Table 1 Characteristics of studies included in the current systematic review
Authors with year of publication | Study design/ study location | Participant (treatment/control) and sex | Age range/mean age (y) | Subjects | Diet type | Duration (month/wk/day) | Outcomes | Side effects | Conclusion | |
|---|---|---|---|---|---|---|---|---|---|---|
Intervention | Control | |||||||||
Ebina et al. [39]. 1985 | Parallel RCT Location: Japan | 44 N (18 T/26 C) (24 M/20 F) | 3 months–6 years | Infants with acute diarrhea and rotavirus infection | HBC (20–50 ml/d) | Market milk | 3 days | Diarrhea, bowel movements, and virus shedding in stool | None | HBC significantly prevented the incidence of diarrhea caused by rotavirus (17% vs.86%; p < 0.05) but had no effect on duration of diarrhea, bowel movements, or virus shedding in stool |
Zadnikova et al. [28] 1987 | Parallel RCT Location: Prague | 46 N (32 T/14 C) | n.d | Premature infants with diarrhea | BC antibodies (6 times daily) | Conventional treatment (i.e., diet, rehydratation, and antibiotics) | 5 days | Number and quality of stool and presence of bacterial pathogens in stool | None | BC antibodies group had a significantly lower frequency of bacterial pathogens in stools (28% vs. 80%; p < 0.05), but BC antibodies had no effect on number and quality of stool |
Zadnikova et al. [28] 1987 | Parallel RCT Location: Prague | 39 N (24 T/15 C) | n.d | Full-term infants with diarrhea | BC antibodies (6 times daily) | Conventional treatment (i.e., diet, rehydratation, and antibiotics) | 5 days | Number and quality of stool and presence of bacterial pathogens in stool | None | BC antibodies group had a significantly lower frequency of bacterial pathogens in stools (30% vs. 80%; p < 0.05), but BC antibodies had no effect on number and quality of stool |
Davidson et al. [43], 1989 | Parallel RCT Location: Australia | 120 N (55 T/65 C) | 3–15 months | Infants admitted to the hospital | HBC (50 ml/d) | Infant formula | 10 days | Rotavirus diarrhea and length of hospital stay | None | HBC protected susceptible children against rotavirus infection (100% vs. 86%; p < 0.01), but the mean length of hospital stay was similar in both groups (HBC 4.4 days, control 3.4 days) |
Rump et al. [36], 1992 | Single-arm pilot CT Location: Germany | 37 N (31 M/6 F) | 1–54 | Patients with AIDS-associated chronic diarrhea | BCI (10 g/day) | - | 10 days | Frequency and duration of diarrhea and stool pathogens | Nausea and flatulence | BCI decreased frequency and quantity of diarrhea in 76% of patients, stool pathogens disappeared following BCI therapy, and diarrhea recurred in 32.4% of patients in the first 10 days after the end of therapy |
Plettenberg et al. [37], 1993 | Single-arm CT Location: Germany | 18 N (18 M) | 26–58 | HIV-positive patients with chronic diarrhea | BCI (10 g/d) | - | 10 days | Stool frequency | None | BCI led to complete (40%) or partial remission (reduction in the frequency of diarrhea ≤ 50%) (24%) of diarrhea |
Okhuysen et al. [44], 1998 | Parallel RCT Location: US | 16 N (5 T/6 C) | 18–45 | Healthy subjects challenged with Cryptosporidium parvum | BACI (10 g three times a day) | Nonfat milk | 5 days | Diarrhea | None | HBC was associated with a trend toward less diarrhea in comparison with placebo group (− 36% vs. 11%; p = 0.08) |
Okhuysen et al. [44], 1998 | Parallel RCT Location: US | 16 N (5 T/6 C) | 18–45 | Healthy subjects challenged with Cryptosporidium parvum | Reinforced BACI (20 g three times a day) | Nonfat milk | 5 days | Diarrhea | None | Reinforced BACI had no significant effect on diarrhea |
Casswall et al. [34], 1998 | Parallel RCT Location: Bangladesh | 24 N (12 T/12 C) | 4–29 month | H. pylori-positive infants | HBCI (1 g/day) | Non-immunized BC (1 g/day) | 1 month | H. pylori infection | n.d | HBCI did not eradicate H. pylori infection in infants |
Sarker et al. [45], 1998 | Parallel RCT Location: Bangladesh | 80 N (40 T/40 C) (80 M) | 4–24 month | Children with rotavirus diarrhea | HBCI (10 g/d) | Milk powder | 4 days | Stool output, stool frequency, duration of diarrhea, and presence of rotavirus in stool | None | HBCI significantly reduced stool output, stool frequency, and total duration of diarrhea (p < 0.05) and resulted in greater recovery (number, 33 vs. 21; p = 0.001) and earlier clearance of rotavirus from stool (mean day, 1.5 vs. 2.9; p < 0.001) |
Huppertz et al. [46], 1999 | Parallel RCT Location: Germany | 27 N (13 T/14 C) (13 M/14 F) | 1 month–18 years | Children with diarrhea caused by E. coli | BC (7 g three times a day) | Gelatin | 14 days | Stool frequency | None | BC significantly reduced stool frequencies (mean reduction, 2 ± 2 vs. 1 ± 3; p = 0.027) |
Khan et al. [16], 2002 | Parallel RCT Location: UK | 14 N (8 T/6 C) (8 F/6 M) | 16–75 | Patients with mild to moderately severe distal colitis | BC enema (100 ml twice daily) + mesalazine (1.6 g ⁄ day) | Bovine serum albumin + mesalazine (1.6 g ⁄ day) | 4 wks | Bowel symptoms: patient well-being, abdominal pain, rectal bleeding, anorexia ⁄ nausea, bowel frequency, stool consistency, and abdominal tenderness | None | BC enema significantly improved bowel symptoms score (mean change, − 2.9 (95% CI; − 0.3, 5.4) vs. 0.5 (95% CI; 2.4, + 3.4)) and inflammation |
Tawfeek et al. [47], 2003 | Parallel RCT Location: Iraq | 59 N (30 T/29 C) (30 M/29 F) | n.d | Healthy infants | Standard formula plus HBCI (polyvalent) (0.5 g/kg/d) | Milk formula without immunoglobulin | 7 days | Diarrheal morbidity and isolation of E.coli in stool | None | HBCI supplementation was associated with reduction in diarrheal morbidity (a lower incidence of diarrhea (1.9 ± 1.1 vs. 3.5 ± 2.6; p < 0.01), lower number of stools per day (3.3 ± 1.3 vs. 6.6 ± 1.4; p < 0.01), and shorter duration of diarrhea (4.5 ± 3.6 vs. 6.5 ± 4.3; p < 0.01)) The isolation of E. coli was positive in 14% of stool cultures in HBCI and 50% in control group |
Tawfeek et al. [47], 2003 | Parallel RCT Location: Iraq | 54 N (25 T/29 C) (28 M/26 F) | n.d | Healthy infants | Standard formula plus HBCI (monovalent) (0.5 g/kg/d) | Milk formula without immunoglobulin | 7 days | Diarrheal morbidity and isolation of E.coli in stool | None | HBCI supplementation had no significant effect on incidence of diarrhea and duration of diarrhea The isolation of E. coli was positive in 40% of stool cultures in HBCI and 50% in control group |
Tawfeek et al. [47], 2003 | Parallel RCT Location: Iraq | 52 N (23 T/29 C) (25 M/27 F) | n.d | Healthy infants | Standard formula plus BCI (0.5 g/kg/d) | Milk formula without immunoglobulin concentrate supplementation | 7 days | Diarrheal morbidity and isolation of E.coli in stool | None | BCI supplementation had no significant effect on incidence and duration of diarrhea The isolation of E. coli was positive in 46% of stool cultures in HBCI and 50% in control group |
Florén et al. [38], 2006 | Single-arm CT Location: Nigeria | 30 N (15 M/15 F) | 20–56 | Patients with HIV-associated diarrhea | BCP (50 g two times a day) | - | 4 wks | Stool evacuations | None | BC decreased stool evacuations per day (7.09 ± 2.7 to 1.39 ± 0.5; p < 0.01) |
Kaducu et al. [42], 2011 | Parallel RCT Location: Northern Uganda | 87 N (45 T/42 C) (60 F/27 M) | ≥ 18 | Patients with HIV-associated diarrhea | BC (50 g twice a day) + standard anti-diarrhea treatment | Standard anti-diarrhea treatment | 4 wks | Daily stool frequency | n.d | BC significantly decreased daily stool frequency (79% vs. 58%; p < 0.001) |
Otto et al. [15], 2011 | Parallel RCT Location: Australia | 30 N (15 T/15 C) | 18–40 | Healthy adults | HBC with sodium bicarbonate (400 mg three times a day) | Lactose | 7 days | Diarrhea, abdominal pain, and isolation of E. coli in stool | None | HBC was significantly effective in protecting against the development of diarrhea caused by ETEC (volunteers with diarrhea, 7% vs.73%; p = 0.0005) and lowering abdominal pain (0% vs. 33%;p = 0.04), but HBC had no significant effect on the number of diarrheal stools and the viability of E.coli |
Otto et al. [15], 2011 | Parallel RCT Location: Australia | 29 N (14 T/15 C) | 18–40 | Healthy adults | HBC without sodium bicarbonate (200 mg three times a day) | Lactose | 7 days | Diarrhea, abdominal pain, and isolation of E.coli in stool | None | HBC was significantly effective in protecting against the development of diarrhea caused by ETEC (volunteers with diarrhea, 36% vs. 86%; p = 0.02) and lowering abdominal pain (14% vs. 36%;p = 0.04), but HBC had no significant effect on the number of diarrheal stools and the viability of E.coli |
Otto et al. [15], 2011 | Parallel RCT Location: Australia | 29 N (14 T/15 C) | 18–40 | Healthy adults | HBC with sodium bicarbonate (400 mg three times a day) | Lactose | 7 days | Diarrhea, abdominal pain, and isolation of E.coli in stool | None | HBC was significantly effective in protecting against the development of diarrhea caused by ETEC (volunteers with diarrhea, 14% vs.86%; p = 0.0004) and lowering abdominal pain (0% vs. 36%;p = 0.04), but HBC had no significant effect on the number of diarrheal stools and the viability of E.coli |
Otto et al. [15], 2011 | Parallel RCT Location: Australia | 29 N (14 T/15 C) | 18–40 | Healthy adults | HBC without sodium bicarbonate (400 mg three times a day) | Lactose | 7 days | Diarrhea, abdominal pain, and isolation of E.coli in stool | None | HBC was significantly effective in protecting against the development of diarrhea caused by ETEC (volunteers with diarrhea, 20% vs. 86%; p = 0.007) and lowering abdominal pain (0% vs. 36%; p = 0.02), but HBC had no significant effect on the number of diarrheal stools and the viability of E.coli |
Balachandran et al. [20], 2016 | Parallel RCT Location: Northern India | 86 N (43 T/43 C) (48 M/38 F) | ≤ 96 h | VLBW infants | Enteral BC (1.2–2 g four times a day) | Placebo | 21 days | NEC occurrence, mortality and NEC clinical signs: abdominal distension, vomiting, pre-feed significant gastric residuals, blood in stool and ileus | None | BC supplementation showed no significant differences in the occurrence of NEC, mortality and NEC clinical signs: abdominal distension, vomiting, pre-feed significant gastric residuals, blood in stool and ileus |
Saad et al. [18], 2016 | Single-arm CT Location: Egypt | 160 N (81 M/79 F) | 1–6 | Children with recurrent URTI and/or diarrhea | BC | - | 4 wks | Episodes of diarrhea and frequency of hospitalization | Skin rashes, itching and diarrhea | BC significantly decreased episodes of diarrhea after 2 months (− 2.4; p < 0.001) and 6 months (− 2.2; p < 0.001) and number of hospital admissions (p < 0.001) |
Gaensbauer et al. [40], 2017 | Parallel RCT Location: Guatemala | 301 N (154 T/147 C) (169 M/147 F) | 6–35 months | Infants with acute non bloody diarrhea | BC and hyperimmune hen’s egg (7 g/d) | Hypoallergenic amino acid-based infant formula | 3 days | Diarrhea duration | None | Combination of BC and hyperimmune hen’s egg had no significant effect on duration of diarrhea |
Eslamian et al. [17], 2018 | Parallel RCT Location: Iran | 62 N (32 T/30 C) (35 M/27 F) | > 18 | ICU-hospitalized patients | Enteral formula plus BC powder (20 g three times a day) | Isocaloric enteral formula plus maltodextrin | 10 days | Abdominal distention, vomiting, diarrhea, constipation, and mortality | None | The incidence of diarrhea was significantly lower in BC group (9%) than in control group (33%), but there were no significant differences in abdominal distention, vomiting, constipation, and mortality at ICU between BC and control group |
Barakat et al. [48], 2019 | Parallel RCT Location: South Africa | 160 N (80 T/80 C) (83 M/77 F) | 6 months to 2 years | Children with acute diarrhea | BC plus standard therapy of acute diarrhea (3 g/d) | Placebo plus standard therapy of acute diarrhea | 1 wk | Frequency of vomiting and diarrhea | None | BC group had a significantly lower frequency of vomiting (10% vs. 71.25%; p < 0.0001), diarrhea (0% vs. 12.50%; p = 0.001), and earlier time of disappearance of vomiting and diarrhea |
Rathe et al. [19], 2019 | Parallel RCT Location: Denmark | 62 N (30 T/32 C) (32 M/30 F) | 1–18 | Children with newly diagnosed ALL | BC (0.5–1 g/kg/d) | Isocaloric whole-milk powder enriched with whey protein isolate powder | 4 wks | Intestinal mucositis, abdominal pain, and diarrhea | None | BC had no significant effect on intestinal mucositis, abdominal pain, and diarrhea |
Sanctuary et al. [35], 2019 | Cross-over RCT Location: US | 8 N (8 T/8 C) (7 M/1 F) | 3.9–10.9 | Children with ASD and GI comorbidities | BCP (0.15 g/lbw/d) + probiotics (Bifidobacterium infantis) | BCP only | 5 wks | Constipation, diarrhea, pain, gas frequency, stool consistency, and gut microbiota | Gassiness and stomachache | BCP significantly reduced frequency of pain associated with bowel movements (-0.94; P = 0.044), diarrhea (-0.88; P = 0.021) and stool consistency (1.06; P = 0.042), BCP had no significant effect on gut microbiota |
Bierut et al. [41], 2020 | Parallel RCT Location: Southern Malawi | 275 N (138 T/137 C) (162 M/113 F) | 9 months | Healthy infants | BC (5.7 g) and dried whole egg powder (4.3 g twice daily) | Isoenergetic unfortified corn/soy flour (15 g) | 3 months | Episodes of diarrhea and fecal microbiota | None | Combination of BC and egg supplementation had no significant effect on episodes of diarrhea and β-diversity of fecal microbiota |