IngredientesThylakoids are membrane-bound compartments inside chloroplasts and cyanobacteria, serving as the site of the light-dependent reactions of photosynthesis. They consist of a thylakoid membrane surrounding an internal aqueous compartment called the thylakoid lumen. The term derives from the Greek word thylakos, meaning "sac" or "pouch," and thus "thylakoid" means "sac-like" or "pouch-like."
Thylakoids are disc-like membranes responsible for photosynthetic light reactions in chloroplasts of green plants. They are among the most abundant biological structures on earth, comprised primarily of galactolipids, and are found inside the chloroplasts of all green leaves as well as all forms of cyanobacteria.
The main sources of thylakoids are dark green leafy vegetables. Spinach (Spinacia oleracea) is the most frequently used source to prepare thylakoid membranes, and its high chlorophyll content suggests it may rank among the highest thylakoid-containing plant foods. All leafy green vegetables contain thylakoids.
As a dietary supplement, thylakoid preparations are most commonly derived from Spinacia oleracea and are marketed under brand names such as Appethyl. Appethyl is owned by the Swedish company Greenleaf Medical AB. The commercial preparation originates from the mesophyll tissue of baby spinach (Spinacia oleracea L.) leaves, which is rich in chloroplasts. The inner membranes of the chloroplasts, organized in structures known as thylakoids, are extracted from baby spinach, concentrated and stabilized into a solid powder form. The major constituents of thylakoid membranes are pigments, proteins and lipids.
Thylakoids as an isolated or concentrated supplement do not have a documented traditional use in any historical herbal or folk medicine tradition. Unlike many botanical supplements with centuries of ethnobotanical history, the use of extracted thylakoid membranes as a therapeutic or nutraceutical agent is an entirely modern development grounded in twentieth- and twenty-first-century plant biochemistry.
The scientific exploration of thylakoids as a food-derived supplement was initiated at Lund University in Sweden, primarily by Professor Charlotte Erlanson-Albertsson and colleagues. Research on the appetite-suppressing and fat-digestion-retarding properties of chloroplast membranes was developed at the Department of Experimental Medical Science at Lund University, with foundational work published beginning in 2007. The effects of what researchers termed "thylakoids" — membrane proteins derived from spinach leaves — on human appetite regulation were systematically examined in clinical contexts from the late 2000s onward, following prior demonstration that thylakoids inhibit lipase/colipase hydrolysis of triacylglycerols in vitro and suppress food intake in animal models.
Green leafy vegetables, including spinach, have been consumed by diverse cultures throughout recorded human history as dietary staples. However, the health properties ascribed to thylakoid extracts — appetite suppression, fat-digestion modulation, and metabolic effects — are not historically attributed to whole-vegetable consumption in traditional medicine systems and represent novel scientific claims first articulated in peer-reviewed literature in the 2000s.
Thylakoids consist of proteins, phospholipids, galactolipids, vitamins, and certain pigments and antioxidants like chlorophylls, flavonoids, and carotenoids. The chlorophyll-containing membranes contain lipids, vitamins A, E, and K, and antioxidants including lutein, zeaxanthin, carotenoids, and chlorophyll.
They consist of protein-bound pigments, including chlorophyll, beta-carotene, lutein, and zeaxanthin, and antioxidants such as carotenoids and vitamin E. In terms of macronutrient proportions, thylakoids are composed of about 70% proteins, antioxidants, and chlorophyll, while the other 30% mostly consists of fat.
A peculiarity of chloroplast membranes, which distinguishes them from other cell membranes, is the great abundance of glycolipids, represented by two neutral galactolipids — monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) — which account for 70% of the entire acyl-lipid moiety, along with the anionic sulfolipid sulfoquinovosyldiacylglycerol. Phosphatidylglycerol is the only phospholipid present in the membranes.
The chloroplast thylakoid membrane is composed of membrane lipids and photosynthetic protein complexes. Galactolipids constitute approximately 80% of the thylakoid lipids, and their biosynthesis is fundamental to chloroplast development.
Chloroplasts are semi-autonomous organelles comprising two envelope membranes, an aqueous matrix known as stroma, and internal membranes called thylakoids. All of the light-harvesting and energy-transducing functions are located in the thylakoids, which form a physically continuous membrane system enclosing an aqueous compartment. The components of thylakoids that provide function as a lipolysis modulator are primarily Photosystems I and II, which are structurally stabilised by chlorophyll.
In standardized supplement preparations, the particle size of thylakoid powders is typically under 315 μm, and commercial thylakoid powder preparations contain approximately 36.4 mg of chlorophyll per gram.
Researchers have found that thylakoids may be heat-sensitive, and that industrial production of high-quality functional food ingredients should be via mild drying techniques. In commercial processing, steps are executed with minimum light exposure and under cool conditions to preserve a maximal activity of the photosynthetic pigments. The patent-protected large-scale manufacturing process described for Appethyl® involves inspection of spinach leaves and washing, mechanical disruption and homogenization, filtration by centrifugation, lyophilisation, and gamma-ray irradiation. The applicant claims that the shelf-life of Appethyl® in cool dry storage conditions is 24 months.
The primary and best-characterized mechanism of action of thylakoids as a dietary supplement is inhibition of pancreatic lipase. Thylakoids have the capacity to inhibit the activity of pancreatic lipase, the main enzyme acting together with colipase during lipolysis of fat in the intestine. Lipase and colipase form a 1:1 complex; it is mainly the protein fraction of the thylakoids that has the capacity to inhibit the lipase–colipase complex, as delipidated thylakoids inhibit lipase–colipase to about the same extent as intact thylakoids.
Due to their high concentration of galactolipids and hydrophobic proteins, thylakoids make lipophilic interactions with dietary fats in the digestive tract, covering the surfaces of lipid droplets and forming stable emulsions. Furthermore, thylakoids strongly bind to the pancreatic lipase–colipase complex and sterically hinder the subsequent lipolysis reaction in the intestine, and their phenolic compounds may also play a role in binding to protein-based digestive enzymes.
A patented extract of spinach containing significant amounts of thylakoids has been shown to have an inhibitory effect on lipase activity; this inhibition is largely mediated by the protein fraction, but the membrane galactolipids may also have a role.
Thylakoids attach to intestinal mucosal surfaces and, through their effects on digestion and absorption, cause high levels of undigested contents to pass to the lower gastrointestinal tract, subsequently triggering the ileal brake, which is an important target for appetite regulation.
The satiety-promoting effects of thylakoids are attributed to decreasing fat digestion through inhibition of pancreatic lipase/colipase activity, which promotes the release of hormones like cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) that signal satiety. When fat remains in the gastrointestinal lumen longer, the appetite-regulating satiety hormones CCK, GLP-1, and leptin are triggered. GLP-1 decreases blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin.
Thylakoids have been found to create a physical "barrier" on the mucosal surface of the intestine in vitro, causing a decreased uptake of methyl-glucose and macronutrients over the intestinal wall.
As thylakoid membranes are nutrients containing lipids and proteins, their digestion by enzymes of the gastrointestinal tract has been studied. When treated with pepsin, trypsin, and gastric and pancreatic juice at 37°C, several of the proteins were degraded within half an hour, while the main parts of the pigment–protein complexes were resistant for hours. This relative proteolytic resistance may be important to their sustained luminal activity.
Reported outcomes in animal and human studies include modulation of gut microbiota, notably by increasing some helpful bacteria such as Lactobacillus reuteri. The composition of microbiota may be influenced by thylakoids in a prebiotic manner. One rat study found lactobacilli were significantly increased in the thylakoid group compared to the control group, in line with other studies reporting anti-obesity effects of lactobacillus. Researchers believe this may be due to a direct influence on the growth of bacteria in the intestines, or may be the result of reduced appetite and food intake that indirectly affects microbiota composition.
In a human study measuring fecal fat and microbiota, the total bacteria and specifically the Bacteroides fragilis group were increased by thylakoid treatment versus placebo, and thylakoids did not cause steatorrhea.
A foundational study examined the effects of thylakoids — membrane proteins derived from spinach leaves — in a single-meal study in humans. Thylakoids had been shown to inhibit lipase/colipase hydrolysis of triacylglycerols in vitro and suppress food intake in rats, but their effects in humans were not yet clear. The aim was to investigate whether thylakoids, when added to a test meal, affect appetite regulation and blood parameters in healthy individuals.
Eleven subjects of normal weight and in good health were given a high-fat meal with or without thylakoids. At 120 minutes following the meal, people who consumed the thylakoid-rich food showed significant increases in CCK levels and reductions in ghrelin. There was also a rise in leptin — an important signal of satiety — at 360 minutes after the meals. People eating the thylakoid pesto had lower insulin levels than those eating control meals, though glucose levels remained unchanged.
A study investigated the addition of thylakoids to a high-carbohydrate meal and its effects upon hunger motivation and fullness, and the levels of glucose, insulin, CCK, ghrelin, and TNF-alpha in overweight women. Twenty moderately overweight female subjects received test meals on three different occasions (two thylakoid-enriched and one control), separated by 1 week. Blood samples and VAS questionnaires were evaluated over a 4-hour period. Addition of thylakoids suppressed hunger motivation and increased secretion of CCK from 180 minutes, and prevented postprandial hypoglycaemia from 90 minutes following food intake, indicating that thylakoids may intensify signals of satiety.
A randomized, placebo-controlled, double-blind, crossover trial investigated cravings and hedonic hunger. Thirty-two women were recruited. The study was conducted at Lund University, Sweden. Each participant received a 5 g supplement of thylakoids (Appethyl, Greenleaf Medical AB, Stockholm, Sweden) on one day and placebo on the other. Compared to placebo, intake of thylakoids significantly reduced hunger (21% reduction, p<0.05), increased satiety (14% increase, p<0.01), reduced cravings for all snacks and sweets during the day (36% reduction, p<0.05), as well as cravings for salty (30%, p<0.01), sweet (38%, p<0.001), and sweet-and-fat (36%, p<0.05) snacks, and decreased subjective liking for sweet (28% reduction, p<0.01). The treatment effects on wanting sweet-and-fat snacks in particular were positively correlated to higher emotional eating scores (p<0.01).
A double-blind, placebo-controlled, randomized crossover-designed study conducted among sixty overweight or obese males and females indicated that supplementation with 5 g of thylakoids could increase satiety, as well as produce a greater increase in the postprandial plasma glucose response compared to the placebo group.
A systematic review of the current human literature on thylakoids' characteristics and their relationship to satiety regulation and weight loss included all clinical trials addressing the effects of thylakoids or chloroplast intake on satiety and weight loss, with a literature search from January 1990 to May 2019 across major databases including Cochrane Library, MEDLINE, Scopus, and EMBASE. However, results of the present trials are described as inconsistent, and a 2024 systematic review and dose-response meta-analysis of randomized controlled trials specifically examined whether thylakoid supplementation is effective in hunger and fullness changes.
In a 3-month long, placebo-controlled, blinded study, thirty-eight overweight women (BMI 25–33 kg/m²) were randomized to consume a daily morning green drink containing 5 grams of spinach extract or a placebo. They were instructed to consume a well-balanced diet (three meals per day) and exercise 30 minutes each day. Two single-meal tests were done on day 1 and day 90 to elucidate the effects of long-term supplementation with thylakoids on appetite, body weight, and metabolic parameters. Researchers concluded that significant weight loss and reduction in cholesterol, along with a decreased urge for palatable food, may be due to increased meal-related GLP-1 release sustained during the 90-day thylakoid intervention, suggesting that green-plant thylakoids may be a potential supplement for appetite and body weight control.
A study investigated the effects of 12 weeks of high-intensity functional training (HIFT) combined with spinach-derived thylakoid supplementation on adipokines and insulin resistance in males with obesity. Sixty-eight participants (mean age: 27.6 ± 8.4 years; mean BMI: 32.6 ± 2.6 kg/m²) were randomly divided into four groups: control, supplement only, training only, and training plus supplement. The eligible participants received 5 g/day of thylakoid-rich spinach extract, or matching placebo as 5 g/day of raw corn starch (one sachet, 30 minutes before lunch) for 12 weeks. A finding of the study was that spinach-derived thylakoid supplementation alone or in combination with HIFT modulates adipokine levels in obese men, and that consuming spinach-derived thylakoid amplified the anti-inflammatory effects of HIFT.
The evidence regarding thylakoid efficacy remains complex and sometimes contradictory. While many clinical trials report significant weight loss and appetite suppression, recent studies focusing on active or well-trained populations have occasionally yielded inconsistent findings, with several investigations demonstrating no statistically significant changes in glycemic parameters or long-term lipid profiles compared to placebo. These inconsistencies suggest that the metabolic benefits of thylakoids might be attenuated in individuals with higher baseline physical activity or different metabolic demands, necessitating further exploration.
An important practical note is that 5 grams of extracted thylakoids is equivalent to approximately 100 grams of spinach. However, humans cannot utilize thylakoids in unprocessed vegetables, since the thylakoids are stacked inside non-digestible plant cell walls. Therefore, the only realistic way to achieve a dose comparable to that used in studies is to consume thylakoids as a supplement.
Thylakoid membranes derived from chloroplasts have been shown to retard fat digestion and lower blood glucose levels after oral intake. In a rat study, food intake was significantly decreased in thylakoid-fed rats compared to control-fed rats over a 10-day study, and an oral glucose tolerance test after 10 days resulted in significantly reduced plasma insulin levels in the thylakoid-fed rats, while no difference was observed for blood glucose levels.
In overweight women, addition of thylakoids to a high-carbohydrate breakfast prevented postprandial hypoglycaemia from 90 minutes following food intake. The supplementation of thylakoids resulted in stabilised insulin levels from 90 minutes (AUC, p < 0.01) compared to the control group.
In animal (pig) studies, dietary thylakoids suppressed blood glucose and modulated appetite-regulating hormones in pigs exposed to an oral glucose tolerance test, as published in Clinical Nutrition (2014; 33(6):1122–1126).
Thylakoids have been reported to have anti-obesity activities, stimulating insulin sensitivity and improving the lipid profile through delayed glucose and lipid absorption, respectively. The evidence for glucose-lowering effects in humans remains preliminary and is mostly confined to postprandial endpoints in short-duration studies.
Thylakoid membranes derived from green leaf chloroplasts affect appetite-regulating hormones, suppress food intake, reduce blood lipids, and lead to a decreased body weight in animals and human subjects.
A three-month study of overweight and obese women found that consuming a dietary supplementation containing 5 g of green-plant membranes per day increased weight loss, reduced total and LDL-cholesterol, and reduced the urge for sweets and chocolate. However, lipid-lowering findings have not been reported consistently across all trials, and the evidence is considered preliminary.
A randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the effects of spinach-derived thylakoid supplementation combined with a calorie-restricted diet on anthropometric and metabolic profiles in obese women with PCOS. In the 12-week trial, 48 females with obesity and PCOS were randomly allocated to either an intervention (5 g/day thylakoid) or placebo (5 g/day cornstarch) group along with calorie-restricted diets.
To the best of the investigators' knowledge, this was the first clinical trial to investigate the effects of thylakoid-rich spinach extract supplementation along with caloric restriction on novel atherogenic, glycemic, and anthropometric indices in addition to renal function in PCOS patients. Supplementation of 5 g/day thylakoid along with a restricted diet resulted in significant reductions in BMI and atherogenic indices (AIP, CRI-I, and CRI-II) compared to placebo, while other anthropometric indices decreased in both the thylakoid and placebo groups.
In PCOS-induced rats, 8 weeks of thylakoid supplementation at a dose of 6 mg chlorophyll per gram of food intake daily significantly improved fasting blood sugar (FBS), luteinizing hormone, insulin resistance, and body weight.
In the human PCOS trial, thylakoid supplementation did not significantly alter energy and dietary nutrient intake in obese women with PCOS, and there were no significant differences in energy and dietary intakes between the two groups. The food intake at the next meal following thylakoid intake was not different between placebo and thylakoid groups.
Since supplementation with thylakoids has been found to produce effects similar to those of prebiotics on satiety and gut hormones, they could be viewed as a prebiotic agent. In a rat study examining gut microbiota composition, the aim was to investigate the effect of dietary thylakoids on the gut microbiota composition, mainly the taxa of lactobacilli and bifidobacteria, in rats fed either a thylakoid-enriched diet or a control diet for 10 days. Food intake was significantly decreased in the thylakoid-fed rats compared to the control-fed rats over the 10-day study.
In a separate human study, the effects of thylakoid supplementation on gut microbiota were investigated in healthy human volunteers (n = 34) receiving thylakoid or placebo treatments for three months. Microbiota was analyzed using 16S rRNA gene sequencing and qPCR. The total bacteria, and specifically the Bacteroides fragilis group, were increased by thylakoid treatment versus placebo, and thylakoids did not cause steatorrhea.
Evidence for thylakoid-specific prebiotic effects in humans is limited to a small number of studies. The broader relevance and reproducibility of these microbiota changes have not yet been established in large-scale human trials.
Attenuation of oxidative stress and inflammation has been reported among the outcomes in animal and human studies on thylakoids. The anti-inflammatory and immunoregulatory functions of thylakoid membranes found in spinach leaves have been explored in preclinical models; for example, immunomodulatory properties of Thykamine (a thylakoid-derived preparation) on alveolar macrophages were demonstrated through regulation of pro- and anti-inflammatory cytokine production.
In the clinical study on a high-carbohydrate meal, test meals resulted in significantly decreased TNF-alpha concentrations between 0 and 240 minutes; however, no significant difference in TNF-alpha concentration between the thylakoid and control breakfasts was found. Anti-inflammatory effects attributable specifically to thylakoid supplementation have not been robustly demonstrated in human clinical trials.
In 2023, the EFSA Panel on Nutrition, Novel Foods and Food Allergens evaluated a health claim submitted by Greenleaf Medical AB for Appethyl® under Article 13(5) of Regulation (EC) No 1924/2006, specifically regarding "Appethyl® and reduction of body weight." The applicant identified five human studies conducted with Appethyl® preparations as pertinent to the claim, and clarified that only the thylakoid preparations used in those studies — which had been standardized for lipase/colipase inhibition capacity — were pertinent to the health claim. The EFSA assessment represents the most rigorous independent regulatory scrutiny of the available evidence base to date.
Spinach-derived thylakoid extract is available as a green powder that can be blended with water or smoothies, and is also sold in other forms including capsules and bars (referred to in product descriptions as "café").
Based on human clinical studies, the following dosages have been reported:
No adverse events or effects have been reported in most human studies. Nevertheless, mild cases of nausea and headaches have been documented in both intervention and control groups of one clinical trial.
No serious adverse events or effects were reported in the craving-reduction crossover trial at Lund University. Mild cases of nausea during or after the snack buffet occurred at three occasions in the placebo group and at two occasions in the treated group.
During the 12-week PCOS trial, no adverse events or symptoms were reported following the intake of thylakoid powder by the participants. Sachet counts showed good compliance, with more than 90% of sachets taken during the course of the trial by both groups.
In the systematic review and meta-analysis, only a few adverse events were reported across all included trials, but none were serious.
While thylakoids work to delay digestion, they do not prevent fat from being digested (causing steatorrhea) to the extent of common drugs known as lipase-inhibitors. They also increase fatty acid oxidation in intestinal cells. A human microbiota study confirmed that thylakoids did not cause steatorrhea at doses studied.
Because thylakoids temporarily retard fat digestion without fully blocking it, they differ mechanistically from pharmaceutical lipase inhibitors such as orlistat. Thylakoids do not prevent fat from being digested to the extent of common drugs known as lipase-inhibitors. No studies have specifically reported clinically significant fat-soluble vitamin malabsorption associated with thylakoid supplementation at the doses studied.
The mean BMI of participants across trials ranged from 25.3 to 35.1 kg/m², showing that most studies were conducted in overweight or obese subjects. The safety profile in lean individuals, children, pregnant women, or individuals with gastrointestinal disease has not been systematically evaluated. These gaps suggest that the effects and tolerability of thylakoids in specific clinical populations requires further exploration.
The Greenleaf Medical company has conducted and supported much of the published research on its supplement. While some consider this a potential conflict of interest, it is uncommon for a company to invest time and money to formally study its own supplement. Researchers and readers evaluating the evidence should be aware of this sponsorship pattern, which is particularly relevant in the context of the EFSA health claim review process.
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Thylakoids extracted from green plants (e.g., spinach) have been shown in human intervention studies to enhance release of appetite-suppressant hormones including GLP-1, CCK, and leptin while suppressing ghrelin. A 3-month human study showed 6.3% body weight loss with thylakoid supplementation.
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