Immunology

Referencesand Professional Synopsis:Senadheera TRL, Dave D, Shahidi F. Sea Cucumber Derived Type I Collagen: A Comprehensive Review. Mar Drugs. 2020 Sep 18;18(9):471. doi: 10.3390/md18090471. PMID: 32961970; PMCID: PMC7551324.

Collagen in sea cucumbers is significant due to its various bioactive properties and potential applications. It is a major component of the sea cucumber’s body wall, contributing to its structural integrity. Sea cucumber collagen is rich in bioactive compounds with antioxidant, antihypertensive, anti-inflammatory, anticancer, antimicrobial, and anticoagulant properties. This makes it a valuable ingredient for functional foods, nutraceuticals, and pharmaceuticals. Additionally, sea cucumber collagen is considered a high-quality alternative to mammalian collagen, which is limited by health risks and religious constraints. It is used in biomedical applications, including tissue engineering, wound healing, and cosmetic products, due to its biocompatibility, low antigenicity, and high biodegradability.

Referencesand Professional Synopsis:Rayman MP. Selenium and human health. Lancet. 2012 Mar 31;379(9822):1256-68. doi: 10.1016/S0140-6736(11)61452-9. Epub 2012 Feb 29. PMID: 22381456.

The document discusses the role of selenium in human health, highlighting its incorporation into selenoproteins that have various effects, including antioxidant, anti-inflammatory, and thyroid hormone production. Overall, low selenium status is linked to increased mortality, poor immune function, and cognitive decline and higher selenium status or supplementation can have antiviral effects, support reproduction, and reduce autoimmune thyroid disease risk.

Benefits on cancer risk (prostate, lung, colorectal, bladder) are evident especially in populations whose intake is inadequate. Selenium intake varies globally, influenced by soil content and dietary habits. Recommended intake averages 60 μg/day for men and 53 μg/day for women. High intake regions include Venezuela, Canada, USA, and Japan; low intake regions include Europe and parts of China.

Selenium supplementation can enhance immune responses, particularly in elderly and cancer patients. It promotes T-cell proliferation and natural killer cell activity.

Selenium is crucial for brain function, with deficiency causing irreversible damage.

Low selenium is associated with seizures, coordination issues, Parkinson’s disease, and cognitive decline. For adult male, selenium is essential for sperm motility and viability.

Supplementation can improve sperm motility. For females, selenium is beneficial in reducing miscarriage and preeclampsia risks.

Selenium supports thyroid hormone production and protects thyroid cells. Supplementation can reduce thyroid autoantibodies and improve thyroid health in autoimmune thyroiditis.

Selenium has potential cardiovascular benefits, but supplementation results are mixed. High selenium status is associated with raised plasma cholesterol.

Prospective studies suggest selenium may reduce the risk of various cancers, but supplementation benefits are inconsistent. The effect of selenium on cancer risk may depend on baseline selenium status and genetic factors.

Bone and joint health

Referencesand Professional Synopsis:Dalbeth N, Choi HK, Joosten LAB, Khanna PP, Matsuo H, Perez-Ruiz F, Stamp LK. Gout. Nat Rev Dis Primers. 2019 Sep 26;5(1):69. doi: 10.1038/s41572-019-0115-y. PMID: 31558729.

This is a comprehensive review of gout, which is a chronic disease caused by monosodium urate (MSU) crystal deposition. Gout typically presents as an acute, self-limiting inflammatory monoarthritis that affects the joints of the lower limb. Elevated serum urate level (hyperuricemia) is the major risk factor for MSU crystal deposition and development of gout. Although traditionally considered a disorder of purine metabolism, altered urate transport, both in the gut and the kidneys, has a key role in the pathogenesis of hyperuricemia. Anti-inflammatory agents, such corticosteroids, NSAIDs and colchicine, are widely used for the treatment of gout flare; recognition of the importance of NLRP3 inflammasome activation and bioactive IL-1β release in initiation of the gout flare has led to the development of anti-IL-1β biological therapy for gout flares. Sustained reduction in serum urate levels using urate-lowering therapy is vital in the long-term management of gout, which aims to dissolve MSU crystals, suppress gout flares and resolve tophi. Allopurinol is the first-line urate-lowering therapy and should be started at a low dose, with gradual dose escalation. Low-dose anti-inflammatory therapies can reduce gout flares during initiation of urate-lowering therapy. Models of care, such as nurse-led strategies that focus on patient engagement and education, substantially improve clinical outcomes and now represent best practice for gout management.

Referencesand Professional Synopsis:Menghini L, Recinella L, Leone S, Chiavaroli A, Cicala C, Brunetti L, Vladimir-Knežević S, Orlando G, Ferrante C. Devil’s claw (Harpagophytum procumbens) and chronic inflammatory diseases: A concise overview on preclinical and clinical data. Phytother Res. 2019 Sep;33(9):2152-2162. doi: 10.1002/ptr.6395. Epub 2019 Jul 4. PMID: 31273865.

The authors performed a review by focusing on the applicative potential of devil’s claw in managing inflammation- and oxidative stress-related diseases. Devil’s claw and its components, particularly harpagoside, show significant pharmacological properties, suggesting potential therapeutic effects in a wide spectrum of pathologies, such as arthritis, osteoporosis, type 1 diabetes mellitus, inflammatory bowel, and neurodegenerative diseases. It thus highlighted the need to perform well-designed clinical trials to confirm the potential applications in clinics.

Referencesand Professional Synopsis:Nakagawa T, Lanaspa MA, Johnson RJ. The effects of fruit consumption in patients with hyperuricemia or gout. Rheumatology (Oxford). 2019 Jul 1;58(7):1133-1141. doi: 10.1093/rheumatology/kez128. PMID: 31004140.

The document reviews the effects of fruit consumption on hyperuricemia and gout, focusing on the role of fructose and other nutrients in fruits.

Key points include:

1) Fructose and Uric Acid: Fructose metabolism produces uric acid, potentially increasing the risk of hyperuricemia and gout.

High fructose corn syrup (HFCS) in soft drinks is particularly problematic.

2) Complex Effects of Fruits: While fruits contain fructose, they also have beneficial nutrients like vitamin C, epicatechin, flavonols, potassium, and fiber, which can mitigate the negative effects of fructose.

3) Clinical Studies: Some studies show fruit intake is associated with a lower risk of gout, while others suggest certain fruits or fruit juices (e.g., orange juice) may increase the risk.

4) Protective Nutrients includes Vitamin C (enhances uric acid excretion and reduces serum uric acid levels), fiber (slows fructose absorption, reducing its impact on uric acid production), potassium (lowers blood pressure and counteracts the effects of uric acid and fructose), and catechins and flavonoids (reduce xanthine oxidase activity, lowering uric acid formation and inflammation). It is thus recommended to reduce intake of refined sugars and fruit juices, but encourage consumption of natural fruits, especially those high in vitamin C and low in fructose, like cherries.

The overall conclusion is that while fructose in fruits can raise uric acid levels, the presence of other beneficial nutrients in fruits generally makes them a healthy choice, particularly when compared to refined sugars and fruit juices.

Referencesand Professional Synopsis:Coppola C, Greco M, Munir A, Musarò D, Quarta S, Massaro M, Lionetto MG, Maffia M. Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts. Curr Issues Mol Biol. 2024 Apr 29;46(5):4063-4105. doi: 10.3390/cimb46050251. PMID: 38785519; PMCID: PMC11119992.

The document is a review on Osteoarthritis, focusing on insights into diagnosis, pathophysiology, therapeutic avenues, and the potential of natural extracts for management. Some natural extracts mentioned for osteoarthritis (OA) management include:Curcumin (from turmeric), Bromelain (from pineapple), Boswellia serrata (Indian frankincense), Harpagophytum procumbens (devil’s claw), Aescin (from horse chestnut), Matricaria chamomilla (chamomile), Glycine soja (wild soybean), Zingiber officinale Roscoe (ginger), Quercetin (a flavonoid found in many fruits and vegetables). These extracts are noted for their anti-inflammatory and antioxidant properties, which can help manage OA symptoms.

Referencesand Professional Synopsis:Rabade A, Viswanatha GL, Nandakumar K, Kishore A. Evaluation of efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis: a systematic review and meta-analysis. Inflammopharmacology. 2024 Jun;32(3):1759-1775. doi: 10.1007/s10787-024-01460-9. Epub 2024 Apr 6. PMID: 38581640.

The document is an updated systematic review and meta-analysis evaluating the efficacy and safety of glucosamine sulfate, chondroitin sulfate, and their combination regimen in the management of knee osteoarthritis. It concluded that chondroitin sulfate showed significant reduction in pain intensity and improvement in physical function compared to placebo and glucosamine sulfate demonstrated a significant reduction in tibiofemoral joint space narrowing, indicating a disease-modifying effect. Both agents exhibited good safety profiles and were well tolerated, with common adverse events including gastrointestinal disturbances, headaches, skin allergies, urinary tract infections, and respiratory tract infections.

Referencesand Professional Synopsis:Ameye LG, Chee WS. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther. 2006;8(4):R127. doi: 10.1186/ar2016. PMID: 16859534; PMCID: PMC1779427.

The document is a research article that systematically reviews the scientific evidence on the effects of nutritional compounds on osteoarthritis, focusing on nutraceuticals and functional foods. Specifically, methylsulfonylmethane (MSM) helps with osteoarthritis symptoms by providing moderate evidence of efficacy. It has been shown to significantly improve pain and functional scores in patients with knee osteoarthritis. Specifically, MSM has been found to reduce pain and improve physical function as measured by the WOMAC index and Likert scale pain index in clinical trials.

Blood glucose maintenance

Referencesand Professional Synopsis:Capece, U.; Moffa, S.; Improta, I.; Di Giuseppe, G.; Nista, E.C.; Cefalo, C.M.A.; Cinti, F.; Pontecorvi, A.; Gasbarrini, A.; Giaccari, A.; et al. Alpha-Lipoic Acid and Glucose Metabolism: A Comprehensive Update on Biochemical and Therapeutic Features. Nutrients 2023, 15, 18. https://doi.org/10.3390/nu15010018

Alpha-Lipoic Acid (ALA) has therapeutic features that include: positive effects on insulin sensitivity, regulation of glucose metabolism and lipid profiles; antioxidant properties and reduction of oxidative stress; treatment of diabetic neuropathy by improving symptoms such as neuropathic pain and nerve function; association with weight loss in some studies; effects on pancreatic beta-cells and potential therapeutic role beyond diabetes; management of conditions like polycystic ovary syndrome (PCOS) and obesity; improvement in nerve blood flow and reduction of oxidative stress; neuroprotection against ischemia-reperfusion injury; potential alternative treatment for diabetic polyneuropathy; impact on cardiovascular autonomic neuropathy and prevention of diabetic macular edema. Specifically, alpha-lipoic acid (ALA) plays a significant role in insulin signaling through multiple mechanisms including: stimulating glucose uptake by promoting GLUT4 translocation and activation, activating AMPK to enhance insulin sensitivity and glucose uptake, acting as a direct binding activator of the insulin receptor, improving insulin signaling, improving insulin sensitivity, glucose disposal, and lipid profiles in individuals with diabetes, counteracting inhibition of glucose-stimulated insulin release, protecting against oxidative stress, reducing insulin resistance, enhancing glucose uptake in skeletal muscle, modulating insulin sensitivity indices and ameliorating insulin resistance, increasing insulin sensitivity in metabolic diseases by decreasing FPG, HbA1c, and insulin concentrations, improving insulin sensitivity in Type 2 Diabetes and obese patients, enhancing glucose disposal rates and insulin-mediated glucose disposal, decreasing insulin resistance in obese patients with PCOS, improving metabolic profiles related to insulin signaling, impacting nerve function and autonomic responses related to insulin signaling, acting as an insulin mimetic agent, stimulating the insulin receptor cascade, activating PI3K, AKT phosphorylation, and p38 MAPK activity for glucose uptake, influencing mitochondrial biogenesis, endoplasmic reticulum activity, and antioxidant enzymes expression, protecting pancreatic beta-cells and influencing insulin secretion, activating the insulin receptor by extracellular binding and AMPK through cell membrane crossing, contributing to the Krebs cycle initiation and potentially modifying insulin structure in certain conditions.

Referencesand Professional Synopsis:Rebecca B. Costello, Johanna T. Dwyer, Leila Saldanha, Regan L. Bailey, Joyce Merkel, and Edwina Wambogo. Do Cinnamon Supplements Have a Role in Glycemic Control in Type 2 Diabetes – A Narrative Review? J Acad Nutr Diet. 2016 November ; 116(11): 1794–1802. doi:10.1016/j.jand.2016.07.015.

A review of 11 randomized clinical trials on cinnamon supplements for adults with type 2 diabetes mellitus showed modest effects on fasting plasma glucose and hemoglobin A1c, albeit characteristics of cinnamon intervention products used in clinical trials varied in terms of manufacturers, doses, placebo formulations, and product formulations.

Referencesand Professional Synopsis:Satyakumar Vidyashankar, Uddagiri Venkanna Babu, Pralhad Sadashiv Patki. Gymnemasylvestre derived compounds inhibit GSH depletion and increase cGMP and nitric oxide to attenuate advanced glycation end products induced hypertrophic growth in renal tubular epithelial cells. Toxicology Reports 2014(1); 834–842. http://dx.doi.org/10.1016/j.toxrep.2014.08.015

Gymnemasylvestre addresses complications of diabetes related to advanced glycation end products (AGE) induced cellular hypertrophy in renal tubular epithelial cells. It helps in restoring nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels, preventing glutathione (GSH) depletion, inhibiting the formation of glutathione disulfide (GSSG), and increasing antioxidant enzyme activities to reduce reactive oxygen species (ROS) generation in cells. Additionally, Gymnemasylvestre aids in reducing markers of cellular hypertrophy, suggesting its role in inhibiting cellular differentiation observed during diabetic nephropathy (DN) complications. This document explores the effects of Gymnema Sylvestre organic extract (GE) on advanced glycation end products (AGE) induced hypertrophic growth in renal tubular epithelial cells. GE demonstrates potential in restoring nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels, preventing glutathione (GSH) depletion, inhibiting glutathione disulfide (GSSG) formation, and enhancing antioxidant enzyme activities to mitigate reactive oxygen species (ROS) generation. The findings suggest that Gymnemasylvestre may play a role in reducing markers of cellular hypertrophy, potentially influencing cellular differentiation observed in diabetic nephropathy (DN) complications.

Referencesand Professional Synopsis:Scott Fuller and Jacqueline M Stephens. Diosgenin, 4-Hydroxyisoleucine, and Fiber from Fenugreek: Mechanisms of Actions and Potential Effects on Metabolic Syndrome. Adv Nutr 2015;6:189–197. doi:10.3945/an.114.007807.

Fenugreek and its components (we here refer to as Diosgenin and 4-OH-Ile) have been studied for their effects on various physiological markers related to metabolic syndrome. Multiple studies have shown their effects on lipid metabolism, adipocyte function, cholesterol homeostasis, and cardioprotection. Diosgenin and 4-OH-Ile have antidiabetic properties and can improve glycemia, insulin concentrations, and lipid levels. 4-OH-Ile acts as an insulin sensitizer and improves insulin sensitivity.

Fenugreek, through its bioactive components, could be part of new strategies to treat metabolic diseases, and further research and clinical trials are ongoing for efficacy and standardization.

Anti-aging breakthroughs

Jun Yoshino, Joseph A. Baur, and Shin-ichiro Imai. NAD+ intermediates: The biology and therapeutic potential of NMN and NR. Cell Metab. 2018 March 06; 27(3): 513–528. doi:10.1016/j.cmet.2017.11.002.

This document provides a comprehensive exploration of the intricate relationship between nicotinamide adenine dinucleotide (NAD+) metabolism and aging.

It discusses the pivotal role of NAD+ intermediates like nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in enhancing NAD+ biosynthesis and their potential health benefits.

The document also covers the impact of NAD+ decline on tissues like muscle, liver, and brain, as well as the effects of NMN and NR administration on various physiological outcomes in different mouse models.

Exciting preclinical results suggest that supplementing NAD+ intermediates could potentially improve human health and shed light on the therapeutic implications for age-related conditions and diseases.