Review of frequently used Kampo prescriptions: Part 4, Ninjin'yoeito

Abstract Background The source of ninjin'yoeito (NYT) is considered the ‘Formulary of Bureau of Taiping People's Welfare Pharmacy’, written around 1241–52 AD. NYT is used to treat patients with chronic fatigue, malaise with qi deficiency, and exhaustion of all five parenchymatous viscera with difficulty in recovering. Key Findings NYT formula consists of 12 crude drugs. NYT extract for medical use is covered by the National Health Insurance system of Japan for convalescence after recovery from diseases, fatigue and malaise, anorexia, perspiration during sleep, cold limbs, and anemia. Studies have shown clinical effects of NYT: treatment of anemia, cancer treatment support, frailty, cognitive dysfunction, apathy, fatigue/malaise, anorexia, and lung diseases. Preclinical studies support clinical studies; activating ghrelin‐neuropeptide Y pathway‐mediated appetite‐enhancing effects, inhibiting muscle volume loss through the Akt/mTOR pathway‐mediated hyperphosphorylation of 4E‐BP1 and FoxO1‐mediated Atrogin‐1, suppressing the hypothalamic–pituitary–adrenal axis by downregulating the sympathetic‐adrenal‐medullary axis and GABA neurons for improving sociability, promoting recovery from skeletal muscle atrophy through the activation of PGC‐1α, hematopoiesis‐promoting effects, and increasing the number of immune cells in immunocompromised models. The incidence of adverse events of NYT was reported as 3.09 or 2.03%. The most significant adverse effects of NYT are gastrointestinal disorders. Conclusion Recently, NYT has been widely used to treat several symptoms and conditions under the National Health Insurance System of Japan. Clinical studies showed the efficacy of NYT to treat anemia, frailty, cognitive dysfunction, anorexia, apathy, and fatigue/malaise, as well as for long‐term cancer treatment support. The pharmacological mechanisms supporting its effects are also being reported.