Dietary amino acid intake and sleep duration are additively involved in future cognitive decline in Japanese adults aged 60 years or over: a community-based longitudinal study.

BACKGROUND: Sleep duration and amino acid intake are independently associated with cognitive decline. This study aimed to determine the longitudinal association between sleep duration and cognitive impairment incidence and to examine the involvement of diet, particularly amino acid intake, in these associations in community dwellers. METHODS: In this longitudinal study in a community-based setting, we analyzed data from 623 adults aged 60-83 years without cognitive impairment at baseline. Sleep duration was assessed using a self-report questionnaire. Amino acid intake was assessed using 3-day dietary records. Cognitive impairment was defined as a Mini-Mental State Examination score ≤ 27. Participants were classified into short-, moderate-, and long-sleep groups according to baseline sleep duration (≤ 6, 7-8, and > 8 h, respectively). Using moderate sleep as a reference, odds ratios (ORs) and 95% confidence intervals (CIs) of short- and long-sleep for cognitive-impairment incidence were estimated using the generalized estimating equation. Participants were classified according to sex-stratified quartiles (Q) of 19 amino acid intake: Q1 and Q2-Q4 were low- and middle to high-intake groups, respectively. Using middle- to high-intake as a reference, ORs and 95% CIs of low intake for cognitive impairment incidence were estimated using the generalized estimating equation in each sleep-duration group. Follow-up period, sex, age, body mass index, depressive symptoms, education, smoking status, employment status, sleep aids use, physical activity, medical history, and Mini-Mental State Examination score at baseline were covariates. RESULTS: Mean follow-up period was 6.9 ± 2.1 years. Adjusted ORs (95% CIs) for cognitive impairment in short- and long-sleep groups were 0.81 (0.49-1.35, P = 0.423) and 1.41 (1.05-1.87, P = 0.020), respectively. Particularly in long sleepers (i.e., > 8 h), cognitive impairment was significantly associated with low cystine, proline, and serine intake [adjusted ORs (95% CIs) for cognitive impairment were 2.17 (1.15-4.11, P = 0.017), 1.86 (1.07-3.23, P = 0.027), and 2.21 (1.14-4.29, P = 0.019), respectively]. CONCLUSIONS: Community-dwelling adults aged ≥ 60 years who sleep longer are more likely to have cognitive decline, and attention should be paid to the low cystine, proline, and serine intake.

Nutrient Profiling of Japanese Dishes: The Development of a Novel Ajinomoto Group Nutrient Profiling System.

Government agencies and private companies have supported the development of nutrient profiling (NP) systems to facilitate the selection of nutrient-dense foods by consumers, promote nutritious food development, and limit excessive advertising of products with low nutritional value. While most NP models were developed to assess individual foods, the Ajinomoto Group Nutrient Profiling System (ANPS) was developed to assess the overall nutritional value of cooked dishes that are culturally specific to Japan. Based on the national dietary recommendations and nutritional surveys, target values were created for 13 dish categories, while considering the combinations of meal units. For the ANPS, the four evaluating elements were protein and vegetables, which should be encouraged, and sodium and saturated fatty acids, which should be limited. The ANPS algorithm for dishes was the sum of the scores of individual elements, with a maximum of 10 points per serving. The sum of scores was then multiplied by 2.5 to convert to the 100-point scale. Convergent validity was tested using the nutrient-rich food index (NRF) score of 6.3. In total, 1,089 popular Japanese dishes were evaluated using the ANPS, and the median score of ANPS was 70.0 points (interquartile range, 55-78.8), and the average score was 67.7 (standard deviation, 16.5) points. Since salt intake is a major health risk in Japan, this tool was designed to evaluate sodium content with high sensitivity, and low-salt dishes significantly improved sodium and ANPS scores compared with regular dishes. The Pearson's correlation coefficient between the total score of NRF 6.3 and ANPS in 1,089 dishes was r = 0.452 (p < 0.0001). This newly developed ANPS could be used to evaluate culture-specific cooked dishes per serving size. It can determine the nutritional values of dishes, with a high sensitivity to sodium content, a major Japanese nutritional issue. Further research is needed to determine the accuracy and usefulness of the ANPS as a system that would lead to changes in eating behavior nationwide.

Decreased circulating branched-chain amino acids are associated with development of Alzheimer's disease in elderly individuals with mild cognitive impairment.

Background: Nutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants. Method: In a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal ("MCI-stable," N = 87) and converted to Alzheimer's disease (AD) ("AD-convert," N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted. Results: Plasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group. Conclusion: The PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status. Clinical trial registration: [https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].

Association between plasma α-aminobutyric acid and depressive symptoms in older community-dwelling adults in Japan.

AIM: To examine the association between depressive symptoms and plasma amino acid related metaboli in older adults. METHODS: A total of 152 older adults aged ≥65 years, residing in Niigata, Japan, were used for analysis. We evaluated depressive symptoms using the Geriatric Depression Scale-15, which has been validated in older community-dwelling individuals, and used a cut off score of ≥5 to classify participants as having depressive symptoms. We used high-performance liquid chromatography-electrospray ionization mass spectrometry to measure the concentrations of plasma amino acid-related metabolites, and carried out logistic regression analysis to assess the association between depressive symptoms and plasma amino acid-related metabolites. RESULTS: Of the 119 older adults (mean age 76.3 years) included in the analysis, 22 were classified as having depressive symptoms (depressive group). There were no significant differences in physical and cognitive impairments between participants in the depressive and non-depressive groups. The plasma α-aminobutyric acid (AABA) level was significantly lower in the depressive group than in the non-depressive group (P < 0.001). Logistic regression analysis showed the best-fit model, which included AABA, leucine, threonine, hydroxyl proline and histidine levels (area under the receiver operating characteristic curve 0.8346; 95% confidence interval 0.7365-0.9326). In particular, the plasma AABA level was strongly associated with depressive symptoms. CONCLUSIONS: Plasma AABA level is significantly associated with depression symptoms in older community-dwelling adults in Japan. Thus, plasma AABA might serve as a potential marker of depression in older adults aged ≥65 years. Geriatr Gerontol Int 2019; 19: 254-258.

A ketogenic amino acid rich diet benefits mitochondrial homeostasis by altering the AKT/4EBP1 and autophagy signaling pathways in the gastrocnemius and soleus.

Muscle biology is important topic in diabetes research. We have reported that a diet with ketogenic amino acids rich replacement (KAAR) ameliorated high-fat diet (HFD)-induced hepatosteatosis via activation of the autophagy system. Here, we found that a KAAR ameliorated the mitochondrial morphological alterations and associated mitochondrial dysfunction induced by an HFD through induction of the AKT/4EBP1 and autophagy signaling pathways in both fast and slow muscles. The mice were fed with a standard HFD (30% fat in food) or an HFD with KAAR (HFDKAAR). In both the gastrocnemius and the soleus, HFDKAAR ameliorated HFD-impaired mitochondrial morphology and mitochondrial function, characterized by decreased mitofusin 2, optic atrophy 1, peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α and PPARα levels and increased dynamin-related protein 1 levels. The decreased levels of phosphorylated AKT and 4EBP1 in the gastrocnemius and soleus of HFD-fed mice were remediated by HFDKAAR. Furthermore, the HFDKAAR ameliorated the HFD-induced autophagy defects in the gastrocnemius and soleus. These findings suggest that KAAR may be a novel strategy to combat obesity-induced mitochondrial dysfunction, likely through induction of the AKT/4EBP1 and autophagy pathways in skeletal muscle.

Plasma Free Amino Acid Profiles Predict Four-Year Risk of Developing Diabetes, Metabolic Syndrome, Dyslipidemia, and Hypertension in Japanese Population.

Plasma free amino acid (PFAA) profile is highlighted in its association with visceral obesity and hyperinsulinemia, and future diabetes. Indeed PFAA profiling potentially can evaluate individuals' future risks of developing lifestyle-related diseases, in addition to diabetes. However, few studies have been performed especially in Asian populations, about the optimal combination of PFAAs for evaluating health risks. We quantified PFAA levels in 3,701 Japanese subjects, and determined visceral fat area (VFA) and two-hour post-challenge insulin (Ins120 min) values in 865 and 1,160 subjects, respectively. Then, models between PFAA levels and the VFA or Ins120 min values were constructed by multiple linear regression analysis with variable selection. Finally, a cohort study of 2,984 subjects to examine capabilities of the obtained models for predicting four-year risk of developing new-onset lifestyle-related diseases was conducted. The correlation coefficients of the obtained PFAA models against VFA or Ins120 min were higher than single PFAA level. Our models work well for future risk prediction. Even after adjusting for commonly accepted multiple risk factors, these models can predict future development of diabetes, metabolic syndrome, and dyslipidemia. PFAA profiles confer independent and differing contributions to increasing the lifestyle-related disease risks in addition to the currently known factors in a general Japanese population.

Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with altering autophagy-associated molecules.

Ketogenic amino acid (KAA) replacement diet has been shown to cure hepatic steatosis, a serious liver disease associated with diverse metabolic defects. In this study, we investigated the effects of KAA replacement diet on nutrition sensing signaling pathway and analyzed whether induction of hepatic autophagy was involved. Mice are fed with high fat diet (HFD) or KAA replacement in high-fat diet (30% fat in food; HFD)-fed (HFD(KAAR)) and sacrificed at 8, 12, 16 weeks after initiation of experimental food. Hepatic autophagy was analyzed in protein expression of several autophagy-associated molecules and in light chain-3 green fluorescent protein (LC-3 GFP) transgenic mice. HFD(KAAR) showed increased AMP-activated protein kinase (AMPK) phosphorylation and enhanced liver kinase B1 (LKB1) expression compared to control HFD-fed mice. The KAA-HFD-induced activation of AMPK was associated with an increased protein expression of sirtuin 1 (Sirt1), decreased forkhead box protein O3a (Foxo3a) level, and suppression of mammalian target of rapamycin (mTOR) phosphorylation compared with the HFD-fed mice. The intervention study revealed that a KAA-replacement diet also ameliorated all the established metabolic and autophagy defects in the HFD-fed mice, suggesting that a KAA-replacement diet can be used therapeutically in established diseases. These results indicate that KAA replacement in food could be a novel strategy to combat hepatic steatosis and metabolic abnormalities likely involvement of an induction of autophagy.