Sodium Ascorbate in the Treatment of Allergic Disturbances

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.

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.

CASE REPORTS --- SODIUM ASCORBATE

CONCLUSION

1. The availability of the sodium salt of ascorbic acid for oral use represents a marked advance in the therapeutic approach to allergy.
2. The increased sensitivity to histamine in suprarenalectomized animals suggests a relationship between adrenal cortical hormone-Sodium-Vitamin C and allergy.
3. In refractory cases of allergy and asthma sodium ascorbate was more effective than ascorbic acid.

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