Alina Kępka

The aging process, along with an inadequate diet and an inflammatory gut response resulting from dysbiosis, contributes to the pathogenesis of Alzheimer’s disease (AD). Modifying the composition of the gut microbiota through appropriate pre/probiotic-rich diets may act as a preventive option for AD. The variety of functions performed by the gut microbiota makes this ecosystem one of the most important systems in the human body. The Mediterranean diet (MedDiet), the Dietary Approaches to Stop Hypertension (DASH), the Mediterranean–DASH Intervention for Neurodegenerative Delay diet (MIND), and the modified ketogenic–Mediterranean diet (MKD) positively affect the intestinal microflora and may reduce the risk of dementia. A ketogenic diet has a neuroprotective effect and improves cognitive function but leads to a significant decrease in the abundance and diversity of bacterial species in favor of harmful bacteria. A Western-style diet (Western diet, WD) rich in processed products, red meat, simple sugars, and saturated fatty acids has a negative impact on gut microbiota function, increasing the risk of AD. Our review supports the hypothesis that factors like a proper diet and a healthy gut microbiota have a positive impact on the prevention of neurodegenerative diseases, including AD. A thorough understanding of the role the microbiota plays in the proper functioning of the nervous system can aid in the prevention of AD by developing new dietary strategies and dietary lifestyles.

Introduction: Alzheimer's disease (AD) is a chronic and incurable neurodegenerative brain disease, of memory with symptoms including progressive loss of memory and loss of behavioural control resulting over the time in the loss of the ability to live independently. Disturbance of cellular homeostasis within the brain tissue in AD leads to multidirectional abnormalities of biochemical parameters, including disturbances in the synthesis and metabolism of carnitine. Carnitine is involved in the transport of long-chain fatty acids across the inner mitochondrial membrane for their oxidation in the β-oxidation cycle. A correct distribution of total carnitine in the cell between free carnitine and acylcarnitine is very important due to the optimal use of fatty acids as an energy source. Disturbances in carnitine homeostasis are observed in AD. Aim: To evaluate the concentration of carnitine in the cerebrospinal fluid (CSF) and plasma in patients with AD. Material and methods: The study was performed in 10 patients with AD and 10 subjects without dementia (control group). The concentration of free (FC) and total carnitine (TC) in the CSF and plasma were determined by spectrophotometric method. Results: AD patients had a significantly lower concentration of FC in CSF compared to the controls (p = 0.025). TC and AC (acylcarnitine) concentrations in CSF did not differ significantly between AD patients and controls (p = 0.05). In plasma FC, TC, AC concentrations did not differ significantly between AD patients and controls (p = 0.05). Conclusions: This study confirms reduced the FC concentration in the CSF of AD patients. The inflammatory process, induced by amyloid deposits, causes FC deficiency in the brain, probably due to a defect in carnitine transport across the blood-brain barrier and/or impaired synthesis in brain tissue. Reduced availability of FC may disrupt the normal metabolism of nerve cells.

Type 1 diabetes is an autoimmune disease caused by the destruction of the beta cells ofthe pancreatic islets responsible for producing insulin. In a state of insulin deficiency, tissuestarvation occurs despite hyperglycemia in the blood. The body therefore uses an alternativeenergy source of fatty acids, which are oxidized by β-oxidation, with the production krótkołańcuofhigh-energy acetyl-CoA molecules. L-carnitine plays a key role in this process. It transportsfatty acid molecules activated to acyl-CoA form from the cytosol to the mitochondrialmatrix, where they are oxidized by β-oxidation, resulting in the formation of ATP. In diabetes,the intensification of β-oxidation, leads to the formation of excess acetyl-CoA, which is notutilized of in the Krebs cycle. As a result, acetyl-CoA accumulates and ketone bodies areformed. L-carnitine plays an important role in the regulation of the amount of acyl-CoA andthe regeneration of free CoA in the mitochondrion and cytosol. The constant regenerationof free CoA due to carnitine restores the balance between the amount of acetyl-CoA formedfrom both fatty acid oxidation and aerobic glycolysis, and inhibits the process of anaerobicglycolysis. Excessively active β-oxidation, results in the accumulation of carnitine esters(acylcarnitines) in serum, finally leading to depletion of free carnitine stores in tissues.This imbalance leads to disturbances energy production in the cells. Carnitine deficiencyis associated with the development of many diabetic complications: hyperlipidemia, retinopathyand neuropathy. Importantly, the concentration of carnitine and acylcarnitines dependson the duration of the disease. In diabetes, free and total carnitine concentrationsare significantly decreased, and the magnitude of this decrease depends on the durationof the disease. L-carnitine supplementation has positive effects such as lowering bloodpressure, reducing inflammation, improving heart function, and exhibiting neuroprotectiveand neurotrophic effects.

The ageing of the population is resulting in neurodegenerative diseases, including Alzheimer’s disease (AD), which are an increasing social, economic and medical problem. Diet and physical activity are now considered as important modifiable factors that help prevent or delay the development of AD and other dementia-related diseases. The pyramid of healthy nutrition and lifestyle is a way of presenting the principles, the implementation of which gives a chance for proper development and a long healthy life. The basis of the pyramid, in the first place, is physical activity. Our review of the literature in the PubMed database supports the hypothesis that complementary factors, such as proper diet, physical exercise and mental activity, have a positive impact on the prevention of neurodegenerative diseases. The nutritional recommendations for healthy adults primarily include the consumption of vegetables, fruits, cereals, legumes, vegetable oils and fishes. Therefore, the introduction of Mediterranean and Asian diets may reduce the risk of the neurodegenerative diseases associated with dementia, whereas dairy products and meat—the main sources of L-carnitine—should be consumed in moderate amounts. The aim of our work is to provide up-to-date knowledge about the appropriate dietary model and healthy lifestyle elements and their impact on good health and the long life of people.

L-carnitine plays an important role in the functioning of the central nervous system, and especially in the mitochondrial metabolism of fatty acids. Altered carnitine metabolism, abnormal fatty acid metabolism in patients with autism spectrum disorder (ASD) has been documented. ASD is a complex heterogeneous neurodevelopmental condition that is usually diagnosed in early childhood. Patients with ASD require careful classification as this heterogeneous clinical category may include patients with an intellectual disability or high functioning, epilepsy, language impairments, or associated Mendelian genetic conditions. L-carnitine participates in the long-chain oxidation of fatty acids in the brain, stimulates acetylcholine synthesis (donor of the acyl groups), stimulates expression of growth-associated protein-43, prevents cell apoptosis and neuron damage and stimulates neurotransmission. Determination of L-carnitine in serum/plasma and analysis of acylcarnitines in a dried blood spot may be useful in ASD diagnosis and treatment. Changes in the acylcarnitine profiles may indicate potential mitochondrial dysfunctions and abnormal fatty acid metabolism in ASD children. L-carnitine deficiency or deregulation of L-carnitine metabolism in ASD is accompanied by disturbances of other metabolic pathways, e.g., Krebs cycle, the activity of respiratory chain complexes, indicative of mitochondrial dysfunction. Supplementation of L-carnitine may be beneficial to alleviate behavioral and cognitive symptoms in ASD patients.

Stress, anxiety and depressive disorders are often characterized by the activation of the stress axis, which results in similar symptoms at some point in these disorders. These disorders are closely related to each other—they occur simultaneously or follow one another. The diagnosis of stress, anxiety and depression is not a perfect procedure currently—it is based on patient observation and an interview with the patient and their family. There are no laboratory tests that would dispel the doubts of the doctor making the diagnosis and allow the appropriate treatment to be implemented as soon as possible. Therefore, this study will review the components of saliva that could be helpful in the quick diagnosis of stress, anxiety and/or depression. Such potential salivary biomarkers could also be useful in monitoring the effectiveness of pharmacological treatment prescribed by a psychiatrist. The following are promising salivary biomarkers of stress, anxiety or depression: cortisol, immunoglobulin A (sIgA), lysozyme, melatonin, α-amylase (sAA), chromogranin A (CgA) and fibroblast growth factor 2 (FGF-2). To the best valuable potential salivary markers of stress, we can include cortisol, lysozyme, sAA and CgA. To differentiate depression from stress, salivary cortisol and melatonin can be helpful. Fluctuations in the concentrations of the above-mentioned substances in saliva indicate a particularly strong relationship with typical human psychological problems, such as stress, depression or anxiety.

The prevention or alleviation of neurodegenerative diseases, including Alzheimer’s disease (AD), is a challenge for contemporary health services. The aim of this study was to review the literature on the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet, dietary carnitine supplements and the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. L-carnitine (LC) plays a crucial role in the energetic metabolism of the cell. A properly balanced diet contains a substantial amount of LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis. In healthy people, carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency. In persons with dysfunction of mitochondria, e.g., with AD connected with extensive degeneration of the brain structures, there are often serious disturbances in the functioning of the whole organism. The Mediterranean diet is characterized by a high consumption of fruits and vegetables, cereals, nuts, olive oil, and seeds as the major source of fats, moderate consumption of fish and poultry, low to moderate consumption of dairy products and alcohol, and low intake of red and processed meat. The introduction of foodstuffs rich in carnitine and the MIND diet or carnitine supplementation of the AD patients may improve their functioning in everyday life.

Aim: The plasma homeostasis of both free and esterified carnitines is mostly regulated by renal tubular reabsorption, which may be disturbed in low birth weight children. The aim of study was to check whether disturbances in excretion of L-carnitine (LC) and its main ester, acetyl-carnitine (ALC), may be the result of renal dysfunction in low birth weight children (LBW). Methods: This study included 59 LBW children (2165 g [1490–2440]) and 22 children with normal birth weight as a reference group (3500 g [3275–3650]). Subjects were divided into three groups: 0–3 months, 4–12 months and over 1 year at the time of testing. Urinary levels of carnitine were measured spectrophotometrically. Results: The urine excretion of Free LC, Free LC/cr, Total LC and Total LC/cr. Were significantly higher in 0–3 and 4–12-month old LBW infants study groups when compared to the reference groups. We found statistically significant higher urine excretion of ALC and ALC/cr. in all age groups of LBW infants compared to the reference group. There was a negative correlation between birth weight and free LC/cr. (r = −0.3, p < 0.05), Total LC/cr. (r = −0.34, p < 0.05), and ALC/cr. (r = −39, p < 0.05), and in the children > 12-month-old strong negative correlation between eGFR and free LC/cr. (r = −0.6, p < 0.05), Total LC/cr. (r = −0.61, p < 0.05), ALC/cr. (r = −0.61, p < 0.05.) Conclusion: Higher urine excretion of both LC and ALC and its negative correlation with birth weight and eGFR may reflect some degree of renal dysfunction in LBW infants.