Re: 타우린 당뇨, 고혈압, 고지혈증에 효과!! 2024년 RCT nature 논문

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Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials

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Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials

• Chih-Chen Tzang, 
• Liang-Yun Chi, 
• Long-Huei Lin, 
• Ting-Yu Lin, 
• Ke-Vin Chang, 
• Wei-Ting Wu & 
• Levent Özçakar 

Nutrition & Diabetes volume 14, Article number: 29 (2024) Cite this article

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Abstract

Background

Metabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to eval‎uate the effects of taurine supplementation on MetS-related parameters.

Methods

We conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control.

Results

Our analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = −3.999 mmHg, 95% confidence interval [CI] = −7.293 to −0.706, p = 0.017), DBP (WMD = −1.509 mmHg, 95% CI = −2.479 to −0.539, p = 0.002), FBG (WMD: −5.882 mg/dL, 95% CI: −10.747 to −1.018, p = 0.018), TG (WMD: −18.315 mg/dL, 95% CI: −25.628 to −11.002, p < 0.001), but not in HDL-C (WMD: 0.644 mg/dl, 95% CI: −0.244 to 1.532, p = 0.155). Meta-regression analysis revealed a dose-dependent reduction in DBP (coefficient = −0.0108 mmHg per g, p = 0.0297) and FBG (coefficient = −0.0445 mg/dL per g, p = 0.0273). No significant adverse effects were observed compared to the control group.

Conclusion

Taurine supplementation exhibits positive effects on multiple MetS-related factors, making it a potential dietary addition for individuals at risk of or already experiencing MetS. Future research may explore dose-optimization strategies and potential long-term benefits of taurine for MetS management.

초록
배경
대사 증후군(MetS)은 심혈관 질환과 제2형 당뇨병의 발생 가능성을 크게 높이는 상호 연결된 위험 요소의 집합체입니다.

타우린은

MetS(대사증후군)의 잠재적 치료제로 떠오르고 있습니다.

이 메타 분석은 무작위 대조 시험(RCT)에 대한 메타 분석으로 타우린 보충제가 MetS 관련 매개 변수에 미치는 영향을 평가하는 것을 목표로 했습니다.

연구 방법
2023년 12월 1일까지 발표된 논문을 대상으로 Embase, PubMed, Web of Science, Cochrane CENTRAL, ClinicalTrials.gov 등의 데이터베이스를 통해 전자 검색을 실시했습니다.

분석은

수축기 혈압(SBP), 이완기 혈압(DBP),

공복 혈당(FBG),

중성지방(TG), 고밀도 지단백 콜레스테롤(HDL-C) 등

기존의 MetS 진단 기준에 초점을 맞췄습니다.

메타 회귀 분석을 통해 치료 기간 동안 투여된 총 타우린 용량에 따른 잠재적인 용량 의존적 관계를 탐색했습니다. 또한 체성분, 지질 프로필, 혈당 조절과 같은 2차 결과도 평가했습니다.

결과
분석에는 25개의 RCT에 참여한 1024명의 참가자가 포함되었습니다. 연구에 사용된 타우린의 일일 복용량은 0.5g/일에서 6g/일 사이였으며, 추적 관찰 기간은 5일에서 365일 사이였습니다. 타우린 보충제는 대조군에 비해 SBP(가중평균차[WMD] = -3.999 mmHg, 95% 신뢰구간[CI] = -7.293 ~ -0.706, p= 0.017), DBP(WMD = -1.509 mmHg, 95% CI = -2. 479에서 -0.539, p= 0.002), FBG(WMD: -5.882 mg/dL, 95% CI: -10.747에서 -1.018, p= 0.018), TG(WMD: -18.315 mg/dL, 95% CI: -25.628에서 -11.002, p<0.001)에서 유의한 차이가 있었지만 HDL-C(WMD: 0.644 mg/dl, 95% CI: -0.244에서 1.532, p= 0.155), 그렇지 않은 것으로 밝혀졌습니다. 메타 회귀 분석 결과, 용량에 따라 DBP(계수 = -0.0108 mmHg/g/g, p= 0.0297)와 FBG(계수 = -0.0445 mg/dL/g/g, p= 0.0273)가 감소한 것으로 나타났습니다.

대조군에 비해 유의미한 부작용은 관찰되지 않았습니다.

결론
타우린 보충제는 여러 MetS 관련 요인에 긍정적인 영향을 미치므로 MetS의 위험이 있거나 이미 경험하고 있는 사람이 식단에 추가할 수 있는 잠재적인 보충제가 될 수 있습니다. 향후 연구에서는 타우린의 용량 최적화 전략과 MetS 관리를 위한 타우린의 잠재적인 장기적 이점을 탐구할 수 있습니다.

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Introduction

Metabolic syndrome (MetS) poses a significant global health challenge, affecting over one billion people [1]. This cluster of interconnected risk factors is diagnosed by the presence of: (1) abdominal obesity with increased waist circumference, (2) high blood pressure, (3) high fasting blood glucose (FBG) levels, (4) high triglyceride (TG) levels, and (5) a low level of high-density lipoprotein cholesterol (HDL-C) [2]. MetS significantly increases the risk of various health problems, including cardiovascular disease, stroke, and type 2 diabetes [3]. Its development is associated with factors like insulin resistance, chronic inflammation, and neurohormonal activation [3].

Taurine (2-aminoethanesulfonic acid), a sulfur-containing amino acid, has gained scientific interest due to its potential to modulate various physiological processes. It is primarily obtained through diet, particularly from foods like shellfish, dark meat, and some energy drinks [4]. Abundant in tissues like the heart, retina, liver, muscle, and platelets, taurine plays crucial roles in osmoregulation, mitochondrial function, maintenance of cell membrane stability, antioxidative defense mechanisms, and regulating cation balance [4].

In addition to its fundamental functions, taurine shows promise for regulating key metabolic parameters associated with MetS. It plays a significant role in controlling lipid metabolism by conjugating with bile salts [4]. Studies have also suggested its potential to improve glycemic markers, including FBG, serum insulin levels, and glycated hemoglobin (HbA1c) [5]. Moreover, taurine may exert anti-inflammatory effects by inhibiting the renin-angiotensin system, a key factor in the development of cardiovascular diseases and obesity [6]. Therefore, taurine has the potential to positively affect MetS.

Despite numerous clinical studies demonstrating the diverse health benefits of taurine, inconsistencies in clinical outcomes make it challenging to definitely determine whether taurine reduces the risk of MetS [7, 8]. To address this knowledge gap, we conducted a meta-analysis of randomized controlled trials (RCTs) to systematically analyze the effects of taurine on modifying the parameters associated with MetS.

소개
대사증후군(MetS)은 10억 명 이상의 사람들에게 영향을 미치는 심각한 글로벌 건강 문제를 야기합니다[1]. 이 상호 연결된 위험 요소의 클러스터는

(1) 허리둘레가 증가한 복부 비만,

(2) 고혈압,

(3) 높은 공복 혈당(FBG) 수치,

(4) 높은 중성지방(TG) 수치,

(5) 낮은 고밀도 지단백질 콜레스테롤(HDL-C) 수치로 진단됩니다 [2]로 확인할 수 있습니다.

(1) abdominal obesity with increased waist circumference,

(2) high blood pressure,

(3) high fasting blood glucose (FBG) levels,

(4) high triglyceride (TG) levels, and

(5) a low level of high-density lipoprotein cholesterol (HDL-C)

MetS는

심혈관 질환, 뇌졸중, 제2형 당뇨병을 비롯한

다양한 건강 문제의 위험을 크게 증가시킵니다[3].

MetS는

인슐린 저항성,

만성 염증,

신경호르몬 활성화와 같은 요인과 관련이 있습니다 [3].

황 함유 아미노산인 타우린(2- 아미노에탄설폰산)은

다양한 생리적 과정을 조절할 수 있는 잠재력으로 인해

과학계의 관심을 받고 있습니다.

타우린은

주로 조개류, 짙은 육류, 일

부 에너지 음료와 같은 식품을 통해

섭취할 수 있습니다[4].

심장, 망막, 간, 근육, 혈소판과 같은 조직에 풍부한 타우린은

삼투압 조절,

미토콘드리아 기능,

세포막 안정성 유지,

항산화 방어 메커니즘,

양이온 균형 조절에 중요한 역할을 합니다[4].

타우린은 기본적인 기능 외에도 MetS와 관련된 주요 대사 매개변수를 조절할 수 있는 가능성을 보여줍니다.

타우린은

담즙산염과 결합하여

지질 대사를 조절하는 데 중요한 역할을 합니다 [4].

연구 결과에 따르면

타우린은 FBG,

혈청 인슐린 수치,

당화혈색소(HbA1c)를 포함한 혈당 마커를 개선할 수 있는 잠재력도 있다고 합니다[5].

또한

타우린은

심혈관 질환과 비만의 주요 요인인

레닌-안지오텐신 시스템을 억제하여

항염증 효과를 발휘할 수 있습니다 [6].

따라서

타우린은

MetS에 긍정적인 영향을 미칠 수 있는 잠재력을 가지고 있습니다.

타우린의 다양한 건강상의 이점을 입증하는 수많은 임상 연구에도 불구하고 임상 결과의 불일치로 인해 타우린이 MetS의 위험을 감소시키는지 여부를 확실히 판단하기는 어렵습니다 [7, 8]. 이러한 지식 격차를 해소하기 위해 무작위 대조 시험(RCT)에 대한 메타 분석을 실시하여 타우린이 MetS와 관련된 매개 변수를 수정하는 데 미치는 영향을 체계적으로 분석했습니다.

Materials and methods

General guidelines

This meta-analysis adhered to the most recent revision of Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines (Table S1) [9]. The review was registered on Inplasy.com under number (INPLASY2023120081). Two authors (T.-C.C. and C.-L.Y.) conducted independent electronic searches in Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov databases using the following keywords (“taurine” OR “taufon”) AND (“metabolic syndrome” OR “diabetes mellitus” OR “obesity” OR “hypertension” OR “dyslipidemia” OR ‘hyperglycemia’). The search covered the inception of each database until December 1, 2023. The detailed search methodology is provided in the Supplementary Material (Table S2). The identified titles and abstracts were initially screened by the two authors to determine their eligibility, followed by a full-text review where necessary. We also manually searched additional databases and checked the reference lists of relevant meta-analyses. This study included publications in all languages.

Inclusion and exclusion criteria

This meta-analysis followed the PICO (population, intervention, comparison, and outcome) settings design: P, human participants; I, taurine supplementation; C, supplementation (including placebo) other than taurine; and O, parameters associated with the diagnosis of MetS.

We included (1) RCTs employing pure taurine and its compounds as the treatment arm, (2) trials with a comparative arm using interventions other than taurine, and (3) studies providing data for pre- and post-intervention assessments of at least one outcome related to MetS.

We excluded (1) non-RCTs, including quasi-experimental studies such as real world observations, trials without a comparing placebo, retrospective studies, cohort studies and case reports; (2) studies with short follow-up periods unlikely to capture effects on MetS (e.g., less than 24 h); (3) trials using herbal treatments with unclear active ingredients; (4) studies lacking data for pre- and post-intervention endpoints; and (5) studies not investigating outcomes of interest.

Trials with follow-up durations less than 24 h and trials with unclear active ingredients were excluded as they did not align with the purpose of the study. Studies lasting less than 24 h primarily focus on the immediate effects of energy drinks, such as changes in heart rate, so we have opted to exclude them. Furthermore, studies that lacked precise quantification of active ingredients or failed to provide a comprehensive list of effective ingredients were excluded since we could accurately attribute observed effects solely to taurine.

Methodological quality appraisal

The methodological quality of the included studies was assessed using the Cochrane risk of bias tool for RCTs (RoB 2, London, United Kingdom), which eval‎uates six main domains: randomization process, intervention adherence, missing outcome data, outcome measurement, selective reporting, and overall risk of bias [10]. Within the RoB 2 framework, intervention adherence can be assessed using two approaches: intention-to-treat and per-protocol. We opted for the per-protocol approach because most RCTs only report data from participants who completed the entire trial course [10].

Primary and secondary outcome

The primary outcomes of this investigation were changes in (1) systolic blood pressure (SBP), (2) diastolic blood pressure (DBP), (3) FBG, (4) TG, and (5) HDL-C. The secondary outcomes included: (1) body composition measures like body weight (BW) and body mass index (BMI), (2) lipid profiles including total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), (3) glycemic profiles including HbA1c, homeostatic model assessment (HOMA), and fasting insulin, and (4) adverse effects. To accommodate studies with no reported adverse events, the number of cells with zero events was adjusted to 0.5 [11].

Data extraction and management

Two independent authors (T.-C.C. and C.-L.Y.) extracted data from the reviewed studies, including demographics, research design, details of taurine and control regimens, and outcome values. To avoid misinterpretation of effects, they carefully considered the direction of the scales used in each trial. In cases where data was missing from published studies, attempts were made to contact the corresponding authors to obtain the original data. Data extraction, conversion, and merging of outcomes from different study arms with varying taurine dosages were performed in accordance with the Cochrane Handbook for Systematic Review of Interventions and relevant medical literature [12,13,14]. For statistical analysis, the outcomes reported after the intervention were extracted, assuming data were available for multiple time points post-treatment.

Statistical analyses

This meta-analysis was conducted using Comprehensive Meta-Analysis software (version 3; Biostat, Englewood, NJ, United States) due to the heterogeneous nature of the study populations [15]. For all continuous outcomes, the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. Odds ratios and their corresponding 95% CIs were used to analyze categorical outcomes (i.e., the rates of treatment-related adverse events), such as the rates of treatment-related adverse events. The effects of outcomes were assessed using WMD, with respective units dependent on the variable. This metric illustrates the magnitude of change observed across the entire taurine intervention, regardless of dose and duration.

Heterogeneity between studies was assessed using I2 and Cochran’s Q statistics. I2 values of 25%, 50%, and 75% were considered indicative of low, moderate, and high heterogeneity, respectively [16]. To investigate potential dose-dependent relationships between taurine and primary outcomes, meta-regression analyses were conducted using the total taurine dose administered throughout the treatment period and the daily dosage. The total dose was calculated as the product of the duration of intake multiplied by the dosage per day. Thus, the coefficient represents the average effect per gram of administered taurine.

A one-study removal sensitivity analysis was conducted to assess whether excluding a specific trial significantly altered the overall effect size [11]. To investigate potential publication bias, we visually examined the distribution of effect sizes in a funnel plot and assessed the statistical significance of Egger’s regression test [9].

Results

Study selection

Our initial search yielded 2517 publications. After removing duplicates and screening titles and abstracts, we deemed 2476 articles irrelevant and discarded them. We then conducted a full-text review of the remaining 41 studies.

Thirteen articles were excluded for various reasons (Table S3): four weren’t RCTs, one used an herbal treatment with unverified active compounds, one was a poster abstract lacking data, six did not report outcomes aligned with our research focus, and one only administered a single dose of the intervention. This resulted in the inclusion of 25 studies [7, 8, 17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39] in our final quantitative analysis (Fig. 1). Data extraction details for these RCTs are presented in Tables 1 and 2.

Fig. 1

The PRISMA flow diagram of the screening and review process.

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Table 1 Summary of trials retrieved to investigate the impact of taurine on metabolic syndrome.

Full size table

Table 2 Summary of taurine interventions administered in the treatment arms of the trials.

Full size table

Study characteristic

Key features of the 25 RCTs, involving 1,024 participants, are summarized in Table 1. Conducted between 1983 and 2021 in diverse locations (Russia, Iran, Japan, Spain, Brazil, Canada, Ireland, China, Austria, Iraq, Denmark, the USA, and Egypt), the studies enrolled participants aged 8–113 years with a wide range of conditions. These included healthy individuals, post-surgical patients, and individuals with conditions such as heart failure, hypertension, coronary heart disease, heart valve defects, cardiomyopathy, type 1 diabetes mellitus, type 2 diabetes mellitus, obesity, alcoholism, and homocystinuria.

Quality assessment

Eighteen studies [8, 17,18,19,20,21,22,23,24,25, 27, 28, 30, 33,34,35,36,37,38] lacked information on allocation concealment, putting them at risk of bias. The remaining seven studies [7, 26, 29, 31, 32, 35, 39] had a low risk of bias, and none had a high risk of bias (Fig. S1, Table 3).

Table 3 Detailed quality assessment of the included studies using Cochrane risk of bias 2 tool.

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Primary outcomesEffects of taurine on SBP/DBP

Taurine supplementation significantly reduced SBP compared to the control group (WMD = −3.999 mmHg, 95% CI = −7.293 to −0.706, p = 0.017, I2 = 84.949) (Fig. 2a). This effect remained consistent even after excluding individual studies on the sensitivity analysis (Fig. S2a). Meta-analysis regression did not reveal a statistically significant linear relationship between total dose and SBP (coefficient = −0.024 mmHg per g, p = 0.113) (Fig. S3a), and a significant relationship between daily dose and SBP (coefficient = −1.1258 mmHg per g/day, p = 0.0055) (Fig. S4a).

Fig. 2

Forest plot of overall effects of taurine on systolic blood pressure (SBP) and diastolic blood pressure (DBP).

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Taurine significantly reduced DBP levels (WMD = −1.509 mmHg, 95% CI = −2.479 to −0.539, p = 0.002, I2 = 14.077) (Fig. 2b). Similar to SBP, this DBP reduction persisted in the sensitivity analysis (Fig. S2b). Moreover, meta-regression analysis showed a significant correlation between total dose and decreased DBP (coefficient = −0.014 mmHg per g, p = 0.026) (Fig. S3b), and a significant relationship between daily dose and DBP (coefficient = −0.3247 mmHg per g/day, p = 0.0182) (Fig. S4b).

Effects of taurine on FBG

Overall, taurine supplementation significantly reduced FBG levels compared to the control group (WMD: −5.882 mg/dL, 95% CI: −10.747 to −1.018, p = 0.018, I2 = 75.457) (Fig. 3). This effect remained consistent even after excluding individual studies in the sensitivity analysis (Fig. S5). Interestingly, meta-regression revealed a significant correlation between total dose and decreased FBG levels (coefficient = −0.495 mg/dL per g, p = 0.0011) (Fig. S6), but no significant relationship between daily dose and FBG (coefficient = −1.5146 mg/dL per g/day, p = 0.0703) (Fig. S7).

Fig. 3

Forest plot of overall effects of taurine on fasting blood glucose (FBG).

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Effects of taurine on TG

Taurine supplementation significantly reduced TG levels compared to the control group (WMD: −18.315 mg/dL, 95% CI: −25.628 to −11.002, p < 0.001, I2 = 35.539) (Fig. 4). This effect remained consistent even after excluding individual studies in a sensitivity analysis (Fig. S8). While meta-regression did not reveal a statistically significant dose-dependent relationship between total dose and TG reduction (coefficient = −0.0522 mg/dL per g, p = 0.0730) (Fig. S9), it revealed a significant relationship between daily dose and TG (coefficient = −3.3600 mg/dL per g/day, p = 0.0062) (Fig. S10).

Fig. 4

Forest plot of overall effects of taurine on triglyceride (TG).

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Effects of taurine on HDL-C

Overall, taurine supplementation did not significantly increase HDL-C levels compared to the control group (WMD: 0.644 mg/dL, 95% CI: −0.244 to 1.532, p = 0.155, I2 = 7.655) (Fig. 5). This observation remained consistent in the sensitivity analysis (Fig. S11). Similarly, meta-regression did not show a statistically significant dose-dependent relationship between total dose and HDL-C levels (coefficient = 0.0037 mg/dL per g, p = 0.2729) (Fig. S12). Moreover, it didn’t reveal a significant relationship between daily dose and HDL-C (coefficient = 0.1370 mg/dL per g/day, p = 0.3200) (Fig. S13).

Fig. 5

Forest plot of overall effects of taurine on high density lipoprotein-cholesterol (HDL-C).

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Publication bias

Funnel plot analysis for all investigated outcomes (SBP, DBP, FBG, TG, and HDL-C) indicated no evidence of publication bias. The distribution effect sizes were symmetric, as confirmed by Egger’s regression test, with p values exceeding 0.5 for all outcomes (p = 0.439, p = 0.213, p = 0.083, p = 0.166, and p = 0.158, respectively) (Figs. S14–S17).

Secondary outcomesEffects of taurine on body composition

Taurine supplementation did not significantly impact BW or BMI compared to the control group. The pooled effect size for BW change was minimal and non-significant (WMD: −0.642 kg, 95% CI: −1.494 to 0.209, p = 0.139) (Fig. S18a). Similarly, the effect size for BMI change was not statistically significant (WMD: −0.296 kg, 95% CI: −0.889 to 0.296, p = 0.327) (Fig. S18b). These findings were further supported by a sensitivity analysis with consistent non-significant effects of taurine on both BW and BMI (Fig. S18c, d).

Effects of taurine on lipid profiles

Taurine demonstrated a significant beneficial effect on lipid profiles. Compared to the control group, taurine supplementation significantly reduced both TC and LDL-C levels. The pooled effect size showed a notable decrease in TC (WMD: −8.305 mg/dL, 95% CI: −13.771 to −2.929, p = 0.003) (Fig. S19a), and a similar statistically significant effect was observed for LDL-C levels (WMD: −6.495 mg/dL, 95% CI: −10.912 to −2.079, p = 0.004) (Fig. S19b). These findings were further validated by a sensitivity analysis showing consistent significant effects of taurine on both TC and LDL-C reduction (Fig. S19c and Fig. S19d).

Effects of taurine on glycemic status

Taurine supplementation positively impacted several glycemic markers. Pooled effect sizes revealed significant reductions in HbA1c (WMD: −0.341%, 95% CI: −0.709 to −0.028, p = 0.070) (Fig. S20a), HOMA index (WMD: −0.693, 95% CI: −1.133 to −0.252, p = 0.002) (Fig. S20b), and fasting insulin levels (WMD: −1.521 mU/L, 95% CI: −2.591 to −0.451, p = 0.005) (Fig. S20c) compared to the control group. A sensitivity analysis showed a consistently non-significant effect on HbA1c reduction (Fig. S20d) but maintained consistent significant effects on both HOMA and fasting insulin (Fig. S20e, f).

Adverse effects

Meta-analysis of the treatment-associated adverse effect rates showed no significant differences between the taurine and control groups (odds ratio = 1.481, 95% CI = 0.843–2.604, p = 0.172) (Fig. S17).

Discussion

Our meta-analysis found that taurine supplementation significantly reduced SBP, DBP, FBG, and TG levels, suggesting an improvement in risk factors associated with MetS. A dose-dependent effect is evident on SBP, DBP, FBG, and TG levels, as influenced by both dose per day and total dose. Even though not all parameters reached statistical significance, the consistent trends point to a higher physiological response to administered substance doses. However, our analysis revealed no discernible dose-dependent effect on HDL-C levels, irrespective of dose per day or total dose. Notably, taurine did not exhibit any apparent adverse effects.

Compared to the control group, taurine demonstrated a significant lowering of both SBP and DBP. The hypotensive effect may be attributed to several mechanisms, primarily through increased nitric oxide availability [15] and enhanced hydrogen sulfide production [14], ultimately leading to improved blood flow dilation [13]. Our findings also revealed a remarkable ability of taurine to effectively reduce FBG levels. This suggests a positive impact on glycemic control, potentially via various mechanisms. These include: reduced hepatic glucose production, inhibition of glucagon activity, elevated uncoupling protein 1 levels [40], enhanced insulin clearance by insulin-degrading enzymes [41], and support for the health of beta-pancreatic cells [42]. Furthermore, taurine may upregulate adiponectin mRNA expression‎ and increase blood adiponectin levels, thereby improving insulin sensitivity [43] and contributing to overall metabolic health.

A previous meta-analysis by Guan et al. [44] found no significant difference in FBG between taurine and control groups, our results revealed a notable reduction. This discrepancy may be due to our inclusion of more studies involving individuals with diabetes, where baseline glucose levels were already elevated [19, 26, 29, 32]. This suggests that taurine’s impact might be less pronounced in those with normal blood sugar regulation.

Taurine significantly reduced TG levels. This is likely due to its ability to enhance TG removal into the bile by stimulating the production of bile acid through heightened hepatic cholesterol 7α-hydroxylase activity. Additionally, taurine increases LDL-C receptor activity, aiding in LDL-C clearance from the blood [45].

While our meta-analysis did not show a statistically significant increase in HDL-C levels, the observed trends suggest potential benefits. HDL serves as a crucial form of endogenous lipid storage by removing excess cholesterol from peripheral tissues. Hepatocytes and intestinal cells are the main internal biosynthesisers that control its levels [46]. Taurine has known effects on promoting cholesterol catabolism, particularly by increasing CYP7A1 activity and bile acid synthesis, which enhances cholesterol removal through feces. Additionally, taurine decreases the expression‎ of ApoB-100 and ApoE, which are major receptors for LDL and VLDL, further aiding in cholesterol clearance [47]. It’s likely that taurine efficiently removes cholesterol, displacing the need for extra HDL clearance. Furthermore, although taurine has been shown to raise serum HDL levels in rats raised on a high-cholesterol diet [47], human trials usually do not include purposefully high-fat diets, and the majority of participants are not obese. Therefore, in contrast to animal research, the effects of taurine on HDL levels in human trials may be less apparent. It is noteworthy that these trends towards elevated HDL-C may have a noteworthy effect on lowering the atherosclerosis index, even in the absence of statistically significant results [48].

Beyond FBG, taurine demonstrates effectiveness in both glycemic control and lipid profiles, with significant reductions observed in TC, LDL-C, fasting insulin, and HOMA levels. Although our analysis revealed only marginal benefits on HbA1c (WMD -0.341 [95% CI: −0.709, −0.28], p = 0.07), this may be attributed to the limited duration and intensity of protocols in the included studies (dosages ranging from 3 to 168 g with tracking periods of eight weeks to three months). Conversely, a meta-analysis conducted by Tao et al. exclusively on patients with diabetes reported significant reductions in HbA1c levels (WMD −0.41 [95% CI: −0.74, −0.09], p = 0.01) [5]. All four of the included trials [26, 29, 32, 36] assessing HbA1c as an endpoint involved individuals with type 2 diabetes, indicating a lack of evidence regarding HbA1c level changes in participants with diabetes. The lack of studies conducted on populations without diabetes could be because these changes are unlikely in this population. Future research may delve deeper into this topic. Since HbA1c not only offers a trustworthy indicator of chronic hyperglycemia but also strongly correlates with the risk of long-term diabetes complications [49], more research is required to fully understand its impact on long-term glycemic control in larger populations.

Taurine did not appear to significantly affect BW or BMI. In the only trial demonstrating a decrease in body mass, Shari et al. [36] administered 1 g taurine daily for 3 months to participants with type 2 diabetes. However, findings from other trials consistently showed negligible effects on body mass within their respective protocols. This suggests that factors like hypocaloric diet and exercise likely have a greater impact on body weight in this context [8].

Taurine is classified as “generally considered as safe” by the United States Food and Drug Administration [50]. In line with this, our study did not reveal any significant differences in treatment-related adverse effects between the taurine and control groups. All reported events were mild and transient, involving primarily gastrointestinal issues, headaches, and fatigue. Notably, no instances of moderate or severe events were associated with taurine supplementation [19, 35, 38].

While previous studies have examined similar endpoints [5, 44], ours is the first to conduct a meta-regression analysis on dose-response relationships, highlighting the effectiveness of taurine in mitigating MetS risk factors in the general population. However, some limitations warrant further consideration.

The observed heterogeneity has the potential to attenuate the true effect of taurine, introducing variability across different populations that may result in diminished statistical significance for parameters such as TG and HDL-C. Several factors contribute to this heightened heterogeneity. Firstly, there is variation in the selection of participants across studies, where individuals with diabetes and obesity, although at high risk for metabolic diseases, may not necessarily be diagnosed with specific disorders. Secondly, inconsistencies in study protocols play a role, with some participants adhering to their regular diet and activity levels [8], while others follow calorie-modified plans [32], potentially influencing results and increasing heterogeneity. Thirdly, our included trials suggest that taurine is more effective in moderating metabolism among studies that exclusively recruit patients with obesity or diabetes, as their TG levels are inherently higher and more prone to decrease compared to those with cardiovascular disease or no definite metabolic disorder.

When examining the impact of taurine on lipid profiles in patients with cardiovascular disease, confounding factors such as concurrent medication use must be considered. Given that a large number of the included studies focus on patients with heart failure, it is important to remember that medications like diuretics, angiotensin-converting enzyme (ACE), and vasodilators, which are commonly prescribed for cardiovascular conditions, can affect lipid levels. Long-term use of ACE inhibitors like enalapril has shown to significantly reduce TC, TG, and Very Low-density lipoprotein (VLDL) in patients [51]. Thiazide-type diuretics, often used for hypertension, may increase TC and VLDL levels in the short term, while HDL-C levels remain unchanged [52].

The authors of some included trials [26, 29, 32] were more aware of the impact of lipid level resulting from concurrent medication use, and specifically instructed participants to maintain their standard therapeutic regimen, diet, and lifestyle, with careful monitoring and controlled for. To better understand taurine’s effects on lipid profiles, future clinical trials should carefully consider and possibly exclude patients using medications known to significantly impact lipid levels.

Direct data on waist circumference, another key MetS criterion, were unavailable for any of the included trials. Despite this, we incorporated BMI as a secondary outcome, which could indirectly reflect the potential impact of taurine on waist circumference due to their strong correlation [53].

Another critical issue is that the majority of included studies on taurine’s effects typically have short durations, lasting no more than two months, with only a few extending up to a year at most. This limited timeframe emphasizes the necessity for longer-term studies to validate taurine’s efficacy thoroughly. Future studies should conduct more future studies to ascertain the duration of taurine’s effects after its cessation. Such extended investigations are crucial to explore its potential incorporation into novel clinical guidelines for the management of MetS and related conditions.

토론

메타 분석에 따르면

타우린 보충제는

SBP, DBP(수축기혈압, 이완기 혈압)

FBG(공복혈당),

TG(중성지방) 수치를 유의하게 감소시켜

MetS와 관련된 위험 요인을 개선할 수 있는 것으로 나타났습니다.

타우린은

하루 복용량과 총 복용량 모두에 영향을 받는 용량 의존적 효과가

SBP, DBP, FBG 및 TG 수치에 뚜렷하게 나타났습니다.

모든 매개변수가 통계적 유의성에 도달하지는 않았지만, 일관된 경향은 투여된 물질 용량에 대한 생리적 반응이 더 높다는 것을 나타냅니다. 그러나 분석 결과, 일일 복용량이나 총 복용량에 관계없이 HDL-C 수치에 대한 뚜렷한 용량 의존적 효과는 발견되지 않았습니다.

특히

타우린은

명백한 부작용이 나타나지 않았습니다.

타우린은

대조군에 비해 SBP와 DBP를 모두 유의미하게 낮추는 것으로 나타났습니다.

이러한 혈압 강하 효과는

주로 산화질소 가용성 증가 [15] 및 황화수소 생성 증가 [14],

궁극적으로 혈류 확장 개선 [13] 등

여러 가지 메커니즘에 기인할 수 있습니다.

연구 결과

타우린이

FBG 수치를 효과적으로 감소시키는 놀라운 능력도 밝혀졌습니다.

이는 잠재적으로

다양한 메커니즘을 통해

혈당 조절에 긍정적인 영향을 미칠 수 있음을 시사합니다.

여기에는

간 포도당 생산 감소,

글루카곤 활성 억제,

결합 해제 단백질 1 수치 상승 [40],

인슐린 분해 효소에 의한 인슐린 청소율 향상 [41],

베타 췌장 세포의 건강 지원 [42] 등이 포함됩니다.

또한

타우린은

아디포넥틴 mRNA 발현을 상향 조절하고

혈중 아디포넥틴 수치를 증가시켜

인슐린 감수성을 개선하고[43]

전반적인 대사 건강에 기여할 수 있습니다.

Guan 등[44]의 이전 메타 분석에 따르면 타우린과 대조군 간에 FBG에 유의미한 차이가 없는 것으로 나타났지만, 본 연구 결과에서는 눈에 띄게 감소한 것으로 나타났습니다. 이러한 불일치는 기저 포도당 수치가 이미 높은 당뇨병 환자를 대상으로 한 연구를 더 많이 포함했기 때문일 수 있습니다 [19, 26, 29, 32]. 이는 혈당 조절이 정상인 사람에게는 타우린의 영향이 덜 두드러질 수 있음을 시사합니다.

타우린은

TG 수치를 크게 낮췄습니다.

이는

간 콜레스테롤 7α-하이드록실라제 활성을 높여

담즙산 생성을 자극하여

담즙으로 TG 제거를 촉진하기 때문일 가능성이 높습니다.

또한

타우린은

LDL-C 수용체 활성을 증가시켜

혈액에서 LDL-C 제거를 돕습니다 [45].

메타 분석 결과 HDL-C 수치가 통계적으로 유의미하게 증가하지는 않았지만, 관찰된 경향은 잠재적인 이점을 시사합니다. HDL은 말초 조직에서 과도한 콜레스테롤을 제거하여 내인성 지질 저장의 중요한 역할을 합니다. 간세포와 장 세포는 그 수치를 조절하는 주요 내부 생합성 기관입니다 [46].

타우린은

특히 CYP7A1 활성과 담즙산 합성을 증가시켜

대변을 통한 콜레스테롤 제거를 향상시킴으로써

콜레스테롤 이화 작용을 촉진하는 효과가 있는 것으로 알려져 있습니다.

또한

타우린은

LDL과 VLDL의 주요 수용체인 ApoB-100과 ApoE의 발현을 감소시켜

콜레스테롤 제거를 더욱 돕습니다 [47].

타우린은 콜레스테롤을 효율적으로 제거하여 추가적인 HDL 제거의 필요성을 대체할 가능성이 높습니다. 또한 타우린은 고콜레스테롤 식단을 먹고 자란 쥐의 혈청 HDL 수치를 높이는 것으로 나타났지만 [47], 인간 대상 임상시험에서는 일반적으로 의도적으로 고지방 식단을 포함하지 않으며 대부분의 참가자는 비만이 아닙니다. 따라서 동물 실험과 달리 인간 실험에서 타우린이 HDL 수치에 미치는 영향은 분명하지 않을 수 있습니다. 통계적으로 유의미한 결과가 없더라도 이러한 HDL-C 상승 경향은 죽상 경화증 지수를 낮추는 데 주목할 만한 영향을 미칠 수 있다는 점은 주목할 만합니다 [48].

타우린은

FBG 외에도 혈당 조절과 지질 프로필 모두에서 효과를 입증했으며,

TC, LDL-C, 공복 인슐린 및 HOMA 수치에서 유의미한 감소가 관찰되었습니다.

분석 결과

당화혈색소(HbA1c)에 대한 효과는

미미한 것으로 나타났지만(WMD -0.341 [95% CI: -0.709, -0.28], p= 0.07),

이는 포함된 연구의 프로토콜 기간과 강도가

제한적(8주에서 3개월의 추적 기간에 3~168g의 용량 범위)이었기 때문일 수 있습니다.

반대로,

당뇨병 환자만을 대상으로 실시한 메타분석에서는

HbA1c 수치가 유의미하게 감소한 것으로 보고되었습니다(WMD -0.41 [95% CI: -0.74, -0.09], p= 0.01)[5].

포함된 4개의 임상시험[26, 29, 32, 36] 모두 HbA1c를 평가변수로 하여 제2형 당뇨병 환자를 대상으로 하였으며, 이는 당뇨병 환자의 HbA1c 수치 변화에 대한 증거가 부족하다는 것을 나타냅니다. 당뇨병이 없는 인구를 대상으로 한 연구가 부족한 것은 이러한 변화가 이 집단에서 일어날 가능성이 낮기 때문일 수 있습니다. 향후 연구에서는 이 주제에 대해 더 깊이 파고들 수 있습니다. HbA1c는 만성 고혈당증의 신뢰할 수 있는 지표일 뿐만 아니라 장기적인 당뇨병 합병증의 위험과도 밀접한 관련이 있으므로[49], 더 많은 인구에서 장기적인 혈당 조절에 미치는 영향을 완전히 이해하려면 더 많은 연구가 필요합니다.

타우린은

체중이나 BMI에 큰 영향을 미치지 않는 것으로 나타났습니다.

체질량 감소를 입증한 유일한 시험에서 Shari 등[36]은 제2형 당뇨병 환자에게 3개월 동안 매일 1g의 타우린을 투여했습니다. 그러나 다른 임상시험의 결과는 각각의 프로토콜 내에서 일관되게 체질량에 미치는 영향이 미미한 것으로 나타났습니다. 이는 저칼로리 식단 및 운동과 같은 요인이 체중에 더 큰 영향을 미칠 수 있음을 시사합니다 [8].

타우린은

미국 식품의약국에 의해 “일반적으로 안전한 것으로 간주”되는 것으로

분류됩니다 [50].

이에 따라 본 연구에서는

타우린 그룹과 대조군 간에 치료 관련 부작용의

유의미한 차이를 발견하지 못했습니다.

보고된 모든 부작용은 경미하고 일시적인 것으로

주로 위장 문제, 두통, 피로와 관련된 것이었습니다.

특히,

타우린 보충제와 관련된 중등도 또는 중증 부작용 사례는

보고되지 않았습니다 [19, 35, 38].

이전 연구에서도 유사한 평가 변수를 조사한 적이 있지만[5, 44], 본 연구는 용량-반응 관계에 대한 메타 회귀 분석을 최초로 수행하여 일반 인구에서 타우린이 MetS 위험 요인을 완화하는 데 효과적이라는 점을 강조했습니다. 그러나 몇 가지 제한 사항은 추가 검토가 필요합니다.

관찰된 이질성은 타우린의 실제 효과를 약화시킬 가능성이 있으며, 다양한 인구 집단에 걸쳐 변동성을 유발하여 TG 및 HDL-C와 같은 매개변수에 대한 통계적 유의성을 떨어뜨릴 수 있습니다. 이러한 이질성이 높아지는 데에는 몇 가지 요인이 기여합니다. 첫째, 당뇨병과 비만이 있는 사람이 대사 질환 위험이 높더라도 반드시 특정 질환으로 진단되지 않을 수 있는 등 연구마다 참가자 선정에 차이가 있습니다. 둘째, 일부 참가자는 규칙적인 식단과 활동 수준을 준수하는 반면[8], 다른 참가자는 칼로리 수정 계획을 따르는 등[32], 연구 프로토콜의 불일치가 결과에 영향을 미치고 이질성을 증가시키는 역할을 합니다. 셋째, 우리가 포함시킨 임상시험에 따르면 비만 또는 당뇨병 환자만을 대상으로 한 연구 중 타우린이 신진대사를 조절하는 데 더 효과적인 것으로 나타났는데, 이는 이들의 TG 수치가 심혈관 질환이 있거나 명확한 대사 장애가 없는 환자에 비해 본질적으로 더 높고 감소하기 쉽기 때문입니다.

심혈관 질환 환자의 지질 프로필에 대한 타우린의 영향을 조사할 때는 약물 동시 복용과 같은 혼란 요인을 고려해야 합니다. 포함된 연구 중 상당수가 심부전 환자에 초점을 맞추고 있으므로 심혈관 질환에 일반적으로 처방되는 이뇨제, 안지오텐신 전환 효소(ACE) 및 혈관 확장제와 같은 약물이 지질 수치에 영향을 미칠 수 있다는 점을 기억하는 것이 중요합니다. 에날라프릴과 같은 ACE 억제제를 장기간 사용하면 환자의 TC, TG 및 초저밀도 지단백질(VLDL)이 크게 감소하는 것으로 나타났습니다 [51]. 고혈압에 자주 사용되는 티아지드 계열 이뇨제는 단기간에 TC 및 VLDL 수치를 증가시킬 수 있지만 HDL-C 수치는 변하지 않습니다 [52].

일부 포함 된 시험의 저자 [26, 29, 32] 약물 동시 사용으로 인한 지질 수치의 영향을 더 잘 알고 있었으며 참가자들에게 표준 치료 요법, 식단 및 생활 방식을 유지하면서 신중한 모니터링과 통제를 지시했습니다. 타우린이 지질 수치에 미치는 영향을 더 잘 이해하기 위해 향후 임상시험에서는 지질 수치에 큰 영향을 미치는 것으로 알려진 약물을 사용하는 환자를 신중하게 고려하고 배제할 수 있어야 합니다.

MetS의 또 다른 주요 기준인 허리둘레에 대한 직접적인 데이터는 포함된 임상시험에서 확인할 수 없었습니다. 그럼에도 불구하고 BMI는 강력한 상관관계로 인해 허리둘레에 대한 타우린의 잠재적 영향을 간접적으로 반영할 수 있는 2차 결과로 포함시켰습니다 [53].

또 다른 중요한 문제는 타우린의 효과에 대한 대부분의 연구가 일반적으로 2개월을 넘지 않는 짧은 기간 동안 진행되었으며, 최대 1년까지 지속된 연구는 극히 일부에 불과하다는 점입니다. 이러한 제한된 기간은 타우린의 효능을 철저하게 검증하기 위한 장기 연구의 필요성을 강조합니다. 향후 연구에서는 타우린 복용 중단 후 타우린 효과의 지속 기간을 확인하기 위해 더 많은 연구를 수행해야 합니다. 이러한 장기 연구는 MetS 및 관련 질환 관리를 위한 새로운 임상 지침에 타우린을 포함시킬 수 있는 가능성을 모색하는 데 매우 중요합니다.

Conclusion

In conclusion, our meta-analysis of RCTs highlights taurine supplementation’s significant potential in mitigating key MetS risk factors, including reductions in SBP, DBP, FBG, and TG levels. This underscores its potential as a complementary therapeutic agent for MetS management, offering a multifaceted approach to glycemic control and cardiovascular health. Future clinical trials should focus on determining optimal taurine dosage and treatment duration, especially in MetS-susceptible populations. Addressing limitations in existing trials, such as variations in dosage, trial duration, sample size, disease severity, and participant characteristics, is crucial for generating robust evidence. As taurine is an inexpensive and easily obtainable supplement, further research can fill knowledge gaps, supporting clinical guidelines on its use as a nutraceutical for MetS prevention and management. Integrating taurine supplementation with established pharmacological interventions may enhance treatment outcomes and overall cardiovascular health in MetS patients.

결론

결론적으로, 

RCT에 대한 메타 분석은 

타우린 보충제가 SBP, DBP, FBG 및 TG 수치의 감소를 포함하여 

주요 MetS 위험 요소를 완화하는 데 상당한 잠재력을 가지고 있음을 강조합니다. 

이는 

혈당 조절과 심혈관 건강에 대한 다각적인 접근 방식을 제공하는 

MetS 관리를 위한 보완적 치료제로서의 잠재력을 강조합니다. 

향후 임상시험은 

특히 MetS에 취약한 집단에서 최적의 타우린 복용량과 치료 기간을 결정하는 데 초점을 맞춰야 합니다. 복용량, 시험 기간, 표본 크기, 질병 중증도, 참여자 특성 등 기존 임상시험의 한계를 해결하는 것은 강력한 증거를 생성하는 데 매우 중요합니다. 타우린은 저렴하고 쉽게 구할 수 있는 보충제이므로 추가 연구를 통해 지식의 격차를 메우고 MetS 예방 및 관리를 위한 건강기능식품으로서의 타우린 사용에 대한 임상 지침을 뒷받침할 수 있습니다. 타우린 보충제를 기존의 약리학적 개입과 통합하면 MetS 환자의 치료 결과와 전반적인 심혈관 건강을 개선할 수 있습니다.

Data availability

All data included in this study are shown in this article or supplementary information, any further request is available by contacting the corresponding authors.

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