Indium

• None scientifically established

• None scientifically established

Indium demonstrates complex and poorly characterized bioavailability, distribution, metabolism, and elimination characteristics that significantly influence its biological effects and practical applications. As a trace element not recognized as essential for human health by mainstream medical and nutritional authorities, indium’s pharmacokinetic properties reflect both its chemical characteristics and limited research findings. Absorption of indium following oral administration is generally poor, with bioavailability typically estimated at approximately 0.5-5% based on limited animal studies and extrapolation from research on other trivalent metals. This relatively poor bioavailability reflects several factors including indium’s limited water solubility in many forms, tendency to form insoluble hydroxides at physiological pH, potential binding to dietary components in the gastrointestinal tract, and limited specific transport mechanisms for absorption.

The primary site of indium absorption appears to be the small intestine, where several mechanisms may contribute to its limited uptake. Passive diffusion likely plays a minimal role given indium’s charged nature and limited lipid solubility, though some absorption through paracellular pathways may occur, particularly with more soluble indium salts. Active transport mechanisms specific to indium have not been well-characterized, though some research suggests potential limited uptake through non-specific divalent metal transporters or other mineral transport systems, albeit with low efficiency compared to essential minerals. Intestinal metabolism does not appear to significantly influence indium absorption, as the element is not subject to the enzymatic transformations that affect many organic compounds.

However, chemical speciation changes including hydrolysis, complexation with dietary components, or precipitation may significantly affect the fraction available for absorption. Several factors significantly influence indium absorption. Chemical form substantially impacts indium bioavailability, with different indium compounds demonstrating markedly different solubility and absorption characteristics. More soluble forms including indium sulfate, indium chloride, or certain indium chelates typically demonstrate higher bioavailability (potentially 2-5%) compared to less soluble forms like indium oxide or metallic indium (typically <0.5%).

This differential absorption creates significant variability in bioavailability depending on the specific indium preparation used in different supplements. Particle size may influence indium absorption, with nanoparticulate formulations potentially demonstrating different absorption characteristics compared to conventional preparations. Some research with other metals suggests enhanced absorption of nanoparticulate forms through various mechanisms including increased surface area, altered cellular uptake pathways, or enhanced paracellular transport, though specific studies with indium nanoparticles remain limited. Food effects appear to substantially impact indium bioavailability, with some research suggesting that consumption with meals may reduce absorption due to binding interactions with various food components, particularly those containing phosphates, phytates, or certain proteins.

These binding interactions may reduce the free fraction available for absorption, suggesting potential benefits to administration on an empty stomach, though specific food effect studies with indium supplements remain limited. Gastrointestinal pH may significantly influence indium solubility and subsequent absorption, with more acidic conditions generally favoring solubility of many indium compounds. This pH dependence suggests potential variability in absorption based on individual differences in gastric acidity or use of acid-reducing medications, though specific studies examining these factors remain limited. Individual factors including age, gastrointestinal function, and overall mineral status may significantly influence indium pharmacokinetics, though specific research on these factors remains very limited.

Age-related changes in gastrointestinal function, including altered pH, transit time, and absorptive capacity, might theoretically affect indium absorption, though specific studies examining age effects on indium bioavailability remain essentially nonexistent. Gastrointestinal disorders affecting absorption function might similarly influence indium bioavailability, though the direction and magnitude of these effects would likely depend on the specific condition and its effects on the limited absorption mechanisms for indium. Distribution of absorbed indium throughout the body follows patterns reflecting its chemical properties and interactions with biological systems. After reaching the systemic circulation, indium distributes to various tissues, with specific distribution patterns influencing its biological effects and potential toxicity.

Plasma protein binding appears extensive for indium, with binding percentages typically exceeding 90% based on limited in vitro data. This high protein binding, particularly to albumin and transferrin, limits the free concentration available for tissue distribution and target engagement, though it may also protect against rapid elimination and potentially reduce acute toxicity. Tissue distribution studies in animals suggest preferential accumulation in the liver, kidneys, spleen, and to a lesser extent in bone and lungs following repeated exposure. This distribution pattern reflects both the role of these organs in metal processing and elimination and the tendency of indium to form insoluble phosphates or hydroxides that may deposit in tissues.

The apparent volume of distribution for indium appears moderate (estimated at 0.5-2 L/kg based on limited animal data), suggesting distribution beyond the vascular compartment but not extensive tissue penetration, likely reflecting its limited lipid solubility and high protein binding. Blood-brain barrier penetration appears limited for most indium compounds based on animal studies, with minimal distribution to the central nervous system under normal conditions. This limited brain penetration likely reflects indium’s charged nature, high protein binding, and the absence of specific transport mechanisms across the blood-brain barrier. Metabolism of indium in the traditional sense of biotransformation does not occur, as elemental metals are not subject to the enzymatic modifications that affect organic compounds.

However, several processes may alter indium’s chemical form and biological activity after absorption. Chemical speciation changes including hydrolysis, complexation with biological ligands, or incorporation into various biomolecules may significantly affect indium’s distribution, activity, and elimination. These chemical transformations may vary between different tissues and may be influenced by local pH, presence of competing metals, and availability of various biological ligands. Protein binding and complex formation with various biomolecules including metallothioneins, transferrin, and other metal-binding proteins may significantly influence indium’s biological activity and residence time in different tissues.

These interactions may sequester indium in certain compartments, potentially reducing its availability for both beneficial and toxic effects while extending its biological half-life. Elimination of indium occurs through multiple routes, with patterns reflecting its limited metabolism and chemical properties. Renal excretion represents a significant elimination pathway for indium, though with relatively low efficiency due to extensive protein binding and limited glomerular filtration of the bound fraction. The limited free indium that undergoes glomerular filtration may be partially reabsorbed in the tubules, further reducing overall renal clearance.

Biliary excretion and subsequent fecal elimination likely represent important routes for indium clearance, with some research suggesting this may be the predominant elimination pathway for many indium compounds. This elimination route may involve hepatic uptake of protein-bound indium, release into bile, and subsequent elimination through feces. Fecal elimination also accounts for the substantial portion of unabsorbed indium, representing the primary route for the majority of ingested material that is not absorbed. The elimination half-life of indium appears prolonged, with estimates ranging from weeks to months for complete elimination based on limited animal data.

This extended elimination reflects indium’s tendency to form insoluble compounds in tissues, extensive protein binding, potential enterohepatic circulation, and limited efficiency of elimination pathways. This prolonged residence time creates potential for accumulation with repeated exposure, even at relatively low doses, highlighting the importance of careful consideration of long-term safety with chronic supplementation. Pharmacokinetic interactions with indium warrant consideration in several categories, though documented clinically significant interactions remain relatively limited due to indium’s minimal therapeutic use. Mineral interactions represent one of the most significant potential pharmacokinetic considerations with indium, as competitive interactions may occur with various essential minerals including zinc, copper, iron, and calcium.

These interactions may potentially affect the absorption, distribution, or elimination of both indium and essential minerals, though specific interaction studies remain limited for most combinations. The potential for such interactions suggests caution when combining indium with mineral supplements. Chelating agents including various therapeutic chelators (e.g., EDTA, DMSA) or dietary components with chelating properties might significantly alter indium pharmacokinetics through enhanced solubilization, altered absorption, or increased elimination. While specific interaction studies are limited, these theoretical interactions could potentially influence both the bioavailability and elimination of indium, with direction and magnitude depending on the specific chelator and conditions of administration.

Medications affecting gastrointestinal pH, particularly acid-reducing agents like proton pump inhibitors or H2 blockers, might theoretically reduce indium absorption by increasing gastric pH and potentially reducing the solubility of many indium compounds. While specific interaction studies are lacking, the pH-dependent solubility of many indium compounds suggests potential for reduced bioavailability when combined with these medications. Bioavailability enhancement strategies for indium have been minimally studied, though several theoretical approaches might be considered based on general principles for improving the absorption of poorly bioavailable metals. Chelation with organic ligands represents a potential approach to enhance indium bioavailability, as appropriate chelation may increase solubility, prevent precipitation at physiological pH, and potentially facilitate absorption through altered chemical properties.

Various chelating agents including organic acids, amino acids, or synthetic chelators might theoretically enhance indium absorption, though specific comparative bioavailability studies validating these approaches remain limited. Nanoparticulate formulations have been explored for various poorly absorbed elements, with potential to enhance bioavailability through increased surface area, altered cellular uptake pathways, or enhanced paracellular transport. While specific studies with indium nanoparticles remain limited, this approach might theoretically improve the poor oral bioavailability of conventional indium preparations, though with need for careful safety evaluation given the potentially altered biological properties of nanoscale materials. Formulation considerations for indium supplements include several approaches that may influence their bioavailability and potential effects.

Chemical form selection represents a critical formulation consideration, as different indium compounds demonstrate substantially different solubility, stability, and potentially different absorption characteristics. Most commercial supplements utilize indium sulfate or other relatively water-soluble indium salts based on theoretical considerations about enhanced bioavailability compared to insoluble indium compounds, though specific comparative bioavailability studies validating these choices remain limited. Particle size control may influence indium absorption, with micronization or other particle size reduction techniques potentially enhancing dissolution rate and subsequent bioavailability. Some commercial products claim enhanced bioavailability through proprietary processing methods affecting particle size or other physical characteristics, though typically without published pharmacokinetic validation.

Delivery system selection may influence indium bioavailability, with various approaches including sublingual formulations, liposomal delivery, or specialized oral formulations claimed to enhance absorption through different mechanisms. While theoretical considerations suggest potential advantages to certain delivery approaches, specific comparative bioavailability studies validating these claims for indium remain essentially nonexistent. Monitoring considerations for indium are complicated by its limited clinical use and the absence of established therapeutic monitoring protocols. Blood or serum indium measurement can be accomplished using specialized analytical methods including inductively coupled plasma mass spectrometry (ICP-MS) or atomic absorption spectroscopy, though such measurements are primarily used in research or occupational exposure contexts rather than clinical monitoring.

The relationship between specific blood concentrations and biological effects remains poorly characterized, further limiting the practical utility of such measurements. Urine indium measurement might potentially provide information about recent exposure and elimination, though the relatively limited urinary excretion of indium reduces the sensitivity of this approach for monitoring. Additionally, the relationship between urinary indium levels and tissue burden or biological effects remains poorly characterized. Tissue indium measurement through biopsy or other invasive sampling would provide the most direct assessment of tissue accumulation but is impractical for routine monitoring and lacks established reference ranges or clear relationships to biological effects.

Special population considerations for indium bioavailability include several important groups, though specific research in these populations remains essentially nonexistent. Elderly individuals may experience age-related changes in gastrointestinal function, renal function, and other physiological parameters that could potentially alter indium absorption, distribution, and elimination. While specific pharmacokinetic studies in this population are lacking, theoretical considerations suggest potentially altered handling in some older adults, which might influence both the magnitude and duration of any biological effects. Individuals with kidney disease might theoretically experience altered indium elimination given the role of renal excretion in indium clearance.

While specific pharmacokinetic studies in this population are lacking, theoretical considerations suggest potential for increased accumulation with repeated exposure in those with significant renal impairment, though the clinical significance remains uncertain given the limited research in this area. Those with gastrointestinal disorders affecting absorption function might experience significantly altered indium bioavailability, though the direction and magnitude of these effects would likely depend on the specific condition and its effects on the limited absorption mechanisms for indium. Individuals with altered mineral status due to dietary factors, medical conditions, or other supplements might theoretically experience different indium pharmacokinetics due to altered competitive interactions or changes in metal-binding proteins. While specific studies examining these interactions remain limited, the potential for complex interactions between different metals suggests consideration of overall mineral status when evaluating indium supplementation.

In summary, indium demonstrates complex pharmacokinetic characteristics reflecting its chemical properties and limited biological role. Oral bioavailability appears poor (typically 0.5-5%) due to limited solubility at physiological pH, absence of specific absorption mechanisms, and potential binding to dietary components. After limited absorption, indium undergoes extensive protein binding, moderate distribution with some accumulation in the liver and kidneys, and slow elimination through both renal and biliary routes with an extended half-life of weeks to months. These pharmacokinetic properties create potential for tissue accumulation with repeated exposure, even at relatively low doses, highlighting the importance of careful consideration of long-term safety with chronic supplementation.

The limited research specifically examining indium pharmacokinetics in humans creates significant uncertainty about optimal formulation approaches, potential interactions, and special population considerations, further complicating evidence-based recommendations regarding indium supplementation.

Indium demonstrates a complex safety profile that requires careful consideration when evaluating its use as a supplement. As a trace element not recognized as essential for human health by mainstream medical and nutritional authorities, indium’s safety characteristics reflect both its chemical properties and limited research findings. Adverse effects associated with indium consumption are incompletely characterized due to extremely limited clinical research specifically evaluating its safety profile as a supplement. Most safety information comes from occupational exposure studies, limited animal research, and theoretical considerations based on indium’s chemical properties.

Gastrointestinal effects represent potential concerns with indium supplementation, though with limited documentation in supplement users. Digestive discomfort, including mild nausea, stomach upset, or indigestion, has been reported anecdotally by some users, potentially reflecting direct irritation of the gastrointestinal mucosa by certain indium compounds, particularly more soluble forms like indium sulfate. However, the frequency and severity of these effects remain poorly characterized due to the absence of systematic safety studies with indium supplements. Kidney effects represent a theoretical concern with indium supplementation given animal studies showing potential nephrotoxicity with certain indium compounds at high doses.

While clinical evidence for significant kidney effects at typical supplemental doses is lacking, the kidneys’ role in eliminating many metals and indium’s tendency to accumulate in renal tissue in animal studies suggest potential for adverse effects with extended use or in vulnerable populations, warranting a cautious approach. Pulmonary effects have been documented primarily in occupational settings with inhalation exposure to indium compounds, particularly indium tin oxide and other particulate forms. While these respiratory concerns are less directly relevant to oral supplementation, they demonstrate indium’s potential biological activity and capacity to cause tissue damage under certain exposure conditions. The documented pulmonary toxicity in occupational settings suggests a generally cautious approach to indium exposure through any route, including supplementation.

Liver effects represent another theoretical concern with indium supplementation given animal studies showing hepatic accumulation and potential hepatotoxicity with certain indium compounds at high doses. While clinical evidence for significant liver effects at typical supplemental doses is lacking, indium’s tendency to accumulate in hepatic tissue in animal studies suggests potential for adverse effects with extended use or in vulnerable populations, warranting a cautious approach. The severity and frequency of adverse effects are influenced by several factors, though with significant limitations in specific data for supplement use. Dosage likely affects the potential for adverse effects, with higher doses creating greater potential for toxicity based on general principles of dose-dependent effects and limited animal toxicity data.

However, the relationship between specific supplement doses and adverse effect risk remains poorly characterized due to limited systematic safety studies. Chemical form significantly impacts potential toxicity, with different indium compounds demonstrating markedly different solubility, bioavailability, and biological activity. More soluble forms including indium sulfate or indium chloride typically demonstrate higher bioavailability and potentially greater systemic exposure compared to less soluble forms, potentially influencing both beneficial and adverse effects. Duration of use likely influences the risk profile, with greater concerns for extended use given indium’s relatively long biological half-life and potential for tissue accumulation with repeated exposure.

The limited research on long-term safety creates significant uncertainty about potential cumulative effects with chronic supplementation, suggesting a cautious approach to extended use. Individual factors including age, renal function, hepatic function, and overall health status likely influence susceptibility to potential adverse effects, though specific research on these factors in the context of indium supplementation remains essentially nonexistent. Contraindications for indium supplementation include several important considerations based on theoretical concerns and limited research findings. Kidney disease represents a significant contraindication for indium supplementation given the kidneys’ role in eliminating many metals and animal studies showing potential nephrotoxicity with certain indium compounds.

Individuals with impaired renal function might theoretically experience greater accumulation and increased risk of adverse effects, suggesting avoidance in this population given the uncertain benefits and potential risks. Liver disease might similarly represent a contraindication given animal studies showing hepatic accumulation and potential hepatotoxicity with certain indium compounds. Those with impaired liver function might theoretically experience altered handling of indium, suggesting avoidance in this population given the uncertain benefits and potential risks. Respiratory conditions, particularly pre-existing pulmonary fibrosis or other interstitial lung diseases, might warrant caution with indium exposure through any route given the documented pulmonary toxicity in occupational settings.

While oral supplementation presents different exposure characteristics compared to inhalation, the established pulmonary toxicity suggests a generally cautious approach, particularly in those with pre-existing respiratory compromise. Pregnancy and breastfeeding warrant significant caution with indium due to the absence of safety data in these populations, indium’s potential for tissue accumulation, and the lack of established benefits that would justify any potential risk to fetal or infant development. The conservative approach given the limited safety data would be to avoid indium during pregnancy and breastfeeding. Medication interactions with indium warrant consideration in several categories, though documented clinically significant interactions remain essentially nonexistent due to indium’s limited therapeutic use.

Mineral supplements might theoretically interact with indium through competitive absorption or other mechanisms, potentially affecting the bioavailability or biological activity of both indium and essential minerals. While specific interaction studies remain limited, the potential for such interactions suggests separating indium administration from mineral supplements by at least 2 hours as a conservative approach. Medications affecting kidney function, including certain diuretics, NSAIDs, or nephrotoxic drugs, might theoretically increase risk of adverse renal effects when combined with indium given animal studies suggesting potential nephrotoxicity with certain indium compounds. While specific interaction studies are lacking, a cautious approach would suggest avoiding this combination given the uncertain benefits of indium supplementation.

Medications affecting liver function, including various hepatotoxic drugs, might theoretically increase risk of adverse hepatic effects when combined with indium given animal studies suggesting potential hepatotoxicity with certain indium compounds. While specific interaction studies are lacking, a cautious approach would suggest avoiding this combination given the uncertain benefits of indium supplementation. Chelating agents including various therapeutic chelators (e.g., EDTA, DMSA) or supplements with chelating properties might significantly alter indium pharmacokinetics through enhanced solubilization, altered absorption, or increased elimination. While specific interaction studies are limited, these theoretical interactions could potentially influence both the bioavailability and elimination of indium, with uncertain clinical significance.

Toxicity profile of indium is incompletely characterized for supplement use but has been more extensively studied in occupational settings and animal models. Acute toxicity parameters like LD50 (median lethal dose) have been examined in animal studies, with values for soluble indium compounds typically in the range of 5-10 mg/kg body weight for intravenous administration and significantly higher for oral administration due to limited absorption. These values suggest moderate acute toxicity compared to many other metals, though still warranting careful dosing consideration. Subchronic and chronic toxicity have been examined primarily in animal studies and occupational settings, with findings suggesting potential for pulmonary, renal, and hepatic effects with extended exposure, particularly to certain indium compounds like indium phosphide or indium tin oxide.

While the exposure routes and doses in these studies differ from typical supplement use, they demonstrate indium’s potential biological activity and capacity to cause tissue damage under certain conditions. Genotoxicity and carcinogenicity have been examined for certain indium compounds, with some research suggesting potential concerns. Indium phosphide has been classified by the International Agency for Research on Cancer (IARC) as “probably carcinogenic to humans” (Group 2A) based on sufficient evidence in experimental animals, though with limited human data. While this classification specifically addresses indium phosphide rather than the indium sulfate or other forms typically used in supplements, it demonstrates the potential for certain indium compounds to cause significant biological effects and suggests a generally cautious approach to indium exposure through any route.

Reproductive and developmental toxicity has been minimally studied for indium, creating significant uncertainty about safety during pregnancy and lactation. The limited available animal data suggests potential for developmental effects at high doses of certain indium compounds, warranting a cautious approach in these populations until more definitive safety data becomes available. Special population considerations for indium safety include several important groups, though specific research in these populations remains very limited. Individuals with kidney disease should generally avoid indium supplementation given the kidneys’ role in eliminating many metals and animal studies showing potential nephrotoxicity with certain indium compounds.

Those with impaired renal function might theoretically experience greater accumulation and increased risk of adverse effects, suggesting avoidance in this population given the uncertain benefits and potential risks. Those with liver disease should similarly approach indium with significant caution given animal studies showing hepatic accumulation and potential hepatotoxicity with certain indium compounds. Individuals with impaired liver function might theoretically experience altered handling of indium, suggesting avoidance in this population given the uncertain benefits and potential risks. Elderly individuals may demonstrate increased susceptibility to potential adverse effects due to age-related changes in kidney function, liver function, and other physiological parameters.

While specific studies in this population are lacking, a conservative approach would suggest either avoidance or minimal doses with careful monitoring if supplementation is considered at all. Children have not been systematically studied regarding indium safety, and routine use in pediatric populations is generally not recommended due to the absence of safety data, no established physiological requirement, and the lack of evidence for any benefit that would justify potential risks in developing systems. Regulatory status of indium varies by jurisdiction, specific formulation, and marketing claims. In the United States, indium exists in a somewhat ambiguous regulatory space.

It has not been approved as a food additive or dietary ingredient with a formal safety determination, yet various indium supplements are marketed under the general provisions of the Dietary Supplement Health and Education Act (DSHEA). The FDA has not explicitly ruled on indium’s status as a dietary ingredient, creating uncertainty about its regulatory standing. The FDA could potentially take enforcement action against indium supplements based on safety concerns or classification as an unapproved new dietary ingredient, though such action has not occurred to date for most products. In Europe, regulatory status varies between different member states, with some countries restricting indium in supplements while others have not taken specific positions.

The European Food Safety Authority (EFSA) has not issued specific opinions on indium safety in food supplements. In Canada, indium is not included on the Natural Health Products Ingredients Database as an approved medicinal or non-medicinal ingredient, effectively restricting its use in natural health products. These varying regulatory positions across major global jurisdictions reflect the limited safety data available for indium and different approaches to managing uncertainty about supplement ingredients without comprehensive safety evaluations. Quality control considerations for indium supplements include several important factors.

Chemical form verification represents a critical quality parameter, as different indium compounds demonstrate markedly different solubility, bioavailability, and potentially different safety profiles. Higher-quality products specify the exact indium compound used (e.g., indium sulfate) rather than simply listing “indium” on the label. Purity verification through appropriate analytical methods represents another important quality consideration, with higher-quality products demonstrating minimal contamination with other metals or substances. As a metallic element, indium can be accurately quantified using various analytical techniques including inductively coupled plasma mass spectrometry (ICP-MS) or atomic absorption spectroscopy.

Dosage accuracy is particularly important for indium given the relatively small amounts typically used in supplements (measured in micrograms) and the potential for toxicity at higher doses. Higher-quality products provide verification of accurate dosing through appropriate analytical testing and quality control procedures. Stability testing is relevant for indium supplements, as certain indium compounds may undergo changes in solubility or chemical form under various storage conditions. Higher-quality products provide verification of stability testing under various environmental conditions and include appropriate packaging and storage recommendations to maintain product integrity.

Risk mitigation strategies for indium supplementation include several practical approaches, though with significant limitations given the uncertain benefits and potential risks. Starting with minimal doses (at the lower end of commercially available products, typically 100 μg or less) would represent a conservative approach if supplementation is undertaken despite the limited evidence base. This approach minimizes potential exposure while allowing assessment of individual tolerance, though without clear markers to evaluate actual benefits. Limiting duration of use to short periods (2-4 weeks) with breaks between supplementation cycles might potentially reduce risk of accumulation given indium’s relatively long biological half-life, though without specific research validating this approach.

This cyclical approach provides opportunities to reassess continued need and benefit while potentially reducing cumulative exposure. Avoiding combination with medications or conditions that might increase risk of adverse effects, particularly those affecting kidney or liver function, represents another risk mitigation strategy. This cautious approach acknowledges the theoretical concerns about renal and hepatic effects based on animal studies. Selecting high-quality products with verified chemical form, purity, and accurate dosing helps ensure consistent exposure and minimize risk of contamination or dosing errors.

This quality control is particularly important given the relatively small amounts of indium typically used in supplements and the potential for toxicity at higher doses. Monitoring kidney and liver function with baseline testing before starting indium supplementation and periodic reassessment during use would represent a conservative approach if supplementation is undertaken despite the limited evidence base. This monitoring might potentially identify early signs of adverse effects before significant damage occurs, though without established protocols or clear relationships between specific laboratory parameters and indium-related toxicity. In summary, indium demonstrates a complex safety profile characterized by limited clinical research specifically evaluating supplement use but significant theoretical concerns based on its chemical properties, animal toxicity studies, and occupational exposure data.

The most significant safety considerations include potential renal and hepatic effects given animal studies showing accumulation and possible toxicity in these organs, though with uncertain relevance to typical supplement doses. The absence of established essential biological roles for indium in humans, combined with its potential for tissue accumulation and documented toxicity of certain indium compounds in occupational and animal studies, suggests a highly cautious approach to indium supplementation. This caution is further warranted by the limited evidence for any therapeutic benefit that would justify potential risks, particularly with extended use. Significant contraindications include kidney disease, liver disease, pregnancy and breastfeeding, and pediatric use, with special caution also warranted in elderly individuals or those with multiple medical conditions.

The varying regulatory positions across major global jurisdictions reflect the limited safety data available for indium and different approaches to managing uncertainty about supplement ingredients without comprehensive safety evaluations.