ORAL CORTICOSTEROIDS

Safetychecker Summary for Oral Corticosteroids
(for details about the summarized interactions, read the full article)

May be Beneficial: Depletion or interference—The medication may deplete or interfere with the absorption or function of the nutrient. Taking these nutrients may help replenish them.	Calcium Chromium Magnesium Melatonin Potassium Selenium Vitamin B6 Vitamin D
May be Beneficial: Side effect reduction/prevention—Taking these supplements may help reduce the likelihood and/or severity of a potential side effect caused by the medication.	Chromium Vitamin A
May be Beneficial: Supportive interaction—Taking these supplements may support or otherwise help your medication work better.	N-acetyl cysteine (NAC)*
Avoid: Reduced drug absorption/bioavailability—Avoid these supplements when taking this medication since the supplement may decrease the absorption and/or activity of the medication in the body.	Ephedra* Magnesium
Avoid: Adverse interaction—Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.	Alcohol Sodium
Check: Other—Before taking any of these supplements or eating any of these foods with your medication, read this article in full for details.	Alder buckthorn* Buckthorn* Licorice Vitamin A* Vitamin C* Vitamin K* Zinc* Diuretic herbs* Grapefruit juice Laxative herbs* Protein

Interactions with Dietary Supplements

Magnesium
Corticosteroids may increase the body’s loss of magnesium.¹ Some doctors recommend that people taking corticosteroids for more than two weeks supplement with 300–400 mg of magnesium per day. Magnesium has also been reported to interfere with the absorption of dexamethasone.²

N-acetyl cysteine (NAC)
One preliminary study found that in people with fibrosing alveolitis (a rare lung disease), supplementation with 600 mg N-acetyl cysteine three times per day increased the effectiveness of prednisone therapy.³

Potassium
Oral corticosteroids increase the urinary loss of potassium.⁴ This may not cause a significant problem for most people. Individuals who wish to increase potassium intake should eat more fruits, vegetables, and juices rather than taking over-the-counter potassium supplements, which do not contain significant amounts of potassium.

Vitamin A
In some people, treatment with corticosteroids can impair wound healing. In one study, topical or internal vitamin A improved wound healing in eight of ten patients on corticosteroid therapy.⁵ In theory, vitamin A might also reverse some of the beneficial effects of corticosteroids, but this idea has not been investigated and no reports exist of such an interaction in people taking both vitamin A and corticosteroids. People using oral corticosteroids should consult with a doctor to determine whether improved wound healing might outweigh the theoretical risk associated with concomitant vitamin A use.

Although blood levels of vitamin A appear to increase during dexamethasone therapy⁶ —most likely due to mobilization of the vitamin from its stores in the liver—evidence from animal studies has also indicated that corticosteroids can deplete vitamin A from tissues.⁷

Vitamin B6
Corticosteroids may increase the loss of vitamin B6.⁸ One double-blind study of people with asthma failed to show any added benefit from taking 300 mg per day of vitamin B6 along with inhaled steroids.⁹ Therefore, while small amounts of vitamin B6 may be needed to prevent deficiency, large amounts may not provide added benefit. Some doctors recommend that people taking corticosteroids for longer than two weeks supplement with at least 2 mg of vitamin B6 per day.

Calcium and Vitamin D
Oral corticosteroids reduce absorption of calcium¹⁰ and interfere with the activation and metabolism of the vitamin,^{11 12 13 14} increasing the risk of bone loss. Doctors can measure levels of activated vitamin D (called 1,25 dihydroxycholecalciferol) to determine whether a deficiency exists; if so, activated vitamin D is only available by prescription. A study of rheumatoid arthritis patients treated with low amounts of prednisone found that those who received 1,000 mg of calcium per day plus 500 IU of vitamin D per day for two years experienced no bone loss during that time period.¹⁵ An analysis of properly conducted trials concluded that supplementation with vitamin D and calcium was more effective than placebo or calcium alone in protecting against corticosteroid-induced osteoporosis.¹⁶ Most doctors recommend 1,000 mg of calcium and 400–800 IU vitamin D per day for the prevention of osteoporosis.

Chromium
Preliminary data suggest that corticosteroid treatment increases chromium loss and that supplementation with chromium (600 mcg per day in the form of chromium picolinate) can prevent corticosteroid-induced diabetes.¹⁷ Double-blind trials are needed to confirm these observations.

Melatonin
A controlled trial found that a single dose of the synthetic corticosteroid dexamethasone suppressed production of melatonin in nine of 11 healthy volunteers.¹⁸ Further research is needed to determine if long-term use of corticosteroids interferes in a meaningful way with melatonin production, and whether supplemental melatonin would be advisable for people taking corticosteroids.

Sodium
Oral corticosteroids cause both sodium and water retention.¹⁹ People taking corticosteroids should talk with their doctor about whether they should restrict salt intake.

Other nutrients
Oral corticosteroids have been found to increase urinary loss of vitamin K, vitamin C, selenium, and zinc.^{20 21} The importance of these losses is unknown.

Interactions with Herbs

Buckthorn, Alder Buckthorn (Rhamnus catartica, Rhamnus frangula, Frangula alnus)
Use of buckthorn or alder buckthorn for more than ten days consecutively may cause a loss of electrolytes (especially the mineral potassium). Because corticosteroids also cause potassium loss, buckthorn or alder buckthorn should be used with caution if corticosteroids are being taken.²²

Ephedra sinica (Ma huang)
Ephedrine is a chemical that occurs naturally in the herb ephedra and is also available as a drug product. Ephedrine enhances the removal of dexamethasone from the body, thereby decreasing the drug’s activity;²³ whether the herb ephedra also has this effect is unknown. Until more is known, people taking dexamethasone should avoid both ephedra and ephedrine-containing products.

Licorice (Glycyrrhiza glabra)
Licorice extract was shown to decrease the elimination of prednisone in test tube studies.²⁴ If this action happens in people, it might prolong prednisone activity and possibly increase prednisone-related side effects. A small, controlled study found that intravenous (iv) glycyrrhizin (an active constituent in licorice) given with iv prednisolone prolonged prednisolone action in healthy men.²⁵ Whether this effect would occur with oral corticosteroids and licorice supplements is unknown.

An animal study has shown that glycyrrhizin prevents the immune-suppressing actions of cortisone—the natural corticosteroid hormone produced by the body.²⁶ More research is necessary to determine if this action is significant in humans taking oral corticosteroids. Until more is known, people should not take licorice with corticosteroids without first consulting a doctor.

Diuretic herbs
Use of corticosteroids may be associated with loss of certain minerals, called electrolytes. Herbs with a diuretic action (i.e., they promote fluid loss from the body through an increase in urine production) may accelerate the electrolyte loss caused by corticosteroids.²⁷ Such herbs include asparagus root, butcher’s broom, cleavers, corn silk, juniper, mate, and parsley. This interaction is theoretical and has not been reported in the medical literature.

Laxative herbs
Like diuretic herbs, herbs with a laxative action could theoretically increase electrolyte loss associated with corticosteroid use.²⁸ Such herbs include aloe, buckthorn, cascara sagrada, rhubarb, and senna. This interaction is theoretical and has not been reported in the medical literature.

Interactions with Foods and Other Compounds

Food
Corticosteroids can cause stomach upset and should be taken with food.²⁹

Protein
Oral corticosteroids can cause loss of body protein. For this reason, medical doctors sometimes recommend a high-protein diet for people taking these drugs.³⁰ However, people with diseases that cause kidney damage should not consume too much protein, as this could worsen their condition. A high-protein diet should be used only after consulting a doctor.

Alcohol
Corticosteroids can irritate the stomach, and alcohol can enhance this adverse reaction.³¹

Grapefruit juice
Taking methylprednisolone with grapefruit juice has been shown to delay the absorption and increase the blood concentration of the drug.³² The mechanism by which grapefruit juice increases the concentration of methylpredniolone in the blood is not known, but it is suspected that it may interfere with enzymes in the liver responsible for clearing the drug from the body. In certain people, grapefruit juice may, therefore, enhance the effects of methylprednisolone. The combination should be avoided unless approved by the prescribing doctor.

1. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 83.

2. Naggar VF, Khalil SA, Gouda MW. Effect of concomitant administration of magnesium trisilicate on GI absorption of dexamethasone in humans. J Pharm Sci 1978;67:1029–30.

3. Behr J, Maier K, Degenkolb B, et al. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression. Am J Respir Crit Care Med 1997;156:1897–901.

4. Thelkeld DS, ed. Hormones, Adrenal Cortical Steroids, Glucocorticoids. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1991, 128b.

5. Hunt TK, Ehrlich HP, Garcia JA, Dunphy JE. Effect of vitamin A on reversing the inhibitory effect of cortisone on healing of open wounds in animals and man. Ann Surg 1969;170:633–40.

6. Shenai JP, Mellen BG, Chytil F. Vitamin A status and postnatal dexamethasone treatment in bronchopulmonary dysplasia. Pediatrics 2000;106:547–53.

7. Georgieff MK, Radmer WJ, Sowell AL. The effect of glucocorticosteroids on serum, liver, and lung vitamin A and retinyl ester concentrations. J Pediatr Gastroenterol Nutr 1991;13:376–82.

8. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 83.

9. Sur S, Camara M, Buchmeier A, et al. Double-blind trial of pyridoxine (vitamin B6) in the treatment of steroid-dependent asthma. Ann Allergy 1993;70:147–52.

10. Hahn TJ, Halstead LR, Baran DT. Effects off short term glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab 1981;52:111–5.

11. Trovato A, Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician 1991;44:1651–8 [review].

12. Chesney RW, Mazess RB, Hamstra AJ, et al. Reduction of serum-1,25-dihydroxyvitamin-D, in children receiving glucocorticoids. Lancet 1978;ii:1123–5.

13. Nielsen HK, Eriksen EF, Storm T, Mosekilde K. The effects of short-term, high-dose prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in monocytes from normal human subjects. Metabolism 1988;37:109–14.

14. Avioli LV. Serum 25-hydroxyvitamin D concentrations in patients receiving chronic corticosteroid therapy. J Lab Clin Med 1977;23:399–404.

15. Buckley LM, Leib ES, Cartularo KS, et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996;125:961–8.

16. Amin S, LaValley PM, Simms RW, Felson DT. The role of vitamin D in corticosteroid-induced osteoporosis. Arthritis Rheum 1999;42:1740–51.

17. Ravina A, Slezak L, Mirsky N, et al. Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium. Diabet Med 1999;16:164–7.

18. Demisch L, Demisch K, Nickelsen T. Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 1987;5:317–22.

19. Sifton DW, ed. Physicians Desk Reference, Montvale, NJ: Medical Economics Company, Inc., 2000, 1765–6.

20. Buist RA. Drug-nutrient interactions—an overview. Int Clin Nutr Rev 1984;4:114 [review].

21. Peretz AM, Neve JD, Famaey JP. Selenium in rheumatic diseases. Semin Arthritis Rheum 1991;20:305–16 [review].

22. European Scientific Cooperative on Phytotherapy (ESCOP). Frangulae cortex, frangula bark. Monographs on the Medicinal Uses of Plant Drugs. Exeter, UK: University of Exeter, Centre for Complementary Health Studies, 1997.

23. Jubiz W, Meikle AW. Alterations of glucocorticoid actions by other drugs and disease states. Drugs 1979;18:113–21.

24. Tamura Y, Nishikawa T, Yamada K, et al. Effects of glycyrrhetinic acid and its derivatives on delta-4–5-alpha- and 5-beta-reductase in rat liver. Arzneimittelforschung 1979;29:647–9.

25. Chen MF, Shimada F, Kato H, et al. Effect of glycyrrhizin on the pharmacokinetics of prednisolone following low dosage of prednisolone hemisuccinate. Endocrinol Jpn 1990;37:331–41.

26. Kumagai A, Nanaboshi M, Asanuma Y, et al. Effects of glycyrrhizin on thymolytic and immunosuppressive action of cortisone. Endocrinol Jpn 1967;14:39–42.

27. Wallace J. A model for drug/nutrient synergies: focus on cortisone drugs. Int J Integrative Med 2000;2:33–9.

28. Blumenthal M (ed.). The Complete German Commission E Monographs. Boston: American Botanical Council, 1998, pp.475–7.

29. Threlkeld DS, ed. Hormones, Adrenal Cortical Steroids, Glucocorticoids. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1991, 128b.

30. Trovato A, Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician 1991;44:1651–8 [review].

31. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 82.

32. Varis T, Kivisto KT, Neuvonen PJ. Grapefruit juice can increase the plasma concentrations of oral methylprednisolone. Eur J Clin Pharmacol 2000;56:489–93.

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Copyright © 2002 Healthnotes, Inc.  All rights reserved. www.healthnotes.com

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over-the-counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2003.

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