Proteomics monitoring of an elite adventure athlete (age 33 years) was conducted over a 28-week period that culminated in the successful, solo, unassisted, and unsupported two month trek across the Antarctica (1500 km). Training distress was monitored weekly using a 19-item, validated training distress scale (TDS). Weekly dried blood spot (DBS) specimens were collected via fingerprick blood drops onto standard blood spot cards. DBS proteins were measured with nano-electrospray ionization liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) in data-independent acquisition (DIA) mode, and 712 proteins were identified and quantified. The 28-week period was divided into time segments based on TDS scores, and a contrast analysis between weeks five and eight (low TDS) and between weeks 20 and 23 (high TDS, last month of Antarctica trek) showed that 31 proteins (n = 20 immune related) were upregulated and 35 (n = 17 immune related) were downregulated. Protein–protein interaction (PPI) networks supported a dichotomous immune response. Gene ontology (GO) biological process terms for the upregulated immune proteins showed an increase in regulation of the immune system process, especially inflammation, complement activation, and leukocyte mediated immunity. At the same time, GO terms for the downregulated immune-related proteins indicated a decrease in several aspects of the overall immune system process including neutrophil degranulation and the antimicrobial humoral response. These proteomics data support a dysfunctional immune response in an elite adventure athlete during a sustained period of mental and physical distress while trekking solo across the Antarctica.

Traumatic brain injury (TBI) is one of the leading causes of death worldwide. There are currently no effective treatments for TBI, and trauma survivors suffer from a variety of long‐lasting health consequences. With nutritional support recently emerging as a vital step in improving TBI patients' outcomes, we sought to evaluate the potential therapeutic benefits of nutritional supplements derived from bovine thymus gland, which can deliver a variety of nutrients and bioactive molecules. In a rat model of controlled cortical impact (CCI), we determined that animals supplemented with a nuclear fraction of bovine thymus (TNF) display greatly improved performance on beam balance and spatial memory tests following CCI. Using RNA‐Seq, we identified an array of signaling pathways that are modulated by TNF supplementation in rat hippocampus, including those involved in the process of autophagy. We further show that bovine thymus‐derived extracts contain antigens found in neural tissues and that supplementation of rats with thymus extracts induces production of serum IgG antibodies against neuronal and glial antigens, which may explain the enhanced animal recovery following CCI through possible oral tolerance mechanism. Collectively, our data demonstrate, for the first time, the potency of a nutritional supplement containing nuclear fraction of bovine thymus in enhancing the functional recovery from TBI.

Polyamines (PAs), including spermidine, spermine and their precursor, putrescine, are ubiquitous molecules that are vital for a variety of physiological processes. Recently, PAs gained research attention because of their roles in promoting longevity and preventing age-related diseases. Circulating and tissue levels of PAs appear to decline with age, while higher intake of PAs in humans is correlated with better health during aging. Many foods, including plants and offal (organ meats), are good sources of dietary PAs, but are consumed much less in regions with prevailing Western diets. Elevating the circulating levels of PAs through dietary supplementation with PA-rich plant extracts or foods, on the other hand, has proven to be challenging, most likely due to their low bioavailability. In this study, we evaluated the effectiveness of nutritional supplements derived from bovine glandular tissues and/or plant material in elevating blood and tissue levels of spermidine, spermine and putrescine in adult rats. We detected appreciable amounts of PAs in the following materials: 1) spermidine-rich supplement (SRS), containing wheat germ, 2) a cytosolic fraction extract of bovine thymus gland (Thymus Cytosolic Fraction – TCF) and 3) a nuclear fraction extract of bovine thymus gland (Thymus Nuclear Fraction – TNF). We showed that all three PA-containing supplements also contain liposomes, with TNF displaying the largest amounts of liposomal PAs, as well as RNAs, among the tested supplements. We demonstrated that oral administration of SRS, TCF and TNF induce rapid changes in blood PA concentrations. Finally, we showed that TNF supplement is superior to SRS and TCF in elevating the levels of spermidine in the blood, liver and heart following a 28-day supplementation period. Considering the importance of PAs in prevention of age-related disease, supplementation with TNF could be a plausible approach towards the maintenance of proper cellular PA homeostasis during aging.

Elevated plasma levels of total homocysteine (Hcy) and S-Adenosylhomocysteine (SAH) are associated with increased risks of neurological and cardiovascular diseases (CVD). Whilst elevated plasma levels of Hcy can be managed through supplementation with B-group vitamins, there are no effective therapies for managing SAH in patients with elevated SAH and normal Hcy. SAH, a by-product of cellular methylation reactions, is considered a more sensitive biomarker for CVD than homocysteine (Hcy). The aim of this study was to determine if a test product containing ashwagandha extract, alpha-glycerylphosphorylcholine and creatine monohydrate, could lower plasma SAH levels in adults with elevated SAH and normal Hcy. In this prospective, randomized, single-blind, placebo-controlled clinical trial, 40 participants with elevated SAH (≥20 nmol/L) and normal Hcy (≤13 μmol/L) were randomized into two groups: 15 participants received the placebo, and 25 participants received the test product. The test product significantly lowered plasma SAH levels by approximately 12% and increased S-Adenosylmethionine (SAM): SAH ratio by approximately 26% after 12 weeks of supplementation compared to baseline. The test product was safe and well-tolerated, with no serious adverse events. No clinically relevant changes in vital signs and safety laboratory parameters were detected. This is the first demonstration of a nutritional product's effectiveness in decreasing plasma levels of SAH in otherwise healthy individuals with elevated SAH and normal Hcy. Hence, this test product offers a unique opportunity for investigating the impact of lowering plasma SAH on the risk of developing CVD and other diseases. Clincaltrial.gov registration: NCT05994794, 2023-08-16.

Inadequate dietary magnesium (Mg) intake is a growing public health concern. Mg is critical for diverse metabolic processes including energy production, macromolecule biosynthesis, and electrolyte homeostasis. Inadequate free Mg²⁺ ion concentration ([Mg²⁺]) in the brain is associated with several neurological and behavioral disorders. Elevating [Mg²⁺]in the brain using oral Mg supplementation has proven to be challenging due to the tight regulation of Mg²⁺ transport to the brain. This study explored the effect of short-term moderate reduction in dietary Mg intake (87% of normal Mg diet for 30 days) on [Mg²⁺] in the cerebrospinal fluid (CSF) ([Mg²⁺]_CSF) and red blood cells (RBCs) ([Mg²⁺]_RBC) in adult male rats. In addition, we investigated the effectiveness of magnesium-rich blend of Swiss chard and buckwheat extracts (SC/BW extract) in increasing brain [Mg²⁺] compared to various Mg salts commonly used as dietary supplements. Animals were assigned to either normal or low Mg diet for 30 - 45 days. Following this, animals maintained on low Mg diet were supplemented with various Mg compounds. [Mg²⁺]_CSF and [Mg²⁺]_RBC were measured at baseline and following Mg administration. Anxiety-like behavior and cognitive function were also evaluated. The present study showed that a short-term and moderate reduction in Mg dietary intake results in a significant decline in [Mg²⁺]_CSF and [Mg²⁺]_RBC and the emergence of anxiety-like behavior in comparison to animals maintained on normal Mg diet. Supplementation with SC/BW extract significantly elevated [Mg²⁺]_CSF and improved animal performance in the novel object recognition test in comparison with animals maintained on reduced Mg intake and supplemented with various Mg compounds. These observations indicate that brain [Mg²⁺] is more sensitive to a short-term and moderate reduction in Mg dietary intake than previously thought and emphasizes the importance of dietary Mg in replenishing brain Mg²⁺ reserves.