Algal Bioactive Peptides: A New Opportunity for Metabolic Health Regulation and Sustainable Nutrition

Chronic non-communicable diseases (NCDs) are a primary cause of global mortality and disability, with hypertension, type 2 diabetes, obesity, and cardiovascular diseases as the core drivers. Faced with this serious public health challenge—with over 830 million people globally living with diabetes and cardiovascular diseases claiming more than 17 million lives annually—current clinical interventions primarily rely on chemical drugs, which are often associated with significant side effects and poor long-term patient adherence. Concurrently, dietary and nutritional interventions, the cornerstone of disease prevention, have not realized their full potential due to the limitations of most functional ingredients, which often exhibit singular bioactivities and insufficient targeting. Furthermore, the substantial consumption of water and land resources and considerable carbon footprint associated with traditional animal and plant protein production models pose an urgent challenge to building a sustainable global food system.

In this context, algal bioactive peptides, derived from the proteins of microalgae, macroalgae, and cyanobacteria, emerge as a new generation of functional food ingredients with unique value in addressing this dual challenge. These small peptide fragments, obtained through targeted enzymatic hydrolysis, have been shown to possess multiple biological activities, including regulation of blood pressure via inhibition of angiotensin-converting enzyme (ACE), control of blood glucose through inhibition of α-amylase and dipeptidyl peptidase-IV (DPP-IV), modulation of lipid metabolism for weight management, and antioxidant and anti-inflammatory effects. More importantly, algae cultivation itself offers high photosynthetic efficiency, extremely low requirements for water and land resources (e.g., requiring far less land to produce an equivalent amount of protein compared to conventional agriculture), and significant carbon sequestration potential. Combined with the peptides' characteristics of easy absorption, relatively clear mechanisms of action, and favorable safety profile, algal peptides present an innovative solution for simultaneously achieving precise nutritional intervention for chronic metabolic diseases and sustainable protein supply.

A review published in Annals of Medicinecomprehensively evaluates the nutritional properties, health mechanisms of action, current applications, and life-cycle sustainability of algal peptides. The review not only affirms their enormous potential but also provides an in-depth analysis of the core bottlenecks facing industrial translation, such as standardized peptide identification, bioavailability, economic viability of large-scale production, and regulatory challenges concerning contaminant control and harmonized standards. It also outlines future R&D directions, thereby providing a scientific basis for research, industrial translation, and policy-making in related fields.

1. Foundational Attributes and Advantages of Algal Peptides

The core value of algal peptides is built upon the inherent resource characteristics and nutritional advantages of algae, which distinguish them from traditional animal- and plant-derived functional peptides.

As the Earth's oldest photosynthetic organisms, algae possess extremely high photosynthetic efficiency (up to 10%–20%), far exceeding that of most terrestrial plants. Their land use efficiency also significantly surpasses that of traditional protein sources: producing 1 kg of algal protein requires only about 2.5 m² of land, compared to 144–258 m² for beef, 42–52 m² for chicken, and 4.6 m² for soybeans. Algae can be cultivated on non-arable land, in wastewater, or seawater, avoiding competition with food production for resources, and can sequester atmospheric CO₂ through photosynthesis. Coupling algae cultivation with industrial flue gas treatment or wastewater purification can establish circular economic models, perfectly aligning with multiple UN Sustainable Development Goals (SDGs), including Zero Hunger and Climate Action.

Algae are a high-quality protein source. The protein content in microalgae ranges from 20% to 60% of dry weight, and 1.3% to 47% in macroalgae. Most algae provide complete protein, containing all essential amino acids for humans, with branched-chain amino acid levels comparable to those in soybeans and eggs. Their Amino Acid Score (AAS) can reach up to 1.16, close to that of milk casein. The Protein Digestibility-Corrected Amino Acid Score (PDCAAS) ranges from 0.63 to 0.84, on par with mainstream plant proteins. Although the tough cell walls of some algae may affect digestibility, this can be significantly improved through appropriate processing techniques like cell disruption.

Humans have consumed algae for over a thousand years. The modern large-scale cultivation of algae began in the 1960s. Today, algal biomass is widely used in food, feed, cosmetics, and pharmaceuticals. Well-established global supply chains exist for species like Spirulinaand Chlorella, providing a solid raw material and industrial foundation for the R&D and commercialization of algal peptides.

2. Efficacy and Mechanisms of Action of Algal Peptides

Algal bioactive peptides regulate systemic health through multiple targets and pathways, with their primary effects concentrated in four areas related to metabolism.

2.1 Antihypertensive Activity

This is the most well-researched area for algal peptides. The mechanisms include: ① Inhibiting the activity of ACE and renin in the Renin-Angiotensin System (RAS), reducing the production of the vasoconstrictor angiotensin II; ② Activating the PI3K/AKT signaling pathway to promote the release of nitric oxide from vascular endothelial cells, inducing vasodilation; ③ Protecting vascular endothelium through antioxidant and anti-inflammatory actions, improving vascular homeostasis; ④ Modulating the sympathetic nervous system to reduce vasoconstrictive signaling.

Peptides with high ACE-inhibitory activity have been isolated from various algae, including macroalgae like wakame (Undaria pinnatifida), nori (Pyropia yezoensis), and dulse (Palmaria palmata), as well as microalgae like Spirulina, Chlorella, and Nannochloropsis. Human clinical trials have confirmed that daily supplementation with 2-4.5 g of Spirulina, 1.5 g of Chlorella, or wakame powder can significantly lower systolic and diastolic blood pressure in individuals with mild-to-moderate hypertension. Japan has approved enzymatic hydrolysates of nori and wakame as Foods for Specified Health Uses (FOSHU).

2.2 Blood Glucose Regulation and Antidiabetic Effects

Algal peptides modulate glucose homeostasis through multiple synergistic mechanisms: ① Inhibiting the activity of α-amylase and α-glucosidase, delaying carbohydrate digestion and absorption to lower postprandial blood glucose spikes; ② Inhibiting DPP-IV activity, prolonging the physiological action of incretins like GLP-1, thereby stimulating insulin secretion; ③ Upregulating the expression of the glucose transporter GLUT-4, enhancing cellular glucose uptake; ④ Reducing oxidative damage to pancreatic β-cells and improving insulin resistance through antioxidant and anti-inflammatory effects.

Active peptides derived from Spirulina, Chlorella, sea lettuce (Ulvaspp.), and Dunaliella salinahave shown clear glucose-lowering potential in vitro and in animal models. Human clinical trials indicate that Spirulinaand Chlorellasupplements can significantly reduce fasting blood glucose and glycated hemoglobin (HbA1c) in type 2 diabetes patients, while also improving lipid profiles.

2.3 Cardiovascular Protection and Lipid Metabolism Regulation

Beyond lowering blood pressure and glucose, algal peptides exert cardioprotective effects via multiple targets: ① Inhibiting pancreatic lipase and HMG-CoA reductase, reducing dietary fat absorption and endogenous cholesterol synthesis; ② Inhibiting adipocyte differentiation and lipid accumulation, while promoting lipolysis by activating signaling pathways like AMPK and PPARγ; ③ Scavenging reactive oxygen species (ROS) and activating the Nrf2 pathway to enhance endogenous antioxidant capacity, mitigating vascular oxidative damage; ④ Inhibiting the expression of endothelial adhesion molecules and platelet activation, reducing the formation of atherosclerotic plaques.

Clinical studies confirm that supplementation with Spirulinaor Chlorellasignificantly improves the lipid profile and enhances vascular endothelial function in individuals with hyperlipidemia.

2.4 Weight Management and Anti-Obesity Effects

Algal peptides counteract obesity through several mechanisms: ① Inhibiting pancreatic lipase activity, reducing dietary fat digestion and absorption; ② Inhibiting key fatty acid synthesis enzymes like ACC, decreasing endogenous lipid production; ③ Activating the AMPK energy-sensing pathway to promote fat breakdown and oxidation; ④ Promoting the browning of white adipose tissue via the PPARγ/UCP-1 pathway, enhancing thermogenesis and energy expenditure; ⑤ Stimulating GLP-1 secretion, delaying gastric emptying, and increasing satiety to reduce food intake; ⑥ Modulating the gut microbiota, improving obesity-related dysbiosis.

Both animal models and human clinical trials have demonstrated that algal peptides can reduce body fat accumulation, lower body weight and BMI, and improve waist circumference and hepatic fat metabolism, showing clear benefits for individuals with metabolic syndrome.

2.5 Other Auxiliary Bioactivities

Additionally, algal peptides possess broad auxiliary activities, including antioxidant, anti-inflammatory, antimicrobial, and gut microbiota-modulating effects. For example, by inhibiting the release of pro-inflammatory cytokines like TNF-α and IL-6, and promoting the proliferation of beneficial gut bacteria, these actions collectively contribute to improving overall metabolic health.

3. Applications of Algal Peptides

3.1 Current Application Status

Currently, algal protein and peptide products are commercially available globally, primarily in forms like powders, capsules, and tablets as dietary supplements. Core product categories center around Spirulinaand Chlorella, targeting areas like basic nutrition, cardiovascular health, antioxidant support, and immune enhancement. Internationally representative producers include Earthrise Nutritionals and Cyanotech (USA), Sun Chlorella (Japan), and E.I.D. Parry (India). However, most commercially available products consist of whole algae biomass or crude extracts. High-purity algal peptide products with a defined single activity remain scarce, mainly limited by efficient separation/purification technologies and high production costs.

3.2 Sustainability

Life Cycle Assessment (LCA) results indicate that algal protein production offers significant environmental advantages. The cultivation process can directly utilize carbon dioxide from industrial exhaust gases for carbon fixation and can be conducted in treated wastewater, enabling nutrient recycling. This substantially reduces greenhouse gas emissions. Compared to traditional livestock farming and agriculture, algal production has extremely low water and land resource consumption. When algae cultivation is coupled with renewable energy, wastewater treatment, and carbon capture, its carbon footprint can be further reduced, making it one of the most sustainable protein sources currently available.

3.3 Bottlenecks and Optimization Pathways

The core challenge for the industrialization of algal peptides is high production costs, which already far exceed those of traditional plant proteins like soy. Downstream processing steps (e.g., harvesting, cell disruption, enzymatic hydrolysis, purification) constitute the major cost components. Several optimization pathways are possible: ① Adopting an algal biorefinery model to co-recover high-value co-products like pigments, oils, and polysaccharides, distributing production costs; ② Reducing raw material costs through large-scale production, open pond cultivation, and nutrient recovery from wastewater; ③ Lowering energy and material consumption in downstream processing through process innovation.

4. Challenges in Algal Peptide Development

• Insufficient Exploration of Species Resources:​ It is estimated that there are 200,000 to 800,000 algal species globally, with only about 30,000 identified. Health-related bioactivity has been deeply studied in only a very few (e.g., Spirulina, Chlorella). A vast number of potentially high-activity algal species remain to be effectively screened and evaluated.
• Immature Preparation Processes and Lack of Standards:​ The tough cell walls of many algae lead to low protein extraction efficiency. Downstream enzymatic hydrolysis and purification processes are energy-intensive and difficult to scale up industrially. The industry lacks standardized preparation and characterization methods, making it difficult to compare and reproduce results from different studies, severely hindering technology translation.
• Unclear Bioavailability and In Vivo Mechanisms:​ Most studies stop at in vitro activity verification. The gastrointestinal stability, absorption, metabolism, and final bioactive forms of algal peptides in the human body remain unclear. Their low oral bioavailability is a key bottleneck limiting efficacy realization.
• Scarcity of High-Quality Clinical Evidence:​ Existing human clinical trials are few, small-scale, short-term, and often use whole algae or crude extracts, preventing confirmation of dose-response relationships and definitive clinical benefits for specific peptides. The evidence strength is insufficient to support robust product claims and regulatory approvals.
• Sensory Properties and Market Acceptance Limitations:​ Algal protein hydrolysates often carry undesirable flavors and colors. In regions without a history of algal consumption, consumer acceptance is low, limiting their widespread application as general food ingredients.
• Incomplete Safety and Regulatory Systems:​ Algae carry risks of accumulating heavy metals (e.g., arsenic, cadmium) and high iodine levels. An assessment system for their allergenic potential is lacking. Globally, unified quality standards and regulatory frameworks for algal peptides are absent, with varying requirements across countries, hindering global market access.

5. Future Development Directions

• AI and Bioinformatics-Driven High-Efficiency Discovery:​ Utilize tools like AlphaFold, molecular docking, and machine learning for high-throughput virtual screening, activity prediction, and rational design of algal peptides. This will accelerate the discovery of novel, highly active, and stable peptides and expand exploration of new resources like extremophile algae.
• Delivery System Innovation to Enhance Bioavailability:​ Develop advanced delivery technologies based on nano-encapsulation, liposomes, etc., to protect active peptides in the gastrointestinal tract, improve their oral absorption efficiency and targeting, and fundamentally address the low bioavailability bottleneck.
• Process Standardization and Cost Optimization:​ Research and develop efficient, low-energy cell disruption, enzymatic hydrolysis, and purification technologies. Establish standardized processes from preparation to characterization. Reduce overall production costs through the high-value integrated utilization of co-products (biorefinery model).
• Building a Robust Clinical Evidence Base:​ Conduct large-scale, long-term, well-designed randomized controlled human clinical trials to clarify the dose-response, long-term safety, and definitive health benefits of specific algal peptides, providing core evidence for product approval and high-end applications (e.g., medical foods).
• Developing Blended Products and Expanding Application Scenarios:​ Investigate the synergistic effects of algal peptides with other algal-derived active components like phycocyanin and polysaccharides to develop composite formulations. Simultaneously, optimize post-processing techniques for deodorization and decolorization to improve sensory properties, enabling expansion into broader application areas like conventional foods and sports nutrition.
• Improving Global Safety and Regulatory Standards:​ Promote the establishment of internationally harmonized quality standards, contaminant limits, and allergenicity assessment protocols for algal peptides. Clarify the regulatory approval pathways for novel algal ingredients to provide an institutional framework for global market access of products.

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Original article:

Khaliq, Muniba, et al. "Navigating the potential of algal peptides: health effects, market applications, and scientific challenges." Annals of Medicine 58.1 (2026): 2637282.