The effect of zinc-biofortified rice on zinc status of Bangladeshi preschool children: a randomized, double-masked, household-based, controlled trial

Abstract

Background Zinc biofortification of rice could sustainably improve zinc status in countries where zinc deficiency is common and rice is a staple, but its efficacy has not been tested. Fatty acid desaturases (FADS) are putative new zinc status biomarkers. Objective Our objective was to test the efficacy of zinc-biofortified rice in preschool-aged children with zinc-deficiency. Our hypothesis was that consumption of zinc-biofortified rice would increase plasma zinc concentration (PZC). Design We conducted a 9-month, double-masked, intervention trial in 12–36 month-old rural Bangladeshi children, most of whem were who were zinc-deficient (PZC < 70 µg/dL) and stunted (n = 520). The children were randomized to receive either control rice (CR) or zinc-biofortified rice (BFR) provided in cooked portions to their households daily, with compliance monitoring. The primary outcome was PZC. Secondary outcomes were zinc deficiency, linear growth, infection-related morbidity, FADS activity indices, intestinal fatty acid binding protein (I-FABP) and fecal calprotectin. We applied sparse serial sampling for midpoint measures and analyzed data by intention-to-treat using mixed-effects models. The trial was registered under NCT03079583. Results At baseline, median (IQR) PZC was 60.4 (56.3–64.3) µg/dL, 78.1% of children were zinc deficient and 59.7% were stunted. Mean ± SD daily zinc intakes from the CR and BFR during the trial were 1.20 ± 0.34 and 2.22 ± 0.47 mg/day, respectively (P < 0.001). There were no significant time-by-treatment effects on PZC, zinc deficiency prevalence, FADS activity, I-FABP or fecal calprotectin (all P > 0.05). There was a time-treatment interaction for height-for-age z scores (P < 0.001) favoring the BFR group. The morbidity longitudinal prevalence ratio (LPR) (95% CI) was 1.08 (1.05,1.12) comparing the BFR and CR groups, due to more upper respiratory tract illness in the BFR group. Conclusions Consumption of zinc-biofortified rice for 9 months providing ∼1 mg of additional zinc daily to Bangladeshi children did not significantly affect PZC, prevalence of zinc deficiency or FADS activity. Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT03079583

Existing knowledge on Zn status biomarkers (1963–2021) with a particular focus on FADS1 and FADS2 diagnostic performance and recommendations for further research

“…No association of serum Zn with dietary or supplemental Zn intakes was seen in the NHANES study even though 8% of participants had serum Zn levels below the cut-off for Zn deficiency ( 14 ). No changes in PZC were seen after the consumption of Zn biofortified grains and foods either in children or adults ( 15 – 18 ). Additionally, PZC does not respond to short-term exposure to Zn fortified foods.…”

“…A recent double-blind randomized controlled trial found no changes in FADS1 nor FADS2 activities in Bangladeshi preschool children, fed Zn biofortified rice diets (providing 1 mg of Zn/day) for 9 months ( 18 ). Several reasons might explain the lack of interaction between desaturases activity and dietary Zn intake.…”

Zinc Fortification: Current Trends and Strategies

“…Plasma fatty acid concentrations, and estimates of fatty acid desaturase activities, based on the ratios of product to precursor omega-6 fatty acids, have been identified as novel biomarkers of zinc status due to a strong correlation with plasma zinc concentrations [ 59 , 60 ]. Additionally, zinc may be more efficiently directed towards fatty acid desaturation when taken with food compared with zinc taken in the fasted state [ 49 ].…”

“…Compared with post-harvest fortification, the lack of a need for special processing reduces the cost of biofortification after the initial crop development. Recent crops targeted for zinc biofortification include wheat [ 36 , 79 , 80 ], rice [ 60 , 81 , 82 ], maize [ 27 , 83 ], pearl millet [ 25 , 84 ], beans [ 43 , 85 ], and bananas [ 86 ].…”

Zinc agronomic biofortification of staple crops may be a cost-effective strategy to alleviate zinc deficiency in Ethiopia

“…A limited number of studies have tested the efficacy and effectiveness of Zn agronomically biofortified cereal flours for improving human Zn status ( 29 – 31 ). While dietary Zn intakes were increased, there is mixed evidence on the effect on biomarkers of Zn status.…”