Dietary Fiber Reduces the Concentrations of Certain Aldehydes in Serum

Shi Shi Jiangsu Province Hospital and Nanjing Medical University First A liated Hospital Qingqing Zhu Jiangsu Province Hospital and Nanjing Medical University First A liated Hospital Shengen Liao Jiangsu Province Hospital and Nanjing Medical University First A liated Hospital Xu Zhu Jiangsu Province Hospital and Nanjing Medical University First A liated Hospital Xiaosu Tang Institution of Environmental Sciences Yanli Zhou (  zhyl88@qq.com ) Jiangsu Province Hospital and Nanjing Medical University First A liated Hospital


Introduction
Exposureomics has revealed the interrelated interactions of physicochemical, human toxicity, ecotoxicological and exposure data (Fan et al. 2016;Jeliazkova et al. 2021). Aldehydes are common organic compounds produced from a variety of sources, such as e-cigarettes and tobacco smoke, environmental exposure, dietary intake and endogenous intermediary metabolism, to which organisms are frequently exposed (O'Brien et al. 2005; Silva et al. 2021). Studies have linked aldehydes to various human diseases (Uchida 2000) due to their cytotoxicity (Xie et al. 2016). Our previous studies have shown that serum isopentanaldehyde is associated with obesity , and that benzaldehyde and isopentanaldehyde are associated with CVD , and these ndings have also been veri ed by another study (Xu et al. 2020).
Dietary ber is widely recognized as a bene cial component derived from vegetables, fruits, legumes, nuts and various grains in plant-based foods. Evidence indicates that an increased proportion of energy-adjusted dietary ber can improve glucose metabolic disorders (Lin et al. 2015; Sekgala et al. 2018), decrease visceral fat (Bajerska et al. 2018) and may protect against coronary artery disease (Basu et al. 2021). Additional evidence comes from recent studies showing that high dietary ber can reduce the risk of intestinal diseases, such as colorectal cancer (Dahm et al. 2010) and Crohn's disease (Ananthakrishnan et al. 2013). In renal diseases, a high-ber diet has also been shown to improve kidney function, reduce in ammation and lower the risk of mortality (Xu et al. 2014).
However, there are few data evaluating dietary ber in regulating potentially harmful organic compounds. A large population-based study proved that exposure to environmental tobacco smoke (ETS) under workplace conditions was associated with low intake of fruits and vegetables (Emmons et al. 1995). Although ETS is a signi cant source of aldehydes, the direct relationship between the two has not been further investigated. The emerging eld of precise nutrition can provide effective strategies for public health through high-dimensional data analysis (Wang and Hu 2018). Therefore, based on the established data, we should explore the role of precise regulation of nutrition to eliminate harmful components. Therefore, using national health examination surveys conducted in 2013-2014, we evaluated the effect of the energy-adjusted dietary ber available in daily life on serum aldehyde concentration.

Study population
The National Health and Nutrition Examination Survey (NHANES) was designed and conducted to continuously monitor the nutritional status and health of American noninstitutionalized civilians by the National Centers for Disease Control and Prevention (CDC). The population was collected from the NHANES surveys in 2013-2014, which were provided online (https://www.cdc.gov/nchs/nhanes/index.htm). We included 10175 participants in total, while 7849 were excluded for missing serum aldehyde data. Participants without dietary ber data (n = 5), aged under 18 (n = 224), and pregnant individuals (n = 18) were further excluded, leaving a total of 1877 people available for the nal analysis (Fig. 1).

Aldehydes measurements
The CDC has developed an automated analytical method using solid phase microextraction (SPME) gas chromatography (GC) and high-resolution mass spectrometry (HRMS) with selected ion mass detection and isotope-dilution techniques to quantify the content of aldehydes in serum. Each sample was measured twice to reduce measurement errors in the laboratory. We selected aldehydes that were detected in > 80% of participants to explore their relationship between dietary ber intake and the serum concentrations of aldehydes, including isopentanaldehyde, butyraldehyde, hexanaldehyde, heptanaldehyde, propanaldehyde, and benzaldehyde.

Dietary ber measurements
As one part of the NHANES survey, all participants were required to complete two 24 h dietary recall interviews. The rst interview was administered by trained personnel in the mobile examination center, and the second interview was conducted by telephone 3 to 10 days later. Dietary ber intake was calculated by the US Department of Agriculture (USDA) Food and Nutrient Databases for Dietary Studies (FNDDS) (https://www.cdc.gov/nchs/tutorials/dietary/SurveyOrientation/ResourceDietaryAnalysis/intro.htm). Daily dietary ber intake was averaged based on the two 24 h recall data and adjusted by the total energy intake.
Covariates included age, sex, education level (< 9th grade, 9−11th grade, high school graduate, college degree, college graduate or above), race (Mexican American, other Hispanic American, non-Hispanic black, non-Hispanic white, and others), hypertension (yes or no) and diabetes (yes or no), body mass index (BMI, kg/m2), past smoking (at least 100 cigarettes in life or not) or alcohol use (at least 12 alcohol drinks per year or not), daily energy intake, physical activity and poverty-income ratio. Total daily energy intake was calculated by averaging the energy intake of diet and dietary supplements. Daily physical activity time was multiplied by the corresponding metabolic equivalent (MET) score to assess physical activity level. The poverty-income ratios were de ned as the ratio of household income to the threshold adjusted by in ation and household size.

Statistical methods
Continuous variables are expressed as the mean (standard deviation, SD) and were compared using a t-test (normal distribution). Categorical variables presented as numbers (frequencies, %) were analyzed by the chi-squared test. Log2 transformation was used because of the skewed distribution of the energy-adjusted dietary ber and all aldehydes. The energy-adjusted dietary ber intake was calculated as grams per day according to the regression residuals of ber on total energy intake. A generalized linear model and restricted cubic spline (3 knots located at the 10th, 50th, 90th) were performed to assess the associations of dietary ber (both in quantiles and continuously) with the serum concentrations of aldehydes after adjusting for cofounding factors, including age, sex, education level, race, smoking status, alcohol use, diabetes, hypertension, body mass index, energy intake, poverty-income ratio and physical activity.
All statistical analyses were performed with R software version 3.6.0. P < 0.05 was considered as signi cant.

Baseline characteristics
The demographic characteristics are displayed in Table 1. Age, educational level, race, hypertension, BMI, smoking, alcohol consumption, physical activity and poverty-income ratio (all P < 0.01) showed signi cant differences in the groups with different levels of energy-adjusted dietary ber intake. Participants with higher dietary ber intake were older, had lower BMIs, had a higher poverty-income ratio, and had a lower likelihood of smoking, drinking and vigorous physical activity.
The restricted cubic spline plots indicated that there was a linear and positive association between dietary ber and benzaldehyde (P for nonlinearity = 0.635, Fig. 2A) and a linear and negative association between dietary ber and isopentanaldehyde (P for nonlinearity = 0.561, Fig. 2B). There was also a nonlinear and negative association between dietary ber and propanaldehyde (P for nonlinearity = 0.043, Fig. 2C). No linear or nonlinear association was found between dietary ber intake and the concentration of any other aldehydes.

Discussion
To the best of our knowledge, we were the rst to observe signi cant correlations between energy-adjusted dietary ber and various serum aldehyde exposures. Dietary ber was negatively associated with isopentanaldehyde and propanaldehyde but positively associated with benzaldehyde. Nonetheless, in the other 3 aldehydes, there was no signi cant trend toward an association with dietary ber.
Previous studies have mainly focused on the involvement of aldehydes in human disease. Nonetheless, no experimental research has shown an effective approach to regulating these 6 aldehyde concentrations in the human body. According to a recent study, no dietary variables were associated with serum isopentanaldehyde and propanaldehyde concentrations (Silva et al. 2021). Our ndings seem to contradict this. However, the study provided strict food consumption information from different sources, such as vegetable, fruit, legume, nut, and seed grain products. In contrast, our study provides a holistic analysis of dietary ber and serum aldehyde. Therefore, this regulatory effect may be related to the increase in the diversity of dietary ber intake sources, further suggesting a combination of dietary ber from multiple sources to modulate serum aldehyde. In addition, our study supplemented the effect of dietary ber on serum benzaldehyde that was not present in the abovementioned study.
The mechanisms by which dietary ber affects the serum concentration of aldehydes may include the following aspects. Isopentanaldehyde is a methyl butyraldehyde formed by replacing the methyl group at the third position of butyraldehyde. According to the Human Metabolome Database, it has been shown to be associated with a substantial number of digestive disorders, such as ulcerative colitis, nonalcoholic fatty liver disease, and Crohn's disease (http://www.hmdb.ca/metabolites/HMDB0006478). These diseases have been shown to be ameliorated by adding dietary ber intake (Ananthakrishnan et al. 2013;Zhao et al.2020). Therefore, this re ects that digestive disease conditions may be regulated by reduced dietary ber, which may in turn reduce the absorption of isopentanaldehyde. Moreover, the speci c mechanism has not been studied and is worth further exploration.
Propanaldehyde is commonly used in the manufacture of plastics and synthetic rubber chemicals and as a disinfectant and preservative. It can be absorbed into the body by inhaling its vapor and ingestion. Propanaldehyde, as a perinatal air poison, was positively associated with autism spectrum disorder (ASD) in high-risk families (Kalkbrenner et al. 2018). Environmental propanaldehyde is usually biodegraded to propionic acid, which is then further degraded to carbon dioxide and water (Urano and Kato 1986). Considering its unknown degradation pathway and harm in vivo, this study provides evidence for high-risk patients to increase dietary ber intake.
The increased concentration of benzaldehyde with dietary ber intake may be because benzaldehyde, as the second most useful avoring agent in foods, is used in the postprocessing of dietary ber (Duff and Murray 1989). The second reason is that the microbial biocatalyst can produce benzaldehyde (Jain et al.). Pichia pastoris can effectively convert benzyl alcohol to benzaldehyde through biotransformation (Duff and Murray 1989). Benzaldehyde can also be catalyzed to form phenylalanine in the presence of a cell extract of Lactobacillus plantarum (Nierop Groot and de Bont 1998); however, the conversion rate of benzaldehyde to benzyl alcohol is reduced in Escherichia coli expressing recombinant carboxylate reductase (Kunjapur et al. 2014). These possible paths may lead to a positive association between benzaldehyde and dietary ber intake.
The limitations of this study include the following aspects. First, this cross-sectional study was designed to describe the association; hence, it cannot conclude and further explain causality. Second, given that this population is an American population, dietary habits exert regional differences. Moreover, due to the lack of potential bowel disturbances, we could not include it as one possible intermediate link. Further research is needed to determine whether these results can be extrapolated to other regions or other ethnicities.

Conclusions
Our study results demonstrated that dietary ber intake was negatively correlated with serum concentrations of isopentanaldehyde and propanaldehyde. Further research is needed to elucidate the underlying mechanisms between dietary ber intake and aldehyde metabolism.
The datasets used and analyzed during the current study are available from https://www.cdc.gov/nchs/nhanes/nhanes_questionnaires.htm.

Competing interests
The authors declare that they have no competing interests or personal relationships that could have appeared to in uence the work reported in this paper.

Funding
Not applicable. No funding was received to assist with the preparation of this manuscript.