Great Smokies Diagnostic Laboratory April 2002 Volume 11, No. 1

Healthy Aging...The Odyssey ContinuesHealthy Aging...The Odyssey Continues

C O M I N G I N O U R N E X T I S S U E :Molecular and genomic analysis uncovers new

targets for modifying health.

F E A T U R E S

4-5 Tools for Choosing Laboratory Assessments in an Optimal Aging Practice By Brad Rachman, D.C., D.A.B.P.M.

6-7 The Challenge in Women’s Health: Understanding the Biological Differences By Elizabeth Lipski, Ph.D., C.C.N.

8-9 A Marriage of Theory and Practice:

GSDL’s New Individual Case Management Research Program

By Patrick Hanaway, M.D., and John Furlong, N.D.

10-11 Case Study: Improving Estrogen Metabolism for Healthy AgingBy Kashi Rai, M.D.

12-13 Diagnosing Digestive Conditions in the ElderlyBy Corene Humphreys, N.D.

16-17 Methylation: the “Linchpin” of Healthy AgingBy Mary James, N.D., with David Perlmutter, M.D.

18-19 Underlying Triggers of Inflammatory ConditionsBy Russel Sher and Todd Nelson

20-21 Detox in Overdrive: Heavy Metal Exposure and Burden in Aging PatientsBy Fred Harvey, M.D., and Jeff Baker, N.D.

26-27 Clinical Genomics – The Next Generation of Healthy Aging Medicine By T. Michael Culp, N.D.

D E P A R T M E N T S3 From the Founder’s Desk

14-15 New Products

22-25 Book Reviews

28 ACE Clinical Genomics Training Announcement

Editor: Eddy Ball, Ph.D.Contributing writers: Eddy Ball, Ph.D., Patrick Runkel, M.A.,Scott Holmes, Elizabeth Lipski,, Ph.D., Patrick Hanaway, M.D.,Kashi Rai, M.D., Corene Humphreys, N.D., David Perlmutter,M.D., Todd Nelson. N.D., Fred Harvey, M.D., Jeff Baker, N.D.,

Russel Sher, D.C., Mary James, N.D.,Brad Rachman, D.C., T. Michael Culp, N.D.,

John H. Furlong, N.D., DeAnna Hatch, Ph.D., Missy West,Deborah Shepard, Ph.D., Jeff Ledford

Art Director: David Barrett

Layout and Design: Paula Bishop

Cover Art: Paula Bishop

Contributing Artists: Paula Bishop,Mary Ann Lawrence, David Barrett,

Merideth Lovejoy, Lisa Coin

Production Management: Rusty Cunning

Smokies Digest is produced and distributed semi-annually by Great Smokies Diagnostic Laboratory:

63 Zillicoa Street, Asheville, NC 28801-1074 1-800-522-4762 • Fax: 1-828-252-9303

cs@gsdl.com • www.gsdl.com

©2002 Great Smokies Diagnostic Laboratory

C O N T E N T S

“You mean you're comparing our lives to a sonnet? A strict form,but freedom within it?”“Yes.” Mrs. Whatsit said. “You're given the form, but you have towrite the sonnet yourself. What you say is completely up to you.”

Madeleine L'Engle, A Wrinkle in Time (1962)

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Clinical Genomics… The Future of MedicineScientists from all over the world have deciphered the entirehuman genome. You can now download from the Internet thenear-complete infrastructure for how to build and run a humanbody. What does this mean to you and your patients?

This spring Great Smokies mounts a bold initiative to apply inno-vative genetic testing in the practice of primary care medicine. Weare introducing a new line of predictive diagnostic genomics testsand sponsoring a series of Clinical Genomics training. In thisissue of the Digest, T. Michael Culp, N.D., offers an introductionto the concepts behind what he rightly describes as “the next-gen-eration of healthy aging medicine.”

Within the framework of Functional Medicine, genetic testingoffers some exciting opportunities for primary care by enhancingpractitioners’ ability to predict patterns of individual biochemicalresponse. These patterns can then be targeted by a specificallyindividualized treatment plan to improve patient outcomes.Advances in genetic testing now make it possible to achieve a levelof diagnostic sophistication and specificity never before possible.

The one-day Clinical Genomics training series began in Marchand runs through June at sites throughout the country. The serieshas been fully approved to offer Continuing Medical Educationcredits to Medical Doctors and Doctors of Osteopathy and foroffering Continuing Education Units to Naturopathic Doctorsand Doctors of Chiropractic.

I am very proud of the exciting ground-breaking work ourGenovations Research and Devlopment team has accomplished indeciphering the clinical utility of genomics. Their innovations willprovide you with unparalleled clinical decision tools.

I believe that “Genomics” will become the dominant language ofthis century. I invite you to join us at an ACE training session anddiscover for yourself how to speak it. You will also learn the waysthat Clinical Genomics can make your practice of medicine moreeffective and rewarding.

Yours in health,

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By Stephen Barrie, N.D.Founder and Chairman of the Board

Stephen Barrie, N.D.Founder and Chairman of the Board

F R O M T H E F O U N D E R ’ S D E S K

Are you receiving the Great Smokies Connection,

our e-mail newsletter? To subscribe, visit

http://www.gsdl.com/education/connection/index.htmlor call 800-522-4762.

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Because Clinical Genomics is grounded inFunctional Medicine concepts and backed byour commitment to total quality, practitionerscan count on:

•Practical Applications: Test results will notmerely expose a genetic predisposition. They willalso point to ways that the effects of a polymor-phism that is prevalent among the patient pop-ulation and relevant to treatable disease condi-tions can be modified by nutrition and lifestylechanges to improve patient outcomes. All teststhat we offer will meet these important criteria.

•Practitioner Support: We are sponsoringhands-on ACE training for practitioners to makecertain genetic testing can be applied effectivelyin primary care practices. We will also provideour high level of professional support to helppractitioners get every possible benefit from testresults in choosing treatment interventions.

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The key to successfulimplementation of an“optimal aging practice”

is the efficient assessment of theunderlying physiological imbal-ances in your patients.Choosing from an increasingarray of functional laboratory

assessments can be a clinically daunting task.Here are three practical tools that allow a practi-tioner to choose appropriate functional tests rel-ative to the eight modifiable risk factors for sub-optimal aging.

The first tool is a two-page functional assess-ment questionnaire. It can be adminis-tered to a new patient, tostructure

an initial evaluation, or to a current patient, toprovide more specific analysis of a condition.The questions are divided into the eight modifi-able risk factors of optimal aging with yes/noanswers. This format allows the practitioner toquickly pinpoint areas of highest metabolic orfunctional impairment that may require furtherinvestigation through laboratory assessment.

The second tool is a chart listing appropriate lab-oratory assessments based on the age of thepatient. This is an excellent screening tool foridentifying areas of physiological imbalance thattend to become more prominent at specific ageintervals. It is also a good starting point for

assessing patients who come to your officeinterested in an optimal aging

program.

Tools for Choosing LaboratoryAssessments in an Optimal Aging Practice

By Brad Rachman, D.C., D.A.B.P.M.

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The third tool correlates com-mon presenting symptoms withlaboratory functional testingappropriate to the condition.Each correlation includes a ratio-nale for choosing specific labora-tory tests. This tool may be usedmost effectively for thosepatients coming in to a practicewith a specific condition thatrequires clinical attention. Usingthis tool, each presenting condi-tion can be assessed from anoptimal aging perspective.

These tools provide the practi-tioner with an easy and practicalsystem for implementing func-tional diagnosis relative to eightsignificant optimal aging para-meters - a system designed tokeep you on the leading edge ofpreventive health care.

Bradley S. Rachman, D.C., D.A.B.P.M., is

a world-renowned lecturer who has devel-

oped innovative courses for patients and

practitioners alike. As Director of the

Department of Medical Science, Dr.

Rachman is inspiring new and exciting

medical education programs at GSDL.

Need more copies of these helpful guides?Your copy of this issue includes an insert withthe materials Dr. Rachman describes. If youneed additional copies, visit our web site(www.gsdl.com) where the questionnaire, theage-based laboratory assessment chart, and thecondition-based laboratory assessment guidecan be downloaded in PDF format.

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FFor much ofour history,healthcare

practitioners havefound it tempting todiscount women’s treat-ment challenges as theconsequences of

hysteria, depression, and other psychosomatic factors. Although the situa-tion is improving, even today women'scomplaints aren't always taken as seriouslyas men's - or understood nearly as well. Asa result, the quality of healthcare forwomen has lagged, impacting accessibilityand hampering research efforts.

A new study from the Netherlands, forexample, reports that women withRheumatoid Arthritis (RA) were more likely than men to have a delay in referralsto specialists, even though disease activitywas similar in both sexes. Similarly, anAustrian study reported that women takelonger to access coronary angiogram thanmen, despite free access to services in that

country’s medical system.

As recently as 1984the National

Institutes onAging published astudy usingdata derivedonly frommen andcalled it

“NormalHuman Aging.”

Prior to 1990women were rarely

subjects for research,

although results were widely extrapolatedfor women’s treatment. Despite new guide-lines issued by NIH in 1990, a significantportion of non-sex-specific research stilldoes not include women and only about1/4 to 1/3 of recent research analyzed dataor results by the sex of the subjects.

Opportunities for Improving Outcomes withFunctional Assessment

In addition to hormone testing and evaluation of estrogen metabolism, thereare now many functional tests available tohelp determine the underlying causes andtriggers for chronic health conditions inwomen patients. Depending on the genetic,lifestyle, and environmental factorsinvolved, each person’s unique biochem-istry will determine which tests are of highest priority. For example: Urinary boneresorption assessment is a useful test forearly identification of bone loss and tomonitor whether treatment is preventingfurther bone loss and development ofosteoporosis. It can be used in conjunctionwith bone mineral density to evaluate thevarious factors that can contribute to bonefracture as a woman ages.

Thyroid dysfunction has been reported tobe three times as high in women withrheumatoid arthritis (RA) as in womenwith non-inflammatory rheumatic diseasessuch as osteoarthritis and fibromyalgia.Some RA patients benefit from treatmentof food and environmental sensitivities.And others improve after effective treatment of dysbiosis and intestinal permeability. RA has especially been linkedwith a genetic predisposition and Proteusbacteria as a trigger for the illness.

The Challenge in Women’s Health: Understanding the Biological Differences

By Elizabeth Lipski, Ph.D., C.C.N.

"Sex-specificmedicine is not onlyabout how womenrespond to disease

and treatmentdifferently than

men. It's also aboutimproving how

health careproviders respond

to thosedifferences."

Phyllis Greenberger,M.S.W., president andCEO of the Society forWomen's HealthResearch (http://www.womens-health.org/about/0frameset.htm)

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There is evidence that women with cardiacconditions can present differently thanmen. Some 50% of women but only 17% ofmen who undergo diagnostic cardiaccatheterization turn out to have normalcoronary arteries – indicating that as muchas 50% of the time chest pain in women isdue to some other cause(s). Assessment ofmineral status and of independent cardiovascular risk factors, such as homocysteine, fibrinogen, Lp(a), and C-reactive protein, can be used to detectother factors contributing to chest pain.

Although Chronic Fatigue Syndrone (CFS)and fibromyalgia (FM) are distinct entities,they have many common characteristics interms of symptoms, diagnosis, and treatment. Several studies have reported ahigh incidence of food sensitivities, leakygut syndrome, and thyroid autoimmunityin FM and CFS.

It’s Worth Looking a Little Deeper

For all of these reasons, it’s important toreally listen to your women patients andbecome sensitive to the implications of sex-

specific health patterns. Women withtreatment-resistant conditions arenot plagued with psychosomaticillness. In fact, clues to their complaints can often be discov-ered by functional analysis andan integrative medicine approachto treatment. Great Smokies cangreatly assist in this process with arange of functional assessments forgetting to the physiological roots ofwomen’s treatment challenges.

Note: Due to space limitations, referencesfor this article will be included with theonline version at www.gsdl.com

Elizabeth Lipski, Ph.D., C.C.N., is a clinical nutritionist in practice on the island of Kauai, HI. She is the author of Digestive Wellness and Leaky GutSyndrome. Her website: http://www.innovativehealing.com

Just How Different Are Women?

• 80% of the population with Osteoporosis are women.• 75% of people with Lupus are women• Twice as many women as men have arthritis • Hypothyroidism is 10 times more prevalent in women

than in men• Fibromyalgia is 9 times more prevalent in women than

in men• Chronic Fatigue Syndrome is three times more

common in women than in men• Migraine headaches affect women three times more

than men • Women experience more pain with greater severity

overall than men • Interstitial cystitis is almost exclusively found in women• Multiple sclerosis occurs more in women than in men• Endocrine imbalance affects women more than men

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Comprehensive,research-orientedand user-friendly;

this is the conceptbehind GSDL’s researchinto functional assess-ment and interventionsin our Individual CaseManagement (ICM)

Research Program. This Research Programis designed to study the impact of functional medicine approaches on illnessand wellness. We provide participants withthe best tools to improve their health andwell-being, as we measure which biochemical parameters are modifiableand which changes lead to improvementin health status. ICM is an essential component of GSDL’s ongoing commit-ment to improve evaluation and treat-ment of individuals in the clinical setting.

This integration of combined nutritionalresearch with objective outcome measuresprovides important insight into effectivefunctional medicine treatment strategies.The ICM Research Program will grow toinclude a number of clinical topics andparticipants, thus making GSDL one ofonly two facilities (along with the Instituteof Functional Medicine in Gig Harbor,WA.) performing clinical research on combined nutritional therapies. The ICMResearch Program also has the potentialto enhance health benefits for GSDLemployees and to provide a model for atruly prevention-based comprehensivehealth and wellness plan for other organizations.

Phase One: Women in Mid-Life

In our initial study, we are working with acohort of peri-menopausal women withclimacteric symptoms, who are not

currently on Hormone ReplacementTherapy (HRT). These women receive awide variety of evaluations, including:medical history and physical examination;anthropometric measurements; laboratory testing for hormone balance, cardiovascular risk, bone resorption, dysglycemia, thyroid function, toxic andnutrient elements, fatty acid profiles, anddigestive health. In addition, participantscomplete an extensive symptom question-naire, quality of life measure [SF-36], andcomputer-assisted cognitive testing.

These comprehensive measures enableGSDL doctors to develop an individual-ized health and metabolic ‘fingerprint’ foreach participant. This profile is then usedto determine the most important areas toaddress clinically. Department of MedicalScience (DMS) practitioners research andconsult as a group to arrive at a plan thatbest fits the participants’ individual needs.I serve as the medical director of this innovative program, and in collaborationwith DMS staff physicians, I oversee themedical concerns of each participant anddetermine the best intervention for thatindividual.

The ICM Research Program evaluates thelaboratory measures and outcome measures of functional status for eachparticipant in response to the followinginterventions: Diet, Vitamin/MineralSupplementation, Exercise, Herbs, andHormones. Recommended products areprovided to the participants, who stay inclose communication with staff physicians and Kay Patrick, GSDL’sClinical Research Coordinator – the“heart” of our program. Follow-up testingof all parameters is provided at appropriate intervals.

At press time, statisti-cal analysis of the ICMdata was still on-going,with a final report onthe correlation of laboratory analyte values with outcomeresults scheduled forpublication in our nextissue of the SmokiesDigest. The final reportwill include a compre-hensive evaluation ofthe improvement of 250analytes throughout thestudy period for each ofthe six participants.

Initial evaluation ofoutcome measures hasalready demonstratedthat the treatment pro-gram was successful inproducing improved out-comes for participants:

☛ 12% improvement inpost-treatment scores onGreat Smokies’ proprietary FunctionalMedicine Index over pre-test values

☛ More than 6% improvement in post-treatment scores on theSF-36 Health Survey(Version 2) – 6.28% Physical Summary,6.36% Mental Summary

☛ 15.3% improvement onthe Kupperman Index

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A Marriage of Theory and Practice: GSDL’s NewIndividual Case Management Research Program

By Patrick Hanaway, M.D., with John Furlong, N.D.

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Evaluating Outcomes

Objective changes in laboratory testing are correlated with validated measures of each participant’s functional outcome and quality-of-life. The integrated treatment plan benefitsthe whole person; thus we evaluate overallhealth and wellness as well as improvement indisease-specific symptoms. The ICM ResearchProgram uses a prospective, clinical researchdesign applying functional medicine testingand functional outcomes research to evaluatethe efficacy of applied nutrition and botanicalinterventions. This research also allows GSDLto develop a database of clinical cases (whilemaintaining patient confidentiality) and analyze participant response to treatment.

Preliminary findings after three months of treatment indicate that our targeted interventions have helped our cohort to realizeimprovement on several measures of health andwellness. When this phase of the research project is complete, final results will be sharedthrough regional Achieving Clinical Excellence(ACE) Seminars and educational venues offeredto clinicians across the country.

Advancing the FunctionalMedicine Model of HolisticTreatment

The ICM Research Program is part of GSDL’songoing effort to provide practitioners with real-life applications of functional medicine.GSDL stands as a leader in functional medicineresearch and education, as we provide case histories, prospective clinical research, testrefinement, controlled clinical trials, and retro-spective analysis.,. Applying the objective resultsof applied nutrition and botanical medicine is astellar example of GSDL’s commitment tomake the cutting edge of functional medicineavailable to physicians around the world.

Patrick Hanaway, M.D., a graduate of WashingtonUniversity Medical School in St. Louis, Dr. Hanaway is inprivate practice with Family to Family in Asheville, N.C.,and serves as a consultant with Great Smokies for the ACEtraining and ICM research programs. He is board-certifiedin family practice and proficient in nutrition, herbology,and several alternative and complementary therapies.

John Furlong, N.D., spent ten years in private practice priorto joining the educational staff of Great Smokies in 1996.He provides practical and technical support for our clients,especially in the areas of women's health, metabolic assessment, and elemental analysis.

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“This integrationof combinednutritional

research withobjective outcome

measuresprovides

important insightinto effective

functionalmedicinetreatment

strategies.”

Structured Assessment Instruments for Pre- and Post-Treatment Evaluation

The Standard Form 36 (SF-36) Health Survey is a widely used multi-purpose, 36-question generic measure ofphysical and mental health. Its eight-scale profile of scores with physical and mental health summary measures was developed in 1988 and standardized in 1990. By 1999, it had been documented in nearly 1,500articles and reports, including reports of nearly 200 randomized controlled trials. Ratings on the SF-36 haverepeatedly been correlated to healthcare expenditures, hospitalization, and morbidity/mortality, making it apowerful tool in preventive medicine. Up-to-date information about the SF-36 is available online at www.sf-36.com

The Kupperman Index is an assessment of symptoms summarized in a menopausal index. It includes suchcomplaints as hot flushes, sweating, sleep disturbances, nervousness, depression, irritability, vertigo, fatigue,arthralgia, headache, tachycardia, and vaginal dryness. To minimize human variability in testing, it is generallyadministered by the same practitioner at pre- and post-treatment. It is described in greater detail by WiklundI et al. A new methodology for evaluating quality of life in postmenopausal women during transdermal estro-gen replacement therapy. Maturitas 1992;14:211-24.

The Functional Medicine Index is a 300+ item health status questionnaire created by the Department ofMedical science as a quality control tool for selecting participants in reference range studies.

Improving Estrogen Metabolism forHealthy Aging – One Woman’s Odyssey

By Kashi Rai, M.D.

My firstconsulta-tion with

Rachael D. (not herreal name) took placein November 2001.Rachael is a 64-yearold woman of averageweight who expressed

concern about symptoms of hormoneimbalance, cardiovascular disease risk(based on consistently high levels of totaland LDL cholesterol), elevated liverenzymes, and breast cancer risk.

She has had a long history of various hormone replacement treatments since herhysterectomy in 1968. Her mother wasdiagnosed with breast cancer in her seventies, which sent a strong message to

Rachael about her own possible risk.

She is a long-time non-smoker,exercises moderately, and is alight drinker. She is carefulabout her diet and has regularconsultations with a nutritional counselor in

Florida, where she lives withher husband. She and her

husband regularly travel tothe New Orleans area, and,on the advice of familyfriends, she scheduled an examination and initial

consultation with meduring a visit with

family here. At herrequest, her physician inFlorida had sent

me results oftests run earlier.

WorkupDuring my workup, I learned thatRachael’s current HRT regimen includedBiest 2.5 mg/d, 2% testosterone cream inthe morning, and 50 mg/d progesterone inthe evening. She was also supplementingwith garlic and red rice yeast extract.Recent health problems included a rootcanal six months earlier and shingles themonth before she saw me. She complainedof hot flashes, disrupted sleep, irritabilityand mood swings, and night sweats.

Based on her presentation and some of thetest results from Florida, I ordered routineblood chemistry, tumor marker andhepatitis titers, and liver enzymes from areference laboratory. I also ordered GreatSmokies’ Women’s Hormonal HealthAssessment (WHHA). Because of a significantly elevated hair antimony on anearlier test, I included a ComprehensiveDetoxification Profile to explore the possible connection between her symptoms and potential toxic exposure.

Results (see Figure 1) indicated that mostof the markers on the WHHA were withinnormal range (most within FunctionalPhysiologic Range as well). Although themarkers 2-hydroxyestrone (2-OHE1) and16alpha-hydroxyestrone (16a-OHE1) were“normal,” the 2-OHE1:16a-OHE1 ratiocould clearly be improved.

I decided to adjust her HRT formulation,reducing her estriol and dosing every otherday while maintaining the level of herestradiol, testosterone, and progesterone. I also prescribed an increase in indole-3-carbinol (found in cruciferous vegetables,such as broccoli and Brussels sprouts) to

"Because of thecompeting nature of the

2-hydroxylation and 16a-hydroxylation

pathways, a ratio of themetabolites 2-OHEstrogen

and 16a-OHE1, 2:16a-OHE1, has beenused as a biomarker for

breast cancer risk.…Recent studies showing

that the ration issignificantly decreased in

women with breastcancer further support

this hypothesis." Haggans CJ et al. CancerEpidemiol Biomarkers Prev2000;9(7):719-25.

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address both her hormone-related symptoms and improving her risk profile inregard to estrogen-dependent diseases (suchas breast cancer).

Although her blood chemistry and livermarkers were normal to slightly elevated,her Phase I caffeine clearance was significantly increased above the referencerange (Phase II was normal). Reduced glutathione was at the lower limit of the reference range and superoxide dismutasewas below reference range. I suggested thatshe try to avoid situations that could lead topesticide exposures, be careful to ask aboutfuture medications that could tax hercytochrome P450 detoxification pathway,and continue taking her supplements ofquercetin (500mg BID) because of its favorable affects on Phase I.

Follow-upWhen Rachael returned to New Orleans inJanuary of this year, I saw her once againand order a followup WHHA to monitorher estrogen metabolism. The treatmentplan had improved her self-assessment ofher symptoms. She reported feeling more“even” in her mood, sounder sleep, fewerand less severe hot flashes, and absence ofnight sweating. Boosting the estradiol content of her HRT had temporarily madeher breasts tender, but her relatively highprogesterone formulation had moderatedthat side effect.

Her test results (see Figure 2) showed a significant increase in 2-OHE1 levels to 448pg/ml and a marked increase in her 2:16a-OHE1ratio to 1.28. There was littlechange in her 16a-OHE1 levels. Based onseveral clinical studies, her ratio suggestsreduced risk for breast cancer.

In the future, I would like to see herincrease the level of her physical activity tosee how it would affect values in the future.Although I am not especially concernedabout elevations in 2-OHE1 and the 2:16a-OHE1ratio, lower levels of the analytes and ratio (to within reference rangevalues) would be preferable, ensuring optimal bone integrity metabolism.

Rachael’s persistent elevations of total andLDL cholesterol – along with lower thanoptimal HDL cholesterol – remain concerns. She is hardly “high-risk,” and shehad normal results on homocysteine andthyroid testing, but her lifestyle and diethave not been able to influence these markers significantly.

Kashi Rai, M.D., is in private practice at For BetterHealth in Metairie, LA. She completed college and medical school at Louisiana State University and a residency in family practice in New Orleans. As part of aholistic approach to health, she is also concerned withhelping patients achieve personal growth and self-empowerment in the course of the healing process.

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Figure 1

Figure 2

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Many elderlypatients present with

such vague and generalizedsymptoms, that it can bedifficult initially to determine the etiology of

their complaints. Studies have found thatconditions such as diarrhea, malabsorption,and parasite infestation are far more com-mon in this age group than previouslythought. Because symptoms such as anemia,low folate/B12 status, cachexia, and failure tomaintain normal body weight can be due tofactors other than age-related physiologicalchanges, older patients with these conditionsneed to be thoroughly investigated in orderto rule out underlyingpathology.

Diarrhea –Increased TransitInterferes withDigestion

Traditionally, chil-dren have been con-sidered the major at-riskgroup for fatal complicationsfrom diarrheal disease. A 1999 report,however, actually found a mortality rate fivetimes higher in patients older than 74 yearsof age. Charting hospital trends of gastroenteritis for 16 years, the report esti-mated a total of 1600 hundred fatalities ayear in the elderly from diarrheal disease.

Because of understandable embarrassmentabout possible fecal incontinence, olderpatients may be reluctant to discuss theirsymptoms. They also may not realize that thecondition may include more than the “classic” symptoms of abnormal frequency,liquidity of stools, or rectal urgency. Indeed,

experiencing three or more bowel move-ments a day without excess fluid can also beconsidered as diarrheal condition possiblylinked to malabsorption or other symptoms.

When symptoms have been present less thantwo weeks, intestinal infection may be pre-sent - caused by bacteria, parasites, or virus. Ithas been estimated that up to one-third ofelderly people in long-term care facilitieshave a positive stool assay for Clostridiumdifficile, which may be the result of increaseduse of antibiotic therapy, rather than age-related changes in Mucosal AssociatedLymphoid Tissue (MALT), neutrophil func-tion, and cellular immunity. Symptoms canrange from asymptomatic or mild diarrheato fulminating colitis. In the absence of overtdiarrhea, unexplained hypoalbuminemia canbe an important indicator of the presence ofthis anaerobic organism.

Infections fromthe parasite Giardia can also have highly vari-ant clinical manifestations. The elderly maypresent with only vague GI symptoms,weight loss, and anemia, or they may experi-ence acute diarrhea requiring hospitalization.

Malabsorption – Robbing theElderly of Essential Nutrients

Although recent studies suggest that adversechanges to the small intestinal villus structure are a consequence of a diseaseprocess affecting the gut, which can occurirrespective of age, there are subtle

Diagnosing DigestiveConditions in the Elderly

By Corene Humphreys, N.D.

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"The mortalityattributable togastrointestinalinfection is 400-

fold greateramong elderlypeople than

among youngeradults."

Cusack MA et al.Giardia in

older people. Age and Aging

2001;30:419-21.

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developments that may affect malabsorptionsyndromes among older patients. Changes inbrush-boarder membrane integrity, for example, have been documented with advancing age. This could explain the increasein lactose intolerance that accompanies age,though the conditions may also be attributedto genetic defects in lactase production exacerbated by the changes in eating patterns orthe introduction of new forms of processedfoods with lactase additives.

Hypochlorhydria and achlorhydria are commonin the elderly, and can lead to important nutrient deficiencies. Reduced folate conjugaseactivity in the intestine can occur as a consequence, as can a vitamin B12 deficiency.Low B12 levels can also occur from reducedsecretion of intrinsic factor, atrophic gastritis,drugs which suppress HCL production, andsmall bowel overgrowth. Low serum folate andB12 levels can therefore be indicative of reducedHCL production.

Hypochlorhydria creates a favorable environment for the overgrowth of organismsin the small bowel. This can result in

nutritional deficiencies due to increased num-bers of bacteria metabolizing dietary nutrientsbefore absorption can occur. A small bowelovergrowth may also be asymptomatic in theelderly (though with severe overgrowth, diar-rhea, abdominal bloating, and pain can occur).

Just Part of the Normal AgingProcess, or Something More?

Not all vague symptomology in the elderly canbe attributed to a physiological decline inhealth. As discerning physicians, we need tothoroughly investigate even the subtlest symptoms of ill health in the elderly, for theycan provide vital clues as to the underlyingcause of their illness. Without identifying thetrue cause of disease, the health and well beingof the elderly may be severely compromised,which can ultimately lead to more severepathology and steady erosion of quality of life.

Prior to joining Great Smokies' Department of MedicalScience, Corene Humphreys, N.D., practiced as a Naturopathand Medical Herbalist in New Zealand. She has also receiveddiplomas in medical laboratory technology, homeopathic medicine, and therapeutic massage.

Useful Laboratory Studies Include:

• Comprehensive Digestive Stool Analysis and Parasitology Profile (CDSA/P) can help to reveal theunderlying cause of diarrhea, and includes identification of pathogenic bacteria (from direct cul-ture), as well as Enzyme Immunosorbent Assay (EIA) testing for pathogenic organisms and para-sites. The panel also includes Digestive Functional Analysis.

• Digestive Function Analysis examines the stool for the presence of meat and vegetable fibers as wellas triglycerides, valerate, iso-butyrate, and chymotrypsin, reflecting pancreatic and stomach func-tion. An additional four analytes are used to assess absorption, and include: LCFA’s, Cholesterol,total cholesterol and short chain fatty acids.

• Lactose Intolerance Breath Test is a simple, non-invasive measurement of hydrogen and methanebreath samples following a challenge drink of lactose to reveal impairment in the metabolism of thisdisaccharide.

• Bacterial Overgrowth of the Small Intestine Breath Test to detect anaerobic organisms in the smallbowel is an analysis of breath samples for the presence of hydrogen and methane following a chal-lenge drink of lactulose.

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Our long-awaited panel oforganic acids and relatedmetabolites is now onlinewith 39 analytes related todigestion, nutrient co-fac-tor adequacy, neuorotrans-mission, and cellular energyproduction. This is quite aremarkable test in that it

measures downstream analytes of metabolicprocesses in a single urinesample. The test is thus capable of providing primafacie evidence of metabolicirregularities that may not beapparent from assessment ofmore conventional, proximate markers alone.

Although measurement oforganic acids has longproven diagnostic for in-born errors of metabolismand for gross insults tometabolic balance, the testcan also provide clinically

useful information in less acute situations,such as the chronically unwell patient with“normal” test results. For these patients, theMetabolic Analysis Profile can help practition-ers finally locate the “smoking gun” responsi-ble for a chronic condition. To provide asmuch clinical utility as possible, we supportthis test with extensive commentary, rangesfor children and adults, and our unique“Interpretation at a Glance” test report.

We have also expanded the reference rangeand revised the test report for Essential andMetabolic Fatty Acids (EMFA) Analysis.Results have been reorganized and we’ve introduced new specialized sections andindices to clarify the clinical significance oftest results. On the report, each patient'sresults will also be directly related to keypathological mechanisms of inflammation,membrane fluidity, oxidative stress, enzymeactivity, and insulin resistance. Moreover, thenew EMFA test report is the latest of a growing number of reports offering theFunctional Physiologic Range (FPR) feature tohelp patients and practitioners evaluate resultsin terms of optimal health and well-being.

Metabolic Analysis Profile Release, Fatty Acid EnhancementsBy Missy West, Product Manager

Malabsorption syndromes can be espe-cially difficult for patients– and for the practitionerswho try to find the rootcauses. Some of the treatments that are oftenvery effective for digestive

complaints, such as probiotic supplementation

and fiber, may only make them worse. Patientsmay present with “textbook” Irritable BowelSyndrome (IBS) – or with clusters of IBS-likesymptoms that are no less mysterious in originor difficult to treat.

However, the true culprits may actually be twocommon, but under-diagnosed conditions–small intestine bacterial overgrowth (BOSI) or

Expanding Digestive Testing – Analysis of Breath Samplesfor Clues In IBS And IBS-like Symptoms

By Jeff Ledford, Product Manager

Recent Developments in

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Although our single-sam-ple serum assessment ofthe metabolites 2- and16alpha-hydroxyestrone(2-OHE1 and 16alpha-OHE1) has proven to bevery popular, from the out-set we had requests for analternative measurement

of urine. However, not just any urine testwould do. Clients who wanted the flexibility ofurine to avoid blood collection in the officealso wanted convenience. The conventional 24-hour collection just wouldn’t do.

To satisfy this need, we’ve developed and fullyvalidated an Estrogen Metabolism Assessmentthat assays the first urine of the day for 2-hydroxyestrogen (2-OHE), of which 2-hydroxyestrone is the predominant metabolite, and 16alpha-OHE1. The analytesare referenced to creatinine to adjust for urinevolume. Along with levels of the analytes andan Estrogen Metabolism Index, the test

reports the 2-OHE:16alpha-OHE1 ratio thathas been associated with risk for (and, in somecases, progression of) estrogen-dependent dis-eases, such as breast and neck cancers, lupus,and osteoporosis.

The test can be especially useful for monitoring a patient’s progress in a treatmentprogram of nutritional and lifestyle changes tomodify the ratio. Indole-3-carbinol containingvegetables, such as broccoli and Brusselssprouts, soya, flax, and exercise have beenshown to influence the ratio (and disease risk)favorably.

Like our serum version, the EstrogenMetabolism Assessment, Urine can be usedwith both premenopausal and menopausalpatients, including those using hormonereplacement therapy. Our laboratory physi-cians recommend that the same sample beused for initial assessment and follow-up forgreater ease of interpretation.

lactose intolerance (LI). BOSI and LI can bothproduce IBS-like symptoms, masking the truecause of the conditions.

BOSI is frequently a complication of parasiteinfection and is associated with pancreatic insufficiency secondary to chronic pancreatitis.Incidence of the condition increases with ageand is possibly the major cause of clinically significant malabsorption and failure to thrivein the elderly. LI occurs in people who cannotabsorb lactose or do not produce sufficient lac-tase, the enzyme that breaks down lactose intosmaller, more easily digested molecules. Thesepatients often experience chronic gastrointesti-nal symptoms and abdominal pain up to severalhours after consuming foods containing lactose.

Our new tests for these conditionsboth involve the ingestion of a challenge sugar (lactulose for BOSIor lactose for LI) and measurementof hydrogen and methane in thebreath after set intervals. This non-invasive assessment offers practitioners an attractive alternative to biopsy for diagnosis.

Work continues on additionalmarkers for the ComprehensiveDigestive Stool Analysis. Watch for announcements of specificenhancements during the next few months.

By Deborah Shepard, Ph.D., Product ManagerA Urine Alternative In Assessment of Estrogen Metabolism

Laboratory Assessment

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Methylation canbe viewed as anovertaxed and

under-appreciated workhorsein the body. This simpletransfer of a methyl group(CH3) from one molecule toanother turns out to be oneof the primary determinants

of health and disease. Indeed, almost all of thedisorders common to aging are caused or exacerbated by deficiencies of the body’s mainmethyl donor, S-adenosylmethionine (SAMe), orby excess homocysteine (Hcy) resulting fromimpaired methylation.

Methylation is a biochemical process that beginswith dietary methionine. With the help of magnesium and adenosine triphosphate,methionine is converted to SAMe. When SAMedonates a methyl group, it metabolizes into Hcy.Hcy is not a bad thing in or of itself. Like cholesterol, it only causes problems if allowed toaccumulate. Assuming the availability of cofactors like vitamins B6, B12, folic acid, andserine, Hcy is recycled to methionine, and thecycle can then repeat itself. Betaine is an alternate cofactor that facilitates methioninerecycling by donating a methyl group. Via B6,Hcy can also enter the transsulfuration pathwayto become cysteine and taurine. With deficiencies of these cofactors, (common in afast-food, meat-based diet), Hcy accumulates,with detrimental effects throughout the body.

Progression to Diseases of Aging

The link between increased blood levels of Hcyand cardiovascular disease is well documented.Levels of Hcy tend to increase with age, and asthey rise, hydrogen peroxide is generated, leading to oxidation of LDL and blood vesselendothelium. Less well-known associations withhigh Hcy include neurological disorders.

Depression, multiple sclerosis, cognitive declinein the elderly, Alzheimer’s and Parkinson’s disease have all been linked to excess Hcy andalterations in B6, B12, or folate metabolism.

In many of these conditions, synthesis of SAMeis impaired. Methylation is vital to the mainte-nance of the myelin sheath, to the turnover ofcatecholamines and neurotransmitters, and tothe production of phosphatidylcholine, coenzyme Q10, and melatonin. SAMe as a supplement has been successfully employed asan anti-depressant since the ‘70s, often out-performing tricyclic anti-depressants in studies.It is interesting to note that poor clinicalresponse to Prozac goes hand in hand with lowfolate levels. In fact, researchers have suggestedthat folic acid might improve the effectivenessof antidepressants. But doesn’t it make moresense to directly address the source of the metabolic problem?

Since the central nervous system (CNS) lacksthe alternate betaine pathway to remethylateHcy, the CNS has a reduced methylation capacity and is particularly vulnerable to Hcy’stoxic effects. Hcy’s neurotoxic actions arethought to result from its interaction with theN-methyl-D-aspartate receptor, resulting inexcessive calcium influx, free radical production,and possible cell death. Ironically, many of theroutine medications prescribed for some ofthese disorders only tend to exacerbate them byfurther raising the levels of Hcy.

Excess Hcy has also been linked to other disorders commonly associated with aging,including obesity, cataracts, osteoarthritis,rheumatoid arthritis, non-insulin-dependentdiabetes, and cancer. Deficient SAMe has beenshown in animal studies to cause DNA strandbreaks in certain areas of the tumor suppressorgene p53. With a defective p53 protein, certaincancer cells can grow out of control. Breast

16

"…there is a strong,graded association

between plasma totalhomocysteine levels

and the risk ofdementia and

Alzheimer’s disease.An increment in the

plasma homocysteinelevel of 5 µmol perliter increased therisk of Alzheimer’s

disease by 40percent."

Seshadri S et al. Plasma homocysteine

as a risk factor fordementia and

Alzheimer’s disease.N Engl J Med

2002;346(7):476-83.

Methylation: the “Linchpin”of Healthy Aging

By Mary James, N.D., with David Perlmutter, M.D.

cancer is also more likely to develop withundermethylation, as it is the methylationof estrogens that produces the methoxye-strogens (downstream from the 2-hydroxye-strogens) so critical to breast cancer protec-tion. Plasma levels of Hcy tend to be higherin postmenopausal women compared withpremenopausal and pregnant women, suggesting a close relationship between Hcymetabolism and estrogen status.

Targeting Pathways andMonitoring Treatment

Laboratory assessment provides an easymeans of detecting hidden disruptions inmethionine metabolism. Hcy is a criticalmarker on the Amino Acids Analysis. Thisprofile also includes measurements ofmethionine, cystathionine, serine, cysteine,and taurine, whose patterns of imbalance

may hint at low levels of the critical nutrientcofactors. Hcy is also measured as an inde-pendent risk factor in the ComprehensiveCardiovascular Assessment. “Loading” thebody with a prescribed amount of L-methionine may help to reveal impairmentsthat might otherwise be missed.

A graduate of National College of Naturopathic Medicine,Mary James, N.D. was in private practice before becom-ing a nutritional consultant for a supplement manufac-turer. With more than seven years experience at GSDL,she is our senior laboratory physician and has consultedwith clients on thousands of test reports.

David Perlmutter, M.D., is a board-certified neurologistwho practices in Naples, FL. and currently serves asadjunct Professor at the Institute for FunctionalMedicine. In addition to his many contributions to peer-reviewed medical literature, Dr. Perlmutter has writtenseveral books, including BrainRecovery.com - PowerfulTherapy for Challenging Brain Disorders.

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"Researchers havesuggested that folicacid might improvethe effectiveness of

antidepressants.But doesn’t it make

more sense todirectly address the

source of themetabolic problem?"

DRUGS WHICH CAN

RAISE HOMOCYSTEINE

valproic acidtrimethoprimtriamterenephenytoin

phenobarbitalprimidone

carbamezepinefelbamate

lamotrigenemetformin

oral contraceptives

Source: Ross Pelton, James B.LaValle, Ernest B. Hawkins.Drug-Induced Nutrient DepletionHandbook. 2nd edition (January2001).Washington, DC:American PharmaceuticalAssociation, 2001. ISBN091658979X

METHYLATION

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By Todd Nelson, N.D., with Russel Sher, D.C.

18

Beyond Tums® - Exploring the UnderlyingTriggers of Chronic Pain and Inflammation

Although considered normal bodily

phenomena by the advertisersof various heartburn andindigestion medications,belching, burping, and bloat-ing are actually signs of phys-

iological imbalance that, if not addressed,may lead to further systemic imbalances anddisease. An excellent example is arthritis, oneof the many common chronic inflammatoryillnesses that are directly affected by the stateof a patient’s gastric function.

Most patients with arthritis, osteo- orrheumatoid, can experience an exacerbationof pain because of low-grade infections andmaldigestion in the intestine that introducetoxins into the circulation, ultimately triggering inflammatory responses in thejoints. These patients commonly complain ofgastric symptoms to their doctor, yet the

problem is addressed only onthe level of symptomatic relief.Antacids or H2 blockers are prescribed to lessen the gastroesophogeal reflux disease(GERD), bloating, or bowel disturbances they are complain-ing about. Unfortunately themedication is usually maskingunderlying problems of upperand lower intestinal dysbiosis,insufficient stomach acid,maldigestion, and malabsorp-tion that may be contributing toarthritis pain. Add to this a leakygut caused by chronic intake ofnon-steroidal anti-inflammatorydrugs (NSAIDS) or steroids torelieve pain, and the intestinalenvironment becomes a primarycontributing factor in circulat-

ing inflammatory and immune-inducingchemicals that exacerbate the disease.

All patients with chronic illness can benefitfrom an assessment of overall intestinal func-tion as it relates to their condition. Adequatedigestion may be assessed through severalfunctional diagnostic tests, particularly theComprehensive Digestive Stool Analysis(CDSA), Amino Acids Analysis, BacterialOvergrowth of the Small Intestine BreathTest, and Lactose Intolerance Breath Test.

The CDSA reports the short chain fatty acids(SCFA’s) valerate and iso-butyrate, which areproduced through bacterial fermentation ofprotein and reflect the presence of undigest-ed protein in the bowel. Generally theseSCFA’s should constitute less than 10% ofthe total concentration of SCFA’s. Causes ofthese elevations may be due to deficient pan-creatic proteases, hydrochloric acid (HCl), ormalabsorption. Triglycerides are the majordietary component of fat. Elevations in thestool may reflect incomplete fat hydrolysis asa result of pancreatic insufficiency.Chymotrypsin is a proteolytic enzyme secreted by the pancreas, and deficiency mayreflect pancreatic insufficiency.

Amino Acids Analysis is an excellent meansof assessing protein digestion. Suspectincomplete proteolysis if anserine and carnosine are elevated and the essentialamino acids are low, although inadequatedietary protein intake would need to be ruledout. Low stomach HCl may lead to lowmethionine, tyrosine, and phenylalanine.Low histidine may result in low stomach HClsince histidine converts to histamine (zincdependent) and histamine converts to HCl.Zinc is also required for peptidase activity,and deficiency can result in low isoleucine,leucine, and valine.

19

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In addition to directly measuring digestivemarkers, two breath tests can offer further indirect evidence of specific malabsorption syndromes. The Lactose Intolerance Breath Testprovides evidence of malabsorption of lactoseand therefore dairy products due to a deficiencyin the enzyme lactase. Also assessed by breathtesting, bacterial overgrowth of in the smallintestine may contribute to the problem andresult in symptoms of bloating, gas, reflux, diarrhea, constipation, and abdominal pain.This condition can be due to insufficient stomach HCl, slow transit time, and medications. Bacteria in the small intestine mayinteract with undigested matter and producesubstances that can be neurotoxic, induceinflammatory and abnormal immune responses, and affect the patient systemically.

Once a thorough assessment is made, there aremany natural therapeutic protocols for

restoring a normal gut environment. Individualtest report commentary and interpretive guidelines (available in our Functional AssessmentResource Manual and online at www.gsdl.com)can provide treatment options. GSDL laboratory physicians are also available to provide consultation on test results.

Todd Nelson, N.D., director of the Tree of Life WellnessCenter, has practiced holistic and integrative clinical medi-cine for over 18 years in the Denver/Boulder, CO area. Hehosts a popular weekly radio talk show on alternative healthand has co-authored books on arthritis and asthma. His spe-cial emphasis is a balanced, educational approach to self-care.

Russel H. Sher, D.C., graduated from Palmer College ofChiropractic and practiced chiropractic from a functionalmedicine perspective for 12 years in Colorado and his nativeSouth Africa before joining GSDL. He leads the Departmentof Medical Science in web-based educational developmentand distance learning programming.

Ron – A Case Report from the Practice ofTodd H. Nelson, N.D.

At age 52, Ron suffered from chronic osteoarthritisand was dependent on 10 ibuprofen tablets daily tocope with his joint pain. He was also taking an H2blocker for GERD. Ironically, he onset of hisGERD was most likely induced by his increasing amounts of ibuprofen intake.After years as a pro basketball player andreferee, his joints had taken a beating, and hehad already undergone one kneereplacement. He entered mycare to see if he could reducehis drug dependency and savehis other joints.

A CDSA/Parasitology stool analysis and gut permeability study were preformed and revealed a 4+ over-growth level of Candida albicans and a 4+ level of the bacteria, Klebsiella peumoniae. His Dysbiosis Index was16, and his lactulose/mannitol ratio on the Intestinal Permeablity Assessment indicated leaky gut.

He was put on a natural protocol to address the problems. Once the infection was cleared, normalintestinal flora restored, and digestive parameters normalized, the toxic load was lessened. Ron alsoadhered to the dietary, supplement, and exercise protocol outlined in my book, Arthritis Survival (Ivker andNelson, Tarcher/Putnum, 2001). He is now free of joint pain, and his most recent test results indicatelowered inflammation and disappearance of gastric dysbiosis. Ron is one of many patients following afunctional medicine approach who is now essentially drug-free and is functioning very well every day.

"The immune defensesystem in particular isknown to be adverselyaffected by the agingprocess, and there is

strong evidence that apoorly functioning

immune system cancontribute to

decreased diseaseresistance and

reduced lifeexpectancy in the

elderly."

Gill HS et al.Enhancement of immunityin the elderly by dietarysupplementation with theprobiotic Bifidobacterium lactis HN019. Am J ClinNutri 2001;74:833-39.

Heavy metaltoxicity isthought by

many to be on thedecline; however, thiscould not be furtherfrom the truth. In fact,arsenic, lead, and mer-

cury are listed as the top three hazardoussubstances respectively in the UnitedStates by the Environmental ProtectionAgency and the Agency for Toxic

Substances and Disease Registry (a divi-sion of the U.S. Department of Healthand Human Services). Unfortunately,most of the research focuses on acute,high dose, heavy metal toxicity. Littleattention has been given to low doseexposure, and its cumulative effects overtime; however, mounting evidence

points toward heavy metals playing animportant role in many chronic illnesses.

Next to young children, older patientsmay be the group most affected by toxicexposure because of natural processes ofaging. In addition to new exposure, agingpeople may be afflicted all over again byexposures that happened many decadesago – long before most people understoodthe dangers. Since bone is a preferred tissue site for storage of toxic elements,

men and women who are now experiencing increased bone

turnover are also experiencing the releaseof stored toxins backinto the blood streamwhere they can impacttissue throughout thebody and overburdenthe body’s detoxification capabilities.

The Elements

Mercury is suspected to be associated withmany neurological disorders, includingattention deficit disorder, autism, andmultiple sclerosis. Chronic fatigue may berelated to mercury - as well as to arsenicand antimony - by interfering with glu-cose metabolism and the citric acid cycle.Low-level exposure, e.g. inhaled vaporizedmetallic mercury amalgams or ingestedmethylmercury from large predatory fish(tuna, swordfish, and shark), seems toaccumulate in the body and subsequentlyresult in various chronic conditions.Mercury may also lower reduced-glutathione levels by inhibiting glu-tathione reductase, resulting in impairedmitochondrial function, decreased detoxification capacity, and insufficientantioxidant reserves.

The main source of arsenic today is “pressure-treated” wood, where it is usedas an anti-fungal and preservative. Whenit is liberated from the wood primarilywhen the wood is cut, burned, sanded, ordegraded, it can then enter the air andwater tables. However, low amounts maybe liberated from unperturbed wood, as itis sometimes seen in families with decks.Humans can be exposed to arsenic bywater, food, or air, and arsenic is considered carcinogenic to humans. Toxiceffects include fatigue, immune dysfunction, vascular damage, neuropa-thy, and various forms of cancer (lung,skin, bladder, liver, kidney, and prostate).

Detox Challenges

In cases of chronic, low-dose exposure,heavy metals can overwhelm detoxifica-tion capacity, leading to tissue deposition.

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By Fred Harvey, M.D., and Jeff Baker, N.D

2020

Detox in Overdrive: Heavy MetalExposure and Burden in Aging Patients

Detox in Overdrive: Heavy MetalExposure and Burden in Aging Patients

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21

Once deposited, toxins can interrupt nor-mal function of those tissues and promoteillness. Many times the patient notices nosymptoms at the time of exposure. And itmay be many years later before symptomsmanifest. Unfortunately, random bloodand urine testing are commonly used forheavy metal detection, which routinelymiss toxicity in the tissues. As a result ofthese factors, many patients whose illnessmay be caused or compounded by heavymetal toxicity go undiagnosed.

Some people may be extremely sensitive tosmall amounts of heavy metal exposure,particularly mercury, which can thenresult in illness. These individuals mayhave protective nutrient insufficiencies or

genetic polymorphisms that inhibit normal elimination of these metals. Inaddition to Elemental Analysis of hair,blood, and urine, a ComprehensiveDetoxification Profile, which includesOxidative Stress Analysis, should be performed and used to monitor effectiveness of interventions.

Fred Harvey, M.D., holds board certification in InternalMedicine and Geriatrics. He is in private practice at theHarvey Center for Integrative Medicine in Sarasota,Florida. Dr. Harvey's focus is on preventive, integrativemedicine, including nutritional and lifestyle intervention.

Jeff Baker, N.D., is a laboratory physician with GSDL and alicensed primary care physician with a doctorate from theNational College of Naturopathic Medicine. Prior to joiningour staff, he was in private practice in Portland, OR.

Elemental Analysis: Choosing the AppropriatePanel for Your PatientThe method of testing for heavy metals should follow the basic sciences and the physiology of heavy metal detoxi-fication. For instance, once a person is exposed to a metal, it is removed from circulation within 2-3 days.Therefore, urine, plasma, and serum will detect heavy metal exposure only within this 2-3 day time frame.

However, many metals are deposited in red blood cells after exposure. Since the lifespan of a red blood cell is approximately 120 days, RBC (Packed Erythrocyte) testing will detect metal toxicity only if the patient is testedwithin 120 days of the exposure. On the other hand, for testing past exposure and tissue levels, hair analysis iswell supported in the literature. Hair concentrates heavy metals that are slowly liberated from tissue stores thatmay otherwise go undetected. Using a provocative challenge (DMSA, DMPS, EDTA, D-Penicillamine, etc.) liber-ates tissue stores of heavy metals that can then be measured in the urine. Therefore, choosing the appropriatemethod of testing is crucial for identifying all stages of heavy metal toxicity.

Test Exposure (Elapsed time since exposure)Elemental Analysis Urine 2-3 daysToxic Element Clearance Profile (identifies current exposure)Elemental Analysis Packed Erythrocytes up to 120 daysElemental Analysis Urine, Provocative Challenge (Pre & Post) Many yearsToxic Element Clearance Profile (with provocative agent) (identifies past exposure and tissue stores)Elemental Analysis Hair, Toxic Element Exposure Profile (identifies past exposure and tissue stores)

"Aging-associated releaseof bone lead into the

circulation is, in fact, apotentially important

source of soft-tissue leadexposure and toxicity.

Indeed, in U.S.population surveys, olderadults have among the

highest blood lead levels,second only to the peak

observed in youngchildren."

Tsaih S-W et al. Influence ofbone resorption on the

moblization of lead frombone among middle-aged

and elderly men: thenormative aging study.Environ Health Perspect

2001:109:995-99.

II’ll begin this review with a paraphraseof George Carlin: ‘to some people theglass is half full; to others it’s half

empty… Me, I want a bigger glass!’ That’s exactly how I feel after completing this compi-lation by Dr. Ghen with contributions by over35 specialists in the field – I’m ready for more.

The Advanced Guide to Longevity Medicine is anexploration of ways to use the tools we’velearned about over the past 100+ years of science and medicine and translate them into anew paradigm of high-function longevity. Thisis an ambitious undertaking, yet Dr. Ghen hasenlisted leaders in numerous scientific and clinical disciplines to pull this off admirably.

BookshelfDoctor’sBB OO OO KK RR EE VV II EE WW SS

If you were to ask women what theydesire of their bodies as they growolder, they might say “youthfulness,”

“energy to stay active,” “mental alertness,”“healthy skin, bones, eyes,” or simply “to feel

good.” Hormone imbalance, defi-ciency, or excess can rob a womanof “youthfulness.” Moreover, med-ical science is constantly alertingwomen about the benefits to theirhearts and bones achieved bykeeping a healthy estrogen level.In a recent book by Uzzi Reiss,M.D., Natural Hormone Balance, theCalifornia obstetrician and gynecologist offers a guide topatients and their practitionersfor helping women feel and looktheir best at any age.

In this thorough discussion ofhormone health, Dr. Reiss reviews

the changes and challenges associated with all ages, how aspects of our

culture have led to these struggles, and thetherapeutic advantages of using “natural”hormones – ones that are the exact chemicalreplicas of ones found in the body.

The book provides a list of common symptoms of hormonal imbalance and, inparticular, problems of estrogen excess or

deficiency, which include fatigue, forgetful-ness, depression, and insomnia. While estro-gen is considered to be the target hormonein the struggle of the modern woman, thereare actually several others that are alsoinvolved, including DHEA, testosterone, andmelatonin. When these hormones work inharmony with one another, their healthy balance promotes the joy of youthfulnessand wellbeing for women of all ages.

This book gives the practitioner tools forworking with a woman as an individual.While blood, urine, or saliva hormone levelscan serve as a baseline, it is imperative torealize that each woman has a distinct bio-chemical makeup and may react much differently to treatment. One women mightfeel her best at a “high normal,” for example,while another might feel optimal with herestrogen levels in the lower part of normal.

Dr. Reiss, a board-certified obstetrician andgynecologist, conveys both the authority hehas gained from years of learning and practicing and the trust he inspires as a healer who treats the whole person. His bookprovides the necessary details and resources,which will allow women and their practitioners to become health partners inthe quest to maintain youthfulness andquality of life as women age.

Natural Hormone Balance for Women: Look Younger,Feel Stronger, and Live Life with Exuberance by Uzzi Reiss M.D./OB-GYN with Martin ZuckerReviewed by DeAnna Hatch, Ph.D.

The Advanced Guide to Longevity Medicineedited by Mitchell J. Ghen, D.O., Ph.D. Reviewed by John H. Furlong, N.D.

Natural Hormone Balancefor Women: Look Younger,Feel Stronger, and Live Life with Exuberance, by Uzzi Reiss M.D./OB-GYNwith Martin Zucker.NewYork: Pocket Books, 2001.ISBN 0-7434-066506

Featured Book

Review

The Advanced Guide toLongevity Medicine, editedby Mitchell J. Ghen, D.O.,Ph.D., with contributingeditors Nancy A. Corso,D.C., Herb Joiner-Bey N.D.,Ronald Klatz, M.D., D.O.,and Allen Kratz, Pharm. D.Landrum, SC: Partners inWellness, 2001. ISBN 1-890694-37-1.

Featured Book

Review

22

23

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For the practitioner treating the patientrather than the disease, the compoundingpharmacy offers expanded treatment

choices, ranging from specialized amino acidformulations and hormone replacementcompounds to alternative delivery designsfor patients with special physical or compli-ance requirements. Pharmaceutical com-pounding can serve as an effective alternativefor those situations when off-the-shelf medications are not the best tools for optimal treatment of the individual patient.

Kudos to Drs. Ghen and Rains for puttingtogether this excellent new desk referenceguide. The Physicians’ Guide can give practitioners the support and direction theyneed for understanding the art of com-pounding and selecting the most highlyqualified professionals available. The 400+pages are almost evenly divided betweenchapters on the qualifications, techniques,and the various products of the compound-ing pharmacy and individual monographswith over 240 unique prescriptions.

The Ghen and Rains Physicians’ Guide to Pharmaceutical Compoundingby Mitchell J. Ghen, D.O., Ph.D., and John R. Rains, Pharmacist, F.A.C.A. Reviewed by Bob Smith

Featured Book

ReviewThe Ghen and RainsPhysicians’ Guide toPharmaceuticalCompounding, by MitchellJ. Ghen, D.O., Ph.D., andJohn R. Rains, Pharmacist,F.A.C.A. Green Bay, WI:IMPAKT Communications,2001. ISBN 1-890694-29-0.

Organized into a distinct chapter format, thebook begins with a specific set of principlesfor a longevity-based practice. From cellulardetoxification, nutrition, and oxygenation toinclusion of psycho-social-spiritual aspects oflife, Dr. Ghen’s model holds essential keys toa wide-ranging assessment. It provides acogent model for clinicians to keep in mindas they explore an individual’s health:enhancement of the dynamic genome/envi-ronment interaction to its optimal endpointin the 21st century.

The following chapters begin with a scholarly,historical review of the basis of aging. Theprocesses of reactive oxygen species generation, advanced glycation end-products,and redox balance are then challenged andhighlighted as to those most amenable tomodification. In Chapter 3 we get someintriguing images of the future from Dr.Klatz, one of the pioneers of longevity medicine and keystone workers in theAmerican Academy of Anti-Aging Medicine.

The book’s other chapters then present anin-depth look at some of the pivotal topics and interventions intrinsic tolongevity medicine practice. Discussion ofBiogenic medicine and new diagnosticand therapeutic methods are supportedby strategies of genetic modification viadiet. The concept of the CRON diet; (calo-rie restricted-optimal nutrition), is one tocounter the epidemic of carbohydrateexcess that results in our skyrocketingrates of dysglylcemia and type II diabetes.

Subsequent discussions include aging andimmune system changes (an excellent article by Dr. Bock), laboratory assess-ments, pros/cons and methods of hor-mone replacement therapy and homeo-pathic human growth hormone, as well asan exhaustive review of probiotics, enzymetherapy, and hormone monitoring. Thesearticles are well written and contain manypearls worthy of incorporation into clinicalpractice.

24

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Drs. Melvyn Werbach and JeffreyMoss have produced an impressive,well-organized, and well-

documented textbook on nutrition. Thisbook abstracts and analyzes thousands ofresearch studies, providing an overview ofthe clinical applications of nutrition in practice as well as nutritional protocols for awide range of clinical disorders.

The Textbook of Nutritional Medicine is primarily aimed at healthcare practitioners whoincorporate nutritional medicine in theirprotocols and is of great value to those skeptics who need scientific verification of

this highly validated field. This book is anextensive compilation of clini-cally relevant information andpractical guidelines coveringnutritional therapies for themost common clinical conditions. Descriptionsinclude medical terminologythat requires a basic understanding of physiologyand pathology.

The book is divided into threeparts; Part One: General evalu-ation and treatment, coveringNutrition and IntegrativeMedicine, CommonNutritional DeficiencySyndromes, LaboratoryTesting in Nutritional

Medicine, Overview of the ClinicalUse of Nutritional Supplements, and

How to Rule Out Food Sensitivities; PartTwo: Nutritional Treatments for SpecificIllnesses, detailing 105 conditions; and PartThree: Useful appendices covering essentialreference information.

In Part One, the authors provide a perspective of the most common nutritional-ly relevant causes of chronic illness which aredivided into five broad categories:Neuroendocrine imbalance, improper nutrition, chemical and/or heavy metal toxi-city, compromised mucosal barriers, and

genetics. This perspective provides a contemporary approach to addressing com-monly encountered clinical conditions froma nutritional and functional point of view.The section on neuroendocrine imbalancesprovides an impressive understanding of thestress response, describing the physiology,causative factors, clinical relevance, and clinical implications.

I found the chapter on Overview of theClinical Use of Nutritional Supplements tobe quite compelling. Much thought andwork has gone into providing a strong argu-ment for the use of nutritional supplementa-tion, which is backed by current statisticscomparing pharmacotherapy (including riskof toxicity) to nutrient supplementation.

One area that is sure to attract interest is thediscussion on genetics (which involves theemerging arena of genomics) and includesan exceptional discussion on nutritionalinfluences on gene expression.

The heart of the book, NutritionalTreatments for Specific Diseases covers the105 most common presenting clinical conditions. Each chapter starts with aNutritional Treatment Guide that lists treat-ments discussed in the text and rates thetreatment according to efficacy. The treat-ment protocols are in-depth and up-to-date.

All practitioners of nutritional medicine willfind this book to be a valuable and succinctresource of advanced, clinically relevantinformation. The insightful perspective,together with scientifically validatedresearch, provides a meaningful educationfor those entering this field.

Not only is this an excellent clinical resourcefor the clinician, but it also provides substantial useful information for those whomake presentations and require referencesand documentation. Overall I found thisbook to be an outstanding clinical resourcethat should be on every nutrition-orientedclinician’s bookshelf.

Textbook of Nutritional Medicineby Melvyn Werbach, M.D. and Jeffrey Moss, DDS, CNS, CCNReviewed by Russel Sher, D.C. Textbook of Nutritional

Medicine, by MelvynWerbach, M.D. and Jeffrey

Moss, DDS, CNS, CCN.Tarzana, CA: Third Line

Press, 1999. ISBN 0-9618550-9-6

Featured Book

Review

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“What can I eat on a yeast free diet?” This is a common question posed by manypatients when embarking on an anti-candi-da regime. Tammy Joseph offers practicaladvice on how to remove yeast-promotingfoods from the diet, a vital step in over-coming systemic fungal infection.

The author speaks from first-hand experi-ence, having successfully eradicated theorganism, predominantly through dietaryintervention. Like many people plagued byovergrowth of Candida, she suffered acluster of vague, but very real symptoms.Also like so many people who are hostingthis unwelcome visitor, she found no relieffrom conventional approaches to hersymptoms. “Doctor after doctor performedexpensive tests, then bestowed a similarverdict, telling me, ‘You’re clearly ill, butyour tests are within the normal range.’”

A chance encounter with a specialist inmetabolic and nutritional disorders, RonRosedale, M.D., marked the beginning ofher turn-around. His nutritional advicesparked her recovery and inspired herbook.

Inside You Are Within Normal Range is a com-prehensive list of foods to avoid, those rec-ommended, as well as handy shopping anddining out tips. Numerous recipes are pro-vided, along with companies that can sup-ply the ingredients - all invaluable informa-tion when initially modifying the diet.

Targeted for the layperson, the book alsooutlines the symptoms of yeast overgrowth,along with diagnostic profiles to assist inidentification. You Are Within NormalRange an ideal book for practitioners tooffer patients, once they have been diag-nosed with a systemic yeast infection.

Yeast Connection Success Storiesby William G. Crook, M.D., Reviewed by Corene Humphreys, N.D.

You Are Within Normal Rangeby Tammy Joseph, Reviewed by Corene Humphreys, N.D.

Dr. William Crook has written yet anotherexceptional book about systemic candida.Differing from his previous work, this book ispredominantly written from the point of viewof patient testimonials - both his own and thatof colleagues - which reflect the importance ofappreciating the body as an integrative whole,rather than as isolated parts.

The engaging testimonials reminded me, onceagain, of the many “faces” this insidious organ-ism can present with. Unlike most acute infec-tions, there is no predictable pattern of symp-toms with yeast dysbiosis - clinical manifesta-tions can affect a multitude of organs. Whatdetermines the emphasis appears to be some-what bio-individual. This, in part, may accountfor the reluctance of conventional medicinepractitioners to acknowledge yeast overgrowthas a clinically significant condition.

The common thread for these patients oftenlies in the prescribing, or over use, of antibiotictherapy. From this point many begin a slow,yet progressive, decline of health.

When conventional medicine fails to identifythe etiology, or rationale, the search begins.For some, it takes many years to find theanswers—a journey that ultimately brings themto the discovery of Crook’s extensive researchin this field.

Screening for candida overgrowth is an invalu-able diagnostic tool for practitioners - especially when conventional laboratory find-ings fail to provide any clinical explanation.

I wholly recommend this book to both the layperson and the practitioner, who can also benefitfrom the commentary by several practitioners included in the final chapter ofthe book.

The road to recovery is not an effortless onefor those afflicted with systemic candida.Adhering to the protocols requires disciplineand commitment. However, reading the suc-cess stories of others offers inspiration to helpstay focused and a sense of camaraderie duringthe challenging times.

Featured Book

ReviewYou Are Within NormalRange, by Tammy Joseph.Self Published:www.youarewithinnormal-range.com, 2001.

Featured Book

ReviewYeast Connection SuccessStories, by William G.Crook, M.D. Jackson, TN:Professional Books, 2002.ISBN 0-939478-26-7

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TThe concept of‘biochemical individuality’ was

first proposed by RogerWilliams in 1956 toexplain variability in disease susceptibility,nutrient needs, and drug

responsiveness among otherwise seeminglyhealthy people. It is only in the wake of theongoing genomic revolution, however, thatpredictive genetic testing has become avail-able to allow us to assess true biochemicalindividuality. For the first time, physicianscan gauge with increasing precision who ismore likely to develop specific diseases, whowill respond favorably (or react adversely) toa particular drug or supplement therapy,and, finally, which nutrients are optimal for

a particular individual’s health andwell-being.

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Genetics is the scientific study ofheredity, one gene at a time.

Genomics is the study of genomes,or the totality of the DNA of a single

species. While genetics studies the laws ofinheritance in an isolatedand linear fashion,Genomics attemptsto look at all ourgenes together

as a flexible,dynamic system

over time, interact-ing with and influenc-

ing our biochemicalpathways and physiology.

The Human Genome Project isthe mapping and sequencing of the

entire human genome. The first draft

of the entire human genome was publishedin April 2001, almost exactly one hundredyears after the rediscovery of Mendel’s“Laws of Heredity.” The human genomeconsists of slightly more than 3 billionnucleotides (give or take a hundred million)and it codes for every protein and everyenzyme made by the human body. Some30,000 to 40,0000 genes are thought toexist in the human genome, yet we knowthe function of slightly less than half ofthem.

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As primary care practitioners, we stand at acritical crossroads where increases in availability of DNA-based testing anddemand by patients for genetic informationand advice necessitate our need to becomeboth genetically literate and genomicallycompetent. The power to read and understand the genetic code of individualswill prove to be every bit as great an advancein clinical diagnostics as when RobertHooke’s improvements to the microscopeallowed scientists to discover that livingorganisms were made up of “cells.”

New methods of investigating the genomeare now being aimed at better understand-ing the multifactorial etiology of the mostprevalent and debilitating health conditionsthat humans face - opening up the poten-tial for astounding clinical applications.

Director of Curriculum Development T. Michael Culp,M.A., N.D,. received his doctoral degree from BastyrUniversity. In addition to his particular expertise intherapeutic and orthomolecular nutrition, Dr. Culp hastaught graduate courses at Bastyr University andAtlantic University of Chinese Medicine.

CClliinniiccaall GGeennoommiiccss – The NextGeneration of Healthy Aging Medicine

By T. Michael Culp, N.D.

"Virtually all humandiseases result from

the interaction ofgenetic susceptibility

factors and modifiableenvironmental factors,

broadly defined toinclude infectious,chemical, physical,

nutritional, andbehavioral factors."

Office of Genetics andDisease Prevention of the

Centers for DiseaseControl and Prevention

(CDC).

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Key Concepts

• Virtually all human diseases result from the interaction of genetic susceptibility and modifiable environmentalfactors, broadly defined to include infectious, chemical, physical, nutritional, and behavioral factors.

• Slight variations in genetic makeup called Single Nucleotide Polymorphisms (SNPs - pronounced “snips”) areassociated with almost all diseases.

• Genetic variations themselves do not cause disease but rather influence a person’s susceptibility to specific envi-ronmental interactions that increase disease risk.

• GENOVATIONS™ offers a unique line of Predictive Genomic Diagnostic Profiles. Each profile focuses on a care-fully selected set of SNPs associated with a particular disease or physiologic imbalance (e.g. cardiovascular, bonemetabolism, detoxification, immune surveillance, etc.).

Touchstones for Genomics Testing

Though many SNPs can be related to a particular disease or function, not all are clinically useful. To assure clinical value, the Genovations™ line of CardioGenomicSM,, OsteoGenomicSM, and ImmunoGenomicSM Profilesassess only SNPs that meet four critical requirements:

Relevant- GENOVATIONS™ SNPs are carefully selected based on their direct influence over specific biochemicalimbalances which create known symptom clusters or diseases.

Prevalent- GENOVATIONS™ SNPs carry clinically significant population prevalence. These are relatively commongenetic predispositions associated with extremely prevalent conditions.

Modifiable-. GENOVATIONS™ profiles focus on genetic variations whose expression is influenced by environmental factors. Each profile contains intervention options based on the patient’s genomic pattern.

Measurable- For each SNP, GENOVATIONS™ profiles provide recommendations for follow-up functional laboratory testing. These functional assessments evaluate and monitor phenotypic expression of genetic tendency,functional integrity, and metabolic reserve.

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