Modelling Salt Intake Reduction with Umami Substance’s Incorporation Into Japanese Foods: A Cross-Sectional Study

Evidence has demonstrated that excess salt intake is associated with the development of several non-communicable diseases. Therefore, reformulating the sodium content of foods is an important global public health effort to achieve salt reduction and improve health. This study aimed to model sodium replacement with 'umami' substances and estimate the possible reduction effects of the umami substances on the daily salt intake among Japanese adults. The umami substances considered in this study include glutamate or monosodium glutamates (MSG), calcium diglutamate (CDG), inosinate, and guanilate.


Background
The latest Global Burden of Disease Study 2019 (GBD) highlighted that the global prevalence of non-communicable diseases (NCDs), as well as inadequate public health efforts to control preventable risk factors, may have spurred the pandemic of coronavirus disease 2019 (COVID-19) (1). In 2013, the World Health Organization (WHO) developed the NCDs Global Monitoring Framework, in which seven NCDs prevention targets were set (2). Of the seven goals, the only speci c goal related to nutrients called for member countries to aim for a 30% reduction in salt intake between 2011 and 2025. Since then, many salt reduction campaigns have been initiated around the world(3), and the global salt reduction movement has been accelerating(4-6), but no country has achieved that 30% reduction goal (7). In the GBD 2019, high salt intake was listed as one of the top dietary risks contributing to the global burden of disease due to NCDs (8) highlighting the need for an urgent approach.
Japan is one of the countries with the most prolonged longevity globally (9). However, a high salt intake is a major dietary risk factor for both mortality and morbidity of its population (8, 10). Japan's nationwide population-based campaign for salt reduction started in the 1960s and successfully reduced the population's salt intake and stroke mortality over time (11). According to the National Nutrition. Survey (NNS) (renamed to the National Health and Nutrition Survey (NHNS) in 2013) revealed that the daily salt intake has steadily decreased from 14.5g in 1973 to 9.5g in 2017 (12). However, Japanese regularly consume more salt than people in other countries (13). For instance, the population averages between 1990 and 2010 in the United Kingdom was 8.83-9.17g/day and 8.74-9.14g/day in the United States (US). The Japanese government aims to reduce the daily salt intake of Japanese adults to 8g by 2023 according to their 10-year national health promotion plan titled The Second Term of National Health Promotion Movement in the Twenty-First Century, also known as "Health Japan 21 (the second term)" (14). Another dietary guideline called the Dietary Reference Intakes for Japanese (DRIs), which was determined based on scienti c ndings to prevent lifestyle-related diseases and extend healthy life expectancy (15), recommends daily salt intake of 7.5g/day for men and 6.5g/day for women. However, the average salt intake for Japanese adults is higher than the recommendations made by both guidelines. The intake target set for the Japanese is unlikely to be attained if current conditions persist (16,17).
Sodium replacement in foods is one of the most widely used approaches to reduce salt intake. The technical challenge is ensuring that the sodium alternative is palatable and safe to eat (18). Umami is a common and familiar taste in Japanese cuisine and is perhaps more known globally as the fth avour discovered by Japanese scientists in 1908, in addition to the classic four basic tastes, such as saltiness, sweetness, bitterness, and sourness (19).
Umami substances, including glutamate or monosodium glutamates (MSG), calcium diglutamate (CDG), inosinate and guanilate have been proposed as enhancers of savory when combined with sodium chloride (NaCl) (20)(21)(22). A large number of studies have suggested the potential of using umami taste and substances as a healthy and natural solution for salt reduction (23)(24)(25). In recent years, academic institutions such as the Institute of Medicine in the United States have identi ed umami substances as candidates for practical salt reduction alternatives (18). Wallace et al. (2019) estimated that incorporating MSG into a savoury seasoning of processed foods in the United States could reduce the sodium intake by at least 3-8% in the population (26). However, given that the source of salt intake is highly dependent on the dietary habits and the cooking processes of each country (27), the effectiveness of the umami substances for reducing salt intake at the population level in the context of other cultures is not well known. Therefore, our study investigates the effects of umami substances substitution on the daily salt intake among Japanese adults using data from the nationwide dietary survey.

Study design and participants
We conducted a cross-sectional study using de-identi ed nationwide data from the 2016 NHNS. The NHNS is a nationally representative household survey conducted annually by the Japanese Ministry of Health, Labour and Welfare (MHLW) to collect data on the population's dietary habits, nutrition intake, and lifestyle (28). Residents from census enumeration areas above the age of one are selected using a strati ed single-stage cluster sample design.
The 2016 survey, the latest large-scale survey data available from the NHNS at the time of the study, encompasses 24,187 households from 475 randomly selected districts. The response rate of households was 44.4%. The NHNS consists of three parts: 1) physical examination, 2) an in-person survey of a weighted single-day dietary record of households, and 3) a self-reported lifestyle questionnaire. Details of the survey design and the procedures used to collect the data are available elsewhere (16, 28). In the present analysis, we included persons older than 20 years old because of Health Japan 21's criteria that required those above the age of 20 to complete and provide the dietary intake data. We further excluded participants who consumed less than 1.5g of salt per day, which is equivalent to the minimum physiological requirement of sodium for survival, because their data may not re ect accurately on the daily diet or may be a measurement error.
This study was performed under the Declaration of Helsinki and approved by the Research Ethics Committee of the Graduate School of Medicine, The University of Tokyo (authorization number 11964). Furthermore, the ethical committee waived the need for informed consent because this study was a secondary analysis of anonymized data routinely collected by the MHLW.

Dietary assessment
The dietary intake survey was conducted on a single designated day by household representatives, who were usually responsible for food preparation. Trained interviewers, mainly registered dietitians, instructed household representatives on how to measure the food and beverages consumed by members of the household and veri ed their compliance with the survey. The proportion of shared dishes, food waste, and foods eaten out were also recorded. The nutrient intake and food consumption were estimated using the dietary record and the corresponding food composition list of the Japanese Standard Tables of Food Composition (29). In addition, food intake (g/day) and overall sodium intake (mg/d) were recorded. Salt equivalent intake (g) was de ned as sodium (mg) × 2.54/1,000. NHNS did not measure urine sodium.

Salt intake modelling
According to an extensive review of the scienti c literature, umami substances such as glutamate or MSG, CDG, inosinate, and gualilate have been used to reduce sodium levels among various mainstream products. Table1 shows the percentage of salt reduction by food group estimated by previous studies using one or more of these umami substances. The food groups listed in Table 1 were then matched with NHNS food categories in consultation with food and nutrition experts (co-authors). In addition, we assumed that the study's participants already consume a certain amount of low-sodium foods containing umami substances in their daily diet. Therefore, the market share of low-salt products was used as a proxy indicator of the baseline consumption of low-sodium foods with umami substances today (30). This market share was estimated from the total sales and the sales of low-sodium foods for 15 food groups based on surveys conducted in 2017 by Fuji Keizai Management Co., Ltd. (a Japanese market research company) among various food companies supplying food products in the country. Low-sodium food was de ned as products labelled with reduced salt, salt cut, salt off, or no salt on the package. The market share of lowsodium products for each food group was also summarized in Table 1. Accordingly, our baseline scenario assumed that the consumers already had a certain amount of low-salt foods containing umami substances. We also considered three alternative scenarios in which consumers in food groups increased the intake of low-sodium food with umami substances from the baseline scenario to 30% (30-percent scenario), 60% (60-percent scenario), and 100% (100-percent scenario or universal incorporation scenario).

Statistical analysis
We rst constructed a linear regression model with overall daily salt intake (g/day, continuous) as a dependent variable. To estimate the contribution to the overall salt intake from 13 selected food items (continuous), we included age (continuous), sex (two groups), food intake (g/day) from the 13 items and other remaining 35 food groups or sub-groups (continuous) in the following model (1).
where Y i and X ij (for j=1, …,13) are the overall daily salt intake and the food intake (g/day) from each of the 13 food items for the ith individual, respectively. Z i is the covariate vector for the other remaining 35 items and sex and age for the ith individual. α,β j ,γ are regression coe cients and ϵ i is a gaussian error term. The regression coe cients were estimates by ordinary least squared method.
The food-speci c upper and lower changes in salt intake by umami substances incorporation were estimated using the current market share of low-sodium products for the jth selected item (denoted as M j ), the upper and lower sodium reduction rates for the jth selected food (denoted as U j and L j , respectively), as well as scenario-based increased consumption (denoted as S k = 30, 60 or 100% increase (k=1, 2, 3)) as follows.
The rst term indicated the original contributions of the jth item to the overall salt intake, In the second term, U j indicates how much salt intake we can reduce by incorporating umami substances and (S k -M j ) indicates how much intake we can change to low-sodium products.
The baseline salt intake and reduced salt intakes for varying scenarios among consumers of each food were estimated by total population, men and women. The percentage-wise contributions of each food to total sodium intake in the diets for total population, men and women were also estimated.
The achievement rate for the dietary goals of salt intake when umami substances were universally incorporated into all selected food groups were then calculated by age groups and sex. Health Japan 21's dietary goal is de ned as a mean daily salt intake of less than 8g (14), while the dietary goal laid down in DRIs is 7.5g of salt for males and 6.5g of salt for females (15). The WHO, on the other hand, recommends a daily salt intake of 5.0g (31). We used STATA version 16 for all analyses (Stata Corp LLC).

Results
A total of 30,820 people joined the NHNS survey in 2016. We excluded ineligible subjects who were less than 20 years old (n=4,595), had missing values on dietary intake (n=4,374), and consumed salt less than 1.5g per day (n=46), yielding a nal analytic sample of 21,805 Japanese persons with an average age of 57.8 (standard deviation Page 6/27 [SD] 17.6 years. Overall, the daily mean salt intake among the Japanese population was 9.95g, which is more than the daily salt intake recommended by Health Japan 21, the DRIs, and the WHO. The sex-speci c and age-speci c mean daily salt intake and the achievement rate of dietary goals are shown in Table 2. Across age groups, salt intake was likely to be higher among older persons than younger persons. Of the total population, 28.7% has already achieved the daily salt intake recommended by Health Japan 21 while 15.3% and 2.8% achieved the daily salt intake recommended by the DRIs and the WHO, respectively. Men had a higher salt intake than women in all age groups. The mean daily salt intake was the highest among men aged 60-69 years (11.43g) and women aged 70-79 years (9.72g), while the lowest mean daily salt intake was among those aged 20-29 years for both men (10.37g) and women (8.60g). The gap in mean daily salt intake between the highest and lowest groups was 2.83g. The achievement rate of dietary goals was higher in women than men across all age groups.
The sex-speci c estimated salt intake and potential reduction of salt intake for each food group in three scenarios are presented in Table 3. The selected food groups consumed by participants on any given day during the survey varied. The percentages of those who consumed the selected foods (i.e., "consumers") among the participants were high for other seasonings (97.9%), soy sauce (85.9%), seasoning salt (83.1%), and miso paste (69.3%), and conversely low for beef (24.71%), cheese (17.3%), butter (14.9%), margarine (14.4%), and other confectionery (15.2%). Compared to women, men were more likely to consume salt, soy sauce, spices and other, ham and sausage, beef, and pickled vegetable, but they also consumed less cheese and other confectionery. The consumers of soy sauce, seasoning salt, and miso paste took more than one gram of salt daily from one food group, and all participants consumed at least one food group.
In the universal incorporation scenario where consumers increased their intake of low-sodium foods replaced with umami substances up to 100%, the highest amount of expected salt reduction was soy sauce (0.45-0.68g), followed by cheese (0.28-0.51g), pickled vegetable (0.50g), ham and sausage (0.11-0.49g), seasoning salt (0.23-0.44g), and miso paste (0.19-0.45g). Negligible reductions in salt intake can be expected for spice and others, beef, and other confectionery (< 0.1g). Table 4 presents salt contributions from different foods to overall salt intake in the diet for all participants in the baseline scenario and potential reduction in salt intakes for all participants in the umami substance's universal incorporation scenario by sex. In the baseline scenario, among all participants, soy sauce (12.5%), miso paste (9.7%), and seasoning salt (8.9%) contributed the most to overall daily salt intake. In contrast, spice and others, beef, cheese, butter, margarine, and other confectionery were minor sources of salt (<1%). Although cheese had a higher reduction in salt intake among the consumers (0.28-0.51g) in the universal umami substance's scenario, there was less impact at the population level (0.05-0.09g) because of few cheese consumers among the overall participants. The total mean daily salt intake from all selected foods was 5.06g for all participants in the baseline scenario, resulting in a 48.0% contribution to the overall salt intake. Thus, the universal incorporation of umami substances into all selected foods could reduce 12.7-2.22g of salt intake for the total population in all participants on average, resulting in a 12.0-21.1% reduction of salt intake. Figure 1 compares sex and age groups-speci c mean daily salt intake between baseline scenario universal umami substance's incorporation scenario. Table 5 shows sex and age groups-speci c potential salt intake after the universal incorporation of umami substances into all selected foods and their rate of achieving various dietary goals. While the salt intake still varied by sex and age group, the difference in the mean salt intake between the highest and lowest groups was slightly smaller. The potential mean daily salt intake in all participants after the universal incorporation of umami substances was 7.73-8.68g; thereby, suggesting a possibility to achieve Health Japan 21's goal of consuming less than 8g of salt daily by 2023. In addition, the rate of those who achieved Health 21 Japan's dietary goal increased from 19.6% to 31.2-46.6% for men and 36.9% to 53.6-70.8% for women. On the other hand, approximately 24.8-38.1% of men and 25.6-39.2% of women could achieve the recommended daily salt intake outlined by the DRIs after the universal incorporation of umami substances into all selected foods.
However, only 2.2-3.8% of men and 6.4-10.8% of women were expected to achieve the WHO's dietary goal of 5g of salt daily, proving that the potential daily salt intake in even the most optimistic scenario still exceeds the global daily salt consumption goal.

Discussion
Excess salt intake is now a global public health challenge (32). Reducing salt intake has been identi ed as one of the most cost-effective measures to improve population health outcomes (31). High sodium intake is a crucial risk factor for chronic disease and has posed a high burden in Japan for decades(8, 10). The current mean daily salt intake in Japan exceeds public recommendations across all age and sex subgroups. This study shows that it is possible to reduce the Japanese population's salt intake by up to 2.22g (21.1%) without compromising the taste of certain food groups by substituting NaCl with umami substances. In addition to reducing the salt intake among consumers, this study demonstrates that the universal incorporation of umami substances in limited foods can effectively reduce salt intake at the population level.
In a previous study using the data from the National Health and Nutrition Examination Survey 2013-2016 in the US, which focused solely on MSG, the overall reduction rate in salt intake among the population was 7.3% (26). However, global recognition of MSG as an effective and practical solution for salt reduction remains a major challenge. I, In a widely reported study from 1968, MSG in Chinese food was suggested to be the cause behind numbness and palpitations in the neck and arms and has been linked to various health problems known as the Chinese restaurant syndrome (33). Following this study, several studies reported MSG association with asthma, urticaria, atopic dermatitis, dyspnea, and tachycardia (34,35). However, more recent studies, including a double-blind placebocontrolled trial, have evaluated the reported reactions to MSG and have con rmed a lack of plausible association between MSG intake and the development of such symptoms. Further studies on the safety of MSG has found the lack of reproducibility of the different symptoms reported by patience who identity to be hypersensitive to MSG (36, 37). a conclusion that that MSG is safe to consume at a normal intake level and that there is no evidence linking the use of MSG foods to long-term medical problems for the general public (39).
Meanwhile, it is true that sodium is also in MSG. Reduction of sodium can also be achieved with sodium-free glutamates such as CDG, inosinate, and guanilate (40). Our study has expanded the scope from solely on MSG to umami substances and selected foods that were widely consumed by the Japanese. As such, our ndings suggest umami substances' potential for a greater impact on reducing salt intake than the previous study. Seasoning salt, soy sauce, miso paste, other seasonings, and processed sh were more commonly consumed in Japan than the other selected food groups. In fact, soy sauce was one of the most consumed foods and, as shown by this study, has the most impact on reducing daily salt intake up to 0.68g among its consumer and 0.37g for the total population.
On the other hand, cheese, spices and other, beef, margarine, and other confectionery have less impact on reducing salt intake on the population level because they are consumed less than the other food groups.
To reduce the Japanese population's daily salt intake, the Japanese government took steps to enforce a new food labelling system and a nutrition labelling system in April 2020 (41,42). These systems made it mandatory for food companies to disclose the amount of sodium in their products to ensure that their consumers are aware of the nutritional content of their foods. However, these measures alone may not be su cient in addressing the problem because lowering sodium intake is not a priority among consumers (43). Furthermore, reducing the sodium in foods may in uence the quality of foods; for example, the replacement of 75% of sodium chloride in sausages decreased the sausages' hardness, chewiness, and cohesiveness (44). Hence, food companies must also provide low-sodium alternatives that can give their consumers the taste and the quality they seek without the harmful amounts of sodium (45). Other alternatives, such as potassium chloride, calcium chloride, and magnesium sulfate, have all been used as substitutes for table salt. However, their bitter taste has repelled consumers and has resulted in their limited use. In contrast, umami substances, which are naturally present in various foods, are widely accepted by consumers (46). As the addition of umami substances have an enhancer effect of avor in foods, the combination of umami substances and the additional avor will be able to reduce the intake of salt more effectively (18, 47).
The food industry should take action to promote the bene ts of eating reduced-salt foods by raising consumer awareness while reducing the salt in their products over time so that consumers can adapt to the changes in the taste (40). Accordingly, the food industry's role is essential in decreasing the daily sodium intake of Japanese people and reducing the Japanese population's various health risks (11). Moreover, reducing salt intake through food science and technological advances is an appropriate method to make the most impactful reduction in sodium intake at the population level (32). Our study provides essential data on the distribution of consumers, the market shares of selected food groups with low-sodium alternatives, and its impact on public health by showing the potential reduction in salt intake. This information may instruct and inspire the food industry to develop more lowsodium products and distribute more low-sodium alternatives in the market.
This study has some strengths. This is the rst study to show the impact of salt reduction by replacing NaCl with umami substances in certain Japanese food products. Using nationally representative data guarantees the study's generalisability to the Japanese population. The modelling assumptions of sodium reduction were determined based on scienti c evidence, made in consultation with food scientists, and were made considering market distributions. This study is subject to similar limitations in other studies concerning dietary patterns (48, 49). First, because the dietary data from the NHNS was based on a weighted single-day dietary record, the analysis may not have captured the long-term dietary patterns. Daily data do not re ect seasonal changes in dietary patterns. In dietary surveys and lifestyle questionnaires, participants' subjective self-reports tend to be associated with social desirability and recall bias. Unfortunately, there is no data to validate their survey responses. In addition, relying on household representatives to record dietary intake in the survey may lead to biased estimates of dietary intake for individual respondents, particularly for those who work and have lunch outside the home (such as in restaurants) on weekdays. NHNS's strati ed two-cluster sampling design may have introduced selection bias, leading to biased estimates. Second, the data on food-speci c salt intake was not publicly available. Thus, the estimation of an individual's food-speci c salt intake by regression method may not have accurately re ected the actual amount of salt intake from each food group. Finally, age group-speci c preferences for varying salt sources and how that may affect the potential overall salt reduction were not considered (50).

Conclusions
The addition of umami substances to certain foods has the potential to reduce the daily salt intake of the Japanese population by 21.1%, which is equivalent to 2.22g of daily salt intake. Universal incorporation of umami substances into limited foods could achieve dietary goals for the Japanese. However, that reduced salt intake level still falls short of the global dietary recommendation of 5g of salt daily. Along with the public health targets, a close collaboration between experts in food science is needed. Further investigation, innovation, and distribution of lowsodium foods are expected to reduce the adult Japanese population's daily salt intake and consequently reduce their chances of developing NCDs. The Research Ethics Committee of the Graduate School of Medicine, The University of Tokyo approved this study (authorization number 11964) and waived the need for informed consent as this study was a secondary analysis of anonymised data that is collected routinely by the MHLW.

Consent for publication
Not applicable.

Availability of data and materials
The data that support the ndings of this study are available from MHLW, but restrictions apply to the availability of these data. The data were used with an approval from MHLW to be utilized for the current study without making it publicly available.

Funding
This article was partially supported by a joint research grant from Ajinomoto Co., Inc. H.U. is employed by the commercial founder, Ajinomoto Co., Inc. The commercial funder provided support in the form of salaries for H.U., but did not have any additional role in the decision to publish or the preparation of this manuscript. This article was also partly funded by a research grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (19H01074).

Competing interests
S.N. and K.S. report a grant from the Ajinomoto Co., Inc. H.U. declares that he is employed by Ajinomoto Co., Inc. and has no other competing interests. All other authors declare no competing interests.    *3 Recommend consumption of no more than 7.5g of salt intake a day for men and 6.0g for women. *4 Recommend consumption of no more than 5g of salt intake a day. Table 3. Estimated mean salt intake from selected food groups in the baseline scenario and potential salt reduction in the 30-, 60-, and 100-percent umami substances' incorporation scenarios by sex Figure  N ( SD: Standard deviation *1 Mean (SD) salt intake from each food among consumer, not all participants. *2 The reduction rate of each food was the same for men and women. 11.9-20.9 * The scenario in which umami substances were universally incorporated into selected food groups  Figure 1 Estimated salt intake after universally incorporating umami substances into foods in (A) the total population, by sex of (B) men, and (C) women, NHNS 2016