Here is some more info from some textbooks from 1954, and earlier
p-Aminobenzoic Acid Deficiency. Relatively little is known about
p-aminobenzoic acid (PABA) deficiency and its incidence in man, or
about the relationship of this vitamin to another in which it is contained,
folic acid. There is good evidence to indicate, however, that it is effective
in the treatment of certain types of hair graying in man. Folic and
pantothenic acids have been reported to have similar effects, and it has
been suggested that p-aminobenzoic acid may act through folic acid
synthesis. There is some reason to believe that pantothenic acid functions
with PABA in hair pigmentation. The effect of PABA ultimately is involved
in melanin formation however, and the oxidation of tyrosine to
melanin may in some manner be related to the apparent relationship
between tyrosine and folic acid (p. 415).
PABA stimulates the growth of rats and chicks on a deficiency diet,
and is a growth requirement for certain microorganisms. In the black or
piebald rat, deficiency results in graying of the hair (nutritional achromotrichia)—
a condition which, like hydroquinone-induced achromotrichia,
can be cured by PABA administration. Female albino rats have been
reported to have lactation disturbances when fed a PABA-deficient diet.
The high efficacy of the sulfonamides in inhibiting bacterial growth indicates
that PABA plays an unusually critical role in cellular metabolism,
particularly since analogues of many other metabolites have not proved
effective therapeutic agents. It would seem, therefore, that PABA occupies
some key metabolic position, which when blocked causes the breakdown
of a number of metabolic sequences. The reversal of sulfanilamide
by folic acid and vitamin B12 indicates indeed that PABA is intimately
related to these substances (see Chapter HID). In view of these considerations
it is remarkable that the physiological effects of PABA and
its deficiency in the higher animals are not more pronounced.
Friedgood (98) reviewed the attributes that Sieve has ascribed to PABA:
“it darkens gray hair; it intensifies the normal pigmentation of the nipples
and mucous membranes of the mouth, vagina, and anus; it eradicates areas
of vitiligo; it induces a return of color and ‘changes the hypertrophy’ d
areas of leukoplakia in the mouth; it causes a decrease or almost complete
disappearance of hyperpigmentation of nevi and freckles; it stimulates
.libido; it re-establishes the menstrual cycle in amenorrhea and increases the
amount of flow in oligomenotrhea; it cures female sterility (12 out of 22
cases); it benefits asthmatic patients in certain instances; and it increases
the appetite and induces a feeling of well-being.”
Although confirmation of all of Sieve’s claims is lacking, the return of
pigmentation in human gray hair has been described by others (94-100)
referred to in the preceding chapter. Furthermore, Costello (103) published
a case of vitiligo successfully treated with PARA. DeVilbiss (99) commented
on the &timulation of libido. Banay (94, 95) mentioned a marked
increase in erotic drive as well as stimulation of appetite. Other physicians
stated in private communications that PABA therapy seems to have
*a favorable action in chronic constipation and appears to contribute to a
feeling of well-being. Most clinicians are of the opinion that asthmatics
are not benefited by PABA, although some cases were noted to be favorably
influenced (48). Doma,rus (104) found PABA to be beneficial in 4 cases
(psychotic episode with psychopathic personality ; alcoholic Korsakow
226 S. ANSDACHEIt
psychosis; chronic alcoholism; and morphine addiction). He believes
that PABA therapy should be further investigated in parasympatheticotonic
conditions and as an adjuvant to morphine withdrawal treatment.
In view of the fact that a diabetic patient went into shock as a result of
combined PABA and insulin therapy (91), it is of interest that PABA appears
to potentiate insulin (143). Insulin was injected subcutaneously
into mice in a dose (Q unit per 18 g. of body weight) which is known not
to reduce the blood sugar to convulsive levels. When PABA was given
either before, simultaneously, or after the insulin, convulsions typical of
insulin shock were produced. At the same level of 1 g. per kg. of body
weight, the simple aromatic amine effected a mild but definite hyperglycemia
in rats. It did not alter the speed, degree, or duration of the hypoglycemia
produced in rabbits by insulin. As determined by the method of
Grattan and Jensen (144), it was noted to deplete the liver of glycogen.
Since mice treated with a cortical extract and PABA had an average liver
glycogen content of about 500 mg. per cent as contrasted with approximately
1700 mg. per cent found in the livers of animals which had received
solely the cortical extract, it may be concluded that the rate a t which the
organism is required to yield its stores of liver glycogen is augmented by the
simple aromatic amine. Conditions favorable for insulin potentiation by
PABA ha+e not been found in clinical trials.
The above data were discussed and extended by Martin (145) who considered
the following facts:
1) PABA acts in the pseudo-potentiation of insulin (143, 145);
2) it produces a mild hyperglycemia in doses of 1 and 2 g. per kg. in
3) it depletes the glycogen reserves of the liver (113);
4) it causes a mild rise in blood pressure in the anesthetized cat, reversed
by 2-( 1)-piperidylmethyl)-] ,4-benzodioxan (146) ;
5) i t is known to inhibit various enzyme systems (142);
it produces hypertrophied thyroids with hyperthyroidism (145, 147,
7) it protects against the action of thyroxine in the intact animal (145).
Martin suggested that these actions of PARA may be motivated via the
pituitary and production of thyrotrophic hormone, as already concluded by
Astwood, et al. (148) and Mackenzie, et al. (147). Therefore, PABA may
be effective clinically in counteracting hypothyroidism and may be contraindicatecl
in cases of hyperthyroidism. Indeed, the action of a number
of agents, including thioureas. sulfanilamide and PABA in producing
hypertrophied thyroids (147-151) has teen demonstrated. These various
substances may be considered to be inhibitors of tissue metabolism, as
firbc suggested by Cutting and Kuzell (152). The peeudo-potentiation
of insulin by these compounds as well as by others, such as e.g. saccharin
(153), can best be explained at present on the baais of the above considera
C. Conclusion : Physiological Importance
From a pharmacological point of view, PABA may be considered to be a
detoxified aniline. Since it does not act like pigments do and since no
results were obtained in cases of faulty pigmentation from its local or
topical application, its physiological effect is not that of an aniline-like dye.
However, the question whether it is to be considered one of the B-vitamins,
can be answered.
By definition, a vitamin B complex factor is
a) a natural constituent of yeast, liver, and/or cereals.
c) a growth-promoting substance for bacteria, yeasts, fungi, and/or
d) a co-enzyme or activator of enzymstic prozesses.
e) physiologically effective in minute amounts.
f) a substance which causes a deficiency diseage when laoking in the diet.
The data presented in the preceding chapters seem to justify the conclusion
that PABA is one of the vitamin B complex factors: i t occurs in
nature as universally as and side by side with most of the B-vitamins; it
is about thirty times more soluble in water than riboflavin; i t is a growth
factor for a variety of microorganisms; its r61e as a phenolase activator has
been suggested; i t has been claimed to bz clinically effective in amounts
comparable to those employed in choline and inositol therapy; deficiency
sjrlnptoms resulting from its absence in the diet have been described.
However, it may be argued that PABA per se is not a vitamin, since the
amounts necessary to show effectiveness experimentally and clinically
are by far greater than the ones ingested in a normal diet. Nevertheless,
it has been suggested (VII, 2) that PABA as found in natural products
may possibly be more efficacious than the simple aromatic amine by
itself. The PABA-peptide, p-aminobenzoyl-2-glutamic acid, although
not known to occur in nature, has been reported (294) to have 8 to 10 times
more anti-sulf onamide activity than equimolecular amounts of PABA
per se. To date, the high potency of the peptide could not be confirmed
experimentally, but further work will undoubtedly yield PABA derivatives
with more clinical effectiveness than has the simple aromatic amine.
As recently as April 1943, Hogan and Kamm (295) remarked that the
status of PABA as a vitamin still is indefinite. Nevertheless, the American
Medical Association (102) commented on PABA as a vitamin in relation
to humangray hair in July of the same year. In a 1044 review of the present
status of the vitamin B complex, Elvehjem (296) stated that the vitaminlike
property of PABA has been demonstrated and that the simple aromatic
amine can undoubtedly produce certain effects in the human, but he is
inclined to believe that its action is indirect. Although the U. S. Food
and Drug Administration (297) prescribed in 1941 that a product designated
as a “vitamin B complex preparation” should furnish demonstrable
amounts of PABA, the same administrative agency (298) made known
about two years later that there was no convincing evidence for PABA to
be a food essential for animals or humans. Indeed, PABA occupies as
peculiar a position as do some of the B-vitamins, such as choline (299).
It may not be classified as a vitamin for animals capable of synthesizing it.
It may be considered to be a vitamin for all species for which it must be
supplied preformed in the diet in order to satisfy tissue demands. According
to Williams’ (300) thesis on vitamins, the significance of PABA
in the intestinal physiology of the animal is just as great whether it is an
indispensable food constituent or is manufactured within body tissues.