RESEARCH NEWS STORY
May 16, 2024

Antioxidant Dietary Supplement “Twendee X®” Can Help Counter Systemic
Sclerosis
Study finds the supplement effective in inhibiting fibrosis and suppressing disease activity
and progression of systemic sclerosis, an intractable disease
Systemic sclerosis (SSc) is a long-term disease characterized by a defective circulatory
system and hardening of the tissue (fibrosis) due to a self-attacking immune system(autoimmunity). Oxidative stress, or an imbalance in the levels of reactive oxygen species(ROS) levels, is known to exacerbate the disease. Now, a new study explores the effects ofTwendee X® (TwX)—a dietary antioxidant supplement, and reveals its potential as
antioxidant therapeutic for treating SSc.
Autoimmune diseases occur when the body’s immune system attacks healthy cells insteadof protecting them. Systemic sclerosis (SSc) is one such autoimmune condition characterized
by faulty circulatory and immune systems, leading to the occurrence of fibrosis (hardeningand scarring of healthy tissue) of the skin and internal organs. SSc is known to affectpatients throughout their lives, thereby, impairing their quality of life. Although precise
mechanisms underlying SSc development and progression are not clearly understood, acomplex interplay of immune, hormonal, environmental, and genetic factors is often
implicated.
Moreover, around 90% of the patients with SSc are known to experience a phenomenon
known as the ‘Raynaud’s phenomenon (RP).’ It is associated with spasms in smaller bloodvessels, leading to decreased blood flow. RP can, in turn, promote an increase in thegeneration of molecules called reactive oxygen species (ROS). The resulting oxidativeenvironment triggers cell damage and fibrosis, further exacerbating the disease. Counteringoxidative stress using antioxidant compounds, is therefore, being increasingly explored as atherapeutic strategy. However, a single antioxidant may not be therapeutically effective indecreasing oxidative stress.
To this end, a team of researchers from Japan, led by Professor Haruhiko Inufusa, who is theChief Research Scientist at the Louis Pasteur Center for Medical Research, and a
distinguished faculty at the Division of Anti-Oxidant Research, Life Science Research Center,Gifu University, has investigated the effectiveness of Twendee X® (TwX)—a dietary
supplement comprising of a combination of eight active antioxidants—in reducing oxidative
stress in SSc mouse models.
Explaining the rationale behind their work published on March 6, 2024, in the International
Journal of Molecular Sciences, Prof. Inufusa says, “Studies have shown that TwX reduces ROS,
protects mitochondrial function, and improves cognition and memory. Daily oxidative stresscare with this supplement can contribute not only to daily health maintenance and disease
prevention but also to the symptomatic improvement of intractable diseases like SSc.”
The eight constituents of TwX include vitamin C, L-glutamine, niacin, L-cystine, coenzyme
Q10, vitamin B2, succinic acid, and fumaric acid. The combined antioxidant effect is likely
more potent than the activity of either compound alone. Previous studies havedemonstrated improvement in cognition, memory, and motor coordination in mousemodels of dementia, and reduction in affected region size, oxidative stress, andinflammation in mouse models of ischemic stroke following treatment with TwX. Based onthese findings, the researchers conducted this study to investigate the effects of TwX in amouse model of SSc created using hypochlorous acid (HOCl).
HOCl induction led to a significant increase in the serum levels of advanced oxidation
protein products (AOPP), mimicking SSc-like features. Further HOCl induction led to thethickening of skin tissues along with local and systemic inflammation, fibrosis, and vascularinjury.
Notably, the AOPP levels of mice treated with TwX were substantially lower than that of thehealthy animals. Moreover, TwX treatment significantly reduced skin thickness,accumulation of the collagen protein, skin levels of hydroxyproline—an oxidative stressmarker, and fibrosis of the skin and lungs. Additionally, TwX treatment significantly reduced
the levels of α-smooth muscle actin (α-SMA), a protein that was elevated in response toHOCl induction and has been shown to activate ROS in fibrotic diseases. HOCl-induced
animals treated with TwX also demonstrated a decreasing trend in the levels ofinflammatory cytokines and activated immune cells involved in inflammatory responses.
Overall, these results suggest that TwX may treat SSc by regulating oxidative stress, andreducing skin and lung fibrosis. Since these findings were observed in a mouse model,
further studies will be needed to establish the effectiveness of TwX in human patients withSSc. Nevertheless, given the benefits of TwX in other oxidative stress-related diseases aswell as the lack of side-effects, TwX holds significant promise as an antioxidant therapeutic
against SSc.
Sharing his concluding thoughts about their study, Prof. Inufusa says, “Although TwX is adietary supplement, it has passed drug-level safety testing and can be used by a wide rangeof people, from children to adults. Moreover, our findings suggest that TwX could potentiallyalleviate the symptoms of intractable oxidative stress-related diseases such as SSc.”
ReferenceAuthors
Title of original paper
JournalDOIAffiliations

Fukka You1,2, Carole Nicco3, Yoshiaki Harakawa1, Toshikazu
Yoshikawa4,5, and Haruhiko Inufusa1,2
The Potential of Twendee X® as a Safe Antioxidant Treatment for
Systemic Sclerosis
International Journal of Molecular Sciences
https://doi.org/10.3390/ijms25053064
1Division of Anti-Oxidant Research, Life Science Research Center,Gifu University, Japan
2Anti-Oxidant Research Laboratory, Louis Pasteur Center for
Medical Research, Kyoto, Japan
3Université Paris Cité, Paris, France
4Louis Pasteur Center for Medical Research, Kyoto, Japan
5School of Medicine, Kyoto Prefectural University of Medicine,Kyoto, Japan
About Professor Haruhiko Inufusa
Professor Haruhiko Inufusa is the Chief Research Scientist at the Louis Pasteur Center for
Medical Research, and a distinguished faculty at the Division of Anti-Oxidant Research, Life
Science Research Center, Gifu University. He has dedicated his research career towards thedevelopment of a dietary supplement that counters oxidative stress. Over the last 15 years
in a global cooperation with various scientists and teams, Prof. Inufusa finally developed theultimate antioxidant formula to counter oxidative stress. He has been awarded for his
outstanding work. He is also a member of various medical and research societies and has
several publications to his credit.
Additional information for EurekAlert
Latest Article Publication Date: 6 March 2024
Method of Research:
Experimental study
Subject of Research:
Animals
Conflicts of Interest Statement: Fukka You, Yoshiaki Harakawa, and Haruhiko Inufusa
are employees of Gifu University. The Division ofAntioxidant Research is a laboratory that has been
established at the Life Science Research Center at GifuUniversity, based on a research fund from the TIMA
Establishment (Liechtenstein). Toshikazu Yoshikawa isan advisor to TIMA Establishment (Liechtenstein). Thesponsor had no control over the interpretation, writing,or publication of this work.

Image 1

Image title: Study finds the potential of Twendee X® in decreasing oxidative stress andfibrosis associated with systemic sclerosis (SSc)
Image caption: Oxidative stress is known to exacerbate fibrosis and autoimmunity. In a new
study, researchers from Japan have investigated the effects of a dietary antioxidant
supplement — Twendee X® — on oxidative stress and fibrosis in a mouse model of SSc, an
intractable autoimmune disease. Given its effectiveness in other oxidative stress-relateddiseases including dementia, Twendee X® holds the promise of being an effective
antioxidant therapeutic against SSc.
Image credit: Maria Sieglinda von Nudeldorf on Openverse
https://openverse.org/image/22e61e43-1a9c-42ec-a6e0-e6152f82d12d
License type: CC BY-SA 4.0
Usage Restrictions: You are free to share and adapt the material. Attribution is required.

Image 2

Image title: Twendee X®, a dietary antioxidant supplement, decreases oxidative stress insystemic sclerosis (SSc) mice model.
Image caption: Twendee X® (TwX) was shown to reduce oxidative stress reflected by theserum advanced oxidation protein product (AOPP) levels in SSc mice models created byinjecting hypochlorous acid (HOCl). The SSc mice were compared with healthy mice injectedwith phosphate-buffered saline (PBS).
Image credit: Haruhiko Inufusa from Louis Pasteur Center for Medical Researchhttps://www.mdpi.com/1422-0067/25/5/3064
License type: CC BY
Usage Restrictions: Credit must be given to the creator.

Image 3

Image title: Twendee X®, a dietary antioxidant supplement, decreases skin fibrosis insystemic sclerosis (SSc) mice model.
Image caption: Twendee X® (TwX) was shown to reduce skin fibrosis reflected by skin
thickness in SSc mice models created by injecting hypochlorous acid (HOCl). The SSc mice
were compared with healthy mice injected with phosphate-buffered saline (PBS).
Image credit: Haruhiko Inufusa from Louis Pasteur Center for Medical Researchhttps://www.mdpi.com/1422-0067/25/5/3064
License type: CC BY
Usage Restrictions: Credit must be given to the creator.