Background: Frequent dairy consumption in childhood has been related to higher growth-hormone concentrations that may affect mammary gland and pubertal development.Objective: We evaluated the relation of dairy intake to breast composition at Tanner stage 4 and age at menarche.Design: A total of 515 Chilean girls are included in the Growth and Obesity Cohort Study. The subjects have been followed longitudinally since they were 3-4 y old (from 2006 to the present). Starting in 2013, diet was assessed every 6 mo via a 24-h recall. The breast fibroglandular volume (FGV) was measured with the use of dual-energy X-ray absorptiometry at Tanner stage 4. The date of menarche was reported every 6 mo. Our analysis included 290 girls with data on prospective diet and breast composition and 324 girls with data on prospective diet and age at menarche.Results: The mean ± SD breast FGV and percentage of fibroglandular volume (%FGV) (i.e., FGV divided by total breast volume times 100) at Tanner stage 4 was 81.7 ± 32.2 cm³ and 42.0% ± 16.7%, respectively. Only sweetened, artificially flavored milk-based drinks were associated with the %FGV with girls who consumed >125 g/d having a %FGV that was 4.5% (95% CI: 0.9%, 8.1%) higher than that of girls who consumed none (P-trend = 0.007). Yogurt intake was associated with a lower FGV. Specifically, girls who consumed >125 g yogurt/d had -10.2 cm³ (95% CI: -20.2, -0.3 cm³) less FGV than did girls who consumed no yogurt (P-trend = 0.03). The majority (90.7%) of girls in our cohort attained menarche before the data analyses with a mean ± SD age at menarche of 11.9 ± 0.7 y. In multivariable models, low-fat dairy, low-fat milk, and yogurt intakes were associated with a later age at menarche. In particular, girls who consumed >125 g yogurt/d had menarche, on average, 4.6 mo (95% CI: 1.9, 7.4 mo) later than girls who consumed no yogurt (P-trend = 0.01).Conclusion: More-frequent consumption of sweetened, artificially-flavored milk-based drinks is associated with a higher %FGV, whereas higher yogurt intake is associated with a lower FGV and delayed age at menarche in Chilean girls.

Background

Elevated body mass index (BMI) is a risk factor for cardiovascular disease, diabetes, cancer, and other diseases. Inflammation or oxidative stress induced by high BMI may explain some of these effects. Millions of people drink arsenic-contaminated water worldwide, and ingested arsenic has also been associated with inflammation, oxidative stress, and cancer.

Objectives

To assess the unique situation of people living in northern Chile exposed to high arsenic concentrations in drinking water and investigate interactions between arsenic and BMI, and associations with lung and bladder cancer risks.

Methods

Information on self-reported body mass index (BMI) at various life stages, smoking, diet, and lifetime arsenic exposure was collected from 532 cancer cases and 634 population-based controls.

Results

In subjects with BMIs <90th percentile in early adulthood (27.7 and 28.6 kg/m(2) in males and females, respectively), odds ratios (OR) for lung and bladder cancer combined for arsenic concentrations of <100, 100-800 and >800 µg/L were 1.00, 1.64 (95% CI, 1.19-2.27), and 3.12 (2.30-4.22). In subjects with BMIs ≥90th percentile in early adulthood, the corresponding ORs were higher: 1.00, 1.84 (0.75-4.52), and 9.37 (2.88-30.53), respectively (synergy index=4.05, 95% CI, 1.27-12.88). Arsenic-related cancer ORs >20 were seen in those with elevated BMIs in both early adulthood and in later life. Adjustments for smoking, diet, and other factors had little impact.

Conclusion

These findings provide novel preliminary evidence supporting the notion that environmentally-related cancer risks may be markedly increased in people with elevated BMIs, especially in those with an elevated BMI in early-life.

Background

The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized.

Objective

We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion.

Methods

A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin. The combined indicator of vitamin B-12 status (cB-12) was computed. Targeted metabolites [166 acylcarnitines, amino acids, sugars, glycerophospholipids, and sphingolipids (liquid chromatography-tandem mass spectrometry)], and untargeted metabolites [247 chemical entities (gas chromatography time-of-flight mass spectrometry)] were measured at baseline and 4 mo after treatment. A peripheral nerve score was developed. Differences before and after treatment were examined. For targeted metabolomics, the data from 18 individuals with adequate vitamin B-12 status (selected from the same population) were added to the before-and-after treatment data set. Network visualizations and metabolic pathways are illustrated.

Results

The injection increased serum vitamin B-12, holotranscobalamin, and cB-12 (P < 0.001), and reduced tHcy and serum MMA (P < 0.001). Metabolomic changes from before to after treatment included increases (P < 0.001) in acylcarnitines, plasmalogens, and other phospholipids, whereas proline and other intermediaries of one-carbon metabolism-that is, methionine and cysteine-were reduced (P < 0.001). Direct significant correlations (P < 0.05 after the false discovery rate procedure) were identified between acylcarnitines, plasmalogens, phospholipids, lyso-phospholipids, and sphingomyelins compared with vitamin B-12 status and nerve function. Multiple connections were identified with primary metabolites (e.g., an inverse relation between vitamin B-12 markers and tryptophan, tyrosine, and pyruvic, succinic, and citric acids, and a direct correlation between the nerve score and arginine).

Conclusions

The human serum metabolome in vitamin B-12 deficiency and the changes that occur after supplementation are characterized. Metabolomics revealed connections between vitamin B-12 status and serum metabolic markers of mitochondrial function, myelin integrity, oxidative stress, and peripheral nerve function, including some previously implicated in Alzheimer and Parkinson diseases. This trial was registered at www.controlled-trials.com as ISRCTN02694183.

Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections)¹ and preventive interventions (for example, multiple-micronutrient supplementation)² that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood³. In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites worldwide⁴, we studied the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks' gestation, against international standards^5,6, and growth and neurodevelopment up to 2 years of age^7,8. We identified five trajectories associated with specific neurodevelopmental, behavioral, visual and growth outcomes, independent of fetal abdominal growth, postnatal morbidity and anthropometric measures at birth and age 2. The trajectories, which changed within a 20-25-week gestational age window, were associated with brain development at 2 years of age according to a mirror (positive/negative) pattern, mostly focused on maturation of cognitive, language and visual skills. Further research should explore the potential for preventive interventions in pregnancy to improve infant neurodevelopmental outcomes before the critical window of opportunity that precedes the divergence of growth at 20-25 weeks' gestation.

Lower ambient temperature (T_a) requires greater energy expenditure to sustain body temperature. However, effects of T_a on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of T_a (-10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average T_a and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and T_a emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18-25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures.

Background

Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

Objectives

A study is presented of the association between FFM and physical activity in relation to age.

Methods

In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution.

Results

PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively.

Conclusions

If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults.