Data provided by Applied Health
side effects, nutrient depletions, herbal interactions and health notes:
• Avoid consuming excessive potassium in foods and supplements when taking Lotensin, including salt substitutes.1
• Alcohol intake should be limited.2
• Lotensin may contribute to a deficiency in zinc. Supplementation may be considered.3
• Avoid arginine in conjunction with these agents, because there is a potential for hyperkalemia to develop.4
• It has been well established that birth control pills tend to cause folic acid depletion and that this can have several possible adverse repercussions, especially in terms of increased risk of cervical dysplasia and vascular thrombosis. » risk of cervical dysplasia: Butterworth et al published promising initial research from a three-month, double-blind, placebo-controlled trial where megadoses of folic acid (10,000 mcg daily) were associated with regression of cervical intraepithelial neoplasia (CIN) among users of oral contraceptives. However, later, Zarcone et al found that folic acid supplements did not alter the course of established cervical dyplasia. Further, at this time, no substantial evidence has been published to support the view that folate supplementation alone can play a significant role in the treatment of cervical cancer. In related research concerning Human Papilloma Virus (HPV), often associated with cervical dysplasia, Kwasniewska et al determined that statistically lower levels of folic acid were found in the women with CIN-HPV (+), and cited other studies that have shown that lower levels of antioxidants coexisting with low levels of folic acid increases the risk of CIN development. Even so, among women not using oral contraceptives, folic acid has not been found to improve abnormal Pap smears.5
• Folic acid deficiency enhances oral contraceptive-induced platelet hyperactivity. In various studies conducted in female rats and in women, oral contraceptives were found to induce a platelet hyperactivity that was related to an oxidative stress. Many researchers suspect oral contraceptives of depleting folate stores and point to cases of megaloblastic anemia which have been reported to occur in women taking oral contraceptives. Moreover, since folate is essential for the metabolism of the atherogenic amino acid homocysteine, the reduction of plasma and erythrocyte folate concentrations is also associated with a moderate hyperhomocysteinemia. Despite the limitations of some of these studies, several authors have suggested that in addition to cigarette smoking inadequate folic acid intake might predispose those taking oral contraceptives to cardiovascular disease such as vascular thrombosis and stroke.6
• : All women taking oral contraceptives could reduce their anti-folate effects through supplementation with folic acid at doses of 400-800 mcg per day. Supplementation with folate is especially important for women who stop using oral contraceptives with the intention (or simply the possibility) of becoming pregnant. Those who are diagnosed with cervical dyplasia or are concerned with increased risks of stroke might particularly benefit from incorporating folic acid into a therapeutic program under the care of a nutritionally trained healthcare professional7
• Several studies have reported an association between the use of oral contraceptives and increased serum levels of Vitamin A. Horwitt et al found that women using oral contraceptives had the lowest average levels of carotenoids corresponding to the highest average levels of vitamin A in the serum, and that estrogens seemed to increase the rate of conversion of carotene to vitamin A. The clinical implications of this potential interactions are uncertain at this time.8
• The use of oral contraceptives may be associated with decreased levels of Vitamin B1. While thiamine levels have not been consistently lower in women on oral contraceptives compared to controls, urinary thiamin levels have been found to be higher in those women on oral contraceptives who also took supplements. The clinical implications of this potential interaction are uncertain at this time.9
• The use of oral contraceptives can be associated with decreased levels of Vitamin B2. The clinical implications of this potential interaction are uncertain at this time. However, insufficient intake of riboflavin is associated with an increased risk of cervical dysplasia. The supplemental levels of riboflavin, 20-25 mg, found in most multi-vitamins are probably adequate to compensate for any potential deficiency due to the use of oral contraceptives.10
• The use of oral contraceptives can be associated with decreased levels of vitamin B3. The clinical implications of this potential interaction are uncertain at this time. However, the tryptophan pathway involving vitamin B6 that is interfered with by oral contraceptives leads to niacin. Consequently, deficiencies of vitamin B6 due to the use of oral contraceptives could lead to a subsequent decrease in the formation of niacin from tryptophan and an increased risk of niacin deficiency. In a related study of a long-acting low dose injectable contraceptive Bamji et al reported a peculiar aberration in the tryptophan-niacin pathway as indicated by rise in kynurenic acid excretion after tryptophan load was observed.The supplemental levels of niacin, 10-25 mg, found in most B-complex or multi-vitamin supplements are probably adequate to compensate for any potential deficiency due to the use of oral contraceptives.11
• Oral contraceptives have been associated with vitamin B6 depletion and depression, most likely associated with interference in the role that vitamin B6 plays in facilitating the tryptophan to niacinamide pathway. In a 1973 double-blind study of women using oral contraceptives who were diagnosed with depression, Adams et al found that 20 mg per day vitamin B6 was associated with decreased depression, especially among the 50% of the women in the study who demonstrated a measurable vitamin B6 deficiency. Subsequent research by Brown, Rose and Adams indicated that oral contraceptives may not directly change the requirement for vitamin B6; instead, supplementation with B6 may prevent a contraceptive-induced change in the activity of enzymes in the pathway of tryptophan metabolism and thereby promote an improvement in glucose tolerance. In regard to adverse cardiovascular effects of oral contraceptives, it is also important to note that pyridoxal 5-phosphate is essential for the metabolism of the atherogenic amino acid homocysteine.Women taking oral contraceptives could reduce their adverse effects upon Pyridoxine levels, and subsequent outcomes such as increased incidence and severity of premenstrual syndrome, through supplementation with vitamin B6. While the typical supplemental dose for pyridoxine is 10-25 mg per day, higher levels in the range of 200-500 mg per day may be indicated in instances such as the use of oral contraceptives where preventive and therapeutic requirements are greater. Women using oral contraceptives and interested in gaining the benefits of Vitamin B6 supplementation should consult with their prescribing physician and/or a nutritionally trained healthcare provider.12
• The use of oral contraceptives, especially those with higher estrogen content, has been consistently associated with decreased levels of vitamin B12. The clinical implications of this potential interaction are uncertain at this time. However, in regard to adverse cardiovascular effects of oral contraceptives, it is also important to note that vitamin B12 is essential for the metabolism of the atherogenic amino acid homocysteine. Women taking oral contraceptives could reduce their adverse effects upon cobalamin levels through supplementation with vitamin B12. While supplemental use of vitamin B12 is not usually considered necessary for most of the population, the suggested dose of cobalamin in vegans is 2-3 mcg per day, and higher levels in the range of 50-200 mcg per day may be indicated in instances such as the use of oral contraceptives. Women using oral contraceptives and interested in potential benefits from vitamin B12 supplementation should consult with their prescribing physician and/or a nutritionally trained healthcare provider.13
• The use of oral contraceptives has been consistently associated with decreased levels of vitamin C as a result of their interference with the metabolism of ascorbic acid. The clinical implications of this potential interaction are uncertain at this time. However, insufficient intake of ascorbate is associated with an increased risk of cervical dysplasia. Some researchers have voiced concern that high doses of ascorbic acid, more than one gram per day, might induce unintentionally high plasma concentrations of ethinylestradiol as the two substances compete for sulfation in the gut wall and the vitamin C interferes with conversion of ethinyl estradiol (EE2) to its sulfates. However, Kuhnz et al reported the absence of an effect of high oral doses of vitamin C on the systemic availability of ethinylestradiol in women using a levonorgestrel-containing combination oral contraceptive. Similarly, Zamah et al had found that an absence of an effect of high vitamin C dosage on the systemic availability of ethinyl estradiol in women using a combination oral contraceptive.Women taking oral contraceptives could reduce their adverse effects upon ascorbate levels through supplementation with vitamin C. While suggested supplemental dose for ascorbate is usually 500-1000 mg per day, higher levels in the range of 1000-2000 mg per day may be indicated in instances such as the use of oral contraceptives. Women using oral contraceptives and interested in potential benefits from Vitamin C supplementation should consult with their prescribing physician and/or a nutritionally trained healthcare provider.14
• Various studies have found that the use of oral contraceptives is most often associated with increased absorption of calcium. In a randomized, controlled clinical trial, amenorrheic subjects using oral contraceptives demonstrated significantly improved spine and total body bone mineral measurements at 12 months than did those in groups receiving medroxyprogesterone or placebo. However, in a study looking at bone mineral density (BMD), Hartard et al found that while the highest BMD values were found in the group of women characterized by long-term exercise and short use of contraceptives, but no such beneficial effect of exercise on BMD was found in the group with a long exercise period and long-term intake of contraceptives.15
• Research has consistently found the use of oral contraceptives as being positively associated with increased absorption of copper and increased serum copper concentration. Even though higher serum copper concentration in women using oral contraceptives is well known, there is still uncertainty about the influence of newer progestin compounds in oral contraceptives on serum copper concentration. In a study involving low-estrogen preparations, Liukko et al noted that copper levels rose significantly while using oral contraception over a 2 year period, but returned to initial levels after the contraceptives were discontinued. In a more recent epidemiological study of 610 nonpregnant and nonlactating women, Berg et al reported that while elevated serum copper concentration was found in users of all types of oral contraceptives, elevation was more pronounced among women taking oral contraceptives with antiandrogen effective progestins like antiandrogens or third generation oral contraceptives containing desogestrel.Recent epidemiological studies have shown an increased mortality from cardiovascular diseases in people with higher serum copper levels. This issue is of particular interest in the light of recent findings of an increased risk of venous thromboembolism in users of oral contraceptives containing newer progestins like desogestrel compared to users of other oral contraceptives.16
• Among women using oral contraceptives, the volume of blood loss associated with menstrual flow is usually decreased. Palomo et al found that use of oral contraceptive pills was not associated with hemoglobin decrease but they did observed a significant rise in saturation of transferrin. While increased iron levels in the blood are not necessarily a problem, over time this decreased monthly blood loss can result in increased iron stores. Consequently, premenopausal women using oral contraceptives may have a decreased need for supplemental iron. Such women would be advised to have their iron levels monitored and consult with their prescribing physician before using supplements containing iron.17
• Though contradictory findings have been published, the oral contraceptives may interfere with manganese absorption. The clinical implications of this potential interaction are uncertain at this time.18
• Research indicates that oral contraceptives interfere with Selenium absorption. Heese et al conducted a study involving 200 female students, half of whom had been taking low-dosage triphasic contraceptive medication for a minimum of 3 months. The differences in mean serum selenium concentrations were statistically significant. Given the emerging literature on the beneficial role of selenium in the prevention of cancer, especially breast cancer, the adverse implications of contraceptive-induced decreases in selenium levels becomes increasingly significant. Apart from supplementation of selenium, intake levels are primarily dependent on the levels of selenium in the soil where foods have been grown. As a nutritional supplement, many nutritionally trained healthcare professionals recommend 100-200 mcg of selenium as the appropriate daily adult dose. Nevertheless, women using oral contraceptives and interested in compensatory selenium supplementation would benefit from consulting with their prescribing physician and/or a nutritionally trained healthcare provider.19
• : The use of oral contraceptives has been associated in some studies with decreased levels of Zinc. The clinical importance of these potential interactions remains unclear. In most individuals moderate supplemental intakes of zinc, 15-25 mg, will prevent deficiencies. The potential for decreased zinc levels due to use of oral contraceptives may raise caution as to the need for higher doses. In such instances supplementation would most likely be in the range of 50 mg taken three times daily. Women using oral contraceptives and interested in potential benefits from zinc supplementation should consult with their prescribing physician and/or a nutritionally trained healthcare provider.20
• Some herbs possess cardiac properties that may interact with the action of Lotensin and may result in an excessive lowering of blood pressure or increased side effects. Such herbs include: black hellebore, calamus, cereus, cola, coltsfoot, devil's claw, European mistletoe, fenugreek, fumitory, digitalis leaf, hedge mustard, figwort, lily of the valley roots, motherwort, pleurisy root, squill bulb leaf scales, white horehound, mate, scotch broom flower, shepherd's purse, and wild carrot21
• Avoid natural licorice products, Ginseng, and Ephedra (Ma huang) which may contribute to high blood pressure.22
• The combined effect of smoking and using birth control pills presents a significantly increased risk suffering a fatal heart attack for women. Research demonstrates a 500% increase in the risk of a fatal heart attack when smoking is added to the risks associated with oral contraceptives alone. These risks are particularly heightened among women over the age of thirty-five who face an especially greater risk of death due to circulatory disease, especially stroke, from the combination of birth control pills and smoking. These contraceptive-related risks may be even greater among those patients with a history of migraines. Fundamentally, the multitude of risks for disease and death associated with smoking are significantly aggravated by the concurrent use of oral contraceptives.23
References1 Burnakis TG & Mioduch HJ: Combined therapy with captopril and potassium supplementation. A potential for hyperkalemia. Arch Intern Med 1984; 144:2371-2372.
1 Good CB, McDermott L, McCloskey B. Diet and serum potassium in patients on ACE inhibitors. JAMA 1995;274:538.
2 Pronsky, ZM: Food-Medication Interactions, 11th edition, 1999
3 Golik A, Zaidenstein R, Dishi V, et al: Effects of captopril and enalapril on zinc metabolism in hypertensive s, J Am Coll Nutr, 1998, 17(1):75-8.
3 Golik A, Modai D, Averbukh Z, et al: Zinc metabolism in patients treated with captopril versus enalapril, Metabolism, 1990, 39(7): 665-7.
4 McKevoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
5 (Butterworth CE, et al. Am J Clin Nutr 1980;33:926; Butterworth CE Jr, et al. JAMA 1992 Jan 22-29;267(4):528-533; Butterworth CE Jr, et al. Am J Clin Nutr 1982 Jan;35(1):73-82; Harper JM, et al. Acta Cytol 1994 May-Jun;38(3):324-330; Lindenbaum J, et al. Am J Clin Nutr 1975 Apr;28(4):346-353; Zarcone R, et al. Minerva Ginecol 1996 Oct;48(10):397-400; Kwasniewska A, et al. Eur J Gynaecol Oncol 1997;18(6):526-530; Prasad AS, et al. Am J Obstet Gynecol 1976 Aug 15;125(8):1063-1069.)
6 (Durand P, et al. Arterioscler Thromb Vasc Biol 1997 Oct;17(10):1939-1046; Harper JM, et al. Acta Cytol 1994 May-Jun;38(3):324-330; Lewis DP, et al. Ann Pharmacother 1998 Jul-Aug;32(7-8):802-817; Lindenbaum J. Curr Concepts Nutr 1983;12:73-87; Pietarinen GJ, et al. Am J Clin Nutr 1977 Mar;30(3):375-380; Prasad AS, et al. Am J Clin Nutr 1975 Apr;28(4):385-391; Prasad AS, et al. Am J Obstet Gynecol 1976 Aug 15;125(8):1063-1069.)
8 (Mooij PN, et al. Contraception 1991 Sep;44(3):277-288; Cumming FJ, Briggs MH. Br J Obstet Gynaecol 1983 Jan;90(1):73-77; Wynn V. Lancet 1975 Mar 8;1(7906):561-564; Horwitt MK, et al. Am J Clin Nutr 1975 Apr;28(4):403-412
9 (Prasad AS, et al. Am J Clin Nutr 1975 Apr;28(4):385-391.)
10 Wynn V. Lancet 1975 Mar 8;1(7906):561-564
11 (Leklem JE, et al. Am J Clin Nutr 1975 Feb;28(2):146-156; Bamji MS, et al. Contraception 1981 Jan;23(1):23-36.)
12 (Rose DP, et al. Am J Clin Nutr 1975 Aug;28(8):872-878; Adams PW, et al. Lancet 1973 Apr 28;1(7809):899-904; Adams PW, et al. Lancet 1976 Apr 10;1(7963):759-764; Brown RR, et al. Acta Vitaminol Enzymol 1975;29(1-6):151-157; Wynn V, et al. J Steroid Biochem 1975 Jun;6(6):965-970; Leklem JE, et al. Am J Clin Nutr 1975 Feb;28(2):146-156; Rose DP, et al. J Clin Pathol 1972 Mar;25(3):252-258.)
13 (Hjelt K, et al Acta Obstet Gynecol Scand 1985;64(1):59-63; Wynn V. Lancet 1975 Mar 8;1(7906):561-564; Steegers-Theunissen RP, et al. Gynecol Obstet Invest 1993;36(4):230-233; Shojania AM, Wylie B. Am J Obstet Gynecol 1979 Sep 1;135(1):129-134.)
14 Wynn V. Lancet 1975 Mar 8;1(7906):561-564; Matsui MS, Rozovski SJ. Clin Ther 1982;4(6):423-440; Briggs MH. Br Med J (Clin Res Ed) 1981 Dec 5;283(6305):1547.)
14 (Shenfield GM. Drug Saf 1993 Jul;9(1):21-37; Back DJ, Orme ML. Clin Pharmacokinet 1990 Jun;18(6):472-484; Kuhnz W, et al. Contraception 1995 Feb;51(2):111-116; Zamah NM, et al. Contraception 1993 Oct;48(4):377-391.)
15 (Hergenroeder AC, et al. Am J Obstet Gynecol 1997 May;176(5):1017-1025; Hartard M, et al. Contraception 1997 Feb;55(2):87-90.)
16 (Liukko P, et al. Gynecol Obstet Invest 1988;25(2):113-117; Horwitt MK, et al. Am J Clin Nutr 1975 Apr;28(4):403-412; Berg G, et al. Eur J Clin Nutr 1998 Oct;52(10):711-715.)
17 (Masse PG, Roberge AG. Contraception 1992 Sep;46(3):243-252; Masse PG, et al. Int J Vitam Nutr Res 1998;68(3):203-207; Mooij PN, et al. Int J Clin Pharmacol Ther Toxicol 1992 Feb;30(2):57-62; Frassinelli-Gunderson EP, et al. Am J Clin Nutr 1985 Apr;41(4):703-712; Palomo I, et al. Rev Med Chil 1990 May;118(5):506-511; Steegers-Theunissen RP, et al Gynecol Obstet Invest 1993;36(4):230-233.)
18 (Heese HD, et al. S Afr Med J 1988 Feb 6;73(3):163-165.)
19 (Heese HD, et al. S Afr Med J 1988 Feb 6;73(3):163-165.)
20 (Holt GA. 1998, 197-198; Werbach MR. 1997, 210-11; Wynn V. Lancet 1975;1:561-564; King JC. J Nutr 1987 Jan;117(1):217-219.)
21 Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-care Professionals. London: The Pharmaceutical Press, 1996.
21 Facts and Comparisons, The Review of Natural Products, Clinisphere 2.0, Wolters Kluwer Company, 2000
21 PDR for Herbal Medicines, 2nd edition, Medical Economics Company, 2000
22 Pronsky, ZM: Food-Medication Interactions, 11th edition, 1999
22 Brinker, F Herb Contraindications and Drug Interactions, Eclectic Medical Publications, 1998
23 (Lewis DP, et al. Ann Pharmacother 1998 Jul-Aug;32(7-8):802-817; Threlkeld DS, ed. Jul 1994; Barinagarrementeria F, et al. Eur Neurol 1998 Nov;40(4):228-233; Becker WJ. Can J Neurol Sci 1997 Feb;24(1):16-21; Salmeron P, et al. Rev Neurol 1997 Jul;25(143):1003-1007.)
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The information in Drug Watch is provided as a courtesy to NewsTarget readers by Applied Health Solutions in cooperation with Healthway Solutions. Although the information is presented with scientific references, we do not wish to imply that this represents a comprehensive list of considerations about any specific drug, herb or nutrient. Nor should this information be considered a substitute for the advice of your doctor, pharmacist, or other healthcare practitioner. Please read the disclaimer about the intentions and limitations of the information provided on these pages. It is important to tell your doctor and pharmacist about all other drugs and nutritional supplements that you are taking if they are recommending a new medication. Copyright © 2007 by Applied Health Solutions, Inc. All rights reserved.