Antioxidant Research

Antioxidant Research

Functions of Antioxidant Supplements

Strong Antioxidant Capacity

Twendee X®, containing 8 ingredients, and Twendee Mtcontrol®, containing 15 ingredients, have over five times the antioxidant capacity of single-component Vitamin C. Additionally, Twendee Mtcontrol® has been shown to possess even higher antioxidant capacity than Twendee X®. A balanced combination of multiple ingredients exhibits more potent effects.

Strong Free Radical Scavenging Ability

Not all products labeled as antioxidant supplements can eliminate free radicals. Various types of free radicals exist, notably superoxide (O2•−), hydroxyl radicals (•OH), and methyl radicals (•CH3). Twendee X®, Twendee Mtcontrol®, and Twendee S® can scavenge these free radicals even at low concentrations.

Graph

Promotion of Energy Production

Mitochondria are essential intracellular organelles that consume oxygen to produce energy. During this process, reactive oxygen species (ROS) are generated as by-products, making mitochondria a source of ROS production. When mitochondrial function declines, it leads to cellular damage and eventual impairment of various functions. Twendee X® protects mitochondria from ROS through its strong antioxidant capacity, preventing functional decline and increasing energy production (ATP and ADP).

Energy production graph

Suppression of Hyperglycemia

Diabetes is a lifestyle disease that increases the risk of numerous conditions, including Alzheimer's disease, heart disease, and cancer. Elevated blood glucose levels lead to increased reactive oxygen species (ROS) and are associated with mitochondrial dysfunction. Twendee X® has been shown to suppress postprandial hyperglycemia and the associated rise in oxidative stress, potentially preventing damage to vascular endothelium. This effect holds promise for future diabetes treatments.

Diabetes illustration

Maintenance of Autophagy Function

Autophagy is a cellular process that maintains internal environments by clearing out unnecessary cells and abnormal proteins. The efficiency of autophagy declines with aging and increased oxidative stress. Accumulated waste that cannot be cleared produces additional oxidative stress, creating a vicious cycle that impairs autophagy function and can lead to neurodegenerative diseases like Alzheimer's.

Twendee X® was shown to maintain autophagy function in diabetic mice at risk of Alzheimer's by preserving LC3 protein expression, essential for the autophagy pathway. This suggests that Twendee X® can support cellular health even under oxidative stress conditions.

Autophagy illustration

Maintenance of Telomere Length

Telomeres are structures located at the ends of chromosomes, deeply involved in cell lifespan and aging. With each cell division, telomeres shorten, eventually leading to cell death. Maintaining telomere length is considered to be linked to anti-aging and longevity. Research suggests that Twendee X® may suppress telomere shortening and extend cell lifespan.

Telomere illustration

Neurogenesis

In the adult brain, neurogenesis occurs throughout life. However, the ability for neurogenesis declines with aging, leading to a decrease in the number of neurons. Research confirmed that Twendee X® prevents age-related decline in neurogenesis, as treated aged mice exhibited higher neurogenic activity compared to younger counterparts.

Neurogenesis illustration

Preventive Effects on Mild Cognitive Impairment (MCI)

Background of the Study
In recent years, cases of dementia have been rapidly increasing, with approximately 7 million patients expected in Japan by 2025. Dementia is a progressively advancing disease, and by the time it is diagnosed, the progression of symptoms is believed to have started 25 years earlier. Therefore, early preventive measures are considered extremely important.

Details and Results of the Clinical Trial
A clinical trial led by the Japan Society for Dementia Prevention investigated the preventive effects of Twendee X® on dementia. The trial targeted patients with mild cognitive impairment (MCI) and was designed as a prospective, multicenter, randomized, double-blind, placebo-controlled interventional study. Results showed significant improvements in Mini-Mental State Examination (MMSE) scores and Hasegawa Dementia Scale (HDS-R), demonstrating that Twendee X® effectively prevented the progression of MCI.

This clinical study was the first to demonstrate worldwide that oxidative stress is a significant factor in dementia development and that antioxidant supplements can prevent its progression.

Clinical trial results

The findings were published on August 24, 2019, in the "Journal of Alzheimer’s Disease," and Twendee X® received a Grade A certification from the Japan Society for Dementia Prevention for its dementia-preventive effects.

Certification

Future Prospects
Twendee X® offers a new approach to dementia prevention, as it is available as a supplement rather than medication, allowing for easy adoption even before a diagnosis. This research underscores the importance of early intervention and suggests potential benefits against other oxidative stress-related conditions.


Monitor Survey Results

To investigate the various effects of Twendee X® and Twendee Mtcontrol®, participants with relevant symptoms were recruited online, and a survey company was commissioned to conduct the research.

Hay Fever

Conducting Organization: Eyes Co., Ltd.
Twendee X® Intake Period: 2 months
Survey Period: February 8, 2017 – May 7, 2017
Participants: 102 females aged 20s to 50s and above

Background
Hay fever is an allergic reaction caused by pollen, leading to symptoms such as sneezing, runny nose, and itchy eyes. These symptoms are triggered by oxidative stress caused by reactive oxygen species (ROS). This survey aimed to evaluate the effects of antioxidant supplements on reducing hay fever symptoms.

Results
86% of participants reported symptom improvement, and 20% no longer needed medication. 90% expressed willingness to use Twendee X® again if symptoms recur. These findings suggest that Twendee X® is effective in managing hay fever symptoms, particularly by reducing oxidative stress.

Hay fever results

Asthma

Conducting Organization: Eyes Co., Ltd.
Twendee X® Intake Period: 4 months
Survey Period: November 8, 2017 – March 18, 2018
Participants: 44 females aged 20s to 50s and above

Background
Asthma symptoms are linked to oxidative stress, which exacerbates airway inflammation. This survey assessed the effectiveness of antioxidant supplements in improving asthma conditions.

Results
Before supplementation, 60% of participants experienced 5+ asthma attacks over 4 months. After 2 months of Twendee X®, 90% had reduced attacks to fewer than 4. This demonstrates the potential of Twendee X® in reducing oxidative stress and improving asthma symptoms.

Asthma improvement
Asthma reduction
Asthma survey

Acne

Conducting Organization: Eyes Co., Ltd.
Twendee X® Intake Period: 2 months
Survey Period: December 23, 2015 – January 25, 2016
Participants: 51 females aged teens to 40s

Background
Acne is influenced by oxidative stress, which contributes to skin inflammation and cellular damage. Twendee X® was tested for its potential to improve acne by reducing oxidative stress.

Results
43% of participants reported significant improvement in acne, and 59% considered Twendee X® highly effective for acne treatment. Furthermore, 70% noted additional skin benefits beyond acne improvement.

Acne results Skin improvement

Infertility

Conducting Organization: Eyes Co., Ltd.
Twendee Mtcontrol® Intake Period: 12 months
Survey Period: December 19, 2018 – December 12, 2019
Participants: 28 couples (females aged 20s to 40s and their partners)

Background
Infertility has been linked to oxidative stress, which affects reproductive health. Twendee Mtcontrol® was evaluated for its impact on improving fertility by reducing oxidative stress.

Results
Among 28 couples, 9 achieved pregnancy during the trial period (4 within 1–6 months, and 5 within 7–12 months). Participants also reported improvements in male reproductive function.

Infertility improvement Pregnancy results

Chronic Fatigue Syndrome (CFS)

Conducting Organization: Eyes Co., Ltd.
Twendee Mtcontrol® Intake Period: 2 months
Survey Period: September 17, 2021 – November 18, 2021
Participants: 23 females aged 10s to 50s

Background
Chronic Fatigue Syndrome (CFS) involves severe fatigue with potential links to oxidative stress. This survey assessed the effects of Twendee Mtcontrol® on CFS symptoms.

Results
Participants reported improvements in key symptoms such as sleep disturbances and fatigue, with 83% noting overall effectiveness.

Chronic fatigue improvement CFS results

Post-COVID-19 Syndrome

Conducting Organization: TIMA Establishment
Twendee X® Intake Period: 1 month
Survey Period: September 2, 2021 – September 28, 2021
Participants: 126 individuals with post-COVID-19 symptoms

Background
Fatigue, brain fog, and other post-COVID-19 symptoms are suspected to be influenced by oxidative stress. Twendee X® was tested for its potential to alleviate these symptoms.

Results
Significant improvements in fatigue, concentration, and other symptoms were reported, particularly in participants with severe conditions.

Post-COVID-19 results

Vaccine Side Effects

Conducting Organization: TIMA Establishment
Twendee X® Intake Period: 1 month
Survey Period: September 2, 2021 – October 18, 2021
Participants: 149 individuals experiencing side effects after COVID-19 vaccination

Background
Oxidative stress is considered a contributing factor to side effects such as fatigue and fever following COVID-19 vaccination. Twendee X® was evaluated for its ability to mitigate these side effects by reducing oxidative stress.

Results
Participants reported reductions in fatigue and other side effects. Significant improvements were observed, suggesting the potential effectiveness of Twendee X® in managing post-vaccination symptoms.

Vaccine side effects improvement

Publications

  1. Neuroprotective Effects of a Novel Antioxidant Mixture Twendee X in Mouse Stroke Model. Momoko Kusaki, Yasuyuki Ohta, Haruhiko Inufusa, et al. J Stroke Cerebrovasc Dis. 2017 Jun;26(6):1191-1196.
  2. Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion. Xia Liu, Toru Yamashita, Jingwei Shang, et al. J Stroke Cerebrovasc Dis. 2019 Jul;28(7):1993-2002.
  3. Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study. Koh Tadokoro, Ryuta Morihara, Yasuyuki Ohta, et al. J Alzheimers Dis. 2019;71(3):1063-1069.
  4. Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion. Xia Liu, Toru Yamashita, Jingwei Shang, et al. J Stroke Cerebrovasc Dis. 2019 Oct;28(10):104310.
  5. Prevention of Cognitive Decline in Alzheimer's Disease by Novel Antioxidative Supplements. Koh Tadokoro, Yasuyuki Ohta, Haruhiko Inufusa, et al. Int J Mol Sci. 2020 Mar;21(6):1974.
  6. Neuroprotective and Therapeutic Effects of Tocovid and Twendee-X on Aβ Oligomer-Induced Damage in the SH-SY5Y Cell Line. Xiao Hu, Toru Yamashita, Haibo Yu, et al. Neurodegener Dis. 2021;21(5-6):117-125.
  7. Effects of Antioxidant Composition Twendee X on Side Effects of SARS-CoV-2 mRNA Vaccine. Fukka Yang, Sho Tanaka, Toshikazu Yoshikawa, et al. Brain Supplement. 2022;4:1-6.
  8. Antioxidant Composition Twendee X May Improve Long COVID Symptoms. Fukka Yang, Sho Tanaka, Toshikazu Yoshikawa, et al. Brain Supplement. 2022;4:7-12.
  9. Why Does the Antioxidant Complex Twendee X® Prevent Dementia? Fukka Yang, Yoshiaki Harakawa, Toshikazu Yoshikawa, et al. Int J Mol Sci. 2023;24(16):13018.
  10. The Effect of Oxidative Stress on the Human Voice. Shigeru Hirano, Haruhiko Inufusa, Fukka Yang. Int J Mol Sci. 2024;25(5):2604.