Taurine, energy drinks, and neuroendocrine effects
ABSTRACTTaurine is an amino acid found abundantly in brain, retina, heart, and reproductive organ cells, as well as in meat and seafood. But it is also a major ingredient in popular “energy drinks,” which thus constitute a major source of taurine supplementation. Unfortunately, little is known about taurine’s neuroendocrine effects. The authors review the sparse data and provide a basic background on the structure, synthesis, distribution, metabolism, mechanisms, effects, safety, and currently proposed therapeutic targets of taurine.
KEY POINTS
- Energy drinks are widely consumed in the United States, with an estimated 354 million gallons sold in 2009, or approximately 5.25 L/year per person over age 10.
- Taurine has been reported to have anti-inflammatory action. Supplementation has been proposed to have beneficial effects in epilepsy, heart failure, cystic fibrosis, and diabetes, and has been shown in animal studies to protect against neurotoxic insults from alcohol, ammonia, lead, and other substances.
- Taurine is an inhibitory neurotransmitter and neuromodulator. It is structurally analogous to gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain.
TAURINE DEFICIENCY
Fetal and neonatal deficiency
Though taurine is considered nonessential in adults because it can be readily synthesized endogenously, it is thought to be conditionally essential in neonatal nutrition.68 It is the second most abundant free amino acid in human breast milk117 and the most abundant free amino acid in fetal brain.118 In cases of long-term parenteral nutrition, neonates can become drastically taurine deficient119 due to suboptimal CSD activity,118 leading to retinal dysfunction.41 Taurine deficiencies can lead to functional and structural brain damage.118 Moreover, maternal taurine deficiency results in neurologic abnormalities in offspring120 and may lead to oxidative stress throughout life.121
In 1984, the FDA approved the inclusion of taurine in infant formulas based on research showing that taurine-deficient infants had impaired fat absorption, bile acid secretion, retinal function, and hepatic function.122 But still under debate are the amount and duration of taurine supplementation required by preterm and low-birth-weight infants, as several randomized controlled trials failed to show statistically significant effects on growth.123 Nonetheless, given the alleged detrimental ramifications of a lack of taurine supplementation, as well as the ethical dilemma of performing additional research trials on infants, it is presumed that infant formulas and parenteral nutrition for preterm and low-birth-weight infants will continue to contain taurine.
Age- and disease-related deficiency
Although taurine deficiency is rare in neonates, it is perhaps inevitable with advancing age. Healthy elderly patients ages 61 to 81 have up to a 49% decrease in plasma taurine concentration compared with healthy individuals ages 27 to 57.124 While reduced renal retention125 and taurine intake126 can account for depressed taurine levels, Eppler and Dawson127 found that tissue and circulating taurine concentrations decrease over the human life span primarily due to an age-dependent depletion of CSD activity in the liver. This effectively impairs the biosynthesis of endogenous taurine from cysteine or methionine or both, forcing a greater reliance on exogenous sources.
While specific mechanisms have not been fully elucidated, taurine deficiency has also been identified in patients suffering from diseases including but not limited to disorders of bone (osteogenesis imperfecta, osteoporosis),128 blood (acute myelogenous leukemia),129 central nervous system (schizophrenia, Friedreich ataxia-spinocerebellar degeneration),130,131 retina (retinitis pigmentosa),132 circulatory system and heart (essential hypertension, atherosclerosis),133 digestion (Gaucher disease),134 absorption (short-bowel syndrome),135 cellular proliferation (cancer),136 and membrane channels (cystic fibrosis),137 as well as in patients restricted to long-term parenteral nutrition.138 However, the apparent correlation between taurine deficiency and these conditions does not necessarily mean causation; more study is needed to elucidate a direct connection.
SAFETY AND TOXICITY OF TAURINE SUPPLEMENTATION
An upper safe level of intake for taurine has not been established. To date, several studies have involved heavy taurine supplementation without serious adverse effects. While the largest dosage of taurine tested in humans appears to be 10 g/day for 6 months,139 a number of studies have used 1 to 6 g/day for periods of 1 week to 1 year.140 However, the assessment of potential acute, subacute, and chronic adverse effects has not been comprehensive. The Scientific Committee on Food of the European Commission141 reviewed several toxicologic studies on taurine through 2003 and were unable to expose any carcinogenic or teratogenic potential. Nevertheless, based on the available data from trials in humans and lower animals, Shao and Hathcock140 suggested an observed safe level of taurine of 3 g/day, a conservatively smaller dose that carries a higher level of confidence. Because there is no “observed adverse effect level” for daily taurine intake,141 more research must be done to ensure safety of higher amounts of taurine administration and to define a tolerable upper limit of intake.
Interactions with medications
To date, the literature is scarce regarding potential interactions between taurine and commonly used medications.
Although no evidence specifically links taurine with adverse effects when used concurrently with other medications, there may be a link between taurine supplementation and various cytochrome P450 systems responsible for hepatic drug metabolism. Specifically, taurine inhibits cytochrome P450 2E1, a highly conserved xenobiotic-metabolizing P450 responsible for the breakdown of more than 70 substrates, including several commonly used anesthetics, analgesics, antidepressants, antibacterials, and antiepileptics.142 Of note, taurine may contribute to the attenuation of oxidative stress in the liver in the presence of alcohol143 and acetaminophen,144 two substances frequently used and abused. Since the P450 2E1 system catalyzes comparable reactions in rodents and humans,142 rodents should plausibly serve as a model for further testing of the effects of taurine on various substrates.
POTENTIAL THERAPEUTIC APPLICATIONS
More analysis is needed to fully unlock and understand taurine’s potential value in healthcare.
Correction of late-life taurine decline in humans could be beneficial for cognitive performance, energy metabolism, sexual function, and vision, but clinical studies remain to be performed. While a decline in taurine with age may intensify the stress caused by reactive oxygen species, taurine supplementation has been shown to decrease the presence of oxidative markers127 and to serve a neuroprotective role in rodents.145,146 Taurine levels increase in the hippocampus after experimentally induced gliosis147 and are neuroprotective against glutamate excitotoxicity.148,149 Furthermore, data in Alzheimer disease, Huntington disease, and brain ischemia experimental models show that taurine inhibits neuronal death (apoptosis).13,150,151 Taurine has even been proposed as a potential preventive treatment for Alzheimer dementia, as it stabilizes protein conformations to prevent their aggregation and subsequent dysfunction.152 Although improvement in memory and cognitive performance has been linked to taurine supplementation in old mice,145,153 similar results have not been found in adult mice whose taurine levels are within normal limits. Taurine also has transient anticonvulsant effects in some epileptic humans.154
Within the male reproductive organs, the age-related decline in taurine may or may not have implications regarding sexuality, as only very limited rat data are available.89–91
In cats, taurine supplementation has been found to prevent the progressive degeneration of retinal photoreceptors seen in retinitis pigmentosa, a genetic disease that causes the loss of vision.155
While several energy drink companies have advertised that taurine plays a role in improving cognitive and physical performance, there are few human studies that examine this contention in the absence of confounding factors such as caffeine or glucose.36,37,95 Taurine supplementation in patients with heart failure has been shown to increase exercise capacity vs placebo.156 This supports the idea that in cases of taurine deficiency, such as those seen in cardiomyopathy,157 taurine supplementation could have restorative effects. However, we are not aware of any double-blind, placebo-controlled clinical trial of taurine alone in healthy patients that measured energy parameters as clinical outcomes.
Although it remains possible that acute supraphysiologic taurine levels achieved by supplementation could transiently trigger various psychoneuroendocrine responses in healthy people, clinical research is needed in which taurine is the sole intervention. At present, the most compelling clinical reason to prescribe or recommend taurine supplementation is taurine deficiency.
