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Biomolecules Nov 2023The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and... (Review)
Review
The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and dermis. This can be primarily attributed to the diminishing population of epidermal stem cells and the reduction in collagen, which is the primary structural protein in the human body. The alterations occurring in the epidermis and dermis due to the aging process result in disruptions to the structure and functionality of the skin. This creates a microenvironment conducive to age-related skin conditions such as a compromised skin barrier, slowed wound healing, and the onset of skin cancer. This review emphasizes the recent molecular discoveries related to skin aging and evaluates preventive approaches, such as the use of topical retinoids. Topical retinoids have demonstrated promise in enhancing skin texture, diminishing fine lines, and augmenting the thickness of both the epidermal and dermal layers.
Topics: Humans; Vitamin A; Skin Aging; Skin; Retinoids; Aging
PubMed: 38002296
DOI: 10.3390/biom13111614 -
Journal of Neurology, Neurosurgery, and... Dec 2023Nutritional peripheral neuropathies are a global problem, heavily influenced by geopolitical, cultural and socioeconomic factors. Peripheral neuropathy occurs most... (Review)
Review
Nutritional peripheral neuropathies are a global problem, heavily influenced by geopolitical, cultural and socioeconomic factors. Peripheral neuropathy occurs most frequently secondary to B-vitamin deficiencies, which is suspected to increase in years to come due to the popularity of vegan and vegetarian diets and increased use of bariatric surgery.This review will focus on the common B-vitamins for which a causal link to peripheral neuropathy is more established (vitamins B, B, B, B and B). We will review the historical human and animal data on which much of the clinical descriptions of vitamin deficiencies are based and summarise current available tools for accurately diagnosing a nutritional deficiency. We will also review recently described genetic diseases due to pathogenic variants in genes involved in B-vitamin metabolism that have helped to inform the phenotypes and potential causality of certain B-vitamins in peripheral neuropathy (B and B).Endemic outbreaks of peripheral neuropathy over the last two centuries have been linked to food shortages and nutritional deficiency. These include outbreaks in Jamaican sugar plantation workers in the nineteenth century (Strachan's syndrome), World War two prisoners of war, Cuban endemic neuropathy and also Tanzanian endemic optic neuropathy, which remains a significant public health burden today. An improved understanding of lack of which vitamins cause peripheral neuropathy and how to identify specific deficiencies may lead to prevention of significant and irreversible disability in vulnerable populations.
Topics: Animals; Humans; Peripheral Nervous System Diseases; Vitamin B Complex; Avitaminosis; Malnutrition; Thiamine; Vitamin A; Optic Nerve Diseases
PubMed: 37536924
DOI: 10.1136/jnnp-2022-329849 -
Science (New York, N.Y.) Mar 2024Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are...
Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.
Topics: Animals; Mice; Adult Stem Cells; Cell Lineage; Cell Plasticity; Epidermis; Hair Follicle; Tretinoin; Wound Healing; Rejuvenation; Cell Culture Techniques; Neoplasms; Mice, Inbred C57BL
PubMed: 38452090
DOI: 10.1126/science.adi7342 -
Drug and Therapeutics Bulletin Oct 2023The body needs small daily quantities of vitamins and minerals, which are usually obtained from the diet. Intravenous vitamins are used for a few serious medical... (Review)
Review
The body needs small daily quantities of vitamins and minerals, which are usually obtained from the diet. Intravenous vitamins are used for a few serious medical conditions (eg, malabsorption syndromes with severe vitamin depletion, Wernicke's encephalopathy or critical illness). Intravenous drips containing high doses of various vitamins and minerals (eg, the so-called 'Myers' cocktail') have been promoted in popular culture to 'reduce stress', 'increase energy' or 'boost immunity', with claims that the intravenous route allows faster absorption of vitamins into the bloodstream than if they are taken orally. There is a lack of high-quality evidence to suggest that high-dose vitamin infusions are necessary or offer any health benefit in the absence of a specific vitamin deficiency or medical condition. There may be harms from taking high (non-physiological) quantities of some vitamins and minerals. Licensed forms of injectable vitamins that are prescription-only medicines should not be advertised to the public and should only be supplied and administered by appropriately qualified healthcare professionals.
Topics: Humans; Vitamins; Minerals; Vitamin A; Vitamin K
PubMed: 37640530
DOI: 10.1136/dtb.2023.000006 -
The British Journal of Dermatology Oct 2023Skin ageing is a complex process involving the additive effects of skin's interaction with its external environment, predominantly chronic sun exposure, upon a... (Review)
Review
Skin ageing is a complex process involving the additive effects of skin's interaction with its external environment, predominantly chronic sun exposure, upon a background of time-dependent intrinsic ageing. Skin health and beauty is considered one of the principal factors perceived to represent overall 'health and wellbeing'; thus, the demand for skin rejuvenation strategies has rapidly increased, with a worldwide annual expenditure expected to grow from $US24.6 billion to around $US44.5 billion by 2030 (https://www.databridgemarketresearch.com/reports/global-facial-rejuvenation-market). Skin rejuvenation can be achieved in several ways, ranging from laser and device-based treatments to chemical peels and injectables; however, topical skin care regimes are a mainstay treatment for ageing skin and all patients seeking skin rejuvenation can benefit from this relatively low-risk intervention. While the most efficacious topical rejuvenation treatment is application of tretinoin (all-trans retinoic acid) - a prescription-only medicine considered to be the clinical 'gold standard' - a hybrid category of 'cosmeceutical' products at the midpoint of the spectrum of cosmetics and pharmaceutical has emerged. This article reviews the clinical manifestations of skin ageing and the available topical treatments for skin rejuvenation, including retinoids, peptides and antioxidants.
Topics: Humans; Skin Aging; Rejuvenation; Skin; Tretinoin; Cosmetics
PubMed: 37903073
DOI: 10.1093/bjd/ljad282 -
International Journal of Molecular... Jan 2024The objective of the present review was to summarize the molecular mechanisms associated with the effects of the vitamins A, C, E and K, and group B vitamins on bone and... (Review)
Review
The objective of the present review was to summarize the molecular mechanisms associated with the effects of the vitamins A, C, E and K, and group B vitamins on bone and their potential roles in the development of osteoporosis. Epidemiological findings have demonstrated an association between vitamin deficiency and a higher risk of developing osteoporosis; vitamins are positively related to bone health upon their intake at the physiological range. Excessive vitamin intake can also adversely affect bone formation, as clearly demonstrated for vitamin A. Vitamins E (tocopherols and tocotrienols), K2 (menaquinones 4 and 7) and C have also been shown to promote osteoblast development through bone morphogenetic protein (BMP)/Smad and Wnt/β‑catenin signaling, as well as the TGFβ/Smad pathway (α‑tocopherol). Vitamin A metabolite (all‑trans retinoic acid) exerts both inhibitory and stimulatory effects on BMP‑ and Wnt/β‑catenin‑mediated osteogenesis at the nanomolar and micromolar range, respectively. Certain vitamins significantly reduce receptor activator of nuclear factor kappa‑B ligand (RANKL) production and RANKL/RANK signaling, while increasing the level of osteoprotegerin (OPG), thus reducing the RANKL/OPG ratio and exerting anti‑osteoclastogenic effects. Ascorbic acid can both promote and inhibit RANKL signaling, being essential for osteoclastogenesis. Vitamin K2 has also been shown to prevent vascular calcification by activating matrix Gla protein through its carboxylation. Therefore, the maintenance of a physiological intake of vitamins should be considered as a nutritional strategy for the prevention of osteoporosis.
Topics: Humans; Vitamins; Cholecalciferol; beta Catenin; Vitamin A; Bone Density; Osteoporosis; Vitamin K; Bone Morphogenetic Proteins; Wnt Signaling Pathway
PubMed: 38063255
DOI: 10.3892/ijmm.2023.5333 -
Molecular Psychiatry Sep 2023Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major...
Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression. In a conservative model adjusting for life style factors and cardiovascular and antidepressant medication use we identified 8 metabolites, including 6 novel, significantly associated with depression. In individuals with depression, increased levels of retinol (vitamin A), 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) (lecithin) and mannitol/sorbitol and lower levels of hippurate, 4-hydroxycoumarin, 2-aminooctanoate (alpha-aminocaprylic acid), 10-undecenoate (11:1n1) (undecylenic acid), 1-linoleoyl-GPA (18:2) (lysophosphatidic acid; LPA 18:2) are observed. These metabolites are either directly food derived or are products of host and gut microbial metabolism of food-derived products. Our Mendelian randomization analysis suggests that low hippurate levels may be in the causal pathway leading towards depression. Our findings highlight putative actionable targets for depression prevention that are easily modifiable through diet interventions.
Topics: Humans; Tandem Mass Spectrometry; Depression; Diet; Metabolome; Vitamin A; Hippurates; Metabolomics
PubMed: 37495887
DOI: 10.1038/s41380-023-02180-2 -
Pharmacology & Therapeutics Aug 2023Vitamin A (VA, retinol) and its metabolites (commonly called retinoids) are required for the proper development of the kidney during embryogenesis, but retinoids also... (Review)
Review
Vitamin A (VA, retinol) and its metabolites (commonly called retinoids) are required for the proper development of the kidney during embryogenesis, but retinoids also play key roles in the function and repair of the kidney in adults. Kidneys filter 180-200 liters of blood per day and each kidney contains approximately 1 million nephrons, which are often referred to as the 'functional units' of the kidney. Each nephron consists of a glomerulus and a series of tubules (proximal tubule, loop of Henle, distal tubule, and collecting duct) surrounded by a network of capillaries. VA is stored in the liver and converted to active metabolites, most notably retinoic acid (RA), which acts as an agonist for the retinoic acid receptors ((RARs α, β, and γ) to regulate gene transcription. In this review we discuss some of the actions of retinoids in the kidney after injury. For example, in an ischemia-reperfusion model in mice, injury-associated loss of proximal tubule (PT) differentiation markers occurs, followed by re-expression of these differentiation markers during PT repair. Notably, healthy proximal tubules express ALDH1a2, the enzyme that metabolizes retinaldehyde to RA, but transiently lose ALDH1a2 expression after injury, while nearby myofibroblasts transiently acquire RA-producing capabilities after injury. These results indicate that RA is important for renal tubular injury repair and that compensatory mechanisms exist for the generation of endogenous RA by other cell types upon proximal tubule injury. ALDH1a2 levels also increase in podocytes, epithelial cells of the glomeruli, after injury, and RA promotes podocyte differentiation. We also review the ability of exogenous, pharmacological doses of RA and receptor selective retinoids to treat numerous kidney diseases, including kidney cancer and diabetic kidney disease, and the emerging genetic evidence for the importance of retinoids and their receptors in maintaining or restoring kidney function after injury. In general, RA has a protective effect on the kidney after various types of injuries (eg. ischemia, cytotoxic actions of chemicals, hyperglycemia related to diabetes). As more research into the actions of each of the three RARs in the kidney is carried out, a greater understanding of the actions of vitamin A is likely to lead to new insights into the pathology of kidney disorders and the development of new therapies for kidney diseases.
Topics: Vitamin A; Kidney; Retinoids; Receptors, Retinoic Acid; Tretinoin; Kidney Diseases
PubMed: 37331524
DOI: 10.1016/j.pharmthera.2023.108481 -
Biomedicine & Pharmacotherapy =... Aug 2023Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid....
Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid. Retinol and all-trans-retinoic acid (atRA) penetrate the blood-brain barrier and are reported to be neuroprotective in several animal models. We characterised the impact of retinol and its metabolites, all-trans-retinal (atRAL) and atRA, on ferroptosis-a programmed cell death caused by iron-dependent phospholipid peroxidation. Ferroptosis was induced by erastin, buthionine sulfoximine or RSL3 in neuronal and non-neuronal cell lines. We found that retinol, atRAL and atRA inhibited ferroptosis with a potency superior to α-tocopherol, the canonical anti-ferroptotic vitamin. In contrast, we found that antagonism of endogenous retinol with anhydroretinol sensitises ferroptosis induced in neuronal and non-neuronal cell lines. Retinol and its metabolites atRAL and atRA directly interdict lipid radicals in ferroptosis since these compounds displayed radical trapping properties in a cell-free assay. Vitamin A, therefore, complements other anti-ferroptotic vitamins, E and K; metabolites of vitamin A, or agents that alter their levels, may be potential therapeutics for diseases where ferroptosis is implicated.
Topics: Animals; Vitamin A; Ferroptosis; Lipid Peroxidation; Tretinoin; Vitamins; Retinaldehyde; Lipids
PubMed: 37236031
DOI: 10.1016/j.biopha.2023.114930 -
Nutrients Dec 2023Cognitive impairment and dementia are burgeoning public health concerns, especially given the increasing longevity of the global population. These conditions not only... (Meta-Analysis)
Meta-Analysis Review
Improving Cognitive Function with Nutritional Supplements in Aging: A Comprehensive Narrative Review of Clinical Studies Investigating the Effects of Vitamins, Minerals, Antioxidants, and Other Dietary Supplements.
Cognitive impairment and dementia are burgeoning public health concerns, especially given the increasing longevity of the global population. These conditions not only affect the quality of life of individuals and their families, but also pose significant economic burdens on healthcare systems. In this context, our comprehensive narrative review critically examines the role of nutritional supplements in mitigating cognitive decline. Amidst growing interest in non-pharmacological interventions for cognitive enhancement, this review delves into the efficacy of vitamins, minerals, antioxidants, and other dietary supplements. Through a systematic evaluation of randomized controlled trials, observational studies, and meta-analysis, this review focuses on outcomes such as memory enhancement, attention improvement, executive function support, and neuroprotection. The findings suggest a complex interplay between nutritional supplementation and cognitive health, with some supplements showing promising results and others displaying limited or context-dependent effectiveness. The review highlights the importance of dosage, bioavailability, and individual differences in response to supplementation. Additionally, it addresses safety concerns and potential interactions with conventional treatments. By providing a clear overview of current scientific knowledge, this review aims to guide healthcare professionals and researchers in making informed decisions about the use of nutritional supplements for cognitive health.
Topics: Humans; Vitamins; Antioxidants; Quality of Life; Dietary Supplements; Minerals; Vitamin A; Cognition; Vitamin K; Aging; Observational Studies as Topic
PubMed: 38140375
DOI: 10.3390/nu15245116