Misako Kawai

Can dietary supplementation of monosodium glutamate improve the health of the elderly

Dietary free l-glutamate has been known for a century to improve taste and palatability. Recent evidence suggests that this effect is mediated through specific l-glutamate receptors located on the taste buds. However, l-glutamate receptors are also present elsewhere in the gastrointestinal tract, such as the stomach. Here, l-glutamate exerts physiologic actions beneficial to gut function by stimulating l-glutamate receptors linked to the gastric vagus nerve. In addition, dietary l-glutamate also appears to be an important energy substrate for gut tissue. Can such l-glutamate effects on taste and gut function be clinically useful? Elderly people often develop health problems related to their nutritional status that can be linked to insufficient energy and nutrient intake. A number of studies have examined the potential usefulness of l-glutamate, added to food in the form of monosodium glutamate (MSG), in promoting better nutrition in the elderly and in patients with poor nutrition. Some positive effects have been observed. This article reviews the physiologic roles of dietary l-glutamate in relation to alimentation and examines the evidence linking the utility of MSG supplementation to the improvement of nutrition in elderly and hospitalized patients.

Gustatory sensation of l- and d-amino acids in humans

Amino acids are known to elicit complex taste, but most human psychophysical studies on the taste of amino acids have focused on a single basic taste, such as umami (savory) taste, sweetness, or bitterness. In this study, we addressed the potential relationship between the structure and the taste properties of amino acids by measuring the human gustatory intensity and quality in response to aqueous solutions of proteogenic amino acids in comparison to d-enantiomers. Trained subjects tasted aqueous solution of each amino acid and evaluated the intensities of total taste and each basic taste using a category-ratio scale. Each basic taste of amino acids showed the dependency on its hydrophobicity, size, charge, functional groups on the side chain, and chirality of the alpha carbon. In addition, the overall taste of amino acid was found to be the combination of basic tastes according to the partial structure. For example, hydrophilic non-charged middle-sized amino acids elicited sweetness, and l-enantiomeric hydrophilic middle-sized structure was necessary for umami taste. For example, l-serine had mainly sweet and minor umami taste, and d-serine was sweet. We further applied Stevens’ psychophysical function to relate the total-taste intensity and the concentration, and found that the slope values depended on the major quality of taste (e.g., bitter large, sour small).

Recombinant curculin heterodimer exhibits taste-modifying and sweet-tasting activities.

Curculin from Curculigo latifolia is a unique sweet protein that exhibits both sweet‐tasting and taste‐modifying activities. We isolated a gene that encodes a novel protein highly homologous to curculin. Using cDNAs of the previously known curculin (designated as curculin1) and the novel curculin isoform (curculin2), we produced a panel of homodimeric and heterodimeric recombinant curculins by Escherichia coli expression systems. It was revealed that sweet‐tasting and taste‐modifying activities were exhibited solely by the heterodimer of curculin1 and curculin2.

Curculin Exhibits Sweet-tasting and Taste-modifying Activities through Its Distinct Molecular Surfaces.

Curculin isolated from Curculigo latifolia, a plant grown in Malaysia, has an intriguing property of modifying sour taste into sweet taste. In addition to this taste-modifying activity, curculin itself elicits a sweet taste. Although these activities have been attributed to the heterodimeric isoform and not homodimers of curculin, the underlying mechanisms for the dual action of this protein have been largely unknown. To identify critical sites for these activities, we performed a mutational and structural study of recombinant curculin. Based on the comparison of crystal structures of curculin homo- and heterodimers, a series of mutants was designed and subjected to tasting assays. Mapping of amino acid residues on the three-dimensional structure according to their mutational effects revealed that the curculin heterodimer exhibits sweet-tasting and taste-modifying activities through its partially overlapping but distinct molecular surfaces. These findings suggest that the two activities of the curculin heterodimer are expressed through its two different modes of interactions with the T1R2-T1R3 heterodimeric sweet taste receptor.

Development of an Umami Taste Sensitivity Test and Its Clinical Use

There is a close relationship between perception of umami, which has become recognized as the fifth taste, and the human physical condition. We have developed a clinical test for umami taste sensitivity using a filter paper disc with a range of six monosodium glutamate (MSG) concentrations. We recruited 28 patients with taste disorders (45–78 years) and 184 controls with no taste disorders (102 young [18–25 years] and 82 older [65–89 years] participants). Filter paper discs (5 mm dia.) were soaked in aqueous MSG solutions (1, 5, 10, 50, 100 and 200 mM), then placed on three oral sites innervated by different taste nerves. The lowest concentration participants correctly identified was defined as the recognition threshold (RT) for MSG. This test showed good reproducibility for inter- and intra-observer variability. We concluded that: (1) The RT of healthy controls differed at measurement sites innervated by different taste nerves; that is, the RT of the anterior tongue was higher than that of either the posterior tongue or the soft palate in both young and older individuals. (2) No significant difference in RT was found between young adults and older individuals at any measurement site. (3) The RT of patients with taste disorders was higher before treatment than that of the healthy controls at any measurement site. (4) The RT after treatment in these patients improved to the same level as that of the healthy controls. (5) The cutoff values of RT, showing the highest diagnostic accuracy (true positives + true negatives), were 200 mM MSG for AT and 50 mM MSG for PT and SP. The diagnostic accuracy at these cutoff values was 0.92, 0.87 and 0.86 for AT, PT and SP, respectively. Consequently, this umami taste sensitivity test is useful for discriminating between normal and abnormal umami taste sensations.

Important Role of Umami Taste Sensitivity in Oral and Overall Health

Our newly developed umami taste sensitivity test revealed the loss of only the umami taste sensation in some elderly patients, whereas the other four basic taste sensations (sweet, salty, sour, bitter) were normal. Such patients all complained of appetite loss and weight loss, resulting in poor overall health. As a treatment for taste disorder patients, improvement of salivary flow has been adopted in our clinic. Umami taste stimulation increases salivary flow rate of not only major but also minor salivary glands. After treatment with umami taste stimulation, patients remarkably regained their appetite, weight and overall health. Sensitivity to umami taste seems to contribute to good overall health in elderly people.

Effects of chemotherapy on gene expression of lingual taste receptors in patients with head and neck cancer.

We aimed to test the hypothesis that chemotherapy changes the gene expression of taste receptors in the tongue to induce dysgeusia in patients with head and neck cancer.

Purification and Characterization of an N-Terminal Acidic Amino Acid-Specific Aminopeptidase from Soybean Cotyledons (Glycine max)

A novel enzyme that catalyzes the efficient hydrolysis of Glu-Glu was isolated from soybean cotyledons by ammonium sulfate fractionation and successive column chromatographies of Q-sepharose, Phenyl sepharose, and Superdex 200. The apparent molecular mass of this enzyme was found to be 56 kDa and 510 kDa by SDS-polyacrylamide gel electrophoresis and Superdex 200 HR 10/30 column chromatography respectively. The enzyme had high activity against Glu-p-nitroanilide (pNA) and Asp-pNA, whereas Leu-pNA, Phe-pNA, Ala-pNA, and Pro-pNA were not hydrolyzed. The synthetic dipeptides Glu-Xxx and Asp-Xxx were hydrolyzed, but Xxx-Glu was not. The digestion of a Glu-rich oligopeptide, chromogranin A (Glu-Glu-Glu-Glu-Glu-Met-Ala-Val-Val-Pro-Gln-Gly-Leu-Phe-Arg-Gly-NH2) using this purified enzyme was also investigated. Glutamic acid residues were cleaved one by one from the N-terminus. These observations indicate that the enzyme removes glutamyl or aspartyl residues from N-terminal acidic amino acid-containing peptides. It is thought that it was an N-terminal acidic amino acid-specific aminopeptidase from a plant.

Assessment of Umami Taste Sensitivity

Patients with gustatory disorders often complain of persistent impairment of umami taste, a synonym for savory or broth-like flavor, even after the recovery of the other four basic taste sensations (sweet, salty, sour, and bitter). Umami taste is important for maintaining not only the quality of life but also good health, and therefore, it seems important to assess and treat the impairment of umami taste perception. At present, however, there is no clinical test for umami taste, even though tests for the other four basic tastes have been widely used in quantitative gustometry. We have developed a new method to clinically assess the sensitivity of umami taste using a filter paper disc (FPD) with monosodium glutamate (MSG) as the prototype umami substance. We found that some elderly patients complained only of the loss of umami taste sensation, whereas the sensation of the other four basic tastes (sweet, salty, sour, and bitter) was normal. Those patients without normal umami taste sensitivity were all over 65 years old, and complained of appetite and weight loss, resulting in poor general health. After treatment, their umami taste threshold recovered, and they regained appetite and weight.

Contribution of Umami Substance to Swallowing

Reflecting progressive aging of society, many special diets for patients suffering from swallowing disorders (i.e. dysphagia diets) have been developed. Texture modification for less risk of aspiration is one of the important elements in dysphagia diets from the viewpoint of safety assurance. However, no attempt has been done to add chemicals to such diets to facilitate swallowing initiation. For this, sensory inputs from the oropharynx play an important role in swallow initiation. Animal studies showed that stimulation by umami taste is effective stimulus of this area. Therefore, to study the effect of umami taste on swallow initiation in humans, we examined the effect of application of Monosodium L-Glutamate (MSG) solution as an umami taste to the oropharynx on the latency of the swallow reflex evoked by electrical stimulation of the oropharynx. Distilled water (DW) and 0.15 M sodium chloride (NaCl) solution (saline) were used as vehicles of MSG. Each of the DW, saline, 0.1 M MSG dissolved with DW (MSGDW) and 0.1 M MSG dissolved with saline (MSG-saline) were slowly injected approximately 1 s prior to electrical stimulation. The amount of each solution was 0.1 ml. No swallow was evoked when each of the solutions was applied to the posterior wall of the oropharynx without electrical stimulation, and the subjects could not discriminate the solutions. Results showed that application of DW to the oropharynx shortened the latency of the swallow reflex, but saline application elongated the latency of the reflex. Also, application of MSG-saline solution counteracts the elongation of the latency induced by saline application. This counteractive effect of MSG was concentrationdependent. Above findings suggest that using MSG as a food additive with NaCl (i.e. salty taste) may serve not only as a flavor enhancer but also as an enhancer of swallow initiation.