Skip to main content
Download PDF
Download ePub

The effect of probiotic-fortified kefir on depression, appetite, oxidative stress, and inflammatory parameters in Iranian overweight and obese elderly: a randomized, double-blind, placebo-controlled clinical trial

Journal of Health, Population and Nutrition volume 44, Article number: 30 (2025) Cite this article

Abstract

Background

It has been shown that the microflora of the gastrointestinal tract undergoes changes in obese individuals. The present study aimed to investigate the effect of kefir fortified with two strains, Lactobacillus helveticus and Bifidobacterium longum, on depression, appetite, oxidative stress, and inflammatory parameters in overweight and obese elderly individuals.

Methods

This study was a double-blind, randomized, and placebo-controlled clinical trial conducted on 67 elderly men aged over 65, who were randomly divided into two groups. One group (n = 35) received one bottle (240 cc) of regular kefir as a placebo, while the intervention group (n = 32) received one bottle of probiotic-fortified kefir for eight weeks. Depression and appetite were evaluated using the Geriatric Depression Scale-15 (GDS-15) and a validated Visual Analogue Scale (VAS), respectively. Oxidative stress parameters were assessed using the standard calorimetric method, and inflammatory parameters were measured via the enzyme-linked immunosorbent assay method (ELISA). The differences between the two groups were compared using the independent samples T-test.

Results

The median age of participant in both groups was 65 years. A significant difference in depression scores and the mean change between the two groups was observed after eight weeks (p = 0.001 and p = 0.042, respectively). Within-group comparison revealed a significant increase in appetite scores in both groups (p < 0.05 for both). Moreover, a significant difference in the changes in total antioxidant capacity (TAC) was noted (p = 0.009). However, no significant differences were observed in other oxidative and inflammatory parameters between the two groups (p˃0.05 for all).

Conclusions

The results demonstrated the positive impact of two specific strains of Bifidobacterium and Lactobacillus on improving depression in the elderly. However, when comparing the two groups, no significant effects were observed on appetite, inflammation, and oxidative stress parameters, except for TAC.

Introduction

According to the World Health Organization (WHO), the elderly individuals are defined as those aged 65 years or older [1]. Several factors, including reduced nutritional needs, changes in basal metabolism, poor eating habits, and inactivity, have contributed to an increased prevalence of overweight and obesity in this population [2]. Obesity is recognized as a risk factor for various health conditions, including diabetes [3], heart failure [4], hypertension [5], and psychological issues such as mood disorders and depression [6]. Additionally, being overweight may further elevate the risk of depression in the elderly [7].

Numerous inflammatory markers are associated with obesity and its related adverse outcomes [8]. Research has shown that changes in the gastrointestinal microflora occur in obese individuals, leading to increased permeability of intestinal epithelial cells and endotoxemia. This, in turn, contributes to insulin resistance and obesity through inflammation pathways [9, 10]. Moreover, substantial evidence suggests that gut microbiota play a critical role in energy regulation, nutrient absorption, fat storage, and the alleviation of anxiety and depression by producing tryptophan, a precursor to serotonin [11,12,13]. In addition, studies indicate that treatment with prebiotics and probiotics may counteract many of the metabolic effects caused by alterations in the gut microflora of obese individuals [10]. As a result, managing obesity remains a key concern, with dietary modification widely recognized as having the most significant impact on addressing this growing epidemic [14].

Evidence suggests that dairy products may contribute to a more favorable body composition [15, 16]. Kefir, a traditional drink produced by fermenting kefir grains with water or milk [17], recognized as a probiotic product [18]. Numerous studies have demonstrated that kefir offers a range of nutritional benefits, including anticancer, antidiabetic, antioxidative, anti-inflammatory, and immunomodulatory properties [19, 20].

Over the past decade, inflammation has been recognized as a significant factor in mood disorders [21]. Clinical studies have also shown that various psychological and physiological stressors can disrupt normal intestinal microbiota, with the most notable impact being a stress-induced reduction in Lactobacillus and Bifidobacterium species [22, 23]. Moreover, a trial involving 55 healthy individuals demonstrated that a combination of Lactobacillus helveticus and Bifidobacterium longum improved mood and anxiety symptoms within 30 days [23]. Additionally, both Lactobacillus helveticus and Bifidobacterium longum play crucial roles in modulating gut-brain communication and systemic inflammation, albeit through distinct pathways [23,24,25].

The consumption of probiotic microorganisms has significantly increased in recent years, particularly through probiotic dairy products [26]. In today’s modern world, people are becoming more health-conscious, prompting changes in diets and lifestyles. These changes often include the incorporation of probiotics and probiotic-based products [27]. Numerous researchers have highlighted the importance of probiotics, leading to extensive investigations into their clinical health benefits [28]. While some studies have demonstrated the positive effects of probiotics on gut microbiota and immune function in adults, there is limited research specifically exploring the impact of probiotic-fortified kefir on appetite regulation, oxidative stress, and inflammatory parameters in elderly men. To our knowledge, no study has examined the effects of probiotic-fortified kefir on depression, oxidative stress, and inflammatory parameters in the elderly. Therefore, this study aimed to evaluate whether kefir enriched with two strains, Lactobacillus helveticus and Bifidobacterium longum, could influence depression, oxidative stress, and inflammatory parameters in overweight and obese elderly individuals.

Methods

Design and setting

This double-blind, parallel, randomized controlled trial was conducted at the Motahari Clinic in Shiraz, Iran. The study’s sample size was calculated based on the previous study [29] with an effect size of d = 0.75, α = 0.05, and β = 80% using G*Power software based on the total antioxidant capacity (TAC) variable. After considering a 20% removal or violation of protocols, 36 participants were included in each of the fortified kefir group and the regular kefir group. Additional details about the study design are provided in a prior publication related to this project [30].

Participants

In this randomized controlled trial, participants were selected based on the following criteria: male gender, a body mass index (BMI) greater than 25, age over 65, willingness to participate, no history of cardiovascular diseases, diabetes, kidney or liver diseases, chronic infectious diseases, digestive disorders, psychological or neurological disorders, no use of antidepressant drugs, no recent use of antibiotics (within the last three months), probiotics (within the last two months), or antioxidant supplements, and not consuming alcohol regularly (more than three units per week). Participants were excluded if they experienced any of the following during the study: changes in medication or diet, concurrent use of other probiotic supplements, unwillingness to continue participation, or intolerance to the intervention.

Randomization

Permuted-block randomization with a fixed block size of four (2:2 ratio) was used to randomize participants via a computer method. Both participants and researchers were blinded to the allocation and randomization process. A trained assistant was responsible for randomly assigning subjects to either the fortified or regular kefir groups.

Blinding

Both participants and investigators involved in outcome assessments were blinded to the group allocation. The appearance (shape, size, and packaging) of the fortified and regular kefir was identical. To maintain blinding, packaging and coding were handled by the company. Additionally, the randomization sequence was kept confidential until the study was completed.

Intervention

In the fortified kefir group, participants consumed one bottle (240 cc) of fortified kefir containing Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (dosage 3 × 109 colony-forming units (CFU) for each of them). The kefir starter culture included LAF4 and Kluyveromyces marxianus). Participants were instructed to consume a bottle of kefir daily with lunch or dinner for eight weeks. In the placebo group, participants received 240 cc of regular kefir under the same schedule. Both the fortified and regular kefir were produced by Pegah Company, Fars, Iran and were identical in shape, size, and packaging.

During the randomized clinical trial, participants were asked not to modify their regular dietary intake and physical activity. Daily reminder messages were sent to encourage adherence to the kefir consumption schedule. Participants also documented their daily kefir intake on a checklist. After two weeks, participants visited the Motahari Clinic to receive their next batch of kefir and return any uneaten bottles. Based on the evaluation of uneaten kefir and the daily checklists, participants who consumed less than 80% of their kefir bottles were excluded from the study.

Outcomes

The primary outcomes of the study were appetite, depression, oxidative stress, and inflammatory markers. Outcome assessments were conducted at baseline and after 8 weeks of intervention. The parameters and their corresponding evaluation methods are outlined below.

Assessment of baseline features

At baseline and after eight weeks, weight was measured using a Seca device (Germany) while participants wore minimal clothing. Height was assessed in a standing position using a non-stretchable, fixed tape. BMI was then calculated using the formula: weight (kg) / height (m²). Waist circumference (WC) and hip circumference (HC) were measured with non-stretchable tape at the level of the iliac crest.

Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) at baseline and at the end of the study [31]. The IPAQ evaluates various aspects of physical activity, including vigorous-intensity activity, moderate-intensity activity, and walking, across different domains such as work, transportation, leisure, and household activities [32]. Based on the metabolic equivalent of task (MET), participants were categorized into three groups: low activity (less than 600 MET-minutes/week), moderate activity (600–3000 MET-minutes/week), and high activity (more than 3000 MET-minutes/week).

At baseline and after eight weeks of intervention, dietary intake was assessed using a 3-day dietary record (one weekend and two weekdays). Initially, all food item portion sizes were converted to grams based on Iranian household measurement guidelines [33]. Then, Nutritionist IV was used to calculate energy, macro-, and micronutrient intake [34].

Biochemical assessment

To measure oxidative and inflammatory markers at the beginning and end of the study, 10 mL fasting blood samples were collected using tubes containing ethylenediaminetetraacetic acid (EDTA). The blood samples were then centrifuged at 3000 revolutions per minute (rpm) for 7 min. The isolated serums were subsequently frozen at -76 °C for future biochemical analysis.

TAC, superoxide dismutase (SOD) activity, catalase, glutathione peroxidase (GPx) activity, and malondialdehyde (MDA) levels were assessed using standard calorimetric methods with a Zelbio (Germany) kit and a microplate reader. Additionally, interleukin 6 (IL-6) and C-reactive protein (CRP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) method with an LDN (Germany) kit.

Depression and appetite assessment

Depression was evaluated using the Geriatric Depression Scale-15 (GDS-15) questionnaire. The GDS-15 was developed by Yesavage and Brink in 1983 and later validated for the Iranian population by Malakouti et al. [35]. Each question on the GDS-15 was scored as either 0 or 1, with the total score for each participant ranging from 0 to 15.

Appetite was assessed using a validated Visual Analogue Scale (VAS) at baseline and at the end of the intervention. The VAS is a 100 mm horizontal line with endpoints representing the most positive and negative ratings of desire to eat, hunger, fullness, and satiety.

Statistical analysis

The normality of the study variables was assessed using the Kolmogorov-Smirnov test. Baseline categorical demographic variables, such as physical activity and education level, were compared between the fortified and regular kefir groups using the chi-square test. Quantitative baseline variables were compared using either the Mann-Whitney U test or the independent samples t-test, depending on their normal distribution. Depression and appetite scores, as well as oxidative and inflammatory markers, were evaluated as outcomes, with differences between the two groups compared using the independent samples t-test. Within-group analysis for both groups was conducted using the paired-sample t-test. All analyses were performed using SPSS version 23 (SPSS Inc., Chicago, Illinois). Statistical significance was set at p < 0.05.

Ethical considerations

This clinical trial was conducted in accordance with the Declaration of Helsinki guidelines, and all participants provided written informed consent. The study was approved by the ethics committee of Baqiyatallah Hospital (ethical approval number: IR.BMSU.BAQ.REC.1401.113) and registered with the Iranian Registry of Clinical Trials (IRCT20130227012628N3; first registration date: 21/02/2023).

Results

In the current study, 72 eligible elderly participants were randomly assigned to either the fortified kefir group (n = 36) or the regular kefir group (n = 36) for eight weeks. After eight weeks of supplementation, 67 participants completed the trial: 32 in the fortified kefir group (2 participants were excluded due to digestive issues, and 2 were excluded for consuming less than 80% of the supplement) and 35 in the regular kefir group (1 participant was excluded for non-compliance with the 80% consumption requirement) (Fig. 1). As shown in Table 1, there were no significant differences in anthropometric, demographic characteristics, or nutrient intakes between the two groups at baseline (p > 0.05 for all).

Fig. 1
figure 1

Flowchart of the study

Full size image
Table 1 Anthropometric and demographic characteristics and nutrient intakes of the study participants at the baseline (n = 67)
Full size table

The depression and appetite scores of elderly participants in both groups are presented in Table 2. At baseline, there were no significant differences in depression and appetite scores between the fortified and regular kefir groups (p > 0.05 for both). However, after eight weeks of supplementation, a significant difference was observed in depression scores and the mean change between the two groups (p = 0.001 and p = 0.042, respectively). Additionally, within-group comparisons showed a significant increase in appetite scores for both groups (p < 0.001 for the fortified kefir group and p = 0.001 for the regular kefir group). Nevertheless, there was no significant difference in appetite scores between the two groups (p > 0.05).

Table 2 The effect of the fortified and regular kefir on depression and appetite scores in elderly participants (n = 67)
Full size table

The effect of fortified and regular kefir on oxidative and inflammatory markers in elderly participants is presented in Table 3. After eight weeks of supplementation, a significant difference was observed in the changes in total antioxidant capacity (TAC) levels (p = 0.009). However, no significant differences were found in IL-6, CRP, and MDA levels, nor in the activity of SOD, catalase, and GPx between the two groups (p > 0.05 for all). Additionally, within-group analyses revealed a significant difference in TAC levels for both the fortified and regular kefir groups (p = 0.033 and p = 0.035, respectively).

Table 3 The effect of the fortified and regular kefir on oxidative and inflammatory markers in elderly participants (n = 67)
Full size table

Discussion

In the present study, a significant reduction in depression was observed in the fortified kefir group compared to the regular kefir group. Additionally, a significant change in TAC was noted in the intervention group compared to the placebo group. However, no significant differences were found between the two groups for the other variables.

The number of individuals suffering from depression and other mood disorders is rapidly increasing. According to the WHO, approximately 300 million people worldwide are affected by depression [36]. Therefore, it is crucial to find new antidepressant treatments to address the issues with current medications, including their high incidence of unwanted side effects, the frequent lack of response, and the prolonged onset of therapeutic effects [37].

As mentioned above, the findings of the current study showed that kefir fortified with probiotics can significantly reduce depression. Our findings are in line with the other studies. In a randomized clinical trial on the effect of Bifidobacterium longum on 44 people with irritable bowel syndrome )IBS( and mild to moderate anxiety or depression for six weeks, it was shown that depression was reduced by supplementing with this probiotic [38]. Also, a study by Soltanmoradi et al. revealed that kefir and Lactobacillus rhamnosus GG could decrease the duration of depression-like activities and increase antidepressant properties in a mouse model [39]. In a cross-sectional study of 26,118 people, the effect of consuming foods containing probiotics on depression was investigated. The results showed that the consumption of probiotic foods may have beneficial effects on depression, especially in men [40]. However, a systematic review and meta-analysis of randomized clinical trials demonstrated that probiotics have a significant effect on reducing depression in the population under 60 years of age and have no effect on the population over 65 [41]. Since there was only one study with people older than 65 years in this meta-analysis, no strong conclusions can be drawn. In general, studies show the important role of probiotics in reducing depression in non-depressed people and patients with depression [41].

The mechanism of probiotics’ effect on depression has been investigated in some studies. Bifidobacterium has been shown to reduce pro-inflammatory immune responses and increase tryptophan, a precursor to serotonin synthesis [42]. Studies have shown that bifidobacteria increase the expression of inflammatory cytokines, such as IL-1 and TNF-α, while also enhancing the activity of natural killer cells [43]. It has also been shown that the consumption of probiotics plays an important role in the levels of brain-derived neurotrophic factor [44, 45] and γ-aminobutyric acid, an important neurotransmitter in depression [46]. Moreover, probiotics can be involved in decreasing depression by reducing pro-inflammatory cytokines that contribute to depression [23, 47, 48]. In addition, gut microbiota may play an essential role in modulating behavior and mood disorders through various mechanisms [49]. Improving gut dysbiosis reduces inflammation, resulting in changes in brain function, mood, and behavior [50].

The findings of the present study indicated the positive effect of kefir fortified with probiotics and regular kefir on the appetite of the elderly, and the improvement of appetite was greater in the intervention group compared to placebo. However, it was not statistically significant. A post hoc analysis of randomized clinical trials showed that supplementation with probiotics (Bifidobacterium longum and Lactobacillus helveticus) in patients with major depressive disorder is related to improved appetite [51]. Moreover, a study by Saito et al. illustrated that Lactobacillus brevis can increase appetite by increasing the production of ghrelin and serotonin [52]. In contrast, some studies have shown that some probiotic strains are related to appetite suppression and reduced food intake [53, 54]. However, the presence of probiotics in kefir may be the reason for the lack of significant change in appetite levels when comparing the two groups in the present study. Also, the difference in species compared to those investigated in the present study may account for the observed variation.

Beneficial effects mediated by probiotics on human health can be caused by changes in gut microbiota [55]. Gut microbiota may affect eating behavior, but the mechanism remains unclear [56]. The appetite system and gut microbiota seem to be related, and microbial metabolites and energy metabolism may be potential mechanisms. Metabolites from microbiota may affect appetite by regulating immune system function and hormone secretion [56]. Also, probiotics may increase appetite by reducing leptin levels, but the exact mechanism is unknown [57]. However, it has been shown that probiotic bacteria such as Bifidobacterium and Lactobacillus can cause a decrease in enterohepatic leptin by reducing the hydrolysis of conjugated hormone in the colon [58].

Our findings indicated that supplementation with probiotics had no significant effect on inflammatory and oxidative stress parameters except TAC. Mixed evidence is available regarding the anti-inflammatory and antioxidant properties of probiotics. While some showed no effect, other studies reported beneficial effects [59,60,61,62]. A meta-analysis study on the effect of probiotics in people with diabetes illustrated that probiotics did not significantly affect CRP levels [63]. Also, in a clinical trial aimed at investigating the effect of Lactobacillus probiotics on inflammatory and oxidative markers in thirty-four subjects with type 2 diabetes, it was shown that Lactobacillus did not exert a significant effect on MDA and IL-6 levels after six weeks of intervention [61]. In contrast, a study by Harisa et al. revealed that Lactobacillus acidophilus could decrease MDA in diabetic rats [64]. Also, in a double-blind, randomized, placebo-controlled study on the effect of probiotics in patients under methadone maintenance treatment programs, it was shown that supplementation with probiotics caused a significant increase in total glutathione and TAC [65].

Although the anti-inflammatory mechanisms of probiotics have not yet been determined, it has been suggested that probiotics play a role in reducing inflammation by producing short-chain fatty acids (SCFAs) [66, 67]. Also, some bacteria (such as Lactobacillus species) reduce inflammation by repairing and maintaining epithelial barriers, thereby reducing the effect of pro-inflammatory stimuli such as lipopolysaccharides [68]. In addition, probiotics can decrease inflammation by increasing the synthesis of antimicrobial peptides [68]. Probiotics can influence the expression of inflammatory markers. For example, certain probiotics can reduce levels of pro-inflammatory cytokines like TNF-α and IL-6 while promoting anti-inflammatory cytokines such as IL-10 [69]. Furthermore, the effect of probiotics on oxidative stress can be attributed to the production of butyrate, which can act as an antioxidant by affecting the levels of non-enzymatic and enzymatic antioxidants and deoxyribonucleic acid (DNA) repair systems [70].

The current research had strengths and limitations. Due to financial constraints, we were unable to examine the participants’ stools, as the actual effects of probiotics on intestinal ecology remain a topic of ongoing debate. Additionally, our study sample consisted solely of men over 65 years old. Given that age and gender are significant factors influencing the gut microbiome, the results may not be applicable to women or individuals under 65. Moreover, since the elderly participants in this study did not experience depression, the findings cannot be generalized to those with depression. Furthermore, the small sample size limits the ability to extrapolate the results to the broader elderly population. Another limitation of this study was controlling for confounding variables, such as diet, physical activity, medication use, and psychosocial factors, all of which can significantly influence appetite, inflammation, oxidative stress, and depression. However, to our knowledge, this is the first study to examine the effects of two specific probiotic strains on oxidative stress, inflammation, appetite, and depression in the elderly. A key strength of the study is its double-blind, placebo-controlled design. Additional strengths include the specific focus on the elderly population, the use of two probiotic strains to allow a more comprehensive evaluation of their effects, and the assessment of multiple health parameters, which may offer insights into synergistic or differential effects on health outcomes.

Conclusions

This study is the first to evaluate the effects of kefir fortified with two bacterial strains on depression, oxidative stress, and inflammatory parameters in overweight and obese elderly individuals in Iran. The findings suggest a positive effect of two specific strains of Bifidobacterium and Lactobacillus on improving depression in this population. Therefore, consumption of kefir fortified with these strains may help alleviate depression in elderly individuals. However, no significant effects were found on appetite, inflammation, or oxidative stress parameters, except for TAC when comparing the two groups. If the results of this study are confirmed by future clinical trials involving depressed individuals, probiotics may serve as an adjunctive treatment for depression, positively influencing the disease process. Further research is required to confirm these findings and explore the mechanisms by which probiotics affect the evaluated parameters.

Data availability

No datasets were generated or analysed during the current study.

References

  1. World report on ageing and health. World Health Organization; 2015.

  2. Inelmen EM, Sergi G, Coin A, Miotto F, Peruzza S, Enzi G. Can obesity be a risk factor in elderly people? Obes Rev. 2003;4(3):147–55.

    Article  CAS  PubMed  Google Scholar 

  3. Asiimwe D, Mauti GO, Kiconco R. Prevalence and risk factors associated with type 2 diabetes in elderly patients aged 45–80 years at Kanungu District. J Diabetes Res. 2020;2020:1–5.

    Article  Google Scholar 

  4. Dădârlat-Pop A, Sitar-Tăut A, Zdrenghea D, Caloian B, Tomoaia R, Pop D, Buzoianu A. Profile of obesity and comorbidities in elderly patients with heart failure. Clin Interv Aging 2020:547–56.

  5. Lin Y-A, Chen Y-J, Tsao Y-C, Yeh W-C, Li W-C, Tzeng I-S, Chen J-Y. Relationship between obesity indices and hypertension among middle-aged and elderly populations in Taiwan: a community-based, cross-sectional study. BMJ open. 2019;9(10):e031660.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Roberts RE, Deleger S, Strawbridge WJ, Kaplan GA. Prospective association between obesity and depression: evidence from the Alameda County study. Int J Obes. 2003;27(4):514–21.

    Article  CAS  Google Scholar 

  7. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67(3):220–9.

    Article  PubMed  Google Scholar 

  8. Cox AJ, West NP, Cripps AW. Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol. 2015;3(3):207–15.

    Article  CAS  PubMed  Google Scholar 

  9. Marik PE. Colonic flora, probiotics, obesity and diabetes. Front Endocrinol 2012, 3.

  10. Sanz Y, Santacruz A, De Palma G. Insights into the roles of gut microbes in obesity. Interdisciplinary perspectives on infectious diseases 2008, 2008.

  11. Gérard P. Gut microbiota and obesity. Cell Mol Life Sci. 2016;73(1):147–62.

    Article  PubMed  Google Scholar 

  12. Babakhani S, Hosseini F. Gut microbiota: an effective factor in the human brain and behavior. Neurosci J Shefaye Khatam. 2019;7(1):106–18.

    Article  Google Scholar 

  13. Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology. 2017;112:399–412.

    Article  CAS  PubMed  Google Scholar 

  14. Rakhra V, Galappaththy SL, Bulchandani S, Cabandugama PK. Obesity and the western diet: how we got here. Mo Med. 2020;117(6):536.

    PubMed  PubMed Central  Google Scholar 

  15. Mozaffarian D. Dairy foods, obesity, and metabolic health: the role of the food matrix compared with single nutrients. Adv Nutr. 2019;10(5):S917–23.

    Article  Google Scholar 

  16. Nouri M, Shateri Z, Faghih S. The relationship between intake of fruits, vegetables and dairy products with overweight and obesity in a large sample in Iran: findings of STEPS 2016. Front Nutr. 2023;9:1082976.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Fiorda FA, de Melo Pereira GV, Thomaz-Soccol V, Rakshit SK, Pagnoncelli MGB, Vandenberghe LPS, Soccol CR. Microbiological, biochemical, and functional aspects of sugary kefir fermentation - A review. Food Microbiol. 2017;66:86–95.

    Article  CAS  PubMed  Google Scholar 

  18. Dahiya D, Nigam PS. Therapeutic and dietary support for gastrointestinal tract using kefir as a Nutraceutical Beverage: dairy-milk-based or plant-sourced Kefir Probiotic products for Vegan and Lactose-intolerant populations. Fermentation. 2023;9(4):388.

    Article  CAS  Google Scholar 

  19. Cai Y, Sounderrajan A, Serventi L. Water kefir: a review of its microbiological profile, antioxidant potential and sensory quality. Acta Scientifci Nutritional Health. 2020;4(6):10–7.

    Article  Google Scholar 

  20. Azizi NF, Kumar MR, Yeap SK, Abdullah JO, Khalid M, Omar AR, Osman MA, Mortadza SAS, Alitheen NB. Kefir and its biological activities. Foods. 2021;10(6):1210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rosenblat JD, Cha DS, Mansur RB, McIntyre RS. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014;53:23–34.

    Article  CAS  PubMed  Google Scholar 

  22. Logan AC, Rao AV, Irani D. Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value. Med Hypotheses. 2003;60(6):915–23.

    Article  PubMed  Google Scholar 

  23. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson J-F, Rougeot C, Pichelin M, Cazaubiel M. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105(5):755–64.

    Article  CAS  PubMed  Google Scholar 

  24. Pasam T, Padhy HP, Dandekar MP. Lactobacillus Helveticus improves controlled cortical Impact Injury-generated neurological aberrations by remodeling of gut-brain Axis Mediators. Neurochem Res. 2025;50(1):3.

    Article  CAS  Google Scholar 

  25. Mohammadi G, Dargahi L, Peymani A, Mirzanejad Y, Alizadeh SA, Naserpour T, Nassiri-Asl M. The effects of probiotic formulation pretreatment (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) on a lipopolysaccharide rat model. J Am Coll Nutr. 2019;38(3):209–17.

    Article  CAS  PubMed  Google Scholar 

  26. Naseem Z, Mir SA, Wani SM, Rouf MA, Bashir I, Zehra A. Probiotic-fortified fruit juices: Health benefits, challenges, and future perspective. Nutrition. 2023;115:112154.

    Article  PubMed  Google Scholar 

  27. Yadav A, Jaiswal P, Jaiswal M, Kumar N, Sharma R, Raghuwanshi S, Prasad G, Bisen PS. Concise review: importance of probiotics yogurt for human health improvement. IOSR J Environ Sci Ver II. 2015;9(7):2319–99.

    Google Scholar 

  28. DJ MK, Kumar R, Poovai P, Kalaichelvan P. Probiotics and the multitude of health benefits. J Res Biology. 2012;2(2):102–13.

    Google Scholar 

  29. Noorifard M, Dabbagh Moghaddam A, Asemi Z, Hamidi Farahani R, Mousavi Jazayeri SM, Ebrahimi E. Effect of Probiotic supplementation on Oxidative Stress Enzymes and Mental Health of Athletes. Ann Mil Health Sci Res. 2019;17(1):e84922.

    Google Scholar 

  30. Noori M, Shateri Z, Babajafari S, Eskandari MH, Parastouei K, Ghasemi M, Afshari H, Samadi M. The effect of probiotic-fortified kefir on cardiovascular risk factors in elderly population: a double-blind, randomized, placebo-controlled clinical trial. BMC Nutr. 2024;10(1):74.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Biernat E, Stupnicki R, Lebiedziński B, Janczewska L. Assessment of physical activity by applying IPAQ questionnaire. Phys Educ Sport. 2008;52(2):83–9.

    Google Scholar 

  32. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–95.

    Article  PubMed  Google Scholar 

  33. Ghaffarpour M, Houshiar-Rad A, Kianfar H. The manual for household measures, cooking yields factors and edible portion of foods. Tehran: Nashre Olume Keshavarzy. 1999;7(213):42–58.

    Google Scholar 

  34. Nutritionist I. N-squared computing. Silverton: Nutritionist IV 1998.

  35. Malakouti K, Fathollahi P, Mirabzadeh A, Salavati M, Kahani S. Validation of geriatric depression scale (GDS-15) in Iran. Pejouhesh Dar Pezeshki (Research Medicine). 2006;30(4):361–9.

    Google Scholar 

  36. Can ÖD, Turan N, Özkay ÜD, Öztürk Y. Antidepressant-like effect of gallic acid in mice: dual involvement of serotonergic and catecholaminergic systems. Life Sci. 2017;190:110–7.

    Article  CAS  PubMed  Google Scholar 

  37. Paschos KA, Veletza S, Chatzaki E. Neuropeptide and Sigma receptors as novel therapeutic targets for the pharmacotherapy of depression. CNS Drugs. 2009;23:755–72.

    Article  CAS  PubMed  Google Scholar 

  38. Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT, Martin F-P, Cominetti O, Welsh C, Rieder A. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153(2):448–59. e448.

    Article  PubMed  Google Scholar 

  39. Soltanmoradi H, Maniati M, Davoodabadi A, Mosapour A, Samavarchi Tehrani S, Pazhoohan M, Daemi F, Khaleghzadeh-Ahangar H. A probiotic supplement, Lactobacillus rhamnosus GG, and kefir separately can improve mood and exhibit potential anti-depressant-like activities in mice. Acta Aliment. 2021;50(3):393–403.

    Article  CAS  Google Scholar 

  40. Kim C-S, Shin D-M. Probiotic food consumption is associated with lower severity and prevalence of depression: a nationwide cross-sectional study. Nutrition. 2019;63:169–74.

    Article  PubMed  Google Scholar 

  41. Huang R, Wang K, Hu J. Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2016;8(8):483.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan T. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170(4):1179–88.

    Article  CAS  PubMed  Google Scholar 

  43. Lim HJ, Shin HS. Antimicrobial and immunomodulatory effects of bifidobacterium strains: a review. J Microbiol Biotechnol. 2020;30(12):1793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ait-Belgnaoui A, Colom A, Braniste V, Ramalho L, Marrot A, Cartier C, Houdeau E, Theodorou V, Tompkins T. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastr Oenterology Motil. 2014;26(4):510–20.

    Article  CAS  Google Scholar 

  45. Gareau MG, Wine E, Rodrigues DM, Cho JH, Whary MT, Philpott DJ, MacQueen G, Sherman PM. Bacterial infection causes stress-induced memory dysfunction in mice. Gut. 2011;60(3):307–17.

    Article  PubMed  Google Scholar 

  46. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences 2011, 108(38):16050–16055.

  47. Luo J, Wang T, Liang S, Hu X, Li W, Jin F. Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat. Sci China Life Sci. 2014;57:327–35.

    Article  PubMed  Google Scholar 

  48. Ait-Belgnaoui A, Durand H, Cartier C, Chaumaz G, Eutamene H, Ferrier L, Houdeau E, Fioramonti J, Bueno L, Theodorou V. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology. 2012;37(11):1885–95.

    Article  CAS  PubMed  Google Scholar 

  49. Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe. 2015;17(5):565–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2010;24(1):9–16.

    Article  PubMed  Google Scholar 

  51. Kazemi A, Noorbala A, Djafarian K. Effect of probiotic and prebiotic versus placebo on appetite in patients with major depressive disorder: post hoc analysis of a randomised clinical trial. J Hum Nutr Dietetics. 2020;33(1):56–65.

    Article  CAS  Google Scholar 

  52. Saito H, Nakakita Y, Segawa S, Tsuchiya Y. Oral administration of heat-killed Lactobacillus brevis SBC8803 elevates the ratio of acyl/des-acyl ghrelin in blood and increases short-term food intake. Beneficial Microbes. 2019;10(6):671–7.

    Article  CAS  PubMed  Google Scholar 

  53. Sanchez M, Darimont C, Panahi S, Drapeau V, Marette A, Taylor VH, Doré J, Tremblay A. Effects of a diet-based weight-reducing program with probiotic supplementation on satiety efficiency, eating behaviour traits, and psychosocial behaviours in obese individuals. Nutrients. 2017;9(3):284.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Bjerg AT, Kristensen M, Ritz C, Holst JJ, Rasmussen C, Leser TD, Wellejus A, Astrup A. Lactobacillus paracasei subsp paracasei L. Casei W8 suppresses energy intake acutely. Appetite. 2014;82:111–8.

    Article  PubMed  Google Scholar 

  55. Fuentes CT, Schellekens H, Hoevenaars N, Ross P, Roy B, Stanton C, Dinan TG, Cryan JF. Identification of novel probiotics to modify appetite and satiety directly targeting the ghrelin receptor. FASEB J. 2016;30:717712–717712.

    Article  Google Scholar 

  56. Han H, Yi B, Zhong R, Wang M, Zhang S, Ma J, Yin Y, Yin J, Chen L, Zhang H. From gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators. Microbiome. 2021;9(1):1–16.

    Article  Google Scholar 

  57. Noormohammadi M, Ghorbani Z, Löber U, Mahdavi-Roshan M, Bartolomaeus TU, Kazemi A, Shoaibinobarian N, Forslund SK. The effect of probiotic and synbiotic supplementation on appetite-regulating hormones and desire to eat: a systematic review and meta-analysis of clinical trials. Pharmacol Res 2022:106614.

  58. Sousa R, Halper J, Zhang J, Lewis SJ, Li W-IO. Effect of Lactobacillus acidophilus supernatants on body weight and leptin expression in rats. BMC Complement Altern Med. 2008;8(1):1–8.

    Article  Google Scholar 

  59. Lin M-Y, Chang F-J. Antioxidative effect of intestinal bacteria bifidobacterium longum ATCC 15708 and Lactobacillus acidophilus ATCC 4356. Dig Dis Sci. 2000;45:1617–22.

    Article  CAS  PubMed  Google Scholar 

  60. Hatakka K, Martio J, Korpela M, Herranen M, Poussa T, Laasanen T, Saxelin M, Vapaatalo H, Moilanen E, Korpela R. Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis–a pilot study. Scand J Rheumatol. 2003;32(4):211–5.

    Article  CAS  PubMed  Google Scholar 

  61. Mazloom Z, Yousefinejad A, Dabbaghmanesh MH. Effect of probiotics on lipid profile, glycemic control, insulin action, oxidative stress, and inflammatory markers in patients with type 2 diabetes: a clinical trial. Iran J Med Sci. 2013;38(1):38.

    PubMed  PubMed Central  Google Scholar 

  62. Songisepp E, Kals J, Kullisaar T, Mändar R, Hütt P, Zilmer M, Mikelsaar M. Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers. Nutr J. 2005;4(1):1–10.

    Article  Google Scholar 

  63. Kasińska MA, Drzewoski J. Effectiveness of probiotics in type 2 diabetes: a meta-analysis. Pol Arch Med Wewn. 2015;125(11):803–13.

    Article  PubMed  Google Scholar 

  64. Harisa G, Taha E, Khalil A, Salem M. Oral administration of Lactobacillus acidophilus restores nitric oxide level in diabetic rats. Aust J Basic Appl Sci. 2009;3(3):2963–9.

    CAS  Google Scholar 

  65. Molavi N, Rasouli-Azad M, Mirzaei H, Matini AH, Banafshe HR, Valiollahzadeh M, Hassanzadeh M, Saghazade AR, Abbaszadeh-Mashkani S, Mamsharifi P. The effects of Probiotic supplementation on opioid-related disorder in patients under Methadone Maintenance Treatment Programs. Int J Clin Pract. 2022;2022(1):1206914.

    PubMed  PubMed Central  Google Scholar 

  66. Kim Y, Keogh J, Clifton P. Probiotics, prebiotics, synbiotics and insulin sensitivity. Nutr Res Rev. 2018;31(1):35–51.

    Article  CAS  PubMed  Google Scholar 

  67. McLoughlin RF, Berthon BS, Jensen ME, Baines KJ, Wood LG. Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. Am J Clin Nutr. 2017;106(3):930–45.

    Article  CAS  PubMed  Google Scholar 

  68. Lescheid DW. Probiotics as regulators of inflammation: a review. Funct Foods Health Disease. 2014;4(7):299–311.

    Article  Google Scholar 

  69. Kalliomäki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet. 2003;361(9372):1869–71.

    Article  PubMed  Google Scholar 

  70. Hamer HM, Jonkers DM, Bast A, Vanhoutvin SA, Fischer MA, Kodde A, Troost FJ, Venema K, Brummer R-JM. Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. Clin Nutr. 2009;28(1):88–93.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We sincerely thank all field investigators, staff, and participants of the present study.

Funding

Not applicable.

Author information

Author notes

  1. Mehran Noori and Zainab Shateri equally contributed to this work and co-first authors.

Authors and Affiliations

  1. Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mehran Noori & Hoseein Afshari

  2. Department of Nutrition and Biochemistry, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran

    Zainab Shateri

  3. Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Science, Shiraz University of Medical Sciences, Shiraz, Iran

    Siavash Babajafari

  4. Department of Food Science and Technology, School of Agriculture, Shiraz University, Shiraz, Iran

    Mohammad Hadi Eskandari

  5. Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Karim Parastouei & Mohammad Ghasemi

  6. Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mohammad Samadi

Authors
  1. Mehran Noori
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Zainab Shateri
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Siavash Babajafari
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Mohammad Hadi Eskandari
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Karim Parastouei
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Mohammad Ghasemi
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Hoseein Afshari
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Mohammad Samadi
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

M.N and Z.S; Contributed to writing the first draft. M.H.E, S.B and M.S; Contributed to all data and statistical analysis and interpretation of data. M.S, K.P, H.G and H.A.; Contributed to the research concept, supervised the work, and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohammad Samadi.

Ethics declarations

Ethics approval

The current research was approved by the Medical Research and Ethics Committee of Baqiyatallah Hospital (IR.BMSU.BAQ.REC.1401.113) and registered at the Iranian Registry of Clinical Trials (IRCT20130227012628N3) at 21/02/2023 and was carried out in accordance with the ethical standards of the Declaration of Helsinki.

Consent to participate

The informed consents were completed by all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Conflict of interest

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Noori, M., Shateri, Z., Babajafari, S. et al. The effect of probiotic-fortified kefir on depression, appetite, oxidative stress, and inflammatory parameters in Iranian overweight and obese elderly: a randomized, double-blind, placebo-controlled clinical trial. J Health Popul Nutr 44, 30 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41043-025-00773-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41043-025-00773-x

Keywords

Journal of Health, Population and Nutrition

ISSN: 2072-1315

Contact us