Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.

Background: Unexplained fatigue is a common complaint. When underlying disease causes have been eliminated, lifestyle measures and supplementation can be indicated. Elaborating on clinical findings that G115^®, a dry extract from the root of Panax ginseng, combined with vitamins and minerals could alleviate fatigue, this open label study aimed at assessing its effect on perceived fatigue and energy. Methods: Healthy adults self-reporting fatigue (n = 103) completed the Multidimensional Fatigue Inventory questionnaire. They rated their perceptions of mental and physical fatigue, energy, performance, and stress at baseline and 15, 30, 60 and 90 days after a daily intake of 40 mg G115^® formulated with vitamins and minerals. Results: Compared with baseline values, mean self-perception of general fatigue was reduced by −7.55 units [95% CI: −8.44; −6.66] (−41.8%, p < 0.0001) at 90 days. All assessed perception ratings (mental and physical fatigue, reduced activity and motivation, performance, and stress) were significantly and steadily improved from two weeks after supplementation up to study’s end. Overall satisfaction with the ability of the product to reduce fatigue reached 85% at Day 90. Conclusion: Daily intake with G115^® extract formulated with vitamins and minerals suggests an improvement of self-perception of fatigue and energy in a fatigued adult population.