Mitragynine is the most abundant alkaloid in kratom. Kratom contains about 40 alkaloids that we know of. All of the alkaloids combined make up only 0.5-1.5% of the total leaf material.
Estimates of percentage of mitragynine in alkaloids range from 12% in Malaysian kratom to 66% in Thai kratom. If alkaloids make up only 1% of leaf, that means the higher potency Thai kratom would contain only 0.66% mitragynine.
The scientific term LD50 describes the lethal dose at which 50% of the test animals have died from a certain substance. There’s a lethal dose for just about everything, including water. The LD50 of caffeine administered orally to albino rats is 367 mg/kg (that’s milligrams of caffeine per kilogram of body weight). Green tomatoes contain a substance called tomatine which can be toxic. Tomatine’s LD50 is said to be 500 mg/kg. That’s a lot of green tomatoes.
The doses above aren’t human equivalent doses (HED). Body surface area must be accounted for, according to this guide. For example, a 367 mg/kg dose in a rat is equivalent to a 59.454 mg/kg dose in a 60 kg (132 lb) human according to FDA draft guidelines. That 60 kg human would need 3,567 mg of caffeine to kill her, roughly 40 cups of coffee in one sitting.
In one study the LD50 of mitragynine was found to have been 547.7 mg/kg in mice, which is consistent with a few other studies. (Although we have seen a 1972 study by Macko where 900 mg/kg of mitragynine was administered to mice with no toxic effects. See Kratom Science Journal Club Episode 6 where we discuss this study).
According to the FDA draft guidelines the human equivalent dose of 547.7 mg/kg in mice would be 44.36 mg/kg. That same 60 kg human would have to take 2,662 mg of mitragynine. Given that mitragynine is 0.66% of alkaloids in the most potent Thai kratom, that person would have to consume 403,300 mg or 403.3 grams of kratom leaf (14.23 oz) in one sitting.
If we take the mean percentage of mitragynine between 12% of alkaloids in Malaysian kratom and the 66% of alkaloids in Thai, then mitragynine would be present in 39% of total alkaloids or 0.39% of kratom leaf of average potency. That would mean to reach the LD50, a person would have to consume 895.3 grams or just under a kilo of average potency kratom in one sitting.
Damaging but not deadly… How much is too much?
In a 2015 study published in Frontiers in Neuroscience by University of Science Malaysia researchers, large rats (weighing about 50 g) given 200 and 500 mg/kg of an alkaloid extract of kratom per day showed damage to liver, kidneys, and lungs.
A 60 kg (132 lb) human equivalent dose for these rodents would be 27 and 67.5 mg/kg of alkaloids per day. Since alkaloids are only present in 1% of plain leaf kratom, a 60 kg human would have to take 162 g (5.71 oz) and 405 g (14.29 oz) per day to achieve these same damaging effects to organs with kratom alone.
Most consumers take 5 to 10 grams of kratom per day, nowhere near the smallest human equivalent dose given to lab animals in the above experiments. Those who take extracts would have to be more careful. Even then, if they obtained a near-100% alkaloid extract (most extracts sold are nowhere near at that level), the massive amounts needed would not produce desirable effects.
Having said that, many people who take large amounts of kratom might suffer from rare side effects such as nausea, headaches, and even hair loss. Dr. Darshan Singh told KratomScience that this may be from adulterated kratom since he doesn’t see these side effects in people in Malaysia, where kratom is grown naturally. However, many Americans could be consuming too much kratom, even if it doesn’t reach levels that would damage internal organs.
Anyone who consumes kratom regularly and experiences undesirable effects should consider lowering or eliminating their intake.