Table 2.
A summary of prebiotic interventions among humans to evaluate their effectiveness and efficacy in altering mineral absorption, bone health outcomes, and intestinal parameters
| Prebiotic/substance | Treatment dose and duration | Study design | Human population description | Measures/analyses | Findings | Abbreviated reference |
|---|---|---|---|---|---|---|
| FOS | 8 g/day FOS or maltodextrin-sucrose (control), for 3 months | Randomized, double-blind parallel design; 2 daily doses of 200 mL of tap water + 4 g FOS or maltodextrin-sucrose | Korean postmenopausal women (n = 26), mean age 60 years and ~ 12 years since menopause | Apparent Ca, P, Fe and Zn absorption; BMD by DXA; bone biomarkers | FOS increased apparent absorption of Ca and Fe but not P and Zn; urinary Ca excretion was not different between groups; serum alkaline phosphatase decreased among FOS group compared to controls | Kim Y, et al. 2004 (Ref. 126) |
| FOS, lactose | 0 or 4 g/day FOS in milk, for 12 weeks | Parallel design; milk consumed as 2 servings per day; 2 groups: Ca and vit-D fortified milk (1000–1200 mg/day Ca and 15 ug/day vit-D) + FOS (4 g/day) and regular milk (500 mg/day), | Premenopausal (n = 136, mean age 41 years) and postmenopausal (n = 121, mean age 59 years) women; Chinese | Bone biomarkers; vit-D status | Postmenopausal women: Ca and vit-D milk + FOS significantly reduced bone resorption (lower CTx) and improved vit-D status; premenopausal women: vit-D status improved but markers of bone turnover were unchanged | Kruger M, et al. 2016 (Ref. 61) |
| GOS | 0 or 20 g/day of transgalactooligosaccharides via 200 mL of yogurt, for 9 days | Placebo-controlled crossover design, DI; sucrose was added to the control yogurt; gradual dose increase from 10 g/day to 20 g/day over 5 days; 19 day washout; Ca intake not reported | Women, 5 + years postmenopausal (n = 12), age 55–65 years | True Ca absorption | GOS increased true Ca absorption; no observable increase in urinary Ca excretion | van den Heuvel E, et al. 2000 (Ref. 27) |
| GOS | 0, 5, or 10 g/day GOS, for 3 weeks | Randomized, double-blind, parallel design, DI; GOS consumed in two milk-based smoothies per day | Adolescent girls (n = 31), age 10–13 years | Fractional Ca absorption; gut microbial community by PCR-DGGE; bifidobacteria by rt-qPCR | 5 g/day GOS group showed the greatest increase in Ca absorption; no dose–response effect observed on Ca absorption; DGGE profiles did not differ by treatment but bifidobacteria content was also increased with 5 g/day GOS | Whisner C, et al. 2013 (Ref. 121) |
| GOS, polydextrose (PDX) | 4 g GOS–PDX mix/L of formula, for 2 weeks | Randomized, double-blind, parallel design, DI; non-prebiotic formula, prebiotic (GOS + PDX in a 1:1 ratio at 4 g/L), human milk + drops of vit A, C, and D | Infants (n = 74), age 56–70 days | Fractional Ca absorption; serum 25-OH vit-D | Human milk resulted in greater total fractional Ca absorption than both formulas; addition of prebiotic did not improve Ca absorption relative to non-prebiotic supplemented formula; Ca absorption efficiency was higher in human milk-fed group | Hicks P, et al. 2012 (Ref. 120) |
| Inulin | 4 formulas with 0.0, 0.75, 1.00, or 1.25 g/day inulin, for 35 days | Randomized, parallel design; 7 day diet run-in, 14 day treatment followed by a 14 day washout period | Healthy, formula-fed infants from Malaysia (n = 36), age 5–12 months | Apparent Ca, Fe, Zn, Mg and Cu absorption; fecal SCFA | 1 g/day inulin increased Fe absorption and retention; 0.75, 1, and 1.25 g/day inulin increased Mg absorption and retention; 0.75 g/day inulin improved Zn absorption and retention; Ca and Cu were unaffected by inulin; SCFAs were not influenced by inulin supplements | Yap K, et al. 2005 (Ref. 119) |
| Inulin | 8 g/day of inulin Synergy1® or sucrose (control), for 3 weeks | Placebo-controlled crossover design, DI; 2 week washout; treatments mixed with 8 oz. Ca-fortified orange juice in morning and evening; participants maintained on diets with 1200 mg/day Ca during study period | Girls, varied race/ethnicity (n = 54), age 10–15 years | Fractional Ca absorption | Ca absorption improved with Synergy1®; those with lower Ca absorption on placebo received the greatest benefit from Synergy1® | Griffin I, et al. 2003 (Ref. 51) |
| Inulin | 10 g/day Synergy1® or maltodextrin (control), for 6 weeks | Randomized, double-blind crossover design, DI; 6-week washout period; measures at 0, 3 and 6 weeks | Postmenopausal women (n = 15), ≥ 10 years past menopause; mean age 72 years | Fractional Ca and Mg absorption; BMD by DXA; bone biomarkers | Inulin increased Ca and Mg fractional absorption; urinary deoxypyridinoline cross-links and osteocalcin concentrations increased across the 6 weeks of inulin supplementation; two-thirds of the cohort responded positively to inulin with regard to mineral absorption and response was predicted by baseline lumbar BMD | Holloway L, et al. 2007 (Ref. 52) |
| Inulin | 0 or 9 g/day of Synergy1®, for 3 weeks | Randomized, double-blind crossover design, SI; Ca-fortified cereal and 1500 mg/day Ca intakes; 2 week washout period | Adolescent girls (n = 14), age 11–13 years; mixed race/ethnicity cohort | Fractional Ca absorption and retention | No significant differences in Ca absorption and retention were observed between treatments | Martin B, et al. 2010 (Ref. 125) |
| Inulin | 0 or 8 g/day of Synergy1®, for 12 months | Parallel design, DI; inulin or maltodextrin control mixed with 180–240 mL of Ca-fortified orange juice and consumed at breakfast | Girls and boys, varied race/ethnicity (n = 95), age 9–13 years | Fractional Ca absorption at baseline, 8 weeks and 12 months; DXA at baseline and 12 months; genotyping | Ca absorption was greater at 8 weeks and 12 months in inulin group; whole-body BMD and BMC were greater at 12 months; FF and Ff Foc1 genotypes had greater responses to inulin compared to control | Abrams S, et al. 2005 (Ref. 47) |
| Inulin | 0 or 8 g/day of Synergy1®, for 12 months | Parallel design, DI; inulin or maltodextrin control mixed with 180–240 mL of Ca-fortified orange juice and consumed at breakfast | Girls and boys, varied race/ethnicity (n = 48), age 9–13 years | Fractional Ca absorption; urinary mineral excretion; responder (> 3% increase in Ca absorption) status | 67% of subjects were classified as “responders;” responders at 8 weeks had greater BMC than non-responders at 12 months | Abrams S, et al. 2007a (Ref. 48) |
| Inulin | 0 or 8 g/day of Synergy1®, for 8 weeks | Parallel design, DI; kinetic modeling performed on responders; inulin mixed with 120 mL Ca + vit-D fortified orange juice; participants maintained on diets with 800–1000 mg/day Ca during study period | Women and men, varied race/ethnicity (n = 13), age 18–27 years | Fractional Ca absorption and kinetic modeling; responder (> 3% increase in Ca absorption) status | Inulin increased Ca absorption in the colon, as measured in “responders,” with colonic absorption defined as > 7 h | Abrams S, et al. 2007b (Ref. 49) |
| ITF, lactose | 1.75 g ITF/cup of fermented milk, for 2 weeks | Parallel design; matched for age, time after menopause, BMI and dietary calcium intake; 175 ml drink consumed at bedtime; mean habitual Ca intake of 906.4 ± 53.2 mg/day; 3 groups: fermented milk (f-milk), fermented milk supplemented with Ca (510 mg/cup) (f-milk + Ca), and fermented milk supplemented with Ca (510 mg/cup), ITF (1.75 g/cup) and caseinophosphopeptides (0.175 g/cup) (f-milk + Ca + ITF + CPP) | Women, 10.5 + years postmenopausal (n = 85), age 48–67 years | Bone biomarkers and hormones; serum minerals; urinary Ca and P | f-Milk, independent of Ca, ITF and CPP additions, decreased nighttime deoxypyridinoline excretion; urinary Ca and P increased during nights for the f-milk + Ca + IFT + CPP group which was attributed to greater intestinal absorption | Adolphi B, et al. 2009 (Ref. 59) |
| Lactose | 3 groups: milk + lactose, milk lacking lactose + glucose, water + Ca (control), for 6–10 weeks | Randomized crossover design, DI; study treatments were administered to normal-lactase or lactase-deficient males | Otherwise healthy, lactase-sufficient and lactase-deficient males (n = 15), age 22–32 years | Fractional Ca absorption | Milk + lactose among lactase-deficient males increased Ca absorption; Ca absorption did not differ among lactase-deficient and sufficient males when consuming milk + glucose | Griessen M, et al. 1989 (ref 30) |
| Lactose | 2 groups: kefir-fermented milk (1600 mg) + calcium bicarbonate (CaCO3, 1500 mg) or CaCO3 alone, for 6 months | Parallel design; included those with and without fracture | Women and men with osteoporosis (n = 40), age 64 + years | Bone biomarkers; BMD by DXA | Kefir with CaCO3 provided no additional benefit to Ca absorption; baseline bone turnover was most predictive of BMD changes at 6 months; kefir was a significant predictor of changes in BMD of the total hip | Tu M, et al. 2015 (Ref. 60) |
| Lactulose | 0, 5, and 10 g/day of lactulose dissolved in 100 mL of water with benzoic acid, for 9 days | Dose–response, placebo-controlled crossover design, DI; aspartame used as placebo control; 19 day washout | Women, 5 + years postmenopausal (n = 12), age 56–64 years | Fractional Ca absorption | Ca absorption increased dose-dependently but difference between 5 and 10 g was not significant; Ca absorption was significantly higher with 10 g lactulose relative to control; Ca excretion did not differ by treatment | van den Heuvel E, et al. 1999a (Ref. 37) |
| Oligofructose | 15 g/day of oligofructose or sucrose (control), for 9 days | Randomized, double-blind crossover design, DI; 19 day washout period; control and treatment were given in 100 mL of orange juice + standard breakfast containing 200 mg Ca | Healthy, male adolescents (n = 12), age 14–16 years | Fractional Ca absorption | Oligofructose increased fractional Ca absorption relative to control; no association was observed between Ca absorption and urinary Ca excretion | van den Heuvel E, et al. 1999b (Ref. 122) |
| Oligofructose and inulin | 8 g/day of oligofructose, Synergy1®, oligofructose + Synergy1®,or sucrose (control), for 3 weeks | Placebo-controlled crossover design, DI; 2 week washout; treatments mixed with 8 oz. Ca-fortified orange juice in morning and evening; participants maintained on diets with 1200–1300 mg/day Ca during study period | Girls, varied race/ethnicity (n = 59), age 11–14 years | Fractional Ca absorption; urinary mineral excretion | Ca absorption was significantly higher in the Synergy1® group; oligofructose consumption did not result in an improvement in Ca absorption relative to control | Griffin I, et al. 2002 (Ref. 50) |
| sc-FOS | 0 or 3.6 g/day sc-FOS, for 24 months | Randomized, double-blind crossover design; interventions provided as chewable chocolate-flavored supplements; 2 supplements taken per day; 3 groups: 800 mg/day Ca, 800 mg/day Ca + 3.6 g/day sc-FOS, or 9 g/day of maltodextrin (control) | Postmenopausal women (n = 300), age 45–75 years; non-osteoporotic; ~ 12–13 years since menopause | BMD by DXA; bone biomarkers; measurements at 0, 12 and 24 months | Ca alone and Ca + sc-FOS did not result in smaller BMD losses compared to maltodextrin control; of women with osteopenia, declines in BMD were smaller among Ca + sc-FOS group compared to maltodextrin; Ca alone and Ca + sc-FOS groups experienced greater declines in C-telopeptides of type I collagen at 12 months compared to maltodextrin; Ca + sc-FOS resulted in greater decline in osteocalcin when compared to maltodextrin at 24 months | Slevin M, et al. 2014 (Ref. 127) |
| sc-FOS | 10 g/day sc-FOS or sucrose (control), for 5 weeks | Randomized, double-blind crossover, design, SI; 3-week washout period; first 4 days 5 g/day sc-FOS at lunch, followed by 10 g/day sc-FOS delivered at lunch and dinner; first 23 d of study participants followed habitual diet, followed by controlled diets containing ~ 900 mg/day Ca, ~ 250 mg/day Mg and ~ 12 g/day fiber | Postmenopausal women (n = 12), > 2 years into menopause without hormone replacement; age 50–70 years | Fractional Ca absorption; bone biomarkers; vit-D metabolites and hormones | No significant difference in Ca absorption on sc-FOS vs. control; slightly higher Ca absorption observed in women > 6 years postmenopausal; urinary Ca excretion and bone turnover markers did not differ by supplement group; 1,25(OH)2D decreased slightly with sc-FOS relative to control but effect was not significant | Tahiri M, et al. 2003 (Ref. 123) |
| sc-FOS | 10 g sc-FOS or maltodextrin (control), daily for 8 days, followed by intermittent consumption up to 36 days | Randomized, double-blind crossover design, DI; 10 g sc-FOS split between two 5 g supplements consumed at breakfast and dinner; 12 day washout period; habitual Ca intake was 316–858 mg/day | Adolescent girls from the Netherlands (n = 14), age 12–14 years | Fractional Ca and Mg absorption; circulating bone biomarkers, vit-D metabolites and related hormones; measures taken at 8 and 36 days | Ca and Mg absorption were unaffected at 8 days; after 36 days, despite intermittent consumption, Mg absorption was improved; after 36 days no effect of sc-FOS was observed for Ca absorption, bone turnover markers or vitamin D metabolites | van den Heuvel E, et al. 2009 (Ref. 124) |
| SCF | Diets containing 0, 10, and 20 g/day of SCF, for 50 days | Placebo-controlled crossover design, SI; 50 day washout; all participants provided with multivitamin-mineral with 200 mg Ca and 400 IU vit-D | Women, 4 + years postmenopausal (n = 12), age 40–78 years | Bone Ca retention by Ca-41; bone biochemical markers | Both 10 and 20 g/day of SCF improved whole-body Ca retention in a dose-dependent manner; bone alkaline phosphatase was the only biochemical marker of bone turnover that changed during the intervention resulting in a significant increase with 20 g/day SCF | Jackman S, et al. 2016 (Ref. 44) |
| SCF | 0 and 12 g/day of SCF, for 3 weeks | Placebo-controlled crossover design (metabolic balance studies), DI; 7 day washout; Ca intake of 600 mg/day | Adolescent boys and girls, mixed race/ethnicity (n = 24), age 12–15 years | Fractional Ca absorption; calcium retention; bone biochemical markers and hormones were measured in urine or serum; phylogenetic diversity of bacterial communities by 16S rRNA sequencing | SCF significantly improved fractional Ca absorption but did not affect Ca retention; improvements in fractional Ca absorption were correlated with increases in Bacteroides, Butyricicoccus, Oscillibacter and Dialister genera but decreases in Actinomyces, Pseudomonas, and Other Erysipelotrichaceae genera; changes in biochemical markers of bone turnover were not observed | Whisner C, et al. 2014 (Ref. 42) |
| SCF | 0, 10, and 20 g/day of SCF, for 4 weeks | Placebo-controlled crossover design, DI; 3 week washout; Ca intake of 800 mg/day during test days | Adolescent girls, Caucasian (n = 28), age 11–15 years | Fractional Ca absorption; bone biomarkers and hormones; phylogenetic diversity of bacterial communities were determined using 16S rRNA sequencing; fecal pH and SCFA concentrations | 10 or 20 g/day SCF increased Ca absorption but the effect was not dose-dependent; diversity of fecal microbial communities increased with increasing SCF dose; increases in Ca absorption with 20 g/day were significantly correlated with increases in Clostridium and unclassified Clostridiaceae but microbes correlating with Ca absorption at this does were not consistent with those observed with 10 g/day SCF; SCFA did not differ by treatment but fecal pH was significantly lower with 20 g/day SCF when compared to 0 and 10 g/day treatments | Whisner C, et al. 2016 (Ref. 43) |
1,25(OH) 2 D 1,25 dihydroxy vitamin D, BMC bone mineral content, BMD bone mineral density, BMI body mass index, Ca calcium, CTx C-telopeptide of type I collagen, Cu copper, DI double-isotope method, DNA deoxyribose nucleic acid, DXA dual-energy X-ray absorptiometry, Fe iron, FOS fructooligosaccharides, GOS galactooligosaccharides, IF isoflavones, ITF inulin-type fructans, Mg magnesium, OVX ovariectomized, P phosphorus, PCR-DGGE polymerase chain reaction-density gradient gel electrophoresis, PDX polydextrose, rRNA ribosomal ribonucleic acid, RS resistant starch, rt-qPCR real-time quantitative polymerase chain reaction, sc-FOS short-chain fructooligosaccharides, SCFA(s) short-chain fatty acid(s), SI single-isotope method, vit-D vitamin D, Zn zinc