ZINC 96

1
MICRONUTRIENTS IN THE ELDERLY Age-related
deficiencies in microelements
Doron Garfinkel, M.D
NUTRITION AND LONGEVITY CONFERENCE, Danone
Institute Israel, March 26, 2001.
2
HEALTH PROMOTION THE ROLE OF NUTRITION
IN PREVIOUS CENTURIES,
DEFICIENCIES OF SPECIFIC NUTRITIONAL ELEMENTS
WERE RESPONSIBLE FOR SIGNIFICANT MORTALITY
AND MORBIDITY IN THE GENERAL POPULATION

20 th.
19 th.
18th.
B.C.
3
DETECTING SPECIFIC NUTRITIONAL DEFICIENCIES
HEALTH PROMOTION IN 20th. CENTURY
DEFICIENCY DISEASE
VITAMIN A NIGHT
BLINDNESS NIACIN
PELLAGRA THIAMINE
BERI BERI

20th. Century
VITAMIN C
SCURVY VITAMIN D
RICKETS PYRIDOXINE, IRON, FOLIC
ACID ANEMIAS IODINE
HYPOTHYROIDISM FLUORIDE

CARIES
4
SUCCESSFUL PREVENTION OFSPECIFIC
NUTRITIONAL DEFICIENCIES
HEALTH PROMOTION IN 20th. CENTURY
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 ( R. D.
A. )
20th. Century
5
HEALTH PROMOTION - 21st CENTURYA NEW ROLE
FOR NUTRITION ???
NUTRITIONAL INTERVENTIONS MAY REPRESENT THE
EASIEST, MOST SIMPLE AND COST
- EFFECTIVE MEANS FOR
21 ST. CENTURY

INHIBITING AGE RELATED PROCESSES DECREASING
MORTALITY MORBIDITY FROM CHRONIC
AGE-RELATED DISEASES
6
EXPANDING HEALTH FRONTIERS IN THE 21ST
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 !
7
MICROELEMENTS
ZINC , COPPER, MAGNESIUM,
SILICON
CHROMIUM , SELENIUM, MOLYBDEN
TIN
BORE, BROMINE
ALUMINUM
LITHIUM, NICKEL
FLUORIDE
VANADIUM, RUBIDIUM, GERMANIUM
(Lead, Arsenic, Cadmium... )
8
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)
9
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
10

INHIBITION OF AGING PROCESSES ....
YES, I SEE ! Z I N C !!
11
?
why zinc ?
12
INHIBITION OF AGING PROCESSES
UNDERFEEDING
WHICH STARTS AT WEANING AND
CONTINUES THROUGHOUT LIFE ,
CAN SLOW DOWN THE
AGING PROCESS
13
INHIBITION OF AGING PROCESSES
THE PRECISE MECHANISM BY WHICH THE
UNDERFEEDING REGIMENS PROLONGS MAXIMAL
LIFESPAN ,
REMAINS UNKNOWN
14
INHIBITION OF AGING PROCESSES
RESTRICTED DIETS HAVE HIGHER
CONCENTRATIONS OF ZINC
AND THEIR ALTERED COMPOSITION
HAS A BENEFICIAL EFFECT ON ZINC
BIOAVAILABILITY
15

• IS AGING INEVITABLE ?
• THE INTRACELLULAR ZINC DEFICIENCY
  HYPOTHESIS OF AGING

D. GARFINKEL , MEDICAL HYPOTHESES 19 117 -
137 , 1986
16
?
why zinc ?
17
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 PHOSPHOGLUCO
MUTASE PHOSPHOLIPASE C PYRUVATE
CARBOXYLASE RETINAL REDUCTASE
18
ZINC METALLOENZYMES INFORMATION HANDLING
ENZYMES
DNA POLYMERASE RNA POLYMERASE REVERSE
TRANSCRIPTASE TdT THYMIDINE KINASE
19
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
20
ZINC IS AN ESSENTIAL FACTOR

• FOR GROWTH,
• DEVELOPMENT
• AND NORMAL FUNCTION
• OF EVERY LIVING CELL

21
IS THERE AN AGE-RELATED ZINC DEFICIENCY ?
zinc
22
PROBLEMS IN ASSESSING ZINC STATUS

• 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

NONE OF THESE MEASUREMENTS PROVIDES A
SENSITIVE INDICATION OF ZINC STATUS
23
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
38195-201
24
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)
25
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
26
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)
27
THE COMPOUND
ZINC SULFATE 300 mg
(68 mg ELEMENTAL ZINC)
A PLACEBO IDENTICAL IN APPEARANCE
28

• EFFECTS OF PROLONGED
• ZINC SUPPLEMENTATION

ON THE AGE - RELATED DECLINE OF THE
IMMUNE SYSTEM
29
IMMUNITY AND ZINC
ZINC DEFICIENCY IS ASSOCIATED WITH IMPAIRED
T-CELL FUNCTION ZINC ADMINISTRATION IMPROVES
CELL - MEDIATED IMMUNITY IN THE ELDERLY
30
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
31
IMMUNOLOGICAL STUDY METHODS
DELAYED - TYPE HYPERSENSITIVITY (DTH) SKIN
REACTIONS TO 7 ANTIGENS WERE ASSESED BY
MULTITEST

Tuberculin, Diphteria, Tetanus, Proteus,
Streptococcus, Candida Trichophyton
32
EFFECT OF ZINC SUPPLEMENTATION ON
PLASMA, RBC MNC ZINC
PLACEBO
PLASMA ug / dL
Z I N C
MNC
RBC
p 0.01
33
EFFECT OF ZINC SUPPLEMENTATION ON
DTH SKIN RESPONSES
NUMBER OF POSITIVE RESPONSES
ZINC
PLACEBO
P lt .001
34
EFFECT OF ZINC SUPPLEMENTATION ON
DTH SKIN RESPONSES
AVERAGE TOTAL INDURATION
Z I N C
TOTAL SCORE
PLACEBO
P lt .001
35
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