Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging

Abstract

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60–75 years) received a single administration of 100, 150, or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18–35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210, and 240 min after tyrosine intake. Working memory was assessed using the N-back task at 90 min after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p < 0.001), and the plasma response was higher than for young adults with the same dose (p < 0.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p = 0.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p = 0.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults

“…A study in adult schizophrenia patients (mean age 37.8 years, SD 6.8) displayed increased errors in a smooth pursuit saccades task in eight patients during three weeks supplementation of 10-g tyrosine daily (Deutsch et al, 1994). In line with an overdose hypothesis, a recent study demonstrated decreased working memory (i.e., n-back) performance with increasing tyrosine dose (from 100-150 to 200 mg/kg) in older adults (aged 60–75 years, mean age: 69.6; van de Rest et al, 2017). This cognitive overdose effect of tyrosine, which has so far been observed only in older adults, may be at least partly caused by a larger effective dose in older adults due to increased peripheral supply of tyrosine.…”

“…This cognitive overdose effect of tyrosine, which has so far been observed only in older adults, may be at least partly caused by a larger effective dose in older adults due to increased peripheral supply of tyrosine. Earlier research demonstrated increased plasma tyrosine levels in fasting older versus young women (Caballero et al, 1991) and increased plasma response in older versus young adults receiving the same dose (van de Rest et al, 2017). Critically, in this latter study, dose-dependent increases in plasma response correlated with dose-dependent decrements in working memory after tyrosine ingestion.…”

“…We expected to find beneficial effects of tyrosine on brain and behavior across the group of older adults. Given our recent findings of age-related differences in the peripheral plasma response to oral tyrosine administration (van de Rest et al, 2017) and given differences in the effect of dopaminergic agents between younger and older adults (Turner et al, 2003), we also explored the possibility that tyrosine’s effects would vary as a function of age. Using a smaller age range, we do not expect generational differences to influence the effects of dopaminergic agents, such as differences in education or computer experience that would differ in a cross-sectional design with larger age differences.…”

“…This upregulation of synthesis capacity has been related to, if anything, worse rather than better neurocognitive functioning relative to young adults (Dreher et al, 2008; Berry et al, 2016). Moreover, a recent study with multiple oral tyrosine doses (100, 150, and 200 mg/kg, but no placebo condition) showed decreased cognitive performance with increased tyrosine dose in older adults (van de Rest et al, 2017). Therefore, in the current placebo-controlled study, administration of a high dose (150 mg/kg) of the dopamine precursor tyrosine might also impair instead of improve neuro-cognitive function in the oldest adults, with presumably the greatest upregulated dopamine synthesis capacity.…”

Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults

“…Aging is accompanied by deficits in inhibitory functions, both in terms of the inhibition of irrelevant information, e.g., sensory suppression (Gazzaley et al, 2008;Healey et al, 2008), as well as in terms of response inhibition, such as in stop-signal tasks (Kramer et al, 1994;Bedard et al, 2002;van de Laar et al, 2011). Two forms of response inhibition have been distinguished: reactive response inhibition is the process of canceling an ongoing response at the moment this is needed (i.e., outright stopping), whereas proactive response inhibition entails the preparation for stopping when this may become necessary, e.g., based on cues held in working memory.…”