Table 2 Clinical trials of dairy products/probiotics on the incidence, duration, and severity of acute infections (N=23)
Author (Year) | Exposure(s) being studied | Study Population | Dairy intervention details | Infectious disease | Measures of infection risk | Duration and/or severity of infection or symptoms | |
|---|---|---|---|---|---|---|---|
N | Age, gender and health status | ||||||
Exposure - whole dairy products (by product-milk, fermented milk, traditional yogurt, and probiotic yogurt) | |||||||
Shinohara et al. (2020) [20] | Milk | Exp: 8 Control: 5 | Adults, healthy | Exp: 250 mL of milk once a week during bowling exercise for one year Control: 250 mL sports drink during bowling exercise once a week for one year | URTI based on questionnaire | Average incident cases: SS decrease (p<0.01) exp vs. control SS inverse correlation (p=0.03) between total dairy consumption and URTI incidence | SS inverse correlation (p=0.01) between total dairy consumption and URTI severity |
Turchet et al. (2003) [21] | Fermented milk with traditional ferments and L. casei DN-114 001 (Actimel®) | Exp: 180 Control: 180 | Adults, healthy | Exp: 100 mL Actimel®, fermented milk with traditional ferments and L. casei DN-114 001, twice daily for 3 weeks Control: none | Clinically verified winter infections | Cumulative incidence: Differences NSS for all pathologies (p=0.662), ENT pathology (p=0.248), influenza syndrome (p=0.815), gastrointestinal syndrome (p=0.836), and bacterial broncho-pneumopathy (p=0.240) | Duration of all pathologies: SS decrease (p=0.024) exp vs. control |
Nagata et al. (2011) [22] | Fermented milk with L. casei Shirota | Exp: 39 Control: 38 | Elderly, hospitalized patients | Exp: 80 mL fermented milk with L. casei Shirota once daily until discharge Control: none | Clinically verified norovirus gastroenteritis | Cumulative incidence occurring in winter season: Differences NSS (no p-value reported) exp vs. control | Duration of vomiting/diarrhea: Differences NSS (no p-value reported) exp vs. control Duration of fever (>37ËšC): SS decrease (p=0.027) exp vs. control Duration of fever (>38ËšC): Differences NSS (p=0.088) exp vs. control |
Fukushima et al. (2007) [23] | Fermented milk with L. johnsonii La1 (NCC533) and S. thermophilus | Exp: 12 Control: 12 | Elderly, hospitalized | Exp: 90 g fermented milk (373 kJ) with L. johnsonii La1 (NCC533) and S. thermophilus through a tube after feeding of EN (3395 kJ) daily for 12 weeks Control: EN diet at 3395 kJ, then administered 373 kJ of the EN in the same manner as the fermented milk daily for 12 weeks Run-in observation period 12 weeks before starting intervention | Clinically verified infection requiring antibiotic | NR | Mean duration of infection (% of days in 12 weeks): SS difference observation period - intervention (p=0.047) exp. vs. control (favors treatment) Mean duration of fever (% of days in 12 weeks): Difference observation period - intervention NSS (p=0.078) exp. vs. control |
Corsello et al. (2017) [24] | Fermented milk with L. paracasei CBA L74 | Exp: 73 Control: 73 | Children attending daycare or preschool, healthy | Exp: 150 mL fermented milk with L. paracasei CBA L74 daily for 3 months Control: 150 mL maltodextrins with an energy content similar to that of the fermented milk daily for 3 months | Clinically verified CID, including GITI or URTI | Cumulative proportion with at least one CID: SS decrease (p=0.002) exp vs. control Proportion of patients with at least one episode of acute gastroenteritis, pharyngitis, laryngitis, tracheitis: SS decrease (0.007, 0.007, 0.029, 0.048, respectively) exp. vs. control Negative binomial regression PPA analysis for CID incidence: IRR=0.64 (95% CI=0.42-0.98) exp. vs. control | Proportion of patients with at least one medication course: SS decrease (p=0.019) exp. vs. control Negative binomial regression PPA analysis for lost days of school: IRR=0.26 (95% CI=0.13-0.53) exp. vs. control |
Nocerino et al. (2017) [25] | Fermented milk with L. paracasei CBA L74 | Exp: 141 Control: 127 | Children attending preschool or daycare, healthy | Exp: 150 mL fermented milk with L. paracasei CBA L74 daily for three months Control: 150 mL maltodextrins with an energy content similar to that of the fermented milk daily for 3 months | Clinically verified CID | Proportion with at least one episode of CID: SS decrease (p<0.0001) exp. vs. control Proportion of patients with at least one episode of acute gastroenteritis, rhinitis, otitis, pharyngitis, laryngitis, tracheitis: SS decrease (<0.0001, 0.003, <0.0001, <0.001, 0.005, 0.018, respectively) exp. vs. control Position regression PPA for CID incidence: IRR=0.36 (95% CI=0.29-0.44) exp. vs. control Binary logistic regression analysis for CID incidence: OR=0.19 (95% CI=0.11-0.37) exp. vs. control | Odds of at least one medication course: OR=0.26 (95% CI=0.15-0.43) exp. vs. control |
Kinoshita et al. (2019) [26] | Traditional yogurt (Meiji Probio Yogurt R1®) | Exp: 479 Control: 482 | Female adults, healthy, healthcare workers | Exp: 112 mL of Meiji Probio Yogurt R-1® (L. delbrueckii ssp. bulgaricus [OLL1073R-1] and S. thermophilus) daily for 16 weeks Control: no yogurt | Common cold or influenza based on self-report of physician diagnosis | Cumulative incidence: Differences NSS for influenza (p=0.91) and common cold (p=0.49) Differences NSS for Kaplan-Meir analysis of influenza and common cold incidence | NR |
Makino et al. (2010) [27] | Traditional yogurt (Meiji Probio Yogurt R1) | Exp 1 (Fungata study): 29 Exp 2 (Arita study): 44 Control 1 (Fungata study): 28 Control 2 (Arita study): 43 | Elderly, healthy | Exp 1: 90 g of Meiji Probio Yogurt R-1® (L. delbrueckii ssp. bulgaricus [OLL1073R-1] and S. thermophilus) daily for 8 weeks Exp 2: 90 g of Meiji Probio Yogurt R-1 (L. delbrueckii ssp. bulgaricus [OLL1073R-1] and S. thermophilus) daily for 12 weeks Control 1: 100 mL milk daily for 8 weeks Control 2: 100 mL milk daily for 12 weeks | Common cold based on based on questionnaire reviewed by clinician and influenza based on receipt of hospital treatment | Odds of cold or influenza: Fungata: OR = 0.29, p=0.103 Arita: OR = 0.44, p=0.084 Meta-analysis: OR = 0.39, p=0.019 | NR |
Meng et al. (2016) [28] | Traditional yogurt Probiotic yogurt with B. animalis subsp. lactis BB‑12 | 30 (cross-over trial) | Adults, healthy | Exp 1: One 8-oz (240 g) serving of yogurt smoothie (BB-12 added pre fermentation) daily for four weeks Exp 2: One 8-oz (240 g) serving of yogurt smoothie (BB-12 added post fermentation) daily for four weeks Exp 3: 1 capsule containing BB-12 daily for four weeks Control: One 8-oz (240 g) serving of yogurt smoothie (no probiotic) daily for four weeks A two-week washout period between treatment periods applied | Common cold or influenza based on questionnaire | Cumulative incident cases of cold or flu: Differences NSS (p=0.1709) baseline (1 month before treatments) vs. all treatments in logistic regression model Mean number of cold or flu episodes: Differences NSS (p=0.2316) baseline (1 month before treatments) vs. all treatments in Poisson regression model | Duration of URTI symptoms (days): SS decrease baseline vs. exp 1 (p<0.01) and baseline vs. control (p<0.05) Number of days in bed or away from work: Differences NSS (p=0.42) baseline vs. exp 1, exp 2, or control Sick score due to cold or flu: Differences NSS (p=0.06) baseline vs. exp 1, exp 2, or control |
Pu et al. (2017) [29] | Probiotic yogurt with L. paracasei N1115 | Exp: 103 Control: 102 | Adults, healthy | Exp: 100 mL of probiotic yogurt three times a day for 12 weeks Control: none | URTI based on questionnaire | Number of URTI events: SS decrease (p=0.030) exp. vs. control Number of persons with URTI: SS decrease (p=0.038) exp. vs. control Mean number of URTI episodes per person: SS decrease (p=0.043) exp. vs. control RR of URTI: RR=0.55 (95% CI: 0.307–0.969) exp. vs. control | URTI score: Difference NSS (p=0.913) exp. vs. control |
Exposure - probiotics (by genus, species and strain) | |||||||
Zhang et al. (2021) [30] | B. animalis subsp. lactis Bl-04 [given in yogurt] | Exp: 62 Control: 61 | Adults, healthy | Exp: 250 g of Qingrun® yogurt (yogurt drink with B. animalis subsp. lactis Bl-04, L casei, L. bulgaricus, and S. thermophilus) once daily for 12 weeks Control: 250 g of control yogurt (yogurt drink with L. casei, L. bulgaricus, and S. thermophilus) once daily for 12 weeks | Common cold and influenza-like illness (URTI) based on questionnaire | OR for common cold: OR=0.38 (95% CI=0.17-0.81) OR for influenza-like illness: OR=0.38 (95% CI=0.17-0.81) SS difference (p=0.0002) in frequency distribution of number of URTI episodes | Duration of URTI symptoms (days): SS decrease (p <0.0001) exp vs. control Severity score of URTI symptoms: SS decrease (p <0.0001) exp vs. control Duration of medication due to URTI (days): SS decrease (p <0.0001) exp vs. control Duration of sick leave due to URTI (days): Difference NSS (p=0.433) exp vs. control |
Guillemard et al. (2010a) [31] | Traditional ferments and L. casei DN-114 001 [given in yogurt drink Actimel®] | Exp: 500 Control: 500 | Adults, healthy, shift workers | Exp: 100mL Actimel®, fermented milk (L. delbrueckii ssp. bulgaricus and S. thermophilus) with added L. casei DN-114 001, twice daily for 3 months Control: Non-fermented dairy drink at same dose and duration | Clinically verified CID, including URTI, LRTI and GITI | Cumulated number of all CIDs by Poisson regression: RR=0.92 (95% CI=0.78-1.09) exp vs. control Cumulated number of CIDs by logistic regression: OR=0.75 (95% CI=0.59-0.95) Proportion with ≥1 CID: SS decrease (p=0.005) exp vs. control Occurrence of CID by logistic regression: OR=0.695 (95% CI=0.540-0.896) | Mean duration of CID episode (days): Difference NSS (p=0.182) exp. vs. control Cumulative time with CIDs per subject (days): Difference NSS (p=0.084) exp. vs. control Cumulative duration of fever (days):.022) exp. vs. control % with severe symptoms: Differences NSS (p-value not reported) exp. vs. control CID-associated total medication: Differences NSS (p-value not reported) exp. vs. control Duration and occurrence of sick leave due to CID: Differences NSS (p-value not reported) exp. vs. control |
Guillemard et al. (2010b) [32] | Traditional ferments and L. casei DN-114 001 [given in yogurt drink Actimel®] | Exp: 537 Control: 535 | Elderly, healthy | Exp: 100mL Actimel®, fermented milk (L. delbrueckii ssp. bulgaricus and S. thermophilus) with added L. casei DN-114 001, twice daily for 3 months Control: Non-fermented dairy drink at same dose and duration | Clinically verified CID, including URTI, LRTI, influenza and GITI | Cumulated number of all CIDs by Poisson regression: Differences NSS (p-value not reported) Mean CID rate by Poisson regression: RR=0.89 (95% CI=0.70-1.14) exp vs. control | Mean duration per episode: SS decrease exp. vs. control for all CID (p=0.008), URTI (p=0.0002), and rhinopharyngitis (p=0.0003) Cumulative duration: SS decrease exp. vs. control for all CID (p=0.009), URTI (p=0.0003), and rhinopharyngitis (p=0.0006) Severity (use of CID-associated medication) and intensity/duration of fever: Differences NSS (no p-value reported) exp. vs. control for each analysis |
Merenstein et al. (2010) [33] | Traditional ferments and L. casei DN-114 001 [given in yogurt drink DanActive®] | Exp: 314 Control: 324 | Children, healthy | Exp: 200 mL strawberry flavored DanActive®, fermented milk (L. bulgaricus and S. thermophilus) with added L. casei DN-114 001, daily for 90 days Control: 200 mL non-fermented dairy drink at same dose and duration | CID, (including GITI, LRTI, URTI) based on parental report | Incidence rate of CIDs per 100-person day: IRR=0.81 (95% CI=0.65-0.99) Incidence rate of GITI per 100-person day: IRR=0.76 (95% CI=0.58-0.99) Incidence rate of URTI per 100-person day: IRR=0.82 (95% CI=0.68-0.99) Incidence rate of LRTI per 100-person day: IRR=0.98 (95% CI=0.82-1.18) | Rate of days with change in activity because of illness per 100-person days: Differences NSS (p=0.91) exp. vs. control Rate of vomiting, stomach pain, constipation, runny nose, cough, decreasing appetite, fever and rash per 100-person days: Differences NSS for each analysis (p=0.10, 0.36, 0.68, 0.39, 0.36, 0.54, 0.99, 0.21, respectively) |
Tiollier et al. (2007) [34] | Traditional ferments and L. casei DN-114 001 [given in yogurt drink Actimel®] | Exp: 24 Control: 23 | Adult male cadets, healthy | Exp: 100 mL Actimel®, fermented milk (L. delbrueckii ssp. bulgaricus and S. thermophilus) with added L. casei DN-114 001, three times daily for 1 month during commando training Control: 100 mL of non-fermented milk three times daily for 1 month during commando training | Clinically verified RTIs | Cumulative number of persons with RTI: Differences NSS (p=0.46) exp. vs. control Incidence of RTI: Difference NSS (p=0.98) exp. vs. control | Mean number of days with symptoms: Difference NSS (p=0.67) exp. vs. control Mean number of symptoms and daily mean number of symptoms: Difference NSS (p=0.23, p-value=not reported) exp. vs. control Proportion of rhinopharyngitis: SS higher (p<0.05) exp vs. control |
Vaisberg et al. (2019) [35] | L. casei Shirota [given in Yakult®] | Exp: 20 Control: 22 | Adult male marathon runners, healthy | Exp: 80 g of Yakult®, fermented milk with L. casei Shirota, daily for 30 days prior to marathon Control: 80 g non-fermented milk daily for 30 days prior to marathon | Upper respiratory symptoms based on self-report | Cumulative proportion with upper respiratory symptoms post-marathon: Differences NSS (p=0.076) exp. vs. control | Duration of upper respiratory symptoms post-marathon: Differences NSS (p=0.089) exp. vs. control |
Van Puyenbroeck (2012) [36] | L. casei Shirota [given in milk] | Exp: 375 Control: 362 | Elderly institutionalized, healthy | Exp: 65 mL fermented milk with L. casei Shirota twice daily for 176 days Control: 65 mL non-fermented milk twice daily for 176 days | Clinically verified RTI | Number of participants with at least one day of symptoms: Difference NSS (p=0.325) exp. vs. control Generalized linear mixed modeling with the outcome of one or more respiratory symptoms: OR=0.8715 (95% CI=0.6168- 1.2887) exp vs. control Multivariate logistic regression analysis with the outcome development of a severe RTI: OR=0.592 (95% CI=0.335-1.049) | Number of days of respiratory symptoms: Difference NSS (p=0.342) exp. vs. control |
Shida et al. (2017) [37] | L. casei Shirota [given in Yakult®] | Exp: 49 Control: 47 | Adults, healthy | Exp: One bottle of Yakult®, fermented milk with L. casei Shirota, daily for 12 weeks Control: One bottle non-fermented milk daily for 12 weeks | Clinically verified URTI, including common cold and influenza | Cumulative proportion of patients with incident URTI: SS decrease (p=0.002) exp vs. control Cumulative proportion of patients with incident cold: SS decrease (p=0.005) exp vs. control Cumulative proportion of patients with incident influenza: SS decrease (p=0.201) exp vs. control Kaplan Meir time-to-event analysis: SS higher (p=0.0008) URTI-free rate exp. vs. control Mean cumulative number of URTI episodes: SS (p=0.004) decrease exp. vs. control | Mean duration of each URTI episode (days): SS decrease (p=0.002) exp. vs. control Mean cumulative days with URTI symptoms: SS decrease (p=0.001) exp. vs. control Mean severity score of URTIs: Differences NSS (=0.966) exp vs. control |
Hatakka et al. (2001) [38] | L. rhamnosus GG [given in milk] | Exp: 282 Control: 289 | Children attending daycare, healthy | Exp: Fermented milk with L. rhamnosus GG (ATCC 53103) three times daily, five days a week, for 7 months (average consumption 260 mL) Control: Non-fermented milk three times daily, five days a week, for 7 months (average consumption 260 mL) | Clinically verified RTI | Age-adjusted logistic regression all infections, acute otitis media, sinusitis, acute bronchitis, and pneumonia: OR=0.75 (95% CI=0.52-1.09), OR=0.78 (95% CI=0.53-1.14), OR=0.86 (95% CI=0.33-2.22), OR=0.80 (95% CI=0.39-1.64), OR=0.83 (95% CI=0.18-3.78) exp vs. control | Mean ITT age-adjusted duration of total, respiratory, and gastrointestinal symptoms (days): Differences NSS (p=0.59, 0.67, 0.74, respectively) exp. vs. control Mean ITT age-adjusted absence due to illness (days): Differences NSS (p=0.09) exp. vs. control Mean ITT age-adjusted total symptoms score: Differences NSS (p=0.36) exp. vs. control Age-adjusted logistic regression for all antibiotic treatment: OR=0.78 (95% CI=0.54-1.11) Correlation between amount of milk consumed and the total number of days of illness: r = − 0.12, p=0.07 Correlation between amount of milk consumed and days with respiratory symptoms: r = − 0.11; p=0.09 Correlation between amount of milk consumed and days with gastrointestinal symptoms: r = − 0.17; p=0.007 |
Sugimura et al. (2015) [39] | Lactococcus lactis ssp. lactis JCM5805 [given in yogurt drink] | Exp: 106 Control: 107 | Adults, healthy | Exp: 100 mL fermented yogurt drink with Lactococcus lactis ssp. lactis JCM5805 daily for 10 weeks Control: 100 mL non-fermented yogurt drink daily for 10 weeks | Clinically verified common cold or influenza | Cumulative incident influenza or common cold cases: Differences NSS (p=0.127) exp. vs. control | Number of days with cough and feverishness: SS decrease (p<0.001 for each) exp. vs. control Number of days with sore throat and headache: Differences NSS (p=0.226 and p=0.958, respectively) exp. vs. control Number of days with moderate/severe cough, sore throat and feverishness: SS decrease (p=0.015, p=0.009, p=0.009, respectively) exp. vs. control Number of days with moderate/severe headache: Differences NSS (p=0.679) exp. vs. control |
Zhang et al. (2018) [40] | L. paracasei, L. casei 431, L. fermentium PCC [in yogurt drink] | Exp: 67 Control: 67 | Adults, unclear (history of cold ≥4 times in the past year) | Exp: 150 mL of fermented yogurt drink with L. paracasei, L. casei 431, L. fermentium PCC once daily for 12 weeks Control: 150 mL of yogurt fermented by starter culture only once daily for 12 weeks | URTI and flu-like illness (no information on method of outcome assessment) | Cumulative proportion with URTI: SS decrease (p=0.002) exp. vs. control Cumulative proportion flu-like illness with fever: SS decrease (p=0.034) exp. vs. control Cumulative proportion URTI symptom without fever: SS decrease (p=0.023) exp. vs. control | Mean duration URTI symptoms (days): SS decrease (p<0.001) exp vs. control Cumulative proportion receiving drug treatment for URTI symptoms: SS decrease (p<0.001) exp. vs. control Cumulative proportion missing work: Differences NSS (no p-value reported) exp. vs. control Severity scores of URTI symptoms: SS decrease (p=0.028) exp. vs. control Mean days of medication: Differences NSS (p=0.064) exp. vs. control Mean number of sick days: Differences NSS (p=0.290) exp. vs. control |
Coman et al. (2017) [41] | L. rhamnosus IMC 501 and L. paracasei IMC 502 [given in milk] | Exp: 5 Control: 5 | Adults, healthy | Exp: 200 mL of fermented milk with L. rhamnosus IMC 501 and L. paracasei IMC 502 once daily for 4 weeks Control: 200 mL of fermented milk with no additional probiotics once daily for 4 weeks | Respiratory symptoms based on questionnaire | Mean change in respiratory symptom scores on Wisconsin Upper Respiratory Symptom Survey: Differences NSS (no p-values reported) exp. vs. control for runny nose, nose closed, sneezing, sore throat, irritated throat, cough, hoarseness, head congestion, chest congestion and tiredness | NR |
Perez et al. (2010) [42] | L. casei CRL431and L. acidophilus CRL730 [given in milk] | Exp: 70 Control: 70 | Children, healthy, low SES | Exp: 90 g fermented milk with S. thermophilus, L. casei CRL431and L. acidophilus CRL730 once daily for at least 4 months Control: 90 g fermented milk with S. thermophilus once daily for at least 4 months | Clinically verified URTI, gastroenteritis, varicella, and pneumonia | Number of patients with URTI, gastroenteritis, varicella, and pneumonia: Differences NSS (0.882, 0.326, 0.476 and 1.00, respectively) exp. vs. control | Days of fever: Differences NSS (p=0.235) exp. vs. control |