Abstract
Background
The global prevalence of childhood and adolescent obesity has reached epidemic proportions. While evidence suggests an inverse relationship between dietary folate intake and adult obesity, whether this association persists in the younger population remains unclear.
Objective
To examine whether dietary folate intake correlates with obesity in children and adolescents.
Methods
Drawing upon the National Health and Nutrition Examination Survey (NHANES), the study modeled the correlation between dietary folate and overweight/obesity or central obesity through logistic regression models and restricted cubic splines in children (aged 6–11) and adolescents (aged 12–19). Sensitivity analysis was conducted to verify the robustness of the correlation. Stratified analysis examined potential differences across populations.
Results
This study included a total of 9,404 participants. In the fully adjusted model, dietary folate intake was negatively correlated with overweight/obesity (OR = 0.89, 95%CI: 0.83–0.97, P = 0.005) and central obesity (OR = 0.87, 95%CI: 0.80–0.94, P < 0.001) in children and adolescents. This correlation was non-linear (P-non-linear < 0.001). When dietary folate intake was below 1.90 and 1.95 (i.e. 190 and 195 mcg/1000 kcal), an increase of 100 mcg/1000 kcal was associated with a 35% reduction in overweight/obesity odds (OR = 0.65, 95%CI: 0.56–0.75, P < 0.001) and a 34% reduction in central obesity odds (OR = 0.66, 95%CI: 0.57–0.77, P < 0.001). Stratified analysis showed that the association was not significant in the children group, but significant in the adolescent group, with the dietary folate intake-central obesity association only existing in female adolescents. Sensitivity analysis supported the robustness of the above association.
Conclusion
The results of this study indicate that when dietary folate intake is below the threshold (190 mcg/1,000 kcal and 195 mcg/1,000 kcal, respectively), its increase is negatively correlated with the odds of overweight/obesity and central obesity in children and adolescents. This study provides important epidemiological clues and scientific hypotheses for exploring dietary intervention strategies for children and adolescents with obesity in the future.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12887-025-06490-y.
Keywords: Dietary folate, Children, Adolescents, Obesity, NHANES
Introduction
The rising incidence of obesity in young people poses an increasingly severe burden on public health systems worldwide and markedly compromises individual health and quality of life [1]. Over the past few decades, its prevalence has soared: from 1990 to 2021 the combined prevalence of overweight and obesity in children and adolescents rose to twice its former level, while the prevalence of obesity expanded to three times the original figure [2]. Obesity during childhood and adolescence not only disturbs growth, endocrine balance and psychosocial development during puberty [3], but also exerts long-term health effects in adulthood, amplifying susceptibility to cardiovascular pathology, metabolic disorders and several cancers [4]. Even more alarming, obesity in these early life stages is associated with an increased risk of premature death in adulthood [5]. Timely and effective interventions on child and adolescent obesity are therefore of critical public-health importance.
Dietary and nutritional strategies are central to the prevention of obesity in children and adolescents [6]. Folate, a water-soluble B-vitamin that cannot be endogenously synthesized, is essential for key metabolic processes [7]. From a physiological functional perspective, folate plays a crucial role in one carbon unit metabolism and is an essential cofactor for DNA synthesis and repair, as well as epigenetic regulation, such as DNA methylation [8]. These basic physiological processes are involved in regulating gene expression related to energy metabolism, fat production, and appetite regulation [9]. In addition, folate is a key cofactor in the demethylation of homocysteine to methionine, and its deficiency can lead to elevated homocysteine levels [10]. Hyperhomocysteinemia is closely associated with increased risk of insulin resistance and metabolic syndrome [11]. These mechanisms collectively suggest that folate may play an important role in the occurrence and development of obesity.
Some studies showed that in adults, higher dietary folate intake is associated with lower odds of overweight and obesity [12, 13]. However, evidence in children and adolescents remains scarce. Only one study, restricted to Mexican–American children (8–15 years old), reported no significant association [14]. In addition, most previous studies have mainly relied on the weight index to define obesity, with BMI (Body Mass Index) being a widely used standard indicator in pediatric practice. However, it mainly reflects the overall weight status and has limitations in distinguishing between fat and muscle mass, as well as identifying fat distribution areas [15]. As a supplement, central obesity evaluated by waist circumference and waist-to-height ratio can provide additional information about abdominal fat accumulation and is often used as a substitute indicator to reflect visceral fat [16, 17]. By combining these indicators, we can more comprehensively evaluate the health risks associated with obesity.
Based on the above biological rationality and existing research gaps, this study utilized the representative database of NHANES in the United States to explore the association between dietary folate intake and overweight/obesity, central obesity in children and adolescents. NHANES provides a unique advantage in accurately assessing the relationship between nutrition and health due to its rigorous standardized data collection methods, such as 24-h dietary recall interviews and direct physical measurements. The results of this study can provide epidemiological clues for future prospective research and potential mechanism exploration.
Methods
Study population
The study retrieved its data from the nationally representative, cross-sectional NHANES in the U.S., which assessed the health and nutritional status of adults and children for public-health purposes. NHANES obtained ethical approvals from the Research Ethics Review Board of the National Center for Health Statistics with informed consent from all participants. Therefore, no additional ethics approval was required for the present study. It is worth noting that due to the cross-sectional nature of NHANES data, the associations observed in this study cannot be interpreted as established causal relationships.
The 2009–2018 survey cycle (n = 49,693) was utilized. In this study, children are defined as individuals aged 6–11 years and adolescents are aged 12–19 years. After excluding individuals aged < 6 or > 20 years (n = 37,288), those missing dietary folate data (n = 1,898), missing obesity-related variables (n = 247), with implausible energy intakes (defined as any 24-h dietary recall energy intake < 400 kcal, n = 12) [18], or lacking other covariate data (n = 844, with missing poverty-income ratio n = 768 and missing physical activity data n = 76), 9,404 children and adolescents remained (Fig. 1).
Fig. 1.
Flowchart of participant selection
Dietary folate intake
We obtained data for the independent variable, dietary folate intake, through two 24-h dietary recalls spaced 3 to 10 days apart. This data only included folate from food sources and did not include any dietary supplements. The first interview was conducted in person at the mobile examination center, while the second was by phone. Daily dietary folate intake (mcg/1,000 kcal) was calculated as Dietary Folate (mcg)/Total Energy (kcal) × 1,000 [19]. Participants were divided into quartiles: Q1 (< 143), Q2 (143–182), Q3 (182–235), Q4 (≥ 235).
Overweight/obesity and central obesity
Overweight/obesity and central obesity served as outcome variables. Overweight/obesity was identified when BMI ≥ the sex- and age-specific 85th percentile, computed as weight (kg)/height2 (m2). Central obesity was present when the waist circumference ≥ the 90th sex- and age-specific percentile, or when the waist-to-height ratio ≥ 0.5, calculated as waist circumference (cm)/height (cm) [20]. Percentile cut-offs were obtained from growth charts of the U.S. Centers for Disease Control and Prevention [21].
Covariates
The covariates in this study included age, sex (male and female), race (Mexican American, Non—Hispanic White, Non—Hispanic Black, Other Race), poverty—income ratio (PIR), physical activity (Inactive and Active), and total energy intake.
Statistical analysis
All analyses were conducted using R software (version 4.1.3) and the “survey” package was applied to fully consider the complex survey design of NHANES. Sampling weights (WTDR2D), stratified variables (strata), and primary sampling units (PSU) were included in the analysis to ensure that the estimates were nationally representative and to calculate robust standard errors. The “tableone” package was used to complete the weighted baseline table, with categorical variables represented by sample size N (weighted%). The inter-group comparisons were conducted by using a weighted chi square test. Continuous variables were represented by weighted mean (SD), and inter-group comparisons were conducted using weighted analysis of variance. Using a weighted logistic regression model, we investigated the association between dietary folate intake and overweight/obesity, central obesity in children and adolescents. The results were expressed as odds ratio (OR) and its 95% confidence interval (CI). We constructed a restricted cubic spline (RCS) using the “rms” package to evaluate the non-linear features of the association between dietary folate intake and outcomes. By comparing the Akaike Information Criterion (AIC) of 3, 4, and 5 node models, the 3-node model with the smallest AIC value was ultimately selected, with node positions set at the 10th, 50th (median), and 90th percentile of dietary folate intake, respectively. If there was a non-linear correlation (P-non-linear < 0.05), a two-stage linear regression model was further used for threshold effect analysis, and the inflection point (i.e. threshold) of the correlation was determined iteratively through maximum likelihood estimation. In addition, the differences in the above associations among different age groups and sex groups were explored through stratified analysis. Finally, to evaluate the robustness of the main research findings, we conducted three sensitivity analyses: using absolute folate intake (mcg/day) instead of energy adjusted intake for model fitting; excluding participants who had used folate dietary supplements from the analysis to focus on dietary sources of folate; and redefining central obesity using a single diagnostic criterion (waist circumference ≥ 90th percentile or waist to height ratio ≥ 0.5). All sensitivity analyses were conducted using the same weighted logistic regression model as the main analysis. A P-value < 0.05 is considered statistically significant.
Results
Baseline characteristics
This study included 9,404 children and adolescents aged 6 to 19, with a relatively balanced proportion of males and females in the sample. In terms of racial composition, non-Hispanic white people were the majority (54.3%), followed by other races (16.4%), Mexican Americans (15.5%), and non-Hispanic black people (13.8%). The average PIR of the entire sample was 2.5. Baseline feature analysis showed that different dietary folate intake groups (Q1-Q4) had differences in sex, race, energy intake, BMI, overweight/obesity and central obesity (P < 0.001 or P = 0.001). In terms of age distribution, the proportion of adolescents (12–19 years old) in the lowest intake group (Q1) (64.4%) was significantly higher than in other groups. In terms of racial distribution, non-Hispanic white individuals had the highest proportion (58.2%) in the Q1 group, while as folate intake levels increased, the proportion of Mexican American and other racial participants gradually increased, while the proportion of non-Hispanic black individuals decreased accordingly. In addition, compared with the Q1 group, participants in the Q2, Q3, and Q4 groups with higher folate intake had significantly lower energy intake, BMI levels, and prevalence of overweight/obesity and central obesity (all P < 0.001) (Table 1).
Table 1.
Baseline characteristics
| Characteristics | Overall | Q1 (< 143) | Q2 (143—182) | Q3 (182—235) | Q4 (≥ 235) | P (value) |
|---|---|---|---|---|---|---|
| N | 9404 | 2358 | 2324 | 2367 | 2355 | |
| Age (%) | < 0.001 | |||||
| Children (6–11 years) | 4458 (43.1) | 939 (35.6) | 1154 (47.3) | 1201 (46.4) | 1164 (43.1) | |
| Adolescents (12–19 years) | 4946 (56.9) | 1419 (64.4) | 1170 (52.7) | 1166 (53.6) | 1191 (56.9) | |
| Sex (%) | 0.567 | |||||
| Female | 4649 (49.2) | 1141 (47.3) | 1181 (50.2) | 1165 (48.9) | 1162 (50.3) | |
| Male | 4755 (50.8) | 1217 (52.7) | 1143 (49.8) | 1202 (51.1) | 1193 (49.7) | |
| Race (%) | < 0.001 | |||||
| Mexican American | 2045 (15.5) | 393 (11.2) | 468 (13.7) | 588 (18.1) | 596 (18.8) | |
| Non-Hispanic White | 2782 (54.3) | 776 (58.2) | 726 (56.6) | 650 (52.1) | 630 (50.3) | |
| Non-Hispanic Black | 2257 (13.8) | 683 (16.6) | 598 (14.5) | 531 (12.2) | 445 (11.9) | |
| Other Race | 2320 (16.4) | 506 (14.0) | 532 (15.2) | 598 (17.6) | 684 (19.0) | |
| PIR (Mean, SD) | 2.5 (1.6) | 2.5 (1.6) | 2.5 (1.7) | 2.4 (1.7) | 2.4 (1.6) | 0.593 |
| Physical activity (%) | 0.247 | |||||
| Inactive | 2153 (22.2) | 574 (24.7) | 548 (22.2) | 507 (20.9) | 524 (21.0) | |
| Active | 7251 (77.8) | 1784 (75.3) | 1776 (77.8) | 1860 (79.1) | 1831 (79.0) | |
| Energy intake (Mean, SD) (kcal) | 1965.9 (683.6) | 2037.8 (726.5) | 1994.0 (680.8) | 1981.5 (663.9) | 1850.0 (646.8) | < 0.001 |
| BMI (Mean, SD) (kg/m2) | 21.7 (6.1) | 22.9 (6.6) | 21.4 (5.7) | 21.3 (5.8) | 21.4 (6.1) | < 0.001 |
| Overweight/obesity (%) | 0.001 | |||||
| No | 5890 (64.1) | 1393 (58.5) | 1460 (65.4) | 1518 (65.7) | 1519 (66.7) | |
| Yes | 3514 (35.9) | 965 (41.5) | 864 (34.6) | 849 (34.3) | 836 (33.3) | |
| Central obesity (%) | 0.001 | |||||
| No | 6046 (65.3) | 1444 (60.1) | 1502 (66.5) | 1558 (66.4) | 1542 (68.2) | |
| Yes | 3358 (34.7) | 914 (39.9) | 822 (33.5) | 809 (33.6) | 813 (31.8) |
PIR Poverty Income Ratio, BMI Body Mass Index
Categorical variables are presented as N (weighted %). Continuous variables are presented as weighted mean (SD)
Association between dietary folate intake and obesity in children and adolescents
The logistic regression analysis results indicated that dietary folate intake was negatively correlated with the obesity odds in children and adolescents. When dietary folate intake was analyzed as a continuous variable, in the fully adjusted model, for every unit increase in dietary folate intake, the ratio of overweight/obesity in children and adolescents was lower (OR = 0.89, 95%CI: 0.83–0.97, P = 0.005), and the ratio of central obesity was also lower (OR = 0.87, 95%CI: 0.80–0.94, P < 0.001) (Table 2). When dietary folate intake was analyzed as a categorical variable (quartiles), compared with the Q1 group (lowest intake group), the Q2, Q3, and Q4 groups had lower ratios of overweight/obesity (OR ~ Q2 ~ = 0.74; OR ~ Q3 ~ = 0.71; OR ~ Q4 ~ = 0.65), corresponding to a decrease of 26%, 29%, and 35% in ratios, respectively. A similar trend was observed in central obesity, with ratios decreasing sequentially (OR ~ Q2 ~ = 0.77; OR ~ Q3 ~ = 0.74; OR ~ Q4 ~ = 0.64), by 23%, 26%, and 36%, respectively (Table 2).
Table 2.
Logistic regression of dietary folate intake and obesity in children and adolescents
| Model 1 | Model 2 | Model 3 | ||||
|---|---|---|---|---|---|---|
| OR (95% CI) | P (value) | OR (95% CI) | P (value) | OR (95% CI) | P (value) | |
| Overweight/obesity | ||||||
| Per SD | 0.92 (0.86–0.99) | 0.020 | 0.90 (0.84–0.97) | 0.009 | 0.89 (0.83–0.97) | 0.005 |
| Categories | ||||||
| Q1 | Ref | Ref | Ref | |||
| Q2 | 0.75 (0.60–0.92) | 0.007 | 0.74 (0.60–0.91) | 0.006 | 0.74 (0.60–0.92) | 0.006 |
| Q3 | 0.74 (0.61–0.88) | 0.001 | 0.70 (0.59–0.84) | < 0.001 | 0.71 (0.59–0.85) | < 0.001 |
| Q4 | 0.71 (0.59–0.85) | < 0.001 | 0.66 (0.55–0.80) | < 0.001 | 0.65 (0.53–0.79) | < 0.001 |
| P (trend) | < 0.001 | < 0.001 | < 0.001 | |||
| Central obesity | ||||||
| Per SD | 0.90 (0.84–0.97) | 0.004 | 0.88 (0.82–0.95) | 0.001 | 0.87 (0.80–0.94) | < 0.001 |
| Categories | ||||||
| Q1 | Ref | Ref | Ref | |||
| Q2 | 0.76 (0.62–0.93) | 0.008 | 0.77 (0.62–0.94) | 0.012 | 0.77 (0.62–0.95) | 0.014 |
| Q3 | 0.76 (0.63–0.92) | 0.006 | 0.74 (0.60–0.90) | 0.004 | 0.74 (0.60–0.91) | 0.006 |
| Q4 | 0.70 (0.58–0.86) | < 0.001 | 0.65 (0.53–0.81) | < 0.001 | 0.64 (0.51–0.79) | < 0.001 |
| P (trend) | 0.001 | < 0.001 | < 0.001 | |||
Model 1: unadjusted; Model 2: adjusted for age, gender, race and PIR; Model 3: adjusted for age, gender, race, PIR, physical activity and energy intake
RCS modeling of dietary folate intake and obesity
RCS showed a significant overall (P-overall < 0.001) and non-linear (P-non-linear < 0.001) association between dietary folate intake and overweight/obesity, central obesity in children and adolescents (Fig. 2).
Fig. 2.
RCS curves for dietary folate intake and obesity in children and adolescents. A Overweight/obesity. B Central obesity
To further quantify the non-linear correlation mentioned above, we conducted threshold effect analysis. The results showed that there was a turning point in the association between dietary folate intake (per 100 mcg/1000 kcal) and overweight/obesity and central obesity in children and adolescents, with values of 1.90 and 1.95 (i.e. 190 and 195 mcg/1,000 kcal), respectively. When the intake was below the respective inflection points, an increase of 100 mcg/1000 kcal in folate intake was associated with a 35% reduction in overweight/obesity odds (OR = 0.65, 95% CI: 0.56–0.75, P < 0.001) and a 34% reduction in central obesity odds (OR = 0.66, 95% CI: 0.57–0.77, P < 0.001). When the intake exceeded the inflection point, this negative correlation no longer had statistical significance (Table 3).
Table 3.
Threshold analysis of dietary folate intake and obesity in children and adolescents
| Adjusted OR (95% CI) | P (value) | |
|---|---|---|
| Overweight/obesity | ||
| Model 1 | 0.88 (0.83–0.92) | < 0.001 |
| Model 2 | ||
| Inflection point (1.90) | ||
| < 1.90 | 0.65 (0.56–0.75) | < 0.001 |
| > 1.90 | 0.97 (0.91–1.04) | 0.504 |
| P(LR) | < 0.001 | |
| Central obesity | ||
| Model 1 | 0.84 (0.80–0.89) | < 0.001 |
| Model 2 | ||
| Inflection point (1.95) | ||
| < 1.95 | 0.66 (0.57–0.77) | < 0.001 |
| > 1.95 | 0.93 (0.86–1.00) | 0.068 |
| P(LR) | < 0.001 | |
The threshold analysis was conducted using a two-piecewise linear regression model with dietary folate density expressed per 100 mcg/1,000 kcal. Odds ratios (ORs) are expressed per 100 mcg/1,000 kcal increment. The inflection points are 1.90 and 1.95 on this scale, which correspond to 190 and 195 mcg/1,000 kcal, respectively. P(LR) represents the p-value for the log-likelihood ratio test
Model 1: Fitting model by standard linear regression; Model 2: Fitting model by two-piecewise linear regression
Dietary folate intake-obesity association by age group and sex
Stratified analysis showed that the association pattern between dietary folate intake and obesity varied by age and sex. No significant association was observed between folate intake and overweight/obesity or central obesity in children aged 6–11 years. However, in adolescents (12–19 years old), the association was clearer. Compared with adolescents in the lowest quartile (Q1), adolescents in the highest quartile (Q4) showed significantly lower overweight/obesity ratios. This negative correlation was observed in both females (OR = 0.50, 95%CI: 0.33–0.76, P = 0.001) and males (OR = 0.63, 95%CI: 0.44–0.90, P = 0.011). Notably, the negative correlation between dietary folate and central obesity only existed specifically in adolescent females (Q4 vs. Q1: OR = 0.42, 95%CI: 0.29–0.62, P < 0.001), while no significant association was observed in adolescent males. Detailed results can be found in Table S1-S2.
Sensitivity analysis
To verify the robustness of the main research results, we conducted a series of sensitivity analyses. Firstly, based on absolute folate intake (mcg/day) instead of energy-adjusted folate intake, the results showed a significant negative correlation with overweight/obesity and central obesity in children and adolescents (all P-trends < 0.05), consistent with the main analysis conclusion (Table S3). Secondly, the reanalysis after excluding participants who had used folate supplements and demonstrated that the negative correlation between dietary folate intake and both obesity outcomes remained significant, indicating that the main association observed in this study did indeed derive from the daily diet (Table S4). Finally, we used a single waist circumference standard (≥ 90th percentile) and waist to height ratio standard (≥ 0.5) to define central obesity, and the results showed a significant negative correlation between dietary folate intake and the odds of central obesity (all P-trends < 0.01), confirming the robustness of this association under different definitions of central obesity (Table S5).
Discussion
This study is based on a nationally representative sample from the United States, exploring the cross-sectional association between dietary folate intake and obesity odds in children and adolescents, and for the first time suggesting a non-linear association between the two. The study found that there is a threshold effect in this association: when the intake is below the inflection points of 190 mcg/1,000 kcal (overweight/obesity) and 195 mcg/1,000 kcal (central obesity), an increase of 100 mcg/1,000 kcal in dietary folate intake is associated with a 35% reduction in overweight/obesity odds (OR = 0.65, 95%CI: 0.56–0.75, P < 0.001) and a 34% reduction in central obesity odds (OR = 0.66, 95%CI: 0.57–0.77, P < 0.001). The finding provides strong quantitative evidence for the potential health benefits of improving folate dietary levels within this intake range. In addition, the above association exhibits significant population heterogeneity, particularly evident in the adolescent population and not observed in the child population. The negative correlation with central obesity is specifically present in adolescent females.
The results of this study corroborate limited previous pediatric research. A study showed that higher serum folate has been linked to a lower risk of obesity in children aged 6–17 years [22]. Another study revealed that children with obesity aged 10–16 years had significantly lower levels of folate in their bodies compared with the healthy group [23]. Our study not only included a more comprehensive population aged 6–19 years on this basis, but more importantly, through exploratory threshold effect analysis, for the first time, suggested a possible non-linear dose–response relationship between dietary folate and obesity in childhood and adolescents. The study proposes a key hypothesis for future research that there may be an intake saturation point for the potential benefits of folate. These exploratory findings point the way for future research, but their potential application value must be validated in prospective studies.
This study found that individuals in the high dietary folate intake (Q4 group) had significantly lower daily total energy intake compared to the low intake group. This phenomenon suggests that the observed associations may be mediated through multiple pathways. Firstly, from a behavioral perspective, foods rich in folate (such as leafy vegetables and whole grains) typically have low energy density and high dietary fiber, which may help increase satiety, limit total energy intake, and thus form the first line of defense against obesity [13, 24]. Secondly, at the biological level, folate may exert its effects through various mechanisms. Studies have confirmed that in children and adolescents with obesity, elevated folate levels are associated with decreased homocysteine levels [25], decreased levels of pro-inflammatory cytokines such as interleukin-6 [26], and improved insulin resistance status [27], all of which are closely related to the risk of obesity [28, 29]. Our threshold effect analysis supports the view that folate may bring metabolic benefits through the aforementioned mechanisms within a specific intake range.
The heterogeneity of associations provides more clues for understanding their underlying logic. The differences in the association between folate and obesity in children and adolescents may reflect metabolic demands and physiological characteristics at different stages of growth and development. No significant association was observed during childhood (6–11 years old). During this stage, the body is in a rapid growth phase, and folate is a key cofactor in DNA synthesis. Its physiological function may prioritize serving basic processes such as cell proliferation and tissue organ development, thereby weakening its observable effects in energy metabolism regulation [30, 31]. Moreover, childhood obesity is more strongly dominated by early life factors such as genetic background, maternal environment, and early epigenetic programming [32, 33], which may, to some extent, mask the independent role of current dietary factors. In contrast, during adolescence (12–19 years old), the growth rate slows down, and the impact of current dietary quality and lifestyle on body fat accumulation is increasing [34]. At the same time, drastic changes in sex hormone levels reshape the metabolic environment, and the role of folate in epigenetic regulation and homocysteine metabolism, which are closely related to metabolic homeostasis, may become more prominent [35, 36]. These factors work together and may make the negative correlation between dietary folate intake and obesity risk more easily detectable in the adolescent population.
In addition, a negative correlation was found between dietary folate intake and the risk of central obesity only in adolescent women. The significant sex difference suggests that there may be unique biological mechanisms behind it, among which the core role of estrogen and its potential synergistic effect with folate metabolism are explanatory directions worth exploration. Adolescence is a period of significant changes in sex hormone levels. Estrogen is known to have a clear regulatory effect on fat distribution, as it tends to promote the deposition of fat in subcutaneous tissues (such as buttocks and thighs) rather than around abdominal organs, providing a relatively better basis for fat distribution in female adolescents [37]. In this specific physiological context, adequate intake of folate may have a synergistic effect with estrogen. Estrogen and folate have been reported to be associated with improving insulin sensitivity and reducing chronic low-grade inflammation [38, 39]. Both may work together to improve the metabolic health of the body through their independent pathways, thereby more effectively synergistically resisting the risk of central obesity. The findings provide new insights into the complex interactions between nutrition and endocrine during critical life periods. Future research can measure the levels of sex hormones, specific epigenetic markers, and folate status in the body to verify this interaction.
The saturation effect observed in this study after exceeding the threshold is biologically reasonable. Folate is a water-soluble vitamin with limited storage in the body. When the intake of folate far exceeds physiological needs, excess folate will be metabolized and excreted through urine [40]. Therefore, beyond the threshold, additional folate does not accumulate in the body to produce new physiological effects. It must be emphasized that our data does not show an increased risk of obesity at higher levels of folate intake. The data only indicates that there is an upper limit to this beneficial association. The saturation effect indicates that in obesity prevention, the goal of nutritional intervention is to achieve sufficient levels rather than to give infinite increments. In addition, the potential complex metabolic effects that ultra-high folate intake may bring (such as masking vitamin B12 deficiency, etc.) [41, 42] also suggest that future research needs to focus on the balance of multiple micronutrients, rather than the isolated analysis of a single nutrient.
From the perspective of public nutrition, our findings have important implications. The threshold effect in this study reflects a dietary pattern with high folate intake. In contrast, the recommended dietary allowance (RDA) for folate—ranging from 200 mcg/day for young children to 400 mcg/day for adolescents—defines the daily absolute intake target that meets the basic needs of the vast majority of the population to prevent deficiencies [43]. It is worth noting that individuals whose diet reaches the threshold of folate we observe are likely to have reached or exceeded the RDA for folate intake through their normal dietary energy intake. This consistency suggests that following existing dietary guidelines may itself be close to achieving the potential maximum protective effect against obesity. The platform effect beyond the threshold further suggests that once a diet with sufficient folate is achieved, further increasing intake may no longer be necessary for obesity prevention.
This study still has some limitations. Firstly, the core limitation lies in the cross-sectional design used in this study, which eliminates the possibility of any causal inference between dietary folate intake and obesity. Secondly, there are multiple limitations in exposure assessment. The intake of dietary folate is obtained through the self-reported 24-h dietary recall method. The inherent recall bias and underreporting of this method may lead to measurement errors, making the estimation of true associations tend to be conservative. Meanwhile, we were unable to use more precise biomarkers (such as serum or red blood cell folate) to reflect the folate nutritional status in the body, which led to limited deeper interpretation of the association between folate levels and obesity. In addition, although we adjusted for total energy intake, the model failed to control for other relevant dietary factors such as vitamin B12, other B vitamins, or overall dietary quality. Due to the fact that foods rich in folate often contain these nutrients, the possibility of residual contamination cannot be ruled out. Thirdly, caution should be exercised in interpreting the results. The intake threshold identified in this study reflects a non-linear association pattern and cannot be directly explained as an exact causal biological degree point. Its universality needs to be verified by prospective studies. Although the large sample size of this study enhances statistical power, it also means that statistically significant associations with small effect sizes and unclear clinical significance may be detected. In addition, subgroup analysis (especially in children) may have insufficient statistical power due to limited samples, and multiple comparisons increase the risk of accidental discovery. Therefore, these results should be considered exploratory and hypothesis-generative. Finally, the data for this study were sourced from the NHANES database in the United States, and caution should be exercised when extrapolating the results to other ethnic or national populations. Despite these limitations, this study provides valuable epidemiological evidence for the association between dietary folate and obesity in children and adolescents by rigorously handling complex survey designs, conducting a series of sensitivity analyses, and exploring non-linear relationships.
Conclusion
This cross-sectional study indicates that higher dietary folate intake is associated with lower odds of overweight/obesity and central obesity in children and adolescents in the United States. The association exhibits non-linear characteristics with potential thresholds of 190 mcg/1000 kcal and 195 mcg/1000 kcal, respectively. It is worth noting that this association is mainly significant in the adolescent population. This study reveals a possible dose–response relationship between dietary folate and obesity in children and adolescents. It provides important scientific hypotheses and epidemiological clues for future prospective cohort studies and intervention trials to verify the causal relationship of these associations.
Supplementary Information
Acknowledgements
Not applicable.
Abbreviations
- NHANES
National Health and Nutrition Examination Survey
- BMI
Body Mass Index
- PIR
Poverty—income ratio
- PSU
Primary sampling units
- OR
Odds ratio
- CI
Confidence interval
- RCS
Restricted cubic spline
- AIC
Akaike Information Criterion
- RDA
Recommended dietary allowance
Authors’ contributions
Conception and design of study: Fugui Yan, Lili Zhang Acquisition of data: Fugui Yan, Xiaoqing Liao Analysis and interpretation of data: Fugui Yan, Xiaoqing Liao, Lili Zhang Drafting of the manuscript: Fugui Yan, Xiaoqing Liao Revising the manuscript critically for important intellectual content: Lili Zhang Approval of the version of the manuscript to be published: Fugui Yan, Xiaoqing Liao, Lili Zhang.
Funding
None.
Data availability
The data and materials in the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data and materials in the current study are available from the corresponding author on reasonable request.