Results from Clinical Studies on Vitamin C and Heart Disease

SERIAL ARTERIOGRAPHY IN ATHEROSCLEROSIS in Human Beings
G. C. Willis, MD; A. W. Light, MD; W. S. Gow, MD
Canad. M. A. J.; Dec 1954, Vol 71

[From the paper] The patients studies by arteriography were selected from Queen Mary Veterans' and St. Anne's Hospitals. All were men, varying in age from 55 to 77, with an average age of 64 years, and were those who had shown many of the clinical manifestations ordinarily considered to be associated with atherosclerosis.

Bilateral femoral arteriography was performed in all cases. [This technique is described in the paper along with remarkable pictures of plaque in human arteries.]

Controls
Case/Age Diagnosis Time observed in Days Change in Plaques Cholesterol before mg/% Cholesterol after mg/% Symptom Changes score
1/72 Severe peripheral atherosclerosis 176 days 2 plaques bigger, 2 unchanged N/A N/A Impending gangrene
2/74 Severe peripheral atherosclerosis 70 days 4 plaques bigger; multiple small plaques unchanged 332 mg/% 290 mg/% No Change
3/63 Diabetes 70 days No Change 240 mg/% 278 mg/% No Change
4/77 Atherosclerotic Heart Disease, diabetes 82 days No Change 216 %/mg 232 mg/% No Chnage
5/59 Severe periph. atherosclerosis 172 days 1 plaque bigger N/A N/A Required amputation
6/62 Diabetes 192 days No Change 332 mg/% 287 mg/% No Change

None of the patients, with the exception of diabetics, was given any special diet. The treated group were given 500 mg of ascorbic acid (vitamin C) orally (three times a day) but otherwise were the same as the control group.

Results in Group Given Ascorbic Acid (500 mg)
Case/Age Diagnosis Time observed in Days Change in Plaques Cholesterol before mg/% Cholesterol after mg/% Symptom Changes score
7/69 Severe atherosclerotic heart disease 62 days 3 plaques bigger, 2 unchanged 350 mg/% 262 mg/% Died 1 month later of pneumonia
8*/59 Severe periph. atherosclerosis Amp. left. 172 days 2 plaques smaller 375 mg/% 360 mg/% No Change
9/72 Periph atherosclerosis, Imp. gangrene 136 days 3 plaques smaller, 3 unchanged N/A N/A Claudication decreased
10*/58 Old myocardial infarction 125 days 2 plaques bigger, several unchanged 323 mg/% 287 mg/% No Changed
11/56 Diabetes, Xanthomatosis. Ang. pectoris 110 days 7 plaques smaller, 7 unchanged 312 %mg 216,240,240 %/mg Xanthomata softer and less painful but same size
12*/64 Hypercholesterolaemia, Old myocardial infarction 105 days 6 plaques bigger, 2 unchanged 560to435 %/mg 485 %/mg No change
13/65 Old myocardial inf. Cerebral thrombosis 116 days 5 plaques unchanged 258 %/mg 255 %/mg No Change
14/61 Diabetes. Old myocardial inf. 96 days 1 plaque smaller, multiple unchanged 255 %/mg 312 No Change
15*/55 Diabetes 100 days 1 plaque smaller, 6 unchanged 221 %/mg 248 %/mg No Change
16/63 Angina pectoris 155 days 3 plaques smaller, multiple unchanged 292 %/mg 390 %/mg Angina much less

Notes: * These cases in error each had a period up to 3 weeks without therapy. All others had continuous therapy.

Conclusions

  1. The problem and the importance of study atherosclerosis objectively during life are outlined and serial arteriography is suggested as a method of study.
  2. Both progression and regression of plaques are observed to occur over relatively short periods of time. Progression and regression did nt co-exist in the same cases during one period of observation.
  3. Preliminary results of ascorbic acid (Vitamin C) therapy in human atherosclerosis are encouraging.

    THE REVERSIBILITY OF ATHEROSCLEROSIS
    G. C Willis
    Canad. M A. J., July 15, 1957, vol. 77

    A total of 77 male and female adult guinea-pigs was rendered scorbutic... After intervals of from 21 to 30 days, 50 of these animals were given ascorbic acid therapy and there remaining 27 were sacrificed.

    The Number of Animals in the Various Experimental Groups, With and Without Atherosclerosis and the Degree of the lesions
    Experiment Total Animals With atherosclerosis Without atherosclerosis Average degree of atherosclerosis
    Scorbutogenic diet 42 days with ascorbic acid added from the beginning 12 0 12 0
    Scorbutogenic diet for periods of from 21 to 30 days 27 11 16 2.5+
    Scorbutogenic diet for 21 to 30 days, then ascorbic acid for 1 to 5 days 25 9 16 2.5+
    Scorbutogenic diet for 21 to 30 days, then ascorbic acid for 7 to 27 days 25 7 18 2.5+

    Conclusions

    No atherosclerosis was found in the controls (with ascorbic acid added from the beginning.) From the paper, When ascorbic acid is given to scorbutic (missing vitamin C) guinea-pigs, the early atherosclerotic lesions resorb quickly. The advanced lesions are considerably more resistant to reversal, apparently because of the islands of lipid whose only contact with the resorbing process is at the surface.

    A correlation is made between the atherosclerosis of the scorbutic guinea-pig and that observed in man, and the results of a previous study of ascorbic acid therapy in human atherosclerosis."

    AN EXPERIMENTAL STUDY OF THE INTIMAL GROUND SUBSTANCE IN ATHEROSCLEROSIS
    G. C. Willis, MD
    Canad. M. A. J, July 1953, Vol 69.

    [from the paper] As the earliest morphologic lesion is a disturbance of the intimal ground substance localized by mechanical stress, it seems logical to direct attention to the nature of this stress and then to its effect on ground substance. For this reason I have recently reviewed the physical principles that govern the load upon arteries and correlated them with the sites of atherosclerosis in experimental animals, in the human with vascular anomalies and finally in the common case with atherosclerosis.
    Show the Results obtained in Each of the Dietary Groups
    Diet Number of Animals Plasma Cholesterol Range Average Plasma Cholesterol Fat staining of spleen Number of Animals with atherosclerosis Number of Animals without Atherosclerosis Average Degree of Atherosclerosis in those having it
    Chronic scorbutic 20 23 to 120 mg.% 80.5 mg.% 0 9 11 2.5+
    Chronic scorbutic with oral ascorbic acid 22 26 to 106 mg.% 53.5 mg.% 0 0 22 0
    Chronic scorbutic with oral ascorbic acid and cholesterol 18 41 to 270 mg.% 162 mg.% 3+ 16 2 2.5 +
    Chronic scorbutic with intra-peritoneal ascorbic acid and cholesterol 18 85 to 301 mg.% 179.4 mg.% 2+ 7 11 1.6+
    Acute Scrobutic 32 17 to 80 mg.% 42 mg.% 0 19 13 2+
    Acute Scorbutic with oral ascorbic acid 16 23 to 77 mg.% 40 mg.% 0 0 16 0
    Acute scorbutic with cholesterol 11 Not Done Not Done 3+ 11 0 2.6+
    Acute scorbutic with oral ascorbic acid and cholesterol 8 Not done Not done 3+ 4 4 2+

    Conclusions

    Willis concludes that ascorbic acid is essential for the maintenance of the ground substance of the arterial intima. Any factor disturbing the ascorbic acid metabolism either systematically or locally results in ground substance injury with subsequent lipid deposit
    1. The mechanical stress important in the localization of atherosclerosis is a stretching of the arterial wall. This is influenced by arterial blood pressure, surrounding tissue pressure, radius of lumen, curvature of artery and arterial fixation.
    2. The stretching force may be linked with the stress which localizes lesions in scurvy.
    3. Ascorbic acid deficiency in guinea pigs produces atherosclerosis regardless of whether scurvy is acute or chronic
    4. Massive doses of parental ascorbic acid my be of therapeutic value in the treatment of atherosclerosis and the prevention of intimal hemorrhage and of thrombosis.

    ASCORBIC ACID CONTENT OF HUMAN ARTERIAL TISSUE
    G. C. Willis, MD; S. Fishman, PhD
    Canad. M. A. J., April 1, 1955, Vol 72

    The ground substance depends on ascorbic acid for its formation and under conditions of ascorbic acid depletion the ground substance undergoes depolymerization. Because of the influence of ascorbic acid upon atherosclerosis in the guinea-pig, it was decided to determine the ascorbic acid content of human arteries under various circumstances, and thus study the metabolism of ther arterial ground substance.
    Ascorbic Acid Content of the aorta in Cases of Sudden Death
    case Diagnosis Hours after death Sex Age Ascorbic Acid content of aorta mg/100 gm
    1 Fatal crush injury of neck 4 M 25 3.0
    2 Electrocution 10 M 25 2.0
    3 Drowning 3 F 25 0.7
    4 Factured skull and ribs 12 M 45 1.6
    5 Fractured skull 10 M 45 3.5
    6 Poisoning, nature unknown 18 M 48 0.7
    7 Cause unknown 12 M 49 1.5
    8 Cause unknown 4 M 50 0.5
    9 Carbon Monoxide poisoning 4 F 51 1.4
    10 Sudden death due to Myocardial Infarction 2 M 56 1.3
    11 Sudden death due to Myocardial Infarction 6 M 60 1.0
    12 Sudden death due to Myocardial Infarction 5 M 65 0.9

    Ascorbic Acid Content of the Aorta in Hospital Cases Treated with Ascorbic Acid Ante Mortem
    Case Diagnosis Ascorbic Acid Therapy Hours after death Sex Age Ascorbic Acid content of aorta
    13 Infectious hepatitis 2.5 I.V. over 5 days 20 M 40 2.8
    14 Post-op gasterectomy for bleeding ulcer 2.0 gm I. V. over 4 days 2 M 50 3.5
    15 Tabes dorsails, Bleeding gastric ulcer 12 gm I. V. over 12 days 14 M 55 1.9
    16 Hepatoma 1.5 gm I. V. over 1 day 8 M 62 1.7
    17 Carcinoma floor of mouth .5 gm I. V 5 days prior to death 15 M 69 0.8

    Ascorbic Acid Content of the Aorta, Carotid Sinus and Internal Carotid Artery in Routine Hospital Autopsies
    Case Diagnosis Hours after death Sex Age Aorta Carotid Sinus Int carotid
    18 Haemangioperieytome of vulva 7 F 18 0.7 0.7 0.8
    19 Staph. septicaemia15 M 19 0.2 0.3 0.8
    20 Thalamic tumour 9 F 19 1.0 --- ---
    21 Uraemia, chronic globerulonephritis 13 M 23 0.6 0.7 2.4
    22 Diabetes, Staph. septicaemia 20 F 51 0.7 0 0
    23 Bronchogenia carcinoma 16 M 55 0.9 --- ---
    24 Carcinoma head of pancreas 12 M 57 1.0 1.4 5.2
    25 Bronchogenia carcinoma 15 M 59 0 --- ---
    26 Myocardial infarc., hypercholesteroliama12 F 59 0 0 0
    27 Carcinoma of tongue 15 M 60 0 --- ---
    28 Hypertension 12 F 621.3 1.2 4.3
    29 Bronchogenia carcinoma 41 M 63 1.1 1.1 1.7
    30 Diabetes, hypertension, cerebral hemorrhage 26 F 65 0.6 0.3 0.8
    31 Thrombosis of the r.int. carotid artery -- M 66 0.2 0.1 0
    32 Uraemia, chronic globerrulonephritis 8 M 66 0.5 --- 0.7
    33 Staph. pyogenes bronchopneumonia 13 F 75 0 0 0
    34 Thrombosis of the r.int. carotid artery 7 M 80 0 0 0
    35 Cerebral astrocytoma 2 M 80 0.4 0.1 0.6
    36 Prostatic carcinoma 4 M 82 0 0 0
    37 Bronchopneumonia 11 F 87 0 --- ---

    Conclusions

    1. A gross and often complete deficiency of ascorbic acid frequently exists in the arteries of apparently well-nourished hospital autopsy subjects. Old age seems to accentuate the deficiency.
    2. The ascorbic acid depletion is probably not nutritional, but rather related to the stress of the fatal illness
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