Vitamin C

Volume II

Alan B. Clemetson

• Publisher: CRC Press
• Year: 2018
• Print ISBN: 9781315898476
• eBook ISBN: 9781351094474
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

The factors affecting blood vitamin C levels are described in detail in this series. Many factors such as aging, smoking, infection, trauma, surgery, hemolysis, hormone administration, heavy metals, pregnancy, alcohol, ionizing radiation and several medicines have been found to cause a disturbance of ascorbic acid metabolism and to reduce blood vitamin C levels. Indeed, abnormalities of ascorbic acid metabolism, due to factors such as smoking, occur much more frequently than does dietary vitamin C deficiency today.It is now known that low blood vitamin C levels are associated with histaminemia (high blood histamine levels), and also that ascorbate-responsive histaminemia is common in apparently healthy people. High blood histamine levels are believed to cause small hemorrhages within the inner walls of the blood vessels and these may lead to the deposition of cholesterol, as an aberrant form of wound healing. Ascorbic acid not only reduces blood histamine levels, but also aids the conversion of cholesterol to bile acids in the liver. The clinical pathological and chemical changes observed in ascorbic acid deficiency are discussed in detail. Several diseases and disorders associated with low blood vitamin C levels are also described. Possible toxic effects resulting from the oxidation of ascorbic acid are noted, and reasons for the use of D-catechin or other chelating fiber to prevent or minimize the release of ascorbate-free radical are detailed. An excellent reference for physicians, nutritionists and other scientists

Chapter 1

I. CLINICAL SIGNS

VASCULAR CHANGES

Bleeding gums, swollen discolored interdental papillae, bruises, large ecchymoses, subperiosteal hematomata, and painful swollen joints are the classical signs of naturally occurring human scurvy. The same signs are seen in guinea pigs after 2 or 3 weeks on an ascorbic acid-deficient diet, but for some reason, these signs are very late to develop in experimentally produced human ascorbic acid deficiency. All are manifestations of “capillary fragility”, which is supposedly the characteristic defect in scurvy; yet clinical examination of the ten volunteers of the Sheffield experiment described by Krebs (1953) revealed none of these signs during the first 17 weeks of total ascorbic acid deprivation. Moreover, no evidence of “capillary fragility” was detectable during that time. After 21 weeks, six of the ten deprived volunteers had developed hyperkeratosis and plugging of the hair follicles of the arms and legs; these enlarged hair follicles subsequently became red, developed petechial hemorrhages, and turned purple.

In fact, after 7 and 8 months of total ascorbic acid deprivation, when two volunteers developed precordial pain and electrocardiographic changes indicative of serious cardiac emergencies (Chapter 24, Volume III), multiple skin petechiae and acne were the main clinical manifestations of scurvy, and the general fitness of the other eight subjects still appeared to be fairly good. Perhaps ascorbic acid deficiency finds our weak spots; certainly the hearts seem to have been the weak spots in these two individuals.

The observations that scurvy does not seem to affect the gums of edentulous infants or old people, but does sooner or later affect the gums of those with teeth, suggest that focal sepsis arising from particles of decaying food between the tooth and the gum may precipitate local signs of scurvy. The foul mouth of scurvy is seen sooner in those with carious teeth and later in those with good dental hygiene.

While we know that classical scurvy can be cured with vitamin C, the evidence that it is usually caused by vitamin C deficiency alone is less obvious. Fox et al. (1940) found plasma ascorbic acid levels in a group of healthy South African miners to be just as low as in a group of miners with frank scurvy. Moreover, Prunty and Vass (1943) conducted urinary saturation tests and found that some nonscorbutic subjects had an ascorbic acid deficiency greater than that of a patient with scurvy. Could it be that a residual trace of ascorbic acid, if it is in the reduced form, can maintaian a normal redox potential in the tissues, but a residual trace of ascorbic acid all in the oxidized form means scurvy?

As so many early writers have noted, scurvy is often precipitated by infection or by other adverse conditions, many of which have been discussed in Volume 1. For instance, infants who are but mildly ascorbic acid deficient may quite rapidly develop scurvy as a result of an infection. A simple method of detecting the prescorbutic state would be very valuable, for petechial hemorrhages are so late to develop, and it seems to be the existence of preclinical scurvy over an extended period of time that predisposes to atherosclerosis and amyloid disease with all their attendant problems, such as coronary thrombosis, cerebral degeneration, and cerebral thrombosis or hemorrhage.

II. MICROVASCULAR FRAGILITY

There seems to be no question that the petechial hemorrhages and the ecchymoses in the skin and the periarticular and subperiosteal hemorrhages of scurvy are due to fragility of the small blood vessels, actually the small venules. However, there does not seem to be any really reliable skin test for measuring what is variously known as capillary fragility, capillary strength, or capillary resistance which can be used to detect the prescorbutic state.

Rumpel (1909) suggested the idea of diagnosing scarlet fever by means of a capillary fragility test; a compression band placed around the upper arm caused the appearance of petechiae at the usual location of the scarlet fever rash, in the antecubital fossa. This test was further elaborated by Rumpel’s assistant, Leede (1911), but there was no means of obtaining an exact pressure.

Hess (1913) and Hess and Fish (1914) introduced the idea of using a sphygmomanometer cuff and described the appearance of many petechiae in the forearm skin of children with scurvy after the application of 80 or 90 mmHg pressure to their upper arms for 3 min. This led to the development of the “Hess test” for capillary fragility, in which a cuff is applied to the upper arm at 100 mmHg for 5 min and a count is made of the number of petechial hemorrhages subsequently appearing in a circle of skin 2.5 cm in diameter in the antecubital fossa.

Stephan (1921) observed positive capillary fragility tests during menstruation and in many diseases besides scurvy; these included scarlet fever, measles, influenza, smallpox, and acute polyarthritis. Nevertheless, Öhnell (1928) found the Hess test to assist in the diagnosis of subclinical scurvy.

According to Göthlin, it was Boye (1929) who introduced the idea of inflating the sphygmomanometer cuff to a pressure midway between the systolic and diastolic arterial pressures, but Göthlin (1931) gave his reasons for preferring to use an infradiastolic pressure, thus avoiding any impairment of arterial blood flow, occluding only the venous return. He usually used a 50-mmHg pressure for 15 min and counted the petechiae subsequently developing in a 6-cm circle in the bend of the elbow (or 4 cm for children). Seven or more petechiae were considered as an abnormal result.

Using his test on a group of 50 children, 11 to 14 years of age, from the free municipal schools of Uppland in Sweden, Göthlin found abnormal capillary fragility in 11; test results of 9 of them were restored to normal within 3 weeks by the simple means of adding an orange a day to their diets. So it would seem that 18% of the children had been ascorbic acid deficient in April and May when this study was conducted. Studying a man aged 47 and a woman aged 38 in a mental institution, he showed that capillary fragility developed after 2 months on reduced ascorbic acid intakes provided by 0.2 and 0.4 cc of orange juice per kilogram of body weight per day, or 13 and 24 ml of orange juice a day, respectively, and that their capillary strengths returned to normal within a few weeks when 0.7 and 1.0 cc of orange juice per kilogram of body weight per day, or 45 and 61 ml of orange juice per day, were provided as minimum antiscorbutic doses.

Hess (1932) stated that, “there are decided individual variations in regard to the reaction to this test, so that although it is true that petechial spots are far more numerous in individuals suffering from latent or active scurvy, the reaction cannot be used as evidence of a deficiency in vitamin C intake.” This is certainly true as thrombocytopenic purpura and acute infectious fevers, such as measles and scarlet fever, also cause capillary fragility; moreover, individual variation is a major factor affecting the results.

Dalldorf (1933) used a small suction cup for a negative pressure test. The cup had a 1-cm inside diameter and a broad lip to allow firm adhesion to the skin; it was applied to the outer surface of the arm at a set pressure for a period of 1 min; the resistance of the capillaries was expressed as the least negative pressure required to produce visible petechiae. Using this method, he estimated that 35 to 66% of children from poor homes in Valhalla, NY, had subclinical scurvy, but he stated that a “consistent feature of the measurements of capillary resistance has been the difference between persons.” He observed that the character of the skin itself partly determines the results of the tests. Dalldorf and Russel (1935) studied both old and young residents of a county home in Valhalla and found that those with capillary fragility all showed an increase in capillary resistance following intravenous injection of 100 mg of ascorbic acid and that this was maintained for several days. They offered these findings as evidence that subclinical scurvy was the most common cause of capillary fragility.

Wright and Lilienfeld (1936) described their own modification of the Göthlin test, requiring a tourniquet on the upper arm to be inflated to a pressure midway between the systolic and diastolic blood pressures for 15 min; petechiae were counted 5 min later in an outlined circular area 2.5 cm in diameter with its upper margin 4 cm below the elbow crease. A normal petechial count is rarely above ten. These authors wrote that, “No laboratory or physical finding has been nearly as helpful in following the clinical course of this group of patients (scorbutics) as the capillary fragility test standardized as described.”

Using Dalldorf’s suction cup method, Roberts et al. (1937) made 5 observations during 1 year on each of 85 children living in an institution near Chicago. The mean capillary strength fell from a high of 46 cmHg in August to a low of 33 cmHg in April; these values coincided closely with the vitamin C intakes of the children, but the authors could not prove a cause and effect relationship.

Göthlin (1937) described a modification of his infradiastolic positive pressure test in which an upper arm cuff is inflated, first to 35 mmHg for 15 min and then an hour later to 50 mmHg for 15 min; petechiae counted within a 6 cm circle in the antecubital fossa after the lower pressure test are scored as 2 each and all petechiae which appear only after the higher pressure test are scored as 1; the two scores are added together. Scores above 8, after inspection with a 5-diopter lens in daylight, are considered as indicating capillary fragility; if the count observed in healthy persons was decreased by 30% or more following 6 d of treatment with ascorbic acid, 300 mg daily, then Göthlin would diagnose the capillary fragility as having been due to vitamin C deficiency.

Bell et al. (1940) used the positive pressure test of Göthlin (1931); the petechial count was found to be affected by the area of skin selected and also on the intensity of the illumination used for inspection. Another problem, common to all positive pressure cuff tests, is that one cannot repeat the test on the same arm for a period of time; one must wait to be sure that all local vascular damage has had time to heal. Göthlin (1933) allowed 2 to 4 weeks between tests. Wright and Lilienfeld (1936) allowed 8 d, but Eddy (1972) has suggested that more than 6 months may be required for complete healing of petechial hemorrhages in elderly vitamin C-deficient individuals.

Negative pressure tests using a 2-cm suction cup, as in the Brown (1949) modification of the Dalldorf resistometer, have the advantage that one can carry out repeated tests on neighboring areas of skin using the thin skin of the inner aspect of the upper arm or the antecubital fossa. However, the results obtained are sometimes contradictory; one may obtain a positive test result at 10 cmHg followed by a negative result at 20 cmHg a few minutes later.

Lavollay and Sevestre (1945) found ascorbic acid to have a positive action on the capillary resistance of both scorbutic and normal guinea pigs, but many workers, including Abt et al. (1936), Farmer (1940, 1944), Crandon et al. (1940), and Rapaport et al. (1940), have found capillary fragility measurements to be unreliable as an index of vitamin C deficiency in human subjects. Reviewing the literature on this subject, Munro et al. (1947) noted that negative responses to capillary fragility te...

Table of contents

• Cover
• Title Page
• Copyright Page
• Table of Contents
• CLINICAL AND PATHOLOGICAL FINDINGS IN ASCORBIC ACID DEFICIENCY
• Chapter 1 Vascular Changes
• Chapter 2 Diabetes Mellitus
• Chapter 3 Anemia
• Chapter 4 Defective Wound Healing
• Chapter 5 Bone Changes
• Chapter 6 Joint Lesions
• Chapter 7 Dental and Periodontal Changes
• Chapter 8 Atherosclerosis
• Chapter 9 Mental Depression
• Chapter 10 Amyloid
• Chapter 11 Venous Thrombosis
• Chapter 12 Decreased Resistance to Infection
• Chapter 13 Liver, Bile, and Gallstones
• INDEX