What about Deprenyl for Dopamine Decline?

Q In a recent article, you discussed the importance of dopamine and its age-related decline, its effects on the body and mind, and how resveratrol can help to slow this decline.

I have heard of similar claims being made about a substance called selegiline (aka L-deprenyl). I know this isn’t exactly a “natural” supplement, but I was wondering if anyone at Life Enhancement is aware of studies regarding selegeline supplementation in regard to age related dopamine decline.

RICH, Philadelphia

A We have followed the selegiline literature for many years. Some life extenders take the drug deprenyl to protect their brains from oxidative damage, increase the levels of brain catecholamine activity, reduce neuronal damage, and possibly slow the progression of Alzheimer’s disease. However, there is some controversy concerning deprenyl. For example, one study showed that while lower doses of deprenyl (0.25, and 0.50 mg/kg/injection) given to rats increased average lifespan, a 1.0 mg/kg dose found that rats began dying earlier than control rats, leading to an inverse U-shaped dose-efficacy relationship.1 That’s not good.

Alternatively, a study published in the later 90s found that at least some of the noted benefits of deprenyl may also be available for those taking high levels of vitamin E daily.2

When a total of 341 patients with Alzheimer’s disease received 10 mg of deprenyl (a MAO-B inhibitor) or 2000 IU of vitamin E (as alpha tocopherol) or a placebo every day for two years, the time of onset for what the scientists termed a primary outcome was measured. (Primary outcomes included death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia.)

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Within the Vedic epics is the Mahabharata, which contains about 100,000 couplets. It is the longest poem ever written. Bacopa is reputed to have played a role in increasing the ability to memorize these great epic poems.
Those taking deprenyl outlasted placebo by an additional 215 days (49% longer) before encountering a primary outcome (655 days for deprenyl vs 440 days for placebo) and those taking the 2000 IU of vitamin E/day outlasted placebo by 230 days (52% longer) before they encountered any negative event from the same set of primary outcomes (670 days for vitamin E vs 440 days for placebo). These were significant delays. Vitamin E slowed the progression of Alzheimer’s disease slightly more than the treatment of choice, deprenyl, for patients with moderately severe impairment.

Also, in a more recent study, scientists at the Jawaharlal Nehru University in New Delhi reported on the protective effect of Bacopa monniera against aluminum-induced oxidative stress in the hippocampus of rats.3 The researchers laced the rats’ drinking water with neurotoxic aluminum chloride and protected some of them with simultaneous administration of bacopa extract or the anti-Parkinson’s drug, deprenyl. Like bacopa, deprenyl is an antioxidant and neuroprotectant; it is thought to have antiaging effects.

By itself, aluminum chloride produced evidence of oxidative stress in the form of lipid and protein oxidation products and lipofuscin (an age-related pigment), as well as necrosis-like changes in the cellular ultrastructure of the hippocampus. Not surprisingly, these results were accompanied by reduced levels of an important antioxidant—the enzyme superoxide dismutase (SOD)—that the researchers were also measuring.

Co-administration of bacopa or deprenyl with the aluminum chloride, however, largely prevented the oxidative damage to the rats’ hippocampal cells and restored SOD levels to near normal. Necrosis-like changes in the cells were eliminated. The authors stated,

… Bacopa’s antioxidative effects appear to be similar to those of L-deprenyl. Oxidative stress … is thought to contribute to the aging process. Bacopa … could thus be considered as a potential antiaging substance. Furthermore, the similarity of Bacopa’s effects with those of L-deprenyl, which is a candidate [anti]aging drug, would also be indicative of its antiaging potential.


  1. Kitani K, Kanai S, Miyasaka K, Carrillo MC, Ivy GO. The necessity of having a proper dose of (-)deprenyl (D) to prolong the life spans of rats explains discrepancies among different studies in the past. Ann N Y Acad Sci 2006 May;1067:375-82.
  2. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med 1997;336:1216-22.
  3. Jyoti A, Sharma D. Neuroprotective role of Bacopa monniera extract against aluminum-induced oxidative stress in the hippocampus of rat brain. Neurotoxicology 2006;27(4):451-7.

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