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Cognitive Frailty in Malaysia: A Perspective for Healthy Aging Through Pyrroloquinoline Quinone as a Nutritional Strategy

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03 September 2026

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03 September 2026

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Abstract
The rapidly aging population of Malaysia highlights the urgent need to address age-related conditions. Cognitive frailty, a reversible condition combining physical frailty and cognitive impairment, poses considerable risks of disability and reduced quality of life among older adults. Pyrroloquinoline quinone (PQQ), a bioactive compound with mitochondria-enhancing and antioxidant properties, shows promise as a functional food ingredient for improving cognitive health. This narrative review aims to explore the relevance of cognitive frailty in Malaysia, the role of PQQ in cognitive health, and the potential of PQQ as a functional food ingredient. A comprehensive literature search was performed using PubMed, Scopus, and Google Scholar. Keywords such as “neuroprotection,” “PQQ,” “mitochondria,” “antioxidants,” and “functional foods” were used to identify preclinical and clinical research published over the last two decades. Articles reporting mechanisms of PQQ action, cognitive effects, and aging were selected and critically appraised for their relevance to cognitive frailty and nutritional interventions. The neuroprotective potential of PQQ lies in its ability to reduce oxidative stress, mitigate inflammation, restore mitochondrial function, prevent cellular senescence, and maintain hormonal balance. Preclinical and clinical studies show that PQQ supplementation benefits memory, learning, and cognitive performance. Nonetheless, research gaps remain in populations affected by cognitive frailty. Challenges include dose optimization, population-specific trials, and regulatory considerations for implementing PQQ as a functional food ingredient. PQQ has potential as a nutritional strategy to mitigate cognitive frailty and improve cognitive health in aging populations, including Malaysia. Further studies are warranted to translate these findings into effective interventions.
Keywords: 
cognitive frailty
;  
healthy aging
;  
mitochondrial function
;  
neuroprotection
;  
pyrroloquinoline quinone
Subject: 
Biology and Life Sciences  -   Aging

1. Introduction

The World Health Organization (WHO) has recognized that the rapidly aging global population is resulting in an increased prevalence of age-related conditions, including cognitive decline and dementia (WHO, 2025). With age, individuals commonly experience a progressive reduction in both their physical and cognitive abilities, increasing their vulnerability to disease and mortality. Malaysia is experiencing a similar demographic shift. By 2030, estimates suggest that 9.3% of the population (approximately 3.4 million individuals) will be aged 65 years and older (Figure 1A). This proportion is expected to rise to approximately 7.8 million, or 18.3% of the population, by 2060 (Figure 1B, Department of Statistics Malaysia [DOSM], 2025). Such a demographic changes underscore the urgent need to address the health and well-being of older adults, particularly to prevent and manage age-related cognitive impairment.
Cognitive frailty (CF), a condition characterized by the coexistence of physical frailty and cognitive impairment, has long been a major concern in aging populations (Donini et al., 2013). Community-based studies indicate that the prevalence of CF in Malaysia is 39.6%, which is higher than that in other Asian countries such as Thailand, China, and Singapore (Malek Rivan et al., 2024). Moreover, Malaysia’s Towards Usual Aging longitudinal study underscored the importance of early detection and timely intervention for cognitive decline to improve long-term health outcomes (Malek Rivan et al., 2019). This study highlighted the multifactorial nature of cognitive decline and emphasized the need for holistic, early-life interventions, including nutritional strategies, to mitigate risks and support healthy aging.
Pyrroloquinoline quinone (PQQ), a bioactive compound with mitochondria-enhancing and antioxidant properties, has gained attention as a potential functional food ingredient for improving cognitive health. PQQ promotes mitochondrial biogenesis (Chowanadisai et al., 2010), reduces oxidative stress (He et al., 2003), supports neuronal survival (Ikemoto, Mohamad Ishak & Akagawa, 2024), and shows therapeutic potential in neurodegenerative diseases (Xie, Zhang, Feng et al., 2025), making it a promising candidate for nutritional strategies targeting CF. The presence of PQQ in natural food sources, such as fermented soybeans, parsley, and green tea, highlights its potential for dietary integration (Kumazawa et al., 1995).
Therefore, present review aims to explore the relevance of CF in Malaysia, examine the role of the PQQ in cognitive health, and assess the potential of PQQ as a functional food ingredient. By evaluating existing research and identifying knowledge gaps, this review contributes to the ongoing discussion on nutritional strategies for cognitive resilience in aging populations.

2. Methodology

A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify relevant studies published over the past two decades. Keywords included “neuroprotection,” “Pyrroloquinoline quinone (PQQ),” “mitochondria,” “antioxidants,” “functional foods,” and “cognitive frailty.” Both preclinical and clinical studies examining the mechanisms of PQQ action, its effects on cognition, and its relevance to aging were included. Articles were critically evaluated for methodological quality and relevance to nutritional strategies targeting cognitive frailty. Reference lists of selected studies were also screened to ensure a comprehensive review. Population statistics for Malaysia, including aging population projections, were obtained from the Department of Statistics Malaysia (DOSM, 2025).

3. Results

3.1. Cognitive Frailty

3.1.1. Underlying Mechanism

CF is a clinically significant condition characterized by the simultaneous presence of physical frailty and cognitive impairment, excluding dementia (Chew et al., 2024; Facal et al., 2021). As a transitional state between healthy aging and pathological decline, CF reflects shared biological pathways that affect muscle and brain functions.
The mechanisms underlying CF are complex and involve several interrelated factors including oxidative stress, mitochondrial dysfunction, chronic inflammation, hormonal imbalances, and impaired energy metabolism (Figure 2, (Carini et al., 2021)). Age-related accumulation of reactive oxygen species (ROS) leads to cellular damage, disrupts mitochondrial homeostasis, and reduces ATP production, ultimately compromising neuronal and muscular performance (El Assar, Angulo & Rodríguez-Mañas, 2020; Ferrucci & Zampino, 2020). Mitochondrial dysfunction triggers proinflammatory signalling, establishing a vicious cycle that accelerates cellular senescence (Chapman, Fielder & Passos, 2019). Moreover, neuroinflammation and vascular dysfunction contribute to reduced cerebral blood flow, impaired synaptic plasticity, and neurodegeneration, while systemic inflammation promotes muscle catabolism and weakness. Declines in anabolic hormones such as insulin-like growth factor-1 (IGF-1) and sex steroids exacerbate both cognitive and physical impairment (Bisset & Howlett, 2019). Therefore, CF arises from the convergence of metabolic, inflammatory, hormonal, and mitochondrial disturbances that link the physical and cognitive domains.

3.1.2. Potentially Reversible Condition

CF is associated with an increased risk of adverse outcomes such as disability, reduced quality of life, and increased mortality in aging populations (Nader et al., 2023; Timmons et al., 2025). Importantly, CF is potentially reversible, distinguishing it from other neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease (Ruan et al., 2015), and highlighting it as a promising target for interventions aimed at mitigating risks related to cognitive functional decline. Therefore, addressing CF through early detection and comprehensive approaches that integrate physical and cognitive health can enhance the overall well-being of older adults and alleviate the healthcare burden associated with aging populations (Kelaiditi et al., 20Facal et al., 2021).
In Malaysia, community-based studies have demonstrated that factors such as age, depression, low niacin intake, and oxidative stress are associated with CF occurrence (Malek Rivan et al., 2019). In practice, interventions for CF in Malaysia have increasingly adopted multidomain approaches, integrating medical care with dietary strategies and lifestyle modifications (Ponvel et al., 2025). For example, the My-AGELESS trial has adapted FINGER lifestyle interventions to the Malaysian context, emphasising physical exercise, cognitive stimulation, dietary counselling, and psychosocial support. This trial aligns with the general medical and nutritional strategies for managing CF. Medical strategies focus primarily on the early detection and management of chronic conditions, such as hypertension, diabetes, and depression, that contribute to frailty and cognitive decline, through the integration of geriatric assessment services in public healthcare. In contrast, nutritional interventions provided through systematic counselling aim to promote optimal niacin and antioxidant intake to combat oxidative stress.
In summary, nutritional strategies play a key role in preventing and managing CF, as both physical and cognitive decline are influenced by dietary factors. Specifically, essential nutrients, such as vitamin D, vitamin B12, folate, omega-3 fatty acids, and antioxidants, are crucial for maintaining muscle mass, neural integrity, and mitochondrial function (Ahn, Wu & Kim, 2025).
Despite ongoing national efforts to address CF, considerable challenges remain in delivering scalable and culturally appropriate interventions across Malaysia’s diverse population. Overcoming these challenges will necessitate interdisciplinary collaboration, increased public health awareness, and robust context-specific research to validate the effectiveness of emerging nutraceuticals within local dietary and healthcare frameworks.

3.2. Pyrroloquinoline Quinone

Various bioactive compounds have been explored for their potential to combat CF (Maksimović et al., 2025; Ristori et al., 2025). Among these, PQQ is particularly promising, owing to its multifaceted biological effects; it complements conventional antioxidants and functional foods, enhances mitochondrial health, and promotes neuroprotection (Charrier et al., 2024; Ikemoto et al., 2024; Xie et al., 2025). Notably, PQQ has been proposed to function as a novel vitamin compound, as it is essential for optimal physiological functions and cannot be endogenously synthesized (Akagawa, Nakano & Ikemoto, 2016). Moreover, dietary deprivation of PQQ causes growth impairment, compromised immune response, and abnormal reproductive function in animals, further supporting its classification as an essential micronutrient (Jonscher, Chowanadisai & Rucker, 2021). Accordingly, we advocate PQQ as a potential nutritional countermeasure to mitigate CF, as its diverse biological functions align well with the key pathological mechanism underlying the disease.

3.2.1. Properties and Global Recognition

PQQ was first discovered in 1979 as a cofactor in enzymes responsible for the oxidation of alcohols (Anthony, 2001; Goodwin & Anthony, 1998). This small, water-soluble quinone compound comprises a pyrroloquinoline moiety linked to the quinone group, enabling it to take part in redox reactions and facilitate electron transfer (Ikemoto, Mori & Mukai, 2017). PQQ occurs naturally in various foods, including breast milk (Kumazawa et al., 1995; Mitchell et al., 1999). It is produced through fermentation by specific microorganisms and can be used as a supplement in the form of a disodium salt (BioPQQ, C14H10N2Na2O11, formula weight: 428.22 g/mol), which is a red powder used for commercial purposes (Figure 3).
In the United States, the Food and Drug Administration (FDA) has appointed PQQ as ‘Generally Recognized as Safe’, which permits its inclusion in dietary supplements and specific foods (U.S. Food and Drug Administration (FDA), 2017). In Europe, PQQ is classified as a "novel food," allowing its regulated use in brain and energy support supplements (Turck et al., 2017). Japan has approved PQQ for use in functional foods and supplements, and China has adopted the disodium salt form of PQQ for various health applications. Across these regions, PQQ is widely incorporated into energy drinks, anti-aging products, and cognitive health boosters, highlighting its global impact as a versatile nutritional ingredient. Importantly, the availability of halal-certified PQQ, such as BioPQQ produced by Mitsubishi Gas Chemical Company Inc., ensures compatibility with Malaysia’s dietary requirements, facilitating its acceptance among Muslim consumers.

3.2.2. Safety and Pharmacokinetics of PQQ

The safety of PQQ has been thoroughly evaluated by the European Food Safety Authority. An intake of 20 mg/day is recommended for functional foods, which is approximately 250 times higher than the estimated dietary background intake (Turck et al., 2017). No adverse effects were observed in animals after 90 days of oral administration of PQQ at 1,000 mg/kg/day, nor in humans consuming 100 mg/day for 24 weeks, confirming that PQQ is a safe bioactive compound (Fukuda et al., 2017).
Pharmacokinetic studies have elucidated the absorption and metabolism of PQQ. In male Swiss–Webster mice administered a single oral dose of radiolabelled (14C) PQQ (1.5 mg/kg), 3.3% of the dose was absorbed within 6 h, with 81% of the absorbed fraction excreted in urine. The remaining radioactivity was primarily distributed in the kidneys, liver, skin, and blood (Smidt et al., 1991).
In humans, healthy adults (n = 10) received PQQ at 0.075, 0.15, and 0.3 mg/kg/day (5.25–21 mg/day) for 7 days (Harris et al., 2013). Only approximately 0.1% of the administered PQQ was recovered unchanged in urine, whereas serum concentrations increased dose-dependently, reaching 14 nM at the highest dose. After a single oral dose of 2 mg/kg (14 mg for a 70 kg adult), the serum levels peaked at approximately 9 nM after 2 h and declined in parallel with urinary excretion. In a high-dose trial (100 mg/day), serum PQQ concentrations reached 16–54 nM after 3 h and returned to baseline within 24 h. Continuous intake for 6 days increased the baseline levels, although a large inter-individual variation (62% relative standard deviation) was observed (Fukuda et al., 2017).
Overall, PQQ is efficiently absorbed from the intestine, rapidly metabolized, and primarily excreted in urine. Peak plasma levels occur within 2–3 h and decline within 24 h. Repeated intake is safe and elevates baseline PQQ levels, despite variations in absorption among individuals.

3.2.3. Molecular Mechanisms to Reverse CF

PQQ is a redox-active compound that exhibits powerful biological effects, which can address the underlying factors contributing to CF. Its actions are mediated through several molecular mechanisms, as summarized in Figure 3.

3.2.4. Reduction of Oxidative Stress

One potential mechanism underlying the effects of PQQ is the activation of antioxidant defences. PQQ acts as an efficient electron acceptor and donor, facilitating redox reactions that neutralise ROS. PQQ reduces oxidative stress by scavenging excess ROS, mitigating mitochondrial and neuronal damage (Ikemoto et al., 2017). By activating the Nrf2 signalling pathway, PQQ upregulates key antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, which further enhances defences against oxidative damage (Kumazawa et al., 1995).

3.2.5. Mitigation of Inflammaging

PQQ decreases the levels of proinflammatory cytokines involved in inflammaging, including tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) (Ma et al., 2019; Mohamad Ishak et al., 2024). By modulating the NF-kB signalling pathway, PQQ reduces the transcription of these inflammatory mediators, thereby lowering chronic inflammation that contributes to cognitive decline and physical frailty (Ikemoto et al., 2024; Mohamad Ishak and Ikemoto, 2023). Moreover, PQQ disrupts the Keap1–Nrf2 complex, thereby activating Nrf2–ARE signalling. This increases the expression of antioxidant genes (e.g., HO-1, NQO1) and reduced ROS, thereby blunting NF-κB activation and downstream cytokine production in aged tissues (Xue et al., 2024).

3.2.6. Restoration of Mitochondrial Function

PQQ enhances mitochondrial biogenesis through the activation of PGC-1α, which regulates mitochondrial replication and function (Chowanadisai et al., 2010). By upregulating PGC-1α and its downstream targets, PQQ promotes increased mitochondrial mass and function, leading to improved ATP production and energy metabolism (Canovai et al., 2023; Xie et al., 2025). At the molecular level, PQQ activates the SIRT1/PGC-1α signalling axis by increasing the intracellular NAD+ pool. As a redox-active o-quinone, PQQ catalyses the oxidation of NADH to NAD+ through continuous redox cycling, thereby elevating the NAD+/NADH ratio without altering the total nucleotide content (Saihara et al., 2017). The increase in NAD+ availability enhances the deacetylase activity of SIRT1, which in turn deacetylates and activates PGC-1α, promoting its nuclear translocation and the transcription of mitochondrial biogenesis genes such as NRF1 and TFAM. PQQ also activates the LKB1/AMPK pathway, which acts in concert with SIRT1 to further stimulate PGC-1α activity, establishing a positive feedback loop that drives mitochondrial renewal and energy homeostasis (Saihara et al., 2017). Through these mechanisms, PQQ may help restore mitochondrial quantity and efficiency in individuals with CF, counteracting age-related declines in energy metabolism and neuronal resilience.

3.2.7. Prevention of Cellular Senescence

The potent antioxidant and anti-inflammatory properties of PQQ contribute to the attenuation of cellular senescence. In various preclinical models, PQQ supplementation has been demonstrated to reduce the expression of p16, p21, and p53 and suppress the senescence-associated secretory phenotype, including IL-6 and MMP-13, thereby preserving tissue integrity and function (Gao et al., 2022; Li et al., 2025; Qin et al., 2019). Recent evidence identifies PQQ as an effective senomorphic agent that directly targets the proinflammatory phenotype of senescent cells. In vitro, PQQ treatment downregulated a broad spectrum of SASP factors, including IL-6, IL-8, MCP-1, and MMPs, in senescent stromal cells, while restoring mitochondrial activity and redox homeostasis (Jiang et al., 2025). These findings suggest that PQQ modulates the secretory behaviour of existing senescent cells rather than merely preventing their formation, thereby alleviating chronic tissue inflammation and functional decline associated with aging.
Direct evidence from aging mouse studies demonstrates that long-term dietary PQQ supplementation lowers senescence markers (p16, p21, and Lamin B1), reduces SA-β-gal positivity, and decreases SASP mediators such as IL-1β, IL-6, and MMP-13 in aged intervertebral disc tissues and IL-1β–treated human nucleus pulposus cells. These effects were accompanied by enhanced cell proliferation and reduced apoptosis, indicating an attenuation of age-related degenerative changes. Importantly, the anti-senescence effects of PQQ were abolished in Nrf2-deficient mice and cells, confirming that the activation of Keap1–Nrf2 pathway is essential for mediating PQQ’s protective action (Xue et al., 2024).

3.2.8. Balance of Hormonal Levels

Preclinical studies have demonstrated that PQQ enhances insulin signalling and improves insulin sensitivity through PTP1B inhibition and mitochondrial improvement, which might modulate the insulin/IGF-1 axis, thereby supporting anabolic processes relevant to muscle and cognitive health (Shi et al., 2022; Yang et al., 2021. However, direct evidence that PQQ increases circulating IGF-1 in mammals is currently lacking, although IGF-1 upregulation has been reported in non-mammalian models (e.g., fish)(Shi et al., 2022), and Insulin/IGF-1 signalling-related effects have been described in invertebrates (Yang et al., 2021).

3.2.9. Enhancement of Cognitive Function

PQQ stimulates the synthesis of nerve growth factor, a neurotrophin critical for neuronal survival, differentiation, and synaptic plasticity (Murase et al., 1993; Yamaguchi et al., 1993). It facilitates neuronal regeneration and enhances synaptic connectivity by promoting nerve growth factor production and supporting mitochondrial function within neurons. These neurotrophic effects highlight PQQ as a promising candidate for protection against age-related cognitive decline and neurodegenerative changes associated with CF.

3.2.10. Integrated Effects

The actions of PQQ on oxidative stress, inflammation, mitochondrial health, cellular senescence, and hormonal balance collectively contribute to its potential in reversing CF. Numerous studies have demonstrated that regular exercise can improve physical function, increase mobility, and promote overall health in aging populations (Lai et al., 2025; Prommaban et al., 2024). Engaging in exercise may complement the effects of PQQ by further reducing oxidative stress and inflammation while promoting mitochondrial health. This action may enhance cognitive resilience and overall health in aging populations.

3.3. Preclinical and Clinical Evidence Supporting PQQ in Cognitive Health

The therapeutic potential of PQQ in cognitive health has been substantiated by an expanding body of preclinical and clinical studies that have collectively highlighted its neuroprotective, anti-inflammatory, and mitochondria-supporting properties (Canovai & Williams, 2025). Preclinical animal models have consistently demonstrated that PQQ supplementation improves memory, learning, and motor coordination. For example, mice administered PQQ exhibited enhanced spatial learning and memory in the Morris water maze test (Ohwada et al., 2008) and improved memory learning ability in aged mice (Yamada et al., 2020). Additionally, PQQ mitigated neurodegeneration in rodent models of Alzheimer’s disease, Parkinson’s disease, and cerebral ischaemia by reducing oxidative stress and promoting mitochondrial biogenesis (Martino Adami et al., 2017; Qin et al., 2015; Zhang et al., 2016; Zhao et al., 2014). Notably, these findings have been reinforced by human studies. Among 64 healthy Japanese volunteers with a mean age of approximately 72 years, a daily dose of 21.5 mg resulted in significant enhancements in various cognitive functions, including composite and verbal memory, reaction time, and executive function, with no reported adverse effects (Shiojima et al., 2022). Similarly, a study involving younger participants (mean age: 41.5 years) receiving 20 mg/day also demonstrated notable improvements after 12 weeks, aligning with findings from older cohorts (Tamakoshi et al., 2023). Furthermore, healthy older adults receiving 20 mg/day of PQQ combined with CoQ10 experienced significant enhancements in attention, information identification, processing power, and immediate memory (Koikeda, Nakano & Masuda, 2011; Nakano et al., 2009). A group of 41 healthy older participants exhibited significant improvements in attention and working memory with just PQQ supplementation (Itoh et al., 2016). Collectively, these studies suggest that PQQ may play a beneficial role in enhancing cognitive function across different age groups, with notable efficacy in older adults. Furthermore, PQQ can improve subjective measures of sleep quality as well as fatigue, suggesting broader benefits for the quality of life (Nakano et al., 2012). Studies on cognitive function are summarized in Table 1.

4. Discussion

Although preclinical and early clinical results indicate the promising benefits of PQQ for cognitive function, several gaps in our understanding remain to be filled before its full potential can be realized in Malaysia. First, although PQQ is already available and safely used as a functional ingredient, most human studies have been conducted in other populations, primarily healthy older adults in Japan and Western countries. As genetic background, diet, and lifestyle can influence the response to nutritional interventions, Malaysia-specific clinical studies are required to confirm the efficacy of PQQ and optimise its intake levels in local populations, especially among older adults with CF. Despite encouraging evidence, current research remains limited, especially in individuals with clinically defined CF. Most existing trials have focused on healthy older adults or those with subjective cognitive complaints rather than those diagnosed with CF. Therefore, future research should prioritise well-designed randomized controlled trials on the efficacy of PQQ across populations stratified by frailty status, cognitive function, and nutritional adequacy. Such studies are essential for clarifying the therapeutic potential of PQQ in maintaining cognitive health and preventing or reversing CF.
Second, although existing evidence supports the safety and efficacy of approximately 20 mg/day of PQQ, dose optimization and long-term safety under different dietary and cultural conditions require further clarification. Comparative studies with other bioactive compounds, such as polyphenols, omega-3 fatty acids, and probiotics, could also help delineate the contribution of PQQ to cognitive resilience in diverse populations.
Third, for practical implementation, challenges related to awareness, regulations, and accessibility need to be overcome. Public knowledge of PQQ remains limited. Although PQQ is available as a dietary supplement, its incorporation into functional foods in Malaysia is still emerging. Regulatory approval should aim to establish clear safety standards, labelling guidelines, and quality control measures to support broader applications.
Future research should focus on biomarker-driven clinical studies in Malaysian cohorts to evaluate mitochondrial function, oxidative stress, and inflammatory markers, thereby strengthening mechanistic evidence. Additionally, population-specific assessments of dietary patterns, lifestyles, and cultural preferences are critical for guiding the development of effective and acceptable functional products. Collaboration between academia, industry, and regulatory agencies is essential for translating scientific findings into practical applications that promote cognitive health and healthy aging in Malaysia.

5. Conclusions

CF poses an urgent public health challenge in Malaysia, where demographic aging is accelerating. Nutritional strategies are central to addressing this issue, and PQQ exhibits great promise owing to its role primarily in mitochondrial biogenesis and antioxidant defence. Preclinical studies have consistently demonstrated that PQQ enhances neuronal survival, memory, and resilience against oxidative stress, and early clinical trials have suggested its benefits for cognition, sleep quality, and overall vitality.
As a naturally occurring compound with a favourable safety profile, PQQ holds strong potential for integration into functional foods and dietary supplements tailored to aging population of Malaysia. However, to realise this translational potential, further research is needed to validate its effects in populations with CF, optimize dosage, and ensure its regulatory and cultural feasibility. By advancing knowledge and bridging science with practice, PQQ could become a cornerstone of nutrition-based strategies to support cognitive resilience and healthy aging in Malaysia.

Acknowledgments

The authors would like to thank all their colleagues for their valuable discussions and technical assistance. we would also like to thank editage (www.editage.jp) for english language editing.

Conflicts of Interest

All authors are salaried employees of the mitsubishi gas chemical company, Inc.

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Table 1. Summary of studies related to cognitive function in middle-aged to elderly populations.
Table 1. Summary of studies related to cognitive function in middle-aged to elderly populations.
Study group PQQ dose Overall outcome Reference
Male Wistar rats (vitamin E-deficient model), oxidative stress-induced cognitive deficit (hyperoxia) 20 mg/kg diet Improved learning ability and memory performance; prevented cognitive deficits caused by oxidative stress; exhibited protective effects even under vitamin E deficiency; synergistic protection with Coenzyme Q10 (CoQ10) observed under hyperoxia. (Ohwada et al., 2008)
64 healthy Japanese volunteers (mean age 72.1 ±3.8 years old) 21.5 mg/day Significant improvements in composite memory, verbal memory, reaction time, complex attention, cognitive flexibility, executive function, and motor speed compared to placebo; improved Digital Everyday Cognition Test and Mini Mental State Examination-Japanese version scores; no adverse events. (Shiojima et al., 2022)
64 healthy Japanese volunteers (mean age 41.5 ± 13.7 years old) 20 mg/day Significant improvements in composite memory and verbal memory after 12 weeks; no adverse events reported. (Tamakoshi et al., 2023)
40 healthy Japanese adults (14 men, 26 women, 50–71 years old) 20 mg/day Significant improvement in language task scores of the Montreal Cognitive Assessment test (p < 0.05).
 (Yamada et al., 2020)
Healthy older adults (45–65 years old) 20 mg/day + CoQ10 (300 mg/day) Significant improvement in attention, information identification, and processing ability. (Nakano et al., 2009)
Healthy older adults (50–70 years) 20 mg/day + CoQ10 (300 mg/day) Significant improvement in immediate memory compared to the placebo group. (Koikeda et al., 2011)
41 healthy older adults (50–70 years) 20 mg/day Significant improvement in attention and working memory. (Itoh et al., 2016)
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