Beyond 'Green': How Chlorophyll and Its Derivatives Can Help with Diabetes

The journal Nutrients published a review by scientists from the University of Padua (Italy), who collected and structured data on how chlorophyll - the green pigment of plants - and its derivatives potentially affect glycemic control and associated mechanisms in diabetes. The authors show that the effects occur not only through antioxidant "support", but also through the digestive tract, microbiota, inhibition of carbohydrate-splitting enzymes, modulation of the incretin system, and even the "insulin-like" action of individual molecules.

Background of the study

Type 2 diabetes mellitus is a chronic metabolic disease where, in addition to hyperglycemia, insulin resistance, low-level inflammation, and oxidative stress play a key role. Against the background of standard pharmacotherapy, there is growing interest in nutrients that could “catch” the early links of pathogenesis - primarily in the intestine, where the lion's share of postprandial glycemic surges and incretin signals are formed. This is where chlorophyll and its derivatives end up: a review in Nutrients systematizes data on how “green” molecules can gently influence carbohydrate metabolism and related pathways without directly interfering with the insulin receptor.

Chlorophyll is an everyday food pigment from dark green vegetables and algae; the EFSA European Menu Assessment gives an average intake of about ≈207 mg of "green" chlorophylls per day in adults, with a large variation between countries. However, the systemic bioavailability of natural chlorophyll is low, with the products of its transformation in the digestive tract - pheophytins/pyropheophytins and pheophorbide - playing a significant role. This explains the focus on local "intestinal" mechanisms and the interest in formulations (e.g. microcapsules) that retain active forms in the intestinal lumen.

The mechanistic logic consists of several branches. First, inhibition of carbohydrate breakdown enzymes: chlorophyll derivatives (pheophorbide a, pheophytin a, pyropheophytin a) inhibit α-amylase and α-glucosidase, smoothing out postprandial glycemia. Second, the incretin axis: in a number of studies, chlorophyll extracts reduced DPP-4 activity, which theoretically supports endogenous GLP-1 (an important circuit in modern diabetology). Third, data are appearing on insulin-like effects of pheophorbide a - increased glucose transport through GLUT1/GLUT4 in cellular and preclinical models. Finally, antioxidant and anti-inflammatory effects of "green" porphyrins, complementing the metabolic effect, have been described at the level of systems physiology.

Despite all the potential, the field remains early: a significant part of the base is in vitro and preclinical; RCTs with strict endpoints (postprandial glycemia, HbA1c, incretin markers) and comparison with standards (acarbose, DPP-4 inhibitors) are needed for clinical recommendations. In parallel, safety should be taken into account: a number of chlorophyll derivatives are porphyrin photosensitizers, which means that the form, dose and direction of delivery (intestinal-local vs. systemic) should be selected carefully. Nevertheless, it is precisely this “intestinal-centric” approach - gentle correction of enzyme and hormonal cascades - that makes chlorophyll a promising candidate in the arsenal of auxiliary nutritional strategies for diabetes.

In Brief: Why It Matters

Diabetes affects hundreds of millions of adults, and the number of patients is growing. Against the background of standard therapy, interest in “green” nutrients is understandable: chlorophyll is widely present in food (dark green vegetables, algae), and the average consumption in Europe was estimated at about 200-400 mg per day, depending on the diet. The review emphasizes that it is chlorophyll derivatives that provide the greatest potential for glycemic control, and the mechanisms themselves are largely “intestinal” - local, without systemic absorption.

What exactly was found (by areas of action)

The paper brings together results from cell, animal, and pilot technology studies; together they build a multi-step scenario.

• Gut and microbiota. Chlorophyll supplementation in diet-induced obese mice improved glucose tolerance, reduced low-grade inflammation, and reshaped the microbiota (including a reduced Firmicutes/Bacteroidetes ratio), which is associated with improved carbohydrate utilization and metabolic unloading.
• Inhibition of "sugar" enzymes. Chlorophyll itself weakly interacts with α-glucosidase, but its derivatives - pheophorbide a, pheophytin a, pyropheophytin a - are able to slow down the breakdown of carbohydrates, acting as inhibitors of α-amylase and α-glucosidase. A number of studies have also shown a physicochemical explanation: by interacting with starch/enzymes, the molecules prevent enzymes from accessing the substrate and increase the proportion of resistant starch, which smooths out postprandial glucose peaks.
• Incretins and DPP-4. Microencapsulated chlorophyll-containing extracts not only inhibited α-amylase/α-glucosidase in vitro, but also suppressed the activity of DPP-4, an enzyme that degrades incretins (GLP-1, etc.), thereby potentially supporting the endogenous insulin response. The effect was carrier-dependent (protein capsules worked better than carbohydrate capsules).
• Antiglycation and complications. Feophorbide a inhibited the binding of advanced glycation end products (AGEs) to their receptor RAGE, a key axis in the development of vascular and tissue complications of diabetes; activity was comparable to the reference inhibitor in model tests.
• “Insulin-like” action. In phenotypic screens in zebrafish larvae and in cell models, pheophorbide a enhanced glucose uptake by interacting with GLUT1/GLUT4 transporters and increasing their membrane availability/stability. This suggests a possible target outside the classical insulin receptor.
• Chlorophyllin (semi-synthetic derivative): Effects on lipid metabolism, oxidative stress, and even intestinal barrier integrity have been shown in mice, indirectly supporting metabolic stability.

How it can work

The "triple fork" is designated. First, physicochemical: complexation with starch and enzymes → slower release of glucose in the intestinal lumen. Second, hormonal-incretin: inhibition of DPP-4 and increase in GLP-1 → better postprandial β-cell response. Third, cell-signaling: individual porphyrin-like derivatives (pheophorbide a) behave as insulinomimetics, enhancing glucose transport through GLUT1/GLUT4 and simultaneously inhibiting the AGE-RAGE axis, which potentially slows down complications. All three lines add up to the idea of "soft diabetic therapy" through the intestine and its interfaces.

What is already known about sources and doses from the diet

Chlorophyll is an everyday nutrient: it is found in the highest amounts in dark green vegetables, bean pods, and algae/microalgae (e.g. chlorella). Based on dietary patterns for Europeans, the average daily intake of "green" chlorophyll was estimated at ~207 mg (with a very "green" plate, the estimates go up). The bioavailability of chlorophyll itself is low (most of it is converted into derivatives and excreted through the intestines), which is precisely what drives formulations/microcapsules and a focus on local mechanisms in the intestinal lumen.

Benefit is good, but where are the pitfalls?

The authors honestly discuss the risks and gaps.

• Photosensitization. A number of chlorophyll derivatives (porphyrin series) are potential photosensitizers. For application, intestinal-targeted forms/carriers and chemical modifications that reduce the release of singlet oxygen and systemic absorption are considered.
• Level of evidence. Much of the data is in vitro, preclinical, or technology models. There are few full-scale clinical trials on glycemic outcomes, so it is too early to talk about the drug/dose/regime.
• Heterogeneity of matrices. Effects depend on the carrier (protein capsules vs. maltodextrin), heat treatment of food (formation of pheophytins/pyropheophytins) and composition of extracts, which makes direct comparisons difficult.

What this might mean in practice (if the results are confirmed)

The prospect is not in a “chlorophyll pill”, but in individual formulas for a specific task: capsules for work in the intestinal lumen (inhibition of α-glucosidase/α-amylase/DPP-4), functional products with controlled release, combinations with fiber/resistant starch, as well as insulin-mimetic molecules of plant origin as a separate direction. In parallel, a rational “green plate” remains a universal, safe background for healthy eating - but this is precisely nutrition, not treatment.

What will science ask for next?

• Randomized clinical trials focusing on postprandial glycemia, incretin markers and tolerability (including phototoxicity).
• Pharmacokinetics and safety of individual derivatives (especially pheophorbide a) with enteric-directed administration.
• Standardized matrices (media types, processing temperatures) and comparable endpoints.
• Comparison with benchmarks (acarbose, DPP-4 inhibitors) to understand the added value of the green strategy.

Who is this news addressed to?

It is important for patients with diabetes and specialists to see the "green" molecules as a perspective, not an immediate replacement for therapy. Any supplements and extracts - only after discussion with a doctor, especially when taking hypoglycemic agents: interference with enzymes and incretins is not a toy. The review is a scientific map of the area, not a ready-made guide to action.

Source: Sartore G., Zagotto G., Ragazzi E. Beyond Green: The Therapeutic Potential of Chlorophyll and Its Derivatives in Diabetes Control. Nutrients 17(16):2653 (2025). https://doi.org/10.3390/nu17162653