DIRECT PRECURSORS OF
GLUTAMATE AND GABA
AND DIET HABITS IN
DOWNS:
AN EPIDEMIOLOGICAL SURVEY ON
460 SUBJECTS
Renato COCCHI,
neurologist and medical psychologist
(IItalian translation) / traduzione in italiano
Summary
To hypothesize
the state of brain neurotransmitters as glutamate and GABA, the dietary habits,
related to the intake of sweet foods and meat or stock broth, had records in
460 Down's syndrome Ss (187 F + 273 M; age at 1st consultation: range: 3 - 511
months, average 70.77; the chromosomal diagnoses parallel both the Italian and
the International limits).
Every
habit was processed according to a 5-point scale, where 1 = refusal and 5 =
active search of the investigated food. As for sweet things, data on 429 Ss,
and as for broth data on 403 Ss, were collected.
No
gender differences were found for both habits. Significant trends resulted for
refusal or scarce interest in sweet things (p <.0005) or in broth (p <
.01).
The
co-graduation between the two dietary habits resulted in Kendall's tau = .39.
These
two mechanisms of a major dietary introduction of glutamate and GABA precursors
do not seem equivalent. They do not probably correspond, at least in part, to
the same metabolic needs.
Key words: Down's syndrome; glutamate precursors; GABA precursors; sweet things; meat or stock broth; dietary habits; epidemiology.
Down
syndrome
Symptoms
Mental
retardation
The
possible state of the brain neurotransmitters glutamic acid and GABA is one of
most important checks. It leads to say the presumable whole neurochemical
balance or unbalance of the Down's brain.
I had
already mentioned to this point, how to one hinge moment of the neurochemical
diagnostic investigation, during the first visit of a trisomic 21 subject.
(Cocchi, 1987).
If we
bear in mind that:
- either
the glucose and the glutamine cross the blood-brain barrier (Ward, Thanki and
Bradford, 1983);
- there doesn't
exist a biochemical limiting step to theirs transit across the blood-brain (
Cocchi, 1990);
- the
plasmatic glutamate does not cross the blood-brain barrier, as the glutamine
does, but in the blood it can transform itself into glutamine (Meister 1956 and
1969);
-
glucose, glutamine and glutamic acid are richly present in diet foods
(Fernstrom, 1977; Growdon and Wurtman, 1979),
then we
may hypothesize the brain state of the glutamate. Through it, we may also
hypothesize the brain state of the GABA. We can do so by investigating diet
habits of the subjects under consultation, as for their diet intake of foods
rich of glucose, of glutamic acid and glutamine.
The
richer foods of these three are i. Sweets, for the glucose, ii. The meat broth
for hydrolysed glutamine and glutamate, iii. The cube broth, for monosodium
glutamate. (Cocchi, 1988).
When I
collected the clinical data during the first visit of Down subjects, I have
always asked about, even if, in infant children I have seen only once, the
parents were unable to give proper answers, and further I did not have the
occasion to ask again for this information.
So, the
epidemiological survey of these food habits forms the purpose of this research.
Materials and methods.
I
reexamined the clinical records of a consecutive, not selected series of 460
Down subjects, personally visited between January 1979 and June 1990.
From them
I collected the following data: sex, age at the first visit; chromosomal
diagnosis, diet habits as for sweets; diet habits as the meat or cube broth.
These
habits, nearly always recorded during the first outpatients' visit, were coded
with a five-steps scale structured as it follows:
1 =
absolute refusal;
2 =
scarce preference;
3 =
normal preference;
4 =
increased preference;
5 = definite
preference for sweets or broth;
unknown =
data not recorded during the first and only visit.
For the
statistic analysis I used the Chi Square test (with Yates' correction) for the
comparisons between genders. The same I did for the comparison between the
scarce and accentuated preference for sweets or broth.
Results.
Epidemiological
data of the sample.
|
F |
187 Ss |
40.65 % |
|
M |
273 Ss |
59.35 % |
|
M/F ratio |
145.99/100 |
|
|
All coming from all Italian regions |
|
|
|
Average age at the first visit: |
|
|
|
Range |
3 - 511 months |
|
|
Average |
70.77 months |
+/- 65.83 |
|
Chromosomal diagnosis: |
|
|
|
Standard trisomy 21 |
416 Ss |
90.43 % |
|
translocations: |
17 Ss |
3.70 % |
|
mosaicisms: |
19 Ss |
4.13 % |
|
Unknown, only clinical diagnosis |
8 Ss |
1.74 % |
Table 1:
Diet habits as for sweets intake, divided to sex and total.
|
Diet habit |
Nr. F Ss |
% |
Nr. M Ss |
% |
Nr. total Ss |
% |
|
1. absolute refusal |
23 |
12.30 |
36 |
13.19 |
59 |
12.83 |
|
2. poor preference, with select choice |
62 |
33.16 |
83 |
29.33 |
145 |
31.52 |
|
3. normal preference |
52 |
27.81 |
76 |
27.84 |
128 |
27.83 |
|
4. increased preference |
43 |
22.99 |
54 |
19.08 |
97 |
21.09 |
|
5. active search of sweets |
1 |
0.53 |
9 |
3.18 |
10 |
2.17 |
|
unknown (data not recorded) |
6 |
3.21 |
15 |
5.30 |
21 |
4.57 |
|
Total |
187 |
100.00 |
273 |
100.00 |
480 |
100.00 |
Gender difference : Chi Square (excluding the unknowns) = 4.67,
with 4 df. N.S.
Table 2: Diet habits as for
broth, divided by gender and total.
|
|
Nr. F Ss |
% |
Nr. M S s |
% |
Nr. total Ss |
% |
|
1. absolute refusal |
31 |
16.58 |
53 |
19.41 |
84 |
18.26 |
|
2. scarce preference |
18 |
9.63 |
17 |
6.23 |
35 |
7.61 |
|
3. normal preference |
88 |
47.06 |
131 |
47.99 |
219 |
47.61 |
|
4. increased preference |
27 |
14.44 |
33 |
12.09 |
60 |
13.04 |
|
5. definite preference |
2 |
1.07 |
3 |
1.10 |
5 |
1.09 |
|
unknown dat not recorded |
21 |
11.23 |
36 |
13.19 |
57 |
12.39 |
|
Total |
187 |
100.00 |
273 |
100.00 |
480 |
100.00 |
Gender difference: Chi Square (excluding the unknowns) = 2,72 with
4 df. N.S.
Table 3:
Distribution of the diet liking, other than the normal, for sweets and
broth.
|
Food habit |
1 |
2 |
4 |
5 |
|
|
Ss Nr. |
Ss Nr. |
Ss Nr. |
Ss Nr. |
|
Sweets: F |
23 |
62 |
43 |
1 |
|
Sweets: M |
36 |
83 |
54 |
9 |
|
|
|
|
|
|
|
Broth: F |
11 |
18 |
27 |
3 |
|
Broth: M |
53 |
17 |
33 |
3 |
Chi Square for sweets (1-2 vs. 4-5) = 108,55 with 3 df and p < 0.0005
Chi Square for the broth (1-2 vs. 4-5) = 12,77 with 3 df and 0, 005
<p< 0.01
Table 4:
Liking for the broth with regard to that for the sweets ( chart with
double entrance ).
|
Nr. of order --> broth |
1 |
2 |
3 |
4 |
5 |
totals |
|
|
|
|
|
|
|
|
|
sweets |
|
|
|
|
|
|
|
1 |
21 |
31 |
21 |
9 |
2 |
84 |
|
2 |
7 |
15 |
20 |
13 |
1 |
56 |
|
3 |
17 |
61 |
72 |
50 |
3 |
203 |
|
4 |
9 |
7 |
16 |
20 |
2 |
54 |
|
5 |
0 |
1 |
0 |
4 |
1 |
6 |
|
|
|
|
|
|
|
|
|
totals |
54 |
115 |
129 |
96 |
9 |
403 |
Kendall's "Tau " co-graduation = 0.39.
Discussion.
The
sample here investigated is a representative one, at least of the Italian
population of Down Ss. I need to clarify that scarce preference for sweets can often
be limited to a choice of ice creams and chocolate.
These two
types of sweets have surely a different metabolic value which we can only think
about. We can think that the cold feeling of the ice cream, which attenuates
the taste of sweet, has even a refreshing effect in subjects bearing badly the
heat. (Cocchi, 1989). The chocolate instead could be sought-after for the
stimulating action of the theobromine ( this one, like any xanthine, could act
on the cyclical AMP ).
From the
results of this epidemiological investigation we notice that diet habits for
sweets and the broth, again do not have any link with the chromosomal
diagnoses. Moreover, I did not found meaningful differences between males and
females.
We may
exclude the share of normal preference, with the same rate for males and
females, from our account. Then we observe a clean and meaningful trend towards
the scarce liking or the refusal, an increased trend for sweets.
This
suggests that, as for the glutamate coming out from the Krebs' cycle, there is
a tendency to its excess. Then it causes the compensatory behaviour of a
reduced diet intake of its precursor.
As for
the glutamate instead deriving from the glutamine, the normal liking for the
broth in the 47.61 % of these Downs does think that the food intake of its
precursor is less manageable.
If we
exclude however the subjects with normal liking, even for the broth there is,
among the remainders, a greater trend towards the scarce preference or its
refusal.
The
calculated rate of the Kendall's "tau" as a coefficient of
co-graduation let us see another thing. These two diet habits have enough a
good relationship by both them, but not in definite way. That leads us to
suppose that they are of different metabolic value, more "normal"
that centred on the glutamine, and more "extraordinary" what pivots
on the glucose.
This
suggestion may find confirmation from the fact that the glutamine is an amino
acid that the human body can produce in several districts (Meister 1956 and
1959). So, it is different from the glucose that it has to derive from a diet
intake of simple sugars or other foods that the body transforms into simple
sugars.
Concerning
instead the links between brain glutamate and GABA, an excess of GABA in the
synapse (Cocchi, Patrucco and Zerbi, 1987 ) can backwards stop the glutamic
acid decarboxylase (GAD). That enzyme synthesizes the GABA from the glutamic
acid (Loescher, 1980 ), in presence of the pyridoxal-phosphate (Ebadi, 1981 ).
The GAD then is a step limiting of the GABA synthesis.
On the
other hand it is known and verified even the opposite. An excess of GABA
turnover can drive to diet behaviour of an increased intake of its precursors,
as an increased intake of sweets ( Cocchi, 1988 ).
Even this
pathway seems a confirmation that the increased GABA synthesis from the glucose
is an "extraordinary" intervention. The organism puts it into action
when the physiological compensation due to a greater peripheral production of
glutamine does not work sufficiently.
On the
other hand, the hospital use of glucose drip-feeds, as a not specific
restorative, explains perfectly in this optics.
Conclusion.
The
survey on diet habits of Down persons as for the intake of precursors of the
glutamate and the GABA may have notable weight to understand the state of these
two brain neurotransmitters, at least in certain brain areas
The
trend, in Down subjects, is towards a normal or scarce liking or refusal for
the broth, and more over for the sweets, which should point out a reduced need
to increase the brain synthesis of both these neurotransmitters.
Even both
these symptoms do not have any link with the type of trisomy 21, and a
significant gender difference did not come out.
The fact
that sweets stretch to being more refused than the broth does think that the
two diet habits have different metabolic value. Sweets are more directed to
crucial needs, and then more easily subject to an increasing or, how to in our
cases, a reducing intake of them.
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First
translated and published on Internet on May, 2002. Copyright by Renato Cocchi,
2002.
Author's address: Renato COCCHI, via Rabbeno, 3
42100 Reggio Emilia (Italy).
renatococchi@libero.it
Italian translation // Testo in italiano
Down syndrome
Symptoms
Mental retardation