Abstract
We examined the association between high-density lipoprotein cholesterol (HDL-C), and exercise and vegetarian diets, in Taiwanese adults, based on the Methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism. Using regression models, we analyzed historical data collected from 9255 Taiwan Biobank (TWB) participants from 2008 through 2015. Exposure to exercise was associated with higher HDL-C (β = 1.0508 and 1.4011 for GG and GA + AA individuals, respectively), whereas a vegetarian diet was associated with lower HDL-C (β = −6.2793 and −4.6359 for those with GG and GA + AA genotype, respectively). We found an interaction between exercise and diet among GG individuals (p = 0.0101). Compared with no exercise/no vegetarian diet, vegetarian diet/no exercise was associated with a 5.1514 mg/dl reduction in HDL-C among those with GG genotype (β = −5.1514, p < 0.0001) and a 4.8426 mg/dl reduction (β = −4.8426, p < 0.0001) among those with GA + AA genotype. Vegetarian diets in combination with exercise predicted a 6.5552 mg/dl reduction in HDL-C among GG individuals (β = −6.5552) and a 2.8668 mg/dl reduction among GA + AA individuals (p < 0.05). These findings demonstrated that vegetarian diet alone was associated with lower HDL-C, no matter the rs1801133 genotype. However, the inclusion of regular exercise predicted much lower levels among GG individuals, whereas levels among GA + AA individuals were relatively higher.
Keywords: lipids, diet, exercise, polymorphism, biobank
1. Introduction
High-density lipoprotein cholesterol is a well-known lipid fraction [1] that has been associated with the risk of heart diseases [2]. Lower levels of HDL-C (i.e., <40 mg/dl and <50 mg/dl for men and women, respectively) have been associated with heightened risk of cardiovascular disease, even though the epidemiological relationship between them remains complex [3]. Lower concentrations of HDL-C have also been associated with systemic inflammation and elevated risk of sepsis [4,5].
Vegetarian diets are important in the prevention and treatment of diseases [6]. However, previous works investigating lipid profiles have reported negative associations between HDL-C and vegetarian diets [7,8,9]. In a separate study, consumption of vegetarian diets was associated with decreased levels of HDL-C, low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), but not with triglycerides (TG) [10]. In addition, vegetarian diets have also shown strong associations with total plasma homocysteine (Hcy) levels [11].
Exercise is among the lifestyle variables previously recommended for boosting lipid profiles [12]. More recent evidence [13] suggested dose–response relationships between HDL-C and exercise intensity. Habitual or a single bout of exercise can positively affect cholesterol metabolism [14]. According to MayoClinic, benefits can be seen with as little as 60 min of moderate aerobic exercise a week [15]. It has been hypothesized that exercise can increase the expression of liver ATP-binding cassette transporters A-1, which play an essential role in the reverse cholesterol transport system [16].
Exercise is believed to provide more benefits for HDL-C than those obtained by eating just vegetarian diets [17]. It is widely believed that exposure to exercise is a great way for vegetarians to boost their HDL cholesterol [15]. As far as we know, investigations have not been carried out to determine whether coupling a vegetarian diet with exercise would predict a reduction or an increase in HDL-C. Such investigations would help to enhance the knowledge of HDL-C response in terms of lifestyle variables.
Besides the lifestyle determinants, genetic factors contribute to variations in HDL-C concentrations. The methylenetetrahydrofolate reductase (MTHFR) gene, an important enzyme for folate metabolism, has been demonstrated to be associated with abnormal lipid levels and coronary artery diseases [18,19,20]. Rs1801133 (also known as C677T) is one of its most common and best-studied polymorphisms, which showed stronger associations with cardiovascular disease risk, especially among Asians [18]. This variant reduces enzyme activity and raises the concentration of total Hcy [21], which is a potential risk factor for dyslipidemia and cardiovascular disease [22]. The significance of this polymorphic variant has already been previously described [23]. Interactions previously reported between C677T and serum lipid levels have been partly linked to lifestyle and environmental factors [24]. Of these factors, exposure to regular exercise has been demonstrated to attenuate central artery stiffening caused by the C677T variant [25].
As stated earlier, exercise and vegetarian diets are some of the modifiable factors previously associated with HDL-C. However, whether the combined effect of these variables on HDL-C is modified by rs1801133 polymorphism has not yet been established. Therefore, we examined the interactive association of exercise and vegetarian diets with HDL-C among Taiwanese individuals, based on MTHFR rs1801133 polymorphism.
2. Methods
Data were obtained from the TWB, an established infrastructure holding data of Taiwanese individuals (aged 30–70 years) recruited from assessment centers across Taiwan, from 2008 through 2015. Before data collection, all participants signed written informed consent. Currently, TWB contains biological, experimental, questionnaire, and physical assessment data, collected from over 129,054 participants from different parts of Taiwan. We obtained ethical approval from the Institutional Review Board of Chung Shan Medical University (CS2-16114).
2.1. Study Participants
At the beginning of the study, data were available for 9287 TWB participants with no history of cancer. However, we excluded 32 individuals with incomplete or missing information. Finally, we analyzed data for 9255 participants (4938 women and 4317 men). Sociodemographic and clinical variables of the participants included sex, age, diet type, smoking, coffee drinking, alcohol intake, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), body mass index (BMI), waist-hip ratio (WHR), uric acid and body fat.
Diet type, smoking, alcohol intake and coffee consumption were assessed through self-reported questionnaires held in the TWB dataset. In our analyses, participants were grouped based on rs1801133 genotypes (i.e., GG and GA + AA) and diet type. They were classified as former vegetarians if they were not currently on vegetarian diets but reported to have consistently consumed them for at least 6 months in their lifetime. Vegetarians included participants who had continuously consumed plant-based food for 6 months or more, and were currently on the diet during the recruitment period. Regular exercise was considered as engaging in at most 3 physical activities lasting 30 min each session, and at least 3 sessions a week. The exercise patterns contained in the TWB questionnaires have already been discussed in our previous publication [26]. Details of the other lifestyle variables included in our model have also been previously described [27].
2.2. Variant Selection/Genotyping
We selected MTHFR rs1801133, which is one of the most common and the best-studied polymorphisms previously associated with serum lipid levels [24]. We performed genotyping using the Axiom Genome-Wide Array Plate System (Affymetrix, Santa Clara, CA, USA). For quality control purposes, we included only participants whose call rates were over 90%, and excluded single nucleotide polymorphisms (SNPs) with low minor allele frequencies (i.e., <0.05). SNPs that were not in Hardy–Weinberg equilibrium (that is, p < 1.0 × 10−3) were also excluded.
2.3. Statistical Analysis
PLINK 1.09 beta and SAS 9.4 software (SAS Institute, Cary, NC, USA) were used to perform analyses. We separated participants into 3 diet categories that included non-vegetarians, former vegetarians and vegetarians (including lacto-ovo-vegetarian and vegan). In total, 443 participants were vegetarians. Among them, 142 were rs1801133-GG individuals without exercise, 100 were rs1801133-GG individuals with exercise, 125 were rs1801133-GA + AA individuals without exercise, and 76 were rs1801133-GA + AA individuals with exercise. We analyzed the categorical variables using the Chi-square test and the continuous variables were described as means ± standard error. Using multivariate linear regression analysis, we estimated the β coefficients and their corresponding p-values. Exercise and vegetarian diets each were considered to be 1 unit of change. A statistically significant beta coefficient indicated that the variable predicted an outcome.
3. Results
The baseline characteristics of participants according to rs1801133 are described in Table 1. There were 5016 individuals with the rs1801133-GG genotype and 4239 with the GG + AA genotype. Overall, vegetarian diet was associated with lower HDL-C among those with rs1801133-GG (β = −6.2793, p < 0.0001) and rs1801133-GG + AA (β = −4.6359, p < 0.0001) genotypes, respectively (Table 2). Exposure to exercise predicted a higher HDL-C among those with both genotypes, with β values of 1.0508 (p = 0.0015) for rs1801133-GG individuals and 1.4011 (p = 0.0001) for rs1801133-GG + AA individuals. Compared to women, men with rs1801133-GG and rs1801133-GG + AA genotypes were associated with lower HDL-C. Their β values were −7.9509 (p < 0.0001) and −7.2069 (p < 0.0001), respectively. The interaction between diet type and exercise exposure was significant only among those with the GG genotype (p = 0.0101). Compared with the non-vegetarian diet, vegetarian diet predicted a decrease in HDL-C in both GG and GA + AA individuals belonging to the exercise (β = −7.9361 and β = −4.5577, respectively, p < 0.05) and no exercise (β = −5.1297 and β = −4.6986, p < 0.0001) groups, respectively (Table 3). With non-vegetarian diet plus no exercise as the reference group, vegetarian diet/no exercise was associated with a 5.1514 mg/dl reduction in HDL-C among GG carriers (β = −5.1514, p < 0.0001) and a 4.8426 mg/dl decrease (β = −4.8426, p < 0.0001) among GA + AA carriers (Table 4). Likewise, a vegetarian diet/regular exercise was associated with a 6.5552 mg/dl reduction in HDL-C among GG carriers (β = −6.5552, p < 0.0001), and a 2.8668 mg/dl decrease in HDL-C among those with GA + AA genotypes. Regular exercise/non-vegetarian diet predicted a 1.3135 mg/dl (β = 1.3135, p < 0.0001) and 1.4301 mg/dl (β = 1.4301 p < 0.0002) reduction in HDL-C among GG and GA + AA individuals, respectively.
Table 1.
Demographic characteristics of participants grouped by rs1801133 genotypes.
| Variable | rs1801133-GG (n = 5016) | rs1801133-GA + AA (n = 4239) | p-Value | ||
|---|---|---|---|---|---|
| N | Mean HDL-C (SE) | N | Mean HDL-C (SE) | ||
| Diet type | 0.9828 | ||||
| Non-vegetarian | 4542 | 54.056 (0.198) | 3842 | 54.010 (0.214) | |
| Former vegetarian | 232 | 54.297 (0.953) | 196 | 53.510 (0.960) | |
| Vegetarian | 242 | 49.591 (0.707) | 201 | 50.010 (0.867) | |
| Exercise | 0.8657 | ||||
| No | 2909 | 53.146 (0.244) | 2451 | 52.993 (0.262) | |
| Yes | 2107 | 54.826 (0.294) | 1788 | 54.900 (0.320) | |
| Sex | 0.5662 | ||||
| Women | 2690 | 58.455 (0.255) | 2248 | 58.363 (0.280) | |
| Men | 2326 | 48.529 (0.234) | 1991 | 48.642 (0.249) | |
| Age (years) | 0.9905 | ||||
| 30–40 | 1313 | 53.998 (0.364) | 1102 | 53.786 (0.394) | |
| 41–50 | 1407 | 53.684 (0.352) | 1182 | 53.483 (0.387) | |
| 51–60 | 1437 | 53.446 (0.353) | 1224 | 54.227 (0.377) | |
| 61–70 | 859 | 54.582 (0.462) | 731 | 53.603 (0.498) | |
| TG (mg/dl) | 0.0046 | ||||
| <150 | 3896 | 56.711 (0.207) | 3395 | 56.300 (0.223) | |
| ≥150 | 1120 | 43.907 (0.273) | 844 | 43.732 (0.297) | |
| LDL-C (mg/dl) | 0.6191 | ||||
| <130 | 3069 | 54.185 (0.257) | 2615 | 54.001 (0.270) | |
| ≥130 | 1947 | 53.327 (0.265) | 1624 | 53.470 (0.304) | |
| WHR | 0.0770 | ||||
| Men < 0.9; women < 0.85 (ref) | 2757 | 56.636 (0.259) | 2252 | 56.206 (0.288) | |
| Men ≥ 0.9; women ≥ 0.85 | 2259 | 50.455 (0.255) | 1987 | 51.067 (0.273) | |
| Body mass index, kg/m2 | 0.0233 | ||||
| 18.5–23.9 (ref) | 2489 | 58.039 (0.265) | 1969 | 57.837 (0.298) | |
| <18.5 | 128 | 66.828 (1.278) | 108 | 65.204 (1.391) | |
| 24–26.9 | 1443 | 50.338 (0.309) | 1298 | 51.276 (0.330) | |
| ≥27 | 956 | 46.517 (0.319) | 864 | 46.953 (0.360) | |
| Body fat (%) | 0.1882 | ||||
| Men < 25; women < 30 (ref) | 2711 | 55.969 (0.268) | 2233 | 55.456 (0.288) | |
| Men ≥ 25; women ≥ 30 | 2305 | 51.363 (0.251) | 2006 | 51.951 (0.280) | |
| Smoking | 0.3176 | ||||
| Nonsmokers | 3893 | 55.378 (0.213) | 3281 | 55.468 (0.233) | |
| Former smokers | 568 | 49.889 (0.513) | 516 | 48.953 (0.476) | |
| Current smokers | 555 | 47.205 (0.500) | 442 | 47.048 (0.549) | |
| Alcohol intake | 0.2371 | ||||
| nondrinkers | 4495 | 54.211 (0.197) | 3820 | 54.199 (0.216) | |
| Former drinkers | 160 | 45.531 (0.821) | 110 | 48.036 (1.005) | |
| Current drinkers | 361 | 53.066 (0.755) | 309 | 50.883 (0.658) | |
| Coffee drinking | 0.4381 | ||||
| No | 3333 | 53.361 (0.227) | 2849 | 53.448 (0.247) | |
| Yes | 1683 | 54.825 (0.332) | 1390 | 54.514 (0.356) | |
| Uric acid, mg/dl | 0.0334 | ||||
| men < 7, women < 6 (ref) | 3851 | 55.528 (0.217) | 3174 | 55.665 (0.236) | |
| men ≥ 7, women ≥ 6 | 1165 | 48.311 (0.328) | 1065 | 48.230 (0.350) | |
SE: standard error; WHR: waist-to-hip ratio; BMI: Body mass index; TG: triglyceride; LDL-C: Low-density lipoprotein cholesterol; HDL-C: High-density lipoprotein cholesterol.
Table 2.
Regression coefficients of lifestyle variables associated with HDL-C according to rs1801133 genotypes.
| Variables | rs1801133-GG | rs1801133-GA + AA | ||
|---|---|---|---|---|
| β | p-Value | β | p-Value | |
| Diet type (ref: Non-vegetarian) | ||||
| Former vegetarian | −0.1917 | 0.7918 | −0.3995 | 0.6222 |
| Vegetarian | −6.2793 | <0.0001 | −4.6359 | <0.0001 |
| p-trend | <0.0001 | <0.0001 | ||
| Exercise (ref: No) | ||||
| Yes | 1.0508 | 0.0015 | 1.4011 | 0.0001 |
| Sex (ref: women) | ||||
| Men | −7.9509 | <0.0001 | −7.2069 | <0.0001 |
| Age (ref: 30–40) | ||||
| 41–50 | 0.5879 | 0.1630 | 0.5495 | 0.2453 |
| 51–60 | 1.0893 | 0.0131 | 1.2023 | 0.0149 |
| 61–70 | 1.7187 | 0.0009 | 1.0543 | 0.0673 |
| TG (ref: <150) | ||||
| ≥150 | −8.2129 | <0.0001 | −8.1116 | <0.0001 |
| LDL-C (ref: <130) | ||||
| ≥130 | 1.1095 | 0.0005 | 1.4316 | 0.0001 |
| WHR (ref: men < 0.9; women < 0.85) | ||||
| Men ≥ 0.9; women ≥ 0.85 | −2.6110 | <0.0001 | −2.4022 | <0.0001 |
| Body mass index, kg/m2 (ref: 18.5–23.9) | ||||
| <18.5 | 6.2828 | <0.0001 | 5.7646 | <0.0001 |
| 24–26.9 | −3.6743 | <0.0001 | −3.1293 | <0.0001 |
| ≥27 | −4.5426 | <0.0001 | −5.0012 | <0.0001 |
| Body fat (ref: Men < 25; women < 30) | ||||
| Men ≥ 25; women ≥ 30 | −1.9773 | <0.0001 | −0.6996 | 0.1201 |
| Smoking (ref: Nonsmokers) | ||||
| Former smokers | −0.0117 | 0.9824 | −0.9565 | 0.0988 |
| Current smokers | −2.7451 | <0.0001 | −1.9437 | 0.0019 |
| Alcohol intake (ref: Nondrinkers) | ||||
| Former drinkers | −1.0938 | 0.2265 | −0.4513 | 0.6793 |
| Current drinkers | 6.0734 | <0.0001 | 3.5075 | <0.0001 |
| Coffee drinking (ref: No) | ||||
| Yes | 0.7415 | 0.0230 | 0.5075 | 0.1650 |
| Uric acid, mg/dl (ref: men < 7, women <6) | ||||
| men ≥ 7, women ≥ 6 | −1.5541 | 0.0001 | −2.1708 | <0.0001 |
Table 3.
Association of vegetarian diet with HDL-C based on rs1801133 genotypes and exercise exposure.
| Variables | rs1801133-GG | rs1801133-GA + AA | ||||||
|---|---|---|---|---|---|---|---|---|
| No Exercise | Exercise | No Exercise | Exercise | |||||
| β | p-Value | β | p-Value | β | p-Value | β | p-Value | |
| Diet type (ref: Non-vegetarian) | ||||||||
| Former vegetarian | 0.8314 | 0.3476 | −2.0019 | 0.1127 | 0.0519 | 0.9581 | −1.3033 | 0.3485 |
| Vegetarian | −5.1297 | <0.0001 | −7.9361 | <0.0001 | −4.6986 | <0.0001 | −4.5577 | 0.0008 |
| p-trend | <0.0001 | <0.0001 | <0.0001 | 0.0007 | ||||
| Sex (ref: women) | ||||||||
| Men | −8.1078 | <0.0001 | −7.7185 | <0.0001 | −6.6446 | <0.0001 | −8.0869 | <0.0001 |
| Age (ref: 30–40) | ||||||||
| 41–50 | 0.4769 | 0.3248 | 0.7870 | 0.3552 | 1.0190 | 0.0585 | −0.8985 | 0.3522 |
| 51–60 | 1.1302 | 0.0369 | 0.9529 | 0.2370 | 1.9337 | 0.0015 | −0.1497 | 0.8691 |
| 61–70 | 1.5450 | 0.0371 | 1.6555 | 0.0523 | 0.3052 | 0.6980 | 0.6124 | 0.5294 |
| TG (ref: <150) | ||||||||
| ≥150 | −7.7074 | <0.0001 | −8.9542 | <0.0001 | −7.7816 | <0.0001 | −8.6927 | <0.0001 |
| LDL-C (ref: <130) | ||||||||
| ≥130 | 1.0732 | 0.0102 | 1.1117 | 0.0276 | 2.1314 | <0.0001 | 0.4474 | 0.4294 |
| WHR (ref: Men < 0.9; women < 0.85) | ||||||||
| Men ≥ 0.9; women ≥ 0.85 | −2.6070 | <0.0001 | −2.6692 | <0.0001 | −2.5188 | <0.0001 | −2.4311 | 0.0001 |
| Body mass index, kg/m2 (ref: 18.5–23.9) | ||||||||
| BMI < 18.5 | 6.1337 | <0.0001 | 6.6755 | 0.0002 | 4.6449 | 0.0002 | 9.2076 | <0.0001 |
| 24–26.9 | −3.6149 | <0.0001 | −3.7077 | <0.0001 | −3.2793 | <0.0001 | −2.9512 | <0.0001 |
| ≥27 | −4.0139 | <0.0001 | −5.3350 | <0.0001 | −5.3062 | <0.0001 | −4.5617 | <0.0001 |
| Body fat (ref: Men < 25; women < 30) | ||||||||
| Men ≥ 25; women ≥ 30 | −2.2468 | <0.0001 | −1.6160 | 0.0119 | −0.7847 | 0.1727 | −0.6886 | 0.3386 |
| Smoking (ref: Nonsmokers) | ||||||||
| Former smokers | −0.1570 | 0.8269 | 0.1372 | 0.8636 | −1.0469 | 0.1701 | −0.5860 | 0.5120 |
| Current smokers | −2.8800 | <0.0001 | −2.5990 | 0.0096 | −2.6090 | 0.0004 | −1.0954 | 0.3494 |
| Alcohol intake (ref: Nondrinkers) | ||||||||
| Former drinkers | −0.7260 | 0.5865 | −1.4799 | 0.2390 | −1.3610 | 0.3676 | 0.6249 | 0.6957 |
| Current drinkers | 6.5085 | <0.0001 | 5.3821 | <0.0001 | 4.8254 | <0.0001 | 1.8587 | 0.0967 |
| Coffee drinking (ref: No) | ||||||||
| Yes | 0.9987 | 0.0167 | 0.3849 | 0.4616 | 0.5014 | 0.2790 | 0.5678 | 0.3391 |
| Uric acid, mg/dl (ref: men < 7, women < 6) | ||||||||
| men ≥ 7, women ≥ 6 | −1.3670 | 0.0065 | −1.7314 | 0.0044 | −1.8402 | 0.0006 | −2.7109 | 0.0001 |
β: beta coefficient; WHR: waist-to-hip ratio; BMI: Body mass index: TG triglyceride; LDL-C: Low-density lipoprotein cholesterol; HDL-C: High-density lipoprotein cholesterol.
Table 4.
Exercise exposure together with vegetarian diets and their association with HDL-C.
| Variables | rs1801133-GG | rs1801133-GA + AA | ||
|---|---|---|---|---|
| β | p-Value | β | p-Value | |
| Exercise and Diet type (ref: no exercise/non-vegetarian) | ||||
| No exercise/Former vegetarian | 0.8068 | 0.3724 | 0.0541 | 0.9577 |
| No exercise/Vegetarian | −5.1514 | <0.0001 | −4.8426 | <0.0001 |
| Regular exercise/non-vegetarian | 1.3135 | 0.0001 | 1.4301 | 0.0002 |
| Regular exercise/Former vegetarian | −0.6585 | 0.5862 | 0.2568 | 0.8464 |
| Regular exercise/Vegetarian | −6.5552 | <0.0001 | −2.8668 | 0.0273 |
| Sex (ref: women) | ||||
| Men | −7.9224 | <0.0001 | −7.2075 | <0.0001 |
| Age (ref: 30–40) | ||||
| 41–50 | 0.6059 | 0.1504 | 0.5663 | 0.2317 |
| 51–60 | 1.0645 | 0.0153 | 1.2121 | 0.0142 |
| 61–70 | 1.6897 | 0.0011 | 1.0612 | 0.0656 |
| TG (ref: <150) | ||||
| ≥150 | −8.2103 | <0.0001 | −8.1141 | <0.0001 |
| LDL-C (ref: <130) | ||||
| ≥130 | 1.1034 | 0.0006 | 1.4310 | 0.0001 |
| WHR (ref: Men < 0.9; women < 0.85) | ||||
| Men ≥ 0.9; women ≥ 0.85 | −2.6201 | <0.0001 | −2.4058 | <0.0001 |
| Body mass index, kg/m2 (ref: 18.5–23.9) | ||||
| <18.5 | 6.3076 | <0.0001 | 5.7872 | <0.0001 |
| 24–26.9 | −3.6710 | <0.0001 | −3.1217 | <0.0001 |
| ≥27 | −4.5409 | <0.0001 | −4.9955 | <0.0001 |
| Body fat (ref: Men < 25; women < 30) | ||||
| Men ≥ 25; women ≥ 30 | −1.9766 | <0.0001 | −0.6998 | 0.1200 |
| Smoking (ref: Nonsmokers) | ||||
| Former smokers | −0.0321 | 0.9518 | −0.9705 | 0.0942 |
| Current smokers | −2.7519 | <0.0001 | −1.9387 | 0.0020 |
| Alcohol intake (ref: Nondrinkers) | ||||
| Former drinkers | −1.1352 | 0.2093 | −0.4382 | 0.6882 |
| Current drinkers | 6.0677 | <0.0001 | 3.5075 | <0.0001 |
| Coffee drinking (ref: No) | ||||
| Yes | 0.7495 | 0.0215 | 0.5110 | 0.1625 |
| Uric acid, mg/dl (ref: men < 7, women < 6) | ||||
| men ≥ 7, women ≥ 6 | −1.5389 | 0.0001 | −2.1757 | <0.0001 |
β: beta coefficient; WHR: waist-to-hip ratio; BMI: Body mass index: TG triglyceride; LDL-C: Low-density lipoprotein cholesterol; HDL-C: High-density lipoprotein cholesterol.
4. Discussion
As far as we understand, this study is the first to determine the relationship between HDL-C and a vegetarian diet together with exercise exposure in Taiwanese adults, based on MTHFR rs1801133 polymorphism. We found that exposure to exercise was linked to higher HDL-C levels in GG and GG + AA individuals, whereas the intake of vegetarian diets was associated with lower levels. Compared to a vegetarian diet alone, vegetarian diets combined with regular exercise led to much lower HDL-C levels among GG individuals, and comparatively higher levels among those with GA + AA genotype.
We believe that several studies have already examined associations between HDL-C, exercise and diets. However, such associations have not been analyzed based on the MTHFR rs1801133 polymorphism as we have done in the current study. In a systemic review [18], the rs1801133 polymorphic variant showed a strong association with lower HDL-C. The standard mean difference (SMD) was −0.10. In our study, we observed similar results in both GG and GA + AA individuals who were on vegetarian diets. As might have been expected, exercise exposure showed positive associations with HDL-C in individuals carrying both genotypes. The mechanism behind these associations needs to be further investigated. Despite this, exercise has been demonstrated to increase the expression of liver ATP-binding cassette transporters A-1, that help to strengthen the reverse cholesterol transport system as mentioned above. Exercise in combination with diet has been associated with biomarkers of metabolic disorders and variations in body composition [28]. However, the effective outcome of the combination was based on the exercise type.
In the current study, men had lower HDL-C compared to women, no matter the genotype. We also found that overweight/obese individuals had lower HDL-C levels than normal-weight individuals with both genotypes. Besides, high levels of triglycerides (TG) also predicted lower HDL-C. These findings are in line with those previously reported by Zhi and his team, wherein overweight and obesity were strongly associated with a higher TG but lower HDL-C in individuals with MTHFR rs1801133 genotypes [24]. Rs1801133 polymorphism has also been suggested to increase obesity risk in both adolescents and children [29]. Serum uric acid was also included in our model. We found that the uric acid levels did not differ greatly among the samples (Table S1). Our analyses also indicated that higher (i.e., men, ≥7 mg/dl and women, ≥6 mg/dl) compared to lower uric acid (men, <7 mg/dl and women, <6 mg/dl) was associated with lower HDL-C, no matter the genotype. Negative associations between serum uric acid and HDL-C have been previously described [30,31]. Of note, polymorphic variants were not included in the model as we have done.
It appears reasonable to state that exercise exposure is one of the great ways for vegetarians to boost their HDL cholesterol [16]. However, our investigation into this area suggests that the association of HDL-C with a vegetarian diet in combination with exercise appears to differ for each Taiwanese individual based on the genotype. Despite these findings, several shortfalls need to be considered. First, recall bias is possible in our study, considering that data on exercise patterns were collected based on self-report. Second, we did not have data on the average daily intake of macro and micronutrients. In addition, we could not present data that indicated how long participants might have followed a vegetarian diet. Moreover, our analyses had a total of 443 vegetarians, 35 of whom were vegans. Because of this, we could not perform a subgroup analysis separately for the vegans. However, we hope that our findings will serve as a base for future studies on HDL-C and the associated lifestyle and dietary changes.
5. Conclusions
In conclusion, our findings revealed that exercise exposure predicted a higher HDL-C among MTHFR rs1801133 GG and GA + AA individuals. A vegetarian diet alone was associated with lower HDL-C. However, the inclusion of regular exercise resulted in much lower levels among GG individuals, whereas levels in GA + AA individuals were somewhat higher. In summary, a vegetarian diet in combination with exercise predicted an increase in HDL-C levels only among individuals with MTHFR rs1801133-GA + AA genotype in Taiwan. These findings point to the likelihood that combination lifestyle therapies might not serve as an alternative means of boosting cholesterol levels in Taiwanese adults with the rs1801133-GG genotype.
Supplementary Materials
The following are available online at https://www.mdpi.com/2072-6643/12/6/1564/s1, Table S1: Mean serum uric acid (mg/dl) levels of the sample.
Author Contributions
Conceptualization, S.-L.C., O.N.N., C.-C.H., C.-C.L., D.M.T., S.-Y.H., M.-C.C. and Y.-P.L.; Data curation, W.-Y.L. and K.-J.L.; Formal analysis, W.-Y.L. and Y.-P.L.; Funding acquisition, K.-J.L.; Methodology, S.-L.C., O.N.N., C.-C.H., K.-J.L., C.-C.L., D.M.T., S.-Y.H., M.-C.C. and Y.-P.L.; Resources, Y.-P.L.; Supervision, M.-C.C. and Y.-P.L.; Validation, S.-L.C., O.N.N., C.-C.H., C.-C.L., D.M.T., W.-Y.L., S.-Y.H. and M.-C.C.; Writing—original draft, S.-L.C. and O.N.N.; Writing—review & editing, C.-C.H., K.-J.L., C.-C.L., D.M.T., S.-Y.H., W.-Y.L., M.-C.C. and Y.-P.L. All authors have read and agreed to the published version of the manuscript.
Funding
This study was supported by the Ministry of Science and Technology (MOST 105-2627-M-040-002; 106-2627-M-040-002; 107-2627-M-040-002).
Conflicts of Interest
The authors have no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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