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).     

Associations of Current,Childhood, and Adolescent Milk Intake with Serum Insulin-like Growth Factor (IGF)-1 and IGF Binding Protein 3 Concentrations in Adulthood

Previous studies have shown that insulin-like growth factor (IGF)-1 levels are positively and IGF binding protein (IGFBP)-3 levels negatively associated with risk of certain cancers. Also, dietary factors may influence the IGF system. We aimed to analyze the associations of current, childhood and adolescent milk intake with IGF-1 levels, IGFBP-3 levels and IGF-1:IGFBP-3 molar ratio in adulthood. Multivariable linear regression analyses by sex and race/ethnicity were performed using cross-sectional data from the Third National Health and Nutrition Examination Survey. A total of 5,805 participants were included in the analyses. Adult IGF-1 levels and IGF-1:IGFBP-3 molar ratio had significant inverse associations (P-trend = 0.02) with adolescent milk intake in non-Hispanic white men, but not in men of other race/ethnicities or in women. There were no associations between current or childhood milk intake and IGF-1 levels or IGF-1:IGFBP-3 molar ratio in adulthood. Current milk intake and childhood milk intake had significant positive associations (P-trend = 0.02) with adult IGFBP-3 levels in non-Hispanic white and non-Hispanic black women, respectively, but no associations were observed in Mexican American women or in men. Overall, there were long-term and short-term associations between milk intake and IGF-1 and IGFBP-3 levels, but the associations varied by race/ethnicity and sex.     

Soy Food Intake and Biomarkers of Breast Cancer Risk: Possible Difference in Asian Women?

Soy foods may protect against breast cancer in Asian but not in Western populations. We examined if the levels of various markers of breast cancer risk and inflammation, as well as the effects of soy food consumption on these markers, differ between Asian and non-Asian premenopausal women in two soy intervention trials. One study randomized 220 women to a 2-yr intervention and the other one randomized 96 women in a crossover design to examine the effects of consumption of 2 daily soy servings on nipple aspirate fluid (NAF) volume; estrogens in serum, NAF, and urine; insulin-like growth factor-1 (IGF-1), IGF-binding protein 3, and inflammatory markers in serum; and mammographic densities. Mixed linear models were applied to assess ethnic differences in biomarkers and response to the soy diet. Serum C-reactive protein, serum leptin, NAF volume, and NAF estrone sulfate were lower, while urinary isoflavones were higher in Asian than in non-Asian women. A significant interaction (p_interaction = 0.05) between ethnicity and soy diet was observed for IGF-1 but not for other biomarkers. The current findings suggest possible ethnic differences in levels of biomarkers for breast cancer risk but little evidence that Asian women respond differently to soy foods than non-Asian women.     

The glycemic index of foods influences postprandial insulin-like growth factor-binding protein responses in lean young subjects

BACKGROUND: Growth in normal and malignant tissues has been linked to hyperinsulinemia and insulin-like growth factors (IGFs). We hypothesized that IGF and IGF-binding protein (IGFBP) responses may be acutely affected by differences in the glycemic index (GI) of foods. OBJECTIVE: We compared the postprandial responses of IGFs and IGFBP to 2 foods of similar macronutrient composition but with greatly different GIs-pearled barley (GI: 25) and instant mashed potato (GI: 85). DESIGN: Ten young lean subjects consumed 50-g carbohydrate portions of the 2 foods or water (extended fast) in random order after an overnight fast. Capillary blood was collected at regular intervals over 4 h for measurement of blood glucose, insulin, and components of the IGF system. RESULTS: Serum IGFBP-1 declined markedly after both meals, but the mean (+/-SEM) change at 4 h was significantly (P < 0.01) more prolonged after the low-GI meal (-55 +/- 20 ng/mL) than after the high-GI meal (-13 +/- 15 ng/mL). Conversely, the change in serum IGFBP-3 concentration at 4 h was significantly (P < 0.05) higher after the low-GI meal (251 +/- 102 ng/mL) than after the high-GI meal (-110 +/- 96 ng/mL); the same pattern was observed at 2 h. Changes in IGFBP-2, free IGF-1, and total IGF-1 responses were minimal and did not differ significantly from those during the 4-h fast. CONCLUSION: Acute changes in IGFBP-3 after low-GI and high-GI foods may provide a biologic mechanism linking cell multiplication with greater consumption of high-GI carbohydrates.     

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.     

Effects of alcohol on insulin-like growth factor I and insulin-like growth factor binding protein 3 in postmenopausal women

BACKGROUND: Increased circulating insulin-like growth factor I (IGF-I) concentrations, frequently adjusted for IGF binding protein 3 (IGFBP-3), have been associated with increased risk of several types of cancer, including colon, prostate, and breast. Studies have suggested that alcohol may affect IGF-I or IGFBP-3; however, controlled feeding studies to assess alcohol's effects on IGF-I or IGFBP-3 have not been conducted. OBJECTIVE: To determine whether chronic, moderate alcohol intake affects serum IGF-I or IGFBP-3 concentrations, we performed a controlled, crossover feeding study. DESIGN: Fifty-three postmenopausal women were randomly assigned to consume 0 g (control), 15 g (one drink), or 30 g (2 drinks) alcohol daily for 8 wk and were rotated through the other 2 intake levels in random order. All foods and beverages were provided during the intervention. Individuals were monitored and calories adjusted to maintain constant weight, and serum was collected at the end of each diet period. RESULTS: Compared with the effects of 0 g alcohol/d, IGF-I concentrations were nearly unchanged by 15 g alcohol/d (0.8%; 95% CI: -3.2%, 3.5%) but decreased significantly by 4.9% (95% CI: -8.0%, -1.6%) with 30 g alcohol/d. IGFBP-3 concentrations significantly increased by 3.0% (95% CI: 0.4%, 5.6%) with 15 g alcohol/d but did not increase significantly with 30 g/d (1.8%; 95% CI: -0.9%, 4.5%). CONCLUSIONS: To our knowledge, this is the first published controlled diet study to find that in postmenopausal women, when weight is kept constant, alcohol consumption reduces the amount of serum IGF-I potentially available for receptor binding. These findings suggest that the effect of alcohol intake should be considered in studies of IGF-I, IGFBP-3, and cancer in postmenopausal women.     

Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial

High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.     

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.     

Nutritional changes among premenopausal women undertaking a soya based dietary intervention study in Hawaii

BACKGROUND: We conducted a 2-year nutritional intervention among premenopausal women. The goal was to incorporate two daily servings of soya into the regular diet. This report describes the dietary modifications and assesses their nutritional adequacy with regard to major nutrients. METHODS: In this analysis of 100 intervention and 106 control subjects, women completed a validated food-frequency questionnaire at baseline; throughout the study, they participated in at least three unannounced 24-h recalls. RESULTS: At randomization, both groups were similar in age and body weight, reported low soya intake, and did not differ by intake of major nutrients and foods. According to the 24-h recalls, women in the intervention group consumed nearly two servings of soya per day, while the control women remained at 0.2 servings. In comparison with the control group, the intervention group consumed fewer dairy products, primarily milk, but also less meat, nuts and seeds. As a result of the dietary modification, the intervention women consumed less-saturated fat and cholesterol and more protein, dietary fibre, calcium and vitamins than the control group. CONCLUSION: These results suggest that women in the intervention group improved the overall quality of their diet by adding two servings of soya per day.     

Colostrum supplementation restores insulin-like growth factor -1 levels and alters muscle morphology following massive small bowel resection

BACKGROUND: Colostrum protein concentrate (CPC) contains a high level of insulin-like growth factor-1 (IGF-1). IGF-1 and IGF binding protein (IGFBPs) may play an important role during the postresection adaptation response. As smooth muscle is an important site for IGF-1 action in the intestine, this study aims to (1) investigate the effect of CPC supplementation on circulating levels and tissue expression of IGF-1, IGF-1 receptor, and IGFBPs following massive small bowel resection (MSBR), and (2) characterize the effect of CPC on the muscular adaptation response following MSBR. METHODS: Four-week-old piglets underwent either a 75% MSBR or sham operation. Piglets received either a polymeric infant formula (PIF) diet or PIF supplemented with CPC for 8 weeks. Serum was analyzed by enzyme-linked immunosorbent assay, and ileal tissue assessed by molecular and histological analysis. RESULTS: There was no difference in IGF-1 or IGFBPs mRNA among groups. CPC treatment resulted in significant increases in circulating levels of IGF-1 and IGFBPs and a concurrent increase in muscle width and the number of muscle cells, but did not alter muscle cell size. CONCLUSIONS: Strategies aimed at increasing muscular adaptation may decrease Gl transit and allow greater mucosal contact time for absorption. We have shown that CPC supplementation following resection results in increased levels of circulating IGF-1, IGFBP-2, and IGFBP-3 and muscular hypertrophy. Our results suggest that IGF-1 and its mediators may play a role in the muscular adaptation response and warrant further exploration as a treatment option for short bowel syndrome.     

Relationship of Dietary Protein and Soy Isoflavones to Serum IGF-1 and IGF Binding Proteins in the Prostate Cancer Lifestyle Trial

High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.     

IGF-1, IGFBP-3, and nutritional factors in young black and white men: the CARDIA Male Hormone Study

Nutritional factors might play a role in regulating serum levels of insulin-like growth factors (IGFs), which are associated with some cancers. We examined the associations of nutritional factors with IGF-1 and IGF binding protein-3 (IGFBP-3). Serum IGF-1 and IGFBP-3 levels and dietary intake were measured in 459 black and 682 white male subjects of the Coronary Artery Risk Development in Young Adults study at the Year 7 (1992-1993) exam. Analysis of covariance and multivariable linear regression were used to assess associations of IGFs with dietary factors by race. IGF-1 was positively associated with magnesium in both black and white men (P = 0.008 and 0.05, respectively). Calcium was positively significantly related to IGF-1 in black men (P = 0.04) and marginally so in white men (P = 0.09). In black men, IGFBP-3 was positively associated with magnesium (P = 0.02), and one serving of milk per day was associated with an 8.23-ng/ml higher IGF-1 concentration (P = 0.05). Tests for interaction, however, revealed no differences between blacks and whites in the associations of nutrients with IGF-1 or IGFBP-3. In conclusion, the associations of dietary factors with serum IGF-1 and IGFBP-3 observed in our study corroborate those from other studies and generally do not differ between black and white men.     

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.     

Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile

Objectives

The present study evaluates the effects of a 6-month treatment with an ACE-inhibitor (ie, fosinopril) on serum concentrations of total IGF-1 and IGF binding protein (IGFBP)-3 in older adults at high risk for cardiovascular disease.

Design

Data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study, a double-blind, crossover, randomized, placebo-controlled trial.

Setting

Participants were recruited from the communities of Winston Salem, NC, and Greensboro, NC.

Participants

Subjects ≥55 years old with high cardiovascular disease risk profile.

Intervention

The intervention consisted of 6-month administration of fosinopril vs. placebo.

Measurements

Serum concentrations of total IGF-1 and IGFBP-3 were measured in 100 participants of the TRAIN study at baseline, 6-month and 12-month follow-up visits. Differences in total IGF-1 and IGFBP-3 concentrations were assessed using two-sided paired t-tests.

Results

The mean age of participants (47% women) was 66.5 (standard deviation 7.2) years. Serum concentrations of total IGF-1 were significantly higher after 6-month treatment with fosinopril compared to placebo (203.73 ng/mL vs 194.24 ng/mL; p=0.02): After ACE-inhibitor intervention, significantly higher serum IGFBP-3 concentrations compared to controls (4308.81 ng/mL vs 4086.93 ng/mL; p=0.03) were also reported.

Conclusions

A six-month treatment with fosinopril increases systemic levels of total IGF-1 and IGFBP-3 in older adults with high cardiovascular risk profile. This may represent a potential biological explanation to the beneficial effects of ACE-inhibition on stroke, ischemic heart disease and insulin resistance.     

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.     

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.     

Markers of fetal growth and serum levels of insulin-like growth factor (IGF) I, -II and IGF binding protein 3 in adults

Fetal growth has been linked with increased risk of cancer and cardiovascular disease later in life. The insulin-like growth factor (IGF) axis has recently been proposed as a predictor of risk of subsequent cancer and cardiovascular disease. However, only few data are available on the possible association between fetal growth and levels of IGFs later in life. We examined the association between markers of fetal growth, i.e. birth weight, birth length and Ponderal Index, from birth records and serum IGF-I, IGF-II, and IGF binding protein 3 (IGFBP-3) levels in 545 middle-aged Danish men and women. We fitted separate multivariate models including birth weight, birth length, Ponderal Index and serum IGF-I, IGF-II, and IGFBP-3, respectively. After adjustment for age, alcohol intake, smoking, diabetes mellitus, systolic and diastolic blood pressure, serum total cholesterol and current height and weight, we found negative associations between birth weight and Ponderal Index, respectively, and serum IGF-II in men, i.e. the mean regression coefficients were -49.41 (95% CI: -87.06-11.77) (microg/l)/kg and -3.49 (95% CI: -6.73-0.25) (microg/l)/(kg/m3), respectively. Furthermore, in men birth weight was negatively associated with the (IGF-I + IGF-II)/IGFBP-3 and IGF-II/IGFBP-3 ratios, which are believed to be indicators of bioavailable IGF and IGF-II, respectively. However, no other associations were found in any of the models. Between 1 and 16% of the variance in serum IGF-I, IGF-II, and IGFBP-3, respectively, could be explained by the statistical models used in the analyses. We found very little support to the hypothesis of an association between fetal growth and the IGF axis throughout life.     

Effect of 3-month treatment of children and adolescents with familial and polygenic hypercholesterolaemia with a soya-substituted diet

Soya protein has well-documented beneficial effects on serum lipid levels in adults, the potential beneficial effect of a prolonged soya protein-substituted diet in children and adolescents with familial (FH) and polygenic hypercholesterolaemia (PH) being unknown. To assess the effect of 3 months' treatment of children and adolescents with FH and PH with a soya-substituted diet on serum lipids and lipoproteins, twenty-three children and adolescents were initially assigned to a standard phase 1 diet for 3 months, after which they were instructed to include soya protein (0.25-0.5 g/kg body weight) into their diet for 3 months. Sixteen patients (ten males and six females, thirteen with FH (eight males and five females), three with PH (two males and one female); mean age 8.8 (sd 4.2) years (range 4-18 years); mean BMI 16.7 (sd 2.6) kg/m2)) completed both phases. The phase 1 diet resulted in a significant reduction of total cholesterol (TC), LDL-cholesterol and apo B by 12.3, 11.8 and 10.6 %, respectively, HDL-cholesterol, TAG, apo A1 and lipoprotein(a) not being different. Dietary intake of soya protein during phase 2 resulted in a significant decrease of TC, LDL-cholesterol and apo B by 7.7, 6.4, and 12.6 %, respectively. TAG, HDL-cholesterol, apo A1, and lipoprotein(a) did not change significantly. Substitution of soya protein for animal protein in a low-fat, fat-modified diet is of additional benefit in many, but not all, children and adolescents with FH and PH when aiming at lowering serum TC, LDL and apo B. It seems to be a feasible long-term dietary lifestyle intervention and may grant additive benefit in the prevention of early vascular disease.     

Serum insulin-like growth factor-I levels among women in Hawaii and Japan with different levels of tofu intake

Insulin-like growth factor-I (IGF-I) has been proposed as the link between diet and breast cancer risk. Due to their estrogen-like structure, soy isoflavones may affect IGF-I levels in a similar way as exogenous estrogens. In a cross-sectional design, we compared IGF-I levels between women with high and low soy intake. The analysis included 611 pre- and postmenopausal women: Japanese in Japan and Japanese and Caucasians in Hawaii. The subjects had participated in a previous study, were never diagnosed with breast cancer, provided a screening mammogram and a blood sample, and completed validated food-frequency questionnaires. The same laboratory analyzed all serum samples for IGF-I and IGF binding protein (IGFBP)-3 by enzyme-linked immunosorbent assay. We estimated covariate-adjusted mean IGF-I and IGFBP-3 levels by tofu intake. The respective mean IGF-I levels were 213, 257, and 255 ng/ml for Japanese in Japan, Japanese in Hawaii, and Caucasians in Hawaii. Tofu intake was higher in Japan than among Japanese and Caucasians in Hawaii (11.0 vs. 9.4 and 4.9 g/1,000 kcal). Mean IGF-I levels were 11% lower among women in the highest tofu intake category compared with the lowest, but the difference in IGF-I levels between the highest and lowest tofu category was only significant among women in Japan. Inclusion of total energy, total protein, meat, and dairy intake did not materially alter the association between tofu consumption and IGF-I levels. These findings suggest that a diet rich in soy foods and low in meats may be related to lower IGF-I levels, but it is unclear whether soy or other characteristics of diet and lifestyle are responsible for this association.     

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.