Submitted March 31, 1947.
FOLLOWING AN EARLIER WORK on high dosage Vitamin C in allergy, it became apparent that a very significant role was played by the inorganic ion sodium when used as the salt of Vitamin C. By a detailed microscopic study of bronchiolar reactions it was demonstrated that Vitamin C had a definite antihistamine effect, or an epinephrine potentiality effect. In practical application it was possible to demonstrate that daily dosages between 1000 mg. to 2000 mg. of Vitamin C afforded in many cases considerable relief from allergic manifestations and in some cases even striking and dramatic improvement. There remained however a group of cases that were either not benefited or were only moderately improved.
Analysis of these latter cases showed as a rule concomitant infection with a history of repeated colds or bronchial infection. They were of the type usually classified as individuals with a lowered resistance to infection.
When, as a result of my technical advance in Vitamin C research there was made commercially available the dry sodium salt of Vitamin C an investigation of its use in allergy was undertaken. Originally, it was believed that the chief advantage of the sodium salt would be in the fact that it was a neutral form of Vitamin C, since the high dosage of Vitamin C entailed a daily amount of 1.5 gram to 2 grams, and gastric irritation was experienced frequently Another factor was the continued and at times undesirable increase in ingested acid.
While the kidney has the power to form ammonia for the purpose of neutralizing an acid urine, it can also produce acid as NaH2P04 and also as free organic acid, provided the pH does not fall much lower than 4.0. When, however, large amounts of acid are introduced into or produced in the body the ammonia producing mechanism of the kidney cannot suffice and the sodium bicarbonate of the blood is depleted for the purpose of neutralizing the acid. The CO2 is exhaled by the lungs and the sodium salt of the acid appears in the urine; hydrochloric acid, for example, is excreted as sodium chloride, sulphuric acid as sodium sulphate.
If acid be fed and base is withheld from the diet for some days, sodium salts are excreted at first and little extra potassium, calcium or magnesium appears. Gradually, as the requirement for base becomes more insistent abnormally large amounts of potassium are excreted. The body manifestly resists potassium loss as long as possible; probably because potassium and magnesium are essential to cell function in a more direct way than sodium. The depression of sodium levels may play an important role in kidney blockage from drugs of the sulfa group. Thus the availability of sodium ascorbate gave us an important agent in acid base equilibrium.
Analysis of blood and tissues shows a remarkable difference in distribution of cations — according to Holmes.
|
Cation |
mgs. in 100 gms. of plasma |
mgs. in 100 gms. of muscle |
|
Sodium |
138.0 |
60. |
|
Potassium |
18.0 |
360. |
|
Calcium |
10.5 |
10.0 |
|
Magnesium |
2.7 |
23. |
It is apparent that tissue cells contain far more potassium than sodium and that sodium loss would come first.
Sodium, however, plays a vital role in connection with the normal metabolism of the adrenal cortex. One could consider that the adrenal cortical hormone, sodium and Vitamin C, bear a reciprocal relationship to each other. It is, therefore, not surprising to find that the cortical hormone protected against histamine shock similar to that of Vitamin C. Thus Ingle showed the protective effect of fragments of viable cortical tissue and of transplants of cortical tissue on the resistance of suprarenalectomized rats to histamine shock. These observations were confirmed by Wyman and Tum Suden. They also showed that the increased susceptibility of the rat to histamine after suprarenalectomy depends on the loss both of medullary and cortical function.
However, Perla and Marmorstan found that when cortin is administered during the early period of insufficiency, the resistance of suprarenalectomized animals is raised to a striking degree, whereas when epinephrin is similarly administered, the resistance is raised to only a slight degree. By the administration of cortin, they were able to raise the resistance of suprarenalectomized rats to histamine almost to the normal level.
A further interesting point arose when the cortical hormone was used in experimental infections. Scott, Bradford, Hartman and McCoy determined theeffect of the cortical hormone on the resistance of normal animals. Three types of intoxication were used; diphtheria toxin in the guinea pig, trypanosome equiperdum infection in the rat and pneumococcus infection in the mouse. No protection was obtained against one minimum lethal dose of toxin by administration of cortical extract in amounts of one and one-half cc. Injections of cortin were commenced after the injection of diphtheria toxin. Similar results were produced in the other infections. All the mice were dead within 32 hours. The administration of cortical extract did not produce any appreciable survival period of white mice following infection with pneumococcus.
Zwemer and Jungeblut showed some protection by the injection of cortical extract in normal guinea pigs against a minimum lethal dose of diphtheria toxin. On the whole the results were not striking although apparently under certain conditions the administration of a large dose of a cortical extract may protect time guinea pig against more than one M.L.D. of diphtheria toxin.
Thaddea, however, observed definitely beneficial effects of injection of cortical hormone when combined with Vitamin C on the resistance of guinea pigs to diphtheria. Cosentino likewise reported favorable results in rabbits infected intraperitoneally with cultures of staphylococcus aureus by the use of Vitamin C and adrenal cortical hormone.
Heuer and Andrus have reported that cortical extract has a protective action against the shock produced by intravenous injection of intestinal loop fluid into dogs. Meek also noted beneficial effects from the administration of cortin to dogs suffering from shock following intestinal distension. There is the further observation of Wolfram and Zwemer in the amelioration of anaphylactic shock in guinea pigs by the prior administration of cortin.
In an earlier paper on Histamine-Adrenalin Balance in Allergy, I pointed out that shock of the most varied sort ranging from severe burns and trauma to poisonings have a common histamine reaction directly analogous to nasal allergy and asthma.
The interrelationship of the adrenal cortical hormone to Vitamin C and Sodium led to the hypothesis that this triad of substances may play a basic role in allergy and that the deficiency of any one or more of these elements would predispose to allergic reactions. The Pottengers had already treated a group of 50 allergic children suffering with asthma by means of whole adrenal gland and a high salt intake. In addition a diet rich in vitamins and minerals was given. Improvement was observed in 84 per cent of the patients.
It now remained to observe the isolated effect of sodium ascorbate. Marine and Baumann had found that daily intraperitoneal injections of various sodium salts such as isotonic sodium chloride, sodium acetate, Ringers solution, prolonged the lives of suprarenalectomized rats to almost three times those of the untreated suprarenalectomized controls. They pointed out the specific value of sodium salts in maintaining the life of the animal. Similar findings were observed by Stewart and Rogoff, although they found that salt solution could not be used as a substitute for cortical hormone. Loeb and his coworkers extended the studies and from their work suggested that suprarenal insufficiency was associated with a primary loss of sodium through the kidney. Harrop and his associates were able to maintain bilaterally suprarenalectomized dogs for as long a period as five months without the use of any suprarenal gland preparation or extract by the administration of sodium chloride and sodium bicarbonate alone. Withdrawal of the salt then produced typical suprarenal insufficiency. It has been shown by Zwemer and Truszkowski that a drop in sodium concentration in the blood is associated with a significant rise in the Potassium concentration. The production of such an electrolyte disturbance as suggested by Gilman and Yannet decreases the natural resistance of unoperated rats to histamine poisoning (Perla and Sandberg).
The interrelationship of histamine sensitivity to adrenal cortical insufficiency and sodium and Vitamin C led to the hypothesis that nasal allergy and asthma may be precipitated by an imbalance of the triad cortical hormone-Sodium-Vitamin C. In view of the reciprocal capacity that exists between them, a study was undertaken on the effect of sodium ascorbate, particularly in those allergic cases that were somewhat refractory to high dosage ascorbic acid. The beneficial effects were strikingly greater than ascorbic acid itself. There was in addition marked freedom from gastric irritation with the use of 2 grams daily. Increased diuresis was noted almost as a rule. Several of the cases were intractable asthmatics who had been refractory to almost all forms of therapy but have remained free from asthma in a fairly continuous level of sodium ascorbate. The seasonal hay fever cases did particularly well.
In reviewing the results obtained with ascorbic acid, calcium ascorbate and sodium ascorbate, it would appear that the inorganic ion plays a very important role. It would seem that many factors influence histamine sensitivity. Among these are enzymatic reactions and toxic factors that are favorably influenced by calcium ion whereas another important group may be related to adrenal cortical insufficiency and be strikingly helped by the sodium ion. In both cases the inorganic ion as the salt of ascorbic acid represent a very desirable form of therapy in allergy.
The use of the sodium salt of ascorbic acid may also play an important role in other conditions such as urinary lithiasis when the solvent action of the ascorbate on carbonates is utilized as well as the solubilizing effect of the sodium ion.
|
(No.) |
NAME |
Age |
Sex |
Diagnosis |
History & Findings |
Treatment & Results |
|---|---|---|---|---|---|---|
|
1 |
G.H. |
8 |
F |
Asthma |
At the age of 5, following an attack of measles, the child developed severe recurrent attacks of asthma, which recurred In a series of attacks every 5 to 6 months. The attacks were difficult to control and the patient was sent to Arizona where she remained for 2 years. While in Arizona her attacks were recurrent, but milder. The patient was brought to New York for further study. Nasal examination revealed bilateral ethmoiditis, associated with post nasal discharge and engorgement of the nasal mucosa. The blood picture showed: hemoglobin, 62%, color index, .6 with a slight leukocytosis and moderate eosinophilia. | The patient was placed on Sodascorbate therapy, 3 tablets 3 times a day. The patient was having asthmatic attacks at the time of examination. During the first week of therapy the attacks became much milder and ceased after the second week of therapy. She was on continuous Sodascorbate therapy 3 tablets 3 times daily for over a year with no recurrence of asthmatic attacks. The child gained in weight. The anemia was treated with twice weekly injections of Ironyl for the improvement of the blood picture. Tonsillectomy was also performed. Patient’s mother’s comment: “The child can now eat most anything without having an asthmatic attack.” |
|
2 |
L.G. |
45 |
M |
Nasal allergy, unknown origin, probably Spring trees |
For 20 years has had attacks of sneezing from March 20 to May 14. Had many series of allergic testing with no specificity found on scratch tests. During his attacks he had itching of the eyes and nose and typical rhinorrhea associated with nasal obstruction. Tests for the Spring trees were also negative. Despite the negative tests the patient had received several series of desensitization injections with Spring grasses as well as the Spring tree pollens, with no benefit. Nasal examination showed a hyperplastic bilateral ethmoiditis with deflected septum: tonsils had been removed: a septum operation had been performed in February of 1945. | In 1945 he was put on high
dosage Vitamin C, 1500 mg. daily with good control of his
attacks. The patient stated that he was satisfied with the
results. In 1946 the patient came to the office on March 13. He was put on Sodascorbate tablets, 3, 100 mg., 3 times a day. On March 18 he returned to the office and examination showed rhinorrhea, but no sneezing. The dosage was increased to 4 tablets 3 times a day. Nasal examination May 1st. showed no congestion, no rhinorrhea or sneezing. The patient stated that he was having a very good season, even better than the one previously. He had no irritation of the stomach or the bladder, although he had complained of gastric irritation and frequency during the preceding year with the plain ascorbic acid. Patient’s comment: “I was never able to sleep from March 21 until May 21, until I started taking the high Vitamin C dosage and later the Sodascorbate tablets.” |
|
3 |
S.R. |
35 |
F |
Hay Fever |
For last 4 years has had
sneezing and running of nose. Hay fever for 17 years.
Asthmatic attacks occasionally in hay fever season. Nasal
plastic 6 years ago. Findings: Nasal mucosa: Hyperplastic and engorged. Turbinates: Inferior turbinates hypertrophied. Discharge: serous discharge: redress and excoriation of both nasal alae. Allergy testing 4+ to dust and feathers and ragweed. Hapamine series given with no benefit. |
Started taking 9 Sodascorbate
tablets daily June 15, 1946. During the month of August,
until Sept. 10 patient was taking 15 tablets per day. During
this time the patient stated that she had no sneezing but a
feeling of stuffiness of the nose. This is the first season
that the patient has not taken hay fever injections. Patient’s Comment: “I had about 10 bad days but these were completely relieved by Sodascorbate.” |
|
4 |
F.S. |
28 |
F |
Hay Fever |
Has had hay fever for last 8
years. About two weeks ago had nasal obstruction with
stuffiness, sneezing and running. Has had hay fever
injection series each season up to the present. Examination: Septum: deflected sharply to the left. Turbinates: Inferior turbinates hypertrophied. Mucosa: Hyperplastic, nasal fossae markedly obstructed. Discharge: Mucoid discharge both middle meati, seromucoid discharge. Transillumination: Moderately diminished both sides. Tonsils: removed. |
Patient started taking Vitamin C —100 mg. tablets 2 t.i.d. August 1st, but complained of nausea and gastric disturbance from the tablets. Discontinued taking tablets after 1 week’s time and returned to the office 4 weeks later with severe nasal congestion, inferior turbinates congested. Given Sodascorbate tablets 5 t.i.d. Patient then returned 1 week later. During this time the nasal congestion was greatly improved, sneezing very little and patient states that this time is usually the worse part of her season. No gastric disturbance. noticeable from the large doses of Sodascorbate in comparison to the smaller dosage of Vitamin C. |
|
5 |
W.L. |
46 |
M |
Hay Fever |
Hay fever for 30 years.
sometimes accompanied by asthmatic attacks. Findings: Nasal mucosa: Hyperplastic. Septum: markedly deflected to right. Inf. Turbinates: Hypertrophic, profuse seromucoid discharge. Bilateral hyperplastic maxillary and ethmoidal sinusitis. |
Started Sodascorbate tablets
July 15, 1 t.i.d. Patient increased dosage and at the time
of the seasonal attack when he would be suffering most, was
taking 4 t.i.d. Did not notice any irritation of stomach or
bladder. This is the first season that this patient has not
had hay fever injections and stated that this is the best
season he has had. Very little sneezing. In previous years
he would be sneezing continually. Patient regulated the
dosage himself in accordance with his needs. Patient’s Comment: “I found Sodascorbate very, very helpful to my hay fever condition. As a matter of fact that is now the 4th of Sept. and so far I have suffered practically not at all.” |
|
6 |
G.R. |
34 |
M |
Asthma |
Asthma in childhood, since age
of 5. Has coughing spells, some hay fever attacks; Is
allergic to molds, pollens, etc. Has had some relief with
ascorbic acid. Findings: Nasal mucosa: Hyperplastic. Nasal discharge: Mucoid discharge both middle meati. Septum: moderately deflected to right |
Patient started Sodascorbate
tablets in January, taking 3 t.i.d. Since the patient is
living out of the state, he reports to us via mail. And as
he knows his condition, he is able to judge the number of
tablets that gives him the most benefit. He states that
taking 1000-1200 mgs. a day he reacts more favorably. With
the taking of this amount, he is more efficient, calm and
less fatigued than otherwise, and with the taking of the
larger doses he has had none of the customary allergic
reactions (swollen eyes, headache, etc.) as he had suffered
previously. Patient’s Comment: “I am very grateful to you for the first intelligent approach to a problem which was becoming a very difficult one to me indeed.” |
|
7 |
G.P. |
38 |
F |
Hay Fever |
Nasal obstruction and
discharge, with sneezing and running since November. Has had
vaccine injections. Tickling in throat, wheezing in chest.
No family history of hay fever or asthma. Findings: Nasal mucosa: Hyperplastic, engorged, allergic in type. Septum: Mid position. Turbinates: polypoid changes Allergic Testing: 4+ ragweed; 3+ timothy. |
Sodascorbate tablets started at
first visit, 3 t.i.d. Patient left the city but reported via
mail that she was continuing with the Sodascorbate tablets
and had increased to 4 t.i.d. with very little sneezing, or
rhinorrhea. Patient’s Comment: “My sneezing seizures seem to be few and far apart.” |
|
8 |
S.D. |
48 |
M |
Hay Fever |
For last 4 weeks in Sept. has
had nasal stuffiness and sneezing moderately. History of hay
fever and asthma. Findings: Nasal mucosa: Congested. Septum: Deflected to right and left. Turbinates: Inferior turbinates hypertrophied. Allergy Testing: Ragweed 4+; timothy 4+. Has had hay fever injections with very little relief at this time of year. |
The first of July the patient
started Sodascorbate tablets. 3 t.i.d. and continued 4-5
weeks then gradually tapered off, taking 2 t.i.d. then 1
t.i.d. Was well through this period. Then for several days
went without Sodascorbate and the nose became congested,
breathing difficult and sneezing. The patient then started
taking 3 t.i.d. again and all symptoms gradually cleared. No
irritation of stomach or bladder noticeable. Patient’s Comment: “Of all the remedies that have been given me in the past for my allergic condition, I must say that Sodascorbate definitely has proven the most effective.” |
From The American Journal of Digestive Diseases, September, 1947, Volume 14, Number 9, pp. 302-305
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