Fisetin and Quercetin are natural compounds found in common foods like strawberries, onions, and citrus fruits. They are widely studied for their antioxidant and anti-inflammatory properties. Both are generally safe as supplements, but understanding their safety profiles is crucial due to potential medication interactions and dosage concerns.
Key Takeaways:
- Fisetin: Found in strawberries; reduces senescent cells and improves cellular health. Safe even at high doses (20 mg/kg/day for 2 days).
- Quercetin: Found in onions and citrus fruits; supports inflammation control and histamine stabilization. Safe up to 2,000 mg/day short-term.
Safety Highlights:
- Fisetin Clinical Use: Safe for short-term high doses; tested in aging, surgery recovery, and cancer trials.
- Quercetin Clinical Use: GRAS status; well-tolerated in COPD and COVID-19 studies, with doses up to 1,000 mg/day for 12 weeks.
Quick Comparison:
| Compound | Natural Sources | Safe Dose Range | Key Benefits |
|---|---|---|---|
| Fisetin | Strawberries | ~20 mg/kg/day (short-term) | Reduces senescent cells, anti-aging |
| Quercetin | Onions, Citrus Fruits | Up to 2,000 mg/day | Anti-inflammatory, antihistamine |
Before combining these with medications, consult a healthcare provider to avoid interactions. Long-term safety data is promising but still evolving.
How These Compounds Work
Fisetin: Effects on Cells and Laboratory Findings
Fisetin works by reducing the burden of senescent cells, primarily through blocking anti-apoptotic pathways [1]. In lab experiments, it shows strong effects at a concentration of 5 μM, where it significantly lowers markers of senescence in murine embryonic fibroblasts (MEFs) [1]. In human aortic endothelial cells undergoing replicative senescence, fisetin has been observed to produce the following outcomes:
| Cellular Marker | Observed Effect |
|---|---|
| Cdkn2a Expression | 71% reduction |
| Mitochondrial ROS | 2.6-fold decrease |
| Endothelium-Dependent Dilation | 20% improvement |
Animal studies further highlight its potential. In aged mice, a dose of 100 mg/kg fisetin reduced senescent cells in white adipose tissue, affecting various cell types such as mesenchymal stem/progenitor cells, T lymphocytes, natural killer cells, and endothelial cells [1].
Quercetin: Antioxidant Properties and Research Insights
Quercetin complements fisetin by acting through distinct but synergistic cellular pathways. It targets PI3Kδ and BCL-2 family proteins, influencing cell survival mechanisms [1]. Lab studies have demonstrated quercetin's ability to impact several key cellular processes:
| Cellular Process | Observed Impact |
|---|---|
| Oxidative Stress | Decreases free radical damage |
| Cell Death Pathways | Regulates apoptosis and autophagy |
| Inflammation | Modulates inflammatory responses |
| Signaling Pathways | Affects PI3K/Akt, NF-κB, JAK/STAT pathways |
In animal models, quercetin has shown promise in managing hyperuricemia by reducing oxidative stress, regulating lipid metabolism, and influencing transporter proteins [4].
Together, fisetin and quercetin offer complementary benefits, with fisetin showing stronger activity in targeting senescent cells. These preclinical findings provide a foundation for exploring their safety and effectiveness in human clinical trials.
Human Trial Results
Fisetin Clinical Tests
Fisetin has shown a strong safety record in clinical studies. A common method used in these trials is the "hit and run" approach, where participants receive a high dose - about 20 mg per kilogram of body weight - for two consecutive days, followed by a 30-day break [5].
Major institutions are actively studying fisetin's potential benefits:
| Institution | Study Focus | Dosage Protocol | Key Findings |
|---|---|---|---|
| Mayo Clinic | SARS-CoV-2 Response | ~20 mg/kg/day | Investigating if fisetin can prevent oxygen status deterioration [5] |
| The Steadman Clinic | Surgical Recovery | 20 mg/kg for 2 days, repeated monthly | Examining its role in platelet-rich plasma (PRP) during post-surgery recovery [5] |
| St. Jude Children's Research Hospital | Cancer Survivor Health | 20 mg/kg on days 1, 2, 30, and 31 | Comparing fisetin alone with a Dasatinib-Quercetin combination [5] |
These studies consistently highlight fisetin's safety across various protocols. For example, a trial involving colon cancer patients found that a lower daily dose of 100 mg reduced inflammatory markers [5].
Similarly, clinical tests on quercetin further support its safety under different dosage regimens.
Quercetin Clinical Tests
Quercetin has also been confirmed as safe through numerous studies. For instance, a trial involving patients with chronic obstructive pulmonary disease (COPD) demonstrated that quercetin was well-tolerated at doses as high as 2,000 mg daily. Tests on lung function, blood profiles, and COPD symptoms showed no safety concerns [7].
At King Edward Medical University, a randomized trial (Dec 2020–Sep 2021) assessed quercetin's use in COVID-19 outpatients. Fifty participants were given quercetin supplements (500 mg Quercetin Phytosome®) three times per day during the first week and twice daily in the second week. The treatment was well-tolerated, with no adverse effects reported [8].
Key dosage insights from studies include:
- Lower doses (50–150 mg daily): Improve plasma quercetin levels without altering antioxidant status or metabolism [6].
- Doses up to 1,000 mg daily: Shown to be safe in studies lasting up to 12 weeks [9].
- Higher doses (>1,000 mg daily): May need additional monitoring, especially for extended use [9].
Quercetin has earned GRAS (Generally Recognized As Safe) status from the FDA as a dietary supplement, further validating its safety [8]. However, long-term safety data for doses of 1,000 mg or more beyond 12 weeks remain limited [9].
Safety Comparison
Side Effect Data
Fisetin and Quercetin come with different side effect profiles depending on dosage levels. Here's a quick comparison of the reported side effects:
| Side Effect Category | Fisetin | Quercetin |
|---|---|---|
| Common Mild Effects | Headaches, stomach discomfort, tingling sensations [10] | Headaches, upset stomach [2] |
| High-Dose Effects | Minor symptoms at doses above 1,000 mg daily [10] | Potential kidney damage at very high doses [2] |
| Safety Threshold | Oral LD50 >5,000 mg/kg (rats) [12] | Safe up to 1,000 mg daily for 12 weeks [11] |
| Usage Restrictions | Consult a healthcare provider if on blood thinners [13] | Not recommended during pregnancy or breastfeeding [2] |
Research shows that Fisetin, even when introduced later in life, demonstrates strong senotherapeutic benefits with minimal side effects [1]. Animal studies back up its safety, with an oral LD50 exceeding 5,000 mg/kg in rats [12]. However, it’s important to remain cautious about potential interactions with other medications.
Medicine Interactions
Understanding how Fisetin and Quercetin interact with other drugs is key to ensuring safe use, especially over the long term. Both compounds influence liver enzymes, which can affect how the body metabolizes medications.
For Fisetin, notable interactions include:
- Blood Thinners: May amplify the effects of Warfarin, raising the risk of bleeding [14].
- Diabetes Medications: Could impact blood sugar levels, requiring careful monitoring [13].
- Liver-Processed Drugs: May alter the speed at which the liver processes certain medications [14].
For Quercetin, interactions include:
- Antibiotics: May reduce the effectiveness of quinolone antibiotics [11].
- Immunosuppressants: Could heighten the effects of cyclosporine [11].
- Blood Pressure and Diabetes Medications: May enhance the effects of these drugs, potentially lowering blood pressure or blood sugar too much [11].
While both Fisetin and Quercetin influence liver enzyme activity, Quercetin has a broader range of potential interactions. This underscores the importance of consulting a healthcare provider before combining these supplements with other medications, particularly for individuals managing chronic conditions or taking multiple prescriptions.
sbb-itb-4f17e23
Quercetin: An Update on Evidence-Based Clinical Use
Long-term Safety and Rules
Expanding on short-term safety findings, long-term studies provide additional evidence supporting the ongoing effectiveness and safety of these compounds.
Long-term Study Results
Research highlights the long-term safety of fisetin and quercetin, building on earlier short-term data. For instance, quercetin has been shown to be safe at doses of up to 1,000 mg daily for a 12-week period [11]. Clinical trials involving dasatinib and quercetin (DQ) have also demonstrated a tolerable safety profile when used to address conditions related to cellular aging [16].
In animal studies, fisetin was found to extend both healthspan and lifespan [1]. Additionally, a pilot study exploring a combination treatment (DQF) suggested that fisetin might help reduce the effects of DQ on epigenetic aging [15]. These findings emphasize the importance of maintaining stringent quality standards to ensure the long-term safety of these supplements.
Quality Standards
Maintaining high-quality standards is critical for ensuring the safety and effectiveness of fisetin and quercetin supplements. The table below outlines the key parameters necessary for quality assurance:
| Quality Parameter | Requirements | Importance |
|---|---|---|
| Manufacturing Facility | FDA-registered, GMP-certified | Ensures consistent quality and compliance with safety protocols |
| Third-Party Testing | Independent lab verification | Confirms the product's purity and potency |
| Storage Conditions | Cool, dry environment | Preserves supplement stability over time |
| Identity Verification | Certificate of Analysis (COA) | Confirms the compound's identity and strength |
| Contaminant Screening | Tests for heavy metals, bacteria, and fungi | Ensures the product is free from harmful substances |
MASI Longevity Science adheres to strict quality protocols by producing its fisetin supplements in Germany using pharmaceutical-grade raw materials. Each batch undergoes independent testing in Swiss laboratories to verify its purity, safety, and effectiveness, ensuring consistent potency for long-term use.
Comparative research further supports fisetin’s strong safety profile [15].
Main Points
Here's a summary of the clinical data discussed earlier, highlighting the safety and effectiveness of these supplements.
Clinical research consistently supports the safety of both fisetin and quercetin. Studies show that fisetin remains safe even at higher doses, with trials often using a "hit-and-run" approach - 20 mg/kg/day administered over two consecutive days [3].
For quercetin, safety data indicates that doses up to 2,000 mg per day are well tolerated, even in patients with chronic obstructive pulmonary disease (COPD), as shown through lung function tests, blood profiles, and patient questionnaires [7]. Additionally, quercetin has been deemed safe at doses of up to 1,000 mg daily over a 12-week period [11].
Key clinical findings include:
| Study Type | Key Finding | Safety Outcome |
|---|---|---|
| Cohort Study | Daily fisetin (100 mg) reduced senescent cell markers | No significant adverse effects [3] |
| Clinical Trial | Fisetin (100 mg/day) combined with chemotherapy decreased IL-8 levels | Well tolerated in cancer patients [3] |
| Stroke Study | Fisetin (100 mg/day) improved disease outcomes | Safe when used with standard treatment [3] |
These results underscore the unique safety characteristics of each compound. Fisetin demonstrates stronger senotherapeutic activity compared to quercetin in cellular studies [1]. Both are considered safe, though fisetin is less efficiently absorbed [10]. It's worth noting that liver function should be monitored with long-term use [17].
This summary connects the clinical findings to practical considerations for those considering long-term supplementation.
FAQs
Are there any interactions between Fisetin, Quercetin, and common medications? What precautions should I take?
Fisetin and Quercetin might interact with certain medications, particularly those prescribed for blood thinning and diabetes. Fisetin, for example, could heighten the risk of bleeding when used alongside anticoagulants like warfarin. It may also influence blood sugar levels, potentially complicating the effects of diabetes medications. Similarly, Quercetin may amplify the effects of blood thinners, which could lead to an increased chance of bruising or bleeding.
If you're considering these supplements, it's crucial to talk to your healthcare provider first. This is especially important if you're on blood thinners, managing diabetes, or dealing with other health conditions. Your doctor can evaluate potential interactions and guide you on the safest way to incorporate these into your routine.
Are Fisetin and Quercetin supplements safe for long-term use?
Fisetin and Quercetin are widely regarded as safe when taken within recommended doses. Research on Fisetin indicates it is generally well-tolerated, even at higher amounts, though some studies have observed potential changes in liver enzyme levels with extended use. Similarly, Quercetin appears safe for short-term use in doses up to 1,000 mg per day, but its safety over periods longer than 12 weeks remains unclear.
While these compounds hold potential, more research is necessary to fully understand their long-term effects. It's always a good idea to consult a healthcare provider before adding any new supplement to your routine, particularly if you have existing medical conditions or take other medications.
What are the health benefits of the antioxidant and anti-inflammatory properties of Fisetin and Quercetin?
Fisetin and Quercetin are natural compounds known as flavonoids, celebrated for their antioxidant and anti-inflammatory abilities. Fisetin plays a key role in reducing oxidative stress by neutralizing free radicals, which helps shield cells from damage. This not only supports brain health but also encourages cellular repair and may even contribute to slowing signs of aging. Its anti-inflammatory effects further aid in minimizing chronic inflammation, promoting better overall health.
Quercetin, on the other hand, is equally effective in addressing oxidative stress and inflammation. It stands out for its ability to inhibit histamine release, making it helpful in managing allergic reactions. Additionally, it supports heart health by addressing inflammation tied to long-term health conditions. When combined, Fisetin and Quercetin work together to improve cellular performance, protect against age-related decline, and encourage a healthier, more vibrant life.
