IngredientsSilks are a class of proteins generated naturally by different arthropods, including silkworms, spiders, scorpions, mites, wasps, and bees. In the context of dietary supplementation and biomedical research, "silk protein" refers primarily to two distinct macromolecular proteins derived from the domesticated silkworm Bombyx mori Linnaeus (Lepidoptera: Bombycidae): silk fibroin (SF) and silk sericin (SS).
Silk produced by Bombyx mori silkworms is composed of two main proteins, namely fibroin and sericin. Silk fibroin constitutes 70–75% of the silk proteins and is a fibrous protein secreted by the silkworm in two strands coming from the right and left sides of the excretory duct. Fibroin is defined as a structural protein that bestows silk with strength, while sericin is characterized as a gum-like protein, tying the two fibrous proteins together and endowing silk proteins with elasticity.
The silk fiber from B. mori cocoon is a twin fiber that consists of two kinds of proteins: silk fibroin and silk sericin. The fibroin consists of a heavy (H) chain of 390 kDa and a light (L) chain of 26 kDa connected by a disulfide bond, as well as a glycoprotein (P25, 30 kDa), which is secreted into the posterior silk gland. The H-chain, L-chain, and P25 are thought to be assembled with the ratio of 6:6:1. The silk fibroin is then stored in the middle silk gland and coated by silk sericin. The proteins are spun out through the anterior silk gland and converted into silk fibers.
The sericin molecule is highly hydrophilic with a molecular weight that ranges from 20 to 400 kDa and consists of 18 amino acids, including essentials.
Bombyx mori silk is composed of 60–80% fibroin, 15–35% sericin, and 1–5% non-sericin components including wax, pigments, sugars and other impurities. Flavonoids, especially quercetin and kaempferol, alkaloids, coumarin derivatives, and phenolic acids, are among the secondary metabolites isolated from the silk cocoon.
Silk proteins are processed and marketed in a variety of commercial and research-grade forms. The principal differentiation is between intact and hydrolyzed forms of each protein:
Extraction of sericin is most commonly achieved through hot-water or alkaline degumming. The outer-layered sericin surrounded on the fibroin is the most soluble in water and is obtained by boiling in 100 °C water for 2 hours. High-temperature and high-pressure (HTHP) methodologies also facilitate sericin extraction. In the 1930s, it was discovered that boiling silk moth cocoons with sodium carbonate salt releases the gum-like sericin protein from the cocoon and frees the polyfibroin filaments for use in various applications.
Fibroin isolation involves removal of sericin via degumming, followed by dissolution in chaotropic solvents such as lithium bromide (LiBr) or calcium chloride (CaCl₂), and subsequent dialysis and drying. Enzymatic hydrolysis — using protease, trypsin, or other enzymes — is then applied to yield bioavailable low-molecular-weight peptide fractions used in oral supplements.
Sericulture necessitates raising silkworms on a diet of mulberry leaves, where they spin cocoons made from a protein called fibroin. Traditionally, sericulture has been a vital source of income for families in various Asian countries, including China, India, and Thailand, and has roots dating back to around 2700 BCE. Silk production remained a closely guarded secret in China for centuries, only spreading to other regions through smuggling and trade routes like the Silk Road.
Sericulture and silk craftsmanship of China, based in Zhejiang and Jiangsu Provinces near Shanghai and Chengdu in Sichuan Province, have an ancient history. Traditionally an important role for women in the economy of rural regions, silk-making encompasses planting mulberry, raising silkworms, unreeling silk, making thread, and designing and weaving fabric. It has been handed down within families and through apprenticeship, with techniques often spreading within local groups.
According to some sources, the first country after China to learn the secret was Korea, where Chinese immigrants started sericulture in about 1200 BC. The industry later spread to Japan.
The silkworm cocoon, both as a traditional Chinese medicine and as the raw material for biocompatible carriers, has been extensively used in the medical and biomedical fields. The primary chemical components of the silkworm cocoon include silk fibroin, silk sericin, and other flavonoid-like bioactive compounds demonstrating various biological effects. These include hypoglycemic, cardioprotective, hypolipidemic, anti-inflammatory, antioxidant, and antimicrobial actions.
The silkworm cocoon was first mentioned as a medicinal agent in the Compendium of Materia Medica, one of China's most important traditional medical texts, where it was recorded for its ability to stop bleeding, quench thirst, and detoxify boils. The silkworm cocoon has pharmacological effects described as collecting astringency, stopping bleeding, quenching thirst, and detoxifying boils. Hence, it was used for the treatment of hematemesis, bloody stools, metrorrhagia, excessive urination, and the pathogenesis of carbuncle and pus.
In traditional medicine, natural silk is regarded as a cognitive enhancer and a cure for ameliorating the symptoms of heart disease, atherosclerosis, and metabolic disorders. In traditional medicine, natural sericin was used as a cognitive enhancer and pain reliever for heart disease, atherosclerosis, and metabolic disorders.
Silk-derived materials such as fibroin have long been used in biomedicine and therapeutically in Southeast Asian countries. Beyond medicinal applications, sericin, a silk protein usually discarded in large quantities by the sericulture and textile industries during the degumming process, can be explored for its application in food packaging and in other food sectors as a functional food and component of food items.
The H chain, which occupies most of the silk fibroin, has the amino acid composition: Gly (46%), Ala (30%), Ser (12%), Tyr (5.3%), Val (1.8%), etc. A general trend in silk fibroin structure is a sequence of amino acids characterized by usually alternating glycine and alanine, or alanine alone. Such configuration allows fibroin molecules to self-assemble into a beta-sheet conformation. These "Ala-rich" and "Gly-rich" hydrophobic blocks are typically separated by segments of amino acids with bulky side-groups (e.g., hydrophilic spacers).
In particular, glycine, alanine, and serine, which account for the largest proportion of silk fibroin, account for 70–80% of all the amino acids, and the amino acid components constituting silk fibroin are known to be amino acid components constituting collagen.
Sericin has a distinct composition compared to fibroin, with glycine content significantly lower (10.00%), while serine is notably higher (33.40%). Sericin's high serine concentration enhances its adhesive properties. The highly hydrophilic nature of sericin is due to the high content of serine and aspartic acid, approximately 33.4% and 16.7% of sericin, respectively. The predominant amino acid groups comprising sericin are serine, glycine, and glutamic acid, and it consists of a polar side-chain made of hydroxyl, carboxyl, and amino groups that enable easy cross-linking, copolymerization, and other reactions.
Non-peptidoid components accompanying sericin have been identified as chiefly responsible for previously reported antioxidant capacity associated with sericin fractions, a conclusion supported by the qualitative detection of flavonoids in the extract but not in the purified sericin fraction. Flavonoids, especially quercetin and kaempferol, alkaloids, coumarin derivatives, and phenolic acids, are among the secondary metabolites isolated from the silk cocoon.
The polar groups (carboxyl, hydroxyl, and amino groups) of amino acid side chains and their organic composition, solubility, and structural organization enable crosslinking, copolymerizations, and combinations with other polymers, which together convey unique properties to sericin as an antioxidant, moisturizing, healing, antibacterial, antimicrobial protectant against ultraviolet radiation, and antitumor agent.
Due to their versatile structures, biocompatibility, and biodegradability, silk proteins can be tailored into intricate structures to meet particular demands. The intrinsic functional groups of both proteins enable their functionalization and cross-linking with various biomaterials to endow the matrix with favorable antioxidant and antibacterial properties.
The antioxidant activity associated with low digestibility of sericin expands its application in the medical field, such as antitumor, antimicrobial and anti-inflammatory agent, anticoagulant, acting in colon health, improving constipation and protecting the body from obesity through improved plasma lipid profile.
In the context of enzymatic hydrolysates and glucose metabolism, silk protein-fed mice showed decreased lipid peroxidation, enhanced antioxidant enzyme activities, and lower blood glucose levels relative to the high-fat group. The HF-F50 animals exhibited significantly lower insulin level, higher glycogen concentration, enhanced hepatic glucokinase activity, and reduced glucose-6-phosphate and phosphoenolpyruvate carboxykinase activities.
Sericin improves blood glucose levels and insulin resistance via PI3K/P-AKT/AMPK pathways. Sericin also reduced the expression of G6Pase, PCK, and ACC, which are related to gluconeogenesis and lipid metabolism in the liver, and decreased the expression of TNF-α, IL-6, P65, and IKKβ related to inflammation. In general, sericin can maintain normal glucose levels and regulate insulin secretion, insulin and lipid metabolism, and inhibition of inflammation.
The hypolipidemic effect of silk protein was partly due to increased fecal lipid excretion, inhibition of lipogenesis, and regulation of adipokine production.
Silk FEH were shown to decrease the levels of the pro-oxidant and pro-inflammatory mediators interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), protecting the cholinergic system from oxidative stress, thus enhancing acetylcholine (ACh) levels in the brain, which is known to promote cognitive functions. In addition, the expression of brain-derived neurotrophic factor (BDNF), which is involved in the survival of neurons, is enhanced, and an increase in the expression of the phosphorylated cAMP response element-binding protein (p-CREB) occurs, which is known to play a positive role in cognitive functions.
Evidence shows that silk proteins exhibit neuroprotective effects in models of neurotoxicity. The antioxidant, neuroprotective, and acetylcholinesterase inhibitory mechanisms of silk proteins could prove promising in the treatment of neurodegenerative diseases.
Fibroin-based materials have been shown to be able to increase cell viability and differentiation, and to promote phenotype-specific cell metabolism. Sericin is added to wound dressings because of its ability to promote wound healing. Sericin can activate fibroblasts to promote collagen type I synthesis.
Silk sericin is a granular protein with adhesive and gelatin-like characteristics, which was shown to be responsible for the proliferation and attachment of several mammalian cell lines, as well as for the activation of collagen production, both in vitro and in vivo.
Sericin was found to induce the apoptotic effect in SW480 colon cancer cells by enhancing caspase-3 activity and reducing Bcl-2 expression, resulting in cell cycle arrest at the S phase. Also, sericin was found to suppress DMBA–TPA-induced skin tumorigenesis in a mouse model and colon tumorigenesis in animal tests.
Specifically prepared silk fibroin enzyme hydrolysates (FEH), with an average molecular weight of approximately 1500 daltons, have been shown to improve cognitive functions in normal, healthy humans. These studies involving silk FEH have focused on various aspects of memory and learning functions and mental focus, and have included children, high school and college students, adults and seniors, ranging in ages from 7–92 years.
One notable placebo-controlled, double-blind human clinical trial investigated the dose-dependent effects of silk fibroin protein enzymatic hydrolysate (FPEH) on memory. Healthy adults with an average age of approximately 55 years were administered doses of 0, 280, 400, and 600 mg of FPEH per day in two divided doses for 3 weeks. The Rey–Kim Auditory Verbal Learning Test and the Rey–Kim Complex Figure Test were used to evaluate memory at baseline and after 3 weeks. The scores for each test were combined into the memory quotient score (MQ). Trial 5 of the Rey–Kim Memory Test showed that as the daily silk FPEH intake amount increased, the number of words remembered significantly increased (ANOVA: F = 2.8258; p = 0.0463).
These studies included children, high school/college students, adults and seniors ranging in age from about 9 to 72 years. The study designs were randomized and placebo-controlled with acute and 3–16 week durations.
Doses of 200–600 mg silk FEH per day for three weeks to 16 weeks have been used. Based on these studies, it can be concluded that silk FEH exhibit beneficial cognitive effects with respect to memory and learning, attention, mental focus, accuracy, memory recall, and overall memory and concentration. These conclusions are supported by studies in rats and mice.
Fibroin hydrolysate is currently sold as a health functional food for memory improvement in Korea.
Evidence strength assessment: The human evidence base for silk FEH and cognition is preliminary to moderate. Multiple randomized, placebo-controlled trials of modest size have been published, predominantly from Korean research groups with some industry involvement. A critical limitation is that a number of the studies were published in Korean language scientific journals for which there was no English translation available, and were translated using Google Translate. Furthermore, at least one key reviewer has served as a consultant for BrainOn Inc. Ltd., and the review was funded in part by BrainOn Inc. Ltd. — a company commercially associated with the ingredient. Independent replication by unaffiliated research groups with large, well-powered trials is currently lacking.
The body of evidence for silk proteins and glycemic control consists almost entirely of animal and in vitro data. Sericin protein from silk-processing waste added to the normal diet at 0.8% (g%) level was administered orally to type 2 diabetic (T2D) mice to investigate its hypoglycemic effects and mechanism. The oral protein was in the form of silk sericin hydrolysate, obtained from a boiling treatment of 0.025% calcium hydroxide solution. The results demonstrated that sericin significantly decreased fasting blood glucose, fasting plasma insulin, and glycosylated serum protein levels. The protein also improved oral glucose and insulin tolerance and enhanced antioxidative activities. Sericin could help maintain normal glucose levels.
In one study, silk sericin was manufactured into hydrolyzed sericin peptide (HSP) powders as a dietary additive to investigate the effect on the gut microbiota of T2D model rats. The results indicated that HSP-augmented dietary administration lowers the fasting glucose level of diabetic rats, and HSP augmentation induces a change in the gut microbiota composition of T2D model rats toward that of normal rats. Some key taxa, including Lactobacillus gasseri, were suggested to be involved in controlling T2D development. This finding provides new insight into developing sericin as functional food or therapeutic prebiotics against T2D in clinical practice.
Mice fed a high-fat diet containing a mixture of silk fibroin and sericin additionally had an increased antioxidant capacity and hypoglycemic effect. Silk peptide and its hydrolyzates increased glucose uptake and lowered leptin expression in 3T3-L1 fibroblasts expressing GLUT 4. Administration of sericin can not only reduce the blood glucose levels in diabetic rats but also has significant therapeutic effects on a variety of complications caused by diabetes.
Evidence strength assessment: Evidence is almost entirely from rodent models and in vitro cell culture. No robust, peer-reviewed human clinical trials for glycemic outcomes were identified in the literature searched. This area remains promising but preclinical.
The effect of silk protein with different fibroin/sericin compositions on body weight and lipid metabolism in high fat-fed mice was investigated. The animals were given experimental diets for 6 weeks: normal control (NC), high fat (HF), and high fat diet supplemented with F100 (pure fibroin), F81 (81:19 fibroin/sericin, w/w), or F50 (50:50 fibroin/sericin, w/w). The silk protein-fed mice showed markedly reduced body weight and enhanced lipid profile relative to the HF group. In general, the amount of body fat, triglyceride, and total plasma cholesterol levels, atherogenic index, and free fatty acid level tended to decrease, while the HDL-cholesterol level increased, with increased amount of sericin in the diet.
Evidence strength assessment: All lipid and body composition data identified are from animal (mouse) studies. Human clinical evidence is currently absent for this application.
Silk proteins have been highlighted in the past decade for tissue engineering and skin regeneration due to their biocompatibility, biodegradability, and exceptional mechanical properties. While silk fibroin has high structural and mechanical stability with high potential as an external protective layer, traditionally discarded sericin has shown great potential as a natural-based hydrogel, promoting cell–cell interactions, making it an ideal material for direct wound contact.
In a mouse model of atopic dermatitis (NC/Nga mice), dietary sericin supplementation was studied for effects on skin hydration. Epidermal hydration in sericin-supplemented mice was higher than in the atopic control group and was similar to that of the normal control group, indicating that dietary supplementation with sericin only improves epidermal hydration to similar levels of the normal control group and that dietary fibroin has no beneficial effects on epidermal hydration. Male NC/Nga mice (5 weeks old) were fed diets supplemented with 1.0% powdered extracts of sericin and fibroin, respectively. Mice were fed the experimental diets for 10 weeks to compare the dietary effects of sericin and fibroin on epidermal hydration.
In a human 3D ex vivo wound model, findings revealed rapid keratinocyte proliferation on both silk fibroin membrane and nonwoven matrices, along with enhanced infiltration in the matrix, suggesting improved early wound closure. Silk fibroin membranes exhibited a significantly improved early regeneration, followed by nonwoven matrices (p < 0.05) compared to untreated wounds, resulting in the formation of multi-layered epidermal structures with complete regeneration.
Sericin also promotes cell proliferation, fibroblast proliferation, collagen production, and cell viability, and prevents UVB-induced apoptosis in human skin keratinocytes.
Animal studies confirm the beneficial influence of silk fibroin in wound healing. Clinical research focusing on fibroin dressings is also promising.
Evidence strength assessment: For topical/wound dressing applications, there is a mix of in vitro, animal, and limited human ex vivo evidence. For oral supplementation effects on skin hydration, evidence is derived from an animal model. Clinical human trials of oral silk protein for skin outcomes are not well established in the peer-reviewed literature.
The therapeutic actions of silk sericin and silk fibroin include antidiabetic effects, cardioprotective properties, and lipid-lowering capabilities. Concurrently, the ability to modulate inflammatory responses and resist oxidative stress broadens their application in disease prevention and treatment.
In a rodent model, the cardioprotective effect showed that pre-treatment of rats with sericin significantly increased the non-enzymatic antioxidants marker in serum and heart tissue (glutathione, vitamin E, and vitamin C). Cardiac markers, oxidative stress markers in serum and heart tissue, serum lipid profiling, and lysosomal hydrolases, and heart apoptotic markers were significantly decreased compared with the isoproterenol group; histopathological studies showed normal architecture of heart in both control and treated rats.
In a chronic rodent toxicity trial involving silk lutein (a protein-bound lutein extract), following four months of treatment, both male and female Wistar rats administered the extract exhibited a significant hypotensive effect, maintaining their systolic blood pressure at approximately 120 mmHg and thereby averting the age-related hypertension observed in control subjects. The extract also significantly reduced serum triglyceride levels in both sexes. The findings confirm the potential as a multipurpose nutraceutical by demonstrating a safe constituent with a favorable toxicological profile and notable cardiovascular effects.
Evidence strength assessment: Cardioprotective evidence is entirely from animal studies. No human clinical trials specifically testing oral silk protein for cardiovascular endpoints were identified.
Sericin is a water-soluble biocompatible protein. Both sericin and silk fibroin are reported to exhibit various neuroprotective, anti-inflammatory, and anti-oxidant properties.
Mechanistic studies in animals and cell culture systems indicate that silk FEH exerts its positive effects on memory and learning by providing neuroprotection via a complex mechanism involving its potent antioxidant and inflammation-inhibiting activities.
Although enzyme-hydrolyzed silk fibroin has been reported to enhance cognitive function, it has been unknown which peptides specifically can improve memory. Three novel peptides were identified from fibroin hydrolysate by LC-MS/MS. Fibroin hydrolysate was obtained by hydrolysis with protease after partial hydrolysis with 5M CaClâ‚‚. Synthesized peptides derived from these sequences improved scopolamine-induced memory impairments in mice.
Evidence strength assessment: There is a meaningful body of human clinical data (randomized, placebo-controlled) for silk FEH and memory/cognitive function, though mostly from a narrow group of researchers with disclosed commercial interests and from Korean-language publications. Mechanistic data from animals and cell cultures is more extensive.
The antioxidant activity associated with low digestibility of sericin expands its application in the medical field as an antitumor and antimicrobial agent, anticoagulant, acting in colon health, improving constipation, and protecting the body from obesity through improved plasma lipid profile.
HSP-augmented dietary administration lowers the fasting glucose level of diabetic rats, and HSP augmentation induces a change in the gut microbiota composition of T2D model rats toward the normal rats. Some key taxa, including Lactobacillus gasseri, were suggested to be involved in controlling T2D development.
Evidence strength assessment: Preliminary and based on animal models only. No human clinical data for gut microbiome effects of oral silk protein has been identified in the current literature.
Various proteins have been demonstrated to have antioxidant properties, and many reports have revealed that peptides and protein hydrolysates could be used as potent alternative antioxidant agents. In addition to its antioxidant effect, sericin protein was found to have potential anticancer activity against many types of cancer cells. Sericin was found to induce the apoptotic effect in SW480 colon cancer cells by enhancing caspase-3 activity and reducing Bcl-2 expression, resulting in cell cycle arrest at the S phase.
Evidence strength assessment: This is exclusively in vitro and animal evidence. No clinical evidence for anticancer effects of orally consumed silk protein exists in the peer-reviewed literature.
Dosage information in the research literature pertains to specific preparations used in individual studies and should not be extrapolated as general therapeutic recommendations.
Silk fibroin is shown to be neither mutagenic nor genotoxic using cell-based assays. A 28-day repeated dose study did not elicit adverse clinical sign observations. Pepsin digestion and bioinformatics analyses did not raise allergenic concerns. Silk fibroin is determined to be safe for oral consumption. Specifically, this comprehensive toxicological assessment included a bacterial reverse mutation test (Ames test) in five bacterial strains, an in vivo erythrocyte test with Sprague Dawley rats at doses up to 1,000 mg/kg body weight/day, and a 28-day sub-chronic study set at 500 mg/kg body weight/day. Together, these studies raise no mutagenic, genotoxic, toxicological, or allergenic concerns with the oral consumption of silk fibroin.
No adverse effects have been reported in association with the use of silk FEH in the clinical studies reviewed.
The silk FEH study material has been approved by the Korean Ministry of Food and Drug Safety as a food ingredient with no limits on the intake amount.
Silk proteins, both fibroin and sericin, contain amino acids which can perform as antigens in the human body. Historically, many reports regarding biological responses to silk noted allergic reactions in humans, especially from sericin. Despite sericin having shown many impressive biological activities, it was not widely used in medical applications due to concerns over hypersensitivity.
However, more recent evidence has substantially revised this view: many in vitro, in vivo, and clinical studies have been performed to investigate this matter. The resulting evidence has shown that sericin itself may not be the cause of these dangerous responses in humans, and suggests that there may be sufficient evidence to promote the use of silk sericin in medical and biological applications.
Research on the source of immunogenicity has clarified: although early reports claimed that sericin was responsible for triggering an immune reaction, Nazarov et al. showed that only the physical association of sericin and fibroin can produce an inflammatory response. Furthermore, it was reported that the sericin peptides have no immunogenicity in vivo and can be used effectively in biomedical applications.
Sericin presents characteristics of good biocompatibility, low immunogenicity, inhibition of inflammatory responses, and good immune regulatory function.
However, different silk-processing methods may trigger intense immune system resistance after implantation into the body. This concern is of greatest relevance to implanted biomaterials rather than orally consumed preparations.
Type I allergic responses and up-regulated levels of specific IgE have been reported in patients after repeated surgical procedures that involved the use of silk sutures. In a case report, recurrent granulomas with remarkable infiltration of eosinophils may have resulted from an IgE-mediated hypersensitivity reaction to silk fibroin.
Allergies associated with silk materials are rare and primarily linked to residual sericin, a glue-like protein that can be effectively removed during processing to ensure fibroin purity and hypoallergenicity.
Skin depigmentation has been observed in renal patients after application of an 8% sericin cream for treatment of dry and itchy skin. This adverse observation was specific to a topical cream form in a renally compromised population and has not been replicated in the oral supplementation literature.
The physicochemical properties of sericin are responsible for numerous applications in biomedicine and are influenced by the extraction method and silkworm lineage, which can lead to variations in molecular weight and amino acid concentration of sericin. This means that bioactivity and safety profiles may differ across commercial preparations depending on how the proteins were extracted and processed.
Because of their stable fiber structure, silk proteins are difficult to digest and absorb when consumed. However, previous studies have shown that enzymatic hydrolysis of fibroin extracted from cocoons into low-molecular-weight peptides improves memory in both animals and humans. Enzymatic hydrolysis breaks down large, complex proteins into smaller peptides and amino acids, thereby increasing their solubility, absorption, and bioavailability in the body. These smaller peptides are more easily transported across biological membranes and may exhibit enhanced biological activity, including neuroprotective effects.
No peer-reviewed sources identified in this search specifically document pharmacokinetic drug interactions with orally consumed silk fibroin or sericin supplements in humans. The glucose-lowering and lipid-modulating effects observed in animal models suggest a theoretical consideration in individuals using antidiabetic or lipid-lowering medications, though this has not been formally studied in humans.
Health conditions that Silk protein may help support.
Body systems that Silk protein may help support.
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