THE EFFECT OF VITAMIN C ON LEAD POISONING

HARRY N. HOLMES, PH.D., KATHRYN CAMPBELL, OBERLIN, OHIO, AND
EDWARD J. AMBERG, M.D., TOLEDO, OHIO

In a large industrial plant where the lead hazard was great due to fine metallic lead dust from filing down lead alloy seams, lead fumes from melting pots, and lead contacts from putty spray guns, there was an exceptional opportunity to diagnose and treat lead absorption and poisoning.

Four hundred men exposed to lead during their daily tenure at the plant were examined physically, and by laboratory methods. The latter consisted of monthly checks on the basophilic aggregation (B.A.), of the blood smear, according to McCord, ¹ and on the degree of stippling, using Wright’s stain. Records of these monthly tests were kept throughout the period of observation from April, 1937, until April 1, 1938. During the last three months of this period weekly tests were recorded on a cooperative group of 34, all of whom had symptoms and showed signs of lead poisoning. In addition to the above-mentioned tests, differentials were recorded on the Wright’s smear, using the classification of Farley and others, ⁹ as used by Steinberg.* Urinalyses were not done due to technical difficulties at the factory.

During the period from April 1, 1937, to November 15, 1937, the gluconate, lactate, and diphosphate salts of calcium were given in the amount daily of from 80 to 100 grains to those who showed lead absorption by physical or laboratory signs. In addition, vitamin D (940 units) and vitamin A (9400 units) were given daily, using an accredited fish-liver oil.

The criterion used was a basophilic aggregation percentage of 1.5 or greater, abnormal stippling, or by request of the ill individual. Biweekly intravenous injections of 10 c.c. of 10 per cent calcium gluconate, together with daily oral therapy with calcium salts and vitamin D, ¹ were given to those whose basophilic aggregation registered higher (3.0 plus). Deleading with halides of potassium and ammonia were not done.

The period of intimate observation of the group of 34 lead poison patients upon whom we base this report began in November, 1937. It was then noted that, in spite of the intensive treatment with calcium and vitamin D, and the prophylactic measures taken by the plant management to reduce the lead hazard, many of the men failed by physical and laboratory standards to recuperate. In some, while there was a return to normal in percentage of basophilic aggregation and degree of stippling, there remained the complaint of ill-health, or abnormal cell morphology, or both.

Most frequent complaints were fatigue, anorexia, sleeplessness, or restless sleep; pains in the legs (gastrocnemius muscles) or in the forearms near the elbow; tenderness on deep pressure over the same areas, and irritability. Less frequently, complaint was made of trembling, constipation, sexual impotence, and joint pain. Observations on these patients consisted mainly of pyorrhea, spongy gums, and poor dentition in 75 per cent; tremor of varying degree, involving fingers and hand, usually bilaterally, and pallor of varying degree in 50 per cent; weakened extensibility at the wrist in about 10 per cent. One of the most striking signs was the surliness encountered in the majority of these subjects.

Ascorbic Acid Treatment.— One of us (E. J. A.) made the observation that the symptoms and signs exhibited by these men were similar to those found in subclinical scurvy. Ascorbic acid oral therapy was instituted in a group of 34 patients with chronic lead poisoning according to the following plan: Of 34 workmen (chronic patients) selected for this novel treatment, 17 were given ascorbic acid alone (at least two months after discontinuing the calcium salt injections), while an equal number continued the calcium therapy and at the same time took tablets of ascorbic acid.

Ascorbic Acid Without Calcium.— In general, the group of 17 patients made a marked gain in vigor, cheerfulness, color of skin, and blood picture. A week, or less than a week, after beginning the treatment of 100 mg. of ascorbic acid daily, most of the men enjoyed normal sleep, lost the irritability and nervousness so common with high calcium treatment of lead poisoning, enjoyed their food more, and no longer had tremors (if observed before). Several cases of leucopenia (probably due to a prolonged calcium therapy somewhat earlier) were cured by the ascorbic acid treatment.

Ascorbic Acid With Calcium.— The gain was less marked and rather irregular in the 17 patients given ascorbic acid with calcium. There was no gain in the number of mature neutrophiles in the blood—in strange contrast with the rapid gain when ascorbic acid alone was given.

In several instances alcohol nullified the good effects of calcium as well as of ascorbic acid, a complication that workmen exposed to lead hazards would do well to avoid.

CASE REPORTS

The detailed blood picture and the clinical observations for 3 workmen who received benefit from vitamin C in chronic lead absorption are outlined:
The blood count was for 200 cells.

WORKMAN 1
CALCIUM GLUCONATE ALONE. LATER ASCORBIC ACID ALONE

*Basophilic aggregation.
Monocytes, none from Feb. 9 to March 16.
Basophiles, 0, 0, 1%, 0, 4% from Feb. 9 to March 16.

Clinically Workman 1 on February 9 showed definite symptoms of chronic lead poisoning with marked tremor, nervousness, irritability, sleeplessness. He was underweight, tired easily, and had a very sallow complexion. His blood picture was discouraging.

By March 16, after five weeks of ascorbic acid treatment, the tremor disappeared, and his complexion greatly improved. The man was very cheerful and no longer tired easily. The blood picture also greatly improved.

WORKMAN 2
CALCIUM SALT THERAPY. LATER ASCORBIC ACID ALONE

*Basophiles, 0, 6%, 1%, 0, 1%, 0 for the six dates.
Monocytes 6%, 10%, 0, 2%, 0, 1% for the six dates.

Clinically Workman 2 showed symptoms of chronic lead poisoning, with moderate tremor, nervousness, irritability, sleeplessness, and pallor. He tired easily. One week after beginning the ascorbic acid treatment, tremor and pallor were gone. He slept well. did not tire, and was extremely cheerful and talkative.

Workman 3 displayed clinically an acute case of lead poisoning in June, 1937, with a basophilic aggregation of 14, strong stippling, etc. Calcium therapy from June to February, 1938, lowered his basophilic aggregation satisfactorily, but three weeks after discontinuing this treatment, it increased considerably with return of the symptoms of acute lead poisoning.

He was then given 100 mg. of ascorbic acid daily for sixteen days and his basophilic aggregation was again lowered to normal (as with calcium therapy), with no clinical symptoms of lead poisoning. The morphology of the red blood cells became nearly normal. The man looked well and felt fine.

House Painters.—The research was transferred to Oberlin to make a study of ordinary house painters. Here it was possible to make analytical determinations of lead and ascorbic acid in the urine. The dithizone method for urinary lead, as described by Ross and Lucas,² and improved, especially in the use of a calculation curve, by Miller³ and his associates, was used.

For the determination of ascorbic acid in urine the titration against the dye, 2.6-dichlorophenolindophenol, as described by Harris and Ray,⁴ or Hawk,⁵ was used. We found it necessary to devise improved methods of collecting twenty-four-hour specimens of urine in order to prevent the usual considerable losses of vitamin C (ascorbic acid) by oxidation. The details are given in another paper. Tests with a number of healthy people convinced us that the common estimate of an average daily urinary excretion of 15 mg. of vitamin C is too low, due to this oxidation loss, and that 25 mg. to 35 mg. is the probable average for healthy persons.

Of 14 painters observed clinically and by differential blood count, 2 were rated by clinical examination as chronic lead absorption patients, and the blood pictures added 5 more. Three of the 7 patients refused to cooperate further; hence we selected only 3 for study and treatment. Seven of the 14 picked up at random showed enough absorption to call for treatment or greater precautions.

CASE REPORTS

Case histories of 3 painters are here given. The final brief deleading was done by Dr. A. C. Siddall, who gave somewhat more potassium iodide than usual. In order to demonstrate more convincingly the value of a diet rich in vitamin C for men exposed to lead hazards, we determined the urinary lead and vitamin C of 2 more painters and gave them a brief deleading treatment. Furthermore, we determined the urinary vitamin C and lead of another painter who for many years had stressed fruits, vegetables, and milk in his diet.

Clinically the first painter and sprayer, who exhibited symptoms of chronic lead poisoning (physician’s report) responded quickly to ascorbic acid treatment. After four days, he felt lazy and sleepy but not tired. Then he quickly changed to “feeling fine,” ready for work, and fresh at the end of a hard day’s work. At the same time there was a decided improvement in his blood picture. His urinary lead quickly fell to nearly normal, and his ascorbic acid excretion rose from 15 mg. per twenty-four hours to the very high value of 51 mg.

PAINTER 1
ASCORBIC ACID TREATMENT FOLLOWED BY DELEADING

Basophiles, 2% May 11, 2% July 7, 2% July 19, 1% Aug. 9.
Monocytes, 1% May 11, 1% July 7, 0 July 19, 2% Aug. 9.

Clinically Painter 2 was rated by one of us (E. J. A.) as showing symptoms of chronic lead poisoning, even to a slight lead line on the gums. His teeth were bad and he tired quickly.

Two days of ascorbic acid treatment made him lazy and sleepy. After three weeks of ascorbic acid, he felt fine and energetic at the end of a hard day’s work. His family noted the change from irritability to cheerfulness.

Urinary lead excretion fell from 0.4 mg. per liter to about 0.1 mg. Ascorbic acid in twenty-four hours’ urine rose from 12 mg. to 86 mg,

Clinically Painter 3 seemed to one of us (E. J. A.) to be in good health, showing no signs of lead poisoning and having no complaints. During the period from May 9 to May 23 his blood picture was not reassuring and plans were made for ascorbic acid treatment. Urine examined for lead showed 0.5 mg. per liter (as compared to the average man’s 0.085 mg.). Vitamin C excretion per twenty-four hours was very low, being only 10 mg.

Two weeks of ascorbic acid treatment decidedly improved his blood picture and astonishingly lowered the urinary lead to 0.18 mg. per liter. Ascorbic acid excretion rose to the level of 31 mg. daily.

PAINTER 2
ASCORBIC ACID TREATMENT CONTINUED THROUGH DELEADING

Basophiles 2% Aug. 9. None on other dates.
Monocytes 0 May 5, 0 July 7, 2% July 14, 2% July 28, 0 Aug. 9.

PAINTER 3
ASCORBIC ACID TREATMENT FOLLOWED BY DELEADING

Basophiles, 2% May 9, 2% May 23, 2% July 7, 1% July 21.
Monocytes, 2% May 9. None on other dates.

Eight days of deleading (ascorbic acid discontinued) brought urinary lead to normal (0.085 mg. per liter), but the ascorbic acid excretion unfortunately fell to 16 mg. per twenty-four hours. Clinically the man seemed in good health throughout the deleading treatment.

Painter 4.—Painter 4, a house painter for twenty-five years, showed the effects of a diet unusually rich in the best vitamin C foods as well as in milk. His health (except for a temporary tooth infection) was good, his urinary lead was only 0.1 mg. per liter, and his ascorbic excretion was 58 mg. per twenty-four hours, an exceptional figure.

Deleading with 80 grains ammonium chloride daily for six days was done (no milk in that period) and the urinary lead was cut to 0.04 mg. per liter.

Painter 5.—The son of Painter 4, Painter 5 was brought up in the same dietary tradition as his father. He was in excellent health and painted for several years. He excreted 0.16 mg. lead per liter of urine. After six days of deleading with ammonium chloride (80 grains daily), his urinary lead excretion fell to 0.05 mg. He was comfortable during deleading. The usual vitamin C excretion had been 40 mg. per twenty-four hours urine.

Painter 6.—Painter 6 was a house painter who for fifteen years faithfully applied the dietary teachings of a religious organization and lived on a diet exceptionally rich in fruits and vegetables (many raw) and milk. He was in excellent health and possessed a good blood picture and a very good vitamin C excretion of 37 mg. per twenty-four hours. His lead excretion was 0.215 mg. per liter after four days of deleading with potassium iodide.

His wife on the same religious diet excreted 50 mg. of vitamin C per twenty-four hours, but in her case the effect of lead on vitamin C was not a factor. His pastor, a painter for thirty years, also living on a diet exceptionally rich in fruits, vegetables, and milk, enjoyed splendid health, and excreted only 0.13 mg. lead per liter in spite of his painting.

DISCUSSION

Administration of 100 mg. of vitamin C daily to each of 34 workmen exposed to factory lead hazards (and diagnosed as suffering from lead absorption) in general decidedly improved their blood picture and their health. Symptoms characteristic of chronic lead absorption usually disappeared. It seems reasonable to suppose that toxic lead ions were removed to a considerable extent from the blood stream. Calcium gluconate or lactate does this by storing the lead in the bones, presumably as lead phosphate. Experience shows some drawbacks to long-continued high calcium medication; hence bone storage should be followed by cautious deleading, with a respite from lead absorption.

A more detailed study of 3 house painters, diagnosed as suffering from chronic lead absorption, strongly reinforced the conclusions drawn from the factory experiments. The observation that 200 mg. daily of vitamin C as a dietary supplement decidedly lowered the urinary excretion of lead is astonishing. With it goes another observation that men actually suffering from lead absorption excrete less vitamin C in the urine than does the average man.

It is difficult to escape the conclusion that toxic lead compounds react with vitamin C to form a poorly ionized salt (lead ascorbate ?) or a complex salt which yields a very low concentration of simple lead ions. If solutions of lead acetate and vitamin C are mixed in a test tube, no precipitate is observed; hence the product is soluble, not to be precipitated in the bones. Cautious addition of sodium hydroxide fails to precipitate lead hydroxide or oxide, normally termed insoluble.

This view of removal of toxic lead ions by reaction with ascorbic acid to form soluble, but poorly ionized, salts or complexes is strengthened by the observation of Greenwald⁶ on the remarkable influence of ascorbic acid on the dissociation (and solubility products) of calcium phosphate and certain other calcium salts. He is of the opinion also that calcium gluconate, lactate, and citrate form complexes with calcium ions. Hastings and McLean⁷ offer a parallel in the fact that citrates lower the concentration of free calcium ions through formation of a soluble complex.

In an excess of enthusiasm over the good diet, one of our painters drank a pint of milk for five days before starting the ascorbic acid treatment. His vitamin C excretion, previously only 10 to 13 mg., quickly rose to 25 mg. and, after he discontinued his daily pint of milk, quickly fell to 15 mg. A similar observation was made with another painter. Evidently sufficient dietary calcium spares vitamin C in the body of a man suffering from lead absorption, probably by forcing some of the lead into the bones as lead phosphate.

A natural fear arises that if ascorbic acid therapy reduces urinary excretion of lead this lead must be stored somewhere in the body, to be released later in toxic form in the blood stream as dietary or other conditions change. This was not true of four or five local house painters who enjoyed several, even many, years of excellent health while painting, evidently because of a diet that we know to be extremely rich in vitamin C. At any rate, we found that they excreted more of this vitamin than does the average healthy individual.

Judging from the statement by Sollman on deleading with potassium iodide, it seems a fair assumption that the compound formed by ascorbic acid and toxic lead ions is preferentially absorbed by the liver and, with the aid of the bile, excreted in the feces. We hope that others interested in this research will determine this by quantitative analysis. He⁸ writes: “Renal excretion of lead depends directly upon the lead compounds circulating at the time in true solution in the blood. . . . The increased excretion (of lead) through use of potassium iodide has been noted by previous workers, although others have failed to confirm it, chiefly because they confined themselves to the urine while the excretion is mainly in the faeces. The iodide causes the reappearance of lead in the faeces from which it had been absent.”

In general, fresh fruits and vegetables (and canned tomatoes.) are very good sources of vitamin C, but the average workman will find the above list definite and practical. On a limited income even raw cabbage and turnips with canned tomatoes are possible as sources of 50 mg. or 100 mg. vitamin C daily.

*Dr. Bernhard Steinberg, Director of Laboratories. Received for publication, November 14. 1938.

REFERENCES

1. McCord, C. P., and Johnson, J.: The Basophilic Aggregation Test, Am. J. Pub. Health 25: 1089, 1935.
2. Ross, J. R., and Lucas, C. C.: A New Method for the Determination of Minute Amounts of Lead In Urine, J. Biol. Chem. 3: 290, 1935.
3. Winter, O. B., Robinson, H. M., Lamb, F. W., and Miller, E. J.: The Determination of Lead, Indust. & Engin. Chem. Analyt. Ed. 7: 265, 1935.
4. Harris, L. J., and Ray. S. N.: Diagnosis of Vitamin C in Subnutrition by Urine Analysis, Lancet 1: 71, 1935.
5. Hawk, P. B., and Bergeim, O.: Practical Physiological Chemistry, ed. 11, Philadelphia. 1937, P. Blakiston’s Son & Co., p. 733.
6. Greenwald, I.: The Dissociation of Some Calcium Salts, J. Biol. Chem. 124: 437, 1938.
7. McLean, F. C., and Hastings, A. B.: A Biological Method for the Estimation of Calcium Ion, J. Biol. Chem. 107: 351, 1934.
8. Sollman, T.: A Manual of Pharmacology, ed. 3, Philadelphia, 1928, W. B. Saunders Co., p. 1049.
9. Parley, D. L., St. Clair, H., and Reisinger, J. A.: Am. J. M. Sc. 180: 336, 1930.

From The Journal of Laboratory and Clinical Medicine Vol. 24, August 1939, No. 11, pp. 1119-1127

HTML Revised 20 November, 2013.
Corrections and formatting © 1999-2003 AscorbateWeb