Creatine

Creatine is a nitrogenous organic acid synthesised in the body from glycine, arginine and methionine, and obtained from meat and fish. As phosphocreatine it is the cell's fastest energy buffer: it regenerates ATP from ADP over the first seconds of high-intensity effort, before glycolysis has spun up.

It is, by a wide margin, the best-evidenced supplement in common use — a rare case where the sports-nutrition consensus and the clinical literature agree.

Forms

Creatine is sold in many chemical forms which differ in solubility and marketing more than in demonstrated benefit:

Monohydrate — the form used in essentially all the research. Cheapest, and the correct default.
HCl, ethyl ester, buffered (Kre-Alkalyn), nitrate, magnesium chelate — better solubility claims, no superiority demonstrated on outcomes. Ethyl ester performs worse in the comparisons that exist.

Creapure is a manufacturing purity designation, not a different molecule.

Loading, or not

Two approaches reach the same muscle saturation:

Loading — ~20 g/day split into four doses for 5–7 days, then 3–5 g/day. Saturates in about a week.
No loading — 3–5 g/day from the start. Saturates in about four weeks.

The endpoint is identical. Loading exists to get there faster and is the phase where GI upset is reported.

Beyond muscle

The neurological literature is the more interesting half and is less well known:

Cognition — effects appear largest in people whose creatine status is lowest: vegetarians, the sleep-deprived, and under acute stress. In well-fed omnivores at rest the effect is small or absent.
Depression — adjunctive creatine has positive trials, particularly in women.
Studied in Parkinson's, Huntington's and traumatic brain injury, with mostly disappointing results in the large trials.
Creatine transporter deficiency is a genuine inborn error of metabolism in which supplementation is treatment.

Cautions

Kidneys. Creatine raises serum creatinine — a laboratory marker of kidney function — without impairing the kidney. This causes real and repeated confusion in clinic. Tell whoever orders the test. In healthy people creatine has not been shown to harm renal function; in existing renal disease it should be discussed rather than assumed safe.
Water retention — intracellular, a few pounds, expected and not fat.
GI upset at loading doses or with poorly dissolved powder; splitting the dose fixes it.
Non-responders exist — people whose muscle creatine is already near saturation from diet gain nothing.