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Doron Garfinkel, M.D, Danone Institute Israel, March 26, 2001. NUTRITION AND LONGEVITY CONFERENCE, Danone Institute Israel, March 26, 2001. Age-related.

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Presentation on theme: "Doron Garfinkel, M.D, Danone Institute Israel, March 26, 2001. NUTRITION AND LONGEVITY CONFERENCE, Danone Institute Israel, March 26, 2001. Age-related."— Presentation transcript:

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2 Doron Garfinkel, M.D, Danone Institute Israel, March 26, NUTRITION AND LONGEVITY CONFERENCE, Danone Institute Israel, March 26, Age-related deficiencies in microelements MICRONUTRIENTS IN THE ELDERLY Age-related deficiencies in microelements

3 HEALTH PROMOTION THE ROLE OF NUTRITION 18th.18th. 19 th. B.C. IN PREVIOUS CENTURIES, 20 th. DEFICIENCIES OF SPECIFIC NUTRITIONAL ELEMENTS WERE RESPONSIBLE FOR SIGNIFICANT MORTALITY AND MORBIDITY IN THE GENERAL POPULATION IN THE GENERAL POPULATION DEFICIENCIES OF SPECIFIC NUTRITIONAL ELEMENTS WERE RESPONSIBLE FOR SIGNIFICANT MORTALITY AND MORBIDITY IN THE GENERAL POPULATION IN THE GENERAL POPULATION

4 DETECTING SPECIFIC NUTRITIONAL DEFICIENCIES 20th. Century VITAMIN A NIGHT BLINDNESS NIACIN PELLAGRA THIAMINE BERI BERI VITAMIN A NIGHT BLINDNESS NIACIN PELLAGRA THIAMINE BERI BERI DEFICIENCY DISEASE HEALTH PROMOTION IN 20th. CENTURY VITAMIN C SCURVY VITAMIN D RICKETS PYRIDOXINE, IRON, FOLIC ACID ANEMIAS IODINE HYPOTHYROIDISM FLUORIDE CARIES VITAMIN C SCURVY VITAMIN D RICKETS PYRIDOXINE, IRON, FOLIC ACID ANEMIAS IODINE HYPOTHYROIDISM FLUORIDE CARIES

5 20th. Century ENRICHING WATER AND FOOD WITH ESSENTIAL NUTRITIONAL ELEMENTS IN ORDER TO AVOID DISEASES CAUSED BY SPECIFIC NUTRIENT DEFICIENCY ENRICHING WATER AND FOOD WITH ESSENTIAL NUTRITIONAL ELEMENTS IN ORDER TO AVOID DISEASES CAUSED BY SPECIFIC NUTRIENT DEFICIENCY THE GOAL: ACHIEVING THE RECOMMENDED DIETARY ALLOWANCE RECOMMENDED DIETARY ALLOWANCE ( R. D. A. ) ( R. D. A. ) THE GOAL: ACHIEVING THE RECOMMENDED DIETARY ALLOWANCE RECOMMENDED DIETARY ALLOWANCE ( R. D. A. ) ( R. D. A. ) HEALTH PROMOTION IN 20th. CENTURY SUCCESSFUL PREVENTION OF SPECIFIC NUTRITIONAL DEFICIENCIES

6 HEALTH PROMOTION - 21st CENTURY A NEW ROLE FOR NUTRITION ??? 21 ST. CENTURY CENTURY NUTRITIONAL INTERVENTIONS MAY REPRESENT THE EASIEST, MAY REPRESENT THE EASIEST, MOST SIMPLE AND MOST SIMPLE AND COST - EFFECTIVE MEANS FOR : COST - EFFECTIVE MEANS FOR : NUTRITIONAL INTERVENTIONS MAY REPRESENT THE EASIEST, MAY REPRESENT THE EASIEST, MOST SIMPLE AND MOST SIMPLE AND COST - EFFECTIVE MEANS FOR : COST - EFFECTIVE MEANS FOR : INHIBITING AGE RELATED PROCESSES DECREASING MORTALITY & MORBIDITY FROM CHRONIC AGE-RELATED DISEASES

7 EXPANDING HEALTH FRONTIERS IN THE 21 ST CENTURY CAN WE PREVENT OR POSTPONE THE OMINOUS CONSEQUENSES OF AGE - RELATED DISEASES BY DIETARY MANIPULATION ? DIETARY MANIPULATION ? CAN WE PREVENT OR POSTPONE THE OMINOUS CONSEQUENSES OF AGE - RELATED DISEASES BY DIETARY MANIPULATION ? DIETARY MANIPULATION ? SPECIFIC NUTRIENT SUPPLEMENTATION ? EFFECTIVE DOSE ? TOXICITY ? THERAPEUTIC RANGE ? R. D. A. or HIGHER?? “MEGADOSES” ??? MAGIC-BOOLET? THERE ARE NO MAGIC B OOLETS !

8 ZINC, COPPER, MAGNESIUM, CHROMIUM, SELENIUM, MOLYBDEN ALUMINUM BORE, BROMINE TIN TIN TIN TIN FLUORIDE LITHIUM, NICKEL SILICONSILICON SILICONSILICON VANADIUM, RUBIDIUM, GERMANIUM (Lead, Arsenic, Cadmium... ) MICROELEMENTS

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

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

11 INHIBITION OF AGING PROCESSES.... YES, I SEE ! Z I N C !!

12 why zinc ? ? ?

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

14 INHIBITION OF AGING PROCESSES THE PRECISE MECHANISM BY WHICH THE UNDERFEEDING REGIMENS PROLONGS MAXIMAL LIFESPAN, REMAINS UNKNOWN THE PRECISE MECHANISM BY WHICH THE UNDERFEEDING REGIMENS PROLONGS MAXIMAL LIFESPAN, REMAINS UNKNOWN

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

16 * * * IS AGING INEVITABLE ? THE INTRACELLULAR ZINC DEFICIENCY HYPOTHESIS OF AGING IS AGING INEVITABLE ? THE INTRACELLULAR ZINC DEFICIENCY HYPOTHESIS OF AGING D. GARFINKEL, MEDICAL HYPOTHESES 19: , 1986 D. GARFINKEL, MEDICAL HYPOTHESES 19: , 1986

17 why zinc ? ? ?

18 ZINC METALLOENZYMES (PARTIAL LIST - OUT OF 200) 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 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

19 ZINC METALLOENZYMES INFORMATION HANDLING ENZYMES ZINC METALLOENZYMES INFORMATION HANDLING ENZYMES DNA POLYMERASE RNA POLYMERASE REVERSE TRANSCRIPTASE TdT THYMIDINE KINASE DNA POLYMERASE RNA POLYMERASE REVERSE TRANSCRIPTASE TdT THYMIDINE KINASE

20 ZINC FINGERS TRANSCRIPTION FACTORS ACTIVATE GENES USING SMALL PROJECTIONS KNOWN AS ZINC FINGERS THAT ARE PERFECTLY SUITED TO DNA RECOGNITION... 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... 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 D. Rhodes & A. Klug Scientific American, February 1993, pp

21 ZINC IS AN ESSENTIAL FACTOR FOR GROWTH, DEVELOPMENT AND NORMAL FUNCTION OF EVERY LIVING CELL

22 IS THERE AN AGE-RELATED ZINC DEFICIENCY ? zinc

23 Z Z AT PRESENT, THERE IS NO SIMPLE AND RELIABLE INDEX OF ZINC STATUS Z Z THERE IS SELDOM A CORRELATION BETWEEN ZINC CONCENTRATIONS IN HAIR OR TOENAILS, ERYTHROCYTES, PLASMA OR URINE Z Z AT PRESENT, THERE IS NO SIMPLE AND RELIABLE INDEX OF ZINC STATUS Z Z THERE IS SELDOM A CORRELATION BETWEEN ZINC CONCENTRATIONS IN HAIR OR TOENAILS, ERYTHROCYTES, PLASMA OR URINE PROBLEMS IN ASSESSING ZINC STATUS PROBLEMS IN ASSESSING ZINC STATUS NONE OF THESE MEASUREMENTS PROVIDES A SENSITIVE INDICATION OF ZINC STATUS

24 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... Walravens PA et al. Am J Clin Nutr 1983; 38: Suggesting an Undetected Zinc Deficiency in Those “Normal” Children...

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

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

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

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

29 EFFECTS OF PROLONGED EFFECTS OF PROLONGED ZINC SUPPLEMENTATION ZINC SUPPLEMENTATION EFFECTS OF PROLONGED EFFECTS OF PROLONGED ZINC SUPPLEMENTATION ZINC SUPPLEMENTATION ON THE AGE - RELATED DECLINE OF THE IMMUNE SYSTEM OF THE IMMUNE SYSTEM

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

31 IMMUNOLOGICAL STUDY METHODS GLUTATHION REDUCTASE, GLUTATHION PEROXYDASE, CATALASE AND SUPER OXIDE DISMUTASE (SOD) - IN RBC. GLUTATHION REDUCTASE, GLUTATHION PEROXYDASE, CATALASE AND SUPER OXIDE DISMUTASE (SOD) - IN RBC. LABORATORY TESTS : MAGNESIUM, CERULOPLASMIN, COPPER, MAGNESIUM, CERULOPLASMIN, COPPER, BETA CAROTEN & VITAMIN E - IN SERUM BETA CAROTEN & VITAMIN E - IN SERUM ZINC in PLASMA, RBC & MONONUCLEARS ZINC in PLASMA, RBC & MONONUCLEARS MAGNESIUM, CERULOPLASMIN, COPPER, MAGNESIUM, CERULOPLASMIN, COPPER, BETA CAROTEN & VITAMIN E - IN SERUM BETA CAROTEN & VITAMIN E - IN SERUM ZINC in PLASMA, RBC & MONONUCLEARS ZINC in PLASMA, RBC & MONONUCLEARS

32 IMMUNOLOGICAL STUDY METHODS IMMUNOLOGICAL STUDY METHODS DELAYED - TYPE HYPERSENSITIVITY (DTH) SKIN REACTIONS TO 7 ANTIGENS WERE ASSESED BY MULTITEST : DELAYED - TYPE HYPERSENSITIVITY (DTH) SKIN REACTIONS TO 7 ANTIGENS WERE ASSESED BY MULTITEST : ;;;; Tuberculin, Diphteria, Tetanus, Proteus, Streptococcus, Candida & Trichophyton

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

34 EFFECT OF ZINC SUPPLEMENTATION ON DTH SKIN RESPONSES ZINC PLACEBO NUMBER OF POSITIVE RESPONSES P <.001

35 EFFECT OF ZINC SUPPLEMENTATION ON DTH SKIN RESPONSES Z I N C PLACEBOPLACEBO AVERAGE TOTAL INDURATION TOTAL SCORE TOTAL SCORE P <. 001

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


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