Down's Syndrome: Nutritional

Intervention
Dr. Chris. M. Reading,
Consultant Psychiatrist
Suite 2a, 2nd Floor
Pacific Medical Centre
8-12 Pacific Parade
Dee Why, NSW 2099
Australia

ABSTRACT

Down's Syndrome patients are known to be of short stature, prone to infections, auto-
immune disease, hypothyroidism, leukaemia, heart defects and later Alzheimer's disease.
They tend to have older mothers, like Alzheimer's disease patients. The latter tend to have
sibs with either Down's Syndrome or lymphoma/leukaemia. Evidence, looking at 28
Down's Syndrome patients, suggests that multiple food allergies, gluten-gliadin sensitivity
or intolerance are causing a coeliac disease-like picture with a malabsorption state for
essential vitamins, minerals and severe autoimmune disease. It is hoped that missed
gluten-gliadin sensitivity or intolerance with or without coeliac disease will be considered
as a cause of abnormal oogenesis and spermatogenesis resulting in trisomy 21 and other
aneuploidies. The machanism most likely is low Bl interfering with sufficient release of
cAMP for normal meiosis. Alternatively exorphins and peptides from foods may suppress
prostaglandin El synthesis, or food sensitivities may alter toxic metal absorption mech-
anisms, which are thought to play a role in the development of Alzheimer's disease.
Adequate vitamin/mineral supplementation, especially Bl, prior to conception and in the
first trimester is recommended for mothers at risk for OS, especially older mothers and a
gluten free diet for those with coeliac disease or gluten-gliadin sensitivity/intolerance.
Hopefully this will prevent conception of a OS child, or prevent heart defects/stigmata if
one is conceived. OS children should be investigated for the above and commence a food
allergy free diet with relevant supplements to meet their needs as early as possible to allow
maximum development.

INTRODUCTION
Down's Syndrome (OS) or Trisomy 21, is the commonest form of chromosomal
aberration known to cause mental retardation. It occurs at a rate of about 1 in
600 live births (Stoller, 1971; Penrose and Smith, 1961.) It accounts for 10-20%
of the institutionalised mentally retarded population (Heller, 1969; Gibson,
1978.)
In 1929, life expectancy was only 9 years (Penrose, 1949.) It rose to 12-15
years by 1947 (Penrose, 1949; Benda 1969) by 1982 the average lfe expectancy
was 35 years (Thase, 1982.) The overall mortality rate is more than 5 times that
of the general population (Oster et al., 1975). According to Thase (1982) there
are increased specific mortality rates for respiratory disease, congenital heart
disease, leukaemia and neurological disorders. The disordered immunology,
particularly T-cell mediated, appears to be related to the increased vulnerability.
The periods of highest risk are: 1. Infancy (due to congenital heart disease,
leukaemia and respiratory disorders); 2. Late adulthood, when Alzheirner-type
dementia (ATD) and declining immunological function are the problems (Thase,
1982). 91

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 AETIOLOGY
The aetiology of Down's Syndrome remains a mystery. Several factors appear
to increase the risk of conceiving a OS child: The incidence of the condition
increases with the age of the mother. Mothers of OS children are usually over
35 (Penrose 1951.)
Other risk factors are: Hyperthyroidism prior to conception or during early
pregnancy (Fialkow et al., 1971). Viral infections, such as hepatitis (Stroller and
Colman, 1969). Anaemia (Harlap, 1973).
Other reported factors are: Depression; Vomiting and fatigue in early preg-
nancy; A history of miscarriage. Vaginal bleeding in the first trimester; Oestriol
production is usually less than normal.

NUTRITIONAL DISORDER (see Tables 1 and 2)

That deficiency in the ability to acquire or handle thiamin, vitamin B1, plays a
part in the causation of OS was suggested by Reading (1976). B1 assays on
three male OS adults, carried out in 1973, were reported in 1979. In 1975, F.
Schmid et al. confirmed low vitamin B1 in 90 OS patients. They also investigated
vitamins B2 and B6. They established a disturbance of vitamin B1 metabolism,
but not (when compared to their controls) a deficiency of intake. They suggested
"disturbances in the phosphorylation or a cell membrane disorder are equally
conceivable".
GENERAL EFFECTS OF DISTURBED VITAMIN Bl METABOLISM
B1 deficiency can cause depression (Marks, 1975,). Similarly, B1 deficiency can
result in apathy, irritability, impairment of memory, concentration and motor
skills. These can respond to B1 therapy. Harrel (1946) measured the progress
in mental and physical skills of 120 children living in an orphanage. Half
received B1 and half did not. Those treated with B1 (2mg daily) showed improv-
ement in acuity of vision, skills at games, reaction time, reading, arithmetical
processes, memory and intelligence tests.
It is known that Bl deficiency is not uncommon in pregnancy. In one survey
of 599 pregnant women (Heller et al., 1974,) 25-30% were found to be depleted
with respect to the erythrocyte transketolase saturation. This proportion
remained constant throughout gestation. In another survey (Migasena et al.,
1974) 42% of pregnant women at full term had B1 deficiency.
Chronic alcoholics are often B1 deficient (Wood and Pennington, 1974; Wood,
1972.) Chronic alcoholic mothers are known to have offspring with cranio-facial
abnormalities, congenital heart defects and dermatoglyphic abnormalities such
as simian palmar creases ijones et al., 1973; Ibid, 1974.) They may also be
mentally retarded (foetal alcohol syndrome).

COMPARISON WITH DOWN'S SYNDROME

The depression, vomiting, fatigue, anaemia and low oestriol production in OS
pregnancy could well benefit the correction of a deficiency of Bl. Equally, the OS
fetus could well benefit from the correction of B1 deficiency in the mother.
Like children of Bl deficient alcoholics, OS patients have cranio-facial abnor-
malities and may have heart defects, simian creases, short little fingers and mental
retardation.
EFFECTS OF DOWN'S SYNDROME ON CHROMATIN

In OS, clumping of chromatin in the iris (of neural tube origin) in the early
foetus results in Brushfield's spots (Ingalls et al., 1957). Thiamin deficiency
92 can cause clumping or condensation of chromatin in certain B1 sensitive cells

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 TABLE 1
VITAMIN LEVELS IN 3 MALE DOWN'S SYNDROME PATIENTS (AGED 22-23 YEARS)

Plasma Levels Functional Tests in erythrocytes

Patient Age when VitA J3 Carotene Vit E Vit C Vit B12 Vit B1 Vit B6 B2
assayed & ETKA EGOT FAD
TPP -- P5P -- %E
date %E ETKA+TPP &E EGOT+P5P
M1 22 Yrs 201.6 0 0.582 0.45 486 9.8 132.5 76.5 430.t 0
-- --
8.11.73 142.2 759.9

M2 23 Yrs 2362 57.1 0.752 0.40 866 15.2 128.3 107.6 306.9 0
-- --
8.11.73 147.8 637.0

M3 22 Yrs 226.1 11.4 1.110 0.95 248 10.8 129.7 68.2 474.2 0
-- --
8.11.73 143.8 797.0

Normal levels 120-230 20-100 >0.70 >0.70 184-800 0-15 >140 0-100. >330 0-5
IU/100ml ug/100ml mg/100ml pg/ml -- --
>160 >600
TPP = Thiamine pyrophosphate; P5P = Pyridoxal-5'-pho sphate; FAD = Flavin Adenine dinucleotide; ETKA = Erythrocyte
transketolase activity; EGOT = Erythrocyte glutamate oxaloacetate transaminase (activity). (Reading et al., 1979) E = Effect.

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\0
(..j.)
 TABLE 2
RESPONSE TO THIAMINE (Bl) TREATMENT IN 3 MALE DOWN'S SYNDROME
PATIENTS, OBSERVED BY STAFF AND RELATIVES, AND BY INTERVIEWING
THE PATIENTS

Before commencing On thiamine 50 mg Off thiamine for over 6

thiamine (Bl) t.d.s. for over 18 mths mths (before
recommencing
thiamine)
Ml Mood Depressed, prone to Far more cheerful, Again became very
(affect) weeping spells often spoke depressed, quiet, shy
spontaneaously, and withdrawn
weeping spells ceased
Workshop Sluggish, unco- Work output Slow, unco-operative
skills operative increased, more
motivated
Behaviour Negativistic. Refused Far less stubborn, and Unco-operative.
to go home at negativistic. Far more Tended to isolate
weekends. Tended to alert & able to stay in
isolate. Pale, anergic group activities.
Happy to go home
M2 Mood Depressed, tearful Far less depressed, Very weepy,
(affect) spoke more depressed
spontaneously, not
weepy
Workshop Very hard to get him to Far more motivated Refused to work,
skills work. Slow and unco- most unco-operative
operative
Behaviour Very attention seeking Far less attention Tended to isolate.
behaviour. seeking behaviour and Attention seeking
Negativistic. much less negativistic behaviour
Hypochondriacal predominant
(headaches and
abdominal pain)
M3 Mood Mood swings. Cheerful, talked Depressed, paranoid.
(affect) Euphoric, paranoid spontaneously Mood swings,
auditory hallucinations euphoric at times
calling him monkey
face, overactive,
depressed at times
Workshop Would refuse to work Motivated to work and Refused to work in
skills in the afternoon. Very output increased the afternoons.
reluctant to work in the Lacked motivation
morning
Behaviour Very negativistic at Cooperative, friendly, Very negativistic.
times refused to go on no violent outbursts. Violent at times,
outings or weekend No psychotic episodes punching staff
leave home. Violent to
staff and patients
* Low in B6 as well. For the trial period had there been minimal or no improvement
on Bl, then B6 would have been added. (Reading, et al., 1979)

(Manocha, 1972). The addition of cAMP to certain cells can cause diffuse
dispersal of chromatin (Kano et al., 1972). This is the opposite of chromatin
94 clumping and condensation. Bl deficiency can upset cAMP release. This occurs at

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the adrenal cortex in response to ACfH thereby upsetting the steroidogenic
action of ACfH (Meikle et al., 1972).
Normal oocyte meiosis is dependent on cAMP (Koch et al., 1974). It is not
known whether B1 deficiency is the cause of meiotic nondisjunction in OS.
However, if B1 deficiency interferes with the release of cAMP by ovarian cells
in response to luteinizing hormone (LH) - just as it can upset release of cAMP
at the adrenal cortex in response to ACTH - then abnormal oocytic meiosis and
meiotic nondisjunction may result. The amount of cAMP released from the
adrenal cortex under the influence of ACTH and from ovarian tissue under the
influecne of LH, is of the same order. Certainly B1 deficiency may result in
anovulation and ovarian atrophy and thereby blight the developing fetal ovary
and oocytes. The daughter is then at risk of having OS children, especially
when she is over 35 years of age and becomes B1 deficient herself. The B1
deficient/damaged oocytes may then be selected for ovulation rather than the
normal ones. Women over 35 tend to shed more damaged ova.
It is of interest that leukaemia occurs more commonly in OS (Schuler et al.,
1972) and that trisomy 21 can occur in bone marrow cells alone; this latter
condition is pre-leukaemic. (It is not known at this stage whether these cells
are B1 dependent as in OS.) It is possible that B1 deficiency is also the factor
blighting the foetal bone marrow development and can, therefore, cause vacuoli-
zation of bone marrow and iris cells in such conditions as B1-dependent Leigh's
Syndrome (Simopoulos et al., 1972; Howard and Albert, 1972). If B1 deficiency
can produce pre-leukaemia then, if it persists, it may induce frank leukaemia
as is sometimes seen in OS children at birth or with aneuploidy of bone marrow
cells.
The above findings and correlative evidence suggest that a B1 deficient state
in the mother prior to conception, or at conception, induces chromosomal
changes such as OS and then continues to act on vulnerable tissues at critical
periods in foetal development. Thus children with an abnormal karyotype (extra
chromosome) and very few stigmata may have had adequate nutrition (in
particular their B-group vitamin needs may have been met) especially during
early pregnancy. (OS children can be born with no heart defects and minimal
brain damage.) Similarly a B1 deficient state in pregnancy may result in a child
with heart defects, mental retardation, and OS facies with a normal karyotype.

CORRECTION OF Bl DEFICIENCY/METABOLISM
In 1979, I concluded that correction of B1 deficiency:
A. Prior to conception and ovulation may result in:- 1. Ovulation of normal oocytes
(not preferential selection of B1 damaged oocytes for ovulation); 2. Normal
oocytic maturation and non meiotic non-disjunction; 3. Far fewer OS births.
B. During the first trimester (especially) and throughout pregnancy may result in:-
1. Normal development of foetal ovaries (so that the daughter hasn't blighted
ovaries (oocytes) and is not at risk to have children with OS many years
later). 2. Normal bone marr~w development (not trisomy 21 and other pre-
leukaemic changes). 3. The birth of a OS child with minimal stigmata,
especially heart defects and mental retardation. 4. Fewer OS children being
born with leukaemia (Bl supplements may prevent the leukaemic change in
the pre-leukaemic trisomy 21 cells).
C. After birth and throughout life in people with OS:- 1. Will help the normal
maturation of the central nervous system. 2. Improve motor skills and
behaviour. 3. Help prevent early senescence. (B1 requirements increase with
age. OS people are more prone to dementia such as Alzheimer's disease.)

Work subsequent to 1979 by Smithells and Tolarova strongly supports the

view that preconceptual supplementation with vitamins, especially folic acid, .95

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 helps prevent recurrence of cleft lip and other neural tube defects (Tolarova
1982; Smithells et al., 1980, 1981, 1983) (see Table 3).

TABLE 3
SOME EVIDENCE THAT VITAMIN SUPPLEMENTS HELP IN THE PREVENTION
OF CONGENITAL ABNORMALITIES

(1) Periconceptional supplementation (2) Prevention of neural tube defects by

with vitamins and folic acid to periconceptional vitamin
prevent recurrence of deft lip supplementation (Smithells, et al.,
(Tolarova, 1982) 1980, 1981, 1983). There were 2 NTD
- 85 pregnancies fully recurrences in 254 vitamin
supplemented - one recurrence supplemented mothers. Significantly
- acting as control, 212 pregnancies fewer than 11 NTD recurrences in 219
not supplemented ended in 15 unsupplemented mothers.
recurrences.

Sufficient supplementation of relevant vitamins/minerals should prevent

conception resulting in OS and where conception has already taken place,
prevent the stigmata.
It was not known in 1979 why the mother of a OS child should be B1 dependent/
deficient or why a OS child should be so, but there are great similarities between
OS children and children with coeliac disease (short stature, proneness to
infections, etc were noted in both instances. New areas of research were con-
sidered.)
Could OS children have gluten/gliadin sensitivity/intolerance with malab-
sorption for B1, B6, etc?
Could this be the case with their mothers or fathers?
In about 20% of OS patients, the extra chromosome 21 originates from the
father and not the mother - more males being born when the error was
maternal, and more females when the error was paternal (Mikkelsen, 1982).

FURTHER RESEARCH
An investigation was undertaken with 28 OS patients (14 male and 14 female,
aged from 3Y2 months to 21 years.) Vitamin and mineral deficiencies, food
allergies, autoimmune disease (including gluten/alpha gliadin sensitivity/intoler-
ance) and cow's milk allergy/intolerance were looked at.

Methodology
Vitamin assays: The patients were fasted for 12 hours overnight and 20-40ml
venuas blood was collected in heparinized test tubes (Reading et al., 1979).
Food allergies were looked at using: 1. The RAST (IgE mediated immediate reation
type 1). 2. Bryan's Cytotoxic Test (BCFT) which is IgM/IgA/IgG/IgD (but not
IgE) mediated. (The relevance of this test for ingested food allergies/intolerance/
hypersensitivity was discussed by me in my addresss to the Schizophrenia
Association of Great Britain's Conference, April 22, 1982. Also by others
(Fennell, 1983; Downing, 1983).
Clinical Immunology: Autoantibodies (Unsworth, 1981), complements C3, C4,
CHSO, immunoglobulins were looked at. Routine biochemistry was undertaken
(minerals; trace elements; fasting blood sugar, etc.).

Vitamin Levels: Males (see Tables 4(i) and 4 (ii))

Vitamin A Retinol and Caroteniods: Of 14 patients none was low in vitamin A
96 Retinol but one supplemented patient (M14) had a slightly raised level. 3 pati-

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 VITAMIN LEVELS IN 13 MALE DOWN'S SYNDROME PATIENTS (AGED 31/2 MONTHS - L1 YEARS)

Plasma Levels Functional Tests in E!]!_throS!L.tes

Patient Age when VitA Vit E Vit C B12 Folic B3 B1 B6 B2
assayed Acid FAD
Retinol Total TPP ETKA P5P EGOT %E
--
Carotenoids %E ETKA+TPP % E EGOT+P5P

M1 31/2 Mths 240 28.8 3.4 1.40 228 8.9 7 56 504 0.86
-155 -
166 789
M3 S 12 Mths 64.8 <1.0 1.06 437 16.1 235 4 38 1.28
-183 -438
191 607
M4 S 14 Mths 132 10.9 0.76 221 14.8 5.5 137 18 0.68
- -422
145 500
M5 17 Mths 19.7 62.3
-
74.6
M6 S 18 Mths 16.8 4.7 0.96 243 14.1 6.1 148 34 0.82
- -824
158 1104
M7 SC 31/z Yrs 525 <2.0 6.4 1.34 498 25.3 15 949 0.78
0.8 -153 -
154 1098
M8 SC 3 Yrs 7 583 88.8 4.04 1.44a 321 14.0 105 10.5 110 56 0.78
- -444
121 689
M9 SC 3 Yrs 9 421 108 7.7 2.34 334 45.2 17 736 o:78
5.5 -104 -
109 878
M10 SC 5 Yrs 96 7.0 0.90 234 18.2 1.8 190 48 376 0.77
- -
194 558
M11 6 Yrs 79.2 8.4 1.99 320 16.1 1.8 122 34 671 0.78
- -
124 909

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M12 S 9 Yrs 100.8 18.5b 1.46c 715 39.9 13 796 1.24
2.6 -173 -
177 898
M13 21 Yrs 254 12.0 0.62 525 10.7 19.3 76 1.03
M14 S 21 Yrs 1076 240.8 4.4 1.2 209 7.9 2.0 220 17 916 0.88
- -
225 1082
Normal ranges 125- 50-250 5-25 0.7- 147- 6.8- 160- <15% >140 <80% >330 <1.3
1000 2.0 664 34.0 200 >160 >600
mg/l J.Lg% mg% pmol/l ng/ml
a = On 250mg Vit C/day. b = On 500mg Vit E/day. c = On 1000mg Vit C/day. S = Supplemented.
\0 C = Cell Therapy. E =Effect.
'-1
 \C)
00

TABLE 4 (ii)
SUMMARY OF VITAMIN DEFICIENCIES IN 13 MALE DOWN'S SYNDROME PATIENTS

VitA Vit E Vit C B12 Folic B3 B1 B6 B2

Retinol Total Acid FAD%
ETKA EGOT
carotenoids TPP -- P5P -- Effect
%E ETKA+TPP %E EGOT+P5P
Number assayed N=6 N=ll N=12 N=12 N=12 N=12 N=2 N=13 N=12 N=12 N=ll N=12
High 1 1 2 1e
Low 3 5 1 1d 2• 7" 2<
Percentage low 27% 41% 8% 50% 15% 58% 19%

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a =Both not supplemented. b = 5 supplemented, 2 not supplemented. c =Both low despite supplementation . d =Not supplemented.
e = Supplemented. E =Effect.

Note. (1) 12/13 (92%) were low in at least one vitamin. (The one not low was supplemented, hence raised B12 and Folic acid.)
(2) 6/12 (50%) were low in two vitamins. (Four supplemented, two not supplemented.) (3) 2/13 (15%) Had three vitamin
deficiencies. (Both were supplemented. One with cell therapy.)
ents had low total carotenoids. Two were low despite supplementation; 1 (M7)·
extremely low.
Vitamin E: Five were low (4 despite supplementation). M3 was very low despite
supplementation.
Vitamin C: One patient was low and not supplemented. 1 patient was high
(2.34mg%- Normal range 0.7-2mg%) but was mistakenly given 500mg of the
vitamin before the test.
Vitamin Bl: Two patients (M5 & M13), both unsupplemented, showed increased
TPP activity and were thus Bl deficient. On ETKA test and ETKA+TPP, seven
patients were low in vitamin Bl despite 5 being supplemented. This supports
what was noted by me and by others (Reading et al., 1979- reporting findings
of 1973; Schmid et al., 1975).
Folic Acid: No patient had low levels but two, supplemented, had raised levels.
Vitamin B3: Only two assays were done. One was high and supplemented. The
other was low despite supplementation.
Vitamin B2: No patient was low but 9 out of 12 were supplemented.
Vitamin B6: By the P5P test, no patient was low. On the EGOT+P5P test, two
patients (M4 & MlO) were low in B6.
Vitamin B12: One patient (supplemented) had raised B12 levels; 5 were in the
lower quarter range (below 276) (Serum levels are not a measure of tissue
stores).
3 cases (Ml, M4 & M6) are under 2 years of age and at risk of juvenile pernicious
anaemia- Ml already has parietal cell antibodies 1:20. M4, M6, MB, MlO were
already supplemented. MlO and M13 have latent pernicious anaemia - MlO
with parietal cell antibodies 1:40 and intrinsic factor antibodies 1:2. Ml3 had
parietal cell antibodies 1:40 and intrinsic factor antibodies 1:4 (Thomas and
Jewell, 1979).

Vitamin Levels: Females (see Tables 5(i) and 5 (ii))

Vitamin A Retinol & Carotenoids: Of 14 patients two were low in total caroteniods
despite supplements. One (F12) was borderline low.
Vitamin E: Three patients were low- 2 (F5 & F12) seriously low. A further 9
were borderline low including one (F7) supplemented with lOOmg vitamin E
per day. Fl, a supplemented patient, had a slightly raised vitamin E.
Vitamin C: Fl had raised levels but supplements had been given on the morning
of the test. Despite supplements, F3 was seriously low whilst FB and Fll were
borderline low (the latter despite lOOOmg the day before the test).
Vitamin Bl: No patient had low Bl on TPP. Four showed low Bl on ETKA and
ETKA+TPP (three received supplements.) Three patients (FB, FlO, F13) were
borderline low, despite supplementation.
Folic Acid: One patient (F12) was low.
Vitamin B3: Two patients only were assessed. Although one was supplemented
both had low B3 levels.
Vitamin B6: One patient was low by P5P test (increased activity) six were low
in B6 on the EGOT and EGOT + P5P tests (4 were supplemented);
Vitamin B12: Two patients (F4 & F12) had seriously low B12 levels and thus
pernicious anaemia, despite vitamin supplementation. F4 had parietal cell anti-
bodies 1:20, but not intrinsic factor antibodies. F12 had thyroglobulin antibodies,
but not parietal cell antibodies. F5 had borderline low B12 and already had
parietal cell antibodies 1:20. Two patients, both supplemented, had raised B12
levels.
Tables 6 and 7 summarise vitamin levels in both male and female patients: 23
out of 27 (85.2%) had one deficiency, 13 out of27 (48.1 %) had two deficiencies, 6
out of 27 (22.2%) had three deficiencies. 99

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 ..... TABLE 5 (i)
0
0 VITAMIN LEVELS IN 14 FEMALE DOWN'S SYNDROME PATIENTS (AGED 1-11 YEARS)

Plasma Levels Functional Tests in E1]J_thro01.tes

Patient Age when VitA Vit E VitC B12 Folic B3 B1 B6 B2
assayed Add FAD
Retinol Total TPP ETKA P5P EGOT %E
Carotenoids %E ETKA+TPP % E EGOT+P5P
Fl S 1 Yr 295 28 2.53 295 25.7 1.3 174 48 487 0.92
-
176 720
F2SCM 1 Yr 115.2 6.3 1.02 257 37 0.2 178 22 889
- 1.01
179 1093
F3 S 15 Mths 0.01 654 9.2 3.4 50
F4 SC 21/2 Yrs 76.8 7.0 1.32 109 12.1 46 733 1.09
1067
F5 21fz Yrs 72.0 0.4 1.07 179 13.9 8.5 140 58 331 0.84
152 520
F6 SC 31/4 Yrs 350 48 10.5 1.18• 423 50.3 10.1 116 74 289 0.84
127 504
F7 S 4 Yrs 76.8 7.7e 1.23b 294 26 3.91 1731 95.2 287 0.67
179 564
F8 S 5 Yrs 550 160.8 6.2 0.86 1695 20.6 6.1 157 46 498 0.88
167 729
F9 51fz Yrs 363 120 6.43 1.7 293 24.7 140 9.0 183 60 282 1.03
200 444
FlO S 6 Yrs 706 110.4 7.94 1.38c 403 28.1 150 6.0 153 48 404
- 0.92
163 598
F11 S 61fz Yrs 76.8 9.5 0.82d 335 10.6 10.3 116 22 746 0.95
123 911
F12 S 7Yrs 52.8 1.0 1.83 67 4.3 6.4 191 24 889 0.9

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207 1102
F13 SC 8 Yrs 26.4 2.3 1.66 317 13.2 5.3 159 52 360 0.94
166 551
F14 S 11 Yrs 445 88.8 8.3 2.26 702 38.6 10.5 129 2 658
- 0.79
143 662
Normal ranges 125- 50-250 5-25 0.7- 147- 6.8- 160- <15% >140 <80% >330 <1.3
1000 2.0 664 34.0 200 >160 >600
mg/1 ,ug% mg% pmol/1 ng/ml
a = On 100mg Vit C/day. b = On 125mg Vit C/day. c = On 500mg Vit C/day. d = On 1000mg Vit C/day.
e = On lOOmg Vit E/day.
f = On 150mg Vit B1/day. S =Supplement ed. M =Mosaic. E = Effect.
r - u 1'
r .... n Th ....... ..... rn. -.r: r: r> ...t ·~ .: -
 TABLE 5 (ii)
SUMMARY OF VITAMIN DEFICIENCIES IN 14 FEMALE DOWN'S SYNDROME PATIENTS

VitA Vit E Vit C B12 Folic B3 B1 B6 B2

acid FAD
Retinol Total ETKA EGOT
TPP -- PSP -- %!E
carotenoids %E ETKA+TPP %E EGOT+PSP
N=13 N=14 N=14 N=14 N=2 N=13 N=12 N=14 N=13 N=13
Number assayed N=6 N=12
3 1 2 1 2• 0 4b 1 6c 0
Low 0 2
16.7% 23% 7% 14% 7% 100% 33% 7% 46%
Percentage low
despite
a = One was low despite supplementa tion. b = Three of these four were supplemente d. c = Four out of six were low
supplementa tion. E = Effect.
low in three
Notes. (1) 11/14 (78.5%) were low in at least one vitamin. (2) 7/14 (50%) were low in two vitamins. (3) 4/14 (28%) were
vitamins.

TABLE 6
VITAMIN LEVELS IN 27 DOWN'S SYNDROME PATIENTS (13 MALE, 14 FEMALE)

Plasma levels Functional Tests in Erythrocytes

VitA Vit E Vit C Vit B12 Folic B3 B1 B6 B2
acid FAD
Retinol Carotenoids ETKA PSP EGOT %!E
TPP --
ETKA+TPP EGOT+PSP

Female no. Assayed 6 12 13 14 14 14 2 13 12 14 13 13

Low 0 2 3 1 2 1 2 0 4 1 6 0

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Assayed 6 11 12 12 14 12 2 13 12 12 11 11
Male no.
Low 0 3 5 1 0 0 1 2 7 0 2 0

Assayed 12 23 25 26 28 26 4 26 24 26 24 24
Total no.
Low 0 5 8 2 2 1 3 2 11 1 8 0

0% 21% 32% 7.6% 7% 3.8% 75% 7.6% 45% 7% 33% 0%

Percentage
TPP = Thiamine pyrophospha te. FAD= Flavin adenine dinucleotide. PSP = Pyridoxal-5'- phosphate. ETKA = Erythrocyte
~
0 transketolase activity. EGOT = Erythrocyte glutamate oxaloacetate transaminase (activity). E = Effect.
~
 TABLE 7
TOTAL NUMBER OF PATIENTS WITH VITAMIN DEFICIENCIES

Male % Female % Total %

(a) One deficiency 12/13 92.3 11/4 78.6 23/27 85.2
(b) Two deficiencies 6/13 46.1 7/14 50.0 13/27 48.1
(c) Three deficiencies 2/13 15.4 4/14 28.6 6/27 22.2
Food Allergies (see Table 8)
12 female patients with DS aged 1-11 years were examined by the RAST and
Bryan's Cytotoxic tests. 40% had low IgE. One patient. (F14) had raised IgE but
still did not show food allergies. However, food allergies can occur with low
IgE (as F2, allergic to cow's milk).
Bryan's Cytotoxic test looked at up to 108 foods at a time while the RAST
test looked at between 3 & 16. The cytotoxic tests detected more positive
reactions for cow's milk, wheat, egg and positives for a far greater variety of
foods.
TABLE 8
FOOD ALLERGIES IN 22 DOWN'S SYNDROME PATIENTS (11 FEMALE, 11 MALE)
USING RAST AND BRYAN'S CYTOTOXIC TEST.

(i) B.C.F.T. (BRYAN'S CYTOTOXIC TEST)

Female Male Total %

11 assayed 11 assayed 22 assayed
Com 4 6 10 45%
Cow's Milk 4 4 8 36%
Wheat 2 4 6 27%
Peanut 2 3 5 22.5%
Bakers yeast 1 2 3 13%
Barley 1 1 2 9%
Malt 1 1 2 9%
Rye 0 2 2 9%
Soyabean 1 1 1 9%
Egg 1 1 2 9%
Oat 1 0 1 4.5%
(ii) R.A.S.T.

Female Male Total %

9 assayed 10 assayed 19 assayed
Cow's milk 3 0 3 15%
Wheat 2 0 2 10%
Chicken 1 1 2 10%
Rye 1 0 1 5%
Egg 1 0 1 5%
Soyabean 0 1 1 5%
(iii) COW'S MILK, WHEAT, CORN ALLERGY/INTOLERANCE IN 24 DOWN'S SYNDROME
PATIENTS POSITIVE ON RAST AND/OR B.C.F.T.

Female Male Total %

No. positive No. positive No. positive
Cow's milk 5 4 9 37.5%
Wheat 4 4 8 33.3%
102 Com 4 6 10 41.6%

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 12 male DS patients, aged 31/2 months to 21 years, were subject to similar
tests. RAST was positive for 2 foods in only one out of 12 patients. BCFf gave
many positives with 11 out of 12 cases (one case was not tested).

Clinical Immunology (see Table 9)

Patients were examined for antibodies associated with autoimmune disease.
The antibodies in question were for reticulin, bile duct, smooth muscle, parietal
cells, gluten/alphagliadin, pancreatic duct and thyroid. 12 male patients and 14
females with DS were assessed.
Table 9 is a summary of the overall autoimmune disease in the 26 patients:
78% were positive for reticulin antibodies; 69% for bile duct antibodies; 58% for
parietal cell antibodies; 47% for smooth muscle and gluten antibodies; 43% for
agliadin antibodies; 35% for thyroglobulin antibodies; 33% for ANF; 30% for
pancreatic duct antibodies; 17% for microsomal thyroid antibodies.

Minerals and Blood Sugar (see Table 10) ·

14 female patients with DS and 13 male patients were assessed for copper,
zinc, iron, calcium, magnesium and aluminium. In addition their fasting blood
glucose was measured. The results are set out in Table 10: 16.6% had low
calcium; 13.6% had low iron, 12.5% had low copper and 8.3% had low zinc
(despite supplementation).
Two female patients had hair analysis (see Table 11); one showed toxic levels
of aluminium, cadmium and lead and high levels of calcium, magnesium and
sodium with low levels of chromium, copper and selenium. The second patient
showed low calcium, iron, manganes, nickel, zinc, selenium and vanadium. 72%
of patients examined had low blood glucose.

DISCUSSION
These assessments indicate that patients with DS are likely to be:- 1. Low in
certain vitamins- despite supplementation. 2. Low in certain minerals/trace
elements - despite supplementation. They have a marked tendency to a low
fasting blood sugar level. 3. At risk for non-IgE mediated food allergies/
intolerance/hypersensitivity as disclosed by Bryan's Cytotoxic test (IgM/IgN
IgG/IgD mediated). This is in accord with tests for autoimmune disease with
clinical immunology. 4. Highly at risk for autoimmune disease. (a) Especially that
seen with wheat/grains/gluten/agliadin intolerance/sensitivity, and commonly
associated with coeliac disease. (b) Pernicious anaemia/gastritis. (c) Collagen
disease, including juvenile SLE. (d) Autoimmune thyroiditis. (e) Chronic active
hepitis. The bile duct antibodies and pancreatic duct antibodies strongly support
impaired hepatic and pancreatic function interfering with normal digestion.
Coeliacs tend to have low trypsin and chymotrypsin.
There is also s0rne evidence that DS patients are likely to have high levels of
toxic metals. Supplementation with too much copper could render this state
worse. If iron levels are too high this could also be deleterious.
Harrel and collegues (1981), under double blind conditions showed that with
vitamin/mineral supplementation plus thyroid hormone, three q_uarters of the
DS children gained between 10 and 25 units in IQ. Their physical appearance
changed notably during the study; there was fluid loss in faces and extremities.
One nine year old child with cataract had the condition arrested. The supple-
mented group gained more height than controls, over four months. There was
also generalimprovement in school work. The observers also noted healthier
hair, skin and nail texture in six cases and cessation of hyperactive behaviour
in six cases. During the trial, all parents were asked to restrict the patients
intake of less nutritious, sugary, foods and soft drinks, and to supply fruit and
milk freely. 103

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 ......
~

TABLE 9
AUTOIMMUNE DISEASE IN 26 DOWN'S SYNDROME PATIENTS (12 FEMALE, 14 MALE)

Reticulin Bile Duct Smooth Parietal Gluten a Gliadin Pancreatic Thyroid Anf a Casein
muscle THY MICRO
Male no tested 10 11 10 11 6 6 7 7 7 7 4
Positive 8 7 5 7 2 2 3 3 2 2 2
Female no tested 13 12 11 13 11 10 6 10 10 11 10
Positive 10 9 5 7 6 5 1 3 1 4 0
Total tested 23 23 21 24 17 16 13 17 17 18 14

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Total positive 18 16 10 14 8 7 4 6 3 6 2
Percentage 78% 69% 47% 58% 47% 43% 30% 35% 17% 33% 14%
THY = Thyroglobulin. MICRO = microsomal.
 TABLE 10
LABORATORY FINDING S IN 27 DOWN'S SYNDRO ME PATIENTS (MINERALS, TOXIC METALS, FASTING BLOOD
GLUCOSE, ESR, IMMUNOGLOBUL INS, COMPLEMENTS, IMMUNE COMPLEXES)

Iron Calcium Mg Al Fasting ESR IgE IgM IgG IgA C3 C4 Immune

Copper Zinc Com-
BL Sugar
Glucose plexes

12 12 7 6 9 8 11 11 11 11 11 7
Male No. tested 12 12 11
2 2 3. 4 5 1 3
Low
2 1 2 2 4
High 1
11 12 12 6 5 10 12 12 12 12 11 11 6
Female No. tested 12 12
1 1 4 6 1 1 1
Low 3
2 3 1 2
High 1 1 1
22 24 24 13 11 19 20 23 23 23 22 22 13
Total No. tested 24 24
2 3 4 8 11 1 1 1 4
Low 3
8.3% 13.6% 16.6% 72.7% 55% 4.3% 4.3% 4.3% 18.8%
Percentag e 12.5%
3 3 5 1 2 6
High 2 1
15% 21% 4.3% 8.6% 46.1%
Percentag e 8.3% 4.1% 13.6%
Thus About
7/10 Down's Syndrom e patients have low fasting blood sugar 1112 Down's Syndrom e patients have low zinc
5/10 Down's Syndrom e patients have low IgE 5/10 Down's Syndrom e patients have immune complexes positive

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1/5 Down's Syndrom e patients have low C4 1/5 Down's Syndrom e patients have high IgM
116 Down's Syndrom e patients have low Calcium 1/8 Down's Syndrom e patients have high iron
118 Down's Syndrom e patients have low iron, copper 1/12 Down's Syndrom e patients have high copper, IgA

......
5l
 TABLE 11
HAIR ANALYSIS RESULTS IN 2 FEMALE DOWN'S SYNDROME PATIENTS

Patient 1 Normal Patient 2 Normal

Aged 6 Yrs Range Aged 2 Yrs Range
Calcium 1155* 375-920 92.5 200-600
Chromium 0.33 0.4-1.6 0.8 0.5-1.50
Cobalt 0.16 0.1-0.4 0.64 0.04-1.00
Copper 17"" 18-50 8.24 12-35
Iron 48" 19-61 19.5 20-50
Lithium 0.34 0.1-1.3 0.02 0.02-0.80
Magnesium 129* 44-98 44.3 25-75
Manganese 1.5 0.6-2.8 0.39 1.00-10.00
Molybdenum 0.22 0.1-0.8 0.17 0.10-0.70
Nickel 1.3 0.15-2.0 0.27 0.30-1.00
Phosphorus 112 92-165 221 100-170
Potassium 147 30-175 126 75-180
Selenium 0.10 0.94-5.75 0.12 3.00-6.00
Sodium 528 85-385 281 150-350
Vanadium 0.33 0.1-0.6 0.71 1.00-2.00
Zinc 175" 125-254 150 160-240
Aluminium 23 <15 7.93 10.00-20.00
Arsentic 0.39 <2.0 3.43 2-5
Cadmium 4.5 <1.6 0.84 1.00-2.00
Lead 19 <18 5.36 20-30
Mercury 0.10 <3.0 2.61 2.50-5.00
" = Serum Levels were normal- See F7. Patient 2 tested on hair analysis only. Note:
Selenium and Copper were low in both patients.

CONCLUSION

It is hoped that the above findings will be considered in the primary, secondary
and tertiary prevention of Down's Syndrome patients.
Table 12 shows the similarities between coeliac disease and Down's Syndrome
using some of the findings. It explains many of the features of Down's Syndrome
and associated conditions in their parents.
Figure 1 shows how normal meiosis may be upset resulting in meiotic non-
disjunction trisomy 21 of DS.
Figure 2 attempts to explain the links between increasing maternal/paternal age
and Down's Syndrome and why Down's Syndrome patients are more at risk for
Alzheimer's disease and leukaemia and why Alkheimer's disease patients tend to
have siblings with Down's Syndrome and leukaemia. The common factor is
coeliac disease or gluten/gliadin sensitivity/intolerance with low B1, B3, B6, etc.

106

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 TABLE 12
SIMILARITIES BETWEEN COELIAC DISEASE AND DOWN'S SYNDROME
Coeliac Disease Dawn's Syndrome
Immunology
Gluten Antibodies + Present 47% (N =26)
aGliadin Antibodies + +43%
Reticulin Antibodies + + 78%
Parietal Cell Antibodies + +58%
Thyroid Antibodies + + 35%
o, C4, rnso Low Low
Immune Complexes + +
IgM Low or High Low or High
IgA Low or High Low or High
Vitamin Deficiencies + +
Mineral Deficiencies + +
Female Prone to spontaneous Present in mothers of DS
abortion/miscarriage patients prior to conception
infertility and with DS pregnancy.
DS sexual dysfunction
Male Prone to infertility Fathers of DS children have?
hypogonadism missed/untreated coeliac
impaired hypothalmic disease or gluten/· gliadin
pituitary intolerance (especially with
regulation increasing age). DS have male
hypogonadism infertility
Stature Short Same
Small head
Circumference
Lymphoma + +
Leukaemia risk
Prone to infections + +
Prone to food allergies + +
Prone to atopies + +
LowETKA + +
Fissured Tongue + +

107

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 (a) Normal loleiosis.

Adequate D6, D)
Vi t C, Ms, l-1n,
Zinc

(b) Abnormal Meiosis.

( 1). PGE 1 Series due to

exorphins o:f' wheat/
grains, dairy products.
(2) +PGE1 Series due to
low V:l.t C, B), B6, Mg,
Mn & Zinc (as in
coeliac disease). +PGE 1 Series LU

~1)
I:f' B1 is low,
made worse by
1'PGE 2
/ '.cAMP low calcium.

)~~:{ ::~
Low PGE1 can
make cAMP low.
? Opioid
~eptides
Trisomy 21 (exorphins)
(DS) can depress
PGE1 and thus
cAMP.

Figure 1. If the mother or father of aDS child has coeliac disease, they could have low Bl, B3,
B6, Vitamin C, Mg, Mn, zinc upsetting oogenesis in the mother or spermatogenesis in the
father and result in Down's Syndrome.

OLDER FATHER OLDER Mal'HER

WJ:TII MJ:SSED COELJ:AC DJ:SEASE AIID RJ:SK Fm ~
m GL11l'EN/IIIGLJ:ADDI SENSJ:TJ:VJ:TY COELJ:AC DJ:SEASE.
DJ:STVRBED HYPanw.AMO (m LATENT) _/•
L_~P~J:~TU~J:~T~AR~Y~REG~~ULt~T~J:~ON~~OF~----------,------~~-~------
' GUPONSETSo\DALS~~=ONOGENESTS _..-.;;;
r~• ~ / / ~~~YTJ:C MATURATJ:ON
(1l.a.
cAMP due to low B1, biotin, Ca and PGE1
·{2 1' PGE2 due to low PGE1 due to low Vit c,
Zn, Mn, Mg + suppression o:f' PGE1
by gluten, 11£liad1n, other prolamin
:f'ract:l.ona or exorph:l.ns with opiate
activity.

EXCESS (1) OLDER

r Mal'HERS
(2) SJ:BS
WJ:TII DS
AND
:!: LYMPH !»!A

DOIIJI' S SYNDRI»>E
(PATHOLOGY OF
COELJ:AC DJ:SEASE)

Flgitre 2. links between Down;s Syndrome, Lymphonal Leukaemia, Alzheimer's Disease

108 and older mothers and fathers.

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