Selenium supplementation decreases CRP and IL-6 and increases TNF-alpha: A systematic review and meta-analysis of randomized controlled trials

https://pubmed.ncbi.nlm.nih.gov/37257335/
This study examines the anti-inflammatory effects of selenium (Se) supplementation by measuring three key inflammatory biomarkers: TNF-α, IL-6, and CRP. Let’s break down what these markers indicate in the body and their relevance to the findings.

1️⃣ What Are TNF-α, IL-6, and CRP?
Marker
What It Measures
Role in Inflammation
Relevance in Disease
Tumor Necrosis Factor-alpha (TNF-α)
A pro-inflammatory cytokine found in plasma
Signals the immune system to activate inflammation, produced by macrophages
High levels are linked to autoimmune diseases, cancer, and sepsis
Interleukin-6 (IL-6)
A cytokine that regulates immune response
Can be pro- or anti-inflammatory, influences fever and acute-phase responses
Elevated in chronic diseases, infections, cardiovascular disease
C-reactive Protein (CRP)
A protein produced by the liver in response to inflammation
A general marker of systemic inflammation
High CRP is linked to heart disease, infections, and chronic inflammation

2️⃣ Key Findings from the Study
🔹 Selenium & CRP (General Inflammation Marker)
Oral selenium supplementation (PO) → No significant effect on CRP.
Intravenous (IV) selenium → Significantly reduced CRP levels, indicating a decrease in systemic inflammation.
🔹 Selenium & IL-6 (Cytokine That Drives Inflammation)
Oral selenium → No significant effect.
IV selenium → Significantly reduced IL-6 levels, showing an anti-inflammatory effect.
🔹 Selenium & TNF-α (Inflammation Trigger)
Mixed results:Some data suggested no effect.
However, a significant increase in TNF-α plasma concentration was observed with IV selenium.

3️⃣ What Does This Mean? (Bottom Line)
✔ IV selenium reduces systemic inflammation by lowering CRP and IL-6, which are major inflammatory markers. This suggests selenium may be useful in conditions with chronic inflammation (e.g., autoimmune diseases, infections, cardiovascular disease).
❌ However, IV selenium increased TNF-α, which could be a double-edged sword:
TNF-α triggers inflammation, which is needed for immune defense.
High TNF-α levels can worsen chronic inflammation in autoimmune diseases.
✔ Oral selenium had little to no effect, meaning dietary selenium alone may not be enough to significantly influence inflammatory markers.

4️⃣ Implications & Next Steps
Selenium supplementation may be useful in clinical settings, but IV administration is more effective than oral intake for reducing inflammation.
The increase in TNF-α warrants caution—selenium may not be suitable for autoimmune patients where TNF-α is already elevated.
More studies are needed to clarify optimal dosing, long-term effects, and individual variations in response to selenium.

How to get Selenium

4️⃣Now, let’s explore how to get selenium from food, when to consider supplements, and alternative anti-inflammatory strategies to help balance your immune response and reduce chronic inflammation.

🔹 Best Natural Sources of Selenium
Since oral selenium had limited impact on inflammation in the study, it’s best to focus on getting selenium from food first, as it is more bioavailable in whole foods.

🛒 Top Selenium-Rich Foods
Food
Selenium Content (mcg per serving)
Additional Benefits
Brazil nuts (1 nut)
~68–91 mcg
Highest natural source, rich in healthy fats & magnesium
Salmon (3.5 oz / 100g)
40–50 mcg
Omega-3s for brain & heart health
Sardines (3.5 oz / 100g)
45 mcg
Anti-inflammatory, rich in CoQ10 & vitamin D
Tuna (3.5 oz / 100g)
60–70 mcg
High in protein & heart-protective nutrients
Eggs (1 large egg)
15–20 mcg
Supports brain function & immunity
Sunflower seeds (1 oz / 28g)
22 mcg
Contains vitamin E & magnesium for heart health
Mushrooms (1 cup, cooked)
20 mcg
Supports immunity & gut health
Chicken or turkey (3.5 oz / 100g)
25 mcg
Lean protein, supports muscle repair
✔ Daily Selenium Goal: 55 mcg for adults (higher for pregnant/lactating women).
✔ Toxicity Risk: Avoid >400 mcg/day (excess selenium can cause toxicity, hair loss, and fatigue).

🔹 Best Strategy:
Eat 1–2 Brazil nuts daily for natural selenium balance.
Include selenium-rich seafood like salmon, sardines, and tuna at least twice per week.
Rotate selenium-rich plant sources (mushrooms, sunflower seeds).

🔹 When to Consider Selenium Supplements?
While food is the best source, supplements may help if you:
✔ Have low dietary intake (vegan/vegetarian or limited seafood consumption).
✔ Have thyroid issues (selenium supports thyroid hormone function).
✔ Have chronic inflammation or autoimmune conditions.

💊 Best Selenium Supplements:
Selenium (Selenomethionine) 100–200 mcg/day – Most bioavailable & safest.
Avoid high doses (>400 mcg/day) due to toxicity risk.
💡 Important: Since IV selenium lowered CRP & IL-6, while oral selenium had no effect, high-dose selenium pills may not provide the same benefits as IV therapy. Stick to food-first approaches whenever possible.

🔹 Alternative Anti-Inflammatory Strategies
If you’re looking for ways to reduce inflammation naturally, here are additional strategies beyond selenium:
🫐 1️⃣ Eat an Anti-Inflammatory Diet
Focus on:
✔ Omega-3-rich foods – Fatty fish, walnuts, flaxseeds.
✔ Antioxidant-rich foods – Berries, leafy greens, cruciferous vegetables.
✔ Herbs & spices – Turmeric (curcumin), ginger, garlic.
✔ Fermented foods – Kefir, yogurt, sauerkraut for gut health.
✔ Healthy fats – Extra virgin olive oil, avocados.
🔹 Foods to Avoid (Pro-Inflammatory Triggers)
❌ Refined sugar & processed foods – Increase CRP & IL-6.
❌ Excess omega-6 fats (vegetable oils, fried foods) – Fuel inflammation.
❌ Ultra-processed meats (hot dogs, bacon) – Linked to oxidative stress.

Effects of selenium supplementation on Polycystic Ovarian Syndrome: a systematic review and meta-analysis on randomized clinical trials

This meta-analysis showed that selenium supplementation has a positive effect on TAC (Total Antioxidant Capacity), and supplementation of selenium does not significantly improve the level of BMI, Weight, LDL, HDL, Triglycerides, Total Testosterone, HOMA-IR, NO, GSH, MDA and FPG.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9901141