{"url":"https://whatshealthyandwhy.com/nutrient-interactions-and-timing/do-supplements-interfere-with-each-other","path":"/nutrient-interactions-and-timing/do-supplements-interfere-with-each-other","alternates":{"json":"https://whatshealthyandwhy.com/api/articles/nutrient-interactions-and-timing/do-supplements-interfere-with-each-other.json","markdown":"https://whatshealthyandwhy.com/nutrient-interactions-and-timing/do-supplements-interfere-with-each-other.md"},"topic":{"slug":"nutrient-interactions-and-timing","name":"Nutrient Interactions and Timing","url":"https://whatshealthyandwhy.com/nutrient-interactions-and-timing"},"slug":"do-supplements-interfere-with-each-other","order":1,"title":"Do Supplements Interfere with Each Other?","question":"Do supplements compete with each other, and does timing matter?","answer":"Sometimes: calcium, iron, zinc, coffee and tea likely cut each other's absorption in single-meal studies, so spacing doses is a cheap precaution.","description":"Which vitamins, minerals, coffee and medicines compete for absorption, what the studies measured, and a simple daily schedule that keeps them apart.","confidence":3,"confidenceNote":"Absorption effects are clear in small single-meal experiments, but whole-diet and long-term effects are smaller or untested, and thyroid findings come from small studies.","evidenceSummary":{"rctCount":4,"observationalCount":7,"metaAnalysisCount":0,"totalParticipants":"380+","replicated":true,"newestStudyYear":2017},"category":{"categoryTitle":"What's Good For You","categorySlug":"good-for-you","subcategoryName":"Supplements & Vitamins","subcategorySlug":"supplements","url":"https://whatshealthyandwhy.com/explore/good-for-you/supplements"},"actions":["Take thyroid medicine alone with water and keep calcium, iron and coffee away from it; calcium carbonate and iron both raised TSH in treated patients [1][2].","Take iron between meals and away from calcium, tea and coffee: 300 to 600 mg of calcium cut iron absorption by 50 to 60 percent in meal tests [3][4].","Take vitamin D with a meal that contains some fat; fat raised vitamin D3 absorption by about a third in a randomized trial [5]."],"cautions":["On levothyroxine or other thyroid medicine? Calcium, iron and coffee all lowered its absorption, so ask your prescriber about timing and have TSH rechecked after you change supplements [1][2][6].","Anemic, pregnant or on iron tablets? Do not rearrange doses yourself; alternate-day schedules were tested only in small groups of iron-depleted women [7]."],"simpleText":"Some supplements compete for the same absorption route. In meal studies, 300 to 600 mg of calcium cut iron absorption by 50 to 60 percent, 600 mg of calcium halved zinc absorption, and coffee and tea blocked iron too [3][8][9]. Calcium, iron and coffee also weakened thyroid medicine [1][2][6]. Single-meal tests can overstate real-life effects, as they did for vitamin C [10], so a simple schedule is enough: keep minerals apart and take fat-soluble vitamins with a meal.","mediumText":"How it works\n\nMinerals such as calcium, iron and zinc share absorption routes in the gut, and some compounds simply bind others. Calcium also lowered the absorption of heme iron, the form found in meat, which points to competition at the gut wall rather than only a chemical reaction [3]. Levothyroxine sticks to calcium carbonate in an acid environment, and iron forms a poorly soluble complex with thyroxine [1][2].\n\nWhat the studies measured\n\n- Calcium and iron. Calcium cut iron absorption by 50 to 60 percent at 300 to 600 mg, and even 165 mg from milk or cheese did the same [3].\n- Calcium and zinc. A 600 mg calcium carbonate supplement taken with a meal cut zinc absorption by 50 percent; adding zinc to the supplement offset it [8].\n- Iron and zinc. High iron doses lowered zinc absorption when both were given in water, but not when given in a meal; iron experts still advise taking iron supplements between meals [4].\n- Coffee and tea. A cup of coffee cut iron absorption from a meal by 39 percent and tea by 64 percent. Coffee an hour before the meal did no harm, but coffee an hour after it still blocked absorption [9].\n- Vitamin C. It boosts iron absorption in single meals, yet across a full day's diet the effect was far smaller [10].\n- Dietary fat. Fat in the meal raised vitamin D3 absorption by about a third [5], though blood vitamin D levels at one and three months were no better in another trial [11].\n\nA simple schedule\n\n1. On waking, with water: thyroid medicine, alone. In one study coffee taken 60 minutes after the tablet did not reduce absorption [6].\n2. With your biggest meal: vitamin D and other fat-soluble vitamins, plus calcium carbonate, which needs food; calcium citrate works at any time. Keep each calcium dose to 500 mg of elemental calcium or less [12].\n3. Between meals: iron, away from calcium, tea, coffee and dairy [4][3]. If a clinician has prescribed iron, taking it every other day absorbed more than daily dosing [7].\n4. At a different meal from calcium: zinc [8].\n\nKeep it in proportion. Single-meal tests overstated vitamin C's effect on iron absorption [10], and the same caution applies to the other pairs. Spacing matters most if you are deficient, pregnant, anemic, or take thyroid medicine. See our pages on iron, vitamin D supplementation and supporting thyroid health.","deepText":"The evidence in detail\n\nMinerals competing with each other\n\nHallberg and colleagues gave 126 volunteers wheat rolls with calcium added in doses of 40 to 600 mg and measured iron absorption. Inhibition was dose related up to 300 mg, and iron absorption fell 50 to 60 percent at 300 to 600 mg of calcium. The same effect appeared when 165 mg of calcium was given as milk, cheese or calcium chloride, and heme iron absorption fell too [3]. Wood and Zheng fed 18 postmenopausal women a controlled diet for 36 days: an extra 468 mg of calcium a day, as milk or calcium phosphate, reduced net zinc absorption and zinc balance by about 2 mg a day. In a second group, 600 mg of calcium as carbonate halved zinc absorption from a single meal, and an extra 7.8 mg of zinc offset the loss [8]. Whittaker's review found that high iron doses lowered zinc absorption when given in solution but not in a meal, and that iron fortification at current levels did not impair zinc absorption [4].\n\nTea, coffee and vitamin C\n\nMorck and colleagues used dual-isotope studies in iron-replete volunteers. A cup of coffee reduced iron absorption from a hamburger meal by 39 percent versus 64 percent for tea, and stronger coffee inhibited more. Coffee an hour before the meal had no effect, while coffee an hour after the meal inhibited as much as coffee taken together with it [9]. For vitamin C, Cook and Reddy measured iron absorption in 12 people across three 5-day periods in which diet vitamin C ranged from 51 to 247 mg a day. Mean absorption did not differ significantly between periods, although vitamin C was positively associated with absorption after adjustment. The authors concluded that vitamin C's effect on a complete diet is far weaker than on single meals, which may explain why long-term vitamin C supplements have not clearly improved iron status [10].\n\nIron dosing schedule\n\nIn two randomized trials in iron-depleted young women, Stoffel and colleagues used isotope-labeled iron. In 40 women, 60 mg of iron on alternate days gave higher cumulative fractional absorption than the same dose on consecutive days (21.8 percent versus 16.3 percent, p=0.0013), with lower hepcidin, a hormone that reduces iron absorption. In 20 women, one 120 mg dose and two 60 mg doses a day absorbed similar amounts, but the split dose raised hepcidin more [7]. The trials were small, short and did not test anemic patients or clinical outcomes.\n\nThyroid medicine\n\nSingh and colleagues followed 20 hypothyroid patients on stable levothyroxine who added 1,200 mg of elemental calcium as carbonate for three months: mean TSH rose from 1.6 to 2.7 mIU/L, free T4 fell, and 20 percent had TSH above the normal range [1]. Campbell and colleagues gave 14 patients 300 mg ferrous sulfate with their thyroxine for 12 weeks in an uncontrolled trial: mean TSH rose from 1.6 to 5.4 mU/L and nine patients had more hypothyroid symptoms [2]. Benvenga and colleagues found that coffee swallowed with the tablets lowered the area under the absorption curve by 36 percent in patients and 27 percent in volunteers, whereas coffee 60 minutes after the tablets did not reduce absorption relative to water alone [6]. All three studies were small, and two were before-and-after designs without a parallel control group.\n\nFat-soluble vitamins and meals\n\nDawson-Hughes and colleagues randomly assigned 50 older adults to a fat-free meal or a meal with 30 percent of calories from fat; after a single 50,000 IU dose of vitamin D3, peak plasma D3 was 32 percent higher (95% CI 11 to 52 percent) with fat. The type of fat made no difference [5]. A second randomized trial in 62 older adults gave monthly 50,000 IU doses with no meal, a high-fat meal or a low-fat meal. Absorption was highest with the low-fat meal, yet 25-hydroxyvitamin D did not differ between groups at 30 or 90 days [11]. Absorption is not the same as status, and these two trials do not agree on the best meal. Trials comparing meal conditions for vitamins A, E and K in supplement users are scarce.\n\nCalcium forms and doses\n\nA clinical review recommends calcium carbonate with a meal, calcium citrate with or without food (the better choice with low stomach acid or acid-blocking drugs), and no more than 500 mg of elemental calcium at one time [12]. This is expert guidance rather than trial evidence.\n\nWhat is not shown\n\nSingle-meal studies overstated vitamin C's effect in a whole-diet comparison [10], and none of the mineral studies measured disease outcomes. The thyroid findings are the most clinically relevant but come from small studies.\n\nBottom line (confidence 3 of 5). Calcium, iron, zinc, coffee and tea reduce each other's or thyroid medicine's absorption in careful experiments. Spacing doses costs nothing, but it matters mainly for people who are deficient, pregnant or on thyroid medicine.","deepTruncated":false,"references":[{"id":"1","title":"Effect of calcium carbonate on the absorption of levothyroxine","authors":"Singh N, Singh PN, Hershman JM","year":2000,"journal":"JAMA","pmid":"10838651","url":"https://pubmed.ncbi.nlm.nih.gov/10838651/"},{"id":"2","title":"Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism","authors":"Campbell NR, Hasinoff BB, Stalts H, et al.","year":1992,"journal":"Ann Intern Med","pmid":"1443969","url":"https://pubmed.ncbi.nlm.nih.gov/1443969/"},{"id":"3","title":"Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans","authors":"Hallberg L, Brune M, Erlandsson M, et al.","year":1991,"journal":"Am J Clin Nutr","pmid":"1984335","url":"https://pubmed.ncbi.nlm.nih.gov/1984335/"},{"id":"4","title":"Iron and zinc interactions in humans","authors":"Whittaker P","year":1998,"journal":"Am J Clin Nutr","pmid":"9701159","url":"https://pubmed.ncbi.nlm.nih.gov/9701159/"},{"id":"5","title":"Dietary fat increases vitamin D-3 absorption","authors":"Dawson-Hughes B, Harris SS, Lichtenstein AH, et al.","year":2015,"journal":"J Acad Nutr Diet","pmid":"25441954","url":"https://pubmed.ncbi.nlm.nih.gov/25441954/"},{"id":"6","title":"Altered intestinal absorption of L-thyroxine caused by coffee","authors":"Benvenga S, Bartolone L, Pappalardo MA, et al.","year":2008,"journal":"Thyroid","pmid":"18341376","url":"https://pubmed.ncbi.nlm.nih.gov/18341376/"},{"id":"7","title":"Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials","authors":"Stoffel NU, Cercamondi CI, Brittenham G, et al.","year":2017,"journal":"Lancet Haematol","pmid":"29032957","url":"https://pubmed.ncbi.nlm.nih.gov/29032957/"},{"id":"8","title":"High dietary calcium intakes reduce zinc absorption and balance in humans","authors":"Wood RJ, Zheng JJ","year":1997,"journal":"Am J Clin Nutr","pmid":"9174476","url":"https://pubmed.ncbi.nlm.nih.gov/9174476/"},{"id":"9","title":"Inhibition of food iron absorption by coffee","authors":"Morck TA, Lynch SR, Cook JD","year":1983,"journal":"Am J Clin Nutr","pmid":"6402915","url":"https://pubmed.ncbi.nlm.nih.gov/6402915/"},{"id":"10","title":"Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet","authors":"Cook JD, Reddy MB","year":2001,"journal":"Am J Clin Nutr","pmid":"11124756","url":"https://pubmed.ncbi.nlm.nih.gov/11124756/"},{"id":"11","title":"Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation","authors":"Dawson-Hughes B, Harris SS, Palermo NJ, et al.","year":2013,"journal":"J Bone Miner Res","pmid":"23427007","url":"https://pubmed.ncbi.nlm.nih.gov/23427007/"},{"id":"12","title":"Calcium supplementation in clinical practice: a review of forms, doses, and indications","authors":"Straub DA","year":2007,"journal":"Nutr Clin Pract","pmid":"17507729","url":"https://pubmed.ncbi.nlm.nih.gov/17507729/"}],"wordCount":1295,"source":{"path":"src/content/topics/nutrient-interactions-and-timing/do-supplements-interfere-with-each-other.md"},"citeAs":"“Do supplements compete with each other, and does timing matter?.” What's Healthy and Why. https://whatshealthyandwhy.com/nutrient-interactions-and-timing/do-supplements-interfere-with-each-other","notice":"General information backed by peer-reviewed research, not medical advice."}