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Toxicology testing has noted that the No Observed Adverse Effect Level (NOAEL; the highest dose not associated with any toxic signs) for HMB oral ingestion in rats is 3490 mg/kg for male rats and 4160 mg/kg for female rats; this is an estimated human equivalent of 558 mg/kg and 665 mg/kg, and assuming a body weight of 150 lbs equates to 38 grams (males) and 45 grams (females). Other animal toxicology testing includes approximately 5g/kg in pigs over 4 days which failed to alter any biochemical parameter or organ weight (Nutritional role of the leucine metabolite B-hydroxy B-methylbutyrate (HMB) 1997; cited via review).
Human toxicological studies have noted that approximately 6 grams HMB daily (78 mg/kg) for one month in untrained young males subject to exercise did not show any toxic effects on serum parameters (half the dose had a spontaneous increase in basophils, considered to be insignificant) and 3 grams of HMB daily for up to 8 weeks in both youth and older persons has similarly failed to alter toxicological parameters in serum and this dose has been safe for one year of administration (study confounded with L-lysine and L-Arginine ingestion). Overall, standard doses of HMB appear to be well tolerated over long periods of time (meta-analysis).
HMB supplementation at up to 3 grams daily has been demonstrated to be very well tolerated, and it is suspected that higher doses are equally safe (but with less human testing). There is not too much safety concern with supplemental HMB *