Bicarbonate's cancer-suppressing properties.

Sodium bicarbonate, also known as baking soda, is a crystalline salt made up of sodium and bicarbonate ions. 

Excess hydrogen ions in a solution e.g. the blood, make it acidic, lowering the pH. When there's an excess of H⁺ ions, such as after metabolic processes (e.g. aerobic glycolysis) that produce acids (e.g., lactic acid), the bicarbonate ions (HCO₃⁻) act as a base, neutralizing excess protons by combining with them. This reduces the concentration of free H⁺ in the blood, effectively raising the pH (making the blood more alkaline). 

Since pH is a logarithmic measure of hydrogen ion concentration, even small changes in H⁺ levels can significantly affect pH.

Oral bicarbonate administration may help:

Neutralize the acid produced by tumors.
Impair cancer cell metabolism by interfering with the acidic microenvironment they rely on for energy production and growth.
Restore normal function to immune cells in the tumor microenvironment, which are often suppressed by acidity.


Dosage: 2.5 grams every 2 hours, 6 or 7 times a day (or 3 times 5 grams) for 7 to 10 days.  



  • Effects of Alkalization Therapy on Chemotherapy Outcomes in Metastatic or Recurrent Pancreatic Cancer:
Twenty-eight patients with metastatic or recurrent pancreatic cancer were assessed in this study. Alkalization therapy consisted of an alkaline diet with supplementary oral sodium bicarbonate (3.0-5.0 g/day). Results: The mean urine pH was significantly higher after the alkalization therapy (6.85±0.74 vs. 6.39±0.92; p<0.05). The median overall survival from the start of alkalization therapy of the patients with high urine pH (>7.0) was significantly longer than those with low urine pH (≤ 7.0) (16.1 vs. 4.7 months; p<0.05). link to study

 

" Here, we show that oral NaHCO(3) selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer. This treatment regimen was shown to significantly increase the extracellular pH, but not the intracellular pH, of tumors by (31)P magnetic resonance spectroscopy and the export of acid from growing tumors by fluorescence microscopy of tumors grown in window chambers. NaHCO(3) therapy also reduced the rate of lymph node involvement, yet did not affect the levels of circulating tumor cells, suggesting that reduced organ metastases were not due to increased intravasation. In contrast, NaHCO(3) therapy significantly reduced the formation of hepatic metastases following intrasplenic injection, suggesting that it did inhibit extravasation and colonization. "

  • Bicarbonate has also been shown to increase the effectiveness of radiation therapy and to reduce side effects.

A case report: GL is a 79 year old man followed in the GU clinic at the Moffitt Cancer Center. He presented with hematuria in January 2004 and was found to have a large right renal cancer with clot extending into the inferior vena cava (stage T3b, N2, Mx). He underwent a nephrectomy with clot removal at the Moffitt Cancer Center in February, 2004. In June, 2005, he developed metastatic disease in his liver. He was treated with Sutent, but the tumor progressed with metastases developing in the subcutaneous tissues and retroperitoneal lymph nodes. He was unable to tolerate ALT-801. In September 2007 he elected to discontinue all conventional therapy and began a self-administered regimen of vitamins, supplements, and 3 “heaping tablespoons” of sodium bicarbonate in water per day (about 40 grams total). As of the date of this submission, he has maintained this therapy with no complications. His weight is stable. He walks 2 miles every day and had cataract surgery in March 2008 without complications. CT scans from Dec 5, 2007 and April 18, 2008 are shown in figure S3. These images are representative in that some of the liver lesions have increased in size, some have decreased, and some have remained stable. Interestingly, the tumors that were necrotic in the initial scan became much less so on the follow-up study. At the time of this submission (2009) the patient remains clinically well. {ref, see Supplementary Materials}.


International Society of Sports Nutrition position stand: sodium bicarbonate and exercise performance {ref}

"For single-dose supplementation protocols, 0.2 g/kg of sodium bicarbonate seems to be the minimum dose required to experience improvements in exercise performance. The optimal dose of sodium bicarbonate dose for ergogenic effects seems to be 0.3 g/kg. Higher doses (e.g., 0.4 or 0.5 g/kg) may not be required in single-dose supplementation protocols, because they do not provide additional benefits (compared with 0.3 g/kg) and are associated with a higher incidence and severity of adverse side-effects. 5. For single-dose supplementation protocols, the recommended timing of sodium bicarbonate ingestion is between 60 and 180 min before exercise or competition. 6. Multiple-day protocols of sodium bicarbonate supplementation can be effective in improving exercise performance. The duration of these protocols is generally between 3 and 7 days before the exercise test, and a total sodium bicarbonate dose of 0.4 or 0.5 g/kg per day produces ergogenic effects. The total daily dose is commonly divided into smaller doses, ingested at multiple points throughout the day (e.g., 0.1 to 0.2 g/kg of sodium bicarbonate consumed at breakfast, lunch, and dinner). The benefit of multiple-day protocols is that they could help reduce the risk of sodium bicarbonate-induced side-effects on the day of competition. 7. Long-term use of sodium bicarbonate (e.g., before every exercise training session) may enhance training adaptations, such as increased time to fatigue and power output. 8. The most common side-effects of sodium bicarbonate supplementation are bloating, nausea, vomiting, and abdominal pain. The incidence and severity of side-effects vary between and within individuals, but it is generally low. Nonetheless, these side-effects following sodium bicarbonate supplementation may negatively impact exercise performance. Ingesting sodium bicarbonate (i) in smaller doses (e.g., 0.2 g/kg or 0.3 g/kg), (ii) around 180 min before exercise or adjusting the timing according to individual responses to side-effects, (iii) alongside a high-carbohydrate meal, and (iv) in enteric-coated capsules are possible strategies to minimize the likelihood and severity of these side-effects. 9. Combining sodium bicarbonate with creatine or beta-alanine may produce additive effects on exercise performance."

Ammonia and bicarbonate: potential mechanisms underlying the benefits of alkali therapy in chronic kidney disease



Caution: Sodium bicarbonate taken in amounts that exceed the capacity of the kidneys to get rid of excess sodium may cause metabolic alkalosis. Do not exceed the maximum recommended dosage.

NaCl (Salt) → % Na (Sodium) = 39.3 %

NaHCO3 (Sodium Bicarbonate) → % Na (Sodium) = 27.4 %

1000mg or 1 gram of Salt contains 393mg Sodium.

1000mg of 1 gram of Sodium Bicarbonate contains 274mg of Sodium.

4 grams of Sodium Bicarbonate contain 1094mg of Sodium.

The Daily Value for sodium is less than 2,300 milligrams (mg) per day.

Americans eat on average about 3,400 mg of sodium per day.

According to the American Heart Association (AHA), the minimum physiological requirement for sodium is less than 500 mg a day.

Potassium bicarbonate can substitute for sodium bicarbonate to reduce sodium intake.


References and Sources

The Role of pH and Bicarbonate in Cancer


Intracellular vs. Extracellular pH in Cancer Cells

Normal cells maintain an intracellular pH (pHi) of around 7.2-7.4 and an extracellular pH (pHe) of 7.35-7.45. Cancer cells demonstrate a paradoxical pH gradient, with an elevated pHi (~7.4-7.6) and a more acidic pHe (~6.5-7.0). This shift is a hallmark of cancer, driven primarily by metabolic changes and the enhanced production of acidic metabolites like lactic acid, a byproduct of aerobic glycolysis (Warburg effect).

Cancer cells preserve a more alkaline pHi than normal cells by activating various acid-extruding mechanisms. These include:

Proton pumps and transporters, such as Na+/H+ exchangers (NHE) and monocarboxylate transporters (MCTs) responsible for exporting protons and lactic acid.
Carbonic anhydrases (CA IX and CA XII) catalyze the hydration of CO2 to bicarbonate (HCO3-) and protons (H+), helping buffer intracellular pH and contributing to extracellular acidification.

By maintaining an alkaline pHi, cancer cells can support their rapid proliferation and metabolic demands. However, the acidification of the extracellular environment is a strategy that promotes tumor invasion and immune evasion.

Key bicarbonate transporters involved in cancer include:

Sodium-bicarbonate cotransporters (NBCs): These transport bicarbonate into cells in exchange for sodium, helping to alkalinize the intracellular space.

Chloride-bicarbonate exchangers (AE1-3): These transport bicarbonate out of the cell in exchange for chloride ions, regulating both intracellular and extracellular pH.

Dysregulation of these transporters in cancer leads to an enhanced capacity to neutralize intracellular acidosis while contributing to extracellular acidification. This dual effect of bicarbonate transporters and CA IX activity is crucial for maintaining the aggressive phenotype of cancer cells, particularly in hypoxic and nutrient-deprived tumor regions.

Acidic Tumor Microenvironment and Its Impact on Cancer Progression


The acidic extracellular pH (pHe) of the tumor microenvironment (TME) is a byproduct of increased lactate production and bicarbonate dysregulation. This acidic environment has profound effects on tumor biology, including:

Promotion of Invasion and Metastasis: Acidic pHe enhances the activity of proteases like matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM), allowing cancer cells to invade surrounding tissues. Additionally, acidity promotes the detachment of cancer cells from the primary tumor and facilitates metastasis by making the ECM more pliable for cell migration.

Resistance to Apoptosis: Acidic conditions protect cancer cells from programmed cell death by modulating apoptotic pathways, such as inhibiting caspase activation. Avoiding apoptosis allows cancer cells to survive in harsh, nutrient-deprived environments.

Angiogenesis and Immune Evasion: Tumor acidosis promotes the secretion of angiogenic factors like VEGF, encouraging the growth of new blood vessels that supply oxygen and nutrients to the tumor. Moreover, acidic pHe suppresses the activity of immune cells, such as cytotoxic T cells and natural killer (NK) cells, aiding the tumor in evading immune surveillance.

Role of Bicarbonate Transporters and pH Sensors in Cancer


Cancer cells rely on an array of pH-regulatory proteins, including bicarbonate transporters and proton-sensing receptors, to adapt to fluctuating pH conditions. The most relevant components include:

Carbonic Anhydrase IX (CA IX): Overexpressed in many solid tumors, especially under hypoxic conditions, CA IX catalyzes the reversible hydration of CO2 to bicarbonate and protons. This enzyme helps maintain pHi while contributing to the acidification of the extracellular milieu. Inhibition of CA IX is an emerging therapeutic strategy aimed at disrupting the acid-base balance in tumors.

Sodium-Bicarbonate Cotransporters (NBC): Cancer cells upregulate these cotransporters to import bicarbonate into the cell, neutralizing excess intracellular protons and maintaining a conducive pHi for growth. Targeting NBC transporters could reduce intracellular alkalinization, making cancer cells more susceptible to the acidic stress they create.

Proton-Sensing G-Protein-Coupled Receptors (GPCRs): These receptors detect extracellular acidity and transmit signals that drive cancer cell survival, migration, and invasion. Proton-sensing GPCRs, such as GPR4, are activated in acidic environments and promote the expression of genes involved in metastasis and angiogenesis.

Molecular Mechanisms Linking pH Dysregulation to Cancer Metabolism


The dysregulated pH in cancer is tightly coupled with metabolic alterations that favor rapid proliferation and survival. Acidification impacts cellular processes by:

Modifying metabolic enzyme activity: Several key enzymes in glycolysis, the TCA cycle, and oxidative phosphorylation are pH-sensitive. By maintaining an alkaline pHi, cancer cells optimize enzyme activity for biomass production and energy generation.

Enhancing glycolysis: Acidic conditions stabilize hypoxia-inducible factor-1α (HIF-1α), a major driver of glycolytic gene expression. This leads to an increased conversion of glucose to lactate, fueling further acidification of the tumor microenvironment.

Shifting redox balance: Acidosis affects cellular redox homeostasis by modulating the activity of NADPH-dependent enzymes, leading to oxidative stress adaptation in cancer cells. This contributes to their ability to resist oxidative damage and maintain proliferation under hostile conditions.

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