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Under the assumption that tryptophan (TRP) metabolism may be modulated by the intensity, duration, and total exercise/energy expenditure of the ultra-marathon, we evaluated the changes in two major TRP metabolic pathway substances [serotonin (5-HT) and kynurenine (KYN)] during a two-day ultra-marathon race. Blood was sampled at three different time points: before the race (baseline), after running 45 km on the first day, and after running 135 km on the second day. Serum TRP concentrations decreased in proportion to the distance covered, and the levels after running 135 km were significantly lower than at baseline and after running 45 km. Serum serotonin (5-HT) concentrations increased significantly after running 45 km but reduced towards baseline levels after running 135 km. Serum kynurenine (KYN) concentrations hardly changed after running 45 km but increased significantly after running 135 km compared with after running 45 km values. Serum FFAs levels increased significantly after running 45 km compared with baseline values, and they elevated even further after running 135 km. Serum albumin concentrations reduced significantly after running 45 km but remained at almost the same level after running 135 km. Serum 5-HT levels tended to be consistently correlated to the completion times on the first and second days. Serum 5-HT concentrations are known to be associated with central fatigue, and may predict exercise performance. KYN levels appeared to reflect the intensity of physical exercise, and its pathway may play a role in reactive oxygen species scavenging systems during a long-duration exercise.

To address preventive effects of n-3 PUFAs/LC n-3 PUFAs on CRTs, a randomized controlled trial was conducted. One-hundred four experimental group participants were advised to increase intake of n-3 PUFAs, including fish/shell fish, fish oil supplements and perilla oils, and to decrease consumption of n-6 PUFAs and fats/oils as a whole for 24 months. One-hundred one control group participants were only cautioned to reduce consumption of fats/oils as a whole. Random allocation was satisfactorily attained, and participants sufficiently complied with our regimen. Intakes, plasma concentrations, and compositions of the RBC and sigmoid colon membranes of n-3 PUFAs, LC n-3 PUFAs, EPA and DHA increased, and the ratios of n-6 PUFAs/n-3 PUFAs and AA/LC n-3 PUFAs decreased without any adverse response. Twenty-four months after the intervention, the multivariate-adjusted hazard ratio (95% confidence intervals) was estimated to be 0.805 (0.536–1.209) with a signal towards the reduced CRT incidence.

To assess oxidative stress (OS) induced by endurance exercise, concentrations of serum reactive oxygen species (ROS) were determined in 70 Japanese male amateur runners completing a two-day ultra-marathon race. Serum ROS levels were analyzed at three time points: before the race (baseline), after the 1st day race (mid-race), and after the 2nd day race (goal) (post-race). The means (SE) of ROS were 151.4(3.7) (U. CARR.), 168.7(4.4), and 156.8(4.4), respectively. Significant positive trends were noted between age and serum ROS concentrations at the three race points (p

Using the urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration, effects of participation in a two-day ultramarathon race period on oxidative DNA damage were investigated in Japanese nonprofessional runners. Before the first day (baseline), after the first day (mid-race) of 40-km running, and after the second day (post-race) of 90 km running, biomaterials were successfully sampled from 95 participants (males, 79; females, 16) who completed the full race. We analyzed urine for 8-OHdG and blood for aspartate aminotransferase (AST), creatine phosphokinase (CPK) and myoglobin, and evaluated fluctuation in the values at three sampling time points. Adjusted baseline urinary 8-OHdG levels (microg/g creatinine) (mean +/- standard deviation) showed no significant differences between males and females, at 2.85 +/- 1.17 and 3.04 +/- 1.56, respectively. In males, mid-race urinary 8-OHdG levels rose to 3.29 +/- 1.15 (p < 0.01), but then returned to 2.73 +/- 1.16 at the post-race time point (p < 0.01). In females, a similar increase to 3.32 +/- 1.47 and subsequent decline to 2.80 +/- 1.47 were noted. In contrast, AST, CPK and myoglobin were increased at both mid- and post-time points and particularly the latter, independent of the sex. Extreme prolonged exercise in a two-day ultramarathon race period causes oxidative DNA damage but antioxidant repair systems are apparently induced to protect against oxidative DNA stress with physical exercise.

We have implemented a randomized controlled dietary intervention in patients polypectomized for tumors of the colorectum to elucidate potential beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on the development of colorectal tumors. Those individuals in the experimental group were advised not only to decrease their consumption of fats/oils as a whole and foods supplying n-6 PUFAs but also to increase intake of foods and supplements containing n-3 PUFAs, while those in the comparison group were cautioned to reduce intake of fats/oils as a whole. Patients' compliance/adherence was monitored with a semi-quantitative food frequency questionnaire and by assessment of fatty acid concentrations in plasma, membranes of red blood cells and sigmoid colon samples. As for endpoints to assess tumor suppressive effects of n-3 PUFAs, the number/multiplicity, sizes and incidence rates of colorectal tumors were compared between the experimental and comparison groups after 12 and 24 months of the dietary intervention. On the specified assumption, the number of pairs needed for achieving statistical significance was calculated to be approximately 60-80. A randomized controlled trial is under way to secure enough patients, sustain compliance/adherence and minimize dropouts.

BACKGROUND: Anthropometric characteristics, lifestyle, and baseline biological markers of Japanese non-professional ultra-marathon runners have not been fully assessed. METHODS: We evaluated anthropometric characteristics, lifestyle, and baseline biological markers of 180 Japanese amateur ultra-marathon runners (144 males [mean age: 50.5±9.4 (standard deviation) years] and 36 females [48.9±6.9]), and compared them with those of participants in a community heath check-up program and with the figures in the literature. We furthermore evaluated baseline blood indices according to monthly running distance with analysis of variance adjusted for age, body mass index, smoking and alcohol drinking habits. RESULTS: The ultra-marathon runners demonstrated more favorable values for body mass index and bone density, and the proportion of smoking, and undertaking physical activity (for both sexes), eating breakfast (for males), and having daily bowel movements (for females), while greater proportion of alcohol drinking habit (for both sexes), than the comparison group. Average monthly running distances and standard deviations (km) were 257.2±128.9 for males and 209.0±86.2 for females. Male runners possessed beneficial markers, including lowered triglyceride and elevated high-density lipoprotein cholesterol, and their values showed hockey-stick (or inverse hockey-stick) patterns depending on their monthly running distance. Some subjects running more than 300 km/month exhibited signs of an over-reaching/training syndrome, including somewhat lowered hemoglobin, ferritin and white blood cell count, and elevated creatine kinase and lactate dehydrogenase. CONCLUSIONS: Together with a desirable lifestyle, Japanese non-professional ultra-marathon runners with vigorous exercise habit demonstrated a preferable health status according to biological indices.

Morbidity and mortality statistics, including incidences of fat-related cancers (FRCs), and dietary intake and sources of fats and oils were compared for Japanese, Mediterranean and American people. Incidences of FRCs, except for steeply increasing colon cancer, have remained low in Japan. Similarly, Mediterranean people enjoy relatively low risks of FRCs compared with American people. The low risks of FRCs in Japanese may be explained by limited intake of fats and oils as a whole, and a low ratio of n-6 polyunsaturated fatty acids (PUFAs) versus n-3 PUFAs through consumption of the latter from marine foods. They also frequently consume vegetables and fruit, and dietary fiber. Mediterranean people moderately consume fats and oils from a large amount of olive oil, containing not only oleic acid but also polyphenols (including flavonoids),mgr;-tocopherol and carotenoids (includingmgr;-carotene), which are antioxidants and anti-carcinogenic as in red wine, vegetables (including herbs) and fruit. The diet also features medium intake of fish and shellfish along with cereals/pasta/bread. From the standpoint of intake of total fat, the low risks of FRCs in Japanese seem "plausible," while the low risks in Mediterranean people may be termed "paradoxical." In summary, limited consumption of fats and oils, moderate intakes of marine foods, and vegetables and fruit, in line with a modest intake of energy may be advocated for promoting health, prolonging life and prevention of lifestyle-related diseases including FRCs.

To clarify preventive effects of n-3 polyunsaturated fatty acids (PUFAs) against colorectal carcinogenesis, we performed a dietary intervention in patients polypectomized for colorectal adenomas/tumors. For the former the following dietary advice was given: (1) decrease intake of fat from 30 to 20% of the total; (2) decrease consumption of n-6PUFAs containing foods, and increase intake of n-3 PUFAs for 2 years. For the comparison group only decreased intake of fat (30–20%) was recommended. Samples of normal sigmoid colon mucosa, obtained by colonoscopic check once a year during the intervention period, were used to investigate COX-2, cell proliferation (Ki67 expression), p53, Bcl-2 and Bax by immunostaining and determine the apoptosis index (AI) by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) in 21 and 20 patients in experimental and comparison groups, respectively, who completed the 2 years of the intervention. After 24 months, the AI and positive cells of Bax and the ratio of Bax/Bcl-2 in normal sigmoid colon mucosa for the experimental group was significantly increased, whereas this change was not found in comparison group. These observations demonstrated for the first time that increased intake of n-3 PUFAs promotes apoptosis of normal colon mucosa in human which is related to effect on Bax or the balance of Bax and Bcl-2.

To the Editor: Oh et al. ([1][1]) investigated the possible inverse association between consumption of fish/ n -3 highly unsaturated fatty acids (HUFAs, marine omega-3 fatty acids mainly consisting of icosapentaenoic acid and docosahexaenoic acid) and the risk of colorectal cancer in the Nurses'

Erratum to ‘Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors’ [Cancer Letters 193 (2003) 17–24] Jinglei Cheng, Kumiko Ogawa, Kiyonori Kuriki, Yoshifumi Yokoyama, Takeshi Kamiya, Kyoji Seno, Harumi Okuyama, Jingwen Wang, Chenhong Luo, Toshiko Fujii, Hiromitsu Ichikawa, Tomoyuki Shirai, Shinkan Tokudome*