Download the effect of low-dose naltrexone (ldn) on laboratory immune

REPORT: LOW-DOSE NALTREXONE (LDN)
EFFECT OF LOW-DOSE NALTREXONE (LDN) ON LABORATORY
IMMUNE VALUES AND SELF-ASSESSMENT TRACK-SHEETS
FOR PHYSIOLOGICAL AND MOOD EFFECTS
PERIOD OF STUDY: 16 WEEKS MARCH – AUGUST 2006
PARTICIPANTS: (20) ASD CHILDREN AND (38) ADULTS
(PRIMARILY PARENTS OR OLDER SIBLINGS OF ASD
CHILDREN), MARCH – AUGUST 2006
PRIMARY INVESTIGATOR: JAQUELYN McCANDLESS, M.D., PRIVATE
PRACTICE, CANOGA PARK, CA AND HONOKAA, HI
CONSULTANT: ARISTO VOJDANI, PHD, DIRECTOR, IMMUNOSCIENCES
LAB, BEVERLY HILLS, CA
EARLY INFORMAL ADVISORS ON THE STUDY:
JAAK PANKSEPP, PHD
PAUL SHATTOCK, PHD
STATISTICAL ANALYSIS PROVIDED BY DAVID GAYLOR, PhD,
ASSISTED BY JACK ZIMMERMAN, PhD
SOURCES OF SUPPORT FOR THIS STUDY
LDN TRANSDERMAL CREAM FOR CHILDREN AND CAPSULES FOR
ADULTS WERE DONATED BY COASTAL COMPOUNDING PHARMACY,
SAVANNAH, GA
PARTICIPANTS PAID FOR DISCOUNTED LAB SERVICES FOR THE
IMMUNE TESTING DONATED BY IMMUNOSCIENCES LAB, BEVERLY
HILLS, CA
OTHER SOURCES OF SUPPORT: NONE
1
TABLE OF CONTENTS:
COVER PAGE
1
TABLE OF CONTENTS
2
HISTORY OF NALTREXONE AND AUTISM
3
USE OF LOW-DOSE NALTREXONE (LDN) IN AUTISM
4
DESCRIPTION IMMUNE TESTS
4-6
ADDITIONAL NOTES RE TESTING: MOLLOY’S WORK
6
STATISTICAL APPROACH AND REGULATORY MARKERS
AND REGULATORY MARKERS
7
16-WEEK IMMUNE TEST RESULTS CHILDREN
8-9
SUMMARY IMMUNE TESTS FOR CHILDREN
9-10
16-WEEK TEST RESULTS, IMMUNE TESTING ADULTS
10
SUMMARY IMMUNE TESTS FOR ADULTS
11
DISCUSSION OF LDN STUDY
11
REFERENCES
13
2
HISTORY OF NALTREXONE AND AUTISM:
NALTREXONE IS AN FDA-APPROVED MEDICATION, A PURE OPIOID
ANTAGONIST, AVAILABLE AS THE BRAND NAME RE VIA AS WELL AS IN
GENERIC FORM AND USED PRIMARILY FOR TREATING OPIATE AND
ALCOHOL ADDICTION SINCE THE 1970’S.
SINCE THE 1970’S, STUDIES HAVE CONSISTENTLY SHOWN A VARIETY
OF IMMUNE SYSTEM DISORDERS IN AUTISTIC CHILDREN. (1)
INFECTIOUS AGENTS, TOXIC CHEMICALS AND DIETARY PEPTIDES
HAVE BEEN SHOWN TO BE TRIGGERS FOR IMMUNE DYSREGULATION
AND AUTOIMMUNITY. (2) THE HYPERSENSITIVITY REACTIONS TO THE
LARGE PEPTIDES FOUND IN CASEIN AND GLUTEN PRODUCTS BY
AUTISTIC CHILDREN INSPIRED RESEARCH INTO THE OPIOID
ANTAGONIST NALTREXONE IN HOPES OF AVOIDING RESTRICTIVE
DIETS TO PREVENT CASEO-OPIOID AND GLUTEO-OPIOID COMPOUNDS
IN THE BRAIN FROM CREATING DELETERIOUS EFFECTS COGNITIVELY
AND BEHAVIORALLY. (3a, 3b, 3c) AN ITALIAN STUDY DONE IN 1996 WITH
VARYING NALTREXONE DOSING SHOWED SIGNIFICANT REDUCTION
OF AUTISTIC BEHAVIORS IN 7 OUT OF 12 CHILDREN. (4) BEHAVIORAL
IMPROVEMENT WAS ACCOMPANIED BY ALTERATIONS IN THE
DISTRIBUTION OF THE MAJOR LYMPHOCYTE SUBSETS WITH INCREASE
IN NORMALIZATION OF THE CD4/CD8 (T/1) RATIO. (5)
NO SIMILAR IMMUNE STUDIES HAVE SINCE BEEN REPORTED ON THE
USE OF NALTREXONE IN AUTISM, WHILE A LARGE BODY OF RESEARCH
HAS POINTED REPEATEDLY TO ENDOGENOUS OPIOID SECRETIONS AS
PLAYING THE CENTRAL ROLE IN THE BENEFICIAL ORCHESTRATION
OF THE IMMUNE SYSTEM. (6) OPIOIDS ARE ENDORPHINS AND OPERATE
AS CYTOKINES, THE PRINCIPAL COMMUNICATION SIGNALERS OF THE
IMMUNE SYSTEM. (7) STUDIES AT UC DAVIS MIND INSTITUTE SHOW
THAT CYTOKINE RESPONSES ELICITED BY THE T-CELLS, B-CELLS, AND
MACROPHAGE CELL POPULATONS FOLLOWING THEIR ACTIVATION
DIFFERS MARKEDLY IN CHILDREN WITH AUTISM COMPARED TO AGEMATCHED CHILDREN IN THE GENERAL POPULATION. (8)
STUDIES WITH NALTREXONE FOR AUTISM HAVE BEEN EQUIVOCAL,
AND SUBJECT TO NON-COMPLIANCE DUE TO THE BITTERNESS OF THE
DRUG WHICH HAS POSED A PROBLEM FOR AUTISTIC CHILDREN, MOST
OF WHOM COULD NOT SWALLOW CAPSULES.
BERNARD BIHARI, MD, A NEW YORK PHYSICIAN STUDYING THE
IMMUNE RESPONSES IN ADDICTED HIV AIDS PATIENTS IN 1985,
DISCOVERED THAT AN ULTRA-LOW DOSE OF NALTREXONE BOOSTS
THE IMMMUNE SYSTEM WITHOUT SIDE EFFECTS OR TOXICITY. HE
FOUND THAT WHEN GIVEN BETWEEN 9PM AND 2 AM THE PITUITARY IS
3
ALERTED AND THE BODY ATTEMPTS TO OVERCOME THE OPIOID
BLOCK WITH AN ENDORPHIN ELEVATION, STAYING ELEVATED
THROUGHOUT THE NEXT 18 HOURS. (9) RESTORATION OF THE BODY’S
NORMAL PRODUCTION OF ENDORPHINS IN THOSE WITH CANCER OR
AUTOIMMUNE DISEASES OR ANY DISEASE CHARACTERIZED BY
INADEQUATE OR DISORDERED IMMUNITY IS THE MAJOR
THERAPEUTIC ACTION OF LDN, WHICH WAS SHOWN TO BE NEEDED
ONLY ONCE DAILY AT BEDTIME FOR IMMUNE OPTIMIZATION.
USE OF LOW-DOSE NALTREXONE (LDN) IN AUTISM
I (DR JM) STARTED USING LDN IN A GROUP OF AUTISTIC CHILDREN
PLUS A FEW ADULTS WITH OTHER AUTOIMMUNE CONDITIONS IN
EARLY 2005 AFTER AN EFFECTIVE TRANSDERMAL CREAM WAS
CREATED WHICH COULD BE APPLIED TO THE CHILDREN AT THEIR
BEDTIME OR AFTER. DOSES WERE 3MG OF LDN CREAM FOR CHILDREN
AND 4.5MG CAPSULES FOR ADULTS PER DR. BIHARI’S DISCOVERY OF
THIS WINDOW OF DOSING FOR OPTIMUM IMMUNE BENEFITS.
POSITIVE RESULTS IN THIS PIONEER GROUP AND THE LACK OF
SIGNIFICANT SIDE EFFECTS LED ME TO DO A LARGER INFORMAL 16WEEK STUDY FROM MAR – AUG 2006 WITH 20 AUTISTIC CHILDREN AND
38 ADULTS (ALMOST ALL PARENTS OF ASD CHILDREN).
A PLASMA IMMUNE PANEL WAS PERFORMED AT THE START AND
FINISH OF THE STUDY INCLUDING TOTAL WBC’S, T-CELLS, B-CELLS,
NATURAL KILLER CELL ACTIVITY, LYMPHOCYTE SUB-POPULATION,
AND BRAIN AUTO-ANTIBODIES.
WEEKLY PHYSIOLOGICAL AND MOOD CHILD ASSESSMENTS AND
PARENTAL SELF-ASSESSMENTS WERE ALSO NOTED ON TRACKSHEETS
THROUGHOUT THE 16-WEEK STUDY PERIOD WITH A NUMBERING
SYSTEM FROM 1-10, NEGATIVE EFFECT TO POSITIVE EFFECT, 5 BEING
NEUTRAL OR NOT/APPLICABLE.
DESCRIPTION:
IMMUNE TESTS PERFORMED FOR 16-WEEK LDN STUDY, MAR – AUG 06
LAB VALUES LDN STUDY:
TOTAL WHITE COUNT (WBC): THERE ARE 5 KINDS OF WHITE CELLS:
NEUTROPHILS, LYMPHOCYTES, MONOCYTES, EOSINOPHILS, AND
BASOPHILS. COUNT CAN BE AFFECTED BY GENERAL HEALTH,
4
INFECTIONS (BACTERIAL RAISE THE NEUTROPHIL COUNT,
VIRUSES GENERALLY LOWER NEUTROPHILS AND CAN RAISE
LYMPHOCYTE COUNT AND STIMULATE IT TO PUT OUT
CYTOKINES)
TOTAL T-CELLS: LYMPH CELLS THAT MATURE IN THE THYMUS,
CONTROL INNATE CELL-MEDIATED IMMUNE RESPONSES AND
ACTIVATE RESPONSES TO MOST ANTIGENS. T-CELLS DEAL WITH
VIRUSES AND PATHOGENS THAT REPLICATE INSIDE CELLS
WHERE THEY CANNOT BE REACHED BY ANTIBODIES.
TOTAL T-HELPER (CD4+): RECOGNIZE ANTIGENS, PRODUCE
CYTOKINES (CHEMICAL MESSENGERS) AND ACTIVATE OTHER T
& B CELLS, CONTROL INTRACELLULAR BACTERIAL INFECTIONS
BY ATTRACTING MACROPHAGES, LEAD ATTACKS AGAINST
INFECTION, CONTROL OTHER CELLS, COUNT DETERMINES
PRESENCE OF IMMUNE DEFICIENCIES AND AUTOIMMUNITY;
COUNT HELPS GUIDE TREATMENT FOR HIV+AIDS. (STUDIES
SHOW ANTI-AIDS DRUGS POTENTIATED BY NALTREXONE). (10)
TOTAL SUPPRESSOR (CD8+)
IMMUNITY “BRAKES”, STOP IMMUNE
RESPONSE AFTER INVADING PATHOGENS ARE DESTROYED,
“KILLER” CELLS SUPPRESSE IMMUNE RESPONSE, ANTIINFLAMMATORY, CYTOTOXIC (KILLS VIRUSES & CANCER CELLS)
T-HELPER/T-SUPPRESSOR THE RATIO OF CD4+ AND CD8+ SHOULD BE 12.5. OVER 2.5 RELATES TO IMMUNE ACTIVATION OR
AUTOIMUNITY, LESS THAN ONE RELATES TO IMMUNE
SUPPRESSION OR DEFICIENCY. HEAVY METALS AND
MYCOTOXINS CAN ALSO SUPPRESS IMMUNE ACTIVITY.
TOTAL NATURAL KILLER
LYMPHOCYTES IN INNATE IMMUNE
SYSTEM, PROVIDE AGGRESSIVE DEFENSE AGAINST CELLS
INFECTED BY MICROORGANISMS, ESP VIRUSES AND CANCER
CELLS, TARGET INFECTIONS BOTH INSIDE AND OUTSIDE THE
CELL INNATELY WITHOUT HAVING TO BE DIRECTED BY THE
CD4+ “HELPER” CELLS; WHEN HIGH USUALLY MEANS VIRUSES.
INCLUDES TOTAL IMMUNOCOMPETENT CELLS (+ CELLS) AND
TOTAL NKHT3 (-CELLS).
TOTAL CD3+ CD 26+: MEMORY LYMPHOCYTES, IMPORTANT CELLS,
FIGHT TOXIC CHEMICALS, HEAVY METALS, MOLDS AND
RELATED MYCOTOXINS, “POLICEMEN”. (THIS IS DPP-1V
PEPDIDASE)
5
IMMUNOREGULATORY CELLS: MAINTAIN HOMEOSTASIS AND
SELF-TOLERANCE
TOTAL CD4+ CD25 (11) : CD4+CD25+ T-REGULATORY CELLS ARE
IMPORTANT IN THE MAINTENANCE OF IMMUNOLOGICAL SELF
TOLERANCE AND IN THE PREVENTION OF AUTOIMMUNE
DISEASE, FIGHT AUTOIMMUNITY, NEED TGF-B & IL-10 CONTACT
TO BECOME POTENT SUPPRESSOR CELLS
IL-10 UNSTIMULATED (11): NEUTRALIZE INFLAMMATION, CREATE
ANTI-INFLAMMATORY CYTOKINES
IL-10 STIMULATED (11): ANTI-INFLAMMATORY IN RESPONSE TO
ANTIGENIC STIMULATION
TGF-BETA 1 UNSTIMULATED (12):
SUPPRESSIVE CYTOKINES
IMMUNOSUPPRESSIVE , CREATE
TGF-BETA 1 STIMULATED (12): SUPPRESSIVE TO ANTIGEN
ADDITIONAL NOTES RE CYTOKINES AND DR. CYNTHIA MOLLOY’S
RECENT WORK ON IMMUNE SYSTEMS OF AUTISTIC CHILDREN
(PLEASE SEE REFERENCE #13, MARCH 06 JOURNAL OF
NEUROIMMUNOLOGY)
MOLLOY’S STUDY FOUND THAT IMMUNE CELLS OF CHILDREN WITH
AUTISM PRODUCED HIGHER LEVELS OF BOTH THE TH1 AND TH2
CYTOKINES THAN IN CONTROLS, DEMONSTRATING POTENTIAL
UNDERLYING HYPERSENSITIVITY TO EXPOSURES IN THE GENERAL
ENVIRONMENT FOR ASD CHILDREN. THE MORE HIGHLY ACTIVATED
T1 AND T2 CYTOKINES CONFIRM THE IMMUNE DYSREGULATION
FOUND IN MANY OTHER STUDIES OF ASD CHILDREN, AND CONFIRM
THAT THESE CHILDREN EXHIBIT HYPER SENSITIVITY IN BOTH INNATE
AND ADAPTIVE SYSTEMS. THE EXCEPTION SHE FOUND WAS IN
RELATIVELY LOWER LEVELS OF THE CRITICAL REGULATORY
CYTOKINE, IL-10. DR. MOLLOY SAYS: “MANY PARADOXICAL FINDINGS
THAT HAVE BEEN REPORTED ABOUT IMMUNE RESPONSES IN AUTISM
COULD POSSIBLY BE EXPLAINED BY THE GENERAL DYSFUNCTION OF
IL-10.” SHE IS PLANNING FURTHER STUDIES ON IL-10.
6
TEST RESULTS FOR 16 WEEK STUDY OF CHILDREN’S IMMUNE
SYSTEMS
STATISTICAL APPROACH: THE DATA FROM THE STUDY WAS SUBJECTED
TO TWO DIFFERENT KINDS OF ANALYSES: QUANTITATIVE AND
QUALITATIVE. THE FORMER INVOLVED TAKING THE RATIOS OF FINAL TO
ORIGINAL VALUES USING THE CONVENTIONAL t-TESTS TO SEE IF THESE
RATIOS WERE SIGNIFICANTLY GREATER THAN ONE.( WHEN THE DATA
EXHIBITED WIDE VARIATIONS, THE LOGS OF THESE RATIOS WERE USED.)
THESE QUANTITATIVE TESTS ASSUME THAT INCREASES IN THE MARKERS
ARE ALWAYS “GOOD,” WHICH IS OBVIOUSLY NOT THE CASE IF THE
MARKER VALUES EXCEEDED THE UPPER LIMIT OF THE NORMAL RANGE.
FOR THIS REASON—AND ALSO BECAUSE THE SCATTER OF THE MARKER
DATA WAS USUALLY GREAT FOR THE CHILDREN (MUCH LESS SO FOR
THE ADULTS)—WE ALSO USED A SIMPLE BINARY TEST FOR EACH
MARKER BASED ON WHETHER IT MOVED IN A “GOOD” OR “BAD”
DIRECTION OR MOVED WITHIN OR OUTSIDE OF NORMAL RANGE..
BECAUSE OF THE SMALL SAMPLE SIZE FOR THE CHILDREN AND THE
TENDENCY FOR THE DATA TO SCATTER DUE TO ONE OR MORE
UNCONTROLLED VARIABLES (INFECTIONS DURING THE SIXTEEN WEEKS,
DIETARY INCONSISTENCIES, ETC.), THESE LATTER TESTS ARE TO BE
TAKEN AS SUGGESTIVE EVEN WHEN THE SIGNIFICANCE LEVEL WAS 95%
OR GREATER. A LARGER SAMPLE SIZE (AT LEAST EQUAL OR GREATER
THAN THAT OF THE PARENTS IN THE STUDY) AND GREATER CONTROL OF
OTHER VARIABLES AFFECTING THE POPULATION OF CHILDREN ARE
CLEARLY NEEDED IN FUTURE STUDIES.
IN WHAT FOLLOWS WE SPEAK OF A MARKER GOING UP OR DOWN OR
STAYING ESSENTIALLY THE SAME. THE CRITERION FOR THESE
STATEMENTS IS BASED ON THE AMOUNT OF CHANGE RELATIVE TO THE
STANDARD DEVIATION OF THE DATA.
REGULATORY MARKERS:
IL-10: IN OUR NON-PLACEBO (AND NON-CONTROLLED) STUDY - THIS
MARKER VARIED WIDELY FROM CHILD TO CHILD AND SEVERAL
INDIVIDUAL CHILDREN SHOWED WIDE CHANGES DURING THE STUDY,
WITH AS MANY CHILDREN RAISING THEIR VALUES AS LOWERING
THEM. THE AVERAGE VALUES WERE RATHER LOW RELATIVE TO THE
NORMAL IL-10 RANGE, AGREEING WITH MOLLOY’S WORK. THUS IN 16
WEEKS LDN DID NOT SEEM TO HELP THIS IMPORTANT REGULATOR
CYTOKINE TO INCREASE; WE AS YET HAVE NO UNDERSTANDING OF
THIS. NONE OF THESE CHANGES WERE STATISTICALLY SIGNIFICANT.
7
TGF-B: THE TGF-B BEGINNING AVERAGE WAS QUITE A LOT HIGHER
THAN THE MEDIAN OF THE NORMAL RANGE AND THE AVERAGE FINAL
AVERAGE WAS LOWER THAN THE MEDIAN VALUE (ALTHOUGH, AGAIN,
THIS CHANGE WAS NOT STATISTICALLY SIGNIFICANT). THIS MAY
MEAN THE IMMUNOSUPPRESSIVE EFFECT OF TGF-B WAS LOWERED ON
THE AVERAGE BY THE LDN, WHICH COULD BE AN INDICATION THAT
AUTOIMMUNITY WAS IMPROVED IN SPITE OF THE IL-10 FINDING,
PROBABLY POINTING TO INFLAMMATION STILL BEING SIGNIFICANT
IN THIS GROUP. THEIR RELATIONSHIP IS AS YET UNCLEAR.
THE SIGNIFICANCE OF THESE VALUES RELATIVE TO THE USE OF LDN
IS DIFFICULT TO UNDERSTAND EXCEPT IN VERY GENERAL TERMS,
OTHER THAN TO SAY THAT LDN IN THIS STUDY DID NOT SEEM TO
STABILIZE THE LEVEL OF IL-10 REGULATORY BENEFIT FOR
INFLAMMATORY ISSUES. 16 WEEKS MAY NOT BE LONG ENOUGH FOR
THIS VALUE TO CHANGE – IT IS ALSO DIFFICULT IN ANY
CIRCUMSTANCE TO DETERMINE AT WHAT PHASE THE INFLAMMATION
REACTION IS IN – THIS WOULD HELP DETERMINE WHETHER IT WOULD
BE PREFERABLE FOR INFLAMMATORY MARKERS TO BE INCREASING
OR DECREASING.
TOTAL WBC: IN REGARD TO THIS MARKER MOST CHILDREN WERE
WITHIN NORMAL RANGE BOTH BEFORE AND AFTER THE TEST. THREE
(3) STARTED BELOW RANGE AND FOUR (4) ENDED UP BELOW RANGE,
THIS RESULT WAS CLEARLY NOT STATISTICALLY SIGNIFICANT.
TOTAL LYMPHS: MOST CHILDREN WERE WITHIN THE NORMAL RANGE
FOR THIS MARKER BOTH BEFORE AND AFTER THE TEST; ONE CHILD
STARTED WITH AN ELEVATED VALUE AND ENDED UP WITHIN NORMAL
LIMITS; ONE CHILD STARTED WITH NORMAL VALUE AND ENDED UP
WITH ELEVATED VALUE. OBVIOUSLY THESE RESULTS WERE NOT
STATISTICALLY SIGNIFICANT.
TOTAL NATURAL KILLER CELL LEVEL: FIFTEEN (15) CHILDREN
MOVED IN A POSITIVE DIRECTION, THREE (3) IN A NEGATIVE
DIRECTION, AND ONE (1) STAYED THE SAME. ALTHOUGH THE t-TESTS
FOR THIS MARKER WERE NOT SIGNIFICANT, A SIMPLE BINARY TEST
SUGGESTS THAT THE CHILDREN AS A GROUP MOVED IN A POSITIVE
DIRECTION WITH A SIGNIFICANCE OF 95%. THE AMOUNT OF
MOVEMENT VARIED CONSIDERABLY.
CD3+CD26: RELATIVE TO THE MEDIAN OF THE NORMAL RANGE,
ELEVEN (11) CHILDREN MOVED TOWARD A BETTER SCORE, TWO (2)
STAYED ESSENTIALLY THE SAME, AND SEVEN (7) MOVED TO A WORSE
SCORE. . ALTHOUGH THE QUALITATIVE TEST WAS NOT QUITE
8
SIGNIFICANT FOR THIS MARKER, THE SCATTER OF THE DATA WAS
SMALL ENOUGH AND THE IMPROVEMENTS OUTWEIGHED THE
LESSENING SCORES QUANTITATIVELY FOR A t-TEST SIGNIFICANCE ON
THE 95% LEVEL—THE ONLY SUCH QUANTITATIVE RESULT FOR THE
GROUP OF CHILDREN. THIS MEANS WE CAN SAY THAT LDN
SIGNIFICANTLY INCREASES THIS MARKER AT THE 95% CONFIDENCE
LEVEL. THE AVERAGE INCREASE WAS 23%.
TOTAL T3: ALL CHILDREN REMAINED WITHIN THE NORMAL RANGE
BOTH BEFORE AND AFTER THE TEST, WITH ELEVEN (11) INCREASING
AND NINE (9) DECREASING (CLEARLY NOT SIGNIFICANT).
TOTAL SUPPRESSOR (CD8+): A MEDIAN OF 900 IS CONSIDERED GOOD;
FOURTEEN (14) CHILDREN MOVED IN THE POSITIVE DIRECTION, TWO
(2) REMAINED ESSENTIALLY THE SAME, AND FOUR (4 ) MOVED IN A
NEGATIVE DIRECTION. ALTHOUGH THE t-TESTS SHOWED NO
SIGNIFICANCE, USING A BINARY TEST, THE DIRECTION OF MOVEMENT
OR “IMPROVEMENT” FOR THIS MARKER WAS STATISTICALLY
SIGNIFICANT ON THE 95% LEVEL.
TOTAL T HELPER (CD4+): THIS MARKER IS A KEY MEASURE OF
IMMUNE SYSTEM HEALTH. DR. VOJDANI SAYS THAT IF VALUES STAY
WITHIN NORMAL RANGE, THE HIGHER THE BETTER. WE FOUND THAT
EIGHTEEN (18) OF THE TWENTY (20) MOVED HIGHER, ONE MOVED
LOWER, AND ONE STAYED ESSENTIALLY THE SAME., WE CONCLUDED
FROM THE BINARY TEST THAT LDN HAD A SIGNIFICANT POSITIVE
EFFECT ON A 99% CONFIDENCE LEVEL. (NOTE: THIS BODES WELL
FOR THE UPCOMING HIV+ AIDS STUDY ON LDN IN AFRICA).
CD4/CD8 RATIO (T-HELPER/T-SUPPRESSOR): THE AVERAGE RATIO OF
EIGHTEEN (18) POSITIVE CD4+ TO THE 14 POSITIVE CD8+ GAVE A
VALUE OF 1.28 FOR THE CD4+CD8+ RATIO, WHICH SHOULD BE
BETWEEN 1-2.5. FOUR (4) CD4+CD8+ RATIOS WERE ABNORMAL IN THE
BEGINNING (TWO TOO HIGH, TWO TOO LOW); ALL OF THE CD4+/CD8+
RATIOS WERE WITHIN NORMAL LIMITS EXCEPT ONE (TOO HIGH) AT
THE END OF THE STUDY; ALTHOUGH THIS RESULT IS ENCOURAGING IT
IS NOT SIGNIFICANT ON THE 95% LEVEL.
SUMMARY, CHILDREN: THOSE TESTS SHOWING THE BENEFIT OF LDN
WITH STATISTICAL SIGNIFICANCE AT LEAST AT THE 95% LEVEL FOR
THE POPULATION OF CHILDREN WERE:
TOTAL NATURAL KILLER CELL LEVEL (QUALITATIVELY)
TOTAL T-HELPER CELL (CD4+) LEVEL (QUALITATIVELY)
TOTAL SUPPRESSOR CELL (CD8+) LEVEL (QUALITATIVELY)
9
CD3+CD26 LEVEL (QUANTITATIVELY)
THOSE TESTS THAT DID NOT SHOW STATISTICAL SIGNIFICANCE:
TOTAL WHITE COUNT
TGF BETA 1 UNSTIM
TOTAL LYMPHS
TOTAL T3 POSITIVE
TOTAL T-CELL
NK ACTIVITY
T-HELPER/T-SUPPRESSOR
IL 10
TOTAL CD4/CD25
(NOTE FROM STATISTICIAN: THE RELATIVE CHANGES FOR TOTAL
LYMPHS, TOTAL T-CELLS, TOTAL T-HELPER, AND TOTAL T3 POSITIVE
WERE HIGHLY CORRELATED, INDICATING THAT THESE EFFECTS TEND
TO VARY IN A SIMILAR MANNER FOR A PARTICULAR CHILD.)
TEST RESULTS 16 WEEK STUDY, ADULT IMMUNE TESTING:
STATISTICAL APPROACH: THE ADULT POPULATION WAS TWICE THAT OF
THE CHILDREN’S AND THE DATA GENERALLY WERE FAR LESS
SCATTERED, INDICATING THAT THE ADULT IMMUNE SYSTEMS WERE
MUCH LESS LIKELY TO BE AFFECTED BY UNCONTROLLED VARIABLES
DURING THE COURSE OF THE STUDY. BECAUSE OF THIS STABILITY IN
THE POPULATION, WE LIMITED OUR ANALYSIS TO THE STANDARD
(QUANTITATIVE) t-TESTS.
TOTAL CD3+CD26: THERE WAS ON THE AVERAGE A 15% INCREASE IN
THIS VARIABLE THAT WAS SIGNIFICANT ON THE 98% CONFIDENCE
LEVEL. SIXTEEN (16) PARTICIPANTS MOVED UP, NINE (9) MOVED DOWN,
AND THIRTEEN (13) SHOWED NO SIGNIFICANT CHANGE.
CD4/CD25: THIS RATIO INCREASED SIGNIFICANTLY ON A 99.9%
CONFIDENCE LEVEL. EIGHTEEN (18) ADULT VALUES INCREASED, 12
DECREASED, AND 8 STAYED ESSENTIALLY THE SAME, THERE WERE
THREE (3) MORE ABNORMAL RESULTS AT END THAN AT BASELINE.
(NOTE: TOTAL CD4/CD25 AND IL-10 UNSTIMULATED WERE HIGHLY
CORRELATED)
NATURAL KILLER CELL LEVEL: LEVEL INCREASED 14% (WITH A
SIGNIFICANCE LEVEL OF 99%). EIGHTEEN (18) VALUES INCREASED,
FIFTEEN (15) STAYED ROUGHLY THE SAME, AND FIVE (5) WENT DOWN,
ALL VALUES WERE GENERALLY LOW BEFORE AND AFTER THE STUDY.
THERE WAS ONE (1) ABNORMAL VALUE AT THE END AND NONE AT THE
BEGINNING.
TOTAL T HELPER (CD4+): THIS INCREASED AN AVERAGE OF 13% (99.5%
LEVEL OF SIGNIFICANCE). TWENTY-SIX (26) OF THE THIRTY-EIGHT (38)
10
PARTICIPANTS INCREASED THEIR LEVEL WHILE STAYING WITHIN THE
NORMAL LIMITS, TWELVE (12) WENT DOWN AND ONE (1) STAYED
ABOUT THE SAME. THERE WERE NO ABNORMAL VALUES AT
BEGINNING OR END OF STUDY. (DR. VOJDANI SAYS INCREASES ARE
GOOD AS LONG AS THEY STAY WITHIN THE NORMAL RANGE).
TOTAL SUPPRESSOR CD8+: VALUE INCREASED 13% (99.5% CONFIDENCE
LEVEL). TWENTY-SIX OF THE THIRTY-EIGHT MOVED UPWARD. THERE
WERE NO ABNORMAL VALUES AT BEGINNING OR END OF THE STUDY.
ALTHOUGH BOTH CD4+ AND CD8+ INCREASED SIGNIFICANTLY, THE
RATIO, CD4+/CD8+ DID NOT CHANGE SIGNIFICANTLY. THERE WERE
NINE ABNORMAL VALUES AT THE BEGINNING AND TEN AT THE END OF
THE STUDY. THE REASON THE RATIO REMAINED CLOSE TO ONE WAS
THAT THE SUPPRESSOR AND HELPER CELLS BOTH INCREASED
PROPORTIONALLY.
TOTAL T3 POSITIVE: INCREASED 13% (SIGNIFICANT ON THE 99.5%
LEVEL). TWENTY-SEVEN ADULTS MOVED UP AND ELEVEN MOVED
DOWN. ALL SCORES BOTH BEFORE AND AFTER WERE WITHIN NORMAL
REFERENCE RANGE.
OF THE REMAINING SEVEN MARKERS, SIGNIFICANT INCREASES WERE
NOTED IN TOTAL LYMPHOCYTES , TOTAL T-CELL , AND TGF BETA 1
UNSTIM .
(NOTE: THE RELATIVE CHANGES FOR TOTAL LYMPHOCYTES, TOTAL
T-CELL, TOTAL T-HELPER, TOTAL SUPPRESSOR AND TOTAL T-3
POSITIVE WERE HIGHLY CORRELATED.)
SUMMARY, ADULTS: IN TERMS OF ABNORMAL VALUES FOR ADULTS:
FIVE VALUES HAD HIGHER ABNORMALS AT THE END (CD4+/CD8+
RATIO, TOTAL NATURAL KILLER, TOTAL CD4/CD25, TGF-BETA
UNSTIMULATED, AND NK CELL ACTIVITY); SIX VALUES STAYED THE
SAME, AND FIVE VALUES IMPROVED FOR THE ADULT GROUP BY THE
END OF THE STUDY.
11
DISCUSSION OF LDN STUDY:
LABORATORY MEASUREMENTS OF THE CHILDREN’S IMMUNE
SYSTEMS VARIED WIDELY. RANGES WERE BROAD IN ALMOST ALL
CATEGORIES. CLEARLY, THERE WERE NOT ENOUGH PARTICIPANTS IN
THE CHILDREN’S GROUP TO COME TO MORE THAN A FEW
STATISTICALLY SIGNIFICANT CONCLUSIONS. HOWEVER, THERE
WERE SEVERAL SUGGESTIVE CONCLUSIONS THAT INDICATE LDN
DOES HAVE A POSITIVE EFFECT ON ASD CHILDREN’S IMMUNE
SYSTEMS. SOME IMPORTANT MARKERS SUCH AS THE CD4+ CELL
COUNT DID GO UP FOR THE MAJORITY OF PARTICIPANTS AND NONE
ENDED UP OUT OF THE REFERENCE RANGE OF NORMAL.
THE ADULT GROUP WAS LARGER AND SIGNIFICANTLY MORE
CONSISTENT IN MAKING IMMUNE SYSTEM IMPROVEMENTS,
ALTHOUGH THE AMOUNT OF IMPROVEMENT FOR THE CHILDREN WAS
ACTUALLY GREATER THAN THAT FOR THE ADULTS, PROBABLY BECAUSE
THEY HAD GREATER IMMUNE IMPAIRMENT GENERALLY. THIS MAY
ALSO BE INFLUENCED BECAUSE THE CHILDREN ARE UNDERGOING
INTENSIVE TREATMENT WITH SPECIAL DIETS, NUTRIENTS, ANTIPATHOGEN STRATEGIES AND OTHER THERAPIES TO IMPROVE THEIR
IMMUNE SYSTEMS (METHYLATION, DETOXIFICATION, HBOT, ETC.)
THE VARIABILITY EXHIBITED BY THE CHILDREN MAY BE BECAUSE OF
THIS CONSTANT ARRAY OF NEW STRATEGIES, TREATMENT OF
FREQUENT GUT INFECTIONS, ETC.
GENETIC INFLUENCE WAS EVIDENCED IN THE PARENTAL GROUP BY
HISTORY SINCE A SIGNIFICANT NUMBER OF THE ADULTS LISTED
ALLERGIES, FATIGUE, AUTOIMMUNE AND GUT ISSUES AS CHIEF
COMPLAINTS IN THEIR QUESTIONNAIRE. I DOUBT THAT AS A GROUP
THEY ARE SPENDING AS MUCH TIME ON THEIR OWN HEALTH AS THEY
SHOULD, EVEN THOUGH MANY WOULD LIKELY BENEFIT BY
ATTENTION TO A BETTER DIET, TESTING FOR THE BEST NUTRIENTS
FOR THEIR METABOLISM, ETC., ALL OF WHICH THEY DO FOR THEIR
CHILDREN. PARENTS OF ASD CHILDREN ARE SUBJECTED TO A LOT OF
DEMANDS WHICH STRESS EMOTIONALLY, PHYSICALLY, AND
FINANCIALLY, NO DOUBT AFFECTING THEIR IMMUNE STATUS.
IMPORTANT MARKERS SUCH AS THE TOTAL T HELPER (CD4+), THE
TOTAL SUPPRESSOR (CD8+) AND CD3+CD26 ALL SHOWED SOME LEVEL
OF STATISTICAL SIGNIFICANCE FOR BOTH GROUPS OF ADULTS AND
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CHILDREN. CLEARLY, MORE STUDIES ARE NEEDED WITH A CONTROL
GROUP AND DONE WITH PARTICIPANTS WILLING TO MAINTAIN THEIR
CHILDREN’S (AND/OR THEIR OWN) NUTRITIONAL SUPPLEMENT
REGIME, DIET AND OTHER STATUS QUO EXCEPT FOR URGENT
SITUATIONS. THIS IS CHALLENGING TO DO IN OUR POPULATION
WHERE MANY TREATMENTS ARE OFTEN DONE SIMULTANEOUSLY.
NOTE ON SAFETY OF LDN: AT THE END OF THIS STUDY IN AUGUST 2006
BEFORE PRESENTING MY FINDINGS TO THE THINK TANK , I QUERIED
THE TWO MOST POPULAR COMPOUNDING PHARMACIES WHICH OFFER
THIS MEDICATION TO THE AUTISM COMMUNITY AS TO NUMBER OF
PRESCRIPTIONS BEING FILLED. THE INVENTOR OF THE EMU-BASED
TRANSDERMAL CREAM, MOLECULAR PHARMACOLOGIST DR. TYRUS
SMITH AT COASTAL COMPOUNDING PHARMACY IN SAVANNAH, GA,
REPORTED THAT HE HAD GIVEN THE SKIN FORMULA TO 50+
PHARMACIES ACROSS THE UNITED STATES, PLUS PHARMACIES
ABROAD WHERE I HAVE TAUGHT (ISRAEL, SCOTLAND, AND HONG
KONG). THE ESTIMATE AT THAT TIME FROM THESE QUERIES WAS
THAT BETWEEN 4000-5000 CHILDREN WERE USING LDN AT THAT TIME
WITH ESTIMATED 75-80% POSITIVE RESPONSE.
THE PRIMARY ADVERSE EFFECT ON THESE CHILDREN WAS SOME
HYPERACTIVITY OR INSOMINA WHEN THEY FIRST STARTED. THIS HAS
ALWAYS SUBSIDED WITH CONTINUING PAST THE EARLY RESPONSES,
LOWERING THE DOSE, OR STOPPING. FOR SOME PARENTS THESE SIDE
EFFECTS WERE INTOLERABLE AND THEY PREFERRED TO STOP THE
MEDICATION. THERE HAVE BEEN NO IRREVERSIBLE NEGATIVE
REPORTS OTHER THAN TWO MOTHERS REPORTING THAT ALLERGIES
WORSENED WHILE ON LDN, AND THEY BOTH STOPPED WITH GRADUAL
RESUMPTION OF THEIR FORMER LEVEL OF ALLERGIC ACTIVITY.
INTERESTINGLY, MANY PARENTS HAVE REPORTED ALLERGY
LESSENING OR EVEN DISAPPEARANCE, BUT CLEARLY ALL THE
CHILDREN ARE UNIQUE. AT THE PRESENT TIME, THE NUMBER OF
FAMILIES ON MY “LDN IN AUTISM” E-LIST NUMBERS MORE THAN 1600.
HERE PARENTS AND SOME PROFESSIONALS (INCLUDING ME WHEN I
HAVE THE TIME) HELP NEW PARENTS GET USED TO THE MEDICATION
AND HELP EACH OTHER WITH SIDE EFFECTS, DOSING QUESTIONS AND
EXPECTATIONS.) THE MOST OBVIOUS AND IMMEDIATE GOOD
EFFECTS OF THIS MEDICATION ARE ON SOCIALIZATION, COGNITION,
AND LANGUAGE. IMMUNE BENEFITS ARE LATER, MORE SUBTLE, AND
REPORTED BY PARENTS AS “BETTER HEALTH.” INTERESTINGLY, THE
GREATEST BENEFIT REPORTED BY THE PARENTS WAS “BETTER
QUALITY OF SLEEP.” FOR SOME PERSONS IN THE STUDY, BOTH ADULT
AND CHILDREN, CHANGING THE DIET TO FURTHER RESTRICT CASEIN
AND GLUTEN HELPED ELIMINATE THE EARLY HYPERACTIVE
RESPONSES.
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