Is it time to reassess alpha lipoic acid and niacinamide therapy in schizophrenia?

Med Hypotheses. 2010 Dec;75(6):572-5. doi: 10.1016/j.mehy.2010.07.034. Epub 2010 Aug 12.


As sulfur containing thiols, alpha lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are powerful antioxidants and free radical scavengers capable of performing many of the same functions as glutathione (GSH). ALA supplementation may help protect mitochondria from oxidative stress, a possible mechanism contributing to certain forms of brain diseases called schizophrenia. Shortly before the advent of antipsychotic medications, two small studies found ALA relieved psychiatric symptoms in schizophrenia. More recently, animal studies have shown ALA augmentation improves mitochondrial function. At pharmaceutical levels, niacinamide helps preserve mitochondrial membrane integrity and acts as an antioxidant. ALA is a precursor for lipoamide, an essential mitochondrial coenzyme and niacinamide is a component of niacinamide adenine dinucleotide (NAD). NADH, the reduced form of NAD, is involved in the reduction of ALA to DHLA within the mitochondria. This is relevant to contemporary research because DHLA increases GSH and low GSH levels contribute to mitochondrial dysfunction and oxidative stress which have been implicated in the pathophysiology of schizophrenia.

MeSH terms

  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Dopamine / metabolism
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Humans
  • Mitochondria / drug effects
  • Mitochondrial Membranes / drug effects
  • Niacinamide / pharmacology
  • Niacinamide / therapeutic use*
  • Schizophrenia / drug therapy*
  • Thioctic Acid / analogs & derivatives
  • Thioctic Acid / metabolism
  • Thioctic Acid / pharmacology
  • Thioctic Acid / therapeutic use*


  • Antioxidants
  • Niacinamide
  • Thioctic Acid
  • dihydrolipoic acid
  • Glutathione
  • Glutathione Disulfide
  • Dopamine