Hexaraphane from Japanese Wasabi and Oxidative Stress: Findings from an Exploratory Study

NOMON & Co. is committed to creating a society in which “productive aging” is the norm. Rather than focusing solely on longevity, we aim to use science to address a broader question: how can we improve quality of life as we age?

To advance this goal, NOMON & Co. conducts exploratory research from multiple perspectives.

This article presents an exploratory study of hexaraphane (6-MSITC), a rare compound derived from Japanese wasabi. The study was led by Ryota Nakajima, Executive Officer at NOMON & Co. and a scientist with a PhD in Pharmaceutical Sciences. We explain how hexaraphane may affect cellular “rust,” or oxidative stress, and what the findings may mean for health.

What This Article Covers

• How oxidative stress arises in the body and how 8-OHdG is used as a marker
• The potential role of hexaraphane in activating NRF2, a cellular defense regulator
• Findings from an exploratory study that measured changes in urinary and seminal oxidative stress markers after four weeks of supplementation
• The potential implications of hexaraphane for brain health and cognitive function

NRF2

A regulatory factor that acts like a cellular defense switch against oxidative stress.

Oxidative Stress in the Body and the Marker 8-OHdG

Through normal processes such as breathing and physical activity, the body continually produces reactive oxygen species. These molecules play important roles in functions including immune defense. However, when produced in excess, they can oxidize DNA within cells and cause damage. This condition is known as oxidative stress—sometimes described as cellular “rust.”

When DNA is oxidatively damaged, one of the resulting products is 8-OHdG (8-hydroxy-2’-deoxyguanosine). Higher levels of DNA-associated 8-OHdG are thought to be linked to aging and elevated health risks, including cancer.

Assessing oxidative stress by measuring 8-OHdG in urine and semen

The body has repair mechanisms that remove damaged DNA components. Unneeded 8-OHdG is excreted in urine, so measuring urinary 8-OHdG can provide an indication of oxidative stress in the body.

Oxidative stress can also affect sperm. Damage to mitochondrial DNA—the genetic material in the structures that supply sperm with energy—may impair function and ultimately reduce motility. Seminal oxidative stress can likewise be assessed by measuring 8-OHdG.

Hexaraphane (6-MSITC) and Antioxidant Activity

Hexaraphane (6-MSITC: 6-methylsulfinylhexyl isothiocyanate; referred to below as hexaraphane) is a rare bioactive compound found in the rhizome of Japanese wasabi. Non-clinical research has reported a range of pharmacological activities, including antioxidant activity¹, anti-inflammatory activity, antibacterial activity, anticancer activity, and inhibition of platelet aggregation²³.

More recently, continued administration of hexaraphane to a mouse model of Alzheimer’s disease was reported to improve cognitive function. The proposed mechanism was activation of NRF2 by hexaraphane, leading to reduced oxidative stress⁵.

Encouraging results have also been reported in humans. In a study conducted by a Tohoku University research group, healthy adults aged 60 years and older took hexaraphane for 12 weeks. Improvements were observed in cognitive functions including episodic memory—the memory of events—and working memory, which supports the temporary storage and use of information⁶.

Study Overview: Intake of a Hexaraphane-Containing Supplement ⁷

To explore the potential of hexaraphane, NOMON & Co. scientist Ryota Nakajima conducted the following clinical study.

• Test product: A supplement containing hexaraphane (6-MSITC), with 1.6 mg per capsule
• Intake: One capsule daily for four weeks
• Efficacy analysis population: 59 adults aged 20 to under 60 years
• Measurements: Urinary or seminal 8-OHdG was measured before and after intake using test kits. Urinary 8-OHdG values were corrected for urinary creatinine.
• Study lead: Ryota Nakajima, Executive Officer / CPO / PhD in Pharmaceutical Sciences, NOMON & Co.
• Study site: Healthcare Systems Co., Ltd.

Study Results

1. Urinary oxidative stress levels (urinary 8-OHdG): Across all 59 participants, the mean value did not change substantially between baseline and the end of the intake period. However, among the 24 participants whose baseline oxidative stress levels were at or above the median, urinary 8-OHdG decreased significantly after four weeks.
2. Seminal oxidative stress levels (seminal 8-OHdG): Among the 29 male participants, seminal 8-OHdG decreased after intake in every participant.

How to read the figures:

The vertical axes show urinary 8-OHdG in Figure 1 and seminal 8-OHdG in Figure 2. The graphs compare each participant’s 8-OHdG levels before and after intake of the hexaraphane-containing supplement.

Discussion

Four weeks of continuous intake of the test product was associated with reductions in urinary and seminal 8-OHdG.

Animal studies have reported that hexaraphane activates NRF2. The reductions in urinary and seminal 8-OHdG observed in this study may therefore have been related to NRF2 activation. Further studies in humans will be needed to build the evidence base for hexaraphane.

References

1. Mizuno K., et al., J.Pharmacol. Sci., 115 (3):320-328, 2011 ↩
2. Uto T., et al., Advances in Pharmacol.Sci. Article ID 614046, 2012 ↩
3. Kuno T., et al., Oncol. Lett. 1: 273-278, 2010. ↩
4. Uruno, A., et al., Molecular and Cellular Biology. (2020). ↩
5. NOUCHI, Rui, et al. Nutrients 15.21 (2023): 4608. ↩
6. Nakajima, R. “Oxidative Stress-Reducing Effects of Japanese Wasabi Powder Extract (6-Methylsulfinylhexyl Isothiocyanate: 6-MSITC) and Report of a Clinical Study.” First Summer Symposium of the Redox R&D Strategy Committee, 2022. ↩