Next Article in Journal
Multi-Objective Optimal Allocation of Regional Water Resources Based on the Improved NSGA-III Algorithm
Next Article in Special Issue
Survival of Listeria monocytogenes in Light and Full-Fat, Modified Atmosphere-Packaged, Sliced Greek Cheese over Shelf Life: Implications for Ready-to-Eat Food Safety
Previous Article in Journal
Artificial Intelligence-Based Models for Estimating and Extrapolating Soiling Effects on Photovoltaic Systems in Spain
Previous Article in Special Issue
Development of Novel Canned Peaches (Fercluse Variety) as a Healthy and Possible Diabetic Food Choice
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Applied Sciences
Volume 15
Issue 11
10.3390/app15115962
applsci-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Biofunctional Miso-Type Sauce Enhanced with Biocarotenoids: How Does Its Habitual Consumption Affect Lipidemic, Glycemic, and Oxidative Stress Markers? A Pilot Cross-Over Clinical Study

by
Olga I. Papagianni
,
Charalampia Dimou
and
Antonios E. Koutelidakis
*
Laboratory of Nutrition and Public Health, Unit of Human Nutrition, Department of Food Science and Nutrition, University of the Aegean, 10 Ierou Lochou & Makrygianni Str., GR-81400 Myrina, Greece
*
Author to whom correspondence should be addressed.
Appl. Sci. 2025, 15(11), 5962; https://doi.org/10.3390/app15115962
Submission received: 25 April 2025 / Revised: 23 May 2025 / Accepted: 23 May 2025 / Published: 26 May 2025
(This article belongs to the Special Issue Current Trends in Food Microbiology: Food Fermentation, Safety, and Production)
Browse Figures
Versions Notes

Abstract

:
Given the increasing incidence of chronic metabolic diseases, fermented functional foods are receiving a growing demand due to their important functional activities. The aim of this pilot clinical study–nutritional intervention is to expand knowledge on how the habitual intake of a biofunctional miso-type sauce, enhanced with biocarotenoids, may affect biomarkers of lipidemia, glycemia, and oxidative stress in healthy volunteers. Using a randomized, cross-over, controlled, and single-blind design, ten healthy participants with a mean age of 23 years, who met the eligibility criteria, supplemented their daily diet with either 20 g of legume-based or the biofunctional miso-type sauce for 30 days, with a one-week washout. Blood samples were taken at baseline and after intervention. The measured parameters included serum total, HDL, and LDL cholesterol, triglycerides, uric acid, glucose, and plasma TAC. After 30 days, the miso-type sauce increased plasma TAC (p = 0.04) and slightly decreased mean triglycerides (p = 0.47) compared with the control sauce. Both sauces resulted in higher LDL cholesterol levels (p = 0.001–0.02), indicating possible negative effects on lipidemic control. However, the miso group showed a lower grade of increment compared with the control. This long-term study partly supports the acute postprandial indications and motivates research expansion, demonstrating that biofunctional miso-type sauce, enhanced with biocarotenoids, may possess a preventive role in chronic dysmetabolism and oxidative stress.

1. Introduction

The recent strategies for the prevention or delay of noncommunicable diseases related to oxidative stress, such as obesity, cardiovascular diseases, and diabetes, have led to an increasing interest in the development of functional foods designed to target reducing the oxidative status and inflammation [1,2]. In this sector, numerous in vitro, animal, and clinical studies highlight the beneficial effect of fermented foods, which possess significant antioxidant, anti-hypertensive, anti-inflammatory, and hypolipidemic activities [1,2]. Khayatan et al. unveiled that including fermented foods in the daily diet may improve several clinical outcomes, which is in agreement with reported properties [1].
Among these, miso, a traditional Japanese sauce which is prepared with fermented soybean paste, has been extensively studied for its possible preventive role against oxidation and chronic dysmetabolism [3,4]. In vitro studies primarily attribute these effects to the metabolic activity of microorganisms, which, during the fermentation process, produce bioactive peptides, increasing the bioavailability of phenolic compounds and inhibiting the activity of digestive enzymes [5]. Additionally, these microorganisms are known to increase the bioaccessibility of crucial isoflavones, leading to improved lipid management, as well as to reduced inflammation and oxidative status [6,7]. Clinical evidence reveals that the consumption of fermented soy foods, including miso, has a regulatory role on concentrations of inflammatory markers, mainly Interleukin-6 (IL-6), but also on C-reactive protein (CRP) and Interleukin-18 (IL-18) levels, reinforcing their healthful impact [3]. Evidence also supports that miso consumption can inhibit the growth of certain tumors, including those affecting the stomach, colon, liver, and lungs, in animal studies. It has also been associated with better hypertension management, reduced insulin resistance, suppression of visceral fat, and reduced lipid accumulation in the liver [3,8].
Our previous clinical study introduced the evaluation of the acute metabolic effect of a novel miso-type sauce, enhanced with biocarotenoids derived from fruit byproducts, throughout the 3 h postprandial phase [4]. Biocarotenoids and polyphenols, which are recovered from fruit byproducts using bioprocesses [5,6], have been assessed to synergistically enhance the activity of novel miso against oxidative stress and pathological features of chronic dysmetabolism. Hydrolytic enzymes produced during the fermentation process on substrates such as barley, wheat, and rice bran have been suggested to further enhance the bioactivity of the final product [9]. The findings of the previous postprandial dietary intervention indicated that consumption of a high-fat, high-carbohydrate meal, which causes acute oxidative stress, containing the functional miso sauce, can increase plasma total antioxidant capacity (TAC) in humans [4].
Furthermore, there are indications that daily miso consumption may reduce insulin resistance in women [10]. The hypocholesterolemic role of miso is demonstrated in a 9-month follow-up, where the daily intake of 50 g of miso by nonvegetarian premenopausal women seems capable of leading to a reduction in total cholesterol values [11]. Although the evidence supports that habitual consumption of miso soup may not significantly alter the HDL cholesterol, triglycerides, glucose, and uric acid levels in diabetic men and women [8], this pilot clinical study extends the evaluation of the acute, postprandial metabolic effect of a novel miso-type sauce enhanced with biocarotenoids from fruit byproducts [4].
Therefore, the aim of the present pilot cross-over clinical study was to further investigate the effect of habitual consumption of the biofunctional miso-type sauce enhanced with biocarotenoids on lipidemic, glycemic, and oxidative biomarkers in healthy volunteers.

2. Materials and Methods

2.1. Study Design

This pilot clinical study was a cross-over, randomized, and single-blind nutritional intervention, conducted from November 2021 to January 2022, at the Laboratory of Nutrition and Public Health of the University of the Aegean (Lemnos, Greece). This study was also carried out following the recommendations of the Declaration of Helsinki, 2013. The Ethics Committee of the University of the Aegean approved the trial protocol (IRB No. 10/30.09.2021).

2.2. Participants

Participants were randomly recruited from Lemnos, Greece, through social media invitations. Potential volunteers were initially screened for medical and nutritional histories and biochemical and anthropometric profiles. Anthropometric assessment (height, body weight, body composition) was carried out using a body composition analyzer (Tanita SC 330, TANITA EUROPE B.V., Amsterdam, The Netherlands), and biochemical evaluation was completed by showing recent (quarterly) biochemical test results. The inclusion criteria were (1) individuals whose age is over 18 years and (2) who provided signed, informed consent. Participants with ages <18 and >65 years, abnormal biochemical and hematological parameters, dietary supplementation (antioxidants, vitamins, minerals) or medication intake, chronic diseases (cardiovascular disease, diabetes, malignancies, liver disease, iron deficiency anemia), heavy smoking (>10 cigarettes/day), consumption of >40 g alcohol/day, and inability to give consent were excluded.
All participants who met the inclusion criteria were provided with a detailed protocol explanation and signed an informed consent form.

2.3. Group Assignment

This trial used a single-blinding methodology, where researchers were blinded to group allocation. Data management and analysis were carried out by an independent biostatistician, unaware of the group allocation to mitigate possible bias related to the single-masking procedure. During each trial period, volunteers were randomly and equally assigned to one of two experimental groups: the Control group or the Miso group, using a concealed simple randomization process, ensuring they were unaware of their group assignment. Participants crossed over from one study arm to the other. In each trial period, individuals who joined the Control group consumed the control sauce, and those who were assigned to the Miso group received the interventional, miso-type sauce.

2.4. Experimental Sauces Composition

In this study, two different types of sauce were investigated:
(A)
Control sauce: Legume-based, made from 50% Greek legume paste (a 1:1 ratio of Afkos and chickpeas), combined with 50% boiled water.
(B)
Miso-type sauce: The novel sauce from fermented Greek legumes, enhanced with biocarotenoids. It was created by fermenting a blend of cereal byproducts and chickpeas (50% of total weight) with 0.05% (w/w) Aspergillus oryzae spores. This innovative sauce was further enhanced with a fruit byproduct extract, comprising 42.5% of the total formulation. The extract is a combination of carrot (30%), orange (30%), apple (20%), banana (10%), and kiwi peel (5%) extracts, making it particularly rich in biocarotenoids.
The preparation processes and composition of the test sauces have been previously described [4]. Table 1 demonstrates the nutritional values of the trial sauces. Notably, the interventional, miso-type sauce offers significant nutritional advantages over the control sauce, offering an additional 56.2 mg of total phenolics and 48.14 mg of total biocarotenoids per daily portion (20 g).

2.5. Experimental Design

The total nutritional intervention was performed in two monthly periods (one month consuming the interventional or the control sauce) using a randomized crossover design, with a 1-week washout period. Volunteers were instructed to maintain their usual diet and physical activity throughout each trial period, with only the addition of the allocated sauce to their intake. They were also requested to inform the evaluators in the case of taking any emergency medication for health reasons throughout the trial periods. Preservation instructions were also given for the trial sauces.
The participants subsequently received 30 daily portions of 20 g each of control or miso-type sauces. These were administered in a random order and efficiently provided in ID-labeled, ready-to-eat plastic containers, with respect to single-blinding and the avoidance of any participant bias. Volunteer compliance was monitored every week through direct telecommunication. Typically, during these calls, a 24 h dietary recall was recorded to ensure that volunteers adhered to the research guidelines.
Each volunteer attended, in a fasted state, the Laboratory of Human Nutrition and Public Health (Department of Food Science and Nutrition, University of the Aegean) during the following days of each trial period: (1) Before taking any dietary regimen (Baseline). (2) On the 31st day after the outset of the respective dietary regimen. Before each blood collection visit, they were asked to follow a 12h fasting period and to abstain from alcohol, caffeine, medications, and dietary supplements for 12 h. A dietary 24 h recall (once a visit) was also collected to ensure compliance with these instructions.
Blood samples (10 mL) were drawn by collaborating doctors. Serum was obtained from clot activator tubes, and plasma was collected in EDTA (ethylenediaminetetraacetic acid) tubes (Weihei Hongyu Medical Devices Co., Ltd., Weihai, China) before centrifugation at 3000 rpm, 4 °C, 15 min, using a tabletop high-speed refrigerated centrifuge (Thermo Scientific ST16R, Thermo Fisher Scientific, Waltham, MA, USA). The serum and plasma samples were kept at −40 °C until analysis. Serum total, High-Density Lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, and uric acid were assessed using an automated biochemical analyzer (COBAS c111, Roche, Basel, Switzerland). Plasma TAC was evaluated by FRAP assay, as previously described by Chusak et al. [12]. Baseline measurements were repeated at the 4-week follow-up visit for each interventional period.
An overview of the visit procedures of the pilot clinical study visits is presented in Figure 1.

2.6. Statistical Analysis

The sample size for this long-term nutritional intervention was calculated using the G*Power 3.1.9.7 software package (3.1.9.7, Erdfelder, Faul, & Buchner, Germany). The calculation was based on prior studies, indicating that the acute consumption of the trial sauces may induce a postprandial difference in plasma TAC between groups of 0.77 mmol/L at the third postprandial hour [4]. To achieve a statistically significant level (p < 0.05), ANOVA Repeated Measures within–between interactions were performed, and it was estimated that 10 participants were adequate to detect a plasma antioxidant capacity difference of 0.77 ± 0.42 mmol/L between the experimental groups, ensuring a statistical power of 95% at 95% confidence level. Accounting for an anticipated 15% dropout rate, 12 subjects were enrolled.
Statistical analysis was conducted with SPSS V21.0 software for Windows (IBM Corporation V.21, New York, NY, USA). The mean age of volunteers, anthropometric and body composition values, and biochemical results are mentioned as Mean ± Standard Deviation (SD) with significance set at p < 0.05. The Kolmogorov–Smirnov test was used to evaluate normality. One-way ANOVA tests examined the variability of the initial characteristics between men and women. Repeated ANOVA Measures were performed to test the group, time, and group-by-time interaction effects on metabolic biomarker responses, followed by Bonferroni post hoc tests. The statistical significance of changes from baseline to 30-day follow-up was evaluated by a within-group two-tailed sample t-test (within-group variation).

3. Results

3.1. Initial Characteristics

Twelve (N = 12) healthy volunteers (six men and six women) entered this pilot study. Two individuals withdrew for personal reasons unrelated to this study. Therefore, this study was completed with the remaining volunteers, and statistical analysis was carried out for 10 participants (4 men and 6 women). Three (N = 3) of them declared being light smokers (<5 cigarettes/day), and five individuals engaged in moderate physical activity in their habits. Muscle and bone mass showed significant differences between men and women (p = 0.016 and 0.015, respectively), while nonsignificant differences (p > 0.05) were observed for the remaining initial characteristics between sexes. No volunteer in either group missed > two consecutive sauces during this study. The initial characteristics of the study participants are presented in Table 2.

3.2. Biochemical and Antioxidant Responses

The profiles of serum total, HDL, and LDL cholesterol, triglycerides, glucose, uric acid, and plasma TAC at baseline and at the 30-day follow-up, as well as the group, time effects, and group × time interactions, are summarized in Table 3. The outcome of the biomarkers tested over the study periods, following the control and the novel miso-type sauce, is illustrated in Figure 2. Baseline biochemical and antioxidant values show variation between the study groups, due to the randomization process and the diversity of participants’ metabolism. Nevertheless, the initial mean concentration of the biomarkers tested did not significantly differ between groups (p > 0.05).

3.2.1. Plasma TAC

The results reveal that the experimental sauces significantly affected plasma TAC (p = 0.01) throughout the trial periods (group × time interaction), despite the absence of any group or time effects (p > 0.05). Under within-group analysis, habitual consumption of the biofunctional miso-type sauce, enhanced with biocarotenoids, significantly increased plasma TAC (p = 0.04, MD = 0.07). On the contrary, after 30 days of consuming the control sauce, the plasma TAC of participants experienced a significant downward trend (p = 0.03, MD = −0.12) (Figure 2g). It is noteworthy that the baseline mean value in the control group was higher than the respective miso group concentration (p = 0.06, MD = 0.14). Even so, at the endpoint, the plasma TAC was nonsignificantly higher in the miso group compared with the control (p = 0.46, MD = 0.05) (Figure 2g).

3.2.2. Serum Lipids

Total cholesterol levels showed significant changes in the baseline and 30 days in either group (time effect: p < 0.001); however, no difference was observed (group effect: p = 0.80) between the two groups. Furthermore, no significant interaction of time and group (group × time interaction: p = 0.25) was determined, showing similar outcomes of total cholesterol in both groups (Figure 2a).
Regarding the effect of the study sauces on HDL cholesterol concentrations, a time effect was detected (p = 0.002). However, the test sauces did not significantly affect (group effect: p = 0.27) the overall HDL cholesterol outcome, and there was no evident group × time interaction (p = 0.18). Serum HDL cholesterol gradually increased from baseline until the final measurement (p = 0.016, MD = 12.25) after 30 days of the control sauce consumption, while after following the habitual intake of the biofunctional miso-type sauce, a nonsignificant increase was found (p = 0.12, MD = 4.12) (Figure 2c).
In the control group, there was a 59.24% increase in LDL cholesterol, compared with baseline values (p = 0.001, MD = 44.29). This increase in the miso group was minor, reaching approximately 17.27% (p = 0.02, MD = 14.9). Time was found to significantly affect the outcome of LDL cholesterol (p < 0.001), resulting in significant differences between the study groups at the 30-day interval (group × time interaction: p = 0.03). The control group was not found to have impacted levels of LDL cholesterol (p = 0.75) (Figure 2d).
Moreover, the concentration of triglycerides did not differ between the study groups (group effect: p = 0.49) throughout the 30 days (time effect: p = 0.41), but a significant group × time interaction (p = 0.03) was detected. The control sauce induced a significant (p = 0.02, MD = 14.72) increase in the average triglycerides value, while the habitual consumption of the biofunctional miso-type sauce led to slightly reduced (p = 0.47, MD = −5.8) triglycerides levels (Figure 2e).

3.2.3. Serum Glucose

The time curve of glucose obtained after the consumption of both control and biofunctional miso-type sauce was significantly different (time effect: p = 0.04); however, repeated measures did not observe significant differences between groups (group effect: p = 0.08), and no significant group × time interaction was found (p = 0.39). Data showed that the biofunctional miso-type sauce induced a 17.01% greater increase in glucose concentration (p = 0.03, MD = 28.7) compared with the control group changes (p = 0.005, MD = 12.5) (Figure 2b).

3.2.4. Serum Uric Acid

According to the two-factor ANOVA, a nonsignificant group × time interaction was found for serum uric acid (p = 0.47). Uric acid was not significantly different among the interventional groups (group effect: p = 0.33), but significant change was detected in uric acid values from baseline to the endpoint (time effect: p = 0.001). In the control group, the mean uric acid significantly increased (p = 0.005, MD = 0.71), while a similar but nonsignificant outcome was found in the miso group (p = 0.16, MD = 0.50) (Figure 2f).

4. Discussion

Maintaining cardiovascular and metabolic health is related to many dietary and lifestyle factors, including maintenance of a healthy lipidemic and glycemic profile, as well as oxidative balance [13]. Lifestyle options, such as the inclusion of traditionally fermented soy products, have been suggested as practical tools to address these oxidative and inflammatory issues related to chronic diseases [4]. In this context, miso intake has been inversely associated with cardiovascular risk in women [14], while daily miso consumption for 9 months has been demonstrated to improve the profile of cholesterolemia [11].
Furthermore, implementing sustainable practices to enhance such foods may provide additional health benefits. Fruit byproduct extracts appear to enhance the antioxidant profile of fermented foods, leading to a synergistic activity [15,16]. Our previous clinical study investigated the acute effect of a miso-type sauce, enhanced with a carotenoid-rich extract from fruit byproducts, on metabolic biomarkers [4]. The findings were highlighted by the postprandial improvement of total plasma antioxidant capacity, serum lipidemic profile (triglycerides, LDL cholesterol), and platelet aggregation in healthy humans after following a high-fat and carbohydrate meal with the novel miso-type sauce [4].
This pilot nutritional intervention–clinical study investigated the effect of the habitual consumption of the innovative biofunctional miso-type sauce, enhanced with biocarotenoids, on biomarkers of oxidative stress, lipidemia, and glycemia. The nutritional intervention showed that the daily consumption of the biofunctional miso-type sauce for 30 days, in the context of the usual diet, led to increased plasma TAC among healthy participants, compared with the adverse effects observed after the control sauce consumption. This finding is fully consistent with those of the acute dietary intervention lasting 3 h [4]. Although postprandial metabolism appears to be directly affected by the presence of antioxidant components in the context of a high-fat, high-carbohydrate meal, it is probable that this effect is maintained during long-term intake. The role of miso as a free-radical scavenger is mainly related to the improvement of the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging ability, as confirmed by Hashimoto and colleagues [17]. There is evidence that habitual miso soup consumption may reduce Renin–Angiotensin System (RAS) activation and oxidative stress, which are related to the pathogenesis of hypertension [18]. However, there are no clinical studies exploring the exact effect of daily miso intake on parameters of oxidative damage.
The demonstrated findings may be attributed to the antioxidant activity of isoflavones, presented in the biofunctional fermented sauce. Evidence supports that biotransformation with microorganisms, including Aspergillus sp., may improve β-glucosidase activity, increasing the isoflavone aglycone content [19]. The potent antioxidant activity of isoflavones has been noted to be exerted in both lipophilic and aqueous phases. It is noteworthy that the bioavailability of isoflavones in their aglycone form, and, by extension, the extent of ROS reduction, also depends on the bioavailability of phytochemicals [20]. In vitro studies on similar fermented products, such as tempeh, indicate that during the prolonged fermentation process, Aspergillus oryzae may exert proteolytic activity, leading to the production of bioactive peptides and amino acids, which are also bioavailable and may enhance the overall antioxidant activity of the product [21]. Furthermore, there are indications that this bioprocess may release antioxidant compounds derived from fruit byproduct extracts, such as polyphenols and carotenoids, and enhance their biological activity [17].
Numerous observational studies suggest that higher concentrations of circulating carotenoids are inversely associated with markers of oxidative stress. The main mechanism describing the effect of carotenoids on oxidative markers is through inhibition of lipid and singlet oxygen peroxidation [22]. It seems that biocarotenoids, which were used for miso-type sauce enhancement, are likely bioavailable, exerting a synergistic effect on the overall antioxidant effect. Based on these data, this pilot nutritional intervention should further highlight the effectiveness of fruit byproducts valorization as a sustainable strategy for the enhancement of functional foods with valuable biocarotenoids to address public health concerns of oxidative stress, as well as indicators of lipidemic and glycaemic dysmetabolism [23].
Moreover, the results suggest a beneficial impact of the daily consumption of the novel, miso-type sauce, enhanced with biocarotenoids from fruit byproducts, on the lipidemic profile of the participants. Specifically, the experimental miso-type sauce induced a reduction in triglyceride levels, compared with the opposite effect obtained after habitual consumption of the control sauce. This finding is in line with the results obtained by the previous, acute clinical study, which explored the outcome throughout a postprandial period of 3 h. Additionally, both sauces increased the concentrations of LDL cholesterol at the endpoint, but following the miso group, these values were slightly lower than following the control group. Partly consistent with the previous data derived from the clinical intervention on postprandial metabolic effects, it seems that the consumption of 20 g biofunctional miso-type sauce/day, followed-up over 1 month, confirms the possible hypolipidemic effect, which was found at the acute level, which was mainly identified in triglycerides outcome [8].
Similar biological impacts have been mentioned in clinical research, investigating the influence of such fermented foods on cholesterolemia biomarkers. Santacroce et al. have evaluated that Jang intake (a Korean fermented soybean paste) in a dose–response ≥1.9 g/day is inversely associated with parameters of Metabolic Syndrome, including hypo- HDL cholesterolemia, after adjusting for covariates, including sodium intake [24]. In a 12-week human intervention, the habitual intake of gochujang, an Aspergillus oryzae-fermented red pepper paste, has been demonstrated to effectively reduce LDL and total cholesterol levels in hypercholesterolemic participants [25]. The role of isoflavones in lipid metabolism has also been studied. The scientific community supports that genistein may affect thermogenesis and lipid accumulation, leading to reduced production of LDL lipids, triglycerides, and free fatty acids [20].
Bioactive peptides isolated from chickpeas, as a raw material in the test sauces, have been stated to significantly reduce serum total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol levels, in the context of a high-fat diet [26,27]. In addition to isoflavones, the increased content of proteins and peptides in the biofunctional, miso-type sauce may synergistically exert higher bioactivity, contributing to the demonstrated lipid-lowering effect [28]. Notably, recent reports indicate that Monacolin K, a secondary metabolite produced by Aspergillus species, may attenuate cholesterol biosynthesis by inhibiting the activity of the enzyme 3-hydroxy-2-methylglutaryl coenzyme A reductase (HMG-CoA reductase). This mechanism may contribute to the improvement of the lipid profile [29].
Previous data indicate that the biofunctional miso-type sauce may attenuate the postprandial rise of LDL cholesterol, 3 h after intake, rather than the control sauce [4], reflecting the possible bioavailability of certain antioxidant compounds (e.g., carotenoids, polyphenols, and bioactive peptides) presented in the miso-type sauce [4]. However, in the present nutritional intervention, both legume-based sauces raised the total and LDL cholesterol levels within the monthly interval. Despite the lack of clinical evidence demonstrating reverse hypocholesterolemic and hypolipidemic effects, it is significant to mention potential factors that may influence these outcomes. Recent reports indicate that chickpea processing methods may affect the structure and functionality of proteins. Ineffective release of bioactive peptides or modification may reduce their binding property towards bile acids or cholesterol; thus, it could affect their hypocholesterolemic activity. Furthermore, during chickpea processing, the release or formation of hydrophobic cores in bioactive peptides may not be favored. It has been recently established that their presence plays a key role in the cholesterol and bile acid binding capacity [30]. Existing data are insufficient to study the stability of hypocholesterolemic peptides in the gastrointestinal tract; therefore, further investigation is needed to draw clear conclusions [30]. Notably, the complex responses to nutritional intervention exhibit individual variability, intensifying the challenges faced in establishing health claims [2].
Additionally, the results from the present study reveal no differences in total cholesterol levels between the two trial groups in this time frame. Currently, few clinical trials have investigated the long-term effectiveness of regular miso on lipemia biomarkers. There is evidence that the intake of 50 g of miso soup/day (45 mg of conjugated isoflavones) for 9 months may reduce total cholesterol concentrations in vegetarian premenopausal women [11]. However, in this pilot intervention, the increase in HDL cholesterol was significantly milder in the miso group compared with the percentage increase observed in the control group. This effect differs from the findings of the previous postprandial clinical study, where a slight decrease was observed in HDL cholesterol levels 3 h after receiving both sauces, likely due to the different postprandial metabolism of this biomarker [31]. Particularly, in the postprandial state, HDL cholesterol concentrations are often affected due to interactions with Triglyceride-Rich Lipoproteins (TRLs) (e.g., chylomicrons and very low-density lipoproteins) [31].
As mentioned above, the bioactive peptides of chickpeas, which were used as the main basis of both trial sauces, can modify lipid metabolism. Studies using rat models have demonstrated that these components can activate the liver X receptor (LXR) and estrogen receptors, which subsequently enhance the expression of genes involved in lipid metabolism [32]. This mechanism promotes an increase in HDL cholesterol levels [29,30]. Although the fermentation process leads to increased bioavailability of functional components, it appears that the inherent activity of chickpea proteins demonstrates similar effects on HDL cholesterol outcomes [33]. Therefore, the lack of difference between the intervention groups suggests that the critical components that affect HDL cholesterol concentration are similarly bioavailable in both sauces.
It could also be argued that HDL cholesterol, as a single biomarker, can be influenced over long periods by specific dietary factors and lifestyle parameters. Studies suggest that increasing the intake of olive oil and nuts, as well as engaging in physical activity, may lead to improved HDL cholesterol levels [17]. However, data on the effect of functional foods, such as the novel miso-type sauce, on these concentrations are limited. Recent research indicates that the triglycerides/HDL cholesterol ratio is a notable indicator of insulin resistance. In fact, Takahashi et al. did not detect any association between habitual miso soup intake and this marker, mentioning the miso type as a variability parameter when assessing its impact [8].
Miso consumption seems to be a good lifestyle strategy for glycemic control improvement in diabetic individuals, while cross-sectional studies show that its inclusion in usual diets may reduce insulin resistance in nondiabetics and cases of gestational diabetes [34]. Contrary to this, our results demonstrate slightly higher glucose concentrations in the miso group compared with the respective levels measured in the control group; however, these results did not influence the glucose-related interactive effect during the 30-day intervention. This contrast aligns with existing research, indicating that certain bioactive peptides produced during the fermentation process of chickpeas may exert antidiabetic activity [27]. Recent studies have demonstrated that various types of miso could serve as functional foods for diabetes prevention. This fermented product may act as a regulator of blood sugar levels through inhibition of digestive enzymes, mainly α-amylase, α-glucosidase, and trypsin [35]. Notably, the research group of Jiang et al. evaluated the α-glucosidase inhibitory activity of rice miso at different fermentation times and found that prolonging the fermentation bioprocess enhanced this activity, largely due to the presence of melanoidins and polyphenols [36].
In addition, the presence of isoflavones and bioactive peptides may enhance insulin secretion and sensitivity, thereby contributing to the regulation of blood glucose levels [37]. Chickpea fermentation has been documented to reduce chymotrypsin and trypsin activity and the concentration of phytates, leading to slower carbohydrate absorption and improved glycemic control [26]. Combining these existing research observations, it would be reasonable to expect an improved glycemic outcome following the consumption of the biofunctional miso-type sauce, compared with the control sauce. Nevertheless, in the present study, the enhanced miso-type sauce failed to achieve any hypoglycemic bioactivity, which may be attributed to unspecified factors in the participants’ overall diet.
The mechanisms by which fermented soy and legume products may influence glucoregulatory properties have been previously explored. However, the multifactorial nature of glucose metabolism and the potential synergistic effects of the test sauce components present ongoing challenges and warrant further investigation. The complex effect of microstructure (particle size, degree of cellular disruption, rheological characteristics) on nutrient bio accessibility and digestion kinetics could explain the differential glucose outcome in the intervention groups [38]. In addition, the biofunctional miso sauce provided higher concentrations of bioactive compounds (e.g., peptides) with potential antidiabetic effects. However, the structure biotransformations, which occurred during bioprocessing, may have influenced the release degree of bioactive compounds during digestion [38]. The biofunctional miso sauce provided higher concentrations of bioactive compounds (e.g., peptides) with potential antidiabetic effects. However, the food matrix structure may be responsible for the gradual facilitation in the accessibility of simple sugars and intracellular starch during digestion.
Therefore, further investigation of the role of bioactive components produced during fermentation and their intricate interactions with the primary sauce constituents is essential [39]. Additionally, various lifestyle, dietary, and biochemical factors and anti-nutrients (e.g., hemoglobin A1c levels, dietary intake, exercise habits, and phytate content) might highlight the possible complex role of the experimental miso-type sauce in glycemic control [17].
This pilot clinical study shows the associations between habitual intake of a biofunctional miso-type sauce, enhanced with biocarotenoids, and markers of lipidemia, glycemia, and oxidative stress. Several limitations should be acknowledged. Firstly, this study was designed as a long-term nutritional intervention to examine the effects of the habitual consumption of the biofunctional miso-type sauce, enhanced with biocarotenoids, on lipidemia, glycemia, and antioxidant status, metabolic indicators within 30 days. However, the study protocol did not include intermediate measurements of the biomarkers tested for more accurate investigation of the metabolic outcomes. Extending the experimental period to 8–12 weeks and incorporating midpoint measurements would offer valuable insights and enable a comprehensive assessment of metabolic alterations. Secondly, the trial population consisted of a small number of healthy participants, leading to a lack of power in the reliability of the findings; therefore, the generalization of the metabolic effects remains a challenge. Moreover, it is unclear whether the results reflect the efficacy for individuals who suffer from chronic diseases associated with oxidative stress and chronic inflammation, such as diabetic and cardiovascular patients. In addition, a week-long washout period between the two interventions may be insufficient to fully eliminate the residual effects of the initial intervention, particularly if certain compounds, such as carotenoids, have a prolonged half-life.
In addition, despite extensive guidelines, the lifestyle factors were not controlled in this trial protocol, so there is a chance that part of the observed results might be related to healthy lifestyle habits during the study period. Also, data management did not include the adjustment of other dietary variables. Therefore, the results of the clinical study may not include the metabolic responses associated with these confounding parameters, limiting the generalizability of the findings. A stricter control of these factors with daily diet records is in order, and further data analysis should examine the effect of the adjustment on the association between the biofunctional miso-type sauce consumption and the biochemical biomarkers. Another limitation of this clinical study procedure is the absence of a nonenriched miso-type sauce control, leading to unclear conclusions regarding whether our findings are attributed to the miso-type sauce itself, to the presence of biocarotenoids, or to the synergy of both. So, the addition of one more experimental group where participants would consume a control miso-type sauce would be crucial.
Concerning future perspectives, further investigation of the impact of habitual intake of the biofunctional miso-type sauce enhanced with biocarotenoids, in a dose–response manner, could be suggested to explore the exact dose at which the bioactive compounds are bioavailable and effective in altering metabolic parameters. Under this design, the determination of plasma carotenoids could lead to safer conclusions about the effectiveness of the enhancement with valuable biocarotenoids, which was performed during the final formulation of the miso-type sauce. Further research should involve a larger sample of participants, including both healthy individuals and those with metabolic or chronic diseases.
Moreover, a possible association between habitual biofunctional miso-type sauce consumption and specific oxidative stress inflammation could yield valuable insights. Measurement of insulin and hemoglobin A1C (HbA1C) could offer more accurate insights into the levels of long-term glycemic control. Additionally, the evaluation of the triglycerides to HDL cholesterol ratio may facilitate a more in-depth investigation of the effectiveness on insulin resistance [17]. Regarding oxidative status, current knowledge should be expanded by the inclusion of novel oxidative stress biomarkers, such as the performance of a Plasma Antioxidant Test (PAT), as well as the evaluation of Reactive Oxygen Metabolites (ROMs) and the Oxidative Stress Index (OSI) [39]. Finally, due to the crucial role of proinflammatory cytokines in the up-regulation of inflammatory reactions, the determination of inflammatory biomarkers, including Interleukin (IL)-6, IL-18, tumor necrosis factor alpha (TNF-α), and the inflammatory high sensitivity C-reactive protein (CRP), is needed to enhance the understanding of the modulatory effects on inflammation status.

5. Conclusions

The results presented in this first long-term pilot clinical study–nutritional intervention indicate that the biofunctional miso-type sauce, enhanced with biocarotenoids, may have a promising biological activity towards improvement of plasma TAC and biomarkers of lipid metabolism, especially triglycerides, among healthy participants. It may be suggested that the habitual consumption of the innovative miso-type sauce would have a preventive role for chronic metabolic diseases, associated with oxidative stress and chronic lipids and glucose dysmetabolism, partly aligning with the results of the previous acute clinical study, which investigated the postprandial effects. The findings encourage further research, particularly large-scale clinical trials, to substantiate the underlying mechanisms and efficacy of daily consumption of the biofunctional miso-type sauce, enhanced with biocarotenoids, in addressing metabolic, oxidative stress, and inflammatory parameters, especially in populations with chronic dysmetabolism conditions.

Author Contributions

Conceptualization, C.D. and A.E.K.; data curation, C.D.; formal analysis, O.I.P.; funding acquisition, C.D.; investigation, O.I.P.; methodology, O.I.P. and A.E.K.; project administration, C.D. and A.E.K.; resources, O.I.P.; software, O.I.P.; supervision, A.E.K.; validation, O.I.P.; visualization, C.D. and A.E.K.; writing—original draft, O.I.P.; writing—review and editing, C.D. and A.E.K. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the General Secretariat for Research and Technology (GSRT) and Hellenic Foundation for Research and Innovation (HFRI) under grant agreement No. 2342 (2018–2020), Greece. Applsci 15 05962 i001.

Institutional Review Board Statement

This study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the University of the Aegean [no 10/30.09.2021].

Informed Consent Statement

All participants provided informed consent prior to their involvement in this study. Consent has also been obtained from the volunteers for the publication of this paper.

Data Availability Statement

The data presented in this study are available upon request from the corresponding author.

Acknowledgments

The authors extend their gratitude to all individuals who participated in this study.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Khayatan, D.; Nouri, K.; Momtaz, S.; Roufogalis, B.D.; Alidadi, M.; Jamialahmadi, T.; Abdolghaffari, A.H.; Sahebkar, A. Plant-Derived Fermented Products: An Interesting Concept for Human Health. Curr. Dev. Nutr. 2024, 8, 102162. [Google Scholar] [CrossRef] [PubMed]
  2. Harahap, I.A.; Suliburska, J.; Karaca, A.C.; Capanoglu, E.; Esatbeyoglu, T. Fermented Soy Products: A Review of Bioactives for Health from Fermentation to Functionality. Compr. Rev. Food Sci. Food Saf. 2025, 24, e70080. [Google Scholar] [CrossRef]
  3. Yang, X.; Nakamoto, M.; Shuto, E.; Hata, A.; Aki, N.; Shikama, Y.; Bando, Y.; Ichihara, T.; Minamigawa, T.; Kuwamura, Y.; et al. Introduction Associations Between Intake of Dietary Fermented Soy Food and Concentrations of Inflammatory Markers: A Cross-Sectional Study in Japanese Workers. J. Med. Investig. 2018, 65, 74–80. [Google Scholar] [CrossRef]
  4. Papagianni, O.; Delli, E.; Vasila, M.; Loukas, T.; Magkoutis, A.; Dimou, C.; Karantonis, H.C.; Koutelidakis, A.E. The Acute Effect of a Novel Miso-Type Sauce, Enhanced with a Carotenoid-Rich Extract from Fruit By-Products, on Postprandial Biomarkers of Oxidative Stress and Inflammation. Nutrients 2022, 14, 1316. [Google Scholar] [CrossRef] [PubMed]
  5. Koutelidakis, A.E.; Dimou, C.; Konstantina, N.; Dimou, C.M. Designing, Developing and Optimizing a Two-Stage Solid State Fermentation Process through Valorization of Cereal Milling and Legume By-Products and Waste Streams for the Production of Novel Functional Protein Rich Type-Miso Nutri-Powder, Using Aspergillus Oryzae. Biomed. J. Sci. Tech. Res. 2022, 44, 35763–35771. [Google Scholar] [CrossRef]
  6. Charalampia, D.; Antonios, K.Ε.; Constantina, N.; Haralabos, K.C. Current Trends and Emerging Technologies in Biopigment Production Processes: Industrial Food and Health Applications. Int. J. Hortic. Agric. Food Sci. 2017, 1, 33–46. [Google Scholar]
  7. On, S.; Na, W.; Sohn, C. Relationship Between Fermented Food Consumption Patterns, Hs-CRP, and Chronic Diseases Among Middle-Aged Koreans: Data from the 2015–2018 Korea National Health and Nutrition Examination. Nutrients 2025, 17, 1343. [Google Scholar] [CrossRef]
  8. Takahashi, F.; Hashimoto, Y.; Kaji, A.; Sakai, R.; Miki, A.; Okamura, T.; Kitagawa, N.; Okada, H.; Nakanishi, N.; Majima, S.; et al. Habitual Miso (Fermented Soybean Paste) Consumption Is Associated with Glycemic Variability in Patients with Type 2 Diabetes: A Cross-Sectional Study. Nutrients 2021, 13, 1488. [Google Scholar] [CrossRef]
  9. Leonard, W.; Zhang, P.; Ying, D.; Adhikari, B.; Fang, Z. Fermentation Transforms the Phenolic Profiles and Bioactivities of Plant-Based Foods. Biotechnol. Adv. 2021, 49, 107763. [Google Scholar] [CrossRef]
  10. Ikeda, K.; Sato, T.; Nakayama, T.; Tanaka, D.; Nagashima, K.; Mano, F.; Joo, E.; Fujimoto, S.; Takahashi, Y.; Kosugi, S.; et al. Dietary Habits Associated with Reduced Insulin Resistance: The Nagahama Study. Diabetes Res. Clin. Pract. 2018, 141, 26–34. [Google Scholar] [CrossRef]
  11. Saeed, F.; Afzaal, M.; Shah, Y.A.; Khan, M.H.; Hussain, M.; Ikram, A.; Ateeq, H.; Noman, M.; Saewan, S.A.; Khashroum, A.O. Miso: A Traditional Nutritious & Health-Endorsing Fermented Product. Food Sci. Nutr. 2022, 10, 4103–4111. [Google Scholar] [PubMed]
  12. Chusak, C.; Pasukamonset, P.; Chantarasinlapin, P.; Adisakwattana, S. Postprandial Glycemia, Insulinemia, and Antioxidant Status in Healthy Subjects after Ingestion of Bread Made from Anthocyanin-Rich Riceberry Rice. Nutrients 2020, 12, 782. [Google Scholar] [CrossRef] [PubMed]
  13. Jensen, G.S.; Beaman, J.L.; He, Y.; Guo, Z.; Sun, H. Reduction of Body Fat and Improved Lipid Profile Associated with Daily Consumption of a Puer Tea Extract in a Hyperlipidemic Population: A Randomized Placebo-Controlled Trial. Clin. Interv. Aging 2016, 11, 367–376. [Google Scholar] [CrossRef]
  14. Nozue, M.; Shimazu, T.; Charvat, H.; Mori, N.; Mutoh, M.; Sawada, N.; Iwasaki, M.; Yamaji, T.; Inoue, M.; Kokubo, Y.; et al. Fermented Soy Products Intake and Risk of Cardiovascular Disease and Total Cancer Incidence: The Japan Public Health Center-Based Prospective Study. Eur. J. Clin. Nutr. 2021, 75, 954–968. [Google Scholar] [CrossRef] [PubMed]
  15. Tlais, A.Z.A.; Fiorino, G.M.; Polo, A.; Filannino, P.; Cagno, R. Di High-Value Compounds in Fruit, Vegetable and Cereal Byproducts: An Overview of Potential Sustainable Reuse and Exploitation. Molecules 2020, 25, 2987. [Google Scholar] [CrossRef]
  16. Erskine, E.; Ozkan, G.; Lu, B.; Capanoglu, E. Effects of Fermentation Process on the Antioxidant Capacity of Fruit Byproducts. ACS Omega 2023, 8, 4543–4553. [Google Scholar] [CrossRef]
  17. Hashimoto, Y.; Hamaguchi, M.; Fukui, M. Fermented Soybean Foods and Diabetes. J. Diabetes Investig. 2023, 14, 1329–1340. [Google Scholar] [CrossRef]
  18. Ito, K. Review of the Health Benefits of Habitual Consumption of Miso Soup: Focus on the Effects on Sympathetic Nerve Activity, Blood Pressure, and Heart Rate. Environ. Health Prev. Med. 2020, 25, 45. [Google Scholar] [CrossRef]
  19. Nurmilah, S.; Frediansyah, A.; Cahyana, Y.; Utama, G.L. Biotransformation and Health Potential of Isoflavones by Microorganisms in Indonesian Traditional Fermented Soy Products: A Review. J. Agric. Food Res. 2024, 18, 101365. [Google Scholar] [CrossRef]
  20. Rizzo, G. Soy-Based Tempeh as a Functional Food: Evidence for Human Health and Future Perspective. Front. Biosci.-Elite 2024, 16, 3. [Google Scholar] [CrossRef]
  21. Bohn, T. Carotenoids and Markers of Oxidative Stress in Human Observational Studies and Intervention Trials: Implications for Chronic Diseases. Antioxidants 2019, 8, 179. [Google Scholar] [CrossRef] [PubMed]
  22. Enciso-Martínez, Y.; Zuñiga-Martínez, B.S.; Ayala-Zavala, J.F.; Domínguez-Avila, J.A.; González-Aguilar, G.A.; Viuda-Martos, M. Agro-Industrial By-Products of Plant Origin: Therapeutic Uses as Well as Antimicrobial and Antioxidant Activity. Biomolecules 2024, 14, 762. [Google Scholar] [CrossRef] [PubMed]
  23. Santacroce, L.; Bottalico, L.; Charitos, I.A.; Castellaneta, F.; Gaxhja, E.; Topi, S.; Palmirotta, R.; Jirillo, E. Exploitation of Natural By-Products for the Promotion of Healthy Outcomes in Humans: Special Focus on Antioxidant and Anti-Inflammatory Mechanisms and Modulation of the Gut Microbiota. Antioxidants 2024, 13, 796. [Google Scholar] [CrossRef] [PubMed]
  24. Lim, J.H.; Jung, E.S.; Choi, E.K.; Jeong, D.Y.; Jo, S.W.; Jin, J.H.; Lee, J.M.; Park, B.H.; Chae, S.W. Supplementation with Aspergillus Oryzae-Fermented Kochujang Lowers Serum Cholesterol in Subjects with Hyperlipidemia. Clin. Nutr. 2015, 34, 383–387. [Google Scholar] [CrossRef]
  25. Patil, N.D.; Bains, A.; Sridhar, K.; Rashid, S.; Kaur, S.; Ali, N.; Chawla, P.; Sharma, M. Effect of Sustainable Pretreatments on the Nutritional and Functionality of Chickpea Protein: Implication for Innovative Food Product Development. J. Food Biochem. 2024, 2024, 5173736. [Google Scholar] [CrossRef]
  26. Hong, L.; Fan, L.; Wu, J.; Yang, J.; Hou, D.; Yao, Y.; Zhou, S. Pulse Proteins and Their Hydrolysates: A Comprehensive Review of Their Beneficial Effects on Metabolic Syndrome and the Gut Microbiome. Nutrients 2024, 16, 1845. [Google Scholar] [CrossRef]
  27. do Prado, F.G.; Pagnoncelli, M.G.B.; de Melo Pereira, G.V.; Karp, S.G.; Soccol, C.R. Fermented Soy Products and Their Potential Health Benefits: A Review. Microorganisms 2022, 10, 1606. [Google Scholar] [CrossRef]
  28. Khosravi, A.; Razavi, S.H. Therapeutic Effects of Polyphenols in Fermented Soybean and Black Soybean Products. J. Funct. Foods 2021, 81, 104467. [Google Scholar] [CrossRef]
  29. Li, J.; Bollati, C.; d’Adduzio, L.; Fanzaga, M.; Cruz-Chamorro, I.; Arnoldi, A.; Sirtori, C.R.; Lammi, C. Food-Derived Peptides with Hypocholesterolemic Activity: Production, Transepithelial Transport and Cellular Mechanisms. Trends Food Sci. Technol. 2024, 143, 104279. [Google Scholar] [CrossRef]
  30. Gugliucci, A. The Chylomicron Saga: Time to Focus on Postprandial Metabolism. Front. Endocrinol. 2023, 14, 1322869. [Google Scholar] [CrossRef]
  31. Shi, W.; Hou, T.; Liu, W.; Guo, D.; He, H. The Hypolipidemic Effects of Peptides Prepared from Cicer Arietinum in Ovariectomized Rats and HepG2 Cells. J. Sci. Food Agric. 2019, 99, 576–586. [Google Scholar] [CrossRef]
  32. Angeles, J.G.C.; Villanueva, J.C.; Uy, L.Y.C.; Mercado, S.M.Q.; Tsuchiya, M.C.L.; Lado, J.P.; Angelia, M.R.N.; Bercansil-Clemencia, M.C.M.; Estacio, M.A.C.; Torio, M.A.O. Legumes as Functional Food for Cardiovascular Disease. Appl. Sci. 2021, 11, 5475. [Google Scholar] [CrossRef]
  33. Alcover, S.; Ramos-Regalado, L.; Girón, G.; Muñoz-García, N.; Vilahur, G. HDL-Cholesterol and Triglycerides Dynamics: Essential Players in Metabolic Syndrome. Antioxidants 2025, 14, 434. [Google Scholar] [CrossRef] [PubMed]
  34. Yu, S.; Wang, W.; Li, S.; Li, J.; Zhao, R.; Liu, D.; Wu, J. Glucoregulatory Properties of Fermented Soybean Products. Fermentation 2023, 9, 254. [Google Scholar] [CrossRef]
  35. Jiang, C.; Ci, Z.; Kojima, M. Antioxidant Activity, α-Glucosidase and Lipase Inhibitory Activity in Rice Miso with Kidney Bean. J. Food Nutr. Res. 2018, 6, 504–508. [Google Scholar] [CrossRef]
  36. Laya, A.; Wangso, H.; Fernandes, I.; Djakba, R.; Oliveira, J.; Carvalho, E. Bioactive Ingredients in Traditional Fermented Food Condiments: Emerging Products for Prevention and Treatment of Obesity and Type 2 Diabetes. J. Food Qual. 2023, 2023, 5236509. [Google Scholar] [CrossRef]
  37. Alshaalan, R.A.; Charalambides, M.N.; Edwards, C.H.; Ellis, P.R.; Alrabeah, S.H.; Frost, G.S. Impact of Chickpea Hummus on Postprandial Blood Glucose, Insulin and Gut Hormones in Healthy Humans Combined with Mechanistic Studies of Food Structure, Rheology and Digestion Kinetics. Food Res. Int. 2024, 188, 114517. [Google Scholar] [CrossRef]
  38. Menzel, A.; Samouda, H.; Dohet, F.; Loap, S.; Ellulu, M.S.; Bohn, T. Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice—Which to Use Regarding Disease Outcomes? Antioxidants 2021, 10, 414. [Google Scholar] [CrossRef]
  39. Jiang, C.; Ci, Z.; Kojima, M. α-Glucosidase Inhibitory Activity in Rice Miso Supplementary with Black Soybean. Am. J. Food Sci. Technol. 2019, 7, 27–30. [Google Scholar] [CrossRef]
Applsci 15 05962 g001
Figure 1. Overview of the visit procedures.
Figure 1. Overview of the visit procedures.
Applsci 15 05962 g001
Applsci 15 05962 g002
Figure 2. Incremental changes in the biochemical and oxidative parameters assessed during the 30-day period, following the experimental groups: (a) Total cholesterol outcome following the control and miso group. (b) Glucose outcome following the control and miso groups. (c) HDL cholesterol outcome following the control and miso groups. (d) LDL cholesterol outcome following the control and miso groups. (e) Triglyceride outcome following the control and miso groups. (f) Uric acid outcome following the control and miso groups. (g) Total antioxidant capacity outcome following the control and miso groups.
Figure 2. Incremental changes in the biochemical and oxidative parameters assessed during the 30-day period, following the experimental groups: (a) Total cholesterol outcome following the control and miso group. (b) Glucose outcome following the control and miso groups. (c) HDL cholesterol outcome following the control and miso groups. (d) LDL cholesterol outcome following the control and miso groups. (e) Triglyceride outcome following the control and miso groups. (f) Uric acid outcome following the control and miso groups. (g) Total antioxidant capacity outcome following the control and miso groups.
Applsci 15 05962 g002
Table 1. Nutritional value of experimental sauces per portion (20 g).
Table 1. Nutritional value of experimental sauces per portion (20 g).
Nutritional Composition per 20 gControl SauceMiso-Type Sauce
Energy (kcal)67.467.4
Carbohydrates (g)7.457.45
Fat, total (g)0.420.42
Protein (g)3.903.99
Saturated fat (g)0.050.05
Unsaturated fat (g)0.370.37
Cholesterol (mg)0.000.00
Dietary fiber, total (g)0.920.92
Sugar, total (g)0.600.60
Phenolics, total (mg)1.4057.60
Biocarotenoids, total (mg)0.0448.16
Antioxidant capacity, total (mg)0.11165.18
Table 2. Initial characteristics of the study participants.
Table 2. Initial characteristics of the study participants.
VariableMean ± SDp Value 1
Age (years)22.80 ± 4.020.68
Anthropometric Characteristics
Body Weight (kg)71.73 ± 19.090.08
Height (cm)168.40 ± 7.760.071
Body Mass Index (index)24.97 ± 4.270.14
Fat Mass (kg)22.38 ± 8.420.42
Muscle Mass (kg)52.25 ± 12.450.01 2
Body Water (kg)53.85 ± 8.790.27
Bone Mass (kg)2.78 ± 0.600.01 2
Waist/Hip Circumference Ratio (index)0.68 ± 0.220.08
Biochemical Characteristics
Total Cholesterol (mg/dL)143.70 ± 21.120.62
Glucose (mg/dL)75.70 ± 12.840.93
HDL Cholesterol (mg/dL)45.37 ± 9.360.08
LDL Cholesterol (mg/dL)81.64 ± 33.320.96
Triglycerides (mg/dL)61.20 ± 21.380.58
Uric Acid (mg/dL)4.30 ± 1.340.69
TAC (mmol/L)0.27 ± 0.090.53
1 p Value: Probability value, represents the significance of differences between men and women for baseline characteristics. 2 Statistical significance at the level of 0.05.
Table 3. Baseline and 30-day follow-up values of biochemical and antioxidant parameters of participants.
Table 3. Baseline and 30-day follow-up values of biochemical and antioxidant parameters of participants.
Baseline30-Day Follow-Upp-Value 1 Group Effectp-Value 1 Time Effectp-Value 1 Group × Time
Interaction
Total cholesterol (mg/dL) Control137.70 ± 25.90195.60 ± 42.100.80<0.001 20.25
Miso141.80 ± 28.20183.60 ± 37.08
Glucose (mg/dL) Control70.80 ± 11.6983.75 ± 9.080.080.04 20.39
Miso81.30 ± 10.40110.00 ± 53.69
HDL cholesterol (mg/dL) Control46.00 ± 3.5358.25 ± 1.750.270.002 20.18
Miso55.37 ± 4.7759.50 ± 4.22
LDL cholesterol (mg/dL) Control74.75 ± 26.69119.05 ± 45.680.75<0.001 20.03 2
Miso86.27 ± 37.68101.17 ± 33.30
Triglycerides (mg/dL) Control58.97 ± 6.7673.70 ± 16.600.490.410.03 2
Miso64.20 ± 29.0558.40 ± 27.10
Uric Acid (mg/dL) Control4.30 ± 1.345.01 ± 1.200.330.001 20.47
Miso4.86 ± 0.825.36 ± 0.54
TAC (mmol/L) Control0.33 ± 0.150.20 ± 0.150.500.001 20.01 2
Miso0.18 ± 0.090.26 ± 0.12
1 p-value: Probability value represents the significance of differences between the study groups. 2 Statistical significance at the level of 0.05.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Papagianni, O.I.; Dimou, C.; Koutelidakis, A.E. Biofunctional Miso-Type Sauce Enhanced with Biocarotenoids: How Does Its Habitual Consumption Affect Lipidemic, Glycemic, and Oxidative Stress Markers? A Pilot Cross-Over Clinical Study. Appl. Sci. 2025, 15, 5962. https://doi.org/10.3390/app15115962

AMA Style

Papagianni OI, Dimou C, Koutelidakis AE. Biofunctional Miso-Type Sauce Enhanced with Biocarotenoids: How Does Its Habitual Consumption Affect Lipidemic, Glycemic, and Oxidative Stress Markers? A Pilot Cross-Over Clinical Study. Applied Sciences. 2025; 15(11):5962. https://doi.org/10.3390/app15115962

Chicago/Turabian Style

Papagianni, Olga I., Charalampia Dimou, and Antonios E. Koutelidakis. 2025. "Biofunctional Miso-Type Sauce Enhanced with Biocarotenoids: How Does Its Habitual Consumption Affect Lipidemic, Glycemic, and Oxidative Stress Markers? A Pilot Cross-Over Clinical Study" Applied Sciences 15, no. 11: 5962. https://doi.org/10.3390/app15115962

APA Style

Papagianni, O. I., Dimou, C., & Koutelidakis, A. E. (2025). Biofunctional Miso-Type Sauce Enhanced with Biocarotenoids: How Does Its Habitual Consumption Affect Lipidemic, Glycemic, and Oxidative Stress Markers? A Pilot Cross-Over Clinical Study. Applied Sciences, 15(11), 5962. https://doi.org/10.3390/app15115962

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop