Elsevier

Nutrition Research

Volume 27, Issue 1, January 2007, Pages 1-12
Nutrition Research

Review Article
Digestion, absorption, and cancer preventative activity of dietary chlorophyll derivatives

https://doi.org/10.1016/j.nutres.2006.12.003Get rights and content

Abstract

The growing body of epidemiological and experimental evidence associating diets rich in fruits and vegetables with prevention of chronic diseases such as cancer has stimulated interest in plant food phytochemicals as physiologically active dietary components. Chlorophyll and its various derivatives are believed to be among the family of phytochemical compounds that are potentially responsible for such associations. Dietary chlorophyll is predominantly composed of lipophilic derivatives including chlorophyll a and b (fresh fruits and vegetables), metal-free pheophytins and pyropheophytins (thermally processed fruits and vegetables), as well as Zn-pheophytins and Zn-pyropheophytins (thermally processed green vegetables). Water-soluble derivatives including chlorophyllides, pheophorbides, as well as a commercial-grade derivative known as sodium copper chlorophyllin (SCC) also contribute to the diversity of dietary chlorophyll derivatives. Although the use of chlorophyll derivatives, especially SCC, in traditional medical applications is well documented, it is perhaps the potential of chlorophyll as a cancer preventative agent that has drawn significant attention recently. Biological activities attributed to chlorophyll derivatives consistent with cancer prevention include antioxidant and antimutagenic activity, mutagen trapping, modulation of xenobiotic metabolism, and induction of apoptosis. Although most research has focused on commercial-grade SCC, the extent to which natural chlorophyll derivatives modulate biomarkers of cancer risk is also being explored. Recent research efforts have also included investigation of the impact of digestive factors on chlorophyll structure and bioaccessibility as a means to better understand the extent to which these pigments may be bioavailable in humans and therefore have more systemic impact in the prevention of cancer.

Introduction

Increased fruit and vegetable consumption has been associated with a decreased cancer risk [1], [2], [3], [4], intensifying interest in plant food phytochemicals as potential physiologically active agents. Chlorophyll is the most ubiquitous of all natural pigments, reaching levels that can exceed 1000 to 2000 ppm wet weight in some species [5], and is responsible for the color of all green plants [6]. Considering the primary role of chlorophyll in photosynthesis and its close association with yellow/orange carotenoid pigments well known for their bioactivity, these blue-green pigments have often been overlooked with regard to their potential physiological impact and role in the prevention of chronic disease.

Chlorophyll and its various derivatives have a long-established history of use in traditional medicine and for therapeutic purposes [7]. Both natural chlorophyll and commercial-grade derivatives such as sodium copper chlorophyllin (SCC) have been widely investigated for a range of beneficial biological activities including wound healing [8], anti-inflammatory properties [9], [10], control of calcium oxalate crystals [11], and internal deodorization [12]. Furthermore, the ability of both natural and commercial chlorophyll derivatives to act as photosensitizers have enabled their utilization as effective agents in photodynamic therapy of cancer [13], [14], [15].

Although these applications illustrate the potential usefulness of chlorophyll derivatives in medical applications, it is perhaps the potential role of these pigments in the prevention of human cancers that has drawn more recent attention. Both SCC and natural chlorophyll derivatives have demonstrated significant biological activities in vitro and in vivo consistent with the prevention of cancer including antioxidant activity, antimutagenic activity, modulation of xenobiotic metabolizing enzymes, and induction of apoptotic events in cancer cell lines. These encouraging results have led to the investigation of chemopreventative effects in humans [16], [17] and further stimulated interest in the absorption and potential tissue distribution of these pigments in humans. Although traditionally assumed to be unabsorbable by humans, limited research efforts have begun to offer evidence supporting the notion that chlorophyll derivatives may in fact be bioavailable. These efforts remain critically important to better understand the mechanism by which dietary chlorophyll derivatives may prevent cancer.

The purpose of this review is to summarize information from relevant scientific studies covering chlorophyll structure; the impact of food processing and digestive conditions; the potential for intestinal uptake and bioavailability; and cancer preventative activities including antioxidant and antimutagenic activity, modulation of xenobiotic metabolism, and induction of apoptosis. Furthermore, an effort is made to further elaborate the differences between research on natural chlorophylls and studies focused on commercially derived semisynthetic derivatives such as SCC.

Section snippets

Chlorophyll structure, stability, and derivatives

Structurally, chlorophyll is a substituted tetrapyrrole with a centrally bound magnesium atom (Fig. 1). The porphyrin macrocycle is further esterified to a diterpene alcohol, phytol, to form chlorophyll. In nature, chlorophyll a and b predominate in higher plants, whereas chlorophyll c, d, and e derivatives are found throughout various photosynthetic algae and diatomic species including brown, red, and yellow-green algae [6]. Furthermore, several additional classes of bacteriochlorophylls, not

Digestive behavior and bioavailability of chlorophyll derivatives

Bioavailability refers to the fraction of any compound ingested and made available for utilization, metabolism, and/or storage by the organism. Information on the bioavailability of chlorophyll derivatives is limited partially because of the general assumption that chlorophyll is unabsorbable by humans. However, considering the natural abundance of chlorophyll in fruit and vegetable tissues, the diversity of derivatives formed through food processing and preparation, and the growing use of

Chlorophyll and cancer prevention

The association of diets rich in phytochemicals with the prevention of cancer has intensified interest in chlorophyll as a class of plant pigments with potential chemopreventative effects. Considering the traditional use of chlorophyll derivatives in medicine [7] and the low toxicity [41], these pigments serve as attractive cancer preventative and potentially therapeutic agents. Research highlighting the bioactivity of chlorophyll in vitro and in vivo as well as potential mechanisms of cancer

Potential mechanism of chlorophyll cancer preventative activity

Several studies have been conducted to elucidate specific mechanisms responsible for the observed cancer preventative activity of chlorophyll derivatives. Focused on in vitro and cell culture–based assays, these efforts have primarily highlighted antioxidant activity, mutagen trapping, modulation of detoxification pathways, and induction of apoptosis as modes of actions responsible, in part, for chlorophyll's protective effects in vivo (Fig. 4).

Conclusions and future directions

Chlorophylls belong to a larger class of phytochemical plant pigments implicated as cancer preventative agents. Investigations highlighting specific derivatives (chlorophylls, pheophorbides, pheophytins, and chlorins), preparations (vegetables, vegetable extracts, and SCC), and protective actions have been reported in the literature. Following the common assumption that chlorophyll is unabsorbable by humans and the strong data to indicate antimutagenic activity in vitro, a central hypothesis

Acknowledgment

The authors thank Rodney Green for assistance in preparation of this manuscript.

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