Twendee X shows promise for reducing oxidative stress in systemic sclerosis

Autoimmune diseases occur when the body’s immune system attacks healthy cells instead of protecting them. Systemic sclerosis (SSc) is one such autoimmune condition characterized by a defective circulatory and immune system, leading to fibrosis (hardening and scarring of healthy tissue) of the skin and internal organs. SSc is known to affect patients throughout their lives, thereby impairing their quality of life. Although the exact mechanisms underlying the development and progression of SSc are not clearly understood, a complex interplay of immunological, hormonal, environmental, and genetic factors is often involved.

In addition, approximately 90% of SSc patients are known to experience a phenomenon known as “Raynaud’s phenomenon (RP). It is associated with spasms in smaller blood vessels, leading to reduced blood flow. RP can, in turn, promote increased production of molecules called reactive oxygen species (ROS). The resulting oxidative environment triggers cell damage and fibrosis, further exacerbating the disease. Therefore, addressing oxidative stress using antioxidant compounds is increasingly being explored as a therapeutic strategy. However, a single antioxidant may not be therapeutically effective in reducing oxidative stress.

To this end, a team of researchers from Japan, led by Professor Haruhiko Inufusa, who is a principal investigator at the Louis Pasteur Medical Research Center, and 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 consisting of a combination of eight active antioxidants – to reduce oxidative stress in mouse models of SSc.

Explaining the rationale behind their work published on March 6, 2024, at International Journal of Molecular Sciencessays Professor Inufusa, “Studies have shown that TwX reduces ROS, protects mitochondrial function, and improves cognition and memory. Taking care of oxidative stress daily with this supplement can contribute not only to daily health maintenance and disease prevention, but also in the symptomatic improvement of incurable diseases such as SSc.”

The eight ingredients of TwX include vitamin C, L-glutamine, niacin, L-cystine, coenzyme Q10, vitamin B2, succinic acid and fumaric acid. The combined antioxidant activity is likely more potent than the activity of either compound alone. Previous studies have shown improvement in cognition, memory and motor coordination in mouse models of dementia and reduction in lesion size, oxidative stress and inflammation in mouse models of ischemic stroke after TwX treatment. Based on these findings, researchers conducted this study to investigate the effects of TwX in a mouse model of SSc created using hypochlorous acid (HOCl).

HOCl induction led to a significant increase in serum levels of advanced oxidation protein products (AOPP), mimicking SSc-like features. Further induction of HOCl led to thickening of skin tissues along with local and systemic inflammation, fibrosis and vascular injury.

Specifically, the AOPP levels of TwX-treated mice were significantly lower than those of healthy animals. In addition, TwX treatment significantly reduced skin thickness, collagen protein accumulation, skin levels of the oxidative stress marker hydroxyproline, and skin and lung fibrosis. In addition, TwX treatment significantly reduced the levels of α-smooth muscle actin (α-SMA), a protein that was elevated in response to HOCl induction and has been shown to activate ROS in fibrotic diseases. HOCl-induced animals treated with TwX also showed a decreasing trend in the levels of inflammatory cytokines and activated immune cells involved in inflammatory responses.

Taken together, these results suggest that TwX may treat SSc by modulating oxidative stress and reducing skin and lung fibrosis. Since these findings were observed in a mouse model, further studies will be needed to establish the efficacy of TwX in human SSc patients. However, given the benefits of TwX in other oxidative stress-related diseases, as well as the lack of side effects, TwX holds considerable promise as an antioxidant therapeutic against SSc.

Sharing his final thoughts on their study, Professor Inufusa says: “Although TwX is a dietary supplement, it has passed drug-level safety testing and can be used by a wide range of people, from children to adults. Additionally, our findings suggest that TwX could potentially alleviate symptoms of intractable oxidative stress diseases such as SSc.”