Relationship between levels of blood lipids, vitamins C, A, and E, serum copper compounds, and urinary excretions of tryptophan metabolites in women taking oral contraceptive therapy.

To evaluate which women using oral contraceptive agents might be at risk, biochemical indices known to be affected by the estrogens and progestogens were studied in women who take oral contraceptive agents, in women who do not use oral contraceptive agents, in women in third trimester of pregnancy and 6 weeks after parturition, and in men with normal and high blood lipid levels. The most consistent changes due to oral contraceptive agents were in serum levels of copper, triglycerides, and vitamin A and in the urinary excretion of xanthurenic acid and niacin derivatives before and after a tryptophan load test. There was only a slight suggestion, with no statistical significance, that serum vitamin C levels decreased when the serum levels of ceruloplasmin were high. The highest blood pressures and serum triglycerides and vitamin A levels were obtained in those women who ingested the highest level of estrogens. Pregnant women had the lowest levels of serum vitamin A. The oral contraceptive agents users had the lowest average levels of carotenoids corresponding to the highest average levels of vitamin A in the serum. Thus, estrogens not only increase the rate of change of tryptophan to niacin but may also increase the rate of conversion of carotene to vitamin A. Relative reactivity to oral contraceptive agents and possible risk to a patient might be evaluated by a profile of blood pressure and serum triglycerides, copper, and vitamin A.

PIP: To determine if methods can be developed which will show those patients for whom oral contraceptive agents (OCAs) constitute a hazard, data on blood lipids, serum levels of Vitamis-A, E, and C and copper are reported. Results of the tryptophan load test are also given. This tes t is related to the levels of pyridoxine in the tissues. The program was designed to show the relationship of any changes to each other, and to get a better understanding of their significance. Results are compared from subjects taking OCAs, from those not taking OCAs, from women in the last trimester of pregnancy, from women after parturition, and from males. All blood and urine samples were taken at 21 days after the beginning of subjects' menstrual periods, except for those who were pregnant and males. There were 49 women taking a variety of OCAs. 32 not taking OCAs served as controls. Included were 22 pregnant women in the last trimesters of their pregnancies. Of these, 11 were tested again 6 weeks postpartum. 9 men with high blood lipids and 12 men with normal lipid levels were also tested. Diastolic blood pressures averaged higher in the group taking OCAs (p less than .01), except for the males who were older or who wer known to have high lipids. Serum cholesterol levels in OCA users were unaltered. Serum phospholipids showed some increase in OCA users (p less than .05). Triglycerides show ed the greatest increase in OCA users (p less than .001), especially in those taking the most estrogen. The pregnant women had high serum levels of cholesterol, triglycerides, phospholipids, and total lipids. All of these levels were found to be less at 6 weeks postpartum. Serum copper levels were increased in all OCA users to above 1.5 mcg/ml but in only 2 of the nonusers to this level. Serum Vitamin-A was increased in the OCA user group (p less than .001). The pregnant women had relatively low levels of Vitamin-A. This increased by 6 weeks after parturition to the level of OCA users. An 8-hour urine collection after a 2-g tryptophan load showed at 6 times increased excretion of xanthurenic acid in those using OCAs as compared with nonusers. An increased ability of pregnant women to convert tryptophan to nictionic acid was shown. It is not known to what degree the biological changes caused by OCAs are undesirable. However, it is assumed that women showing the greatest changes are at greater risk. Analyses which may serve as incicators of potential risk include serum triglycerides, copper, and Vitamin-A levels. Carbohydrate intolerance and triglyceride elevation have been associated. Blood pressure measurements should be included in any profile.

Oral contraceptives and ascorbic acid.

Plasma, leukocyte, and platelet ascorbic acid levels are decreased in women ingesting oral contraceptive steroids. Studies have shown that it is the estrogenic component of the oral contraceptive agents that is associated with the decresased ascorbic acid concentrations. Urinary excretion of ascorbic acid does not appear to be increased by the steroids. Although serum levels of copper are increased by estrogens and oral contraceptives, ascorbic acid catabolism does not appear to be increased (unpublished). Our preliminary data on tissue uptake of ascorbic acid suggest that changes in tissue distribution are one possible answer for the observed effects of the steroids on blood levels of ascorbic acid.

PIP: Plasma, leukocyte and platelet ascorbic acid levels have been shown to decrease in in women using oral contraceptives (OC). Supplemental ascorbic acid therapy ranging from 50-200 mg/day showed no difference between the values for supplemented and nonsupplemented OC use. Measurement of plasma ascorbic acid after supplementation with 500 mg ascorbic acid/day for 14 days showed that adequate supplementation to reach tissue saturation and maximum fasting plasma levels occurred in control subjects but not in OC users. Other studies indicated that when women were maintained for 75 days on high ascorbic acid intake, the plasma levels in OC users were lower than in controls. Studies in humans and animals suggest that the estrogen in OCs cause decreased plasma and tissue levels of ascorbic acid. Women taking oral progestin (.35 mg daily norethisterone) and depot progestin (150 mg medroxyprogesterone acetate im every 3 months) had similar leukocyte plasma and platelet levels of ascorbic acid to controls. 625 mg daily of conjugated estrogens showed lower plasma and leukocyte levels than controls. Whereas increase of urinary excretion of ascorbic acid during OC therapy has not been shown, an increase in serum copper levels has been shown under OC use and estrogen influence. It is suggested that an increased catabolism of ascorbic acid accounts for the decreased plasma and tissue levels in humans and animals with estrogen or OC steroids. Other unconfirmed or disputed suggestions include decreased absorption, changes in tissue distribution and decreased levels of reducing compounds. Tissue uptake patterns in steroid-treated animals appear altered suggesting that changes in tissue distribution may be associated with observed changes in ascorbic acid blood levels in OC users.

Plasma reduced and total ascorbic acid in healthy women: effects of smoking and oral contraception.

This is the first report of both reduced (RAA) and total (TAA) plasma ascorbic acid levels in women who smoke and are on oral contraception. 155 normal healthy subjects were investigated. A study questionnaire was completed including age, method of contraception, smoking status, and food intake at breakfast, prior to attending the clinic. Biochemical assays were promptly carried out without knowledge of subject's clinical or dietary status. One-way analysis of variance revealed that oral contraception per se, barrier or IUD methods have no effect on plasma ascorbic acid levels. The mean values (mg/dl +/- SD) for plasma RAA between smokers and nonsmokers were 0.512 +/- 0.241 and 0.601 +/- 0.263; and that for TAA were 0.565 +/- 0.232 and 0.682 +/- 0.231, respectively. Significant decreases in both plasma RAA (p less than 0.05) and TAA levels (p less than 0.001) were observed in smokers. Age was an interacting variable. No association of smoking or oral contraceptive use was seen with RAA or TAA levels among women less than 26 years, but decreases in both RAA and TAA levels were evident among smokers aged 26 years or older. The present study emphasizes the total exposure to smoking, e.g., pack years, is a significant confounding variable in the study of plasma ascorbic acid levels.

An improved method for the measurement of leucocyte ascorbic acid concentrations.

PIP: An improved method for measuring leucocyte ascorbic acid concentrations which employs sodium metrizoate instead of dextraven for separation of red blood cells out of the supernatant fluid is described. Results of duplicate analyses by the dextraven and metrizoic methods are described in school children, students, adults, and geriatric subjects, and it is shown that consistent results are obtained by both methods. Parallel analyses were performed onthe same samples of blood by the two methods. The metrizoic method gave values for leucocyte ascorbic acid concentrations 1.6 times as high as those obtained by the dextraven method. The time required for separation of the red cells was 3 times as long and contamination of the supernatant fluid with red blood cells was much greater in the dextraven method. The longer period required for separation of red cells in the dextraven method allowed a greater release of ascorbic acid from the leucocytes into the supernatant fluid than in the metrizoic method. This accounts for the higher leucocyte ascorbic acid concentrations found in the metrizoic method.^ieng

The effect of vitamin C supplementation on lactating women in Keneba, a West African rural community.

A study of vitamin C requirements was undertaken in the village of Keneba, The Gambia, during the rainy season, when the intake of vitamin C-rich foods is very low. The effect of four supplementary levels of vitamin C (0, 24, 47 and 60 mg/day), together with a milk and biscuit food supplement which provided 34 mg vitamin C/day, was studied for a five-week period. Plasma ascorbate increased from 0.25 to 0.72 mg/dl; buffy coat ascorbate increased from 14.7 to 24.3 micrograms/10(8) cells and breast milk ascorbate increased from 3.4 to 5.5 mg/dl as intake increased from 34 to 103 mg/dl. Breast milk ascorbate approached a plateau at the high intakes. A fasting plasma ascorbate of at least 0.3 mg/dl in 97.5% of the population of lactating women in Keneba would require a daily vitamin C intake of about 117 mg. No differences between vitamin C supplementation levels were observed with respect to changes in plasma iron, total iron-binding capacity or its percentage saturation. Whole blood histamine levels showed a slight downward trend as the vitamin C intake increased.

Effect of exogenous testosterone propionate & progesterone on testicular ascorbic acid & cholesterol in relation to spermatogenesis.

PIP: The effect of exogenous testosterone propionate (TP) and progesterone on testicular ascorbic acid and cholesterol in relation to spermatogenesis was investigated in rat, mouse, guinea pig, pigeon, and toad. TP and progesterone were injected at a dose of 4 mg/100 gm body weight. The results revealed a significant increase (p less than .001 or p less than .05) in testicular ascorbic acid and cholesterol levels after treatment in all species of animals except the toad where the cholesterol level decreased after progesterone treatment. Histologically, these hormones inhibited spermatogenesis in all species studied.^ieng

Cholesterol and ascorbic acid in semen under varied clinical conditions.

PIP: Fresh semen samples were collected from a total of 269 individuals attending the Family Welfare Planning Clinic. 29 had azoospermia following vasectomy, 12 had azoospermia due to spermatogenic defect, and the remainder had varying grades of sperm density and motility. Physical and morphological evaluations of the semen samples were made. Ascorbic acid was estimated in whole semen by the method of Roe an Kuether. Total cholesterol in plasma was determined. The total cholesterol concentration showed a gradual decline in the group with sperm count of 1-20 million/ml to the lowest level in the group with a count of 61-80 million. It then increased progressively up to the counts of 101-120 million/ml. Ascorbic acid concentration was significantly higher in patients with azoospermia due to defective spermatogenesis. The azoospermic specimens of vasectomized individuals contained significantly higher level of ascorbic acid than in dysspermatogenic azoospermia. The percentages of motile sperm in samples were unrelated to either cholesterol or ascorbic acid concentrations.^ieng

[Vitamin C determination in urine samples during sex cycle as a way of evaluating the ovulation date]. / Przydatnosc oznaczania witaminy C w moczu w przebiegu cyklu plciowego u kobiet dla rozpoznawania jajeczkowania.

PIP: Concentrations of Vitamin-C in the urine were determined in 35 women, 25 with normal ovulation and 10 with anovulatory cycles, in an attempt to evaluate the day of ovulation. The concentration was determined daily for 8 days after the oral administration of 500 mg of ascorbic acid. Results were confirmed by comparing the urine content of ascorbic acid with concentrations of luteinizing hormone determined in simulataneous serological tests. This method of ovulatory diagnostics proved to be effective and simple.^ieng

Effect of oral contraceptives on ascorbic acid status of young women consuming a constant diet.

PIP: The effects of various combined oral contraceptives (OCs) on plasma, leukocyte, and urinary levels of ascorbic acid were studied in 10 well-nourished women. Based on dietary records, prestudy ascorbic acid intake ranged from 100 to 500 mg/day. By the end of the 1st day of treatment, no marked alterations in plasma or leukocyte ascorbic acid levels, or in tissue ascorbic acid absorption, were observed. After the subjects had lived in a metabolic unit for 8 or 12 days, in which they received a constant diet containing about 155 mg/day ascorbic acid, there was still no marked differences between the treatment group and controls in plasma, leukocyte, and urinary ascorbic acid. The results are contrary to previously reported findings which suggest that OC use adversely affects ascorbic acid status.^ieng

Effects of oral contraceptives on vitamin metabolism.

PIP: Literature on the effects of oral contraceptives (OCs) on vitamin metabolism is reviewed. OCs have been reported to markedly increase serum levels of Vitamin-A. OCs may induce a thiamine deficiency and lower levels of Vitamin-B2. Concentrations of ascorbic acid in platelets, white cells, plasma, and urine are decreased by OCs. Decreased plasma and red blood cell concentrations of folic acid have been reported in OC users, though it does not appear that absorption of folate polyglutamate is affected. OC users may develop megaloblastic anemia because of folic acid deficiency. OCs have been reported to markedly reduce serum levels of Vitamin-B12. Some OC users who excrete abnormal amounts of tryptophan metabolites have some degree of true Vitamin-B6 deficiency. Evidence of altered tryptophan metabolism and/or absolute Vitamin-B6 deficiency has been found in emotionally depressed women taking OCs. OCs, especially estrogens, produce tryptophan metabolism abnormalities in the great majority of users. An effect of OCs on alpha-tocopherol plasma concentrations has yet to be demonstrated in humans.^ieng