Maintain Your Brain

An Exclusive Interview with Durk Pearson & Sandy Shaw®

Maintain your Brain the Durk Pearson & Sandy Shaw Way

CONTINUED FROM PART I

First appeared in the May 2004 issue

Taurine and Amyloid-Beta Neurotoxicity

Durk There are a number of things that can be done to reduce the neurotoxicity of amyloid-beta. In 2003, Dawson demonstrated that taurine could reduce amyloid-beta’s toxicity to cholinergic neurons in tissue culture, and he hypothesized that taurine deficiency in the brain could be responsible, at least in part, for age-related neurodegeneration, such as occurs in Alzheimer’s. His hypothesis emphasized that taurine had been shown to provide protection against both free radicals and inflammatory agents.

In 2004, Louzada et al. also demonstrated that taurine reduces amyloid-beta’s toxicity to cholinergic neurons in tissue culture, and they discovered details of the mechanism. They showed that amyloid-beta killed cholinergic neurons by glutaminergic excitotoxicity and that taurine provided substantial protection from this attack. Actually, free radical damage and excitotoxicity are closely related: if excessive concentrations of an excitotoxin cause a neuron to fire more rapidly than can be sustained by the mitochondria’s ability to supply energy in the form of ATP, lots of free radicals are produced, and calcium builds up faster in the neuron than ATP-powered pumps can remove it, thereby triggering apoptotic cell death.

These views are further supported by a 1992 paper by Pomara et al., who measured the cerebrospinal fluid levels of amino acids in ten patients with mild-to-moderate dementia (probable Alzheimer’s) and found that glutamate was elevated (P = 0.001) and taurine reduced (P = 0.006) compared with normal controls of similar age.

This is why we’ve added 1 gram of taurine to each serving of our choline-containing drink mix. A typical dietary intake of taurine is a few hundred milligrams per day (mostly from meat and fish). Your body has a limited ability to make taurine from cysteine, but this metabolic route is in competition with production of the antioxidant glutathione, which also requires cysteine. The taurine supplement is beneficial in three ways: for the protection it provides from amyloid-beta neurotoxicity, for its properties as an antioxidant, and for its ability to spare cysteine for glutathione production.

Amyloid-Beta and Green Tea Polyphenol Antioxidants

Sandy There are additional useful antioxidants. For example, we include green tea polyphenols in our new formulation, because they’ve been shown to be protective against amyloid-beta toxicity (Levites et al. 2003).


An amyloid-beta deposit in brain tissue.
Durk That’s in tissue culture—and the evidence isn’t just in vitro. Tissue cultures aren’t always an accurate model for the whole brain. There’s epidemiological evidence that people who drink five cups of green tea per day have a lower incidence of Alzheimer’s disease—a lesser likelihood of getting it at any given age—than people who don’t drink green tea. Now, the epidemiological data alone are not sufficient to prove the case for polyphenols—maybe it’s something else in the green tea, or maybe it’s something else they’re eating. However, when you have both the tissue-culture results and the epidemiological data, that’s pretty good. Therefore, we’ve put the equivalent of five cups’ worth of green tea a day of epigallocatechin gallate and the other green tea polyphenols in the encapsulated part of our new brain maintenance system.

Sandy Also, the green tea polyphenols are anti-inflammatory, and it’s now known that inflammation is importantly involved in the development of Alzheimer’s.

Amyloid-Beta and Antioxidant Vitamins E and C

Durk In addition, there are epidemiological data showing that people who eat larger amounts of vitamin E and vitamin C in their diets have a lower incidence of Alzheimer’s disease (age-adjusted, of course) (Engelhart et al. 2002). Dietary E reduces the incidence of Alzheimer’s in those without the APOE-4 gene, which is a risk factor for Alzheimer’s (Morris et al. 2002). For the most part, supplement studies have not shown consistently positive results, probably because the durations of supplement use were too short. For the exceptions, see Sano et al. 1997 for vitamin E, and Morris et al. 1998 for vitamin C. No benefits were observed with a C + E supplement in Masaki et al. 2000. On the other hand, a very strong protective effect was found in those who took relatively high doses of both C and E supplements, but not in those who took only C or only E (Zandi et al. 2004). This study found an adjusted Alzheimer’s incidence odds ratio for C + E supplement users of 0.22 (95% confidence interval of 0.05 to 0.60). Theoretically, a combination of antioxidants might work better.

A free radical is a molecule with an unpaired electron. In order to get rid of that free radical, you have to go through a step-wise process of transferring the unpaired electron from one molecule to another, and another, each having less energy, each being less reactive and having a longer lifetime, until you can finally get rid of it by pairing it up with another long-lived free radical. So in general you need a combination of free radical scavengers to get the results you want. Otherwise, if you just have one, it ends up being bottlenecked there. For example, if you have vitamin E alone, you end up with a tocopheryl radical.

Sandy You want to hand that tocopheryl radical’s unpaired electron off to another antioxidant, but if you don’t have adequate quantities of other antioxidants, you’re going to have a bunch of tocopheryl radicals hanging around. And they do damage as well—not as much damage as the radicals they’ve quenched, but they still need to be eliminated.

Durk Theoretically, you’d expect that vitamin E and vitamin C together would do a lot better than either E or C alone. In addition to having C in our formulation, the type of E we have is rather special and expensive: it’s D-alpha-tocopheryl succinate. Now, the reason we use the D-isomer alone rather than the usual D,L mixture is that the blood-brain barrier is remarkably picky, and there are stereospecific transporters that more readily carry the D-isomer of vitamin E across the barrier than the L-isomer. The D- and L-isomers are both perfectly good antioxidants—in vitro (in a test tube), you won’t see any difference—but you’ve got to get vitamin E into the brain, and the D-isomer is best in that regard. Also, we use the succinate ester rather than the less expensive acetate ester, because there are specific transporters for succinate in the blood-brain barrier, as well as in membranes around the mitochondria; those are the free radical hotbeds of activity, where you especially want to deliver antioxidants. (See Meydani 1995 for a review on vitamin E.)

Amyloid-Beta and Turmeric Curcuminoid Antioxidants


Turmeric root (Curcuma longa)
Durk We have another very interesting antioxidant in our formulation—actually, a whole set of antioxidants, in the form of turmeric root, which is a tropical spice. It’s used as a principal flavoring agent in curry, but it’s not the only one. It’s noteworthy that people who eat a lot of curry have a lower incidence of Alzheimer’s disease. In fact, the people of rural India eat a lot of curry because the turmeric and other spices in it act as antimicrobials, helping to prevent food spoilage in areas that don’t have refrigeration. These spices extend the amount of time a bowl of food can sit around and still be edible, without becoming rancid or causing food poisoning. In a particular part of rural India, it has been found that elderly people (aged 70–79) who eat a lot of curry (meaning a lot of turmeric) have less Alzheimer’s than Americans of similar age who don’t eat a lot of curry (Ganguli et al. 2000).

Sandy Part of that difference is due to a lower incidence, in the Indian population, of the APOE-4 genotype. Nevertheless, that does not explain all the difference. So we’ve included an amount of turmeric in our new formulation that’s well within the range eaten by the people in India. This is not a huge amount—it’s a dietary quantity.

Durk You have to be a little careful with antioxidants. With vitamins E and C, you can take high doses without their becoming pro-oxidants. With other antioxidants, if you have too much, you can actually cause more free radicals than if you had a smaller amount—they can become pro-oxidants. Sandy and I have been taking the same amount of the turmeric root that we’ve put into our new formulation for about three years now. We’ve been taking turmeric not only as a prophylactic against Alzheimer’s disease but also to help prevent cancer and inflammatory diseases. We’ve also been using galantamine for two to three years.

A lot of work has been done on the constituents of turmeric; that’s good, because the data on human beings are epidemiological. Researchers working with cholinergic neurons in vitro have found that turmeric and the various antioxidants in it are effective in protecting the neurons against damage or death caused by amyloid-beta (Park et al. 2002).

What’s particularly interesting to us is that curcumin (that’s one of the principal antioxidants in turmeric) is protective, but there are other closely related compounds in turmeric that are even more effective. One of these is about twice as effective; one is 3 times, one is about 5 times, and one is about 10 to 15 times as effective. So if people are taking curcumin alone as a preventive for Alzheimer’s, they’ll probably be helping themselves (if they get the dose right), but taking the entire turmeric package will work better, because there are even more powerful antioxidants in there, and they have evolved together to work . . .

Sandy . . . they work together as an integrated system.

Durk In turmeric, the root is the longest-lasting part of the plant, and it protects itself with a system of antioxidants whose collective action has been optimized by evolution. An example of what can happen if you isolate a single antioxidant from the turmeric root—curcumin, for example—can be found in some mouse experiments. Mice don’t normally develop Alzheimer’s disease, but if you genetically engineer them to produce the Alzheimer’s amyloid-beta preprotein that is then split to produce the human version of amyloid-beta, they do develop Alzheimer’s. As they get old, they develop memory losses; they develop plaques and tangles.

Sandy It looks a lot like the human version of Alzheimer’s, to the extent that a mouse can have it.

Durk There are some differences in the distribution of plaques and tangles in the brain, but they particularly go after the cholinergic areas, so in general, it’s a pretty good model. Researchers found that if they got the right dose of curcumin, they could slow down the development of memory loss dramatically and also reduce the size of the plaques at any age. If they used too high a dose of curcumin, however, it would actually speed up the deterioration (Lim et al. 2001). (See also Frautschy et al. 2001.)

Sandy But that’s curcumin all by itself.

Durk Right. That’s one of the reasons we use the whole turmeric root, because the root not only has things that are more effective than curcumin, the plant has evolved a complete antioxidant package that works as a system.

Sandy And this is an antioxidant package that people have been consuming for thousands of years.

Durk But we’ve also got some other things in there. We’re doing our best to use all the knowledge that’s currently available on the subject.

Sandy We wanted to include as many of the things we’ve been taking as possible, in an easy-to-use system, for convenience. So most of the things we’ve been studying, and most of the things we’ve been taking ourselves for long-term protection of our cognitive abilities, have been incorporated into our new system. That’s why there are so many things in there.

Alzheimer’s, Homocysteine, Folic Acid, Vitamin B6, and Vitamin B12

Durk It got to be quite a lot of things we were taking every day. We have 800 mcg of folic acid, 15 mg of vitamin B6, and 500 mcg of vitamin B12 in the formulation, and the reason for that is multifold. There was an interesting epidemiological study among nuns . . .

Sandy . . . in the American Journal of Clinical Nutrition (Snowdon et al. 2000). The researchers measured nutritional markers in the blood of 30 nuns. The nuns with the highest levels of serum folate had much less atrophy of their neocortex with aging than the nuns with the lowest levels of folate, who had a lot of neocortical atrophy—meaning that they were more likely to get Alzheimer’s disease than the high-folate nuns. (See also Miller 1999 for a review, and Clarke et al. 1998.) There could be a number of reasons for this. For one thing, folic acid is a vital nutrient for the repair of DNA damage—and, of course, as people get older, they suffer more and more DNA damage . . .

Durk . . . particularly in their mitochondria. And when the mitochondria become damaged, they start spewing out more free radicals.

Sandy Exactly. Their ability to repair DNA damage declines with age, so having a nutrient that’s able to protect against DNA damage and to repair it is beneficial.

Durk Also, it’s thought that folic acid can act very much like tetrahydrobiopterin, which is a necessary cofactor for producing nitric oxide from arginine (Hyndman et al. 2002). If you don’t have enough tetrahydrobiopterin, you can uncouple nitric oxide synthase from the production of nitric oxide and end up producing superoxide radicals (Vasquez-Vivar et al. 2003). And if you have superoxide radicals along with nitric oxide, you’ll end up forming peroxynitrite, which is a powerful brain-damaging oxidant that causes cellular apoptosis. In addition, the folic acid/B6/B12 combination lowers homocysteine levels, and it’s known that homocysteine increases free radical stress in the brain too.

Sandy It’s a neurotoxin, in fact.

CONTINUED IN PART III

References

  • Allen HE, Halley-Henderson MA, Hass CN. Chemical composition of bottled mineral water. Arch Environ Health 1989 Mar-Apr;44(2):102-16.
  • Alvarez G, Munoz-Montano JR, Satrustegui J, Avila J, Bogonez E, Diaz-Nido J. Lithium protects cultured neurons against beta-amyloid-induced neurodegeneration. FEBS Lett 1999 Jun 25;453(3):260-4.
  • Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK. Enhancement of hippocampal neurogenesis by lithium. J Neurochem 2000 Oct;75(4):1729-34.
  • Christen Y. Oxidative stress and Alzheimer disease. Am J Clin Nutr 2000 Feb; 71(2):621S-9S.
  • Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998 Nov;55(11):1449-55.
  • Cohen BM, Renshaw PF, Stoll AL, Wurtman RJ, Yurgelun-Todd D, Babb SM. Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy study. JAMA 1995 Sep 20;274(11):902-7.
  • Dal-Bianco P, Maly J, Wober C, Lind C, Koch G, Hufgard J, Marschall I, Mraz M, Deecke L. Galanthamine treatment in Alzheimer’s disease. J Neural Transm Suppl 1991;33:59-63.
  • Dawson R Jr. Taurine in aging and models of neurodegeneration. Adv Exp Med Biol 2003;526:537-45. Review.
  • Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, Breteler MM. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002 Jun 26;287(24):3223-9.
  • Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 2001 Nov-Dec;22(6): 993-1005.
  • Ganguli M, Chandra V, Kamboh MI, Johnston JM, Dodge HH, Thelma BK, Juyal RC, Pandav R, Belle SH, DeKosky ST. Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study. Arch Neurol 2000 Jun;57(6):824-30.
  • Gellerstedt N. Our knowledge of cerebral changes in normal involution of old age. Uppsala-Lak/Foren Forh 1933;38:193-408.
  • Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002 Dec;43(7):1173-9.
  • Hyndman ME, Verma S, Rosenfeld RJ, Anderson TJ, Parsons HG. Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function. Am J Physiol Heart Circ Physiol 2002 Jun;282(6):H2167-72.
  • Jope RS, Bijur GN. Mood stabilizers, glycogen synthase kinase-3beta and cell survival. Mol Psychiatry 2002;7 Suppl 1:S35-45. Review.
  • Levites Y, Amit T, Mandel S, Youdim MB. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (–)-epigallocatechin-3-gallate. FASEB J 2003 May;17(8):952-4. Epub 2003 Mar 28.
  • Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001 Nov 1;21(21):8370-7.
  • Louzada PR, Lima AC, Mendonca-Silva DL, Noel F, De Mello FG, Ferreira ST. Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer’s disease and other neurological disorders. FASEB J 2004 Mar;18(3):511-8.
  • Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000 Mar 28;54(6): 1265-72.
  • Meydani M. Vitamin E. Lancet 1995 Jan 21;345(8943):170-5. Review.
  • Miller JW. Homocysteine and Alzheimer’s disease. Nutr Rev 1999 Apr;57(4): 126-9. Review.
  • Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK. Lithium-induced increase in human brain grey matter. Lancet 2000 Oct 7;356(9237):1241-2. Erratum: Lancet 2000 Dec 16;356(9247):2104.
  • Morris MC, Beckett LA, Scherr PA, Hebert LE, Bennett DA, Field TS, Evans DA. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alz Dis Assoc Disord 1998 Sep;12(3):121-6.
  • Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002 Jun 26; 287(24):3230-7.
  • Park SY, Kim DS. Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer’s disease. J Nat Prod 2002 Sep;65(9):1227-31.
  • Phiel CJ, Wilson CA, Lee VM, Klein PS. GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature 2003 May 22;423(6938): 435-9.
  • Plaitakis A, Duvoisin RC. Homer’s moly identified as Galanthus nivalis L.: physiologic antidote to stramonium poisoning. Clin Neuropharmacol 1983 Mar; 6(1):1-5.
  • Pomara N, Singh R, Deptula D, Chou JC, Schwartz MB, LeWitt PA. Glutamate and other CSF amino acids in Alzheimer’s disease. Am J Psychiatry 1992 Feb; 149(2):251-4.
  • Raskind MA, Peskind ER, Wessel T, Yuan W. Galantamine in AD: a 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 2000 Jun 27;54(12):2261-8.
  • Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proc Natl Acad Sci USA 2004 Jan 6;101(1): 284-9. Epub 2003 Dec 19.
  • Roth M, Tomlinson BE, Blessed G. Correlation between scores for dementia and counts of “senile plaques” in cerebral grey matter of elderly subjects. Nature 1966;209:109-10.
  • Roth M, Tomlinson BE, Blessed G. The relationship between quantitative measures of dementia and of degenerative changes in the cerebral grey matter of elderly subjects. Proc Roy Soc 1967;60:254-60.
  • Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997 Apr 24;336(17):1216-22.
  • Schrauzer GN, Shrestha KP. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res 1990 May;25(2):105-13.
  • Snowdon DA, Tully CL, Smith CD, Riley KP, Markesbery WR. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun Study. Am J Clin Nutr 2000 Apr;71(4):993-8.
  • Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology 2000 Jun 27;54(12):2269-76.
  • Vasquez-Vivar J, Kalyanaraman B, Martasek P. The role of tetrahydrobiopterin in superoxide generation from eNOS: enzymology and physiological implications. Free Rad Res 2003 Feb;37(2):121-7. Review.
  • Woodruff-Pak DS, Vogel RW 3rd, Wenk GL. Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. Proc Natl Acad Sci USA 2001 Feb 13;98(4):2089-94. Epub 2001 Feb 06.
  • Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci 1992 Apr;15(4):117-22. Review.
  • Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC; Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol 2004 Jan;61(1):82-8.

CONTINUED IN PART III

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