Targeting the Gut Microbiome and Metabolic Pathways to Enhance Immunotherapy Outcomes in Cancer Care

By Dr. Nalini Chilkov, L.Ac., O.M.D.
Founder, OutSmart Cancer® System

Introduction

Immunotherapy has revolutionized the treatment landscape for many types of cancer. Yet, response rates remain variable and unpredictable. Immune checkpoint blockade (ICB) therapies are often undermined by tumor-induced immunosuppression, systemic inflammation, and adverse effects stemming from immune hyperactivation. Emerging evidence highlights the gut microbiome and metabolic environment as critical modulators of immunotherapy efficacy and tolerance.

Response to immunotherapy  can be enhanced by optimizing  the health of the microbiome, supporting robust immunity, and promoting systemic metabolic health. These are fundamental elements of the OutSmart Cancer® System.

The Gut-Immune-Cancer Axis

The gut microbiome is now recognized as a powerful regulator of immunity, metabolism, and systemic inflammation. Composed of trillions of microorganisms, this ecosystem influences T-cell function, immune checkpoint pathways, and the tumor microenvironment (TME).

Key mechanisms include:

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• Modulation of T-cell activation and exhaustion.
• Regulation of dendritic cell antigen presentation.
• Production of immunomodulatory metabolites (e.g., short-chain fatty acids, indoles, inosine).
• Maintenance of gut barrier integrity, reducing systemic endotoxemia.

Clinical studies show that high microbial diversity (α-diversity) and the presence of specific beneficial strains—such as Faecalibacterium prausnitzii, Akkermansia muciniphila, and Bifidobacterium longum—are associated with improved response rates to immune checkpoint blockade and reduced risk of immune related adverse events【6】.

Conversely, gut dysbiosis—often caused by antibiotics, low-fiber diets, or systemic inflammation—can impair immune surveillance and reduce therapeutic benefit. Patients with Proteobacteria-dominant microbiomes show poorer outcomes and increased toxicity【6】.

Diet and the Microbiota-Immune Interface

The Mediterranean Diet: A Clinical Standard

The OutSmart Cancer Diet is a low glycemic modification of the well-studied Mediterranean Diet (MD) which emphasizes vegetables, legumes, whole grains, fruits, nuts, olive oil, and modest intake of fish and poultry. It has been shown to:

• Increase SCFA-producing bacteria (e.g., Clostridium cluster XIVa, F. prausnitzii).
• Reduce inflammation and enhance immune regulation.
• Improve absorption of essential micronutrients (vitamin D, iron, folate).

The OutSmart Cancer® Diet reduces the carbohydrate intake of the Mediterranean Diet to achieve lower normal glucose and insulin levels to reduce the insulinogenic growth signaling and to support mitochondrial fatty acid rather than glucose dominant energy metabolism.

The OutSmart Cancer® Diet also encourages patients to include small portions of a variety of natural fermented foods in their daily diets as a source of a wide spectrum of healthy microorganisms to support a diverse and robust intestinal microbiome.

In a 2023 study published in JAMA Oncology, adherence to the MD was associated with significantly higher objective response rates and progression-free survival in advanced melanoma patients treated with ICB【6】.

High-Fiber Diets and Whole Plant Foods

Soluble dietary fiber from vegetables fuels beneficial microbes and promotes production of butyrate, a SCFA with anti-inflammatory and immune-supportive properties. High-fiber diets:

• Increase microbial diversity.
• Decrease gut permeability and systemic LPS levels.
• Support regulatory T-cell activity and mucosal immunity.

A landmark 2021 Science study showed that patients with higher fiber intake and no probiotic use had significantly better responses to ICB (82% vs. 59%) and prolonged PFS【6】.

Metabolic Interventions: Fasting and Caloric Restriction

Cancer cells exhibit high metabolic demands and are less adaptable to nutrient scarcity. Modifying caloric intake alters host metabolism, immune cell dynamics, and the TME—shifting the balance in favor of immune activation and tumor suppression.

Short-Term Water Fasting (STWF)

STWF involves complete abstinence from food for 72–120 hours with maintained hydration. It:

• Decreases IGF-1, insulin, and glucose levels.
• Increases ketone bodies and autophagy.
• Protects normal cells from chemotherapy-induced toxicity (differential stress resistance).
• Enhances cytotoxic T-cell and NK cell activity【1,2】.

Fasting-Mimicking Diet (FMD)

The FMD replicates the benefits of fasting while providing limited caloric intake (plant-based, low-protein, high-fat) for 5 days. Clinical trials have demonstrated that FMD:

• Lowers systemic inflammation and metabolic markers (glucose, IGF-1).
• Depletes immunosuppressive cells (MDSCs, Tregs).
• Enhances ICB efficacy and reduces irAEs in melanoma and NSCLC patients【3】.

Time-Restricted Eating (TRE)

TRE aligns eating patterns with circadian rhythms by confining caloric intake to 8–10 hours daily. Benefits include:

• Improved insulin sensitivity, weight management, and lipid profiles.
• Reduced inflammatory cytokines (TNF-α, IL-6).
• Increased microbial diversity and butyrate-producing bacteria【4,5】.

Functional Nutrients and Immune Support

Vitamin D

Vitamin D (VD) modulates both innate and adaptive immunity. It enhances mucosal barrier integrity, reduces inflammatory cytokine production, and promotes regulatory T-cell function. VD deficiency is common in cancer patients and may:

• Increase gut permeability and systemic inflammation.
• Correlate with higher rates of irAEs.
• Impair microbiome diversity【6】.

Omega-3 Fatty Acids

Omega-3 polyunsaturated fatty acids (PUFAs) such as EPA and DHA:

• Suppress NF-κB activation and COX-derived pro-inflammatory mediators.
• Increase SCFA-producing gut bacteria.
• Are associated with improved B-cell and NK cell activity.

Safe dosing ranges from 1.5 to 3 g/day. These fatty acids are generally well-tolerated and help preserve lean body mass and immune tone【6】.

Clinical Integration: Actionable Strategies

Step 1: Dietary Guidance

• Emphasize a low carb OutSmart Cancer® modified Mediterranean-style diet.
• Encourage high-fiber, unprocessed plant foods.
• Minimize processed meat, alcohol, and refined sugar.

Step 2: Fasting Protocols

• STWF (72 hours) or FMD (5-day cycles) in supervised settings.
• TRE (8–10 hour eating window) as a sustainable, daily intervention.

Step 3: Supplement Wisely

• Test and correct vitamin D insufficiency.
• Supplement omega-3s if inflammatory burden or cachexia is present.

Step 4: Preserve the Microbiome

• Avoid non-essential antibiotic use near ICB initiation.
• Favor food-based prebiotics over commercial probiotics unless indicated.

Step 5: Educate and Empower

• Teach patients how lifestyle and nutrition influence outcomes.
• Reinforce the message: Cancer is not in control. You are.

Conclusion

A paradigm shift is underway in oncology—one that embraces the whole patient, not just the tumor. By targeting the gut microbiome and metabolic pathways, we can optimize immunotherapy outcomes, reduce adverse effects, and empower patients to play an active role in their healing.

Create a body where cancer cannot thrive.
Support the Tumor Microenvironment. Strengthen the immune system. Transform outcomes.

Bibliography

1. Brandhorst S., Longo V. D. (2019). Fasting and fasting-mimicking diets for chemotherapy augmentation. GeroScience, 41(4), 387–398. https://doi.org/10.1007/s11357-019-00072-5
2. Dorff T. B., et al. (2016). Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer, 16, 360. https://doi.org/10.1186/s12885-016-2370-6
3. Vernieri C., et al. (2022). Fasting-mimicking diet is safe and reshapes metabolism and antitumor immunity in patients with cancer. Cancer Discovery, 12(1), 90–107. https://doi.org/10.1158/2159-8290.CD-21-0030
4. Wilkinson M. J., et al. (2020). Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with metabolic syndrome. Cell Metabolism, 31(1), 92–104.e5. https://doi.org/10.1016/j.cmet.2019.11.004
5. Di Francesco A., et al. (2018). A time to fast. Science, 362(6416), 770–775. https://doi.org/10.1126/science.aau2095
6. David A., Lev-Ari S. (2024). Targeting the Gut Microbiome to Improve Immunotherapy Outcomes: A Review. Integrative Cancer Therapies, 23:1–10. https://doi.org/10.1177/15347354241269870

 

Clinical Implications for Integrative Oncology Practice

As integrative oncology physicians, we are entrusted with guiding patients toward dietary patterns that support their health during and after cancer treatment. Understanding the role of red and processed meats in the cancer terrain empowers us to educate patients about evidence-based choices that can influence cancer outcomes and survivorship.

Dietary Counseling and Cancer Prevention

In clinical practice, discussions about meat consumption should be personalized. Patients with a history of colorectal, breast, or prostate cancer may benefit from eliminating processed meats and limiting red meat intake. Encourage the adoption of dietary patterns rich in anti-inflammatory, antioxidant, and fiber-rich foods, such as the Mediterranean or plant-forward diets, which have been shown to support immune function and reduce chronic inflammation—key factors in the Cancer Terrain.

Key Recommendations for Physicians:

• Assess Meat Intake: Routinely inquire about red and processed meat consumption during dietary assessments, especially for patients with known cancer risk factors or histories.
  
• Promote Plant-Based Proteins: Recommend legumes, nuts, seeds, and organic tofu or tempeh as alternatives to red meat. These options provide adequate protein without the carcinogenic risks associated with processed meats. 
• Educate on Cooking Methods: Advise patients to avoid high-temperature cooking methods that generate carcinogens. Recommend steaming, stewing, or baking at lower temperatures. 
• Encourage Dietary Diversity: Promote a diet abundant in colorful vegetables, fruits, whole grains, and phytonutrient-rich herbs and spices to support detoxification pathways and healthy cellular function. 

A Broader Perspective on Risk Reduction

While no single food causes or cures cancer, dietary patterns can shape the Cancer Terrain—the internal environment that influences whether cancer will develop or progress. By reducing exposure to known dietary carcinogens and increasing intake of protective compounds, patients can take an active role in their healing journey.

Conclusion

The link between red and processed meat consumption and cancer risk is supported by robust evidence, particularly for colorectal and breast cancers. Integrative oncology physicians must translate this knowledge into actionable guidance, empowering patients to make informed dietary choices. This approach not only aligns with cancer prevention but also fosters overall health and vitality—goals that resonate deeply with our patients' aspirations to Get Well, Stay Well, and Live Well Beyond Cancer.

References

1. IARC Monographs. Red Meat and Processed Meat. International Agency for Research on Cancer. https://www.iarc.who.int/wp-content/uploads/2018/07/pr240_E.pdf 
2. Farvid MS, et al. Meat intake and risk of breast cancer: A systematic review and meta-analysis. Int J Cancer. 2021;149(8):1512-1524. https://pubmed.ncbi.nlm.nih.gov/34455534 
3. Zhao Z, et al. Red and processed meat consumption and gastric cancer risk: A systematic review and meta-analysis. Oncotarget. 2017;8(18):30563-30575. https://pmc.ncbi.nlm.nih.gov/articles/PMC5444765 
4. Lippi G, et al. Red meat consumption and cancer risk: A critical review. Crit Rev Food Sci Nutr. 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10577092 
5. Diallo A, et al. Red and processed meat intake and prostate cancer risk: A systematic review and meta-analysis of prospective studies. Nutrients. 2022;14(5):1036. https://pubmed.ncbi.nlm.nih.gov/35198587 
6. IARC Monograph Volume 114. Red Meat and Processed Meat. WHO Publications. https://publications.iarc.who.int/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Red-Meat-And-Processed-Meat-2018 
7. IARC Q&A. Carcinogenicity of consumption of red and processed meat. https://www.iarc.who.int/wp-content/uploads/2018/11/Monographs-QA_Vol114.pdf 

To your health, healing, and wholeness.
Create a Body Where Cancer Cannot Thrive.

PART ONE 

Red Meat Consumption and Cancer Risk 

​The relationship between red meat consumption and cancer risk has been extensively investigated. Epidemiological studies and meta-analyses have provided insights into how red meat and processed meat intake may influence the incidence of various cancers.​+5PMC+5PubMed+5

Several mechanisms are proposed to elucidate the correlation between the consumption of red and processed meat and the risk of cancer.  These mechanisms include:

• Heme Iron: The high concentration of heme iron in red meat facilitates the formation of N-nitroso compounds, acknowledged carcinogens that may induce damage to the gastrointestinal lining.
• Cooking Methods: The utilization of elevated-temperature cooking techniques, such as grilling and barbecuing, promotes the synthesis of heterocyclic aromatic amines and polycyclic aromatic hydrocarbons, which possess carcinogenic potential.
• Processing Chemicals: Processed meats frequently incorporate nitrates and nitrites, which can undergo transformation into N-nitroso compounds during the digestive process, thereby contributing to carcinogenesis.

Cancers Linked To Red Meat Consumption

Colorectal Cancer

The International Agency for Research on Cancer (IARC) has classified processed meat as “carcinogenic to humans” (Group 1) and red meat as “probably carcinogenic to humans” (Group 2A), with a significant association observed between processed meat consumption and colorectal cancer. Specifically, an analysis estimated that every 50-gram portion of processed meat consumed daily increases the risk of colorectal cancer by about 18%. ​

Breast Cancer

A comprehensive systematic review and meta-analysis indicated that high red meat intake is positively associated with an increased risk of breast cancer. Similarly, high processed meat intake was linked to a higher risk of breast cancer. ​PubMed+2PubMed+2PMC+2

Gastric Cancer

The association between red and processed meat consumption and gastric cancer risk has yielded mixed results. Some case-control studies suggest a positive association, while cohort studies have not consistently supported this link. Therefore, the evidence remains inconclusive. ​PubMed+2PMC+2PMC+2PMC

Pancreatic Cancer

Research has indicated a potential link between high red meat consumption and an increased risk of pancreatic cancer. However, further studies are needed to confirm this association. ​IARC PublicationsPMC

Prostate Cancer

A systematic review and meta-analysis of prospective studies suggested that increased consumption of total meat and processed meat might be associated with a higher risk of prostate cancer. ​PMC+2PubMed+2PubMed+2

Conclusion

The body of evidence suggests a positive association between red and processed meat consumption and the risk of several cancers, notably colorectal and breast cancer. While the exact mechanisms remain under investigation, it is prudent for healthcare professionals to consider these findings when advising patients on dietary choices. All patients are advised to limit red meat consumption and eliminate all processed meats. The OutSmart Cancer® diet  recommends poultry fish, eggs and legumes as healthy sources of protein It is plant strong, rich in fruits, vegetables, and healthy fats may be supports a healthy and lower risk tumor microenvironment.

Dr. Valter Longo, a prominent figure in the field of biogerontology, has extensively researched the intersection of nutrition, fasting, and cancer therapy. His recent work, particularly encapsulated in his 2025 publication, Fasting Cancer: How Fasting and Nutritechnology Are Creating a Revolution in Cancer Prevention and Treatment, provides a comprehensive overview of his findings and methodologies.

Key Insights from Fasting Cancer

In Fasting Cancer, Dr. Longo presents decades of research highlighting how controlled dietary interventions, specifically fasting and fasting-mimicking diets (FMDs), can enhance cancer treatment outcomes. He elucidates that while cancer cells are adept at exploiting various nutrients for growth, they become particularly vulnerable during fasting states. In contrast, healthy cells activate protective mechanisms under these conditions, leading to a differential stress response that can be therapeutically advantageous. ​

A notable quote from Dr. Longo emphasizes this concept:​

“While we have learned that you cannot starve cancer with fasting alone, since cancer steals from other cells and finds a way to stay alive even if the patient fasts, you can use fasting-mimicking diets to make the cancer cells so weak or desperate that the right therapy will kill them.”  

Furthermore, the book discusses how integrating his Longevity Diet—a plant-based nutritional regimen—and plant-based ketogenic diets can support and potentially amplify the efficacy of conventional cancer therapies. Dr. Longo underscores the importance of patients actively participating in their treatment plans through dietary strategies, aiming to make therapies more effective and less toxic

Recent Research Highlights

Dr. Longo's recent studies have provided empirical support for the benefits of FMDs in oncology:​

1. Breast Cancer Study (2024): A sub-analysis of the NCT03340935 trial indicated that incorporating FMD cycles with first-line carboplatin-based chemotherapy was associated with improved overall survival in patients with advanced triple-negative breast cancer.
2. Chronic Lymphocytic Leukemia (2024): Research demonstrated that cyclic FMD, when combined with Bortezomib and Rituximab, effectively treated chronic lymphocytic leukemia, suggesting a synergistic effect between FMD and these therapeutic agents. ​
3. T-Cell Leukemia (2023): Findings revealed that FMD inhibited autophagy and, in combination with chemotherapy, promoted T-cell-dependent leukemia-free survival, highlighting the potential of FMD to enhance immune-mediated cancer clearance.

 These studies collectively suggest that FMDs can play a pivotal role in reprogramming cancer cell metabolism, improving the efficacy of standard treatments, and reducing adverse side effects.

Intermittent Fasting and Cancer Metabolism:   A Four Part Series

The OutSmart Cancer® System recommends intermittent fasting for 13 hours of calorie restriction per 24 hour cycle with the appropriate assessment, monitoring and guidance of a health care provider.

While the results are promising, it's important to note that more extensive clinical trials are needed to establish standardized guidelines for implementing IF in oncology.

Personalized approaches should be considered, as the effects of IF may vary depending on cancer type, stage, and individual patient factors.

 Therefore, personalized approaches, clinical supervision and monitoring and further research are needed to fully understand and optimize the use of IF in cancer treatment.

Intermittent fasting represents a multifaceted approach to cancer prevention and treatment, leveraging metabolic, immunological, and cellular mechanisms. As research in this field continues to evolve, IF may become an important adjunct to conventional cancer therapies and part of the OutSmart Cancer® System for Creating a

 For Part 5 simply publish the blog post but a newsletter does not have to be sent

Intermittent Fasting and Cancer Metabolism:  Selected References

Part 5: Intermittent Fasting: Selected References

1. Anemoulis, et al. (2024). Intermittent Fasting on Cancer: An Update. EJ Clinical Medicine.
2. de Groot, S., et al. (2022). Effect of fasting on cancer: A narrative review of scientific evidence. Nutrition Reviews, 80(10), 2159-2177.
3. Clifton, K. D., et al. (2021). Intermittent fasting in the prevention and treatment of cancer. CA: A Cancer Journal for Clinicians, 71(6), 527-546.
4. Ferro, K., et al. (2023). Impact of Fasting on Patients With Cancer: An Integrative Review. Clinical Journal of Oncology Nursing, 27(6), 619-625.
5. Nencioni, A., et al. (2018). Fasting and cancer: molecular mechanisms and clinical application. Nature Reviews Cancer, 18(11), 707-719.
6. Harvie, M., & Howell, A. (2023). Intermittent fasting interventions to leverage metabolic and circadian rhythms for cancer prevention and control. JNCI Monographs, 2023(61), 84-93.
7. Morales-Suárez-Varela, M., et al. (2020). Effect of intermittent fasting on cancer prevention: a systematic review. European Journal of Public Health, 30(Supplement_5), ckaa166.216.

1. Stringer, A. M., et al. (2018). Autophagy and intermittent fasting: the connection for cancer therapy? Clinics, 73(suppl 1), e814s.
2. Longo, V. D., & Mattson, M. P. (2014). Fasting: molecular mechanisms and clinical applications. Cell metabolism, 19(2), 181-192.
3. Brandhorst, S., & Longo, V. D. (2016). Fasting and caloric restriction in cancer prevention and treatment. Recent Results in Cancer Research, 207, 241-266.
4. Antunes, F., et al. (2018). Autophagy and intermittent fasting: the connection for cancer therapy? Clinics, 73(suppl 1), e814s.
5. Lee, C., & Longo, V. D. (2016). Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene, 35(15), 1475-1490.
6. Safdie, F. M., et al. (2009). Fasting and cancer treatment in humans: A case series report. Aging (Albany NY), 1(12), 988-1007.
7. de Groot, S., et al. (2019). Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nature communications, 11(1), 3083.
8. Freedland, S. J., et al. (2024). Researchers Look to Fasting as a Next Step in Cancer Treatment. Cedars-Sinai Discoveries.
9. Cheng, C. W., et al. (2014). Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell stem cell, 14(6), 810-823.
10. Di Biase, S., et al. (2016). Fasting-mimicking diet reduces HO-1 to promote T cell-mediated tumor cytotoxicity. Cancer cell, 30(1), 136-146.
11. Caffa, I., et al. (2020). Fasting-mimicking diet and hormone therapy induce breast cancer regression. Nature, 583(7817), 620-624.
12. Wei, S., et al. (2017). Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science translational medicine, 9(377), eaai8700.
13. Buono, R., & Longo, V. D. (2018). Starvation, stress resistance, and cancer. Trends in Endocrinology & Metabolism, 29(4), 271-280.

Intermittent Fasting and Cancer Metabolism:   A Four Part Series

PART 3: Intermittent Fasting and Insulin Like Growth Factor (IGF-1)

 

Intermittent fasting (IF) reduces insulin-like growth factor 1 (IGF-1) levels through several specific mechanisms:

1. Protein Restriction: The reduction in IGF-1 is primarily attributed to the restriction of protein intake, particularly essential amino acids, during fasting periods8.

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1. Calorie Restriction: The decrease in overall calorie intake during fasting supports the reduction in IGF-1 levels8.
2. Insulin Reduction: Fasting leads to a significant decrease in circulating insulin levels, which in turn promotes the reduction of IGF-182.
3. Metabolic Switch: IF induces a metabolic switch that mimics water fasting, leading to a decrease in IGF-1 levels. For example, a 4-day fasting-mimicking diet (FMD) can reduce IGF-1 levels by approximately 45%3.
4. IGFBP-1 Increase: Fasting causes a substantial increase in IGF binding protein 1 (IGFBP-1), which can bind to IGF-1 and reduce its bioavailability. Studies have shown that prolonged fasting can lead to a 5-fold increase in IGFBP-13.
5. Signaling Pathway Modulation: IF down-regulates nutrient signaling pathways such as TOR-S6K and PKA, which are involved in IGF-1 regulation3.
6. Hepatic Gene Expression: Fasting specifically decreases IGF-1 mRNA in the liver, indicating a direct effect on IGF-1 gene expression4.

It's important to note that the effects of IF on IGF-1 levels can vary depending on the specific fasting protocol. For instance, while prolonged fasting and fasting-mimicking diets have shown significant reductions in IGF-1, some studies on time-restricted eating (TRE) have not observed changes in IGF-1 levels over shorter periods6.

These mechanisms collectively contribute to the reduction of IGF-1 levels during intermittent fasting, which may have implications for various health outcomes, including cancer prevention and treatment123.

Intermittent fasting (IF) has shown promising effects on tumor growth across various cancer types, though the impact can vary depending on the specific cancer and fasting protocol.

 Overview of how IF affects tumor growth in different cancers:

Breast Cancer

IF has demonstrated significant potential in reducing tumor growth and progression in breast cancer. It lowers insulin-like growth factor 1 (IGF-1) levels, which are associated with cancer cell proliferation. This reduction in IGF-1 enhances the efficacy of breast cancer treatments by making cancer cells more susceptible to apoptosis1.

Hepatocellular Carcinoma

In hepatocellular carcinoma, IF has been shown to prime the tumor microenvironment, enhancing the delivery and effectiveness of nanomedicine. Fasting improved vascular normalization and increased the permeability of tumor blood vessels, allowing for more efficient delivery of therapeutic agents1.

Leukemia

IF has shown promising results in B cell and T cell acute lymphoblastic leukemia. Through the regulation of the leptin receptor via the protein PR/SET domain 1 (PRDM1), fasting can suppress and potentially reverse the course of these types of leukemia4.

Colon and Prostate Cancer

IF has been associated with a reduction in IGF-1 levels, which is particularly relevant for colon and prostate cancers. Increased IGF-1 levels are attributed to these cancers due to suppressed apoptosis, boosted cell proliferation, and genetic instability4.

Intermittent Fasting and Cancer Metabolism:   A Four-Part Series

 Intermittent fasting (IF) has emerged as a promising dietary intervention in cancer prevention and treatment. Recent studies have shed light on the potential mechanisms by which IF may influence cancer progression and therapy outcomes.

The OutSmart Cancer® System recommends intermittent fasting for 13 hours of calorie restriction per 24 hour cycle with the appropriate assessment, monitoring and guidance of a health care provider.

PART 1 Intermittent Fasting: Mechanisms of Action

IF has been shown to modulate several key pathways involved in cancer biology:

1. Metabolic Regulation: IF can reduce circulating levels of insulin-like growth factor 1 (IGF-1), which is associated with cancer cell proliferation1. This reduction may enhance the efficacy of cancer treatments by making cancer cells more susceptible to apoptosis.
2. Autophagy Enhancement: IF induces autophagy, a cellular “housekeeping” mechanism that can selectively target and destroy cancer cells4. This process may improve the effectiveness of anticancer therapies.
3. Immune System Modulation: Fasting periods can increase the activity of natural killer (NK) cells and cytotoxic T lymphocytes, enhancing the immune response against tumors1.
4. Oxidative Stress Reduction: IF has been observed to decrease levels of proinflammatory cytokines and increase anti-inflammatory markers, creating a less favorable environment for cancer progression1.

General Tumor Growth Inhibition

Across various cancer types, IF has been observed to:

1. Alter energy metabolism of tumor cells, inhibiting their growth2.
2. Enhance antitumor immune responses2.
3. Increase cancer sensitivity to chemotherapy and radiotherapy2.
4. Reduce glucose levels in the blood, making it harder for glucose-dependent cancers to grow6.

Mechanisms of Action

The impact of IF on tumor growth is mediated through several mechanisms:

• Metabolic Switch: IF induces a state of ketosis, which can be detrimental to cancer cells that rely heavily on glucose for rapid proliferation1.
• Immune System Enhancement: Fasting increases the activity of natural killer (NK) cells and cytotoxic T lymphocytes, improving the immune response against tumors1.
• Oxidative Stress: IF can increase reactive oxygen species (ROS) in cancer cells while decreasing their antioxidant defenses, leading to increased oxidative stress and enhanced chemotherapeutic action4.
• Signaling Pathway Modulation: IF affects the IGF-1/mTOR signaling pathway, which is known to influence cancer etiology4.

Is there a safe level of alcohol consumption?

In January of 2025, the US surgeon general issued a report warning that alcohol is associated with multiple cancers.

 More than half of Americans are unaware of the link between alcohol consumption and cancer.  This includes many health care providers.  There is still an outdated belief that a moderate amount of red wine is beneficial to cardiovascular health and has additional health benefits.  The link between the benefit of alcohol to cardiovascular disease is also becoming controversial in light of more recent evidence.

 I would challenge this view and state that an abundance of phytophenols and stilbenes, including resveratrol found in red wine are the source of any benefit, not the alcohol, which is a known hepatotoxin, neurotoxin, cardiotoxin, endocrine disruptor, and carcinogen. 

 An abundance of plant pigment-derived compounds are the good actors in red wine, providing a rich source of antioxidants and phytochemicals with positive epigenetic health effects that can be readily consumed in many other healthier sources in fruits and vegetables and botanical medicines without the accompanying risk factors of alcohol consumption. 

While alcohol, like tobacco, has been a socially acceptable and even medically acceptable social intoxicant, “alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimizes health loss is zero. The widely held view of the health benefits of alcohol needs revising.”.

 In other words, there is no safe level of alcohol consumption.  All levels of alcohol consumption come with significant risk factors.

Which cancers are linked to alcohol consumption

“Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.”

 

How does alcohol cause damage?

o   Metabolic by products bind to DNA, damaging cells and fueling tumors

o   Dysregulation of hormonal metabolism of estrogen

o   Acts as a solvent for other environmental toxins increasing toxic exposure

o   Increases inflammation

While some believe that the social aspects of alcohol consumption contribute to health and longevity, as noted in the super healthy long lived Blue Zone cultures where alcohol is part of a way of life, there is a growing interest in non-alcoholic designer beverages  that serve the same social and celebratory function.   In fact, one can toast with a glass of sparkling water with a splash of flavor added for conviviality and connection.

As many cancer treatments can damage heart function, I also recommend limiting alcohol intake to patients who have been treated with doxorubicin which damages the myocardium and to those patients with have arrythmia for which alcohol increases dysregulation.

I do advise all patients to avoid alcohol use as it is a known carcinogen.  And if this is not something they wish to adopt as a way of lifelong term, I recommend that they refrain from alcohol use if they have known body burden of cancer, during cancer treatment and strictly for the first 2 years after completing cancer treatment.  This is the period when recurrence is most common.   I also recommend, if abstinence is not an option, that they limit alcohol intake to one glass a few times a year at a wedding or holiday celebration.  

 OutSmart Cancer patients are highly motivated to do everything that they can to contribute to a good outcome.  In this patient population, particularly those patients who are looking for a health outcome and a health model, implementing the OutSmart Cancer® System starting with the OutSmart Cancer® Diet guidelines can be a reasonable first step and foundation to Getting Well, Staying Well and Living Well Beyond Cancer and to Creating a Body Where Cancer Cannot Thrive.

 

Selected References

(1)   Griswold, Max G et al. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 The Lancet, Volume 392, Issue 10152, 1015 – 1035

(2)   Alcohol and Cancer Risk 2025, Report of US Surgeon General Alcohol and Cancer Risk 2025. Report of US Surgeon General  https://www.hhs.gov/surgeongeneral/priorities/alcohol-cancer/index.htmlchrextension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.hhs.gov/sites/default/files/oash-alcohol-cancer-risk.pdf

(3)   https://peterattiamd.com/alchohol-intake-and-cardiovascular-disease-risk/

(4)   Biddinger KJ, Emdin CA, Haas ME, et al. Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Netw Open. 2022;5(3):e223849. doi:10.1001/jamanetworkopen.2022.3849

(5)   Bagnardi, V., Rota, M., Botteri, E. et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose–response meta-analysis. Br J Cancer 112, 580–593 (2015). https://doi.org/10.1038/bjc.2014.579

(6)   Di Credico, G., Polesel, J., Dal Maso, L. et al. Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration. Br J Cancer 123, 1456–1463 (2020). https://doi.org/10.1038/s41416-020-01031-z

(7)   https://www.bluezones.com/2018/09/new-study-says-theres-no-safe-level-of-alcohol/

(8)   CDC Alcohol Use and Your Health https://www.cdc.gov/alcohol/index.html

(9)   https://www.nytimes.com/wirecutter/reviews/best-non-alcoholic-drinks/

(10)Dulf PL, Mocan M, Coadă CA, Dulf DV, Moldovan R, Baldea I, Farcas AD, Blendea D, Filip AG. Doxorubicin-induced acute cardiotoxicity is associated with increased oxidative stress, autophagy, and inflammation in a murine model. Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun;396(6):1105-1115. doi: 10.1007/s00210-023-02382-z. Epub 2023 Jan 16. PMID: 36645429; PMCID: PMC10185623.

 (11)Steven K Clinton, Edward L Giovannucci, Stephen D Hursting,
The World Cancer Research Fund/American Institute for Cancer Research Third Expert Report on Diet, Nutrition, Physical Activity, and Cancer: Impact and Future Directions, The Journal of Nutrition, Volume 150, Issue 4,2020, https://doi.org/10.1093/jn/nxz268

Approximately 20% of all patients who die of lung cancer in the US are non-smokers.  Cases of lung cancer in non-smokers are on the rise.  While a history of smoking is the primary cause of lung cancer, 10-20% of all lung cancer diagnoses occur in non-smokers or in people who have smoked less than 100 cigarettes in their lifetimes.

• Take a Thorough Toxic Exposures History
• Identify Environmental Risk Factors for Lung Cancer in Non-Smokers
• Nutriceutical and Botanical Interventions
•               Support Healthy Lung Structure and Function
•               Enhance Cancer Immunity
• Employ Appropriate Lung Cancer Screening
• Recognize Signs and Symptoms of Lung Cancer
• Apply The OutSmart Cancer System

Include a comprehensive history of known toxic exposures

at home, work, medical treatments and travel over the lifetime of your patient as part of a thorough intake and assessment.

Identify Environmental Risk Factors for Lung Cancer in Non-Smokers include exposures to

 Radon Gas: an invisible odorless gas that may concentrate inside homes in areas where there is a naturally high level of uranium in the soil. The Environmental Protection Agency publishes a guide to testing and reducing radon gas at home. Radon gas gives off radioactive particles that can damage genetic material in  the lung epithelia increasing risk of lung cancer.  1 in 15 homes in the US may have unsafe levels of radon gas.

 Secondhand Smoke is environmental tobacco smoke from cigarettes, pipes and cigars containing nicotine and carcinogens.  There is no safe level of exposure for secondhand smoke. 20-30% of lung cancers in non-smokers are linked to exposure to secondhand smoke.

 Carcinogens in the workplace include asbestos, heavy metals, nickel, cadmium, beryllium, arsenic, uranium, diesel exhaust and coal fumes.  There is a higher rate of lung cancer among gas station attendants, bus and truck drivers and hairdressers. Firefighters are exposed to a wide range of toxic chemicals and fumes from burning materials.

 Air pollution: Twenty nine percent of lung cancer deaths can be attributed to air pollution which is more prevalent in urban environments, automobile plants, oil refineries,  dry cleaning plants and around construction sites and wood-burning stoves.  Some artists may work with paints and materials that contain heavy metals and use volatile solvents and glues in their work.

 Gene Mutation and Family History of a first degree relative or multiple family members a family member diagnosed at a young age increase risk.  Eight percent of lung cancers are linked to genetic mutations.

 Nutriceutical and Botanical Interventions

• Support healthy Lung Structure and Function
• Enhance Cancer Immunity 

Vitamin A deficiency is linked to histopathological changes to the pulmonary epithelial lining.  Vitamin A deficiency during pregnancy leads to compromised lung development in the fetus.   Chronic Vitamin A deficiency is a common problem in many parts of the world.

Vitamin A plays a main role in regulating antioxidant defences, cell growth and differentiation. Consequently, numerous studies have focused on the association between vitamin A and various types of cancer (1, 2)

 Recommended dose of Vitamin A as retinol : 1500-3000mcg per day. This is a conservative dose.  Higher doses can be administered when tracking serum levels to achieve optimum but not excessive levels.

 Serum Zinc levels and Zinc: Copper ratios are inversely related to lung cancer risk as well as resistance to respiratory infections. (3).  Zinc supplementation has been shown to induce apoptosis and enhance anti-tumor efficacy of chemotherapy agents in the treatment of lung cancer (4)

Recommended Dose of Zinc chelate: 30mg three times per day

The Chinese herb Astragalus is widely used as a lung tonic and for promoting lung immunity and cancer immunity in traditional and modern Chinese Medicine and has been shown to enhance survival and reduce mortality from lung cancer.  (5) Astragalus may contraindicated with concurrent use of immunotherapy treatments with  PD-1 and PDL-1 inhibitors due to its immune stimulating effects and may exacerbate adverse effects of immunotherapy treatment. Caution is advised.

Recommended dose of Astragalus root (available in capsules and granules) 1000-2000mg 3x per day.

 Lung cancer is the leading cause of cancer related deaths in the US.  Lung cancer accounts for more deaths than breast cancer, colorectal cancer and prostate cancer combined.  These four cancers are the most prevalent cancers in the US. However, we have active screening and more effective treatments and more long term survival with breast, prostate and colorectal cancers than with lung cancer.  We do not have any regular screening programs for lung cancer and less success with treatment and survival.  Lung cancer is usually a lethal cancer.  Early detection is crucial.

Screening for detection of lung cancer includes high radiation exposure from CT scans which carries its own inherent risks.  Screening is typically done only in high-risk individuals.   There is now the option of a new MRI technology that can identify lung cancer without the use of radioactive gadolinium.   As this technology becomes more widely available and more cost effective, it may come into wider use and lead to earlier diagnosis and better outcomes.   Currently this MRI technology is provided by Prenuvo (prenuvo.com) in several cities in the US. The five-year survival rate for lung cancer caught at stage 1 is 65% vs. 5% for those diagnosed at Stage 4 I recommend making use of  Prenuvo MRI technology for lower risk radiation free screening for early detection.

 Signs and Symptoms of Lung Cancer

• A cough that doesn’t go away or gets worse over time
• Coughing up blood
• Chest pain or discomfort
• Trouble breathing
• Wheezing
• Hoarseness
• Loss of appetite
• Weight loss for no reason
• Fatigue
• Trouble swallowing
• Swelling in the face and/or the neck
• Recurrent lung infections, including pneumonia

 The OutSmart Cancer® System is a health model for creating a body where cancer cannot thrive.  The OutSmart Cancer® System includes the promotion of robust health and enhanced cancer immunity through the OutSmart Cancer® Diet, OutSmart Cancer® Nutriceutical and Phytochemical Supplements and OutSmart Cancer® Lifestyle and Self Care Guidelines.

Every cancer patient deserves a plan for their health

and not just a plan for their disease.

 Selected references:

1. Herzog R., Cunningham-Rundles S. Immunologic impact of nutrient depletion in chronic obstructive pulmonary disease. Curr. Drug Targets. 2011;12:489–500. doi: 10.2174/138945011794751500

 2. Yu N., Su X., Wang Z., Dai B., Kang J. Association of dietary vitamin A and β-carotene intake with the risk of lung cancer: A meta-analysis of 19 publications. Nutrients. 2015;7:9309–9324. doi: 10.3390/nu7115463

3. Wang, Y., Sun, Z., Li, A. et al. Association between serum zinc levels and lung cancer: a meta-analysis of observational studies. World J Surg Onc 17, 78 (2019). https://doi.org/10.1186/s12957-019-1617-5

4. Kocdor H, Ates H, Aydin S, Cehreli R, Soyarat F, Kemanli P, Harmanci D, Cengiz H, Kocdor MA. Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer. Drug Des Devel Ther. 2015 Jul 27;9:3899-909. doi: 10.2147/DDDT.S87662. PMID: 26251569; PMCID: PMC4524380.

5. Dugoua JJ, Wu P, Seely D, Eyawo O, Mills E. Astragalus-containing Chinese herbal combinations for advanced non-small-cell lung cancer: a meta-analysis of 65 clinical trials enrolling 4751 patients. Lung Cancer (Auckl). 2010 Jul 8;1:85-100. doi: 10.2147/lctt.s7780. PMID: 28210109; PMCID: PMC5312465.