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.
PHARMACOLOGY OF TAURINE
Chemical structure
Taurine, or 2-aminoethane sulfonic acid, is a conditionally essential amino acid, ie, we can usually make enough in our own bodies. It was first prepared on a large scale for physiologic investigation almost 90 years ago, through the purification of ox bile.39 It can be obtained either exogenously through dietary sources or endogenously through biosynthesis from methionine and cysteine precursors, both essential sulfur-containing alpha-amino acids.40 Both sources are important to maintain physiologic levels of taurine, and either can help compensate for the other in cases of deficiency.41
The structure of taurine has two main differences from the essential amino acids. First, taurine’s amino group is attached to the beta-carbon rather than the alpha-carbon, making it a beta-amino acid instead of an alpha-amino acid.42 Second, the acid group in taurine is sulfonic acid, whereas the essential amino acids have a carboxylic acid.43 Because of its distinctive structure, taurine is not used as a structural unit in proteins,43 existing mostly as a free amino acid within cells, readily positioned to perform several unique functions.
Synthesis
De novo synthesis of taurine involves several enzymes and at least five pathways,44 mostly differing by the order in which sulfur is oxidized and decarboxylated.45
The rate-limiting enzyme of the predominant pathway is thought to be cysteine sulfinate decarboxylase (CSD), and its presence within an organ indicates involvement in taurine production.44 CSD has been found in the liver,46 the primary site of taurine biosynthesis, as well as in the retina,47 brain,48 kidney,49 mammary glands,50,51 and reproductive organs.52
Distribution
Taurine levels are highest in electrically excitable tissues such as the central nervous system, retina, and heart; in secretory structures such as the pineal gland and the pituitary gland (including the posterior lobe or neurohypophysis); and in platelets25 and neutrophils.53
In the fetal brain, the taurine concentration is higher than that of any other amino acid,54 but the concentration in the brain decreases with advancing age, whereas glutamate levels increase over time to make it the predominant amino acid in the adult brain.54 Regardless, taurine is still the second most prevalent amino acid in the adult brain, its levels comparable to those of gamma-aminobutyric acid (GABA).55
Taurine has also been found in variable amounts in the liver, muscle, kidney, pancreas, spleen, small intestine, and lungs,56 as well as in several other locations.45,57
Taurine is also present in the male and female reproductive organs. In male rats, taurine and taurine biosynthesis have been localized to Leydig cells of the testes, the cellular source of testosterone in males, as well as the cremaster muscle, efferent ducts, and peritubular myoid cells surrounding seminiferous tubules.58 More recently, taurine has been detected in the testes of humans59 and is also found in sperm and seminal fluid.60 Levels of taurine in spermatozoa are correlated with sperm quality, presumably by protecting against lipid peroxidation through taurine’s antioxidant effects,61,62 as well as through contribution to the spermatozoa maturation process by facilitating the capacitation, motility, and acrosomal reaction of sperm.63
In female rats, taurine has been found in uterine tissue,64 oviducts,65 uterine fluid (where it is the predominant amino acid),66 and thecal cells of developing follicles of ovaries, cells responsible for the synthesis of androgens such as testosterone and androstenedione.65 Taurine is also a major component of human breast milk67 and is important for proper neonatal nutrition.68
Metabolism and excretion
Ninety-five percent of taurine is excreted in urine, about 70% as taurine itself, and the rest as sulfate. Most of the sulfate derived from taurine is produced by bacterial metabolism in the gut and then absorbed.69 However, taurine can also be conjugated with bile acids to act as a detergent in lipid emulsification.70 In this form, it may be subjected to the enterohepatic circulation, which gives bacteria another chance to convert it into inorganic sulfate for excretion in urine.69
MECHANISMS AND NEUROENDOCRINE EFFECTS
As a free amino acid, taurine has widespread distribution and unique biochemical and physiologic properties and exhibits several organ-specific functions; however, indisputable evidence of a taurine-specific receptor is lacking, and its putative existence71 is controversial.72 Nonetheless, taurine is a neuromodulator with a variety of actions.
Neurotransmission
Taurine is known to be an inhibitory neurotransmitter and neuromodulator.73 It is structurally analogous to GABA, the main inhibitory neurotransmitter in the brain.45 Accordingly, it binds to GABA receptors to serve as an agonist,74,75 causing neuronal hyperpolarization and inhibition. Taurine has an even higher affinity for glycine receptors75 where it has long been known to act as an agonist.76 GABA and glycine receptors both belong to the Cys-loop receptor superfamily,77 with conservation of subunits that allows taurine to bind each receptor, albeit at different affinities. The binding effects of taurine on GABA and glycine receptors have not been well documented quantitatively; however, it is known that taurine has a substantially lower affinity than GABA and glycine for their respective receptors.76
Catecholamines and the sympathetic nervous system
Surprisingly little is known about the effects of taurine on norepinephrine, dopamine, and the human sympathetic nervous system.78 Humans with borderline hypertension given 6 g of taurine orally for 7 days79 experienced decreases in epinephrine secretion and blood pressure, but normotensive study participants did not experience similar results, possibly because of a better ability to regulate sympathetic tone. Mizushima et al80 showed that a longer period of taurine intake (6 g orally for 3 weeks) could elicit a decrease in norepinephrine in healthy men with normal blood pressure. Other similar studies81–83 also suggested interplay between taurine and catecholamines, but the extent is still undetermined.
Growth hormone, prolactin, sex hormones, and cortisol
Taurine appears to have a complex relationship with several hormones, although its direct effects on hormone secretion remain obscure. Clinical studies of the acute and chronic neuroendocrine effects of taurine loading in humans are needed.
In female rats, secretion of prolactin is increased by the intraventricular injection of 5 μL of 2.0 μmol taurine over a 10-minute period.84 Ikuyama et al85 found an increase in prolactin and growth hormone secretion in adult male rats given 10 μL of 0.25 μmol and 1.0 μmol taurine intraventricularly, yet a higher dose of 4.0 μmol had no effect on either hormone. Furthermore, prolactin receptor deficiency is seen in CSD knockout mice, but the receptor is restored with taurine supplementation.86
Mantovani and DeVivo87 reported that 375 to 8,000 mg/day of taurine given orally for 4 to 6 months to epileptic patients stimulated the secretion of growth hormone. However, in another study, a single 75-mg/kg dose of oral taurine did not trigger an acute increase in levels of growth hormone or prolactin in humans.88 Energy drinks may contain up to 1,000 mg of taurine per 8-oz serving, but the effects of larger doses on growth hormone, which is banned as a supplement by major athletic organizations because of its anabolic and possible performance-enhancing effects, remain to be determined.
Taurine may have effects on human sex hormones, based on the limited observations in rodents.89–94
Although human salivary cortisol concentrations were purportedly assessed in response to 2,000 mg of oral taurine,95 the methods and reported data are not adequate to draw any conclusions.
Energy metabolism
Mammals are unable to directly use taurine in energy production because they cannot directly reduce it.25 Instead, bacteria in the gut use it as a source of energy, carbon, nitrogen, and sulfur.96 However, taurine deficiency appears to impair the cellular respiratory chain, resulting in diminished production of adenosine triphosphate and diminished uptake of long-chain fatty acids by mitochondria, at least in the heart.97
Taurine is present in human mitochondria and regulates mitochondrial function. For example, taurine in mitochondria assists in conjugation of transfer RNA for leucine, lysine, glutamate, and glutamine.98 In TauT knockout mice, deficiency of taurine causes mitochondrial dysfunction, triggering a greater than 80% decrease in exercise capacity.99 Several studies in rodents have shown increased exercise capacity after taurine supplementation.100–102 In addition, taurine is critical for the growth of blastocytes, skeletal muscle, and myocardium; it is necessary for mitochondrial development and is also important for muscular endurance.103,104
Antioxidation, anti-inflammation, and other functions
Taurine is a major antioxidant, scavenging reactive oxygen and protecting against oxidative stress to organs including the brain,97,105,106 where it increasingly appears to have neuroprotective effects.107,108
Cellular taurine also has anti-inflammatory actions.3 One of the proposed mechanisms is taurine inhibition of NF-kappa B, an important transcription factor for the synthesis of pro-inflammatory cytokines.4 This function may be important in protecting polyunsaturated fatty acids from oxidative stress—helping to maintain and stabilize the structure and function of plasma membranes within the lungs,109 heart,110 brain,111 liver,112 and spermatozoa.61,62
Taurine is also conjugated to bile acids synthesized in the liver, forming bile salts70 that act as detergents to help emulsify and digest lipids in the body. In addition, taurine facilitates xenobiotic detoxification in the liver by conjugating with several drugs to aid in their excretion.25 Taurine is also implicated in calcium modulation113 and homeostasis.114 Through inhibition of several types of calcium channels, taurine has been shown to decrease calcium influx into cells, effectively serving a cytoprotective role against calcium overload.115,116
