4. Discussion
Anxiety, cognitive impairment, cancer, gastrointestinal tract, Hostility, Anger, Depression, Fatigue, Different gastrointestinal metabolites, Confusion, cognition, mood, and sleep
CANCER, MINOR, CHRONIC INFLAMMATION, TYPE 2 DIABETES, DISEASES
The present exploratory study was conducted to gain insight into the effect of LPHEAL9 on the gut–brain axis. Measurements of stress, cognition, mood, and sleep were investigated after intake of LPHEAL9 or placebo for 12 weeks. The primary findings in this study indicated a positive impact on cognitive performance, especially memory functions, after intake of LPHEAL9 compared to placebo. These results may be connected to the improvements over time seen by LPHEAL9 in sleep quality, overall mood, and awakening cortisol. Perceived stress (PSS) was reduced significantly in both the LPHEAL9 and the placebo groups, with no difference between the groups. Thus, a large placebo effect on subjects with moderate stress was seen. This observation aligns with a study testing The connection between stress and sleep has been known for a long time. One of the causes of this connection is the “fight or flight” response arising from stressful situations. This leads to increased heart rate and blood pressure, as well as increased levels of cortisol and adrenaline, responses that greatly affect sleep quality and duration of sleep [Mood is defined as a transient state of mind, and one of the most common methods used to measure it is the POMS questionnaire. Apart from the overall score obtained from this test, there are six pre-defined sub-scores (Anger–Hostility, Confusion–Bewilderment, Depression–Dejection, Fatigue–Inertia, Tension–Anxiety, Vigor–Activity, and Friendliness). In the current study, all the sub-scores were significantly improved within the LPHEAL9 group from baseline to week 12. The placebo group reported minor but still significant changes within four of the six sub-scores. For three of the sub-scores, there was a trend for a difference in favor of LPHEAL9 compared to placebo, namely Anger–Hostility, Depression–Dejection, and Confusion–Bewilderment. Similar results were obtained in a study with a probiotic blend given to healthy individuals, where significant within-group differences were observed only for the above-mentioned sub-scores related to the “negative” subscales of mood [In the present study, the subjects were challenged using cognition tests before and after treatment. Generally, many cognition tests are used to evaluate if the subject has cognitive impairment, but in a study with healthy and relatively young subjects, as in the present case, it may not be surprising that some cognition tests were too easy (four choice reaction time and Corsi blocks). But the more difficult tests (numeric working memory, rapid visual information processing, paired associate learning, and word recall) were found to be applicable to evaluate differences due to treatment. One of the most significant results in the present study is that intake of LPHEAL9 improved working memory compared to the placebo group in the word recall test. The effect of LPHEAL9 on working memory agrees with a similar study that tested the effect of Different mechanisms can explain the effects of LPHEAL9 on cognition. It is known that LPHEAL9 survives the passage through the gastrointestinal tract [The cognitive function can be influenced by components derived from the metabolism of tryptophan such as kynurenine, as shown in a study with In the present study, the biomarker brain-derived neurotrophic factor (BDNF) was measured. BDNF is important for the survivability and growth of neurons and thus affects learning and memory [Elevated stress has been connected to increased pro-inflammatory properties; therefore, three pro-inflammatory markers were used in this study. Galectin-3 has been shown to be involved in different diseases associated with chronic inflammation, cancer, and type 2 diabetes [Different gastrointestinal metabolites, such as short-chain fatty acids, branched-chain amino acids (BCAA), and peptidoglycans, can also affect the gut–brain axis [This study has some limitations. As this was an exploratory trial without any pre-existing data as a basis for power calculations, the study was underpowered for some variables, which restricted the interpretation of the data. Furthermore, a fecal microbiota analysis could have added data for a suggestive mechanism of the actions behind the observed effects of LPHEAL9. A final limitation of this study was that placebo effects were observed for several variables. However, this may be difficult to overcome when evaluating subjective measurements in healthy and fairly young individuals and when the baseline scores for some of the endpoints were near normal, making it difficult to demonstrate an improvement. In future studies, measurements less influenced by a placebo response should preferably be selected, for example, by including additional performance challenges.