Description: <b>"Antioxidants</b> are compounds that inhibit oxidation, a chemical reaction that can produce free radicals." <br>
For example Vitamin C (normally Antioxidant), Vitamin e, and Trolox are anti-oxidants. <br>
Berries: Blueberries, Strawberries, Raspberries, Blackberries <br>
Fruits: Grapes, Pomegranates, Oranges, Apples <br>
Vegetables: Spinach and other leafy greens, Kale, Broccoli, Brussels sprouts <br>
Nuts and Seeds: Walnuts, Almonds, Flaxseeds, Chia seeds <br>
Beverages: Green tea, Black tea <br>
Spices and Herbs: curcumin, Ginger, Garlic, Cinnamon <br>
Other: Dark chocolate (with high cocoa content), Beans and legumes, Tomatoes (rich in lycopene) <br>
<br>
Antioxidants are compounds that help neutralize free radicals—unstable molecules that can damage cells and contribute to the development of chronic diseases including cancer. <br>
<br>
Cancer Prevention: <br>
Mechanism: Antioxidants protect cells from oxidative damage caused by free radicals, which can lead to mutations in DNA. Over time, these mutations might initiate or promote the growth of cancer cells. <br>
Dietary Role: Eating a diet rich in antioxidants (fruits, vegetables, and other plant-based foods) has been associated with a lower risk of some cancers. Many epidemiological studies suggest that diets high in natural antioxidants are linked to a reduced risk of cancer. <br>
<br>
During Cancer Treatment: <br>
Controversy: There is debate about whether taking antioxidant supplements during chemotherapy or radiation therapy is beneficial or harmful. Many therapies such as Chemotherapy raise the ROS(Reactive oxygen Species) intentionally to kill cancer cells. Some theory applies that antioxidants might prevent the ROS from being raised, and hence reduce treatment effectiveness. Some laboratory and clinical studies indicate that antioxidants might protect not only healthy cells but also cancer cells against the oxidative damage intentionally induced by these treatments. This could potentially reduce the effectiveness of cancer therapies. Another theory is there is a differential effect from taking antioxidants. Meaning the antioxidants help protect normal cells, but not the cancer cells. <br>
Recommendation: Many oncologists recommend caution with high-dose antioxidant supplements during active cancer treatment. Instead, a balanced diet with naturally occurring antioxidants is typically advised. <br>
<br>
thiol-containing antioxidants: -Contain a functional –SH (sulfhydryl) group <br>
-Can undergo oxidation to form disulfide bonds. This reversible redox behavior allows these molecules to neutralize reactive oxygen species (ROS). <br>
-Thiol antioxidants (like N‑acetylcysteine or glutathione) are potent because the –SH group can directly scavenge ROS. <br>
-There is concern that supplementation with thiol antioxidants during chemotherapy could neutralize some of the ROS generated by the treatment, potentially reducing the intended cytotoxic effects on cancer cells. <br>
Examples: <br>
-NAC <br>
-GSH <br>
-NMPG <br>
-dihydrolipoic acid (reduced form of ALA) <br>
-Cysteamine <br>
-Ergothioneine <br>
-Thioredoxin <br>
<br>
Non-thiol ROS scavengers: <br>
-Act by donating electrons or hydrogen atoms to free radicals, thereby stabilizing them or converting them into less reactive species. <br>
-Non‑thiol antioxidants (like vitamin C, vitamin E, flavonoids, etc.) have different mechanisms of action and may not interact as directly with ROS in the specific context of chemotherapy-induced cell death. <br>
-That said, even non‑thiol antioxidants could potentially interfere with chemotherapy in some cases. For example, high doses of vitamin C or vitamin E might also diminish the oxidative stress essential for the efficacy of some chemotherapeutics. <br>
Examples <br>
-Ascorbic Acid(VitC) <br>
-Vitamin E <br>
-Flavoniods (Quercetin) <br>
-Carotenoids(beta-carotene) <br>
-Resveratrol <br>
-Coenzyme Q10 (ubiquinone) <br>
-Curcumin (indirectly disrupt thiol systems)<br>
-Polyphenols (ferulic acid and caffeic acid) <br>
-manganese(III) <br>
-tetrakis( (4-benzoic acid) <br>
-porphyrin chloride (MnTBAP) <br>
-SOD <br>
<br>
*** NOTE: <br>
Thiol AntiOxidants could block ROS generation caused by Gambogic Acid, but not NON-Thiol AntiOxidants. <br>
-Thiol-based antioxidants directly support glutathione and thioredoxin buffering and are most likely to protect cancer cells from ROS- or thiol-dependent therapies. Non-thiol antioxidants may act as radical scavengers, redox modulators, or—under certain tumor-specific conditions—pro-oxidants. Therefore, the likelihood that an antioxidant interferes with cancer therapy depends less on whether it ‘scavenges ROS’ and more on whether it restores thiol redox homeostasis or activates cytoprotective signaling pathways such as NRF2.<br>
<br>
OTHER CLASSES of antioxidants <br>
1. Enzymatics Antioxidants (SOD, Catalase, GPXs) <br>
-proteins that catalyze reactions to detoxify reactive oxygen species (ROS). <br>
2. Non-Enzymatic (Small-Molecule) Antioxidants. <br>
Further divided to Thiol-Based Antioxidants, vs Non-Thiol Based Antioxidants. <br>
3. Metal-Binding Proteins and Chelators (Ferritin, Transferrin) <br>
These compounds limit oxidative damage indirectly by sequestering transition metals (like iron and copper) that catalyze reactive oxygen species formation via the Fenton reaction. <br>
4. Indirect Antioxidants (Nrf2 Activators): (Sulforaphane, Curcumin)
enhance the body’s own antioxidant defenses by upregulating the expression of antioxidant enzymes. <br>
<br>
<br>
<pre>
Cancer-Relevant Antioxidant Matrix
(Oral/achievable doses)
</pre>
<table>
<tr> <th>AntiOxidant</th> <th>Oral</th> <th>Pro-ox.</th> <th>Thiol </th> <th>Effect</th><th>Effect on</th> <th>NRF2 up</th> <th>NRF2 up</th> <th>Cancer</th> <th>Chemo</th> <th>Mechanism </th></tr>
<tr> <th>Compound</th> <th>Dose/day</th> <th>Cancer</th> <th>Buffer</th> <th>on ROS</th> <th>ROS</th> <th>risk</th> <th>in</th> <th>Redox.</th> <th>Compatibility</th> <th>and</th> </tr>
<tr> <th> </th> <th> </th> <th> </th> <th>Idx 0-4</th> <th>cancer</th> <th>Normal</th> <th>Cancer</th> <th>Normal</th> <th>Buffer</th> <th> </th> <th>Notes</th> </tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=203&word=NRF2">Salinomycin</a></td>
<td>0.2–1 mg</td><td>Yes</td><td>0</td><td>↑3</td><td>↓1</td>
<td>0</td><td>0</td><td>0</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Redox-active anticancer agent (not a classic antioxidant): mitochondrial ion dysregulation; CSC targeting; ROS-mediated apoptosis</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=387&word=NRF2">Disulfiram</a> (+Cu)</td>
<td>250–500 mg</td><td>Yes</td><td>1</td><td>↑3–4</td><td>↓1–2</td>
<td>0–1</td><td>0–1</td><td>0–1</td><td>Cond.[M][D]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Redox-active anticancer agent: copper-dependent redox cycling; proteasome inhibition; CSC toxicity (formulation/copper availability matters)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=388&word=NRF2">PEITC</a></td>
<td>40–100 mg</td><td>Yes</td><td>3</td><td>↑3</td><td>↓1–2</td>
<td>0–1</td><td>0–1</td><td>1–2</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Redox-active stressor: GSH depletion; mitochondrial ROS amplification; ASK1/JNK activation (timing with ROS-therapy still relevant at higher doses)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=36&word=NRF2">Withaferin A</a></td>
<td>5–20 mg</td><td>Yes</td><td>1–2</td><td>↑3</td><td>↓1–2</td>
<td>1</td><td>1</td><td>1–2</td><td>Cond.[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Redox-active anticancer agent: ROS-mediated apoptosis; vimentin targeting; ER–mitochondrial stress (dose/timing sensitive)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=42&word=NRF2">Betulinic Acid</a></td>
<td>200–600 mg</td><td>Yes</td><td>0–1</td><td>↑2–3</td><td>↓1–2</td>
<td>0</td><td>0</td><td>0–1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Direct mitochondrial membrane permeabilization; ROS as an amplifier in some models (not a classic antioxidant)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=164&word=NRF2">Ursolic Acid</a></td>
<td>150–450 mg</td><td>Yes</td><td>1</td><td>↑2–3</td><td>↓2</td>
<td>1</td><td>1</td><td>1</td><td>Cond.[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Mitochondrial ROS; AMPK–mTOR modulation; NF-κB/STAT3 inhibition (context-dependent redox direction)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=162&word=NRF2">Thymoquinone</a> (TQ)</td>
<td>100–400 mg</td><td>Yes</td><td>2–3</td><td>↑2–3</td><td>↓2</td>
<td>2–3</td><td>2–3</td><td>1–2</td><td>Cond.[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Quinone redox cycling; tumor-selective ROS; NRF2 induction is context-dependent (often stronger in normal cells than many cancers, but not guaranteed)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=65&word=NRF2">Curcumin</a></td>
<td>1–4 g</td><td>Yes</td><td>2</td><td>↑2–3</td><td>↓2</td>
<td>3</td><td>2</td><td>1</td><td>Cond.[T][D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Redox cycling; mitochondrial ROS; metal chelation; NRF2 activation can be adaptive in tumors (bioavailability limits systemic exposure; effects often local/GI or formulation-dependent)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=140&word=NRF2">Quercetin</a></td>
<td>500–1000 mg</td><td>Yes</td><td>2</td><td>↑2–3</td><td>↓2</td>
<td>1–2</td><td>2–3</td><td>1</td><td>Cond.[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Auto-oxidation; not a thiol donor; context-dependent—can reduce xCT/GPX4 defenses in some tumors and promote ferroptosis; NRF2 activation more consistent in normal cells than cancers</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=73&word=NRF2">EGCG</a> (green tea)</td>
<td>400–800 mg</td><td>Yes</td><td>2</td><td>↑2–3</td><td>↓2</td>
<td>2–3</td><td>1–2</td><td>1–2</td><td>Cond.[T][D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Redox-active polyphenol: H2O2 generation; iron-mediated ROS; dose/timing sensitive near ROS-dependent therapy windows (higher-dose extracts have context-specific safety considerations)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=94&word=NRF2">Honokiol</a></td>
<td>200–600 mg</td><td>Yes</td><td>1–2</td><td>↑2–3</td><td>↓2–3</td>
<td>1</td><td>1</td><td>1–2</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Mitochondrial ROS induction; generally weaker NRF2 activation than strong NRF2 inducers</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=41&word=NRF2">Berberine</a></td>
<td>500–1500 mg</td><td>Yes</td><td>2</td><td>↑2–3</td><td>↓2</td>
<td>1–2</td><td>1–2</td><td>1–2</td><td>Cond.[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">ETC complex I inhibition; AMPK–ROS coupling; dose-dependent cytostatic vs cytotoxic effects (drug-interaction potential via transporters/enzymes is context-dependent)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=141&word=NRF2">Resveratrol</a></td>
<td>500–2000 mg</td><td>Yes</td><td>1</td><td>↑1–2</td><td>↓2</td>
<td>2</td><td>1–2</td><td>1–2</td><td>Cond.[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Mitochondrial complex inhibition; ROS induction at higher doses; NRF2 effects variable by dose/cell type (low systemic bioavailability; metabolites dominate)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=139&word=NRF2">Pterostilbene</a></td>
<td>100–300 mg</td><td>Yes</td><td>1</td><td>↑1–2</td><td>↓2</td>
<td>1</td><td>1</td><td>1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Mitochondrial stress signaling; generally lower NRF2 activation than resveratrol; better oral exposure than resveratrol (still context-dependent)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=119&word=NRF2">Lycopene</a></td>
<td>15–75 mg</td><td>Context</td><td>0–1</td><td>↔1–2</td><td>↓2–3</td>
<td>1</td><td>1–2</td><td>0–1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Mostly antioxidant at diet/supplement doses; generally low NRF2 perturbation; redox behavior is context-dependent (oxygen tension, metals, baseline oxidative stress)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=149&word=NRF2">Selenium</a> (org.)</td>
<td>200–400 µg</td><td>Yes(sel.)</td><td>3</td><td>↑1–2</td><td>↓2–3</td>
<td>1–2</td><td>2–3</td><td>2–3</td><td>Compatible[F]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Effects depend strongly on selenium species and baseline selenium status; prevention benefit not established; avoid chronic high dosing near UL (form-dependent redox cycling/thiol stress)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=149&word=NRF2">SeNPs</a> (oral)</td>
<td>50–200 µg</td><td>Yes(tumor)</td><td>3</td><td>↑2–3</td><td>↓2–3</td>
<td>0–1</td><td>1–2</td><td>2–3</td><td>Compatible[F]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Redox-selective ROS in cancer cells in some models; form/size dependent; smaller particles may increase ROS and timing sensitivity; human oral exposure evidence is form-dependent</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=166&word=NRF2">Vitamin C</a> (oral)</td>
<td>≤2–3 g</td><td>Limited</td><td>1–2</td><td>↔1</td><td>↓2–3</td>
<td>↔0–1</td><td>↔1–2</td><td>1–2</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Oral absorption is saturable; oral dosing mainly supports antioxidant tone; IV vitamin C is mechanistically different (pharmacologic plasma; pro-oxidant H2O2 mechanisms)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=194&word=NRF2">β-Carotene</a></td>
<td>20–30 mg</td><td>High-risk</td><td>0–1</td><td>↔1–2</td><td>↓2</td>
<td>1</td><td>1–2</td><td>1</td><td>Caution[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">RCT harm signal in smokers/asbestos-exposed groups (increased lung cancer and mortality); can act pro-oxidant in high-oxygen/smoking contexts—avoid in smokers/high-risk lung exposure settings</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=156&word=NRF2">Sulforaphane</a></td>
<td>30–100 mg</td><td>Indirect</td><td>2</td><td>↔0–1</td><td>↓3–4</td>
<td>3–4</td><td>3–4</td><td>3–4</td><td>Caution[M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Strong NRF2/Phase II inducer; often cytoprotective in normal tissue; may support tumor stress tolerance/chemoresistance in some contexts (mechanism-dependent)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=122&word=NRF2">Melatonin</a></td>
<td>10–50 mg</td><td>Selective</td><td>1</td><td>↔0–1</td><td>↓3–4</td>
<td>1–2</td><td>1–2</td><td>1–2</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Antioxidant enzyme upregulation + mitochondrial signaling; generally cytoprotective in normal tissue; tumor effects are context-dependent (not a strong thiol donor)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=356&word=NRF2">CoQ10</a> (oxidized)</td>
<td>100–300 mg</td><td>Possible</td><td>1–2</td><td>↔0–1</td><td>↓2–3</td>
<td>↔0–1</td><td>↔1–2</td><td>2</td><td>Cond.[M][F]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">ETC redox buffering; form dependent (ubiquinone vs ubiquinol); may alter ROS signaling and antioxidant tone (mechanism/timing dependent)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=118&word=NRF2">Luteolin</a></td>
<td>50–200 mg</td><td>Yes</td><td>1</td><td>↑1</td><td>↓2–3</td>
<td>1–2</td><td>1–2</td><td>1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Selective tumor ROS induction in some models; relatively modest NRF2 activation vs strong NRF2 inducers (context-dependent)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=32&word=NRF2">Apigenin</a></td>
<td>50–200 mg</td><td>Yes</td><td>1</td><td>↑1</td><td>↓2–3</td>
<td>1–2</td><td>1–2</td><td>1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Mild tumor ROS induction; kinase/redox signaling; generally low NRF2 activation at oral doses (context-dependent)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=316&word=NRF2">Kaempferol</a></td>
<td>50–200 mg</td><td>Yes</td><td>1</td><td>↑1</td><td>↓2–3</td>
<td>1–2</td><td>1–2</td><td>1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Kinase/redox signaling; modest tumor ROS effects; NRF2 activation variable and context-dependent</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=85&word=NRF2">Genistein</a></td>
<td>30–100 mg</td><td>Yes</td><td>1</td><td>↑1</td><td>↓2–3</td>
<td>1–2</td><td>1–2</td><td>1–2</td><td>Cond.[D][H][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Dose-dependent redox modulation; hormone/receptor context (estrogenic); can shift survival signaling depending on tumor subtype</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=78&word=NRF2">Fisetin</a></td>
<td>100–500 mg</td><td>Yes</td><td>1</td><td>↑1</td><td>↓2–3</td>
<td>1–2</td><td>1–2</td><td>1</td><td>Compatible[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Flavonoid; mild ROS induction in cancer cells; dose-dependent behavior; not a direct thiol donor</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=127&word=NRF2">Myricetin</a></td>
<td>50–250 mg</td><td>Yes</td><td>1</td><td>↑1–2</td><td>↓2–3</td>
<td>1–2</td><td>1–2</td><td>1</td><td>Compatible[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Flavonoid antioxidant with context-dependent tumor ROS effects; can be pro-oxidant under metal/ROS-rich conditions</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=74&word=NRF2">Ellagic Acid</a></td>
<td>200–800 mg</td><td>Yes</td><td>0–1</td><td>↑1–2</td><td>↓2–3</td>
<td>1</td><td>1</td><td>0–1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Tumor-selective mitochondrial ROS reported; generally weaker NRF2 induction than sulforaphane; parent bioavailability limited vs metabolites</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=383&word=NRF2">Urolithin A</a> (UA)</td>
<td>250–1000 mg</td><td>Yes (sel.)</td><td>0–1</td><td>↑1–2</td><td>↓2–3</td>
<td>0–1</td><td>1</td><td>0–1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Mitophagy induction; selective tumor ROS in some models; generally low NRF2 activation; supports mitochondrial quality control</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=386&word=NRF2">Spermidine</a></td>
<td>5–20 mg</td><td>Context</td><td>0–1</td><td>↔1</td><td>↓1–2</td>
<td>0–1</td><td>1</td><td>0–1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Autophagy inducer; polyamine biology; mild ROS modulation; NRF2 effects usually indirect via stress/translation programs (context-dependent)</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=29&word=NRF2">α-Lipoic acid (ALA)</a></td>
<td>300–600 mg</td><td>Limited</td><td>2</td><td>↔0–1</td><td>↓2–3</td>
<td>1–2</td><td>1–2</td><td>1</td><td>Cond.[D][M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Thiol redox cycling (DHLA active); dose-dependent redox behavior; timing/dose sensitive near ROS-dependent therapy windows</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=51&word=NRF2">Caffeic</a> / Ferulic</td>
<td>100–500 mg</td><td>Context</td><td>0–1</td><td>↔1</td><td>↓2–3</td>
<td>1</td><td>1</td><td>0–1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Polyphenols with mild redox cycling; generally modest NRF2 effects; mostly antioxidant at dietary-equivalent doses</textarea></td>
</tr>
<tr>
<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=128&word=NRF2">Naringenin</a> / Hesp.</td>
<td>50–200 mg</td><td>Limited</td><td>0–1</td><td>↔1</td><td>↓3–4</td>
<td>0–1</td><td>0–1</td><td>0–1</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Mostly antioxidant; low pro-oxidant signaling at oral doses; generally supportive of normal-cell redox buffering</textarea></td>
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<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=382&word=NRF2">Astaxanthin</a> (ASTX)</td>
<td>4–12 mg</td><td>No</td><td>0</td><td>↔0</td><td>↓3–4</td>
<td>0</td><td>0</td><td>0</td><td>Cond.[M]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Membrane/lipid antioxidant; may reduce efficacy of lipid-peroxidation/ROS-dependent therapy if taken peri-infusion (mechanism-dependent)</textarea></td>
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<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=307&word=NRF2">Vitamin E</a> (α-toc.)</td>
<td>200–800 IU</td><td>No</td><td>1–2</td><td>↔0–1</td><td>↓3–4</td>
<td>0</td><td>1–2</td><td>2–3</td><td>Caution[M][D]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Lipid radical scavenger; can blunt lipid peroxidation-based cytotoxicity (radiation/anthracyclines/platinums). Prevention RCT signal: increased prostate cancer risk with vitamin E supplementation in SELECT</textarea></td>
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<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=307&word=NRF2">Trolox</a> (Vit E)</td>
<td>20–200 mg</td><td>No</td><td>1–2</td><td>↔0–1</td><td>↓3–4</td>
<td>0</td><td>1–2</td><td>2–3</td><td>Caution[M][D]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Chain-breaking antioxidant; can blunt lipid peroxidation-based cytotoxicity; caution with ROS-dependent modalities (timing/dose dependent)</textarea></td>
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<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=364&word=NRF2">N-acetylcysteine</a></td>
<td>600–1800 mg</td><td>No</td><td>4</td><td>↓1–2</td><td>↓3–4</td>
<td>2</td><td>3–4</td><td>4</td><td>Caution[M][D]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Direct thiol/GSH precursor; strongly increases redox buffering; higher likelihood of reducing efficacy of ROS-dependent chemo/radiation (especially near infusion/radiation windows); preclinical progression/metastasis signals exist in some models</textarea></td>
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<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=381&word=NRF2">Glutathione</a> (oral)</td>
<td>250–1000 mg</td><td>No</td><td>4</td><td>↓1</td><td>↓3–4</td>
<td>2</td><td>3–4</td><td>3–4</td><td>Caution[M][D]</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Thiol redox buffering; oral bioavailability variable but directionally increases thiol buffering; can reduce ROS-based cytotoxicity depending on timing/dose</textarea></td>
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<td><a href="https://nestronics.ca/dbx/tbResList.php?qv=349&word=NRF2">Lutein</a> / Zeaxanthin</td>
<td>10–20 mg</td><td>No</td><td>0</td><td>↔0</td><td>↓3–4</td>
<td>0</td><td>0</td><td>0</td><td>Compatible</td>
<td ><textarea readonly rows="1" cols="25" wrap="soft">Structural antioxidants; membrane protection without strong redox cycling; generally low interaction with ROS-dependent therapy at diet-level doses</textarea></td>
</tr>
</table>
<pre>
Compatible – No known interference at oral doses
Cond. (Conditional) – Timing, dose, or regimen dependent
Caution – Likely to interfere with ROS-dependent therapies
[T] = Timing-sensitive (avoid peri-infusion / ROS-dependent window)
[D] = Dose-dependent (low vs high dose behave differently)
[M] = Mechanism-dependent (NRF2, ETC, thiol buffering, metal chelation)
[H] = Hormone- or receptor-dependent
[F] = Form-dependent (chemical form matters)(organic vs nano)
*NRF2 Explanation not necessarily reflected in ratings (example Quercetin)
-NRF2↑ in normal cells is the dominant pattern
-In cancer cells, NRF2 upregulation is possible, but not dominant, and often context-suppressed by stronger pro-oxidant mechanisms.
Smaller <50 nm SeNPs generate ROS more efficiently; may interfere with ROS-dependent chemo if given concurrently
Chemo compatibility assumes ROS-dependent cytotoxic modalities (e.g., anthracyclines, platinum agents, radiation). Non-ROS-dependent therapies may not share these constraints.
*β-carotene is incompatible primarily in smokers / high-oxygen tissues (RCT harm signal in smokers/asbestos-exposed groups)
Arrows show whether ROS increases (↑), decreases (↓), or neutral/variable (↔)
Thiol Buffering Index (0–4):
| TBI Score | Meaning |
| --------- | ------------------------------------------------------------------------------------------------------ |
| 0 | No effect on thiol pools; does not buffer redox stress (mostly non-thiol antioxidants) |
| 1 | Minimal indirect thiol effect; may slightly modulate thiol-dependent enzymes |
| 2 | Moderate indirect thiol effect; may perturb thiols or partially modulate GSH/Trx system |
| 3 | Significant thiol buffering; contributes to redox stabilization in cancer cells |
| 4 | Strong direct thiol donor; substantially increases GSH/thioredoxin pools; higher chemo interference risk |
Note the table is very general, and database searches and details should be researched for each compound of interest.
Example: Luteolin can show NRF2 down in cancer cells
</pre>