A daily iron and vitamin sachet for 120 stroke patients in Rome: fatigue scores ended 6 points lower than rehab alone, but nobody got a placebo and nobody checked their iron

Fatigue is one of the most common problems after a stroke. A 2016 review of 22 studies with 3,491 stroke survivors put it at about half of them, and it is not simply sleepiness: it is a lasting lack of energy that makes rehabilitation, work and daily life harder. There is no established treatment. A study published on 25 October in the journal Nutrients tested whether a daily nutrient sachet, taken alongside rehabilitation, could help.

The trial was run by researchers at the Fondazione Policlinico Universitario A. Gemelli and the Università Cattolica del Sacro Cuore in Rome. It took 120 adults who had had a stroke, were in hospital rehabilitation and had clear post-stroke fatigue; people with severe cognitive problems or aphasia, unrelated serious infections or inflammation, or severe psychiatric illness were left out. Average age was about 71, and a little under half were women. A computer split them evenly. Half took one sachet a day of SiderAL Med, a food for special medical purposes made by the Italian company PharmaNutra, for four weeks in hospital and one month after going home; the other half had standard care. Both groups had the same intensive physical, occupational and cognitive therapy. The sachet was then stopped, and everyone was checked again at 16 weeks.

The sachet is a broad mix rather than a single nutrient. Each one gives 30 mg of iron in the maker's sucrosomial form (wrapped in a phospholipid and sugar-ester coating meant to improve absorption), 75 mcg of vitamin D (3,000 IU), 94 mg of magnesium, 200 mg of calcium from algae, 6 mg of zinc, 150 mcg of vitamin B12, 200 mcg of folate, 75 mg of vitamin C, 50 mg of vitamin E, other B vitamins, vitamins A and K, selenium, copper and iodine. Iron deficiency was not a condition for joining, and the patients' iron, ferritin and haemoglobin were not measured.

Both groups felt less tired over time. The main measure was the change in the Modified Fatigue Impact Scale, a 21-question survey scored from 0 to 84, from the start to the end of the eight weeks of supplement. At the start the median scores were 40.5 in the sachet group and 44 in the control group. After allowing for starting scores, the sachet group finished 6.2 points lower, with a likely range of 1.2 to 11.2 points (p = 0.015). The groups' paths also differed on physical and thinking-related fatigue and on balance (the Berg scale), a short physical performance test and the six-minute walk. They did not differ significantly on the psychosocial part of the fatigue scale, on independence in daily activities, on arm and leg strength on the affected side or on quality of life.

The researchers also measured two blood markers. IL-6, a signal of inflammation, and myeloperoxidase, an enzyme linked to oxidative stress, moved differently in the two groups, with falls in the sachet group, and in that group higher IL-6 at 16 weeks went with more fatigue. Some of the marker changes eased back once the sachet stopped. A third marker, the anti-inflammatory IL-10, was too low to measure in everyone. Phase angle, a body-scan reading of cell health, improved within the sachet group but not by more than in the control group. Two people on the sachet had mild nausea that passed; no one stopped taking it.

The authors name the biggest weakness themselves: there was no placebo. The control group had no dummy sachet, and patients and therapists knew who was taking the real one, which matters most for a self-reported score like fatigue; only the people doing the assessments and the analysis were blinded. The sample size was not worked out in advance. Because iron status was never checked, the study can't say whether iron, any other ingredient or the combination made the difference, or whether anyone was deficient to begin with. It was a single centre, and the trial builds on an earlier pilot by the same group. PharmaNutra funded the study with a research grant and supplied the product; the paper says it had no role in the design, analysis or writing, and the authors declare no conflicts of interest. They call for double-blind, placebo-controlled trials across several centres.