Francesco Branca

Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Low birthweight and adult insulin resistance: the “catch-up growth” hypothesis

Epidemiological studies have shown a close correlation between intrauterine growth retardation (IUGR) and the onset of insulin resistance, non-insulin-dependent diabetes mellitus (NIDDM), hypertension, hyperlipidaemia, and cardiovascular diseases in adult life.1-6 To explain this association, the concept of re-programming has been introduced: intrauterine exposure to insufficient nutrient supply during critical periods of fetal life would permanently affect the development and function of the endocrine system, leading to metabolic changes, including reduced insulin sensitivity.5 6 nnAlthough knowledge of the mechanisms involved in the re-programming process might allow new strategies for early prevention of long term metabolic disturbances to be developed, the pathophysiological link between fetal growth impairment and adult diseases is still unclear.nnIn 1992 Hales and Barker7 proposed the model of the “thrifty phenotype,” suggesting that intrauterine malnutrition would lead to insulin resistance and decreased β cell mass, thus predisposing to NIDDM. According to this hypothesis, the endocrine alterations induced by intrauterine malnutrition are intended to divert the limited nutrient supply to maintain survival and development of vital organs, such as the brain, at the expense of growth.nnMore recently, the “fetal salvage” hypothesis has been formulated.8 The finding that prepubertal IUGR children show a far greater insulin response than normal birthweight children, challenges the previously proposed β cell hypoplasia. …

Energy and nutrient dietary reference values for children in Europe: methodological approaches and current nutritional recommendations.

The Expert Group on the Methodological Approaches and Current Nutritional Recommendations in Children and Adolescents was convened to consider the current situation across Europe with regard to dietary recommendations and reference values for children aged 2-18 years. Information was obtained for twenty-nine of the thirty-nine countries in Europe and a comprehensive compilation was made of the dietary recommendations current up to September 2002. This report presents a review of the concepts of dietary reference values and a comparison of the methodological approaches used in each country. Attention is drawn to the special considerations that are needed for establishing dietary reference values for children and adolescents. Tables are provided of the current dietary reference values for energy and for the macronutrients, vitamins, minerals, trace elements and water. Brief critiques are included to indicate the scientific foundations of the reference values for children and to offer, where possible, an explanation for the wide differences that exist between countries. This compilation demonstrated that there are considerable disparities in the perceived nutritional requirements of European children and adolescents. Although some of this diversity can be attributed to real physiological and environmental differences, most is due to differences in philosophy about the best methodological approach to use and in the way the theoretical approaches are applied. The report highlights the main methodological and technological issues that will need to be resolved before harmonization can be fully considered. Solving these issues may help to improve the quality and consistency of dietary reference values across Europe. However, there are also considerable scientific and political barriers that will need to be overcome and the question of whether harmonization of dietary reference values for children and adolescents is a desirable or achievable goal for Europe requires further consideration.

Intrauterine growth retardation: evidence for the activation of the insulin-like growth factor (IGF)-related growth-promoting machinery and the presence of a cation-independent IGF binding protein-3 proteolytic activity by two months of life.

Thirty-seven children with intrauterine growth retardation (IUGR) were enrolled in a 3-mo longitudinal study. Weight, length, and knee-heel length(by knemometry) were measured at birth and at 7, 14, 30, 60, and 90 d. GH, IGF-I, IGF binding protein (BP)-3, IGFBP-1, and C-peptide were measured at birth and at 2 mo. IGFBP-3 Western immunoblotting and proteolytic activity assay were also performed. Twenty-five newborns with birth weight appropriate for gestational age were chosen as controls. At birth IUGR newborns showed levels of GH and IGFBP-1 significantly higher, and IGF-I, IGFBP-3, and C-peptide significantly lower than control subjects. At 2 mo GH and IGFBP-1 levels decreased, whereas IGF-I, IGFBP-3, and C-peptide rose, attaining the concentrations found in control subjects at birth. Baseline peptide levels as well as their 2-mo variations did not correlate with the gain in weight, supine length, and knee-heel length recorded at 3 mo. Fourteen of nineteen IUGR cord blood samples showed the presence of the intact ∼42-39-kD IGFBP-3 doublet and the major ∼29-kD fragment. At 2 mo the IGFBP-3 band pattern was characterized by the predominance of a ∼18-kD fragment in 6 of 19 tested IUGR infants. The incubation of 2-mo IUGR samples with normal adult serum induced the appearance of the ∼18-kD band, which was not modified by the addition of EDTA. These results suggest that: 1) the IGF-related growth-promoting mechanism is impaired in IUGR children at birth but is fully restored at 2 mo; 2) the cord blood levels of GH, IGF-I, IGFBP-3, IGFBP-1, and C-peptide are not predictive of the weight and length gain during the first 3 mo of life; 3) IUGR children have at least two different IGFBP-3 proteases, one cation-dependent protease that is present at birth and able to yield the major ∼29-kD IGFBP-3 fragment and a second one, with a different activation timing, which exhibits cation independence and induces the formation of a ∼18-kD IGFBP-3 form.

Bone turnover in malnourished children

Pyridinoline (PYD) and deoxypyridinoline (DPD) are cross-linking aminoacids of collagen that are located mainly in bone and cartilage. When bone matrix is resorbed these cross-links are quantitatively excreted in the urine and therefore represent specific markers. We have measured the urinary excretion rate of PYD and DPD in 46 severely malnourished boys to assess their skeletal turnover and to relate this to their subsequent rate of growth. The children were aged 13 months (SD 6), and height-for-age was -3.6 (1.6) Z-score, and weight-for-height was -2.4 (0.8) Z-score. PYD excretion when malnourished and after recovery was 11.2 (4.6) nmol h-1m-2 and 32.2 (10.8) nmol h-1m-2 and DPD excretion was 2.6 (1.3) nmol h-1m-2 and 7.5 (3.0) nmol h-1m-2, respectively. The ratio of the two cross-links did not change with recovery. These data show that cartilage and bone turnover is much lower in the malnourished than in the recovered child. There was no difference in the degree of depression of turnover between the children with marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain during recovery was significantly related to cross-link excretion, age, and weight-for-height on admission. These three factors accounted for 44% of the variance in the height velocity of the children. PYD and DPD excretion rate could be used to assess therapeutic interventions designed to alleviate stunting.

Soy isoflavones increase preprandial peptide YY (PYY), but have no effect on ghrelin and body weight in healthy postmenopausal women.

BackgroundSoy isoflavones show structural and functional similarities to estradiol. Available data indicate that estradiol and estradiol-like components may interact with gut satiety hormones such as peptide YY (PYY) and ghrelin, and thus influence body weight. In a randomized, double-blind, placebo-controlled, cross-over trial with 34 healthy postmenopausal women (59 ± 6 years, BMI: 24.7 ± 2.8 kg/m2), isoflavone-enriched cereal bars (50 mg isoflavones/day; genistein to daidzein ratio 2:1) or non-isoflavone-enriched control bars were consumed for 8 weeks (wash-out period: 8-weeks). Seventeen of the subjects were classified as equol producers. Plasma concentrations of ghrelin and PYY, as well as energy intake and body weight were measured at baseline and after four and eight weeks of each intervention arm.ResultsBody weight increased in both treatment periods (isoflavone: 0.40 ± 0.94 kg, P < 0.001; placebo: 0.66 ± 0.87 kg, P = 0.018), with no significant difference between treatments. No significant differences in energy intake were observed (P = 0.634). PYY significantly increased during isoflavone treatment (51 ± 2 pmol/L vs. 55 ± 2 pmol/L), but not during placebo (52 ± 3 pmol/L vs. 50 ± 2 pmol/L), (P = 0.010 for treatment differences, independent of equol production). Baseline plasma ghrelin was significantly lower in equol producers (110 ± 16 pmol/L) than in equol non-producers (162 ± 17 pmol/L; P = 0.025).ConclusionSoy isoflavone supplementation for eight weeks did not significantly reduce energy intake or body weight, even though plasma PYY increased during isoflavone treatment. Ghrelin remained unaffected by isoflavone treatment. A larger and more rigorous appetite experiment might detect smaller differences in energy intake after isoflavone consumption. However, the results of the present study do not indicate that increased PYY has a major role in the regulation of body weight, at least in healthy postmenopausal women.

Investigating the role of natural phyto-oestrogens on bone health in postmenopausal women.

Research on the bone effects of natural phyto-oestrogens after menopause is at a relatively early stage. Published studies are few, difficult to compare and often inconclusive, due in part to design weaknesses. Currently, many questions remain to be answered including to what extent a safe daily intake may prevent postmenopausal bone loss. These questions can only be addressed by conducting well-planned, randomised clinical trials that take into consideration present knowledge in the oestrogen, phyto-oestrogen and bone fields. This review is intended to provide hints for critical decision-making about the selection of subjects, type of intervention, suitable outcome measures and variables that need to be controlled.

Evidence for associations between common polymorphisms of estrogen receptor beta gene with homocysteine and nitric oxide.

Backgroundu2003Homocysteine and asymmetric dimethylarginine (ADMA) affect nitric oxide (NO) concentration, thereby contributing to cardiovascular disease (CVD). Both amino acids can be reduced in vivo by estrogen. Variation in the estrogen receptor (ER) may influence homocysteine and ADMA, yet no information is available on associations with single nucleotide polymorphisms in the estrogen receptor genes ERα (PvuII and XbaI) and ERβ (1730G→A and cx + 56 G→A). Objectiveu2003To find relationships between common polymorphisms associated with cardiovascular disease and cardiovascular risk factors homocysteine and ADMA. Methodsu2003In a cross-sectional study with healthy postmenopausal women (n = 89), homocysteine, ADMA, nitric oxide metabolites (NOx), plasma folate and ERα and β polymorphisms ERα PvuII, ERα XbaI; ERβ 1730G→A (AluI), ERβ cx + 56 G→A (Tsp509I) were analyzed. Resultsu2003Women who are homozygotic for ERβcx + 56 G→A A/A exhibited higher homocysteine (p = 0.012) and NOx (p = 0.056) levels than wildtype or heterozygotes. NOx concentration was also significantly affected by ERβ 1730 G →A polymorphism (p = 0.025). The ERβ (p < 0.001) and ERα (p < 0.001) polymorphisms were in linkage disequilibrium. Conclusionsu2003Women who are homozygotic for ERβcx + 56 G→A A/A may be at increased risk for cardiovascular disease due to higher homocysteine levels.

Food matrix and isoflavones bioavailability in early post menopausal women: A European clinical study

The estrogenic effects of soy isoflavones (IF) on symptoms of menopause are of particular interest. The aim of the present study was to improve compliance of IF in two IF-enriched foods providing the same IF circulating levels in postmenopausal women. Forty-two healthy postmenopausal women (mean age: 53.28 years) were recruited for a randomized, crossover, multicenter trial conducted in the Netherlands, Italy and France. Over 18 days, volunteers were assigned to two groups and supplemented with two different IF-enriched foods (100 mg IF aglycones/two servings). The first group had to eat two biscuits daily for three days. After a wash-out period (11 d), they received cereal bars for three days. The second group started with the cereal bars and finished with biscuits. After IF intake, plasma and urinary levels of genistein, daidzein, O desmethyl angolensin and equol significantly increased and returned to baseline level after the washout period. There was no difference between biscuits and cereals bars intake, as shown by group values at each end of experimental period (day 4 or day 18). Both matrixes are comparable in terms of IF-circulating levels and could be used independently.

Salt iodisation and public health campaigns to eradicate iodine deficiency disorders in Armenia

BACKGROUNDnIodine deficiency disorders (IDD) are endemic in the mountain regions of Armenia. Universal salt iodisation has been chosen as the control measure.nnnOBJECTIVESn(1). To measure the prevalence of iodine deficiency in the Armenian population; (2). to evaluate household use of iodised salt; and (3). to monitor iodised salt promotion strategies.nnnDESIGNnCross-sectional study on a nationally representative sample of 2627 households, including 3390 children under five and 2649 women of fertile age. Cluster sampling design on four population strata: residents, refugees, rural and urban.nnnRESULTSnThyroid was palpable in one-third of the women, 6% of them having a visible goitre. Median of urinary iodine excretion in children was 139.5 microg l-1. One-third of the children showed low urinary iodine concentration. Iodised salt was consumed in 66% of the households. The national IDD control programme included modernisation of the Yerevan Salt Factory, legislative regulation of the iodine content of the salt, and public information by the media.nnnCONCLUSIONSnArmenia was still an endemic zone for goitre in 1997. The iodine status of children under five in 1997 was not considered alarming even though 33% of them had low values of urinary iodine. After four years of intervention strategies, the use of iodised salt has increased by 17%. Further efforts should be made to control salt imports and to monitor IDD indicators in vulnerable groups.