Effectiveness Of Chitosan In Weight Loss Biology Essay


Chitosan or D-glucosamine polymer is the deacetylated form of chitin which is a polysaccharide found in the exoskeletons of crustaceans such as crabs, shrimps, shell fish and lobsters. Currently, chitosan has received considerable attention for its applications in the biomedical industry, particularly on the use of chitosan as a primary ingredient in the dietary supplement for weight loss and cholesterol management in order to reduce the risk of cardiovascular diseases which is the leading cause of death in the world. The use of chitosan as a dietary supplement either directly or in the form of chitosan derivatives has been largely attributed to the fat-and bile acid binding capacities and physio-chemical properties of chitosan and in particular to the strong ability of chitosan to bind with triglycerides, fatty acids and other sterol compounds in the gastrointestinal tract, decreasing their absorption (Izani et al., 2009).

Although chitosan (sold as "oil trappers" and "oil magnets") has been evaluated in a number of research study trials (in vitro and in vivo) and is available readily as a dietary supplement over the counter, its efficacy remains in dispute.

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Thus, the aim of this paper is to evaluate and asses the effectiveness of chitosan as a treatment for weight loss and in cholesterol management. In doing so, the following areas would be taken into consideration:-

Structure and physio-chemical properties of chitosan

Cholesterol lowering effects of chitosan (in vivo and in vitro)

Controlled clinical studies

Health risks of using chitosan for weight loss

In light of literature findings, some recommendations for future research would be provided.

2.0 Structure and Physio-chemical Properties of Chitosan

Chitosan a copolymer of D-glucosamine (GLCN) (~80 %) and N-acetyl-D-glucosamine (20%) units is the N-deacetylated product of chitin (Zhou et al; 2006; Tharanathan & Kittur; 2003) which is the second most abundant polysaccharide after cellulose. Figure 1 shows the molecular structures of chitin and chitosan.

(a) Chitin

(b) Chitosan

Figure 1: Molecular structures of (a) chitin and (b) chitosan (Stephen, 1995).

Although many chemical and physical properties of chitin exist, only a few relevant properties such as solution properties of chitosan and its subsequent effect on fat absorption would be thoroughly discussed. Chitosan behaves as a dietary fibre and exhibits substantial viscosity in vitro (Gallaher et al; 2000) and is not metabolised and has no nutritive or caloric value. Chitosan is more crystalline in nature which presumably makes chitosan more accessible to reagents. It also possesses reactive hydroxyl and primary amine groups which makes it more nucleophilic and basic (Ormond et al; 1998).

Lipids are digested in the stomach and intestines. The four steps involved in the transport of fat into our bloodstream firstly includes the acidolytic breakdown of food in the stomach, lipolysis of the fats including triglycerides into fatty acids and beta-mono glycerides followed by formation of soluble mixed micelles with bile acids and finally absorption through the intestines (phd). Thus, chitosan when consumed will be subjected to gastric mixtures in the stomach in which it will dissolve. The mechanism for this is that, a proportion of the primary amine group on the chitosan molecules become protonated and thus acquires a positive charge. Hence the solvated polycationic chitosan molecules coagulate if a particle or molecule carrying multiple negative charges is added to a solution (Stephen, 1995) and this further means that dissolved chitosan is mixed with the dietary fat to form a chitosan-fat complex. The complex subsequently gets in the small intestine and this gel-trapped dietary fat is excreted into the faeces (Kanauchi et al, 1995). In short, chitosan could reduce fat absorption from gastrointestinal tract by binding with anionic carboxyl groups of fatty and bile acids.

Various studies on animals have reported that chitosan polymers bind (electrostatic bonding) to negatively charged molecules such as fats, fatty acids (oleic, linolenic and stearic acids) and other lipids and inhibit fat absorption which ultimately could assist in reducing high levels of blood cholesterol (Izahi et al; 2009; Ardakni et al; 2009; Rodriguez & Albertengo et al; 2005; Ormond et al; 1998). Chitosan can also interfere with normal emulsification of neutral lipids (i.e, cholesterol, other other sterols) by binding them with hydrophobic bonds ( Ylitalo et al; 2002).

Due to the electrostatic and hydrophobic bonding processes discussed earlier on, large polymer compounds form which is weakly broken down by the digestive process. However, in the intestine, chitosan becomes insoluble (increased pH~6.3). Thus, it forms aggregates with fatty acids, cholesterol and fats leading to the inhibition of their absorption and recycling from the intestine to the liver. A rise of pH decreases the chitosan cationity but it also increases the surface charge density of lipids (Liu et al; 2008).

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Various research studies on the in vitro binding of lipid with chitosan under the conditions mimicking the gastrointestinal track have reported that chitosan binds up the excess fat before in could be absorbed. Fats bound to chitosan thus becomes non absorbable and unable to enter the bloodstream.

The interaction between chitosan and sunflower oil under stomach and duodenal digestive chemical conditions was also studied by Rodriguez and Albertengo, (2005). 1 g of chitosan and different amounts of sunflower oil related to the different lipid contents in the human diet (4.0 g corresponding to 12 % lipid intake, 10.0 g corresponding to 30 % lipid intake, 16.0 g corresponding to 48 % of lipid intake and 32 g corresponding to 96 % of lipid intake) was utilised in the digestive chemical experimental model to study the oil and chitosan interaction. The results obtained indicated that chitosan dissolved in acidic medium (pH 1-2 and gastric conditions) and emulsified oil before forming a flocculus under higher duodenum pH (~6.3) value. This flocculus then entrapped dietary oil and inhibited duodenal absorption and enhanced lipid excretion with the faeces. Best results were obtained with lower lipids content in diet and were independent of the chitosan characteristics. This result could be assumed to reduce weight. In this study, the digestive chemical experimental model was later operated with different types (processed differently and from various source) of chitosan and 10.0 g sunflower oil to evaluate the influence of chitosan characteristics. Results obtained were independent of the chitosan characteristics.

Similar results were also obtained by Izahi (2009) whose study demonstrated that chitosan emulsifies olive oil and ghee at low pH but flocculus formation of lipid by chitosan is accomplished at higher pH due to precipitation of uncharged chitosan along with lipid adsorbed on it.

3.0 Lipid and Cholesterol Lowering Efficacy in Animals

Several studies have investigated the hypocholesterolemic and hypolipidemic effects of chitosan in vitro and in vivo. Generally, the chitosan was found to possess hypercholesterolemic properties and posed no disadvantages or risks to the subjects except in a few studies (discussed in section….).

3.1 Rodents

In a 2009 study, Arakani et al studied the effects of chitosan on normal as well as raised blood lipid levels in rats and reported that chitosan decreased cholesterol and LDL (i.e cholesterol in high density lipoproteins considered to be 'bad') by 44 % in the group of rats kept on a fatty diet (0.5 % cholic acid, 2 % cholesterol and 5 % soya oil) with chitosan extract for 15 days. However, chitosan did not have any effect on triglyceride and HDL (cholesterol in high density lipoproteins considered to be 'good') levels in cases of hypercholesterolemia and chitosan supplement at the higher dose of 10 % retarded growth of the animals.

Similarly Ormrod et al; (1998) studied the effect of chitosan on inhibition of hypercholesterolemia and atherogenesis in mouse with apolipoprotein E-deficiency and reported that blood cholesterol levels were significantly lower by 64 % than control levels in the chitosan (5 % in the diet) fed animals for 20 weeks. The study reported that when the area of aortic plaque in the two groups were compared, a highly significant inhibition of atherogenesis in both the whole aorta (42 %) and the aortic arch (50 %) was observed in the chitosan fed animals with the conclusion that chitosan could be used to inhibit the development of atherosclerosis in individuals with hypercholesterolemia.

Further, Miura et al; (1995) affirmed that chitosan improved lipid metabolism in normal and neonatal streptozotocin -induced diabetic mice and reported significant decline in cholesterol, triglyceride levels in normal mice.

Zhang et al ;( 2008) studied the mechanisms of hypolipidemic activity of chitosan in rats on various lipids metabolites and reported that chitosan containing diets generally reduced the liver lipid levels and increase faecal excretion of fats. They also confirmed that longer term feeding of chitosan resulted in a better hypolipidemic effect.

3.2 Chickens

The inhibition of cholesterol absorption from the intestines and the plasma cholesterol lowering activity also occurs in broiler chickens (Fazdan et al; 1997). When broiler chickens were fed on a diet containing various viscosities (94, 82 and 76%) deacetylated chitosan, the total plasma cholesterol and HDL cholesterol concentrations was reduced and an increased HDL: total cholesterol ratio in comparison with chickens in the control (Razdan and Pettersson; 1994). Plasma triglycerides were reduced in chicken fed with low viscosity chitosan. The ileal fat digestibility was reduced by 26 % in the chitosan fed group in comparison with the control group.

3.3 Rabbits

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Hirano and Akiyamo; (1995) reported the almost total absence of the hypocholesterolaemic action of chitosan in high serum cholesterol rabbits. The serum cholesterol and triglycerol levels of rabbits remained unaffected by a 20g/kg chitosan supplemented diet by intravenous injection with chitosan of low molecular weight (c3000) or chitosan oligosaccharides daily at a dose of 45 mg/kg of body weight.

Other studies which reportedly experimented on the efficiency of chitosan in decreasing lipids and cholesterol in animals also documented details on the influence of other physiochemical properties of chitosan such as molecular weight, viscosity and degree of deacetylation and relevant reaction mechanisms.

3.4 Effect of Degree of Acetylation and Viscosity

Various studies on cholesterol-lowering action of chitosan with different degree of acetylation in rats, mice or hamsters fed cholesterol-rich diets have been reported.

Liu et al; (2008) determined the hypocholesterolemic effects of chitosan preparations with different physiochemical properties and reported that when chitosan particle size is finer, its degree of deacetylation and molecular weight is relatively higher, the hypocholesterolemic effect is better in the sense that these reduce plasma triglyceride, total cholesterol and LDL levels and elevate the HDL more effectively.

Izahi et al; 2009 experimented on how the purity of chitosan (treated and untreated) and the ratio of chitosan to lipid influence the adsorption of lipid (olive oil and ghee) on chitosan and reaffirmed that chitosan binds with ghee quantitatively to an extent which depends on degree of deacetylation in chitosan. Chitosan containing six or more units with moderate degree of deacetylated glucosamines are more effective in blocking the absorption of cholesterol and lipids in the intestinal tract. Chitosan with higher viscosity indices (molecular size) of greater than eight residues have equivalent potency (Koide, 1998).

However, the above is contrary to the report by Zhou et al; (2006) who maintained that bonding capacities of chitosan with bile acids and triglycerides had no correlation with degree of deacetylation in vitro.

Similar results were reported by Trautwein et al; (1997) who compared the effects of chitosan differing in their degree of deacetylation (92 % (CHI92) and 79 % (CHI92) deacetylated) on cholesterol and bile acid mechanisms in hamsters fed cholesterol rich diet. The diet consisted of semi purified, gall stone-inducing diets containing 5 % fat, 0.4 % cholesterol and 10 % cellulose with or without supplements of 8 % and 4 % of each chitosan for 5 weeks. 8 % CHI79 significantly reduced plasma lipids (total cholesterol) and triglycerides compared to the control diet. 8 % CHI92 produced only a minor hypocholesterolaemic effect (-10 %). At 4 % CHI79 and CHI92, no distinctions were found between the CHI92 and CHI79. They added that the cholesterol lowering effect seemed mainly related to an increased excretion of natural steroids.

Thus, more relevant studies such as determining the physio-chemical properties that maybe associated to the binding capacities of chitosan against fat and bile binding sites need to be done (Zhou et al; 2006). Treated chitosan gave a better binding to lipid in comparison with untreated chitosan and the ratio of chitosan to lipid used was found to affect the amount of lipid bound per gram of chitosan to lipid. The study further claimed that about 5-30 % free ammonia (-NH2) groups in chitosan remain as acetylated form which structurally resembles the repeating units of chitin which is less effective in binding with the lipid as evidenced from its less hypolipidemic activity in other studies.

According to Xian et al; (2011), chitosan contains three types of reactive functional groups, an amino/acetylmide group as well as both primary and secondary hydroxyl groups at the C-2, C-3 and C-6 positions respectively. The amino contents are the main reason for the differences between the structures and physical properties.

Enhancing the action of chitosan….??

4.0 Clinical Studies

Many clinical studies have been conducted to study the hypocholesterolemic effect of chitosan on humans or the effect of chitosan in weight loss in obese or overweight. Some of these studies have utilised chitosan as a supplementary drug and evaluated the effectiveness of the drug rather than chitosan itself. Other studies have also focussed on modified water soluble chitosan. Some hypocholesterolemic effect was analysed based on serum cholesterol while others were analysed on fats in faecal excretion. Weight loss was entirely evaluated based on initial and final weight of subjects. Latest way to evaluate efficacy of chitosan or dietary supplement??

4.1 Hypocholesterolemic Effects

The first study by Maezaki et al (1993) reported its findings on the hypocholesterolemic effect of chitosan in adult males. The study confirmed that when 3-6 g/day of chitosan (in the form of biscuits) was given in the diet to 8 healthy males, total serum cholesterol significantly decreased and serum HDL-cholesterol significantly increased and so did the excreted amounts of primary bile and cholic acids in the feces. Opposite results was obtained when chitosan intake was removed or decreased. The total bile acid excretion and significantly increased excretion of primary bile acid suggests a mechanism for decreasing cholesterol by chitosan.

Similalry, Bokura & Kobyashi (2003) in a randomised, double-blind, placebo-controlled trial reported that chitosan is safe and effective for lowering serum total cholesterol; however, the effect of chitosan for decreasing cholesterol is mild.

Liao et al; (2007) reported that both water soluble and water insoluble chitosan supplementations lowered blood lipids and maintained normal calcium, magnesium and iron status in elderly hyperlipidermic patients.

Contrary finding was reported in a pilot study by Gades & Stern; (2002) who reported that chitosan supplementation when consumed as per the directions of the manufacturer, did not affect fat absorption in healthy males fed on a high diet. The study was conducted by analysing fat content of faeces.

Gades & Stern; (2005) tested (on customised diet plans ) the fat trapping capacity of a chitosan product in man and women and stated that fat trapping was clinically insignificant and that for men it would take more than 7 months to lose 1 pound of body fat while for women, no fat trapping occurred. This is in contradiction to what has been reported by Bokura and Kobyashi (2003) on effect of chitosan on women. No literature was found to substantiate why studies on men and women gave slightly different results, but it appears the groups were chosen on the assumption that each group maintain their diets differently.

Similar results were confirmed by Gades & Stern (2007) when the effect of a few weight loss supplements was exclusively tested on males. The studies conducted by Gades & Stern in 2002, 2005 and 2007 indicated that fat trapping claims associated with chitosan cannot be substantiated.

4.2 Weight Loss

Egras et al (2011), from an evidence based review of fat modifying supplemental weight loss products, reasoned that chitosan is well tolerated with the most common adverse effects being gastrointestinal. Based on the review it appears that chitosan may be effective in aiding weight loss. But more data is needed in order for chitosan to be recommended.

Pittler et al (1999) examined the effects of chitosan on weight loss in 34 patients (with body mass index (BMI) of 26 kg/m2) in a randomised, double placebo-controlled trial and reported that no difference in body weight between the test and control groups were observed.

Wuolijoki et al (1999) reported that microcrystalline chitosan did not significantly alter serum total and HDL cholesterol, but slightly increased serum triglycerides compared to placebo.

From the above three findings, it appears that it is unlikely that chitosan can bind with fat in the intestine of humans as claimed by dietary supplement providers.

However, Schiller et al; (2001) reported that a rapidly soluble chitosan was efficacious in facilitating weight loss and reduced body fat in overweight and mildly obese individuals. The study was a randomised, double-blind, placebo controlled examination of effects of a rapidly soluble chitosan dietary supplement. The product used here was modified soluble chitosan.

Based on the in vivo and in vitro tests measuring the efficacy of chitosan to bind fat and lipids, it was postulated that the same would be observed when chitosan is taken orally by humans. However, such does not seem to be the case. Not too many details are available in order to document some of the reasons for the discrepancies observed.

But the ability of chitosan to bind triglycerides in vitro can be inhibited in the presence of certain excipients used in the encapsulation or tableting process. Certain lubricants such as magnesium stereate and binders including calcium phosphate can reduce chitosan's ability to bind triglycerides (Schiller et al; (2001).

Mhurchu et al (2008) indicates that the differences may be due to poor correlation some direct faecal fat assays show with the faecal energy excretion. The question whether chitosan-bound fat in the faeces in measured completely by standard assays. Since other methodologies to assess fat absorption corroborate a positive effect such as the radio isotopic method employed by Blum (2000) suggests that chitosan decreased fat absorption.

Mhurchu et al (2008) also implies that in order to evaluate the efficacy of any weight loss treatments, measurements of full body composition should be carried out and not just the changes in body weight (on a weighing scale).

5.0 Adverse Effects of Using Chitosan Supplements

Some of the adverse effects of using chitosan supplements include the following list summarised from various studies.

Decreases bone mineral content and mineral absorption. ( Deuchi et al;

Causes constipation. Pittler et al ; 1999

Causes nausea, vomiting, indigestion, abdominal swelling and pain ( Gao et al, 2011).

6.0 Conclusion

Chitosan shows good hypercholesterolea and lipidimedic

oes reduce fat absorption in the stomach and subsequently reduces plasma cholesterol in many studies carried out in vitro and invivo.