When to take

When to take supplements: which questions have been measured?

The timing topic divides into four independent questions, and each has a different level of evidence. The sections below summarize data given in detail on each supplement’s own timing page on the site.

Are fat-soluble supplements taken with a fatty meal?

Vitamin D is fat-soluble. NIH reports that the presence of fat in the gut increases vitamin D absorption and that some absorption continues without fat. ^[1] In the randomized trial by Dawson-Hughes and colleagues with 50 healthy older adults, after a 12-hour fast a single high dose of D3 was given with a fat-free or a fatty meal; the plasma D3 peak at hour 12 was 32% higher with the fatty meal (95% CI 11–52). ^[2] This is an experimental single high-dose administration; it cannot be translated directly to daily use.

For omega-3 and coenzyme Q10, measured timing data are limited: for omega-3 there is a single-dose, product-specific pharmacokinetic comparison; coenzyme Q10 is a fat-soluble molecule, but whether taking it with a fatty meal changes the clinical result was not measured in the studies reviewed on the Q10 timing page. Details are given by omega-3 timing and the Q10 page below. For vitamins K2, E and A and for curcumin as well, the effect of meal-related timing on clinical outcomes was not measured in the studies reviewed in the relevant guides; being “fat-soluble” is an absorption assumption, not a measured timing rule.

Iron: empty stomach, alternate-day use, tea and coffee

The 2021 guideline of the British Society of Gastroenterology (BSG) writes that absorption of iron salts is markedly impaired with food and that taking it with food can reduce bioavailability by up to 75%. ^[3] NIH, in turn, states that side effects of high-dose iron (stomach upset, constipation, nausea) may lessen when it is taken with food. ^[5] The difference between them is that one emphasizes absorption and the other tolerance. According to the guideline, the absorption-reducing effect of tea disappears within 60 minutes. ^[3]

The strongest data for alternate-day use is the 2017 study by Stoffel and colleagues: in 40 women aged 18–40 with low iron stores (ferritin ≤25 µg/L), the same amount (60 mg) was given daily for 14 days or on alternate days for 28 days; the cumulative absorption fraction was 21.8% in the alternate-day group and 16.3% in daily takers. In the second study in the same publication (20 women, crossover design), a single morning dose was compared with a split morning-evening dose; splitting did not significantly increase absorption. ^[4] These are short-term absorption measurements, not clinical outcomes such as the rate of hemoglobin recovery. Details are on the iron timing page.

How are intervals between minerals and with medicines expressed?

Mineral intervals are given with the same wording on all pages of the site:

• Iron and calcium: NIH reports that it has not been conclusively shown that calcium affects iron absorption, yet experts recommend taking calcium and iron supplements at different times of day. ^[5]
• Iron and zinc: NIH reports that taking supplements containing 25 mg or more of elemental iron at the same time as a zinc supplement may reduce zinc absorption and plasma zinc level; iron in fortified foods does not markedly inhibit zinc absorption. ^[7]
• Zinc and magnesium: NIH’s magnesium fact sheet reports that very high amounts of supplemental zinc (142 mg/day in one study) can impair magnesium absorption and balance. ^[6] The relation between zinc and copper concerns not a time interval but high amounts over weeks; details are in the zinc guide.
• Magnesium and medicines: NIH recommends at least 2 hours between oral bisphosphonates and magnesium; for tetracycline and quinolone antibiotics, it states the antibiotic should be taken at least 2 hours before or 4–6 hours after magnesium. ^[6]
• The medicine’s own information for quinolones: MedlinePlus writes that for ciprofloxacin, antacids and multivitamins containing calcium, magnesium hydroxide, aluminum hydroxide, zinc or iron should be taken at least 6 hours before or 2 hours after ciprofloxacin. ^[8]

Medicine intervals do not replace the medicine’s leaflet and the instructions of the prescribing physician or pharmacist; changing medicine times personally is not the purpose of this page. All interactions are collected in a separate guide.

Timing for creatine and protein powder

In the randomized, double-blind, placebo-controlled trial by Dinan and colleagues, 34 collegiate athletes doing resistance training took placebo, 5 g of creatine monohydrate within one hour before training or 5 g of creatine monohydrate within one hour after training for 8 weeks; lean mass and strength increased to a similar extent in the three groups. ^[9] The trial is small. Details are on the creatine use page.

For protein, in the meta-analysis by Schoenfeld and colleagues (23 studies for hypertrophy, 525 people), once total protein intake was controlled, peri-workout intake had no significant additional effect on strength and hypertrophy; the strongest determinant for hypertrophy was total protein intake. ^[10] The methods of this meta-analysis have been criticized; for this reason, the result does not establish that timing is ineffective. In the 7-day crossover study by Mamerow and colleagues in 8 healthy adults, even distribution of protein across the day gave 25% higher 24-hour muscle protein synthesis than a distribution shifted toward the evening; this is a measurement of protein synthesis, not muscle mass. ^[11] Details are on the protein powder timing page.

Melatonin: the supplement with the most clearly measured clock effect

The direction of melatonin’s effect varies with the circadian time at which it is taken. In the study by Burgess and colleagues, 34 healthy adults aged 18–42 took 0.5 mg of melatonin or placebo for three days; the largest phase advance was seen with intake 2–4 hours before the onset of the evening (in the afternoon). ^[12] The study was done in a laboratory under dim light. The legal status of melatonin in Türkiye is a separate topic and is covered with sources on the melatonin page.

Probiotics, green tea extract and caffeine

For probiotics, the only comparison measuring the relation to meals is a laboratory model: in the upper gastrointestinal tract model of Tompkins and colleagues, the bacteria of a single commercial product showed the best survival when the product was given with a meal or 30 minutes before a meal; no human outcome was measured. The lead author’s institution is a company that makes probiotics. ^[13] For green tea extract, EFSA states that a single bolus dose in the fasted state significantly increased the area under the plasma concentration-time curve of EGCG compared with dosing with food and with split doses. ^[14] Tea and coffee are mentioned in the BSG guideline as beverages that can reduce iron absorption. ^[3]

Supplement timing: table

There is also a separate timing page for vitamin C; the measured information concerns amount (vitamin C timing).

What is decisive before the clock time?

1. Whether the supplement is needed. Timing does not solve the problem of unnecessary or overlapping products; this question is covered in the guide do you need supplements.
2. Interval from medicines. Of all the headings, this is the most concrete and numerical.
3. Relation to meals. Measured for vitamin D, iron and green tea extract.
4. Regular use. For most supplements, the effect of the clock time itself on health outcomes has not been measured; this is not evidence of “no difference” but information that “no difference has been shown.”

The instructions on the product label and principles of label reading are given in the guide how to read a label, and general safety topics in the guide are supplements safe. The summary on the vitamin and mineral side is on the page when to take vitamins; for basic concepts, the page what are supplements can be consulted.

What is known and not known about timing?

Known: Vitamin D absorption increases in the presence of fat. ^[1] With iron, food can reduce absorption and the effect of tea disappears within 60 minutes. ^[3] In a short-term study, alternate-day iron gave higher cumulative absorption than daily iron. ^[4] For some mineral and medicine pairs, time intervals are given in the sources. ^[6] For melatonin, the time of intake changes the direction of the effect. ^[12]

Not known: The long-term result of a morning-evening comparison for creatine, protein, magnesium, vitamin D and other supplements; the effect of a fatty meal on clinical outcomes for all fat-soluble supplements; the clinical meaning of the “best” order in supplement combinations.

This guide does not recommend a personal dose or time. With regular medicine use, pregnancy, kidney disease or malabsorption, supplements and their timing are planned together with a physician or pharmacist.