Neuroinflammation is a chronic inflammatory response in the brain, often triggered by factors like infection, brain injury, toxic metabolites, or autoimmune processes. It involves the activation of specialized immune cells in the brain, called microglia, which release pro-inflammatory molecules. In the last post, we saw how ME/CFS and fibromyalgia are both characterized by chronic inflammation. Several studies have demonstrated peripheral and neuroinflammation in both conditions. This chronic inflammation explains many of the symptoms of these conditions: pain, fatigue, exercise intolerance, and immune abnormalities.

The Role of Oxidative Stress in Chronic Inflammation

Oxidative stress is a significant driver of neuroinflammation. It results in excessive production of reactive oxygen species (ROS), or free radicals, which damage cell membranes and tissues. Chronic oxidative stress stimulates inflammatory pathways, creating a vicious cycle. This involves major players like TNF, NFkB, and Nrf2. Understanding and targeting these pathways is key to reducing neuroinflammation.

It is still unknown why chronic oxidative stress and inflammation persist in some individuals and not in others. In the meantime, some strategies can be used to combat chronic inflammation. Many, many treatments are purported to reduce inflammation, but one must consider the major players: TNF, NFkB, and Nrf2. While other anti-inflammatory measures, like diet, may be useful, treatments that affect these 3 elements will be most effective.

Why Polyphenols Are Key to Combating Neuroinflammation

Polyphenols can be divided into various groups. The largest of which are flavonoids. Common flavonoids include quercetin, found in onions, leeks, and broccoli, and anthocyanidins, found in red wine and berries. Also common are the catechins, found in green tea, red wine, and chocolate. Mentioned earlier on the blog is the polyphenol sulforaphane, a sulfur-heavy isothiocyanate. Another polyphenol, considered a non-flavonoid, is the popular compound resveratrol. Curcumin is also a popular polyphenol belonging to the group curcuminoids. Let’s look at some of the most extensively studied supplements in more detail.

Supplements for Reducing Neuroinflammation

1. Curcumin: A Natural Anti-Inflammatory Powerhouse

Curcumin, derived from turmeric, reduces systemic inflammation by lowering cytokines like IL-6 and TNF-α. Studies show its potential to enhance gut permeability and block T cell activation, reducing inflammation via the gut-brain axis.

Highlights:

• Reduces IL-6 and TNF-α.

• Enhances gut-brain axis function.

Read more specifics about curcumin here.

2. Quercetin: Fighting Oxidative Stress and Inflammation

Quercetin is a flavonoid found in onions, leeks, and broccoli. It binds with iron to prevent oxidation, reduces nitric oxide production, and stabilizes mast cells to lower histamine-related inflammation. Quercetin also blocks inflammatory cascades triggered by NFkB.

Highlights:

• Reduces oxidative stress.

• Blocks NFkB pathways.

• Supports immune system balance.

3. Resveratrol: Supporting Brain Health and Gut Integrity

Resveratrol, a polyphenol found in red wine and berries, reduces neuroinflammation by modulating NFkB and increasing anti-inflammatory cytokines like IL-10. It also strengthens gut barrier function, preventing bacterial translocation and supporting the gut-brain axis. Resveratrol supplementation significantly decreased C-reactive protein (CRP), a marker of systemic inflammation and TNF among patients with metabolic syndrome and related disorders.

Highlights:

• Decreases systemic inflammation (CRP, TNF).

• Strengthens gut and brain barriers.

• Enhances protective enzymes like SOD and HO-1.

4. Sulforaphane: A Neuroprotective Nutritional Hero

Sulforaphane, abundant in broccoli sprouts, is a potent activator of Nrf2, a key anti-inflammatory regulator. It also reduces oxidative stress and supports liver detoxification.

Highlights:

• Activates phase II detoxification enzymes.

• Inhibits NFkB.

• Enhances brain cell protection.

  Much more on sulforaphane can be found in a prior post. Read it here.

5. Berberine: An Anti-Inflammatory Plant Alkaloid

Berberine, although not a polyphenol, has similar anti-inflammatory effects. It lowers inflammatory cytokines like TNF, IL-1b, and IL-6 while improving metabolic health and reducing oxidative stress. Berberine has been shown in randomized controlled trials to lower lipids and improve insulin resistance. In other clinical trials, berberine can reduce the risk of cardiovascular disease by reducing blood vessel inflammation.

Highlights:

• Reduces nitric oxide synthesis.

• Lowers systemic inflammation.

• Supports cardiovascular health.

The Bioavailability Challenge: How to Maximize Results

Polyphenols often have poor bioavailability. However, these tips can help enhance their absorption:

• Curcumin: Take with fats or black pepper extract (bioperine).

• Quercetin: Consume with fatty meals for better uptake.

• Resveratrol: Choose liposomal or nanoparticle formulations.

• Sulforaphane: Combine with mustard seeds or use glucoraphanin-rich supplements.

• Berberine: Opt for liposomal forms over pH-buffered versions.

Remember that most polyphenols are fat-soluble, so they are best consumed in the presence of fats. Look for polyphenol supplements that are formed in nanoparticles, liposomes, or micelles.

Berberine is poorly absorbed in the gut. Liposomal forms are not commonly available but are preferred over pH-buffered forms like berberine HCl.

Sulforaphane absorption can be enhanced with the addition of mustard seeds. Glucoraphanin, a sulforaphane precursor, or broccoli sprout supplements are common and found to be equally bioavailable.

Conjugated curcumins such as nanocurcumin or curcumin-like analogs are developed to increase their bioavailability and potential neuroprotective efficacy. Curcumin is fat soluble so its absorption is enhanced in the presence of fats. It’s also shown to be more bioavailable in the presence of bioperine, a compound found in black pepper.

Final Thoughts on Neuroinflammation and Supplements

Neuroinflammation is at the root of many chronic and neurodegenerative conditions. Supplements like curcumin, quercetin, resveratrol, sulforaphane, and berberine provide a natural, research-backed approach to reducing inflammation and oxidative stress. Enhancing bioavailability ensures maximum benefit, offering hope for those managing neuroinflammatory conditions.

References

Tarique Hussain, Bie Tan, Yulong Yin, Francois Blachier, Myrlene C. B. Tossou, and Najma Rahu, “Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 7432797, 9 pages, 2016.

Vauzour, D. (2012) Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxidative Medicine and Cell Longevity. 914273.

Frandsen JR & Narayanasamy P (2018) Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway. Redox Biol. 14:465-473.

Wang J. et al. (2018) Connection between Systemic Inflammation and Neuroinflammation Underlies Neuroprotective Mechanism of Several Phytochemicals in Neurodegenerative Diseases. Oxid Med Cell Longev. 2018:1972714.

Tabrizi R et al (2018) The effects of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Food Funct. 13;9(12):6116-6128. 

Lu DY, Tang CH, Chen YH, Wei IH. (2010) Berberine suppresses neuroinflammatory responses through AMP-activated protein kinase activation in BV-2 microglia. J Cell Biochem. 110(3):697-705.