Fasting-Mimicking Diet Reduces Trimethylamine N-Oxide Levels and Improves Serum Biochemical Parameters in Healthy Volunteers

Funding Information: Funding: This study was performed within the Latvian Council of Science project “Trimethylamine-N-oxide as a link between unhealthy diet and cardiometabolic risks” No. Izp-2018/1-0081, supervised by M.D.; and M.V. received funding from the European Social Fund and the state budget within the project No. 8.2.2.0/20/I/004 “Support for involving doctoral students in scientific research and studies”. Publisher Copyright: © 2022 by the authors.Elevated plasma levels of trimethylamine N-oxide (TMAO) have been proposed as a diet-derived biomarker of cardiometabolic disease risk. Caloric restriction is the most common dietary intervention used to improve cardiometabolic health; however, novel trends suggest a fasting-mimicking diet (FMD) as a more feasible alternative. FMD is a variation of intermittent fasting, based on caloric restriction and limitation of protein sources of animal origin, applied in daily cycles during a 5-day period. As TMAO is intensively produced by gut microbiota after the consumption of animal-derived products, we aim to investigate whether a 5-day FMD affects plasma TMAO levels and markers of metabolic health. To investigate whether an increase in vegetable intake possesses similar effects on TMAO levels and metabolic parameters, healthy volunteers (n = 24) were subjected to a 5-day FMD and 19 volunteers served as a reference group (VEG). This group of volunteers consumed an additional four servings of vegetables per day, but otherwise stayed on their usual diet. FMD resulted in a twofold decrease in plasma TMAO levels, which was not evident in the volunteers from the VEG group. Moreover, FMD led to a weight loss of 2.8 ± 0.2 kg and a subsequent reduction in BMI compared to baseline. The FMD group exhibited a significant elevation in plasma ketone bodies (14-fold compared to baseline) and a decrease in IGF-1 levels by 37 ± 8 ng/mL. Since fasting glucose and C-peptide levels decreased, all volunteers in the FMD group showed improved insulin sensitivity and a decreased HOMA-IR index. In contrast, in the VEG group, only a slight reduction in plasma levels of fasting glucose and triglycerides was noted. In conclusion, we show that FMD is a viable strategy to reduce plasma levels of TMAO by limiting caloric intake and animal-derived protein consumption. The reduction in the level of TMAO could be an additional benefit of FMD, leading to a reduced risk of cardiometabolic diseases.publishersversionPeer reviewe

Stress-Related Immune Response and Selenium Status in Autoimmune Thyroid Disease Patients

Autoimmune thyroid disease (AITD), including Graves' disease (GD) or Hashimoto's thyroiditis (HT), occurs due to genetic susceptibility and environmental factors, among which the role of stressful events remains controversial. This study investigated the relationship between the number and impact of stressful life events in AITD patients with selenium status, and the Th1/Th2/Th17 immune response. The study population included three groups: HT ( n = 47), GD ( n = 13), and a control group ( n = 49). Thyroid function parameters, autoantibody levels, and the plasma levels of cytokines, selenium, selenoprotein P (SeP), and glutathione peroxidase 3 (GPx) activity were measured. Participants filled out the Life Experiences Survey. No significant differences in the number of stressful life events were found among the patients with HT, GD, and the controls. A higher (median (interquartile range)) negative stress level (8 (4-12)) than a positive stress level (3 (1-9)) was found in the HT group. The HT group showed a correlation between SeP and the positive stress level: r s = -0.296, p = 0.048, and the GD group between GPx and the negative stress level (r s = -0.702, p = 0.011). Significant positive correlations between thyroid peroxidase antibody level and the total number of major life events ( p = 0.023), the number of major life events in the last 7-12 months, and the number of major life events with no impact and a negative stress level were found. We suggest that the measurements of Th2-related cytokines and selenoproteins could be used as biomarkers for the development of AITD in cases where stress is considered a component cause of the pathogenic mechanism of the disease.publishersversionPeer reviewe

Assessment of iodine and selenium nutritional status in women of reproductive age in Latvia

Funding Information: Funding: This work was supported by the Fundamental and applied research project Nr. lzp2018/2-0059. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background and Objectives: Adequate dietary intake of iodine and selenium is essential during pregnancy. While iodine is vital for maternal thyroid function and fetal development, selenium contributes to the regulation of thyroid function and thyroid autoimmunity. This study aimed to assess the consumption of iodine-and selenium-containing products by women of reproductive age and the iodine and selenium nutritional status of pregnant women in Latvia. Materials and Methods: Population health survey (2010–2018) data were used to characterize dietary habits in women of reproductive age. Additionally, 129 pregnant women in the first trimester were recruited; they completed a questionnaire and were tested for thyroid function, urinary iodine concentration (UIC), and serum selenium and selenoprotein P levels. Results: The use of some dietary sources of iodine (e.g., milk and dairy products) and selenium (e.g., bread) has decreased in recent years. Less than 10% of respondents reported the use of iodized salt. The use of supplements has become more common (reported by almost 50% of respondents in 2018). Dietary habits were similar in pregnant women, but the use of supplements was even higher (almost 70%). Nevertheless, most supplements used in pregnancy had insufficient contents of iodine and selenium. Thyroid function was euthyreotic in all women, but 13.9% of participants had a thyroid peroxidase antibodies (TPO-ab) level above 60 IU/mL. The median UIC (IQR) was 147.2 (90.0–248.1) µg/gCr, and 52.8% of pregnant women had a UIC below 150 µg/gCr. The mean selenium (SD) level was 101.5 (35.6) µg/L; 30.1% of women had a selenium level below 80 µg/L. The median selenoprotein P level was 6.9 (3.1–9.0) mg/L. Conclusions: Iodine nutrition in Latvian population of pregnant women was near the lower limit of adequate and a third of the population had a selenium deficiency. Supplements were frequently used, but most did not contain the recommended amounts of iodine and selenium.publishersversionPeer reviewe

Stress-Related Immune Response and Selenium Status in Autoimmune Thyroid Disease Patients

Autoimmune thyroid disease (AITD), including Graves’ disease (GD) or Hashimoto’s thyroiditis (HT), occurs due to genetic susceptibility and environmental factors, among which the role of stressful events remains controversial. This study investigated the relationship between the number and impact of stressful life events in AITD patients with selenium status, and the Th1/Th2/Th17 immune response. The study population included three groups: HT (n = 47), GD (n = 13), and a control group (n = 49). Thyroid function parameters, autoantibody levels, and the plasma levels of cytokines, selenium, selenoprotein P (SeP), and glutathione peroxidase 3 (GPx) activity were measured. Participants filled out the Life Experiences Survey. No significant differences in the number of stressful life events were found among the patients with HT, GD, and the controls. A higher (median (interquartile range)) negative stress level (8 (4–12)) than a positive stress level (3 (1–9)) was found in the HT group. The HT group showed a correlation between SeP and the positive stress level: rs = −0.296, p = 0.048, and the GD group between GPx and the negative stress level (rs = −0.702, p = 0.011). Significant positive correlations between thyroid peroxidase antibody level and the total number of major life events (p = 0.023), the number of major life events in the last 7–12 months, and the number of major life events with no impact and a negative stress level were found. We suggest that the measurements of Th2-related cytokines and selenoproteins could be used as biomarkers for the development of AITD in cases where stress is considered a component cause of the pathogenic mechanism of the disease