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The effect of Tai Chi on plasma homocysteine in 1176 adults: a propensity score matching-based study

BMC Cardiovascular Disorders volume 25, Article number: 61 (2025) Cite this article

Abstract

Background

Tai Chi is a low-impact form of exercise that involves a series of slow movements that flow together. Increased plasma homocysteine(Hcy) levels are associated with an increased risk of cardiovascular diseases and may be reduced by exercise. This study aimed to compare plasma Hcy levels and the risk of hyperhomocysteinemia in 1,176 adults with and without Tai Chi exercises.

Methods

This study included 1176 participants from Chenjiagou who adhered to Tai Chi exercise (Tai Chi group, n = 397) and physical examination participants (control group, n = 779). In the Tai Chi group, the type of exercise was 24 simplified forms of Tai Chi, at least 3 times/week for 30–60 min/ time. The median duration of practice for Tai Chi group was 26.5 (11,41) years. Participants in the control group had no regular exercise habits. Baseline data and blood samples were collected from both the groups. Plasma Hcy in the two groups was determined by using the enzyme-linked immunosorbent assay (ELISA) Kit for Hcy. The primary outcome was the difference in Hyc levels between the two groups and the secondary outcome was the effect of Tai Chi on the risk of hyperhomocysteinemia. Propensity score matching(PSM) and other statistical methods were used to balance confounding bias matching and to analyze the effect of Tai Chi on plasma Hcy levels.

Results

In total, 326 pairs of participants were successfully matched between the Tai Chi group and control group. After matching, the plasma Hcy level of the Tai Chi group was 12.30(10.38, 18.16) umol/L, and that of the control group was 14.69(10.63, 20.29) umol/L, and there was a statistical difference between the two groups (P = 0.008). The prevalence of hyperhomocysteinemia (P<0.001) was significantly lower in the Tai Chi group. Univariate analysis showed that the risk of hyperhomocysteinemia in the control group was 2.37 times higher than that in Tai Chi group. After adjusting for confounding factors, the risk of hyperhomocysteinemia in the control group was 3.67 times higher than that in Tai Chi group.

Conclusions

Tai Chi exercise may be associated with lower homocysteine levels and is a promising aerobic exercise for Hcy control.

Trial registration number

ChiCTRl900023059 (Chinese Clinical Trial Registry). The registration date: 2019.5.9.

Peer Review reports

Background

Homocysteine (Hcy) is a sulfur-containing non-essential amino acid named because its chemical properties are similar to those of cysteine. It was first identified in 1932 as an important biological compound [1]. Hcy is an intermediate product of cysteine and methionine metabolism that is widely found in foods and proteins [2]. Hcy levels vary between men and women, with the normal range usually being 5–15 umol/L [3]. It is suggested that hyperhomocysteinemia can be diagnosed when the concentration of plasma Hcy exceeds 15 umol/L [4]. In recent years, the prevalence of hyperhomocysteinemia has been increased globally [5], especially in India, where it has reached 89.8% with a higher prevalence in men than in women [6]. This may be due to an unbalanced diet, poor living habits, obesity, or genetics [7,8,9]. More and more researches shows Hcy is an independent risk factor for cardiovascular and cerebrovascular diseases [10, 11], including ischemic heart disease [12], cognitive decline [13, 14] and cardiovascular disease mortality rates [11, 15]. Elevated Hcy levels increase the risk of atherosclerosis by causing endothelial damage, promoting inflammatory responses, and increasing oxidative stress [3].

Current treatments to control Hcy levels include folic acid and vitamin B12, which effectively promote the folate-dependent Hcy metabolic pathway [16]. However, the safe and effective dose of folic acid supplementation in the general population is low (0.4-1 mg/day), and excessive supplementation may increase the risk of cancer and reduce immunity [17].

Previous studies found that aerobic exercise could significantly reduce plasma Hcy levels and reduced the risk of hyperhomocysteinemia [18, 19]. Tai Chi (TC) is a traditional physical and mental exercise that originated in China and has become increasingly popular in the West. Tai Chi is based on slow intentional movements, often in coordination with breathing and images, designed to strengthen and relax the body and mind and enhance the natural flow of qi”, or life energy [20]. In contrast to yoga and other sports, It is highly acceptable, strong interesting and multi-effect physiological effects [21]. A meta-analysis found that Tai Chi can significantly improve glucose and lipid metabolism, such as by reducing fasting blood glucose, glycated hemoglobin, triglycerides, low-density lipoprotein and increased high-density lipoprotein, but different studies have reported different effects on lipid metabolism indicators [22,23,24]. In addition, studies also found that Tai Chi may be beneficial in improving bone mineral density, bone gla protein levels, and relieving osteoporotic pain in patients with osteoporosis [25, 26]. The above studies suggest that Tai Chi can help improve metabolic diseases however, whether it has a beneficial effect on plasma Hcy metabolism remains controversial [27,28,29]. Therefore, this study aimed to compare plasma Hcy levels and the risk of hyperhomocysteinemia in 1,176 adults with and without Tai Chi exercise (registration number ChiCTRl900023059. The registration date: 2019.5.9).

Methods

Study design and population

In our study, the residents of Chenjiagou Village who insisted on the Tai Chi exercise (located in Zhaobao Town in Wenxian County, North bank of the Yellow River, south of the Taihang Mountains, Henan Province, China) were selected as the research group (Tai Chi group). The Tai Chi exercise was simplified to a 24-style exercise, including Rising power, Part the mustang’s mane from side to side, the white crane bright wings, left and right arm knee down step, Swing the lute, Reverse curl from side to side, Hold the finch’s tail left, Hold the finch tail to the right, Single whip, cloud hand, Single whip, high probing horse, Push off your right foot, Double peaks through ears, Turn and kick to the left, left down independent, Shuttle left and right, Bottom stitch, Submarine needle, Flash arm, Turn and move the hammer, as sealed as closed, Cross hand, close. The frequency of Tai Chi exercise was at least 3 times/week, and each lasting 30–60 min (including 10 min warm-up and 5 min recovery). Chenjiagou is the birthplace of Chen-style Tai Chi. The participants were familiar with Taiji’s movements and norms. The control group comprised physical examination participants who without regular exercise habits(≥ 3 times/week, at least 30 min at a time) in our hospital. In total 1485 participants were assessed for eligibility. Of these, 121 participants aged 18 years and below were excluded, as were 188 participants who discontinued Tai Chi training, had regular exercise habits or had incomplete data. The detailed process is illustrated in Fig. 1.

Fig. 1
figure 1

Participant selection flow chart of this study

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Data collection

In 2019, our team conducted a cross-sectional registration survey of Chenjiagou residents. Uniform training was given to the survey team. The baseline data of the residents were collected through face-to-face interviews and questionnaires. The questionnaire included general information, normal lifestyles, complicated diseases, medical history, drug use, and details of Tai Chi exercises. Professional medical staff ensured the quality of the filling and data authenticity. Professional clinical nurses collected fasting venous blood from the participants to conduct laboratory tests. In the control group, baseline data such as gender, age, body mass index (BMI), blood lipids, comorbidities (including hypertension, diabetes, and hyperhomocysteinemia), plasma Hcy (diagnosed with hyperhomocysteinemia when greater than 15 umol/L), diet, smoking history, alcohol consumption were collected.

Inclusion criteria

(1) age > 18 years; (2) complete baseline data; (3) All participants did no oral intake of Vitamin B6, Vitamin B12, folic acid, or antiepileptic drugs, antineoplastic drugs; and (4) The participants were given informed consent.

Exclusion criteria

(1) Those who give up Tai Chi exercise are excluded; (2) Those with regular exercise habits in physical examination participants were excluded; (3) Participants who stayed up late for long periods or drank heavily were excluded; (4) Vegetarians and pregnant women were excluded (previous studies [30,31,32] have reported that vegetarian patterns and pregnancy may affect Hcy levels in humans); (5) Participants with liver failure, renal failure, hypothyroidism, or malignancy were excluded.

Blood sample processing and testing

Blood samples from fasting subjects were obtained using ethylene diamine tetraacetic acid (EDTA) as an anticoagulant at the Department of Clinical Laboratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, China. Approximately 5 mL venous blood was collected from participants. Blood samples were immediately chilled at < 4 °C and centrifuged (3500r, 8 min) within 1 h of collection using a Thermo Fisher Heraeus FRESCO 17 centrifuge. Plasma was immediately frozen at -79 °C until Hcy determination. Serum samples were also stored in a -79 degree freezer. Total plasma Hcy from approximately 5 mL of venous blood was obtained from the participants and determined using an enzyme-linked immunosorbent assay (ELISA) Kit for Hcy (Cloud-Clone CORP. Wuhan, China, CED984Ge). The ELISA method used to measure the plasma Hcy levels was reliable and validity [33]. This kit is a competitive inhibition enzyme immunoassay technique for the in vitro quantitative measurement of Hcy in plasma. Sensitivity and the minimum detectable dose was less than or equal to 40.22ng/mL. And assay range is 98.77-8,000ng/mL. Specific operations were performed according to the manufacturer’s instructions. The reference range for Hcy in our laboratory is 0 ~ 15.0 umol/L.

Primary and secondary outcomes

The primary outcome was the difference in Hcy levels between the two groups and the secondary outcome was the effect of Tai Chi on the risk of hyperhomocysteinemia.

Statistical analysis

All data were statistically analyzed using SPSS 27.0. The measurement data of normal distribution were expressed \(\:\stackrel{-}{x}\)±s, and the independent sample t test was used for comparison between groups. The measurement data of skewness distribution are expressed as M(P25, P75), and Mann-Whitney U test was used for comparison between groups. Categorical variables were expressed as rates or constituent ratios, and Pearson’s X2test were used for inter-group comparisons. Propensity score matching was used to balance the confounding factors between the two groups. In this study, missing data comprised approximately 2.8% of the analytical sample. Therefore, we directly removed the missing values.

Propensity score matching

Propensity score (PS) methods are typically employed in the data analyses of non-randomized experiments, where a PS is calculated to describe patient characteristics. The estimated PS was subsequently used to balance the baseline characteristics between the two comparison groups so that the treatment effect could be estimated by comparing the groups, as in the experiment [34]. It is widely used in epidemiological observational studies to reduce bias in estimates of the effect of an exposure due to confounding indications. The nearest neighbor matching method is one of the most commonly used matching methods in PSM [35]. The nearest neighbor matching method matches the study subjects in the treatment group, and all individuals can be successfully matched, fully utilizing the information in the treatment group [36]. It typically includes 1:1 matching or 1:n matching. it was necessary to select based on the number of control groups. If the number of samples in the control group was large, a one-to-many matching was considered; otherwise, a one-to-one matching was considered. The caliper value is the allowable range of error when the two groups of subjects are matched based on the PS value. Caliper matching is a matching method based on the nearest-neighbor matching method. Studies have reported that the most appropriate caliper value is 20–25% of the standard deviation of the propensity index in the two groups or an absolute difference in PS between the two groups (caliper value) of 0.02 or 0.03 [37, 38].

In our study, the PSM process was implemented using SPSS 27 extension PS-matching for statistical analyses. The first step was to determine Whether Tai Chi exercise was used as the dependent variable, and confounding factors such as sex, age, BMI, TC, TG, HDL-C, LDL-C, creatinine, uric acid, Folic, vitamin B12, hypertension history, and diabetes history were used as predictive variables (independent variables). Logistic regression was used to estimate propensity score values. In the second step, PS was calculated for each participant based on the regression results. Finally, individuals in the two groups were matched according to PS to achieve a between-group balance of confounding factors. The balance of covariates was tested. Based on previous research and theoretical basis [39,40,41,42], we used the 1:1 nearest neighbor matching method for matching. The matching tolerance was 0.03. Variables were considered to be well balanced between groups when the absolute value of the standard difference was less than 0.1 (10%).

Finally, logistic regression analysis was used to evaluate the influence of Tai Chi training on hyperhomocysteinemia. Relative risk was expressed as the odds ratio (OR) and 95% CI. All statistical tests were bilateral and a p-value < 0.05 was considered statistically significant.

Results

Population characteristics

After screening, 1176 participants were included finally in this study. The participants selection process is illustrated in Fig. 1. The median age was 50 (39,62) years, and 42.9% were male. There were 397 participants in the Tai Chi group (33.8%) and 779 participants in the control group (66.2%). The median duration of practice for Tai Chi group was 26.5 (11,41) years. A total of 461 participants (39.2%) had hyperhomocysteinemia. Among the participants, 10.4% had diabetes, 45.7% had hypertensive, 19.2% were vegetable/fruit eaters, 30.8% were smokers, and 15.4% were alcohol drinkers. Detailed demographic data are summarized in Table 1.

Table 1 Baseline characteristics of participants in the study
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Baseline covariates before and after PSM

The baseline covariates between the balanced Tai Chi and control groups were analyzed using PSM. Characteristics of the baseline covariates before and after matching are summarized in Table 2. 326 participants in the Tai Chi group and 326 participants in the control group were successfully matched 1:1. Before matching, there were significant differences in sex, age, BMI, creatinine, current smoking, preference for vegetables/fruits, and coexisting diseases (diabetes and hypertension) between the two groups (P ≤ 0.05). They were mismatched samples. After matching, there were no significant differences in any variables between the two groups. The unbalanced covariates between the two groups were balanced (P > 0.05). In other words, after applying of PSM, they became matched samples.

Table 2 Change of baseline covariates before and after PSM between Tai Chi group and control group
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Univariate and multivariate analysis for Effect of Tai Chi on plasma homocysteine concentration and the risk of hyperhomocysteinemia

After matching, the median duration of practice for Tai Chi group was 26 (13,41) years. Plasma Hcy levels of Tai Chi group was 12.30(10.38, 18.16) umol/L, and the control group was 14.69(10.63, 20.29) umol/L. There were statistical differences between the two groups (Z=-2.66, P = 0.008), see Fig. 2 and Supplementary Table 3. 95 cases of hyperhomocysteinemia occurred in 326 participants in the Tai Chi group (29.1%), whereas in the control group, 161 hyperhomocysteinemia cases occurred in 326 participants (49.4%). The prevalence of hyperhomocysteinemia was also significantly different between the two groups (X2 = 28.02, P<0.001, see Supplementary Table 3). Univariate logistic regression analysis showed that the risk of hyperhomocysteinemia in the control group was 2.37 times higher than that in the Tai Chi group (OR 2.373, 95%CI 1.718∽3.277). After adjusting for six clinical factors, including age, sex, hypertension, uric acid lever, current drinking history, and current smoking, the risk of hyperhomocysteinemia in the control group was 3.67 times that in the Tai Chi group (OR 3.67, 95%CI 2.439–5.528), (Table 3)

Fig. 2
figure 2

Comparison of plasma Hcy levels between Tai Chi group and Control group, and there were statistical differences between the two groups (Z=-2.66, P = 0.008)

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Table 3 Univariate and multivariate analysis for effect of Tai Chi exercise on risk of hyperhomocysteinemia
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Discussion

We investigated whether long-term Tai Chi exercise affects plasma Hcy concentrations in adults and observed whether it affects the prevalence and risk of hyperhomocysteinemia. Palasuwan et al. did not find any effect of more than 3 h of yoga or tai chi exercise per week for 1 year on total Hcy concentrations [27]. However, in our study, the plasma Hcy concentrations were significantly lower in the Tai Chi group than in the control group, which was consistent with the findings of Zhang et al. [28]. Their results also showed that compared with the control group, 12 weeks of Tai Chi training had a positive effect on Hcy levels, significantly reduced triglyceride and fasting blood glucose levels, and improved balance. But the sample size in their study was small, and the intervention period was relatively short. Another study on the effect of Tai Chi exercise on the antioxidant capacity of premenopausal and postmenopausal women also confirmed that 8 weeks of Tai Chi training can significantly reduce plasma Hcy levels [29], there are also limitations of samples. Our study addressed not only the effect of Tai Chi exercise on Hcy levels but also the effect of Tai Chi exercise on the prevalence and risk of hyperhomocysteinemia. The prevalence of hyperhomocysteinemia and plasma Hcy levels in the Tai Chi group were significantly lower than those in the control group. After adjusting for confounding factors, the risk of hyperhomocysteinemia in the control group was 3.67 times higher than that in Tai Chi group. However, the biological mechanisms by which Tai Chi influences Hcy levels require further exploration. Direct evidence of the mechanism by which Tai Chi affects Hcy levels is still lacking. Study [43] had shown that Hcydecreases the ability of cells to detoxify hydrogen peroxide by impairing intracellular antioxidant enzymes, specifically glutathione peroxidase (GPx). The overexpression of cellular GPx can compensate for the effects of homocysteinemia. Palasuwan A found that 8-weeks of Tai Chi training significantly increased erythrocyte GPx activity and whole blood GPx activity, while significantly decreasing Hcy levels compared to pre-training data [29]. This suggests that Tai Chi exercise increases GPx activity and may directly or indirectly reduce plasma tHcy levels.

Tai Chi is considered a moderate-intensity aerobic exercise [44]. There may also be other explanations for the effects of aerobic exercise on Hcy levels. Studies have shown that in addition to effective nutrient supplementation, physical activity can alter Hcy production by increasing protein and/or methyl renewal [45]. During exercise, protein renewal is accelerated, methionine catabolism is increased, and Hcy levels are reduced, particularly during long-term moderate-intensity exercise. As reported in previous study [18], Wang et al. investigated the association between regular aerobic exercise and hyperhomocysteine (hHcy) in participants with hypertension. The results showed an inverse association between regular aerobic exercise and hyperhomocysteinemia in participants with hypertensive. Animal experiments [19] also showed that compared to the HHcy group (18.88 ± 6.13 µmol/L), plasma Hcy concentration was significantly reduced in the HHcy + aerobic exercise (14.79 ± 3.05 µmol/L). However, high-intensity and prolonged physical activity accelerates methyl renewal and increases the demand for creatine, thereby increasing Hcy production [46]. In addition, exercise can also increase the content of B vitamins in the body, increasecoenzymes in the process of Hcy metabolism, and thus reduceplasma Hcy levelsc. The effects of Taiji on Hcy levels may also be related to these mechanisms [47,48,49,50,51].

Our study has several advantages. In this study, propensity score matching was applied to avoid the influence of confounding factors such as age, sex, body mass index, blood pressure, and blood glucose, and 321 pairs of valid data were obtained. Compared with previous studies, the sample size was significantly larger, and confounding factors were controlled as much as possible.

This study had some limitations. First, PSM was applied to eliminate the influence of confounding factors. However, the PSM method has limitations in that it excludes a portion of cases, which may cause selection bias and affect the generalizability of the results. However, we relaxed the inclusion criteria as much as possible when designing the study protocol to increase the sample size and representativeness. In the future, multi-center, large-sample clinical trials and statistical models are required to directly adjust for confounding variables. Second, our study was limited because the intervention starting point of the participants in the Tai Chi group is inconsistent. Further large randomized controlled studies are required to confirm our findings. Third, we did not select non-Tai Chi personnel from the same regions as the Tai Chi group. The population studied was specific to Chenjiagou, and there may have been regional differences. It should be emphasized that this specific population may limit the generalizability of our findings. Fourth, although we made efforts to include as many factors as possible that could influence plasma Hcy levels, other confounding factors such as genetics and diet were not considered. These factors may have affected the balance between the two groups. In future, we will conduct a multi-center, randomized controlled trial, during which we aim to collect more detailed baseline data from participants, including information on the region, ethnicity, carbohydrate intake, salt consumption, and variations in proteomic profiles related to differential proteins and metabolic pathways associated with Hcy. Fifth, our data were collected through self-reported questionnaires and interviews, which may have been subject to recall or voluntary response bias. To mitigate recall and voluntary response bias, we developed a structured questionnaire and provided standardized training to data collectors conducted by a professional epidemiologist. We performed a double verification of the subjective information provided by the participants and validated the accuracy of this information by consulting their family members. Sixth, we followed the approach of previous research [52, 53] and measured the participants’ folate and vitamin B12 levels using the Beckman folate assay kit (chemiluminescence method) on fasting serum samples. But not using red blood cell samples to test for folate is indeed a flaw in this study. Finally, as this was a cross-sectional study, survivor bias was possible, and a causal relationship could not be determined. However, further longitudinal studies are required to confirm these conclusions. We can further clarify the beneficial mechanism of Tai Chi exercise on Hcy levels through the detection of related biomarkers or through molecular studies.

Conclusions

Our results suggest that Tai Chi exercise is associated with lower Hcy levels. Tai Chi is a promising aerobic exercise that may be a new form of exercise for Hcy control. More high-quality longitudinal or randomized controlled studies are needed to prove the causal relationship between Tai Chi and Hcy. The possible mechanisms by which Tai Chi affects Hcy levels, such as biomarkers, were also explored. It is recommended that public health and clinical departments encourage Tai Chi exercise in the hope that it will reduce the adverse risk of cardiovascular and cerebrovascular diseases caused by Hcy.

Data availability

The datasets used in this study are available from the corresponding author upon request.

Abbreviations

Hcy:

Homocysteine

PSM:

Propensity score matching

BMI:

Body mass index

TC:

Total Cholesterol

TG:

Triglyceride

HDL-C:

High-density lipoprotein Cholesterol

LDL-C:

Low density lipoprotein Cholesterol

OR:

Odds ratio

TC-group:

Tai Chi group

BMI:

Body mass index

EDTA:

Ethylene Diamine Tetraacetic Acid

ELISA:

Enzyme-linked immunosorbent assay

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Acknowledgements

Thanks to all participants for their contributions to this study, and we appreciate the reviewers’ valuable comments.

Funding

This study was supported by the Henan Medical Science and Technology Project(grant number: LHGJ20220865).

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Authors and Affiliations

  1. Department of Cardiac Rehabilitation, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, China

    Yingchun Gu, Juncai Bai, Yang Li, Ling Han & Dongwei Wang

Authors
  1. Yingchun Gu
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  2. Juncai Bai
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  3. Yang Li
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  4. Ling Han
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  5. Dongwei Wang
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Contributions

GYC, BJC and WDW wrote the main manuscript text and GYC, LY and HL prepared the Tables 1, 2 and 3 and Fig. 1. GYC and BJC provides research ideas. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Dongwei Wang.

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Ethical approval

This study followed the ethical guidelines of the Declaration of Helsinki and was approved by the Medica Ethics Committee of Zhengzhou Central Hospital Affiliated to Zhengzhou University( Approval number: 201901). All participants volunteered to sign written informed consent.

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Not applicable.

Competing interests

The authors declare no competing interests.

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12872_2025_4519_MOESM1_ESM.docx

Supplementary Material 1: Supplementary Table 3 Comparison of homocysteine and prevalence of hyperhomocysteinemia between two groups.

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Gu, Y., Bai, J., Li, Y. et al. The effect of Tai Chi on plasma homocysteine in 1176 adults: a propensity score matching-based study. BMC Cardiovasc Disord 25, 61 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12872-025-04519-9

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12872-025-04519-9

Keywords

BMC Cardiovascular Disorders

ISSN: 1471-2261

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