Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. METHODS AND RESULTS: In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (-1.31 mmol/L; p = 0.02) and 120 min (-1.60 mmol/L, p = 0.02) and total glucose area under the curve (-3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. CONCLUSION: This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.

Carnosine Did Not Affect Vascular and Metabolic Outcomes in Patients with Prediabetes and Type 2 Diabetes: A 14-Week Randomized Controlled Trial.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with prediabetes and type 2 diabetes mellitus (T2DM). Carnosine has been suggested as a potential approach to reduce ASCVD risk factors. However, there is a paucity of human data. Hence, we performed a 14-week double-blind randomized placebo-controlled trial to determine whether carnosine compared with placebo improves vascular and metabolic outcomes in individuals with prediabetes and T2DM. In total, 49 patients with prediabetes and T2DM with good glycemic control were randomly assigned either to receive 2 g/day carnosine or matching placebo. We evaluated endothelial dysfunction, arterial stiffness, lipid parameters, blood pressure, heart rate, hepatic and renal outcomes before and after the intervention. Carnosine supplementation had no effect on heart rate, peripheral and central blood pressure, endothelial function (logarithm of reactive hyperemia (LnRHI)), arterial stiffness (carotid femoral pulse wave velocity (CF PWV)), lipid parameters, liver fibroscan indicators, liver transient elastography, liver function tests, and renal outcomes compared to placebo. In conclusion, carnosine supplementation did not improve cardiovascular and cardiometabolic risk factors in adults with prediabetes and T2DM with good glycemic control. Therefore, it is improbable that carnosine supplementation would be a viable approach to mitigating the ASCVD risk in these populations. The trial was registered at clinicaltrials.gov (NCT02917928).

Transcriptome analysis of the effects of polarized photobiomodulation on human dermal fibroblasts.

BACKGROUND: Photobiomodulation (PBM), the therapeutic use of light, is used to treat a myriad of conditions, including the management of acute and chronic wounds. Despite the presence of clinical evidence surrounding PBM, the fundamental mechanisms underpinning its efficacy remain unclear. There are several properties of light that can be altered in the application of PBM, of these, polarization-the filtering of light into specified plane(s)-is an attractive variable to investigate. AIMS: To evaluate transcriptomic changes in human dermal fibroblasts in response to polarized PBM. RESULTS: A total of 71 Differentially Expressed Genes (DEGs) are described. All DEGs were found in the polarized PBM group (P-PBM), relative to the control group (PC). Of the 71 DEGs, 10 genes were upregulated and 61 were downregulated. Most DEGs were either mitochondrial or extracellular matrix (ECM)-related. Gene Ontology (GO) analysis was then performed using the DEGs from the P-PBM vs. PC group. Within biological processes there were 95 terms found (p < 0.05); in the molecular function there were 18 terms found (p < 0.05); while in the cellular component there were 32 terms enriched (p < 0.05). A KEGG pathways analysis was performed for the DEGs found in the P-PBM vs. PC group. This revealed 21 significantly enriched pathways (p < 0.05). Finally, there were 24 significantly enriched reactome pathways when comparing the DEGs of the P-PBM vs. PC groups (p < 0.05). DISCUSSION AND CONCLUSIONS: The P-PBM DEGs were almost always down regulated compared to the comparator groups. This may be explained by the P-PBM treatment conditions decreasing the amount of cellular stress, hence causing a decreased mitochondria and ECM protective response. Alternatively, it could point to an alternate mechanism, outside the mitochondria, by which PBM exerts its effects. Additionally, PBM appears to have a more widespread effect on the mitochondria than previously thought, opening up many new avenues of investigation in the process.

The effects of polarized photobiomodulation on cellular viability, proliferation, mitochondrial membrane potential and apoptosis in human fibroblasts: Potential applications to wound healing.

Photobiomodulation (PBM) is a widely used therapeutic intervention used to treat several chronic conditions. Despite this, fundamental research underpinning its effectiveness is lacking, highlighted by the lack of a definitive mechanism of action. Additionally, there are many treatment variables which remain underexplored, one of those being the effect of polarization the property of light that specifies the direction of the oscillating electric field. When applied to PBM, using linearly polarized light, when compared to otherwise identical non-polarized light, may enhance its biological efficacy. As such, we investigated the potential biological effects of polarized PBM when compared to non-polarized and non-irradiated controls in the domains of cellular viability, proliferation, apoptosis and mitochondrial membrane potential (ΔΨ) within cells exposed to oxidative stress. It was noted that polarized PBM, when compared to non-polarized PBM and non-irradiated controls, demonstrated mostly increased levels of cellular proliferation and ΔΨ, whilst decreasing the amount of cellular apoptosis. These results indicate that polarization may have utility in the clinical application of PBM. Future research is needed to further elucidate the underpinning mechanisms of PBM and polarization.

Carnosine as a potential therapeutic for the management of peripheral vascular disease.

AIMS: To evaluate the potential role of carnosine in the management of peripheral vascular disease. DATA SYNTHESIS: Peripheral vascular disease is growing in its burden and impact; however it is currently under researched, and there are a lack of strong, non-invasive therapeutic options for the clinicians. Carnosine is a dipeptide stored particularly in muscle and brain tissue, which exhibits a wide range of physiological activities, which may be beneficial as an adjunct treatment for peripheral vascular disease. Carnosine's strong anti-inflammatory, antioxidant and antiglycating actions may aid in the prevention of plaque formation, through protective actions on the vascular endothelium, and the inhibition of foam cells. Carnosine may also improve angiogenesis, exercise performance and vasodilatory response, while protecting from ischemic tissue injury. CONCLUSIONS: Carnosine may have a role as an adjunct treatment for peripheral vascular disease alongside typical exercise and surgical interventions, and may be used in high risk individuals to aid in the prevention of atherogenesis. CLINICAL RECOMMENDATION: This review identifies a beneficial role for carnosine supplementation in the management of patients with peripheral vascular disease, in conjunction with exercise and revascularization. Carnosine as a supplement is safe, and associated with a host of beneficial effects in peripheral vascular disease and its key risk factors.

The effect of vitamin D supplementation on circulating osteoprogenitor cells: A pilot randomized controlled trial.

Circulating osteoprogenitor (COP) cells are a relatively newly discovered mesenchymal precursors population in the peripheral blood. While some aspects of their physiology have been documented in vitro, little is known about their behavior in vivo. To facilitate understanding regarding their potential role in the management of musculoskeletal disease, more research into how these cells respond to growth factors and hormones in vivo is still required. To this end, we performed a randomized controlled pilot study investigating the effect of vitamin D supplementation on COP cells in healthy older adults. Twenty-two individuals were recruited and stratified through their baseline vitamin D levels into deficient (<35 nmol/L), insufficient (35-49 nmol/L) and sufficient (>50 nmol/L) groups, and then randomized to receive either a 50,000 IU bolus dose of vitamin D, along with a 1000 IU daily supplement for six weeks, or the 1000 IU supplement alone. Participants were assessed at baseline, week three, and week six, with the primary outcome being a change in the number of COP cells. Secondary outcomes were vitamin D, markers of bone formation and resorption, parathyroid hormone, and calcium. The study showed that, independently of the dosing, increasing vitamin D levels led to a concomitant 52% increase in COP cell number (p < 0.001). There were no differences between strata, or any of the secondary outcomes in the trial. This suggests that COP cells are regulated in some way by vitamin D, similar to the bone marrow mesenchymal stem cell. Future studies are needed to evaluate the long-term effects of vitamin D supplementation, and how COP cells may be involved in chronic musculoskeletal disease.

Nutritional Interventions for COVID-19: A Role for Carnosine?

As COVID-19 continues to take an enormous toll on global health, the effort to find effective preventive and treatment strategies has been unparalleled in recent history [...].

The Effects of Bariatric Surgery on Vitamin B Status and Mental Health.

Diet is a modifiable factor that ensures optimal growth, biochemical performance, improved mood and mental functioning. Lack of nutrients, notably vitamin B, has an impact on human health and wellbeing. The United Arab Emirates is facing a serious problem of micronutrient deficiencies because of the growing trend for bariatric surgery, including Roux-en-Y gastric bypass and sleeve gastrectomy. People undergoing bariatric surgery are at high risk of developing neurological, cognitive, and mental disabilities and cardiovascular disease due to deficiency in vitamin B. Vitamin B is involved in neurotransmitter synthesis, including γ-aminobutyric acid, serotonin, dopamine, and noradrenaline. Deficiency of vitamin B increases the risk of depression, anxiety, dementia and Alzheimer's disease. In addition, vitamin B deficiency can disrupt the methylation of homocysteine, leading to hyperhomocysteinemia. Elevated homocysteine levels are detrimental to human health. Vitamin B deficiency also suppresses immune function, increases the production of pro-inflammatory cytokines and upregulates NF-κB. Considering the important functions of vitamin B and the severe consequences associated with its deficiency following bariatric surgery, proper dietary intervention and administration of adequate supplements should be considered to prevent negative clinical outcomes.

Anti-cancer effects of polyphenol-rich sugarcane extract.

Plant polyphenols have an array of health benefits primarily thought to be related to their high content of anti-oxidants. These are commonly undervalued and knowledge of their biological properties have grown exponentially in the last decade. Polyphenol-rich sugarcane extract (PRSE), a natural extract from sugar cane, is marketed as high in anti-oxidants and polyphenols, but its anti-cancer activity has not been reported previously. We show that, PRSE exerts anti-cancer properties on a range of cancer cells including human (LIM2045) and mouse (MC38, CT26) colon cancer cells lines; human lung cancer (A549), human ovarian cancer (SKOV-3), pro-monocytic human leukemia (U937) and to mouse melanoma (B16) cell lines; whereas no effects were noted on human breast (ZR-75-1) and human colon (HT29) cancer cell lines, as well as to human normal colon epithelial cell line (T4056). Anti-proliferative effects were shown to be mediated via alteration in cytokines, VEGF-1 and NF-κB expression.

The Role of Bioactive Compounds from Dietary Spices in the Management of Metabolic Syndrome: An Overview.

Metabolic syndrome (MetS) is a combination of physiologically dysregulated parameters that can include elevated fasting blood glucose, high blood pressure, central obesity, increased triglyceride levels, insulin resistance, diabetes, elevated low density lipoprotein levels, and reduced high density lipoprotein levels in the blood. Effective clinical management of MetS is critical as it is strongly associated with long lasting and fatal complications in patients. Alongside standard care of lifestyle changes and medication, dietary supplements derived from herbal resources could be an alternative therapeutic strategy that is safe, efficient, culturally acceptable, and has few side effects. Of the dietary supplements, spicy foods have always been considered a great source of functional bioactive compounds. Herbal therapy is broadly used in many countries as a treatment or as a preventive measure in the management of MetS risk factors, including blood glucose, blood pressure, and blood lipid levels. Herein, an attempt is made to evaluate the recent studies in the management of MetS with herbal alternatives, and to explore the possibility of their use as therapeutic treatments or supplements.

The effects of photobiomodulation on human dermal fibroblasts in vitro: A systematic review.

Photobiomodulation (PBM) is reported to impart a range of clinical benefits, from the healing of chronic wounds to athletic performance enhancement. The increasing prevalence of this therapy conflicts with the lack of understanding concerning specific cellular mechanisms induced by PBM. Herein, we systematically explore the literature base, specifically related to PBM (within the range 600-1070 nm) and its influence on dermal fibroblasts. The existing research in this field is appraised through five areas: cellular proliferation and viability; cellular migration; ATP production and mitochondrial membrane potential; cellular protein expression and synthesis; and gene expression. This review demonstrates that when fibroblasts are irradiated in vitro within a set range of intensities, they exhibit a multitude of positive effects related to the wound healing process. However, the development of an optimal in vitro framework is paramount to improve the reliability and validity of research in this field.

Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?

The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. Infection can cause fever, dry cough, fatigue, severe pneumonia, respiratory distress syndrome and in some instances death. COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. There are currently no effective anti-SARS-CoV-2 viral drugs or vaccines. COVID-19 disproportionately affects the elderly, both directly, and through a number of significant age-related comorbidities. Undoubtedly, nutrition is a key determinant of maintaining good health. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19. In this paper, evidence surrounding the role of these dietary components in immunity as well as their specific effect in COVID-19 patients are discussed. In addition, how supplementation of these nutrients may be used as therapeutic modalities potentially to decrease the morbidity and mortality rates of patients with COVID-19 is discussed.

Good, better, best? The effects of polarization on photobiomodulation therapy.

Photobiomodulation therapy (PBMT) is a widely adopted form of phototherapy used to treat many chronic conditions that effect the population at large. The exact physiological mechanisms of PBMT remain unsolved; however, the prevailing theory centres on changes in mitochondrial function. There are many irradiation parameters to consider when investigating PBMT, one of which is the state of polarization. There is some evidence to show that polarization of red and near-infrared light may promote different and/or increased biological activity when compared to otherwise identical non-polarized light. These enhanced cellular effects may also be present when the polarized light is applied linear to the tissue direction. Herein, we synthesize the current experimental and clinical evidence pertaining to polarized photobiomodulation therapy; ultimately, to better inform future research into this area of phototherapy.

Polyphenol Rich Sugar Cane Extract Inhibits Bacterial Growth.

Plants that are primarily used as a food source commonly have undervalued biological properties beyond the basic supply of nutrients. One important example of this are the antimicrobial properties of plants. Inclusion of natural and food grade antimicrobial ingredients in recipes to prevent food spoilage and disease transmission, or in cosmetic products to prevent transient and pathogenic bacteria would have world-wide public health implications. A patented natural polyphenol rich sugar cane extract (PRSE), is marketed as a high anti-oxidant and polyphenol ingredient, but its anti-microbial activity has not been reported previously. We determined the anti-bacterial properties of PRSE on common human pathogens relating to a range of diseases including food poisoning, tooth decay, acne and severe skin infections using disc/well diffusion experiments. Our findings indicate that PRSE is an efficient antimicrobial, which could be included at differing dosages to target a range of food borne and environmental pathogens.

Polarized light therapy: Shining a light on the mechanism underlying its immunomodulatory effects.

This study investigates the immunomodulatory effects of polychromatic polarized light therapy (PLT) on human monocyte cells. While there is some evidence demonstrating a clinical effect in the treatment of certain conditions, there is little research into its mechanism of action. Herein, U937 monocyte cells were cultured and exposed to PLT. The cells were then analyzed for change in expression of genes and cell surface markers relating to inflammation. It was noted that 6 hours of PLT reduced the expression of the CD14, MHC I and CD11b receptors, and increased the expression of CD86. It was also shown that PLT caused downregulation of the genes IL1B, CCL2, NLRP3 and NOD1, and upregulation of NFKBIA and TLR9. These findings imply that PLT has the capacity for immunomodulation in human immune cells, possibly exerting an anti-inflammatory effect.

Therapeutic applications of polarized light: Tissue healing and immunomodulatory effects.

As the population grows and ages, non-pharmaceutical options for the treatment and management of wounds, disease and injury are required to ensure adequate care. Polarized light therapy (PLT) utilizes visible-spectrum polarized light for a number of clinical applications. The advantage of polarized light is that it is able to penetrate the skin to a depth of up to 5 cm, reaching deeper tissues involved in wound healing. PLT has been shown to accelerate the healing process for ulcers, surgical wounds and dermal burns as well as a small number of musculoskeletal injuries. As research into the histological and physiological effects of PLT is largely absent, studies related to other light therapy modalities, largely low-level laser therapy, may pave the way to identify putative mechanisms by which PLT might exert its effects. Changes to cell signalling and secretion of substances required for wound healing have been identified in response to phototherapies. The reviewed literature suggests that PLT may be efficacious in some wound and injury healing contexts, though a gap in the literature exists regarding its mechanisms of action. Future studies should fully explain the therapeutic effects of PLT and the physiological mechanisms underpinning them.

Conservative management of a traumatic meniscal injury utilising osteopathy and exercise rehabilitation: A case report.

Meniscal injury is one of the most common knee soft tissue injuries, commonly affecting young athletes and an older, degenerative population. Treatment largely depends on the type and extent of the injury with arthroscopic repair or meniscectomy being mainstays. Although non-surgical approaches have been described, there is no published literature regarding a combination of indirect osteopathic techniques and rehabilitation in the management of these injuries. The current case report follows a 20-year-old male presenting with a 5-day history of acute knee pain, following trauma during an Australian Rules Football (AFL) match. An 8-week management plan of indirect osteopathic techniques and a tailored rehabilitation program was implemented. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Lower Extremity Functional Scale (LEFS) questionnaires were utilised to measure outcomes. After the 8-week treatment and rehabilitation program, the patient had exceeded the minimum detectable change score for all outcome measures. This case report suggests that osteopathic manipulative treatment and rehabilitation may be an alternative, non-surgical approach in the management of post-traumatic meniscal injuries.