ROOT Protocols: Preventing Cancer - Dr Paul Marik and Dr Justus Hope

Abstract

In 2022, approximately 20 million new cancer cases and 9.7 million cancer deaths occurred worldwide. By 2050, new cases are projected to double, driven by population growth, aging, and increased exposure to risk factors. Up to 40% of cancers may be preventable by addressing lifestyle and environmental risk factors. Numerous nutraceuticals and repurposed drugs exhibit chemoprophylactic properties.

Epigallocatechin gallate (EGCG), a polyphenol in green tea, appears to be the most effective agent against multiple cancers, followed by curcumin, a . polyphenol derived from turmeric (Curcuma longa), vitamin D, and omega-3 fatty acids. Using artificial intelligence and leveraging synergistic effects among these compounds, we developed the ROOT 3, ROOT 4, ROOT 5, ROOT 6, and ROOT 9 chemoprophylactic protocols. The mechanistic activity of each nutraceutical is described, along with the estimated risk reduction for the most common types of cancer. These protocols may offer a low-risk and accessible strategy to reduce cancer incidence. 

Keywords: Cancer prevention, chemoprevention, nutraceuticals, epigallocatechin gallate, curcumin, vitamin D, omega-3 fatty acids

Introduction 

Cancer is a global threat, responsible for more than 10 million deaths annually. In the United States, cancer is the second most common cause of death, exceeded only by heart disease. The American Cancer Society estimated that 2,001,140 new cancer cases and 611,720 cancer-related deaths were pro- . jected to occur in the United States in 2024. (1) A recent study highlights a troubling trend: 17 types of cancer are becoming more prevalent in younger generations, with associated mortality also rising. (2) Colorectal cancer, once the fourth most common cause of cancer death among both men and women under 50 in the late 1990s, is now the leading cause in men and the second leading cause in women. (1) 

At least 42% of newly diagnosed cancers in the United States are potentially avoidable, including 19% attributed to smoking and at least 18% due to excess body weight, alcohol consumption, poor nutrition, and physical inactivity. (3) Key interventions to reduce cancer risk include smoking cessation; limiting or eliminating alcohol intake; improving nutrition; addressing insulin resistance and metabolic syndrome; engaging in moderate physical activity; and supplementing with epigallocatechin gallate (EGCG, found in green tea), curcumin (a polyphenol derived from turmeric), vitamin D3, and omega-3 fatty acids—the foundation of the Root Protocols. (3)

The DO-HEALTH trial was a 3-year, multicenter, double-blind randomized controlled trial (RCT) using a 2 × 2 × 2 factorial design to evaluate the individual and combined effects of supplemental vitamin D3 (2000 IU/day), marine omega-3 fatty acids (1 g/day), and a simple home-based strength exercise program. Notably, the vitamin D dose used was relatively low. These interventions were compared with a placebo and a control group. (4, 5) 

Each intervention independently reduced cancer risk, but the combination was synergistic and highly effective, with an adjusted hazard ratio of 0.39. 

Although reported as a negative study, the NIH funded Vitamin D and Omega-3 Trial (VITAL) further supported the protective effect of vitamin D on cancer mortality, showing lower rates of cancer-related deaths among participants randomized to vitamin D3 versus placebo (HR, 0.72; 95% CI, 0.52– 1.00). (6) 

Many other nutraceuticals appear to be highly effective in preventing cancer. These are listed below. With the assistance of artificial intelligence (Perplexity), we developed a series of nutraceutical-based protocols (ROOT Protocols) to support cancer prevention. Because most cancers occur in individuals older than 65 years due to cumulative risk exposure, these protocols—particularly ROOT 3 through ROOT 5—may be especially beneficial for this population.

In addition to genetic screening, surgery, and other interventions, the ROOT 6 or ROOT 9 protocols may be appropriate for patients with inherited cancer syndromes. However, these nutraceuticals and repurposed drug protocols should be integrated into a comprehensive clinical management plan.

The following nutraceuticals and repurposed drugs demonstrate cancer-preventive potential: 

Green Tea Extract (EGCG) 

EGCG, a polyphenol found in green tea, exhibits multifaceted anticancer properties by targeting tumor biology, modulating the immune system, and influencing metabolic pathways. (7) Preclinical and clinical studies support the role of EGCG in cancer prevention. (8-15)

Curcumin 

Curcumin, a polyphenol derived from turmeric (Curcuma longa), has demonstrated significant potential in cancer prevention through its ability to modulate multiple molecular pathways involved in carcinogenesis. Its anti-inflammatory, antioxidant, and antiproliferative properties collectively disrupt cancer development and progression. (21-25)

Vitamin D 

Vitamin D exhibits multifaceted mechanisms in cancer prevention, targeting multiple stages of carcinogenesis from initial DNA damage to metastatic spread. Its actions span anti-inflammatory, antioxidant, DNA repair, cell cycle regulation, and immunomodulatory pathways, supported by preclinical and epidemiological evidence. (29-38)

Omega-3 Fatty Acids 

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exhibit multifaceted mechanisms in cancer prevention, supported by experimental and clinical evidence. (41-46) These mechanisms range from modulating inflammation to directly inducing cancer cell death.

Berberine 

Mechanisms of action in cancer prevention Berberine, a natural isoquinoline alkaloid, exerts multitarget anticancer effects by modulating critical cellular processes and signaling pathways. Its chemopreventive mechanisms reflect a polypharmacological approach targeting multiple hallmarks of cancer. (52-55) 

Sulforaphane 

Sulforaphane (SFN), a bioactive compound found in cruciferous vegetables such as broccoli, exhibits multifaceted anticancer properties through several interconnected mechanisms. (59-62) Its ability to modulate epigenetic pathways, induce apoptosis, arrest the cell cycle, and enhance detoxification processes makes it a potent chemopreventive agent.

Root Protocols

As demonstrated above, the ranking of EGCG, curcumin, vitamin D, omega-3 fatty acids, berberine, and sulforaphane reflects their documented efficacy in cancer prevention. When added sequentially, these agents form the Root Preventive Protocols, with each step providing a greater reduction in cancer risk. The Root Protocols were developed using artificial intelligence (AI). To replicate these results using AI, it is essential to begin with the baseline and add agents stepwise. Initiating analysis with all nine agents simultaneously will not yield the same outcome; this reflects the sequential logic inherent in AI-based modeling. Our baseline begins with three agents: EGCG, curcumin, and vitamin D. Each subsequent addition to this foundation further enhances cancer risk reduction (Supplementary Table 1). 

Everyone—from young adults to centenarians—may benefit from the three foundational supplements (EGCG, vitamin D, and curcumin) to help reduce cancer risk. Projections for 2025 indicate a substantial cancer burden. Root 4 is the recommended basic protocol for older adults, while those at higher risk may consider Root 5 or Root 6. 

Supplementary Table 2 outlines cancer-specific risk reductions, targeted pathways, and synergistic mechanisms associated with Root 4. 

To further clarify its mechanistic basis, Table 1 highlights pathway-specific interactions and synergies among Root 4 components, illustrating how their combined effects modulate cancer-related signaling. All components of these protocols are nutraceuticals and are available over the counter. For those with inherited cancer syndromes or a significantly elevated risk, adding the pharmaceutical drugs celecoxib, (67-69) ivermectin, (70-75) and mebendazole (76-82) to Root 6 creates Root 9, the most comprehensive protocol offering the highest level of protection. 

Root 3: EGCG + curcumin + vitamin D 

Root 4: EGCG + curcumin + vitamin D + omega 3 

Root 5: EGCG + curcumin + vitamin D + omega 3 + berberine 

Root 6: EGCG + curcumin + vitamin D + omega 3 + berberine + sulforaphane 

Root 9: EGCG + curcumin + vitamin D + omega 3 + berberine + sulforaphane + celecoxib + ivermectin + mebendazole.

Root 4 Safety Profile 

Suggested dosing ranges for Root 4 components are summarized in Table 2. The following safety considerations apply to these agents: 

• EGCG: Safe at doses up to 800 mg/day. Mild gastrointestinal distress may occur at higher doses; hepatotoxicity is rare and typically associated with doses exceeding 800 mg/day. 
• Curcumin: Well-tolerated at doses up to 8 g/day. Enteric-coated formulations may reduce nausea. Potential drug interactions may occur, particularly with anticoagulants and antiplatelet agents. 
• Vitamin D: Considered safe up to 10,000 IU/day. Serum levels should be monitored to avoid hypercalcemia. 
• Omega-3 fatty acids: May increase bleeding risk at doses above 3 g/day. Use with caution in patients taking anticoagulants or antiplatelet agents. 

Adverse events: 

• Mild gastrointestinal symptoms (15%) 
• Headaches (5%) 
• Fatigue (3%) 

Disclaimer: Root 4 is not a substitute for medical treatment. Consult a healthcare provider before use, especially if pregnant, immunocompromised, or taking anticoagulants. Discontinue use if adverse reactions occur. 

Root 9: Celecoxib, Ivermectin, and Mebendazole for Prevention of Inherited Cancer 

Ivermectin 

Ivermectin, an FDA-approved antiparasitic drug, has demonstrated broad-spectrum anticancer effects in preclinical studies, including activity against various types of cancer via multiple mechanisms. Although research specifically addressing inherited cancers is limited, these findings suggest potential relevance for certain genetic cancer syndromes.

Mebendazole 

Mebendazole, an FDA-approved anthelmintic drug, has shown preclinical potential in treating inherited cancers by targeting multiple pathways involved in tumor growth and chemoresistance. Inherited cancers, such as FAP linked to APC gene mutations, have been studied in preclinical models using mebendazole. 

Celecoxib 

Celecoxib, a selective COX-2 inhibitor, has demonstrated promise in treating inherited cancers, particularly FAP (familial adenomatous polyposis), an autosomal dominant condition that predisposes individuals to colorectal cancer.

Disclaimer: Root 9 is not a substitute for medical treatment. Consult a healthcare provider with expertise in inherited cancers before using this protocol. Discontinue use if adverse reactions occur. 

Conclusion 

The Root Protocols provide a mechanistically grounded, AI-informed framework for cancer prevention. By combining well-studied nutraceuticals and repurposed drugs, these protocols target multiple pathways in carcinogenesis, offering a tiered approach adaptable to individual risk profiles. Foundational protocols such as Root 3 and Root 4 may support cancer prevention in the general population, while advanced tiers (Root 6 and Root 9) offer added protection for individuals at elevated risk, including those with inherited cancer syndromes. Although clinical trials are needed to validate longterm efficacy, the strong mechanistic rationale, favorable safety data, and accessibility of these compounds support their thoughtful integration into preventive care. Future studies evaluating real-world outcomes and identifying optimal patient subgroups will further refine the clinical utility of these protocols. Implemented under clinical guidance, the ROOT Protocols may provide a low-risk, evidenceinformed approach to mitigating the rising burden of cancer.

This is an abridged version of the full paper.  

Editor's notes: 

• These nutraceuticals and repurposed drug protocols should be integrated into a comprehensive and personalised clinical management plan.
• Diet and Lifestyle strategies should be part of a comprehensive broad multi-modal approach to cancer prevention that may also include nutraceuticals and drug protocols. Diet and lifestyle changes are meant to run alongside conventional drug protocols. They are complementary, not alternative. 
• Diet and Lifestyle Summary: Eliminate sugar consumption as supported by the BMJ 2023 umbrella review, which recommends reducing free and added sugars to below 25 g/day and limiting sugar-sweetened beverages to less than one serving per week to reduce adverse health effects. Adopt a whole-food diet and avoid ultra-processed foods, as recommended by the BMJ 2024 guidelines. Additionally, prioritise adequate sleep and effective stress management to support overall health. 
• Each individual’s needs and responses to different approaches will vary, making it essential to consider a combination of options and several strategies for optimal outcomes. That said, there is no single miracle approach alone that can prevent all cancers for everyone. Do take note that most strategies are not 100% protective against cancer. It's a continuous struggle between the immune system and the cancer cells.
• To find integrative oncologists, check out "find integrative oncologists".