Researched and written by Keith Bishop, Clinical Nutritionist, Cancer Coach, Retired Pharmacist, and founder of Prevail Over Cancer.
Acidic Terrain: How pH Influences Cancer Risk and Progression
Cancer doesn’t grow in a vacuum—it thrives in environments shaped by metabolism, inflammation, and cellular stress. One of the most overlooked yet critical factors? pH balance. While blood pH is tightly regulated between 7.35 and 7.45, other body compartments, including the tumor microenvironment, can become significantly more acidic. This shift isn’t just a biochemical quirk; it may actively promote cancer growth, immune evasion, and treatment resistance.
Acidic Microenvironments and Cancer Progression
Cancer cells often rely on aerobic glycolysis (the Warburg effect), producing lactic acid even in the presence of oxygen. This leads to a localized drop in extracellular pH, often reaching 6.5–6.9 in solid tumors.[i] Acidic conditions:
In a pan-cancer single-cell RNA-seq study, researchers found that acidic tumor niches were associated with stress-response gene modules and immune evasion signatures across multiple cancer types.[iii]
Tumor acidosis in tumors favors cell metabolism, assists tumor growth, and allows the cells to adapt to stress.[iv]
pH Across Body Compartments
Here’s how pH varies across the body:[v]
Compartment |
Typical pH Range |
Notes |
Blood |
7.35–7.45 |
Tightly regulated |
Cytosol (intracellular) |
~7.2 |
Slightly acidic due to metabolism |
Lysosomes |
4.5–5.0 |
Required for enzymatic digestion |
Stomach |
1.5–3.5 |
Protein breakdown and microbial defense |
Small intestine |
6.0–7.4 |
Neutralized by pancreatic bicarbonate |
Skin |
4.5–5.5 |
The acid mantle protects against pathogens |
Vaginal canal |
3.8–4.5 |
Maintains microbial balance |
Urine |
4.5–8.0 |
Reflects systemic acid-base status |
Saliva |
6.2–7.6 |
Influenced by hydration, diet, and stress |
Tumor microenvironment |
6.5–6.9 |
Acidic due to glycolysis and poor perfusion |
Urine and Saliva: Windows into Systemic pH
While blood pH remains stable, urine and saliva pH fluctuate based on diet, stress, hydration, and metabolic load. These fluids offer non-invasive clues about systemic acid-base balance and may reflect the biochemical terrain that tumors inhabit.
A recent review in Nature Reviews Urology emphasized that urine, in direct contact with bladder tumors, can carry transcriptomic and epigenetic signals of tumor biology.[vi] Though not diagnostic on their own, alkaline urine may correlate with better outcomes, especially in observational studies tracking metabolic health and cancer recurrence.
Observational Insights: Alkaline Urine and Outcomes
An observational framework published in the British Journal of Cancer explored real-world data from multiple oncology centers. One study arm noted that patients with more alkaline urine profiles had lower recurrence rates and better immune profiles, though causality remains unproven.[vii] These findings support the idea that acid-base balance may influence cancer biology, but also highlight the need for controlled trials.
An observational study of people with liver cancer found that a urine pH > 7.0 tended to live twice as long as people with a uinre pH < 7.0.[viii]
pH Regulators (NHE-1) and Cancer Survival
Researchers also found that targeting pH regulators (e.g., NHE-1) helps disrupt cancer cell survival.[ix] [x] Mild alkalosis enhances NHE1 activity in normal cells but inhibits its activity in cancer cells.[xi]
There is also an observational link between higher urine pH and better outcomes in people with breast cancer, pancreatic cancer, and Non-Small-Cell Lung Cancer. [xii]
Alkalinizing Agents Enhance Immunotherapy by Shifting Tumor pH
A 2021 study published in Biological and Pharmaceutical Bulletin demonstrated that oral alkalinizing agents like sodium bicarbonate and potassium-sodium citrate can raise the extracellular pH of tumors, improving the effectiveness of anti-PD-1 immunotherapy in a murine melanoma model. Researchers found that increased serum bicarbonate levels correlated with higher urinary pH and enhanced antitumor responses. This suggests that systemic alkalization may influence the tumor microenvironment, making it less hostile to immune cells and more responsive to checkpoint inhibitors. The study highlights a potential role for urinary pH as a non-invasive biomarker to monitor terrain shifts and predict immunotherapy outcomes.[xiii]
Context Matters: pH Is Just One Piece of the Puzzle
Alkalizing the body is not a standalone cancer cure. pH modulation must be integrated into a broader strategy that includes:
The terrain theory—popularized by Claude Bernard and later revisited in integrative oncology—suggests that the biological “soil” matters as much as the “seed.” pH is one marker of that soil’s health.[xiv]
Food and Supplement Synergy Table
Item |
Mechanism |
pH Impact |
Cancer-Relevant Benefit |
Leafy greens |
Rich in magnesium and potassium |
Alkalizing |
Anti-inflammatory, antioxidant, supports detox enzymes |
Lemon water |
Citrate metabolism (alkaline ash effect) |
Alkalizing (post-metabolically) |
Enhances liver detox pathways, supports hydration |
Magnesium citrate |
Buffers acidity via bicarbonate interaction |
Alkalizing |
Supports mitochondrial function, reduces oxidative stress |
Baking soda (supervised) |
Direct bicarbonate buffer |
Strong alkalizing effect |
May reduce tumor acidity, enhances immune cell viability |
Cucumber |
High water content and alkaline minerals |
Mildly alkalizing |
Hydrating, supports lymphatic flow and detoxification |
Avocado |
Rich in potassium and glutathione precursors |
Alkalizing |
Antioxidant, supports cellular repair and immune modulation |
Chlorella or spirulina |
Dense in magnesium, chlorophyll, and amino acids |
Alkalizing |
Supports detox, immune activation, and terrain resilience |
Potassium bicarbonate (clinical use) |
Direct buffering agent |
Alkalizing |
May support systemic pH balance and reduce tumor acidity |
Bone broth (vegetable-based) |
Rich in minerals and amino acids |
Mildly alkalizing |
Gut healing, supports mineral absorption, and terrain repair |
Pairing Alkalizing Foods with Supplement Protocols for Cancer Terrain Optimization
Why This Matters
The tumor microenvironment often becomes acidic due to glycolytic metabolism and poor perfusion. This acidity suppresses immune function, promotes invasion, and reduces treatment efficacy. Pairing alkalizing foods with targeted supplements can help buffer systemic and local pH, support mitochondrial health, and enhance immune resilience.
Food + Supplement Pairings
Food |
Supplement |
Synergistic Mechanism |
Terrain Benefit |
Leafy greens (spinach, kale, chard) |
Magnesium citrate or glycinate |
Magnesium supports ATP production and buffers acidity; greens provide potassium and chlorophyll |
Anti-inflammatory, mitochondrial support |
Lemon water (morning or pre-meal) |
Potassium or Sodium bicarbonate (under supervision) |
Citrate metabolism yields alkaline ash; potassium bicarbonate buffers extracellular pH |
Enhances detox, supports systemic alkalinity |
Cucumber, celery, zucchini |
Electrolyte blend (Mg, K, Na) |
Hydrating foods pair with minerals to support renal clearance and acid-base balance |
Lymphatic flow, hydration, renal terrain support |
Avocado |
Glutathione precursors (alpha-lipoic acid) |
Avocado provides potassium and lipid cofactors; supplements support redox and detox systems |
Cellular repair, antioxidant defense |
Chlorella or spirulina |
Trace mineral complex (zinc, selenium, iodine) |
Algae provide magnesium and chlorophyll; minerals support enzymatic buffering and immunity |
Immune modulation, terrain resilience |
Vegetable-based bone broth |
Digestive enzymes or bitters |
Broth provides minerals and amino acids; enzymes enhance absorption and buffering potential |
Gut integrity, mineral uptake |
🧪 Timing & Integration Tips
Monitoring & Feedback
🧠 Clinical Caveats
Urine and Saliva pH Cancer - Final Thoughts
Monitoring urine and saliva pH can offer practical, low-cost insights into systemic terrain. When paired with evidence-based interventions, it becomes a tool for empowerment—not oversimplification. Acidic microenvironments favor cancer, but shifting the terrain requires a multidimensional approach.
Next Steps
Reference Sources
[i] Hamaguchi R, Isowa M, Narui R, Morikawa H, Okamoto T, Wada H. How Does Cancer Occur? How Should It Be Treated? Treatment from the Perspective of Alkalization Therapy Based on Science-Based Medicine. Biomedicines. 2024; 12(10):2197. https://doi.org/10.3390/biomedicines12102197
[ii] Bogdanov, A., Bogdanov, A., Chubenko, V., Volkov, N., Moiseenko, F., & Moiseyenko, V. (2022). Tumor acidity: From hallmark of cancer to target of treatment. Frontiers in Oncology, 12, 979154. https://doi.org/10.3389/fonc.2022.979154
[iii] GEO Accession viewer. Nih.gov. Published 2024. Accessed October 10, 2025. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203612
[iv] Groessl S, Kalis R, Snaebjornsson MT, et al. Acidosis orchestrates adaptations of energy metabolism in tumors. Science. 2025;390(6769). doi: https://doi.org/10.1126/science.adp7603
[v] Hall JE, Hall ME. Guyton, and Hall Textbook of Medical Physiology. 14th edition. Published in 2021. https://books.google.com/books?hl=en&lr=&id=H1rrDwAAQBAJ&oi=fnd&pg=PP1&dq=Hall+JE,+Hall+ME.+Guyton,+and+Hall+Textbook+of+Medical+Physiology.+14th+edition.+Published+in+2021.&ots=tK1ut2Ct2p&sig=yShlCEXuhr6ee2UksGt4fj_DCrc#v=onepage&q&f=false
[vi] Maas, M., Todenhöfer, T., & Black, P. C. (2023). Urine biomarkers in bladder cancer — Current status and future perspectives. Nature Reviews Urology, 20(10), 597-614. https://doi.org/10.1038/s41585-023-00773-8
[vii] Barghout, S. H., Meti, N., Chotai, S., Kim, C. J., Patel, D., Brown, M. C., Hueniken, K., Zhan, L. J., Raptis, S., Deutschman, C., Grant, B., Pienkowski, M., Moriarty, P., De Almeida, J., Goldstein, D. P., Bratman, S. V., Shepherd, F. A., Tsao, M. S., Freedman, A. N., . . . Liu, G. (2025). Adaptive Universal Principles for Real-world Observational Studies (AUPROS): An approach to designing real-world observational studies for clinical, epidemiologic, and precision oncology research. British Journal of Cancer, 132(2), 139-153. https://doi.org/10.1038/s41416-024-02899-x
[viii] Isowa, M., Hamaguchi, R., Narui, R., Morikawa, H., & Wada, H. (2023). Effects of alkalization therapy on hepatocellular carcinoma: A retrospective study. Frontiers in Oncology, 13, 1179049. https://doi.org/10.3389/fonc.2023.1179049
[ix] Hu, Y., Lou, J., Jin, Z., Yang, X., Shan, W., Du, Q. ... Xie, R. (2021). Advances in research on the regulatory mechanism of NHE1 in tumors (Review). Oncology Letters, 21, 273. https://doi.org/10.3892/ol.2021.12534
[x] Schammim R. Amith, Larry Fliegel; Regulation of the Na+/H+ Exchanger (NHE1) in Breast Cancer Metastasis. Cancer Res 15 February 2013; 73 (4): 1259–1264. https://doi.org/10.1158/0008-5472.CAN-12-4031
[xi] Celi AB, Mechali A, Beltramone N, et al. Targeting pH Regulation in Cancer: Combined Mild Alkalosis and NHE1 Inhibition as a Potential Therapy for Clear Cell Renal Cell Carcinoma. Published online February 13, 2025. doi: https://doi.org/10.21203/rs.3.rs-5875263/v1
[xii] Kachi, S., Hamaguchi, R., Narui, R., Morikawa, H., Okamoto, T., & Wada, H. (2025). Cancer can be suppressed by alkalizing the tumor microenvironment: the effectiveness of “alkalization therapy” in cancer treatment. Oncologie, 27(3), 393-401. https://www.degruyterbrill.com/document/doi/10.1515/oncologie-2024-0673/html
[xiii] Ando H, Emam SE, Kawaguchi Y, et al. Increasing Tumor Extracellular pH by an Oral Alkalinizing Agent Improves Antitumor Responses of Anti-PD-1 Antibody: Implication of Relationships between Serum Bicarbonate Concentrations, Urinary pH, and Therapeutic Outcomes. Biological and Pharmaceutical Bulletin. 2021;44(6):844-852. doi: https://doi.org/10.1248/bpb.b21-00076
[xiv] Robin ED. Claude Bernard. JAMA. 1979;242(12):1283. doi: https://doi.org/10.1001/jama.1979.03300120037021