The use of magnetic resonance spectroscopy (MRS) to monitor cellular bioenergetics during weight loss may provide novel insights regarding metabolic functioning.Changes were noted in 18 sedentary, moderately overweight women following a 7-week program consisting of a low-fat, 422-428 MJ/day (1010-1025 kcal/day) diet, a progressive walking program, a vitamin-mineral-fortified, isolated-protein meal supplement drink and a weekly group meeting. Mitochondrial energy production and utilization were assessed by measuring the concentrations of inorganic phosphate (Pi) and phosphocreatine (PCr) through magnetic resonance spectroscopy. Anthropometric changes were also monitored.Dietary analysis of subjects' pre-intervention food records showed intakes of numerous vitamins and minerals below 100% of the Recommended Dietary Allowances (RDA), most commonly for folic acid, vitamin E, magnesium, iron and zinc. Relative to pre-intervention levels, final measurements showed that all women lost body weight, ranging from 2.6 to 10.0 kg. Body mass index declined in all subjects, from 0.55 to 3.86 kg/m2. All subjects lost fat mass, ranging from 0.9 to 10.4 kg. Seventeen of 18 women showed a decline in their percentage of body fat, ranging from 2.3 to 10.1%. Twelve of 18 subjects showed an increase of 0.1-3.5 kg of fat-free mass, with half of these values increasing by>1.0 kg. No changes from baseline levels were found in the Pi/PCr ratio over 7 weeks under resting, exercise or recovery conditions, suggesting a preservation in muscle energy function over the course of the study while the subjects were losing fat mass and total body weight.The possible metabolic advantage associated with a program that employs moderate energy restriction, repletion of vitamin and mineral intakes to RDA levels, and a regular aerobic exercise program is proposed.