Wednesday, September 10, 2025

Natural Products & Repurposed Drugs: A Visual Guide to Synergy

Natural supplements can be a helpful addition to cancer therapy. For example, they can act as supportive agents that make tumor cells more sensitive to chemotherapy drug, a process known as chemosensitization. Integrating therapies through a scientific approach may lead to substantially improved results.  I’ve created a visual guide highlighting synergistic interactions, key pathways, and processes between various compounds. These represent some of the most effective natural substances and repurposed drugs that impair cancer growth and metastatic potential through multiple mechanisms. However, while many compounds demonstrate potent anti-cancer effects in laboratory settings or animal models, they often prove ineffective due to poor bioavailability, unreliable because of hormesis, or even unsafe because of the difficulty in dosing. Understanding these hurdles is key to evaluating complementary treatments. Synergistic combinations could potentially overcome these limitations. This is the core focus of this blog. That said, a critical point to highlight is that supplements, herbs, and repurposed drugs can interfere with cancer treatments. Always consult your healthcare provider or oncologist before taking supplements, as they can interfere with treatment efficacy, increase bleeding, or cause immune impairment from high doses, and therefore should be avoided during active cancer treatment, unless otherwise directed by a licensed medical professional. Refer to the 'Safe Use' page for more critical safety information.  
  1. Artemisinin ðŸ›ˆ ðŸŸ¥CT FER ST3 HIF  →   DHA docosahexaenoic acid ðŸ›ˆ ST3 FER  
  2. Curcumin ðŸ›ˆ ST3 G3 MT  Emodin  Celecoxib ðŸŸª COX-2  Luteolin ðŸ›ˆ  Apigenin ðŸ›ˆ 
    •  2:3 Docosahexaenoic acid ðŸ›ˆ  Butyrate ðŸ›ˆ   Citric acid🛈 Gi RL RA → Graviola ðŸ›ˆ
      •  Melatonin   Andrographis ðŸ›ˆ 
          • Danshen  AM▼ ðŸ›ˆ  Naringin ðŸ›ˆ RA   3:2 Quercetin  
        •  Shikonin ICD GI E⏷NK Apigenin          Fisetin ðŸ›ˆ ↑→  Aspirin ðŸŸª PDK  
    • Gallic acid ðŸ›ˆ FER  Chlorogenic acid ðŸ›ˆ                                         
    •  Taurine RA                                                                                         
    •   EGCg  +24h  ðŸ›ˆ FAS Bcl2  Quercetin   Grapeseed extract ðŸ›ˆ AA E  P. linteus
    •  Nigella Sativa   Thymoquinone  ðŸ›ˆ AA HIF NFi  Emodin
    •  Vitamin C ðŸ›ˆ HIF  LDHAi  Vitamin K2 ðŸ›ˆ E⏷* 
      •  Bicarbonate ðŸ›ˆ  LDHAi
      •  Magnesium RL 
      •  Juglone CCAA  Selenium (selenite)
      •  Vitamin K3
      •  Quercetin ðŸ›ˆ  Piperlongumine 
            • Thymoquinone Bcl2/BAX
      •  Ashwagandha/Withaferin A ðŸ›ˆ CAPE/Propolis ðŸ›ˆ
    •   Vitamin D  ðŸ›ˆ  Lactoferrin RA  Linolenic acid ðŸ›ˆ
              • +72h Artemisinin    -1h Ivermectin 🟪 P-gp
          •   Aspirin ðŸŸª PDK  Ferulic acid ðŸ›ˆ
          •   Lycopene ðŸ›ˆ AI FAK  Capsaicin
          • → Î³-Tocotrienol
    •  Sulforaphane ðŸ›ˆ HIF ST5 nrf2▲!    Dihydrocaffeic Acid 
    •  Galangal  Tulsi  Piper nigrum
      •   Berberine ðŸ›ˆ MT CT HIF RMDR  Zinc
    •  Oligomeric proanthocyanidins 
    •  Garcinol ðŸ›ˆ 
    •  Lactoferrin   
    •  Carnosic acid  Fisetin ðŸ›ˆ  Quercetin  Caffeic acid  Coumaric acid ðŸ›ˆ
    • Mistletoe AA  Chaga ðŸ›ˆ  Rosmarinic acid ðŸ›ˆ RMDR EGFR   Cinnamon RA  Berberine

    Explanation of symbols & colors

    Top 10 natural substances (refer to spreadsheet); yellow colored
     anticancer synergy with Artemisinin
     ↑ ↘ ↗ additive or synergistic anticancer effect (at a minimum, evidence from preclinical studies)  sequential 
     ferroptosis 
     combination may offer hepatoprotective effects
     likely to be a good anticancer combination (mechanistically, or closely related to similar synergies)
     offset IL-8 upregulation
    🟥 ROS Classification of Natural Compounds in Cancer Therapy
    🟪 I've included a few non-oncology drugs that could enhance their anti-cancer action if combined with specific supplements. Repurposing non-oncology drugs is a promising approach to enhancing cancer therapy.
    Link to blog or forum post
    🛈 Information about the substance
    LD: Low dose
    See Key Pathways and Processes below

    Enhancing Absorption and Bioavailability


    Consuming fat-soluble supplements alongside dietary fats, such as ghee or coconut oil, can enhance 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. While some combinations work through additive rather than truly synergistic mechanisms, they deliver meaningful therapeutic benefits through multi-pathway targeting.

    Citric acid-mediated ferroptosis strategy


    Click to expand the diagram

    For more information on this ferroptosis model, please refer to the forum post.


    Key Pathways and Processes

    Code Description Code Description
    ICD Immunogenic cell death ST3 STAT3 inhibition
    Gi Inhibitor of glycolysis ST5 STAT5 inhibition
    CT Cytotoxic PDK PDK inhibition
    RMDR Reversing/sensitizing multidrug resistance RA Reduces ammonia
    MT Multiple targets HDACi HDAC inhibition
    CCAA Cell cycle arrest and apoptosis MiR Modulate immune response
    FAS Fatty acid synthase inhibition E⏷ Reduces estrogen
    AA Anti-angiogenic RAS Reducing Ras activity
    EGFR Epidermal growth factor receptor Inhibition TGFβi Inhibition of TGF-β
    LR Lactate reduction LDHAi Inhibition of LDHA
    FER Ferroptosis induction, avoid co-administration of FER inhibitors: Vitamin K, and other substances. * don't use in a ferroptosis strategy NK Stimulates the production of NK cells
    AMPK AMPK activator G3 Galectin 3 inhibition: MCP, curcumin, spiraeoside (red onions), QiShenYiQi, formic acid (apples, strawberries, raspberries, honey, nettles)
    COX-2 COX-2 inhibitor T Activation of T cells
    AI Anti-inflammatory β-CAT Inhibition of β-catenin protein
    FAK Focal adhesion kinase downregulation hsp90 Inhibition of HSP90
    SERM Selective estrogen receptor modulator Jak2 JAK2 inhibition
    HIF Hypoxia-inducible factor inhibition drug resistance▼ 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.
    AM ▼▲ Autophagy modulation E! Caution in hormonal cancers
    NO▼ Nitric Oxide EMT Epithelial-Mesenchymal Transition Inhibition
    ROSI Reduces oxidative stress and inflammation TGF-β TGF-β inhibition
    NFi NF-κβ inhibition TMA Target the metabolic adaptability of cancer cells

    ⚠️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 ensure that any additions to the standard treatment further improve its effectiveness

    Drug interactions

    Always verify potential interactions between your supplements and any medications you are taking. Be aware of how different nutrients interact with each other. Some supplements enhance the absorption of other nutrients, while others may compete. Supplements, herbs, and repurposed drugs can interfere with cancer treatments. Supplements may reduce treatment efficacy, increase bleeding, or cause immune impairment from high doses, and should be avoided during active cancer treatment unless recommended by a doctor.



    For informational and research purposes only, none of my writing should be considered medical advice.

    1 comment:

    1. 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.

      ReplyDelete