Estimation of inter-individual variability of protein requirement by indicator amino acid oxidation method

It is now generally believed that elderly may have slightly higher dietary protein requirements than those of the young-middle-aged adults. We have previously conducted related studies by the indicator amino acid oxidation (IAAO) technique, but more research data are needed to revise the protein requirements of the elderly. The main objective was to reevaluate the dietary protein requirements of healthy Chinese adults (65-80y) without sarcopenia by using the IAAO technique. Nine healthy adult men and seven healthy adult women participated in the study, with protein intakes ranging from 0.1 to 1.8 g/(kg·d). Diets that delivered energy at a 1.5 resting energy expenditure (REE) were isocaloric. The amounts of phenylalanine and tyrosine needed to remain constant for each protein dosage. By applying a nonlinear mixed-effects model analysis on the F13CO2 data, which revealed a breakpoint in F13CO2 in response to graded protein intakes, the mean protein requirement was calculated. The mean estimated average requirement (EAR) for healthy elderly Chinese adults without sarcopenia was determined to be 0.94 g/(kg·d). The protein recommended nutrient intake (RNI) determined using various derivation approaches ranged from 1.13 to 1.36 g/(kg·d). The EAR for Chinese adults without sarcopenia aged 65-80 years in this study is 6.8% higher than the current recommended EAR [0.88 g/(kg·d)]. The RNI derived using various derivation approaches are all greater than the current RNI [0.98 g/(kg·d)]. This trial was registered with the Chinese clinical trial registry as ChiCTR2200061382.

L-Arg (L-Arg) is a nonessential amino acid but has many physiological roles. Accordingly, L-Arg has been used in various fields, but there is only limited information available about its safety upon overdose. Generally, the no observed adverse effect level (NOAEL) is used when setting the upper amount for chemical substances. Recently, systematic reviews have been used to assess the safety as well as the effectiveness and usefulness of them. Therefore, we conducted an assessment of the safety of the oral intake of L-Arg in healthy subjects by using gastrointestinal symptoms as an index. We limited the study design to only double-blind randomized controlled trials and searched PubMed, Cochrane Library, EBSCOhost, and Ichushi-Web from inception until May 2021. Assessment of the quality of studies was conducted using the Cochrane Collaboration tool and Jadad score, and the random effects model was used for data analysis. Ultimately, 34 studies were selected for inclusion in this work. The dosage of L-Arg used in the studies ranged from 2000 to 30,000 mg/day (or / one-time dose), and the treatment duration was 1 to 84 days. The increased risk of gastrointestinal symptoms associated with L-Arg intake from 23 studies (647 participants in total) in which such symptoms were reported was 0.01 (95% confidence interval: -0.02 to 0.04), which was not significant difference. NOAEL was estimated as 7531 mg/ one-time dose by using a weighted change-point regression model. (UMIN000046133)

Systematic reviews can be used not only to evaluate the efficacy and usefulness of a drug or food ingredient, but also as a safety assessment method. One of the aims of safety assessment is to estimate the no observed adverse effect level and the lowest observed adverse effect level. However, no methodology to statistically estimate the no observed adverse effect level from systematic review results has yet been reported. Estimation of the no observed adverse effect level involves a search for the dose above which adverse events occur is even exploration of the thresholds in dose response. To search for the dose above which adverse events occur, we examined an estimation method using the weighted change-point regression model, which includes the weights of each study used for systematic reviews in the model. This model could be applied to safety data of an omega-3 study in the form of a systematic review. We demonstrated that the dose response to omega-3 intake regarding adverse events had a threshold value and that the no observed adverse effect level could be estimated using the developed model.