Article from Townsend Letter
Longevity, Cardiovascular Disease, and Taurine
by Pushpa Larsen, ND
Japan enjoys the second longest life expectancy in the world at 85.03 years, exceeded only by Hong Kong with a life expectancy of 85.29 years, a difference of about three months.1 Japan also has the lowest rate of cardiovascular mortality with a mere 31 deaths from ischemic heart disease per 100,000 people.2 (In comparison, Canada ranks 16th and the US 46th in longevity, and have 86 and 110 deaths form ischemic heart disease per 100,000 people, respectively.) In 1982, a Japanese researcher, Yukio Yamori, proposed to the World Health Organization a worldwide epidemiological study to investigate the relationship of diet with hypertension and cardiovascular mortality. The original study was accomplished over a period of 20 years and eventually included 61 populations in 25 countries. Over 14,000 participants, evenly divided between males and females and ranging in age from 48-56, participated.3-6
The CARDIAC study (CARdiovascular DIsease and Alimentary Comparison) used the 24-urine taurine level as a marker for seafood intake. One of the most interesting findings was the comparison of Japanese Okinawans still living in Okinawa and those who had emigrated to Brazil, of which there were two populations studied: Okinawans living in Sao Paolo close to the southeast coast of Brazil, and Okinawans living in Campo Grande, more than 600 miles inland. Of the Japanese, Okinawans have the longest life expectancy and the lowest mortality from cardiovascular disease. Both Brazilian populations of Okinawans had substantially lower taurine levels than Japanese Okinawans. This is not surprising as the Brazilian diet has considerably more roasted meats and less seafood than a traditional Japanese diet. Taurine levels were lowest in Okinawans living in Campo Grande—far from a source of fresh seafood—who ate fish on average only once every two weeks. The lifespan of this population was a stunning 17 years shorter than Okinawans living in Japan, “an effect related to the very high IHD mortality. Low fish consumption and reduced T intake appeared to increase IHD.”4
Taurine Basics
Taurine, more formally known as 2-aminoethanesulfonic acid, is chemically a very simple compound: C2H7NO3S. It is ubiquitous in the tissues of most mammals and is particularly high in cardiac and skeletal muscle as well as the brain, the retina, and other neural tissue. Its effects on cells is both wide-ranging and profound. Its name hails back to ox bile, Bos taurus, from which it was first isolated.
Taurine is classified as a conditionally essential amino acid. It does not participate in the formation of proteins and does not meet the technical definition of an “essential” amino acid, in that it can be synthesized in the body. It is synthesized from methionine and cysteine in the pancreas, liver and other tissues, albeit at fairly low levels. Humans do, however, retain taurine in the tissues in greater amounts than some other species and do not often develop the overt deficiency symptoms seen in cats and foxes.7 The main source of taurine is dietary and a lack of taurine in the diet can have severe repercussions on health, as seen in the Campo Grande population of Okinawans. Ripps and Shen, in their review of its functional properties, assert that taurine is “undoubtedly one of the most essential substances in the body.”8
Mechanisms and Actions
Taurine has a number of functions that result in cytoprotection. These are summarized well by Shaffer, et al. as displayed in Table 1.t Cytoprotective Actions of Taurine Table
These mechanisms include antioxidant actions, improvement of energy metabolism, modulation of gene expression, mitigation of endoplasmic reticulum stress, neuromodulation, quality control and detoxification, calcium homeostasis, and osmoregulation. This last is a particularly important cytoprotective function of taurine. All cells are sensitive to fluctuations in volume that can lead to cell death if not properly regulated. The uptake and release of taurine allows cells to maintain a normal volume in the face of osmotic stress from other sources. The osmoregulatory function is important for cell survival in all types of cells. 7,9
Taurine has been shown to mitigate mitochondrial oxidative stress induced by a wide array of substances, including “ozone, nitrogen dioxide, bleomycin, amiodarone, arsenic, iron, Adriamycin and catecholamines.”7 Taurine seems to also hinder oxidative stress by protecting antioxidant enzymes from the effects of reactive oxygen species (ROS) generated by the mitochondria. There are a number of conditions in which the body’s inability to deal with ROS overproduction is a contributing factor. Among these are cardiovascular disease, renal injury induced by diabetes, inflammatory diseases, lipid peroxidation of photoreceptors in the eye, reperfusion injury, and several neurological diseases, all of which may be improved with taurine.8 Taurine does not directly scavenge free radicals other than HOCl, which is thought to help limit myocardial damage. However, taurine may help regulate the generation of ROS in the mitochondria, which can slow down the series of events leading to an apoptotic cascade.9
The various mechanisms by which taurine exerts its benefits could fill (and has filled) several articles and is beyond the scope and intention of this one. What is striking is that taurine’s many actions affect cells of all types, which suggests that a taurine deficiency could lead to a wide range of symptoms. For example, quality control and detoxification, by which the body restores or eliminates damaged cells and organelles, decreases in taurine-deficient cells. Taurine regulates crucial ratios that help stabilize some membranes, affecting their fluidity as well as transport activity and the activity of enzymes associated with the membranes. Because of the broad effects of a taurine deficiency, it follows that taurine as a therapeutic may have similarly broad applications.
Taurine and Cardiovascular Disease
Taurine levels in myocardial cells is species dependent. Species with the fastest heart rates have higher levels of taurine. This has led some researchers to speculate that taurine is somehow associated to the heart’s workload. Taurine is especially important in heart failure.
Congestive Heart Failure. The reduced contractile ability characteristic of heart failure is related to a set of conditions that are taurine dependent. Taurine-deficient hearts exhibit a loss of myofibrils thought to be related to increased apoptosis due to the lack of the regulatory effects of taurine. Taurine-deficient hearts are also less sensitive to calcium, an essential element in muscular contraction. Taurine is also important to the phosphorylation of a phosphoprotein found in the sarcoplasmic reticulum, phospholamban. When phosphorylated, increased Ca2+ uptake by the SR results in relaxation of the heart muscle.9
Taurine has been approved for the treatment of congestive heart failure in Japan for several years. In addition to relieving breathlessness with exertion and fluid retention, it can also reduce or completely eliminate the need for CHF drugs such as digoxin. Although increasing diuresis and improving contractile force are beneficial, perhaps the most important effect of taurine on CHF has to do with inhibition of norepinephrine and angiotensin II. These molecules decrease the contractile ability of the heart by increasing afterload pressure and other effects. Taurine has been found to increase exercise capacity of CHF patients and may prolong lifespan.7
Hypertension. Taurine has proved to be effective in preventing hypertension from developing in several animal models. Various factors have been identified, including decreases in oxidative stress, sympathetic tone, and inflammation, combined with improved kidney function and Ca2+ homeostasis.7 Two human clinical studies also found benefits from taurine for hypertension. Katakawa reported improved endothelial function which he attributed to taurine’s effects in reducing oxidative stress.10 In a study by Sun, 120 prehypertensive patients received 1.6 grams of taurine per day, or placebo, for a period of 12 weeks. Patients receiving taurine had decreases in both systolic and diastolic BP, compared to patients in the placebo wing of the trial, who experienced no decrease in BP. The higher the initial blood pressure, the greater improvement was seen with taurine supplementation.11.
Atherogenesis. Taurine has several beneficial effects on vascular tissue, which inhibit or reverse the atherosclerotic process. These include inhibition of apoptosis, inflammation, and oxidative stress, as mentioned above. Taurine can also reverse intima medial thickening and arterial stiffness, which probably account for some part of improvements in blood pressure.
Taurine inhibits proliferation of vascular smooth muscle cells in culture. Smooth muscle cell proliferation is a part of the cascade of events leading to intimal media thickening and the development of atherosclerotic plaques. Taurine is also important to the health of vascular endothelial cells, decreasing apoptosis and protecting them through its anti-inflammatory and antioxidant activity and the modulation of intracellular calcium. Dysfunction in endothelial cells cultured from smokers was attenuated by the addition of taurine, which upregulated the expression of NO synthase.12
Stroke. Stroke is a leading cause of death and disability. A main contributor to neuronal death during stroke is the large accumulation of glutamate in the synaptic clefts as glutamate uptake is compromised by lack of ATP to glutamate transporters. This ultimately results in influxes of Ca2+, compromised mitochondrial function and the generation of ROS, all of which contribute to cellular distruction.13 Taurine helps protect cells from the toxic effects of excess glutamate by reducing the overload of calcium and reducing oxidative stress.7
What Else Is Taurine Good For?
This article is focused on the cardiovascular benefits of taurine, but if we are considering longevity, it is worth mentioning a few other conditions in which taurine can be useful. A lack of taurine contributes to a broad range of pathologies, including renal dysfunction, pancreatic βcell dysfunction, and decreased vision to the loss of photoreceptors in the retina.8 Supplemental taurine reduces markers for inflammation in obesity and may improve lean body mass.7
Diabetes. Schaffer and Kim assert, “There is overwhelming evidence that taurine therapy reduces pathology associated with diabetes, obesity and the metabolic syndrome.”7 Patients with Type I diabetes have low plasma and platelet taurine levels.7 Taurine decreases advanced glycation end products (AGE) and lipid peroxidation in the kidney, thus improving diabetic nephropathy. 8
Mitochondrial Disease. MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a mitochondrial disease that shares characteristic symptoms with taurine deficiency.13 Supplementing MELAS patients with taurine has been helpful. In one such case a 29-year-old woman who had no response to standard pharmaceutical therapy for epileptic and stroke-like episodes, had a complete cessation of these events shortly after starting on oral taurine. In a second case, a 21-year-old male was diagnosed with MELAS and put on anticonvulsant therapy that did little to decrease his stroke-like episodes, which included visual loss and sensory aphasia. Upon starting taurine supplementation, the episodes ceased. In both cases the patients’ serum levels of taurine increased by 5- and 10-fold, respectively.7 Schaffer reports that taurine therapy also returns mitochondrial respiratory function to normal in these patients.
Taurine and the Eye. All ocular tissues contain taurine, although the retina has the highest levels.8 In a normal retina, the concentration of taurine is at least 10 times that of any other amino acid.8 Taurine is required for the survival of retinal ganglion cells.7 Taurine also protects rod outer segments from photic damage.8 Severe degenerative changes to photoreceptors are common in animals that do not synthesize adequate levels of taurine, including cats, monkeys, and humans, if they do not get adequate dietary taurine.8
Taurine in the Brain. No brain region that has been tested fails to contain or uptake taurine: “At each of these sites, there is evidence of taurine’s ability to ameliorate certain forms of neuropathology.”8 Taurine is a weak agonist of the GABAA, glycine, and NMDA receptors.7
While taurine does seem to have some mild anticonvulsant effects, those effects are inconsistent.8 In human clinical trials, about one third of patients had a reduction in epileptic seizures with taurine administration.7
Interestingly, taurine meets all criteria but one for the definition of being a neurotransmitter. Those criteria are 1) the enzymes and biochemistry necessary for biosynthesis exist in presynaptic neurons; 2) it is released by presynaptic depolarization and affects post synaptic cells, and the mechanism for doing that is calcium-dependent; 3) its action is terminated by degradation or re-uptake, and there is an antagonist; and 4) there is a specific receptor on post-synaptic cells. Of these criteria, taurine lacks only the identification of a post-synaptic receptor.8
Sarcopenia. Taurine is a common ingredient in nutritional formulas intended to improve sports performance and muscle development, and there are a number of studies that show improvement in exercise performance with taurine supplementation. Less researched, but germane to the issue of longevity, is whether sarcopenia in older men and women can be reversed or slowed with the use of taurine. Taurine plays a role in regulating two pathways involved in the degradation of muscle proteins and myocyte death, the calpain pathway and the capsase pathway. Both are calcium-dependent and taurine’s regulatory effect on intracellular calcium concentrations helps keep these pathways in check. Taurine also appears to influence protein catabolism in aging muscle via the stimulation of inhibitory pathways.14
Dietary Sources of Taurine
Taurine is most abundant in shellfish such as scallops, oysters, clams, mussels, prawns, and octopus. It is also high in many saltwater fish. Taurine levels in freshwater fish were not found, but one source suggested that fresh had a higher capacity for synthesizing taurine than saltwater fish, so presumably fish of any kind would provide decent levels of taurine. Red meats contain some taurine, although significantly less than fish and shellfish. Best meat sources of taurine are dark meat of turkey and chicken. Dairy products and eggs contain relatively little taurine and one researcher found no detectable levels on taurine in legumes, nuts, or vegetables.15
Taurine levels in vegetarians and vegans are generally much lower than for omnivores.16 In one study, plasma taurine levels in vegans were about 78% of the control values, and 24-hour urine taurine values were only 29% of control values. The difference between plasma and urine values becomes important when you are measuring taurine levels in your patients.
Testing for Taurine: Reference Ranges and Expected Ranges
I work for a lab that does taurine testing and was involved with the development of the taurine reference ranges. We chose to collect a 24-hour sample and report our results in µmoles/24 hours. The strong epidemiological research that assessed taurine levels worldwide used this collection period and unit of measure, and we wanted to be able to compare results, not to a “normal” population, but to what the research had demonstrated were healthy levels of taurine – the point at which cardiovascular disease mortality actually starts to drop. The results were very clear in the research. For men, that point is when they reach 24-hour urine taurine values of 2000 µmol/24h or more. Once taurine levels fall below 1000 µmol/24h in men, cardiovascular disease mortality rises steeply. For women, the steep rise begins when taurine levels fall below 750 µmol/24h.
Laboratories, including ours, usually develop a reference range based on collecting samples from a large group of “normal” individuals. The ends of the reference range are determined by calculating the standard deviation setting the range between two standard deviations on either side of the mean. That is a perfectly acceptable method to use for most applications, but there is a very real problem in using that method to assess taurine levels.
A “normal” population of individuals in the United States (or Canada) is probably not eating much fish or seafood. There will be some exceptions to this, but for most people, fish once every couple of weeks—like the Campo Grande population—is probably closer to the norm. So if we set a reference range based on that norm, a patient with very low taurine values could easily be within the normal reference range. Since the purpose of this test is to assess cardiovascular mortality risk in order to better treat our patients, knowing that they are “normal” is not that useful. Remember, the US ranks 46th in longevity and has more than three times the number people dying from heart disease as Japan. Rather than using a “normal” reference range, we chose to use an “expected” range, in which the patient’s values are measured against what the expected levels would be in a healthy—or in this case, lower risk—population.
A second thing to consider is whether plasma levels can be “translated” to urine values for the purposes of assessing risk. Aside from the differences in collection, methodology and units of measure, the difference between plasma and urine values is dramatic, as seen in the study of taurine levels in vegans. Urine values when compared to the control group told a much different story than plasma levels. This underscores the importance of using a 24-hour urine sample to measure against the expected urine range for a low risk population.
Supplementing with Taurine
What if your patient doesn’t like fish, or is allergic to fish? Or what if they are a committed vegan? Is supplemental taurine as beneficial as taurine obtained from eating seafood? Yamori, et. al., in their 1996 study, reported taurine levels in a Tibetan population which ate no fish or other meat because of their religious beliefs. This population also tended to eat a high amount of salt. As a result, about 40% of the population had high blood pressure, which was double the world average of 20% for hypertension prevalence. Many of these individuals, who ranged in age from 48-56 (or fairly young by today’s standards), had severe hypertension, with systolic values over 200 mmHg. Yamori and his team did an intervention study with this group in which each person took 1 gram of taurine, in their tea, three times a day for a total of 3 grams of supplemental taurine daily. Within two months, subjects experienced a significant drop in both systolic and diastolic blood pressure.3
Three grams a day, in divided doses does seem to be a pretty typical dosing regimen for taurine. Taurine is a very inexpensive supplement and is available in capsules as well as powders that can be added to smoothies. It is also a common ingredient in so-called energy drinks or sports drinks. A 250 mL can of a popular energy drink contains 1000 grams of taurine. However, energy and sports drinks containing taurine may also include 90-300 mg of caffeine, as well as sugar or aspartame, and should not be considered a useful source for this nutrient in most cases.
References:
Author bio:
Pushpa Larsen, ND graduated from Bastyr University in Naturopathic Medicine, Naturopathic Midwifery, and Spirituality, Health and Medicine. She worked as a Research Clinician for the Bastyr University Research Institute and as Affiliate Clinical Faculty for Bastyr University, training students in her clinic. She practiced in West Seattle for 10 years before joining Meridian Valley Lab as a Consulting Physician eleven years ago. She is currently the manager of Consulting and Education and a member of the test Development Team. Dr. Larsen has consulted with hundreds of doctors every year on the use and interpretation of, 24-hour urine hormone profiles, blood viscosity tests and other tests offered by Meridian Valley Lab. She is working with Dr. Jonathan Wright on the development of an educational program for health care practitioners in Bio-identical Hormone Replacement Therapy following Dr. Wright’s principle of “copy nature.”
Consult your doctor before using any of the treatments mentioned in this article.
Reprinted with permission from the January, 2021 Townsend Letter, and Pushpa Larsen, ND.
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