**5. Biological activity of the Maillard Reaction Products (MRPs)**

The Maillard reaction is of outstanding importance for the formation of flavor and color of heated foods. Despite the unquestionable beneficial effects on the sensory quality of food products, the Maillard reaction products may be harmful for human health.

Protein nutritional impairment, consequence of the destruction of essential amino acids or the decrease in their bioavailability, is one of the oldest known nutritional implication of this reaction (Delgado-Andrade *et al.*, 2007a; Seiquer *et al*., 2006). The decrease in the availability of several amino acids, mainly lysine, which may correspond to 50%, is noticeable (Rerat *et al.*, 2002). Total lysine contents in breakfast cereal products can decrease from 20-54% as a result of processing (Rutherfurd *et al.,* 2007; Torbatinejad *et al.,* 2005). Comparing the effects of diets with different MRPs contents on dietary protein utilization in in male adolescents indicated that the consumption of a diet rich in MRPs resulted in 47% higher nitrogen fecal excretion, 12% lower apparent nitrogen and 6% lower nitrogen digestibility. Therefore, the protein apparent absorption absorption and digestibility were significantly lower (Seiquer *et al*., 2006).

The bioavailability of minerals can also be affected by MRPs, since these compounds are able to chelate minerals interfiring, therefore, with their solubility (Delgado-Andrade *et al.,* 2011). The effects of diets with different Maillard reaction products contents on iron biological utilization showed that significant decrease on dietary iron availability occurred when diets rich in MRP were consumed (García *et al,* 2009a). It was also observed a negative influence on dietary phosphorus absorption in male adolescents exposed to a rich-MRPs diet, as a result of an increased phosphorus fecal excretion concomitant to a decrease in its apparent absorption (Delgado-Andrade *et al.*, 2011). Magnesium and calcium bioavailability can also be affected by the presence of Maillard reaction products in the diet (Delgado-Andrade *et al.,* 2007b; García *et al.,* 2009b).

The results of studies on the genotoxic and mutagenic potential of the MRPs are controversial. While there are studies indicating that the MRPs can cause mutations, no association between MRPs and genotoxicity was found by Wagner et al (2007). In *in vitro* systems, melanoidins mixtures have negligible mutagenic effects (Somoza, 2005), while 5 hydroxymethylfurfural (HMF) is considered a potentially carcinogenic to humans and some epidemiological studies have found an association between acrylamide intake and the occurence of tumors the occurrence of tumors (Capuano & Fogliano, 2011).

The formation of advanced glycation end products (AGEs) is observed during normal ageing and occurs inside as well as outside of cells (Nass *et al.,* 2007). These compounds, when cross linking with proteins profoundly affect protein functionality and irreversibly modify chemical properties and functions of diverse biological structures (Barbosa *et al.,* 2008), which seems to be implicated in inflammatory processes and diabetic complications, such as nephropathy and vascular disease (Jakus & Rietbrock, 2004; Linden *et al*., 2008; Mostafa *et al.,* 2007).

AGEs accumulate in various tissues during aging, including skin, neural, vascular, renal and cardiac tissues, collagens and crystalline lens. In the skin, glycation is involved in many metabolic processes and, along with aging, affects the functionality of certain cells, such as the synthesis of fibroblasts, enzyme activation of matrix degradation (metalloproteinases) and the organization of the matrix (Hartog *et al*., 2007; Pageon, 2010; Pawlak *et al*., 2008). It is proposed that the accumulation of the advanced glycation end products (AGEs) and the

The Maillard reaction is of outstanding importance for the formation of flavor and color of heated foods. Despite the unquestionable beneficial effects on the sensory quality of food

Protein nutritional impairment, consequence of the destruction of essential amino acids or the decrease in their bioavailability, is one of the oldest known nutritional implication of this reaction (Delgado-Andrade *et al.*, 2007a; Seiquer *et al*., 2006). The decrease in the availability of several amino acids, mainly lysine, which may correspond to 50%, is noticeable (Rerat *et al.*, 2002). Total lysine contents in breakfast cereal products can decrease from 20-54% as a result of processing (Rutherfurd *et al.,* 2007; Torbatinejad *et al.,* 2005). Comparing the effects of diets with different MRPs contents on dietary protein utilization in in male adolescents indicated that the consumption of a diet rich in MRPs resulted in 47% higher nitrogen fecal excretion, 12% lower apparent nitrogen and 6% lower nitrogen digestibility. Therefore, the protein apparent absorption absorption and digestibility were significantly lower (Seiquer *et* 

The bioavailability of minerals can also be affected by MRPs, since these compounds are able to chelate minerals interfiring, therefore, with their solubility (Delgado-Andrade *et al.,* 2011). The effects of diets with different Maillard reaction products contents on iron biological utilization showed that significant decrease on dietary iron availability occurred when diets rich in MRP were consumed (García *et al,* 2009a). It was also observed a negative influence on dietary phosphorus absorption in male adolescents exposed to a rich-MRPs diet, as a result of an increased phosphorus fecal excretion concomitant to a decrease in its apparent absorption (Delgado-Andrade *et al.*, 2011). Magnesium and calcium bioavailability can also be affected by the presence of Maillard reaction products in the diet (Delgado-

The results of studies on the genotoxic and mutagenic potential of the MRPs are controversial. While there are studies indicating that the MRPs can cause mutations, no association between MRPs and genotoxicity was found by Wagner et al (2007). In *in vitro* systems, melanoidins mixtures have negligible mutagenic effects (Somoza, 2005), while 5 hydroxymethylfurfural (HMF) is considered a potentially carcinogenic to humans and some epidemiological studies have found an association between acrylamide intake and the

The formation of advanced glycation end products (AGEs) is observed during normal ageing and occurs inside as well as outside of cells (Nass *et al.,* 2007). These compounds, when cross linking with proteins profoundly affect protein functionality and irreversibly modify chemical properties and functions of diverse biological structures (Barbosa *et al.,* 2008), which seems to be implicated in inflammatory processes and diabetic complications, such as nephropathy and vascular disease (Jakus & Rietbrock, 2004; Linden *et al*., 2008;

AGEs accumulate in various tissues during aging, including skin, neural, vascular, renal and cardiac tissues, collagens and crystalline lens. In the skin, glycation is involved in many metabolic processes and, along with aging, affects the functionality of certain cells, such as the synthesis of fibroblasts, enzyme activation of matrix degradation (metalloproteinases) and the organization of the matrix (Hartog *et al*., 2007; Pageon, 2010; Pawlak *et al*., 2008). It is proposed that the accumulation of the advanced glycation end products (AGEs) and the

occurence of tumors the occurrence of tumors (Capuano & Fogliano, 2011).

**5. Biological activity of the Maillard Reaction Products (MRPs)** 

products, the Maillard reaction products may be harmful for human health.

*al*., 2006).

Andrade *et al.,* 2007b; García *et al.,* 2009b).

Mostafa *et al.,* 2007).

activation of the receptor for AGEs in the retina could play a significant role in the initiation and progression of age-related macular degeneration and cataracts (Pawlak *et al.*, 2008). Kalousová *et al.* (2002) and most recently, Mostafa *et al.* (2007) showed that AGEs level in plasma proteins are elevated in patients with diabetes. The high blood glucose levels favor the occurrence of spontaneous reactions (glycation) between glucose and proteins, resulting in the formation and excessive deposition of AGEs (Magalhães *et al.*, 2008). In patients with renal failure AGEs accumulation occurs due to the decrease in the extent of degradation and elimination from the body and, also, to increased exposure to oxidative stress. On the other hand, the AGEs and products derived from the process of oxidation promote damage in the renal tissue, leading to greater accumulation of AGEs, creating a vicious cycle (Hartog *et al.*, 2007). The increase in consumption of heated, cooked or roasted food of AGEs accumulation.

Fig. 7. AGE-RAGE interaction and its association with atherosclerosis (Based on Hartog et al., 2007).

Among the mechanisms by which AGEs may contribute to the development and progression of vascular complications of diabetes, is the interaction of these compounds with receptors on the surface of various cell types, such as RAGEs (Receptors for Advanced Glycation End Products) (Marchetti, 2009). The AGE-RAGE interaction in the endothelial cells activates the transcription of nuclear factor-kappaB (NF-κB), with the induction of proinflammatory cytokines, such as the tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1) and enhances the expression of the vascular cell adhesion molecule-1 (VCAM-1) (Basta, 2008; Magalhães *et al*., 2008; Méndez *et al*., 2010; Muscat *et al*., 2007). In addition, this interaction in monocytes induces their activation to macrophages and promotes monocyte chemotaxis, and in smooth muscle

not modified the antioxidant enzymes activity (superoxide dismutase, glutathione

287

Fig. 8. Possible biological effects of the Maillard Reaction Products (MRPs) and Advanced

For food industry, coping with the Maillard reaction and the effects of the reaction products in food and in health is important to the improvement and development of food products. This chapter discussed the positive and negative aspects of the Maillard reaction in food products. The positive contributions of the Maillard reaction are sensory attributes generation, such as color, flavor, aroma and texture. The negative aspects are off-flavor development, flavor loss, discoloration, and loss of protein nutritional value. In the food industry, the role of flavor and color either desirable or undesirable is the key in the manufacture of products of consistent sensory quality. Contradictory knowledge about the effects of Maillard Reaction Products on health indicates that studies are needed to further expand the AGEs and MRPs database as well as development of methods for reducing MRPs generation during home cooking and food processing. Understanding the chemical, nutritional and toxicological consequences of browning reactions and related transformations, *in vitro* and *in vivo,* can lead to better and safer foods and improved human

Glycation End Products (AGEs) (Based on Somoza 2005).

**6. Conclusion** 

health.

peroxidase and catalase) (Seiquer *et al.*, 2008).

cells, is associated with increased cellular proliferation (Marchetti, 2009). Besides, some studies demonstrate that AGEs may promote atherogenesis by oxidizing low density lipoproteins (LDL) (Basta *et al*.*,* 2004). Indeed, AGE form crosslinks with low-density lipoprotein (LDL), which become more atherogenic and less susceptible to absorption and subsequent clearance. In addition, LDL modified by AGEs is more easily captured by receptors located on macrophages, generating foam cells (cells with fat droplets and cholesterol) (Hartog *et al.,* 2007; Vasdev *et al*., 2007) (Figure 7).

It has also been suggested that AGEs are involved in neurodegenerative diseases, such as Alzheimer and Parkinson (Grillo & Colombato, 2008; Sato *et al.,* 2006b), arthritis *(Vytásek et al., 2010),* loss of bone mass (Ding *et al.,* 2006) and promotion of changes in the function and/or structure of DNA and RNA molecules (Li *et al.,* 2008).

Considering AGEs as important mediators of pathological processes, investigations aiming to verify the action of chemical compounds against the synthesis of AGEs and its possible use in therapy of patients with several metabolic complications are in course of development. Substances present in foods, such as pyridoxamine, allyl cysteine (component of garlic extract), phenolic compounds, taurine and carnosine, showed significant anti-AGE effects, but, at present, there is no indication of food components able of reducting AGEs generation *in vivo* (Barbosa *et al.,* 2008). Despite of this, dietary therapies also appear to be an effective alternative in the control of diseases associated with accumulation of AGEs.

Restricting the consumption of fried, grilled or baked foods seems to be the most effective way of decreasing AGEs endogenous *pool*. Dietary AGEs restriction seems to be a successful strategy in suppression of inflammatory molecules in diabetes, implying eventual prevention or delay of atherosclerosis (Vlassara *et al*., 2002). Several studies indicate that Maillard reaction products from the diet increase the endogenous AGEs pool and, whether this might become a health problem is yet controversial. There are many gaps that must be evaluated before conclusions can be drawn as, for example, the fate of MRPs in the organism. Notwithstanding, several researchers advocate towards the decrease of MRPs ingestion and, therefore, food industry has an important role by considering processes towards the production of foods with lower contents of MRPs.

On the other hand, there are authors who advocate for MRPs as substances that may promote benefits, such as increases in immunity and decreases in the toxicity of some nitrosamines. Figure 8 is a summary of the main biological effects attributed to Maillard Reaction Products (MRPs) /Advanced Glycation End Products (AGEs).

Some studies suggest the MRPs exert positive influence on the gut microbiota (Tuohy *et al.,* 2006). It has been shown that anaerobic bacteria, particularly *Bifidobacteria* strains, are able to use bread melanoidins as carbon source (Borrelli & Fogliano, 2005). Maillard Reaction products in roasted cocoa beans, for example, were able to inhibit the growth of *E. coli* spp. and *Enterobactercloaceae* (Summa *et al.*, 2008).

Furthermore, MRPs exhibit antioxidant activity (Açar *et al.*, 2009; Chang *et al.,* 2011; Chawla *et al.*, 2009; Rao *et al.*, 2011; Summa *et al.*, 2008). Melanoidins from roasted coffee and biscuits exerted protective effects against oxidative stress on human hepatoma HepG2 cells (Goya *et al.*, 2007; Martín *et al.*, 2009). Regarding coffee antioxidant activity, more than 50% of the observed antioxidant activity is due to the low molecular weight compounds linked to the melanoidin skeleton, promoting a chelating ability that is also involved in the shelf life of the product (Delgado-Andrade & Morales, 2005). *In vivo*, a MRPs rich diet was able to suppress lipid peroxidation and to increase antioxidant activity of plasma, although it has not modified the antioxidant enzymes activity (superoxide dismutase, glutathione peroxidase and catalase) (Seiquer *et al.*, 2008).

Fig. 8. Possible biological effects of the Maillard Reaction Products (MRPs) and Advanced Glycation End Products (AGEs) (Based on Somoza 2005).
