Liposomal Iron: Ferrous Fumarate and Dosing

Iron is one of the oldest supplements in the pharmacy and still one of the most poorly tolerated. That combination has driven decades of formulation work, and more recently a rethink of something more basic than formulation, which is how often iron should be taken at all.

How iron is absorbed

Dietary iron arrives in two forms. Haem iron, from meat and fish, is absorbed relatively efficiently. Non-haem iron, from plant foods and from most supplements, is absorbed far less efficiently and is heavily influenced by everything else in the meal.

Absorption occurs principally in the duodenum, and the body has no active mechanism for excreting excess iron. Regulation therefore happens entirely at the point of absorption, and the regulator is a peptide hormone called hepcidin.

Hepcidin controls ferroportin, the protein that moves iron out of intestinal cells into the bloodstream. When hepcidin rises, ferroportin is degraded and iron absorption falls.

This matters enormously for supplementation, because an oral iron dose itself raises hepcidin, and that rise lasts longer than the dose does.

The alternate day finding

Moretti and colleagues, and subsequently Stoffel and colleagues in a randomised trial published in Lancet Haematology, examined what happens when iron is given daily versus on alternate days.

The finding was consistent and counter-intuitive. A single iron dose produces a hepcidin rise that persists for around twenty-four hours, meaning a second dose given the following morning lands while absorption is still suppressed. Giving iron on alternate days allowed hepcidin to return towards baseline, and fractional absorption was higher per dose.

Twice-daily dosing, long the standard clinical instruction, fared worst on this measure.

This research is why a supplement may direct alternate day dosing. It is a deliberate application of published pharmacology rather than an attempt to make a pack last longer. It also tends to reduce the gastrointestinal complaints that cause people to abandon iron supplements, since less unabsorbed iron remains in the gut.

Why ferrous fumarate

Iron salts differ in elemental iron content and in tolerability.

Ferrous sulfate is the long-standing clinical reference. Well studied, cheap, frequently associated with gastrointestinal complaints

Ferrous fumarate carries a high elemental iron percentage by weight and is widely used in both prescription and supplement contexts

Ferrous gluconate has lower elemental content per gram, so larger doses are needed

Iron bisglycinate is a chelated form often marketed on tolerability

Ferrous iron, the two-plus oxidation state, is absorbed more readily than ferric iron, which must be reduced before uptake. Fumarate is a ferrous salt, which is the relevant starting point.

Delivery

This is a dry liposomal capsule using the SAIFx system, with sunflower lecithin phospholipids and acacia gum.

The rationale for encapsulating iron is more specific than for most nutrients. Free iron in the intestinal lumen is the direct cause of most of iron's tolerability problems, and it also participates in oxidative reactions in the gut. A phospholipid structure changes how the iron is presented. This is the formulation logic. It is not a claim about outcomes.

What affects absorption

This is genuinely useful practical content and carries no claims risk, since it describes nutrient interactions rather than product benefits.

Increases non-haem iron absorption Vitamin C taken at the same time. This is itself an authorised claim: vitamin C increases iron absorption

Reduces non-haem iron absorption

Tea and coffee, through polyphenols

Calcium, including dairy and calcium supplements

Phytates in wholegrains, pulses and nuts

Some medications, including proton pump inhibitors and certain antibiotics

Spacing an iron supplement away from tea, coffee and dairy is the most commonly given practical advice, and it is well supported.

Iron Health Facts

Iron contributes to normal cognitive function. Iron contributes to normal energy-yielding metabolism.

Iron contributes to normal formation of red blood cells and haemoglobin.

Iron contributes to normal oxygen transport in the body. Iron contributes to the normal function of the immune system.

Iron contributes to the reduction of tiredness and fatigue. Iron has a role in the process of cell division.

Dose and practical considerations

One capsule every other day, providing 25 mg of iron, which is 179 percent of the Nutrient Reference Value. Preferably with food.

Safety points that must appear on the PDP.

Iron is one of the few supplement nutrients where accidental overdose is a genuine and serious risk, particularly in children. Keep out of the sight and reach of children.

The body cannot excrete excess iron. Anyone with haemochromatosis, another iron storage disorder, or a condition requiring repeated transfusions must not take iron supplements except under clinical supervision.

Iron status should be assessed by a GP through a blood test rather than guessed at. Persistent tiredness has many possible causes and warrants proper investigation rather than self-treatment.

Iron interacts with several medicines, including levothyroxine, some antibiotics and bisphosphonates, where separation in timing is usually required. Check with a pharmacist.

Common questions

Why every other day rather than daily? An iron dose raises hepcidin, the hormone that suppresses iron absorption, for around a day afterwards. Randomised research has found that alternate day dosing allows hepcidin to fall back, improving fractional absorption per dose.

What is the difference between ferrous and ferric iron? Ferrous is the two-plus oxidation state and is more readily absorbed. Ferric iron must be reduced before uptake.

Why does iron upset the stomach? Unabsorbed iron remaining in the intestinal lumen is the main driver. Lower and less frequent dosing tends to reduce this.

Should I take iron with vitamin C? Vitamin C increases non-haem iron absorption, and this is an authorised claim. Taking them together is well supported.

How do I know if I need iron? Through a blood test arranged by your GP. Iron status should not be assumed from symptoms, and the body cannot excrete excess iron, which makes unnecessary supplementation a real consideration.

References

Ganz T. Hepcidin and iron regulation, 10 years later. Blood. 2011;117(17):4425-4433.
Moretti D, Goede JS, Zeder C, et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015;126(17):1981-1989.
Stoffel NU, Cercamondi CI, Brittenham G, et al. 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. The Lancet Haematology. 2017;4(11):e524-e533.
Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anaemic women. Haematologica. 2020;105(5):1232-1239.
Hurrell R, Egli I. Iron bioavailability and dietary reference values. American Journal of Clinical Nutrition. 2010;91(5):1461S-1467S.
Hallberg L, Hulthén L. Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. American Journal of Clinical Nutrition. 2000;71(5):1147-1160.
NICE Clinical Knowledge Summaries. Anaemia, iron deficiency. National Institute for Health and Care Excellence.
Great Britain Nutrition and Health Claims Register. Department of Health and Social Care, gov.uk.

Food supplements are not a substitute for a varied and balanced diet and a healthy lifestyle.

Liposomal Iron: Ferrous Fumarate and Alternate Day Dosing