NHANES Data Links Iron Deficiency to Risk of Depression in Young Men

New data from an analysis of a nationwide survey suggests iron deficiency could play a role in likelihood of depression among young adult males.

An analysis of data from the National Health and Examination Survey (NHANES) from 2017 through 2020, results of the study suggest ferritin, serum iron, and transferrin deficiencies were all associated with an increased likelihood of depression in young adults, but investigators note this association was only observed in young men and not women.¹

“To the best of our knowledge, this is the first study to include three measurements of iron deficiency to examine their associations with young adult depressive symptoms and depression as well as examine sex differences,” wrote investigators.¹

In recent decades, a renewed emphasis on addressing stigma and combatting improving treatment have revolutionized management and discussions around mental health, including depression. Citing previous research suggesting iron deficiency could contribute to depression^2,3, the current study was led by Cherry Y. Leung, PhD, RN, and Minjung Kyung, both of the Department of Community Health Systems in the School of Nursing at University of California San Francisco (UCSF), to investigate how associations between a trio of measurements for iron with Patient Health Questionnaire-9 (PHQ-9) depressive symptoms and depression among young adult males and females.¹

Supported by the National Institutes of Health National Institute of Nursing Research, the UCSF duo leveraged data from the 2017–2018 and 2019–2020 NHANES datasets. From these survey cycles, investigators obtained data from 15,560 survey responses, including 1281 from adults aged 18-25 years.¹

Following exclusion of those with inflammatory disorders and those without complete data, 917 young adults were identified for inclusion in the study. Among this cohort, 90 had depression and 827 did not. The mean depressive symptom score for the cohort was 3.5 (Standard Deviation [SD], 4.3), with mean scores of 2.9 (SD, 3.9) and 4.1 (SD, 4.7) for males and females, respectively.¹

The primary outcome of interest for the study was presence of depressive symptoms over the past two weeks, which was assessed using the PHQ-9. For the purpose of analysis, depression was defined as having a PHQ-9 score of 10 or more. Investigators pointed out multivariable Poisson and logistic regression models, with adjustment for several demographic and clinical variables, were used to assess the prevalence of depression and associations between iron deficiency and depressive symptoms.¹

Initial analysis revealed more females (12.5%) than males (6.8%) had PHQ-9 scores meeting the criteria for depression. Results also indicated more females than males met the criteria for the 3 measurements of iron deficiency: ferritin (168 females, 13 males), serum iron (154 females, 49 males), and transferrin saturation (120 females, 22 males).¹

After adjustment for sex, age, race/ethnicity, ratio of family income to poverty, mental health professional, BMI, physical activity, dietary iron intake, and dietary supplements, results suggested serum iron deficiency (β = 0.22, P < .01) and transferrin deficiency (β = 0.33, P < .001) were associated with more PHQ-9 depressive symptoms.¹

Further analysis indicated males with ferritin (Odds Ratio [OR], 14.13; 95% Confidence Interval [CI], 1.51-132.21; P < .05), serum iron (OR, 4.84; 95% CI, 1.02-22.92; P < .05), and transferrin deficiency (OR, 13.79; 95% CI, 3.59-53.06; P < .001), compared to no deficiency, were associated with a higher odds of PHQ-9 depression. In contrast, ferritin deficiency was associated with a reduced likelihood of PHQ-9 depression when compared to no ferritin deficiency among females (OR, 0.34; 95% CI, 0.11-0.97).¹

Before concluding, investigators called attention to limitations within their study to consider. These included, but were not limited to, the cross-sectional nature of the study design, a low prevalence of depression relative to previously published estimates, reliance of self-reported data, and potential for confounding as a result of inflammation or inflammatory disorders.¹

“It is crucial that future studies examine depression stratified by sex and the differing risk factors, including biological, behavioral, and social determinants,” investigators wrote.¹ “Additionally, our study highlights the need for more resources allocated to young adults, especially females, to identify both iron deficiency and other modifiable nutritional risk factors, including supplement intake, related to depression, as iron deficiency can be prevented with adequate nutritional intake.”

References:

1. Leung CY, Kyung M. Associations of iron deficiency and depressive symptoms among young adult males and Females: NHANES 2017 to 2020. Prev Med Rep. 2023;37:102549. Published 2023 Dec 12. doi:10.1016/j.pmedr.2023.102549
2. Mills NT, Maier R, Whitfield JB, et al. Investigating the relationship between iron and depression. J Psychiatr Res. 2017;94:148-155. doi:10.1016/j.jpsychires.2017.07.006
3. FastStats - depression. Centers for Disease Control and Prevention. November 6, 2023. Accessed January 17, 2024. https://www.cdc.gov/nchs/fastats/depression.htm.