The association between dietary selenium intake and telomere length in hypertension

Abstract

Telomere length is closely linked to biological aging, oxidative stress, and the development of cardiovascular diseases. This study aimed to assess the association between dietary selenium intake and telomere length in individuals with hypertension. Data on dietary selenium intake were captured through the National Health and Nutrition Examination Survey (NHANES) computer‐assisted dietary interview system (CADI). Telomere length determination entailed selecting blood samples from all participants in the NHANES database. The analysis was performed using Analysis System software, with Empower stats utilized for data analysis. Results showed that there was a significant association between dietary selenium intake and telomere length in hypertension, particularly within the female group. In female hypertension cases, a 1 mcg increase in dietary selenium intake corresponded to a telomere length increase of 1.19 bp, even after adjusting for age, race, BMI, marital status, physical activity, energy intake, and stroke history. The relationship between dietary selenium intake and telomere length exhibited a linear pattern in female hypertension patients. This study identified a positive association between dietary selenium intake and telomere length in hypertension, particularly within the female group.

1. INTRODUCTION

Hypertension is a common cardiovascular disease and a leading cause of premature death globally. Hypertension is widely recognized as the primary cause of conditions such as stroke and heart failure. ¹ , ² Notably, it accounts for 54% and 45% of deaths attributed to stroke and cardiovascular diseases, respectively. ³ The high prevalence of hypertension and its serious complications pose significant challenges to healthcare systems in many societies. ⁴ In hypertension, endothelial cells play a crucial role in dilating arteries by releasing nitric oxide, thereby promoting the relaxation of blood vessels. The reduction in nitric oxide bioavailability and the presence of oxidative stress may contribute to the development of hypertension. ⁵ , ⁶ Selenium, an essential microelement in the body, plays a crucial role in antioxidant defenses and anti‐inflammation. ⁷ Researches have indicated associations between serum selenium levels, selenium intake, and hypertension. ⁸ , ⁹

Telomeres, comprised of repetitive sequences of six nucleotides (TTAGGG), act as protective caps at the ends of linear eukaryotic chromosomes. Telomere length undergoes shortening through mitosis in somatic cells. ¹⁰ Maintenance of telomeres is influenced by genetic factors and is subject to the cumulative impact of nongenetic factors over a person's lifespan. Both genetic and nongenetic factors can interact, and telomere length is intricately linked to biological aging, oxidative stress, and the development of cardiovascular diseases. ¹¹ , ¹² , ¹³

Previous studies have identified a correlation between dietary intake of trace elements and telomere length in hypertension, including elements such as dietary copper and dietary magnesium. ¹⁴ , ¹⁵ Additionally, studies have revealed associations between dietary selenium and telomere length in newborns, ¹⁶ middle‐aged and older adults, ¹⁷ as well as individuals with diabetes. ¹⁸ However, the relationship between dietary selenium and telomere length remains unexplored within the hypertension group.

This study aims to assess the connection between dietary selenium and telomere length in individuals with hypertension, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database.

2. METHODS

2.1. Study design and population characteristics

The study drew data from the NHANES database, encompassing a total of 21 004 participants from the years 1999 to 2002. Following the identification of individuals with hypertension, 4207 participants were initially included. Subsequently, 3004 participants remained after the removal of missing data related to dietary selenium and telomere length. Further refinement, involving the exclusion of missing data for stroke history, marital status, BMI (Body Mass Index), and physical activity, resulted in a final sample of 2734 participants with hypertension. Within this cohort, there were 1331 males and 1403 females, distributed among 537 Mexican Americans, 1425 non‐Hispanic whites, 581 non‐Hispanic blacks, 127 other Hispanics, and 64 individuals from other races. The average age and BMI of this study population were 60.07 ± 16.32 years and 29.78 ± 6.53 kg/m², respectively. Notably, 747 participants reported no aerobic activity, and 156 had a history of stroke.

2.2. Key data collection and processing

Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) average ≥90 mmHg, or self‐reported hypertension. The NHANES computer‐assisted dietary interview system (CADI) recorded data on dietary selenium intake, subsequently collected, and evaluated using the University of Texas Food Intake Analysis System and the United States Department of Agriculture Survey Nutrition Database. ¹⁹ Telomere length determination involved selecting blood samples from all participants in the NHANES database. Quantitative PCR methods were then employed to measure telomere length (T/S ratio) relative to standard reference deoxyribonucleic acid (DNA). ²⁰ The T/S ratio, which refers to the Telomere‐to‐Single copy gene ratio, was further converted to base pairs (bp) using the formula: base pairs = 3274 + 2413 × [T/S], calculated by comparing the telomere restriction fragment (TRF) length analyzed via Southern blot and the T/S ratio of DNA samples using human diploid fibroblast IMR90. ²¹

2.3. Covariates processing

The covariates considered in the analysis encompassed age, sex, race, marital status, BMI (calculated as weight divided by height squared [kg/m²]), physical activity, stroke history, and energy intake. Marital status was categorized as married or living with a partner, widowed, divorced or separated, or never married. Physical activity was classified into four levels according to NHANES criteria: no aerobic activity, low activity (predominantly sitting during the day and infrequent activity), moderate activity (standing or walking all the time during the day without frequent extraction of items, or carrying lightweight items or frequent mountain climbing), and high activity (having to work at high loads or carrying heavy objects). ²² Stroke history was identified through participants' self‐reports on whether or not they had experienced a stroke.

2.4. Statistical analysis

Data analysis was conducted using the Analysis System software, employing statistical software packages R (http://www.R‐project.org) and Empower stats (www.empowerstats.com, X&Y Solutions, Inc., Boston, MA). Initially, the data were stratified into male and female groups to characterize the hypertension participants, utilizing mean ± standard deviations or numbers and proportions for expression. Subsequently, interaction analysis was conducted based on age, sex, race, marital status, physical activity, and family history, to explore the relationship between dietary selenium and telomere length. Generalized linear models were employed to assess the association between dietary selenium intake and telomere length in hypertension patients. The first model remained unadjusted, while the second model incorporated adjustments for sex, age, race, BMI, and marital status. The third model extended these adjustments to include physical activity, energy, and stroke history. Notably, an interaction effect of sex on the relationship between telomere length and dietary selenium in hypertension patients was identified. Finally, generalized linear models were applied to evaluate the association between dietary selenium intake and telomere length in different sex groups of hypertension patients. The first model remained unadjusted, while the second model considered adjustments for age, race, BMI, and marital status. The third model expanded these adjustments to include physical activity, energy, and stroke history. Additionally, spline smoothing was utilized to observe the sex‐specific relationship between telomere length and dietary selenium in hypertension.

3. RESULTS

The study encompassed 2734 participants diagnosed with hypertension. The study population comprised 1331 males and 1403 females, with an average age of 60.07 ± 16.32 years. Hypertensive participants exhibited variations in marital status, BMI, physical activity, energy intake, selenium intake, and telomere length between males and females. Detailed characteristics of hypertensive participants in different sex groups are presented in Table 1.

TABLE 1.

Characteristics of the hypertension participants (N = 2734).

Characters	Total	Male (n = 1331)	Female (n = 1403)	p
Age, year	60.07 ± 16.32	59.51 ± 16.12	60.60 ± 16.49	.081
Race, %				.551
Mexican American	537 (19.64%)	261 (19.61%)	276 (19.67%)
Other Hispanic	127 (4.65%)	54 (4.06%)	73 (5.20%)
Non‐Hispanic white	1425 (52.12%)	709 (53.27%)	716 (51.03%)
Non‐Hispanic black	581 (21.25%)	278 (20.89%)	303 (21.60%)
Other race	64 (2.34%)	29 (2.18%)	35 (2.49%)
Marital status				<.001
Married or living with partner	1718 (62.84%)	975 (73.25%)	743 (52.96%)
Widowed	434 (15.87%)	81 (6.09%)	353 (25.16%)
Divorced or separated	355 (12.98%)	147 (11.04%)	208 (14.83%)
Never married	227 (8.30%)	128 (9.62%)	99 (7.06%)
BMI, kg/m2	29.78 ± 6.53	29.18 ± 5.67	30.34 ± 7.20	<.001
Physical activity				<.001
No aerobic activity	747 (27.32%)	338 (25.39%)	409 (29.15%)
Low activity	1503 (54.97%)	710 (53.34%)	793 (56.52%)
Moderate activity	371 (13.57%)	186 (13.97%)	185 (13.19%)
High activity	113 (4.13%)	97 (7.29%)	16 (1.14%)
Stroke history				.184
No	2578 (94.29%)	1247 (93.69%)	1331 (94.87%)
Yes	156 (5.71%)	84 (6.31%)	72 (5.13%)
Energy, kcal	1912.80 ± 902.78	2199.01 ± 1002.80	1641.27 ± 695.15	<.001
Selenium intake, mcg	97.87 ± 58.34	112.77 ± 67.02	83.75 ± 44.31	<.001
Telomere Length, bp	5611.04 ± 596.52	5580.55 ± 584.36	5639.97 ± 606.62	.009

Abbreviations: BMI, Body Mass Index; bp, base pairs.

We found significant differences between dietary selenium and telomere length using stratified analysis. We further analyzed various interacting factors, including sex, race, marital status, physical activity, and history of stroke, in relation to dietary selenium and telomere length. Our analysis revealed that sex was identified as the interacting factor in the relationship between dietary selenium and telomere length (p = .0237). Details are presented in Table 2.

TABLE 2.

Relationship between dietary selenium intake and telomere length in hypertension (N = 2734).

Characters	N	β (95% CI)	p	p for interaction
Sex				.0237
Female	1403	1.92 (1.21, 2.63)	<.0001
Male	1331	0.94 (0.48, 1.41)	<.0001
Race, %				.1152
Mexican American	537	0.69 (−0.12, 1.50)	.0949
Other Hispanic	127	0.97 (−1.42, 3.37)	.4264
Non‐Hispanic white	1425	1.60 (1.04, 2.16)	<.0001
Non‐Hispanic black	581	0.44 (−0.31, 1.19)	.2484
Other race	64	1.10 (−0.52, 2.71)	.1885
Marital status				.6932
Married or living with partner	1718	1.00 (0.52, 1.49)	<.0001
Widowed	434	0.58 (−0.58, 1.74)	.3297
Divorced or separated	355	0.41 (−0.66, 1.48)	.4524
Never married	227	0.64 (−0.43, 1.71)	.2443
Physical activity				.8956
No aerobic activity	747	1.05 (0.30, 1.81)	.0065
Low activity	1503	0.96 (0.45, 1.48)	.0002
Moderate activity	371	1.22 (0.07, 2.36)	.0379
High activity	113	0.51 (−0.84, 1.86)	.4613
Stroke history				.1370
No	2578	1.07 (0.68, 1.46)	<.0001
Yes	156	−0.49 (−2.32, 1.35)	.6044

The association between dietary selenium intake and telomere length in hypertension patients was examined using various models through a generalized linear model, as outlined in Table 3. Following adjustments for sex, age, race, BMI, marital status, physical activity, energy, and stroke history, we observed a significant correlation between dietary selenium intake and telomere length in individuals with hypertension. Specifically, a 1 mcg increase in dietary selenium intake corresponded to a telomere length increase of 0.51 bp (β = .51 [95% CI: 0.02, 0.99]). This association persisted even after controlling for various factors, highlighting the significance of dietary selenium in influencing telomere length in hypertension.

TABLE 3.

Association between dietary selenium intake and telomere length in hypertension in different models.

Participants	Models	β (95% CI)	p	p* for trend
All participants
	Model 1	1.25 (0.86, 1.64)	<.0001	<.0001
	Model 2	0.54 (0.16, 0.91)	.0048	.0007
	Model 3	0.51 (0.02, 0.99)	.0410	.0055

Model 1 adjust for: none.

Model 2 adjusts for: sex; age; race; BMI; marital status.

Model 3 adjusts for: sex; age; race; BMI; marital status; physical activity; energy; stroke history.

The correlation between dietary selenium intake and telomere length in hypertension across different sex groups was examined using various models through a generalized linear model, as presented in Table 4. Notably, a significant association between dietary selenium intake and telomere length was observed specifically in female hypertension patients, following adjustments for age, race, BMI, marital status, physical activity, energy, and stroke history. In this subset, a 1 mcg increase in dietary selenium intake corresponded to a telomere length increase of 1.19 bp (β = 1.19 [95% CI: 0.32, 2.06]). This relationship remained evident in the linear pattern depicted in Figure 1, highlighting the consistent association between dietary selenium intake and telomere length in female hypertension patients.

TABLE 4.

Association between selenium and telomere length in hypertension in different sex models.

Participants	Models	β (95% CI)	p	p* for trend
Sex
Male	Model 1	0.94 (0.48, 1.41)	<.0001	<.0001
	Model 2	0.24 (−0.20, 0.69)	.2880	.0790
	Model 3	0.18 (−0.40, 0.76)	.5498	.0713
Female	Model 1	1.92 (1.21, 2.63)	<.0001	<.0001
	Model 2	1.17 (0.49, 1.85)	.0008	.0028
	Model 3	1.19 (0.32, 2.06)	.0074	.0277

Model 1 adjust for: none.

Model 2 adjusts for: age; race; BMI; marital status.

Model 3 adjusts for: age; race; BMI; marital status; physical activity; energy; stroke history.

FIGURE 1.

Association between dietary selenium intake and telomere length in hypertension in males and female.

4. DISCUSSION

In this study, we amalgamated data from NHANES 1999−2000 and NHANES 2001−2002, encompassing a total of 2734 US participants diagnosed with hypertension. Among them were 1331 males and 1403 females, with an average age of 60.07 ± 16.32 years. Significant correlations were found between dietary selenium intake and telomere length, particularly in females with hypertension. Adjustments for various factors revealed that a 1 mcg increase in dietary selenium intake correlated with a telomere length increase of 0.51 bp overall, and 1.19 bp specifically in females with hypertension. Our investigation delved into the connections between dietary selenium intake and telomere length. A key discovery in our study was the positive association between dietary selenium intake and telomere length, particularly pronounced in the female population with hypertension. Furthermore, we identified a linear relationship between dietary selenium intake and telomere length in women with hypertension.

Telomeres have long been recognized as biomarkers of human aging, crucial for maintaining genome stability and integrity. ²³ , ²⁴ Recent evidence suggests a positive association between telomere length and healthy living, coupled with a negative correlation with age‐related diseases such as cardiovascular disease, obesity, and diabetes. ²⁵ Adopting a healthy lifestyle, including an antioxidant‐rich diet like the Mediterranean diet, may exert a positive influence on the aging process and mitigate telomere attrition rates. ²⁶ Furthermore, various trace elements such as magnesium, iron, selenium, and copper have been confirmed to exhibit significant correlations with telomere length. ¹⁴ , ¹⁵ , ¹⁸ , ²⁶ Wu and colleagues demonstrated that a deficiency in dietary selenium in mice can lead to DNA damage and heightened aging responses. ²⁷ This phenomenon may arise from insufficient selenium intake, contributing to telomere shortening in colon cells in mice. Additionally, a prior cross‐sectional study identified a positive relationship between dietary selenium intake and telomere length in middle‐aged and older adults in the United States. Our study's findings align with this previous research, however, our study population specifically comprises individuals with hypertension, enhancing the specificity of our results.

The mechanism underlying the impact of dietary selenium intake on telomere length in hypertensive patients remains elusive and may be attributed to several factors. Firstly, human telomere length naturally diminishes with age, contributing to overall bodily aging. ²⁸ Concurrently, telomere attrition is significantly associated with coronary artery disease. ²⁹ Oxidative stress and inflammation, pivotal factors in telomere attrition, are also implicated in age‐related diseases such as hypertension and atherosclerosis. ³⁰ , ³¹ , ³² In vivo, selenium primarily functions through selenium‐containing proteins (selenoproteins). ³³ Selenium or antioxidant selenoproteins can curb excessive immune responses during inflammation by regulating immune cell differentiation and function, thus suggesting increased selenium intake could help mitigate inflammation‐induced telomere attrition. ³⁴ Additionally, elevated oxidative stress, linked to telomere shortening, could be mitigated by selenium's antioxidant properties via selenoproteins, potentially preserving telomere length. ³⁵ Secondly, selenium, a constituent of glutathione peroxidase (GPx), functions by reducing inflammation mediated by reactive oxygen species (ROS), mitigating DNA damage, and fostering telomere length. ³⁶ In vitro studies have indicated that selenium supplementation enhances telomerase expression, subsequently extending telomere length. ³⁷ Additionally, the antioxidant properties of selenoproteins are believed to contribute to cellular protection during aging. ³⁸ Thirdly, hypertensive patients tend to produce more ROS, impairing the antioxidant defense system and intensifying oxidative stress. ³⁹ Adherence to the Mediterranean diet has been demonstrated to reduce the prevalence of type 2 diabetes and cardiovascular disease, possibly owing to the antioxidant and anti‐inflammatory effects inherent in this dietary pattern, which can impact telomere length. ⁴⁰ , ⁴¹ However, the relationship between dietary selenium and hypertension remains unclear, and the protective effect on hypertension may hinge on the baseline selenium intake in the population. ⁴² Consequently, further studies are imperative to elucidate the intricate relationship between dietary selenium intake and telomere length in hypertensive patients.

The findings of our current study align with previous research, underscoring the observed connection between dietary selenium intake and telomere length, particularly in women. ¹⁷ Notably, our study's sample size was smaller than that of Shu and colleagues, as we specifically focused on individuals with hypertension and rigorously controlled for various factors, including age, race, marital status, BMI, physical activity, energy intake, and stroke history. Significant sex‐dependent differences in the activity of glutathione peroxidase (GPx) and selenoproteins such as GPx1 and GPx‐3 exist, implying that women may exhibit higher antioxidant enzyme activity than men. ⁴³ , ⁴⁴ Additionally, studies have reported that females tend to have significantly longer telomeres than males, suggesting a sex‐related regulatory role in telomere length. ⁴⁵ Previous research has indicated that estrogen and other related hormones can protect telomeres from shortening. ⁴⁶ Estrogen, in particular, can inhibit the production of ROS and enhance their scavenging and degradation, signifying that women may possess a superior antioxidant status compared to men. ⁴⁷ Moreover, animal experiments have demonstrated that female mice exhibit lower selenium requirements than their male counterparts, possibly linked to sex differences in telomere attrition. ⁴⁸ However, the specific sex differences between selenium intake and telomere length in the hypertensive population remain unclear, warranting further studies for validation.

This study identifies the association between dietary selenium intake and telomere length in hypertension. Considering selenium is an essential micronutrient with antioxidant properties, and it plays a crucial role in various physiological processes. Therefore, a dietary intervention aimed at increasing selenium intake could potentially impact telomere length and cardiovascular health outcomes in hypertensive patients. However, further well‐designed randomized controlled trials are needed to elucidate the causal relationship between selenium intake, telomere length, and cardiovascular outcomes in this population, as well as to determine the optimal dosage and duration of selenium supplementation for maximizing cardiovascular benefits while minimizing potential risks.

This study is subject to certain limitations. Firstly, the study population was derived from the NHANES database, and the observational nature of the study design complicates the establishment of a causal relationship between dietary selenium and telomere length. Secondly, the assessment of dietary selenium intake relied on 24‐h dietary recall interviews, a method susceptible to biases introduced by variations in participants' diets. Thirdly, our study sample exclusively comprised individuals with high blood pressure in the United States, potentially limiting the generalizability of the findings to populations in other regions. Consequently, additional studies are imperative to provide further insights and clarify the relationship between dietary selenium intake and telomere length in hypertensive patients.

5. CONCLUSIONS

In summary, our study revealed a significant association between dietary selenium intake and telomere length in hypertensive patients, particularly in women. These findings offer a foundation for considering dietary selenium intake in the management of hypertensive patients in the future. However, further validation through prospective studies is essential to solidify and extend these insights.

AUTHOR CONTRIBUTIONS

Cui Liang conceived the study and wrote the manuscript. Ruixue Zhao and Jiaqi Du collected the data and conducted data analysis. Guojun Zhao contributed to study design and data analysis. Yanzhou Zhang edited the manuscript. All authors have screened the manuscript and agreed to publish.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

Liang C, Zhao R, Du J, Zhao G, Zhang Y. The association between dietary selenium intake and telomere length in hypertension. J Clin Hypertens. 2024;26:990–996. 10.1111/jch.14861

DATA AVAILABILITY STATEMENT

The data for this study are accessed publicly at the National Center for Health Statistics (https://www.cdc.gov/nchs/nhanes/).