What’s in a number? Zinc deficiency cut-offs and bringing the micronutrient data community together

Adequate intake of zinc, an essential mineral, is critical for proper immune function, reproductive health, and children’s growth and development. Children under 5 years old who do not get enough zinc are at significantly higher risk of diarrhea and other infectious diseases.  Today, available data suggests wide-spread global levels of zinc deficiency with a 2020 review reporting zinc deficiency in 23 of 25 low- and middle-income countries with national data in any vulnerable age group[1],[2]. Unfortunately, and as a result, an estimated 116,000 child deaths are attributed to zinc deficiency each year. 

Assessing the prevalence of zinc deficiency in a population is essential for focusing evidence-based advocacy efforts and implementing interventions that prevent deaths and adverse health outcomes. For many micronutrients, including zinc, a biomarker (i.e., serum zinc concentration) is the best way to assess the prevalence of deficiency in a population.

A frequent matter of debate is where one draws the cut-off between deficient and adequate levels of a biomarker. Ideally, there is a value that corresponds to the onset of clinical signs of deficiency. However, there is some inherent variability in what that value is between individuals and population groups that make this approach challenging.  An alternative method is to set the cut-off by applying a statistical approach based on the distribution of values from a healthy population. For example, one could define “increased risk of deficiency” as those who fall below the 2.5th percentile.

For zinc, internationally recognized reference cut-offs were developed by International Zinc Nutrition Consultative Group (IZiNCG) nearly 20 years ago using serum zinc data from the US National Health and Nutrition Examination Survey (NHANES). These cut-offs were used as part of the 2016-18 India Comprehensive National Nutrition Survey (ICNNS), one of the largest surveys of micronutrient status ever conducted. They found that 31% of adolescents, 16% of school-aged children, and 17% of preschool-aged children were zinc deficient. The ICNNS findings indicate that approximately 38 million Indian children and 71 million Indian adolescents have an elevated risk of zinc deficiency.

This year, Pullakhandam, et al. published new serum zinc concentration reference cut-offs for the Indian population that are 10-18 ug/dL lower than the IZiNCG recommended cut-offs (65-70 ug/dL), resulting in fewer people being categorized as zinc deficient. These newly proposed cut-offs were derived by applying a statistical-based approach to the presumably healthy children included in the ICNNS. After applying these new, lower cut-offs, the authors concluded that zinc deficiency is not a serious public health problem in any state or any child age group in India.

Commentaries from IZiNCG and the Forum’s Micronutrient Data Innovation Alliance (DInA)  about Pullakhandam et al.’s approach have now been published in European Journal of Clinical Nutrition. The commentary from IZiNCG highlights technical limitations with Pullkahandam, et al.’s approach and questions whether children in the reference population can be considered truly “healthy.” Some of the children categorized as healthy had some degree of undernutrition and may have been at least mildly zinc deficient, which would result in a lower than desirable cut-off.

The commentary from DInA discusses the public health decision-making perspective. If a micronutrient deficiency can cause severe disease, a higher cut-off may be warranted to limit the number of people categorized as sufficient who are truly deficient. By contrast, if the intervention needed to prevent or treat the micronutrient deficiency is expensive, a lower cut-off may be appropriate to limit the number of people categorized as deficient who are not. Given that the consequences of zinc deficiency can be severe (e.g. increased risk of infectious morbidity, impaired linear growth) and effective, low-cost preventive interventions are available, one might argue for a higher serum zinc concentration cut-off.

While it’s important to reach consensus on internationally agreed upon cut-off values, populations across the world are inherently heterogeneous, and new data may shift these values.  However, it is critical that data on micronutrient status be collected using standardized methods and published with the distribution statistics from the biomarker (in addition to the percent deficient).  

This expert exchange raises a pertinent issue facing the micronutrient and data global community on the importance of coordination and knowledge exchange. The micronutrient data landscape faces multiple challenges – first of which is the insufficient data and quality data –in addition to inconsistent standards, such as agreement cutoffs. This shows the multiple fronts where these challenges can be opportunities to come together. The comparability of data, for example, directly across studies and geographies can help facilitate tracking progress in addressing zinc deficiency globally and guide the allocation of the limited resources for micronutrient data and interventions. 

To support the micronutrient community on these types of issues, the Forum’s Micronutrient Data Innovation Alliance will seek to improve the micronutrient and large-scale food fortification data availability, accessibility, and use to support the needs of national decision-makers. Through its diverse network of members, DInA will provide a platform for collaboration between global and national actors to drive impactful agendas to reduce micronutrient deficiency. DInA is open to all interested stakeholders, and you can join us by becoming a member today and signing up for its newsletter.

[1] Gupta S, Brazier AKM, Lowe NM. Zinc deficiency in low‐and middle‐income countries: prevalence and approaches for mitigation. J Hum Nutr Diet. 2020;33(5):624–43. 

[2] The WHO-recommended threshold for defining zinc deficiency as a public health issue is 20% or higher population prevalence

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