ORALS

SESSION: OxidativeTueAM-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Haruhiko Inufusa; Koji Fukui; Session Monitor: TBA

11:35: [OxidativeTueAM01] OS Plenary
WHY TWENDEE X SUCCESSFULLY PREVENTED DEMENTIA?
Haruhiko Inufusa¹ ; Fuhua Yang¹ ; Yoshiaki Harakawa¹ ; Toshikazu Yoshikawa² ; ¹Gifu University, Gifu, Japan; ²Louis Pasteur Medical Research Center, Kyoto, Japan;
Paper Id: 152 [Abstract]

Many different types of dementia exist, with Alzheimer's disease (AD) accounting for the majority of cases. The greatest risk factor for AD is aging, which is the result of oxidative stress that has accumulated over the years. In addition, amyloid-β accumulated in the AD brain generates free radicals that cause inflammation in the surrounding neurons, leading to mitochondrial dysfunction and eventual neurodegeneration. In other words, the development of AD is the result of a vicious cycle of oxidative stress, inflammation, and mitochondrial dysfunction established over a long period of time, and the progression of AD is no exception. The pathogenesis of AD is said to occur 20 years before clinical symptoms appear. Therefore, starting treatment after the onset of symptoms could be too late to be effective. Twendee X (TwX, Oxicut®︎) is an antioxidant formula shown to have a preventive effect for human mild cognitive impairment (MCI) in a multicenter, randomized, double-blind, placebo-controlled, prospective intervention trial. Previous studies have shown that in diabetes, which hastens cognitive decline, TwX intake not only lowers blood glucose levels but also suppresses autophagy dysfunction. TwX has also been shown to positively affect neurogenesis in the hippocampal dentate gyrus, telomere elongation, and mitochondrial function. This suggests that TwX may prevent or halt the progression of dementia from all angles. This study suggests that TwX may not only prevent dementia, but may also aid in its treatment.

References:
1. Tadokoro K, Morihara R, Abe K, et al. Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study. J Alzheimers Dis. 2019; 71(3): 1063-1069. 2. Inufusa H. Characterization of cell protection effects of Twendee X by oxidative stress. J World Mitochondria Soc. 2016; 2: 42. 3. Haruhiko I. Composition for protection against cytotoxic effects. Tima Foundation. Patent No. 5777821. 2015-9-9. 4. Feng T, Yamashita T, Abe K, et al. In Vitro Free Radical Scavenging Activities of Dietary Supplements by Electron Spin Resonance. Brain Supplements. 2020; 2: 1-12.

SESSION: OxidativeTueAM-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Haruhiko Inufusa; Koji Fukui; Session Monitor: TBA

12:25: [OxidativeTueAM03] OS
IMPROVEMENT QUALITY OF LIFE WITH ANTIOXIDANT COMPOSITION
Fuhua Yang¹ ; Yoshiaki Harakawa¹ ; Toshikazu Yoshikawa² ; Haruhiko Inufusa¹ ; ¹Gifu University, Gifu, Japan; ²Louis Pasteur Center, Kyoto, Japan;
Paper Id: 106 [Abstract]

Hangovers after drinking, acne on face, constipation, lack of sleep and lethargy, worries and anxiety, and lifestyle-related diseases all have a significant impact on the quality of daily life. Quality of life is based on the individual's physical and mental health. For example, hangover reduces the quality of normal life. Improving the quality of daily routines is important for healthy longevity and a fulfilling life. Twendee X (TwX, Oxicut®︎) and Twendee S (TwS, SUPALIV®︎) are composition of antioxidant supplements containing a total of eight vitamins, amino acids and CoQ10.TwX and TwS contain the same ingredients but in different mixture ratio and amount. Twendee Mtcontrol (TwM, Mtcontrol®︎) is based on TwX with seven additional ingredients. In this study, consumption was monitored after 1-2 months of of TwS, TwX, and TwM. TwS taken to prevent hangover after drinking, the unpleasant smell by themselves of the next morning disappeared at the same time. TwX taken to improve acne on the face, the patient slept well at the same time. TwM taken to improve fatigue, the patient had an improved bowel movement at the same time. As shown above, a wide range of improvements in daily life have been reported. These results suggest that TwS, TwX, and TwM may regulate the rhythm of daily life.

References:
1) Novel compositions and uses thereof WO 2008071790 A3. 2) Antioxidant composition and its use in diabetes EP 1932542 A1. 3) Hirano S, Inufusa H, Yoshikawa T, et al. Anti-oxidant Twendee X, for maintenance of Singing voice. Brain Supplement. 2023; 5; 1-7. 4) Fukui K, You F, Inufusa H, et al. Twendee X, a mixed antioxidant supplement, improves congnitive function, coordination, and neurotrophic factor expression in long-term vitamin E-deficient mice. J clin Biochem Nutr. 2023 Mar;72(2):93-100.

SESSION: OxidativeTueAM-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Haruhiko Inufusa; Koji Fukui; Session Monitor: TBA

12:50: [OxidativeTueAM04] OS
COMBINATION SUPPLEMENT, TWENDEE X IMPROVES LEARNING DYSFUNCTION IN LONG-TERM VITAMIN E-DEFICIENT MICE
Koji Fukui¹ ; Fuhua Yang² ; Yoshiaki Harakawa² ; Toshikazu Yoshikawa³ ; Haruhiko Inufusa² ; ¹Shibaura Inst. of Technology, Saitama, Japan; ²Gifu University, Gifu, Japan; ³Louis Pasteur Center, Kyoto, Japan;
Paper Id: 154 [Abstract]

Vitamin E deficiency accelerates in vivo oxidation and is closely related to aging. Accumulation of oxidative products increases risk of developing serious disorders such as dementia and cardiovascular events [1]. Normally, our bodies maintain a balance between oxidation and reduction, but the redox balance gradually collapses as we age. To prevent oxidation, we should take supplements. The supplement market is growing year by year all over the world. One combination supplement is Twendee X, which contains 8 substances [2]. However, the detailed scientific evidence for Twendee X has not yet been elucidated. In this study, long-term vitamin E-deficient mice were fed Twendee X and measured cognitive and motor functions using the Morris water maze and rota-rod tests [3]. Vitamin E-deficient mice had significantly impaired cognitive and motor functions, learning rate was comparable to normal aged mice. Treatment with Twendee X significantly improved both dysfunctions. However, serum indices did not differ with or without Twendee X. These results indicate that Twendee X has a potential as a powerful antioxidant supplement through protection against in vitro oxidation.

References:
[1] Yoshida, N, Kato, Y, Takatsu, H, et al., Biomedicines 10 (2022) 28.
[2] Tadokoro, K, Morihara, R, Ohta, Y, et al., J Alzheimer’s Dis, 71 (2019) 1063-1069.
[3] Fukui, K, Onodera, K, Shinkai, T, et al., Ann NY Acad Sci, 928 (2001) 169-176.

SESSION: OxidativeTuePM1-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Christian Andre Amatore; Koji Fukui; Session Monitor: TBA

14:30: [OxidativeTuePM106] OS
APPLICATION OF AN ANTIOXIDANT COMBINATION PRODUCT IN THE TREATMENT OF SYSTEMIC SCLEROSIS
Fuhua Yang¹ ; Yoshiaki Harakawa¹ ; Toshikazu Yoshikawa² ; Haruhiko Inufusa¹ ; ¹Gifu University, Gifu, Japan; ²Louis Pasteur Center, Kyoto, Japan;
Paper Id: 107 [Abstract]

Systemic sclerosis (SSc) is a disease of hardening of the skin and internal organs which is presumed to be caused by a complex combination of autoimmunity, fibrosis, and vascular lesions, yet the detailed mechanism is unknown. There is no established treatment, and women are at higher risk of developing the disease than men.
The involvement of reactive oxygen species (ROS) in Raynaud's phenomenon and anti-PDGFR (Platelet-Derived Growth Factor Receptor)-stimulating autoantibodies in SSc has been suggested. In fact, dermal fibroblasts of SSc patients produce large amounts of ROS themselves, which induce collagen synthesis. Therefore, SSc is considered to be closely associated with elevated levels of oxidative stress.
Twendee X (TwX, Oxicut®︎) is an antioxidant compound with mitochondrial protection properties that contains eight different ingredients, and studies have shown that TwX can potentially improve intestinal microbiota, chronic fatigue syndrome, sleep apnea, and more.
We tested whether TwX has an ameliorative effect on SSc using a hypochlorous acid (HOCl)-induced SSc mouse model. Mouse SSc induced by oxidants such as HOCl is said to exhibit clinical and biological manifestations very similar to those observed in human SSc, including skin and visceral fibrosis, vascular damage, and autoimmunity.
One month prior to the 6-week HOCl administration, mice were given drinking water (Control) or TwX-containing water ad libitum, and were dissected 2 days after the last HOCl administration to compare their skin lesions, immune status, and major protein expression with the Control group. The study showed that TwX had a favorable effect on clinical, immune, and physiological parameters in HOCl-induced SSc mice.
These results suggest that TwX may aid in the treatment and prevention of SSc.

References:
1) Batteux F, Kavian N, Servettaz A. New insights on chemically induced animal models of systemic sclerosis. Current opinion in rheumatology. 2011
2) Ogawa F, Shimizu K, Takehara K, et al. Serum levels of 8-isoprostane, a marker of oxidative stress, are elevated in patients with systemic sclerosis. Rheumatology (Oxford). 2006;45(7):815-8.
3) Sambo P, Baroni SS, Orlandini G, et al. Oxidative stress in scleroderma: maintenance of scleroderma fibroblast phenotype by the constitutive up-regulation of reactive oxygen species generation through the NADPH oxidase complex pathway. Arthritis and rheumatism. 2001 Nov;44(11):2653-64.
4) Novel compositions and uses thereof WO 2008071790 A3.
5) Antioxidant composition and its use in diabetes EP 1932542 A1.

SESSION: OxidativeTuePM1-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Christian Andre Amatore; Koji Fukui; Session Monitor: TBA

14:55: [OxidativeTuePM107] OS
TWENDEE MT CONTROL IMPROVES COGNITIVE FUNCTION IN AGED MICE
Koji Fukui¹ ; Fuhua Yang² ; Yugo Kato³ ; Shuya Yuzawa⁴ ; Ayuta Kishimoto⁴ ; Takuma Hara⁴ ; Yuki Kanome⁴ ; Yoshiaki Harakawa² ; Toshikazu Yoshikawa⁵ ; Haruhiko Inufusa² ; ¹Shibaura Inst. of Technology, Saitama, Japan; ²Gifu University, Gifu, Japan; ³Tottori University, Yonago, Japan; ⁴Shibaura Institute of Technology, Saitama, Japan; ⁵Louis Pasteur Center, Kyoto, Japan;
Paper Id: 153 [Abstract]

Aging is a universal degenerative disease. Aging is classified into physiological and pathological. The progression rate of pathological aging varies among individuals, and reactive oxygen species is deeply involved in pathological aging. One of the most serious phenomena during aging is dementia. To prevent age-related neurodegenerative disorders, treatment with antioxidants is effective. Twendee Mt Control which is a supplement contains 15 substances and anyone can buy it. However, the detailed scientific evidence is not enough. In the present study, we treated combination supplement to aged mice, and measured their cognitive and motor functions. We purchased aged mice and treated them with Twendee Mt Control for one month. Cognitive and motor functions were measured by the Morris Water maze and rota-rod test [1]. Normal aged mice had significantly reduced learning ability. Treatment with Twendee Mt Control improved significantly. Twendee Mt Control significantly improved time-to-fall scores on the rota-rod test. Finally, treatment with Twendee Mt Control showed a high training effect in the treadmill test. These results indicated that treatment with Twendee Mt Control has a potential as a powerful antioxidant supplement through protection against age-related neuronal and motor dysfunctions.  

References:
[1] [1] Fukui, K, Onodera, K, Shinkai, T, et al., Ann NY Acad Sci, 928 (2001) 169-176.

SESSION: OxidativeTuePM1-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Christian Andre Amatore; Koji Fukui; Session Monitor: TBA

15:20: [OxidativeTuePM108] OS
OLD AGE ODOR AND OXIDATIVE STRESS
Haruhiko Inufusa¹ ; Fuhua Yang¹ ; Yoshiaki Harakawa¹ ; Toshikazu Yoshikawa² ; ¹Gifu University, Gifu, Japan; ²Louis Pasteur Medical Research Center, Kyoto, Japan;
Paper Id: 151 [Abstract]

Why does baby smell good while the elderly has a distinctive odor? According to a publication by Shiseido Research Center in 2001(1), 2-nonenal is an unsaturated aldehyde with unpleasant odor caused by oxidative degradation reactions of ω-7 unsaturated fatty acids such as palmitoleic acid and bacenic acid found on the skin surface. This means that age-related oxidative stress is a cause of 2-nonenal. In other words, an increase in oxidative stress due to aging is the cause of age-related odor. We measured the change in age-related odor by reducing oxidative stress. Antioxidant composition Twendee X (TwX) was given who has age related odor for 4 weeks. The portable odor sensor KUNKUN BODY (Konica Minolta) was used for 10 participants to measure aging odor. Seventy-four participants were also monitored questionnaires. Several participants whose odor KUNKUN BODY scores were 80-100, which dropped scores to zero after 3 weeks. Seventy-two of the 74 cases showed a decrease in age-related odor. Oxidative stress increases with age and is a cause of many diseases. The development of age-related odors suggests increased oxidative stress. Reduction of age-related odors with the antioxidant composition TwX is suggested not only to reduce bad odors but also to maintain health.

References:
1.Inufusa H. Characterization of cell protection effects of Twendee X by oxidative stress. J World Mitochondria Soc. 2016; 2: 42. 2. Haruhiko I. Composition for protection against cytotoxic effects. Tima Foundation. Patent No. 5777821. 2015-9-9. 3. Haze S, Gozu Y, Nakamura S, Kohno Y, Sawano K, Ohta H, Yamazaki K. 2-Nonenal newly found in human body odor tends to increase with aging. J Invest Dermatol. 2001 Apr;116(4):520-4.

SESSION: OxidativeTuePM2-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Fuhua Yang; Christian Andre Amatore; Session Monitor: TBA

16:50: [OxidativeTuePM211] OL
ALLERGIC DISEASES AND OXIDATIVE STRESS
Yoshiaki Harakawa¹ ; Fuhua Yang¹ ; Toshikazu Yoshikawa² ; Haruhiko Inufusa¹ ; ¹Gifu University, Gifu, Japan; ²Louis Pasteur Medical Research Center, Kyoto, Japan;
Paper Id: 104 [Abstract]

There are various allergic diseases existing. In Japan, about 1 in 2 of the population suffers from some sort of allergic disease, making it a national disease. Familiar examples include asthma, rhinitis, atopic dermatitis, and hay fever. These symptoms are largely related to oxidative stress, which increases due to inflammation caused by allergens such as pollen and dust invading the body. As the number of patients increases and the burden of medical costs rises, a treatment without side effects is needed. Twendee X (TwX) is a safety-tested, mixed antioxidant supplement composed of vitamins and amino acids. To evaluate whether TwX improves these symptoms, a questionnaire survey was conducted on the symptoms of several allergic diseases. The results showed that about 80% of the participants showed improvement in most diseases after taking TwX compared to before. The results suggest TwX can contribute to the future treatment of allergies as well as to the reduction of health care costs.

References:
1) Inufusa H, Greiffenclau M, Novel compositions and uses thereof. Patent Cooperation Treaty (PCT) 2,008,071,790. priority date 2006-12-15. 2) Inufusa, H. Characterization of cell protection effects of Twendee X by oxidative stress. J World Mitochondria Soc. 2016, 2, 42. 3) Inufusa, H. Composition for protection against cytotoxic effects. TIMA Foundation. Patent No. 5777821, 2015-9-9.

SESSION: OxidativeTuePM3-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Haruhiko Inufusa; Session Monitor: TBA

17:55: [OxidativeTuePM313] OL
ANTIOXIDANTS AS A POTENTIAL TREATMENT FOR ULCERATIVE COLITIS
Yoshiaki Harakawa¹ ; Fuhua Yang¹ ; Toshikazu Yoshikawa² ; Haruhiko Inufusa¹ ; ¹Gifu University, Gifu, Japan; ²Louis Pasteur Medical Research Center, Kyoto, Japan;
Paper Id: 105 [Abstract]

Ulcerative colitis (UC) is defined as a diffuse, nonspecific inflammation of unknown origin that continuously damages the colonic mucosa from the rectal side, often leading to erosions and ulcers. It is associated with frequent abdominal pain and sometimes diarrhea with bloody stools. There are more than 160,000 cases of the disease in Japan, but no cure has yet been established.
Although the exact cause of the disease has not yet been clarified, oxidative stress has long been implicated, as it has been observed that reactive oxygen species (ROS) increase in inflamed tissues. Reduction of ROS and improvement of oxidative stress may improve UC.
Twendee X (TwX, Oxicut®︎) is an antioxidant supplement containing eight active ingredients consisting of vitamins and amino acids; Twendee Mtcontrol (TwM, Mtcontrol®︎) is a supplement with seven active ingredients added to TwX to increase its antioxidant capacity. The therapeutic effects of antioxidants were tested in a mouse model of UC with dextran sodium sulfate (DSS), a commonly used treatment in UC research. TwX and TwM were found to ameliorate the negative physical effects of UC in the DSS model.
The results suggest that antioxidant treatment may be effective for UC.

References:
1. Japan Intractable Diseases Information Center. 2023. https://www.nanbyou.or.jp/. Accessed 15 Jun 2023.
2. Lih-Brody L, Powell SR, Collier KP, Reddy GM, Cerchia R, Kahn E, Weissman GS, Katz S, Floyd RA, McKinley MJ, Fisher SE, Mullin GE. Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Dig Dis Sci. 1996 Oct;41(10):2078-86.
3. Nakase H, Uchino M, Shinzaki S, Matsuura M, Matsuoka K, Kobayashi T, Saruta M, Hirai F, Hata K, Hiraoka S, Esaki M, Sugimoto K, Fuji T, Watanabe K, Nakamura S, Inoue N, Itoh T, Naganuma M, Hisamatsu T, Watanabe M, Miwa H, Enomoto N, Shimosegawa T, Koike K. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J Gastroenterol. 2021 Jun;56(6):489-526.
4. Kim JJ, Shajib MS, Manocha MM, Khan WI. Investigating intestinal inflammation in DSS-induced model of IBD. J Vis Exp. 2012 Feb 1;(60):3678.