Zinc Lactate
Introduction
Section titled “Introduction”Zinc lactate is a chemical compound that serves as a common dietary supplement for delivering the essential trace element zinc to the body. It is derived from the reaction of lactic acid with zinc, forming a salt that is typically well-absorbed. As a crucial micronutrient, zinc plays a fundamental role in a vast array of physiological processes, impacting overall health and well-being.
Biological Basis
Section titled “Biological Basis”Zinc is an indispensable cofactor for more than 300 enzymes, influencing critical metabolic pathways, DNA synthesis, protein function, and gene expression. It is vital for the proper functioning of the immune system, supporting the development and activity of immune cells essential for defense against pathogens. Beyond its enzymatic roles, zinc is integral to cell division, growth, and tissue repair, including wound healing. It also contributes to maintaining the integrity of cell membranes, acts as an antioxidant by protecting against oxidative stress, and is necessary for the senses of taste and smell. Due to its salt form with lactate, zinc lactate is generally recognized for its high bioavailability, ensuring efficient uptake and utilization by the body.
Clinical Relevance
Section titled “Clinical Relevance”Zinc lactate is widely utilized to prevent or treat zinc deficiency, a condition that can lead to various health issues such as impaired immune function, delayed growth and development in children, skin abnormalities, hair loss, and poor wound healing. Supplementation with zinc lactate is often recommended for individuals at risk of deficiency, including those with certain gastrointestinal disorders, pregnant and lactating women, and individuals following restrictive diets. Clinical research has explored zinc’s benefits in supporting immune responses, potentially reducing the duration of common colds, and its role in eye health and dermatological conditions. While beneficial, it is important to consume zinc within recommended limits, as excessive intake can lead to adverse effects like nausea, vomiting, and interference with copper absorption.
Social Importance
Section titled “Social Importance”The ubiquitous role of zinc in human health underscores its significant social importance. Zinc deficiency remains a global public health concern, particularly affecting vulnerable populations in low-income regions, impacting childhood morbidity and mortality, and overall productivity. Consequently, public health strategies often include zinc supplementation programs and food fortification initiatives. In broader society, zinc lactate is a popular ingredient in over-the-counter dietary supplements, multivitamin formulations, and even oral care products, reflecting widespread consumer recognition of zinc’s contribution to general wellness, immune support, and healthy bodily functions.
Limitations
Section titled “Limitations”Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Studies often involve cohorts of moderate size, such as 459 female monozygotic twin pairs or 411 individuals from 150 nuclear families, which can limit the statistical power to detect genetic associations of modest effect with zinc lactate.[1]This constraint means that genuine genetic variants that exert smaller influences on zinc lactate levels might go undetected, leading to potential false negative findings.[2] While some research utilizes meta-analysis to combine data across studies and enhance power, single-cohort analyses remain susceptible to these limitations. [3]
The reliance on genotyping arrays with limited SNP coverage, such as 100K or 300K SNP chips, may result in an incomplete representation of the genome and potentially miss true associations within or near gene regions. [4] Although imputation techniques can increase marker density, their effectiveness is contingent on the quality of reference panels and the imputation threshold applied (e.g., R-squared > 0.3), which can still lead to the exclusion of relevant, less well-imputed variants. [3]Furthermore, findings from genome-wide association studies (GWAS) frequently require replication in independent cohorts, and discrepancies can arise due to differences in study design, population-specific linkage disequilibrium patterns, or issues of effect size inflation, where initially observed effects are often larger than those found upon replication.[5]
Generalizability and Phenotype Heterogeneity
Section titled “Generalizability and Phenotype Heterogeneity”A significant limitation is the predominant focus on populations of European descent, with cohorts consisting of individuals of white European ancestry or Australian adult female monozygotic twin pairs of European descent. [1]This restricted ancestral representation limits the generalizability of identified genetic associations for zinc lactate to other ethnic groups, where genetic architecture, allele frequencies, and linkage disequilibrium patterns can differ substantially.[6]Consequently, genetic variants found to influence zinc lactate levels in European populations may not have the same effects or even be present in non-European populations, calling for more diverse studies.
The accurate measurement and definition of the zinc lactate phenotype are critical, and variations in these aspects can impact the interpretation of genetic associations. For instance, the time of day when blood samples are collected or the menopausal status of participants are known to influence other serum markers, suggesting that similar physiological and environmental factors could confound zinc lactate levels.[1] While studies often attempt to correct for covariates like age or remove outliers, residual variability from unmeasured factors or subtle differences in phenotype ascertainment across studies can still introduce heterogeneity and obscure true genetic effects. [1]
Unexplained Variance and Remaining Knowledge Gaps
Section titled “Unexplained Variance and Remaining Knowledge Gaps”Despite the identification of statistically significant genetic associations, current research often explains only a fraction of the total heritability for complex traits, including zinc lactate, leaving a substantial portion of the genetic variation unaccounted for.[1] This phenomenon, often referred to as “missing heritability,” suggests that many genetic factors, such as rare variants, complex gene-gene interactions (epistasis), or structural variations, are not fully captured by common SNP arrays and additive genetic models employed in typical GWAS. [7]Consequently, the complete genetic architecture underlying zinc lactate remains largely unexplored.
The influence of environmental factors and potential gene-environment interactions on zinc lactate levels represents another area with significant knowledge gaps. Studies acknowledge the role of common environmental effects shared by family members or twins, as well as individual-specific environmental factors.[1]However, detailed investigation into specific environmental confounders and their interactions with genetic predispositions is often limited. For instance, while pooled sex analyses are common, they may overlook sex-specific genetic effects or interactions between genetic variants and lifestyle, physiological states, or environmental exposures that differentially impact zinc lactate in males and females.[1]
Variants
Section titled “Variants”Genetic variations play a crucial role in an individual’s response to nutrients and susceptibility to various health conditions, many of which can be influenced by zinc. Key genes involved in zinc transport, metabolism, and related pathways demonstrate how variants can modify the body’s zinc requirements and its interaction with zinc lactate. For instance, theSLC30A8gene encodes a beta-cell-specific zinc transporter, ZnT-8, which is critically involved in moving zinc into insulin secretory granules.[8] Variants in SLC30A8have been linked to susceptibility to type 2 diabetes, implying that altered zinc handling in pancreatic beta-cells can impact glucose-induced insulin secretion.[9]Given zinc’s fundamental role in insulin synthesis, storage, and secretion, individuals with certainSLC30A8variants might have altered zinc homeostasis within these cells, potentially affecting their metabolic health and making zinc lactate supplementation a relevant consideration for supporting optimal beta-cell function.
Another significant gene influencing metabolic pathways is SLC2A9, also known as GLUT9, which functions as a urate transporter and also contributes to glucose transport.[10] Variants in SLC2A9are strongly associated with serum uric acid levels and the risk of gout, with pronounced sex-specific effects.[10]Notably, the metabolism of glucose, influenced byGLUT9, can lead to changes in lactate and other organic anions. [11] For example, the non-synonymous variant rs16890979 in GLUT9significantly impacts serum uric acid levels, andrs10489070 is in strong linkage disequilibrium with it, also affecting urate concentrations.[12] Similarly, the rs6855911 variant has been shown to correlate with uric acid levels in different population cohorts.[11]These variations suggest that individuals might have altered lactate dynamics and urate regulation, where zinc lactate, containing both zinc and lactate, could interact with these metabolic pathways.
The HK1gene, encoding Hexokinase 1, is a critical enzyme in glycolysis, the metabolic pathway that breaks down glucose to produce energy and lactate.[13] Variations in HK1have been associated with glycated hemoglobin levels in non-diabetic populations, reflecting its impact on glucose metabolism.[13] Altered HK1activity due to genetic variants could affect cellular lactate production, a component of zinc lactate, and overall energy status. Furthermore, theBCL11Agene, known for its role in regulating fetal hemoglobin production and ameliorating beta-thalassemia, encodes a zinc-finger protein.[14] Zinc-finger proteins are a class of DNA-binding proteins that require zinc ions for their structural integrity and function, directly linking BCL11A activity to zinc availability. [15] Variants such as rs11886868 and rs10837540 in BCL11Aaffect fetal hemoglobin levels[14]indicating that optimal zinc status, potentially supported by zinc lactate, is important for the function of such zinc-dependent proteins and related physiological processes.
Genes involved in the metabolism of other trace elements, such as iron, can also have implications for zinc. The TF(transferrin) andHFEgenes are central to iron homeostasis and significantly explain variations in serum transferrin levels.[1]Transferrin is the primary protein responsible for transporting iron in the blood, and its levels can influence iron absorption and distribution. A notable variant, the C282Y mutation inHFE, is a well-known risk factor for hereditary hemochromatosis, a condition characterized by iron overload. [1] Given that zinc and iron absorption pathways can interact and compete, genetic variations that alter iron metabolism, such as those in TF and HFE, may indirectly influence the absorption or utilization of zinc. Therefore, managing iron status in individuals with these variants could have implications for their zinc requirements, where zinc lactate could contribute to maintaining a balanced trace element profile.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| chr11:70644848 | N/A | zinc lactate measurement |
Biological Background
Section titled “Biological Background”Genetic Regulation and Cellular Function
Section titled “Genetic Regulation and Cellular Function”The regulation of F cell production, which refers to cells containing fetal hemoglobin, is influenced by specific genetic determinants. A quantitative trait locus (QTL) associated with variations in F cell production has been identified and mapped to chromosome 2p15.[15] Within this genomic region lies a gene responsible for encoding a zinc-finger protein. [15]This protein is a critical component of cellular regulatory networks, where _zinc-finger protein_s often function as transcription factors, modulating gene expression patterns and thereby orchestrating various cellular processes and metabolic pathways essential for cell development and differentiation.
Key Biomolecules and Regulatory Networks
Section titled “Key Biomolecules and Regulatory Networks”At a molecular level, the zinc-finger protein identified on chromosome 2p15 serves as a pivotal biomolecule within the intricate regulatory networks that control F cell synthesis. [15]The “zinc-finger” motif denotes a structural domain within the protein that coordinates zinc ions, which are indispensable for the protein’s proper folding and its ability to interact specifically with DNA or RNA. This precise interaction is fundamental for the protein to execute its role in influencing gene transcription, thereby affecting various downstream signaling pathways and metabolic activities integral to hematopoietic cell fate and function.
Pathophysiological Processes and Systemic Effects
Section titled “Pathophysiological Processes and Systemic Effects”Dysregulation of the gene encoding this zinc-finger protein, leading to altered expression or function, can disrupt the homeostatic control of F cell production. [15]Alterations in F cell levels have significant pathophysiological implications, particularly in conditions where the sustained production of fetal hemoglobin can have therapeutic benefits, influencing the overall severity of certain hematological disorders. Thus, the actions of thiszinc-finger protein exert systemic consequences on red blood cell biology and the broader hematopoietic system, impacting physiological balance at the tissue and organ level.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Zinc Homeostasis and Insulin Signaling
Section titled “Zinc Homeostasis and Insulin Signaling”Zinc plays a crucial role in maintaining proper cellular function, particularly within pancreatic beta-cells where its precise transport is vital for insulin production and secretion. The zinc transporterZnT-8, also known as SLC30A8, is specifically expressed in beta-cells and localizes within insulin secretory granules, mediating the sequestration of zinc into these vesicles.[8]This intricate process is integral to the proper crystallization of insulin and its subsequent regulated release in response to glucose stimulation, thereby directly influencing systemic glucose homeostasis. The functional significance extends to disease-relevant mechanisms, as genetic variations, such as single nucleotide polymorphisms (SNPs) in theSLC30A8gene, have been strongly associated with susceptibility to type 2 diabetes (T2D) in various populations, underscoring its role as a key component in disease pathology.[9]
Metabolic Regulation and Energy Flux
Section titled “Metabolic Regulation and Energy Flux”Cellular energy metabolism is tightly regulated, with glycolysis serving as a fundamental pathway for ATP production and the generation of essential metabolic intermediates. Dysfunctions in glycolytic enzymes, as observed in erythrocyte enzyme abnormalities, can compromise cellular energy status and lead to pathological conditions, highlighting the critical importance of precise metabolic regulation and flux control.[16]Lactate, a crucial intermediary metabolite and a primary product of anaerobic glycolysis, reflects the cellular metabolic state and contributes to systemic metabolic regulation. Facilitative glucose transporters, includingSLC2A9 (GLUT9), are essential for cellular glucose uptake, directly impacting the flux of glucose through metabolic pathways and thus overall energy homeostasis.[10] These transporters are intricately involved in maintaining the delicate balance of metabolic fuel availability and utilization.
Transcriptional Control and Protein Modification
Section titled “Transcriptional Control and Protein Modification”Zinc plays a critical structural and catalytic role in numerous proteins, including the vast family of zinc-finger proteins, which are prominent regulators of gene expression. These proteins utilize zinc ions to stabilize their characteristic finger-like motifs, enabling specific interactions with DNA, RNA, and other proteins. [15] By binding to regulatory regions of target genes, zinc-finger proteins can activate or repress transcription, thereby orchestrating cellular differentiation, growth, and adaptive responses to environmental cues. Beyond direct transcriptional control, zinc can also influence protein modification and stability by serving as a cofactor or structural component for enzymes that mediate these modifications, contributing to post-translational regulation and allosteric control. This widespread involvement of zinc in protein structure and function highlights its essentiality in maintaining complex cellular regulatory networks and their functional significance.
Integrated Metabolic and Transport Networks
Section titled “Integrated Metabolic and Transport Networks”The body’s metabolic landscape is characterized by deeply interconnected pathways that constantly crosstalk and influence one another, forming complex regulatory networks crucial for systems-level integration. For example, the facilitative glucose transporterSLC2A9 (GLUT9) plays a pivotal role beyond glucose transport, functioning as a newly identified urate transporter that significantly influences serum urate levels, urinary excretion, and susceptibility to gout.[10]This transporter exhibits metabolic flux control, with its activity linked to fructose metabolism and demonstrating pronounced sex-specific effects on uric acid concentrations.[10]Such multifaceted roles underscore a critical link between carbohydrate metabolism and purine catabolism, showcasing an intricate network interaction and hierarchical regulation at a systems level, with implications for disease-relevant mechanisms.
Furthermore, lipid metabolism, encompassing the regulation of cholesterol and triglyceride levels, represents another integrated system influenced by multiple genetic and environmental factors. Key components include genes such asHMGCR, involved in cholesterol synthesis, LCAT (lecithin-cholesterol acyltransferase), and ABCG8, which functions as a hepatic cholesterol transporter. [17]Common genetic variants within these genes are associated with plasma lipid concentrations and influence the risk of coronary artery disease. These pathways are under sophisticated hierarchical regulation by transcription factors likeHNF4A and HNF1A, which are essential for maintaining hepatic gene expression and overall lipid homeostasis. [18] Dysregulation in any of these interconnected pathways can lead to metabolic disorders, where understanding compensatory mechanisms and identifying therapeutic targets is critical for effective intervention in conditions such as dyslipidemia.
References
Section titled “References”[1] Benyamin B, et al. “Variants in TF and HFEexplain approximately 40% of genetic variation in serum-transferrin levels.”Am J Hum Genet, 2008.
[2] Benjamin EJ, et al. “Genome-wide association with select biomarker traits in the Framingham Heart Study.” BMC Med Genet, 2007.
[3] Yuan X, et al. “Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.” Am J Hum Genet, 2008.
[4] O’Donnell CJ, et al. “Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI’s Framingham Heart Study.”BMC Med Genet, 2007.
[5] Sabatti C, et al. “Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.”Nat Genet, 2008.
[6] Pare G, et al. “Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women.” PLoS Genet, 2007.
[7] Yang Q, et al. “Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study.”BMC Med Genet, 2007.
[8] Chimienti, F. et al. “Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules.”Diabetes, vol. 53, no. 9, 2004, pp. 2330–2337.
[9] Omori, S. et al. “Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population.” Diabetes, vol. 57, no. 3, 2008, pp. 791–795.
[10] Vitart, V. et al. “SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout.”Nat Genet, vol. 40, no. 4, 2008, pp. 437–442.
[11] Li, S. et al. “The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts.”PLoS Genet, vol. 3, no. 11, 2007, e194.
[12] McArdle, P. F. et al. “Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish.”Arthritis Rheum, vol. 58, no. 11, 2008, pp. 3617–3621.
[13] Pare G, et al. “Novel association of HK1with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women’s Genome Health Study.”PLoS Genet, 2008.
[14] Uda, M. et al. “Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia.”Proc Natl Acad Sci U S A, vol. 105, no. 5, 2008, pp. 1620–1625.
[15] Menzel, S. et al. “A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15.” Nat Genet, vol. 39, no. 10, 2007, pp. 1197–1199.
[16] van Wijk, R. and van Solinge, W. W. “The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis.” Blood, vol. 106, no. 12, 2005, pp. 4034–4042.
[17] Willer CJ, et al. “Newly identified loci that influence lipid concentrations and risk of coronary artery disease.”Nat Genet, 2008.
[18] Kathiresan, Sekar, et al. “Common variants at 30 loci contribute to polygenic dyslipidemia.” Nature Genetics, vol. 41, no. 11, 2009, pp. 1155–1163.