Taurine

GENERAL:

• Life span extension of 10-12% in mice (Taurine deficiency as a driver of aging, 2023)

• Reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammation.

• Improved overall health span including bone, muscle, brain, pancreas, fat, gut and immune health.

• Blood Taurine levels are associated with better health outcomes like lower obesity, inflammation, diabetes in 12,000 older European adults (2023)

• Physical performance: Supplementation (1-3 g/day) appears effective for improving aerobic performance (VO2max, time to exhaustion), anaerobic performance (power, strength), recovery (decreased muscle damage), and metabolic markers (lower lactate, creatine kinase, phosphorus, inflammation; increased fat oxidation) (Taurine in sports and exercise, 2021)

METABOLIC HEALTH:

• Significantly reduced blood pressure and improved endothelial function in humans with metabolic disorders (meta-analysis, 2020).

• Significantly reduced HbA1c, fasting insulin, insulin resistance in diabetic patients (meta-analysis, 2022)

• Lowered triglycerides and cholesterol in individuals with metabolic disorders (meta-analysis, 2020, 2004)

INFLAMMATION:

• Decreased markers like TNF-alpha, IL-1beta, IL-6 in leukocytes and macrophages (2014)

• Reduced TNF-alpha induced NF-Kβ inflammation and oxidative stress (2007)

• Reduced obesity-induced inflammation (29% drop in hs-CRP) and oxidative stress markers (2014).

• Reduced inflammatory cytokines like IL-6 and marginally APACHEII score in traumatic brain injury patients (2021)

• Improved symptoms in infection and inflammatory diseases like acne, ear infection, arthritis when applied topically (Taurine and inflammatory diseases, 2014)

• TGF-Beta: In light of abundant rodent data, inclusion of taurine in nutraceutical regimens intended to oppose pathological fibrosis seems appropriate, particularly as this agent is safe and inexpensive. (A nutraceutical strategy for downregulating TGFβ signalling, 2021)

HEART DISEASE:

• Reduced blood pressure and improved endothelial function in prehypertensive humans (2016)

• Improved left ventricular function, exercise tolerance and ejection fraction in heart failure patients (Effects and Mechanisms of Taurine as a Therapeutic Agent, 2018; 2011)

• Decreased ventricular arrhythmias and cholesterol/triglycerides in heart failure patients (2011)

CANCER:

• Induced apoptosis, inhibited proliferation in colorectal, nasopharyngeal, cervical, breast cancer cells (Zhang et al., 2014; He et al., 2018; Li et al., 2019; Chen et al., 2016)

• Increased efficacy of chemotherapies like cisplatin and checkpoint inhibitors when combined with taurine (Kim & Kim, 2013; Chen et al., 2023; Ping et al., 2023)

• Correlated with cancer development/prognosis - levels significantly lower in cancers like lung, breast, pancreas (Omura, 2016; Wang et al., 2014)

Taurine deficiency as a driver of aging, 2023

INTRODUCTION

Aging is an inevitable multifactorial process. Aging-related changes manifest as the “hallmarks of aging,” cause organ functions to decline, and increase the risk of disease and death. Aging is associated with systemic changes in the concentrations of molecules such as metabolites. However, whether such changes are merely the consequence of aging or whether these molecules are drivers of aging remains largely unexplored. If these were blood-based drivers of aging, then restoring their concentration or functions to “youthful” levels could serve as an antiaging intervention.

RATIONALE

Taurine, a semiessential micronutrient, is one of the most abundant amino acids in humans and other eukaryotes. Earlier studies have shown that the concentration of taurine in blood correlates with health, but it is unknown whether blood taurine concentrations affect aging. To address this gap in knowledge, we measured the blood concentration of taurine during aging and investigated the effect of taurine supplementation on health span and life span in several species.

RESULTS

Blood concentration of taurine declines with age in mice, monkeys, and humans. To investigate whether this decline contributes to aging, we orally fed taurine or a control solution once daily to middle-aged wild-type female and male C57Bl/6J mice until the end of life. Taurine-fed mice of both sexes survived longer than the control mice. The median life span of taurine-treated mice increased by 10 to 12%, and life expectancy at 28 months increased by about 18 to 25%. A meaningful antiaging therapy should not only improve life span but also health span, the period of healthy living. We, therefore, investigated the health of taurine-fed middle-aged mice and found an improved functioning of bone, muscle, pancreas, brain, fat, gut, and immune system, indicating an overall increase in health span. We observed similar effects in monkeys. To check whether the observed effects of taurine transcended the species boundary, we investigated whether taurine supplementation increased life span in worms and yeast. Although taurine did not affect the replicative life span of unicellular yeast, it increased life span in multicellular worms. Investigations into the mechanism or mechanisms through which taurine supplementation improved the health span and life span revealed that taurine positively affected several hallmarks of aging. Taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammation. An association analysis of metabolite clinical risk factors in humans showed that lower taurine, hypotaurine, and N-acetyltaurine concentrations were associated with adverse health, such as increased abdominal obesity, hypertension, inflammation, and prevalence of type 2 diabetes. Moreover, we found that a bout of exercise increased the concentrations of taurine metabolites in blood, which might partially underlie the antiaging effects of exercise.

CONCLUSION

Taurine abundance decreases during aging. A reversal of this decline through taurine supplementation increases health span and life span in mice and worms and health span in monkeys. This identifies taurine deficiency as a driver of aging in these species. To test whether taurine deficiency is a driver of aging in humans as well, long-term, well-controlled taurine supplementation trials that measure health span and life span as outcomes are required.

A nutraceutical strategy for downregulating TGFβ signaling: prospects for prevention of fibrotic disorders, 2021

(“In light of abundant rodent data, inclusion of taurine in nutraceutical regimens intended to oppose pathological fibrosis seems appropriate, particularly as this agent is safe and inexpensive”)

Recent studies indicate that the antihypertensive, antiatherosclerotic and brain-protective benefits of taurine administration may in large measure reflect increased expression of enzymes which synthesize H2S—namely CBS and CSE.230 231 This effect has been demonstrated to date in vascular tissues and the brain, but it may well be operative in other tissues. In light of H2S’s ability to downregulate TGFβ activity cited above, it is notable that taurine has been shown to exert anti-fibrotic effects in a number of rodent models of fibrosis, in a range of tissue, including lungs, liver, heart, kidney, pancreas and penis.232–244 Conversely, in mice with a genetic knockout of the taurine transporter, marked cardiac fibrosis is noted.245 An economical explanation of these findings could be that taurine controls TGFβ activity by supporting endogenous H2S generation. In any case, in light of abundant rodent data, inclusion of taurine in nutraceutical regimens intended to oppose pathological fibrosis seems appropriate, particularly as this agent is safe and inexpensive.

Tissue cysteine levels can be rate-limiting for H2S synthesis, and those levels tend to decline in the elderly.246 247 Supplemental N-acetylcysteine (NAC) can also boost tissue levels of the key antioxidant glutathione, which can participate in mechanisms that reverse the pro-inflammatory effects of hydrogen peroxide on signaling pathways.248–252 Hence, NAC supplementation has been recommended for the elderly, and might be expected to at least modestly aid control of fibrotic syndromes in this group, both by opposing the pro-fibrotic impact of Nox4-derived hydrogen peroxide, and by enhancing H2S synthesis.247 250 251 Consistent with this speculation, oral administration of NAC has shown favorable effects in multiple rodent models of pathogenic fibrosis.253–267 Moreover, NAC also has been shown to downregulate TGFβ signaling in cell cultures.268

Taurine may be a key to longer and healthier life, 2023

The research conducted by Columbia University Irving Medical Center, published on June 8, 2023, suggests that taurine, a molecule produced in the body, may be essential for aging and that taurine supplementation can lead to a longer and healthier life in animals. The key results and findings of this study are:

1. Taurine Deficiency and Aging: The researchers found that taurine levels decline with age. For example, 60-year-olds have only about one-third of the taurine levels compared to 5-year-olds.

2. Taurine Supplementation in Animals: The study showed that taurine supplementation can slow down the aging process in worms, mice, and monkeys.

3. Extended Lifespan in Mice: Taurine supplementation increased the average lifespan by 12% in female mice and 10% in male mice, which is equivalent to three to four extra months (or about seven to eight human years).

4. Health Benefits in Mice: Mice supplemented with taurine exhibited suppressed age-associated weight gain, increased energy expenditure, increased bone mass, improved muscle endurance and strength, reduced depression-like and anxious behaviors, reduced insulin resistance, and a younger-looking immune system.

5. Cellular Benefits: On a cellular level, taurine decreased the number of “zombie cells” (old cells that do not die but release harmful substances), improved mitochondrial performance, reduced DNA damage, increased survival after telomerase deficiency, increased the number of stem cells in tissues, and improved cells’ ability to sense nutrients.

6. Health Benefits in Monkeys: Middle-aged rhesus monkeys given daily taurine supplements for six months showed benefits similar to the mice, including prevented weight gain, reduced fasting blood glucose, decreased markers of liver damage, increased bone density, and improved immune system health.

7. Association with Human Health: In a study of 12,000 European adults aged 60 and over, higher taurine levels were associated with better health, including fewer cases of type 2 diabetes, lower obesity levels, reduced hypertension, and lower levels of inflammation. However, this doesn’t establish causation.

8. Taurine Levels and Exercise: In another experiment, taurine levels significantly increased among athletes and sedentary individuals after a strenuous cycling workout, suggesting some health benefits of exercise may come from an increase in taurine.

The study’s lead researcher, Dr. Vijay Yadav, emphasizes that only a randomized clinical trial in humans will definitively determine if taurine has health benefits. Current taurine trials are underway for obesity, but none measure a wide range of health parameters. Dr. Yadav suggests that taurine should be considered for anti-aging strategies since it is naturally produced, non-toxic, can be obtained through the diet, and can be boosted by exercise.

Taurine (link)

A few studies in overweight or obese patients suggest taurine may reduce triglycerides and improve lipid metabolism (17), increase adiponectin levels, and decrease inflammation and lipid peroxidation (18). However, long-term supplementation did not affect insulin response or blood glucose levels in patients with type 2 diabetes (19). Other studies suggest potential decreases in blood pressure (20) (43) (44) and benefit in older patients with congestive heart failure (21) (22). It may also help manage muscle cramps in patients with chronic liver disease (45), improve cognitive function in dementia patients (46), and reduce stroke-like episodes in patients with a rare genetic disorder (47). Other preliminary data suggest taurine co-administration reduced chemotherapy-induced nausea and vomiting in acute lymphoblastic leukemia (23), but more studies are needed.

The effects of taurine supplementation on diabetes mellitus in humans: A systematic review and meta-analysis (2022)

Of 2206 identified studies, 5 randomized controlled trials were eligible and were included in our analysis (N = 209 participants). Compared with the control group, taurine could significantly reduce HbA1c (SMD −0.41[95% CI: −0.74, −0.09], p = 0.01), Fasting Blood Sugar (SMD − 1.28[95% CI: −2.42, −0.14], p = 0.03) and HOMA-IR (SMD − 0.64[95% CI: −1.22, −0.06], p = 0.03). In addition, taurine also reduced Insulin (SMD −0.48 [95% CI: −0.99, 0.03], p = 0.06) and TG (SMD −0.26 [95% CI: −0.55, 0.02], p = 0.07), but did not reach statistical significance.

Taurine supplementation is beneficial in reducing glycemic indices, such as HbA1c, Fasting Blood Sugar, HOMA-IR in diabetic patients, but has no significant effect on serum lipids, blood pressure and body composition in diabetic patients. Taurine emerges as a new option for the management of patients with diabetes. Further studies are needed to understand the potential effect of taurine in diabetic patients.

The effects of taurine supplementation on obesity, blood pressure and lipid profile: A meta-analysis of randomized controlled trials (2020)

There were 12 eligible peer-reviewed studies meeting the inclusion criteria. Most studies were conducted in patients with liver or metabolic dysregulation (diabetes, hepatitis, fatty liver, obesity, cystic fibrosis, chronic alcoholism, and cardiac surgery). The taurine dosage varied from 0.5 to 6 g/d for 15 days to 6 months. Pooled effect sizes suggested a significant effect of taurine administration on systolic blood pressure (weighted mean difference (WMD): -4.67 mm Hg; 95%CI, -9.10 to -0.25), diastolic blood pressure (WMD: -2.90 mm Hg; 95%CI, -4.29 to -1.52), total cholesterol (WMD: -10.87 mg/dl; 95%CI, -16.96 to -4.79), and triglycerides (WMD: -13.05 mg/dl; 95%CI, -25.88 to -0.22); however, it had no effect on fasting blood glucose (WMD: 0.06 mg/dl), HDL-C (WMD: 0.90 mg/dl), LDL-C (WMD: -6.17 mg/dl), as well as on body mass index (WMD: -0.46 kg/m2) and body weight (WMD: -0.47 kg) as the anthropometric measures. These findings indicate that, in patients with liver dysregulation, taurine supplementation can lower blood pressure and improve the lipid profile by reducing total cholesterol and triglyceride levels.

Taurine as a possible antiaging therapy: A controlled clinical trial on taurine antioxidant activity in women ages 55 to 70 (2022)

Methods: A double-blind study was conducted with 24 women (61.4 ± 4.2 y, body mass index 31.4 ± 5.1 kg/m²). The participants were randomly assigned to either a control group (GC, n = 11), supplemented with placebo (1.5 g of starch); or a taurine group (GTAU, n = 13), supplemented with taurine (1.5 g), for 16 wk. As primary outcomes, taurine and oxidative stress marker levels were determined in plasma samples. Anthropometry, functional capacity testing, and plasma mineral levels were evaluated as secondary outcomes. The evaluations were performed pre- and postintervention. Food consumption was assessed before, during, and after the intervention. The results were analyzed by two-way repeated analysis of variance measures mixed model, with the Sidak post hoc (P < 0.05).

Results: Taurine and superoxide dismutase (SOD, antioxidant enzyme) plasma levels were increased in the Taurine group. SOD levels also were higher than in the GC group after supplementation. Glutathione reductase levels decreased regardless of the intervention. Malondialdehyde levels increased only in the GC participants.

Conclusion: Taurine supplementation prevented the decrease in the antioxidant enzyme SOD, suggesting taurine as a strategy to control oxidative stress during the aging process.

The effects of Taurine supplementation on inflammatory markers and clinical outcomes in patients with traumatic brain injury: a double-blind randomized controlled trial (2021)

Background: Traumatic brain injury is a public health concern and is the main cause of death among various types of trauma. The inflammatory conditions due to TBI are associated with unfavorable clinical outcomes. Taurine has been reported to have immune-modulatory effects. Thus, the aim of this study was to survey the effect of taurine supplementation in TBI patients.

Methods: In this study, 32 patients with TBI were randomized into two groups. The treatment group received 30 mg/kg/day of taurine in addition to the Standard Entera Meal and the control group received Standard Entera Meal for 14 days. Prior to and following the intervention, the patients were investigated in terms of serum levels of IL-6, IL-10, hs-CRP and TNF-α as well as APACHEII, SOFA and NUTRIC scores, Glasgow coma scale and weight. In addition, the length of Intensive Care Unit stay, days of dependence on ventilator and 30-day mortality were studied. SPSS software (version 13.0) was used for data analysis.

Results: Taurine significantly decreased the serum levels of IL-6 (p = 0.04) and marginally APACHEII score (p = 0.05). In addition, weight loss was significantly lower in taurine group (p = 0.03). Furthermore, taurine significantly increased the GCS (p = 0.03). The groups were not different significantly in terms of levels of IL-10, hs-CRP, and TNF-α, SOFA and NUTRIC scores, 30-day mortality, length of ICU stay and days of dependence on ventilator.

Conclusion: According to the results of the present study, taurine supplementation can reduce the IL-6 levels as one of the important inflammatory markers in these patients; and enhances the clinical outcomes too.

The effects of taurine supplementation on oxidative stress indices and inflammation biomarkers in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial (2020)

Fifty patients with T2DM were randomly allocated to two groups to consume either taurine (containing 1000 mg taurine), or placebo (containing crystalline microcellulose) three times per day for 8 weeks. Anthropometric data, dietary intake, serum total antioxidant capacity (TAC), malondialdehyde (MDA), the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were assessed before and after intervention.

There was a significant increase in SOD (5.1%, p = 0.004) and CAT (4.22%, p = 0.001) after 8 weeks of taurine supplementation. In addition, serum levels of MDA (26.33%, p = 0.001), hs-CRP (16.01%, p = 0.001), and TNF-α (11.65%, p = 0.03) significantly decreased in the taurine group compared with baseline. Following treatment, the taurine group had fewer serum levels of MDA (p = 0.04), hs-CRP (p = 0.002) and TNF-α (p = 0.006) than the placebo group. Also, a significant increase was observed in SOD (p = 0.007), and CAT (p = 0.001) in the taurine group compared with the placebo group. There were no differences in the serum levels of IL-6 or TAC.

The findings of this study showed that taurine supplementation improved some oxidative stress indices and inflammatory biomarkers in patients with T2DM.

Protective and therapeutic effectiveness of taurine supplementation plus low calorie diet on metabolic parameters and endothelial markers in patients with diabetes mellitus: a randomized, clinical trial (2022)

120 patients with T2DM were randomly allocated to take either Taurine (containing 1 g Taurine, n = 60) or placebo (n = 60) three times per day for an eight-week period. Moreover, all patients were on a low-calorie diet. The primary outcome was fasting blood glucose (FBG) and endothelial markers including sera intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule (VCAM), and matrix metallopeptidase 9 (MMP-9). The secondary outcome was dietary intake, anthropometric indices, serum insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), total antioxidant capacity (TAC), tumor necrosis factor (TNF), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and lipid profile.

After 8 weeks, Taurine-supplemented patients had a considerable decrease in serum insulin and HOMA-IR compared to placebo group. However, Taurine supplementation did not improve other metabolic parameters including lipid profiles, glycated hemoglobin, and fasting blood glucose (FBG). There was a significant decline in MDA, TNF, and hs-CRP levels after these eight-week period of Taurine supplementation. In addition, the Taurine group had fewer serum levels of endothelial dysfunction markers than the placebo group.

Taurine supplementation significantly reduced insulin and HOMA-IR, as well as oxidative stress, inflammation, and endothelial markers in individuals with T2DM.

Taurine Supplementation Improves Functional Capacity, Myocardial Oxygen Consumption, and Electrical Activity in Heart Failure (2017)

In a double-blind and randomly designed study, 16 patients with heart failure were assigned to two groups: taurine (TG, n = 8) and placebo (PG, n = 8). TG received 500-mg taurine supplementation three times per day for two weeks.

Significant decrease in the values of Q-T segments (p < 0.01) and significant increase in the values of P-R segments (p < 0.01) were detected following exercise post-supplementation in TG rather than in PG. Significantly higher values of taurine concentration, T wave, Q-T segment, physical capacities, and lower values of cardiovascular capacities were detected post-supplementation in TG as compared with PG (all p values <0.01).

Taurine significantly enhanced the physical function and significantly reduced the cardiovascular function parameters following exercise. Our results also suggest that the short-term taurine supplementation is an effective strategy for improving some selected hemodynamic parameters in heart failure patients. Together, these findings support the view that taurine improves cardiac function and functional capacity in patients with heart failure. This idea warrants further study.

The Effects of Taurine Supplementation on Metabolic Profiles, Pentosidine, Soluble Receptor of Advanced Glycation End Products and Methylglyoxal in Adults With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial (2020)

In this double-blind randomized controlled trial, 46 patients with T2DM were randomly allocated into taurine and placebo groups. Participants received either 3,000 mg/day taurine or placebo for 8 weeks. Metabolic profiles, pentosidine, MGO and soluble receptors for advanced glycation end products levels were assessed after 12 h of fasting at baseline and completion of the clinical trial. Independent t test, paired t test, Pearson correlation and analysis of covariance were used for analysis.

The mean serum levels of fasting blood sugar (p=0.01), glycated hemoglobin (p=0.04), insulin (p=0.03), homeostasis model assessment-insulin resistance (p=0.004), total cholesterol (p=0.01) and low-density lipoprotein cholesterol (p=0.03) significantly were reduced in the taurine group at completion compared with the placebo group. In addition, after completion of the study, pentosidine (p=0.004) and MGO (p=0.006) were significantly reduced in the taurine group compared with the placebo group.

The results of this trial show that taurine supplementation may decrease diabetes complications through improving glycemic control and advanced glycation end products.

Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial (2019)

The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNALeu(UUR), resulting in failure to decode codons accurately.

After the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNALeu(UUR) was measured before and after the trial.

The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNALeu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine.

The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNALeu(UUR) in MELAS.

Taurine supplementation associated with exercise increases mitochondrial activity and fatty acid oxidation gene expression in the subcutaneous white adipose tissue of obese women (2019)

A randomized and double-blind trial was developed with 24 obese women (BMI 33.1 ± 2.9 kg/m2, 32.9 ± 6.3 y) randomized into three groups: Taurine supplementation group (Tau, n = 8); Exercise group (Ex, n = 8); Taurine supplementation + exercise group (TauEx, n = 8). The intervention was composed of 3 g of taurine or placebo supplementation and exercise training for eight weeks. Anthropometry, body fat composition, indirect calorimetry, scWAT biopsy for mitochondrial respiration, and gene expression related to mitochondrial activity and lipid oxidation were assessed before and after the intervention.

No changes were observed for the anthropometric characteristics. The Ex group presented an increased resting energy expenditure rate, and the TauEx and Ex groups presented increased lipid oxidation and a decreased respiratory quotient. Both trained groups (TauEx and Ex) demonstrated improved scWAT mitochondrial respiratory capacity. Regarding mitochondrial markers, no changes were observed for the Tau group. The TauEx group had higher expression of CIDEA, PGC1a, PRDM16, UCP1, and UCP2. The genes related to fat oxidation (ACO2 and ACOX1) were increased in the Tau and Ex groups, while only the TauEx group presented increased expression of CPT1, PPARa, PPARγ, LPL, ACO1, ACO2, HSL, ACOX1, and CD36 genes.

Taurine supplementation associated with exercise improved lipid metabolism through the modulation of genes related to mitochondrial activity and fatty acid oxidation, suggesting a browning effect in the scWAT of obese women.

Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects (2004)

Thirty college students (age: 20.3+/-1.7 years) with a body mass index (BMI) >/=25.0 kg/m(2), and with no evidence of diabetes mellitus were selected and assigned to either the taurine group (n=15) or the placebo group (n=15) by double-blind randomization. Taurine 3 g/day or placebo was taken orally for 7 weeks. Triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and plasma glucose were measured before and after supplementation. The atherogenic index (AI) was calculated as (TC-HDL-C)/HDL-C. There were no differences in any baseline parameter between the two groups. Taurine supplementation decreased TG and atherogenic index (AI) significantly. Body weight also reduced significantly in the taurine group. These results suggest that taurine produces a beneficial effect on lipid metabolism and may have an important role in cardiovascular disease prevention in overweight or obese subjects.

Effect of taurine treatment on insulin secretion and action, and on serum lipid levels in overweight men with a genetic predisposition for type II diabetes mellitus (2004)

Design: 20 nondiabetic subjects were included in a double-blinded, randomized, crossover study, receiving a daily supplementation of 1.5 g taurine or placebo for two periods of 8 weeks. The subjects were overweight first-degree relatives of T2DM patients. An intravenous glucose tolerance test (IVGTT) was used to measure first-phase insulin secretory response, and a euglycemic hyperinsulinemic clamp was used to determine peripheral insulin action.

Results: Mean plasma taurine concentration was 39 +/- 7 (s.d.) micromol/l after placebo and 131 +/- 62 micromol/l after taurine intervention (P < 0.0001). There was no significant difference after taurine intervention compared to placebo in incremental insulin response (Insincr.) neither during the IVGTT, nor in insulin-stimulated glucose disposal during the clamp. Insulin secretion, adjusted for insulin sensitivity, was also unchanged. There was no significant effect of taurine supplementation on blood lipid levels as well.

Conclusion: Daily supplementation with 1.5 g taurine for 8 weeks had no effect on insulin secretion or sensitivity, or on blood lipid levels. These findings in persons with an increased risk of T2DM are in contrast to those from animal studies, and do not support the assumption that dietary supplementation with taurine can be used to prevent the development of T2DM.

The Role of Taurine in Mitochondria Health: More Than Just an Antioxidant, 2021

Taurine is a naturally occurring sulfur-containing amino acid that is found abundantly in excitatory tissues, such as the heart, brain, retina and skeletal muscles. Taurine was first isolated in the 1800s, but not much was known about this molecule until the 1990s. In 1985, taurine was first approved as the treatment among heart failure patients in Japan. Accumulating studies have shown that taurine supplementation also protects against pathologies associated with mitochondrial defects, such as aging, mitochondrial diseases, metabolic syndrome, cancer, cardiovascular diseases and neurological disorders. In this review, we will provide a general overview on the mitochondria biology and the consequence of mitochondrial defects in pathologies. Then, we will discuss the antioxidant action of taurine, particularly in relation to the maintenance of mitochondria function. We will also describe several reported studies on the current use of taurine supplementation in several mitochondria-associated pathologies in humans.

Impact of taurine on red blood cell metabolism and implications for blood storage, 2020

Taurine is an antioxidant that is abundant in some common energy drinks. Here we hypothesized that the antioxidant activity of taurine in red blood cells (RBCs) could be leveraged to counteract storage-induced oxidant stress.

STUDY DESIGN AND METHODS:

Metabolomics analyses were performed on plasma and RBCs from healthy volunteers (n = 4) at baseline and after consumption of a whole can of a common, taurine-rich (1000 mg/serving) energy drink. Reductionistic studies were also performed by incubating human RBCs with taurine ex vivo (unlabeled or 13C15N-labeled) at increasing doses (0, 100, 500, and 1000 μmol/L) at 37°C for up to 16 hours, with and without oxidant stress challenge with hydrogen peroxide (0.1% or 0.5%). Finally, we stored human and murine RBCs under blood bank conditions in additives supplemented with 500 μmol/L taurine, before metabolomics and posttransfusion recovery studies.

RESULTS:

Consumption of energy drinks increased plasma and RBC levels of taurine, which was paralleled by increases in glycolysis and glutathione (GSH) metabolism in the RBC. These observations were recapitulated ex vivo after incubation with taurine and hydrogen peroxide. Taurine levels in the RBCs from the REDS-III RBC-Omics donor biobank were directly proportional to the total levels of GSH and glutathionylated metabolites and inversely correlated to oxidative hemolysis measurements. Storage of human RBCs in the presence of taurine improved energy and redox markers of storage quality and increased posttransfusion recoveries in FVB mice.

CONCLUSION:

Taurine modulates RBC antioxidant metabolism in vivo and ex vivo, an observation of potential relevance to transfusion medicine.

Summarizing health benefits of Taurine

Taurine is an amino sulfonic acid that is ubiquitous in animal tissues and is found in high concentrations in excitable tissues such as muscles, brain, retina and central nervous system (Jacobsen & Smith, 1968). It plays a vital role in several physiological processes and its deficiency leads to pathological conditions. 

Anti-Oxidative Effects

Taurine acts as an antioxidant and protects cells against oxidant-induced injury by sustaining normal electron transport chain function, maintaining glutathione stores, upregulating antioxidant responses, stabilizing cell membranes and preventing calcium accumulation in cells (Baliou et al, 2021). A study in mice showed that pre-treatment with 100mg/kg taurine daily for 5 days protected against aluminum-induced acute liver toxicity by reducing oxidative stress markers like malondialdehyde while increasing antioxidant markers like glutathione and antioxidant enzymes (El-Sayed et al, 2011).

Anti-Inflammatory Effects

Taurine exerts anti-inflammatory effects in cardiovascular disease models by inhibiting proinflammatory cytokines like interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). A rat study showed that 300mg/kg taurine reduced LPS-induced increases in these cytokines in the liver (Qaradakhi et al, 2020). Another study showed the anti-inflammatory chloramine derivative of taurine (TauCl) inhibited leukocyte infiltration in mice by suppressing actin polymerization and MAP kinase activation (Kim et al, 2022). 

Metabolic Effects

Dietary taurine was shown to significantly improve lipid metabolism in obese mouse models, with one study showing that 20% dietary taurine increased HDL cholesterol and reduced total cholesterol and triglycerides (Shin et al, 2017). Taurine may also have beneficial effects on glucose metabolism and insulin sensitivity based on studies in rat models (Lourenço & Camilo, 2002).

Cardiovascular Effects

Taurine may have protective effects against coronary heart disease, hypertension and heart failure through antioxidant, anti-inflammatory and blood pressure lowering mechanisms (Wójcik et al, 2010). One study showed 1.6g daily taurine for 12 weeks significantly reduced blood pressure and improved endothelial function in prehypertensive humans (Sun et al, 2016).

Neuroprotective Effects

Due to its role in osmoregulation, prevention of excitotoxicity and anti-inflammatory effects, taurine protects against neurological disorders like stroke, Alzheimer's disease and epilepsy (Lipton et al, 2015). Taurine treatment was shown to reverse electroretinographic abnormalities caused by taurine deficiency in rats, suggesting a protective effect on vision (Shimada et al, 1992).

Anti-Cancer Effects  

Taurine has shown anti-cancer effects in animal studies by inducing apoptosis in cancer cells, inhibiting angiogenesis and cell growth, among other actions (Ma et al, 2022). While human trials are lacking, taurine treatment appears non-toxic which enhances its potential as an adjuvant cancer therapy.

Safety and Tolerability

Most human interventions demonstrate taurine supplementation to have high safety and tolerability. A study giving 1.5g/day taurine to cats for 6 months showed no adverse effects (Sturman & Messing, 1992). Common side effects are mild like diarrhea which tend to be transient (Rösner et al, 2010).

Conclusion

In conclusion, taurine supplementation demonstrates antioxidant, anti-inflammatory, metabolic, cardiovascular, neurological and anti-cancer benefits in animal models and early human studies. Larger, long-term human trials are required to establish clinical efficacy and optimal dosing. But current evidence suggests taurine may be a promising preventive and therapeutic agent against various oxidative stress-related diseases.

Taurine, a naturally occurring amino acid, has garnered significant attention in recent years for its potential therapeutic benefits, particularly its anti-inflammatory effects. This summary synthesizes the findings from various studies, underscoring the diverse applications of taurine in mitigating inflammation across various disease contexts.

Functional Role of Taurine in Aging and Cardiovascular Health: An Updated Overview (2023)

Santulli et al. (2023) provide an overview of the scientific literature on the functional roles of taurine related to aging and cardiovascular health. Taurine is a naturally occurring amino acid found in high levels in tissues like skeletal muscle, brain, heart, and retina. It plays diverse physiological roles, including as an antioxidant, osmolyte, bile acid conjugator, and neuromodulator. The review focuses specifically on the effects of taurine supplementation on longevity, cell senescence, unfolded protein response, telomere attrition, sirtuin activity, stem cell function, and cardiovascular parameters like blood pressure, endothelial function, metabolism, and athletic performance.

Key conclusions highlighted in the review are:

Taurine Supplementation May Increase Lifespan:

• Animal studies show 10% lifespan extension in mice supplemented with 15-30 mg taurine/day (human equivalent dose 3-6 g for 80 kg adult)

• Improved muscle endurance, strength and overall health indicators

• Shaping of gut microbiota also observed

Taurine Deficiency Linked to Cell Senescence:

• Mice lacking taurine transporter exhibit high senescence markers and rapid aging

• Removing senescent cells with senolytics restores some lifespan

• Adding taurine reduces senescent cell burden by up to 3-fold in aged mice

Taurine Deficiency Induces Unfolded Protein Response:

• Lack of taurine transport causes endoplasmic reticulum stress in mouse skeletal muscle

• Taurine alleviates detrimental effects of unfolded protein response during cellular stress

Taurine May Prevent Telomere Attrition:

• Taurine increases telomerase expression in human stem cells, maintaining differentiation potential

• Correlation between taurine and telomere length in mice

• Mitigates effects of TERT deficiency in zebrafish model

Taurine Activates Sirtuin-1, a Longevity Protein:

• Direct activation shown in liver, heart and brain tissue

• Leads to p53 inhibition and reduced apoptosis

• Likely binding directly to Sirtuin-1 protein

Taurine Maintains Stem Cell Pools:

• Increases stem cell survival, regeneration, and "stemness"

• Essential for embryonic stem cell development

• Benefits neural, bone, cartilage and muscle stem cells

Taurine Has Cardioprotective Effects:

Blood Pressure

• 3 g/day reduces systolic BP 5.2 mmHg (meta-analysis)

• Improves endothelial nitric oxide production

Cardiac Function

• Reverses atrophic cardiac remodeling in animal models

• Clinical trials show improved LV function and exercise tolerance

Vascular Function

• Modest enhancement of endothelium-dependent relaxation

• Reduces dysfunction in patients with diabetes or hypertension

Metabolism

• May increase insulin sensitivity and improve lipid profiles

• Limited evidence for effects in humans

Athletic Performance

• Some evidence on reduced muscle damage and oxidative stress

• Unclear if peripheral to effects of caffeine in energy drinks

Safety and Supplementation

• Typical dietary intake estimated between 40-400 mg/day

• Supplements available from 500 mg to 2 g per dose

• Adverse effects noted at 3 g/day but generally well tolerated

• Caution advised for high doses and with medication interactions

In summary, evidence from cell, animal and human studies indicates taurine may promote longevity, mitigate age-related cell senescence, preserve stem cell function, and exert antioxidant and anti-inflammatory cardiovascular benefits. Taurine supplementation appears reasonably safe at moderate doses but further research is needed to confirm therapeutic efficacy.

Anti-Inflammatory and Antioxidant Effects

1. Sports and Exercise (Kurtz et al, 2021): Taurine supplementation shows potential in enhancing athletic performance, reducing muscle damage, and improving recovery. It lowers lactate, creatine kinase, and inflammatory markers while boosting peak power and glycolytic/fat oxidation markers. Effective doses range from 1-3 g/day over 6-15 days, though findings are varied and call for more definitive conclusions

2. Cardiovascular Health (Qaradakhi et al, 2020; Santulli et al, 2023): Taurine demonstrates benefits in cardiovascular health, potentially by inhibiting the renin-angiotensin system. It helps regulate blood pressure, improves cardiac fitness, and enhances vascular health. Its anti-inflammatory effects are pivotal in managing cardiovascular diseases, including hypertension and cardiac dysfunctions.

3. Neurological Disorders (Jakaria et al, 2019): Taurine shows promising results against neurological disorders like neurodegeneration, stroke, epilepsy, and diabetic neuropathy. It protects against nervous system injuries and has therapeutic roles against neurodevelopmental disorders, warranting further clinical studies.

4. Cancer and Inflammation (Baliou et al, 2020): Taurine induces anti-inflammatory responses and can enhance cancer therapy outcomes by overcoming cellular resistance. It’s being explored for its potential in cancer and inflammation therapies.

5. Liver Disease and Toxin-Induced Injury (Ji et al, 2023): Taurine ameliorates toxin-induced liver injury by restoring mitochondrial function and reducing oxidative stress and inflammation. It's particularly effective against liver pathology caused by mycotoxins in piglets.

6. Diabetic Nephropathy (Ma & Yang et al, 2022): Taurine significantly prevents oxidative stress, inflammation, and apoptosis in diabetic nephropathy, suggesting its role in alleviating kidney tissue damage.

7. Oxidative Stress in Obesity (Rosa et al, 2014): In obese individuals, taurine supplementation can significantly reduce markers of inflammation and oxidative stress, indicating its potential in managing obesity-related complications.

8. Sarcopenia (Scicchitano & Sica, 2018): Taurine could ameliorate age-associated skeletal muscle dysfunction by reducing oxidative stress and inflammation, indicating its potential in combating sarcopenia.

9. Chronic Kidney Disease (Li et al, 2019): Taurine plays a role in protecting against chronic kidney disease progression, emphasizing its therapeutic potential in renal health.

Disease Modulation and Therapeutic Potential

10. COVID-19 (van Eijk et al, 2022): With its antiviral, antioxidant, and anti-inflammatory effects, taurine could play a role in modifying COVID-19 disease progression. This underlines its potential as a therapeutic agent in managing the pandemic.

11. Hyperlipidemia (Nam et al, 2021; Dong et al, 2021): Taurine ameliorates obesity, diabetes, and hyperlipidemia-related pathologies. It modulates lipid metabolism and has anti-inflammatory and antioxidant effects, suggesting its role in managing lipid disorders.

12. Lung Inflammation (Ommati et al, 2022): Taurine alleviates lung inflammation and histological changes associated with cirrhosis-induced lung injury, highlighting its potential as a protective agent against respiratory complications in liver diseases.

13. Male Reproduction (Li et al, 2023): Taurine promotes endocrine function in the male reproductive system, enhances sexual ability, and protects against reproductive damage caused by various factors including drugs, pollutants, and radiation.

14. Sepsis and Infection (Ma et al, 2023; Supinski et al, 2020): In sepsis models, taurine reduces hyperinflammation and multi-organ dysfunction. It also prevents infection-induced diaphragm dysfunction, underlining its potential in sepsis management.

15. Aging and Cardiovascular Health (Santulli et al, 2023; Qi et al, 2023): Taurine's antioxidant properties make it a candidate for anti-aging strategies, particularly in improving cardiovascular health and mitigating chronic low-grade

The Anti-Inflammatory Effect of Taurine on Cardiovascular Disease (2020)

Introduction

• Taurine is an amino acid found abundantly in animal tissues including the brain, retina, muscles and organs. It influences cellular functions like osmoregulation, antioxidation, ion movement and bile acid conjugation (Bkaily et al, 2020).

• Taurine exerts anti-inflammatory effects, improves diabetes, and may protect against coronary heart disease (CHD) possibly by inhibiting the renin-angiotensin system (RAS) (Wojcik et al, 2010).

Taurine Deficiency

• Taurine deficiency in cats leads to cardiomyopathy and retinal degeneration (Hayes et al, 1975; Pion et al, 1987).

• Low neonatal plasma taurine levels correlate with impaired mental development at 18 months in infants (Wharton et al, 2004).

• Children with defective taurine transporter gene develop cardiomyopathy like seen in animal models, indicating taurine's role in human cardiac function (Ansar et al, 2019).

• Maternal taurine deficiency associates with lower newborn size which may increase CAD risk later (Barker et al, 2005).

• In taurine transporter knockout mice, impaired mitochondrial complex I and elevated superoxide causes ER stress and cardiac apoptosis (Ramila et al, 2015).

Effects of Taurine on Cardiovascular System

• Higher meat intake associates with greater CVD mortality versus higher seafood intake populations (Mozaffarian & Rimm, 2006), suggesting taurine's cardioprotective effects.

• Higher taurine intake correlates with reduced CHD risk (Yamori et al, 1996).

• Taurine reduced atherosclerosis in rabbits' left main coronary artery (Zulli et al, 2009).

• Taurine dose-dependently relaxes rat thoracic aorta via opening an unspecified potassium channel, improving impaired vasorelaxation in CVD (Niu et al, 2008).

Effects on Renin-Angiotensin System

• In diabetic rats, taurine reduces cardiomyocyte AT2R expression (Li et al, 2005).

• In neonatal rat cardiomyocytes, short-term taurine blocks Ang II-induced cell proliferation possibly by inhibiting Na+/Ca2+ exchanger to maintain calcium homeostasis (Takahashi et al, 1997; Azuma et al, 2000; Takahahsi et al, 1998).

• In rabbits, taurine reduced atherogenic RAS components like ACE, AT1R, AT2R and ACE2 (Zulli et al, 2009).

• In rats with hypertension, taurine countered ACE overactivation by upregulating ACE2, reducing blood pressure (Lv et al, 2017).

Effects in Diabetes and Obesity

• In type 1 diabetic rats, taurine prevented beta cell damage, reduced glucose and fructosamine, increased insulin and glycogen (Gavrovskaya et al, 2008).

• Taurine prevented hyperglycemia in alloxan-induced diabetic rabbits (Tenner et al, 2003; Winiarska et al, 2009).

• Taurine alters electrical potential of beta cells, causing decreased insulin secretion (L’Amoreaux et al, 2010).

• In diabetic OLETF rats, taurine improved insulin resistance and reduced glucose and lipids but did not reverse existing complications (Kim et al, 2012).

• In prediabetic humans, 8 week taurine supplementation did not improve insulin sensitivity or lipid levels (Brons et al, 2004).

• Obesity associates with greater CAD risk (Ades & Savage, 2017) but taurine supplementation reduces obesity-induced inflammation (Rosa et al, 2014).

• Taurine deficiency promotes obesity; supplementation or activating its synthesis could reduce obesity, a CAD risk factor (Murakami, 2015; Tsuboyama-Kasaoka et al, 2006).

• In obese mice, taurine supplementation inhibited adipogenesis leading to weight loss (Kim et al, 2019).

Anti-Inflammatory Effects

• Chronic inflammation in type 2 diabetes accelerates atherosclerosis (Martens et al, 2006; Lee et al, 2017). As taurine is anti-inflammatory, it may prevent CAD.

• Taurine localizes in immune cells like leukocytes, lymphocytes and neutrophils (Fazzino et al, 2006; Wang et al, 2009).

• Taurine reduces TLR2 expression and NF-Kβ activation, decreasing inflammation in rat mastitis models (Miao et al, 2011).

• Taurine's metabolites, taurine chloramine (TauCl) and taurine bromamine (TauBr), exert anti-inflammatory effects by inhibiting cytokines, oxidative stress and inflammation.

• TauBr downregulates TNFα-induced NF-Kβ inflammation which may benefit CVD patients (Tokunaga et al, 2007).

• TauCl inhibits TLR 2, 4, 9 activation and NF-Kβ nuclear migration in immune cells, reducing pro-inflammatory molecules (Kim & Cha, 2005; Kim et al, 2011).

Human Clinical Studies

• In heart failure patients, 2 week 3000mg/day taurine improved exercise capacity, reduced cholesterol, triglycerides, CRP and post-exercise inflammatory markers (Beyranvand et al, 2011; Ahmadian et al, 2017).

• In patients undergoing coronary bypass, 30-45 day 9g/kg taurine decreased ventricular dysfunction (Jeejeebhoy et al, 2002).

• 6 gram taurine daily for 6 weeks improved left ventricular function in heart failure (Azuma et al, 1992).

• Two siblings with defective taurine transporter gene developed cardiomyopathy. 100mg/kg taurine supplementation for 24 months restored plasma taurine levels and cardiac function (Ansar et al, 2019).

• 1600mg taurine daily for 12 weeks reduced blood pressure in pre-hypertensive patients (Sun et al, 2016). While 6000mg for 7 days decreased pressure via the sympathetic system in hypertensive patients (Militante & Lombardini, 2002).

• Type 2 diabetics also had improved vascular function and reduced platelet aggregation with 1500mg taurine daily for 90 days (Moloney et al, 2010; Franconi et al, 1995).

• Higher doses (3000mg daily) reduced glucose, oxidative stress and inflammation in type 2 diabetes patients but lower doses had no effect (Maleki et al, 2020; Shari et al, 2019).

Conclusions

• Clinical trials show taurine supplementation improves heart function, is anti-hypertensive, beneficial in pre-hypertension and type 2 diabetes.

• Foods high in taurine like seafood may prevent CAD and prolong life expectancies but more clinical investigations are required to confirm taurine supplementation as an adjuvant CVD treatment.

Taurine and Inflammation

Taurine, a sulfur-containing amino acid, has emerged as a potent anti-inflammatory agent with numerous health benefits across various disease models. The research on taurine's anti-inflammatory properties is extensive, spanning from cellular studies to animal models and human trials. This summary encapsulates the key findings from significant studies, highlighting taurine's role in mitigating inflammation.

1. Anti-Inflammatory Mechanisms in Various Models:

   - Taurine Chloramine Production: Kim & Cha (2014) demonstrated that taurine reacts with hypochlorous acid in activated neutrophils to form taurine chloramine (TauCl), which significantly inhibits the production of inflammatory mediators like superoxide, nitric oxide, TNF-alpha, interleukins, and prostaglandins. This reaction is crucial in mitigating inflammatory responses.

   - Cardiovascular and Diabetic Health: Qaradakhi et al. (2020) highlighted taurine's potential in improving cardiovascular health and diabetes management by inhibiting the renin-angiotensin system. The study emphasized taurine's role in blood pressure regulation, improved cardiac fitness, and enhanced vascular health.

   - Muscle Aging and Sarcopenia: Scicchitano & Sica (2018) reviewed taurine's capacity to counter chronic inflammation and oxidative stress in muscle aging and sarcopenia. Taurine was found to modulate pathways regulating muscle homeostasis and protein catabolism, suggesting its potential to ameliorate age-related skeletal muscle decline.

2. Clinical Applications in Disease Models:

   - Traumatic Brain Injury: Su et al. (2014) found that post-injury taurine injection significantly suppressed brain levels of various inflammatory cytokines in a traumatic brain injury model. This study underscored taurine's potential as an anti-neuroinflammatory agent.

   - Bovine Mammary Epithelial Cells: Wang et al. (2021) showed that taurine increased autophagic degradation of intracellular bacteria in bovine mammary epithelial cells infected with Streptococcus uberis, reducing bacterial load and inflammation. This study provided insights into taurine's anti-inflammatory mechanism via autophagy regulation.

   - Liver Inflammation: In a study by Qiu et al. (2018), taurine supplementation significantly inhibited inflammasome activation and inflammatory cytokine release in an arsenic-induced liver inflammation model, highlighting its cytoprotective anti-inflammatory effect.

3. Human Studies and Trials:

   - Obesity and Inflammation: Rosa et al. (2014) conducted a study in obese humans and rats, showing that 3g per day taurine supplementation for 8 weeks significantly reduced systemic levels of high-sensitivity C-reactive protein by 29%, without altering body weight. This finding is crucial in understanding taurine's role in mitigating systemic inflammation in obesity.

   - Exercise and Inflammation: A randomized trial cited by Chupel et al. (2018) found that combined taurine supplementation and exercise training in elderly humans significantly reduced plasma levels of inflammatory cytokines, indicating its efficacy in decreasing systemic inflammation.

4. Rodent Models:

   - Neutrophil Recruitment and Cytokine Production: Velloso et al. (2018) and Ozsarlak-Sozer et al. (2016) found that taurine pre-treatment in rodent models reduced neutrophil recruitment and production of inflammatory markers like TNF-α and IL-1β in response to various inflammatory stimuli. These studies contribute to understanding taurine's preventive role in inflammation.

5. Protective Effects Against Oxidative Stress:

   - Baliou et al. (2021) reviewed the protective effects of taurine against oxidative stress in conditions like hypertension, muscle disorders, and cardiac dysfunction. Taurine's antioxidant actions include sustaining electron transport, maintaining glutathione levels, and stabilizing cellular membranes.

6. Performance and Recovery Enhancemen<t:

   - Aerobic and Anaerobic Performance: Kurtz et al. (2021) concluded that taurine might improve time to exhaustion, anaerobic performance, recovery, and decrease markers like creatine kinase, lactate, and inflammatory cytokines, though they emphasized the need for further research to understand

Protective and therapeutic effectiveness of taurine supplementation plus low calorie diet on metabolic parameters and endothelial markers in patients with diabetes mellitus: a randomized, clinical trial (2022)

Methods

In the current clinical trial, 120 patients with T2DM were randomly allocated to take either Taurine (containing 1 g Taurine, n = 60) or placebo (n = 60) three times per day for an eight-week period. Moreover, all patients were on a low-calorie diet. The primary outcome was fasting blood glucose (FBG) and endothelial markers including sera intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule (VCAM), and matrix metallopeptidase 9 (MMP-9). The secondary outcome was dietary intake, anthropometric indices, serum insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), total antioxidant capacity (TAC), tumor necrosis factor (TNF), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and lipid profile.

Results

After 8 weeks, Taurine-supplemented patients had a considerable decrease in serum insulin and HOMA-IR compared to placebo group. However, Taurine supplementation did not improve other metabolic parameters including lipid profiles, glycated hemoglobin, and fasting blood glucose (FBG). There was a significant decline in MDA, TNF, and hs-CRP levels after these eight-week period of Taurine supplementation. In addition, the Taurine group had fewer serum levels of endothelial dysfunction markers than the placebo group.

Conclusions

The evidence from our study revealed that Taurine supplementation significantly reduced insulin and HOMA-IR, as well as oxidative stress, inflammation, and endothelial markers in individuals with T2DM.

Oxidative stress and inflammation in obesity after taurine supplementation: a double-blind, placebo-controlled study (2014)

Purpose: Some researchers found decreased levels of plasma taurine in obese subjects and animals, and reduced expression of an important enzyme of taurine synthesis. These evidences, coupled with the metabolic imbalance of obesity and the possible anti-inflammatory and antioxidant effects of taurine, highlighted the use of taurine as a supplement in obesity treatment. The aim of the present study was to investigate whether taurine supplementation, associated with nutritional counseling, modulates oxidative stress, inflammatory response, and glucose homeostasis in obese women.

Methods: A randomized double-blind placebo-controlled study was conducted with 16 women with obesity diagnosis and 8 women in the normal weight range. The obese volunteers were matched by age and body mass index and randomly assigned to either the placebo (3 g/day starch flour) or taurine (3 g/day taurine) group. The study lasted 8 weeks, and the experimental protocol included nutritional assessment and determination of plasma sulfur amino acids, insulin, and adiponectin, serum glycemia, and markers of inflammatory response and oxidative stress.

Results: Plasma taurine levels were significantly decreased (41%) in the obese volunteers. Both the placebo and taurine groups showed significant reduction in weight (3%), with no differences between groups. Different from placebo, taurine-supplemented group showed significant increase in plasma taurine (97%) and adiponectin (12%) and significant reduction in the inflammatory marker hs-C-reactive protein (29%) and in the lipid peroxidation marker thiobarbituric acid reactive substances (TBARS) (20%).

Conclusions: Eight weeks of taurine supplementation associated with nutritional counseling is able to increase adiponectin levels and to decrease markers of inflammation (high-sensitivity C-reactive protein) and lipid peroxidation (TBARS) in obese women.

Role of taurine, its haloamines and its lncRNA TUG1 in both inflammation and cancer progression. On the road to therapeutics? (Review) (2020)

This review article by Baliou et al. (2020) discusses the role of taurine, its haloamines, and the long non-coding RNA TUG1 in inflammation and cancer progression. The key points are:

Taurine:

• Taurine is an amino acid abundant in mammalian tissues that plays important roles in processes like osmoregulation, cytoprotection, immune modulation, and more. It has anti-oxidant and anti-inflammatory properties.

• In inflammation, taurine accumulates at sites of inflammation and in immune cells like neutrophils and macrophages. It helps protect these cells from oxidative damage. Taurine also reduces the secretion of pro-inflammatory cytokines like TNF-alpha and IL-8, making it a promising therapeutic agent for inflammatory diseases.

• In cancer, taurine can have cytostatic (inhibiting growth) or cytotoxic (killing cells) effects against tumor cells. Proposed mechanisms include: 1) anti-oxidant activity reducing ROS in cells, 2) enhancing chemotherapy drug efficacy while reducing side effects, 3) enhancing immune rejection of cancer cells, and 4) inducing apoptosis.

• Taurine has shown anti-cancer effects against colon, lung, liver, pancreatic, brain, skin, breast and other cancers in preclinical studies. For example, in colon cancer cells, taurine upregulates p53 and apoptosis while downregulating proteins like Bcl-2.

• An important clinical application is that taurine can reduce the toxic side effects of chemotherapies like doxorubicin, allowing higher therapeutic doses. It is proposed as an adjuvant therapy alongside chemotherapy.

Taurine Haloamines:

• When taurine reacts with substances released by activated neutrophils like hypochlorous acid (HOCl), it forms haloamines like N-chlorotaurine (TauCl) and N-bromotaurine (TauBr).

• TauCl and TauBr have microbicidal effects against bacteria, fungi, viruses and other pathogens at concentrations around 10-50 μM. Proposed mechanisms include oxidation of microbial proteins and membranes.

• TauCl and TauBr also have anti-inflammatory effects by reducing cytokines like TNF-alpha, IL-1beta, IL-6 and more in leukocytes and macrophages. They induce expression of heme oxygenase-1 which helps resolve inflammation.

• In animal models, TauCl had anti-arthritic effects and reduced inflammation and bone/cartilage damage in rheumatoid arthritis. But effects of systemic TauCl on arthritis models are more complicated.

• TauBr helped resolve acne symptoms in 65% of antibiotic-resistant patients in one small trial. And TauCl showed good tolerability in human infections/inflammation in Phase 2 trials. But more studies are still needed on haloamines' clinical applications.

The lncRNA TUG1:

• The long non-coding RNA TUG1 is overexpressed in many cancers and affects processes like proliferation, metastasis, drug resistance, and energy metabolism.

• Proposed mechanisms include: 1) interacting with PRC2 complex for epigenetic regulation of genes, and 2) acting as a "sponge" for miRNAs, preventing them from inhibiting target mRNAs.

• In colon cancer for example, TUG1 causes Wnt pathway activation and epithelial-mesenchymal transition, enhancing invasion. In pancreatic cancer, it promotes acquisition of stem-like, drug resistant properties.

• But in lung cancer, TUG1 appears to be a tumor suppressor inhibited by oncogenic signals. So its role differs across cancer types.

• TUG1 also confers resistance to chemotherapies - silencing it re-sensitized resistant cancer cells to drugs like doxorubicin, cisplatin and paclitaxel in some studies. Further research into overcoming chemoresistance mechanisms is warranted.

In conclusion, the review summarizes the therapeutic potential of taurine, haloamines like TauCl/TauBr which are derived from it, and the non-coding RNA TUG1, in treating inflammatory disorders and cancers. More clinical trials are needed to translate the promising preclinical findings with these compounds into practice. Combining taurine or its derivatives with chemotherapies could help overcome limitations like toxicity and drug resistance. And targeting oncogenic lncRNAs like TUG1 is a promising new avenue in cancer therapy. Further research should better characterize the molecular interactions of these compounds to expand their clinical applications.

Taurine and inflammatory diseases (2014)

This paper reviews the role of taurine and its derivatives in immune function and inflammation, with a focus on their activity in inflammatory diseases like rheumatoid arthritis (RA). 

The key points are:

• Taurine is an antioxidant that protects tissues from oxidative damage during inflammation. It neutralizes hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) in neutrophils, forming the less toxic taurine chloramine (TauCl).

• TauCl and taurine bromamine (TauBr) have antimicrobial and anti-inflammatory properties. At inflammatory sites they inhibit cytokines like TNF-α, IL-1β, IL-6, IL-8 and more. They also suppress immune cell activity and induce leukocyte apoptosis.

• These taurine derivatives link oxidative stress pathways and the heme oxygenase-1 (HO-1) antioxidant system through activating transcription factor Nrf2. This induces HO-1 expression.

• In infectious and inflammatory diseases like acne, otitis, and arthritis, TauCl/TauBr improve symptoms when applied topically. Systemically they degrade too fast, limiting effects.

• In RA fibroblast-like synoviocytes (FLS), TauCl inhibits cytokines, MMPs and proliferation at 200-500μM. This reduces joint inflammation and damage. It acts via NFκB, AP-1 and HO-1.

• In collagen-induced arthritis (CIA) in mice, systemic TauCl reduces arthritis incidence, via anti-inflammatory effects. Locally it also protects from bone/cartilage damage by inhibiting osteoclasts.

Conclusions

• Taurine is an antioxidant protecting tissues from oxidative damage during inflammation, through neutralizing HOCl and forming less toxic TauCl/TauBr

• TauCl/TauBr have broad antimicrobial, anti-inflammatory and antioxidant properties, inhibiting cytokines, immune cells, and inducing HO-1 expression

• In acne, otitis, and other infectious or inflammatory conditions, topical TauCl/TauBr improve symptoms

• In RA, TauCl decreases FLS production of inflammatory and tissue damaging mediators, protecting joints

• In CIA, TauCl reduces arthritis incidence and severity systemically and locally through its anti-inflammatory and bone protective effects

So taurine and its derivatives may have therapeutic potential in many inflammatory diseases by targeting oxidative stress, inflammation and immune pathways.

Key Numerical Results

• Taurine makes up ~50% of the amino acid pool inside human neutrophils (Bouckenooghe et al. 2006)

• Physiological levels of TauCl reach up to 100μM at inflammatory sites (Marcinkiewicz and Kontny 2012)

• 200-500μM TauCl inhibited cytokine production by 40-60% in RA FLS (Kontny et al. 1999)

• In adjuvant arthritis in rats, intraperitoneal TauCl administration improved symptoms (Wojtecka-Łukasik et al. 2005)

• Systemic TauCl reduced arthritis incidence or delayed onset in the CIA model depending on timing (Kwaśny-Krochin et al. 2002)

So in summary, Marcinkiewicz and Kontny (2012) review the antioxidant, antimicrobial and anti-inflammatory properties of taurine and its derivatives in immune and inflammatory conditions. They inhibit key pathways and may have therapeutic benefits applied topically or systemically in diseases like RA. Further research into improving effectiveness, especially for systemic treatment, is warranted.

Taurine and Cancer

Taurine is an amino acid found abundantly in excitatory tissues such as the heart, brain, retina and skeletal muscles. In recent years, accumulating studies have shown that taurine supplementation protects against pathologies associated with mitochondrial defects and oxidative stress, including aging, mitochondrial diseases, metabolic syndrome, cancer, cardiovascular diseases and neurological disorders (Jong et al., 2021).

Taurine acts as an antioxidant and reduces oxidative stress by improving retinal reduced glutathione, malondialdehyde, superoxide dismutase and catalase activities. It also has antiapoptotic effects in retinal tissues. However, the protective mechanisms exerted by taurine against retinal damage remain to be further investigated (Castelli et al., 2021). 

Taurine levels in normal tissues are around 4-6 ng. But in examined cases of adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, uterus, ovary and lung, as well as in breast cancer, taurine levels were strikingly reduced to 0.0025-0.0028 ng (Omura, 2016). The lowest taurine levels of 0.0002-0.0005 ng were found in Zika virus infected babies from Brazil with microcephaly (Omura, 2016).

In human colorectal cancer cells, taurine treatment induced apoptosis through increased expression of the p53 upregulated proapoptotic protein PUMA. Taurine also increased PTEN tumor suppressor activity and p53 activation in a dose-dependent manner (Zhang et al., 2014). Taurine was also found to inhibit proliferation and induce apoptosis in human nasopharyngeal carcinoma cells through PTEN activation and Akt inactivation (He et al., 2018). 

In cervical cancer SiHa cells, taurine upregulated the pro-apoptotic proteins p73, p53 PUMA and caspase-3. It also promoted phosphorylation of YAP. Overexpression of the MST1 protein enhanced taurine's induction of apoptosis (Li et al., 2019). In breast cancer animal models, taurine attenuated tumor growth and metastasis, and reversed cancer-induced metabolic changes related to energy, glucose, amino acid and nucleic acid metabolism (Chen et al., 2016).

The overexpression of taurine transporters SLC6A6 and SLC6A8 has been associated with cancers such as colon, breast and prostate cancer. Thus, inhibitors of these transporters have potential as anti-cancer agents, with further studies warranted on their development and therapeutic use (Stary & Bajda, 2023). In lung cancer, blocking cellular taurine intake was found to restore sensitivity to ferroptosis in tumors. Exogenous taurine suppressed ferroptosis in prostate cancer cells as well, indicating taurine's role in desensitizing cancer cells to this form of regulated cell death (Zhang et al., 2022; Xiao et al., 2024). 

Metabolically, elevated lactate and taurine levels were biomarkers distinguishing normal pancreas tissue from pre-cancerous metaplasia and invasive pancreatic tumors, suggesting these could aid cancer screening and monitoring (Wang et al., 2014). In ovarian cancer, acquired cisplatin resistance correlated with increased taurine accumulation and volume regulation capacity, due to increased taurine transporter expression and activity (Sørensen et al., 2014). The histone deacetylase inhibitor trichostatin A reduced taurine transporter activity in cisplatin resistant ovarian cancer cells (Lambert et al., 2020).

Multiple studies found combining taurine supplementation with chemotherapy agents such as cisplatin increased their efficacy against cervical, melanoma and lung cancer cells, by enhancing apoptosis and inhibiting angiogenesis and inflammation (Kim & Kim, 2013; Kim et al., 2017; Chen et al., 2023). Taurine also enhanced the efficacy of PD-1 checkpoint blockade immunotherapy against cancer by boosting CD8+ cytotoxic T lymphocyte proliferation and function (Ping et al., 2023).

In conclusion, extensive evidence from animal and cell culture studies demonstrates that taurine supplementation can inhibit cancer cell proliferation, induce apoptosis, reduce metastasis and enhance the efficacy of other anti-cancer therapies like chemotherapy and immunotherapy. Taurine does this by modulating key proteins and pathways related to apoptosis, cell survival, tumor suppression, oxidative stress, ferroptosis and metabolism. Some studies have also found lower taurine levels correlate with higher risk or poorer prognosis in certain cancers. More clinical trials are now warranted to clarify whether taurine deficiency contributes to cancer development in humans, and whether taurine supplementation could be a safe, effective adjuvant treatment for cancer patients.