Original articleIntake of tryptophan-enriched whey protein acutely enhances recall of positive loaded words in patients with multiple sclerosis
Introduction
Aside from morphological changes such as cerebral atrophy, lesion burden and changes in gray matter volume within brain structures, the high prevalence of mood disturbances and cognitive deficits in multiple sclerosis (MS) patients is related to neurotransmitter deregulation [1], [2]. Albeit that the exact role of serotonin in MS is indistinct, there are clear indications that axonal degeneration, pro-inflammatory cytokines and MS-related lesion affects the metabolic pathway of tryptophan (TRP; precursor of serotonin) leading to serotonergic deregulations [3], [4], [5], [6] and consequently serotonergic dysfunctions like anxiety, low mood, attentional and memory problems [7], [8]. In addition, MS reduces TRP availability [1], [2], blocks platelet serotonin uptake sites and inhibits central serotonin re-uptake transport system and lowers serotonin turnover [9], [10]. These findings imply that affective and cognitive dysfunctions in MS patients are at least partly mediated by a deregulation in serotonin metabolism, and elucidate the fact that MS patients are more susceptible to develop depressive symptoms.
Administration of selective serotonin reuptake inhibitors show a trend towards efficacy in MS related depression, but are associated with adverse effects such as nausea or headache [11]. An alternative approach to increase the availability of TRP, an essential amino acid that is required in sufficient amounts to prevent body weight loss but also memory impairments [12]. The intake of TRP enriched diet or proteins with high amount of TRP such as α-lactalbumin increase brain serotonin concentrations [13], improve learning and memory [14], [15] and mood [16], [17], [18], [19]. Yet, little information is available about the effects of TRP in relation to neuropsychological functions in MS. In 1975, one study reported that seven days of TRP administration elevated cerebrospinal fluid TRP and improved MS symptoms without having any side effects [20].
Given the line of evidence that MS can deregulate the metabolism of serotonin and based on the effects of TRP enrichment on affective and cognitive functions, we hypothesize that intake of a TRP-enriched diet in MS patients normalizes serotonin metabolism and subsequently ameliorates neuropsychological dysfunctions. The purpose of the present study is to evaluate acute and dose-dependent effects of a TRP enriched whey-protein mixture on mood and cognition function in MS patients. Since it was demonstrated that subjects with personal history of mood disorders and higher baseline depression scores have a higher serotonergic vulnerability (for review see Ref. [21], our secondary aim was to investigate whether MS patients with depressed mood could benefit more from a TRP enriched diet.
Section snippets
Participants
From a total of 40 MS patients who were screened at the Academic MS Center Limburg (Zuyderland Medical Center, Sittard, the Netherlands; Fig. 1), we enrolled 32 MS patients based on the following criteria: male or non-pregnant, non-lactating female between 18 and 55 years of age, diagnosed with MS, according to the McDonald criteria [22] and cognitively intact (i.e., Mini Mental State Examination (MMSE) score of 21 or more). The subjects did not exhibit any indications of nutritional,
General characteristics
The main characteristics of all subjects enrolled in this study are summarized in Table 2. One patient dropped out after the third session due to personal reasons. The majority of patients were females with the relapsing remitting type of MS. Except for the CES-D, EDSS and the MMSE scores, overall demographic and clinical features were similar between groups. CES-D and EDSS scores were higher in the DM group. The mean MMSE score was slightly, but significantly, higher in the DM group. However,
Discussion
We found memory-improving effects three hours after the intake of a TRP enriched whey protein diet in MS patients. This effect occurred when increasing TRP/ΣLNAA ratio to 15% by adding L-TRP to a whey protein mixture and was irrespective of the presence of depressed mood. Increasing the TRP availability did not induce a significant change mood states in MS patients.
The finding that subjects with depressed mood had lower mood states than control subjects merely confirms that the groups were
Conflict of interest
There is no conflict of interest to declare.
Acknowledgments
The author's responsibilities were as follows – CL, AB, ND and RH: designed research study; CL and WJ: conducted the study, collected and managed the data and samples, and drafted the manuscript; ND: conducted the amino acid analyses; CL and GH: analyzed data; and CL, AB, ND and RH: interpreted the data critically, reviewed the manuscript, and approved the final draft.
The authors thank the MS patients who participated in the study, the laboratory from the Zuyderland Medical Center and the staff
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