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I N T E R N A T I O N A L

ANTI i

Are You Concentrating? Improve your mind

interview Eat Yourself Fit We taljt t tionist Karen Kaufman about weight loss

plus T h e Need For Antiaging Medicine Why Preventative medicine is a must T h e Oldest Smart Drug T h e continuing benefits of Pyritinol Inhibit Your A G E Prevent your cross - linking BEC5 Cream Su Real people di they reversed

April/May 2006 Volume 6 Issue 2 $6.50 USA ÂŁ3.50 UK â‚Ź5.30 Europe

cutting-edge

information

to

improve

your

optimal

health

span


European Congress on Anti-Aging and Preventative Medicine Hofburg Congress Centre - Vienna - Austria

Dear colleagues

October 18th - 21st 2006 A new Europe is being formed, resulting in fresh cultural, societal and scientificperspectives. Europe is becoming strongly integrative while assuming a new role on the world stage. Vienna at the very heart of this expending Europe offers all conference participants a sophisticated overview of State-of the-Art anti aging research, a distinguished panel of speakers and a superb social programme with a strong cultural emphasis.

Congress Office Tra\ el Agency: AUSTROPAINTERCONVENTION Verkehrsburo Group Mrs. Kristin Volmer Friedrichsrrasse 7 A 1010 Vienna Austria Tel: +43 i 588 00 518 Fax: +43 I 588 00 520 I Mail: antiaging200661interconvention.at v\ \vv\ .antiaging \ i e n n a 2 0 0 6 . a t

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April/May 2006

W e want to show you why Vienna enjoys a reputation as central Europe's prime conference address. Its role in historical anti-aging science, its significance as the founding city of ESAAM, its scientific energies and its unparalleled c h i c beauty combine to make an outstanding conference experience. Amongst Vienna's roll-call of artists, scientists and thinkers, 2006 also sees major anniversaries of Sigmund Freud and W.A. Mozart, part of a superb social programme. Welcome to Vienna, welcome to the heart of Europe.


welcome

advisors

All too often some people react incorrectly when they hear the term "antiaging medicine." Some think they are too young for it, others too old! The reality is that antiaging is for everyone who has reached adulthood.

point out that over population will lead to disaster and that as "mainstream" medicine can't afford comprehensive health-care at today's prices and numbers of people, how could it possibly manage in such a future?

The concept of an "old" person being an incapable one is changing fast. Today, people in their 60's and well beyond that are literally climbing mountains, pushing themselves both physically and mentally to levels that were unheard of just a few decades ago.

The answers to such derisory questions are featured in this magazine. When you begin to comprehend the hurdles that we face and the position we are currently in, then the choices are few. Any sane individual can understand that preventative medicine, as a life long holistic health program- is the only sensible choice.

But much more can be done, the future will be full of "old" people (by today's standards), however they will be lucid and agile, fully supportive and contributing to the community, enriching society with their vast range of experience and skills. Yet some think that dying young is the only way the planet can survive! They

I hope that after reading this issue of the Antiaging Magazine with the facts and figures we place before you, will allow you to understand more clearly why we believe that there is a real need for antiaging medicine.

T h e International A n t i a g i n g M a g a z i n e

is p r o u d t o b e regularly

c o n t r i b u t e d , a i d e d a n d s u p p o r t e d by t h e f o l l o w i n g l e a d i n g p r o f e s s i o n a l s :

Mircea Dumitru, M.D., Ph.D. is the Editor of the International Journal of Gerontology and Geriatrics, based in Mexico City. Dr. Dumitru was also the personal assistant to Professor Ana Asian, the famous Bucharest physician who developed Gerovital-H3.

Garry F. Gordon. M.D., DO, M.D. (H) is a world-renowned expert in chelation therapy behind many publications, including The Chelation Answer. He is advisor to the American Board of Chelation Therapy and examiner for all chelation physicians, being responsible for Peer Reviewed Chelation Therapy in Arizona.

John lonescu, Ph.D. is one of Europe's leading dermatologist researchers. His work into the causes and progression of numerous skin diseases has led him to develop a comprehensive diagnostic system to enable genetic identification of metabolic failures, which can then result in individualized detox and anti-aging therapies.

Karen Kaufman MS. CCN is a graduate of Skidmore College and received a Master of Science Degree in nutrition from the University of New Haven in Connecticut. She has worked at U-Mass Memorial Health Center and Medical School and currently maintains a private practice. She is also a member of the board of trustees of the Lupus Foundation of New England.

Marios Kyriazis, M.D., MSc.. MIBiol. has a postgraduate qualification in Gerontology from the King's College, University of London, and a postgraduate qualification in Geriatric medicine granted by the Royal College of Physicians. He has written extensively on longevity and healthy aging and is a founding member of the British Longevity Society.

Phil Micans

Robert Mason. Ph.D. was schooled in information technology and realized the

Editor-in-chief

potential for research in the (then) coming information revolution. The result was the formation of an organization conducting global medical database research.

Declaration

if.»

Vitamin Technology. Since 1986 he has been actively involved in antiaging

Copyright IAS 2006.

John Morgenthaler has been active in the field of nutritional medicine since

All copyrights are acknowledged. Whilst every effort has been made to ensure accuracy, no responsibility can be accepted for inaccuracies, howsoever caused. No liability can be accepted for illustrations, photographs, artwork or advertising materials while in transmission or with the publisher or their agents. All information is correct at time of going to print. Not for public broadcast or copy without written permission from IAS Ltd. Terms and conditions may change without notice.

Publisher: International Antiaging Publishing, P O Box 6 Sark, G Y 9 OSB Great Britain

Tel:+44 208

The International Antiaging Magazine focuses on the latest nutritional, hormonal and drug therapies in use now that show promise in combating the signs of aging. These signs include the physical, mental and internal changes consisting of the diseases and disorders that include cancer, arthritis and senile dementia etc. However, the main focus is upon prevention of such aging diseases and disorders for the "healthy-aging" individual.

181^105j

Fax: +44 208 1 8 1 > W f

Advertising: advertising@antiagingmagazine.com Subscription Enquiries: subscription@antiaging-

The information offered within is done so under the terms and conditions of IAS Ltd., and may change without notice. It is for educational purposes only and does not replace the advice of your health professional/ physician. Furthermore all statements may not necessarily be those of IAS Ltd., and none have been evaluated by a regulatory body such as the FDA. The International Antiaging Magazine accepts no responsibility for the accuracy of advertising, or for any action bought by the person or people responding to an advert.

U K £21.00 Euros €31.80 Rest of the world $39.00

President of international Antiaging Systems.

1986. As a founder of Smart Publications, John has co-authored numerous health books, including Smart Drugs. Stop the FDA, Better Sex Through Chemistry. Natural Hormone Replacement tor Women, and GHB: The Natural Mood Enhancer.

Walter Pierpaoli, M.D. is a pioneering research physician who introduced the concept of melatonin supplements to the world through his best selling book,

for Life Sciences has been established in Italy.

Jonathan Wright, M.D. is Medical Director of the Tahoma Clinic in Washington State. Working with natural medicines since 1973, Dr. Wright is a distinguished pioneer in nutrition and vitamin therapy. He is a recognised sex hormone expert and has authored and co-authored numerous ground-breaking publications.

Imre Zs.-Nagy, M.D. is Professor of Gerontologyy at the University of

magazine.com

Annual subscription (6 copies)

Magazine.

Chairman to the International Antiaging Conference and is also the Vice

Biomedical Research, Switzerland. Recently the Walter Pierpaoli Foundation Disclaimer IAS 2006.

E-mail:

medicine. Today, Phil is the Editor of the International Antiaging

The Melatonin Miracle. He is Director of the Jean Choay Institute for

G i O f e

editor@antiaging-magazine.com

Phil Micans, PharmB., MS has degrees in Pharmacology and Food and

International Antiaging Magazine is published by IAS Ltd and distributed in the USA by DSW. 75 Aberdeen Road. Emigsville PA 17318-0437. Application to mail at periodicals mailing rates is pending at Manchester, PA. Postmaster: send address changes to International Antiaging Magazine, c/o PO Box 437, Emigsville, PA 17318-0437

Debrecen, Hungary. He is a teacher in expenmental gerontology and was a pupil of the science of Fritz Verzar. He has published 275 papers, chapters and books, given 340 scientific lectures. He is founder (1982) and Editor-inChief of the journal Archives of Gerontology and Geriatrics. Listed alphabetically by last name

April/May 2006 i a m

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YOUR QUESTIONS ANSWERED What are the best chelation products available? Dr. Garry Gordon is considered by many to be the world's leading expert on oral chelation and has formulated some specialist products. Dr. Gordon's two core chelation products are called Essential Daily Defense and Heavy Detox.

Betaine HCL 50 mg Carrageenan (Red Algae) 600 mg Papain 100 mg Silica 40 mg Red Yeast 100 mg dl-Methionine 50 mg Beta-Sitosterol 100 mg Crataegus 6 (Hawthorne Berry) 5 mg

What does 1-capsule of Heavy Detox supply? Succinic Acid 65 mg D-Glucuronolactone 250 mg Selenium 100 meg How much are Essential Daily Defense and Heavy Detox? Essential Daily Defense is available from IAS for $24.95 for 100 capsules (plus S&H). Heavy Detox is available from $48.95 for 45 capsules (plus S&H). Where can I buy all these chelation products? These and other forms of detox agents are available from IAS

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contents P 6 Are you conce

BEC5 cream success stories As we produce our articles and editorials we are aware that they should feature the clinical references, but we also know that people do like to read about people! In this contribution, you can read real people's comments on how they reversed their skin cancers with the remarkable BEC5 skin cream.

Pyritinol: The Oldest Smart Drug

Attention deficit disorder (or ADHD) is a virtual plague, affecting not only millions of adults, but millions of children too. This article is the first of 3 to feature the numerous proven techniques that can be used to enhance concentration and improve vigilance and awareness. V

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We shouldn't believe that because something is old that it is of no use, or for that matter has even been surpassed yet! So we thought we would remind you of one of the first smart drugs to be developed. Pyritinol is a vitamin B6 derivative that has been shown not only to improve brain energy and memory, but also to enhance the activity of the immune system.

P20 *

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Inhibit Your AGE One of the major theories of aging is associated with proteins cross-linking or glycosylation. This process creates "harder" and more impervious membranes and cells creating molecules known as: Advanced Glycated End products or AGEs. In this article you can learn more about AGE itself and the products and protocols that can slow and even reverse their impact.

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, letters This article presents facts and figures from the world's governments and regulatory bodies illustrating the changing make up of our societies. As the baby boomer generation reach their 50's and 60's, they are set to change the face of health and medicine. Conventional medicine is too costly and too immobile to cope with a "top heavy" population model. Antiaging/ preventative medicine offers a real alternative solution, as the holistic and versatile for the new century.

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Are you

Concentrating?

The deterioration of concentration 'Concentration' is the ability to sustain focused attention on a given object. In fact, you are concentrating right now, as you read these words (lets see if you can make it right to the end!). Concentration can be external - such as relating to other people, driving a car or eating your lunch - or internal - such as thoughts, feelings or sensations. Although animals can concentrate to some extent (a lion, for example, focusing on its chosen prey), only humans can concentrate on

"It I s lileely t h a t w.p to a

third of adults w i l l experience a gradual decline I n their m e n t a l capabilities, a s they get older"

distractions relate to your body, your thoughts and your emotions: Hunger, tiredness, illness, boredom, stress, daydreaming... Some of these can be easily dealt with once they are identified. Others require practice and/or additional help before they can be managed. The reasons behind continuing poor concentration - that is, when it feels like a permanent, irreversible condition - are either related to some form of brain impairment (due to an impact or disease) or to a number of age-related changes that take place in the brain. This article will focus on the latter of these causes, the gradual deterioration of concentration and general mental dexterity with age. The causes of age-related mental decline

things that do not yet exist (such as a building that exists only in the mind of

As most people age they will

its architect), or on such abstract

experience symptoms of mental

notions as 'infinity', 'justice' or

deterioration, such as short-term

'eternity'.

memory loss and difficulties learning new information. Aside from the

Paradoxically, the power of concentration also involves the ability to pay no attention to irrelevant distractions. These are things that can intrude on your concentration to divert or disrupt the sustained, focused attention. Like concentration itself, these intrusions can be divided into external and internal distractions.

various forms of age-related

they get older. This, while not

External distractions relate to the

that accumulate over the years,

physical environment: Noise,

contributing to damaging changes in

interruptions from other people,

our brains as we get older:

dementia, it is likely that up to a third of adults will experience a gradual decline in their mental capabilities as interfering with everyday life, is sufficient to impair concentration and memory. This decline is due to many factors

television, work responsibilities...

6

Once identified, these distractions are

Diet - Clinical tests demonstrate that

often easy to deal with. Internal

diets with a high fat intake produce

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April/May 2006

i n the f i r s t

of three

articles,

o n overcoming age-related m e n t a l decline, we the

look, at

power of concentration,

a n d Wow to m a i n t a i n I t Into

old

age.


significantly higher risks of mental deterioration. The same has been found for a diet high in saturated fat and cholesterol. Fish, on the other hand, was found to produce a much lower risk of mental decline.1 Stress -Studies have shown that stress, both everyday stress and major traumatic stress, causing a rise in the stress hormone epinephrine leads to mild cognitive impairment compared with those possessing normal levels of epinephrine.2 Vascular disease - Cerebrovascular disease occurs in the arteries that pass blood to the brain. The result is a reduced rate of blood flow which in turn causes nerve cells in the brain to die prematurely. This was demonstrated in a study of 4 0 0

"Arms, o f t h e b o d y w i t h h i g h e^vergy o u t p u t , s u c h a s t h e brcdiA-, are p a r t i c u l a r l y v/uli/verable t o d a m a g e f r o m , free r a d i c a l s " middle-to-old aged men, which revealed that vascular risk factors, such as excessive alcohol intake and higher than normal homocysteine levels, are associated with reduced mental processing capacity and information processing speed. 3 Free radicals - These are unstable molecules that are prone to react with other molecules in a damaging process known as oxidation. Areas of the body with high energy output, such as the brain, are particularly vulnerable to damage from free radicals. Animal studies have suggested that diets high in antioxidants (including, for example, superoxide dismutase and glutathione peroxidase, as well as vitamins C and E) can delay age-related memory loss. 4

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Inflammation - A number of studies

inflammation was the decisive factor.

have found a clear link between

5

inflammation and cognitive impairment. One study, for instance,

All of these health issues bring about

of 2 6 3 2 elderly participants found

changes to the brain that are

that those suffering from metabolic

associated with a lessening of

syndrome (a group of symptoms

mental capacity. A crucial

including high blood pressure, high

consequence is the decrease in the

insulin levels, obesity and abnormal

number of neurotransmitters in the

blood lipid levels) as well as high

brain, such as serotonin and

inflammation levels were more likely

acetylcholine. In addition, the

to experience cognitive impairment

number of nerve impulses and nerve

than those suffering from neither.

cells will also reduce, and the

Those with metabolic syndrome and

quantity of blood passing through the

low inflammation, however, were

brain will diminish. This is particularly

found not to be at increased risk of

important as the oxygen and

mild cognitive impairment. That is, it

nutrients that are required for the

appears that the level of

brain to function correctly are carried into the brain by the blood.

"All of these health tssw.es bring about changes to the brain that are associated with a lessening of mental capacity.'

Fortunately, many of the problems associated with memory loss and other neurological disturbances are correctable. However, too often in the past, physicians have viewed these detrimental changes to the brain as an inevitable

How can I have increased alertness & concentration, without the usual 'highs & lows' from stimulants that disrupt my normal sleep pattern?

consequence of aging. Indeed, conventional medicine has had little to offer people who visit their physician describing a small decline in their memory or mental abilities.

Modafinil & Adrafinil

are class-leading eugeroic drugs that reinvented stimulatory alertness for millions of people around the world. These are remarkable products that offer stimulation without affecting sleep. They increase mental & physical alertness and concentration, reducing the desire to nap (sleep), and yet at the same time display no addictive or "coming-down" side effects.

For further details about Modafmil & Adrafinil

developments, however, have uncovered a number of possible causes behind 'agerelated' mental decline and identified

www.antiaging-systems.com

therapies to

Call: ( U S A ) 4 1 5 9 9 2 5 5 6 3

confront it.

Outside U S A + 4 4 2 0 8 1 2 3 2 1 0 6 i a m

Recent

April/May 2006

enable people to

'too oftew i n the past, physicians have viewed these detrimental c h a f e s to the brain as an inevitable oo^sequeM'e of aging."


What can be done about it? The best way to maintain a healthy, active brain is to maintain a healthy, active body. This means plenty of exercise, a balanced diet and a good night's sleep. On top of this, there are a number of supplements that can compensate, at least partially, for the causes of agerelated mental decline that I've mentioned. In general these supplements fall into one of three categories: brain stimulants, nerve cell enhancers and blood flow promoters. There are often secondary benefits, however, that cross the category " t h e s e sutpplemet/vts f a l l wtto ÂŁ>iA,e o f t h r e e c a t e g o r i e s : b r a l ^ s t i m u l a n t s , i/verve c-ell

ei^kaMers

and

blood

flow

promoters.' boundaries. The following examples of supplements indicate some of the more popular choices from each of the categories. Brain stimulants Adrafinil and Modafinil are the sole members of a new class of drugs called Eugeroics, which literally translates as 'good arousal'. Adrafinil is designed to bring about increased levels of vigilance and alertness, while Modafinil is a psychostimulant used to improve memory and brighten moods. The basis of Eugeroics' uniqueness lies in their ability to stimulate only when stimulation is required, unlike most other 'brain wakening' drugs. Adrafinil and Modafinil selectively stimulate adrenergic receptors in the brain that normally respond to norepinephrine (noradrenaline), a neurotransmitter linked to alertness,

April/May 2006

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levels m-ay be associated with agerelated iA.ewr0n,fll "iiacreased m a o

deterioration a n d

Parkinson's disease. " learning, and memory. This highly focused activity profile may account for Adrafinil and Modafinil's relative lack of adverse side effects compared to conventional stimulants which have a much broader spectrum of activity. Unlike these other stimulants, there are no 'highs and lows'; minimal anxiety, agitation and insomnia; sleep patterns remain unaffected; and they are nonaddictive.

neurotransmitters in the central nervous system and peripheral tissues. Increased MAO levels may be associated with age-related neuronal deterioration and Parkinson's disease. Although Parkinson's disease remains the only FDA approved indication for Deprenyl in the USA, with a number of ongoing clinical studies evaluating its efficacy in Alzheimer's disease, anecdotal reports from both physicians and patients refer to dramatic improvements in an impressive range of diseases.

Centrophenoxine rejuvenates nerve cells by reducing their levels of Nerve cell enhancers lipofuscin. Lipofuscin is the name given to the biochemical clutter that Deprenyl is a potent neuro-protector accumulates in the body's cells over and a selective MAO-B inhibitor. MAOtime. The more lipofuscin a cell A and MAO-B are the primary accumulates, the less functional it enzymes responsible for degrading becomes. In aged animals, levels of lipofuscin can reach up to 30% Make a difference to mood, memory of cell volume.

and life enhancement... for less than 50 cents per day

Numerous animal

Deprenyl (selegiline) has long been approved for use in Parkinson's disease, but the work of Professor Knoll and others shows that regular low dose use of deprenyl can J i aid in the general protection速!' age related memory g j decline, supporting libido function and increasing well f t being. Just a few milligrams a day can make a difference M to mood, memory and life enhancement. T h e liquid is ideally supportive for low dose use because 1 drop = 1 mg. Furthermore its cost effectiveness means that most individuals pay less than 50 cents per day. We offer Deprenyl in both a 1 liquid, and a 50 x 5mg tablet format.

Further details available at:

www.antiaging-systems.com/a2; Call: (USA) 1 415 992 "5563" Outside USA +44 208 123*2106 Restrictions on its sale/ delivery may app||fp some countries.

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April/May 2006

experiments measuring memory and learning abilities have demonstated how aged animals with their lipofuscin levels reduced by Centrophenoxine have their memory and learning abilities restored to a level similar to that of a healthy young animal.

Blood flow promoters Hydergine has been known of since the 1940s. It stimulates blood flow to the brain, increasing the delivery of oxygen and relieving symptoms of deteriorating mental activity. This was demonstrated in an experiment where two groups of cats were anaesthetized and their brains electronically monitored. The blood supply to all the cats' brains was reduced (and therefore the oxygen supply). The cats in the 'no Hydergine' group had brain damage within 5 minutes and died within 15 minutes. However, the cats in the 'Hydergine treated' group had strong brain wave patterns up to 45 minutes later. Nicergoline has alpha-adrenolytic action which activates the brain's metabolism and improves arterial flow, lowers vascular resistance and improves the use of glucose and oxygen. Currently used in the battle to treat senile dementia, Nicergoline has been found to improve mental agility through enhancing perception and vigilance. In this way it differs from the effects of Hydergine (to which it is chemically similar). That is, Hydergine extends the period of useful mental workload, and has been designated as an IQ booster, whereas Nicergoline appears to enhance clarity, perception and vigilance. Xanthinol Nicotinate (XN) is a form of Niacin (vitamin B3) that passes easily through cell membranes. It is the most potent form of Niacin available. XN has been shown to increase brain glucose metabolism and boost brain ATP levels as well as improve brain blood flow. As such, XN has been used to treat insufficient blood flow to the arteries and the extremities, short-term memory disorders and lack of brain energy


that compromises vigilance, concentration and attention. Furthermore, XN has been clinically shown to improve the reaction speed of the elderly. Picamilone is a chemical derived from gamma-amino-butyric acid (GABA) and nicotinic acid. It rapidly crosses the blood-brain barrier to increase the rate of intracranial and cortex blood circulation. Picamilone has been cited as a better vasodilator than either Hydergine or Vinpocetine. Studies carried out in Russia have shown that patients with mild to moderate memory impairment and emotional, hearing and speech difficulties, noticeably improved after taking a course of Picamilone. Aging is all in the mind

Your brain is the most intricate part of your body. Which is not surprising, as it controls virtually every metabolic function required to keep you alive. Held within the compact and remarkable structure of the brain are several thousand miles of interconnected nerve cells which control not only every movement, but every thought, sensation and emotion that make us what we are. Just a few years ago, doctors and

"it is g e n e r a l l y accepted t h a t \M£\Atal decline is ko lovu^er a i t ii/uevitable

co\A,s,ec\y.e\^ce of agu/vg." govern physical health can also help to preserve mental health. By identifying areas of risk now, such as in your diet and lifestyle, you may be able to stave off any serious mental decline in the future. And, thanks to the rejuvenating powers of supplements, only some of which have been mentioned in this article, it may be possible to pre-empt mental decline and maintain youthful mental agility for the rest of your life. If you're still reading this article then your concentration can't be too bad. But remember, prevention is better than cure. It's never to late, or too early, to get a better brain! In the following articles in this series, difficulties, such as Attention Deficit Disorder and Alzheimer's Disease,

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bffi

& LitL Lid.

References:

1 Solfrizzi V et al 2005; Solfrizzi V et

2000. 2 Karlamangla AS et al 2005. 3 Aleman A et al 2005. 4 Joseph JA

the quantity of nerve impulses and

et a I 1998; Perrig WJ et al 1997. 5

nerve cells would go down, and the

Yaffe K et al 1998.

amount of oxygen reaching the brain would dwindle. Now, however, opinions have changed and it is

The same lifestyle factors that

Enhances brain glucose Prevents brain dendrite decline Aids mood Helps myelin sheath repair Increases rate of learning

and final article, I will focus on

unavoidable and unstoppable. They

consequence of aging.

overcome them. Then, in the third

Panza F et al 2004; Capurso A et al

decline is no longer an inevitable

and how supplements can help to

of age-related cognitive decline was

generally accepted that mental

This nutrient enhances the function of Nerve Growth Factor and increases production of the brain neurotransmitter acetylcholine (most affected in Alzheimer's disease).

I will discuss specific mental

al 2003; Solfrizzi V et al 1999;

neurotransmitters would decrease,

Phosphatidlyserine

scientists assumed that the process

believed that the number of

BRAIN FOOD TO IMPROVE MEMORY & INCREASE LUCIDITY

For details on how to advertise in the International Antiaging Magazine, email your media pack request to: advertising@antiagingmagazine.com

Centrophenoxine increases the brain's use of glucose and improves brain energy levels. It removes lipofuscin build up in the brain, heart, lung and skin cells, and is vital for the efficient communication of a cell to transfer potassium and sodium across its membranes. It also removes the visible signs of excessive lipofuscin build up - age or liver spots.

I

60 x 250mg capsules $29.95

addition to my smart-nutrient regime. H.C, Washington

For more information about this unique brain enhancer go to: www.antiaging-systems.com Call: (USA toll-free) 866 800 4677

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in the news Memantine effective in Alzheimer's disease over long term Memantine is safe and effective in the long term, according to an openlabel 24-week extension of a 28week, randomised, double-blind trial in patients with moderate to serve Alzheimer's disease. Patients taking placebo in the initial trail were switched to Memantine for the 24week extension, and the authors saw significant benefit for these patients relative to the rate of decline experienced while on placebo (using the same efficacy measures). Patients switched to active treatment did not completely catch up with the patients who continued taking Memantine throughout the whole trail. The study is published in the Archives of Neurology (2006; 63:49). Switch to aromatase inhibitor improves survival Replacing Tamoxifen with Anastrozole (Arimidex) improves survival of patients with early breast cancer compared with continuing on Tamoxifen for five years, according to results from the first study to show a survival benefit of changing hormonal therapy. The meta-analysis of three trials with similar design included 4,600 women with hormone-sensitive early breast cancer who were randomised to switch to Anastrozole after two to three years of Tamoxifen or to remain on Tamoxifen for five years. The results showed that women changing to an Anastrozole gained a 29 percent improvement in survival compared with those remaining on Tamoxifen. The risk of diseases recurrence was reduced by 45 percent and risk of distant recurrence fell by 39 percent. Reporting the findings at the San Antonio breast cancer symposium last week, Walter Jonat, of the University Of Kiel, Germany, said: "Results from previous study showed that survival is improved if patients start treatment with an aromatase inhibitor rather than Tamoxifen. This meta-analysis shows that survival is

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calendar of events also increased if patients already on Tamoxifen are switched to anastrozole." Geoff Saunders, Macmillan cancer network pharmacist for Greater Manchester commented: "These findings are encouraging us towards using aromatase inhibitors at an earlier stage in the treatment of breast cancer. The evidence indicates that's we should start women with early breast cancer with an aromatase inhibitor at diagnosis. Those already on Tamoxifen should be switched early, rather than remaining on Tamoxifen foe five years." Could health professionals be recommending the wrong sun protection message? It has been suggested that the socalled Sunsmart campaign, which encourages people to "always cover up" is killing more people than it is saving! This is due to the association between vitamin D deficiency and various diseases, in particular various types of cancer. According to Oliver Gillie, author of; "sunlight robbery" the Sunsmart programs should be abandoned. Dr. Gillie said that the advice aims to try to prevent skin cancer, but that the evidence now indicates that skin cancer is associated with sunburn rather than normal exposure to the sun. Instead, Dr. Gillie proposes a new policy, which he calls "Sunsafe" this recommends: • To sunbathe without burning, everyday if possible. • The middle of the day (in the UK) being a good time for sunbathing. Brian Diffey, Professor of medical physics, University of Newcastle thinks that it is irresponsible to expose ourselves randomly to ultraviolet and suggests that vitamin D deficiency could be addressed through supplements. He stated: "It may not be reasonable to expect people to modify their lifestyle to get more sun exposure. We live in a time-poor society and on average spend only 14 minutes a day outside."

MAY 2006

Date: May 3-6, 2006 Name: 3rd International Conference on Antiaging and Longevity Medicine Place: Acapulco, Mexico Contact: www.med-estetica.com

JUNE 2006

Date: June 16-18, 2006 Name: 1st International Anti-Aging Symposium Place: Tokyo, Japan Contact: www.imagina.jp/aiset/english

JULY 2006

Date: July 14-16, 2006 Name: International Anti-Aging Congress Place: Chicago, Illinois, USA Contact: www.worldhealth.net

SEPTEMBER 2006

Date: September 15-17, 2006 Name: London Antiageing Conference Place: London, England Contact: www.antiageingconference.com Date: September 7-10, 2006 Name: The Australasian Conference on Anti-Aging Medicine Place: Bali, Indonesia Contact: www.asiaantiaging.net/2006/ main/default.asp

OCTOBER 2006

Date: October 18-21, 2006 Name: European Congress on AntiAging Medicine Place: Vienna, Austria Contact: www.antiaging-vienna2006.at Date: October 13-15, 2006 Name: International Conference on Healthy Ageing and Longevity Place: Melbourne, Australia Contact: www. longevityinternational.com Date: October 5-8, 2006 Name: Antiaging and Integrative Medicine Place: Geneva, Switzerland Contact: www.saaam.org

DECEMBER 2006

Date: December 7-10, 2006 Name: International Anti-Aging Congress Place: Las Vegas, Nevada, USA Contact: www.worldhealth.net

If you organize or attend an event that you think will be of interest to our readers please contact: editor@antiaging-magazine.com


t's generally known that the average life expectancy is getter longer, increasing year on year, figure illustrates the life expectancy for the USA from 1900 to 2050 and similar trends can be presented for all the developed and indeed developing countries.

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Presently, the average 65-year old in the developed world can expect to live to be 79 and the average woman can expect to live to be 82. The changes taking place can be exacerbated when you realise that a child born in 1997 can expect to live 29-years longer than one born in 1900, representing a 60% increase.

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Yet this could just be a "drop in the bucket" compared to what some scientists believe is already possible. Many believe that today's existing knowledge about the human biological system and the technology that is already available, will mean that many more people will be able to regularly live beyond 100, perhaps even regularly beyond 120 and who knows where. For the theory is- that the longer you live, the more chance you have to expose yourself to new technologies that can further extend lifespan.

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Naturally none of this is worthwhile, unless we are also

iFigure 1

1900 1910 1920 1930 1940 1950 1960 1970 1930 1990 2000 2010 2020 2 0 M 2040 2050

enhancing or maintaining a good standard of health, thus improving the optimal health span as well as the life span.

April/May 2006 i a m

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"extending life span based upon the costs and impracticalities of the current standard healthcare system, is unlikely to be feasible" Simply extending life span based upon the costs and impracticalities of the current standard healthcare system, is unlikely to be feasible.

To see how obvious it is that the elderly population is growing at a far greater rate than any other part of society, look at igure . This graph illustrates that individuals over the age of 65

are expected to grow at a rate of 200% between 2000 and 2050. Whilst the growth rate of those between the ages of 15 and 64 will expand at 16% and those under 15 years of age at only 5%. But the single biggest increase is attributable to those over 80, with an expected increase of more than 400%! Indeed, this 80+

The life span of the baby boomers

age bracket is by far the fastest growing population group. Putting this into perspective; in the year 2000 there were 600 million people in the world aged 60 and over. There will be 1.2 billion by 2025 rising to 2 billion in 2050. And this is not singularly a developed world issue. Today, about two thirds of all older people are living in the developing world; by 2025, it will be 75%. Aging factors

Not only is the average lifespan becoming much longer, (thus increasing the numbers of elderly individuals in the population), but we are also about to see the impact of the baby boomers upon society. The baby boomers are those individuals born between the Second World War and the Korean War and they represent the largest single section of the population and for whom as they age, are now beginning to move into their geriatric period. As they have impacted every single area of commerce and society of their generation because of their sheer numbers, we can now expect this same impact for all their geriatric requirements.

Whilst it's common knowledge that the older one is, the more likely we are to be treated for a disease or ailment, figure helps to highlight this. It shows by groups of varying ages, their percentage of the total drug consumption. This particular study looks at the years of 1990, 2000 and 2001 and whilst there are variations between the years, it is clear that the overall trend is up, and that apart from birth and childhood diseases, the older you are, the more likely you are to be prescribed medication. For example, someone who is 75 is likely to use 4-times as many drugs than someone who is 45.

Taking Italy as an example, we can study their current and forecasted populous. Figu is for the year 2000, here we can see a typical apple shaped graph with still seemingly reasonable numbers of the working age-group, (i.e. income generating). is

The question we have to ask ourselves is, what does this mean to society if we let these facts meet our previous graph showing the over 65's increasing by 200%?

the graph for 2025 and it changes quite dramatically, it looks more like one of those old-fashioned spinning tops for children. Now there are now many more people in the over 50's age groups. And when we look at the projections for 2050 in we see that the demographics appear to look like an inverted pyramid, with for the first time, massive numbers in their 60's, 70's and 80's. But we don't have to wait until 2050, as it is estimated that the 65 plus age group will start to experience a surge of growth from 2010. j a m

April/May 2006

Source: US Census Bureau www.census.gov/ipc/www/idbpyr.html

Another factor that advances with age is disability, as shown in . While the graph shows similar results for France, Germany, the Netherlands and the UK, the consensus is that the older we are, the more likely we are to suffer from some form of disability- many of which may need some type of care with its concurrent cost. Indeed, as 1 7 highlights at the age of 55 there is a 1 in 5 chance of having a disability, rising to 1 in 2 at the age of 75 and so on. Again, let us pose the


to aging- for by literally being older it dramatically increases our chances of acquiring them.

question, what happens if we let these figures meet those in the aging population demographics already mentioned? Consider that old-age dependency rates will rise in every major world region over the next 20-years, and that the burden in 2025 is expected to be at least 50% larger than it was in 1998. In just 14-years time society will consider 1 in 5 of its population as elderly.

According to the statistics, only 10% of all health-care costs are spent on the first three. In other words, 90% of the total health-care budget is spent on degenerative disease.

Source: World Health Organisation Ageing & Health: www.who.int/hpr/ageing

However an aging populous could have benefits; on the upside, an increase of just 6years extra life expectancy in the United States, between the years of 1970 and 1990 translated into an additional gross national product of $57 trillion dollars, and those figures were based on a 1992 report. But for those who say we can't afford to introduce preventative medicine, consider that in June 2000 the University of Chicago estimated that curing heart disease would be worth $48 trillion Dollars, and curing Cancer would be worth $47 trillion Dollars. Perhaps the question should be, can we afford not to introduce preventative medicine!

Source: Lehman Brothers Equity Research

France (Male)

But why are health costs so high? Clearly there are a number of factors here, including the need for highly trained staff, specialist equipment and premises, as well as liability insurance etc. All these factors are clearly present in the treatment of a disease, and obviously it could all be significantly reduced if far fewer people were actually sick in the first place!

Germany

Looking more closely at drug development, we see that the pharmaceutical companies are mainstays of the Fortune 500. Indeed, 10 drug companies registered more profits than the 490 remaining Fortune 500 companies combined!

The Netherlands

Aging's financial burden Looking more closely at one example of an aging disease, we can begin to see more clearly the financial costs involved. Alzheimer's Disease is currently the 12th leading cause of death and it is perhaps an accurate example of an aging disease, because it very rarely affects anyone under the age of 60. At present, there is a 1 in 7 chance of being diagnosed with Alzheimer's Disease if you are over the age of 65. That figure rises to a massive, and rather alarming 1 in 2 chance if you are over the age of 85. In fact, the risk of Alzheimer's Disease doubles every 5-years after the age of 65. In the United States alone, $80 to

In the United States alone, that translates into around $700 billion Dollars every year! Thus, if we really want to make a big impact on health-care in the world, we must focus on this 90%, we must focus on the degenerative diseases of aging. If we can slow or prevent the signs of aging from occurring, we could eliminate overnight the majority of disease and therefore the majority of its cost, both in financial and human terms.

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Source: Association for the advancement of assistive technology in Europe

$100 billion Dollars is spent every-year on Alzheimer's health-care, or lost in earnings, and it has been estimated that curing Alzheimer's Disease could be worth as much as $1.5 trillion Dollars. If we take into account all the age-related diseases and disorders, is it possible to get an overall view of the financial costs involved? Essentially all

diseases fall into one of four categories, they are either:

We are reminded that high margins/ profits are required for R&D and the approval process. Naturally, not all drugs become approved and thus the average cost of approving a new drug- just in the United States- was estimated in 2002 to be $800 million.

Inherited or genetic disease. Infectious disease. Trauma. And finally, degenerative "90% of the total health-care diseases- which budget is spent on degenerative for argument, we can suggest disease" are attributable April/May 2006 i a m I 15


perhaps just biochemical changes. For example, rather than treating an end-point disease to accept that hormonal change itself, or reduced inflammatory markers is good enough to prove a substance's worth, leaving the physician free to

"the average cost of approving a new drug- just in the United States- was estimated in 2002 to be $800 million" When going for approval, the most important question iscan the molecule be patented? After all, who is going to risk millions of Dollars to approve a molecule that anyone can sell? But as it is so difficult to patent a natural molecule, it means the accent is upon the artificial. Then once approved, a flood of press releases and marketing follows with the blessing of the authorities, after all they have approved it for use in disease X etc. This then leads to greater public

awareness. This is a reality of the way things work, and as such greatly impedes the small guys and the natural molecule brigade and is one of the major obstacles to be faced. For the commercial reality is, that claims can't be made about substances that aren't approved and approval is expensive and requires strong patents. Problems for the widespread introduction of preventative medicine There are a number of issues that impede the introduction of preventative/ antiaging medicine, these include: Patents: Which have already been mentioned. Approval: Apart from the prohibitive cost of the approval process, there is also the fact that products have to be tested to correspond to a given disease or disorder. There is no current acceptance of disease prevention, or of aging itself, therefore if the category fails to exist it is clearly difficult to start an approval process! There will have to be a change to the categories to accept

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use these tools as they see fit. Another issue is the fact that most often substances for approval are tested singularly. Whilst more often than not, a combination of substances work synergistically together, and is especially true of natural molecules and is the foundation of a holistic approach to medicine. Unfortunately, single item

substances are tested individually to prove their lone merit, however the results could be so much greater when combined with its methylation agents, enzymes etc. c Studies: In preventative medicine, we really need negative studies. By this I mean, we want to keep healthy people healthy. The types of clinical trials that need to be run mean using healthy people, utilizing the substances in question and then showing that over time the people who were in the trial were less prone to disease etc. Again, all to often the trials run are the exact opposite, take a sick person and try to

make them healthier. That is not the ultimate goal of preventative medicine and therefore it becomes another hurdle in the battle of the current approval mechanism. d) Time: As usual it is not on our side. Once again the ultimate goal of antiaging medicine is to extend both the optimal health and the life span. Trials in humans need to be run over decades to prove their worth, although many are willing to accept that when we see positive results in a short to medium period that we can't afford to wait for the end-point, otherwise the data is of little relevance to today's generation. Insurance: Very little tends to be reimbursable through insurance at present. Therefore as preventative/ antiaging medicine falls to cash-only patients, the numbers of people engaging in it is restricted. f: Scope: Asking the questionwhat do you prevent in your healthy patient? Brings up numerous issues of the vastness of the possible scope. In its widest sense the


"we need to develop techniques to measure healthy people, to try to determine just how healthy the healthy patient is!" goals and aims are enormous, obviously because aging is affecting every part and every system of our body's. Of course, one can concentrate on specific areas, perhaps those that are most likely to be lethal, or even be of the greatest concern to the patient themselves. In its broadest sense, using all the skills and technologies that are available to us, including examination, observation, blood work, scanners and good oldfashioned questions and family background etc., the testing could potentially become enormous and is clearly limited by the issues of cost and convenience. Measurement: Finally on the issue of measurement, we need to develop techniques to measure healthy people, to try to determine just how healthy the healthy patient is! Furthermore, we need to move away from the idea of normal and think more along the lines of optimal. A major criticism of antiaging medicine is that it is suggested that advice and substances are given "ad-hoc", and that, as by definition, healthy patients don't feel much difference in some cases, so the advice and recommendations are taken on "faith." So is there any way that we can show that the use of various protocols or products, such as the bio-identical hormones, are not only impacting the level of that particular hormone, but are also affecting the aging status of the patient as a whole? Clinical application issues Looking at the status of the actual measurement of aging and health today, what challenges do clinics face in

adopting preventative medicine?

Firstly, we can recognise that there is a lack of scientific measurement within the industry, with no clear path to follow. b Secondly, any solution requires it to be quantitative, and standardization is lacking within the field. Plus, consider that any measurement that takes place has to be seen to be changeable within a relatively short period of time. From the patient's perspective, results have to be achievable within a reasonable time frame. Ward Dean, M.D., noted in his 1988 publication, Biological Aging Measurement: "It is assumed that with increased automation and computerization, that data will be more easily collected and analyzed, to rapidly improve the accuracy and cost effectiveness of aging measurement. I hope this book will be useful in assisting to accomplish this goal." Dr. Dean's foresight has now been incorporated into systems such as Inner-Age and undoubtedly this type of information gathering and analysis will only become more common as the years go on. [Ed.- See www.innerage.com] What's the answer to world aging? In the very near future, the world has to ask itself some basic questions. For example: Can we expect the future working generations to pay 70% or even more tax, to support the same health-care program for a top-heavy society? It is estimated that if the policy of early retirement continues, (i.e. between the age of 55 and 60), that in just

C o -enzyme ENERGY FOR CoQ 10 is an essential part of the mitochondrial system that converts the food we eat into ATP - the body's energy currency. CoQ 10 is found in every cell in the body. CoQ 10 is a powerful natural antioxidant, which means that it protects us from harmful free radicals. CoQ 10 is also one of many substances in the body that tend to decline as people age or develop certain diseases. It is one of the most important natural energy molecules cited as being of great I importance in heart health. It helps the body support normal cholesterol levels and keeps your heart energized. get older, our body produces less CoQ 10 ' and so taking a supplement can help to maintain our vitality. This optimal health supplement comes in 120 x 30mg capsules from just $29.95 To order call Antiageing Nutrition

+44 207 1 17 0107 www.antiageing-nutntion.com

Worried about the mercury in your dental amalgams?

EZ Defence Gum A unique, great tasting chewing gum containing EDTA that is specially formulated for people with teeth amalgams. One gum can be chewed after each meal and helps grasp the mercury released from the amalgam by masticating into the gum. Once the orange flavor is finished the gum should be removed and disposed of and not swallowed.

100 t a b l e t s $24.95

EZ Defense is a highly effective way to remove toxins from the body. This is an easy way to detox for anyone that has a hard time swallowing pills. Also, as most of us now find we have considerable amount of metal dental work, EZ Defense Gum can help to remove heavy metals from the gums and saliva.

(USA toll-free) 866-800-4677 www.antiaging-systems.com

April/May 2006

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"in just 20-years time there will

health, adopt the holistic

only be 2 people in employment for use of natural substances each retired person!" 20-years time there will only be 2 people in employment for each retired person! Thus, it appears that older people will be a necessary component of the workplace, continuing to contribute to society, if only in order to support themselves. That's another reason why we need a fit, lucid and agile older society. Do we continue as we are? Can we allow an ever increasing elderly population to meet an already stretched health-care budget, and simply increase the numbers of people who are ending their lives in suffering? There are already discussions in the UK about whether or not certain drugs, particularly ones that are expensive and perhaps have a small benefit- should be given to the elderly. These questions have currently been raised in regard to certain senile dementia drugs and cancer drugs. They are likely represent the "thin end of the wedge" and that we are all going to hear a lot more debate and indeed decision on such matters.

Antiaging medicine Whether or not one likes the terminology, antiaging medicine itself represents the ultimate preventative medicine. The model is based upon the very early detection, prevention and reversal of aging-related disorders. The science of antiaging medicine is truly multidisciplinary, for it is represented by advances in the fields of biochemistry, biology and physiology and enhanced by contributions from mind/ body medicine, molecular genetics and the new emerging medical technologies.

The only other answer to population control is a high death rate. Do you wish to live in a society that considers euthanasia necessary, perhaps dependant merely upon chronological age, or maybe a ratio of your health-care cost and age?

Antiaging medicine has its foundation in what Nobel Laurate, Linus Pauling described as orthomolecular. Furthermore, antiaging medicine accepts that aging diseases and disorders can and should be prevented, rather than simply treated. Today there are literally thousands of physicians, scientists and researchers around the world involved in the research and treatment of aging. Huge strides are being made in the understanding and control of the aging process. Our challenge is to bring together the international research, and to utilize whatever molecules and techniques that may be necessary for the long-term health of the patient- according to that science.

Or will we introduce antiaging medicine and revolutionise health-care by concentrating on the true prevention of disease? We could reduce the overall cost of

Ultimately, that means changing the way the patent system and the approval system operates. Big steps. But if we remember to educate and prove to the public that

3; At the end of the day, for those who state; "there are too many people already," one of the answers is a low birth rate. Are we ready for societies that dictate who, when and indeed if you can have children?

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and allow our elderly to live in dignity and self reliance, by remaining lucid and useful to the community at large.

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this is the common sense they have been looking for, then usually no one stands in the way of a ground-up revolution for very long.

enlightened first are compelled to pursue the light in spite of others." We could say the same today about antiaging medicine.

Conclusion

If we too can grasp the fundamental fact that we need to be pro-active about aging instead of just being tolerant of it, then mankind will be able take into its hands the possibility to radically alter the way we think about and approach "health." If we don't allow dogma, vested interests and other imposed restrictions to stand in our way, then the door is already open to us.

We stand at the threshold of a new paradigm, for the first time in history we understand some principles of why we age, how we can measure biological aging and how we can slow and treat its affects. Through the use of lifestyle choices, chelation, nutrition, hormones, drugs and the emerging technologies, we now have the ability to delay, reduce and even prevent the appearance of numerous disorders and diseases. I envisage in the decade to come that thousands of antiaging clinics will be established. People will attend these clinics for regular checks and through the use of biological aging markers, an individual's rate of aging and risk from particular degenerative disease will be measured. Steps will then be taken to slow and eradicate these biological aging signs before they become diseases, and therefore difficult and expensive to treat. In other words, the traditional recognition and diagnosis of disease will change forever. One could consider these aging but otherwise "healthy" individuals attending antiaging clinics, in much the same way as individuals visit the dentist today, for their preventative checks and measures. However, as is usual with all great advances, mankind will probably experience the vested interests of the establishment and dogma, that together- will attempt to slow down, or perhaps even prevent the wide-scale use of antiaging medicine. After his discovery, Christopher Columbus said: "Human progress has never been achieved with unanimous consent. Those who are

References: 1. US Department of Health and Human Services, January 2000. 2. United States Census Bureau. US Department of Commerce, May 1995. 3. American Academy of Antiaging Medicine, www.worldhealth.net 4. De Grey, A. 2004 Journal of Rejuvenation, Mary Ann Liebert Publications. 5. US Census Bureau: www.census.gov/ipc/www/idbp yr.html 6. World Health Organisation Ageing & Health: www.who.int/hpr/ageing 7. Lehman Brothers Equity Research. 8. Association for the advancement of assistive technology in Europe. 9. United States Census Bureau, May 1995. 10. United States Department of Commerce, 1992. 11. The Economist, 3 June, 2000. 12. National Vital Statistics Reports, Vol. 47, No. 20, June 30, 1999. 13. United States Health-Care and Finance Administration, 1996. 14. Physicians for a national health program, June 25, 2003. 15. Life Extension Magazine, May 6, 2002. Life Extension Foundation.


letters Q: As a child I was operated on regularly by the drill-flll-blll brigade of dentists and as a result have numerous mercury containing amalgams. Having recently learnt many of the problems associated with even so-called relatively low dose mercury contamination and recognised many of my own personal issues such as memory below par for my age, lack of energy and irritability, I wish to start a program of amalgam removal. My dentist has recommended it is done as slowly as possible. My question is; is there any method of chelation/ protection I can be doing now and during the removal period? A: We are very pleased to report that one of Britain's leading dentists; Dr. Brian Halverson is joining our advisory team shortly and will be offering advice on all forms of dental health. He, like us, is very concerned about the numerous health-related problems that current dental procedures may be causing, especially ones that lead to the accumulation of heavy metals such as mercury. This is a big problem, especially so for dental staff who are exposed to high levels of contaminants on a regular basis. Indeed, dentists are now in a profession that has one of the highest incidences of Alzheimer's disease. (Remember the expression "Mad as a Hatter" from the Alice in Wonderland book? That came about because the Hatters poisoned themselves by using mercury in the process of shaping the hats). Back to the problem at hand, EDTA (a type of vinegar molecule), allicin (from garlic) and malic acid (from apples) as well as vitamin C, are all excellent oral chelators of various heavy metals. In the case of mercury, which is a particularly difficult molecule to "shift" it can be rendered harmless by the regular use of selenium (found in walnuts) which binds itself to mercury. We believe that chelation, (the removal of heavy metals) is actually a lifelong requirement because we are all exposed to heavy metals through the contamination of air, food and water etc. by industry, (especially the burning of fossil fuels for electrical production).

World chelation expert, Garry Gordon, M.D. has formulated a number of high quality, efficacious products for this purpose. He recommends that 3 capsules daily of his Essential Daily Defense should be taken by everyone everyday. However during the amalgam removal period this could be increased to 6 capsules per day, (this contains all the ingredients mentioned above). In addition, as you have particular concerns of mercury, the ultimate selenium containing product is called Heavy Detox. It may be used 1 capsule, (each capsule contains lOOmcg selenium as well as Succinic acid and Glucuronolactone) per 50 lbs of bodyweight for a cycle of 1-month on, 1-month off. Lastly, a unique chewing gum containing EDTA that is specially formulated for people with teeth amalgams is called EZ Defense Gum. One gum can be chewed after each meal, this helps grasp the mercury released from the amalgam by masticating into the gum. Once the orange flavor is finished the gum should be removed and disposed of and not swallowed, (that would simply take the captured mercury down into the stomach!)

wants to achieve, where their weaknesses lie and what their medical/ family background is etc. Most folks want an improvement to their memory, but we have to go further and ask would that be short term memory, medium term, long term or is the problem one of a lack of concentration or easily induced boredom etc? Consider that if you are not learning new material well then you are less likely to remember it well later, (this is termed memory imprinting). The classic "smart drugs" are piracetam, oxiracetam, aniracetam and pramiracetam. The conclusion of Dr. Mason's article published in the February/ March 2006 Antiaging Magazine was that pramiracetam is the most potent, so that could be the simple answer, but remember that some experimentation is required, both with the product and its dose to find what's best for you. Cost may also be a factor of course, which is why most people usually begin with piracetam- as it is the cheapest. One thing to bear in mind is that combining different/ synergistic

Q: I would like to know, in your opinion what's the best smart drug?

substances can often achieve the best results. Proven substances that often work well alongside those already mentioned are; centrophenoxine, deprenyl, hydergine, phosphatidylserine and vinpocetine.

A: This is a difficult question to answer precisely because there are so many possibilities, including what the patient

Send your questions, letters & comments to: editor@antiaging-magazine.com

April/May 2006

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CREAM Patients tell us their stories of success using a remarkable new cream in the battle against skin cancer

One of the issues we often face with reporting new international breakthroughs in the Antiaging Magazine is that people (including physicians) don't understand that if the treatment is such a breakthrough why either ( I ) it hasn't been reported by the media in their country in a big way or (2) why their own authorities aren't looking at implementing it into general medical practice. There are a number of reasons why that happens, much simply revolves around patents and the approval process, it takes an interested pharmaceutical company with very deep pockets to take on any approval process [Ed. Recent estimates place the cost of approving the average drug in the USA at over a Billion Dollars]. If a product is natural it is extremely difficult to patent, and therefore if a strong patent can't be applied no company is going to inject

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millions of Dollars to start the process, hence it gets dropped by the wayside. As the media is generally lazy and investigative reporting is all but dead, they tend to rely on press releases, which will be released by the pharmaceutical company when a product reaches stage-ll clinical trials. But naturally, if that doesn't happen there are no press releases, therefore there is not a massive generation of interest in product X etc. This is one of the reasons why the Antiaging Magazine exists, to highlight international breakthroughs in all kinds of products and protocols, ensuring of course that the clinical and scientific studies are highlighted. Over the years we've bought numerous interesting ideas and substances to the fore, perhaps two of the most remarkable has

been work of Dr. Mark Babizayev with nacetylcarnosine and the creation of Can-C eye-drops, in which there have been numerous cases of cataract reversal, and also the w o r k of Dr. Bill Cham with BEC5 cream, a natural plant extract that has been clinically proven to reverse nonmelanoma skin cancer. [Ed.- As reported in v5 i6 and v6 i I versions of the Antiaging Magazine], We're aware that general articles and reports of clinical stories, even editorials do not really "bring to life" the personal side of breakthroughs, so listed below are just some of the testimonials and comments that patients have had to say about using BEC5 cream. We hope it gives you an insight into the remarkable difference this product has given for many people suffering with various forms of skin cancer. As May has now been designated "skin cancer awareness month" we thought this was particularly appropriate for this issue.


"I have good news to report. After one month applying BEC5 cream twice a day, the lesion is now 50% covered with new tissue. It took me a while to be able to distinguish the new from the old eschar which needed debridement. I had the help of a doctor for this. It still burns slightly when I apply it but I can deal with that. For the record the original dime sized lesion grew to a scary-looking large quarter size of raw flesh before it started to heal. I did use Neosporin twice for 4 hours only when it was oozing yellow. And I had difficulty keeping it moist when it reached as far as my hairline. But I found that as long as it was totally covered by the Micropore, it was okay. Thank you so much for telling me about this. It is by far the best approach we have to healing

squamous cell carcinoma and keratoses." Marie,

Spain

"I think it's a wonderful product and I am very glad that I discovered where to obtain it.You don't know how much I have worried and stressed over the last year or two about the damage on the side of my nose.

ago tested positive for superficial skin cancer. I have had the lesion for many months and it started as a dry spot. When it became a lesion it would not heal even though the doctor said that it was not cancerous. Your cream worked in less than a week. So even if it is not cancer at least it worked. Thanks." Leif,

It had started to grow very slowly in the past year or so and I knew something would have to be done about it, and I was not looking forward to going to a plastic surgeon to have it removed." Don,

Oregon.

Canada.

"I'm optimistic that BEC5 will heal my B C C on the tip of my nose. I didn't want MOHS surgery, or Effudex as one is invasive and the other is a form of chemotherapy. I prefer all natural!" Ravelle,

Florida.

"The lesion has disappeared. I have an appointment with the skin specialist on Feb. 23.The doctor's test next to the lesion 2 months

May is skin cancer awareness month! BEC5 cream the answer for skin c a n c e r Doctors & dermatologists of highly respected hospitals now advise that skin cancers may not require surgery, chemo or laser therapies!* Dermatologists at the Royal London Hospital recently concluded their stage III clinical studies by saying: "BEC5 is a topical preparation which is safe and effective, an ideal therapy for outpatient...it is a cost effective treatment for both primary and secondary skin cancer." A natural cream with a 78% success rate within 8-weeks BEC5 Curaderm is a glycoalkaloid extract of the Australasian plant, the "Devil's apple" (Solanum sodomaeum).lt has been shown to shown to selectively destroy cancer cells. Over 50,000 patients have already had success with BEC5 Curaderm. "Or. Rino Ceno & Sangesta Punjabi, St Barts Hospital. London (letter on file). "*BÂŁC5 cream applied twice daily, success measured as zero presence of basal cell carcinomas. Note restrictions may apply in some countries. This product and its statements have not been evaluated by the FDA.

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"My dermatologist marked with a pen the two locations.The areas he marked are the areas he said he would remove with surgery if I so elected. I intend to use Curaderm instead." Dennis,Texas.

"The BEC5-Curaderm has helped 3 areas. One A K was always painful to touch and now it's gone and healthy.The second area was a "Liver Spot" and it's almost gone after 2 weeks... very impressive! The 3rd was a black thickened area. Two dermatologists looked at it and were not worried about it (like melanoma!) but they didn't want to treat it either. I have been applying the Curaderm for over 4 weeks and it has resolved remarkably. All the thickness has "sloughed" and there is just a bit of pin-red left. I expect it to be normal in another week or two." Dave,

Ohio.

"The treatment has progressed well.Treated 3 lesions ostensibly fairly superficial, but healthy tissue has grown back so now I have ceased treatment, Many thanks" Allan,

Michigan.

"I have received BEC5-Curaderm and have begun using it exactly as prescribed. I know the info very well as my sister has had great success in using it thus my reason for purchase. W e are very aware of the skin cancer story having had many removed in the past so it is with great thanks that you have made this available to the public." Shirley,

Australia.

"Just want to let you know that I have used BEC5 with great results. Have used it as directed and after 10 days noticed the regrowth of normal skin tissue! I've continued using it twice a day and cannot thank you enough for total success!" Heidi,

California.

"I applied the cream several times and felt no sensation at all. I woke Wednesday morning and found that the wound had dried up and looked like the skin was scabbing over. Saturday morning the scab was completely gone and my nose appeared as if it had been sunburned and was peeling or like a scab had recently fallen off. The skin did not look quite normal but it had the look of a healthy and

healing skin without much trace of the patch of red skin that had worried me for the past 5 years. Within another week everything looked natural again. I know this miraculous lotion really does kill the skin cancer cells." Garla,

"I have finished my treatment for my B C C with BEC5. It has been just over two weeks now and I have been told there is no tumor visible either above or below the skin. I have also had a thermal imaging test done which shows up any activity which has come back clear. I am so grateful to Dr. Cham for developing this cream. Without BEC5 I was facing extensive surgery as the B C C was on the tip of my nose the cost amounting to over $5000 for Plastic Surgery not to mention the scars I would have been left with and more than that the terror and fear I felt when told what my options were.Thank you for giving me back my life. Karen,

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April/May 2006

of therapy (c).

Australia.

Editor: We welcome your comments about any treatment you have undertaken. Please tell us about your experiences and they may become published in a future edition of the Antiaging Magazine.

Clinical diagnosis of a BCC on the nose of a patient before treatment with BEC-5 and the site of treated BCC after completion

Mexico.

cream (a), during therapy (b),


in the news

A r e you getting enough 'D'? Vitamin D levels are now at an all time low due to the use of sun blockers and poor diets. Yet optimal vitamin D levels are vital for strong bones and healthy blood pressure. Beyond Bone Defense, formulated by Carry Cordon, M.D. contains the highest strength of vitamin D - 1200 IU. One capsule can provide a broad spectrum of protection by significantly improving your vitamin D levels. Ignore the circadian clock at your peril In the 10 November 2005 issue of Nature a physiologist at Yale School of Medicine commented on the complex factors controlling the circadian rhythm. From algae to human beings, all living things have built-in clocks that are synchronised to the earth's 24-hour rotation. When deprived of environmental factors, such as being kept in constant darkness, these clocks gradually drift out of synchrony with the earth's rotation. In animals, the clocks that control rest and activity depend on groups of neurons situated in the central nervous systems. An important question is how oscillations of the cellular clocks within the organism are coordinated. Studies of the fruit fly, Drosophila, have revealed two anatomically distinct groups of neurons that independently control morning and evening peaks of activity. When fruit flies are synchronised to light-dark cycles and then released into constant darkness, morning and evening peaks still persist, but run free and gradually drift out phase with the earth's

rotation. An investigation has been carried out into whether the morning or evening oscillator predominates or whatever the two interact to establish a constant phase relationship. It seems that the morning peak controls the evening one, possibly by maintaining an hour-byhour influence. An alternative explanation is that the evening peak is free-running, maintaining its own faster intrinsic period but being reset once a day by the morning surge. It is possible that the mechanism involves a neuropeptide that has been given the name pigment-dispensing-factor and is expressed by morning-peak cells. In the absence of this factor, the evening peak is advanced by some two hours in fruit flies. Whether oscillators in the human brain communicate in a similar fashion is unknown. Obviously, sleeping and waking and the functions they involve are highly important factors in determining a healthy or a hazardous lifestyle. To ignore them is asking for trouble, and our present ideas of a busy life expose us to lurking dangers.

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WHICH THYROID NATURAL OR SYNTHETIC?

Thyroid decline affects every cell in our body, resulting in a wide range of age-related problems , but the question many people ask is which is best - natural or synthetic? Thyroid supplements c o m e in two f o n n s . Whole-natural supplements and synthetic supplements. It is almost always better to use a whole-natural thyroid extract because the synthetic versions usually only comprise of one of the thyroid hormones, (such as, T3 or T4), whereas, wholenatural thyroids cover a fuller spectrum of thyroid hormones (including T 1 . T 2 , T3 and T4). Scientific data strongly supports the idea that a small daily serving of whole thyroid extract as a dietary supplement can have a wide range of positive influences. Studies have shown that those who took 1/4 grain of thyroid combined with minerals and vitamins over a period of 10 years showed significant improvement in cardiovascularprotective function. Just a small regular whole thyroid supplement can raise energy levels, allow clearer thinking and improve bowel function. Natural thyroids such as Armour are preferred by many physicians over the synthetic versions for their more gentle and comprehensive approach to thyroid health. Find out more about the role of thyroids and the different versions available at:

www.antiaging-systems.com/a2z/thyroid.htm April/May 2006 j a m

23 -L


yritinol is perhaps the oldest smart-drug (nootropic) which is still in use- because it has been continuously used and researched in Europe since 1961. There was much published research in the 1980's and 1990's which are a testament to the wide range of uses, safety and efficacy of pyritinol.

P

Pyritinol is almost identical to pyridoxine (vitamin B6), yet it has no B6 activity (4). It has been used in a wide range of disorders, for example, in patients suffering from cerebral trauma (1) and pyritinol has also shown excellent benefit on the clinical course of victims of coma (caused by head injury), helping in many cases to return coma patients to more or less normal waking consciousness (2). What is more, pyritinol has also been used successfully to treat rheumatoid arthritis patients (3). One of the keys to understanding pyritinol's wide mode of action was first revealed in 1989. Two Czech scientists, Drs. Pavlik and Pilar performed sophisticated experiments on 6 nootropic drugs to determine their free radical-quenching power, proving pyritinol to be far superior to the acknowledged antioxidant nootropics. They stated: "There is growing evidence that free-radical interactions are implicated in the pathogenesis of many diseases including radiation injury, atherosclerosis, arthritis, cancer and aging. The most dangerous [kind] of oxygen radicals is the hydroxyl radical that can attack proteins, lipids, nucleic acids and almost any molecule of a living cell. If the production of hydroxyl radical escapes the control mechanisms, then substantial damage to cell functions [and structure] may occur. It was found that pyritinol exerts a pronounced scavenger action against [the worst kind of free radicals] the hydroxyl radicals." (5) It is interesting to note that brain proteins were protected from hydroxyl radical damage by pyritinol in these experiments. 24

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April/May 2006

As will now be explained, the superior hydroxyl radical antioxidant effect of pyritinol is what provides much of its immune, arthritis and neuroprotective benefits. Three of the most common 'free radicals' that are continuously being produced in human cells are superoxide radical (SOR), hydrogen peroxide (H202) and the hydroxyl radical (HR). SOR's are normally produced through white blood cell, germ killing activities, energy metabolism and in many disease states. In fact, "it is believed that the activity of superoxide is at least partly responsible for aging and most if not all degenerative diseases." (6a)

Pyritinol: The ongoing benefits of the oldest smart drug

Fortunately the body has two different enzymes; copperzinc SOD and manganese SOD, to neutralise SOR. SOD converts SOR into oxygen and H202. Whilst H202 is less cell-damaging than SOR, but it is still injurious if it accumulates in cells. However SOD production drops with age. (6b) Although H202 has some uses in the body, (e.g. white blood cells secrete it to kill germs), the body needs to continuously rid itself of H202 and this is highlighted by the fact that our cells possess two completely different enzymes; catalase and glutathione peroxidase, to ensure neutralization of H202. Uncontrolled H202 can damage cell membranes and structures, as well as promote inflammation. The brain is particularly vulnerable to damage by H202 (6c). Unfortunately, under conditions all too common in our cells, SOR and H202 will react with each other. The product of this reaction is a free radical even more damaging than superoxide, it is known as the hydroxyl radical. (6d) To make matters worse, human cells have no enzymatic defence against the hydroxyl radical (HR). It is normally quenched primarily by cholesterol, vitamin C or proanthocyanidins. (6e) (Thus,

the elevated cholesterol levels found in most modern humans may actually be a defensive tactic used by the body to quench the excesses of the hydroxyl radical induced by our toxic modern diet, environment and lifestyles). HR's are so injurious to cells that when huge uncontrollable numbers of them are generated in a person exposed to massive levels of X-ray or gamma radiation, the flesh may literally melt from the bones within hours!


I I

I

the treatment of cognitive disorders." (5) Increased brain cell energy Another key benefit of pyritinol has been known since the 60's, that is its ability to enhance or normalize glucose transport through the blood-brain barrier and also to increase brain cell energy production from glucose (7). In a placebo-controlled, doubleblind study, Hoyer and colleagues examined 87 patients suffering from various brain disorders. Careful measurements of cerebral blood flow, oxygen uptake, glucose uptake and cerebral metabolic rate were taken. Of the 45 patients receiving pyritinol, 27 suffered from disturbed glucose uptake/ cerebral energy metabolism. "Cerebral uptake of glucose, which was reduced to approximately 50% of the normal value, increased significantly with pyritinol treatment and returned to normal. The clinical disturbances generally also improved to the same extent as did the disturbed glucose metabolism." (7) Enhanced glucose transport As Pavlik and Pilar note: "There are clinical reports that support the opinion that pyritinol has a [hydroxyl] scavenger effect. Camus [et al] (1978) and Berry (1986) used pyritinol successfully for the treatment of some cases of rheumatoid arthritis. [Ed.So did Lemmel et al, reporting in 1993. (3)] The protection of cartilage and synovial protein against free-radical induced degradation may be an important factor in the

treatment of rheumatoid arthritis. The same line of reasoning may be applied to some cases of stroke or brain trauma, where the generation of hydroxyl free-radicals is abundant and where pyritinol was successfully used for treatment. The potency of pyritinol to protect proteins in the brain against radical induced polymerization, in conjunction with recent reports that pyritinol enhances cholinergic transmission in the brain, substantiates its use for

Pyritinol's ability to enhance glucose transport through the blood-brain barrier when it is low is a highly significant benefit. Although the brain is usually less than 2% of total bodyweight, the brain must produce and use about 20% of the body's total energy production. Under normal, non-fasting conditions, the brain can only 'burn' glucose for fuel. Unlike virtually all other body cells, nerve cells cannot use fat as a fuel. Brain cells also cannot store any

significant amount of glucose, they are completely dependent upon a continuous delivery of glucose from the blood, through the blood-brain barrier. Thus, brain glucose uptake is a major rate-limiting factor for crucial brain energy production. Low cerebral glucose uptake necessarily translates into low brain carbohydrate energy metabolism. So brain energy metabolism is very important to maintain optimal, healthy brain function and brain carbohydrate metabolism is impaired in a variety of dementias. (8) "The degree of reduction in brain carbohydrate metabolism is correlated with the severity of the dementia." Pyritinol is good for optimal brain carbohydrate metabolism, and hence good for the brain and the mind! Effective immune enhancer A surprising effect of pyritinol was first reported in 1993. Pyritinol can be an effective immune enhancer through its stimulation of neutrophil migration (9). Neutrophils are a major type of white blood cell (WBC), they typically constitute about 60% of the total number of WBC's in the blood. Wherever there is a wound, cut, sore, abrasion etc., neutrophils are attracted to leave the bloodstream and travel to the site of injury/ infection, this is called the process of chemotaxis. Once at the site of injury, neutrophils proceed to engulf germs, especially bacteria that may now be growing at the injury site. Neutrophils then secrete a powerful mix of free radicals and oxidants, such as SOR, H2 02 and hypochlorous acid. These destroy the germs before they can seriously

April/May 2006 i a m

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multiply and overwhelm the body. However, neutrophils sooner or later die "in the line of duty" from their own germ-killing free radical barrage.

pyritinol enhances neutrophil survival through reducing the hydroxyl radical excesses that normally lead to neutrophil death. Another key property of pyritinol is its vigilanceenhancing effect. Pyritinol increases nerve activity in the locus coeruleus (LC). (11) "In humans, the number of neurons in the [LC] declines with advancing age. Degeneration appears to advance slightly faster in males than females. The [LC] is a brain area that is particularly susceptible to neuronal degeneration in Alzheimer's disease. Plus there are many studies indicating a role of this system in control of attention, learning and memory." (11)

One neutrophil averages 5 to 20 germ kills before succumbing. The free radicals that neutrophils release also typically promote inflammation at the site of injury, a process that all too easily gets out of control. Excessive inflammation promotes excessive swelling, tenderness, redness, heat and pain at the injury site. The pus that forms with cuts and wounds is in large part made up of dead neutrophils. In a study with rabbit neutrophils, Elferink and De Koster found that pyritinol, used orally, strongly promoted neutrophil migration to injury site, but did not increase free radical levels or inflammation (9). Given the earlier discussion on pyritinol's antioxidant effects, this differential effect of pyritinol on neutrophil activity, (i.e. increasing migration, but not free radicals or inflammation) becomes comprehensible. When large numbers of neutrophils release huge amounts of SOR and H202, this generates huge quantities of inflammatory, tissuedamaging hydroxyl radicals. Yet pyritinol is a powerful quencher of HR's. Thus pyritinol is able to reduce HRinduced inflammation and tissue damage- the unpleasant side effect that usually accompanies successful germkilling by neutrophils. Immune defence Neutrophils comprise the body's first line of the immune defence as they are normally first to arrive at wound/ injury sites. Yet our modern sugarrich diet has been shown in multiple studies to significantly 26

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EEG Power

impair neutrophil activity. When human volunteers were given various forms and levels of sugar in drinks, the number of germs a neutrophil could kill before dying from its own free radical release typically dropped 50 to 80%! The effect began within one hour of sugar intake, peaked at two hours, and was still significant five hours after sugar ingestion (10). Thus a sugarrich diet literally enhances neutrophil self-destruction, yet

"Pyritinol has also been shown to produce a vigilance response in healthy human volunteers. More recently, using topographic brain mapping of EEG, it has been shown that 600 mg. of pyritinol resulted in an increase of changes indicative of improved vigilance. Specific studies of the effects of pyritinol on memory using a battery of seven tests have shown that repeated daily doses of pyritinol 300 mg. improved memory performance over a wide range of measures in volunteers aged from 16 to 66 years." (4) Who might benefit? 1. Pyritinol may be useful in various forms of dementia, organic brain syndrome, head injury, stroke aftermath, coma, and cerebral circulatory disorders. Vinpocetine, piracetam and phosphatidylserine may be useful synergists with pyritinol. 2. Pyritinol may be useful as an anti-brain aging nootropic


drug. 3. Pyritinol may be useful as an aid to increased focus and concentration, memory, alertness and information processing in both young and old, normal or mildly brain dysfunctional persons. 4. Pyritinol may be useful in Attention Deficit Disorder (ADD), hyperkinetic, or mildly retarded children to increase drive, alertness, concentration and learning ability. (12, 13)

reversible." (3) However, they also note a general trend in the pyritinol-arthritis literature of about 2% potentially serious adverse effects involving blood, kidney or liver, which makes it important for regular monitoring of liver enzymes, urine status and blood cell status when using pyritinol to treat rheumatoid arthritis. Therefore, pyritinol should be used in rheumatoid arthritis treatment only with the knowledge and supervision of a physician.

2. G. Dalle Ore et al (1980) "The Influence of the Administration of Pyritinol on the Clinical Course of Traumatic Coma", J Neuroserg Sci 24, 1-8. 3. E.-M. Lemmel (1993) "Comparison of Pyritinol and Auranofin in the Treatment of Rheumatoid Arthritis" Br J Rheumatol 32, 375-82. 4.1. Hindmarch et al (1990) "Psychpharmacalogical Effects of Pyritinol in Normal Volunteers" Neuropsychobiol 24, 159-64. 5. A. Pavlik & J. Pilar (1989) "Protection of Cell Proteins Against Free-Radical Attack by

5. Pyritinol may be useful as part of a health-optimizing antioxidant program, along with vitamins C and E, selenium, zinc and lipoic acid. 6. Pyritinol may be useful in the treatment of rheumatoid arthritis. In a large, double blind yearlong trial comparing pyritinol to a standard antirheumatoid drug (Auranofin), the response rate was superior for pyritinol (78% vs. 59%, at one year). "Every individual efficacy parameter showed a numerical trend for better results in the pyritinol group." (3)

Doses

Nootropic Drugs: Scavenger Effects of Pyritinol Confirmed by

A wide range of doses have been used in pyritinol studies. These have ranged from as low as 100 mg. twice daily (12) to 200 mg. three times daily (14) or 200 mg. four times daily. (15) For anti-aging, cognitionenhancing or antioxidant purposes, 100 mg. pyritinol two or three times daily is generally safe and adequate. Higher doses (400 mg. to 800 mg. daily) should probably be used only with physician supervision, just to err on the safe side.

Electron Spin Resonance Spectroscopy" Nueropharmacol 28, 557-61. 6. R. Bradford & H. Allen, Oxidology, Chula Vista, CA: R.W. Bradford Foundation, 1997. A:p.65 B:p323 C:p.l42 D:p.66 E:p.l75. 7. S. Hoyer et al (1977) "Effect of Pyritinol-HCL on Blood Flow and Oxidative Metabolism of the Brain in Patients with Dementia" Arzneim Forsch/Drug Res 27, 671-74. 8. R. Branconnier (1983) "The Efficacy of the Cerebral Metabolic Enhancers in the Treatment of Senile Dementia" 19, 212-19.

Side-Effects Most published studies on pyritinol report few if any side effects, with skin rashes and/or gastric upset occasionally noted. E.g. "In general, the tolerability of the drug was good. Practically no problems occurred during the trial. None of the reported symptoms were rated as serious nor persisted over a long period of time." (14) "No undesirable side-effects were observed." (13) "There were no significant differences in the incidence of adverse reactions in the drug and placebo group. No significant changes were observed in any [clinical laboratory] parameters." (1) The one major exception to pyritinol's low side-effect profile occurred in the largescale rheumatoid arthritis trial. The authors note that pyritinol side effects "were mostly nuisance events, which led to stopping therapy [in rare cases], but did not constitute a health risk for the patient and were fully and rapidly

Pyritinol may be taken either on empty stomach or after food, as desired. Persons only prone to insomnia should probably only take pyritinol morning and early afternoon. There may be a mutual enhancement of action between pyritinol and other nootropic drugs, allowing/ requiring lower doses of some or all the drugs in order to avoid an over-excitation effect.

9. J. Elferink & B. de Koster (1993) "Differential Stimulation of Neutrophil Functions by Pyrithioxine" Int J Immunopharmac 15, 641-46.

the Supergerms", NY: PocketBooks, 1997. Pp.124-27. 11. H.-R. Olpe et al (1985) "Locus Coeruleus as a Target for

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Acad Sci 444, 394-405. Effects of Pyrithioxine on the Behavior and Intellectual

Pyritinol has a very long established and well tested history. The fact that it displays immune enhancing, antioxidant, anti-arthritis, antiinflammation effects, as well as its memory/ cognitive enhancement benefits, with few contraindications and minor side effects, makes it a extremely beneficial indeed almost holistic aid, all in spite of its own old age!

3, 323-27.

References

(1980) "A Placebo-Controlled

Functioning of Learning-Disabled Children" S.Afr Med J 48. 224546. 13. D. Lane O'Kelly (1975) "Pyritinol in the Treatment of Chronic Alcoholics" J Int Med Res 14. K. Fischhof et al (1992) "Therapeutic Efficacy of Pyritinol in Patients with Senile Dementia of the Alzheimer Type (SDAT) and Multi-lnfarct Dementia (MID)" Neuropsychobiol 26, 65-70. 15. A. Cooper & R. Magnus Study of Pyritinol ('Encephabol')

1. K.Kitamura (1981) "Therapeutic

in Dementia"

Effect of Pyritinol on Dequelae of Head

Pharmatherapeutica 2, 317-22.

Injuries" J Int Med Res 9, 215-21.

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12. G. Logue et al (1974) "The

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interview

i The C DJjrJjjrJ OJJ coMwectitjiJS b et w e y jj body mass, J uiJ iJ j_rJ j_rJ iJ cJ jJ.j jjjsijJjij and ;J £j JJJ ^J £jj 3 £*£]£>=*:

Karen Sadowsky Kaufman is a forthright nutritionist with a keen and open mind, as well as a passion for research. Her alternative perspective, bom from experience of her own personal needs as well as those of her patients, combined with a thirst for knowledge, has meant she has also worked alongside highly respected physicians and researchers. Her expertise gives Karen a unique and fascinating insight into numerous health problems. In this interview she outlines the issues of inflammation, insulin and their roles in diseases and weight control.

A A M : Karen, can you please tell us about your credentials? Karen: Certainly. I have a Master of Science degree f r o m the University of N e w Haven in Connecticut. I have worked in the nutrition and antiaging field for the past 10 years and have had the privilege o f working with James South and Ward Dean, both of w h o m I consider to be mentors. A A M : W h y did you choose this particular area of specialization? Karen: I actually developed a serious chronic illness in 1991. Initially, 1 did not get a diagnosis, but f r o m the start it w a s clear I had developed some sort of a u t o i m m u n e , inflammatory, connective tissue disease. That disease w a s systemic lupus erythematosus (SLE). I w a s extremely debilitated by unremitting fatigue, severe pain in nearly every joint and intermittent 'brain fog.' I realized 1 could not continue in my career which required a lot of energy. I had always been interested in health and nutrition, so I went back to school to pursue a professional degree. In addition, at the time I w a s diagnosed with this a u t o i m m u n e disease, the treatments that conventional medicine had to o f f e r were in many cases worse than the disease itself! I was searching for novel and non-toxic w a y s to recover m y health. This w a s how I b e c a m e interested in innovative groups such as IAS, because it w a s clear the disease was attacking my central nervous

Interviewed by Phil Micans

system- so I needed to avail myself of every possible 'smart d r u g ' and nutrient to preserve my brain function.

28

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April/May 2006


diabetes. Type-I diabetes was previously AAM: How did you go from that personal

known as juvenile onset diabetes. Type-II

interest to the broader concerns you have

diabetes was known as adult onset diabetes

today?

since it previously affected people at mid-life or later. So many overweight children were

" many chronic illnesses and diseases of aging are caused by inflammation"

Karen: I began recovering my health through

developing 'adult onset' diabetes, which is

targeting the chronic inflammation in my

really a disease of excess glucose and

body with diet, exercise, supplements and

insulin, so the disease had to be renamed. I

this hypothesis was a University of

'smart drugs.' Inflammation is at the root of

am extremely concerned about this.

California Los Angeles School of Medicine

so much 'evil' and we are now learning that

The person that is best known for asserting

professor of pathology, Roy L. Walford,

many chronic illnesses and diseases of aging

AAM: What troubles you the most about

M.D. He wrote Maximum Lifespan, Beyond

are caused by inflammation, i.e. heart

this situation?

the 120 Year Diet, and The Anti-Aging Plan.

Karen: Basically an overweight child is

experiment of the 1990s.

disease, cancer and the complications of diabetes.

Perhaps he is best known for the Biosphere much more likely to become an overweight

Today, many more physicians and scientists

AAM: Tell us why do you want to speak

adult. Some statistical algorithms suggest if

are asserting that calorie restriction (CR)

out about the issue of obesity at this

we stay on this same path, one in two

might extend life in a laboratory setting in

particular point in time?

children alive today will develop type-II

animals, but it is premature and possibly

diabetes by the time they reach adulthood. It

even dangerous to assume that CR can work

Karen: It's an interesting story. When 1

is not just the diabetes that is the problem. It

in the real world amongst humans.

finished graduate school, 1 vowed to be a

is the micro and macro vascular

Before 1 get into the details, I must mention

nutritionist that did not focus on weight loss,

complications that go along with it, things

the obvious. It is very difficult to test this

primarily because diets have a failure rate of

such as blindness, specifically retinopathy,

hypothesis in humans. It is impossible to do

93% or more. Today 1 feel I no longer have

peripheral neuropathy, limb amputations and

a 'double blind placebo controlled trial' when it comes to nutrition. The studies

that luxury because there is a pandemic of

heart disease. It's well known that diabetes

obesity. Diets may not work by themselves,

speeds up the aging process. It's the excess

involve a small number of people. Non-

but there are lifelong strategies people can

glucose and excess insulin that really causes

believers would most certainly find hundreds

adopt to preserve their health and quality of

the body to breakdown from the inside out.

of flaws in the research. But, personally I

life while simultaneously extending their

But the tragedy is that diabetes is a largely

find the results very intriguing. I think the

lifespan.

avoidable disease, but we must make

AAM: What prompted your change in

some dramatic

focus?

changes to our lifestyle.

Karen: The results of some provocative studies have recently made the headlines.

AAM: You

They may seem quite opposite at first glance,

mentioned some

but they are connected in some very

recent studies

important ways. The first involves the

were published

epidemic of obesity. The second involves

that suggest there

some intriguing results from the first ever

may be a way to

trials that have examined the affect of calorie

truly extend life.

restriction (CR) in humans.

Can you tell us more about that

AAM: Could you please give our readers

research?

some specifics? Karen: Yes, Karen: The most astonishing headlines relate

although some say

to the number of overweight individuals in

calorie restriction

the US, as well as the rapid rise in the

may not result in a

prevalence of obesity. Today, two-thirds of

longer life, but it

adults in the US are overweight or obese. An

will feel like it!

individual who is overweight or obese is at

AAM: Ha ha!

risk for developing some diseases that may

Karen: No

not necessarily shorten one's lifespan, but

seriously, for the

these diseases certainly affect one's quality

last six decades

of life. I am talking about diseases such as

researchers have

type-II diabetes, heart disease and cancer etc.

been extending the

Obesity is affecting children and adolescents

lives of laboratory

as well. The increase in the number of

rats, insects and

overweight/ obese children and adolescents

worms by reducing

prompted the medical profession to rename

their caloric intake.

Improve memory, vigilance and concentration with

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April/May 2006 i a m

29


interview

"preliminary evidence that calorie restriction can extend life in humans" studies provide preliminary evidence that calorie restriction can extend life in humans as well. AAM: I know you are excited about this new data. With the above caveat, are you ready to share the specifics with our readers? Karen: Absolutely. The first study was published in January, 2006 in the Journal of the American College of Cardiology and was the result of research undertaken at the University of Washington in St. Louis by Luigi Fontana, M.D, PhD. There are a number of people around the USA who have been voluntarily practicing CR. While they do restrict their calories, they work hard to eat a nutrient dense diet. Their diet avoids empty calories, particularly calories from white flour and sugar. The researchers looked at 25 individuals between the ages of 41 to 65 who had been reducing their calories to 1,400-2,000 calories per day for six years, and compared them with individuals who consumed the average American diet which is 2,000-3,000 calories per day. The study looked at heart function as a measure of 'primary aging.' Although people in the calorie restriction group had been eating a low calorie diet for only six years, their heart function, when compared to the control group, resembled the heart function of people 15 years younger. In the case of the group practicing calorie restriction, many of the subjects had parents, grandparents or siblings who suffered heart attacks or strokes. That makes it unlikely that the CR group had a more favorable genetic make up. Some subjects had actually been taking medication for high blood pressure before starting the CR plan. Other biomarkers for aging were lower in the members of the Caloric Restriction for Optimal Nutrition Society (CRONS). These markers included markers of inflammation such as C reactive protein (CRP) and tumor necrosis factor alpha (TNFa). Previously, these researchers had found that people on the very low calorie diet had low blood levels of cholesterol and triglycerides, blood pressure scores equivalent to much younger individuals, a lower risk of developing diabetes and reduced body fat. The findings taken together suggest that the people practicing calorie

30

i a m

April/May 2006

restriction have a longer life expectancy because they are more likely not going to die from a heart attack, stroke or diabetes. This suggests the quality of their life will also be better. Members of CRONS try to consume between 10% and 25% fewer calories than average Americans while maintaining proper nutrition. Accordingly, their diet resembles the Mediterranean diet. This published study was the first of many studies examining members of the CRONS. The research was supported by a number of organizations including the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institute of Health. AAM: That sounds like extremely detailed and interesting research. You mentioned a different area of investigation. Can you tell us more about that? Karen: Yes. The results of another investigation, called the Comprehensive Assessment of the Long Term Effects of Reducing Intake of Energy (CALERIE) study, were published in the April 5, 2006 issue of the Journal of the American Medical Association. This study recruited 48 middle aged overweight, non-obese men and women and randomly assigned them to one of four diets: control (weight maintenance diet); CR (calorie intake reduced by 25% of normal); CR with exercise (calorie intake by 12.5%, energy expenditure increased by 12.5%); very low calorie diet (890 calories per day until 15% weight loss, then weight maintenance diet). The study was conducted at Pennington Biomedical Research Center, Louisiana State University, Baton Rouge. After six months, the control group lost about 1 % of their body weight. The three intervention groups all lost significantly more weight (as expected). The CR group and the CR plus energy expenditure group lost about 10% of their body weight. The very low calorie diet group lost 14% of their body weight. However, weight loss was not the primary focus of the study and positive results were observed for markers of aging. The lead author, Leonie Heilbronn, M.D. stated: Our results indicate that prolonged calorie restriction caused a reversal in two of three previously reported biomarkers of longevity, (fasting insulin levels and core body temperature)...and a reduction in DNA fragmentation, reflecting less DNA damage. As one of the most widely held theories of aging is that free radicals AKA reactive oxygen species- assault DNA, which therefore affects normal cell function and


interview potentially leads to cancer, this makes sense. Another related theory of aging suggests the excess blood glucose causes the 'sugaring or browning' of all cells and all cellular function is compromised. This is one of the main reasons diabetes and metabolic syndrome causes so much morbidity and mortality. There have been extensive studies in animals, including mice. In 2004 researchers established that CR even when started in late middle age in mice, significantly extended life. So it may never be too late in life to begin CR and reap the health benefits. In 2005, a study in mice suggested one mechanism of the anti-aging affect of CR is the increase nitric oxide (NO). NO is so important in relaxing the walls of blood vessels and preventing that hardening of the arteries. So here we are beginning to understand that CR works on several important mechanisms to improve both quality of life and longevity. AAM: That's all very interesting Karen, but what does that mean for the general population, and those of us who are interested in optimal health and longevity? Do we all have to be thinking about near starvation?

"Preventing those spikes in glucose and insulin is also the best way to prevent diabetes, metabolic syndrome, overweight/ obesity, heart disease, stroke and cancer"

Karen: Don't get me wrong, this is not a call for everyone to go on a very low calorie diet. Scientists would say the evidence is only preliminary and the studies were very small. Be aware that a very low calorie diet can lead to malnutrition. Those interested in this lifestyle change should make sure they do a lot of reading and get the advice of a qualified nutritional professional. Let me read you part of an editorial that appeared in the New York Times on Sunday, April 9, 2006, Frank Bruni writes: If living to 99 means forever cutting the porterhouse into eighths, swearing off the baked potato and putting the martini shaker into storage, then 85 sounds a whole lot better, and I'd ratchet that down to 79 to hold onto the Haagen-Dazs, along with a few shreds of spontaneity. It's all a matter of priorities. AAM: So I guess the obvious question is: is there any way of having the cake and eating it too? Karen: My answer is a resounding yes. But it takes some strategizing. CR prevents spikes in both glucose and insulin. Preventing those spikes in glucose and insulin is also the best way to prevent diabetes, metabolic syndrome, overweight/ obesity, heart disease, stroke and cancer. The good news is that there are things known

as calorie restriction mimetics; Metformin is the best known and it also has the longest history of success. Currently Metformin is prescribed (Ed.- off label) to help prevent diabetes in susceptible individuals. I see no reason why it shouldn't be taken almost like a vitamin at this point. Acarbose is also a drug being used to prevent type-II diabetes in the prediabetic population. Acarbose is a substance that blocks the absorption of refined carbohydrates thereby preventing the spike in glucose, which would then be followed by a spike in insulin. In 2002, David Sinclair, M.D., professor of pathology at Harvard Medical School, claimed that he and a team of researchers discovered a way to genetically mimic the life-extending effects of CR, without the severe food deprivation. His studies were done in yeast and focused on the Sir2 protein. Later, he and his team asserted that the compound; resveratrol- a key antioxidant found in red wine and other substances, can slow the aging process without CR. Of course, it is important not to overeat and maintain an active lifestyle. But there are other natural products that have shown the ability to regulate blood glucose and insulin. The best of these 'weight loss' products contain the important minerals chromium and vanadium. In addition, green and black tea extracts can help boost metabolism. Cinnamon extract, gymnema sylvetra extract, and bitter melon extract may have a certain synergy that can assist in weight loss. AAM: Karen, you've discussed a lot of important and fascinating information here. Is there anything you'd like to conclude with? Karen: Phil, I'd like to thank you for letting me present what I consider to be some critical health and longevity issues. The data at this point is suggesting that CR may indeed extend life while maintaining health and vibrancy. But that means one has to start thinking about eating to live, rather than living to eat. Eating after all, is one of life's greatest pleasures. You know I am a huge believer in the health enhancing power of the right foods along with an active lifestyle. I am also a realist. My guess is many people are interested in reaping all the benefits of CR, but few will be interested in the arduous lifestyle changes required. I commend organizations such as IAS for making available some important pharmaceuticals and nutrients that may well mimic CR. AAM: Thank you Karen, as always it's a pleasure to talk with you. April/May 2006 i a m

31


I

t is now well established that the

protein

process of glycosylation is

cross-linking,

one of the most important

but also protein-to-

causes of aging, perhaps equally as

DNA, or protein-to-lipid

important as the process of oxidation (free

cross-linking, which is equally

radical damage). During everyday

damaging to the organism. Recently, a

metabolism, sugar molecules (such as

condition called 'carbonyl stress' has been

glucose and fructose), and reactive

described. It involves increased levels of

aldehydes and/or ketones may attach to

reactive carbonyl compounds which make

free amino groups on proteins, a process

cross-linking much more likely (1).

inflammatory cytokines such as Tumor

called non-enzymatic glycosylation (glycation). This reaction is also sometimes called the Maillard reaction. It results in a glycated protein, i.e. a protein carrying sugar (or similar) molecules on it. This glycated protein (also called an Amadori product) may then react with any other proteins resulting in irreversible bonding between the two. This bonding process is

Necrosis Factor alpha Cross-linking results in formation of large (TNF-a) and insoluble aggregates of damaged proteins in the tissues. These aggregates have been named A G E s (Advanced Glycosylation interleukin 6. In End products) (or 'post-Amadori addition, some A G E s products', or 'glycotoxins') and are immunogenic (causing may then go on to age-related auto-immunity) or interact with free mutagenic (increasing the risk of cancer),

named 'cross-linking'.

radicals whereas others increase the activity of

Affected molecules can be anything from

and

collagen and elastin, to enzymes and

cause further

immunoproteins. Facilitators during crosslinking are the carbonyl groups which act

tissue injury, through chronic oxidation.

like glue, fixing the two proteins Although a steady rate of A G E together. Carbonyls are chemical formation happens as a result of normal groups which are formed aging (starting after the age of 20), as a result of a sugar formation of A G E s is accelerated during (or an hyperglycemic states such as diabetes. aldehyde or a ketone or a

Copper, iron and other metals may hasten

adhesion molecules, reduce protein degradation rate and reduce cell proliferation, all of which ensure that the risk of degenerative disease is increased. Also, A G E s stimulate apoptosis, resulting in excessive loss of cells and contributing further to the risk of degeneration. Some A G E s up-regulate genes which are involved in chronic inflammation reactions.

A G E formation.

free radical) reacting with aminoacids on a protein. In

At the clinical level, cross-linking Once formed, A G E s inhibit cellular

addition, carbonyls

contributes significantly to diabetic transport processes, stimulate cells to

can be formed in other situations

complications, lower immunity and produce more free radicals (such as increased risk of cancer, atherosclerosis

involving lipids or DNA so they are not superoxide and nitric oxide), and activate necessarily restricted to proteins. So, carbonyls may cause not only protein-to32

iaitl

April/May 2006

and hypertension, Alzheimer's disease


crosslinking but also against protein-to-DNA crosslinking (6).

Another important carnosine activity is anticrosslinking effects.

'carnosinylation', which is a process whereby carnosine attaches to the protein bearing a carbonyl group, thus blocking the carbonyl from attaching to another protein.

Other not yet widely available inhibitors are Tenilsetam, OPB9195,

It is just like placing a piece of paper (carnosine) between two proteins bearing

phenazinediamine (2,3-

glue (carbonyls). In other words, carnosine

diaminophenazone), and many others still

reacts with carbonylated proteins to form

in development (4).

carnosine-carbonyl-protein adducts. These

Many cross-link inhibitors are nucleophilic

adducts are then removed by proteolysis

traps, (scavengers) for reactive carbonyl

and degradation. Conveniently, carnosine

intermediates. They are also copper

also stimulates and enhances the process of

chelators, and so they minimize the risk of

proteolysis (7).

(through the formation of amyloid, which is a type of AGE), cataract, kidney damage, skin aging, and other age-related diseases (2). both cross-linking and consequent AGErelated damage. In addition, they block The process of cross-linking through glycation was hitherto thought to be irreversible, and this was one typical example of the immutability of aging. There are hundreds of compounds aimed at preventing cross-linking, but during the past few years, new products have also been developed directed specifically at breaking the abnormal bonds between

soluble receptors (sRAGEs) or specific receptors (RAGEs) which recognize AGEs. Some soluble receptors circulate freely, whereas specific ones can be found on macrophages, fibroblasts and endothelial cells. When an A G E molecule interacts with a R A G E it forms an adduct which is then prone to create more damage through

Carnosine has a direct antioxidant action, and it also has a sparing effect on other antioxidants such as glutathione. It is a strong chelator of copper thereby reducing the copper-mediated damage during A G E activity. Finally, it has a possible, yet unconfirmed, bond-breaking capability by dissolving certain bonds (S-S bonds) on cross-linked proteins.

oxidation and increased metal toxicity.

already cross-linked proteins, practically At the clinical level, carnosine reduced

reversing protein aging (3). Both classes of drugs, the cross-link inhibitors and the

Carnosine

glycosylation metabolism in humans (8).

cross-link breakers, have been found to offer remarkable benefits at the clinical level.

The dipeptide carnosine (beta alanyl- L-

One of the most important developments

histidine) is a naturally-occurring agent

regarding carnosinc is its ability to

found in muscle and nervous tissue (5).

prevent and cure age-related

Carnosine has been hailed as one of the

cataract, and possibly

most promising cross-link inhibitors. It has

glaucoma and

multiple actions and as such it has been

other

Cross-link Inhibitors

There are several commercially available inhibitors of cross-linking. Examples of these include carnosine, aminoguanidine, metformin, acarbose, and pyridoxamine. Some of these (like acarbose and metformin) are already in use as antidiabetic drugs but new research coming to

urinary products of free radical and

called a pluripotent agent. One way carnosine works is by scavenging for free carbonyl groups. Carnosine is one of the few cross-link inhibitors that is not only active against proteinto-protein

light is now emphasizing their additional

April/May 2 0 0 6

i a m

33


3 of the best cross-linking inhibitors available Carnosine Aminoguanidine Pyridoxamine Carnosine 50 x 100mg caps $19.95

age-related eye conditions (9). In this

(12). Methylglyoxal, and the related

respect the form of carnosine used is N-

compound, glyoxal, are both reactive

acetyl-carnosine. This curative action of

carbonyl agents (alpha-dicarbonyls) which

carnosine is perhaps related to its ability to

are blocked by the quanidine molecule,

stimulate proteolysis and thus dissolve

(remember that metformin is a guanidine-

protein aggregates in the lens.

containing drug). Specifically, the guanidine moiety of metformin combines

People taking 50 mg. to 300 mg. of

with methylglyoxal dicarbonyls to form

carnosine a day have not reported any side

guanidine-dicarbonyl adducts which are

effects whereas those taking higher doses

then eliminated from the tissues (13). With

(1000 mg. to 1500 mg. a day) have

reduced amounts of carbonyl groups in the

reported occasional histamine-related

tissues, the likelihood of cross-linking is

allergic reactions.

reduced. This mechanism of action is similar to that of aminoguanidine (below),

Camosine

which, as the name suggests, it is also a

Metformin

guanidine-containing molecule. Metformin (brand names Glucophage,

Aminoguanidine

Aminoguanidine 1 0 0 X 75mg tabs $24.95

m m m s K

Metforal) is a standard anti-diabetic drug

More recent experiments show metformin

(dimethyl-biguanide) used worldwide both

to have widespread activities as a cross-

against insulin-dependent and against non-

link inhibitor. It reduces cross-linking of

insulin-dependent diabetes. Although it is

fibrin proteins which take part in the

used primarily to increase peripheral

clotting of blood. Exaggerated cross-

sensitivity to insulin and lower blood

linking of fibrin results in abnormal blood

glucose, metformin has several other

clotting and therefore an increased risk of

important actions which are not yet

thrombosis with consequent myocardial

appreciated by many physicians.

infarction or stroke. Metformin reduces

Pyridoxamine

Pyridoxamine 60 x 50mg tabs $24.95

fibrin cross-linking and therefore, Metformin lowers cholesterol, reduces

ultimately, reduces the risk of thrombosis

body fat, stimulates antioxidant defenses

(14).

(10) and it is also an effective inhibitor of glycation. It reduces the formation of

In summary, with regards to glycation,

AGEs, particularly those affecting

metformin has a dual effect- it lowers

It is now well established that the

collagen. In that respect, it prevents

blood glucose, and as new research is

process of glycosylation is one of the

diastolic stiffness in the myocardium of

revealing, it is an effective inhibitor of

most important causes of aging, perhaps

diabetic dogs (11). It has direct anti-

cross-linking through carbonyl

equally as important as the process of

glycation effects and improves cross-

trapping.

oxidation (free radical damage).

linking induced damage to nerves in

Cross-linking is the process that causes

diabetic rats. Its main mechanism of action

Metformin should be

food to turn yellow and become tough

is its carbonyl trapping ability, as will be

used under

with age. Similarly with humans, cross-

explained below.

medical

linking may be responsible for many of

M

the problems of old age, including senile cataracts, thickening of the arteries, some cancers and damage to the immune system.

To order call: +1-866-800-4677 ROW +44-208-123-2106 www.antiaging-systems.coni

34

i a m

April/May 2006

^MpMM

In a clinical trial examining 57 people with type 2 diabetes, treatment with metformin was shown to rcduce the concentration of methylglyoxal in a dose dependent

<|

l


supervision with monitoring of the liver

tendons

and kidney function. The dose is 500 mg.

and skin

twice to three times a day. Dr Ward Dean

which shows its

recommends that everybody who is over

potential for prevention of

the age of 40 should be taking metformin,

muscle and joint age-related

and research into the anti-glycation

stiffness, and skin aging wrinkles. (16) It

benefits of metformin supports this

limits the development of diabetic

recommendation, as a preventative anti-

complications in animals and it has shown

nausea

AG E drug.

promising actions in improving diabetic

or headache.

nephropathy in double blind human trials

There are two main

(17). In addition, it is a weak copper

varieties of

chelator. Copper chelation is important in

aminoguanidine, the hydrochloride

An agent structurally similar to metformin

A G E induced damage, as high amounts of

and the bicarbonate variety. Although the

is aminoguanidine, (sometimes called

free copper are more likely to increase

bicarbonate variety is more commonly

Pimagidine) which has been studied

AGE-induced injury.

available, the hydrochloride version is

Aminoguanidine

relatively extensively and the reports have been encouraging. As with the case of metformin, aminoguanidine is also a guanidine-containing agent, and it therefore acts as a carbonyl trapping agent (15).

Aminoguanidine prevents cardiac enlargement in animal studies by reducing the risk of

5

O %

cardiac collagen. Also, it prevents cross-linking between

2

0.5

ÂŁ

5 S

fat molecules) and therefore

reducing the numbers of free carbonyl

reduces the risk of blockage of

groups. In particular, it is active against

the arteries, particularly the

certain aldehydes which contribute to

small arteries that feed the

cross-linking, (e.g. alpha-oxoaldehyde, and

nerves (18).

1=

H â&#x20AC;˘

1 Pyridoxamine

1 1 l20

40

Aminoguanidine 60

80

100

% labeling

It is such a strong carbonyl scavenger that

It is an effective inhibitor of cross-linking

small quantities, are necessary for the

initiated by glucose molecules, but not as

normal functioning of the metabolism).

effective in situations involving

This can, on rare occasions, give rise to

cross-linking

Pyridoxa!

1

In vitro c o m p a r i n g t h e f o r m a t i o n of A G E s on bovine s e r u m a l b u m i n w h e n exposed to glucose. N o t e t h e d r a m a t i c r e d u c t i o n w h e n a m i n o g u a n i d i n e or p y r i d o x a m i n e are a d d e d , (khatami, et al. Life Sciences, 1988)

removal of carbonyl groups (which, in

prevents collagen

DHA

1

it can sometimes result in excessive

any case, Aminoguanidine

Vitamin C

1

0

malondialdehyde). Aminoguanidine is

ribose-related cross-linking. In

Control

1

1

5

* 5 U 0.1

lipoproteins, (proteins carrying

1 1

10

glycation-induced damage to

guanidine-dicarbonyl adducts, thereby

glycosylation.

o

-0.1 nr

Aminoguanidine too works by forming

active mainly during the early stages of

S A

believed to be the most active (bioavailable) as it is more soluble. Aminoguanidine may be used together with carnosine which is active both in early and late stages of glycosylation, or together with metformin, particularly in diabetics.

toxicity particularly if aminoguanidine is used in excessive doses (over 600 mg.

Acarbose

daily without medical supervision). In theory, the concomitant use of

Another drug used in diabetes, Acarbose

pyridoxamine (see below) can reduce the

(Glucobay) is an alpha-glucosidase

likelihood of this potential problem.

inhibitor. Alpha-glocosidases are enzymes which facilitate the breakdown of complex

The dose is 150 mg. once or twice a day, but diabetics may use double this dose. Side effects are rare and mild and include

carbohydrates, (such as starch) into smaller sugar molecules which are then absorbed through the intestinal wall. Acarbose blocks this, therefore inhibiting the absorption of certain sugar molecules such as maltose and sucrose, while allowing the absorption of glucose and lactose, which

April/May 2006

iaill

35


III*. are needed for energy. In this way the overall absorption o f carbohydrates is reduced and this lessens the risk o f glycation-induced damage and A G E

possible mechanism could be its ability to protect the glomerular

formation.

membranes, (where filtering Acarbose's main activities include a reduction o f blood lipids (reduced uptake

urine takes place in the kidney) against the effects of cross-linking (22).

of triglycerides), an aid to weight loss, as well as being an important anti-glycation activity (19). As with the case o f metformin, acarbose has hitherto been used primarily to reduce blood glucose and therefore improve the symptoms o f diabetes. However, new research is unraveling its anti-glycation properties which are in addition to its glucoselowering actions. For this reason, acarbose is not only indicated for treatment of diabetes, but also for treatment of diabetic complications and other AGE-related

Acarbose is safe but it may have side properties effects such as abdominal pain and cramps, (28). It is most bloatedness and diarrhea. These are due to effective in the later excessive amounts of unabsorbed stages of glycosylation and carbohydrates in the bowel. The usual dose therefore, for full protection, it is 50 mg. to 100 mg. daily but the may be used together with maximum should be kept to 300 mg a day aminoguanidine which is active in the early to prevent these side effects. For greater stages of glycosylation. In fact, comparison benefits, it may be worth using acarbose studies with aminoguanidine suggest that, together with other cross-link inhibitors although both are effective against AGEs, such as carnosine. (Ed.- Acarbose is best pyridoxamine may be a more versatile taken by chewing the tablets, usually just agent to use against glycosylation, in order before or during meals).

damage.

to avoid the low risk o f potential toxicity problems with aminoguanidine mentioned

Several studies have shown that Acarbose

Pyridoxamine

above (29).

reduces the formation o f glycated proteins (including the glycated hemoglobin A l e which is a marker for diabetes). Animal models show an ability o f acarbose to slow down the rate o f protein glycation and delay renal, brain and eye complications o f

There are three different vitamers o f Pyridoxamine does not affect the levels o f Vitamin B6: pyridoxal, pyridoxine (the blood glucose. It inhibits both form traditionally used in supplementation) methylglyoxal and glycoaldehydes which and pyridoxamine. All of these are are most active following lipid naturally occurring. Pyridoxamine is found peroxidation. It forms methylglyoxalin animal sources, whereas pyridoxine is

diabetes (20).

pyridoxamine dimers which are inactive also found in plant sources. All three and eliminated easily (30).

Other studies confirm its effectiveness in protecting against nephropathy, neuropathy I retinopathy in diabetes, by its ability i lower A G E formation (21). With ^regard to the kidney^protecting effects of

variants have a certain degree of anti-crosslinking actions, but pyridoxamine is the strongest and most significant o f the B vitamins. Trials are in progress to evaluate the product's safety and efficacy in preventing diabetic complications.

from using very high doses of pyridoxine, but the use o f pyridoxamine is thought to be free from these side effects. The reason is that pyridoxamine needs to be

_ acarbose, it was shown that

There have been reports o f neurotoxicity

phosphorylated (i.e. it needs the addition of Pyridoxamine prevents the formation o f A G E s by 25 to 50% and ameliorates

phosphate on the main molecule) before it can become active.

diabetes-related kidney dysfunction, (it improves albuminuria, plasma creatinine hyperlipidemia). It works by

Cross-link Breakers

^trapping reactive carbonyl The most important cross-link breaker is ^groups (27) and exhibits the drug Alagebrium (ALT-711), an orally free radical active compound. This is a thiazolium scavenging

j a m

April/May 2006

product (dimethyl-3-phenacyl-thiazolium


Summary jji; w^r

rodents,

canines and

primates. A 4 0 % i

reduction on age-related left ventricular stiffness (in

^ ^

I

dogs) was reported after just one

month o f treatment (37). Other

stiffness and heart failure (38).

pyridoxamine, carnosine, metformin and acarbose, whereas others are now becoming available. No cross-link breakers

these will be marketed within a few years. Soon after, combinations o f inhibitors and breakers are bound to follow.

manufactured It

available are aminoguanidine,

are commercially obtainable as yet, but

experiments support its effectiveness against hypertension, cardiovascular

chloride)

The best cross-link inhibitors currently

by the Alteon

Corporation in the US. A related compound is PTB (dimethyl-Phenacyl-Thiazolium Bromide), which has actions similar to the chloride variety. Alagebrium is not an enzyme as such, but it has enzymatic

It has also been studied in a number of

effective in reversing some o f the complications o f diabetes, improving myocardial and arterial stiffness, heart failure, and reducing blood pressure (39).

linked proteins and free the proteins which are then able to function again normally.

1. Suzuki D, Miyata T, Kurokawa K. Carbonyl Stress. Contrib Nephrol 2001,134:36-45 2. Dukic-Stefanovic S, Schinzel R, Rieder R A G E s in brain aging: AGE-inhibitors as

properties. It has been shown to actually break the covalent bonds between cross-

References

human clinical trials. It was found to be

However, far from being unique,

neuroprotective and anti-dementia drugs?

Alagebrium is in a group o f 375 other cross-link breakers developed by Alteon alone!

Biogerontology 2001, 2(1): 19-34 3. Melton L. Age breakers-Rupturing the body's sugar-protein bond might turn back the clock, Sci A m 2000, 283(1): 16

Alagebrium breaks the bonds although, in theory, the bonds may then re-form, (because the carbonyl group is still active on the freed protein), Alagebrium has benefits which persist after the drug is

Thinking about your cholesterol level?

stopped (Alteon Corporation, personal communication). In other words, if the proteins are cross-linked again, Alagebrium will divide them once more, and i f they are then rebound, it will keep on separating them. For this reason, it may be necessary to use a combination o f the cross-link inhibitor carnosine together with Alagebrium for full protection against cross-linking. In that situation, when the bond is broken, carnosine will immediately bind to the carbonyl group (i.e. it will 'carnosinylate' the protein) and therefore cross-linking of that particular protein will not take place for the second time. The Alagebrium molecule will then be free to

Think about Metformin Metformin is a standard anti-diabetic drug (dimethyl-biguanide) used worldwide both against insulin-dependent and against non-insulin-dependent diabetes. Although it is used primarily to increase peripheral sensitivity to insulin and lower blood glucose, metformin has several other important actions. Metformin lowers cholesterol levels and helps prevent low-density lipoproteins ('bad cholesterol') from attaching to blood platelets and arteries, thereby reducing the risk of blood clotting. Due to the sugar stabilizing properties of Metformin, it is also a useful aid for dieters, helping to prevent sugar cravings.

seek out other cross-linked proteins to work on.

Alagebrium can reverse aortic stiffening in

Learn about the many benefits of Metformin by visiting: www.antiaging-systems.com/a2z/metformin.htm or call +1 415 992 5563

April/May 2006 i a m 37


38

4. Bonnefont-Rousselot D, Antioxidant and

Pimagedine: a novel therapy for diabetic

the formation of antigenic AGEs. Biochem

anti-AGE therapeutics, J Soc Biol

nephropathy. Exp Opin Investig Drugs

Biophys Res C o m m 1996,220( 1): 113-119

2001,195(4):391 -398

2002, 11(4):565-574

30. Nagaraj RH et al. Effect of

5. Gariballa A., Sinclair A. Carnosine:

18. Coppey LJ, Gellet JS et al. Effect of

pyridoxamine on chemical modification of

Physiological properties and therapeutic

treating streptozotocin-induced diabetic

protein carbonyls in diabetic rats. Arch

potential. Age Aging 2000, 29:207-210

rats with sorbinil, myoinositol or

Biochem Biophys 2002, 402( 1): 110-119

6. Hipkiss A, Brownson C. Carnosine

aminoguanidine. Int J Exp Diabetes

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i a m

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Issue 8: April/May 06  

In this issue: Improving your concentration The need for antiaging medicine Inhibiting your AGE BEC5 cream success stories The world’s o...

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