Probiotic Supplementation and Micronutrient Status in Healthy Subjects: A Systematic Review of Clinical Trials

Nutrients
Q1
Aug 2021
Citations:44
Influential Citations:3
Systematic Reviews / Meta-Analyses
87
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Methods
Healthy humans across age groups including children and adults; sexes mixed; some subgroups included iron-deficient athletes and vegan subjects; study designs included randomized double-blind placebo-controlled trials, cross-over trials, open-label randomized multicenter trials, randomized trials without blinding, and non-randomized trials.
Intervention
Regimens varied across 14 trials: probiotic or synbiotic supplements delivered via yogurt/fermented milk, fortified beverages, capsules or tablets, or powders; single- and multi-strain products used. Examples include synbiotic tablet with L. plantarum, L. acidophilus, B. infantis, B. lactis and FOS (45 × 10^9 CFU) daily for 10 weeks; L. reuteri NCIMB30242 supplementation (dose not stated); probiotic yogurt containing L. paracasei DN-114 001 (3.6 × 10^8 CFU/g) with 100 g/day in weeks 1–2 and 200 g/day in weeks 3–4; yogurt containing L. acidophilus La1 (5 × 10^9 CFU) in two cups daily for several weeks; L. plantarum 299v capsules (~10^10 CFU per capsule) for four weeks; VSL#3 probiotic mixture (112 billion lyophilized bacteria) used in older subjects; L. helveticus fermented milk (≥10^8 CFU/mL) in geriatrics; synbiotic regimens in children; and other conventional yogurt–based probiotics. Durations ranged from 7 days to 6 months; daily intake was common.
Results
Probiotic intake in healthy subjects may improve micronutrient status, notably vitamin B12 and folate, calcium, zinc and iron. Two of three folate/B12 trials reported improvements; calcium status improved in multiple pediatric and postmenopausal studies; zinc status improved in some trials, particularly with zinc co-supplementation; iron status improvements were variable, with some ferritin and Hb changes and evidence for increased non‑heme iron absorption with certain Lactobacillus strains; vitamin D status improved in some cases (e.g., L. reuteri NCIMB30242 and multi-strain regimens in bariatric patients) but not in others (e.g., pregnant women with HN019 synbiotic); effects appear strain-, dose-, duration-, and baseline-nutrient-status-dependent. Additional well-designed double-blind randomized controlled trials are needed to identify the most effective strains and regimens.
Limitations
High heterogeneity across studies (age, strains, doses, durations, administration form) and predominantly moderate-to-high risk of bias; only one study had low risk of bias; several trials nonrandomized or lacking blinding; small to moderate sample sizes; limited dietary control; many studies conducted in Europe; insufficient gut microbiota data to explain mechanisms; attribution to specific strains in multi-strain products is difficult.

Abstract

Micronutrient deficiencies are a worldwide public health concern. Emerging evidence supports the ability of probiotics to enhance micronutrient status, which could aid in the prevention of non-communicable disease-associated malnutrition. This system...