The beta blockers, propranolol and metoprolol, have been shown to inhibit CoQ10-dependent enzymes (Kishi, 1977). In a small clinical trial, administration of 60 mg per day of CoQ10 appeared to reduce the incidence of drug-induced malaise in patients receiving propranolol (Hamada, 1984). In another study, supplementation with 90 mg per day of CoQ10 reduced the cardiovascular side effects of an ophthalmic solution of timolol in patients with glaucoma. In healthy volunteers, CoQ10 did not impair the effectiveness of ophthalmic timolol in lowering intraocular pressure (Takahashi, 1989).
CoQ10 has also been reported to decrease the cardiotoxicity of doxorubicin (Adriamycin) and other anthracyclines (daunorubicin and adryblastin) in both animals (Domae, 1981) and humans (Judy, 1984; Cortes, 1978; Iarussi, 1994). Anthracycline cardiotoxicity appears to result in part from depletion of CoQ10 or interference with its action in cardiac mitochondria, effects that can be reversed by CoQ10 supplementation (Ogura, 1979; Combs, 1977). CoQ10 did not interfere with the anticancer effect of doxorubicin (Conklin, 2005). To the contrary, since the use of doxorubicin is frequently limited by its cardiotoxicity, preventing cardiotoxicity could allow for an increase in the doxorubicin dosage, which would enhance its anticancer effect.
In men with combined hyperlipidemia, treatment with gemfibrozil significantly decreased serum CoQ10 levels, even after adjustment for serum cholesterol levels (Aberg, 1998). The clinical significance of this finding is not clear.
Administration of CoQ10 (10 mg per kg of body weight per day intraperitoneally) decreased gentamicin-induced nephrotoxicity in rats (Upaganlawar, 2006). CoQ10 (100 mg per kg per day intraperitoneally) also decreased the ototoxicity of gentamicin in guinea pigs (Fetoni, 2012).
Hydroxymethylglutaryl (HMG)-CoA reductase inhibitors (statin drugs) inhibit cholesterol synthesis by blocking the conversion of HMG-CoA to mevalonic acid. The biosynthesis of CoQ10 also requires mevalonic acid as a precursor. Therefore, treatment with statin drugs may inhibit CoQ10 synthesis. Statins have been reported in most (Ghirlanda, 1993; Bargossi, 1994; Rundek, 2004; Folkers, 1990; Miyake, 1999; Colquhoun, 2005) , but not all (Bleske, 2001), studies to lower plasma CoQ10 levels.
In an uncontrolled trial, supplementation with 100 mg per day of CoQ10 resolved statin-induced muscle pain in 3 of 18 patients (Caso, 2007). However, double-blind trials using 100-400 mg per day of CoQ10 have produced conflicting results: a significant improvement in symptoms (Fedacko, 2013; Skarlovnik, 2014; Bookstaver, 2012), or equivocal outcomes (Young, 2007; Bogsrud, 2013). In another randomized trial, administration of a high dose (600 mg per day) of ubiquinol (the reduced form of CoQ10) appeared to exacerbate muscle pain in patients with simvastatin-induced myalgia (Taylor, 2015). A systematic review and meta-analysis published in 2020 included 8 studies (321 patients) and concluded that CoQ10 does not benefit myalgia from statin therapy or improve adherence to statin treatment (Kennedy, 2020).
A meta-analysis of 6 studies (n=302) on the effects of CoQ10 on statin induced myopathy found an insignificant increase in plasma CK activity and only a trend toward a decrease in muscle pain compared to the control group (Banach, 2015). Forty one subjects who developed muscle pain while participating in a RCT with simvastatin vs. placebo were randomized to simvastatin 20 mg/d with either CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks (Taylor, 2015). Before and after treatment muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured. Only 36% of patients on the statin complained of muscle pain, and CoQ10 did not reduce muscle pain in that group.
A product containing red yeast rice extract, berberine, policosanol, astaxanthin, coenzyme Q10, and folic acid (Armolipid Plus) was given to 30 patients with moderate dyslipidemia and metabolic syndrome in an 8-week randomized double-blinded crossover trial (Ruscica, 2014). They either took the Armolipid Plus or placebo then underwent 8 weeks of treatment with pravastatin10 mg per day. There was a significant reduction in lipids with the Armolipid Plus similar to pravastatin (total cholesterol -12.8 vs. -16 %, LDL -21.1% vs. -22.6% and an increase in HDL 4.8%).
In summary, CoQ10 alone has not been found to significantly improve symptoms of myopathy in patients on statins. One small trial showed an improvement in lipids when CoQ10 was used in a combination product (Ruscica, 2014).
Nucleoside reverse transcriptase inhibitors are known to cause mitochondrial dysfunction. In HIV-infected patients being treated with a nucleoside reverse transcriptase inhibitor, supplementation with CoQ10 (100 mg twice a day for 3 months) improved general well-being compared with placebo, but appeared to aggravate pain in patients with peripheral neuropathy (Rabing Christensen, 2004).
There have been several case reports in which supplementation with CoQ10 appeared to interfere with the effect of warfarin (Landbo, 1998; Spigset, 1994). In rats, administration of CoQ10 (10 mg per kg of body weight per day for 8 days) decreased the effect of warfarin, apparently by increasing the serum clearance of the drug (Zhou, 2001). However, in a double-blind trial, administration of 100 mg per day of CoQ10 for 4 weeks had no effect on the International Normalized Ratio (INR) in 21 patients on long-term warfarin therapy (Engelsen, 2002). Thus, the sporadic case reports of an interaction between CoQ10 and warfarin may have been due to random fluctuations in INR values, rather than to CoQ10.
In a case report, supplementation with CoQ10 relieved muscle symptoms in an HIV-infected man with zidovudine-induced myopathy (Rosenfeldt, 2005).
Beta blockers suppress nighttime melatonin secretion, which might explain why these drugs sometimes cause insomnia. Treatment with melatonin (2.5 mg each night for 3 weeks) has been reported to improve beta blocker-associated insomnia (Scheer, 2012).
Treatment with melatonin (2 mg of a controlled-release preparation 2 hours before bedtime for 6 weeks) has been reported to facilitate withdrawal from benzodiazepines in patients with insomnia (Garfinkel, 1999). However, other studies have not duplicated this effect and a 2015 systematic review and meta-analysis that included 6 randomized controlled trials with 322 participants found that melatonin did not improve the odds of successful benzodiazepine discontinuation (Wright, 2015).
Co-administration of fluvoxamine and melatonin markedly increased the bioavailability of melatonin in healthy male volunteers (Härtter, 2000). This is due to the fact that fluvoxamine inhibits CYP1A2, the primary metabolic enzyme of melatonin.
Melatonin has been reported to decrease olanzapine-induced weight gain and to improve psychiatric symptoms in patients with schizophrenia (Modabbernia, 2014).
In patients receiving nifedipine in the morning for hypertension, administration of melatonin at night increased blood pressure, suggesting that melatonin may interfere with the antihypertensive effect of nifedipine (Lusardi, 2000).
Both aspirin and fish oil (which contains EPA and DHA) inhibit platelet aggregation. Combining fish oil and aspirin has been reported both to increase (Larson, 2008) and decrease (Jakubowski, 1979) the anti-aggregatory effect of these substances when given by themselves. There have been no reports of a clinically significant increase in bleeding risk associated with the use of aspirin and fish oil in combination (as compared with aspirin alone), for example, Hull, 2018.
Although nonsteroidal anti-inflammatory drugs (NSAIDs) and omega-3 fatty acids each inhibit inflammation by affecting prostaglandin synthesis or metabolism, concurrent treatment with an NSAID did not diminish or enhance the beneficial effect of omega-3 fatty acids in patients with rheumatoid arthritis (Kjeldsen-Kragh, 1992).
Both clopidogrel and the omega-3 fatty acids present in fish oil are platelet inhibitors. Clopidogrel is an inactive drug that must be metabolized by hepatic cytochrome P450 enzymes to its active form. The antiplatelet effect of clopidogrel is reduced in people who have a common loss-of-function polymorphism of the cytochrome P450 enzyme, CYP2C19. Patients who have this polymorphism are frequently prescribed a higher-than-normal dose of clopidogrel. A supplement providing 460 mg per day of EPA and 380 mg per day of DHA potentiated the anti-platelet effect of clopidogrel in patients who had the CYP2C19 loss-of-function polymorphism, but not in patients who did not have this polymorphism (Gajos, 2012). That finding raises two possibilities for patients who have the CYP2C19 loss-of-function polymorphism. First, combining fish oil with a standard dose of clopidogrel might be an effective treatment strategy. Second, the addition of fish oil to a higher-than-normal dose of clopidogrel might result in excessive inhibition of platelet function.
Treatment with SAMe (200 mg 3 times per day) prevented the increase in the bile cholesterol saturation index and reversed abnormalities of liver function tests in women taking oral contraceptives (Di Padova, 1984; Frezza, 1987). These findings suggest that SAMe may help prevent oral contraceptive-induced gallstones and hepatotoxicity.
Administration of omeprazole decreased beta-carotene absorption in healthy volunteers, presumably because it reduced gastric acid secretion (Tang, 1996). It might be expected that other drugs that decrease gastric acidity would also decrease beta-carotene absorption.
Treatment with bile salt sequestrants such as cholestyramine and colestipol may decrease intestinal absorption of fat-soluble nutrients, including vitamin A and beta-carotene (Probstfield, 1985).
Isotretinoin (13-cis retinoic acid) may interfere with the processing of vitamin A in the retina. In a case report, a teenager with cystic fibrosis who had been receiving long-term oral vitamin A supplementation developed night blindness after starting isotretinoin for cystic acne. The night blindness resolved after the dosage of vitamin A was increased (Welsh, 1999).
Cyclosporine and alkylating chemotherapies have evidence for reducing vitamin E levels. Low vitamin E levels have been associated with an increased risk of chemotherapy-associated toxicity. However, no good systematic reviews have provided adequate evidence for vitamin E supplementation during chemotherapy (Jonas, 2000; Pace, 2003; Ladas, 2004).
In children with liver transplants, co-administration of a water-soluble liquid vitamin E preparation (D-alpha-tocopherol-polyethylene-glycol-1000 succinate [TPGS]; Eastman Chemical Products, Inc., Kingsport, TN) with oral cyclosporine significantly increased cyclosporine levels by 83%, compared with administration of cyclosporine alone. Chronic administration of TPGS allowed for a 40-72% reduction in the cyclosporine dose in 4 of 6 children with liver transplants (Weijl, 1998).
In a case report, supplementation with 1,200 IU per day of vitamin E for 2 months appeared to enhance the effect of warfarin. In a partially double-blind trial, however, of 13 patients who received 800-1,200 IU per day of vitamin E for 4 weeks, none had an increase in their International Normalized Ratio (INR). In contrast, of 4 patients who received placebo, 2 had an increase in their INR (which seemed to suggest a potentiation of the effect of warfarin). One of these increases met the criteria for a probable drug effect, and the other met the criteria for a possible drug effect. The authors of this report concluded that it is difficult in sporadic case reports to conclude that a change in INR or prothrombin time is caused by a specific warfarin-nutrient interaction. In another study, administration of 100-400 IU per day of vitamin E for 4 weeks had no effect on coagulation parameters in 12 patients receiving warfarin. Thus, it seems unlikely that vitamin E in doses up to 1,200 IU per day potentiates the effect of warfarin in humans (Kim, 1996).
Treatment with anticonvulsants may promote the development of vitamin D deficiency (Lee, 2015; Nettekoven, 2008). Anticonvulsant-induced vitamin D deficiency may contribute to the low bone mineral density and osteomalacia that are seen in some epileptic patients. The dosage of vitamin D required to maintain a serum 25(OH)D level of at least 15 ng/ml varied considerably in patients taking anticonvulsants, from 400-4,000 IU per day (Collins, 1991).
Treatment with anti-tuberculosis drugs (i.e., isoniazid and rifampicin) may interfere with vitamin D metabolism (Bengoa, 1984) and lead to biochemical evidence of vitamin D deficiency (Kovacs, 1994).
Hypercalcemia resulting from excessive vitamin D intake might precipitate cardiac arrhythmias in patients taking digoxin (Garabedian-Ruffalo, 1984).
Treatment with glucocorticoids may lower serum levels of 1,25(OH)2D (Chesney, 1978). Some (Buckley, 1996), but not all (Adachi, 1996), studies found that supplementation with calcium and vitamin D prevents glucocorticoid-induced bone loss.
In a case report, a 39-year-old female developed numbness and tingling in both feet and in the left leg while taking amitriptyline for depression. These side effects were controlled by taking 500 mg per day of pyridoxine in divided doses; 400 mg per day was ineffective (Meadows, 1982).
Certain anticonvulsants may promote the development of vitamin B6 deficiency (Meeuwisse, 1968; Mintzer, 2012). Conversely, administration of large doses of pyridoxine (80-200 mg per day) reduced serum phenytoin and phenobarbitone levels in epileptic children (Hansson, 1976). Pyridoxine is an effective treatment for epilepsy in some cases; however, it should be used with caution by patients taking anticonvulsants.
Laboratory evidence of vitamin B6 deficiency is common in women taking oral contraceptives (Thorp, 1980; Adams, 1976). In a double-blind trial, administration of pyridoxine (20 mg twice a day for 2 months) improved depression in women taking oral contraceptives who had laboratory evidence of vitamin B6 deficiency (Adams, 1973). However, pyridoxine did not relieve depression in women who did not have vitamin B6 deficiency (Adams, 1974).
In another study, supplementation with 100 mg per day of pyridoxine was of possible benefit in improving impaired glucose tolerance secondary to the use of oral contraceptives (Spellacy, 1972). However, another trial concluded that 1.5-5.0 mg per day of vitamin B6 appeared to be adequate to meet the needs of most oral contraceptive users (Bossé, 1979).
Hydralazine has been reported to interfere with vitamin B6 metabolism (Kirkendall, 1958). In case reports, 2 patients with hydralazine-induced peripheral neuropathy showed rapid and marked improvement after treatment with 25-50 mg per day of pyridoxine. Supplementation with pyridoxine did not inhibit the antihypertensive effect of hydralazine (Raskin, 1965).
Isoniazid can promote the development of vitamin B6 deficiency in a dose-dependent manner (Pellock, 1985). Pyridoxine at a dose of 50 mg per day almost totally prevented peripheral neuropathy resulting from treatment with large doses of isoniazid. Larger doses of pyridoxine were not more effective than 50 mg per day (Ross, 1958). In case reports, 3 patients developed pyridoxine-responsive anemia during treatment with isoniazid and p-aminosalicylic acid (McCurdy, 1966). It is not known whether vitamin B6 interferes with the therapeutic effect of isoniazid.
Vitamin B6 can exacerbate symptoms in parkinsonian patients who are taking levodopa by itself (i.e., without a peripheral decarboxylase inhibitor such as carbidopa), and is, therefore, contraindicated in such patients. The apparent explanation for this adverse interaction is that vitamin B6 increases the peripheral metabolism of levodopa, thereby decreasing the amount available for uptake into the brain (Leon, 1971). However, in patients taking levodopa with a peripheral decarboxylase inhibitor, vitamin B6 supplementation does not increase the peripheral metabolism of levodopa (because the peripheral metabolism is blocked) (Mars, 1974) and does not worsen symptoms of Parkinson's disease (Cotzias, 1971; Klawans, 1971). To the contrary, one group of investigators found that concurrent administration of 25 mg of pyridoxine enhanced the effect of levodopa in the presence of a peripheral decarboxylase inhibitor (Yahr71), presumably by increasing the conversion of levodopa to dopamine in the brain (Mars, 1972).
Parkinsonian patients receiving levodopa-carbidopa had a significantly lower mean plasma concentration of PLP (78 vs. 154 nmol/L; p < 0.02) and a significantly higher mean plasma homocysteine concentration (11.6 vs. 8.8 µmol/L; p < 0.02), when compared with parkinsonian patients not taking these drugs (Miller, 2003). In rats, administration of a large dose of carbidopa decreased serum and tissue levels of PLP (Airoldi, 1978).
The evidence reviewed above suggests that in patients with Parkinson's disease who are receiving levodopa-carbidopa, supplementation with a moderate dose of vitamin B6 (perhaps 25-50 mg per day) could correct marginally low vitamin B6 status while potentially improving neurological symptoms and protecting against the development of hyperhomocysteinemia.
Penicillamine has been reported to cause vitamin B6 deficiency, which may play a role in the development of penicillamine-induced neuropathy (Rothschild, 1982; Levy, 1982; Hollister, 1966).
Phenelzine acts as a vitamin B6 antagonist. In a case report, treatment with phenelzine was associated with the development of a sensorimotor peripheral neuropathy apparently secondary to vitamin B6 deficiency (Rumsby, 1979; Heller, 1983).
Tranylcypromine can form a Schiff base with PLP, rendering the vitamin inactive. In a case report, a patient developed carpal tunnel syndrome while taking tranylcypromine and improved after supplementing with 300 mg per day of pyridoxine (Harrison, 1983).
Administration of theophylline markedly decreased plasma concentrations of PLP in healthy volunteers, asthmatics, and experimental animals. Vitamin B6 deficiency may play a role in the development of some of the adverse effects of theophylline, including tremor and seizures (Ubbink, 1990; Bartel, 1994; Weir, 1990; Shimizu, 1994).
Pellagra (skin lesions, diarrhea, and disturbances in affect) has been reported as a side effect of long-term anticonvulsant therapy. In a case report, these side effects were reversed by supplementation with niacinamide (100 mg twice a day) plus a multivitamin (Lyon, 2002).
However, niacinamide in doses of 41-178 mg per kg of body weight per day has also been reported to inhibit the metabolism of primidone and carbamazepine in humans, which could potentially increase the toxicity of these drugs (Bourgeois, 1982).
Case reports have suggested that the use of niacin and statin drugs in combination increases the risk of adverse events (Alsheikh-Ali, 2007). In a randomized study of people with cardiovascular disease, low HDL-cholesterol levels, and hypertriglyceridemia, the combination of simvastatin and extended-release niacin, as compared with simvastatin plus placebo, increased the risk of ischemic stroke, gastrointestinal disorders, and hepatobiliary infections (Teo, 2013; Anderson, 2014).
Isoniazid has been reported to cause pellagra in malnourished individuals, which was reversible by supplementation with niacin or niacinamide. Isoniazid presumably interferes with vitamin B3 absorption or metabolism because of its structural similarity to niacinamide (Comaish, 1976; Darvay, 1999; Bender, 1979).
Anticonvulsants interfere with folic acid absorption and may cause folate deficiency. While correction of folate deficiency may improve the neurological side effects and some of the other side effects of anticonvulsants, administration of large doses of folic acid may decrease blood levels of phenytoin, phenobarbital, and carbamazepine, potentially interfering with seizure control. Folic acid mouth rinse (0.1% solution) has been used successfully to treat phenytoin-induced gingival hyperplasia (Drew, 1987), and oral administration of 0.5 mg per day of folic acid was effective for preventing gingival hyperplasia in children who had recently started taking phenytoin (Arya, 2011).
Folate deficiency, in some cases severe enough to cause megaloblastic anemia, has been reported in oral contraceptive users (Wynn, 1975). Megaloblastic changes in cervical epithelium resembling cervical dysplasia have also been observed in women taking oral contraceptives. These changes were reversed in some (Butterworth, 1980; Butterworth, 1982; Ran, 1990), but not all (Butterworth, 1992; Zarcone, 1996), studies by supplementation with 5-10 mg per day of folic acid.
Methotrexate is a folate antagonist. Folate deficiency increases susceptibility to the toxic effects of methotrexate. In patients with rheumatoid arthritis, administration of folic acid or folinic acid reduced methotrexate toxicity without decreasing its efficacy (Morgan, 1994; van Ede, 2001). However, folic acid supplementation may interfere with the efficacy of methotrexate in the treatment of cancer.
Trimethoprim may cause folate deficiency by inhibiting folic acid absorption and by inhibiting dihydrofolate reductase (an enzyme involved in the synthesis of the biologically active form of folic acid) (Zimmerman, 1987). Folic acid in typical doses does not appear to interfere with the antibacterial activity of trimethoprim.
Histamine-2 (H2) blockers and proton pump inhibitors (PPIs) have been reported to inhibit the absorption of vitamin B12 from food, but not the absorption of crystalline vitamin B12 from supplements (Salom, 1982; Steinberg, 1980; Streeter, 1982; Marcuard, 1994). This difference is due to the fact that the release of protein-bound vitamin B12 in food requires an acid environment for the action of proteolytic enzymes. In a case report, megaloblastic anemia secondary to vitamin B12 deficiency developed in a 51-year-old man who had taken omeprazole for 4 years (Bellou, 1996).
In guinea pigs, administration of colchicine decreased vitamin B12 absorption as a result of a decrease in the number of vitamin B12-intrinsic factor receptors in the intestinal mucosa (Stopa, 1979). It would be prudent to give a vitamin B12 supplement to patients on long-term treatment with colchicine.
Use of oral contraceptives may lead to a deficiency or a suboptimal serum level of vitamin B12 (Hjelt, 1985; Wertalik, 1972).
Metformin has been reported to inhibit the absorption of vitamin B12 in a dose-dependent manner (Al Amin, 2021). Discontinuation of the drug corrected vitamin B12 malabsorption in only about half of cases (Wulffelé, 2003; Adams, 1983; Tomkin, 1972). In a case report, a diabetic woman developed vitamin B12-responsive megaloblastic anemia after 8 years of metformin treatment (Callaghan, 1980).
Nitrous oxide oxidized vitamin B12 in vitro and interfered with the function of vitamin B12 in vivo (Amess, 1978). Administration of nitrous oxide to vitamin B12-deficient patients can precipitate significant neurological dysfunction (Nestor, 1996; Schilling, 1986). Because of the high cost of screening for vitamin B12 deficiency, it has been recommended that vitamin B12 be given perioperatively to all patients who are going to receive nitrous oxide, except perhaps patients receiving it for a very short period of time (Mayall, 1999).
Clinicians should be alert to B12 status amongst patients taking proton pump inhibitors (PPIs) (Al Amin, 2021; Stover, 2010). Prolonged PPI use in older adults causes a decrease in B12 status, which does not seem fully preventable by oral supplementation with RDA amounts of B12. Although histamine H2-receptor antagonists also decrease the absorption of vitamin B12, they do not seem to cause clinical vitamin B12 deficiency even after long-term use (Dharmarajan, 2008).
Co-administration of 2 g of vitamin C and aluminum hydroxide (an antacid), as compared with administration of aluminum hydroxide by itself, increased urinary excretion of aluminum, presumably because of an increase in intestinal aluminum absorption. In rats given aluminum hydroxide, co-administration of vitamin C increased the concentration of aluminum in liver, brain, and bone (Domingo, 1991). These observations raise the possibility that vitamin C increases the absorption of other forms of aluminum as well. Since aluminum may play a role in the pathogenesis of osteoporosis and Alzheimer's disease, vitamin C should not be taken at the same time as aluminum-containing antacids.
Administration of vitamin C (500 mg twice a day) to a man with low vitamin C levels who was receiving the neuroleptic drug, fluphenazine, for bipolar disorder resulted in a 25% decrease in plasma fluphenazine levels and a deterioration of his clinical condition (Dysken, 1979). In case reports, supplementation with vitamin C (2 g 3 times per day) appeared to reverse amenorrhea and irregular menses associated with neuroleptic use (Kanofsky, 1989).
Aspirin has been reported to increase urinary excretion of vitamin C and to decrease platelet vitamin C concentrations (Sahud, 1971). Vitamin C supplementation may therefore be beneficial for people on long-term aspirin therapy.
In patients receiving large doses of glucocorticoids, administration of 2 g per day of vitamin C corrected glucocorticoid-induced defects in polymorphonuclear neutrophil function, an effect that might help prevent the increase in susceptibility to infections associated with long-term glucocorticoid use (Chretien, 1973).
In a case report, supplementation with vitamin C appeared to enhance the efficacy of levodopa (Sacks, 1975).
In patients with a history of gastritis, ingestion of 500 mg of vitamin C along with levothyroxine appeared to increase the bioavailability of the drug (Jubiz, 2014).
In healthy volunteers, administration of 2 g of vitamin C 30 minutes before a dose of propranolol significantly reduced the bioavailability of the drug. This effect appeared to be due to a combination of decreased drug absorption and an alteration in drug metabolism (Gonzalez, 1995).
Administration of 500 mg of vitamin C along with 250 mg of tetracycline increased the blood level of tetracycline after 2 hours by 3- to 15-fold, compared with the level after administration of tetracycline alone. Similar effects were seen with oxytetracycline and chlortetracycline (Freinberg, 1957).
Thiazide diuretics decrease urinary calcium excretion. The use of thiazide diuretics might increase the risk of developing hypercalcemia in people taking large doses of calcium and vitamin D (Nojaba 2021; Drinka, 1984).
Calcium and some other minerals can bind to fluoroquinolones (such as ciprofloxacin, norfloxacin, levofloxacin, and gemifloxacin) and markedly reduce their absorption (Pletz, 2003; Jellin 1999). It is recommended that mineral-containing supplements not be taken within 1-2 hours before or 2-6 hours after taking fluoroquinolones (recommendations vary according to the drug being used). These recommendations also apply to high-calcium foods such as milk and calcium-fortified orange juice.
It is a common practice that people take their antibiotics with food to prevent an upset stomach, therefore it is helpful to provide the patient with recommendations of foods that will not inerefere with the medication. Examples include grains, meats or whole fruits. Dairy products including cheese and yogurt, fruit juices and fortified cereals should be avoided.
Simultaneous ingestion of calcium has been shown to inhibit the absorption of levothyroxine (Singh, 2000; Schneyer, 1998; Zamfirescu, 2011). It is recommended that levothyroxine be taken at least 1 hour before or 2-4 hours after the ingestion of substances that interfere with its absorption.
Many patients on thyroid medcations are unaware of this interaction, and thus take their medications with their morning meal or vitamins. It is helpful to provide suggestions for your patients to make their regimen more manageable such as taking thyroid medications first thing upon waking to lengthen the time between medication and food/supplements.
Concurrent administration of calcium or certain other minerals with tetracyclines may interfere with the absorption of the drugs (Mapp, 1976).
Supplementation with calcium and/or vitamin D can cause a recurrence of atrial fibrillation in patients receiving verapamil (Garabedian-Ruffalo, 1984).
In patients commencing glucocorticoid treatment, mean urinary chromium excretion increased by 57% after 3 days of treatment. Chromium supplementation (600 μg per day for 2 weeks, followed by 200 μg per day, as chromium picolinate) improved glycemic control in 38 of 41 patients with glucocorticoid-induced diabetes, even though the dosage of hypoglycemic medication was reduced by 50% (Ravina, 1999; Ravina, 1999). A study in rats confirmed the ability of chromium to improve glucocorticoid-induced abnormalities of glycemic control and insulin sensitivity (Kim, 2002).
The NIH Office of Dietary Supplements states there is potential for drug interactions with insulin, metformin and other diabetes medications; this interaction is still theoretical interactions as it is based on mechanism of action of chromium serum glucose levels (NIH, 2021).
The NIH Office of Dietary Supplements states there is potential for drug interactions with insulin, metformin and other diabetes medications; this interaction is still theoretical interactions as it is based on mechanism of action of chromium serum glucose levels (NIH, 2021).
Treatment with drugs that suppress gastric acid secretion may decrease the absorption of nonheme iron (Ito, 2010; Skikne, 1981).
Close surveillance for nutrient depletions in patients on long term PPI's is recommended. In particular patients with history of anemia on drugs that suppress gastric acid secretion should be advised about supplementation away from medications.
Iron supplementation (256 mg per day of ferrous sulfate for 4 weeks) reduced the severity of angiotensin-converting enzyme (ACE) inhibitor-induced cough (Lee, 2001). However, ingestion of iron at the same time as captopril decreased the absorption of unconjugated captopril (the active form of the drug), apparently because of a chemical interaction between ferric ions and captopril in the gastrointestinal tract (Schaefer, 1998).
Iron may decrease the absorption of bisphosphonates. Iron and bisphosphonates should therefore be taken at least 2 hours apart (Rx List, 2016).
Iron and other minerals can bind to fluoroquinolones (such as ciprofloxacin, norfloxacin, levofloxacin, and gemifloxacin) and markedly reduce their absorption (Marchbanks, 1993). It is recommended that mineral-containing supplements not be taken within 1-2 hours before or 2-6 hours after taking fluoroquinolones (recommendations vary according to the drug being used).
Iron forms chemical complexes with levodopa and carbidopa. Administration of 325 mg of ferrous sulfate along with levodopa/carbidopa reduced the bioavailability of levodopa by 30% and the bioavailability of carbidopa by more than 75% (Campbell, 1990). If a patient receiving levodopa/carbidopa requires iron supplementation, the iron should be taken several hours before or after administration of the drug.
Iron has been shown to inhibit the absorption of levothyroxine (Campbell, 1992), apparently by forming a complex with it. It is recommended that levothyroxine be taken at least 1 hour before or 2-4 hours after iron supplements.
Patients may benefit from specific guidance on separating medications from foods. In this case recommending that levothyroxine is taken upon waking and iron in the evening helps to identify the need for these to substances to be apart from each other.
Iron decreases the absorption of penicillamine by chelating it in the intestinal tract (Harkness, 1982).
Concurrent administration of iron with tetracyclines (including minocycline) may interfere with the absorption of the drugs (Mapp, 1976).
Of 115 children (aged 7-17 years; 87% males) treated with risperidone for a mean of 2.4 years, 59% had laboratory evidence of mild or frank iron deficiency (Calarge, 2013). That finding raises the possibility that risperidone depletes iron.
Proton pump inhibitors and, to a lesser extent, histamine-2 (H2) blockers may promote the development of magnesium deficiency (Regolisti, 2010; Hess, 2012; Markovits, 2014).
Angiotensin-converting enzyme (ACE) inhibitors may decrease urinary magnesium excretion (Stevenson, 1991). In patients taking ACE inhibitors, magnesium supplements should be used with caution and serum magnesium levels should be monitored.
Administration of the beta-2 agonists, salbutamol and rimiterol, decreased plasma magnesium and potassium levels in healthy volunteers (Phillips, 1980). The combination of a beta-2 agonist and theophylline may produce a greater degree of magnesium and potassium deficiency than would a beta-2 agonist alone (Smith, 1985). Drug-induced magnesium deficiency could explain in part the loss of efficacy of beta-2 agonists that occurs in some asthmatic patients receiving regular treatment with these drugs (Rolla, 1988). Deficiencies of magnesium and potassium might increase the risk of cardiac arrhythmias and sudden death in asthmatic patients treated with beta-2 agonists (Guideri, 1985).
Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone) and loop diuretics (e.g., furosemide, bumetanide) increase urinary magnesium excretion and in some cases cause clinically significant magnesium depletion (Wacker, 1961; Sheehan, 1982). Diuretic-induced magnesium deficiency may also decrease the effectiveness of the diuretic (Tan, 1983). In contrast, potassium-sparing diuretics (e.g., triamterene, spironolactone) may decrease urinary magnesium excretion (Devane, 1981).
Magnesium supplements can decrease absorption of oral bisphosphonates and therefore a 2 hour separation is recommended between the two (Dunn, 2001).
Although magnesium oxide is often prescribed for constipation in Parkinson's disease, magnesium can reduce the bioavailability of levodopa and carbidopa (Kashihara, 2019).
Magnesium can reduce the absorption of tetraclyclines since it forms insoluble complexes with these antibiotics in the gut (Sompolinsky, 1972). Separate magnesium supplementation and tetracyclines by 2 hours.
Selenium supplementation has been reported to decrease a number of side effects of cancer chemotherapy, including nephrotoxicity, bone marrow suppression, leukopenia, infections, hair loss, gastrointestinal symptoms, and muscle damage (Hu, 1997; Sieja, 2004; Asfour, 2006; Sundström, 1989; Ghorbani, 2013).
Administration of these common drugs for heart failure or hypertension may cause zinc deficiency by causing increased urinary excretion of zinc (Cohen, 2006). There have been some reported cases of loss of captopril to patients with essential hypertension significantly increased 24-hour urinary zinc excretion by 3.8-fold. Administration of enalapril increased 24-hour urinary zinc excretion nonsignificantly by 65% (Golik, 1990). In a patient with hypertension and impaired kidney function, treatment with captopril resulted in loss of taste sensation, alopecia, and other symptoms of zinc deficiency that resolve after supplementation with zinc. These symptoms resolved after supplementation with 91 mg per day of zinc (as zinc sulfate) for a few weeks (Smit, 1983).
Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone) and loop diuretics (e.g., furosemide, bumetanide) increase urinary excretion of zinc (Reyes, 1982; Wester, 1980). Zinc deficiency is more likely in patients with cirrhosis treated with diuretics (Chiba, 2013.)
Zinc and some other minerals can bind to fluoroquinolones (such as ciprofloxacin, norfloxacin, levofloxacin, and gemifloxacin) and markedly reduce their absorption (Campbell, 1992). It is recommended that mineral-containing supplements not be taken within 1-2 hours before or 2-6 hours after taking fluoroquinolones (recommendations vary according to the drug being used).
It has been recommended that patients receiving penicillamine for conditions other than copper overload be supplemented with zinc and copper, because penicillamine increases urinary excretion of these minerals (Garabedian-Ruffalo, 1986). Zinc appears to reduce the effectiveness of penicillamine at low doses (0.5-1 gm/day) but not at high doses.
Interactions between penicillamine and zinc are complex (Ambanelli, 1978; Høyer, 1982), and one group of investigators stated that zinc and penicillamine are toxic when given together at doses that are harmless when given separately Horrobin, 1978). Advise patients to take penicillamine and zinc two hours apart.
Concurrent administration of zinc with tetracyclines may reduceinterfere with the absorption of these drugs by 30 to 40% (Penttilä, 1975.)
Melatonin secretion may be suppressed by certain medications including aspirin and ibuprofen (Zeitzer, 1999), and by light.
