{"slug":"transferrin-saturation","name":"Transferrin saturation","aliases":["Iron saturation","TSAT"],"kind":"biomarker","system":"mitochondria","unit":"%","unitNote":"Calculated as serum iron divided by total iron-binding capacity, times 100.","answer":"Transferrin saturation is the share of the blood's iron-carrying protein that is actually carrying iron. Below 20 percent, with a ferritin of 30 or more, is functional iron deficiency, which about 15 percent of US adults meet and which the heart-failure trials treated; mortality sat lowest at about 24 to 40 percent in US and Danish cohorts; 45 percent or more is the threshold at which liver guidelines start a hemochromatosis workup, and 50 percent or more carried about 1.4 times the mortality in 45,159 Danes. Serum iron swings by about a quarter from day to day, so one value is a draft, not a verdict.","summary":"Transferrin saturation measures how much of the iron transport protein is loaded with iron, so it reads the iron that is moving rather than the iron that is stored. Laboratories call about 15 or 20 to 45 or 50 percent normal. The evidence places functional deficiency below 20 percent, the lowest mortality between about 24 and 40, and the hemochromatosis screening line at 45. It falls with inflammation and varies by about a quarter from one day to the next, which is why it is read beside ferritin, hemoglobin and C-reactive protein.","whatItIs":[{"text":"Transferrin is the protein that carries iron through the blood. Transferrin saturation is serum iron divided by total iron-binding capacity, times 100: the fraction of the carrier's seats that are filled. Ferritin reports the warehouse; saturation reports the delivery trucks, the iron that is on its way to the bone marrow and to every cell that burns oxygen.","cites":["stack2014","sun2024"],"grade":"A"},{"text":"A low saturation with a normal ferritin is called functional iron deficiency: stores exist but iron is not reaching circulation. Defined as a ferritin of 30 ng/mL or more with a saturation under 20 percent, it affected an estimated 15 percent of US adults in the 2017 to 2020 national survey of 8,021 people, slightly more than the 14 percent with absolute deficiency, and it outnumbered absolute deficiency in every group except women under 50.","cites":["tawfik2024"],"grade":"C"},{"text":"Saturation is also the first number to move in hereditary hemochromatosis, which is why the liver guidelines use it as the screening test. About 1 in 250 people of northern European descent carry two copies of the C282Y variant of the HFE gene, and fewer than 10 percent of them develop fully expressed disease; in a primary-care screening study of 99,711 people, the homozygote prevalence was 0.44 percent in non-Hispanic whites and far lower in every other group.","cites":["bacon2011","adams2005"],"grade":"A"}],"labRange":{"typical":"About 15 or 20 to 45 or 50 percent, depending on the laboratory","claims":[{"text":"The lower limit laboratories print, 15 to 20 percent, is close to the 20 percent line that the research definitions of functional iron deficiency use. The upper limit, 45 to 50, is close to the line at which hepatology guidelines ask for a repeat test and HFE genotyping. So the laboratory range roughly brackets the two clinical thresholds, which is unusual among blood tests, but it says nothing about where risk sat inside the range.","cites":["tawfik2024","bacon2011","easl2022"],"grade":"A"},{"text":"In the US national survey the median saturation was 23.4 percent, with a quarter of adults below 17.1 and a quarter above 31.1. Half of the population therefore sits in the lower third of what the laboratory calls normal.","cites":["sun2024"],"grade":"B"}]},"evidence":{"headline":"Mortality sat lowest at about 24 to 40 percent in 15,823 and 29,166 US adults and at about 32 to 34 percent in 161,921 Danes; it rose below about 20 percent and again above 50, where 45,159 Danes carried about 1.4 times the mortality. Forty-five percent is where guidelines start a hemochromatosis workup, a screening line rather than an outcome threshold.","scale":{"min":0,"max":70,"ticks":[0,10,20,30,40,50,60,70]},"bands":[{"label":"Common laboratory reference range","low":20,"high":50,"tone":"lab","source":"Typical US laboratories"},{"label":"Functional iron deficiency (with ferritin 30 or more)","low":0,"high":20,"tone":"caution","source":"Tawfik 2024; FAIR-HF definition"},{"label":"Lowest mortality in cohorts","low":24,"high":40,"tone":"evidence","source":"Stack 2014; Mitchell 2022; Sun 2024"},{"label":"Cohorts disagree","low":40,"high":45,"tone":"neutral","source":"Stack 2014 (higher) versus Sun 2024 (lower)"},{"label":"Hemochromatosis screening threshold","low":45,"high":70,"tone":"caution","source":"AASLD 2011; EASL 2022"},{"label":"Higher mortality in cohorts","low":50,"high":70,"tone":"caution","source":"Ellervik 2011; Sun 2024"}],"claims":[{"text":"In 29,166 US adults followed for a median of 18.8 years, the relationship between saturation and death was J-shaped: below 20 percent, lower saturation meant higher all-cause and cardiovascular mortality, and above 50 percent risk rose again. Against the lowest quartile (under 17.1 percent), the three higher quartiles each carried about 6 to 8 percent lower all-cause mortality. An association, adjusted for the usual confounders, in a population whose median saturation was 23.4.","cites":["sun2024"],"grade":"B"},{"text":"In 15,823 adults from the earlier US survey, followed to 2006, the same J-shape appeared. Against a saturation of 23.7 to 31.3 percent, people under 17.5 had 1.45 times the all-cause mortality and 2.09 times the cardiovascular mortality; 17.5 to 23.7 carried 1.27 and 1.90 times; and above 31.3 carried 1.23 and 1.59 times. The authors placed the survival optimum between 24 and 40 percent.","cites":["stack2014"],"grade":"B"},{"text":"In 161,921 Danish adults with routine blood tests, the saturation associated with the lowest all-cause mortality was 33.9 percent in women and 32.3 percent in men when C-reactive protein was under 10 mg/L, and 28.7 and 30.6 percent when it was 10 or higher. Both low and high saturations carried higher mortality in each sex, and the pattern held when inflammation was present.","cites":["mitchell2022"],"grade":"B"},{"text":"At the high end, in 45,159 Danes followed for up to 18 years, a saturation of 50 percent or more carried 1.4 times the all-cause mortality of values below 50 (1.3 in men, 1.5 in women), rising stepwise to 2.2 times at 80 percent or more against under 20. The population-attributable risk was 0.8 percent, because so few people sit that high. A meta-analysis with a third cohort put the odds at 1.3.","cites":["ellervik2011"],"grade":"B"},{"text":"At the low end, the heart-failure trials are the clearest evidence that a saturation under 20 percent is worth acting on. In 459 people with chronic heart failure and a ferritin under 100, or 100 to 299 with a saturation under 20 percent, intravenous iron left 50 percent feeling much or moderately better at 24 weeks against 28 percent on placebo, with or without anemia. In 1,108 people stabilized after acute heart failure, the same definition and treatment cut heart-failure hospitalizations by about a quarter (rate ratio 0.74) without changing cardiovascular death.","cites":["anker2009","ponikowski2020"],"grade":"A"},{"text":"Genetics point in both directions, which fits the J. People whose variants give them lifelong higher iron status had slightly lower coronary disease risk (odds ratio 0.95 per standard deviation of saturation) in a Mendelian randomization built on two coronary disease meta-analyses of 60,801 and 63,746 cases. In 257,953 people from the Norwegian HUNT study and others, genetically higher serum iron and saturation raised all-cause mortality in linear analyses, with weak evidence of benefit only at the very low end of the distribution.","cites":["gill2017","moksnes2022"],"grade":"B"},{"text":"A saturation of 45 percent or more, or a ferritin above the laboratory's upper limit, is the American liver guideline's trigger for HFE genotyping in someone with suggestive symptoms, findings or family history. The 45 percent cutoff is chosen for sensitivity; it also catches people with minor secondary iron loading, and in people under 35 a normal ferritin with a saturation under 45 had a 97 percent negative predictive value for excluding overload. The European guideline sets provisional iron overload in C282Y homozygotes at a saturation above 45 percent with ferritin above 200 ng/mL in women, and above 50 percent with ferritin above 300 in men and postmenopausal women.","cites":["bacon2011","easl2022"],"grade":"A"},{"text":"Carrying the genotype is not the same as having the disease. Among 203 C282Y homozygotes followed for 12 years in Melbourne, iron-overload-related disease developed in 28.4 percent of men and 1.2 percent of women. In 132,542 Danes followed up to 27 years, the 422 homozygotes had 1.72 times the diabetes and 2.22 times the liver disease of non-carriers but no excess heart disease, and the diabetes excess persisted in homozygotes whose saturation was normal; carriers of one copy, or of H63D, had no excess risk.","cites":["allen2008","mottelson2024"],"grade":"B"}]},"levers":[{"name":"Oral iron, in moderate doses on alternate days","effect":"raises it, with absorption best at lower, spaced doses","claim":{"text":"In 54 iron-depleted young women, hepcidin was still raised 24 hours after a single morning dose of 60 mg or more of elemental iron, and absorption of the next day's dose fell by 35 to 45 percent; a sixfold larger dose (40 to 240 mg) delivered only threefold more iron. Lower doses and alternate-day dosing maximize what is absorbed. Iron supplements belong under a physician's direction once the cause of a low saturation is known.","cites":["moretti2015"],"grade":"B"}},{"name":"Iron treatment in iron-deficient athletes","effect":"raises it, with a moderate gain in aerobic capacity","claim":{"text":"Pooling 17 studies of iron-deficient, non-anemic endurance athletes, iron treatment had a large effect on saturation (Hedges' g 0.74) and a moderate effect on maximal oxygen uptake (g 0.61); courses beyond 80 days added the least to ferritin.","cites":["burden2015"],"grade":"B"}},{"name":"Blood donation","effect":"lowers it, with iron stores","claim":{"text":"In the US REDS-II study of blood donors, iron depletion rose with donation frequency and a shorter interval between donations; among female frequent donors who returned, 27 percent had absent iron stores and 62 percent had iron-deficient red-cell production. A low saturation after a run of donations is a reason to pause and recheck, not a disease.","cites":["cable2012"],"grade":"B"}},{"name":"Alcohol","effect":"raises it above about two drinks a day","claim":{"text":"In the US national survey, the 915 adults drinking more than two alcoholic drinks a day had a significantly higher prevalence of every marker of iron overload, including a saturation above 45, 50 and 60 percent, than the 8,839 nondrinkers; any alcohol was associated with 40 percent less iron-deficiency anemia. Alcohol and fatty liver are more common explanations for a raised iron panel than hemochromatosis.","cites":["ioannou2004","kowdley2019"],"grade":"C"}},{"name":"Inflammation and infection","effect":"lower it within hours, without any change in body iron","claim":{"text":"Inflammation raises hepcidin, which locks iron inside cells. In six healthy volunteers given a three-hour infusion of interleukin-6, urinary hepcidin rose 7.5-fold and, two hours after the infusion, serum iron had fallen 34 percent and saturation 33 percent. A saturation drawn during a cold, after surgery or beside a raised C-reactive protein reads low for reasons that have nothing to do with iron stores.","cites":["nemeth2004"],"grade":"C"}}],"caveats":[{"text":"Serum iron, the numerator, is the least stable analyte on an iron panel. In 20 healthy adults sampled for 31 consecutive days, the day-to-day coefficient of variation for plasma iron was 26.7 percent in men and 29.0 percent in women, and three to ten measurements were needed to pin down a person's level; in 11 young men the within-day variation was 12.9 percent and the day-to-day 26.6 percent. A single saturation of 18 or 47 percent can be 24 or 38 the next week.","cites":["borel1991","statland1976"],"grade":"C"},{"text":"The morning-draw rule is older than the evidence for it. One study of 11 men found the daily peak at 2 PM; a Mayo Clinic study of 20 volunteers drawn at 8 AM, noon and 4 PM found no consistent diurnal pattern, with morning higher than afternoon in only half of them, and between-day variation as large as within-day. Consistency matters more than the clock: the same time of day, the same fasting state, every time.","cites":["statland1976","dale2002"],"grade":"C"},{"text":"A raised saturation is confirmed before it is acted on. The liver guideline no longer requires a fasting sample, since fasting did not improve detection of C282Y homozygotes, but advises confirming an elevated saturation with a second determination, reasonably on a fasting specimen. Iron tablets and infusions perturb the same system: in iron-depleted women, hepcidin was still raised 24 hours after a single oral dose of 60 mg or more.","cites":["bacon2011","moretti2015"],"grade":"A"},{"text":"Saturation is read beside ferritin and hemoglobin, never alone. The functional-deficiency definition itself requires a ferritin of 30 or more, and the heart-failure definition pairs a saturation under 20 with a ferritin of 100 to 299. A high ferritin with a normal saturation usually points to inflammation or fatty liver rather than iron overload, and in people with liver disease a raised ferritin is more often fatty liver or alcohol than hemochromatosis.","cites":["tawfik2024","anker2009","kowdley2019"],"grade":"A"},{"text":"The cohort optimum of about 24 to 40 percent is an association in people who were not treated to any target. People with low saturation in these surveys were older, sicker and more inflamed; adjustment narrows but cannot close that gap, and the heart-failure trials prove benefit only in heart failure.","cites":["stack2014","sun2024","anker2009"],"grade":"B"}],"seeAPhysician":["A transferrin saturation of 45 percent or more on a repeat, fasting draw, especially with a ferritin above about 200 (women) or 300 (men): the guideline trigger for HFE genotyping.","A saturation under 20 percent with fatigue, breathlessness, restless legs, hair loss or a low hemoglobin, which needs a search for the cause (blood loss, poor absorption, inflammation) before iron is taken.","A parent, sibling or child with hemochromatosis or a known HFE C282Y genotype, whatever the saturation reads today.","A saturation that drifts upward over successive years together with a rising ferritin, an elevated liver enzyme, or more than about two drinks a day.","Any iron supplement or infusion already in use with a saturation that is now high; the dose and the next test belong with the prescriber."],"openQuestions":["No trial has treated people without heart failure, kidney disease or anemia to a saturation target and measured outcomes; the 24 to 40 percent optimum is a cohort observation, not a tested goal.","Whether a low saturation with a normal ferritin, functional deficiency, causes harm in otherwise healthy adults, or mostly marks inflammation and illness, is unresolved; the trials that treated it enrolled people with heart failure.","The upper edge of the low-risk span is disputed: the top quartile (above 31.3) carried higher mortality in one US cohort and lower mortality (above 31.1) in a larger one from the same surveys.","Whether saturation should be drawn fasting and in the morning rests on small, conflicting studies; a modern biological-variation study of saturation in healthy adults is missing.","C282Y homozygotes with a normal saturation still carried excess diabetes risk in Denmark, which suggests saturation alone may miss some of the genotype's harm; whether that changes who should be genotyped is open.","Sex- and age-specific optimal saturations have not been established; the Danish optimum differed by only a point or two between women and men."],"questions":[{"q":"Is a transferrin saturation of 18 percent low?","a":"It sits below the 20 percent line that defines functional iron deficiency when ferritin is 30 or more, and in the US cohorts the band under about 20 carried higher mortality. But serum iron varies by about a quarter from day to day and falls within hours of inflammation, so one 18 is a reason to repeat the test beside ferritin, hemoglobin and C-reactive protein, not a diagnosis."},{"q":"What is an optimal iron saturation?","a":"No trial has set one. In US and Danish cohorts the lowest mortality sat at about 24 to 40 percent, with the Danish optimum near 32 to 34; risk rose below about 20 and again above 50. A physician's zone inside that window is a judgment, and this page says so."},{"q":"Is 50 percent iron saturation hemochromatosis?","a":"Not by itself. Forty-five percent is the guideline threshold to repeat the test fasting and, if it holds, check ferritin and the HFE gene; the European guideline calls it provisional overload in C282Y homozygotes only when ferritin is also raised. Alcohol and fatty liver raise saturation too, and even among people with two C282Y copies, overload disease developed in about 28 percent of men and 1 percent of women."}],"citations":[{"id":"stack2014","authors":"Stack AG, Mutwali AI, Nguyen HT, Cronin CJ, Casserly LF, Ferguson J","title":"Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population","journal":"QJM","year":2014,"pmid":"24599805","doi":"10.1093/qjmed/hcu045","type":"cohort","finding":"J-shaped mortality in 15,823 NHANES III adults; against 23.7 to 31.3 percent, under 17.5 carried 1.45 times the mortality and above 31.3 carried 1.23 times; survival optimum 24 to 40 percent.","url":"https://pubmed.ncbi.nlm.nih.gov/24599805/"},{"id":"sun2024","authors":"Sun Y, Peng W, Lin S, Cui J, Lu J","title":"Iron metabolic biomarkers and the mortality risk in the general population: a nationwide population-based cohort study","journal":"Journal of the Endocrine Society","year":2024,"pmid":"38623382","doi":"10.1210/jendso/bvae063","type":"cohort","finding":"J-shaped association of transferrin saturation with all-cause and cardiovascular mortality in 29,166 NHANES adults over a median 18.8 years; higher risk below 20 and above 50 percent; median 23.4 percent.","url":"https://pubmed.ncbi.nlm.nih.gov/38623382/"},{"id":"tawfik2024","authors":"Tawfik YMK, Billingsley H, Bhatt AS, et al.","title":"Absolute and functional iron deficiency in the US, 2017-2020","journal":"JAMA Network Open","year":2024,"pmid":"39316402","doi":"10.1001/jamanetworkopen.2024.33126","type":"cross-sectional","finding":"Functional iron deficiency, ferritin 30 or more with saturation under 20 percent, in 15 percent of US adults; absolute deficiency in 14 percent.","url":"https://pubmed.ncbi.nlm.nih.gov/39316402/"},{"id":"bacon2011","authors":"Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS","title":"Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases","journal":"Hepatology","year":2011,"pmid":"21452290","doi":"10.1002/hep.24330","type":"guideline","finding":"Saturation of 45 percent or more, or ferritin above normal, prompts HFE testing; confirm a raised saturation on a second, reasonably fasting, specimen; 1 in 250 of northern European descent are C282Y homozygous.","url":"https://pubmed.ncbi.nlm.nih.gov/21452290/"},{"id":"adams2005","authors":"Adams PC, Reboussin DM, Barton JC, et al.","title":"Hemochromatosis and iron-overload screening in a racially diverse population","journal":"New England Journal of Medicine","year":2005,"pmid":"15858186","doi":"10.1056/NEJMoa041534","type":"cross-sectional","finding":"Among 99,711 primary-care participants, C282Y homozygote prevalence was 0.44 percent in non-Hispanic whites; most undiagnosed homozygotes had raised ferritin and saturation.","url":"https://pubmed.ncbi.nlm.nih.gov/15858186/"},{"id":"easl2022","authors":"European Association for the Study of the Liver","title":"EASL Clinical Practice Guidelines on haemochromatosis","journal":"Journal of Hepatology","year":2022,"pmid":"35662478","doi":"10.1016/j.jhep.2022.03.033","type":"guideline","finding":"Provisional iron overload in C282Y homozygotes: saturation above 45 percent with ferritin above 200 in women; above 50 percent with ferritin above 300 in men and postmenopausal women.","url":"https://pubmed.ncbi.nlm.nih.gov/35662478/"},{"id":"mitchell2022","authors":"Mitchell NH, Jørgensen HL, Vojdeman FJ, et al.","title":"Association of ferritin and transferrin saturation with all-cause mortality, and the effect of concurrent inflammation: a danish cohort study","journal":"Scandinavian Journal of Clinical and Laboratory Investigation","year":2022,"pmid":"36218336","doi":"10.1080/00365513.2022.2129435","type":"cohort","finding":"In 161,921 Danes, lowest mortality at a saturation of 33.9 percent (women) and 32.3 percent (men) without inflammation, 28.7 and 30.6 with CRP 10 or higher.","url":"https://pubmed.ncbi.nlm.nih.gov/36218336/"},{"id":"ellervik2011","authors":"Ellervik C, Tybjærg-Hansen A, Nordestgaard BG","title":"Total mortality by transferrin saturation levels: two general population studies and a metaanalysis","journal":"Clinical Chemistry","year":2011,"pmid":"21228252","doi":"10.1373/clinchem.2010.156802","type":"cohort","finding":"Saturation of 50 percent or more carried 1.4 times the all-cause mortality in 45,159 Danes, 2.2 times at 80 or more versus under 20; population-attributable risk 0.8 percent.","url":"https://pubmed.ncbi.nlm.nih.gov/21228252/"},{"id":"anker2009","authors":"Anker SD, Comin Colet J, Filippatos G, et al.","title":"Ferric carboxymaltose in patients with heart failure and iron deficiency","journal":"New England Journal of Medicine","year":2009,"pmid":"19920054","doi":"10.1056/NEJMoa0908355","type":"rct","finding":"In 459 heart-failure patients with ferritin under 100, or 100 to 299 with saturation under 20 percent, intravenous iron improved symptoms in 50 percent versus 28 percent on placebo.","url":"https://pubmed.ncbi.nlm.nih.gov/19920054/"},{"id":"ponikowski2020","authors":"Ponikowski P, Kirwan BA, Anker SD, et al.","title":"Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial","journal":"Lancet","year":2020,"pmid":"33197395","doi":"10.1016/S0140-6736(20)32339-4","type":"rct","finding":"Same iron-deficiency definition; intravenous iron cut heart-failure hospitalizations (rate ratio 0.74) in 1,108 patients after acute heart failure, with no effect on cardiovascular death.","url":"https://pubmed.ncbi.nlm.nih.gov/33197395/"},{"id":"gill2017","authors":"Gill D, Del Greco M F, Walker AP, Srai SKS, Laffan MA, Minelli C","title":"The effect of iron status on risk of coronary artery disease: a Mendelian randomization study-brief report","journal":"Arteriosclerosis, Thrombosis, and Vascular Biology","year":2017,"pmid":"28684612","doi":"10.1161/ATVBAHA.117.309757","type":"mendelian-randomization","finding":"Genetically higher iron status modestly lowered coronary artery disease risk; odds ratio 0.95 per standard deviation of transferrin saturation.","url":"https://pubmed.ncbi.nlm.nih.gov/28684612/"},{"id":"moksnes2022","authors":"Moksnes MR, Graham SE, Wu KH, et al.","title":"Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT","journal":"Communications Biology","year":2022,"pmid":"35710628","doi":"10.1038/s42003-022-03529-z","type":"mendelian-randomization","finding":"Genetically higher serum iron and transferrin saturation increased all-cause mortality in linear analyses, with weak evidence of benefit at the very low end.","url":"https://pubmed.ncbi.nlm.nih.gov/35710628/"},{"id":"allen2008","authors":"Allen KJ, Gurrin LC, Constantine CC, et al.","title":"Iron-overload-related disease in HFE hereditary hemochromatosis","journal":"New England Journal of Medicine","year":2008,"pmid":"18199861","doi":"10.1056/NEJMoa073286","type":"cohort","finding":"Iron-overload-related disease in 28.4 percent of male and 1.2 percent of female C282Y homozygotes followed 12 years.","url":"https://pubmed.ncbi.nlm.nih.gov/18199861/"},{"id":"mottelson2024","authors":"Mottelson M, Helby J, Nordestgaard BG, et al.","title":"Mortality and risk of diabetes, liver disease, and heart disease in individuals with haemochromatosis HFE C282Y homozygosity and normal concentrations of iron, transferrin saturation, or ferritin: prospective cohort study","journal":"BMJ","year":2024,"pmid":"39653412","doi":"10.1136/bmj-2023-079147","type":"cohort","finding":"C282Y homozygotes had 1.72 times the diabetes and 2.22 times the liver disease, no excess heart disease; diabetes risk persisted with normal saturation; heterozygotes had no excess risk.","url":"https://pubmed.ncbi.nlm.nih.gov/39653412/"},{"id":"moretti2015","authors":"Moretti D, Goede JS, Zeder C, et al.","title":"Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women","journal":"Blood","year":2015,"pmid":"26289639","doi":"10.1182/blood-2015-05-642223","type":"rct","finding":"Doses of 60 mg or more raised hepcidin and cut next-dose absorption by 35 to 45 percent; a sixfold dose increase absorbed only threefold more iron.","url":"https://pubmed.ncbi.nlm.nih.gov/26289639/"},{"id":"burden2015","authors":"Burden RJ, Morton K, Richards T, Whyte GP, Pedlar CR","title":"Is iron treatment beneficial in, iron-deficient but non-anaemic (IDNA) endurance athletes? A systematic review and meta-analysis","journal":"British Journal of Sports Medicine","year":2015,"pmid":"25361786","doi":"10.1136/bjsports-2014-093624","type":"meta-analysis","finding":"Across 17 studies, iron treatment raised transferrin saturation (Hedges' g 0.74) and maximal oxygen uptake (g 0.61) in iron-deficient non-anemic athletes.","url":"https://pubmed.ncbi.nlm.nih.gov/25361786/"},{"id":"cable2012","authors":"Cable RG, Glynn SA, Kiss JE, et al.","title":"Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study","journal":"Transfusion","year":2012,"pmid":"22023513","doi":"10.1111/j.1537-2995.2011.03401.x","type":"cohort","finding":"Iron depletion rose with donation frequency; 27 percent of returning female frequent donors had absent iron stores and 62 percent iron-deficient erythropoiesis.","url":"https://pubmed.ncbi.nlm.nih.gov/22023513/"},{"id":"ioannou2004","authors":"Ioannou GN, Dominitz JA, Weiss NS, Heagerty PJ, Kowdley KV","title":"The effect of alcohol consumption on the prevalence of iron overload, iron deficiency, and iron deficiency anemia","journal":"Gastroenterology","year":2004,"pmid":"15131790","doi":"10.1053/j.gastro.2004.01.020","type":"cross-sectional","finding":"More than two drinks a day raised the prevalence of every iron-overload marker, including saturation above 45, 50 and 60 percent; any alcohol lowered iron-deficiency anemia by 40 percent.","url":"https://pubmed.ncbi.nlm.nih.gov/15131790/"},{"id":"kowdley2019","authors":"Kowdley KV, Brown KE, Ahn J, Sundaram V","title":"ACG clinical guideline: hereditary hemochromatosis","journal":"American Journal of Gastroenterology","year":2019,"pmid":"31335359","doi":"10.14309/ajg.0000000000000315","type":"guideline","finding":"Fatty liver and alcoholic liver disease are more common than hemochromatosis among people with raised ferritin who are not C282Y homozygotes; ferritin under 1,000 marks low risk of advanced fibrosis.","url":"https://pubmed.ncbi.nlm.nih.gov/31335359/"},{"id":"nemeth2004","authors":"Nemeth E, Rivera S, Gabayan V, et al.","title":"IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin","journal":"Journal of Clinical Investigation","year":2004,"pmid":"15124018","doi":"10.1172/JCI20945","type":"laboratory","finding":"In six volunteers, a three-hour interleukin-6 infusion raised urinary hepcidin 7.5-fold and dropped serum iron 34 percent and saturation 33 percent within two hours.","url":"https://pubmed.ncbi.nlm.nih.gov/15124018/"},{"id":"borel1991","authors":"Borel MJ, Smith SM, Derr J, Beard JL","title":"Day-to-day variation in iron-status indices in healthy men and women","journal":"American Journal of Clinical Nutrition","year":1991,"pmid":"1897480","doi":"10.1093/ajcn/54.4.729","type":"laboratory","finding":"Over 31 consecutive days in 20 healthy adults, the coefficient of variation for a single plasma iron determination was 26.7 percent in men and 29.0 percent in women.","url":"https://pubmed.ncbi.nlm.nih.gov/1897480/"},{"id":"statland1976","authors":"Statland BE, Winkel P, Bokelund H","title":"Variation of serum iron concentration in young healthy men: within-day and day-to-day changes","journal":"Clinical Biochemistry","year":1976,"pmid":"1248108","doi":"10.1016/s0009-9120(76)80008-2","type":"laboratory","finding":"In 11 healthy men, within-day variation of serum iron was 12.9 percent with the peak at 2 PM, and day-to-day variation was 26.6 percent.","url":"https://pubmed.ncbi.nlm.nih.gov/1248108/"},{"id":"dale2002","authors":"Dale JC, Burritt MF, Zinsmeister AR","title":"Diurnal variation of serum iron, iron-binding capacity, transferrin saturation, and ferritin levels","journal":"American Journal of Clinical Pathology","year":2002,"pmid":"12090432","doi":"10.1309/2YT4-CMP3-KYW7-9RK1","type":"laboratory","finding":"In 20 healthy volunteers drawn at 8 AM, noon and 4 PM, no consistent diurnal pattern; morning higher than afternoon in only half; between-day variation similar to within-day.","url":"https://pubmed.ncbi.nlm.nih.gov/12090432/"}],"written":"2026-10-10","updated":"2026-10-10","reviewed":true,"reviewedOn":"2026-10-10","related":{"essays":["ferritin-of-20-what-the-lab-calls-normal"],"glossary":["Ferritin","hsCRP","Reference range","Optimal range"],"symptoms":["fatigue","athletic-recovery","hair-loss"],"entries":["ferritin","hs-crp","alt","fasting-insulin"]},"url":"https://taggehealth.com/labs/transferrin-saturation","author":"Daniel Tagge, MD","publisher":"Tagge Health","license":"Free to read and cite with attribution to the URL above.","inPractice":"I like to see transferrin saturation between about 25 and 45 percent, drawn fasting in the morning, read beside ferritin, hemoglobin and C-reactive protein, and repeated before I act on it. The floor is my judgment: the cohorts put the lowest mortality at roughly 24 to 40, and under 20 is where functional deficiency begins and where the heart-failure trials treated, so 25 gives a margin above both. The ceiling is the screening line, not an outcome line: at 45 or more I repeat it fasting and, if it holds, check ferritin and the HFE gene before anything else. A saturation that drifts up over the years in someone who drinks is as often alcohol or liver fat as it is genes, and a low one with a normal ferritin is a question about inflammation, absorption and blood loss before it is a prescription for iron."}