Ascorbate (Vitamin C) clearly linked to disease and healing

Stone Morbidity Index
(ascorbate/deHydroAscorbate ratio)
Disease died survived convalescent normal
[None] 15
Meningitis 0.3 0.7 2.8
Tetanus 0.5 1.3 5.0
Pneumonia 0.4 1.0 4.0
Typhoid Fever 0.4 1.3 4.5

The Healing Factor
“Vitamin C” Against Disease

1972 book by Irwin Stone,
inspiration to Linus Pauling

Chapter 27

Wounds, bone fractures, and shock

It has been known for hundreds of years that wounds will not heal and that healed old wounds and scars reopen in people deprived of ascorbate and afflicted with scurvy. Scurvy also weakens the bones and renders them more susceptible to fracture. In the forty years since the discovery of ascorbate, there have been so many papers published on the beneficial relationship of ascorbate to wound healing, on the improved strength of the scar tissue, and on the faster healing of bone fractures, that it is just impossible to fully review this vast volume of work within a brief chapter. However, the interested reader can refer to the papers presented at the Scientific Conference on vitamin C, held by the New York Academy of Sciences in 1960 (1). The papers by Abt and Schuching, Robertson, Gould, Crandon, Fullmer, and Lee are of particular interest in this connection.

The utilization of ascorbate in wound healing is now so well documented that there are many surgeons who routinely provide their patients with 1 or 2 grams of ascorbate a day, postoperatively, to aid in their healing and recovery. In spite of the vast number of published papers, it is still not known whether these are the optimal levels for this purpose and whether the patients would benefit from the administration of higher amounts. This should be the subject of further research.

Of particular interest at this point is the recent work of Dr. Steinberg (1), of Jewish Memorial Hospital in New York City, in the successful treatment of gangrene of the legs and feet with sodium ascorbate. In five cases of long-standing gangrene, resistant to other forms of treatment and some scheduled for amputation, the administration of up to 5 grams of sodium ascorbate daily, in addition to other treatment brought about improvement and healing in a few weeks. These cases of gangrene were caused by arteriosclerotic occlusion, diabetic endarteritis, and polycythemia vera. While the ascorbate status of the patients was not determined, it is likely they were suffering from severe chronic subclinical scurvy. Much follow-up work is needed on this promising lead in the treatment of gangrenous lesions.

But even in wound healing, the full potential of ascorbate may not be entirely exploited. For instance, there is a critical shortage of hospital beds and all the medical and other facilities necessary to maintain them. Research should be instituted to determine if the daily routine administration of a few grams of ascorbate to hospital admissions would hasten their recovery and shorten their hospital stay. Many patients now entering hospitals are already in a prescorbutic state. If their hospital stay could be shortened by 25 percent, it would be equivalent to building and staffing a new facility for every four in existence, at only pennies a day per patient.

[Stone] Morbidity Index – A new Diagnostic Tool

Another idea of medical treatment which requires more investigation is the use of ascorbate as a diagnostic and prognostic tool. Blood samples are usually taken from patients and a variety of examinations are made on them. It is rare, however, that a determination of ascorbate is ever made on these blood samples. Because of complications in the methodology developed over the years, the determination of ascorbate in blood has lost much of its diagnostic value and has fallen into disrepute.

The methods in use during the 1930s determined the true, “reduced” ascorbate in the blood. In 1943, when new procedures were introduced, what was determined was the “total” ascorbate, which included not only the “reduced” ascorbate but the “oxidized” dehydroascorbate and other decomposition products. The actual results obtained by these two different types of methods were not comparable and caused much confusion, which still exists. While it is possible to separately determine the ascorbate and the dehydroascorbate by these techniques, it was seldom carried out and reported in the research work of the past forty years.

The development of a possible valuable diagnostic tool was delayed for four decades due to a lack of appreciation of the simple physicochemical facts involved. What is needed in these determinations is not the “total” or the “reduced” ascorbate, but the ratio of the two components, ascorbate and dehydroascorbate. In 1955, Chakrabaryi and Banerjee (2), after reviews of the prior work, pointed out the paradox of dehydroascorbate which, at low levels, behaves essentially like ascorbate in giving protection from or curing scurvy, but is toxic at high levels. They determined both the ascorbate and dehydroascorbate in the blood of many of their patients. They found that the ascorbate levels went down and dehydroascorbate levels went up as their patients became sicker and finally died from meningitis, tetanus, pneumonia, and typhoid fever. If the patients survived, the trend was reversed. Hoffer and Osmond (2), in 1963, cited many other references relating to mental stress and mental disease affecting the ascorbate blood levels and also first calculated the Ascorbate / Dehydroascorbate ratios which showed some startling statistics. These figures, along with some others which I calculated from another paper (3), are assembled in the following table.

[Stone] Morbidity Index as Prognostic Tool and Index of Survival

Disease and
(mg/100 ml)
(mg/100 ml)
(mg/100 ml)
Normal 28 0.93 0.87 0.06 14.0
  died 8 1.22 0.27 0.95 0.3
  survived 17 1.04 0.43 0.61 0.7
  convalescent 11 0.72 0.53 0.19 2.8
  died 13 1.09 0.36 0.73 0.5
  survived 12 0.92 0.52 0.41 1.3
  convalescent 12 0.89 0.74 0.15 5.0
  died 7 0.98 0.30 0.68 0.4
  survived 19 0.83 0.43 0.40 1.0
  convalescent 15 0.75 0.59 0.16 4.0
Typhoid Fever
  died 4 0.80 0.24 0.56 0.4
  survived 19 0.80 0.45 0.35 1.3
  convalescent 15 0.83 0.68 0.15 4.5
Tubercular Meningitis
  chronic 17 0.83 0.50 0.33 1.5

Normal 16 0.95 0.89 0.06 14.8
Cholera 21 0.99 0.62 0.37 1.7
Smallpox 16 1.07 0.51 0.56 0.9
Pyogenic Meningitis 16 0.80 0.35 0.45 0.7
Tubercular Meningitis 16 0.92 0.74 0.18 4.2
Gonorrhea 16 0.79 0.53 0.26 2.0
Syphilis 16 0.92 0.74 0.18 4.2
(Top section figures are from Chakrabarti et al. (2); bottom section figures were calculated by the author from the data of Bhaduri et al. (3).)

[Editor’s note: The following new table, which was not in Stone’s book, summarizes the above table:]

Stone Morbidity Index
(ascorbate/deHydroAscorbate ratio)
Disease died survived convalescent normal
[None] 15
Meningitis 0.3 0.7 2.8
Tetanus 0.5 1.3 5.0
Pneumonia 0.4 1.0 4.0
Typhoid Fever 0.4 1.3 4.5
(Figures are from Chakrabarti et al. (2))

Inspection of the figures on this table shows the inadequacy of “total” ascorbate blood levels as a diagnostic measurement. Because of the high dehydroascorbiate levels, many of the dead patients had higher “total” levels than the survivors. With many investigators during the past three decades reporting “total” ascorbate in their work, it can easily be discerned how the present confusion and lack of confidence in blood ascorbate determinations resulted. The “reduced” ascorbate levels are a superior indicator, but most significant is the ratio of Ascorbate to Dehydroascorbate which I term the “morbidity index”.

The “normals” had a morbidity index of approximately 15 although an individual taking high levels of ascorbate would have even a higher index. Those who were critically sick but survived had a morbidity index of about 1.0, while those who died had much less, 0.3, to 0.5. During convalescence of the survivors, the morbidity index jumped to 3.0 to 5.0.

There is a logical physicochemical explanation for these variations. Ascorbate and dehydroascorbate, as explained in earlier chapters, are members of a reversible oxidation-reduction system. The redox potential depends on the relative amounts of each component of the systems. For healthy tissue processes, that ratio must favor high amounts of ascorbate and very low levels of dehydroascorbate in order to keep the redox potential low. In pathology, the tissue potentials approach more oxidative levels as the disease progresses, and recedes again as the disease clears up.

Incalculable time has been wasted by hundreds of investigators over the past forty years of research work. They were trying to relate ascorbate blood levels to a disease process, but they did not realize these simple facts and determined and reported only either “total” ascorbate or “reduced” ascorbate. Much of the confusion during the past four decades is due to this inadequate data.

The value of megascorbate therapy may be in maintaining the redox tissue potentials at the necessary low levels and maintaining the morbidity index in the upper brackets. The constant presence of high ascorbate levels may suppress the formation of the toxic dehydroascorbate.

Here we have in a potentially valuable tool which may aid the physician in determining how sick his patient really is and his chances for survival. Further research should resolve the question of how valuable a tool the morbidity index really can be.


Shock is a very dangerous condition of general bodily collapse that can rapidly appear as a result of the stresses of severe, traumatic injuries, burns, major surgery, massive hemorrhage, abdominal injury, and dehydration. The fundamental defect in shock is failure of effective blood flow and hence impaired transport of vital materials in the blood to the organs and tissues. This is brought on by increased permeability of the capillaries, resulting in loss of blood plasma into the surrounding tissues. The lowered blood volume, with its increased percentage of blood cellular constituents, is more difficult to pump through the arteries and veins. The volume of blood being pumped from the heart is low and the blood pressure is low. The patient is usually in a state of collapse with a pallid, moist skin and impaired mental faculties. It is necessary to rapidly correct this condition and usually the first measures are to assure proper breathing and replace the blood’s volume of fluid.

The use of ascorbate in the treatment of shock has been repeatedly suggested in many papers over the past thirty years. These papers include reports not only of successful experiments on laboratory animals, but on case histories on man. There is a perfectly good rationale for this use of ascorbate because of its long-known beneficial effects in preventing capillary fragility and the fact that hemorrhage is a characteristic symptom of ascorbate depletion. In 1941, in experiments on cats bled of 50 percent of their blood volume, Stewart and coworkers (4) were able to prolong the animals’ lives with an intravenous injection of ascorbate. Ungar (4), in 1942 and 1943, was able to prevent traumatic shock and death in injured guinea pigs by an injection of ascorbate of 100 milligrams or more per kilogram of body weight. In 1943, nearly three decades ago, he noted that particular emphasis should be laid on the possibility of utilizing his observations in the treatment of human traumatic and surgical shock.

Further tests on guinea pigs, reported in 1944 by McDevitt and coworkers (4), showed ascorbate increased their resistance to trauma and improved their survival. In studies on eleven human subjects undergoing major surgery they sampled the patients’ blood for ascorbate determinations before, during, and after the operations. Of the eleven cases, five had subnormal ascorbate levels before the operation and eight had levels markedly below normal immediately postoperatively or within twenty-four hours.

Hemorrhagic shock induced in guinea pigs by a standardized bleeding procedure was the subject of a 1946 paper by de Pasqualini (4). She found that if the guinea pigs were given 200 milligrams of ascorbate five minutes before the start of bleeding, it prevented shock and 94 percent of her eighteen test animals survived, while 90 percent of the seventeen animals not given ascorbate died.

Holmes (5), in 1946, discussed the use of ascorbate to relieve the increased capillary permeability occurring in shock. He cites the successful results of a group of cooperating surgeons using ascorbate to successfully treat surgical shock. Another surgeon used it successfully preoperatively and postoperatively in fifty serious abdominal operations. In approximately 2,000 cases of dental extractions, ascorbate was administered thirty to forty-five minutes before the extraction, preventing shock and postoperative weakness. It was also employed in thirty-five cases of mine injuries, in which instances it helped the injured to survive the long trip to the hospital. He also cites the experience of other cooperating physicians. He noted that there was no question on the value of adequate amounts of ascorbate in the maintenance of a healthy condition of the capillary walls and that it may also be useful in combating the anoxia of shock. The highest blood levels of ascorbate were reached after two or three hours on oral administration and in three to five minutes when given intravenously.

In 1946, S.M. Levenson and associates (6), reported on the use of ascorbate, vitamins B1, and B2, and nicotinic acid in severe injury, hemorrhage, and infections in humans. They concluded that their work adds further support to the idea that large doses of these materials may serve a useful purpose in treating acutely ill patients. In 1962, a conference and workshop on hemorrhagic shock was held at the Rockefeller Institute. As reported in Science by Simeone (6), Dr. Levenson presented a paper revealing that injured animals suffer for biochemical scurvy. Levenson’s claim that ascorbate could influence the mortality from hemorrhagic shock was “viewed with skepticism.”

In 1947, Zerbine (7), reported on a duodenal ulcer operation where the patient went into postoperative shock. Prompt administration of 2 grams of ascorbate, intravenously, pulled him out of the shock within minutes. Continued large dosages of ascorbate made the patient’s recovery “uneventful.” Zerbini noted that his one observation is merely suggestive but that “further studies would obviously seem worthwhile.” In the course of tests in eighty surgical operations, Pataky and associates (7) reported in 1957 that they were able to inhibit the passage of plasma through the intact vessel walls, and to control surgical shock with large doses of ascorbate. Kashchevskaia (7), in a 1958 paper from the Soviet Union, showed that ascorbate is intimately involved in the state of shock.

Strawitz and coworkers (8), using rats to determine the effect of ascorbate and methylene blue in hemorrhagic shock, reported in 1958 that both agents significantly reduced the mortality rates and, in addition, ascorbate lengthened the survival period.

In 1963, Santomé and Gomez (9), using dogs as experimental animals, checked the earlier work of Sayers et al. on rats in hemorrhagic shock. They found an increase in the blood ascorbate levels and a highly significant decrease in the blood ascorbate levels and a highly significant decrease in the adrenal gland ascorbate, in spite of the higher levels in the blood. The higher blood level is likely to be an artifact because the liver rapidly synthesized ascorbate under the stress and it poured it into a reduced volume of blood. The low ascorbate levels in the adrenal glands are probably a more reliable criteria of the response to the heavy stresses to which the animals were subjected.

In a paper published in 1967, Kocsard-Varo (9) discussed microcirculation (the capillary system), capillary permeability, and ascorbate. She made the following interesting observations which involved her in the study of the microcirculation. She found that in nosebleed due to high blood pressure, if a 1-1,000 adrenaline solution were applied to the surface of the nasal mucous membrane or if ascorbate were injected individually, the bleeding would continue. However, if they were both done simultaneously, the blood flow stopped “instantaneously, as if one turned off a faucet. The bleeding does not recur.” Ascorbate has a known protective action on adrenaline in the circulation.

The electron microscope studies of the capillary bed of ascorbate-deficient guinea pigs, by Gore and coworkers (10), published in 1968, disclosed the ultrastructural basis for the capillary defects, the microdiscontinuities and microlesions which lead to capillary fragility.

The above review of the highly suggestive research over the past three decades illustrates the possible usefulness of ascorbate in the prevention and treatment of traumatic, hemorrhagic, and surgical shock. Yet how much use is being made of this data in present-day shock therapy? In a paper published in 1969 by Weil and Shubin (11), workers in the Shock Research Unit of a large medical school and hospital, there is not a single mention of ascorbate.

With shock still claiming so many victims in highway accidents and battlefield casualties, the need for more work in this area is urgent.



Scientific Conference on Vitamin C.
Annals New York Academy of Sciences, vol. 92, Article 1. 1961.

Abt AF, von Schuching S.
Catabolism of L-Ascorbic-I-C14 Acid as a Measure of its Utilization in the Intact and Wounded Guinea Pig on Scorbutic Maintenance and Saturation Diets.
Annals New York Academy of Sciences, vol. 92: pp. 148-158. 1961.

van B. Robertson W.
The Biochemical Role of Ascorbic Acid in Connective Tissue.
Annals New York Academy of Sciences, vol. 92: pp. 159-167. 1961.

Gould BS.
Ascorbic Acid-Independent and ASscorbic Acid-Dependent Collagen-Forming Mechanisms.
Annals New York Academy of Sciences, vol. 92: pp. 168-174. 1961.

Crandon JH et al.
Ascorbic Acid Economy in Surgical Patients.
Annals New York Academy of Sciences, vol. 92: pp. 246-267. 1961.

Fullmer HM et al.
Role of Ascorbic Acid in the Formation and Maintenance of Dental Structures.
Annals New York Academy of Sciences, vol. 92: pp. 286-294. 1961.

Lee RE.
Ascorbic Acid and the Peripheral Vascular System.
Annals New York Academy of Sciences, vol. 92: pp. 295-301. 1961.

Personal communication from Dr. Marvin D. Steinberg, Director, Department of Podiatry, Jewish Memorial Hospital, New York, New York.


Chakrabarti B, Banerjee S.
Dehydroascorbic Acid Level in Blood of Patients Suffering from Various Infectious Diseases.
Proceedings Society Experimental Biology and Medicine, vol. 88: pp. 581-583. 1955.

Hoffer A, Osmond H.
Scurvy and Schizophrenia.
Diseases of the Nervous System, vol. 24: pp. 1-12. May 1963.

3. Bhaduri JN, Banerjee S.
Ascorbic Acid, Dehydroascorbic Acid and Glutathione Levels in Blood of Patients Suffering from Infectious Diseases.
Indian Journal of Medical Research, vol. 48: pp. 208-211. 1960.

Ungar G.
Effect of Ascorbic Acid on the Survival of Traumatized Animals.
Nature, vol. 149: pp. 637-638. 1942.

Ungar G.
Experimental Traumatic “Shock”.
Lancet, vol. 1: pp. 421-424. 1934.

Stewart CP et al.
Intravenous Ascorbic Acid in Experimental Acute Haemorrhage.
Lancet, vol. 1: pp. 818-820. 1942.

McDevitt E et al.
Vitamin C in Peripheral Vascular Failure.
Southern Medical Journal, vol. 37: pp. 208-211. 1944

de Pasqualini CD.
The Effect of Ascorbic Acid on Hemorrhagic Shock in the Guinea Pig.
American Journal of Physiology, vol. 147: pp. 598-601. 1946.

5. Holmes HN.
The Use of Vitamin C in Traumatic Shock.
The Ohio State Medical Journal, vol. 42: pp. 1261-1264, 1946.

Levenson SM et al.
Ascorbic Acid in Relation to Severe Injury, Hemorrhage and Infection in the Human.
Annals of Surgery, vol. 124: pp. 840-856. 1946.

Simeone FA.
Hemmorrhagic Shock: Metabolic Effects.
Science, vol. 141: pp. 536-542. 1963.


deJ. Zerbini E.
Vitamin C in Gastric Resection for Peptic Ulcer.
Archives of Surgery, vol. 54: pp. 117-120. 1947.

Pataky Z et al.
Vitamin C in the Control and Prevention of Surgical Shock.
Zentralblatt für Chirurgie, vol. 82: pp. 883-887. 1957.

Kashchevskaia LA.
Dynamics of Blood Ascorbic Acid in State of Shock.
Biulleten Eksperimental ’noi Biologii i Meditsiny (Moskva), vol. 42: pp. 60-66. 1957.

8. Strawitz JG et al.
The Effect of Methylene Blue and Ascorbic Acid in Hemorrhagic Shock.
Surgical Forum, vol. 9: pp. 54-58. 1958.

Santomé JA, Gomez OA.
Ascorbic Acid and Hemorrhagic Shock. I. Changes in Plasma and Whole Blood.
Acta Physiologica Latino-Americana, vol. 13: pp. 150-154. 1963.

Santomé JA, Gomez OA.
Ascorbic Acid and Hemorrhagic Shock. II. Changes in the Whole Adrenal Gland and in the Adrenal Cortex.
Acta Physiologica Latino-Americana, vol. 13: pp. 155-158. 1963.

Kocsard-Varo G.
The Physiologic Role of Adrenalin, Nor-Adrenalin and Vitamin C in Homeostasis.
Journal Otolaryngological Society of Australia (Melbourne), vol. 2: pp. 68-74. 1967.

10. Gore I et al.
Capillary Hemorrhage in Ascorbic-Acid-Deficient Guinea Pigs.
Archives of Pathology, vol. 85: pp. 493-502. 1968.
11. Weil MH, Shubin H.
The “VIP” Approach to the Bedside Management of Shock.
Journal American Medical Association, vol. 207: pp. 337-340. 1969.
(and many more in the decades since 1972, when this book was published)

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Editor’s notes:

 –Dave Yost, 2008-01 - this page
2003-12-25 Published here
2008-01-24 Modified