Micronutrients: which values are worth measuring before you take anything
Four tests with a clear consequence, three tests that mislead, and the supplements where more is measurably worse. What the evidence supports, in practice.

A typical first appointment arrives with seven to twelve supplements. High-dose vitamin D, magnesium for cramps, a B complex, omega-3, sometimes selenium for the thyroid, and a multivitamin as general insurance. The reasoning behind it is almost always the same: I wanted to do something.
Micronutrient therapy is one of our treatment areas, which is exactly why precision matters here. A measured deficiency with a targeted correction is well-supported medicine. A handful of capsules without a finding behind them is frequently ineffective and in several documented cases harmful.
This article sets out which four measurements carry a clear consequence, which three widely sold tests mislead, and where the evidence argues against taking something at all.
First: intake and status are two different things
The German figure most often cited in supplement marketing is that 82 percent of men and 91 percent of women fall below the reference intake for vitamin D. That number comes from the National Nutrition Survey II (Max Rubner-Institut, 2008) and describes dietary intake.
For vitamin D that tells you little, because most of it is synthesised in skin under sunlight. The relevant quantity is blood status, which the Robert Koch Institute measured in 6,995 adults in DEGS1 (Rabenberg et al., BMC Public Health, 2015): the mean was 45.6 nmol/L, 30.2 percent fell below 30 nmol/L, 61.6 percent below 50 nmol/L, with pronounced seasonal variation.
Thirty percent is a meaningful number. Ninety-one percent describes something else entirely. When you encounter one of these percentages, it is worth asking whether intake or blood level is meant.
In short
- Intake data from dietary surveys says little about your blood level.
- For vitamin D, the measured proportion below 30 nmol/L in Germany is around 30 percent.
- For iron and B12 status in Germany, no comparable national status data exists.
Four measurements with a clear consequence
1. Ferritin, alongside an inflammation marker
The 2020 WHO guideline sets the thresholds: iron deficiency in otherwise healthy adults at a ferritin below 15 µg/L. Where infection or inflammation is present, a value below 70 µg/L may indicate iron deficiency, because ferritin rises during inflammatory processes and can mask a depleted store.
That distinction gets collapsed regularly in practice. A ferritin of 60 µg/L in someone without inflammation is a normal value. Applying the inflammation threshold to healthy people manufactures deficiencies that are not there. This is why CRP belongs alongside a ferritin measurement.
For fatigue in women without anaemia, two randomised trials exist. Verdon and colleagues (BMJ, 2003) found that among 144 women on 80 mg iron daily, fatigue fell 29 percent versus 13 percent on placebo, with the decisive caveat that only women with ferritin at or below 50 µg/L improved. Vaucher and colleagues (CMAJ, 2012) confirmed this in 198 women: 47.7 versus 28.8 percent reduction, with no effect on quality of life, depression or anxiety. A systematic review of 18 trials (Houston et al., BMJ Open, 2018) gives a standardised mean difference of −0.38 for fatigue, without improvement in objective physical capacity.
The harm side belongs in the calculation: ferrous sulfate causes gastrointestinal side effects with an odds ratio of 2.32 versus placebo, independent of dose (Tolkien et al., PLoS One, 2015). And for intravenous iron in non-anaemic iron deficiency, a Cochrane review (Miles et al., 2019) concludes that evidence of benefit is insufficient.
2. Vitamin B12 in defined risk groups
This is where the cleanest evidence for targeted measurement sits. A randomised, placebo-controlled trial over 4.3 years in 390 people with type 2 diabetes (de Jager et al., BMJ, 2010) showed a mean B12 decline of 19 percent on metformin and a 7.2 percentage point increase in the absolute risk of deficiency. That is a randomised, causal finding.
Other groups with documented risk: people on proton pump inhibitors (Lam et al., JAMA, 2013: odds ratio 1.65 with use over two years), vegans (Pawlak et al., Nutrition Reviews, 2013: high deficiency prevalence across all age groups), and older adults, among whom atrophic gastritis affects 8 to 9 percent of those over 65.
On measurement quality: the British Committee for Standards in Haematology guideline (Devalia et al., British Journal of Haematology, 2014) states that serum B12 "lacks the specificity and sensitivity required of a robust diagnostic test." With borderline values and genuine clinical suspicion, methylmalonic acid or holotranscobalamin are the next steps.
3. Vitamin D in defined situations
The current Endocrine Society guideline (Demay et al., Journal of Clinical Endocrinology & Metabolism, 2024) suggests against routine 25-hydroxyvitamin D testing in all populations considered. Germany's IGeL-Monitor rates vitamin D deficiency screening as a self-pay service "unclear," since no studies exist on the benefit of screening asymptomatic people.
The reason lies in the endpoint trials. VITAL, with 25,871 participants on 2,000 IU daily over a median 5.3 years, found no effect on cancer (HR 0.96) or cardiovascular events (HR 0.97) (Manson et al., NEJM, 2019) and no effect on fractures (HR 0.98) (LeBoff et al., NEJM, 2022). The D-Health trial in 21,315 Australians over 60 found no effect on all-cause mortality (HR 1.04) (Neale et al., Lancet Diabetes & Endocrinology, 2022).
Measurement stays useful in osteoporosis, malabsorption, chronic kidney disease, use of certain antiepileptics, very low sun exposure, and before starting higher-dose supplementation. For baseline provision, the German Federal Institute for Risk Assessment names 20 µg (800 IU) daily as sufficient for 97.5 percent of the population, and considers products supplying 50 or 100 µg nutritionally unnecessary.
One dose-related finding deserves attention: in a randomised trial of 311 adults over three years (Burt et al., JAMA, 2019), bone mineral density at the radius declined dose-dependently, by 1.2 percent on 400 IU, 2.4 percent on 4,000 IU and 3.5 percent on 10,000 IU daily.
4. Folate before and in early pregnancy
DEGS1 data show serum folate below 4.4 ng/mL in 12 percent of women and 16 percent of men (Mensink et al., Journal of Health Monitoring, 2016). For reducing neural tube defect risk, a considerably higher red cell folate threshold applies, which the large majority of women in Germany do not reach. This is the one context where a general supplementation recommendation rests on solid ground.
Three tests that mislead
Serum magnesium, and intracellular magnesium too
The National Institutes of Health Office of Dietary Supplements puts it plainly: less than one percent of total body magnesium is in serum, and serum levels do not accurately reflect total body magnesium or concentrations in specific tissues.
What often follows is an offer of a whole-blood or intracellular magnesium test. The same source states that among the alternatives, meaning erythrocyte, salivary, urinary and ionised magnesium plus the magnesium loading test, no single method is considered satisfactory. The critique of the serum value is fair, and it does not by itself qualify the alternative on offer.
On the most common use case: a 2020 Cochrane review (Garrison et al.) concludes for muscle cramps in older adults that magnesium "is unlikely to reduce the frequency or severity of muscle cramps," with gastrointestinal side effects in 11 to 37 percent versus 10 to 14 percent on placebo.
Hair mineral analysis
A study in JAMA (Seidel et al., 2001) sent samples of the same hair to multiple commercial laboratories. Results differed more than tenfold for twelve minerals, and reference ranges varied so widely that classifications conflicted for nearly all minerals. The authors explicitly recommend that practitioners refrain from using such analyses to assess individual nutritional status.
MTHFR genotyping
The practice guideline of the American College of Medical Genetics and Genomics (Hickey et al., Genetics in Medicine, 2013) states that MTHFR polymorphism testing has "minimal clinical utility." A gene variant on its own justifies neither a particular folate form nor a particular dose.
Where the evidence argues against taking something
| Supplement | What the trials found |
|---|---|
| Beta-carotene | ATBC (NEJM, 1994) in 29,133 smokers: 18 percent more lung cancer, 8 percent higher all-cause mortality. CARET (NEJM, 1996) replicated this at RR 1.28 and was stopped early. |
| High-dose vitamin E | SELECT (JAMA, 2011) in 34,887 men: 17 percent more prostate cancers on 400 IU daily. |
| Antioxidants generally | Cochrane review of 78 trials covering 296,707 participants (Bjelakovic et al., 2012): beta-carotene RR 1.05 and vitamin E RR 1.03 for all-cause mortality. |
| Selenium | SELECT: no cancer reduction. Stranges et al. (Annals of Internal Medicine, 2007): HR 1.55 for incident type 2 diabetes on 200 µg daily. EFSA upper limit 255 µg/day. |
| Omega-3 as a supplement | VITAL (NEJM, 2019): no effect on cardiovascular events (HR 0.92) on 1 g daily. STRENGTH (JAMA, 2020) was halted for futility at 4 g daily. A meta-analysis of 81,210 participants (Gencer et al., Circulation, 2021) found HR 1.25 for atrial fibrillation, rising to 1.49 above 1 g daily. |
| Multivitamins | 390,124 adults over up to 27 years (Loftfield et al., JAMA Network Open, 2024): no survival benefit. The USPSTF (JAMA, 2022) issues Grade D for beta-carotene and vitamin E, and an I statement for multivitamins. |
A distinction belongs with omega-3. REDUCE-IT (NEJM, 2019) showed a 25 percent reduction in the primary endpoint for prescription icosapent ethyl in a narrowly defined high-risk group on statin therapy, alongside a higher rate of hospitalisation for atrial fibrillation (3.1 versus 2.1 percent). That is a prescription medicine in a defined indication.
Upper limits that matter in practice
- Vitamin B6: EFSA lowered the tolerable upper intake level to 12 mg daily in 2023. The relationship between excess B6 intake and peripheral neuropathy is well established. Many B-complex products on the German market sit substantially above this.
- Selenium: EFSA upper limit 255 µg daily, with hair loss as an early sign. Thyroid-support products frequently supply 200 µg, leaving little headroom above dietary intake.
- Vitamin D: EFSA upper limit 100 µg (4,000 IU) daily for adults. Chronically excessive intake can lead to kidney stones, renal calcification and declining kidney function (BfR, 2020).
- Magnesium: 350 mg daily from supplements, with rising risk where kidney function is impaired.
- Iron: WHO flags ferritin above 150 µg/L in menstruating women and above 200 µg/L in men as indicating overload risk.
How we work
- History first. Dietary pattern, medication (metformin, proton pump inhibitors and antiepileptics above all), menstrual heaviness, sun exposure, pre-existing conditions, and the complete list of supplements already being taken.
- Measure selectively. Full blood count, ferritin with CRP, B12 with a follow-up test at borderline values, vitamin D where an indication exists. Every value gets an answer in advance to the question of what changes at which result.
- Dose with a target and an endpoint. A correction gets a dose, a target range and a follow-up date. Once the target is reached, the dose is adjusted or stopped.
- Review what you already take. At most first appointments the list can be shortened considerably, often in favour of one or two products with a finding behind them.
- Food stays part of the plan. For most of your micronutrient supply, diet is the more effective lever, and that part of the conversation belongs inside the 60 minutes.
Conclusion
Targeted micronutrient therapy works when a measured deficiency sits behind it and the correction is monitored. Iron deficiency with fatigue, B12 deficiency on metformin or with a vegan diet, folate before pregnancy: these are situations with solid evidence.
Broad prophylactic use has shown no benefit in large randomised trials, and for beta-carotene, high-dose vitamin E, selenium and high-dose omega-3 there are signals of harm.
If you currently take several supplements, bring the packaging and your most recent lab results to your first appointment. We go through both and decide what stays, what goes, and which measurement carries a real consequence in your situation.
References
- Max Rubner-Institut. Nationale Verzehrsstudie II, Ergebnisbericht Teil 2. Karlsruhe, 2008.
- Rabenberg M, Scheidt-Nave C, Busch MA, et al. Vitamin D status among adults in Germany – results from DEGS1. BMC Public Health. 2015;15:641. doi:10.1186/s12889-015-2016-7
- Mensink GBM, Weißenborn A, Richter A. Folate status in Germany. Journal of Health Monitoring. 2016;1(2):24–28. doi:10.17886/RKI-GBE-2016-040.2
- World Health Organization. WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations. Geneva, 2020. ISBN 978-92-4-000012-4
- Verdon F, Burnand B, Fallab Stubi C-L, et al. Iron supplementation for unexplained fatigue in non-anaemic women. BMJ. 2003;326(7399):1124. doi:10.1136/bmj.326.7399.1124
- Vaucher P, Druais P-L, Waldvogel S, Favrat B. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin. CMAJ. 2012;184(11):1247–1254. doi:10.1503/cmaj.110950
- Houston BL, Hurrie D, Graham J, et al. Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults. BMJ Open. 2018;8(4):e019240. doi:10.1136/bmjopen-2017-019240
- Miles LF, Litton E, Imberger G, Story D. Intravenous iron therapy for non-anaemic, iron-deficient adults. Cochrane Database of Systematic Reviews. 2019;12:CD013084. doi:10.1002/14651858.CD013084.pub2
- Tolkien Z, Stecher L, Mander AP, et al. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults. PLoS One. 2015;10(2):e0117383. doi:10.1371/journal.pone.0117383
- de Jager J, Kooy A, Lehert P, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency. BMJ. 2010;340:c2181. doi:10.1136/bmj.c2181
- Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435–2442. doi:10.1001/jama.2013.280490
- Pawlak R, Parrott SJ, Raj S, et al. How prevalent is vitamin B12 deficiency among vegetarians? Nutrition Reviews. 2013;71(2):110–117. doi:10.1111/nure.12001
- Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. British Journal of Haematology. 2014;166(4):496–513. doi:10.1111/bjh.12959
- Demay MB, Pittas AG, Bikle DD, et al. Vitamin D for the prevention of disease: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. 2024;109(8):1907–1947. doi:10.1210/clinem/dgae290
- Manson JE, Cook NR, Lee I-M, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. New England Journal of Medicine. 2019;380(1):33–44. doi:10.1056/NEJMoa1809944
- LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental vitamin D and incident fractures in midlife and older adults. New England Journal of Medicine. 2022;387(4):299–309. doi:10.1056/NEJMoa2202106
- Neale RE, Baxter C, Duarte Romero B, et al. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes & Endocrinology. 2022;10(2):120–128. doi:10.1016/S2213-8587(21)00345-4
- Burt LA, Billington EO, Rose MS, et al. Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength. JAMA. 2019;322(8):736–745. doi:10.1001/jama.2019.11889
- Bundesinstitut für Risikobewertung. Vitamin D: Einnahme hochdosierter Nahrungsergänzungsmittel unnötig. Statement No. 035/2020, 31 July 2020.
- IGeL-Monitor (Medizinischer Dienst Bund). Screening for vitamin D deficiency. Rating: "unclear", 9 November 2022.
- National Institutes of Health, Office of Dietary Supplements. Magnesium – Fact Sheet for Health Professionals.
- Garrison SR, Korownyk CS, Kolber MR, et al. Magnesium for skeletal muscle cramps. Cochrane Database of Systematic Reviews. 2020;9:CD009402. doi:10.1002/14651858.CD009402.pub3
- Seidel S, Kreutzer R, Smith D, et al. Assessment of commercial laboratories performing hair mineral analysis. JAMA. 2001;285(1):67–72. doi:10.1001/jama.285.1.67
- Hickey SE, Curry CJ, Toriello HV. ACMG practice guideline: lack of evidence for MTHFR polymorphism testing. Genetics in Medicine. 2013;15(2):153–156. doi:10.1038/gim.2012.165
- The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New England Journal of Medicine. 1994;330(15):1029–1035. doi:10.1056/NEJM199404143301501
- Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine. 1996;334(18):1150–1155. doi:10.1056/NEJM199605023341802
- Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews. 2012;3:CD007176. doi:10.1002/14651858.CD007176.pub2
- Klein EA, Thompson IM, Tangen CM, et al. Vitamin E and the risk of prostate cancer (SELECT). JAMA. 2011;306(14):1549–1556. doi:10.1001/jama.2011.1437
- Stranges S, Marshall JR, Natarajan R, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes. Annals of Internal Medicine. 2007;147(4):217–223. doi:10.7326/0003-4819-147-4-200708210-00175
- Manson JE, Cook NR, Lee I-M, et al. Marine n−3 fatty acids and prevention of cardiovascular disease and cancer. New England Journal of Medicine. 2019;380(1):23–32. doi:10.1056/NEJMoa1811403
- Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events (STRENGTH). JAMA. 2020;324(22):2268–2280. doi:10.1001/jama.2020.22258
- Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia (REDUCE-IT). New England Journal of Medicine. 2019;380(1):11–22. doi:10.1056/NEJMoa1812792
- Gencer B, Djousse L, Al-Ramady OT, et al. Effect of long-term marine ɷ-3 fatty acids supplementation on the risk of atrial fibrillation. Circulation. 2021;144(25):1981–1990. doi:10.1161/CIRCULATIONAHA.121.055654
- Loftfield E, O'Connell CP, Abnet CC, et al. Multivitamin use and mortality risk in 3 prospective US cohorts. JAMA Network Open. 2024;7(6):e2418729. doi:10.1001/jamanetworkopen.2024.18729
- US Preventive Services Task Force. Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. JAMA. 2022;327(23):2326–2333. doi:10.1001/jama.2022.8970
- EFSA Panel on Nutrition, Novel Foods and Food Allergens. Scientific opinion on the tolerable upper intake level for vitamin B6. EFSA Journal. 2023;21(5):e08006. doi:10.2903/j.efsa.2023.8006
- EFSA Panel on Nutrition, Novel Foods and Food Allergens. Scientific opinion on the tolerable upper intake level for selenium. EFSA Journal. 2023;21(1):e07704. doi:10.2903/j.efsa.2023.7704

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