During the past four years one of us made occasional observations indicating a lowering of the body level of vitamin C during hay-fever attacks.

Histamine Theory

Other workers developed the interesting theory that histamine, C5H6N9, although a normal constituent of the blood, is thrown into the blood stream in excessive amounts during allergic attacks and that this excess histamine is responsible for some of the unpleasant symptoms. On the assumption that histamine might react with vitamin C, or ascorbic acid, we mixed water solutions of the two substances but observed no reaction in absence of free oxygen. Upon bubbling a slow stream of air through the solution it was easy to detect evolution of ammonia. Titration with 2,6-dichlorophenol-indophenol showed loss of vitamin C. Later we learned that this reaction was already known. Since there is a little dissolved oxygen in blood serum, the body furnishes the proper conditions for very slow reaction.


The Results Given in Table 1 are Significant. The sign “—” Means There Was No Determination or Dosage for That Column


Vitamin C in
24-hour urine
before dosage

Excretion of C
after one week
of 100 mg daily

after one week
of 100 mg daily

after week
of 200 mg daily

after dosage
of 500 mg daily


49 mg

“Immense improvement.” Gain after two days


8 mg

218 mg ? (after dose of 200 mg daily)

No relief Distinct gain “No hay fever” after 3 days


8 mg

1-6 mg (after 2 days of 600 mg rose to 96 mg)

No relief

“Much better” after 2 days


42 mg

90 mg

No relief Slight gain “Almost no hay fever” after 4 days


20 mg

35 mg

Some relief Decided relief “Almost no hay fever” after 2 days


11 mg

73 mg

No relief No relief “Hay fever practically gone” after 3 days


6 mg

1-6 mg (after 3 days of 500 mg rose to 102 mg)

Some relief

Great relief after 3 days


16 mg

(after 12 days rose to 221 mg)

Great relief


Little relief Great relief


Little relief Great relief


Little relief “Felt fine”


“Better physical condition” “Highly favorable reaction. More refreshing sleep” after 2 days


16 mg

106 mg ?

No relief

“Distinctly better” after 3 days


Great relief in few days


“Much less tired”


Definitely improved


9.5 mg

105 mg

Some relief


“It helped”


Began in July. “No hay fever at all—after years of suffering”


0-5 mg

67 mg (after 10 days of 200 mg daily)

Vast improvement. From weakness to vigor


(Invalid from asthma.) After 1 week became astonishingly vigorous and healthy




No relief No relief Little relief


63 mg

118 mg ?

No relief

No relief after 3 days


10 mg

Broke out in rash and quit


1000 mg gave great relief the next day

Required Replacement of Vitamin C

A low level of vitamin C in the body causes weakness as well as other ills, so it is apparent that losses due to hay fever should be made good by a diet extremely rich in this vitamin, or even, in severe attacks, by administration of the pure synthetic product.

Many tests of this idea have been made by others, but there has been much confusion as to the ascorbic acid required for relief.

We therefore experimented 1 with twenty-five hayfever sufferers in Oberlin at three levels of vitamin intake; 100 mg, 200 mg and 500 mg daily, administered during the ragweed season from August 15 to September 15.


In most instances we were able to determine the 24-hour urinary excretion 2 of vitamin C before giving first dose. Whenever possible we determined the excretion again after one week. It is the general opinion that a healthy individual of average weight excretes from 30 to 50 mg of vitamin C daily in the urine.

With ordinary methods of collection we have observed considerable loss by oxidation, so we used the very simple but effective method previously devised by Holmes and Campbell. 3

The maximum pollen count in Cleveland, thirty-five miles from Oberlin, averaged about 87 for the last half of August and about 80 for the first half of September. “Sneezing begins at 15.” Oberlin, away from Lake Erie, has more pollen than Cleveland.

The initial daily vitamin C excretion of twelve (including three not charted) averaged only 10 mg, indicating a very low level, due to destruction or inactivation of the vitamin. One excreted 20 mg, three were satisfactory and the others were not measured.

Usually, after a week of treatment the excretion rose to excellent levels, in some instances indicating body saturation. Strangely enough, patients No. 1 and No. 4 showed very good vitamin C levels before starting treatment, yet they were greatly benefited by adequate dosage.

It is evident from the table that only five sufferers made a noticeable gain in health after a week of 100 mg daily dosage, while twelve gained decidedly after a similar period of 200 mg dosage and eight reported improvement after three or four days at the 500 mg level. One got almost immediate relief after a single dose of 1,000 mg. Apparently there was distinct gain with 88 per cent of the patients.


We strongly recommend that pharmaceutical firms prepare 250 mg tablets of vitamin C (or capsules to be emptied on the tongue) in order to lower the cost and to simplify dosage. The patient (after consulting the family physician, as was done in our own recorded experiments) would do well to begin with a daily 250 mg dose and, if no decided improvement results after one week, to try 500 mg daily until satisfactory progress is observed. After that he might get along comfortably on 250 mg or less during the season.

Since excess vitamin C is excreted rapidly in the urine, it is impossible to go beyond body saturation. Rarely are any irritating effects observed, yet one of our patients reported development of a rash.


Patients objecting to the acidity of ascorbic acid are advised to mix with the vitamin an amount of baking soda nearly equivalent chemically. If the vitamin is visibly crystalline, equal volumes of vitamin and sodium bicarbonate are used; if the vitamin is in a fluffy powder form, about one third that volume of sodium bicarbonate will serve. It is a mistake to mix water solutions to be kept for days, as oxidation occurs rapidly in the neutralized vitamin solution. We proved, by tests on several people, that after keeping a mixture of the dry powders eight hours and then administering there was no apparent loss of the vitamin. Patients with gastric ulcer, usually on a diet low in vitamin C because of difficulty with the roughage of vegetables and the acidity of fruits, may profit by the observation above.


Severance Chemical Laboratory,
Oberlin College


  1. These investigations were aided through the Commission on Influenza, Board for the Investigatin and Control of Influenza and Other Epidemic Diseases in the Army, Preventative Medicine Division, Office of the Surgeon General, United States Army.
  2. Miss Jean Risinger assisted us with some of the analytical work
  3. Holmes, H.N. and Campbell, K., Jour. Lab. Clin. Med., 24:1293, 1939

From Science, Volume 96, Number 2500, November 27, 1942, pp. 497-499

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