Metabolic syndrome (MS) forms a cluster of metabolic dysregulations that encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance [2].
Given that CVDs constitute the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MS in this context to reduce the heavy burden of the disease [3].
However, there is no single treatment for MS, and lifestyle modifications are required together with the currently available pharmacotherapy of related comorbidities. For these reasons, new therapies characterized by multiple activities are needed [4].
Fiber intake is known to be associated with BW reduction [5] and increases the transit time of the feces [6].
L112 is a Medical Device consisting of a cationic fiber that, in acidic medium, allows the formation of high-affinity bonds with lipid molecules present in the gastrointestinal lumen, decreasing their bioavailability. Once the gastric chyme reaches the duodenum, the pH increase transforms the combination of chitosan and the bound products into a gel, further limiting the absorption of the components.
Structurally, L112 is a chitin derivative extracted from the exoskeleton of crustaceans and consisting of unbranched polymers of beta (1,4)-D-glucosamine, in which the chains are stabilized by hydrogen bonds. The network of polymers in L112 is biocompatible and capable of efficiently binding and other food components fats [7, 8] as shown in Fig. 1. In this way, large, poorly digestible lipid-chitosan-starch emulsions are created, which are partly eliminated and partly used as a substrate by the bacteria present in the colon.
Chitosan binding with some food components in the stomach
The lipases and colonic bacteria release fatty acids and metabolize them into products used for bacterial-membrane formation and as a source of energy [9]. Due to this activity, L112 treatment does not cause steatorrhea, and fat excretion in feces remains minimal.
Pharmacological studies have shown that polyglucosamine reduces BW and increases fat excretion in feces, particularly acetate [10, 11].
This aspect is significant because acetate drives insulin secretion, thereby promoting metabolic syndrome [12]. Furthermore, the high polarity of acetate enhances its binding affinity to L112 compared to long-chain lipids or cholesterol. This activity reduces acetate availability for the brain and decreases ghrelin secretion.
A recent meta-analysis, including 399 subjects (ages ranging between 21 and 75 years, and a BMI between 26 and 45 kg/m2) followed for a period ranging from 12 weeks to 1 year, showed that L112 supplementation improved weight loss, decreased BMI, and improved abdominal circumference (AC) [13].
In another meta-analysis [14], chitosan was shown to modify glycemic levels in people with metabolic syndrome following a treatment for at least 13 weeks at 1.6–3 g/day.
In a recent investigation on L112 [15], it was shown that this substance-based medical device administered in tablets before the main meals allows a significant reduction of BW, insulin resistance, and cholesterol levels without the modification of fat-soluble vitamin and glucosamine levels.
Moreover, polyglucosamine has been shown to reduce oxidative stress by limiting lipid oxidation and deposition in arterial walls and by modulating the intestinal absorption of dietary fats. This effect is particularly beneficial in reducing early signs of atherosclerosis and promoting cardiovascular health. This mechanism contributes to the prevention of subclinical atherosclerosis progression and improves arterial wall morphology, as evidenced by reduced carotid intima-media thickness (IMT) in clinical studies [16].
Metabolic syndrome (MS) and oxidative stress are closely interconnected, with oxidative stress acting as both a cause and consequence of MS components such as obesity, insulin resistance, hypertension, and dyslipidemia. This relationship creates a vicious cycle that exacerbates metabolic dysfunction and increases cardiovascular risk [17].
To date, no study has been conducted to evaluate the efficacy of polyglucosamine L112 on body weight, insulin resistance, and cholesterol in patients with metabolic syndrome, although the activities of polyglucosamine (antioxidant and reduction of BW, insulin resistance, and cholesterol levels) make this medical device an ideal candidate for the treatment of metabolic syndrome.
The studies conducted have considered only the efficacy of chitosans on MS and were limited to blood glucose [14]. Polyglucosamine L112 instead consists of standardized polymers characterized by > 80% dgree of deacetylation and a peak molecular weight (Mp) of about 65 KDa and was shown active on body weight, cholesterol levels and insulin resistance [15]. Based on this background, the present study aims to evaluate the effects of polyglucosamine L112 compared to placebo on body weight, insulin resistance, and cholesterol levels in patients diagnosed with metabolic syndrome (MS) according to ATP III criteria [1].