Chlorophyllin

• Antioxidant
• Detoxification
• Anti-mutagenic
• Anti-carcinogenic

• Wound healing
• Odor control
• Skin health
• Internal deodorizing
• Anti-inflammatory

Chlorophyllin exerts its biological effects through multiple mechanisms. As a semi-synthetic derivative of chlorophyll, it has a water-soluble structure with a central metal ion (typically copper or sodium) that contributes to its stability and activity. One of its primary mechanisms is complex formation with mutagens and carcinogens, particularly polycyclic aromatic hydrocarbons, heterocyclic amines, and aflatoxins. This molecular trapping prevents these harmful compounds from being absorbed in the gastrointestinal tract and reduces their bioavailability, thereby decreasing DNA damage and mutation risk.

Chlorophyllin also exhibits potent antioxidant properties by directly scavenging reactive oxygen species (ROS) and upregulating endogenous antioxidant defense systems. It can neutralize various free radicals including superoxide, hydroxyl, and peroxyl radicals, protecting cellular components from oxidative damage. Additionally, chlorophyllin modifies carcinogen metabolism by inhibiting cytochrome P450 enzymes, particularly CYP1A1 and CYP1B1, which are responsible for activating procarcinogens to their genotoxic forms. This inhibition reduces the formation of DNA-damaging metabolites.

Chlorophyllin also demonstrates anti-inflammatory effects by suppressing pro-inflammatory cytokines and inhibiting nuclear factor-kappa B (NF-κB) activation. In cell cycle regulation, chlorophyllin can induce cell cycle arrest, particularly at the S-phase, by affecting the expression of cell cycle regulatory proteins such as E2F4 and ribonucleotide reductase. This contributes to its anti-proliferative effects in cancer cells. For wound healing applications, chlorophyllin stimulates tissue granulation and epithelialization while exhibiting antimicrobial properties against various bacteria.

Its deodorizing effects stem from its ability to bind and neutralize odor-causing compounds containing nitrogen or sulfur. In skin health, topical chlorophyllin can reduce inflammation, promote collagen synthesis, and protect against UV-induced damage. Some evidence suggests chlorophyllin may also have epigenetic effects by influencing DNA methylation patterns and histone modifications, potentially reversing aberrant epigenetic changes associated with disease development.

The typical dosage range for chlorophyllin supplements is 100-300 mg per day, divided into 2-3 doses. Most commercial supplements contain 50-100 mg per capsule or tablet.

Chlorophyllin has limited systemic absorption, with most of the compound remaining in the gastrointestinal tract. Studies have detected chlorophyllin-derived metabolites in serum, primarily chlorin e4 ethyl ester, indicating some degree of absorption, though at relatively low levels (estimated at 5-15% of ingested dose).

Liposomal delivery systems can increase absorption by encapsulating chlorophyllin in phospholipid bilayers, Micronization to reduce particle size may improve dissolution and absorption, Formulation with phospholipids or other lipid carriers can enhance bioavailability, Taking with meals containing some fat may improve absorption of the limited amount that can be absorbed systemically

For internal deodorizing effects or binding to dietary toxins, chlorophyllin should be taken with meals to maximize interaction with food components in the gastrointestinal tract. For systemic effects, consistent daily dosing is recommended to maintain steady levels of any absorbed metabolites. When used specifically to bind dietary carcinogens or toxins, taking chlorophyllin before or with meals containing potentially problematic foods is optimal to ensure the binding occurs during digestion.

Chlorophyllin undergoes limited metabolism in the gastrointestinal tract, with some demetallation and side chain modifications. The copper ion in copper chlorophyllin may be partially absorbed independently of the chlorin structure. Most unabsorbed chlorophyllin is excreted in feces, giving it a characteristic green color. Absorbed metabolites are primarily eliminated through biliary excretion and appear in feces, with minimal urinary excretion.

Limited data suggests that absorbed chlorophyllin metabolites may distribute to the liver and kidneys, with minimal penetration into other tissues. Some evidence indicates that chlorophyllin or its metabolites can cross the blood-brain barrier, though at very low concentrations.

Gastrointestinal pH can affect stability and solubility, Presence of dietary components that may bind to chlorophyllin, Individual variations in gut microbiota composition, Gastrointestinal transit time, Concurrent medications that may affect absorption

• Temporary green discoloration of urine and feces
• Mild gastrointestinal discomfort
• Nausea (rare)
• Diarrhea (rare)
• Temporary yellow or green discoloration of the tongue (with liquid formulations)
• Mild allergic reactions (rare)

• Known hypersensitivity to chlorophyllin or its components
• Pregnancy and lactation (due to insufficient safety data)
• Severe liver or kidney disease (precautionary)
• Photosensitivity disorders (for topical applications)

• May interfere with medications that require precise timing relative to meals, as chlorophyllin can affect gastrointestinal transit time
• Potential interaction with photosensitizing drugs when used topically
• May reduce absorption of orally administered drugs if taken simultaneously (theoretical)
• May interfere with guaiac-based fecal occult blood tests, producing false-negative results

No established upper limit. Studies have used doses up to 300 mg daily without significant adverse effects. A 13-week toxicity study in rats showed no adverse effects at doses equivalent to approximately 1500 mg/day for humans.

Medical Conditions: Individuals with gastrointestinal disorders should use with caution as chlorophyllin may temporarily alter bowel habits.

Diagnostic Tests: Should be discontinued at least 72 hours before scheduled fecal occult blood tests to avoid interference.

Topical Use: Patch testing recommended before widespread application to rule out contact sensitivity.

Long Term Use: While no significant adverse effects have been reported with long-term use, periodic monitoring of liver and kidney function is advisable for those taking high doses chronically.

Acute: Very low acute toxicity. Animal studies show LD50 values far exceeding therapeutic doses.

Chronic: 13-week subchronic toxicity studies in rats showed no adverse effects at doses up to 1500 mg/day human equivalent.

Genotoxicity: No evidence of genotoxicity in standard assays; in fact, chlorophyllin demonstrates anti-mutagenic properties.

Carcinogenicity: No evidence of carcinogenic potential; studies suggest anti-carcinogenic effects.

Pediatric: Limited data available; should only be used under medical supervision.

Geriatric: Generally well-tolerated; may start with lower doses.

Renal Impairment: Use with caution; start with lower doses.

Hepatic Impairment: Use with caution; start with lower doses.

Pregnancy: Avoid use due to insufficient safety data.

Lactation: Avoid use due to insufficient safety data.

In the United States, sodium copper chlorophyllin has multiple regulatory classifications depending on its intended use. As a dietary supplement, it falls under the Dietary Supplement Health and Education Act (DSHEA) of 1994, which does not require pre-market approval but does mandate adherence to Good Manufacturing Practices (GMPs). The FDA has previously approved chlorophyllin as an ingredient in certain over-the-counter (OTC) internal deodorant products, though in 2003, the FDA determined that there was insufficient evidence to generally recognize chlorophyllin as safe and effective for this purpose. For use in food, sodium copper chlorophyllin is listed as a color additive exempt from certification and is permitted in citrus-based dry beverage mixes at levels not exceeding 0.2% in the dry mix.

For topical applications, chlorophyllin is included in various wound care products, some of which have been classified as medical devices.

Eu: In the European Union, sodium copper chlorophyllin is approved as a food additive designated E141ii (‘Copper complexes of chlorophyllins’). It is authorized for use in various food categories with specific maximum levels as outlined in Regulation (EC) No 1333/2008 on food additives. As a supplement ingredient, it falls under the Food Supplements Directive 2002/46/EC. For cosmetic applications, it is listed in the Cosmetic Ingredient Database (CosIng) and permitted for use in cosmetic products.

Canada: Health Canada has approved sodium copper chlorophyllin as both a food coloring agent and a Natural Health Product (NHP) ingredient. As a food coloring, it is permitted in various food categories with specified maximum levels. As an NHP ingredient, it has been approved for use in supplements with claims related to internal deodorizing and as an antioxidant.

Australia: The Australian Therapeutic Goods Administration (TGA) lists chlorophyllin as an approved ingredient for listed complementary medicines (equivalent to dietary supplements). For food use, Food Standards Australia New Zealand (FSANZ) permits sodium copper chlorophyllin as a food coloring (INS 141ii) with specific limitations.

Japan: In Japan, sodium copper chlorophyllin is approved as a food additive under the Japan Food Chemical Research Foundation. It is also permitted in certain quasi-drug products for internal deodorizing purposes.

China: The National Medical Products Administration (NMPA) of China permits sodium copper chlorophyllin as both a food additive and an ingredient in health food products (similar to dietary supplements). It is also approved for use in certain topical preparations.

Dietary Supplements: In the US, chlorophyllin supplements must be labeled as dietary supplements and include a Supplement Facts panel. They cannot make disease treatment claims but may make structure/function claims with appropriate disclaimers. In the EU, supplements must comply with the Food Supplements Directive labeling requirements, including recommended daily dose and warning statements.

Food Coloring: When used as a food coloring, it must be declared in the ingredient list as ‘Sodium Copper Chlorophyllin,’ ‘Chlorophyllin Copper Complex,’ or by its E-number (E141ii) in regions where E-numbers are recognized.

Cosmetics: In cosmetic products, it typically appears in the ingredient list as ‘Sodium Copper Chlorophyllin’ or ‘CI 75810’ (its Colour Index number).

Medical Devices: For wound care products classified as medical devices, labeling requirements vary by region but generally include intended use, directions, warnings, and precautions.

Claim Limitations: One of the primary regulatory challenges for chlorophyllin supplements is the limitation on health claims. Despite evidence for certain benefits, particularly in cancer prevention, manufacturers cannot make disease prevention claims without drug approval.

Varying Standards: The varying regulatory standards across different regions create challenges for global marketing and distribution of chlorophyllin products.

Classification Ambiguity: The multiple potential classifications of chlorophyllin products (supplement, food additive, cosmetic ingredient, or medical device component) can create regulatory ambiguity.

Quality Standards: There is a lack of harmonized quality standards specifically for chlorophyllin as a supplement ingredient, leading to potential variations in product quality.

In recent years,

there has been increased regulatory scrutiny of natural colorants, including chlorophyllin, with some authorities reviewing safety data and usage levels. The European Food Safety Authority (EFSA) conducted a re-evaluation of copper complexes of chlorophyllins (E 141(ii)) as a food additive in 2015 and identified some data gaps, though

it continues to be permitted for use.

There has also been growing interest from regulatory bodies in the potential health benefits of chlorophyllin, particularly its anticarcinogenic properties, though

this has not yet translated into approved health claims in most regions.

Medium

The typical cost for chlorophyllin supplements ranges from $0.30 to $1.00 per 100 mg dose, depending on brand, formulation, and quality. For a standard daily dose of 100-300 mg, this translates to approximately $9-30 per month for supplementation.

Chlorophyllin offers moderate value for its cost

when compared to other supplements with similar applications. For internal deodorizing purposes,

it provides good value as an effective and relatively affordable option with minimal side effects. For detoxification and cancer prevention, particularly in populations exposed to dietary carcinogens like aflatoxins,

it offers potentially significant value given the seriousness of the conditions

it may help prevent, though more expensive than basic antioxidants. For topical applications, specialized chlorophyllin formulations for skin care or wound healing tend to be more expensive ($15-50 per product) but may offer unique benefits not easily replicated by other compounds.

Source material quality and sustainability practices, Manufacturing process complexity, Standardization and quality control measures, Formulation type (tablets, capsules, liquids, topicals), Additional ingredients in the formulation, Brand positioning and marketing approach, Packaging (light protection requirements increase packaging costs), Third-party testing and certifications, Scale of production

Bulk Purchasing: Buying larger quantities can reduce the per-dose cost by 20-30%.

Subscription Services: Many supplement companies offer subscription discounts of 10-15% for regular deliveries.

Combination Products: For certain applications, combination products containing chlorophyllin along with synergistic compounds may offer better value than purchasing supplements separately.

Dietary Sources: While chlorophyllin itself is not found in foods, increasing consumption of chlorophyll-rich foods (spinach, parsley, chlorella) may provide some similar benefits at a lower cost, though with different bioavailability and efficacy profiles.

Properly stored chlorophyllin supplements typically have a shelf life of 2-3 years. Liquid formulations generally have shorter shelf lives (1-2 years) compared to dry powder or tablet forms.

Store in a cool, dry place away from direct sunlight. Optimal temperature range is 15-25°C (59-77°F). Avoid exposure to high humidity. Keep container tightly closed when not in use. For liquid formulations, refrigeration after opening may extend stability.

Light exposure: Chlorophyllin is photosensitive and can degrade when exposed to strong light, particularly UV radiation, Heat: Temperatures above 40°C (104°F) can accelerate degradation, Oxidation: Exposure to air and oxidizing agents can cause degradation of the tetrapyrrole ring structure, Extreme pH: Very acidic conditions (pH < 3) can cause demetallation and structural changes, Moisture: High humidity can promote hydrolysis reactions and microbial growth in powder formulations, Metal ions: Certain metal ions can catalyze oxidative degradation

Tablets: Generally stable for 2-3 years when properly formulated with appropriate excipients and stored correctly.

Capsules: Similar stability to tablets, though gelatin capsules may be more susceptible to humidity-related degradation than tablets.

Liquid Extracts: Less stable than solid forms, typically stable for 1-2 years. May require preservatives and protection from light.

Topical Formulations: Stability varies widely based on the formulation. Creams and ointments typically have shelf lives of 1-2 years, while solutions may be less stable.

Food Colorant: When used as a food colorant (E141ii), stability depends on the food matrix, processing conditions, and storage. Generally more stable in alkaline than acidic foods.

High-performance liquid chromatography (HPLC) to monitor chemical degradation, Spectrophotometric analysis to track changes in absorption spectrum, pH monitoring for liquid formulations, Accelerated stability testing at elevated temperatures and humidity, Photostability testing under controlled light conditions, Microbial testing for liquid formulations and topical products

Antioxidants: Addition of antioxidants like vitamin E, ascorbic acid, or BHT can help prevent oxidative degradation.

Chelating Agents: EDTA or citric acid can bind metal ions that might catalyze degradation reactions.

PH Buffers: Maintaining optimal pH (usually slightly alkaline) can enhance stability.

Packaging: Amber glass containers, opaque bottles, or blister packs can protect from light. Oxygen barrier packaging can reduce oxidation.

Coating: Enteric coating of tablets can protect from stomach acid degradation for oral supplements.

Freeze Drying: Lyophilization can enhance long-term stability of powder formulations.

Dry formulations (tablets, capsules, powders) remain stable for their labeled shelf life if stored properly after opening. Liquid formulations should ideally be used within 1-3 months after opening, depending on the presence of preservatives and storage conditions. Topical formulations typically remain stable for 6-12 months after opening if stored properly.

Synthesis Methods

Natural Sources

Quality Considerations

Commercial Production

Regional Variations

Chlorophyllin, as a semi-synthetic derivative of chlorophyll, has a relatively recent history compared to many natural remedies, with its development and medical applications primarily occurring in the 20th century. The story begins with chlorophyll itself, which has been used in traditional medicine across various cultures for centuries. Green plant preparations were used in ancient Chinese, Ayurvedic, and Native American medicine for wound healing, pain relief, and various internal ailments, though the active component was not identified as chlorophyll until much later.

The modern history of chlorophyllin began in the 1940s when scientists developed methods to modify natural chlorophyll to create a water-soluble derivative by removing the phytol tail and replacing the central magnesium with copper or sodium. This modification significantly enhanced stability and created a compound with practical medical applications. Dr. Benjamin Gruskin is often credited with pioneering the medical use of chlorophyllin in the 1940s, particularly for wound healing.

During World War II, chlorophyllin gained prominence in military medicine for treating infected wounds and burns. The 1940s and 1950s saw an explosion of clinical reports on chlorophyllin’s efficacy in wound healing, with notable publications by Bowers (1947) and Carpenter (1949) documenting its benefits in surgical and traumatic wounds. These early clinical observations noted chlorophyllin’s ability to accelerate wound healing, reduce inflammation, control odor, and provide antimicrobial effects.

The 1950s marked the beginning of chlorophyllin’s use as an internal deodorizer. Landmark studies by Siegel (1960) and Weingarten and Payson (1951) demonstrated its effectiveness in controlling odors associated with colostomies and ileostomies. This application expanded to include treatment of trimethylaminuria (fish odor syndrome) and general body odor management.

In the 1960s and 1970s, chlorophyllin became popular in geriatric care for managing incontinence-related odors, as documented by Young and Beregi (1980). It was also incorporated into various consumer products including deodorants, mouthwashes, and breath fresheners.

The 1980s and 1990s saw a shift toward scientific investigation of chlorophyllin’s antimutagenic and anticarcinogenic properties. Pioneering work by Dashwood and colleagues demonstrated chlorophyllin’s ability to inhibit the mutagenicity of aflatoxin B1 and heterocyclic amines. This research laid the groundwork for understanding chlorophyllin’s mechanism of action in binding to carcinogens and preventing DNA damage.

The early 2000s marked a significant milestone with the publication of a human intervention trial by Egner et al. (2001) in Qidong, China, which demonstrated that chlorophyllin supplementation could reduce aflatoxin-DNA adducts in populations at high risk for liver cancer. This study provided the first human evidence for chlorophyllin’s potential as a chemopreventive agent.

In recent years, chlorophyllin has experienced renewed interest in dermatology and cosmetic applications. Studies by Sigler and Stephens (2015) and others have investigated its benefits for photodamaged skin, acne, and rosacea when applied topically.

Throughout its history, chlorophyllin has maintained a dual identity as both a therapeutic agent and a food colorant (designated as E141ii in Europe). Its use as a natural green food coloring has been widespread in the food industry, particularly for products where stability is required under processing conditions.

Today, chlorophyllin continues to be used in various applications including dietary supplements, wound care products, topical skin treatments, internal deodorizers, and food colorants. Modern research continues to explore its potential benefits in cancer prevention, detoxification, gut health, and anti-aging applications, building upon its rich historical foundation while employing contemporary scientific methodologies to better understand its mechanisms and efficacy.

Hayes M, Ferruzzi MG. Update on the bioavailability and chemopreventative mechanisms of dietary chlorophyll derivatives. Nutr Res. 2020;81:19-37., Perez-Galvez A, Viera I, Roca M. Carotenoids and chlorophylls as antioxidants. Antioxidants (Basel). 2020;9(6):505.

Investigation of chlorophyllin as a chemopreventive agent in populations exposed to environmental carcinogens, Evaluation of topical chlorophyllin formulations for photoaging and inflammatory skin conditions, Assessment of chlorophyllin’s effects on gut microbiome composition and metabolic health markers

Long-term clinical trials assessing cancer prevention outcomes rather than biomarkers, Studies on chlorophyllin’s effects on gut microbiome composition and function, Research on potential systemic effects beyond the gastrointestinal tract, Comparative studies of different chlorophyllin formulations and their relative bioavailability, Investigation of potential epigenetic mechanisms, Studies in diverse populations with varying dietary patterns and environmental exposures