Compendium of the most significant studies with reference to properties, intake, effects.

Smith RG. Enzymatic debriding agents: an evaluation of the medical literature. Ostomy Wound Manage. 2008 Aug;54(8):16-34. 

Abstract. Although debridement is an essential part of wound care, information to guide evidence-based decisions is limited in the literature. Assuming studies to ascertain the effectiveness of pharmaceutically based enzymatic debridement products are more prolific than studies using nonpharmaceutical debridement options, a literature review was conducted to provide an evidence base to justify current wound care practice. Information on collagenase- and papain-urea-based products was reviewed with emphasis on their functional components, mechanisms of action, and patient considerations. The Medline Database, Cochrane Database of Systematic Reviews, InfoPOEMs, Institute for Clinical Systems Improvement, National Guideline Clearinghouse, and Primary Care Clinical Practice Guidelines were searched for documents published between 1967 and 2007 using the following terms: enzymatic debridement, collagenase, papain-urea, papain-urea chlorophyllin copper complex, wounds, and diabetic foot wounds. Sixteen of of 44 relevant citations obtained fit the established criteria for readability, accuracy, reliability and validity of information. Four of the 16 studies included a control treatment, the external validity of 13 studies was limited due to small sample size, and only four studies reported a statistically significant difference in treatment outcome. Predicted bias and publication bias were common. Of the studies detailed herein, three qualified as A level, 13 qualified as B level, and none were considered to provide C level evidence. Although clinicians can glean practical information from the homogenized findings regarding patient demographics, wound type, and therapeutic goals, future studies designed to meet the criteria of level A evidence are needed to provide evidence for the use of enzymatic debridement agents.

McCook JP, Stephens TJ, Jiang LI, Law RM, Gotz V. Ability of sodium copper chlorophyllin complex to repair photoaged skin by stimulation of biomarkers in human extracellular matrix. Clin Cosmet Investig Dermatol. 2016 Jul 25;9:167-74. doi: 10.2147/CCID.S111139. 

Abstract. Purpose: To examine the effect of sodium copper chlorophyllin complex on the expression of biomarkers of photoaged dermal extracellular matrix indicative of skin repair. Patients and methods: Following a previously published 12-day clinical assessment model, skin biopsy samples from the forearms of four healthy females with signs of photoaged skin were obtained and samples were analyzed by immunohistochemistry for key biomarkers of aging skin after each subject was treated with a test material consisting of a gel containing a liposomal dispersion of sodium copper chlorophyllin... Conclusion: The results of this human biopsy study suggest that both retinoids and sodium copper chlorophyllin complex have beneficial effects on biomarkers of photoaged skin. Products containing both sodium copper chlorophyllin complex and retinols may provide a dual approach to reversing age-related decreases in hyaluronic acid (HA) in the skin: inhibition of the breakdown of HA via sodium copper chlorophyllin complex by inhibition of hyaluronidase, and stimulation of HA synthases by retinol.

McCook JP, Dorogi PL, Vasily DB, Cefalo DR. In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and chlorophyllin analogs. Clin Cosmet Investig Dermatol. 2015 Aug 12;8:443-8. doi: 10.2147/CCID.S86863.

Abstract. Background: Inhibitors of hyaluronidase are potent agents that maintain hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and anti-microbial agents. Sodium copper chlorophyllin complex is being used therapeutically as a component in anti-aging cosmeceuticals, and has been shown to have anti-hyaluronidase activity. In this study we evaluated various commercial lots of sodium copper chlorophyllin complex to identify the primary small molecule constituents, and to test various sodium copper chlorophyllin complexes and their small molecule analog compounds for hyaluronidase inhibitory activity in vitro. Ascorbate analogs were tested in combination with copper chlorophyllin complexes for potential additive or synergistic activity. ...Results: The most active small molecule component of sodium copper chlorophyllin complex was disodium copper isochlorin e4, followed by oxidized disodium copper isochlorin e4. Sodium copper chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase inhibitory activity down to 10 µg/mL. The oxidized form of copper isochlorin e4 disodium salt had substantial hyaluronidase inhibitory activity at 100 µg/mL but not at 10 µg/mL. Ascorbate derivatives did not enhance the hyaluronidase inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs were always the dominant components of the small molecule content of the commercial lots tested; oxidized copper isochlorin e4 was found in increased concentrations in older compared to newer lots tested. Conclusion: These results support the concept of using the hyaluronidase inhibitory activity of sodium copper chlorophyllin complex to increase the hyaluronic acid level of the dermal extracellular matrix for the improvement of the appearance of aging facial skin.

Zhong S, Bird A, Kopec RE. The Metabolism and Potential Bioactivity of Chlorophyll and Metallo-chlorophyll Derivatives in the Gastrointestinal Tract. Mol Nutr Food Res. 2021 Apr;65(7):e2000761. doi: 10.1002/mnfr.202000761. 

Abstract. Chlorophyll is the vivid chromophore which imparts the green color to plant leaves, and is consumed by humans through green vegetables. The basic porphyrin structure of chlorophyll binds magnesium in plants, but can bind different divalent metals (e.g., copper, zinc, iron) facilitated by food processing techniques and/or chemical synthesis. This review covers the known elements of chlorophyll and metallo-chlorophyll absorption, distribution, metabolism, excretion in vitro and in vivo. The review discusses what is understood about the ability of these novel metallo-chlorophyll derivatives to deliver essential metals. This review also detail chlorophyll and metallo-chlorophyll toxin binding properties which largely occur during digestion, focusing on toxins including dioxins, heterocyclic aromatic amines, polyaromatic hydrocarbons, and aflatoxin. Finally, the article highlights the gaps in the understanding of the metabolism and metal and toxin-binding bioactivity of this family of molecules. © 2021 Wiley-VCH GmbH.