Circadian Light Hygiene Is Associated with Anemia Markers in Young Adults

Anemia remains a significant global health challenge, with wide-ranging impacts on morbidity and quality of life [1]. Hematological variables such as hemoglobin (HGB), hematocrit (HCT), and mean corpuscular hemoglobin (MCH) serve as critical biomarkers for assessing erythropoietic function and oxygen transport capacity. While aging, lifestyle factors, and environmental cues—including sleep patterns and light exposure—are well recognized to influence multiple physiological domains such as mood regulation, cognitive performance, metabolism, eating behavior, and immune function, there is a notable paucity of research investigating the relationship between light exposure, circadian light hygiene, and hematological variables or anemia-related markers. Circadian light hygiene can be defined as daily light exposure patterns, characterized by sufficient dynamic range and regularity to support circadian entrainment and prevent adverse health outcomes, often requiring strategic management in modern society [2,3,4]. Recent investigations underscore light’s multifaceted influence on health, encompassing metabolic regulation and circadian integrity. Specifically, light impacts mammalian metabolism independently of circadian rhythms through retinal and hypothalamic pathways, affecting glucose homeostasis and thermogenesis [5,6], with aberrant exposure potentially contributing to metabolic diseases. Light’s therapeutic applications include photobiomodulation for treating illnesses and modulating inflammation, potentially influencing micronutrient deficiencies implicated in anemia [3,7]. The effects of light, both positive and negative, on health are mediated through visual and non-visual systems, impacting circadian disruption and immune modulation, with outcomes contingent on individual age and physiological status [2,3,4,8]. The pervasive nature of anemia, impacting approximately 25% of the global population [9], emphasizes its critical public health relevance. While recent data from the US reveals notable sex-related disparities, with prevalence at 13.0% in females compared to 5.5% in males [10], US prevalence is generally lower than global averages and also lower than in Russia, where sex-related differences are also observed [11]. Anemia prevalence frequently diverges from iron deficiency trends [12], implicating inflammation and other micronutrient deficiencies as key contributors to hemoglobin variability, potentially modulated by circadian disruptions from light exposure. Circadian rhythms, primarily entrained by light, orchestrate numerous biological processes, yet their potential role in modulating erythropoiesis and red blood cell indices remains underexplored in human populations. Circadian regulation of hematopoiesis has been demonstrated in animal models, where hematopoietic stem cells exhibit oscillatory release influenced by sympathetic nervous system innervation [13,14]. Intriguingly, human red blood cells (RBCs), despite lacking nuclei and transcriptional machinery, exhibit cell-autonomous circadian oscillations sustained by non-transcriptional mechanisms such as peroxiredoxin redox cycles [15]. Recent advances have further elucidated RBC circadian physiology; for example, Beale et al. [16] employed dielectrophoresis to characterize daily rhythms in RBC membrane electrophysiology, while Beale et al. [17] developed a novel biochemical assay revealing daily hemoglobin oxidation rhythms in RBCs that correlate with core body temperature cycles and nitric oxide signaling, suggesting a functional role for RBC circadian rhythms in thermoregulation. These findings underscore the physiological relevance of circadian timing mechanisms within erythrocytes and support the hypothesis that circadian light exposure could influence hematopoietic variables. To address this gap, the present study examined associations between objectively measured circadian light exposure—quantified by seven-day actigraphy with blue light exposure (BLE) metrics—and hematological variables in a cohort of 85 healthy young adults. Participants were recruited during a single autumn month in Tyumen, Russia, and provided a morning blood sample for complete blood count analyses. Physical activity and sleep duration were also analyzed using actigraphy to explore their potential relationship with anemia. The inclusion of these factors was also motivated by their impact on general health and the recognition of their role in the pathogenesis of various conditions. Notably, studies have indicated a U-shaped association between sleep duration and anemia risk [18], and a dose-dependent decrease in depression risk with higher physical activity [19].

This study revealed significant associations between circadian light hygiene and key hematological variables in healthy young adults. A larger BLE NA was independently linked to higher HGB and MCH, while a later BLE acrophase correlated with lower HGB, HCT, and MCH, alongside larger RDW-CV. A later PA acrophase and a later habitual bedtime were also associated with a lower MCH. These findings suggest that circadian light patterns may modulate hematopoiesis, particularly through effects on erythrocytic indices, independently of sex for MCH and RDW-CV. Currently, there is a limited scope of studies characterizing the circadian rhythms of CBC components as evident from a recent review [27], particularly in relation to environmental light cues, which underscores the novelty of our investigation into how circadian light hygiene modulates these variables.

Our previous research at high latitudes found that seasonal changes in circadian light hygiene are associated with changes in morning cortisol, with higher values linked to polar seasons and later timing of physical activity and light exposure [28], altered morning lipids (higher low-density-lipid cholesterol being linked to elevated light at night, higher high-density-lipid cholesterol being linked to earlier timing of light exposure) [28,29,30], and higher clock gene (NR1D1) expression with more abundant light exposure [30]. All these seasonal changes were coupled with a delayed-phase melatonin phase and reduction is its relative amplitude [28]. Notably, the 24 h mean melatonin concentration remained relatively stable despite substantial changes in ambient light patterns [28]. However, since these variables exhibit circadian rhythmicity, single-morning measurements preclude differentiation between associations with overall 24 h means and changes in phase. In this context, it is pertinent that in contrast to HGB and HCT, which demonstrate pronounced 24 h rhythms [27,31], MCH and RDW display minimal 24 h variation. For instance, Sennels et al. [31] reported negligible amplitudes for MCH (0.27% relative amplitude) and RDW (0.16% relative amplitude) in healthy males, with no significant circadian rhythm (p > 0.5). Similarly, Hilderink et al. [32] found small within-subject biological variation for MCH (CVI = 0.8%) and RDW (CVI = 0.37%), indicating stability across time points, and no diurnal fluctuations in healthy populations. This result suggests that the observed associations between circadian light exposure and MCH or RDW-CV cannot be attributed to the modulation of their endogenous rhythms, as these variables do not fluctuate significantly over the 24 h day. However, it cannot be excluded that circadian light hygiene may influence the acrophase of HGB and/or HCT, which show pronounced 24 h patterns (e.g., HGB amplitude = 3.28% in [15]). Furthermore, these findings imply that light may exert non-circadian effects on MCH, potentially through pathways independent of any rhythmic modulation, warranting further mechanistic studies. The observed associations between circadian light hygiene and MCH, despite MCH’s minimal intrinsic circadian rhythmicity, suggest a role for indirect photic modulation rather than direct phase-shifting of MCH itself. Light’s potent chronobiotic influence likely optimizes the upstream regulatory mechanisms of erythropoiesis. Specifically, robust light cues, such as a large NA BLE and an earlier BLE acrophase, may entrain circadian rhythms of key metabolic regulators like NR1D1 [30,33], as evidenced by studies showing NR1D1 upregulation in response to bright light exposure [30]. Critically, NR1D1 functions as a heme receptor, directly sensing intracellular heme concentrations to coordinate circadian rhythms with metabolic processes, including those involved in heme synthesis and turnover [34,35]. NR1D1 also can receive feedback from dietary iron [36]. Given that MCH reflects hemoglobin content, and heme is a fundamental component of hemoglobin, NR1D1′s direct interaction with heme positions it as a key modulator of red blood cell maturation. Furthermore, the secondary associations of MCH with bedtime and the acrophase of physical activity, which are themselves strongly modulated by circadian light exposure, support the hypothesis that light patterns indirectly influence MCH by synchronizing broader circadian physiology underpinning hematopoiesis, with NR1D1 acting as a central sensor of metabolic state within this network.

For mechanistic context, it has been previously established that mouse hematopoietic stem cells (HSCs) and their progenitors exhibit robust circadian rhythms, with peak activity occurring approximately 5 h after light onset [13], leading to higher stem cell mobilization. These rhythms are regulated by sympathetic nervous system-mediated noradrenaline secretion, which modulates CXCL12 expression in the bone marrow niche. Importantly, unlike humans, mice are nocturnal and their resting period occurs during the daylight phase when HSC release peaks. This neurally driven circadian release of HSCs may promote stem cell niche regeneration and tissue homeostasis. Our findings suggest that in humans, circadian light patterns could similarly influence hematopoiesis via adrenergic pathways, potentially accounting for the observed associations between BLE and erythrocytic variables such as MCH. Furthermore, the amount of brain iron regulates circadian rhythms by modulating PER1 expression and clock genes like Clock and Bmal1. Iron deficiency enhances locomotor activity, and iron overload inhibits it [37]. This relation provides further insight into how iron homeostasis may interact with circadian factors in hematopoiesis.

The present findings carry important clinical implications within the broader context of anemia. Anemia, characterized by diminished hemoglobin and impaired oxygen delivery, contributes substantially to the global disease burden. Our study suggests that circadian light hygiene—through its entrainment of endogenous rhythms—may represent a modifiable environmental factor influencing erythropoietic variables. Notably, the exclusive association of blue light exposure metrics with MCH, a key indicator of red blood cell hemoglobin content, underscores a potential mechanistic link between circadian photic input and red blood cell quality. Given the scarcity of prior research in this domain, these results highlight the need to consider circadian light exposure as a novel factor in hematological health. It is particularly relevant for populations at risk of circadian disruption, such as shift workers or individuals residing at extreme latitudes, who may be more susceptible to anemia. In line with this line of thought, Alves et al. [38] demonstrated that poor sleep quality among firefighters, a shift-work profession prone to circadian disruption, correlates negatively with hematological variables (e.g., RBC, HGB, HCT), potentially inhibiting erythropoiesis even within reference ranges. Future longitudinal and interventional studies are essential to elucidate causality and evaluate whether optimizing circadian light hygiene could serve as a non-pharmacological strategy to mitigate anemia risk and improve erythropoietic status. In a related vein, Zhu et al. (2025) [39] found that hemoglobin levels exhibit a nonlinear U-shaped association with respiratory infection risk (lowest risk at mid-range HGB, with elevated risk at both low and high extremes), modified by chronotype, which underscores the broader implications of circadian disruptions for hematological health and infection susceptibility, as highlighted in this discussion on light hygiene’s effects on erythropoiesis. Future research should prioritize longitudinal studies to establish causality. Multi-month prospective cohorts tracking circadian LE/BLE patterns alongside serial CBC components in populations prone to light disruption (e.g., shift workers, high-latitude residents) can reveal long-term effects on erythropoiesis and anemia risk. Specifically timed bright blue-enriched light to optimize BLE may directly test whether improved circadian light hygiene enhances erythrocytic indices and NR1D1-mediated heme regulation. Mechanistic studies incorporating biomarkers like melatonin and ferritin are also warranted to elucidate photic cue–hematopoiesis pathways.

Physical activity exhibits a complex relationship with hematological markers of anemia, potentially enhancing erythropoiesis while risking hemolysis or iron depletion, yet none of the reviewed studies consider the timing of exercise relative to circadian rhythms. Hu and Lin [40] note that exercise can increase hemoglobin and red cell mass via stimulated erythropoiesis, offering benefits for anemia management despite controversial results. Caimi et al. [41] found that trained athletes have improved red blood cell deformability and elevated MCV and MCHC, although a higher VO₂max correlates with lower MCH and MCHC. Mairbäurl [42] describes “sports anemia” in athletes as dilutional hematocrit decline due to plasma expansion that is offset by an increased total red cell mass and hemolysis favoring younger, more flexible cells. Wouthuyzen-Bakker and van Assen [43] highlight exercise-induced iron deficiency anemia in females from iron losses. Cichoń-Woźniak et al. [44] observed in trained male rowers that baseline ferritin concentrations influence post-exercise iron responses: lower-ferritin participants (<75 µg/L) showed transient iron increases followed by declines, while higher-ferritin participants (>75 µg/L) exhibited only decreases, suggesting that baseline iron stores modulate acute iron regulation without altering hepcidin or interleukin-6. Nam et al. [19] indirectly support the protective role of exercise against depression in anemic individuals. These findings suggest that physical activity modulates erythropoiesis variably, with circadian timing unexplored, potentially interacting with light-entrained hematopoiesis, as our study on circadian light exposure shows.

The strong association of larger NA BLE and earlier BLE acrophase with higher MCH and lower RDW-CV suggests a significant role for robust circadian entrainment in hematopoiesis. Given the minimal 24 h variability of MCH and RDW-CV, these findings likely reflect indirect, long-term influences on erythropoiesis. We propose that pronounced daily fluctuations in light intensity (large NA BLE) and an earlier timing of the BLE peak act as potent chronobiological cues, and favor the circadian clock’s synchronization in the bone marrow. This precise timing may enhance iron homeostasis and promote more uniform erythroid differentiation and hemoglobinization, thereby increasing hemoglobin content per cell (higher MCH) and fostering greater consistency in RBC size (smaller RDW-CV). Our findings suggest that individuals at risk of anemia, particularly those with low daylight exposure and disrupted circadian rhythms (e.g., shift workers), can optimize their circadian light hygiene. Seeking bright blue-enriched light exposure earlier in the day can advance light acrophase and increase normalized amplitude.

Study Strengths: A key strength of this investigation is the study’s homogeneous cohort, with participants examined at the same location in Tyumen, Russia, over a single autumn month, thus minimizing environmental biases from variable light exposure. Additionally, the use of the normalized amplitude (NA) of BLE accounts for inter-individual variability in light exposure, providing a more precise measure of circadian light hygiene and enhancing the reliability of associations with hematological variables. Notably, even when incorporating mean and amplitude of PA, mean LE, or chronotype score as potential confounders, the significant associations between blue light exposure (amplitude and timing) and hematological variables (HGB, MCH, RDW-CV) persisted, indicating that circadian light hygiene exerts an independent influence. To further enhance transparency, we have included a completed JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies as, affirming the methodological robustness of our study. Supplementary Table S2

Study Limitations: Our study is subject to several limitations. Circadian light hygiene is inherently dependent on the photic environment; thus, our results may not generalize to different seasons or latitudes with markedly divergent daylight patterns. Furthermore, the narrow age range of participants likely contributed to the observed lack of age-specific effects on most variables, limiting generalizability to broader age demographics. Future research should investigate these associations across diverse environmental contexts and age groups to ascertain broader applicability. While our findings link circadian BLE to erythrocytic variables, the absence of reticulocyte counts in routine CBCs precludes direct exploration of erythropoiesis impacts. Future studies should incorporate reticulocyte analysis to investigate direct effects on erythropoiesis, potentially leveraging known circadian human stem cells and iron pathways. Furthermore, as electrophoresis was not performed due to reliance on routine CBC data, deeper analysis of hemoglobin profiles was not possible, though it could offer broader insights into hematological responses in future research. Additionally, the cross-sectional design precludes causal inferences, necessitating longitudinal research to elucidate time-related relationships.

This research reveals significant associations between circadian light exposure patterns and hematological variables, particularly MCH, HGB, and RDW-CV, in young adults during the light-deficient fall season. Larger NA BLE and earlier BLE acrophase were linked to higher MCH and smaller RDW-CV, and NA BLE was independently associated with higher HGB. These findings underscore the supportive role of circadian light hygiene in maintaining hematological health, providing a foundation for future investigations into light’s impact on hematopoiesis.