Doron Garfinkel, M.DDoron Garfinkel, M.D
NUTRITION AND LONGEVITY CONFERENCE, ,
Danone Institute Israel, March 26, 2001.Danone Institute Israel, March 26, 2001.
NUTRITION AND LONGEVITY CONFERENCE, ,
Danone Institute Israel, March 26, 2001.Danone Institute Israel, March 26, 2001.
MICRONUTRIENTS IN THE ELDERLY
Age-related deficiencies in microelementsAge-related deficiencies in microelements
MICRONUTRIENTS IN THE ELDERLY
Age-related deficiencies in microelementsAge-related deficiencies in microelements
HEALTH PROMOTION THE ROLE OF NUTRITIONHEALTH PROMOTION THE ROLE OF NUTRITION
18th.18th.18th.18th. 19 th.19 th.19 th.19 th.
B.CB.C..
IN PREVIOUS CENTURIES,IN PREVIOUS CENTURIES,
20 th.20 th.20 th.20 th.
DEFICIENCIES OF SPECIFIC NUTRITIONAL DEFICIENCIES OF SPECIFIC NUTRITIONAL
ELEMENTS WERE RESPONSIBLE FOR ELEMENTS WERE RESPONSIBLE FOR
SIGNIFICANT MORTALITY AND MORBIDITY SIGNIFICANT MORTALITY AND MORBIDITY
IN THE GENERAL POPULATIONIN THE GENERAL POPULATION
DEFICIENCIES OF SPECIFIC NUTRITIONAL DEFICIENCIES OF SPECIFIC NUTRITIONAL
ELEMENTS WERE RESPONSIBLE FOR ELEMENTS WERE RESPONSIBLE FOR
SIGNIFICANT MORTALITY AND MORBIDITY SIGNIFICANT MORTALITY AND MORBIDITY
IN THE GENERAL POPULATIONIN THE GENERAL POPULATION
DETECTING SPECIFIC NUTRITIONAL DEFICIENCIES
DETECTING SPECIFIC NUTRITIONAL DEFICIENCIES
20th. Century20th. Century20th. Century20th. Century
VITAMIN A NIGHT BLINDNESS VITAMIN A NIGHT BLINDNESS
NIACIN PELLAGRANIACIN PELLAGRA
THIAMINE BERI BERITHIAMINE BERI BERI
VITAMIN A NIGHT BLINDNESS VITAMIN A NIGHT BLINDNESS
NIACIN PELLAGRANIACIN PELLAGRA
THIAMINE BERI BERITHIAMINE BERI BERI
DEFICIENCY DEFICIENCY DISEASEDISEASEDEFICIENCY DEFICIENCY DISEASEDISEASE
HEALTH PROMOTION IN 20th. CENTURYHEALTH PROMOTION IN 20th. CENTURY
VITAMIN C SCURVYVITAMIN C SCURVY
VITAMIN D RICKETSVITAMIN D RICKETS
PYRIDOXINE, IRON, FOLIC ACIDPYRIDOXINE, IRON, FOLIC ACID ANEMIAS ANEMIAS
IODINE HYPOTHYROIDISMIODINE HYPOTHYROIDISM
FLUORIDE CARIESFLUORIDE CARIES
VITAMIN C SCURVYVITAMIN C SCURVY
VITAMIN D RICKETSVITAMIN D RICKETS
PYRIDOXINE, IRON, FOLIC ACIDPYRIDOXINE, IRON, FOLIC ACID ANEMIAS ANEMIAS
IODINE HYPOTHYROIDISMIODINE HYPOTHYROIDISM
FLUORIDE CARIESFLUORIDE CARIES
20th. Century20th. Century20th. Century20th. Century
ENRICHING WATER AND FOOD WITH ENRICHING WATER AND FOOD WITH ESSENTIAL NUTRITIONAL ELEMENTS ESSENTIAL NUTRITIONAL ELEMENTS
IN ORDER TO AVOID DISEASES CAUSED IN ORDER TO AVOID DISEASES CAUSED BY SPECIFIC NUTRIENT DEFICIENCYBY SPECIFIC NUTRIENT DEFICIENCY
ENRICHING WATER AND FOOD WITH ENRICHING WATER AND FOOD WITH ESSENTIAL NUTRITIONAL ELEMENTS ESSENTIAL NUTRITIONAL ELEMENTS
IN ORDER TO AVOID DISEASES CAUSED IN ORDER TO AVOID DISEASES CAUSED BY SPECIFIC NUTRIENT DEFICIENCYBY SPECIFIC NUTRIENT DEFICIENCY
THE GOAL: THE GOAL:
ACHIEVING THE ACHIEVING THE
RECOMMENDED DIETARY ALLOWANCE RECOMMENDED DIETARY ALLOWANCE
( R. D. A. )( R. D. A. )
THE GOAL: THE GOAL:
ACHIEVING THE ACHIEVING THE
RECOMMENDED DIETARY ALLOWANCE RECOMMENDED DIETARY ALLOWANCE
( R. D. A. )( R. D. A. )
HEALTH PROMOTION IN 20th. CENTURYHEALTH PROMOTION IN 20th. CENTURYSUCCESSFUL PREVENTION OF
SPECIFIC NUTRITIONAL DEFICIENCIESSUCCESSFUL PREVENTION OF
SPECIFIC NUTRITIONAL DEFICIENCIES
HEALTH PROMOTION - 21st CENTURY
A NEW ROLE FOR NUTRITION ???
HEALTH PROMOTION - 21st CENTURY
A NEW ROLE FOR NUTRITION ???
21 ST.21 ST.
CENTURYCENTURY
21 ST.21 ST.
CENTURYCENTURY
NUTRITIONAL INTERVENTIONS 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 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 INHIBITING AGE RELATED PROCESSES
DECREASING MORTALITY & MORBIDITY DECREASING MORTALITY & MORBIDITY
FROM CHRONIC AGE-RELATED DISEASESFROM CHRONIC AGE-RELATED DISEASES
EXPANDING HEALTH FRONTIERS IN THE 21ST CENTURY
EXPANDING HEALTH FRONTIERS IN THE 21ST CENTURY
CAN WE PREVENT OR POSTPONECAN WE PREVENT OR POSTPONE
THE OMINOUS CONSEQUENSES OF THE OMINOUS CONSEQUENSES OF
AGE - RELATED DISEASES BY AGE - RELATED DISEASES BY
DIETARY MANIPULATION ?DIETARY MANIPULATION ?
CAN WE PREVENT OR POSTPONECAN WE PREVENT OR POSTPONE
THE OMINOUS CONSEQUENSES OF THE OMINOUS CONSEQUENSES OF
AGE - RELATED DISEASES BY AGE - RELATED DISEASES BY
DIETARY MANIPULATION ?DIETARY MANIPULATION ?SPECIFIC NUTRIENT SUPPLEMENTATION ?SPECIFIC NUTRIENT SUPPLEMENTATION ?EFFECTIVE DOSE ? EFFECTIVE DOSE ? TOXICITY ? THERAPEUTIC RANGE ? TOXICITY ? THERAPEUTIC RANGE ?
R. D. A. or HIGHER?? “MEGADOSES” ??? R. D. A. or HIGHER?? “MEGADOSES” ???MAGIC-BOOLET?
THERE ARE NO MAGIC BOOLETSBOOLETS !
ZINC , COPPER, MAGNESIUM, ZINC , COPPER, MAGNESIUM, CHROMIUM , SELENIUM, MOLYBDEN CHROMIUM , SELENIUM, MOLYBDEN
ALUMINUM ALUMINUM BORE, BROMINE
BORE, BROMINETIN
TIN FLUORIDE
FLUORIDE LITHIUM, NICKEL
LITHIUM, NICKEL
SILICON
SILICON
VANADIUM, RUBIDIUM, GERMANIUM
VANADIUM, RUBIDIUM, GERMANIUM
(Lead, Arsenic, Cadmium... )(Lead, Arsenic, Cadmium... )
MICROELEMENTS MICROELEMENTS
TESTING “ANTI-AGING” CLAIMS TESTING “ANTI-AGING” CLAIMS
IN MOST CASES,IN MOST CASES, THERE ARE NO THERE ARE NO RELIABLE, CONTROLLED STUDIESRELIABLE, CONTROLLED STUDIES
THAT HAVE BEEN SUGGESTED TO THAT HAVE BEEN SUGGESTED TO INDUCE AN “ANTI - AGING” EFFECTINDUCE AN “ANTI - AGING” EFFECT
(OR AN INHIBITING EFFECT ON AGE-RELATED DISEASES)
THAT HAVE BEEN SUGGESTED TO THAT HAVE BEEN SUGGESTED TO INDUCE AN “ANTI - AGING” EFFECTINDUCE AN “ANTI - AGING” EFFECT
(OR AN INHIBITING EFFECT ON AGE-RELATED DISEASES)
REGARDING THE EFFICACY AND/OR REGARDING THE EFFICACY AND/OR SAFETY OF NUTRITIONAL ELEMENTSSAFETY OF NUTRITIONAL ELEMENTSREGARDING THE EFFICACY AND/OR REGARDING THE EFFICACY AND/OR SAFETY OF NUTRITIONAL ELEMENTSSAFETY OF NUTRITIONAL ELEMENTS
SEARCHING “ANTI-AGING” AGENTS
SEARCHING “ANTI-AGING” AGENTS
IN OUR ATTEMPT TO DISCOVER NUTRITIONALIN OUR ATTEMPT TO DISCOVER NUTRITIONAL
“ “INHIBITORS” OF AGE-RELATED DISEASES, INHIBITORS” OF AGE-RELATED DISEASES,
IT WOULD BE LOGICAL TO CONCENTRATE IT WOULD BE LOGICAL TO CONCENTRATE ON FACTORS KNOWN TO HAVE BOTH:ON FACTORS KNOWN TO HAVE BOTH:
IN OUR ATTEMPT TO DISCOVER NUTRITIONALIN OUR ATTEMPT TO DISCOVER NUTRITIONAL
“ “INHIBITORS” OF AGE-RELATED DISEASES, INHIBITORS” OF AGE-RELATED DISEASES,
IT WOULD BE LOGICAL TO CONCENTRATE IT WOULD BE LOGICAL TO CONCENTRATE ON FACTORS KNOWN TO HAVE BOTH:ON FACTORS KNOWN TO HAVE BOTH:
BENEFICIAL EFFECTS ON LIVING CELLSBENEFICIAL EFFECTS ON LIVING CELLS
DECREASED CONCENTRATIONS AND/OR DECREASED CONCENTRATIONS AND/OR
ACTIVITY IN ELDERLY PEOPLEACTIVITY IN ELDERLY PEOPLE
INHIBITION OF AGING PROCESSES ....INHIBITION OF AGING PROCESSES ....
YES, I SEE !YES, I SEE ! Z I N C !!Z I N C !!
why zinc ? why zinc ?
??
INHIBITION OF AGING PROCESSES INHIBITION OF AGING PROCESSES
WHICH STARTS AT WEANING AND WHICH STARTS AT WEANING AND
CONTINUES THROUGHOUT LIFE , CONTINUES THROUGHOUT LIFE , CAN SLOW DOWN CAN SLOW DOWN THE AGING PROCESS THE AGING PROCESS
UNDERFEEDING
INHIBITION OF AGING PROCESSES 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
INHIBITION OF AGING PROCESSES INHIBITION OF AGING PROCESSES
““RESTRICTED DIETSRESTRICTED DIETS””
HAVE HIGHER CONCENTRATIONS OF HAVE HIGHER CONCENTRATIONS OF
ZINCZINC
AND THEIR ALTERED COMPOSITION AND THEIR ALTERED COMPOSITION
HAS A BENEFICIAL EFFECT ON HAS A BENEFICIAL EFFECT ON
ZINC BIOAVAILABILITYZINC BIOAVAILABILITY
* * ** * *
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: 117 - 137 , 1986
D. GARFINKEL ,
MEDICAL HYPOTHESES 19: 117 - 137 , 1986
why zinc ? why zinc ?
??
ZINC METALLOENZYMES (PARTIAL LIST - OUT OF 200)
ZINC METALLOENZYMES (PARTIAL LIST - OUT OF 200)
ALCOHOL DEHYDROGENASEALDOLASEALKALINE PHOSPHATASEALKALINE PROTEASECARBONIC ANHYDRASECARBOXYPEPTIDASES A, B, CDIPEPTIDASEGLYCERALDEHYDE PHOSPHATE DEHYDROGENASELEUCINE AMINOPEPTIDASEPHOSPHOGLUCOMUTASEPHOSPHOLIPASE CPYRUVATE CARBOXYLASERETINAL REDUCTASE
ALCOHOL DEHYDROGENASEALDOLASEALKALINE PHOSPHATASEALKALINE PROTEASECARBONIC ANHYDRASECARBOXYPEPTIDASES A, B, CDIPEPTIDASEGLYCERALDEHYDE PHOSPHATE DEHYDROGENASELEUCINE AMINOPEPTIDASEPHOSPHOGLUCOMUTASEPHOSPHOLIPASE CPYRUVATE CARBOXYLASERETINAL REDUCTASE
ZINC METALLOENZYMESINFORMATION HANDLING ENZYMESZINC METALLOENZYMES
INFORMATION HANDLING ENZYMES
DNA POLYMERASERNA POLYMERASEREVERSE TRANSCRIPTASETdTTHYMIDINE KINASE
DNA POLYMERASERNA POLYMERASEREVERSE TRANSCRIPTASETdTTHYMIDINE KINASE
ZINC FINGERSZINC 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. 32-39 D. Rhodes & A. Klug Scientific American, February 1993, pp. 32-39
ZINC IS AN ESSENTIAL
FACTOR
ZINC IS AN ESSENTIAL
FACTOR FOR GROWTH, FOR GROWTH,
DEVELOPMENTDEVELOPMENT
AND NORMAL FUNCTIONAND NORMAL FUNCTION
OF EVERY LIVING CELLOF EVERY LIVING CELL
IS THERE AN AGE-RELATED ZINC DEFICIENCY ?
IS THERE AN AGE-RELATED ZINC DEFICIENCY ?
zinczinc
AT PRESENT, THERE IS NO SIMPLE AND RELIABLE INDEX OF ZINC STATUS
THERE IS SELDOM A CORRELATION BETWEEN ZINC CONCENTRATIONS IN HAIR OR TOENAILS, ERYTHROCYTES , PLASMA OR URINE
AT PRESENT, THERE IS NO SIMPLE AND RELIABLE INDEX OF ZINC STATUS
THERE IS SELDOM A CORRELATION BETWEEN ZINC CONCENTRATIONS IN HAIR OR TOENAILS, ERYTHROCYTES , PLASMA OR URINE
PROBLEMS INASSESSING ZINC STATUS
PROBLEMS INASSESSING ZINC STATUS
NONE OF THESE MEASUREMENTS PROVIDES NONE OF THESE MEASUREMENTS PROVIDES
A SENSITIVE INDICATION OF ZINC STATUSA SENSITIVE INDICATION OF ZINC STATUS
ASSESSING ZINC STATUSASSESSING ZINC STATUS
In Apparently Normal Children with Poor In Apparently Normal Children with Poor
Growth but No Evidence of Zinc Deficiency, Growth but No Evidence of Zinc Deficiency,
Zinc Supplementation Induced a Significant Zinc Supplementation Induced a Significant
Increase in Height with No Significant Change Increase in Height with No Significant Change
in Plasma Zinc Levels... in Plasma Zinc Levels...
Walravens PA et al. Am J Clin Nutr 1983; 38:195-201
Suggesting an Undetected Zinc Deficiency
in Those “Normal” Children...
IS A THERAPEUTIC TRIAL IS A THERAPEUTIC TRIAL OF ZINC ADMINISTRATIONOF ZINC ADMINISTRATION
Brit. Med. J. 1981 (Editorial)
ASSESSING ZINC STATUSASSESSING ZINC STATUS
THE CORNERSTONE OF THE DEFINITION
AND DETECTION OF ZINC DEFICIENCY
THE CORNERSTONE OF THE DEFINITION
AND DETECTION OF ZINC DEFICIENCY
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 HYPOTHESISTESTING THE HYPOTHESIS
WE CAN PERFORM THERAPEUTIC TRIALS
TO ASSESS EFECTS OF ZINC SUPPLEMENTATION ON MEASURABLE
AGE - RELATED PROCESSES
THE SUBJECTS THE SUBJECTS
HEALTHY MALES AND FEMALES AGED 40 - 65 , WHO PARTICIPATE IN A LONGITUDINAL STUDY OF AT LEAST 5 YEARS
HEALTHY MALES AND FEMALES AGED 40 - 65 , WHO PARTICIPATE IN A LONGITUDINAL STUDY OF AT LEAST 5 YEARS
(STARTED 1989AT THE WOLFSON MEDICAL CENTER)
THE COMPOUND 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
EFFECTS OF PROLONGED EFFECTS OF PROLONGED ZINC SUPPLEMENTATIONZINC SUPPLEMENTATION
EFFECTS OF PROLONGED EFFECTS OF PROLONGED ZINC SUPPLEMENTATIONZINC SUPPLEMENTATION
ON THEON THE
AGE - RELATED DECLINE AGE - RELATED DECLINE
OF THE IMMUNE SYSTEMOF THE IMMUNE SYSTEM
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
IMMUNOLOGICAL STUDY METHODS IMMUNOLOGICAL STUDY METHODS
GLUTATHION REDUCTASE, GLUTATHION GLUTATHION REDUCTASE, GLUTATHION PEROXYDASE, CATALASE AND SUPER PEROXYDASE, CATALASE AND SUPER OXIDE DISMUTASE (SOD) - IN RBC.OXIDE DISMUTASE (SOD) - IN RBC.
LABORATORY TESTS :
MAGNESIUM, CERULOPLASMIN, COPPER, MAGNESIUM, CERULOPLASMIN, COPPER, BETA CAROTEN & VITAMIN E - IN SERUMBETA CAROTEN & VITAMIN E - IN SERUM
ZINC in PLASMA, RBC & MONONUCLEARSZINC in PLASMA, RBC & MONONUCLEARS
MAGNESIUM, CERULOPLASMIN, COPPER, MAGNESIUM, CERULOPLASMIN, COPPER, BETA CAROTEN & VITAMIN E - IN SERUMBETA CAROTEN & VITAMIN E - IN SERUM
ZINC in PLASMA, RBC & MONONUCLEARSZINC in PLASMA, RBC & MONONUCLEARS
IMMUNOLOGICAL STUDY METHODSIMMUNOLOGICAL STUDY METHODSDELAYED - TYPE HYPERSENSITIVITY (DTH) SKIN REACTIONS TO 7 ANTIGENS
WERE ASSESEDBY MULTITEST :
DELAYED - TYPE HYPERSENSITIVITY (DTH) SKIN REACTIONS TO 7 ANTIGENS
WERE ASSESEDBY MULTITEST :
;;;;;;;;
Tuberculin, Diphteria, Tetanus, Proteus, Streptococcus, Candida & Trichophyton
EFFECT OF ZINC SUPPLEMENTATION ON PLASMA, RBC & MNC ZINC
EFFECT OF ZINC SUPPLEMENTATION ON PLASMA, RBC & MNC ZINC
30
80
130
180
Z I N CZ I N CPLACEBO
PLASMA ug / dLPLASMA ug / dL
RBC
MNC
p = 0.01
EFFECT OF ZINC SUPPLEMENTATION ON DTH SKIN RESPONSES
EFFECT OF ZINC SUPPLEMENTATION ON DTH SKIN RESPONSES
0
1
2
3
4
5
N0
P < .001
ZINCZINC
PLACEBOPLACEBO
NUMBER OF POSITIVE RESPONSES
P < .001P < .001
EFFECT OF ZINC SUPPLEMENTATION ON DTH SKIN RESPONSES
EFFECT OF ZINC SUPPLEMENTATION ON DTH SKIN RESPONSES
0
5
10
15
20
P < .001
Z I N CZ I N C
PLACEBOPLACEBOPLACEBOPLACEBO
AVERAGE
TOTAL INDURATION
TOTALSCORETOTALSCORE
P < P < ..001001
CONCLUSIONS 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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