Appetite and Cravings

Charlotte Erlanson-Albertsson

Thylakoids suppress appetite via GLP-1

J Am Coll Nutr. 2015 Nov 2; 34(6): 470–477.
Published online 2015 Jun 1. doi:  10.1080/07315724.2014.1003999
PMCID: PMC4600649
PMID: 26029978

Acute Effects of a Spinach Extract Rich in Thylakoids on Satiety: A Randomized Controlled Crossover Trial


Objective: By retarding fat digestion, thylakoids, the internal photosynthetic membrane system of green plants, promote the release of satiety hormones. This study examined the effect of consuming a single dose of concentrated extract of thylakoids from spinach on satiety, food intake, lipids, and glucose compared to a placebo.
Design: Sixty overweight and obese individuals enrolled in a double-blind randomized crossover study consumed the spinach extract or placebo in random order at least a week apart. Blood was drawn for assessments of lipids and glucose before a standard breakfast meal, followed 4 hours later by a 5 g dose of the extract and a standard lunch. Visual analog scales were administered before lunch and at intervals until an ad libitum pizza dinner served 4 hours later. Two hours after lunch a second blood draw was conducted. Mixed models were used to analyze response changes.
Results: Compared to placebo, consuming the spinach extract reduced hunger (p < 0.01) and longing for food over 2 hours (p < 0.01) and increased postprandial plasma glucose concentrations (p < 0.01). There were no differences in plasma lipids and energy intake at dinner, but males showed a trend toward decreased energy intake (p = 0.08).
Conclusions: At this dose, the spinach extract containing thylakoids increases satiety over a 2-hour period compared to a placebo. Thylakoid consumption may influence gender-specific food cravings.
Key words: thylakoids, spinach, satiety, food cravings, fat digestion


Appetite reflects a complex interaction among the external environment, the behavioral profile, and subjective states as well as the storage and utilization of energy [1]. Thus, the initiation and termination of ingestive behavior has both metabolic and nonmetabolic components. An eating episode can be sparked by metabolic need, hedonic drive, or an interaction between the two. A neural network sensitive to energy status signals has been identified as the homeostatic control system for the regulation of food intake and energy balance [2]. The system is powerfully designed to protect the lower limits of adiposity by modulating the processing of cognitive and reward functions [2]. However, in the modern world, humans often eat in the absence of any metabolic feedback requiring replenishment of diminished reserves. This nonhomeostatic or hedonic eating involves cognitive, reward, and emotional aspects. Cues that have a reward associated with them, once learned, trigger motivational wanting to secure these rewards [3].
The photosynthetic membrane of chloroplasts consists of a system of paired membranes, the thylakoids. The thylakoid membrane system forms a physically continuous 3-dimensional network that encloses an aqueous space, which is the thylakoid lumen [4]. Approximately 70% of the thylakoid mass consists of the membrane proteins and their bound pigments, such as chlorophyll, carotenes, and xanthophylls. The remaining 30% largely consists of the membrane lipids such as galactolipids, phospholipids, and sulfolipids [5].
Thylakoid membranes are found in green plants such as spinach. A patented [6] extract of spinach containing significant amounts of thylakoids has been shown to have an inhibitory effect on lipase activity [7]. This inhibition is largely mediated by the protein fraction [7], but the membrane galactolipids may also have a role [8]. Delayed fat digestion increases the production of the satiety hormones cholecystokinin [9,10] and glucagon-like peptide-1 (GLP-1) [11], as has been demonstrated in human trials. Additionally, in humans [9] and pigs [12], ingestion of the extract has been shown to suppress the hunger hormone ghrelin. Among the gut hormones involved in appetite regulation, GLP-1 in particular has been associated with the regulation of reward-induced eating behavior [13]. Thylakoid-induced increase in the precursor for enterostatin a peptide involved in appetite suppression and thermogenesis has also been demonstrated [7].
In studies with rats and mice [14,15], significant reductions in body weight and percentage body fat occurred when the diet was supplemented with the spinach extract containing thylakoids. In overweight women, a breakfast meal supplemented with 3.7 or 7.4 g of the spinach extract suppressed subjective hunger compared to a control in a crossover study, with no statistical difference between the 2 doses [10]. Overweight women consuming 5 g of the spinach extract for 3 months demonstrated 43% greater loss of body weight compared to a placebo. The women also exhibited a decreased the urge for sweet and chocolate by 95% and 87%, respectively. The reduced urge for sweets was significant after a single dose and was sustained throughout the study, demonstrating that no tolerance developed during the 3 months of daily usage [11]. Further, unlike pharmaceutical lipase-inhibiting drugs, the thylakoids temporarily delay but do not prevent fat digestion. Thus, the excretion of undigested fat, which is an unpleasant side effect of lipase inhibitor drugs, is avoided.
In this study, subjective satiety ratings and food intake following a single administration of thylakoids from spinach leaves or a placebo were measured. The hedonic and reward responses to food-related stimuli were also evaluated. Plasma glucose and lipid concentrations were measured. It was hypothesized that thylakoid supplementation would produce an increase in satiety that would be accompanied by the appropriate changes in glucose and lipid measures.


Gastroenterology. 2017 Mar; 152(4): 730–744.
The vagus nerve in appetite regulation, mood and intestinal inflammation
Kirsteen N. Browning,1 Simon Verheijden,2 and Guy E. Boeckxstaens2,3,*

 Schematic representation of the cholinergic anti-inflammatory pathway
VNS of the intact vagus nerve stimulates both afferent and efferent fibers. Electrical stimulation of afferent nerve fibers activates neurons in the NTS leading to activation of not only both ipsi- and contralateral efferent vagus nerves, but also of an adrenergic pathway resulting in release of norepinephrine (NE) in the spleen and the production of dopamine (DA) in the adrenal gland. In the spleen, NE reduces TNF production by splenic macrophages both directly, via actions on β2 adrenoceptor activation, and indirectly, via activation of CHAT+ T cells releasing ACh. Activation of presynaptic α7nAChR on adrenergic nerve fibers by choline or other α7nAChR agonists may increase NE release contributing to their anti-inflammatory properties. Stimulation of the efferent vagus nerve dampens α7nAChR+ resident muscular macrophages in the gastrointestinal tract via activation of cholinergic enteric neurons. The immune cell(s) modulated in the lamia propria, however, still need to be identified. The extent to which efferent vagus fibers exert an anti-inflammatory effect in the spleen by synapsing with adrenergic postganglionic (α7nAChR+) neurons in the celiac ganglion is a matter of debate since no anatomical or electrophysiological evidence supporting this connection is available. As the vagus nerve innervates the thymus, Peyers’ patches and other myeloid organs, one may hypothesize that cholinergic modulation of immune cells (α7nAChR+ macrophages, CHAT+, T cells) occurs in these organs. Under conditions of systemic inflammation, these cells subsequently migrate, or get trapped in the spleen, via the circulation.