Branched chain amino acids harbor distinct and often opposing effects on health and disease.

BACKGROUND: The branched chain amino acids (BCAA) leucine, isoleucine, and valine are essential nutrients that have been associated with diabetes, cancers, and cardiovascular diseases. Observational studies suggest that BCAAs exert homogeneous phenotypic effects, but these findings are inconsistent with results from experimental human and animal studies. METHODS: Hypothesizing that inconsistencies between observational and experimental BCAA studies reflect bias from shared lifestyle and genetic factors in observational studies, we used data from the UK Biobank and applied multivariable Mendelian randomization causal inference methods designed to address these biases. RESULTS: In n = 97,469 participants of European ancestry (mean age = 56.7 years; 54.1% female), we estimate distinct and often opposing total causal effects for each BCAA. For example, of the 117 phenotypes with evidence of a statistically significant total causal effect for at least one BCAA, almost half (44%, n = 52) are associated with only one BCAA. These 52 associations include total causal effects of valine on diabetic eye disease [odds ratio = 1.51, 95% confidence interval (CI) = 1.31, 1.76], valine on albuminuria (odds ratio = 1.14, 95% CI = 1.08, 1.20), and isoleucine on angina (odds ratio = 1.17, 95% CI = 1.31, 1.76). CONCLUSIONS: Our results suggest that the observational literature provides a flawed picture of BCAA phenotypic effects that is inconsistent with experimental studies and could mislead efforts developing novel therapeutics. More broadly, these findings motivate the development and application of causal inference approaches that enable 'omics studies conducted in observational settings to account for the biasing effects of shared genetic and lifestyle factors.

The three branched chain amino acids (BCAAs) leucine, isoleucine, and valine are important building blocks of muscle proteins that are obtained from the diet. Many studies in human populations have examined whether BCAAs affect health and disease. These human studies report results that are inconsistent with results from highly controlled animal studies. Because interest in the therapeutic targeting of BCAAs is growing, we wanted to better understand these discrepancies. Briefly, we used data from a large database that captured many diseases (e.g., cardiovascular disease, cancers, and respiratory disease) and new statistical methods. Our results showed that discrepancies between human studies and animal studies may reflect errors in the ways human studies were designed and conducted. As a result, these human studies may provide a flawed picture of BCAA effects that could mislead efforts developing novel therapeutics.

Sleep disturbances among cancer survivors.

PURPOSE: We investigated sleep disturbances among cancer survivors compared to similarly aged women without cancer history. METHODS: We identified 2067 women with a history of cancer other than breast or non-melanoma skin cancer at enrollment in the Sister Study, a US-wide cohort of women with a family history of breast cancer. Cancer survivors were matched with up to 5 cancer-free women (N = 9717) on age at enrollment. An index age (for covariate classification) was defined as the age at cancer diagnosis for survivors and the same age for their matched comparators. Sleep disturbances included duration, sleep medication usage, insomnia symptoms, long sleep-latency onset (≥30 min to fall asleep), frequent night awakenings (waking ≥3/night, ≥ 3 times/week), frequent napping (≥ 3 times/week), and a composite outcome of ≥ 1sleep disturbance. Multivariable linear regression (effect estimate, 95% confidence interval (CI)) and logistic regression (odds ratio, OR, 95% CI) were used for continuous and dichotomous outcomes, respectively. RESULTS: At enrollment, cancer survivors were on average 13.8 years (range=0, 62) from diagnosis. After adjustment for age at enrollment and depression, diabetes, hypertension, and menopausal status prior to the index age, sleep disturbances were generally not more common among cancer survivors compared to those without cancer. However, among cancer survivors, those > 2 years from diagnosis were more likely to report ≥ 1 sleep disturbance (OR=1.44; 1.07, 1.93) compared to survivors 0-2 years from diagnosis. CONCLUSION: Addressing sleep disturbances may improve well-being for cancer survivors.