MICRONUTRIENTS IN THE ELDERLY Age-related deficiencies in microelements Doron Garfinkel, M.D

NUTRITION AND LONGEVITY CONFERENCE, Danone Institute Israel, March 26, 2001.

HEALTH PROMOTION THE ROLE OF NUTRITION IN PREVIOUS CENTURIES, B.C

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18th.

19 th.

20 th.

HEALTH PROMOTION IN 20th. CENTURY DETECTING SPECIFIC NUTRITIONAL DEFICIENCIES DEFICIENCY DISEASE 20th. Century VITAMIN C SCURVY VITAMIN D RICKETS PYRIDOXINE, IRON, FOLIC ACID ANEMIAS IODINE HYPOTHYROIDISM FLUORIDE CARIES

HEALTH PROMOTION IN 20th. CENTURY SUCCESSFUL PREVENTION OF SPECIFIC NUTRITIONAL DEFICIENCIES THE GOAL: 20th. Century ACHIEVING THE RECOMMENDED DIETARY ALLOWANCE ( R. D. A. )

HEALTH PROMOTION - 21st CENTURY A NEW ROLE FOR NUTRITION ???

21 ST.

CENTURY INHIBITING AGE RELATED PROCESSES DECREASING MORTALITY & MORBIDITY FROM CHRONIC AGE-RELATED DISEASES

EXPANDING HEALTH FRONTIERS IN THE 21 ST CENTURY CAN WE PREVENT OR POSTPONE THE OMINOUS CONSEQUENSES OF AGE - RELATED DISEASES BY DIETARY MANIPULATION ?

SPECIFIC NUTRIENT SUPPLEMENTATION ?

EFFECTIVE DOSE ? TOXICITY ? THERAPEUTIC RANGE ?

MAGIC-BOOLET?

R. D. A. or HIGHER?? “MEGADOSES” ???

THERE ARE NO MAGIC BOOLETS !

MICROELEMENTS

ZINC , COPPER, MAGNESIUM, CHROMIUM , SELENIUM, MOLYBDEN S I I L (Lead, Arsenic, Cadmium... ) C O N

TESTING “ANTI-AGING” CLAIMS IN MOST CASES, THERE ARE NO RELIABLE, CONTROLLED STUDIES REGARDING THE EFFICACY AND/OR SAFETY OF NUTRITIONAL ELEMENTS THAT HAVE BEEN SUGGESTED TO INDUCE AN “ANTI - AGING” EFFECT (OR AN INHIBITING EFFECT ON AGE-RELATED DISEASES)

SEARCHING “ANTI-AGING” AGENTS IN OUR ATTEMPT TO DISCOVER NUTRITIONAL “INHIBITORS” OF AGE-RELATED DISEASES, IT WOULD BE LOGICAL TO CONCENTRATE ON FACTORS KNOWN TO HAVE BOTH: BENEFICIAL EFFECTS ON LIVING CELLS DECREASED CONCENTRATIONS AND/OR ACTIVITY IN ELDERLY PEOPLE

INHIBITION OF AGING PROCESSES ....

YES, I SEE !

Z I N C !!

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why zinc ?

INHIBITION OF AGING PROCESSES

UNDERFEEDING WHICH STARTS AT WEANING AND CONTINUES THROUGHOUT LIFE , CAN SLOW DOWN THE AGING PROCESS

INHIBITION OF AGING PROCESSES

THE PRECISE MECHANISM BY WHICH THE UNDERFEEDING REGIMENS PROLONGS MAXIMAL LIFESPAN , REMAINS UNKNOWN

INHIBITION OF AGING PROCESSES

“ RESTRICTED DIETS ” HAVE HIGHER CONCENTRATIONS OF ZINC AND THEIR ALTERED COMPOSITION HAS A BENEFICIAL EFFECT ON ZINC BIOAVAILABILITY

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IS AGING INEVITABLE ? THE INTRACELLULAR ZINC DEFICIENCY HYPOTHESIS OF AGING D. GARFINKEL , MEDICAL HYPOTHESES 19: 117 - 137 , 1986

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why zinc ?

ZINC METALLOENZYMES (PARTIAL LIST - OUT OF 200) ALCOHOL DEHYDROGENASE ALDOLASE ALKALINE PHOSPHATASE ALKALINE PROTEASE CARBONIC ANHYDRASE CARBOXYPEPTIDASES A, B, C DIPEPTIDASE GLYCERALDEHYDE PHOSPHATE DEHYDROGENASE LEUCINE AMINOPEPTIDASE PHOSPHOGLUCOMUTASE PHOSPHOLIPASE C PYRUVATE CARBOXYLASE RETINAL REDUCTASE

ZINC METALLOENZYMES INFORMATION HANDLING ENZYMES

DNA POLYMERASE RNA POLYMERASE REVERSE TRANSCRIPTASE TdT THYMIDINE KINASE

ZINC FINGERS

TRANSCRIPTION FACTORS ACTIVATE GENES USING SMALL PROJECTIONS KNOWN AS ZINC FINGERS THAT ARE PERFECTLY SUITED TO DNA RECOGNITION . . . ZINC FINGERS PLAY A KEY PART IN REGULATING THE ACTIVITY OF GENES IN MANY SPECIES, FROM YEAST TO HUMANS...

D. Rhodes & A. Klug Scientific American, February 1993, pp. 32-39

ZINC IS AN ESSENTIAL FACTOR

FOR GROWTH, DEVELOPMENT AND NORMAL FUNCTION OF EVERY LIVING CELL

IS THERE AN AGE-RELATED

ZINC DEFICIENCY ?

zinc

PROBLEMS IN ASSESSING ZINC STATUS

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AT PRESENT, THERE IS NO SIMPLE AND RELIABLE INDEX OF ZINC STATUS

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THERE IS SELDOM A CORRELATION BETWEEN ZINC CONCENTRATIONS IN HAIR OR TOENAILS, ERYTHROCYTES , PLASMA OR URINE NONE OF THESE MEASUREMENTS PROVIDES A SENSITIVE INDICATION OF ZINC STATUS

ASSESSING ZINC STATUS

In Apparently Normal Children with Poor Growth but No Evidence of Zinc Deficiency, Zinc Supplementation Induced a Significant Increase in Height with No Significant Change in Plasma Zinc Levels... Suggesting an Undetected Zinc Deficiency in Those “Normal” Children...

Walravens PA et al. Am J Clin Nutr 1983; 38:195-201

ASSESSING ZINC STATUS

THE CORNERSTONE OF THE DEFINITION AND DETECTION OF ZINC DEFICIENCY IS A THERAPEUTIC TRIAL OF ZINC ADMINISTRATION Brit. Med. J. 1981 (Editorial)

TESTING THE HYPOTHESIS

IF WE ALL DEVELOP AN AGE - RELATED ZINC DEFICIENCY BUT ITS DETECTION IS IMPOSSIBLE WE CAN PERFORM THERAPEUTIC TRIALS TO ASSESS EFECTS OF ZINC SUPPLEMENTATION ON MEASURABLE AGE - RELATED PROCESSES

THE SUBJECTS

HEALTHY MALES AND FEMALES AGED 40 - 65 , WHO PARTICIPATE IN A LONGITUDINAL STUDY OF AT LEAST 5 YEARS (STARTED 1989 AT THE WOLFSON MEDICAL CENTER)

THE COMPOUND

ZINC SULFATE 300 mg (68 mg ELEMENTAL ZINC) A PLACEBO IDENTICAL IN APPEARANCE

EFFECTS OF PROLONGED ZINC SUPPLEMENTATION

ON THE AGE - RELATED DECLINE OF THE IMMUNE SYSTEM

IMMUNITY

AND

ZINC

ZINC DEFICIENCY IS ASSOCIATED WITH IMPAIRED T-CELL FUNCTION ZINC ADMINISTRATION IMPROVES CELL - MEDIATED IMMUNITY IN THE ELDERLY

IMMUNOLOGICAL STUDY METHODS

LABORATORY TESTS : GLUTATHION REDUCTASE, GLUTATHION PEROXYDASE, CATALASE AND SUPER OXIDE DISMUTASE (SOD) - IN RBC.

MAGNESIUM, CERULOPLASMIN, COPPER, BETA CAROTEN & VITAMIN E - IN SERUM ZINC in PLASMA, RBC & MONONUCLEARS

IMMUNOLOGICAL STUDY METHODS

DELAYED - TYPE HYPERSENSITIVITY (DTH) SKIN REACTIONS TO 7 ANTIGENS WERE ASSESED BY MULTITEST :

;;;;

Tuberculin, Diphteria, Tetanus, Proteus, Streptococcus, Candida & Trichophyton

EFFECT OF ZINC SUPPLEMENTATION ON PLASMA, RBC & MNC ZINC PLASMA ug / dL PLACEBO Z I N C p = 0.01

RBC MNC

EFFECT OF ZINC SUPPLEMENTATION ON DTH SKIN RESPONSES N 0 3 2 5 4 1 0 NUMBER OF POSITIVE RESPONSES ZINC PLACEBO

EFFECT OF ZINC SUPPLEMENTATION ON DTH SKIN RESPONSES TOTAL SCORE AVERAGE TOTAL INDURATION Z I N C PLACEBO P < .

001

CONCLUSIONS

PROLONGED ZINC SUPPLEMENTATION MAY INHIBIT THE AGE- RELATED DECLINE IN CELLULAR IMMUNITY ( AT LEAST AS RELATED TO DTH SKIN TESTS) PROLONGED ZINC SUPPLEMENTATION IN ADULTS IS REFLECTED IN INCREASED PLASMA ZINC CONCENTRATIONS