Hexaraphane/6-MSITC and Memory in Older Adults: Evidence From a Double-Blind Randomized Controlled Trial

“What was that person’s name again?” Many people find themselves asking this question more often after their 60s.

Age-related memory decline becomes noticeable for many people during this period of life¹. Difficulty connecting names with faces, recalling the content of a conversation, or organizing the steps required to prepare a meal may seem minor. Yet these everyday challenges can reduce confidence and motivation and may also affect relationships with family members².

In recent years, studies have suggested that nutritional approaches may help mitigate declines in memory function³. One candidate is hexaraphane/6-MSITC, a compound derived from Japanese wasabi that has been discussed previously in this publication.

The clinical study reviewed here was published in Nutrients in 2023 by Professor Rui Nouchi of the University of Human Environments—who was affiliated with Tohoku University when the paper was published—and colleagues. Healthy adults aged 60 and older consumed hexaraphane/6-MSITC for 12 weeks. The researchers evaluated cognitive outcomes using a double-blind randomized controlled trial, a design intended to reduce bias.

What You Will Learn

• How the study tested memory outcomes in healthy adults aged 60 and older
• Why the group taking hexaraphane/6-MSITC showed significantly greater improvements in working memory and episodic memory tests than the placebo group
• An untested hypothesis from NOMON & Co. scientists addressing why hippocampus-dependent memory could change even though animal data indicate relatively low concentrations of hexaraphane/6-MSITC in the hippocampus

Aging and Cognitive Function: Why Memory Matters

Cognitive function includes memory, attention, judgment, processing speed, and other domains. Among these, memory is known to decline approximately linearly with age¹. In other words, it does not necessarily deteriorate suddenly. Rather, it may decline gradually over time. Studies have also reported that reduced memory function is directly associated with a lower quality of daily life². Memory problems are often noticeable to the individual, but gradual progression may be difficult to recognize, making early attention important.

Research in nutrition has examined associations between cognitive function and dietary patterns or components including the Mediterranean diet, blueberries, and lutein³⁴. Within this broader field, researchers have also begun to study compounds found in Japanese wasabi. Hexaraphane/6-MSITC is a Japanese wasabi-derived compound with reported antioxidant and anti-inflammatory properties. These features have prompted investigation into whether it could be relevant to declines in cognitive function associated with oxidative stress and chronic inflammation⁵⁶.

Previous trials had reported cognitive findings primarily in middle-aged populations⁷⁸. However, a rigorous clinical trial had not examined healthy adults aged 60 and older. This study was the first such attempt.

Study Design and Results

Study Design

The study used a double-blind randomized controlled trial design. Neither the participants nor the researchers knew who was taking hexaraphane/6-MSITC during the study, reducing the risk that expectations would influence the results.

Double-blind randomized controlled trial

A study in which participants are randomly assigned to receive either the test substance or a placebo. Neither the participants nor the researchers know which treatment each person receives during the trial. This design reduces expectation-related bias and supports a more objective comparison between groups.

• Design: Double-blind randomized controlled trial
• Participants: 72 healthy adults aged 60–80 years; mean age 65.43 years; 19 men and 53 women
• Groups: Hexaraphane/6-MSITC group, 36 participants: A wasabi-extract capsule containing 0.8 mg/day of hexaraphane/6-MSITC
• Groups: Placebo group, 36 participants: A capsule without the active ingredient
• Intervention period: 12 weeks; one capsule taken daily before bedtime
• Outcomes measured: A broad set of cognitive functions, including executive function, episodic memory, processing speed, working memory, attention, short-term memory, reasoning, and visuospatial ability
• Institutions: Institute of Development, Aging and Cancer, Tohoku University / Smart-Aging Research Center
• Registration number: UMIN 000032694

Results

1. Working memory improved significantly relative to placebo

Working memory was assessed with a backward digit-span test, in which participants repeat a sequence of spoken numbers in reverse order. The hexaraphane/6-MSITC group showed a statistically significant improvement relative to the placebo group. Working memory is particularly important in tasks requiring several steps, such as hearing a telephone number and writing it down immediately or managing multiple steps while following a recipe.

2. Episodic memory improved significantly relative to placebo

The study also found significant between-group improvements across three measures of episodic memory, or memory for events:

• Logical memory test, immediate recall: How much of a short story participants remembered immediately after hearing it
• Logical memory test, delayed recall: How much participants remembered 30 minutes later
• Face–name associative memory test: How well participants remembered pairs of faces and names

Episodic memory allows people to remember everyday events, such as what they ate yesterday or what they discussed with someone. Difficulty remembering people’s names is one of the most common memory complaints among older adults⁹. Changes in this domain may therefore be relevant to daily life, although the study did not directly measure quality-of-life outcomes resulting from the test-score differences.

3. No significant differences in other cognitive domains

No significant between-group differences were observed in processing speed, attention, inhibitory control—as measured by a Stroop test—reasoning, or visuospatial ability.

Discussion

The reported improvements were limited to memory-related outcomes. Why might memory, but not the other cognitive domains measured, have changed?

The authors proposed that the antioxidant and anti-inflammatory properties of hexaraphane/6-MSITC may have helped maintain neuroplasticity by limiting oxidative stress and inflammation in the hippocampus, a brain region central to memory. The hippocampus is highly vulnerable to oxidative stress and contributes to both working memory and episodic memory¹⁰, providing a biologically plausible hypothesis.

Hippocampus

A brain region involved in the formation of memory.

However, one question remains. In a separate mouse study by García-Yagüe and colleagues in 2026, the concentration of orally administered hexaraphane/6-MSITC reaching the hippocampus was approximately one-quarter of that measured in the cerebral cortex¹¹. Details of that study are available in this NOMON & Co. article. If relatively little hexaraphane/6-MSITC reaches the hippocampus, why might hippocampus-dependent memory outcomes change? The clinical paper does not fully answer this question.

NOMON & Co. scientists have proposed the following hypotheses. Both remain untested and should be regarded as directions for future research rather than established mechanisms.

Hypotheses From NOMON & Co. Scientists

Hypothesis 1

Low-concentration triggering and amplification through the Keap1–NRF2 pathway

NRF2 activation may not increase in direct proportion to the amount consumed. Even a small amount of hexaraphane/6-MSITC reaching cells could reduce NRF2 degradation and initiate coordinated antioxidant and anti-inflammatory defenses. If the concentration reaching the hippocampus is sufficient to trigger this response, antioxidant capacity could increase despite relatively low tissue exposure.

Hypothesis 2

Improved mitochondrial function

The hippocampus has particularly high energy demands. If reductions in oxidative stress and inflammation associated with hexaraphane/6-MSITC indirectly improve mitochondrial function, secondary effects might emerge in this energy-intensive region. No study has yet demonstrated a direct effect of hexaraphane/6-MSITC on mitochondria, so this hypothesis requires testing.

These hypotheses could help explain the apparent contrast between relatively low hippocampal exposure and changes in memory tests, but experimental validation is needed.

Significance and Future Directions

This was the first double-blind randomized controlled trial to examine whether hexaraphane/6-MSITC could influence memory function in healthy adults aged 60 and older.

Notable features include:

• Rigorous design: The double-blind randomized controlled design reduced expectation-related bias.
• Practical dose: The study tested 0.8 mg/day.
• Safety context: A previous study reported no adverse effects in a safety evaluation using five times this dose¹².
• Relevance of the measured domains: Story recall and face–name associative memory reflect areas in which older adults commonly experience difficulty.

Future Research

The study was relatively small, with 72 participants, and included only older Japanese adults. Larger, multicenter, and multiethnic trials are needed. Brain-imaging studies and measurements of biomarkers could also help clarify the mechanism and determine the reproducibility and clinical relevance of the observed effects.

References

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4. Nouchi, R. et al. "Effects of Lutein and Astaxanthin Intake on the Improvement of Cognitive Functions." Nutrients 12, 617 (2020) ↩
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11. Carnicero-Senabre, D. et al. "Hexaraphane as a potential therapeutic strategy for tauopathies." Redox Biol. (2026) ↩
12. Okunishi, I. et al. "Safety Evaluation of 6-MSITC and Wasabi Sulfinyl." Food Sci. Technol. Res. 26, 813–824 (2020) ↩