As whole person care providers we must seek to understand our cancer patients’ ache of feeling physically or psychologically separated from loved ones, the toll of feeling unseen, unheard, or misunderstood. These wounds—of isolation, loneliness, and disconnection—are real; they affect the body/mind and spirit as profoundly as cancer treatments.  Today's research offers compelling evidence, and more importantly, meaningful tools we can use together to heal not just cancer, but its hidden burden: social isolation.

1. Why This Matters

A. Social Isolation Impacts Outcomes

• A major 2023 meta-analysis of 90 longitudinal studies found that social isolation increased all-cause mortality by 32%, and specifically elevated cancer-related death by 24% (HR 1.24; 95% CI 1.19–1.28) acsjournals.onlinelibrary.wiley.com+3nature.com+3pubmed.ncbi.nlm.nih.gov+3.

• For breast cancer survivors, being isolated increased recurrence risk by 43%, and their cancer-specific mortality by 64%oncologynurseadvisor.com.

B. Loneliness Deeply Affects the Mind

• In survivors aged ≥50, those with high loneliness faced a 67% higher risk of death compared to those with minimal lonelinessfrontiersin.org+15oncologynurseadvisor.com+15jnccn.org+15.

• Patients often fall silent under stress: fear of burdening others, the stigma of visible illness, or shame around changes in identity or body image. Studies link isolation with anxiety, depression, poor sleep, and negative self-image.

C. Biology & Behavior—How Isolation Impacts Health

• Isolation intensifies inflammation, suppresses immune surveillance, and dysregulates cortisol and autonomic balance—all biologic stressors that may fuel tumor growth and impair treatment response.

• Behaviorally, isolated patients are more likely to skip appointments, neglect medications, eat poorly, and withdraw from activity—all of which undermine recovery.

2. Caring Steps : Talk to Patients, Make Referrals

In my practice, I see four essential elements:

A. Gentle Screening

At key moments—diagnosis, treatment transitions, and follow-up—I ask open questions:

• “How connected have you felt lately?”

• “Do you often wish for someone to talk to?”
  Using brief tools like the UCLA Loneliness Scale or a simple social network check, I watch for signals that isolation may be causing you avoidable pain.

B. Compassionate Listening + Referrals

If loneliness is weighing on you, I invite you to share what’s behind it. Then:

• Connect patients with  oncology social work team.

• Refer  to psycho-oncology counselors skilled in therapies like CBT or Mindfulness-Based Stress Reduction—both shown to reduce loneliness and psychological distress.

C. Peer Connection

• In-person peer groups (especially helpful for breast, colorectal, or lung cancer survivors) reduce anxiety, restore hope, and ease isolation.

• Online communities and forums can connect patients with people who truly understand; they offer emotional reinforcement and practical tips, and studies show they boost treatment adherence and well-being.

• Buddy systems or livestream peer meetups: simple but powerful — just a 30-minute weekly check-in can build resilience and normalize your experience.

D. Tailored Lifestyle & Community Integration

• Encourage gentle group exercise (yoga, walking groups), which supports physical function and elevates moodverywellhealth.com.

• Partner with local nonprofits—Cancer Support Community, Lance Armstrong Foundation, or metastatic breast cancer groups—to link you with trusted activities and meaningful companionship.

• Promote spiritual or creative engagement—whether in nature, art, music, faith—to enhance connectedness and purpose.

3. A Compassionate Clinical Blueprint for Care Givers and Patients

Step	What I Do	What You Do	Why It Matters
1️⃣ Screen	Start the conversation with caring assessment	Be honest about how you're feeling	So I can see and not overlook your need
2️⃣ Listen & Refer	Provide support and arrange referrals	Attend support sessions or therapy	To reconnect you to someone who understands
3️⃣ Engage Peer Support	Introduce you to peer groups and online communities	Join at least one group or buddy partnership	Shared stories can heal isolation
4️⃣ Promote Activity & Community	Prescribe gentle group activity; connect with local resources	Try a new group or routine weekly	Movement + community = nourishment
5️⃣ Monitor & Adapt	Re-check loneliness and mental health periodically	Share back what’s working and what's hard	To fine-tune your support over time

4. A Story of Connection

Meet “Maria,” age 60, recovering from colorectal cancer surgery.
At first, she was stoic and quiet about her isolation. Gentle questions revealed she felt she “had no one who really gets it.” I referred Maria to a psychotherapist skilled in CBT and to a local colorectal cancer peer support group. Over weeks, she began a low-impact walking class with fellow survivors and joined an online forum. Her mood lifted. She slept better, showed up for her follow ups on time, and started gardening again—something she loved before. Three months later, she told me: “I thought I was alone in this fight. Now I know I’m not.”

5. What the Research Tells Us

• Moderate-to-severe loneliness in survivors aged 50+ increases mortality by nearly 70%health.compmc.ncbi.nlm.nih.gov+6verywellhealth.com+6acsjournals.onlinelibrary.wiley.com+6health.com+2time.com+2verywellhealth.com+2jnccn.orgen.wikipedia.org+2oncologynurseadvisor.com+2nature.com+2.

• Group-based peer support lowers anxiety, depression, and improves hope and copingojrd.biomedcentral.com.

• Therapies like CBT and mindfulness significantly reduce loneliness and emotional distress.

• Online communities reinforce connection, enhance adherence, and provide emotional and informational supporten.wikipedia.org.

6. Let Patients Know How They Can Take Action  

1. Reach out. Tell me or a member of your care team when you’re feeling alone.
2. Accept help. Let others in—whether it's family, peers, or professionals.
3. Stay in motion. Join gentle group exercise or activity-based support.
4. Log in. Explore online groups that feel safe, moderated, and aligned with your needs.
5. Give Feedback. Check in during follow-ups: Is this working? What needs adjusting?

7. Final Reflections: Connect, Comfort, Inspire

Together, we can do more than treat cancer. We can heal loneliness, restore hope, and rebuild a sense of connecting and belonging—step by step, day by day.

Cancer is a journey, and the lonely road is much harder to walk. The science shows that isolation isn’t just painful—it’s dangerous. But the good news is that connection, community, and compassion change outcomes. They lower stress, boost immunity, improve adherence, and may even help prevent recurrence.

As your physician, I care about your scans—and your soul. I see your strength, but also the hard days. I’m here with you—not just in the clinic, but in calling in help, helping you rebuild your social world, and walking this path together.

References

1. 1. Wang F, Gao Y, Han Z, et al. A systematic review and meta-analysis of 90 cohort studies of social isolation, loneliness and mortality. Nat Hum Behav. 2023;7(8):1307‑1319. doi:10.1038/s41562-023-01617-6 academic.oup.comen.wikipedia.org+7nature.com+7ideas.repec.org+7
2. 2. Holt‑Lunstad J, Smith TB, Layton JB. Social relationships and mortality risk: a meta-analytic review. JAMA Netw Open. 2023;6(1):e236921. doi:10.1001/jamanetworkopen.2023.6921 en.wikipedia.org+1en.wikipedia.org+1
3. 3. Oncology Nurse Advisor. Loneliness and isolation for cancer patients: risk and interventions. Oncology Nurse Advisor. 2025. bps.org.uk+4oncologynurseadvisor.com+4academic.oup.com+4
4. 4. Cancer Phys Outcomes; retrospective longitudinal study of 3447 cancer survivors aged ≥50 found those with highest loneliness had HR = 1.67 for mortality. Oncology Nurse Advisor. 2024. thetimes.co.uk+2oncologynurseadvisor.com+2pressroom.cancer.org+2
5. 5. Medical News Today. Social isolation, loneliness may raise mortality risk, study finds. Med News Today. 2023. sciencedirect.com+15medicalnewstoday.com+15jamanetwork.com+15
6. 6. Nature. Loneliness among adult cancer survivors in the United States; estimated 35.9% experienced moderate-severe loneliness. Sci Rep. 2025;14:85126. nature.com
7. 7. Mediation analysis study: social isolation–cancer mortality link is 74% mediated by health behavior. Health Psychol. 2021;40(1):e1‑e10. sciencedirect.com+1researchgate.net+1

 

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:

[Read More]

• 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