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The TNFSF9 rs348373 Variant and Fluid Intelligence: What Your Genotype May Mean for Brain Inflammation Balance

Fluid intelligence is one of the brain’s core “thinking on your feet” skills. It includes problem-solving, reasoning, processing speed, and working memory. These abilities help you learn new concepts, adapt to unfamiliar situations, and juggle information in real time. Many factors shape fluid intelligence, including sleep quality, stress load, exercise habits, nutrition, and overall health. Genetics can also play a role by influencing biological pathways that support or strain brain function.

One gene that has been linked to differences in fluid intelligence is TNFSF9. TNFSF9 is best known for its role in immune signaling, especially in activating inflammatory responses when the body detects threats such as infection or tissue damage. Because inflammation can also occur in the brain, and TNFSF9-related signaling is expressed in brain cells such as neurons and astrocytes, variation in this pathway may influence cognitive performance over time.

How TNFSF9 May Affect Brain Function

Inflammation is a normal part of healthy immunity. It helps the body respond to threats and repair damage. The challenge is that when inflammatory signaling becomes too high or too persistent, it can create “background noise” for the brain. In the brain, higher or more persistent neuroinflammation may interfere with optimal brain signaling and plasticity. Plasticity is the brain’s ability to adapt, learn, and strengthen connections, which supports reasoning, processing speed, and working memory.

Research has linked TNFSF9 genetic variation with measures of fluid intelligence. The exact mechanism is still being studied, but a leading explanation is that a higher inflammatory tendency in the brain can make it harder for neural circuits to operate at peak efficiency. This does not mean genetics are destiny. It means you may have a tendency that can be helped or worsened by lifestyle patterns.

Why Brain Inflammation Balance Matters for Fluid Intelligence

Fluid intelligence depends on fast, coordinated communication across brain networks. When inflammatory signaling rises, it may affect how smoothly neurons send and receive messages. Over time, this can influence:

  • Processing speed: how quickly you take in information and respond
  • Working memory: how well you hold and manipulate information in your mind
  • Reasoning: how effectively you connect ideas and solve problems
  • Mental stamina: how long you can stay sharp before you feel foggy or drained

Because TNFSF9 is part of immune activation, habits that support a calmer, well-regulated inflammatory response may help protect cognitive performance over time, especially for people who carry the effect allele at rs348373.

Practical Steps for Everyone

Regardless of genotype, lifestyle has a major impact on inflammation balance and day-to-day brain performance. These strategies support the brain’s ability to stay clear, efficient, and resilient.

  • Sleep: Aim for a consistent schedule and 7 to 9 hours when possible. Poor sleep can raise inflammatory signaling and reduce working memory and processing speed.
  • Exercise: Combine aerobic activity with resistance training. Regular movement is a powerful lever for lowering chronic inflammatory load and supporting brain health.
  • Diet: Prioritize fiber-rich, whole-food meals that support gut microbes. The gut and immune system are tightly connected, and gut balance can influence inflammation that affects the brain.
  • Stress management: Chronic stress can push inflammatory pathways upward. Build a daily downshift practice you can stick with, such as paced breathing, mindfulness, yoga, or walking outdoors.
  • Alcohol: Many people notice clearer thinking and better sleep when alcohol becomes infrequent. If you drink, consider scaling it down or reserving it for rare occasions.
  • Ultra-processed foods: Frequent intake can amplify inflammatory signaling in many people. Use a simple rule of thumb: most packaged foods should have a short, recognizable ingredient list.

Diet Strategies for TNFSF9 rs348373 and Inflammation Balance

Diet is one of the most consistent ways to influence inflammatory tone. If your TNFSF9 result includes the effect allele, the goal is not perfection. The goal is a weekly pattern that lowers chronic inflammatory load so brain signaling and plasticity can support strong reasoning, processing speed, and working memory.

A practical approach is a Mediterranean-style template built around plants, fiber, and healthy fats. Emphasize:

  • Vegetables: at least 2 to 3 cups per day
  • Fruit: 1 to 2 servings per day
  • Beans and lentils: 3 to 5 times per week
  • Nuts and seeds: a small handful daily
  • Extra-virgin olive oil: as the main fat
  • Fish: especially salmon, sardines, or trout 2 to 3 times per week for omega-3s

Fiber deserves special attention. Fiber feeds gut microbes that make short-chain fatty acids (like butyrate) that help regulate inflammatory tone. A helpful target is about 25 to 40 grams of fiber per day by combining legumes, oats, chia or flax, berries, and cruciferous vegetables.

Also consider blood sugar stability. Big blood sugar spikes can amplify inflammatory signaling. Pair carbohydrates with protein and fat, choose minimally processed starches (such as oats, quinoa, or sweet potato), and limit sugary drinks and “dessert grazing.”

Supplement Options That May Support Inflammation and Cognition

Supplements can be useful “add-ons,” especially if diet, sleep, and exercise are already moving in the right direction. They are not a replacement for lifestyle. If you use supplements, track real-world outcomes over a consistent trial period, such as less brain fog, steadier focus, or improved next-day clarity.

  • Omega-3 fish oil (EPA/DHA): A practical first choice if you do not eat fatty fish several times per week. Often used to support inflammatory tone and overall brain health.
  • Curcumin: A concentrated turmeric extract, ideally formulated for absorption. Commonly used to support inflammatory pathways. Many people pair it with meals and monitor how they feel over 4 to 8 weeks.
  • Magnesium: Often glycinate or threonate forms for better tolerance. Can support relaxation, sleep quality, and neuronal function, especially if stress or sleep disruption is part of your cognitive picture.
  • Vitamin D: If low on labs, correcting it can support immune regulation. Rather than guessing, base dosing on a blood test.
  • Fiber supplements: If fiber intake is hard to hit consistently, psyllium or partially hydrolyzed guar gum can help close the gap and support gut-immune balance.

Always check supplement-medication interactions with a clinician, especially if you use blood thinners, diabetes medications, blood pressure medications, or antidepressants.

Genetic Interpretations for rs348373 (TNFSF9)

2 effect alleles: TT

You have the TT genotype at rs348373, which means you carry two copies of the effect (“T”) allele. This variation is associated with relatively poorer performance on tests of fluid intelligence compared with carriers of the more common “C” allele. TNFSF9 helps activate immune signaling pathways that drive inflammation, and this signaling is also active in brain cells such as neurons and astrocytes. Higher or more persistent neuroinflammation may interfere with optimal brain signaling and plasticity, which can influence reasoning, processing speed, and working memory over time.

Recommendations

  • Use an everyday anti-inflammatory eating pattern built around a Mediterranean-style template: vegetables, fruit, beans and lentils, nuts and seeds, olive oil, and fish 2 to 3 times per week.
  • Prioritize fiber to support the gut-immune-brain connection, aiming for about 25 to 40 grams per day when possible.
  • Reduce ultra-processed foods by choosing packaged foods with short, recognizable ingredient lists and keeping fast food and fried snacks as occasional rather than daily.
  • Keep blood sugar swings modest by pairing carbohydrates with protein and fat and limiting sugary drinks and frequent desserts.
  • Make sleep a cornerstone: consistent schedule, morning light exposure, and a wind-down routine that reduces late-night screens and heavy meals.
  • Exercise as an anti-inflammatory lever: aim for about 150 minutes per week of aerobic training plus 2 to 3 days per week of resistance training. Movement after meals can help regulate inflammation and blood sugar.
  • Consider add-ons if needed: omega-3s if fish intake is low, curcumin as a polyphenol option, magnesium if sleep or stress is an issue, vitamin D based on labs, and fiber support if diet falls short.
  • If brain fog or low cognitive stamina is persistent, consider discussing basic labs with a clinician, such as iron and ferritin, B12, vitamin D, thyroid markers, HbA1c, and an inflammation marker like hs-CRP.
1 effect allele: TC

You have the TC genotype at rs348373, which means you carry one copy of the effect (“T”) allele. This variation is associated with relatively lower fluid intelligence performance on average compared with people who carry two “C” alleles, though individual outcomes vary widely. TNFSF9 is involved in activating immune and inflammatory pathways, and because these signals are also present in the brain, a higher inflammatory tendency may interfere with optimal neural signaling and plasticity that support reasoning, processing speed, and working memory.

Recommendations

  • Keep the same anti-inflammatory foundations, but focus on consistency more than perfection.
  • Use “daily anchors” that help keep inflammation in check: a high-fiber breakfast (oats with chia and berries), a big salad or veggie-heavy bowl most days, and omega-3 rich meals a few times per week.
  • Pay attention to personal triggers that reliably worsen brain fog, often ultra-processed snacks, heavy refined carbs, or frequent alcohol. Treat them as “sometimes foods” and build replacements you can stick with.
  • Support recovery during stressful periods with a 2 to 4 week “tighten the basics” reset: earlier bedtime, more outdoor walking, higher-fiber meals, and less alcohol.
  • Consider a streamlined supplement approach if needed: omega-3s if fish intake is low, magnesium if sleep or stress is an issue, and fiber support if your diet often falls short.
0 effect alleles: CC

You have the CC genotype at rs348373, which means you carry two copies of the non-effect (“C”) allele. This variant is generally associated with better performance on tests of fluid intelligence compared with carriers of the minor “T” allele. TNFSF9 helps regulate immune signaling that can trigger inflammation, and because this pathway is also active in brain cells, maintaining balanced inflammatory activity may support efficient brain signaling over time.

Recommendations

  • Use a “maintenance” approach: plenty of plants, steady fiber intake, and regular fish or other omega-3 sources to support brain resilience.
  • Focus on long-term brain protection by maintaining good sleep, regular exercise, and a lifestyle that keeps inflammation low as you age.
  • Avoid drift over time, such as sliding sleep schedules, decreasing activity, or creeping ultra-processed food intake.
  • Keep your brain challenged with ongoing learning and stay socially engaged to support cognitive resilience.
  • Use supplements only if driven by diet gaps, labs, or symptoms rather than genetics alone.

Building Cognitive Strength Through Lifestyle Training

Fluid intelligence improves most when you combine brain challenge with good recovery. Consider “progressive challenge” activities that push you slightly beyond your comfort zone a few times per week. This can include learning a language, learning music, speed-reading drills, or timed problem-solving. Pairing learning with regular movement often helps people feel more focused and improves how well new skills stick.

Important Note

This information is educational and not medical advice. Genetics influence tendencies, not destiny. Your sleep, diet quality, activity, stress load, and overall health have a major impact on real-world cognitive outcomes. If you have ongoing brain fog, low mood, or major changes in attention or memory, consider discussing symptoms and appropriate testing with a qualified healthcare professional.

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

🧬 Genetic Tests:

🧪 Blood Tests:

📄 Genetic Report: