Chlorophyllin

Chlorophyllin

1. Identity: Chemical Names, Natural Source, and Preparations

Definition and Nomenclature

Chlorophyllin refers to any one of a group of closely related water-soluble salts that are semi-synthetic derivatives of chlorophyll, differing in the identity of the cations associated with the anion. The most studied chlorophyllin, sodium copper chlorophyllin (SCC), is a semi-synthetic mixture of sodium copper salts derived from chlorophyll. Its most common form is a sodium/copper derivative used as a food additive and in alternative medicine. As a food coloring agent, copper complex chlorophyllin is known as Natural Green 3 and has the E number E141.

Its chemical formula is typically represented as C₃₄H₃₁CuN₄Na₃O₆, with a molecular weight of approximately 724.15 g/mol, and it appears as a dark green powder. The compound is also listed under CAS numbers 11006-34-1 and 85536-03-4 for different salt forms.

Chemical Composition

The two principal copper-containing compounds commonly found in commercial sodium copper chlorophyllin are trisodium copper chlorin e6 and disodium copper chlorin e4. Both have porphyrin ring structures with a central copper atom replacing the magnesium atom found in natural chlorophylls, lack a phytol tail, and are water-soluble.

A commercial-grade sodium copper chlorophyllin (SCC) has been developed as a mixture of Cu–chlorine derivatives prepared by the saponification of chlorophyll with NaOH, followed by a replacement of the Mg²⁺ atom by Cu. This two-step semi-synthetic process converts the fat-soluble natural pigment into a stable, water-soluble compound.

Metallo-chlorophyll derivatives, including chlorophyllins, can be chemically synthesized or produced in industrial food processing; these compounds contain zinc, iron, or copper in place of the central magnesium atom. While copper-substituted SCC is by far the most commercially prevalent and most studied form, iron chlorophyllin and zinc chlorophyllin are recognized variants with distinct properties.

Natural Source

Chlorophyllin is derived from natural chlorophyll extracted from green plants, such as alfalfa or nettles, through processes involving saponification and metallation. Chlorophyll a and chlorophyll b represent about 99% of the chlorophyll species found in edible plants, while some algae and microalgae contain minor quantities of chlorophyll c pigments. Alfalfa (Medicago sativa) is the predominant industrial source for the natural chlorophyll that is subsequently processed into SCC.

Common Forms and Preparations

Oral preparations of sodium copper chlorophyllin (also called chlorophyllin copper complex) are available as a dietary supplement and as an over-the-counter drug (Derifil) used to reduce odor from colostomies and ileostomies, or to reduce fecal odor due to incontinence. Chlorophyllin is the active ingredient in a number of internally-taken preparations intended to reduce odors associated with incontinence, colostomies, and similar procedures, as well as body odor in general. It is also available as a topical preparation, purportedly useful for treatment and odor control of wounds, injuries, and other skin conditions, such as for radiation burns.

In the late 1950s, chlorophyllin was added to papain and urea-containing ointments used for the chemical debridement of wounds in order to reduce local inflammation, promote healing, and control odor. Chlorophyllin-containing papain/urea ointments are still available in the US by prescription. Additional commercial forms include liquid drops (intended for mixing with water), capsules, tablets, topical gels and creams, and dental/oral care products such as toothpaste and mouthwash.

In the food industry, sodium copper chlorophyllin serves as a natural green food coloring agent. Its vibrant hue and stability make it an attractive alternative to synthetic dyes. Its use as a food additive is regulated by authorities such as the FDA and the European Food Safety Authority (EFSA) to ensure safety and appropriate application.

2. Traditional and Historical Use

Early 20th-Century Research Origins

In the late 1930s, Temple University researcher Benjamin Gruskin was interested in the use of chlorophyll on infectious wounds and ulcers, but his experiment left him with mixed results. This early research nonetheless laid the groundwork for subsequent pharmaceutical development.

Research in the 1940s indicated that chlorophyllin slowed the growth of certain anaerobic bacteria in the test tube and accelerated the healing of experimental wounds in animals. These findings led to the use of topical SCC solutions and ointments in the treatment of persistent open wounds in humans. In 1947, the American Journal of Surgery reported that chlorophyll derivatives helped reduce the noxious odor of injured patients at a war hospital.

Mid-20th Century Clinical and Commercial Adoption

During the late 1940s and 1950s, a series of largely uncontrolled studies in patients with slow-healing wounds, such as vascular ulcers and pressure (decubitus) ulcers, reported that the application of topical SCC promoted healing more effectively than other commonly used treatments.

The deodorizing effects of chlorophyll were observed as early as the 1940s and 1950s and prompted doctors to administer chlorophyll to reduce fecal and urinal odor in patients with colostomies and ileostomies. Commercialization accelerated in the late 1940s and 1950s, with chlorophyllin introduced in pharmaceuticals for wound healing and odor control; studies by F. Howard Westcott demonstrated its efficacy in reducing bad breath and body odor, leading to over-the-counter products like deodorants and ointments.

By the 1950s, chlorophyll was marketed as a powerful deodorizer and detoxifier and quickly showed up on store shelves in an array of products, including toothpaste, soap, and chewing gum. The origins of these medical claims were rooted in findings from research by F. Howard Westcott in the 1940s that it was an odor blocker. The commercial value of this attribute led to many companies creating brands containing the compound in 1950–1953 in particular. It was used as a marketing tool to promote toothpaste, sanitary towels, soap, and other products.

The primary rationale for internal use comes from early reports in the 1940s and 1950s, when chlorophyllin was administered orally to reduce odors in patients with colostomies, ileostomies, and in those with incontinence or chronic wounds. It was also used to cleanse and accelerate the healing of open wounds, decrease the inflammation in radiation burns, and decrease odor in patients with colostomies or who were incontinent of urine or feces.

In Europe, copper complexes of chlorophyllins were approved as a food colorant (E141) following the establishment of E-number systems in the early 1960s, enabling its use in beverages and confectionery post-World War II to meet demand for natural green pigments.

SCC has been used orally as an internal deodorant and topically in the treatment of slow-healing wounds for more than 50 years without any serious side effects. Clinical use in nursing homes and wound care settings persisted even after the mid-1950s marketing controversies described in section 5 below.

3. Key Constituents and Active Compounds

Primary Bioactive Components

Sodium copper chlorophyllin (SCC) is a water-soluble and bright green mixture derived from natural chlorophyll that has potential antimutagenic and antioxidant properties. As a mixture rather than a single pure compound, the principal constituents are trisodium copper chlorin e6 and disodium copper chlorin e4, both of which are chlorin-type porphyrins.

A placebo-controlled clinical trial found that significant amounts of copper chlorin e4 were detectable in the serum of people taking chlorophyllin tablets (300 mg/day), indicating that it is indeed absorbed. In vitro studies have found chlorin e4 to have a higher stability than chlorin e6.

Structural Relationships to Natural Chlorophyll

The basic structure of chlorophyll is a porphyrin ring similar to that of heme in hemoglobin. In the conversion to SCC, two chemical modifications occur from natural chlorophyll: (1) the central magnesium ion is replaced by copper, and (2) the hydrophobic phytol tail is cleaved off by saponification. The result is a molecule that retains the core porphyrin chromophore but gains water solubility and greater chemical stability.

Given the porphyrin ring heme-like structure of iron chlorophyllin, it may be an alternative delivery route for iron, suitable also for vegetarians and vegans, yet there are few studies investigating the use of iron chlorophyllin for this purpose.

4. Mechanisms of Action

Molecular Complexation with Carcinogens

Chlorophyll and sodium copper chlorophyllin are able to form tight molecular complexes with certain chemicals known or suspected to cause cancer, including polyaromatic hydrocarbons found in tobacco smoke, some heterocyclic amines found in cooked meat, and aflatoxin-B1. The binding of chlorophyll or SCC to these potential carcinogens may interfere with gastrointestinal absorption of potential carcinogens, reducing the amount that reaches susceptible tissues.

Mechanistic studies suggest that chlorophyllin can act as an "interceptor molecule" through the formation of tight molecular complexes with carcinogens such as AFB1. Thus, chlorophyllin may diminish the bioavailability of dietary carcinogens by impeding their absorption and by shuttling them through the fecal stream, leading to reduced DNA adduct and tumor burden.

Antioxidant Activity

Chlorophyllin can neutralize several physically relevant oxidants in vitro, and limited data from animal studies suggest that chlorophyllin supplementation may decrease oxidative damage induced by chemical carcinogens and radiation. Studies have shown that chlorophyllin has immunostimulatory, anti-inflammatory, and antiviral effects in addition to antioxidant and radioprotective properties.

Antimutagenic Activity

Chlorophyllin is a potent antimutagen in a range of short-term genotoxicity assays in vitro and in vivo. Sodium/copper chlorophyllin (CHL) is a water-soluble derivative of chlorophyll that exhibits antimutagenic activity in several short-term genotoxicity assays and inhibits carcinogen-DNA binding in vivo.

In vitro, it binds to some environmental mutagens such as the polycyclic aromatic hydrocarbons benzo[a]pyrene and dibenzo[a,i]pyrene. Chlorophyllin also binds to acridine orange.

Antibacterial Effects

Research in the 1940s indicated that chlorophyllin slowed the growth of certain anaerobic bacteria in the test tube and accelerated the healing of experimental wounds in animals. More recently, a study evaluated the photosensitizing effectiveness of sodium copper chlorophyllin, a natural green colorant commonly used as a food additive (E-141ii), to inactivate methicillin-sensitive and methicillin-resistant Staphylococcus aureus under red-light illumination.

Inhibition of Hyaluronidase

Sodium copper chlorophyllin complex has demonstrated, both in vitro and in vivo, the ability to inhibit hyaluronidase. Hyaluronidase degrades hyaluronic acid, a key structural component of the dermal extracellular matrix, and its inhibition is considered relevant to anti-aging and wound-supportive applications in the skin.

5. Scientific Evidence by Area of Use

5.1 Aflatoxin Interception and Liver Cancer Chemoprevention

Evidence strength: Moderate (one landmark RCT; limited to high-exposure populations)

Aflatoxin-B1 (AFB1), a liver carcinogen produced by certain species of fungus, is found in moldy grains and legumes, including corn, peanuts, and soybeans. In hot, humid regions of Africa and Asia with improper grain storage facilities, high levels of dietary AFB1 are associated with increased risk of hepatocellular carcinoma.

In a randomized, double-blind, placebo-controlled chemoprevention trial, researchers tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Adherence to the study protocol was outstanding, and no adverse events were reported.

A cross-over study in three volunteers that used accelerator mass spectrometry to study the pharmacokinetics of an ultra-low dose of aflatoxin-B1 found a 150-mg dose of either SCC or chlorophyll could decrease absorption of aflatoxin-B1.

Chlorophyll and CHL treatment each significantly impeded AFB1 absorption and reduced C_max and AUCs (plasma and urine) in one or more subjects.

Because of the long time period between AFB1 exposure and the development of cancer in humans, an intervention trial might require as long as 20 years to determine whether SCC supplementation can reduce the incidence of hepatocellular carcinoma in people exposed to high levels of dietary AFB1. The Qidong trial is therefore considered proof-of-concept for biomarker reduction rather than direct evidence of cancer prevention. The findings are also specific to populations with unavoidably high dietary aflatoxin exposure and may not generalize to low-exposure Western populations.

5.2 Internal Deodorization (Odor Control)

Evidence strength: Weak to moderate; largely historical uncontrolled studies; limited contemporary RCT evidence

In the absence of such needed scientific proof, it can at least be said that chlorophyllin, taken as a tablet, has been extensively used in the past to treat fecal and urinary odor. A 1980s double-blind, placebo-controlled trial found modest benefit in reducing fecal odor in elderly nursing home patients, but the sample size was small and the effect size modest.

Research shows that taking chlorophyllin by mouth does not reduce urinary odor in older adults who have a urinary catheter. No large, well-controlled modern trials exist, and systematic reviews note the lack of robust, contemporary data.

Trimethylaminuria is a hereditary disorder characterized by the excretion of trimethylamine, a compound with a "fishy" or foul odor. One study in a small number of Japanese patients with trimethylaminuria found that oral SCC (60 mg three times daily) for three weeks significantly decreased urinary trimethylamine concentrations. Chlorophyllin remains an ingredient in some over-the-counter internal deodorant products, and it is occasionally recommended for individuals with trimethylaminuria ("fish odor syndrome"), though the evidence here is also largely anecdotal.

5.3 Wound Healing (Topical Use)

Evidence strength: Weak to moderate; largely uncontrolled historical case series; limited placebo-controlled data

Research in the 1940s indicating that chlorophyllin solutions slowed the growth of certain anaerobic bacteria in the test tube and accelerated the healing of experimental wounds in animals led to the use of topical chlorophyllin solutions and ointments in the treatment of persistent open wounds in humans. During the late 1940s and 1950s, a series of largely uncontrolled studies in patients with slow-healing wounds, such as vascular ulcers and pressure (decubitus) ulcers, reported that the application of topical SCC promoted healing more effectively than other commonly used treatments.

In the Western literature, there are older reports that are purely descriptive. For instance, some describe several patients who apparently derived symptomatic relief using chlorophyllin to decrease urine odor due to incontinence, or decrease skin pain that resulted from radiation burns after pelvic radiotherapy.

In the late 1950s, chlorophyllin was added to papain and urea-containing ointments used for the chemical debridement of wounds in order to reduce local inflammation, promote healing, and control odor. Chlorophyllin-containing papain/urea ointments are still available in the US by prescription. The evidence base for these formulations is principally derived from case series and uncontrolled clinical experience rather than large randomized trials.

5.4 Skin Conditions: Photodamage, Acne, and Aging

Evidence strength: Preliminary; small pilot studies only; placebo-controlled trials are lacking

A pilot study in 10 women (ages 40 years or older) with noticeable photodamage and solar lentigines found that twice daily topical application of a gel containing 0.66% SCC complex salts for eight weeks improved various clinical measures, including tactile and visual roughness of facial skin, skin radiance, fine lines, pore size, and overall photodamage.

A previous study demonstrated inhibition of hyaluronidase activity in vitro by sodium copper chlorophyllin complex. In a single-center, randomized, controlled, 12-day clinical trial, both the test material containing 0.05% sodium copper chlorophyllin complex and the positive control tretinoin cream 0.025% increased the presence of procollagen 1, fibrillin 1, and epidermal and dermal mucins, which are biomarkers of dermal repair, compared to the negative control.

A few case reports have also observed some improvement in facial redness and rosacea with application of topical SCC. While the reports from these studies are interesting, placebo-controlled clinical trials are needed to determine whether SCC may have utility in treating various skin conditions.

5.5 Leukopenia

Evidence strength: Very preliminary; single small study

Chinese clinical literature has documented an interest in chlorophyllin for hematological support. A study analyzing the therapeutic effect of sodium copper chlorophyllin tablets in treating 60 cases of leukopenia was published in the Chinese Journal of Integrative Medicine in 2005. The body of evidence is limited to this single small Chinese study and has not been independently replicated in controlled Western trials.

5.6 Antioxidant and Radioprotective Effects

Evidence strength: Preclinical (in vitro and animal data); no definitive human RCTs

Chlorophyllin scavenges radiation-induced free radicals and reactive oxygen species. A 2026 animal study evaluated the protective effects of sodium copper chlorophyllin against barium chloride-induced oxidative damage; animals received SCC (40 mg/kg) for 14 days prior to toxic exposure, and toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. These findings are preclinical and have not been translated to human clinical outcomes.

5.7 Iron Bioavailability (Iron Chlorophyllin)

Evidence strength: Very preliminary; mainly in vitro and early-phase clinical investigation

In vitro studies demonstrate that iron chlorophyllin is as good as heme in delivering iron to intestinal cells, and significantly better than the most common supplemental form of iron (i.e., ferrous sulfate) when incorporated into most food matrices. However, work in this area is nascent and has not yet been validated in humans. A 2019 study by Ding et al. suggests a positive effect of iron chlorophyllin on hemoglobin values in iron-deficiency anemia in children and adults after 1 month of treatment.

6. Body Systems and Health Areas of Association

• Gastrointestinal system: Internal deodorization of colostomy and ileostomy-related odors; reduction of fecal odor from incontinence; proposed binding of dietary carcinogens in the intestinal lumen.
• Hepatic system: Reduction of aflatoxin-induced DNA adducts as a biomarker of hepatocellular carcinoma risk in high-exposure populations.
• Skin and wound healing: Topical use for slow-healing wounds, vascular and pressure ulcers, radiation burns, photodamaged skin, acne, and enlarged pores.
• Metabolic/hereditary odor disorders: Reduction of urinary trimethylamine in trimethylaminuria.
• Antioxidant defense: Free radical scavenging activity demonstrated in vitro and in animal models.
• Hematological (iron chlorophyllin only): Preliminary evidence for enhanced iron delivery and improved hemoglobin in iron-deficiency anemia.

7. Dosage Forms and Reported Dosages

The following dosages are drawn directly from the scientific and clinical literature cited above; they do not represent recommendations.

• Aflatoxin chemoprevention (oral tablets): 100 mg of chlorophyllin three times a day for 4 months in the landmark Qidong RCT.
• Aflatoxin pharmacokinetics crossover study (oral capsules): Capsules containing 150 mg of purified chlorophyllin were administered as a single co-treatment dose.
• Trimethylaminuria (oral SCC): 60 mg three times daily for three weeks.
• Internal deodorization (from secondary sources): 100 mg of chlorophyllin for reduction of odor from incontinence/bladder catheterization; 300 mg daily if odor was not controlled.
• Copper absorption study (oral tablets): 300 mg/day of chlorophyllin tablets used in a placebo-controlled clinical trial examining serum copper chlorin e4.
• Topical photodamage (gel): Twice daily topical application of a gel containing 0.66% SCC complex salts for eight weeks.
• Topical photoaged skin (biopsy study): Test material containing 0.05% sodium copper chlorophyllin complex applied for 12 days.
• Oxidative stress animal study: SCC at 40 mg/kg for 14 days in mice.

8. Safety Considerations and Interactions

Regulatory Status and General Safety

The Joint FAO/WHO Expert Committee on Food Additives (JECFA) also found no adverse effects in a rat feeding study of up to 3% SCC in the diet for up to 2 years. The results showed no indications of adverse effects in rats at any of the doses tested from the prolonged consumption of the color additive. In addition, there was no evidence of metal toxicity.

Acute toxicity is not an anticipated problem and CHL products are considered Generally Regarded as Safe (GRAS). They have been extensively studied in multiple animal species and are commercially available in over-the-counter formulations.

Chlorophyllin is commonly used in small amounts as a coloring agent in foods. When used in larger doses as medicine, chlorophyllin is possibly safe when taken for up to 3 months. It might make the skin more sensitive to the sun. There is not enough reliable information to know if chlorophyllin is safe to use for longer than 3 months.

Copper Content and Potential Copper Toxicity

Chlorophyllin contains copper, which can cause serious adverse effects when taken in high doses for an extended period of time. No copper storage occurred in liver, kidney, or spleen of rats at dietary levels of 0.1 percent, or 1 percent of sodium and potassium chlorophyllin copper complex. There was no effect on iron storage at these levels. The copper atom in SCC is tightly chelated within the porphyrin ring, which is considered to reduce bioavailable ionic copper exposure compared to inorganic copper salts, though this has not been fully characterized in long-term human studies.

Chlorophyllin could theoretically enhance the effects of photosensitizing drugs, increasing sensitivity to sunlight. Additionally, its copper content might interact with medications used to treat Wilson's disease, a condition affecting copper metabolism.

Photosensitivity

Chlorophyllin might make the skin more sensitive to the sun. This is consistent with the behavior of other porphyrin-class compounds, which can act as photosensitizers. Users taking oral chlorophyllin supplements should be aware of potential increased UV sensitivity.

Gastrointestinal Effects and Pigmentation of Excreta

The green pigment will appear in urine and feces, which can be alarming to patients unaware of this effect. The green pigment in clothing is extremely hard to wash out. Aside from that, there seems little, if any, evidence that chlorophyllin can cause any harm.

Drug Interactions

Chlorophyllin inhibits CYP3A activity. CYP3A4 is a major cytochrome P450 enzyme involved in the metabolism of a large proportion of pharmaceutical drugs; inhibition of this enzyme could theoretically increase plasma levels of co-administered medications that are CYP3A substrates. When used in combination with immunosuppressant agents, caution is warranted due to human research suggesting that chlorophyll normalizes T lymphocyte and IgA counts. These interactions remain largely theoretical or based on preliminary data and have not been rigorously characterized in clinical pharmacokinetic studies.

Pregnancy and Lactation

Since the side effects of chlorophyll use are still not very clear, pregnant or breastfeeding mothers are advised to avoid the use of chlorophyll in the form of herbal supplements. No controlled safety data are available for these populations.

Staining

The color green will appear in all sorts of strange places as a result of chlorophyllin therapy, and urine and feces will turn green. This is a cosmetic and practical issue rather than a safety concern, but has been cited as one reason for the decline in clinical use of the compound in Western medicine despite its continued use elsewhere.

References

• Linus Pauling Institute, Oregon State University — Chlorophyll and Metallo-Chlorophyll Derivatives (Micronutrient Information Center)
• Egner PA et al. — Chlorophyllin intervention reduces aflatoxin–DNA adducts in individuals at high risk for liver cancer (PMC / PNAS, 2001)
• Egner PA et al. — Chlorophyllin intervention reduces aflatoxin–DNA adducts in individuals at high risk for liver cancer (PNAS, 2001)
• Jubert C et al. — Effects of Chlorophyll and Chlorophyllin on Low-Dose Aflatoxin B1 Pharmacokinetics in Human Volunteers (PMC / Cancer Prevention Research, 2009)
• Linus Pauling Institute — Effects of chlorophyll and chlorophyllin on low-dose aflatoxin B(1) pharmacokinetics in human volunteers
• PubChem — Chlorophyllin, copper sodium complex (CID 9875143)
• Wikipedia — Chlorophyllin
• ScienceDirect Topics — Chlorophyllin (overview)
• DrugBank — Sodium copper chlorophyllin: Uses, Interactions, Mechanism of Action
• International Foundation for Gastrointestinal Disorders (IFFGD) — Chlorophyllin: Is It Effective Odor Control?
• WebMD — Chlorophyllin: Overview, Uses, Side Effects, Precautions, Interactions, Dosing
• McCook JP et al. — Ability of sodium copper chlorophyllin complex to repair photoaged skin by stimulation of biomarkers in human extracellular matrix (PMC, 2016)
• Sigler ML, Stephens TJ — Assessment of the Safety and Efficacy of Topical Copper Chlorophyllin in Women With Photodamaged Facial Skin (Journal of Drugs in Dermatology, 2015)
• U.S. FDA Federal Register — Listing of Color Additives Exempt From Certification; Sodium Copper Chlorophyllin (2002)
• PMC — Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats
• PMC — Fifty Years of Aflatoxin Research in Qidong, China: A Celebration of Team Science to Improve Public Health (2025)
• Oregon State University Newsroom — Supplement Reduces Risk of Aflatoxin-Related Liver Cancer
• PMC — Photodynamic Inactivation of Methicillin-Resistant Staphylococcus aureus by a Natural Food Colorant (E-141ii)
• PMC — Protective Effects of Sodium Copper Chlorophyllin and/or Ascorbic Acid Against Barium Chloride-Induced Oxidative Stress in Mouse Brain and Liver (2025)
• ClinicalTrials.gov — Evaluation of Iron Bioavailability From Iron Chlorophyllin (NCT04602247)
• National Geographic — The science behind the chlorophyll water social media trend