DEFICIENCY OF VITAMIN C AND

VITAMIN P IN MAN*
BY HAROLD

(From the

SCARBOROUGH, M.B., Ph.D. Edin.

Clinical Laboratories, Royal Infirmary, Edinburgh)

BENTSATH

(50 mg.
aqueous
c.cm.) of flavanones prepared from orange peel accor
ing to the method described by Szent-Gyorgyi (1938
The same preparation was also given by mouth to case

preparation
1

All of these fractions were free from ascorbic acid.

most cases ascorbic acid and vitamin-P concentrat
were given by mouth, the former in solution, the latt
as an aqueous suspension
(1 g. in about 50 ml.

water).

(1936, 1937) first suggested that the

The capillary resistance was determined by a positiv
full clinical syndrome of scurvy in the guineapig was
pressure technique. In this procedure the capillaries a
produced by a combined deficiency of vitamins C and P. ruptured by an increase of intracapillary pressure pr
duced by the application of venous obstruction to t
This suggestion was based on experiments said to show
arm for a certain time.
The ruptured capillaries a
that the length of survival of guineapigs on the ShermanLa Mer-Campbell scurvy-producing diet could be enumerated as petechial haemorrhages in the forea
after release of the pressure. The pressure (mm. H
increased from 28-5 to 44 days by the administration of
and the time (min.) for which it was permitted to a
supplements of vitamin P. At autopsy the animals are indicated in
each case in the upper left-hand corn
which had received these supplements showed signifi- of each chart. The pressure varies
with each patie
cantly fewer haemorrhages in the tissues. It was and is regulated so as to be just infradiastolic. T
concluded that a deficiency of vitamin P is in part
time for which the pressure is permitted to act is vari
responsible for the haemorrhages of scurvy, which according to the response obtained. Thus, if t
should therefore be regarded as a mixed deficiency of
capillary resistance is low, many petechise will be induc
in a short time ; whereas, if the capillary resistance
vitamins C and P. It was considered that clinical signs
high, a longer period of occlusion will be required bef
of a deficiency of vitamin P alone could not be produced
petechiae can be enumerated in the forearm.
in the guineapig. Zilva (1937) has shown that the postThe capillary resistance is determined in terms
mortem appearances described by Bentsath and his
the number of petechiae produced. A normal capill
colleagues in the animals treated with supplements of resistance by this method is 0-20 (mean 20").
vitamin P closely resemble the condition found in
decrease in the number of petechial haemorrhages und
guineapigs receiving minute doses (0-1 mg. daily) of these conditions is accordingly taken as a sign of
increased capillary resistance. Capillary-resistance
ascorbic acid. Zilva (1937) and Moll (1937) could not
find any evidence for the existence of vitamin P from terminations are recorded as a graph. Spontaneo
are recorded as vertical lines on the char
dietary experiments with guineapigs. Szent-Gyorgyi haemorrhages
The amount of this haemorrhage has been roug
(1937, 1938) has since reported his failure to repeat his assessed by determinations of the total area (sq. cm.)
original experiments upon which the existence of vita- surface haemorrhage. In cases 3 and 4 body-weight
min P

was

et al.

based.

problem of vitamin P has been studied again

A low capillary
more recently (Scarborough 1939).
resistance in people with various forms of nutritional
deficiency was found to be associated with a deficiency of
vitamin P, but no clinical syndrome was described.
Zacho (1939) observed that the capillary resistance of
scorbutic guineapigs could only be restored to normal
by the addition of ascorbic acid and vitamin P to the
diet. Moreover, less haemorrhage was found at autopsy
The

kg.), haemoglobin level (as a percentage of the norm

100% 16-0 g. per 100 c.cm.), and knee flexion (in degre
have also been determined (figs. 3 and 4). By the
term is signified the angle to which either the right
the left leg can be flexed on the thigh at the knee.
scurvy movement at this joint is often limited, in
=

Todhunter

absence of hsemarthrosis, because of either pain

haemorrhage into the muscles of the thigh. Figs. 3
4 show that the measurement of this angle is a c
venient and satisfactory guide to the progress of
scorbutic process in the early stages of treatment.

guineapigs
receiving supplements of lemon-juice show fewer haemorrhages than do animals receiving equivalent amounts of

FIG. 1-Chart of case 1, sho

that the capillary resist
was within normal limits,

in scorbutic animals treated with vitamin P.

et al. (1940) have found that scorbutic

pure ascorbic acid.

The present communication demonstrates the existence of deficiencies of both vitamin C and vitamin P in
man.
In two cases clinical evidence of a deficiency of
vitamin P alone has been induced experimentally.
MATERIAL AND METHODS

The six people studied in this investigation all had a

clinical deficiency of vitamins but, apart from this, were
free from other obvious organic disease, except case 1,
whose blood gave a positive Wassermann reaction.
Cases 4, 5, and 6 gave a history of chronic alcoholism.
All were in bed in hospital during the investigation.
On admission each patient was immediately submitted
to rigid dietary control, the diet being as far as possible
free from vitamins A, the B complex, C, D, and E.
Insufficient is known about vitamins K and P to permit
their certain exclusion from a human dietary. The
calorific value of the diet was unrestricted.
Vitamin P was administered as an active fraction
prepared from oranges, but the precise nature of the
active substances present in the fractions has not been
determined. For oral administration two different
fractions were used : (1) a crude yellow powder deposited
spontaneously during the desiccation of Californian
Valencia orange-juice ; and (2) a purer preparation
obtained from (1) by extraction with pyridine and
repeated crystallisations from aqueous pyridine. In
case 5 vitamin P was administered parenterally ; the
* The
work reported here formed part of a study of vitamin
deficiencies carried out during the tenure of a Beit Memorial
Fellowship in 1939.

that administration of vit

P did not control the
c u t a n e o su
haemorrha
which, however, were arr
immediately by the adm
stration of ascorbic acid.
FIG. 2-Chart of case 2, sho
that the administratio
vitamin P increased the c
lary resistance but did
arrest the spontane
haemorrhages, whereas
administration of asc
acid stopped the haemorr
at once, although it di
affect the capillary resist
RESULTS

CASE l.-A widower, aged 62, had had two weeks p

ecchymosis, and oedema of both legs. He had lived alon
nine months, during which his diet had contained no f

green vegetables, or meat. There was no histor

alcoholism. His blood gave a strongly positive Wasserm
reaction.
There
was
slight cedema. Subcutan
haemorrhage : 74 sq. cm. Diagnosis : scurvy.

Fig. 1 shows that on admission and throughout

period during which observations were made his capil

resistance was within normal limits. Administratio

vitamin P did not control the subcutaneous hea
rhages, which, however, were arrested immediatel
the administration of ascorbic acid.
CASE 2.-A female, aged 37, with four years weakn
intermittent diarrhoea, dyspepsia, and dyspnoea on exer
A month before admission she developed swelling and ble
of the gums. Owing to diarrhoea and dyspepsia her diet
been restricted for the last six weeks almost entirely to b