Iron Deficiency May Be Linked to Depression and Poorer Life Quality

Low blood levels of ferritin — the main form of iron stored in cells — are significantly associated with more severe depressive symptoms and poorer quality of life in multiple sclerosis (MS) patients, a small study from Poland reports.

Data showed no link between the levels of other measures of iron metabolism and fatigue severity.

Larger and comparative studies, particularly in patients with chronic fatigue, are needed to confirm these preliminary findings, its researchers wrote.

The study, “The Role of Iron Metabolism in Fatigue, Depression, and Quality of Life in Multiple Sclerosis Patients,” was published in the International Journal of Environmental Research and Public Health.

Iron is a micronutrient essential for several biological processes, and poorly regulated iron metabolism (leading either to iron deficiency or overload) is associated with several diseases.

Iron balance in the brain is even more delicate, given that nerve cells do not renew. Iron accumulation in the brain damages cells, as does oxidative stress (an imbalance between the production of free radicals and the ability of cells to detoxify them).

Such damaging iron buildup has been observed in the brains of patients with several neurodegenerative disorders, including Parkinson’s and Alzheimer’s disease. In MS patients, previous studies showed iron dysregulation (either deficiency or accumulation) in several brain regions and a general imbalance in iron-associated oxidative stress in blood samples.

However, research so far evaluating bodywide changes in iron metabolism in MS patients reports inconsistent, and even contradictory, findings.

In addition, while links between molecules involved in iron metabolism and patient fatigue and depression have been evaluated for several disorders, MS is not among them.

Researchers in Poland set out to assess the potential associations between changes in iron metabolism and the severity of fatigue, depressive symptoms, and life quality in people with MS.

Their study enrolled 90 patients (62 women and 28 men), ages 19 to 67, recruited at three Polish MS centers. Most (78%) had the relapsing-remitting MS (RRMS), 14 had secondary progressive MS (SPMS), and six had primary progressive MS (PPMS).

Participants had moderate disability — as assessed with the expanded disability status scale (EDSS) — with more than 90% of them (57 women and 26 men) scoring 3.5 or lower on this scale.

The team analyzed patients’ blood levels of iron and iron-related molecules, including ferritin and transferrin, as well transferrin saturation (the potential capacity of transferrin to bind to iron in blood), and other measures of iron-binding capacities. (Ferritin is the main form of stored iron, while transferrin is an iron-transport protein that controls the levels of free iron in biological fluids.)

Fatigue was assessed with the nine-item Fatigue Severity Scale, depression using the 21-question Beck Depression Inventory, and quality of life through the Functional Assessment of MS; all are patient questionnaires.

Analyses placed MS patients’ blood parameters within normal ranges for the general adult population, taking into account age and gender. However, 32 patients showed altered transferrin saturation, 27 had changes in iron binding capacities, and 19 had abnormally low or high iron levels.

Women had significantly higher levels of transferrin and one measure of iron binding capacity than did men. SPMS patients also showed a trend toward higher ferritin levels (123 microgram/L) than did people with RRMS (59 microgram/L).

More than half of the participants (34 women and 16 men) did not have particularly severe fatigue symptoms, and results suggested an absence of significant depression. Men appeared to have significantly better quality of life than did women, with their scores representing a good life quality and a moderate quality among women.

Notably, patients with lower ferritin levels had significantly more severe depressive symptoms and a poorer quality of life. No other significant links between iron metabolism and MS features were identified.

Fatigue severity and depressive symptoms were both significantly linked to a deterioration in life quality, supporting their negative affect on life for those with MS.

“Ferritin deficiency in MS patients is associated with an exacerbation of depressive disorders and a decline in quality of life,” the researchers concluded. “Symptoms of fatigue in MS patients are inversely proportional to mood and quality of life.”

The researchers noted, however, that larger studies which include patients with more severe fatigue and depression, as well as healthy individuals for comparison, are needed to confirm their findings.

“Knowledge about the relationship between the values of the parameters of iron metabolism in the blood of MS patients and their mood and the intensity of fatigue may affect the possibility of their regulation and thus improve the quality of life of people with multiple sclerosis,” they wrote.