Integrative Approaches of Bioassay and Computational Analysis for Discovering Potential Bioactive Compounds and Predictive Toxicity.

Changes in eating habits are brought about by drastic changes in lifestyle and environment, and, it has been pointed out, are strongly involved in the increase in neurological diseases and onset of cancer in younger adult ages. There is a wide variety of chemical substances in food, and there is a need to analyze the effects of complex exposures on complex mechanisms of action and to develop methods for evaluating and predicting them. The power of molecular nutrition needs to create an integrated approach to human nutrition in line with the grand social challenges of diet-related illnesses. The current article aims to explore some of these areas where integration is appropriate. Therefore, in this symposium, we will introduce the contents of four performers who are conducting cutting-edge research. 1) Chemoprevention by vitamin A and its derivatives, 2) Toxicity prediction of natural compounds from a developing database of bioactive gradients from Kampo medicine, 3) Toxicity prediction of chemicals using pluripotent stem cells. 4) Detection of bioactive compounds in "Aji" or "Umami" in food. By detecting and predicting the biological activity and toxicity of chemical substances such as nutrients in foods, it will be possible to provide better molecular information on dietary components. In addition, we will introduce next-generation health and prevention methods.

Effect of Docosahexaenoic Acid and Eicosapentaenoic Acid Supplementation on Sleep Quality in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-omega-3 fatty acids with various functions-influence sleep in children and young adults. However, only limited studies on their effects on sleep in middle- and old-aged adults have been reported. Therefore, we investigated the effects of DHA and EPA on sleep quality in subjects aged ≥ 45 years. We performed a randomized, placebo-controlled, double-blinded, parallel-grouped study, in which we randomly assigned 66 healthy Japanese males and females. Each individual received six 480 mg capsules containing 576 mg DHA and 284 mg EPA per day (DHA/EPA group, n = 33), or corn oil (placebo group, n = 33), for 12 weeks. Before and after the intervention, the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA) and the sleep state test were conducted. In the DHA/EPA group, factor III (frequent dreaming) scores among the OSA-MA scores were significantly improved compared to the placebo group. Additionally, sleep state tests revealed that sleep efficiency improved in the DHA/EPA group. To our knowledge, this study is the first to report that DHA/EPA improves sleep quality in middle- and old-aged individuals, even at doses lower than those administered in previous studies.

Comprehensive Safety Assessment of l-Lysine Supplementation from Clinical Studies: A Systematic Review.

BACKGROUND: Despite the widespread use of l-lysine in dietary supplements, the safety information pertinent to excessive l-lysine ingestion is limited and, to the best of our knowledge, there is no published systematic review of safety. OBJECTIVE: The objective of this study was to assess the clinical safety of l-lysine supplementation of a regular diet. METHODS: We searched PubMed, Cochrane Library, Ichushi Web, and EBSCOhost using the relevant keywords, "l-lysine" and "clinical trial." To investigate all adverse events observed during intervention trials, we included all intervention studies with orally ingested l-lysine without restricting background factors, environment, study designs, and sample sizes. RESULTS: We identified 71 articles, which included 3357 study subjects. The l-lysine doses ranged from 16.8 to 17.5 g/d, and the dosing period ranged from 1 to 1095 d. The observed adverse events were mainly subjective gastrointestinal tract symptoms; however, the risk analysis for incidence of gastrointestinal symptoms was not statistically significant (risk ratio of 1.02). CONCLUSION: The provisional no-observed-adverse-effect level in healthy human subjects was based on gastrointestinal symptoms and identified at 6.0 g/d. The review protocol was registered at umin.ac.jp as UMIN000028914 before the beginning of the study.

Safety assessment of L-lysine oral intake: a systematic review.

Currently, the use of amino acids in supplements and functional foods is increasing globally. However, there are no guidelines for the upper limit of ingestion for the safe use of these amino acids. Safety evaluation of chemical substances is generally performed through non-clinical and clinical studies. However, amino acids that have these safety data are limited. Therefore, we used a systematic review approach for evaluating the safety of amino acids. In the present study, we evaluated the safety of L-lysine added to an ordinary diet in humans. Using PubMed, Cochrane Library, Ichushi Web, and EBSCOhost as search databases, we comprehensively searched human studies on oral ingestion of L-lysine. Ultimately, 71 studies were selected for evaluation. Of these, 12 studies were of relatively high quality with Jadad scores ≥ 3. The dose range of L-lysine in the selected studies was 16.8-17,500 mg/day, and the range of dosing period was 1-1095 days. The observed adverse events were mainly subjective symptoms related to the gastrointestinal tract such as nausea, stomachache, and diarrhea. The provisional no-observed-adverse-effect level obtained based on these gastrointestinal symptoms was 6000 mg/person/day. Integrated analysis of the risk for developing gastrointestinal symptoms revealed that the risk ratio was 1.02 (95% CI, 0.96-1.07; p = 0.49); thus, no significant increase was observed. (UMIN000028914).

Fish protein hydrolysate exhibits anti-obesity activity and reduces hypothalamic neuropeptide Y and agouti-related protein mRNA expressions in rats.

Fish protein is a source of animal protein that is consumed worldwide. Although it has been reported that the intake of Alaska pollack protein (APP) reduces body fat accumulation and increases muscle weight in rats, the mechanisms underlying these effects are poorly understood. As a possibility, peptides released from APP in the gastrointestinal tract are important to the functions of APP. In the present study, we examined the effects of APP hydrolysate digested artificially with pepsin and pancreatin on white adipose tissue and skeletal muscle. We found that APP hydrolysate group shows significantly lower weight of white adipose tissue and higher weight of soleus muscle than the control group. We also found that APP hydrolysate group reduces food intake and mRNA expressions of neuropeptide Y and agouti-related protein in the hypothalamus compared with the control group. These results may imply that APP hydrolysate exhibits anti-obesity activity by the reduction of appetite and the enhancement of basal energy expenditure by skeletal muscle hypertrophy in rats. The downregulation of orexigenic gene by APP hydrolysate in the hypothalamus may contribute to the reduction of appetite. These results suggest that the effect of APP on anti-obesity and muscle hypertrophy may be induced by peptides released from APP in the gastrointestinal tract.

Eicosapentaenoic and docosahexaenoic acids-rich fish oil supplementation attenuates strength loss and limited joint range of motion after eccentric contractions: a randomized, double-blind, placebo-controlled, parallel-group trial.

PURPOSE: This study investigated the effect of eicosapentaenoic and docosahexaenoic acids-rich fish oil (EPA + DHA) supplementation on eccentric contraction-induced muscle damage. METHODS: Twenty-four healthy men were randomly assigned to consume the EPA + DHA supplement (EPA, n = 12) or placebo (PL, n = 12) by the double-blind method. Participants consumed EPA + DHA or placebo supplement for 8 weeks prior to exercise and continued it until 5 days after exercise. The EPA group consumed EPA + DHA-rich fish oil containing 600 mg EPA and 260 mg DHA per day. Subjects performed five sets of six maximal eccentric elbow flexion exercises. Changes in the maximal voluntary contraction (MVC) torque, range of motion (ROM), upper arm circumference, muscle soreness as well as serum creatine kinase, myoglobin, IL-6, and TNF-α levels in blood were assessed before, immediately after, and 1, 2, 3, and 5 days after exercise. RESULTS: MVC was significantly higher in the EPA group than in the PL group at 2-5 days after exercise (p < 0.05). ROM was also significantly greater in the EPA group than in the PL group at 1-5 days after exercise (p < 0.05). At only 3 days after exercise, muscle soreness of the brachialis was significantly greater in the PL group than in the EPA group (p < 0.05), with a concomitant increase in serum IL-6 levels in the PL group. CONCLUSION: Eight-week EPA + DHA supplementation attenuates strength loss and limited ROM after exercise. The supplementation also attenuates muscle soreness and elevates cytokine level, but the effect is limited.

Effects of krill oil containing n-3 polyunsaturated fatty acids in phospholipid form on human brain function: a randomized controlled trial in healthy elderly volunteers.

BACKGROUND: Krill oil, rich in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) incorporated in phosphatidylcholine, has been reported to have many effects on physiological function. However, there are few studies using psychophysiological methods published that describe the effects of krill oil on brain function. We investigated the influence of ingestion of krill oil on cognitive function in elderly subjects by using near-infrared spectroscopy and electroencephalography. METHODS: A randomized, double-blind, parallel-group comparative study design was adopted. Forty-five healthy elderly males aged 61-72 years were assigned to receive 12 weeks of treatment with: medium-chain triglycerides as placebo; krill oil, which is rich in n-3 PUFAs incorporated in phosphatidylcholine; or sardine oil, which is abundant in n-3 PUFAs incorporated in triglycerides. Changes in oxyhemoglobin concentrations in the cerebral cortex during memory and calculation tasks were measured. The P300 component of event-related potentials was also measured during a working memory task. RESULTS: During the working memory task, changes in oxyhemoglobin concentrations in the krill oil and sardine oil groups were significantly greater than those in the medium-chain triglyceride group at week 12. The differential value for P300 latency in the krill oil group was significantly lower than that in the medium-chain triglyceride group at week 12. With regard to the calculation task, changes in oxyhemoglobin concentrations in the krill oil group were significantly greater than those in the medium-chain triglyceride group at week 12. CONCLUSION: This study provides evidence that n-3 PUFAs activate cognitive function in the elderly. This is especially the case with krill oil, in which the majority of n-3 PUFAs are incorporated into phosphatidylcholine, causing it to be more effective than sardine oil, in which n-3 PUFAs are present as triglycerides.

Effects of Garcinia cambogia extract on serum sex hormones in overweight subjects.

(-) Hydroxycitric acid (HCA), an active ingredient extracted from the Garcinia cambogia fruit rind, has been commonly used as a dietary supplement for weight management. Given the controversy over HCA related testicular toxicity in animal studies, we investigated changes in serum sex hormones levels as an extension of our previous double-blind placebo-controlled trial in human subjects, in which 44 participants received either G. cambogia extract (1667.3 mg/day equivalent to 1000 mg HCA/day) or placebo for 12 weeks. Compared to the placebo group, administration of the extract did not significantly alter the serum testosterone, estrone, and estradiol levels. Similarly, hematology, serum triacylglycerol and serum clinical pathology parameters did not reveal any significant adverse effects. The results of this preliminary investigation indicate that ingestion of G. cambogia extract at dose levels commonly recommended for human use does not affect serum sex hormone levels and blood parameters.

Dietary Garcinia cambogia does not modify skin properties of mice with or without excessive sucrose intake.

The influence of 3.3% Garcinia cambogia extract on the properties of mouse skin with or without 10% sucrose water loading was investigated. Mice (7-week-old) were given free access to a control diet or a diet containing Garcinia cambogia extract. They were also given water alone or both water and sucrose water. Their skin was compared by both biochemical and histological methods. The collagen and triacylglycerol contents were not significantly different among the four groups. Similarly, electron microscopy revealed no differences in the thickness of the dermis layer or the subcutaneous tissue layer. Mice given the diet containing Garcinia cambogia tended to have a reduced total number of adipocytes, but not significantly. These results suggest that Garcinia cambogia supplementation for at least 4 weeks does not induce a negative effect on skin properties in mice irrespective of excessive sucrose intake.