Psoriasis is deeply connected to oxidative stress, a condition where harmful molecules called reactive oxygen species (ROS) overwhelm the body’s defenses. This imbalance leads to inflammation, skin cell damage, and worsened psoriasis symptoms. Key takeaways:
- What happens? Excess ROS damages proteins, lipids, and DNA, triggering immune responses that worsen psoriasis.
- Why it matters: Oxidative stress doesn’t just affect the skin - it’s linked to systemic issues like cardiovascular problems and mood disorders.
- How it’s measured: Markers like MDA (high in psoriasis) and reduced antioxidants like catalase reveal oxidative stress levels.
- Treatment options: Biologic drugs (e.g., anti-IL-17), antioxidants (e.g., sulforaphane), and dietary changes (e.g., Mediterranean diet) show promise in reducing oxidative stress and improving symptoms.
Understanding and managing oxidative stress can significantly improve outcomes for psoriasis patients.
Oxidative Stress Effects on Psoriasis
Immune System Response Changes
In psoriasis, the buildup of reactive oxygen species (ROS) sets off a chain reaction of inflammation, starting with the activation of dendritic cells. These cells play a central role by driving the IL-23/IL-17 axis. Specifically, dendritic cells release IL-23, which transforms naïve T cells into Th17 cells. This process ramps up the production of IL-17 isoforms - IL-17A increases 6.7-fold, IL-17C by 4.1-fold, and IL-17F by 8-fold - intensifying skin inflammation [12][42].
IL-17 is widely recognized as a critical cytokine in the progression of psoriasis [36]. These immune-driven changes don’t just fuel inflammation; they also undermine the structural integrity of skin cells, which we’ll explore further in the next section.
Skin Cell Growth and ROS
ROS wreak havoc on skin cells by damaging their essential components and setting off inflammatory responses. This is particularly concerning for skin tissue, as it naturally encounters higher ROS levels compared to other parts of the body [2].
Here’s how ROS impacts skin cells:
- Direct Damage: ROS oxidize fatty acids, producing harmful byproducts.
- Inflammatory Signals: They attract neutrophils to psoriatic lesions, worsening inflammation.
- Cell Death: ROS can overwhelm cells with calcium, leading to their death.
On top of this direct damage, ROS disrupt mitochondrial function, adding even more stress to already vulnerable psoriatic skin cells.
Cell Energy Problems in Psoriasis
Mitochondrial damage caused by ROS doesn’t just reduce cellular energy - it also amplifies inflammatory signals through mitochondrial ROS (mtROS) and disrupts keratinocyte function, which contributes to the formation of psoriatic plaques. Recent studies using mouse models have shown that weakened antioxidant defenses, such as reduced extracellular superoxide dismutase, intensify IL-23-driven inflammation by increasing the accumulation of immune cells [3][1][6].
Measuring Oxidative Stress in Psoriasis
High Stress Markers
Certain biomarkers provide clear evidence of heightened oxidative stress in psoriasis. One such marker is malondialdehyde (MDA), a byproduct of lipid peroxidation. Studies show that MDA levels are significantly higher in people with psoriasis compared to healthy individuals, and these levels often correlate with the severity and duration of the disease [5].
Another key marker, 8-hydroxy-2′-deoxyguanosine (8-OHdG), is elevated in both urine and blood samples of psoriatic patients. This rise in 8-OHdG is strongly linked to increased inflammation, with 83.3% of cases showing this pattern [6].
Low Antioxidant Markers
In psoriasis, several antioxidant markers show decreased activity, as summarized below:
| Antioxidant Marker | Location | Change in Psoriasis |
|---|---|---|
| Paraoxonase-1 | Tissues and serum | Significantly decreased |
| Sirtuin 1 | Skin fibroblasts | Reduced activity |
| Catalase (CAT) | Red blood cells | Decreased function |
| Glutathione peroxidase (GPx) | Blood plasma | Reduced levels |
These reduced antioxidant levels, particularly in catalase and glutathione peroxidase, contribute to elevated plasma MDA levels, which are a hallmark of plaque psoriasis flare-ups [7]. The imbalance in these markers highlights the distinction between localized oxidative stress in the skin and systemic stress affecting the entire body.
Local vs. Body-Wide Stress Levels
Research has revealed notable differences in oxidative stress markers when comparing localized skin lesions to systemic levels. For instance, a study by Yldirim et al. found no significant increase in serum MDA levels in psoriatic patients compared to healthy controls. However, skin biopsy samples from psoriatic lesions showed a marked rise in MDA levels [8].
"Although the involvement of oxidative stress in psoriasis remains undisputable, future research is needed to explore the utility of assessing circulating serum, plasma, urinary and/or skin biomarkers of oxidative stress and of studying polymorphisms in genes regulating the redox balance, as well as how can these findings be translated into the management of psoriasis, as well in understanding its pathogenesis and evolution." - Elena-Codruța Cozma et al. [8]
Another study by Emre et al. highlighted that tissue malondialdehyde concentrations were significantly higher in psoriatic lesions compared to unaffected skin (p = 0.003). Elevated oxidative stress markers in saliva and urine further confirm psoriasis as both a localized and systemic condition [4]. This duality underscores the complex role of oxidative stress in psoriasis, impacting both individual lesions and the body as a whole.
Treatment Methods for Oxidative Stress in Psoriasis
Biologic Drugs and Their Antioxidant Effects
Biologic therapies have shown effectiveness in reducing oxidative stress in psoriasis by targeting specific inflammatory pathways. For instance, TNF-α inhibitors like etanercept, infliximab, and adalimumab work by suppressing pro-inflammatory cytokines, which helps lower oxidative stress levels [9]. These therapies are opening doors to more targeted antioxidant treatments.
Among biologic options, IL-17 inhibitors have demonstrated particularly strong results. A 2019 study by Elnabawi et al. revealed that patients treated with anti-IL-17 therapy experienced a 12% reduction in non-calcified plaque burden after one year, outperforming IL-12/23 inhibitors and non-biologic treatments.
| Treatment Outcome | Anti-IL-17 | Conventional Treatment |
|---|---|---|
| Coronary Flow Reserve | 19% improvement | No significant change |
| Pulse Wave Velocity | 11% reduction | Minimal change |
| Oxidative Stress Markers | Significant reduction | No reduction or increase |
Emerging Antioxidant Treatments
To complement biologic therapies, new antioxidant-focused approaches are being developed to directly address oxidative stress. For example, ROS-responsive nanomedicine has shown promise in improving drug delivery specifically to psoriatic lesions.
One standout compound is sulforaphane (SFN), a natural antioxidant found in cruciferous vegetables. SFN activates the KEAP1-NRF2 pathway, boosting the body’s natural antioxidant defenses and reducing inflammation linked to psoriasis [10].
Dietary and Supplementary Interventions
In addition to advanced medical treatments, diet and supplements can provide extra antioxidant support. A clinical study demonstrated that psoriasis patients taking 20 g of Immunocal daily for three months experienced significant improvements in their PASI scores, attributed to increased glutathione production.
Certain natural compounds also play a role in managing oxidative stress and inflammation:
- Resveratrol, known for its cellular renewal benefits, supports the body’s antioxidant defenses. MASI Longevity Science’s Resveratrol supplement is designed to enhance these effects.
- Curcumin, found in turmeric, inhibits phosphorylase kinases, helping to reduce pro-inflammatory cytokines.
- Selenium + CoQ10 works by suppressing TNF-α activity, effectively lowering oxidative stress markers.
- Dimethyl fumarate, a cytokine modulator, has been linked to a 55% mean reduction in PASI scores.
| Compound | Primary Mechanism | Clinical Outcome |
|---|---|---|
| Curcumin | Inhibits phosphorylase kinases | Reduces pro-inflammatory cytokines |
| Selenium + CoQ10 | Suppresses TNF-α | Decreases oxidative stress markers |
| Dimethyl fumarate | Modulates cytokine production | 55% mean PASI reduction |
Lastly, adopting a Mediterranean diet can help manage psoriasis symptoms. This diet emphasizes antioxidant-rich foods like fruits, vegetables, and healthy fats while avoiding inflammatory triggers, offering a natural way to reduce oxidative stress and inflammation.
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Avoid 6 Mistakes: Psoriasis, Psoriatic Arthritis (SIBO, IMO, Candida, Leaky Gut, Histamine Food)
Conclusion: Research Findings and Treatment Options
Oxidative stress plays a key role in psoriasis, a condition affecting about 3–4% of the global population [10]. People with psoriasis often experience higher levels of reactive oxygen species (ROS) and reduced antioxidant defenses, which together drive inflammation and disrupt normal skin cell function.
One study focusing on generalized pustular psoriasis (GPP) demonstrated promising results. After just one month of treatment, d-ROM levels dropped from 423.2 ± 95.0 to 343.0 ± 82.1 U.Carr (p = 0.005), while GPPASI scores improved significantly, decreasing from 21.6 ± 2.7 to 12.8 ± 4.0 (p = 0.0006) [11]. These outcomes highlight the potential of antioxidant-based approaches in managing psoriasis.
Emerging therapies, such as sulforaphane (SFN), show promise by activating the NRF2 pathway, which helps counter oxidative damage and inflammation [10].
Effective management strategies combine:
- Targeted medical therapies
- A Mediterranean diet and regular exercise
- Antioxidant supplementation tailored to patient needs
New drug-delivery technologies are also expanding the range of available treatments [4]. By blending medical, dietary, and lifestyle approaches, ongoing research continues to advance the possibilities for managing psoriasis more effectively.
FAQs
What role does oxidative stress play in causing and worsening psoriasis symptoms?
Oxidative stress plays a major role in both triggering and worsening psoriasis symptoms. It leads to an overproduction of reactive oxygen species (ROS) - unstable molecules that can harm cells and fuel inflammation. This imbalance throws off the normal processes in skin cells, causing keratinocytes (the primary cells in the outer layer of the skin) to grow excessively while their natural cell death slows down. The result? Thickened skin and the formation of plaques that are hallmarks of psoriasis.
On top of that, oxidative stress activates inflammatory pathways, ramping up immune responses and making the condition even worse. Many people with psoriasis also have a weaker antioxidant defense system, leaving their skin more prone to ongoing inflammation and tissue damage. Addressing oxidative stress could be a key step in managing psoriasis symptoms and supporting healthier skin.
What are the best antioxidants for managing oxidative stress in psoriasis, and how do they help?
Some powerful antioxidants that can help manage oxidative stress in psoriasis include curcumin, sulforaphane, and vitamins C and E. These substances play a role in reducing oxidative damage while promoting healthier skin.
- Curcumin: Known for its anti-inflammatory properties, curcumin works to neutralize reactive oxygen species (ROS), which are harmful molecules that contribute to psoriasis progression.
- Sulforaphane: Found in cruciferous vegetables like broccoli and kale, sulforaphane enhances the body's natural antioxidant defenses. It does this by activating the KEAP1-NRF2 pathway, which helps reduce psoriasis symptoms.
- Vitamins C and E: These two vitamins form a powerful duo against oxidative stress. Together, they protect skin cells from damage and support overall skin health.
Adding these antioxidants to your diet or taking them as supplements might help reduce oxidative stress and ease psoriasis symptoms. However, it’s always a good idea to talk to a healthcare provider before making any changes to your routine.
Can changes in diet and exercise help reduce oxidative stress and improve psoriasis symptoms?
Making adjustments to your diet and exercise routine can have a meaningful impact on reducing oxidative stress and managing psoriasis symptoms. Studies suggest that an anti-inflammatory diet - packed with omega-3 fatty acids, antioxidants, and whole, unprocessed foods - can help reduce inflammation and oxidative stress, both of which are closely tied to psoriasis flare-ups. Steering clear of processed foods and opting for nutrient-rich choices can also promote better skin health.
Staying physically active is just as crucial. Regular exercise not only aids in maintaining a healthy weight but also helps lower oxidative stress and inflammation, which might lead to fewer psoriasis outbreaks. Plus, being active can boost overall well-being and may even help extend remission periods. By embracing these lifestyle changes, you can take a proactive step toward managing psoriasis and enhancing your quality of life.
