Hormesis is defined as a dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition, and has been recognized as representing an overcompensation for mild environmental stress. The beneficial effects of mild stress on aging and longevity have been studied for many years. In experimental animals, mild dietary stress (dietary restriction, DR) without malnutrition delays most age-related physiological changes, and extends maximum and average lifespan. Animal studies have also demonstrated that DR can prevent or lessen the severity of cancer, stroke, coronary heart disease, autoimmune disease, allergy, Parkinson's disease and Alzheimer's disease. The effects of DR are considered to result from hormetic mechanisms. These effects were reported by means of various DR regimens, such as caloric restriction, total-nutrient restriction, alternate-day fasting, and short-term fasting. Mild dietary stress, including restriction of amount or frequency of intake, is the essence of DR. For more than 99% of their history, humans lived as hunter-gatherers and adapted to restrictions in their food supply. On the other hand, an oversufficiency of food for many today has resulted in the current global epidemic of obesity and obesity-related diseases. DR may be used, therefore, as a novel approach for therapeutic intervention in several diseases, when detailed information about effects of mild dietary stress on human health is obtained from clinical trials.

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The aim of this study was to investigate whether the Trp64Arg polymorphism of the β₃-adrenergic receptor gene (ADRB3) is associated with weight changes in obese Japanese men at 4-year follow-up. The participants were 145 obese Japanese men [age: 35.8±5.3 y; body mass index (BMI): 27.5±3.3 kg/m²]. The participants were divided into two groups according to the Trp64Arg genotype: (1) with the Arg64 allele of the ADRB3 (Trp64Arg and Arg64Arg genotypes, n=50); (2) without the Arg64 allele of the ADRB3 (Trp64Trp genotype, n=95). The ADRB3 genotyping was performed by denaturing high performance liquid chromatography (DHPLC). Body weight, BMI, and blood pressure were determined at baseline and at 4 years. After 4 years, the participants with the Arg allele of the ADRB3 significantly increased their body weight (2.1±4.7 kg, p=0.002) and BMI (0.64±1.6 kg/m², p=0.006) whereas the participants without the Arg allele of the ADRB3 did not significantly change in these parameters (body weight: −0.36±4.2 kg, p=0.41; BMI: −0.24±1.5 kg/m², p=0.12). The results in this study showed that the Arg allele of the ADRB3 is associated with long-term changes in body weight in obese individuals. This polymorphism may become an indicator in personalized weight loss programs in obese men.

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Previously, using the breath hydrogen test, we investigated seasonal variations in the amount of unabsorbed dietary carbohydrate from the intestine after breakfast in female Japanese university students and young Polish subjects. In the study we found that there were significant seasonal variations in both countries with the smallest unabsorbed dietary carbohydrate in autumn and the biggest in winter. Considering the theory of human adaptation to living environments, we suggested a hypothesis that this seasonal variation in the efficiency of carbohydrate absorption in the intestine may reflect human adaptation and/or a response to seasonal change in the living environment. In order to prove this hypothesis, we carried out the same examination in Chiang Mai, Thailand, where there is different seasonal change in the living environment from that of Japan and of Poland. In this examination, we measured the amount of unabsorbed dietary carbohydrate (UDC) from the intestine after breakfast and the oro-cecal transit time (OCTT) of the breakfast in female Thai university students using the same method and experimental protocol as previously carried out with Japanese subjects. We conducted the examination in April (the hot season), in August–September (the rainy season), and in November–December (the dry season) of 2008, at the Medical School of Chiang Mai University, Chiang Mai. The results are summarized as follows: (1) there were no significant seasonal variations in the amounts of unabsorbed dietary carbohydrate from breakfast in Thai subjects; (2) there were no significant seasonal variations in the oro-cecal transit times of breakfast or a soluble indigestible trisaccharide (lactosucrose) solution in Thai subjects; (3) there were no significant differences in the oro-cecal transit times of breakfast between the two countries in any season; (4) the UDC of Thai subjects was significantly less than that of the Japanese subjects in the three seasons. These results suggest that differences in seasonal change in a living environment have different effects on seasonal variations in the efficiency of carbohydrate absorption in the intestine after breakfast.

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We examined the relationship between the coefficient of variation in the R-R intervals (CVR-R) using electrocardiograms and the ultrasonic intima-media thickness (IMT) of the carotid artery, an atherosclerotic parameter, in type 2 diabetes mellitus (DM) patients with diabetic neuropathy (n=47, males/females: 29/18; mean age: 62 years). In this study, the CVR-R-related indexes, including CVR-R at rest (CVR-R_rest), CVR-R with deep breaths (CVR-R_breath) and their difference (CVR-R_breath minus CVR-R_rest: CVR-R_dif), were defined. Data such as body mass index, smoking habits, hemoglobin A1c, blood pressure, and serum low-density lipoprotein were collected. A significant inverse correlation was observed between max-IMT and CVR-R_dif (β=–0.34, p=0.042), but not CVR-R_rest or CVR-R_breath, in multivariate analyses adjusted for all the data. Therefore, the CVR-R_dif may serve as a clinical index for the diabetic autonomic neuropathy-atherosclerosis relation in type 2 DM patients.

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