Maintain Your Brain

An Exclusive Interview with Durk Pearson & Sandy Shaw®

Maintain your Brain
the Durk Pearson & Sandy Shaw Way

CONTINUED FROM PART II

First appeared in the May 2004 issue

Lithium as a Brain Food

Durk Then we have another unusual substance in our formulation: lithium, in small amounts—7 mg per day on an elemental basis. To explain its inclusion, let me start out with a bit of history. One hundred to 150 years ago, we didn’t have the kind of mechanistic medicine that we do now, where we often know what’s going on down at the molecular level. There wasn’t much knowledge, even 100 years ago, about why things went wrong, but there was a lot of empirical knowledge—for example, that nitroglycerin could treat angina. That’s interesting, but it was only a decade ago that we finally learned why it works (it’s broken down to produce nitric oxide).

In the case of lithium, the first clue that we got came from European health spas. Some mineral springs in Europe acquired the reputation of being able to rejuvenate old people: the springs made them feel better—made them function better—and improved their memories. They generally seemed to restore old people.

The way the idle rich went to health spas in Europe was very different from the way Americans go to health spas and get a massage and three days later go back home. Rich Europeans would go for a month or two, which was long enough that something in the water might have an effect. At these spas, in fact, people were encouraged to consume as much water as they possibly could. One of the most famous spas, with the best reputation, was in Vichy, France, and to this day, Vichy water is still bottled and sold all around the world, including the United States. It contains 3.5 mg of lithium per liter (Allen et al. 1989). There are some reasons for thinking that this might have some interesting effects. I might add that I have an 1892 Scientific American Cyclopedia of Receipts, Quotes and Queries, containing a formula for making Vichy water—synthetic Vichy water—which pharmacists would dispense in their drugstores because it made people feel better. And it has the same 3.5 mg per liter of lithium in it.

Lithium has some very interesting effects, and it doesn’t take a lot. Most people think of lithium as something you take at the level of hundreds of milligrams a day.

Sandy That’s when you’re taking it for bipolar disorder (manic depression), which requires a lot of lithium. You have to be very careful at those levels, because the therapeutic dose is not that much lower than the toxic dose.

Durk Those quantities are about 20 to 30 times as much as we have in our formulation. What evidence is there that a small amount of lithium would have any effect in human beings? There’s an interesting study that was done in 27 Texas counties over a 10-year period. Some of the people living there got their water from rivers, and some got it from wells, and there was a pretty big difference in the lithium levels between them. The researchers found that the people getting the higher levels of lithium had some interesting mental effects, even after adjusting for socioeconomic factors, urbanization, etc.

Sandy The suicide, homicide, and rape levels were significantly higher in the areas where the drinking water contained considerably less lithium than elsewhere (Schrauzer et al. 1990).

Durk With regard to nonviolent crimes such as theft and car theft, there was no significant difference, but the researchers did find differences in drug abuse. Although there was no significant difference in alcohol or marijuana arrests, there were statistically significantly lower rates of opiate and cocaine arrests in the areas that had the higher lithium levels. We’re talking here about 70 to 160 mcg per liter of lithium.

Sandy Exactly. So even at those very low levels, lithium obviously has mood-altering effects. With serious bipolar disorders, lithium treatment requires much larger amounts, but in the general population, such as that in this study, there were statistically significant improvements in violent crime and suicide rates with relatively small amounts.

Durk Also, there are papers showing that lithium is capable of lowering the neurotoxicity of amyloid-beta—the researchers used higher levels, such as those used in treating bipolar disorder (Alvarez et al. 1999; Phiel et al. 2003; Jope et al. 2002). But we’re talking about prevention, where a very small change in toxicity over a long period of time can, like compound interest, plausibly produce some pretty big results years later. Also, researchers have found that lithium causes the release of neurotrophic factors that induce neurons to repair themselves and grow rather than die off when they’re under stress . . .

Sandy . . . such as brain-derived neurotrophic factor, which is one of the most important for protecting neurons from damage and preventing them from dying (Hashimoto et al. 2002).

Durk And, in fact, it has been found that lithium causes an increase in gray matter (Moore et al. 2000). The gray matter of the brain consists mainly of the neuronal bodies, and it shrinks—particularly as people get older—more so than the white matter. This is especially true in people with Alzheimer’s: they actually lose neurons. The gray matter shrinks because the number of neurons that are still alive diminishes.

Sandy Another thing is that lithium has been found to enhance neurogenesis of hippocampal neurons—in other words, the creation of new hippocampal neurons (Chen et al. 2000). That’s important because the hippocampus is the center of memory and the organization of all your memories, and it’s one of the few areas of the brain where it’s possible for new neurons to grow. So the fact that lithium can enhance hippocampal neurogenesis (at least in the rodent brain and cultured cells) is very interesting.

DHA and EPA, Essential Fatty Acid Brain Foods

Sandy DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), which are essential for healthy brain function, can be produced in only limited and inadequate amounts in your body. Your central nervous system has the highest concentrations of these nutrients. EPA is a powerful anti-inflammatory compound. DHA is necessary to prevent excessive excitation of electrically excitable tissues. Both of these factors are relevant to maintaining brain health, and there is epidemiological evidence that people who eat a diet rich in coldwater fatty fish (which are rich in DHA and EPA) have a lower age-adjusted incidence of Alzheimer’s. Therefore, those who use our new brain maintenance system should take 1.5 to 2 grams per day of DHA + EPA. Because of manufacturing and stability considerations, these nutrients are provided in soft gelatin capsules, separate from the hard gelatin capsules that contain the galantamine, green tea polyphenols, vitamins C and E, turmeric, folic acid, vitamins B6 and B12, and lithium.

Multiple Mechanisms to Help Maintain Your Brain

Durk So what we’re trying to do here is conceptually similar to the modern treatment of people who are candidates for eventual symptomatic cardiovascular disease. For someone who has high blood pressure, the doctor will usually prescribe two or three or even four medicines at relatively small doses, each of which works by a different mechanism to get that blood pressure down. Because even if you don’t feel bad due to high blood pressure, if you allow it to go on decade after decade, guess what—you’re a good candidate for an eventual stroke or heart attack. By understanding the mechanisms and dealing with the problems before they become symptomatic, we can make the intervention a lot more successful. Cardiovascular disease is dropping quite rapidly, even though the population is aging quite rapidly.

Sandy We didn’t mention this earlier, but it has been discovered that, in some young adults who have a known genetic risk factor for Alzheimer’s in the APOE-4 gene, the same kinds of brain abnormalities that occur much more markedly in Alzheimer’s disease are visible via PET imaging, which measures glucose consumption across the brain (Reiman et al. 2004). This is decades before symptomatic Alzheimer’s occurs.

Durk These are people in their 20s or 30s, but their genetic makeup makes it more likely for them to develop Alzheimer’s when they get to, say, their 70s.

Sandy Not everyone who gets Alzheimer’s has this APOE-4 gene. However, the kinds of changes that take place early in those with APOE-4, i.e., the decreased brain metabolism, especially in certain areas, also occur in people who don’t have the gene as they develop symptomatic Alzheimer’s.

Durk What we’re trying to do is provide several modest protective effects, thereby reducing the degree of age-related damage that would normally occur over many decades before a person became symptomatic. We’re trying to nourish, maintain, and protect cholinergic neurons to help reduce the risk of Alzheimer’s, rather than waiting until it happens and then treating it. If a cardiologist said, “You don’t have cardiovascular disease until you have a heart attack or a stroke,” many people would probably think, Gee, this guy must be developing Alzheimer’s.

Sandy [Laughter] For the short-term benefit—what’s going to be happening in the meantime—it’s useful to note that we’re still as productive as we can recall ourselves being decades ago, and I haven’t noticed any decline in our cognitive abilities.

Durk We’re not losing our car keys either.

Sandy The idea is that we should continue with what we’re doing and keep going. If we did more extensive testing, say functional MRI testing, it would be possible to detect changes in the brain that may or may not be occurring as a result of taking a supplement formulation. That’s not something that most people would want to do, but it’s available, and let’s hope it becomes less expensive as time goes on.

Durk Anyway, we now feel confident enough in all the data on all the different ingredients, and besides, we’ve been taking these things ourselves for quite some time (nearly 30 years in the case of choline and vitamin B5). We want other people to enjoy their advantages too, and we hope it will be possible to protect against the brain damage that can eventually cause Alzheimer’s, in much the same way that you can protect yourself and prevent cardiovascular disease from developing. You can do this by dealing with the damaging mechanisms early . . .

Sandy . . . and remembering that the changes that occur in Alzheimer’s, such as the development of plaques and tangles, also occur in normal aging, but to a lesser extent. Yet it might be possible to decrease these age-related changes too, by using such a supplement formulation.

Durk The FDA has recently recognized a condition of memory deterioration called mild cognitive impairment. I think it’s exactly the same mechanism as Alzheimer’s and just hasn’t gone as far yet. If you didn’t die of something else, I suspect that mild cognitive impairment would eventually turn into Alzheimer’s when the feedback cycle of increased free radical activity and excitotoxicity, causing increased production of amyloid-beta, causing more free radical activity and excitotoxicity, etc., eventually ran away and exceeded your ability to cope with it.

Sandy On the other hand, even if you were just aging normally, a successful reduction in the rate of these mechanisms (which might, if you lived long enough, develop into Alzheimer’s) would put you on track to preserving your memory and cognitive abilities—which has been one of our core goals all along.

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.

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