Compositions that supplement and support nitric oxide availability to skin and methods of use include a first agent that is a precursor of nitric oxide, a second agent that facilitates production of nitric oxide by the first agent, and a third agent that antagonizes (i) nucleotide activation of skeletal muscle ryanodine receptors or (ii) cellular calcium influx. The first, second and third agents are mixed to form a composition suitable for topical application to skin. The composition may include an adenosine, arginine, carnosine, niacinamide, and a magnesium ion source, wherein application of the composition to a skin region increases cutaneous blood flow in the skin region compared to cutaneous blood flow in a similar skin region not treated with the composition, as measured by doppler ultrasound.