Ole G Mouritsen

Abstract

Diet and lifestyle have an impact on the burden of ill health and non-communicable ailments such as cardiovascular disease (including hypertension), obesity, diabetes, cancer and certain mental illnesses. The consequences of malnutrition and critical unbalances in the diet with regard to sugar, salt and fat are becoming increasingly manifest in the Western world and are also gradually influencing the general health condition for populations in developing countries. In this topical mini-review I highlight the lack of deliciousness and umami (savoury) flavour in prepared meals as a possible reason for poor nutritional management and excess intake of salt, fat and sugar. I argue that a better informed use of the current scientific understanding of umami and its dependence of the synergetic relationship between monosodium glutamate and certain 5´-ribonucleotides and their action on the umami taste receptors will not only provide better-tasting and more flavoursome meals but may also help to regulate food intake, in relation to both overeating and nutritional management of elderly and sick individuals. Keywords umami, flavour, glutamate, MSG, 5´-ribonucleotides, taste receptor, synergy, salt, fat, sugar, palatability, food additive University of Southern Denmark; Denmark Nordic Food Lab, Denmark Corresponding author: Ole G Mouritsen, MEMPHYS-Center for Biomembrane Physics, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, 55 Campusvej, DK-5230 Odense M, Denmark Email: ogm@memphys.sdu.dk Nutrition and Health 21(1) 56-75 ª The Author(s) 2012 Reprints and permission: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0260106012445537 nah.sagepub.com 56 Introduction The general health of the world’s population is under siege as a result of dramatic changes in conditions of life. In particular, environmental changes and changes in lifestyle, including diet, are seriously affecting the burden of ill health (Lopez et al. 2006). A growing global population, together with changes in the agriculture and fishing industries, presents new challenges to meeting the increasing demands for healthy foodstuffs and proper distribution of the world’s goods. We are faced with two paradoxes. First, in the Western world, despite access to excessive amounts of versatile food supplies and a high level of public education, we have witnessed a rapid increase in diet-related lifestyle diseases, such as cardiovascular disease including hypertension, overweight, obesity, diabetes, cancer and certain mental illnesses (Ezatti et al. 2002). Second, in many developing countries there are recurrent incidences of hunger catastrophes and malnutrition, and, at the same time, in other developing countries, as well as in countries where people are gradually adopting a Western lifestyle, we see a virtual upsurge in the same diet-related lifestyle diseases that are pestering the Western world. Health is more than the absence of disease. According to the definition in the World Health Organization’s constitution, the health of a population also includes quality of life (QOL), i.e. aspects of social well-being as well as maintenance of full physical and mental modalities (WHO, 2006). Many countries find themselves with a growing population of elderly individuals as well as with more individuals who are going through complicated hospitalization and medical treatments involving drugs as well as chemo- and radiotherapy. The QOL of these individuals is often diminished owing to a lack of appetite, leading to malnutrition and derived secondary diseases such as gastric malfunctioning, anorexia, aphasia and a number of other physiological dysfunctions (Kawai et al., 2009; Uneyama et al., 2009). Another aggravating condition is loneliness: an increasing number of adults live single lives and it is well known that elderly people in particular tend to eat less food, and particularly less well-prepared and unhealthy food, if they eat their meals in solitude. The appetite, the choice and acceptance of food, the amount of food consumed, and the satiety and satisfaction after a meal are factors that appear to be linked to the sensory perception of food (Sørensen et al., 2003). Food flavour (i.e. taste, smell and chemaesthetic sensation) may have an important influence on the amount of food taken in and the degree of satiety. Hence, the palatability of the food becomes an important factor. Still, official dietary recommendations and guidelines (Brug and Oenema, 2006) seldom take food palatability into account (Mithril et al., 2012). A key example is the recommendation of a daily intake of 600 g green vegetables; difficult for most people, presumably because of a lack of palatability and interesting taste for many vegetables. As a consequence, people eat considerably fewer vegetables or they flavour their vegetable dishes with large amounts of salt, fat or sugar to make them more palatable. In theWestern world, flavouring of home-made or industrially produced meals in order to make them palatable is most often accomplished by the addition of salt, sugar or fat. The less palatable the dish, the more additives are used. In the case of salt, epidemiological studies have indicated that the global increase in cardiovascular diseases and hypertension (Bibbins-Domingo et al., 2010; Strauss, 2010) is probably caused by an Mouritsen 57 57 increased intake of salt (He and MacGregor, 2010). Similarly, an increased consumption of sugar is believed to be a major cause of diabetes, obesity and overweight (Palou, 2009). The jury is still out with regards to fat and lifestyle diseases (Kromhout et al., 2002; Kuller, 1997), in particular the role of saturated fat and cholesterol, although it is now documented that trans-fatty acids constitute a risk factor (Stender et al., 2006) and that an imbalance between the intake of ω-3 and ω-6 fatty acids is the cause of several neurological disorders and mental illnesses (Hibbeln et al., 2006; Mouritsen and Crawford, 2007; Peet et al., 1999; Simopoulos, 2002). Salt in the form of sodium chloride (NaCl) is an effective agent to regulate saltiness, and sugar in the form of table sugar (sucrose) readily imparts sweetness. Each of these taste modalities is one of the five basic tastes: salty, sweet, sour, bitter and umami. Sweetness is often preferred by tasters to cover undesirable flavours of two other basic tastes, bitter and sour. Fat is not considered to give rise to a basic taste, although whether there are fat taste receptors is still in discussion (Bachmanov and Beauchamp, 2007). In any case, certain fats provide taste and aroma and contribute to the sensation and pleasure of eating, presumably because they are associated with mouthfeel and texture (Drewnowski, 1997). Both sugar and fat contain energy and contribute significantly to caloric intake, whereas salt mostly plays a role in the electrolytic balance of cells. There is, however, a third and powerful way to impart delicious taste to food and meals (Halpern, 2000; Yamaguchi, 1998; Yoshida, 1998): the fifth taste, umami, a concept or term that is mostly overlooked in the Western world (Mouritsen and Styrbæk, 2011), although we have plenty of sources of it in Western cuisine. The umami taste is often associated with meaty and savoury flavours. Umami is stimulated by free monosodium glutamate (MSG), the sodium salt of the amino acid glutamic acid, in a peculiar synergy with certain free 5′-ribonucleotides, specifically inosinate (inosine-5′-monophosphate, IMP) and guanylate (guanosine-5′-monophosphate, GMP), which, in a synergistic fashion, potentiate the umami receptors’ sensitivity to glutamate (Zhang et al., 2008). As described below, umami is, literally speaking, the essence of deliciousness, and it can enhance the sensory perception of a meal and, moreover, limit our craving for salt, fat and sugar and suppress the sensation of bitterness. I shall advocate in this paper that umami may be part of the solution to providing healthier, less caloric and more satisfying meals to the population. Control of and optimization of umami may be a key to regulating and adjusting food intake to the levels that are natural for human physiological functions. Umami can be imparted to food by the natural occurrence of umami compounds or by adding these artificially as food additives. It is interesting to note that the human modalities of taste sensation are likely to have been shaped and conditioned during evolution (Krebs, 2009; Mouritsen and Styrbæk, 2011). It is believed that the human preference for sweet taste directed man to food with carbohydrates and plenty of energy and calories; saltiness indicates foods with vital ions, such as sodium and potassium; sour suggests whether a fruit or vegetable is ripe; and bitter is a warning signal of potenially poisonous compounds. Hence, the ability to taste these four basic tastes has been subject to an evolutionary pressure. Finally, umami signals amino acids and proteins. Umami may, consequently, be an ancient signal of nutritious food. The evolutionary advantage, encoded in the human neural system, of sensing umami is supported by recent brain-imaging studies (Araujo et al., 2003; Chen et al., 58 Nutrition and Health 21(1) 58 2011), which show that umami is represented in the anterior part of the orbitofrontal cortex, a cortical region that represents information about the reward value of other primary and secondary reinforcers as well as gustatory responses (Araujo et al., 2003). It is interesting to note that the human fetus and the newborn baby are primed to savour umami: amniotic fluid (2.2 mg/100 g) and human breast milk (19 mg/100 g) both contain free glutamate. In fact, mother’s milk is distinctly characterised by both sweet (lactose) and umami (glutamate) flavour. It has recently been documented that our ancestors, the early hominines, used fire and heat to prepare food almost two million years ago (Comody et al., 2011; Wrangham, 2009). Homo is unique in eating a diet that is rich in cooked and non-thermally processed food (Organ et al., 2011): Homo sapiens is a cook! Cooking and fermenting meat and vegetables release large amounts of free glutamate and nucleotides, and hence lead to food and meals enriched in umami flavour. It is likely that our preference for delicious food with umami taste has been encoded in our sensory system over millions of years. The layout of this article is as follows. First, a brief review of umami flavour is provided, and it is pointed out in which raw foodstuff materials it is prevalent and how processing of the food can enhance umami. The umami taste receptors are described, with particular attention to the synergy in the binding of glutamate and 5′-ribonucleotides via an allosteric mechanism. The importance of umami in the traditional Japanese cuisine is highlighted, in particular in relation to the soup broth dashi and its use in the classic Japanese temple cuisine that is strictly vegan. Focus will then be on glutamate (MSG), its natural occurrence and its use as a flavour-enhancing food additive. It is pointed out that glutamate is a multifunctional compound, as it plays a key role in food palatability and acceptability, it has a nutritional role, it plays physiological roles in the oral cavity and the gastrointestinal system, it serves as a neurotransmitter, it influences the digestion of food by a specific activation of the brain–gut axis, and hence it is of significance for energy homeostasis. It is then discussed how our current scientific understanding of umami may not only provide for better-tasting meals but may actually help to regulate food intake, in relation to both overeating and nutritional management for elderly and sick individuals, as well as lower the need for additional salt, sugar and fat. Umami and flavour synergies Although recognised in Asia as a taste over the last thousand years and proposed in Japan as a unique basic taste more than a hundred years ago, the term umami has only caught on very slowly in theWestern world (O’Mahony and Ishii, 1986; Fernstrom, 2009; Mouritsen and Styrbæk, 2011; Mouritsen et al., 2012). It was the Japanese chemist Kikunae Ikeda who, in a short paper, written in Japanese and published in 1909 (Ikeda, 2002), proposed the term umami to describe the essence of delicious taste (umai[旨い] = delicious; mi[味] = essence, inner being or taste). Ikeda suggested umami to signify a unique and savoury taste sensation as the fifth basic taste that is separate and independent of the four classical basic taste modalities: sour, sweet, salty and bitter. The scientific basis for Ikeda’s suggestion was his finding of large amounts of free glutamic acid in the form of its sodium salt MSG in one of the ingredients, konbu, that enters the classical Japanese soup broth, dashi. Konbu is a large brown alga or Mouritsen 59 59 sea tangle (kelp), Saccharina japonica, which Ikeda found to contain 2–3 g/100 g dry weight free L-MSG (Ikeda, 2002). A large part of this glutamate seeps out in the warm aqueous extract of konbu (Mouritsen et al., 2012). Ikeda proposed that MSG is for the umami taste what kitchen salt (sodium chloride) is for the salty taste or what table sugar (sucrose) is for the sweet taste. The second ingredient in dashi besides konbu is an extract of a fermented fish product called katsuobushi. One of Ikeda’s colleagues later found that katsuobushi releases large amounts of the free nucleotide inosinate (Kodama, 1913) and that, together with glutamate, this compound elevates the umami taste. The importance of this interplay was realised in the work by Kuninaka (1960), who discovered another 5′-ribonucleotide, guanylate, to be enriched in dried shiitake, which are used instead of katsuobushi in vegetarian variants of dashi. Kuninaka’s work suggested that there is a peculiar synergistic and highly non-linear relationship between glutamate and free nucleotides in the sensation of umami. The first clue to a scientific understanding, in molecular terms, of the sensing of umami was provided in 2000 when the first umami receptor was discovered (Chaudhari et al., 2000; Kunishima et al., 2000), the metabotropic glutamate receptor, taste-mGluR4, which is a dimeric G-protein-coupled receptor located in the membranes of the taste cells in the taste buds of the tongue. taste-mGluR4 is a truncated version of the glutamate receptor mGluR4 found in the brain and it is selectively sensitive to L-glutamate. Later, two other umami receptors were found, T1R1/T1R3 (Li et al., 2002; Nelson et al., 2002), and a special mGlu receptor (San Gabriel et al., 2005) that is related to the brain glutamate receptor mGluR1. At present it is unknown whether the different umami receptors use different signalling pathways (Jyotaki et al., 2009; Yasuo et al., 2008). It is interesting to note that Ikeda’s landmark paper on umami from 1909 was translated into English only in 2002 (Ikeda, 2002) after the discovery of the umami receptors. Only after establishing the taste physiological basis for umami were Western scientists convinced of umami being a real basic taste in the same ranks as salt, sour, bitter and sweet. The T1R1/T1R3 receptor is of particular interest for understanding how to enhance umami flavour in food. In contrast to taste-mGluR4, which is sensitive only to L-glutamate, T1R1/T1R3 is also stimulated by 5′-ribonucleotides, in particular inosinate and guanylate, which, in a synergistic fashion, potentiate the receptor’s sensitivity to glutamate. The allosteric interaction between the binding sites for glutamate and nucleotides on the receptor’s Venus fly trap motif constitutes the molecular mechanism behind the synergy discovered by Kuninaka (1960). This synergy lies behind all classical preparations of dashi (Yamaguchi and Ninomiya, 2000). Importantly, umami also enters some kind of interaction with other tastes, in particular sweet and salty (Fuke and Ueda, 1996), but also bitter. A particularly complex relationship has been found between the umami receptor and the receptors for sweet and bitter (Temussi, 2009). Although a molecular understanding of these interactions is still missing, they are important for the practical use of umami to make food more palatable with less salt and sugar. These interactions possibly also lie behind the observation that the taste sensation of pure MSG appears to be different among individuals, probably because umami interacts strongly with sweet and salty tastes. Moreover, the difference in chemical composition of different individuals’ saliva, with various small amounts of other 60 Nutrition and Health 21(1) 60 substances such as nucleotides, has lead to confusion regarding MSG as the source of a unique taste or simply a taste enhancer (Bachmanov, 2010). The taste of pure MSG is not particularly strong or pleasant, and different individuals describe it as salty, soapy, broth-like or even unpleasant. The taste threshold for pure MSG is typically 0.01–0.03% by weight and about twice as low as that for NaCl. For comparison, the threshold values for inosinate and guanylate are 0.012% and 0.0035%, respectively (Maga, 1983). However, when adding small amounts of these nucleotides to an MSG solution, the threshold value can be lowered with up to three orders of magnitude (Maga, 1983). MSG in excess amounts makes the food less palatable and an optimum amount appears to be around the concentration found in many natural foods, typically 0.1–0.8% by weight. The synergy in umami taste is usually described as a consequence of basic umami (glutamate) and synergetic umami (5′-ribonucleotides). However, a number of other compounds can also lead to the sensation of umami. In particular, another amino-acid salt, aspartate (monosodium aspartate, MSA), can stimulate basal umami but with an intensity that is only about 8% of that of glutamate (Chandrashekar et al., 2006; Li et al., 2002). Similarly, a range of other 5′-ribonucleotides has been suggested to provide for synergetic umami (Yamaguchi and Ninomiya, 1998); the most prominent example is adenylate (adenosine- 5′-monophosphate, AMP). Natural occurrence of umami Glutamic acid is one of the most abundant amino acids in plants and animals. Most of it, however, is bound in proteins, where it constitutes about 40% and 10–20% of the protein mass in animal and plant tissues, respectively. Hence, glutamic acid and its salts are some of the most common ingredients in foodstuffs. Many common foods have a large potential for umami, provided that the glutamic acid can be released. Similarly, most nucleotides in living organisms are bound in nucleic acids, such as DNA, RNA and ATP, and in order for umami flavour to be produced, these nucleic acids have to be degraded and free nucleotides have to be released. Consequently, most raw organic foodstuff materials have to be processed in order to break down the proteins into free amino acids and the nucleic acids into free nucleotides in order to provide for umami. One may in fact interpret the development of cooking and cuisines across the world as a perpetual attempt to release umami compounds in the food (Mouritsen and Styrbæk, 2011). Processes such as cooking, boiling, steaming, simmering, roasting, braising, broiling, smoking, drying, maturing, marinating, salting, ageing and fermenting all contribute to the degrading of the cells and the macromolecules of which the foodstuff is made. Of these processes, fermenting, by microbes such as yeast and bacteria or by enzymes, is by far the most potent method of freeing umami compounds. Tables 1 and 2 provide a selection of foodstuffs, some raw and some processed, along with their concentration of free glutamate and nucleotides as determined in the international literature (Giacometti, 1979; Komata, 1990; Maga, 1983; Ninomiya, 1998, 2002). The data in Tables 1 and 2 shows that the two ingredients in the classic Japanese dashi, konbu and katsuobushi, have the highest levels of free glutamate and nucleotides, respectively. Of unprocessed products, ripe tomatoes and potatoes have high amounts of Mouritsen 61 61 Table 1. Selection of data for free glutamate (MSG) occurring naturally in various raw and processed foods. Glutamate stimulates umami taste. Food item MSG (mg/100 g) Meat and poultry Cured ham 337 Duck 69 Chicken 44 Beef 33 Pork 23 Egg 23 Fish and shellfish Marinated anchovies 1200 Sardine 280 Octopus 146 Scallop 140 Sea urchin 140 Oyster 130 Blue mussel 105 Caviar 80 Shrimp 40 Mackerel 36 Vegetables Tomato (dried) 648 Tomato (fresh) 200 Potato (cooked) 180 Corn 130 Green peas 106 Potato (raw) 102 Soy bean 66 Green asparagus 49 Carrot 20 Milk and dairy products Parmigiano Reggiano 1000–2700 Roquefort 1280 Stilton 820 Cheddar 182 Human breast milk 19 Cow’s milk 1 Fungi Shiitake (dried) 1060 Shiitake (fresh) 71 Champignon 42 Fruits and nuts Walnut 658 Strawberry 45 Avocado 18 (continued) 62 Nutrition and Health 21(1) 62 glutamate, and certain fish and shellfish have high amounts of nucleotides. However, it is only after sun-drying the tomatoes or marinating and fermenting the seafood that very high amounts of glutamate and nucleotides develop. It appears from Tables 1 and 2 that umami is not a flavour that is found only in the Japanese kitchen, but, in fact, is associated with well-known and common foods and food ingredients in Western cuisine. Many types of food contain naturally occurring large amounts of free MSG, the most well known of which are Marmite, fish sauces, mature hard cheeses such as Parmesan, blue cheeses, sun-dried tomatoes, anchovy paste, soy sauce, cured ham and so on. Similarly, synergy in umami sensation is used extensively in Western food pairing, such as tomatoes with anchovies, vegetables with meat, eggs with bacon, green peas with scallops, and so on. Needless to say, umami and umami synergies are used extensively in flavouring industrially processed foods and convenience foods. MSG as an additive for flavouring food When, in 1909, Ikeda discovered MSG as the compound behind umami, he immediately realised the technological importance of his discovery and took out a patent for the production of pure MSG to be used as an artificial flavouring agent in foodstuffs (Sano, 2009), leading the way to the establishment of the international company Ajinomoto that now produces approximately two million tonnes of MSG annually, approximately one-third of the world’s production. MSG is produced industrially by hydrolysis of proteins that come mostly from plant material. Table 1. (continued) Food item MSG (mg/100 g) Algae (seaweeds) Konbu (Saccharina japonica) 1400–3200 Laver, nori (Porphyra yezoensis) 1378 Wakame (Undaria pinnatifada) 9 Soup broths Dashi from konbu (Saccharina japonica) 22–145 Dashi from dulse (Palmaria palmata) 10–40 Western chicken soup 18 Chinese chicken soup 14 Fermented and processed products Marmite 1960 Fish sauce 828–1383 Soy sauce 782–1264 Miso 500–1000 Worchestershire sauce 34 Sources: Giacometti, 1979; Komata, 1990; Maga, 1983; Mouritsen and Styrbæk, 2011; Mouritsen et al. 2012; Ninomiya, 1998, 2002; Ozawa et al., 2004, 2005. Mouritsen 63 63 MSG is now used across the world as a flavour enhancer, potentiator and additive in a wide variety of foodstuffs (Kawai et al., 2009; Maga, 1983) and its uses are increasing, not least in convenience foods and for increasing the acceptance of new flavours (Prescott, 2004). The total MSG production corresponds to an average daily consumption of approximately one gram of MSG per person globally. In Asia, in particular China and Japan, the consumption per inhabitant is probably up to three times the average (Biesalski et al., 1997; Giacometti, 1979), and it has been estimated that in some Chinese restaurants a customer may, in a single meal, get as much as 5 g or more (Yang et al., 1997). Table 2. Selection of data for free nucleotides (di-sodium adenosine-5´-monophosphate (adenylate, AMP), di-sodium guanosine-5´-monophosphate (guanylate, GMP), di-sodium inosine-5´- monophosphate (inosinate, IMP)) occurring naturally in various raw and processed foods. These nucleotides provide for umami flavour in synergy with glutamate (Table 1). ‘–’ denotes below measurable limit. A blank cell denotes that data are not available. Food item IMP (mg/100 g) GMP (mg/100 g) AMP (mg/100 g) Fish and shellfish Katsuobushi 687 52 Anchovy paste 300 5 Sardine 193 6 Scallop – – 172 Mackerel 215 – 6 Tuna 286 – 6 Salmon 154 – 6 Lobster – – 82 Cod 44 23 Shrimp 92 – 87 Squid – – 184 Crab 5 5 32 Vegetables and fungi Tomato (sun-dried) – 10 Tomato (fresh) – – 21 Potato (boiled) – 2 4 Shiitake (fresh) – 16–45 Shiitake (dried) – 150 Green asparagus – – 4 Meat and poultry Chicken 201 5 13 Pork 200 2 9 Beef 70 4 8 Seaweed Laver, nori (Porphyra yezoensis) 9 5 52 Milk Human breast milk 0.3 Sources: Maga, 1983; Ninomiya, 1998, 2002. 64 Nutrition and Health 21(1) 64 In Europe, MSG, as a food additive, has to be declared as E621 on food product labels. Other compounds pertaining to glutamic acid carry the labels E620 to E624. MSG is added to processed and industrially produced foods or sprinkled together with condiments on dishes after preparation (Bellisle, 1999). Typically, manufacturers may add an amount of MSG that corresponds to the natural occurrence of free glutamate in common foodstuffs, such as ripe tomatoes or mature cheeses, i.e. 0.1–0.8% by weight (Beyreuther et al., 2007). Pure nucleotides such as IMP (E630–E635), GMP (E626–E629) or AMP (E634–E635) are also used as food additives, and often they are mixed with MSG. A note on safety issues related to MSG MSG is historically linked to the so-called Chinese restaurant syndrome (Kwok, 1968), which was associated with the reporting of certain physiological effects following the intake of Chinese meals in which MSG was used as a flavour enhancer. The syndrome includes an ill-defined set of symptoms, such as numbness and tingling, flushing, muscle tightness, migraine headache and bronchoconstriction in some asthmatics (for a recent list of references, see Jinap and Hajeb, 2010). Since the first report of possible adverse effects of MSG, it has become the most intensively studied food additive. The most comprehensive study targeting the Chinese restaurant syndrome complex is an American multicentre double-blind, placebo-controlled, randomized investigation that selectively included subjects who claimed or reported hypersensitivity to MSG (Geha et al., 2000). The study concluded that the alleged reactions to MSG failed to show reproducibility. The conclusion of many other controlled and double-blind clinical investigations focusing on specific symptoms is that there is no consistent scientific evidence for any harmful effects of MSG, specifically in relation to asthma and asthmatic bronchospasm (Williams and Woessner, 2009) or exacerbations of migraine headache (Woods et al., 2006). In Europe, the Scientific Committee for Food of the Commission of the European Communities (SCF, 1991) has declared MSG as safe and has not specified any value for an acceptable daily intake. Similarly, a report from the Federation of American Societies for Experimental Biology (FASEB, 1995) concluded that there was no significant scientific documentation for adverse effects, although there may be a small part of the population (∼1%) that may react within an hour to very large doses of MSG (> 3 g) on an empty stomach. This conclusion seems to have been endorsed by the US Food and Drug Administration (Hattan, 1996). As many common types of natural foods, such as ripe tomatoes, cheeses and other fermented products, contain large amounts of free glutamate, which, chemically, is exactly the same as industrially produced pure MSG, it would in any case be difficult to understand how MSG in even high amounts could exert any health hazard. Later in this article I will return to the body’s uses of glutamate for metabolic and neural purposes. Despite MSG having been declared as a safe food additive in the highest category, there is a strong current trend among consumers to ask for so-called label-free products, i. e. foods that have, for example, no added MSG. This is a very sensitive issue that is marred by science illiteracy, which in some cases is exploited by the industry. One way Mouritsen 65 65 of distracting the consumer’s attention from the fact that glutamate has been added to the food is by administering or hiding it in a less pure form, as hydrolysed vegetable protein or yeast extract, both of which have large amounts of glutamate but do not need to be declared on the MSG label. Sometimes products carry the labels ‘No added MSG’ or ‘No MSG’, which consumers might read to indirectly indicate that one should worry about MSG (Dillon, 1993). Paradoxically, some of these products may contain large amounts of naturally occurring glutamate or glutamate that is supplied via the addition of hydrolysed protein or yeast extract. Interaction of umami with other basic tastes MSG exerts a complex interplay with the sensation of sweet, sour, salty and bitter. The most important interaction is that with salty. MSG shares a sodium ion with kitchen salt, NaCl. Taste physiological experiments show, in accordance with Ikeda’s original observation (Ikeda, 2002), that for fixed sodium concentration, and when varying the ratio between MSG and NaCl in an aqueous solution, the tasters find that lowering the amount of NaCl counterintuitively increases the salty taste and increases the satisfaction with the food (Fuke and Shimizu, 1993). This suggests that, by insightful use of MSG as an additive or via its natural occurrence in certain foodstuffs, it is possible to lower the amount of NaCl in cooking. Adding 0.1–0.8% by weight MSG to food can reduce the need for salt by 30–40% without affecting palatability (Yamaguchi and Takahashi, 1984). MSG cannot replace sugar, but it turns out that in foodstuffs with only a little sweetness, or other foodstuffs with a natural occurrence of free glutamate, e.g. a concentrate of the inner pulp of ripe tomatoes, the addition of pure MSG enhances the sweetness (Mouritsen and Styrbæk, 2011). The mechanism of this enhancement is not understood in detail, but it may reflect that the umami receptor dimer T1R1/T1R3 shares the component T1R3 with the receptor for sweet, T2R3/T1R3 (Galindo-Cuspinera and Breslin, 2006; Temussi, 2009). Hence, umami by this type of sweetness enhancement can help to suppress an undesirably sour taste in pickles and tomato products. MSG, however, does not seem to lower the taste threshold for sweet. MSG is known not to increase the palatability of sweet fruits. In many cases, the optimal umami taste in relation to the other taste modalities may vary from individual to individual (Yeomans et al., 2008). The most notable effect of MSG on the threshold of a basic taste is for bitter (Temussi, 2009), for which it has been found, in some cases, to lower the threshold by 30 times. Still, it appears that MSG can suppress a bitter taste, presumably because MSG lowers the intensity of the bitter taste. (One can easily convince oneself of this effect by adding a very small amount of MSG to a cup of coffee.) Physiological and nutritional roles of glutamate An adult will typically consume 50 g of protein each day, which corresponds to about 10– 20 g glutamic acid bound in proteins and about 1–2 g free glutamate. As glutamic acid is not an essential amino acid, it can be synthesised in the human body, which produces about 50 g free glutamic acid per day. Glutamic acid plays a key role in the synthesis of other non-essential amino acids (Kawamura and Kare, 1986). 66 Nutrition and Health 21(1) 66 Glutamate is vital for the normal functioning of the digestive tract and our digestive system (Reeds et al., 2000). Glutamic acid and glutamate are effectively (5–10 g glutamate per hour) absorbed in the gastrointestinal system by an active transport system located in the mucosal cells where up to 95% is metabolized and turned into energy, most of it consumed for digestion. In the digestive system, the body cannot discriminate between glutamate from different sources, as the glutamate ion is, in all cases, in aqueous solution in the digestive tract. Glutamate is the substrate for various biochemical processes such as glutathione and glutamine synthesis, and it is a precursor for other amino acids such as proline and arginine. Only a very small amount of glutamate in the intestinal system makes it into the bloodstream, and blood levels are rather insensitive to the glutamate content in the diet. Excess glutamate is degraded in the liver (Bellisle, 1999). The stomach and the intestines have a developed system of nerves that to some extent function autonomously and independent of the oral taste system, but it is also connected to the brain via the vagus nerve that constitutes a gut–brain axis (Niijima, 1991). Experiments on rats (San Gabriel et al., 2005) have discovered a glutamate receptor, mGluR1, in the fundic glands in the stomach. Binding of glutamate to this receptor signals, via the vagus nerve, to the brain. The brain in turn signals back to the fundic glands to release proteases, thereby providing for gastric phase regulation of protein digestion (Uneyama et al., 2008). Only glutamate, and none of the other amino acids (or glucose or sodium chloride), can activate the signalling pathway along the gut–brain axis. By coupling to this pathway, sensing of glutamate at the oral umami receptors could possibly be a signal to the body that protein-rich food is on the way. It has also been found that gustatory stimulation by glutamate induces the secretion of pancreatic juices in dogs (Ohara et al., 1988). In this way umami taste sensed at the tastebuds at the tongue may facilitate the body’s alertness to be ready to digest the food and regulate appetite. The total effect of these mechanisms is a homeostatic control of energy. Glutamate has been found to stimulate saliva and immunoglobulin A secretion, which has implications for immunological and nutritional status (Hayakawa et al., 2008; Schiffman, 1998; Uneyama et al., 2009). The stimulation of saliva production by glutamate has a longer time duration than that of sourness, e.g. MSG has a stimulation time profile longer than 10 minutes compared with about 2 minutes for citric acid (Uneyama et al., 2009). Glutamate exerts another vital function in vertebrates as a neurotransmitter, in particular in the brain where it acts as a chemical signal between the neurones. Glutamate activation of neural receptors is important for maintaining the plasticity of the neural network, and hence for memory and learning. There is very little transport of glutamate over the blood–brain barrier and the neural cells produce and recycle themselves the glutamate they need for signalling. Hence, the alleged effects of dietary glutamate on brain function are likely to be unfounded (Takasaki, 1978). There have been some reports suggesting that glutamate may induce obesity and overweight, but recent studies have indicated that this is not the case (Ebert, 2010). Discussion The preference for high-fat food has been claimed to be a universal human trait (Drewnowski, 1997). Fat has an aroma and contributes to the mouthfeel and texture of food, Mouritsen 67 67 which are considered desirable. However, lessons from the classic, strictly vegan, Japanese temple cuisine, shōjin ryōri (‘The enlightened kitchen’) (Fujii, 2005), demonstrate that it is possible to produce healthy and delicious food virtually without using fats and oils. The trick discovered by the Buddhist monks is to enhance umami by appropriate choices of combinations of ingredients. The temple kitchen, as well as the entire traditional Japanese cuisine (Tsuji, 1980; Mouritsen, 2010), revolves around the soup broth dashi, produced as an aqueous extract of konbu and katsuobushi, the perfect combination to invoke synergy in the umami taste (see Tables 1 and 2). In contrast toWestern cooking, in which the cook adjusts the taste of a dish at the end, usually by adding salt, sugar, vinegar and various spices, the Japanese approach is to start with the taste, which usually is a dashi broth in which vegetables, pulses, grains, seaweed, fungi, wild herbs and other greens are steamed or simmered. Later adjustments of taste are then made by adding fermented products, e.g. soy sauce, miso, mirin or sake, which all contribute umami. These ingredients will also provide delicious flavour to less flavourful, non-fermented staples of this simple cuisine, such as protein-rich soy and wheat products such as tofu, yuba and fu. It is interesting that, until recently, obesity was not a major problem in Japan. A possible reason may be that the traditional Japanese diet focuses on umami. Umami in the food helps to regulate appetite and food intake by the homeostatic principle functioning along the gut–brain axis, and hence limiting the caloric uptake (Kondoh et al., 2009). Umami may therefore be part of the solution for limiting fat and energy intake. One study has shown that it is possible, by regulating umami taste, to reduce the fat content by up to 30% without compromising palatability (Bellisle, 2008). The optimal way to achieve this is, however, very dependent on the type of food as well as individual preferences. Umami is also a way to reduce salt intake while retaining palatability (Yamaguchi and Takahashi, 1984). A particular interesting possibility with added functionality is the use of certain seaweeds for providing umami flavour in foods (Mouritsen et al., 2012), and hence reducing the need for adding salt. At the same time, seaweeds contribute their own salts that generally are dominated by potassium salts rather that sodium salts (Holdt and Kraan, 2011; Mouritsen, 2009, 2012). Hence, appropriately chosen seaweeds can serve to reduce salt in, for example, meat products such as sausages (Lopez-Lopez et al., 2009). Elderly individuals, as well as people who are subject to intensive hospitalization and chemo- and radio-therapeutic treatments, may suffer from permanent or transient impairment of taste and smell faculties, which leads to loss of appetite, resistance to eating, malnutrition and, in some cases, anorexia. All these conditions tend to lower QOL. Increasing umami in their meals may be part of a solution to their problems. A simple way to do this is by reduction and concentration of flavour compounds in boiling water and sauces. At the same time, increasing umami will lower the need for salt and sugar in the food. Glutamate stimulates appetite and enhances saliva and immunoglobulin A secretion that leads to a smoothening of mastication and swallowing (Uneyama et al., 2009). Immunoglobulin A secretion promotes the immune system and oral health, protecting teeth and mucosa from infections. A larger saliva volume improves the nutritional status by promoting digestion and nutrient availability in the gut (Kawai et al., 2009; Schiffman, 1998; Tomoe et al., 2008; Toyama et al., 2008; Yamamoto et al., 2009). Hence, optimizing umami in food served to elderly persons may improve their QOL well into their eighties and nineties. 68 Nutrition and Health 21(1) 68 The concept of umami is generally not used systematically to improve meals at institutions and hospitals. Even in Japan, where umami is a natural and accepted element of the taste language, studies at hospitals for elderly people have shown (Kawai et al., 2009) that, whereas the salt concentration in meals is relatively tightly regulated (361–1516 mg/100 g), the variation of glutamate is rather large (16–697 mg/100 g). Dietitians obviously do not take full advantage of using umami as a control parameter to optimize the menus. One reason may be that there are many factors influencing the appetite and we know only little about their mutual interactions. There is an urgent need for more quantitative research identifying the role of flavour and flavour combination for appetite regulation (Sørensen et al., 2003). As described above, the term umami was coined by Ikeda (1909) (see 2002 translation) based on his findings of high levels of free glutamate in the dashi extract of the large brown seaweed konbu (Saccharina japonica). The dashi is also imparted with mild sweet taste notes, mostly from the sugar alcohol mannitol, but also from the sweet amino acids proline, serine and alanine deriving from the seaweed (Mouritsen et al., 2012). It is interesting that other types of seaweed, except for the red laver nori (Porphyra spp.), are not commonly used for the purpose of contributing umami, and, for example, wakame (Undaria pinnatifada), often found in Asian soups, contains only a little free glutamate (Ninomiya, 1998) and is used mostly for texture purposes. It has been pointed out that other types of seaweeds, for example from the North Atlantic and North Pacific cold waters, may have an interesting but mostly overlooked potential to contribute glutamate and umami in cooking (Mouritsen, 2012). Recently it was discovered that the red seaweed dulse (Palmaria palmata) releases large amounts of free glutamate in warm aqueous extracts, which therefore can serve a similar role to dashi, as both a soup broth and an infusion fluid for a number of other products, such as cheeses, bread and ice cream (Mouritsen et al., 2012). It is likely that further exploration of the algal cuisine (Mouritsen, 2012) may point to a range of new and sustainable sources for umami flavour. Conclusions In this article I have reviewed the concept of umami flavour and its biochemical and physiological basis. Umami has been linked to the presence of free glutamate (MSG) in food and it has been pointed out that the sensation of umami is intimately linked to a synergy mechanism at the umami receptors involving co-binding of the glutamate ion and certain free 5′-ribonucleotides, in particular inosinate, guanylate and adenylate. These umami substances are found in abundance in only a few raw materials, but can be produced and released in large amounts in processed food, for example by cooking, fermenting, maturing and ageing. Naturally occurring or added umami compounds can serve a nutritional role and can flavour meals that are not themselves flavourful (Löliger, 2000). Glutamate and umami have a number of attractive effects in relation to improving nutrition and health. Glutamate can be used for dietetic purposes because of its ability to encourage an individual’s choice of certain foods stimulated by an attraction to umami (Bellisle, 2008). Free glutamate in the diet can provoke a visceral response from the Mouritsen 69 69 stomach, intestines and portal vein (Jinap and Hajeb, 2010). In this way glutamate can stimulate the appetite in elderly individuals, and hence increase food acceptance and intake. Glutamate can reduce total sodium in a meal by 30–40% without reducing palatability. It also works well to enhance the palatability of fat-reduced meals, thereby suggesting a viable route to lower caloric intake of fats and oils. The current scientific insight into how umami is produced and enhanced could potentially be better exploited to optimise and regulate food intake, and lead to greater satiety and satisfaction after less comprehensive and less caloric portions. Altogether, a focus on umami may be a way of counteracting many of the diet-related lifestyle diseases, such as cardiovascular disease, including hypertension, obesity and diabetes. Intelligent uses of umami may provide for better nutritional management and reduced intake of salt, fat and sugar without compromising palatability. A focus on umami may not only provide for better tasting and more flavourful meals but also could help to regulate food intake, in relation to both overeating and nutritional management for elderly and sick individuals. Lessons from the enlightened Japanese kitchen, where umami is used extensively to produce flavourful and delicious dishes from only vegetable sources, may carry over to the modern Western kitchen, where most people have trouble with consuming the recommended 600 g of vegetables and greens daily. Since 1968 and the proposal of the Chinese restaurant syndrome (Kwok, 1968), MSG has had a bad name. Even if all scientific evidence points to the fact that MSG is harmless as a food additive, some still claim MSG to have adverse effects. What remains, however, is that glutamate as a food additive is the most intensively studied food ingredient, and international results from very extensive biochemical, toxicological, and clinical and epidemiological investigations have led the Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization andWorld Health Organization to classify MSG in the safest category for food additives (Jinap and Hajeb, 2010). This category also contains common food ingredients such as table salt, baking powder and vinegar. The only concern for extensive use of these food additives seems to be the possibilities they open for disguising food of poor quality and of a dubious origin. Notwithstanding the nutritional and health benefits of umami and the proper use of glutamate as a food additive, umami is, first of all, synonymous with delicious and fulfilling food. The enjoyment of good food is one of the great pleasures of life and undoubtedly a key contributor to QOL. The culinary applications of umami should therefore be a key focus in the home kitchen, the food industry and gastronomy (Marcus, 2005; Mouritsen and Styrbæk, 2011). In order to disperse the knowledge of umami to a wider audience to inform more people about delicious taste and the possibilities of regulating food intake and improving nutrition and health, it is necessary to translate science-based results and conclusions to practitioners in home kitchens, institutional kitchens, restaurants and the food industry. This translation must result in concrete advice and recipes. To this end, the last few years have witnessed the appearance of a few special cookbooks on umami and its use in modern Western cuisine (Blumenthal et al., 2009; Kasabian and Kasabian, 2005; Mouritsen and Styrbæk, 2011). One of these (Mouritsen and Styrbæk, 2011) not only provides recipes but also presents the scientific background of umami in lay terms. 70 Nutrition and Health 21(1) 70 Funding This work was supported by a grant (J.nr. 3414-09-02518) from the Danish Food Industry Agency. 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