Slowing Alzheimer’s in its early stages …And may help prevent full-blown Alzheimer’s
Ludwig van Beethoven, the great German composer, died in 1827. The cause of his death was liver disease, the result of heavy alcohol consumption throughout his life. In a scientific paper published the same year, two Germans researchers1—anatomist and physiologist Friedrich Tiedemann and chemist Leopold Gmelin—discovered that the gallbladder of an ox contained a constituent that they named taurine (derived from the Greek word for bull or ox—tauros). Had taurine been discovered earlier, it could have made all the difference. In both England and the United States, taurine was examined for pharmacological use by the 1840s, or even earlier.2
Taurine Reduces Liver Damage and Hearing Function
Across the years, taurine has been found to affect the development of the central nervous system, stimulate the influx and adhesion of calcium at the membrane of a cell, stabilize protein folding, help regulate blood pressure, and more. Taurine also acts as a thermoregulator, a protein-folding agent, an anti-inflammatory agent, an antioxidant agent, an osmoregulator (regulating and maintaining the proper balance of solutes or salts of body fluid), and has even been found to help with heart disorders.
Of interest to Beethoven devotees, taurine has been found to decrease the damage of alcohol in the liver. Also, there is scientific evidence supporting the use of taurine for hearing loss,3 a progressive problem that haunted Beethoven for most of his life. In fact, it prevented him from hearing his great 9th Symphony (the “Ode to Joy”), the premier of which he “conducted” in 1824.
In a paper published in 1985,4 concentrations of free amino acids were measured in the cerebral cortices of post-mortem brains from 5 cases of Alzheimer (AD)-type dementia and 8 histologically normal controls. The concentrations of taurine in the AD brains were significantly lower in the inferior temporal cortex (ITC). The ITC is located on the inferior convexity of the temporal lobe in primates, including humans, and is crucial for visual object recognition. Mild cognitive impairment and early stage AD are diagnosable through a test that measures visual object recognition.5
The focus of drug progress has shifted
towards testing therapies in
early-stage patients who have
underlying brain pathology but
little to no functional impairment.
The reduced level of taurine in AD brains shows that it could be involved in AD. In one study, scientists found that people with the highest levels of taurine have the lowest incidence of Alzheimer’s disease.6 (See “Dodging the Bullet” in Durk Pearson & Sandy Shaw’s Life Extension News, in the July 2005 issue of this publication.)
Taurine Found Effective Against Alzheimer’s
In a new study, researchers from Korea Institute of Science and Technology (KIST) have discovered that taurine may be effective in treating Alzheimer’s disease.7 In case you didn’t know, as society ages dementia rises, and 60 to 80 percent of dementias are cases of AD. Once you’re further along the path to memory oblivion, there is no retreat and no cure. Your symptoms worsen and you eventually die.
A draft guidance may benefit
the study of nutrients that
work in the pre-stage of AD.
Clinical trials with dementia drugs have been disappointing, and twelve years have elapsed since the clinical approval of Memantine, the last Alzheimer’s drug. Memantinehas only been shown to have a modest effect in moderate-to-severe AD. Resulting from this developmental retardation, the focus of drug progress has shifted towards testing therapies in early-stage patients who have underlying brain pathology but little to no functional impairment.
FDA’s Guidance May Move Therapies in the Right Direction
In 2013, the FDA released a striking new draft guidance suggesting fast-tracked regulatory pathways for drugs that improve cognitive deficits in the early stages of AD.* This may benefit the study of nutrients that work in the pre-stage of AD. Nonetheless, while the new regulation provides flexibility for mechanisms of drugs, the selection criteria of patients for clinical trials are strongly restricted. This is contradictory. The FDA requires these cognitive enhancers to be assessed in patients with early cognitive impairment paired productively with appropriate biomarkers of AD, such as amyloid plaques and tau tangles. This reduces the size of the groups of those who may benefit.
* Food and Drug Administration. Guidance for industry Alzheimer’s disease: developing drugs for the treatment of early stage disease. FDA Download. February 2013. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM338287.pdf. Accessed: December 27, 2015.
The therapeutic effects of taurine
are dementia-specific, which may
have great clinical impacts.
Nevertheless, the scientists at KIST proposed taurine—a curative and orally safe substance—that they thought might fit into above-mentioned standards. In their study, oral treatment of taurine retrieved the spatial working memory and hippocampal-dependent memory in the demented transgenic mouse expressing human amyloid plaques. Beyond these benefits, taurine also decreased levels of amyloid-β aggregates in the cortex. But unlike acetylcholinesterase inhibitors, the therapeutic effects of taurine are dementia-specific, which may have great clinical impacts.
Complementing a Prior Study
According to the KIST researchers, their study complements a previous study conducted at the College of Staten Island in New York City that reported the ability of taurine to improve learning and retention in an aged mouse model.8 Unlike the demented transgenic mouse model used in the Korean study, which expressed human Aβ and amyloidogenesis, the aged mouse model induced retinal degeneration.
The cognitive impairment induced in the Staten Island study was through aging and its consequences. On the other hand, the cognitive impairment produced in the KIST study was acquired through increased production and aggregation of human Aβ peptides.
Analysis of the Demented Transgenic Mice Korean Study
In the KIST study, taurine was found to improve hippocampal memory in APP/PS1 (demented transgenic) mice when added to drinking water. In the researchers’ words, “Here we report that taurine in drinking water rescues Alzheimer-like learning and memory deficits of adult APP/PS1 demented transgenic mice without modifying the behaviors of cognitively normal mice.”
To evaluate the hippocampal memory of demented transgenic mice, the researchers performed the Y-maze test, after taurine was orally administered to the mice via drinking water for 6 weeks. Two days after the Y-maze, the passive avoidance test was given.
“Here we report that taurine in
drinking water rescues Alzheimer-like
learning and memory deficits of adult
demented transgenic mice without
modifying the behaviors of cognitively
Taurine Enhances Working Memory
Figure 1. The Y Maze Test.
The KIST researchers found that taurine supplementation significantly improved behavioral performance of the demented transgenic mice on the Y-maze test as compared to the water only demented transgenic group. The spatial working memory of demented transgenic mice was recovered up to control mice. They found insignificant changes among the total number of arm entries, dismissing hyperactivity as a possible argument for cognitive improvement.
Figure 2. The Passive Avoidance Test.
Unlike acetylcholinesterase inhibitors,
taurine seems to be dementia-
specific, which may have
great clinical impacts as a
selective cognitive enhancer.
Taurine Enhances Behavioral Performance
Consistent with the results obtained from the Y-maze, taurine significantly enhanced behavioral performance of the demented transgenic mice in the pass avoidance tasks as compared to the non-treated demented transgenic group. The hippocampal memory of the taurine-treated demented transgenic mice recovered to the level similar to that of wild-type mice. Similar to the results from the Y-maze test, behavioral alterations of the controls by taurine treatment was insignificant.
Improvement in Aging and Aβ Associated Deficits
In addition to improving deficits associated with ageing and Aβ, taurine proved to be effective with other forms of dementia: hypoxia-induced learning impairment, ischemic stroke-induced learning impairment, chemical-induced sporadic dementia of Alzheimer’s type, and alcohol-induced brain impairment.
Consistent with the Korean findings, taurine has been reported as ineffective to enhance spatial learning and memory in cognitively normal mice. Accordingly, unlike acetylcholinesterase inhibitors, taurine seems to be dementia-specific, which may have great clinical impacts as a selective cognitive enhancer.
Brain Food for Better Brain Function
Taurine is a brain food that helps brain function, including the maintenance of proper cerebral receptor function. Taurine is also a neuromodulator, a natural sulfur-containing amino acid, which is important in the regulation of electrically active tissues (such as the heart and brain), to modulate the activating effects of noradrenaline (see “Feed Your Head” in the July 1999 issue of this publication; the nutrient soda is no longer available but the ideas discussed are still relevant).
Taurine helps prevent excessive sensitivity to noradrenaline, which may be subjectively experienced as jitteriness and overstimulation. Taurine helps to promote a mellow mood without sedation or tranquilization. The best food source of taurine is red meat. Taurine is a derivative of cysteine, an amino acid, which contains a thiol group. Taurine is one of the few known naturally occurring sulfonic acids. In the strict sense, it is not an amino acid, as it lacks a carboxyl group, but it is often called one, even in scientific literature. It does contain a sulfonate group and may be called an amino sulfonic acid.
Insignificant Amount in Food
Taurine also occurs naturally in seafood, especially in high concentrations in squid, shrimp, and oysters. Along with high meat concentrations, the mean daily intake from omnivore diets was determined to be around 58 mg (range from 9 to 372 mg) and to be low or negligible from a strict vegan diet.1 In another study, taurine intake was estimated to be generally less than 200 mg/day, even in individuals eating a high-meat diet.2 According to another study, taurine consumption was estimated to vary between 40 and 400 mg/day.3 But that’s not enough!
How Does Taurine Save Memory?
The results from the Korean study indicate that taurine may play a role in preventing cognitive impairment in AD-like mouse model by decreasing Aβ, but measures of this effect were small. So it is not clear how taurine induces improvement of abnormal behaviors in AD model mice without the significant inhibition of Aβ amyloidogenesis. Analysis suggests that taurine weakly decreases Aβ levels in the insoluble fraction of brain lysates (broken down cell membranes) but rarely alters concentrations of soluble Aβ, including monomers and oligomers.
Also, histochemical (the branch of science dealing with the chemical components of cellular and subcellular tissue) analyses reveal that taurine does not affect β-sheet-rich plaques.
As the current methods to isolate Aβ in brain lysates into soluble, insoluble and guanidine-soluble fractions do not clearly define the contents, it is difficult to indicate specific alterations of monomers, oligomers, protofibrils and plaques. However, the levels of protofibrils with immature β-structures may be decreased by taurine treatment.
The Korean study’s results suggest that
taurine has a potential in
treating deleterious effects on
cognitive functions of AD.
Existence of protofibrils often provides confusing results in biochemical analyses measuring levels of high molecular weight Aβ aggregates. It is also unclear exactly how taurine interacts with Aβ or by what mechanism it decreases the Aβ level. There have been proposals regarding calcium and chloride modulation, but further studies are needed to reveal how taurine decreases Aβ concentration in the brain.
One hypothesis on how taurine can affect Aβ levels is the direct interaction between taurine and Aβ peptides in the brain. Previous studies on influences of taurine on amyloidogenesis have been controversial.
Hypotheses of Taurine Mechanisms
However, in the presence of 20 mM of taurine at pH of 5.5, Aβ40 peptides accelerated in aggregation but not at pH of 7.439. Another hypothesis suggests that sulfonic acid group in taurine may bind to Aβ peptides and prevent glycosaminoglycans from binding to Aβ, thereby inhibiting Aβ aggregation.
It is surmised that new studies may
determine that the positive actions of
taurine might potentially be useful in
the early stage of AD.
The structural similarity of homotaurine (tramiprosate), a former drug candidate, and taurine suggests that taurine may also interfere in glycosaminoglycans recruiting Aβ41.
KIST researchers observed the increased expression of glial fibrillary acidic protein(GFAP), a marker for astrocytosis in the brains of taurine-treated mice by taurine, in both wild-type and transgenic mice. Because many investigations reported reduced reactive astrocytes by taurine treatment, additional studies are warranted to determine correlation of taurine supplementation and GFAP alterations. Although such explorations may be beyond the scope of the current study, it is noteworthy that long-term administration of high-dose taurine (200 mg/kg/day, intraperitoneal) was also found to induce over-expression of GFAP during improvement of the spatial learning and memory ability in Sprague-Dawley rats.
Taurine increases hippocampal
neurogenesis in aging mice.
To summarize, the KIST results suggest that taurine treatment rescued cognitive deficits in demented transgenic mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviors of cognitively normal mice. In the cortex of the experimental demented transgenic mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, the findings suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.
Potential to Treat Cognitive Dysfunctions in AD
The Korean study’s results suggest that taurine has a potential in treating deleterious effects on cognitive functions of AD. The researchers felt it incumbent to say that taurine is already in clinical uses for congestive heart failure and liver disease, with no known side effects. Current prescription limits taurine supplementation to one year. But, there is little evidence of adverse evidence for long-term taurine use. Beneficial effects for the use of taurine have also been found in athletes and in sleep-deprived students.
I hasten to add that because taurine has been demonstrated to be effective when taken in drinking water, that this is a plus and great convenience for the AD patients. It is surmised that new studies may determine that the positive actions of taurine might potentially be useful in the early stage of AD.
“The fact that taurine increases the
stem cell pool is particularly exciting,
as the renewal of the stem cell pool is
limited in adults.”
Could it Be Neurogenesis?
In a recent Life Extension News (see Volume 18 No. 6 in the October 2015 issue), Durk Pearson & Sandy Shaw point to a recent finding showing that taurine increases hippocampal neurogenesis in aging mice.9 Quoting the paper, “We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors.” “Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis.”
Durk & Sandy write: “This is a very impressive benefit from ingesting adequate amounts of taurine, which is a sulfur-containing amino acid not incorporated into proteins; it is found in large amounts in the brain, but also in the liver and kidney. Its concentration in the brain decreases with aging. The fact that taurine increases the stem cell pool is particularly exciting, as the renewal of the stem cell pool is limited in adults.”
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