Natural supplements can be very helpful adjuvants to drug therapies, for example, through chemosensitization of tumor cells. Unfortunately, it seems that very often there's little or no follow-through when readily available natural products show great potential in cancer treatment. However, rational combination therapies can significantly improve outcomes. I’ve created a visual guide with arrows and symbols highlighting synergistic interactions, key pathways, and processes between various compounds. These represent some of the safest and most effective natural substances for inhibiting cancer growth and proliferation through multiple mechanisms.
- Artemisinin 🛈 ⓟ CT FER ST3 HIF → ↓ DHA docosahexaenoic acid 🛈 ST3 FER
- → Citric acid 🛈 Gi RL RA → Melatonin 🛈 E⏷ ↘ → Shikonin 🛈 Ⓟ
- → Honokiol 🛈 LDHAi RMDR → Orlistat 🟪 FAS FER → EGCg 🛈 FAS * AA → IP6 🛈
- → Metformin 🟪 → Shikonin ↓ 🛈 → Luteolin FER ↑ ↗ → Ivermectin 🟪 β-CAT
- → Diclofenac 🟪 MCT1/4 → D-limonene 🛈 p53 Bcl2 ↓
- → Caffeine ↓→ Piperlongumine 🛈 Berberine 🛈
- → Berberine → ↓ Andrographis 🛈 → ↑ Melatonin ↓
- → Apigenin 🛈 → Curcumin 🛈 → Thymoquinone 🛈 AA HIF
- → Baicalein 🛈 HIF AA ST3 hsp90 → Silibinin 🛈 Jak2 β-CAT
- → Oroxylin-A Gi → ↑ Chrysin 🛈
- → γ-Tocotrienol HIF ST3
- → Aspirin 🟪 Bcl2 FAS→ ↑ Vitamin D 🛈 → Lactoferrin RA
- → Modified Citrus Pectin 🛈 G3 → Ursolic acid 🛈 FAS E⏷→ Luteolin ↓ ST3
- → Magnolol ↓ 🛈 β-CAT + Ai 🛈 ↗ Piperine ↑10x → Curcumin↑→ I3C 🛈 * E⏷
- → Berberine 🛈 ↓LDHAi → Coptidis Rhizoma EMT
- → ↓Curcumin 🛈 RMDR → Luteolin 🛈 TGF-β → Silibinin 🛈
- → Piperlongumine 🛈 CT FER ST3 → Sanguinarine → Berberine 🛈 → Caffeine
- → Allicin 🛈 FER RMDR → Ginger/6-Shogaol 🛈 ICD NO▼ → Anthocyanin 🛈 AM▼
- + HDACi 🛈 → Melatonin 🛈 → Curcumin ↓ → Cannabidiol 🛈 → Magnolol
- → Rosmarinic acid 🛈
- → Ivermectin 🟪 P-gp
- → Ursolic acid 🛈 FAS E⏷
- → ↓ Apigenin 🛈 CCAA ↓ → Salvia miltiorrhiza 🛈 FER → ↓ Astragalus 🛈 T ˃
- Curcumin 🛈 ST3 G3 MT → Emodin → Celecoxib 🟪 COX-2 → Luteolin 🛈 → Apigenin 🛈
- → 2:3 Docosahexaenoic acid 🛈 → Butyrate 🛈 → Citric acid🛈 Gi RL RA → Graviola 🛈
- → Gallic acid FER → Chlorogenic acid 🛈
- → Taurine RA ↓
- ⇒ EGCg 🛈 FAS Bcl2↗ → Quercetin → Grapeseed extract 🛈 AA E⏷ → P. linteus
- → Honokiol ↓ 🛈 CSC
- → Baicalin 🛈 → Magnolol 🛈 Ⓟ
- → Luteolin ↓ 🛈 nrf2▼ TGFβi → Celecoxib 🟪 nrf2▲ → Berbamine 🛈 ST3
- → ↑ Curcumin → Chrysin HIF → Silibinin 🛈
- → IP6 & Inositol 🛈
- → Ginger / 6-Shogaol 🛈 AM▼ → Licorice → Boswellia CCAA Ⓟ
- → Chlorogenic acid 🛈 RAS → Theobromine 🛈 AA E⏷
- → Cinnamon RA
- →↓ Milk Thistle 🛈 → Baicalein 🛈 HIF AA ST3 → Salvia miltiorrhiza 🛈 AM▼
- → Nigella Sativa ↓ ↓ Thymoquinone 🛈 AA HIF NFi → Emodin
- → Vitamin C 🛈 HIF LDHAi → Vitamin K2 🛈 E⏷* ↑
- ⇒ Bicarbonate 🛈 → Galla Chinensis LDHAi
- → Magnesium RL
- → Juglone CCAA → Selenium (selenite)
- → Vitamin K3
- → Quercetin 🛈 → Piperlongumine
- → Thymoquinone Bcl2/BAX
- → Ashwagandha 🛈 → CAPE 🛈
- → ↓ Vitamin D 🛈 → Lactoferrin RA → Linolenic acid 🛈
- → Sulforaphane 🛈 HIF ST5 nrf2▲! ↑ → Dihydrocaffeic Acid
- → Galangal → Tulsi → Piper nigrum
- → ↓ Berberine 🛈 MT CT HIF RMDR → Zinc
- → Oligomeric proanthocyanidins
- → Garcinol 🛈
- → Carnosic acid↓ → Fisetin 🛈 → Quercetin → Caffeic acid → Coumaric acid 🛈
- Mistletoe AA → Chaga 🛈 → Rosmarinic acid 🛈 RMDR EGFR → Cinnamon RA
→ anticancer synergy with Artemisinin
→ ferroptosis
→ combination may offer hepatoprotective effects
→ likely to be a good antineoplastic combination
(OTC) medications: I've included a few non-oncology drugs that, if used in combination with specific supplements, could enhance their anti-cancer action. Repurposing non-oncology drugs is an attractive approach to improving cancer therapy.
Enhancing Absorption and Bioavailability
Consuming fat-soluble supplements alongside dietary fats like ghee butter or coconut oil can improve their absorption and utilization in the body. The ideal dosage for the compounds discussed in this blog is uncertain and would vary based on the type of cancer, the specific target, and the individual patient's response to the treatment.
Timing: Optimizing Supplement Intake for Enhanced Efficacy
It might be beneficial to take anticancer supplements late at night and to include a time during the night in your supplementation schedule, e.g., 3AM "study suggests that nighttime is the right time for cancer to grow and spread in the body and that administering certain treatments in time with the body's day-night cycle could boost their efficiency" {ref|ref}.
Synergistic Combinations
A natural substance may show potential against cancer. Still, its effectiveness is often limited by the need for excessively high concentrations to achieve significant benefits (in vitro concentrations not achievable in vivo). However, if synergies exist, those same substances may become significantly more effective at lower concentrations. Such combinations of nutraceuticals can also be used to overcome drug resistance or to sensitize cancer cells to therapeutic agents.
Key Pathways and Processes
- ICD Immunogenic cell death
- Gi inhibitor of glycolysis
- CT cytotoxic
- RMDR reversing/sensitizing multidrug resistance
- MT multiple targets
- CCAA cell cycle arrest and apoptosis
- FAS fatty acid synthase inhibition
- AA anti-angiogenic
- EGFR epidermal growth factor receptor Inhibition
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- LR lactate reduction
- FER ferroptosis induction, avoid co-administration of FER inhibitors: Vitamin K, and other substances.
- * Take separately and at least two hours apart from ferroptosis inducers unless it's a synergistic combination.
- AMPK ampk activator
- COX-2 cox-2 inhibitor
- AI anti-inflammatory
- FAK focal adhesion kinase downregulation
- SERM selective estrogen receptor modulator
- HIF hypoxia-inducible factor inhibition drug resistance▼
- AM ▼▲autophagy modulation
- NO▼ Nitric Oxide
- ROSI reduces oxidative stress and inflammation
- NFi NF-κβ inhibition
- ST3 STAT3 inhibition
- ST5 STAT5 inhibition
- PDK inhibition
- RA reduce ammonia
- HDACi HDAC inhibition
- MiR modulate immune response
- E⏷ reduces estrogen
- RAS reducing Ras activity
- TGFβi inhibition of TGF-β
- LDHAi inhibition of LDHA
- NK stimulates the production of NK cells (additionally, check #7 here)
- G3 galectin 3 inhibition: MCP, curcumin, spiraeoside (red onions), QiShenYiQi, formic acid (apples, strawberries, raspberries, honey, nettles)
- T activation of T cells
- β-CAT: inhibition of β-catenin protein.
- hsp90 Inhibition of HSP90
- Jak2 JAK2 inhibition
- nrf2 Nuclear factor-erythroid 2 related factor. The transcription factor NRF2 exhibits a dual role in cancer. Its impact can vary depending on conditions such as cancer stage, cancer type, mutations, and cancer therapy.
- E! Caution in hormonal cancers
- EMT Epithelial-Mesenchymal Transition inhibition
- TGF-β inhibition
- Please refer to the spreadsheet for more details on the effects of 100 supplements against 30 anticancer variables.
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Drug interactions
Be aware of drug interactions, e.g., concurrent use of natural products with anticoagulants may result in prolonged bleeding times and should be avoided.
Safe and responsible use of natural supplements and repurposed medications
Supplements should only be taken under the supervision of your healthcare provider or oncologist. Supplements or herbal preparations shouldn't be combined with chemotherapy, radiotherapy, immunotherapy, or any other cancer treatment unless the safety and efficacy of such combinations are established. It's vital to make sure anything you add to the standard treatment will further improve its effectiveness.
For informational purposes only, none of my writing should be considered medical advice.
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Moved Piperlongumine back to #1 since it's now available as a supplement and should be a good combination with Artemisinin because of overlapping anti-cancer mechanisms (CT,FER,ST3). A good spot right under curcumin.
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