Cognitive Function | TUSC3 (rs240657)

TUSC3 rs240657 and Magnesium: What Your Genotype May Mean for Cognition

If you have results from the PlexusDx Cognition and Brain Health Genetic Report and you see TUSC3 rs240657, you are looking at a gene pathway tied to how your body handles magnesium - a mineral that helps brain cells communicate efficiently. Magnesium supports healthy nerve signaling, synaptic function, and the “electrical readiness” of neurons. When magnesium availability is lower, neural signaling may be less efficient, and learning, memory, and overall cognitive performance can feel more sensitive to stress, sleep disruption, or low mineral intake.

TUSC3 has been linked to cognitive performance because it may influence magnesium absorption or transport and, in turn, overall cellular magnesium levels. Rare loss-of-function mutations in TUSC3 can cause significant intellectual impairment. More common variants, like rs240657, have also been associated with differences in cognitive ability in otherwise healthy people. In practical terms, this makes TUSC3 rs240657 a “nutrient-dependent” pathway: supportive strategies often focus on maintaining steady magnesium intake through diet and, when appropriate, supplementation to support optimal brain function.

Why Magnesium Matters for Brain Signaling, Learning, and Memory

Magnesium helps neurons communicate effectively and supports learning, memory, and overall brain signaling. When cellular magnesium availability is lower, cognitive performance may be more vulnerable to everyday strainors like short sleep, chronic stress, irregular meals, and dehydration. Some people notice this as brain fog, slower processing, reduced focus, or feeling mentally “tapped out” more quickly when routines get off track.

The encouraging part is that magnesium is a foundational nutrition lever you can influence. Because the pathway is nutrient-dependent, it can be helpful to treat magnesium as a consistent habit - not a once-in-a-while supplement - especially if your genetics suggest less efficient magnesium handling.

Practical Steps for Everyone (No Matter Your Genotype)

Regardless of which rs240657 genotype you have, many people do best when they combine steady magnesium intake with “brain-forward” basics that support cognitive resilience day to day. These include consistent sleep timing, regular movement, stable blood sugar, hydration, and a whole foods eating pattern that regularly includes magnesium-rich options. Even with a favorable genotype, magnesium status still depends heavily on diet and lifestyle, so consistency matters.

• Build magnesium into your daily routine rather than relying on occasional “catch-up” days.
• Pair magnesium-rich foods with adequate protein (to support neurotransmitter building blocks), omega-3 fats, and colorful polyphenol foods (to support neuronal membranes and neuroinflammation balance).
• Support sleep and stress routines so your brain can use nutrients effectively and maintain steady performance.

Diet Recommendations for TUSC3 rs240657 (Magnesium & Cognition)

If you carry one (GA) or two (GG) copies of the G effect allele, treat magnesium as a “foundational” brain-health nutrient you want consistently present in your diet. Aim to build magnesium-rich foods into at least 2–3 eating occasions per day so your intake is steady. This approach supports nerve signaling, synaptic function, and the day-to-day “readiness” of neurons for learning, recall, and clear thinking.

Practical magnesium-rich anchors include leafy greens (spinach, Swiss chard, kale), nuts and seeds (pumpkin seeds, chia, hemp, almonds, cashews), legumes (black beans, lentils, edamame), whole grains (oats, quinoa, brown rice), avocado, dark chocolate/cocoa, and seafood (especially salmon, mackerel, sardines). A simple pattern that works for many people is a high-fiber breakfast (oats + chia/hemp + cacao), a legume-based lunch (lentil bowl or bean salad), and a leafy green side at dinner (sautéed spinach or a big salad), with pumpkin seeds as an easy add-on.

Because magnesium in plant foods can be bound by phytates (in some grains and legumes), you may absorb more if you use traditional preparation methods. Consider choosing sprouted or sourdough grains, soaking and rinsing beans and lentils, or relying more on cooked greens (which can be easier to consume in meaningful volume). This can be a simple way to get more benefit from the same food choices.

Also think about what can work against magnesium status. Frequent ultra-processed foods, very high added sugar intake, and heavy alcohol patterns can make it harder to maintain steady magnesium availability. If you’re caffeine-sensitive or prone to anxiety, keep caffeine earlier in the day and pair it with food. Some people notice fewer “wired/tired” dips when they stabilize blood sugar and mineral intake together.

If you have the AA genotype (0 effect alleles), you can still benefit from the same magnesium-forward eating pattern, but you may not need to be as aggressive. The goal remains consistency: adequate magnesium supports learning, memory, processing speed, and resilience to stress and sleep disruption.

Supplement Recommendations (Magnesium Strategy for rs240657)

For GG or GA carriers, supplementation can be a practical backstop - especially if you have signs of low intake or higher demand, such as muscle cramps or twitching, poor sleep quality, tension headaches, constipation, high stress load, heavy sweating, or a diet low in greens, legumes, and whole grains. A common, cautious approach is to start low and titrate: 100–200 mg of elemental magnesium in the evening for 1–2 weeks, then increase to 200–400 mg per day as tolerated. Many people prefer taking magnesium with dinner or 30–60 minutes before bed to support relaxation and sleep continuity.

Different forms can feel different for different goals. If constipation is the main issue, magnesium citrate is often effective, but it is more likely to loosen stools. For sleep, stress, and muscle tension support, magnesium glycinate (bisglycinate) is commonly chosen because it is usually gentler on the gut. Magnesium L-threonate is often marketed for cognition; evidence is still evolving, but some people try it for brain-focused goals. If you experiment with it, track outcomes like sleep quality, focus, recall, and anxiety for 4–8 weeks to decide whether it is worth continuing.

To make magnesium supplementation safer and more effective, be mindful of timing and interactions. Magnesium can bind certain medications and reduce absorption, so separate it by at least 4 hours from levothyroxine, and commonly 2–4 hours from tetracycline or fluoroquinolone antibiotics and bisphosphonates. If you also take iron or zinc, consider separating those as well to reduce competition for absorption.

Magnesium supplements may not be appropriate - or may require medical supervision - if you have kidney disease, significant heart rhythm conditions, or are on medications that affect electrolyte balance (certain diuretics, for example). If you’re unsure, this is a quick check-in with a clinician or pharmacist.

For AA carriers, supplementation is optional and should be based on diet reality and symptoms. If your diet already includes magnesium-rich foods daily and you sleep well, you may do fine without supplements. If you do supplement, staying at the lower end (for example, 100–200 mg per day) may be enough.

Lifestyle Recommendations (Protecting Brain Performance When Magnesium Handling Is Less Efficient)

If you’re GG or GA, your cognition may feel more sensitive to “magnesium-draining” conditions like chronic stress, short sleep, heavy sweating without repletion, dehydration, and inconsistent meals. The most impactful lifestyle move is often sleep consistency. Aim for a stable sleep and wake window, keep the room cool and dark, and reduce bright screens for the last hour before bed. Magnesium can support relaxation physiology, but it tends to work best when your schedule also supports circadian rhythm.

If your main complaint is brain fog, try tightening the basics for 2–3 weeks before adding a long list of nootropics. A simple baseline - regular sleep, magnesium-rich foods daily, hydration, and movement - makes it easier to tell what is actually helping. Many people are surprised by how much clearer they feel when they remove a few common “friction points” rather than chasing complicated stacks.

Stress management is especially relevant because stress hormones can shift mineral balance and increase perceived cognitive strain. Build a simple daily downshift that you’ll actually repeat: a 10-minute brisk walk after meals, slow exhale-focused breathing, a short evening stretch routine, or a brief mindfulness session. Regular aerobic exercise (even 20–30 minutes most days) is consistently linked with better executive function and memory, and it may help buffer the cognitive impact of poor sleep or stress. Strength training 2–3 times per week can also help by improving metabolic health - stable glucose and insulin signaling are strongly tied to clear thinking and sustained attention.

Finally, treat hydration and stimulants as real cognition levers. Dehydration can mimic low focus and slower processing speed, so aim for steady fluid intake, especially if you sweat a lot, and consider electrolyte support if you are active. Keep alcohol modest because it can impair sleep architecture and influence magnesium status. If you use caffeine, keep it earlier in the day and avoid using it to compensate for short sleep. That pattern tends to amplify anxiety, reduce sleep quality, and worsen the very cognitive symptoms people are trying to fix.

Genetic Interpretations for rs240657 (TUSC3)

When to Talk to Your Healthcare Provider

If you have concerns about cognition, persistent brain fog, sleep disruption, or symptoms that may reflect low magnesium intake (such as muscle cramps or twitching, tension headaches, or constipation), consider talking with your healthcare provider. They can help you decide whether magnesium supplementation is appropriate for you, discuss timing with medications, and interpret any relevant lab work in the context of your overall health.

PlexusDx does not provide medical advice. This information is educational and intended to help you understand how TUSC3 genetics and magnesium intake may relate to cognition and brain health. 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