Cognitive Function | UGT2A1 (rs10518065)

The UGT2A1 rs10518065 Variant and Oxidative Stress: What Your Genotype May Mean for Brain Health

Oxidative stress is a normal part of life. Your body constantly produces reactive oxygen species (often called “free radicals”) as a byproduct of metabolism, immune activity, and everyday exposures. When free radicals outpace your body’s defenses, they can damage cells, trigger inflammation, and affect DNA. Because the brain uses a lot of oxygen and relies on delicate cell membranes and signaling networks, it is especially sensitive to oxidative damage over time.

The UGT2A1 gene has been linked to pathways that support glutathione, one of the body’s most important antioxidant systems. Glutathione helps neutralize reactive molecules before they cause harm. Research has associated variation in UGT2A1 (often studied at rs10518065) with differences in overall cognitive performance, suggesting that some versions of this genetic variant may be tied to reduced antioxidant protection and a higher vulnerability to oxidative stress. For many people, this shows up as subtle, gradual effects on memory, processing speed, mental clarity, and resilience during high-stress or low-sleep periods.

How UGT2A1 Connects to Glutathione and Cognitive Performance

UGT2A1 is involved in the body’s defense against oxidative stress. In the context of brain health, the key idea is antioxidant capacity: how well your body can “buffer” oxidative load so that neurons and support cells can do their jobs efficiently. Glutathione is central to this. When glutathione-related defenses are less robust, the brain may be more prone to oxidative-stress–related impacts on cognition, especially when lifestyle factors increase total oxidative burden.

Genetics are not destiny, but they can help you prioritize. If your UGT2A1 rs10518065 genotype suggests reduced antioxidant protection (especially if you carry one or two G alleles), the most useful strategy is to lower your day-to-day oxidative load while consistently supplying the raw materials and lifestyle signals your body uses to maintain glutathione balance.

Practical Steps for Everyone

Regardless of genotype, oxidative stress is heavily influenced by lifestyle and environment. These foundational habits help support antioxidant defenses and protect cognitive performance over time.

• Diet foundation: Follow a Mediterranean-style, whole-food eating pattern built around colorful plants, extra-virgin olive oil, nuts/seeds, legumes, and high-quality proteins. Aim for 5–9 servings of fruits and vegetables daily, with emphasis on deep-colored options and cruciferous vegetables.
• Fiber and gut support: Target 25–40 g/day of fiber from beans, oats, chia/flax, vegetables, and berries to support inflammatory balance. If tolerated, include fermented foods (such as yogurt/kefir, kimchi, or sauerkraut) a few times per week.
• Sleep consistency: Prioritize a consistent sleep window and protect the first half of the night when deep sleep is highest. Use practical levers like morning sunlight, dim lights at night, and stopping caffeine earlier in the day.
• Exercise balance: Aim for 150–300 minutes/week of moderate cardio plus 2–3 strength sessions/week, with at least one true recovery day. Regular activity supports mitochondrial efficiency and upregulates your body’s internal antioxidant defenses over time.
• Reduce top exposures: Do not smoke or vape and minimize secondhand smoke. Treat heavy alcohol use as a major oxidative-stress driver. Address chronic inflammation sources (including oral health and gum inflammation).
• Track key health metrics: Keep an eye on blood pressure, glucose/A1c, lipids, and other routine health measures, because cardiometabolic strain can increase brain oxidative stress over time.

Diet Recommendations (UGT2A1 rs10518065: Oxidative Stress and Glutathione Support)

If you carry one or two G alleles (GA or GG) at UGT2A1 rs10518065, your priority is to lower total oxidative load while consistently supplying the raw materials your body uses to maintain glutathione. Start with a “glutathione-friendly” eating pattern most days: a Mediterranean-style, whole-food diet built around colorful plants, extra-virgin olive oil, nuts/seeds, legumes, and high-quality proteins. Aim for 5–9 servings of fruits and vegetables daily, with extra emphasis on deep-colored options such as berries, cherries, pomegranate, leafy greens, beets, and purple cabbage, because they are dense in plant compounds that help buffer oxidative stress.

Make cruciferous vegetables a daily anchor (broccoli, Brussels sprouts, kale, arugula, cabbage), since they support antioxidant-response signaling and provide sulfur-containing compounds often used in glutathione-related pathways. Add allium foods (garlic, onions, leeks) frequently for additional sulfur support. For protein, include cysteine-rich and selenium/zinc-supportive foods several times per week - examples include eggs, poultry, fish, yogurt/kefir (if tolerated), beans/lentils, pumpkin seeds, and Brazil nuts. If you eat seafood, prioritize omega-3-rich fish (salmon, sardines, trout) 2–3 times per week to support neuroinflammation balance, which often travels with oxidative stress.

To actively reduce oxidative burden, be strategic with the “big drivers.” Keep added sugar and ultra-processed foods low, since frequent glucose spikes increase oxidative stress. Avoid repeatedly heating oils at high temperatures, and choose gentler cooking methods (steam, bake, sauté, slow-cook) more often than deep-frying or charring. If you drink alcohol, treat it like an oxidative-stress “tax”: for GG carriers, consider limiting to rare occasions and keeping intake modest; for GA carriers, be mindful of cumulative weekly intake; and for AA carriers, moderation still matters because lifestyle can override genetic advantage.

If you have the AA genotype (0 effect alleles), you may have more resilient glutathione-linked protection in the research tied to this UGT2A1 variant, but you still benefit from the same foundation - think of it as maintaining your “antioxidant capacity” rather than needing to compensate for vulnerability. For AA carriers, the win is consistency: a steady antioxidant-rich diet plus good sleep and exercise habits tends to preserve cognitive performance over time.

Supplement Recommendations (Targeted Support for Glutathione and Oxidative Balance)

For GG and GA carriers, supplements can be a practical way to support glutathione status and overall antioxidant balance - especially during high-demand seasons like poor sleep stretches, heavy training blocks, high stress, travel, or illness recovery. The most direct and commonly used option is N-acetylcysteine (NAC), which provides cysteine, a key building block for glutathione. Many people do well starting low and adjusting based on tolerance, because NAC can cause mild gastrointestinal upset in some individuals. Another supportive approach is glycine to help ensure all glutathione components are available.

Some individuals prefer more direct glutathione options, such as liposomal glutathione or S-acetyl glutathione. Responses vary, so a practical strategy is to trial one approach for 6–8 weeks and track how you feel (mental clarity, stress resilience, recovery, and “brain fog” tendencies), ideally alongside strong lifestyle habits.

Because antioxidant systems rely on micronutrients as enzyme cofactors, consider the “supporting cast” if your diet is inconsistent: selenium (often supported with Brazil nuts a few days per week), zinc, and magnesium are common gaps that can indirectly affect oxidative balance and neurologic function. Omega-3 fish oil (EPA/DHA) can be a strong add-on if you do not eat fatty fish regularly, since it supports membrane health and inflammatory balance - two factors that influence cognitive performance under oxidative stress. If your goal is brain-health longevity, creatine monohydrate (especially useful for people who eat little red meat) may support cellular energy buffering, which can matter when oxidative stress strains mitochondrial function.

A smart way to personalize supplementation for UGT2A1 rs10518065 is to “ladder” support based on genetic risk and lifestyle load: GG carriers often benefit from a more consistent glutathione-support plan (for example, NAC or a glutathione form plus omega-3s), GA carriers may reserve heavier support for higher-stress periods while maintaining strong diet habits, and AA carriers can focus on basics (omega-3s if needed, magnesium if low, and food-first antioxidant variety) unless life circumstances raise oxidative demand.

Important safety note: Supplements can interact with medications and medical conditions. If you take blood thinners, blood pressure medications, diabetes medications, nitroglycerin, chemotherapy agents, or psychiatric medications, or if you’re pregnant or breastfeeding, talk with a clinician before starting NAC, high-dose antioxidants, or concentrated herbal products. Also avoid stacking many antioxidant supplements at high doses - more is not always better, and excessively blunting oxidative signaling can interfere with beneficial exercise adaptations for some people.

Lifestyle Recommendations (Reduce Oxidative Load, Protect Cognition, Build Resilience)

For UGT2A1 rs10518065 - especially GG or GA - lifestyle is where you often get the biggest return because oxidative stress is frequently driven more by sleep debt, chronic stress, inactivity, smoking, heavy alcohol use, and inflammation than by any single nutrient. Start with sleep as your “antioxidant amplifier.” Aim for a consistent sleep window and protect the first half of the night. Practical levers include morning sunlight within an hour of waking, dimming lights at night, keeping the bedroom cool and dark, and stopping caffeine earlier (many people do best cutting caffeine 8–10 hours before bedtime; sensitive individuals may need more). If you frequently wake unrefreshed, treat sleep as a performance project and consider screening for sleep apnea risk, stabilizing bedtime and wake time, and limiting alcohol since it can fragment sleep and raise oxidative stress.

Exercise is another high-impact lever because it improves mitochondrial efficiency and upregulates endogenous antioxidant defenses over time. The key is dosing: too little activity reduces resilience, but extreme overtraining without recovery can increase oxidative load. A balanced target for most people is 150–300 minutes/week of moderate cardio plus 2–3 strength sessions/week, with at least one recovery day. If you are a GG carrier, prioritize recovery like it is part of the workout: adequate protein, hydration, and sleep, and avoid stacking multiple high-intensity days when life stress is already high. Add low-effort “movement snacks” during the day (like a 5–10 minute walk after meals) to support blood sugar control and lower inflammatory signaling.

Stress management matters because chronic stress activation can increase oxidative and inflammatory pathways. Keep it simple and consistent: a daily 10-minute practice (breathwork with longer exhales, mindfulness, prayer, or journaling) plus “stress hygiene” (boundaries, fewer late-night screens, and planned downtime). Cognitive stimulation is also protective: regular learning, complex hobbies, and social connection help maintain processing speed and executive function, especially when oxidative stress might otherwise chip away at resilience.

Finally, avoid the highest oxidative exposures: do not smoke or vape, minimize secondhand smoke, address chronic gum inflammation, and keep up with routine health metrics because cardiometabolic strain increases brain oxidative stress over time. If you are AA at rs10518065, you are not “immune” - you are simply starting with a more favorable baseline, so these same habits help preserve long-term cognition and brain health.

Genetic Interpretations for rs10518065 (UGT2A1)

When to Talk to Your Healthcare Provider

If you have concerns about oxidative stress, brain fog, or cognitive changes over time, consider discussing them with your healthcare provider - especially if symptoms are persistent or worsening. A clinician can help interpret your genetic result in the context of your overall health, lifestyle, and any medications you take, and can guide safe use of supplements and targeted changes.

PlexusDx does not provide medical advice. This information is educational and intended to help you understand how UGT2A1 rs10518065 may relate to oxidative stress, glutathione support, and cognitive performance. Always consult your healthcare provider before making changes to your diet, supplement routine, or exercise plan, or if you have concerns about your health.

If this genetic variant is present in your PlexusDx results, the following tests and reports are commonly used to explore it further:

🧬 Genetic Tests:

• Functional Health Genetic Test

🧪 Blood Tests:

• Women's Health and Wellness Blood Test
• Men's Health and Wellness Blood Test

📄 Genetic Report:

• Cognition and Brain Health Genetic Report