid hormone concentrations were measured at baseline and post intervention. RESULTS: At baseline, vitamin D status was low in both the vitamin D group (47.9 (s.d. 16.0)) and the control group (55.5 (s.d. 18.6) nmol/l 25(OH)D). Post intervention vitamin D status was significantly higher in the vitamin D-treated group (86.5 (s.d. 24.5)) compared to the control group (48.3 (s.d. 16.8) nmol/l) (P<0.0001). There was no significant effect of supplementation on bone turnover markers or PTH concentrations. CONCLUSIONS: This study suggests that young adults in Northern Ireland do not consume an adequate daily dietary intake of vitamin D to maintain plasma vitamin D concentrations in the wintertime. A daily supplement of 15 microg vitamin D(3) significantly increased vitamin D status in these individuals to levels of sufficiency. Achievement of an optimum vitamin D status among young adults may have future positive health implications.     

Lycopene in serum, skin and adipose tissues after tomato-oleoresin supplementation in patients undergoing haemorrhoidectomy or peri-anal fistulotomy

Lycopene, the main carotenoid found in tomatoes and tomato-based products, has been reported to be protective against several types of cancer. Assessment of changes in plasma concentration of carotenoids following ingestion of lycopene-rich food sources does not necessarily predict changes in lycopene concentration or distribution of its isomers in other body tissues. Our aim was to determine the relationship between concentrations of lycopene and other tomato carotenoids in human serum and body tissues after tomato-oleoresin supplementation. Tomato lycopene oleoresin (30 mg/d) or a placebo was administered for 1 to 7 weeks to seventy-five volunteers undergoing elective haemorrhoidectomy or peri-anal fistulotomy. Carotenoid concentration and isomer distribution in blood and in the surgically removed skin and adipose tissues was measured by HPLC. The serum concentration of lycopene increased after supplementation from 0.26 (SD 0.12) to 0.52 (SD 0.25) micromol/l (n 35; P<0.0001). In the placebo group (n 40), lycopene serum concentration did not change significantly. Serum lycopene concentration after treatment was 2.2-fold greater in the lycopene group than in the placebo group, a slightly higher ratio than that found in skin and adipose tissue (1.6- and 1.4-fold higher than the placebo, respectively). A significant correlation between serum and tissue concentrations was found for both beta-carotene and lycopene in the placebo group, whereas in the lycopene-supplemented group the correlation between serum and tissues remained the same for beta-carotene but for lycopene was weak. Lycopene supplementation did not significantly change the proportion of all-trans v. cis isomers in the serum and tissues, despite the fact that more than 90 % of the supplemented lycopene was in the all-trans form. These results show that tomato-oleoresin supplementation increases lycopene concentrations in serum and in adipose tissue and skin. The ability to increase lycopene levels in tissues is one of the prerequisites for using it as a food supplement with health benefits.     

肝细胞癌合并肝硬化患者术后应用重组人生长激素联合肠外营养对生长激素/胰岛素样生长因子-1轴的影响

目的：探讨肝细胞癌合并肝硬化患者术后应用重组人生长激素（rhGH）联合肠外营养（PN）对生长激素（GH）／胰岛素样生长因子-1（IGF-1）轴的影响。方法：24例行根治性切除的肝癌患者随机分为PN组（n=12）和rhGH＋PN组（n=12）。术前、术后1d和6d测血清GH、IGF-1、IGFBP-3，用RT-PCR法检测肝组织（包括癌组织，癌旁组织和术后6d肝穿刺组织）IGF-1 mR-NA、IGFBP-3 mRNA的表达，肝组织行Ki67免疫组织化学染色。同时选12例因胆石症或肝血管瘤行手术的患者作为正常对照。结果肝细胞癌合并肝硬化患者血清GH水平高于正常对照组，而血清IGF-1、IGFBP-3水平低于正常对照组；术后6d，血清GH、IGF-1、IGFBP-3水平、肝组织IGF-1 mRNA、IGFBP-3m RNA表达水平、肝Ki67指数，rhGH＋PN组均高于PN组。PN组中位无瘤生存期是11．2个月，rhGH＋PN组中位无瘤生存期是11．4个月；PN组6个月、12个月无瘤生存率分别是71．1％、46.2％，rhGH＋PN组6个月、12个月无瘤生存率分别是72．2％、59、0％，差异均无统计学意义（P〉0.05）。结论：rhGH＋PN有利于改善肝细胞癌合并肝硬化患者术后GH／IGF-1轴。     

Effects of 6-month multivitamin supplementation on serum concentrations of alpha-tocopherol, beta-carotene, and vitamin C in healthy elderly women

OBJECTIVE: The aim of this study was to evaluate the effect of supplementation with nutritional doses of antioxidant nutrients on the serum concentrations of ascorbic acid, alpha-tocopherol, and beta-carotene in healthy elderly women. METHODS: The study was performed as a randomized placebo-controlled, double-blind trial. Two hundred forty-one free-living, healthy women aged 60 years and older were recruited by newspaper advertisement in Hanover, Germany and its environs. As 21 women dropped out, data of 220 women (aged 60-91 years median 63 years) were included in this evaluation. Subjects were randomly assigned to receive either a multivitamin/mineral or placebo capsule with identical appearance for six months containing 36 mg 36mg vitamin E, 150 mg vitamin C, and 9 mg beta-carotene. Serum concentrations of vitamin C, alpha-tocopherol, and beta-carotene were measured initially and after six months of supplementation. Data were analyzed with the SPSS 10.0 program. RESULTS: Median serum concentrations of alpha-carotene and vitamin E increased significantly in the supplemented group (p=0.000), whereas no significant modifications were observed in the placebo group. Median vitamin C concentration of the supplemented group did not differ from baseline after intervention, but that of the placebo group was significantly decreased after six months (p=0.000). In comparison to estimated desirable serum concentrations of > 30 micromol/L vitamin E, 50 micromol/L vitamin C, and > 0.4 micromol/l beta-carotene at baseline, lower concentrations were found in 21.1%, 6.9%, and 1.0% of all subjects, respectively. After supplementation none of the members of the supplemented group had tocopherol concentrations below 30 micromol/L and only one woman of the supplemented group had a serum beta-carotene concentration below 0.4 micromol/L. The change in serum concentrations of vitamin C and E in the supplemented group depended on the status at baseline. CONCLUSION: A six-month supplementation with physiological doses of antioxidant vitamins improves the blood concentration of these nutrients even in relatively well-nourished elderly women or, as seen for vitamin C, prevents reduction of serum concentrations. Prevalence of suboptimal serum concentrations can be reduced.