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Iron
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A lot of people taking isotretinoin (Accutane) experience musculoskeletal side effects such as muscle pain (myalgia), stiffness, joint pain, and back pain.
One possible explanation involves L-carnitine metabolism. Isotretinoin may increase urinary carnitine loss, potentially reducing carnitine availability. A lack of carnitine could then potentially contribute to muscle aches, stiffness, and other musculoskeletal symptoms.
There is actually an interesting study from 1999 that investigated this.
The researchers followed 230 patients receiving isotretinoin. During treatment, they observed reduced serum L-carnitine levels and increased urinary carnitine excretion. 40 patients developed muscle aches and lower-extremity stiffness.
Of those 40 patients, 20 received L-carnitine at 100 mg/kg/day, while 20 received placebo. The results were quite striking: the symptoms disappeared within 5–6 days in all 20 patients receiving L-carnitine, whereas the patients receiving placebo continued to report myalgia.
What about the dose?
The study used a very high oral dose of 100 mg/kg/day. For someone weighing 90 kg, that's 9 g/day.
One reason a high oral dose may have been used is that the absolute bioavailability of oral L-carnitine at pharmacological doses is relatively low, generally reported at around 5–18%.
At high oral doses, side effects such as gastrointestinal upset and a fishy body odor can occur.
An injection has a much higher bioavailability, so it can achieve the same systemic exposure with a much smaller administered dose. This could reduce dose-related gastrointestinal side effects.
Whether a much lower oral dose could produce the same effect is also unknown, since the 1999 study only tested the 100 mg/kg/day dose.
So overall, I think the L-carnitine hypothesis is pretty interesting. The evidence is definitely not extremely strong, as this was a relatively small study, but it might be worth taking if you're dealing with musculoskeletal side effects from Accutane.
One possible explanation involves L-carnitine metabolism. Isotretinoin may increase urinary carnitine loss, potentially reducing carnitine availability. A lack of carnitine could then potentially contribute to muscle aches, stiffness, and other musculoskeletal symptoms.
There is actually an interesting study from 1999 that investigated this.
The researchers followed 230 patients receiving isotretinoin. During treatment, they observed reduced serum L-carnitine levels and increased urinary carnitine excretion. 40 patients developed muscle aches and lower-extremity stiffness.
Of those 40 patients, 20 received L-carnitine at 100 mg/kg/day, while 20 received placebo. The results were quite striking: the symptoms disappeared within 5–6 days in all 20 patients receiving L-carnitine, whereas the patients receiving placebo continued to report myalgia.
What about the dose?
The study used a very high oral dose of 100 mg/kg/day. For someone weighing 90 kg, that's 9 g/day.
One reason a high oral dose may have been used is that the absolute bioavailability of oral L-carnitine at pharmacological doses is relatively low, generally reported at around 5–18%.
At high oral doses, side effects such as gastrointestinal upset and a fishy body odor can occur.
An injection has a much higher bioavailability, so it can achieve the same systemic exposure with a much smaller administered dose. This could reduce dose-related gastrointestinal side effects.
Whether a much lower oral dose could produce the same effect is also unknown, since the 1999 study only tested the 100 mg/kg/day dose.
So overall, I think the L-carnitine hypothesis is pretty interesting. The evidence is definitely not extremely strong, as this was a relatively small study, but it might be worth taking if you're dealing with musculoskeletal side effects from Accutane.
