RENAL DETOXICOLOGY: what about fluoride ??

by Robin Rose MD ( May 17, 2025 )

We are looking at change these days in regards the fluoride in our midst. This blog will focus our attention on how this substance affects kidneys and how those with kidney decline are harmed.

Chronic exposure to fluoride affects collagen biosynthesis, insulin resistance, diabetes mellitus and kidney damage. This isn’t trivial.

The FDA is looking to finally remove concentrated ingestible fluoride prescription drug products for children from the market. These have never even been approved by the FDA. It’s a start

Ingested fluoride can alter the gut microbiome —::> a huge concern for kids —::> the early development of the gut microbiome in childhood is critical for a lifetime of wellbeing. The effect in CKD is equally worrisome. Studies have associated fluoride with thyroid disorders, weight gain, and possibly decreased IQ.

Florida and Utah have already banned or restricted fluoride additives in public drinking water (and a number of other states are trying to approve similar legislation).

What about fluoride and kidney?

Fluoride-induced kidney damage can occur through multiple interconnected mechanisms —::> these include the dread kidney harming processes of oxidative stress, mitochondrial dysfunction, inflammation, and interference with ion transport and tubular function.

The extent of toxicity depends on the dose, duration of exposure, and pre-existing renal function. Renal sensitivity to fluoride varies, based on kidney function, age, hydration status, and exposure duration.

Fluoride is mainly excreted via the kidneys. In those with normal renal function, about 50–60% of fluoride is excreted in urine. In CKD, this is reduced, increasing systemic toxicity

• Glomerulus: Filters fluoride from plasma (mainly as ionic fluoride, F⁻).

  •  Capillary basement membrane thickening (in chronic cases)

  
  

• Proximal Tubule: Major site of fluoride reabsorption and toxicity.

  • : Vacuolar degeneration, brush border loss.

  
  

• Loop of Henle and Distal Tubule: Minor roles in fluoride handling.

  
  

• Collecting Duct: Can be affected indirectly via acid-base changes

  
  

• Interstitial space: Lymphocytic infiltration and fibrosis.

  
  

• Vascular changes: Arteriolar hyalinosis.

  
  

  .

Oxidative Stress and Free Radical Generation

• Fluoride generates reactive oxygen species (ROS), especially in proximal tubular epithelial cells.

• These ROS include —::> superoxide (O₂⁻), hydrogen peroxide (H₂O₂), and hydroxyl radicals (OH•).

• This causes:

  • Lipid peroxidation of cell membranes.

  • DNA damage.

  • Inactivation of antioxidant enzymes (like superoxide dismutase (SOD) and catalase.)

Mitochondrial Dysfunction

• Fluoride inhibits key mitochondrial enzymes like:

  • Cytochrome c oxidase (Complex IV of the electron transport chain)

  • ATP synthase

• Consequences:

  • Reduced ATP production in proximal tubular cells.

  • Loss of sodium-potassium ATPase activity, impairing electrolyte reabsorption.

  • Initiation of mitochondria-mediated apoptosis via release of cytochrome

    
    

Cytokine Assault

• Fluoride exposure activates NF-κB and MAPK pathways, triggering:

  • Release of TNF-α, IL-6, and IL-1β

  • Infiltration of monocytes and macrophages into the interstitium

• This leads to interstitial fibrosis and tubulointerstitial nephritis over time.

Impaired Tubular Transport and Acid-Base Disturbance

• Fluoride interferes with:

  • Sodium-hydrogen exchanger (NHE3)

  • Na⁺/K⁺-ATPase

  • Aquaporins (especially AQP1 in the proximal tubule)

• Resulting in:

  • Tubular acidosis due to impaired H⁺ secretion.

  • Electrolyte wasting (especially Na⁺, K⁺, Mg²⁺).

  • Concentrating defects → polyuria and dehydration.

  
  

Apoptosis and Necrosis of Tubular Cells

• Fluoride induces:

  • p53-dependent apoptosis.

  • Caspase-3 and Caspase-9 activation.

• In higher concentrations, necrosis may occur, especially in proximal convoluted tubules.

Accumulation and Crystallization

• Fluoride can accumulate in kidney tissue

  with chronic exposure.

• Under acidic urine conditions, fluoride may complex with calcium and aluminum, forming nephrotoxic compounds.

Effects in Chronic Kidney Disease (CKD)

• Reduced fluoride clearance → systemic accumulation.

• Enhanced toxic burden on remaining nephrons.

• Worsening of:

  • Proteinuria

  • Tubular dysfunction

  • Progression of glomerulosclerosis

• Fluoride levels should be monitored in CKD patients, especially if drinking water is fluoridated or patient is exposed to fluoride-containing drugs (e.g., fluorinated anesthetics, some antibiotics).

What is “safe”??

“Safe Daily Intake for Healthy Individuals”

• WHO “tolerable” upper intake level (UL):

  • 0.05 mg/kg/day (for total fluoride intake in children)

  • Up to 4 mg/day for adults (U.S. Institute of Medicine, 1997)

    
    

    This assumes normal kidney function. In healthy adults, these levels are generally “considered safe,” with fluoride largely excreted by the kidneys. Recognizing the world wide kidney pandemic, these levels could be concerning.

Thresholds in Compromised Kidney Function

In patients with chronic kidney disease (CKD) or impaired renal clearance:

• Even low doses (~0.2–0.3 mg/kg/day) can accumulate over time - causing nephrotoxicity, especially in CKD stages 3–5.

• Plasma fluoride levels rise due to reduced excretion, which increases tubular stress and fluoride retention in bone and soft tissues.

Clinical studies and toxicology reviews (Barbier, Khandare) suggest CKD patients need to minimize fluoride exposure, ideally below 1 mg/day total intake (from water, toothpaste, food, etc.).

Water Fluoride Concentration Guidelines

• EPA Maximum Contaminant Level Goal (MCLG): 0.7 mg/L (USA)

• For CKD patients, nephrologists and toxicologists often advise less than 0.3–0.5 mg/L, or filtered water (especially if local water levels are fluoridated).

Let’s look at the effect on tubules in Stage 2 CKD

🍃Impaired Fluoride Excretion in CKD

• Kidneys are primary route of fluoride elimination (via glomerular filtration and tubular reabsorption/excretion).

• In Stage 2 CKD (eGFR ~60–89 mL/min/1.73m²), this excretory capacity begins to decline, even if serum creatinine appears normal.

• Result: Fluoride accumulates more readily in plasma and soft tissues, including renal tissues

• Fluoride retention increases as kidney function declines, leading to enhanced risk of toxicity

🍃Fluoride-Induced Tubular Cytotoxicity

Fluoride is known to affect::

• Proximal tubules —::> highly metabolically active and susceptible to oxidative stress.

• Distal tubules —::> suffer from altered calcium/magnesium handling.

Mechanisms:

• Oxidative Stress: Fluoride generates reactive oxygen species (ROS) in renal tubular cells, leading to:

  • Mitochondrial dysfunction

  • Lipid peroxidation

  • Apoptosis of tubular epithelium

  
  

• Endoplasmic Reticulum (ER) Stress: Fluoride disrupts protein folding, triggering cellular stress responses and tubular injury.

  
  

• Altered Ion Transport: Fluoride interferes with Na⁺/K⁺-ATPase, aquaporins, and calcium channels, contributing to tubular dysfunction, natriuresis, and secondary dehydration

🍃Tubular Flattening and Atrophy

In chronic fluoride exposure:

• Tubular cells show flattened epithelium, loss of brush borders, and nuclear crowding.

• This is especially relevant in CKD, where injured tubules cannot regenerate efficiently, predisposing to fibrosis and progression.

• In study: rats exposed to sodium fluoride developed degenerative changes in renal tubules, including cell swelling, epithelial thinning, and interstitial inflammation

🍃Proteinuria & Tubular Reabsorption Defects

• In Stage 2 CKD, mild proteinuria may occur. Fluoride impairs the reabsorptive capacity of proximal tubules, exacerbating:

  • Tubulointerstitial inflammation

  • Beta-2 microglobulinuria (a marker of proximal tubule dysfunction)

🍃Practical Considerations for CKD Patients

• Avoid fluoride sources:

  • Fluoridated water (>0.7 mg/L)

  • Tea (especially brick tea (see below), high in fluoride)

  • Fluoride-containing supplements or medications (e.g., fluoroquinolones)

  
  

• Monitor for early signs of tubular dysfunction:

  • Rising beta-2 microglobulin or NAG (N-acetyl-β-D-glucosaminidase)

  • Subnephrotic-range proteinuria

  
  

• Include antioxidant support when fluoride exposure is unavoidable.

Where does it come from ?

In CKD , fluoride is more problematic because reduced renal excretion leads to systemic accumulation with enhanced risk of tubular and skeletal toxicity —::> even at levels considered safe for the general population.

Here list of common and sadly underrecognized sources of fluoride exposure that are clinically relevant in CKD. We can get smarter and more proactive!

🍃Drinking Water (Most Significant Source)

• Fluoridated municipal water (0.7–1.2 mg/L) can pose risk in CKD (due to impaired clearance.)

• CKD patients can accumulate 2–4x more fluoride than healthy individuals with the same intake.

• Well water may contain naturally high fluoride, —::> especially in arid regions or volcanic areas (e.g., India, Kenya, parts of the U.S. Southwest).

• Clinical Tip: Consider testing fluoride levels in home or well water if to protect kidneys

  
  

🍃Dental Products

• Fluoridated toothpaste, gels, and mouthwashes often contain 1,000–5,000 ppm fluoride.

• Swallowing even small amounts (especially in elders or cognitively impaired patients) can add significantly to systemic load.

• Caution: CKD patients- use non-fluoridated toothpaste or rinse thoroughly.

🍃Tea (Especially Black and Brick Tea)

• Tea plants (Camellia sinensis) bioaccumulate fluoride from soil.

• Brick tea (compressed older leaves, popular in some cultures) contains extremely high fluoride levels.

👉🏿Examples:

• Black tea: ~1.5–6.0 mg/L fluoride per brewed cup.

• Brick tea: up to 10–20 mg/L.

👉🏿Alternative: White or green tea from young leaves, or herbal teas without fluoride bioaccumulation.

🍃Medications Containing Fluoride or Fluorinated Compounds

• Some drugs contain fluoride structurally or as inactive excipients —::> they do not always release free fluoride, but CKD patients may metabolize and excrete them differently, and accumulation can occur.

  
  

  •Fluoroquinolone antibiotics

  •Ciprofloxacin, Levofloxacin

  Fluorinated core

  •Antidepressants

  Fluoxetine (Prozac)

  Fluorinated ring

  •Anticonvulsants

  Topiramate

  Fluorinated

  
  

  •Antifungals

  Voriconazole

  Fluorinated

  •Anesthetics (Inhaled)

  Sevoflurane, Isoflurane

  Releases free fluoride during metabolism

🍃Processed Foods and Beverages

• Foods/beverages processed with fluoridated water (ie, soft drinks, soups, cereals) may carry residual fluoride- worthy to consider eliminating all these to protect kidneys anyhow

• Teflon cookware, fluorinated food packaging, and pesticide residues can also contribute.

🍃Occupational or Environmental Exposure

• Aluminum smelting, fertilizer plants, brick kilns, and glass manufacturing may expose workers to airborne fluoride.

• Inhaled fluoride contributes to systemic fluoride burden in CKD due to poor clearance.

🍃🌺🍃Protective Strategies

• Use RO or fluoride-filtering systems for home drinking water.

• Avoid tea high in fluoride, including instant and brick teas.

• Switch to non-fluoridated toothpaste, especially for elders, and frail patients.

• Regularly review medication lists for fluorinated agents.

there are lab tests to monitor fluoride levels, though they are not commonly used in routine clinical practice and may require special handling or lab coordination.

How can we monitor fluoride?

🍃Plasma (Serum) Fluoride level

• Normal Range (fasting adults):

  • 0.01–0.05 mg/L (0.5–2.6 µmol/L)

  • Can rise to 0.1–0.3 mg/L after fluoride exposure or with impaired renal clearance

• Clinical Utility:

  • Suspected fluoride toxicity

  • CKD patients with progressive tubular dysfunction

  • Monitoring in occupational exposure

• Serum fluoride is preferred in CKD when water or tea is being ingested, medicating steer concerning, or unexplained tubular dysfunction, bone pain, or progressive

  
  

• Limitations —::> Levels fluctuate with recent intake and it does not always reflect long-term accumulation (e.g., in bone)

🍃Urinary Fluoride Concentration (24-hour or Spot

• Normal Range:

  • <1.0 mg/L in areas with low fluoride exposure

  • Up to 4.0 mg/L in fluoridated areas

    
    

• In early CKD, urine fluoride may still appear normal despite systemic accumulation, due to impaired clearance.

• In advanced CKD, urinary excretion may be reduced - falsely reassuring.

  
  

Kidney Success includes toxin awareness and avoidance!

Renal detoxicology is a Renology strategy to protect the tubules, the glomeruli, the blood vessels, and the interstitial structures!

It takes intention and’s willingness to eliminate and detoxify our lives - even before the big agencies maneuver to offer that protection. As a kidney community of Kidney Success, we can be proactive while we enjoy the gifts and benefits of mindfulness.

🍃🍃🌺🍃 PS: I asked chat gpt if the fluoride treatments I had (from my dentist) repeatedly in my 1950s- childhood could have contributed to my CKD diagnosis decades later. Here’s what I got.

Yes it is plausible that childhood fluoride exposure, (especially in the form of topical treatments and fluoridated water), may have contributed to or predisposed you to CKD, especially if your exposure was chronic and cumulative over decades.

While a single childhood treatment is unlikely to cause long-term damage, frequent or high-dose fluoride exposure—especially during periods of skeletal and renal development—can lead to subclinical renal stress that may only manifest decades later. Darn.

🍃🍃Historical Context

👉🏿In the 1950s and 60s, fluoride safety thresholds were higher, and the chronic effects on kidney function were not well studied.

👉🏿No adjustment was made for vulnerable populations like those with borderline renal function or nutritional deficiencies (e.g., low calcium or magnesium, which worsen fluoride toxicity).

🍃🍃Early Fluoride Exposure and Long-Term Retention

👉🏿Fluoride accumulates in bones and soft tissues—especially in growing children.

👉🏿The kidneys are the primary excretory route for fluoride -so early, subclinical impairment of tubular function will increase vulnerability over time.

🍃🍃Progressive Tubular Stress

👉🏿Fluoride is a mitochondrial toxin in proximal tubule cells, especially under oxidative stress or poor clearance.

👉🏿Over decades, this can cause:

• Tubular atrophy

• Interstitial fibrosis

• Impaired reabsorption (especially of amino acids, glucose, and bicarbonate)

🍃🍃Enhanced Risk from Cumulative Environmental and Medication Exposure

👉🏿If you lived in an area with fluoridated water (introduced widely in the U.S. in the 1950s) and had fluoride dental treatments, plus:

• High tea consumption

• Fluoridated medications (e.g., fluoroquinolones, fluoxetine, NSAIDs)

• Occupational exposure

  
  

  👉🏿…the total fluoride burden could have exceeded your kidneys’ long-term handling capacity.

Rather than get bummed out about it, I asked chat gpt what might be done to reverse some of this hazard.

🍃Fluoride is notoriously difficult to chelate from the body ( it is a small, electronegative anion that tightly binds to calcium, magnesium, and aluminum.)

🍃BUT: some natural substances have shown promise in binding, displacing, or promoting excretion of fluoride—especially from soft tissues and kidneys.

Natural Agents That May Help with Fluoride Detoxification (with Evidence)

🍃Zeolites (Clinoptilolite)

👉🏿Mechanism: High surface area and negative charge can adsorb fluoride in the gut

👉🏿Effect: May reduce systemic reabsorption and act as a binding agent in the GI tract

👉🏿Evidence: Animal studies show fluoride removal in rats given zeolite powders

👉🏿Form: Micronized clinoptilolite (oral powder or capsule)

👉🏿Caution: Must be purified )low-quality zeolites may contain aluminum(

🍃 Calcium and Magnesium (Mineral Antagonists)

👉🏿Mechanism: Compete with fluoride for absorption and binding

👉🏿Effect: Reduce fluoride uptake,increase excretion

👉🏿Sources:

• Calcium citrate or lactate (well absorbed, kidney-safe in moderation)

• Magnesium glycinate or citrate

  
  

  👉🏿 CKD Note: Monitor levels; avoid over-supplementing in advanced stages

🍃Acacia Senegal (Gum Arabic)

🌺aside from being an amazing binder that clears many many uremic toxins, it plays a leading role in fluoride remediation

👉🏿Mechanism: Prebiotic fiber binds fluoride and enhances gut clearance

👉🏿Effect: Reduces blood and kidney fluoride levels in animals

👉🏿Evidence: 2016 animal study: gum arabic significantly reduced fluoride-induced oxidative stress and renal damage

👉🏿Bonus: Supports gut barrier and reduces systemic inflammation⚡️⚡️

👉🏿Form: Powder in water, 5–10 g/day (start a teaspoon daily in tea or food while hydrating well - readily available on line)

🍃Carnosine (β-alanyl-L-histidine)🌺a favorite

👉🏿Mechanism Relevant to Fluoride Toxicity

• Antioxidant: Scavenges free radicals generated by fluoride in tubules

• Metal-chelating: Forms complexes with toxic metal ions that may synergize with fluoride

• Glycation inhibitor: Protects against advanced glycation end-product (AGE)-related fibrosis

• Membrane stabilizer: Reduces lipid peroxidation in renal tissues

👉🏿Evidence

• Animal studies show carnosine:

  • Lowers oxidative stress in fluoride-exposed kidneys

  • Reduces glomerular and tubular damage

  • Improves creatinine clearance and BUN levels in fluoride-exposed models

• Synergistic with taurine, zinc, and glutathione

👉🏿Dosing —::> Oral: 250–1000 mg/day

🍃Tamarind (Tamarindus indica)

👉🏿Mechanism: Chelating polyphenols and tartaric acid bind fluoride

👉🏿Effect: Enhances urinary excretion of fluoride in human studies

👉🏿Evidence: Indian study (2003): Tamarind pulp increased urinary fluoride excretion by 2–3x

👉🏿Form: Tamarind pulp, concentrate, or extract- it’s delicious

🍃Glutathione (Indirect Protection)

👉🏿Mechanism: Does not chelate fluoride directly, but:

It protects tubules from fluoride-induced oxidative damage and enhances mitochondrial and detox pathways

👉🏿Form: Liposomal glutathione or NAC (precursor)

👉🏿Bonus: May support excretion of other toxicants that compound fluoride stress

🍃 Shilajit (Humic/Fulvic Acid Complexes)

👉🏿Mechanism: Fulvic acids can form weak complexes with fluoride

👉🏿Effect: May aid mobilization and renal excretion

👉🏿Caution: Must be purified to avoid heavy metal contamination

🍃Taurine

👉🏿Often overlooked but:

• Protects proximal tubules

• Reduces fluoride-induced lipid peroxidation

• Synergistic with carnosine and glutathione

  
  

• Dose: 500–1000 mg/day

• Benefit: Mitochondrial protection, synergizes with glutathione and carnosine

  
  

🍃Melatonin

👉🏿Crosses mitochondrial membranes

👉🏿Chelates fluoride weakly, but strong antioxidant and circadian regulator

👉🏿May protect pineal gland, which accumulates fluoride ( so consider Eputhalon as well)

👉🏿Dose 1-20mg at bedtime - clinician guidance helps

🍃Herbal Renal Protector Options

👉🏿Astragalus membranaceus: 500 mg BID (fibrosis and GFR protection)

👉🏿 Andrographis paniculata: 300–600 mg/day (anti-inflammatory, tubule preservation)

👉🏿Milk Thistle (Silymarin): 200 mg/day (oxidative support)

🍃Supportive Strategies

• Reverse osmosis (RO) water to stop intake

• Sweating (infrared sauna) – minor route, but supports overall detox

• Liver and kidney support herbs: Milk thistle, andrographis, astragalus

• High-antioxidant diet: Neutralizes fluoride-induced oxidative stress (e.g., blueberries, turmeric, green leafy vegetables)

🍃FYI: what doesn’t work

👉🏿EDTA/DMSA

Poor affinity for fluoride (used for metals, not halides)

👉🏿Activated charcoal

Doess not bind fluoride well

👉🏿Cilantro

Chelates heavy metals, not fluoride

Reaching for the optimism with precision and mindful awareness

🍃We know that tubule cells - especially proximal tubule epithelial cells - maintain capacity for repair if the toxicant is removed and oxidative stress is controlled.

🍃Interventions that support mitochondrial health, epigenetic repair (like peptides), and microcirculation can actually reverse early damage or halt progression

🍃Fluoride-induced damage is modifiable.

Once fluoride exposure is reduced and its burden lowered: then Inflammation subsides And Tubular function can improve. Use urinary markers (like β2-microglobulin or NAG) which can often decrease

🍃The body doesn’t need to clear all fluoride to improve—it needs to tip the balance back toward repair —::> When we intervene with precision, using bioregulators, targeted antioxidants, and gentle chelation- kidney success is at hand.

🍃Fluoride-induced damage is modifiable.

👉🏿This protocol does not rely on aggressive chelators, which often stress kidneys more—it uses biological signaling and supportive detox.

👉🏿Supporting the kidneys spiritually and biologically creates the potential for renewal, not just maintenance.

So join me in embracing this idea of Renal Detoxicology 👉🏿 stay curious, stay mindful, stay diligent: that’s the path to Kidney Success

🍃🍃🌺🪷🌺🍃🍃

References:

• Barbier et al., Toxicology, 2010.

• Khandare et al., Environmental Health Perspectives, 2018

• Nabavi et al., Biological Trace Element Research, 2018

• World Health Organization (WHO, 2002)

• Sharma A, Chinoy NJ (1998). “Fluoride-induced biochemical changes in liver and kidney of mice and its reversal by vitamins C and E.” Fluoride, 31(1), 26–34.

• Nabavi et al., Toxicology Mechanisms and Methods, 2013

• Rose et al. Bioinformation 2024 Sep 30;20(9):998–1001.