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. 2020 Nov 26;8:584010. doi: 10.3389/fbioe.2020.584010

TABLE 1.

State of the art of known biological effects of investigated low molecular weight OHAs.

Oligomer Observed biological effects
3HB The oral administration of the 3-hydroxybutyric acid salts increased ketonemia in Wistar rats and conducted to the improvement of body control by the reduction of fat mass and amelioration of serum lipid profile suggesting that ketone supplements could be helpful in the treatment of obesity and metabolic diseases (Caminhotto et al., 2017). Some gastrointestinal disturbances were observed in vivo in individuals who consumed a high dose of 3HB (Clarke et al., 2012). A high quantity of 3HB could be harmful because it may conduct to acidosis (Newman and Verdin, 2017). The 3HB may produce eye, skin and respiratory irritations (National Library of Medicine, 2020c).
4HB The 4HB does not bind to a significant extent to plasma proteins. High doses of 4HB produced hypotension, bradycardia, tachycardia, hypothermia, unconsciousness, acute respiratory acidosis and gastrointestinal disturbances. After ingestion, 4HB is easily absorbed and it is able to cross the blood-brain barrier. It is rapidly metabolized and excreted through the lungs (Busardò and Jones, 2015). The 4HB may produce eye damage, drowsiness or dizziness (National Library of Medicine, 2020a).
3HV The 3HV may produce eye, skin and respiratory irritations (National Library of Medicine, 2020b).
4HV The 4HV is marketed as a dietary supplement and replacement for 4HB as at higher doses it shares some effects with 4HB such as sedation, catalepsy, and ataxia (Carter et al., 2005).
O3HB Low molecular weight O3HB (smaller than 20 monomeric units) are constituents of cells and are covalently attached to proteins located within membranes and organelles (Reusch, 2013).
O3HB, O3HV, O4HB, O4HV, O(3HB3HV) The in vitro cytotoxicity of the OHAs against mouse fibroblasts decreased with increasing OHAs side chain length (Sun et al., 2007).

3HB, 3-hydroxybutyrate; 3HV, 3-hydroxyvalerate; 4HB, 4-hydroxybutyrate; 4HV, 4-hydroxyvalerate; O3HB, oligomers of 3HB; O3HV, oligomers of 3HV; O4HB, oligomers of 4HB; O4HV, oligomers of 4HV, O(3HB3HV) denotes co-oligomers of 3HB/3HV with various monomeric unit distributions, and O(4HB4HV) denotes co-oligomers of 4HB/4HV with various compositions.