Lithium ion (Li+)

evidence_access

Primary abstract

experimental_model

Mouse collecting-duct study.

limitations

Residual inner-medullary reduction persisted in Scnn1a knockout; not every AQP2 change required this entry route.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Fewer water channels can reduce water recovery from urine.

primary_references

alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse collecting-duct study. · source_derived_draft · unverified_draft

## lithium-aqp2-down Fewer water channels can reduce water recovery from urine. Chronic lithium reduced AQP2 in cortex/outer medulla and inner medulla of control mice. Model: Mouse collecting-duct study. Limitations: Residual inner-medullary reduction persisted in Scnn1a knockout; not every AQP2 change required this entry route. Evidence access: Primary abstract alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734

evidence_access

Primary abstract

experimental_model

Mouse pharmacology and biochemical complex assays.

limitations

A second pathway alongside direct enzyme inhibition, not a complete explanation of mood stabilization.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Lithium can change how signaling proteins assemble.

primary_references

A beta-arrestin 2 signaling complex mediates lithium action on behavior. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18191226/ · DOI 10.1016/j.cell.2007.11.041

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse pharmacology and biochemical complex assays. · source_derived_draft · unverified_draft

## lithium-arrestin-complex Lithium can change how signaling proteins assemble. Lithium disrupted a beta-arrestin2–Akt–PP2A complex and altered Akt/GSK3 signaling in mice. Model: Mouse pharmacology and biochemical complex assays. Limitations: A second pathway alongside direct enzyme inhibition, not a complete explanation of mood stabilization. Evidence access: Primary abstract A beta-arrestin 2 signaling complex mediates lithium action on behavior. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18191226/ · DOI 10.1016/j.cell.2007.11.041

evidence_access

Primary full text

experimental_model

Monkey COS-7; 10 mM LiCl, LC3 and pathway assays.

limitations

Not evidence that every lithium exposure increases completed autophagic flux or human longevity.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Cellular recycling can change through a route outside mTOR.

primary_references

Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Monkey COS-7; 10 mM LiCl, LC3 and pathway assays. · source_derived_draft · unverified_draft

## lithium-autophagy Cellular recycling can change through a route outside mTOR. Lithium increased autophagy markers through an IMPase-linked route without the mTOR inhibition detected with rapamycin. Model: Monkey COS-7; 10 mM LiCl, LC3 and pathway assays. Limitations: Not evidence that every lithium exposure increases completed autophagic flux or human longevity. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

evidence_access

Primary abstract

experimental_model

Rat primary cortical neurons; companion excitotoxicity experiments.

limitations

Time-dependent culture finding; not guaranteed human blood BDNF elevation.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A survival-supporting signal rose over days.

primary_references

Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat primary cortical neurons; companion excitotoxicity experiments. · source_derived_draft · unverified_draft

## lithium-bdnf-induction A survival-supporting signal rose over days. Lithium increased cellular BDNF in rat cortical neurons after three days. Model: Rat primary cortical neurons; companion excitotoxicity experiments. Limitations: Time-dependent culture finding; not guaranteed human blood BDNF elevation. Evidence access: Primary abstract Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4

evidence_access

Primary abstract

experimental_model

Rat recombinant enzyme; calcium also inhibited activity.

limitations

Not a quantitative human exposure-to-organ-injury model.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

One lithium-sensitive enzyme connects two metabolic branches.

primary_references

A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat recombinant enzyme; calcium also inhibited activity. · source_derived_draft · unverified_draft

## lithium-bpnt1-lithium One lithium-sensitive enzyme connects two metabolic branches. Submillimolar lithium chloride inhibited rat RnPIP hydrolysis of both PAP and Ins(1,4)P2. Model: Rat recombinant enzyme; calcium also inhibited activity. Limitations: Not a quantitative human exposure-to-organ-injury model. Evidence access: Primary abstract A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034

evidence_access

Primary full text

experimental_model

Mouse embryonic fibroblasts; 10 mM LiCl versus matched NaCl.

limitations

High experimental exposure; knockout occlusion supports a pathway but does not prove clinical cartilage damage.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The lithium response depended on this Golgi enzyme.

primary_references

Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse embryonic fibroblasts; 10 mM LiCl versus matched NaCl. · source_derived_draft · unverified_draft

## lithium-bpnt2-lithium-gag The lithium response depended on this Golgi enzyme. LiCl reduced intracellular and secreted GAG sulfation in wild-type mouse fibroblasts, with no further reduction after Bpnt2 knockout. Model: Mouse embryonic fibroblasts; 10 mM LiCl versus matched NaCl. Limitations: High experimental exposure; knockout occlusion supports a pathway but does not prove clinical cartilage damage. Evidence access: Primary full text Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293

evidence_access

Primary abstract

experimental_model

Mouse locomotor monitoring and suprachiasmatic-nucleus assays.

limitations

Association does not establish that GSK3 is the sole circadian target.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A brain clock and its signaling proteins changed together.

primary_references

Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090054/ · DOI 10.1111/j.0953-816X.2004.03322.x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse locomotor monitoring and suprachiasmatic-nucleus assays. · source_derived_draft · unverified_draft

## lithium-clock-mouse A brain clock and its signaling proteins changed together. Lithium-associated period lengthening accompanied altered SCN GSK3 expression and phosphorylation in mice. Model: Mouse locomotor monitoring and suprachiasmatic-nucleus assays. Limitations: Association does not establish that GSK3 is the sole circadian target. Evidence access: Primary abstract Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15090054/ · DOI 10.1111/j.0953-816X.2004.03322.x

evidence_access

Primary full text

experimental_model

39 bipolar donors and 23 controls; ex-vivo clock measurements.

limitations

Not a validated clinical test for choosing treatment.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Cells from different people did not respond identically.

primary_references

Patient fibroblast circadian rhythms predict lithium sensitivity in bipolar disorder. · 2021 · https://pubmed.ncbi.nlm.nih.gov/32404948/ · DOI 10.1038/s41380-020-0769-6

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 39 bipolar donors and 23 controls; ex-vivo clock measurements. · source_derived_draft · unverified_draft

## lithium-clock-person-specific Cells from different people did not respond identically. Lithium effects on circadian rhythms varied across bipolar patient-derived fibroblasts; longer-period cells had muted responses. Model: 39 bipolar donors and 23 controls; ex-vivo clock measurements. Limitations: Not a validated clinical test for choosing treatment. Evidence access: Primary full text Patient fibroblast circadian rhythms predict lithium sensitivity in bipolar disorder. · 2021 · https://pubmed.ncbi.nlm.nih.gov/32404948/ · DOI 10.1038/s41380-020-0769-6

evidence_access

Primary abstract

experimental_model

Cortical slices and synaptosomes; concentration-response experiments.

limitations

Do not merge acute addition with chronic in-vivo treatment.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

An immediate effect can differ from long-term adaptation.

primary_references

Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9653192/ · DOI 10.1073/pnas.95.14.8363

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cortical slices and synaptosomes; concentration-response experiments. · source_derived_draft · unverified_draft

## lithium-glutamate-acute An immediate effect can differ from long-term adaptation. Acute lithium exposure lowered glutamate-uptake capacity in mouse cortical preparations without changing apparent substrate affinity. Model: Cortical slices and synaptosomes; concentration-response experiments. Limitations: Do not merge acute addition with chronic in-vivo treatment. Evidence access: Primary abstract Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9653192/ · DOI 10.1073/pnas.95.14.8363

evidence_access

Primary abstract

experimental_model

Mice treated in vivo, followed by synaptosome assays.

limitations

A duration-dependent difference explained in the same paper, not an unresolved contradiction.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Longer exposure produced an opposite uptake response.

primary_references

Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9653192/ · DOI 10.1073/pnas.95.14.8363

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mice treated in vivo, followed by synaptosome assays. · source_derived_draft · unverified_draft

## lithium-glutamate-chronic Longer exposure produced an opposite uptake response. Chronic lithium treatment increased synaptosomal glutamate uptake in mice at a reported blood lithium level of 0.7 mM. Model: Mice treated in vivo, followed by synaptosome assays. Limitations: A duration-dependent difference explained in the same paper, not an unresolved contradiction. Evidence access: Primary abstract Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9653192/ · DOI 10.1073/pnas.95.14.8363

evidence_access

Primary abstract

experimental_model

Rat hepatocytes; 20 mM glucose; concentration/time dependence.

limitations

Isolated cells, not a diabetes treatment trial.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A carbohydrate-storage response depends on the available carbon source.

primary_references

Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hepatocytes; 20 mM glucose; concentration/time dependence. · source_derived_draft · unverified_draft

## lithium-glycogen-glucose A carbohydrate-storage response depends on the available carbon source. LiCl stimulated glycogen synthesis from glucose in normal and diabetic-rat hepatocytes, with increased glycogen-synthase activity ratio. Model: Rat hepatocytes; 20 mM glucose; concentration/time dependence. Limitations: Isolated cells, not a diabetes treatment trial. Evidence access: Primary abstract Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164

evidence_access

Primary abstract

experimental_model

Rat hepatocytes; simultaneous synthase and phosphorylase activation.

limitations

Context-dependent null result, not an unexplained contradiction.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Changing the starting substrate changed the outcome.

primary_references

Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hepatocytes; simultaneous synthase and phosphorylase activation. · source_derived_draft · unverified_draft

## lithium-glycogen-substrate-null Changing the starting substrate changed the outcome. LiCl did not increase glycogen accumulation with lactate and pyruvate in the same hepatocyte study. Model: Rat hepatocytes; simultaneous synthase and phosphorylase activation. Limitations: Context-dependent null result, not an unexplained contradiction. Evidence access: Primary abstract Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164

evidence_access

Primary abstract

experimental_model

Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms.

limitations

The abstract does not resolve every mammalian isoform; no systemic magnesium depletion was measured.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Magnesium availability changes inhibition of a signaling enzyme.

primary_references

Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms. · source_derived_draft · unverified_draft

## lithium-gsk3-magnesium Magnesium availability changes inhibition of a signaling enzyme. Lithium competitively inhibited mammalian GSK3 with respect to magnesium, but not ATP or substrate. Model: Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms. Limitations: The abstract does not resolve every mammalian isoform; no systemic magnesium depletion was measured. Evidence access: Primary abstract Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

45 lithium-treated patients versus 42 on other psychotropics; desmopressin challenge.

limitations

Observational comparison cannot remove all confounding; urinary AQP2 is a marker, not a full tissue inventory.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Human kidney findings connect the cellular route to water balance.

primary_references

Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 45 lithium-treated patients versus 42 on other psychotropics; desmopressin challenge. · source_derived_draft · unverified_draft

## lithium-human-concentration Human kidney findings connect the cellular route to water balance. Urine-concentrating impairment and lower urinary AQP2/cAMP correlated with lithium-treatment duration in patients. Model: 45 lithium-treated patients versus 42 on other psychotropics; desmopressin challenge. Limitations: Observational comparison cannot remove all confounding; urinary AQP2 is a marker, not a full tissue inventory. Evidence access: Primary abstract Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408

evidence_access

Primary abstract

experimental_model

Human enzyme kinetics, fluorescence and structural modeling.

limitations

Binding-site assignment is model-supported; treatment benefit is not established by enzyme inhibition.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Lithium can interrupt the recycling step.

primary_references

Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme kinetics, fluorescence and structural modeling. · source_derived_draft · unverified_draft

## lithium-impa-lithium Lithium can interrupt the recycling step. The human IMPase study supported lithium binding at the second metal site in its catalytic model. Model: Human enzyme kinetics, fluorescence and structural modeling. Limitations: Binding-site assignment is model-supported; treatment benefit is not established by enzyme inhibition. Evidence access: Primary abstract Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766

evidence_access

Primary full text

experimental_model

Monkey COS-7 cells; 10 mM LiCl, 24-hour metabolite assay.

limitations

Combined IP1–2 measurement; this exposure exceeds typical clinical serum concentrations.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Blocking recycling lets upstream material accumulate.

primary_references

Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Monkey COS-7 cells; 10 mM LiCl, 24-hour metabolite assay. · source_derived_draft · unverified_draft

## lithium-inositol-phosphate-accumulation Blocking recycling lets upstream material accumulate. Lithium treatment increased mono/bis-phosphorylated inositol species in COS-7 cells, consistent with inhibited recycling. Model: Monkey COS-7 cells; 10 mM LiCl, 24-hour metabolite assay. Limitations: Combined IP1–2 measurement; this exposure exceeds typical clinical serum concentrations. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

evidence_access

Primary abstract

experimental_model

Purified calf-brain INPP1.

limitations

Do not substitute signaling IP3, Ins(1,4,5)P3, for the distinct Ins(1,3,4)P3 substrate.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The same enzyme can respond differently depending on its substrate.

primary_references

Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified calf-brain INPP1. · source_derived_draft · unverified_draft

## lithium-inpp1-substrate-specific The same enzyme can respond differently depending on its substrate. Lithium inhibited bovine INPP1 differently by substrate: Ki about 6 mM for Ins(1,4)P2 versus 0.5–1 mM for Ins(1,3,4)P3. Model: Purified calf-brain INPP1. Limitations: Do not substitute signaling IP3, Ins(1,4,5)P3, for the distinct Ins(1,3,4)P3 substrate. Evidence access: Primary abstract Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

evidence_access

Primary full text

experimental_model

Monkey COS-7; 10 mM LiCl, 1 mM myo-inositol rescue.

limitations

Cell-culture rescue is not a clinical supplement recommendation.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Availability of the precursor changes a signaling messenger.

primary_references

Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Monkey COS-7; 10 mM LiCl, 1 mM myo-inositol rescue. · source_derived_draft · unverified_draft

## lithium-ip3-decrease Availability of the precursor changes a signaling messenger. Lithium lowered IP3 in the COS-7 experiments; added myo-inositol raised it relative to lithium alone. Model: Monkey COS-7; 10 mM LiCl, 1 mM myo-inositol rescue. Limitations: Cell-culture rescue is not a clinical supplement recommendation. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

evidence_access

Primary abstract

experimental_model

Cloned human transporter kinetic analysis.

limitations

Net flux depends on citrate and ion concentrations; not unconditional stimulation at every substrate level.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A stronger apparent response can coexist with a lower maximum rate.

primary_references

Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cloned human transporter kinetic analysis. · source_derived_draft · unverified_draft

## lithium-nact-affinity A stronger apparent response can coexist with a lower maximum rate. Lithium shifted human NaCT toward higher substrate affinity and lower transport capacity. Model: Cloned human transporter kinetic analysis. Limitations: Net flux depends on citrate and ion concentrations; not unconditional stimulation at every substrate level. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

evidence_access

Primary abstract

experimental_model

Expressed human transporter and human liver-cell experiments.

limitations

Not evidence that trace lithium has the same effect or that citrate salt ingestion determines the response.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A sodium-coupled carrier links lithium to carbon metabolism.

primary_references

Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Expressed human transporter and human liver-cell experiments. · source_derived_draft · unverified_draft

## lithium-nact-human A sodium-coupled carrier links lithium to carbon metabolism. Lithium stimulated human NaCT-mediated citrate transport at concentrations relevant to prescription exposure. Model: Expressed human transporter and human liver-cell experiments. Limitations: Not evidence that trace lithium has the same effect or that citrate salt ingestion determines the response. Evidence access: Primary abstract Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

evidence_access

Primary abstract

experimental_model

Transporters cloned from eight species.

limitations

Explicit species difference; no contradiction between correctly scoped records.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The human result cannot be assumed in rodents.

primary_references

Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transporters cloned from eight species. · source_derived_draft · unverified_draft

## lithium-nact-rat The human result cannot be assumed in rodents. Lithium inhibited rat NaCT while stimulating primate transporters in the same comparative study. Model: Transporters cloned from eight species. Limitations: Explicit species difference; no contradiction between correctly scoped records. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

evidence_access

Primary full text

experimental_model

Rat PC12; 10 mM LiCl; expression switched off before clearance measurement.

limitations

Engineered protein models do not establish treatment of Huntington or Parkinson disease.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Recycling changed the persistence of aggregation-prone proteins.

primary_references

Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 96–102

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat PC12; 10 mM LiCl; expression switched off before clearance measurement. · source_derived_draft · unverified_draft

## lithium-protein-clearance Recycling changed the persistence of aggregation-prone proteins. Lithium accelerated clearance of expressed mutant huntingtin and alpha-synuclein in inducible PC12 models. Model: Rat PC12; 10 mM LiCl; expression switched off before clearance measurement. Limitations: Engineered protein models do not establish treatment of Huntington or Parkinson disease. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium.

limitations

Supports altered feedback, not direct lithium binding to human CaSR.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Calcium feedback to the parathyroid gland was reset.

primary_references

Alterations in parathyroid dynamics in lithium-treated subjects. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9284708/ · DOI 10.1210/jcem.82.9.4218

trigger_kind

biomarker_context Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 384–390

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium. · source_derived_draft · unverified_draft

## lithium-pth-setpoint Calcium feedback to the parathyroid gland was reset. Chronic lithium-treated patients required a higher calcium level for comparable PTH suppression during calcium/citrate infusions. Model: Seven lithium-treated women versus seven controls; mean set-point 5.08 versus 4.88 mg/dL ionized calcium. Limitations: Supports altered feedback, not direct lithium binding to human CaSR. Evidence access: Primary abstract Alterations in parathyroid dynamics in lithium-treated subjects. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9284708/ · DOI 10.1210/jcem.82.9.4218

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Kidney handling controls removal.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 608–614

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-renal-elimination Kidney handling controls removal. Lithium is not metabolized and is eliminated primarily through the kidneys. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

evidence_access

Primary abstract

experimental_model

Human neuron-like cell culture.

limitations

Same paper as the tau-phosphorylation result, not independent replication.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The altered protein interacted more strongly with the cellular scaffold.

primary_references

Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9312151/ · DOI 10.1074/jbc.272.40.25326

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 184–190

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human neuron-like cell culture. · source_derived_draft · unverified_draft

## lithium-tau-microtubules The altered protein interacted more strongly with the cellular scaffold. Lithium increased tau–microtubule binding and microtubule assembly in the NT2N study. Model: Human neuron-like cell culture. Limitations: Same paper as the tau-phosphorylation result, not independent replication. Evidence access: Primary abstract Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9312151/ · DOI 10.1074/jbc.272.40.25326

evidence_access

Primary abstract

experimental_model

Cultured human NT2N neurons.

limitations

Does not demonstrate dementia prevention in people.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A signaling enzyme changes chemical marks on a structural protein.

primary_references

Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9312151/ · DOI 10.1074/jbc.272.40.25326

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 176–182

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human NT2N neurons. · source_derived_draft · unverified_draft

## lithium-tau-phosphorylation A signaling enzyme changes chemical marks on a structural protein. Lithium reduced tau phosphorylation through reversible GSK3 inhibition in human NT2N neurons. Model: Cultured human NT2N neurons. Limitations: Does not demonstrate dementia prevention in people. Evidence access: Primary abstract Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9312151/ · DOI 10.1074/jbc.272.40.25326

evidence_access

Primary abstract

experimental_model

Primary and neoplastic human-cell preparations; dose-response assays.

limitations

Historical cell-line identities and experimental conditions limit extrapolation.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Thyroid growth signaling can change independently of hormone release.

primary_references

Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16322400/ · DOI 10.1530/eje.1.02038

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 408–414

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary and neoplastic human-cell preparations; dose-response assays. · source_derived_draft · unverified_draft

## lithium-thyroid-beta-catenin Thyroid growth signaling can change independently of hormone release. LiCl inhibited GSK3beta and stabilized free beta-catenin in cultured human thyrocytes. Model: Primary and neoplastic human-cell preparations; dose-response assays. Limitations: Historical cell-line identities and experimental conditions limit extrapolation. Evidence access: Primary abstract Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16322400/ · DOI 10.1530/eje.1.02038

evidence_access

Primary abstract

experimental_model

Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L.

limitations

Compartment-model inference; not evidence that lithium simply removes iodine from the body.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Making thyroid hormone and releasing it are separate steps.

primary_references

The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 392–398

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L. · source_derived_draft · unverified_draft

## lithium-thyroid-release Making thyroid hormone and releasing it are separate steps. Lithium reduced hormonal and nonhormonal thyroid iodine release in human radioiodine kinetic studies. Model: Eight kinetic studies in seven thyrotoxic women; serum lithium about 1 mEq/L. Limitations: Compartment-model inference; not evidence that lithium simply removes iodine from the body. Evidence access: Primary abstract The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094

evidence_access

Primary abstract

experimental_model

Human radioiodine compartment modeling.

limitations

Not demonstrated inhibition of a particular deiodinase; do not infer selenium depletion.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Blood hormone concentration reflects both release and removal.

primary_references

The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 400–406

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human radioiodine compartment modeling. · source_derived_draft · unverified_draft

## lithium-thyroid-turnover Blood hormone concentration reflects both release and removal. Five kinetic studies also required slower serum hormone disappearance to fit lithium-associated observations. Model: Human radioiodine compartment modeling. Limitations: Not demonstrated inhibition of a particular deiodinase; do not infer selenium depletion. Evidence access: Primary abstract The use of lithium in the treatment of thyrotoxicosis. · 1972 · https://pubmed.ncbi.nlm.nih.gov/4115707/ · DOI 10.1172/JCI107094

evidence_access

Primary abstract

experimental_model

Human cultured thyrocytes; TCF4 versus CREB pathway perturbation.

limitations

High cell-culture exposure; not a quantified human goiter or cancer risk.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Blocking a downstream regulator weakened the growth response.

primary_references

Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16322400/ · DOI 10.1530/eje.1.02038

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 416–422

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured thyrocytes; TCF4 versus CREB pathway perturbation. · source_derived_draft · unverified_draft

## lithium-thyroid-wnt-growth Blocking a downstream regulator weakened the growth response. At 5 mM LiCl, thyrocyte proliferation increased; dominant-negative TCF4 reduced this response by about half. Model: Human cultured thyrocytes; TCF4 versus CREB pathway perturbation. Limitations: High cell-culture exposure; not a quantified human goiter or cancer risk. Evidence access: Primary abstract Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/beta-catenin signalling. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16322400/ · DOI 10.1530/eje.1.02038

evidence_access

Primary abstract

experimental_model

Rat primary cortical neurons.

limitations

Pathway interpretation supported by inhibitor and antibody experiments; not direct lithium binding to TrkB.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The BDNF receptor became more active after a delay.

primary_references

Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 216–222

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat primary cortical neurons. · source_derived_draft · unverified_draft

## lithium-trkb-activation The BDNF receptor became more active after a delay. Lithium increased TrkB Tyr490 phosphorylation after five days in rat cortical cultures. Model: Rat primary cortical neurons. Limitations: Pathway interpretation supported by inhibitor and antibody experiments; not direct lithium binding to TrkB. Evidence access: Primary abstract Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Site-directed mutagenesis and enzyme kinetics

exposure

Magnesium and lithium titrations

limitations

Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Human recombinant protein

plain_language

Lithium can interfere with a magnesium-linked step of inositol recycling.

primary_references

[ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x

tissue_or_cell_type

Purified IMPA1

trigger_kind

machinery_impairment Imported condition classification; unverified.

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 275–286

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis and enzyme kinetics · source_derived_draft · unverified_draft

### ino-impa-lithium Li+ inhibited human inositol monophosphatase; parallel changes in Li+ and Mg2+ affinity across mutants supported a shared metal-binding site. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lithium can interfere with a magnesium-linked step of inositol recycling. organism: Human recombinant protein tissue_or_cell_type: Purified IMPA1 experimental_model: Site-directed mutagenesis and enzyme kinetics limitations: Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone. exposure: Magnesium and lithium titrations evidence_span: {"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"} [ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Sodium loss can slow lithium removal.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 576–582

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-diuretic-sodium Sodium loss can slow lithium removal. Diuretic-associated sodium loss can reduce lithium clearance. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Another compound class can change renal handling.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 616–622

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-xanthine-excretion Another compound class can change renal handling. Xanthine preparations can increase urinary lithium excretion and lower serum levels. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

experimental_model

2025 SSKI manufacturer label; 1 g KI/mL formulation.

exposure_category

Study-specific exposure, including pharmacological and in-vitro conditions; normal is the schema fallback outside the three availability categories.

limitations

Label warning, not a quantified primary interaction trial; applicability depends on exposure and patient context.

nutrient_topic

Potassium iodide research collection; shared-anion and comparator studies are not all KI interventions. · Potassium iodide

plain_language

Different drugs can converge on reduced thyroid function.

primary_references

SSKI product label, July 2025 · manufacturer label; DailyMed lists UNAPPROVED DRUG OTHER; not a trial or FDA approval · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca1d3449-ea29-49a4-8863-365ec95f1553

Potassium iodide: thyroid and non-thyroid mechanisms, interactions and discovery questions (2026-09-18) · lines 456–462

AI-assisted research curation; primary-study references, chemical references and label statements individually identified. Not publisher full text. · supports · 2025 SSKI manufacturer label; 1 g KI/mL formulation. · source_derived_draft · unverified_draft

## ki-lithium Different drugs can converge on reduced thyroid function. The label warns that lithium or antithyroid drugs can add to hypothyroid and goitrogenic effects. Model: 2025 SSKI manufacturer label; 1 g KI/mL formulation. Limitations: Label warning, not a quantified primary interaction trial; applicability depends on exposure and patient context. Evidence location: Primary abstract SSKI product label, July 2025 · manufacturer label; DailyMed lists UNAPPROVED DRUG OTHER; not a trial or FDA approval · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca1d3449-ea29-49a4-8863-365ec95f1553

evidence_access

Primary abstract

experimental_model

Mild AD; six-week titration; serum target 0.5–0.8 mmol/L.

limitations

Short duration and different disease stage; neither proves lifelong efficacy nor rules out every regimen.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A cell mechanism did not translate into measured target effects in this trial.

primary_references

Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19573486/

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 552–558

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mild AD; six-week titration; serum target 0.5–0.8 mmol/L. · source_derived_draft · unverified_draft

## lithium-ad-short-null A cell mechanism did not translate into measured target effects in this trial. A 71-person ten-week AD trial found no treatment effect on CSF biomarkers or lymphocyte GSK3 activity. Model: Mild AD; six-week titration; serum target 0.5–0.8 mmol/L. Limitations: Short duration and different disease stage; neither proves lifelong efficacy nor rules out every regimen. Evidence access: Primary abstract Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19573486/

evidence_access

Primary abstract

experimental_model

Randomized placebo-controlled crossover; six-week periods.

limitations

Small trial; reduced lithium entry was inferred, not directly measured in patient kidney cells.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Blocking a sodium channel improved the measured water response.

primary_references

Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 344–350

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized placebo-controlled crossover; six-week periods. · source_derived_draft · unverified_draft

## lithium-amiloride-human Blocking a sodium channel improved the measured water response. Amiloride increased maximal urine osmolality and AQP2 excretion in an eleven-patient crossover trial during lithium therapy. Model: Randomized placebo-controlled crossover; six-week periods. Limitations: Small trial; reduced lithium entry was inferred, not directly measured in patient kidney cells. Evidence access: Primary abstract Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse Arrb2 knockout comparison.

limitations

Does not abolish every molecular lithium effect.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Removing the scaffold removed this lithium response.

primary_references

A beta-arrestin 2 signaling complex mediates lithium action on behavior. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18191226/ · DOI 10.1016/j.cell.2007.11.041

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 200–206

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Arrb2 knockout comparison. · source_derived_draft · unverified_draft

## lithium-arrestin-loss Removing the scaffold removed this lithium response. Arrb2 knockout prevented the reported lithium effects on Akt/GSK3 signaling and associated mouse behaviors. Model: Mouse Arrb2 knockout comparison. Limitations: Does not abolish every molecular lithium effect. Evidence access: Primary abstract A beta-arrestin 2 signaling complex mediates lithium action on behavior. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18191226/ · DOI 10.1016/j.cell.2007.11.041

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse knockout-derived primary neurons versus wild-type littermates.

limitations

Genetic failure is not a dietary BDNF deficiency or human therapeutic test.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The protective response required intact survival machinery.

primary_references

Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 224–230

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout-derived primary neurons versus wild-type littermates. · source_derived_draft · unverified_draft

## lithium-bdnf-loss The protective response required intact survival machinery. Lithium failed to protect cortical neurons from Bdnf heterozygous or homozygous knockout mice against glutamate toxicity. Model: Mouse knockout-derived primary neurons versus wild-type littermates. Limitations: Genetic failure is not a dietary BDNF deficiency or human therapeutic test. Evidence access: Primary abstract Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12504924/ · DOI 10.1016/s0028-3908(02)00217-4

evidence_access

Primary abstract

experimental_model

330 randomized bipolar-I patients; open-label treatment with masked event review; up to two years.

limitations

Combination run-in and open-label design matter; the trial does not identify a single molecular mediator.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Clinical mood efficacy has its own evidence, separate from dementia hypotheses.

primary_references

Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20092882/ · DOI 10.1016/S0140-6736(09)61828-6

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 560–566

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 330 randomized bipolar-I patients; open-label treatment with masked event review; up to two years. · source_derived_draft · unverified_draft

## lithium-bipolar-relapse Clinical mood efficacy has its own evidence, separate from dementia hypotheses. Lithium monotherapy had fewer new mood-episode interventions than valproate in BALANCE; adding valproate was not clearly superior to lithium alone. Model: 330 randomized bipolar-I patients; open-label treatment with masked event review; up to two years. Limitations: Combination run-in and open-label design matter; the trial does not identify a single molecular mediator. Evidence access: Primary abstract Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20092882/ · DOI 10.1016/S0140-6736(09)61828-6

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Constitutive Bpnt1 knockout mice.

limitations

Genetic absence is not equivalent to dietary lithium exposure or partial drug inhibition.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Loss of clearance lets the by-product build up.

primary_references

Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 128–134

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Constitutive Bpnt1 knockout mice. · source_derived_draft · unverified_draft

## lithium-bpnt1-loss-pap Loss of clearance lets the by-product build up. Bpnt1 knockout raised mouse liver PAP up to about 50-fold. Model: Constitutive Bpnt1 knockout mice. Limitations: Genetic absence is not equivalent to dietary lithium exposure or partial drug inhibition. Evidence access: Primary abstract Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse knockout; tissue-dependent phenotype.

limitations

Not evidence that routine lithium treatment causes this knockout syndrome.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The accumulated by-product accompanied a failure of protein production.

primary_references

Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 136–142

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout; tissue-dependent phenotype. · source_derived_draft · unverified_draft

## lithium-bpnt1-loss-translation The accumulated by-product accompanied a failure of protein production. Bpnt1-deficient mice showed repressed translation, abnormal nucleoli and liver injury. Model: Mouse knockout; tissue-dependent phenotype. Limitations: Not evidence that routine lithium treatment causes this knockout syndrome. Evidence access: Primary abstract Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110

evidence_access

Primary abstract

experimental_model

Cloned rat enzyme; biochemical substrate assays.

limitations

The paper proposes consequences for sulfotransferases/RNA processing; those downstream effects were not all tested.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Clearing a sulfur-pathway by-product uses another metal-dependent enzyme.

primary_references

A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 112–118

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cloned rat enzyme; biochemical substrate assays. · source_derived_draft · unverified_draft

## lithium-bpnt1-substrate Clearing a sulfur-pathway by-product uses another metal-dependent enzyme. Cloned rat RnPIP hydrolyzed PAP and Ins(1,4)P2 in magnesium-dependent reactions. Model: Cloned rat enzyme; biochemical substrate assays. Limitations: The paper proposes consequences for sulfotransferases/RNA processing; those downstream effects were not all tested. Evidence access: Primary abstract A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Nestin-Cre conditional mouse knockout.

limitations

No significant gross perineuronal-net or tested behavioral abnormalities were detected; not a lithium treatment experiment.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

This enzyme also changes the brain extracellular matrix.

primary_references

Bisphosphate nucleotidase 2 (BPNT2), a molecular target of lithium, regulates chondroitin sulfation patterns in the cerebral cortex and hippocampus. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34920982/ · DOI 10.1016/j.jbior.2021.100858

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 168–174

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Nestin-Cre conditional mouse knockout. · source_derived_draft · unverified_draft

## lithium-bpnt2-brain-loss This enzyme also changes the brain extracellular matrix. Nervous-system Bpnt2 deletion lowered chondroitin-4-sulfation and increased chondroitin-6-sulfation in selected brain regions. Model: Nestin-Cre conditional mouse knockout. Limitations: No significant gross perineuronal-net or tested behavioral abnormalities were detected; not a lithium treatment experiment. Evidence access: Primary abstract Bisphosphate nucleotidase 2 (BPNT2), a molecular target of lithium, regulates chondroitin sulfation patterns in the cerebral cortex and hippocampus. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34920982/ · DOI 10.1016/j.jbior.2021.100858

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse embryonic fibroblast pellets; complementation and sulfation assays.

limitations

Sulfation depends on compartment and substrate; not a universal human sulfur requirement.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The enzyme must work, not merely be present.

primary_references

Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 152–158

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse embryonic fibroblast pellets; complementation and sulfation assays. · source_derived_draft · unverified_draft

## lithium-bpnt2-catalysis The enzyme must work, not merely be present. Wild-type Bpnt2 restored GAG sulfation in knockout fibroblasts; catalytic-dead D108A did not. Model: Mouse embryonic fibroblast pellets; complementation and sulfation assays. Limitations: Sulfation depends on compartment and substrate; not a universal human sulfur requirement. Evidence access: Primary full text Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Fluid loss can amplify exposure.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 568–574

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-dehydration Fluid loss can amplify exposure. Dehydration can promote lithium retention and toxicity. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

3xTg and J20 mice on low-lithium diets.

limitations

Same study as the other depletion records, not independent replications.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Lower availability worsened an experimentally measured pathology.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 440–446

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 3xTg and J20 mice on low-lithium diets. · source_derived_draft · unverified_draft

## lithium-depletion-amyloid Lower availability worsened an experimentally measured pathology. Lithium depletion increased amyloid deposition in AD-model mice. Model: 3xTg and J20 mice on low-lithium diets. Limitations: Same study as the other depletion records, not independent replications. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse neurons, oligodendrocytes and microglial analyses.

limitations

Not a universal linear relation between serum lithium and enzyme activity.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The enzyme connects availability to downstream responses.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 456–462

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse neurons, oligodendrocytes and microglial analyses. · source_derived_draft · unverified_draft

## lithium-depletion-gsk3 The enzyme connects availability to downstream responses. Lithium depletion increased GSK3beta expression and activation-associated signals in mouse brain. Model: Mouse neurons, oligodendrocytes and microglial analyses. Limitations: Not a universal linear relation between serum lithium and enzyme activity. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse brain comparison with pharmacological IMPase rationale.

limitations

A scoped null measurement, not proof that inositol is irrelevant in every lithium setting.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Trace depletion did not reproduce every pharmacological pathway.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 496–502

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse brain comparison with pharmacological IMPase rationale. · source_derived_draft · unverified_draft

## lithium-depletion-inositol-null Trace depletion did not reproduce every pharmacological pathway. Endogenous lithium depletion did not change brain inositol in the reported mouse comparison. Model: Mouse brain comparison with pharmacological IMPase rationale. Limitations: A scoped null measurement, not proof that inositol is irrelevant in every lithium setting. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Primary microglia from dietary-depletion experiments.

limitations

Cell isolation and model context retained; not a human immune-treatment result.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Brain immune cells became less effective at clearing amyloid.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 464–470

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary microglia from dietary-depletion experiments. · source_derived_draft · unverified_draft

## lithium-depletion-microglia Brain immune cells became less effective at clearing amyloid. Microglia from lithium-depleted mice showed impaired amyloid uptake and degradation. Model: Primary microglia from dietary-depletion experiments. Limitations: Cell isolation and model context retained; not a human immune-treatment result. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse dietary-depletion, histological and molecular comparisons.

limitations

Not a demonstrated human demyelinating disease mechanism or a substitute for established nutrient-deficiency diagnoses.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The cells and insulation around nerve fibers were affected.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 472–478

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse dietary-depletion, histological and molecular comparisons. · source_derived_draft · unverified_draft

## lithium-depletion-myelin The cells and insulation around nerve fibers were affected. Lithium-depleted mice showed loss of oligodendrocytes and myelin-associated signals. Model: Mouse dietary-depletion, histological and molecular comparisons. Limitations: Not a demonstrated human demyelinating disease mechanism or a substitute for established nutrient-deficiency diagnoses. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse brain imaging, protein and structural comparisons.

limitations

Same experimental program as the other depletion records; requires independent replication.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Connections between nerve cells also changed.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 480–486

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse brain imaging, protein and structural comparisons. · source_derived_draft · unverified_draft

## lithium-depletion-synapses Connections between nerve cells also changed. Dietary lithium depletion reduced synaptic markers and synapse density in the studied mice. Model: Mouse brain imaging, protein and structural comparisons. Limitations: Same experimental program as the other depletion records; requires independent replication. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Dietary-depletion experiment; hippocampal phospho-tau measurements.

limitations

Transgenic mouse result; not proof of human causation.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A second pathological protein response changed.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 448–454

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dietary-depletion experiment; hippocampal phospho-tau measurements. · source_derived_draft · unverified_draft

## lithium-depletion-tau A second pathological protein response changed. Lithium depletion increased phosphorylated tau in 3xTg mice. Model: Dietary-depletion experiment; hippocampal phospho-tau measurements. Limitations: Transgenic mouse result; not proof of human causation. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Wild-type and transgenic AD mouse paradigms; regimen-specific effects.

limitations

Animal depletion does not define a human requirement or safe supplement dose.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The study experimentally lowered the brain pool.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 432–438

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wild-type and transgenic AD mouse paradigms; regimen-specific effects. · source_derived_draft · unverified_draft

## lithium-dietary-depletion The study experimentally lowered the brain pool. Dietary lithium depletion reduced endogenous cortical lithium by about half in the mouse experiments. Model: Wild-type and transgenic AD mouse paradigms; regimen-specific effects. Limitations: Animal depletion does not define a human requirement or safe supplement dose. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Collecting-duct-specific mouse knockout and chronic lithium treatment.

limitations

Protection supports ENaC-mediated entry; connecting-tubule expression remained intact.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A sodium channel helps lithium reach vulnerable kidney cells.

primary_references

alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 320–326

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Collecting-duct-specific mouse knockout and chronic lithium treatment. · source_derived_draft · unverified_draft

## lithium-enac-entry A sodium channel helps lithium reach vulnerable kidney cells. Collecting-duct Scnn1a deletion protected lithium-treated mice against polyuria and loss of urine concentration. Model: Collecting-duct-specific mouse knockout and chronic lithium treatment. Limitations: Protection supports ENaC-mediated entry; connecting-tubule expression remained intact. Evidence access: Primary abstract alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21051735/ · DOI 10.1681/ASN.2010070734

evidence_access

Primary abstract

experimental_model

Biochemical concentration titrations.

limitations

This is assay speciation, not evidence that lithium exhausts ATP or that extra magnesium improves clinical outcomes.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

ATP and free magnesium must be considered together.

primary_references

Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 24–30

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical concentration titrations. · source_derived_draft · unverified_draft

## lithium-gsk3-atp-magnesium ATP and free magnesium must be considered together. ATP concentrations exceeding magnesium progressively inhibited GSK3 in the assay through free-magnesium chelation. Model: Biochemical concentration titrations. Limitations: This is assay speciation, not evidence that lithium exhausts ATP or that extra magnesium improves clinical outcomes. Evidence access: Primary abstract Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

CHIR99021 and companion PF-04802367 rescue assays.

limitations

Inhibitor rescue supports partial mediation, not a single-target explanation.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Blocking the downstream enzyme helped test the proposed chain.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 488–494

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · CHIR99021 and companion PF-04802367 rescue assays. · source_derived_draft · unverified_draft

## lithium-gsk3-rescue Blocking the downstream enzyme helped test the proposed chain. GSK3 inhibition restored amyloid uptake/degradation in microglia from lithium-depleted mice. Model: CHIR99021 and companion PF-04802367 rescue assays. Limitations: Inhibitor rescue supports partial mediation, not a single-target explanation. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human postmortem cohorts; elemental mapping and fractionation.

limitations

Association cannot establish the direction of disease causation or a clinical diagnostic threshold.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Where lithium is located may matter more than a total measurement.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

trigger_kind

biomarker_context Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 424–430

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human postmortem cohorts; elemental mapping and fractionation. · source_derived_draft · unverified_draft

## lithium-human-brain-association Where lithium is located may matter more than a total measurement. Human brain analyses found lithium enrichment in amyloid plaques and lower non-plaque lithium associated with cognition. Model: Human postmortem cohorts; elemental mapping and fractionation. Limitations: Association cannot establish the direction of disease causation or a clinical diagnostic threshold. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

evidence_access

Primary abstract

experimental_model

Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations.

limitations

Historical mechanistic model; not a universal count for all conformations or family members.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Inositol recycling uses metal-dependent chemistry.

primary_references

Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 32–38

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations. · source_derived_draft · unverified_draft

## lithium-impa-metal Inositol recycling uses metal-dependent chemistry. Kinetics, modeling and mutagenesis supported a two-metal catalytic model for human inositol monophosphatase. Model: Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations. Limitations: Historical mechanistic model; not a universal count for all conformations or family members. Evidence access: Primary abstract Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766

evidence_access

Primary full text

experimental_model

Rat PC12; 1 mM myo-inositol with 10 mM LiCl.

limitations

Time-dependent and incomplete effects; not proof that oral inositol reverses mood stabilization.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A connected nutrient can counter an experimentally induced response.

primary_references

Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat PC12; 1 mM myo-inositol with 10 mM LiCl. · source_derived_draft · unverified_draft

## lithium-inositol-rescue A connected nutrient can counter an experimentally induced response. Added myo-inositol attenuated lithium-enhanced mutant-protein clearance in PC12 cells. Model: Rat PC12; 1 mM myo-inositol with 10 mM LiCl. Limitations: Time-dependent and incomplete effects; not proof that oral inositol reverses mood stabilization. Evidence access: Primary full text Lithium induces autophagy by inhibiting inositol monophosphatase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16186256/ · DOI 10.1083/jcb.200504035

evidence_access

Primary abstract

experimental_model

Purified calf-brain enzyme.

limitations

Free-ion assay concentrations do not establish dietary antagonism.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A mineral that activates one enzyme can inhibit another.

primary_references

Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified calf-brain enzyme. · source_derived_draft · unverified_draft

## lithium-inpp1-calcium-manganese A mineral that activates one enzyme can inhibit another. Calcium and manganese each inhibited the calf-brain enzyme by about half near 6 micromolar under the reported assay conditions. Model: Purified calf-brain enzyme. Limitations: Free-ion assay concentrations do not establish dietary antagonism. Evidence access: Primary abstract Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

evidence_access

Primary abstract

experimental_model

Calf-brain enzyme purification and kinetics.

limitations

In-vitro cofactor concentration is not a human blood target.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A second recycling enzyme also depends on magnesium.

primary_references

Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Calf-brain enzyme purification and kinetics. · source_derived_draft · unverified_draft

## lithium-inpp1-magnesium A second recycling enzyme also depends on magnesium. Purified calf-brain INPP1 showed cooperative magnesium dependence, with half-maximal stimulation near 0.3 mM. Model: Calf-brain enzyme purification and kinetics. Limitations: In-vitro cofactor concentration is not a human blood target. Evidence access: Primary abstract Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mean daily carbonate dose 195 mg; serum SD 0.13 mEq/L among completers.

limitations

Completer exposure is not the whole randomized population or a recommended target.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The actual exposure matters when comparing trials.

primary_references

Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41770546/ · DOI 10.1001/jamaneurol.2026.0072

trigger_kind

biomarker_context Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 544–550

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mean daily carbonate dose 195 mg; serum SD 0.13 mEq/L among completers. · source_derived_draft · unverified_draft

## lithium-mci-2026-exposure The actual exposure matters when comparing trials. Completers in the 2026 trial had mean serum lithium 0.17 mEq/L, with substantial variability. Model: Mean daily carbonate dose 195 mg; serum SD 0.13 mEq/L among completers. Limitations: Completer exposure is not the whole randomized population or a recommended target. Evidence access: Primary full text Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41770546/ · DOI 10.1001/jamaneurol.2026.0072

evidence_access

Primary full text

experimental_model

NCT03185208; 83 randomized, 80 started; two years; prespecified P<.01.

limitations

Verbal-recall difference P=.05 and exploratory amyloid subgroups are not positive primary results.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The newer pilot did not confirm its primary efficacy hypotheses.

primary_references

Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41770546/ · DOI 10.1001/jamaneurol.2026.0072

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · NCT03185208; 83 randomized, 80 started; two years; prespecified P<.01. · source_derived_draft · unverified_draft

## lithium-mci-2026-primary-null The newer pilot did not confirm its primary efficacy hypotheses. None of six coprimary outcomes met the prespecified significance threshold in the 2026 low-dose lithium trial. Model: NCT03185208; 83 randomized, 80 started; two years; prespecified P<.01. Limitations: Verbal-recall difference P=.05 and exploratory amyloid subgroups are not positive primary results. Evidence access: Primary full text Low-Dose Lithium for Mild Cognitive Impairment: A Pilot Randomized Clinical Trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41770546/ · DOI 10.1001/jamaneurol.2026.0072

evidence_access

Primary abstract

experimental_model

Amnestic MCI; lithium carbonate target 0.25–0.5 mEq/L; NCT01055392.

limitations

Single trial; population, exposure, endpoints and follow-up differ from later studies.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

One small human trial reported a favorable result.

primary_references

Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30947755/ · DOI 10.1192/bjp.2019.76

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Amnestic MCI; lithium carbonate target 0.25–0.5 mEq/L; NCT01055392. · source_derived_draft · unverified_draft

## lithium-mci-positive One small human trial reported a favorable result. A 61-person trial reported cognitive/functional stability with lithium versus decline with placebo over two years. Model: Amnestic MCI; lithium carbonate target 0.25–0.5 mEq/L; NCT01055392. Limitations: Single trial; population, exposure, endpoints and follow-up differ from later studies. Evidence access: Primary abstract Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30947755/ · DOI 10.1192/bjp.2019.76

evidence_access

Primary abstract

experimental_model

Human liver-cell tracer/transport study.

limitations

Does not establish that this pathway explains clinical weight change.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Transported citrate can enter lipid-building pathways.

primary_references

Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver-cell tracer/transport study. · source_derived_draft · unverified_draft

## lithium-nact-lipids Transported citrate can enter lipid-building pathways. Lithium increased NaCT-mediated use of extracellular citrate for lipid synthesis in human liver cells. Model: Human liver-cell tracer/transport study. Limitations: Does not establish that this pathway explains clinical weight change. Evidence access: Primary abstract Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12826022/ · DOI 10.1042/BJ20030827

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Site-directed human transporter mutagenesis.

limitations

Engineered variant, not evidence of a common human nutritional phenotype.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A protein variant can change responsiveness independently of intake.

primary_references

Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 296–302

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Site-directed human transporter mutagenesis. · source_derived_draft · unverified_draft

## lithium-nact-variant A protein variant can change responsiveness independently of intake. F500W increased baseline transport but nearly eliminated additional lithium stimulation of human NaCT. Model: Site-directed human transporter mutagenesis. Limitations: Engineered variant, not evidence of a common human nutritional phenotype. Evidence access: Primary abstract Species-specific influence of lithium on the activity of SLC13A5 (NaCT): lithium-induced activation is specific for the transporter in primates. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25617245/ · DOI 10.1124/jpet.114.221523

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction.

limitations

Small historical study; magnitude is not universal for all NSAIDs.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A medicine can raise lithium exposure by slowing its removal.

primary_references

Indomethacin increases plasma lithium. · 1979 · https://pubmed.ncbi.nlm.nih.gov/444956/ · DOI 10.1136/bmj.1.6171.1115

trigger_kind

biomarker_context Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction. · source_derived_draft · unverified_draft

## lithium-nsaid-clearance A medicine can raise lithium exposure by slowing its removal. Indomethacin raised plasma lithium while lowering renal lithium clearance in seven studied people. Model: Three psychiatric patients and four volunteers; approximately 31% mean clearance reduction. Limitations: Small historical study; magnitude is not universal for all NSAIDs. Evidence access: Primary abstract Indomethacin increases plasma lithium. · 1979 · https://pubmed.ncbi.nlm.nih.gov/444956/ · DOI 10.1136/bmj.1.6171.1115

evidence_access

Primary full text

experimental_model

Synthetic human Aβ42 oligomers/fibrils and controlled salt solutions.

limitations

Does not establish superior human brain delivery or product safety.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The salt preparation changed measured binding.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Synthetic human Aβ42 oligomers/fibrils and controlled salt solutions. · source_derived_draft · unverified_draft

## lithium-orotate-binding The salt preparation changed measured binding. Lithium orotate showed lower amyloid binding than carbonate in the study’s equilibrium-dialysis assays. Model: Synthetic human Aβ42 oligomers/fibrils and controlled salt solutions. Limitations: Does not establish superior human brain delivery or product safety. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

evidence_access

Primary full text

experimental_model

Mouse behavioral assays with locomotor/visual control comparisons.

limitations

Not evidence of proven human dementia prevention.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Behavioral outcomes accompanied the molecular findings.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse behavioral assays with locomotor/visual control comparisons. · source_derived_draft · unverified_draft

## lithium-orotate-model-memory Behavioral outcomes accompanied the molecular findings. Lithium orotate improved memory measures in AD-model and ageing wild-type mice. Model: Mouse behavioral assays with locomotor/visual control comparisons. Limitations: Not evidence of proven human dementia prevention. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

evidence_access

Primary full text

experimental_model

3xTg and J20 mouse regimens; matched carbonate and sodium-orotate comparisons.

limitations

Experimental drinking-water concentration is not a human dose; no human orotate trial is established here.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Replacement improved a model outcome.

primary_references

Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 3xTg and J20 mouse regimens; matched carbonate and sodium-orotate comparisons. · source_derived_draft · unverified_draft

## lithium-orotate-model-pathology Replacement improved a model outcome. Low-dose lithium orotate reduced amyloid pathology in the studied AD mouse models. Model: 3xTg and J20 mouse regimens; matched carbonate and sodium-orotate comparisons. Limitations: Experimental drinking-water concentration is not a human dose; no human orotate trial is established here. Evidence access: Primary full text Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse double-mutant genetic experiment.

limitations

Does not justify sulfur restriction; a pathway perturbation is not a nutritional prescription.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Reducing what enters a blocked pathway can rescue its consequences.

primary_references

Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110

trigger_kind

machinery_impairment Imported condition classification; unverified.

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse double-mutant genetic experiment. · source_derived_draft · unverified_draft

## lithium-pap-synthesis-rescue Reducing what enters a blocked pathway can rescue its consequences. Reducing PAP synthesis genetically rescued the Bpnt1-knockout phenotype. Model: Mouse double-mutant genetic experiment. Limitations: Does not justify sulfur restriction; a pathway perturbation is not a nutritional prescription. Evidence access: Primary abstract Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23479625/ · DOI 10.1073/pnas.1205001110

evidence_access

Primary abstract

experimental_model

15 healthy adults; about 19 mmol extra potassium over 24 hours at the higher dose.

limitations

Not evidence that every lithium user develops potassium depletion.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

The potassium response depended on exposure.

primary_references

Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 15 healthy adults; about 19 mmol extra potassium over 24 hours at the higher dose. · source_derived_draft · unverified_draft

## lithium-potassium-excretion The potassium response depended on exposure. Potassium excretion increased after 600 mg lithium carbonate but not after 300 mg in the volunteer study. Model: 15 healthy adults; about 19 mmol extra potassium over 24 hours at the higher dose. Limitations: Not evidence that every lithium user develops potassium depletion. Evidence access: Primary abstract Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Blood-pressure medicines can change exposure.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-ras-interaction Blood-pressure medicines can change exposure. Renin–angiotensin-system antagonists can increase steady-state lithium concentrations. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A signaling interaction differs from a clearance interaction.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-serotonergic-interaction A signaling interaction differs from a clearance interaction. Serotonergic co-medication can increase serotonin-syndrome risk with lithium. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

evidence_access

Official prescribing information

experimental_model

Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06.

limitations

Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Not all renal drug interactions increase exposure.

primary_references

Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. · source_derived_draft · unverified_draft

## lithium-sglt2-interaction Not all renal drug interactions increase exposure. SGLT2 inhibitors may lower serum lithium. Model: Official prescribing information, sections 5, 7 and 12; updated 2026-07-06, prescribing text revised 2023-06. Limitations: Regulatory clinical statement; not an experiment resolving a single molecular target. No dosing recommendation follows. Evidence access: Official prescribing information Lithium and lithium carbonate prescribing information; DailyMed set c84cce95-cfcb-4426-aac6-d2f48f946ada, updated July 6 2026; prescribing text revised June 2023 · 2026 · https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c84cce95-cfcb-4426-aac6-d2f48f946ada

evidence_access

Primary abstract

experimental_model

15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake.

limitations

Salt doses describe the experiment, not dosing advice; a test dose can perturb a clearance measurement.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Lithium exposure can change sodium balance.

primary_references

Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake. · source_derived_draft · unverified_draft

## lithium-sodium-excretion Lithium exposure can change sodium balance. Single 300- and 600-mg lithium-carbonate doses increased 24-hour sodium excretion by about 17 and 48 mmol, respectively. Model: 15 healthy volunteers; randomized blinded crossover and fixed sodium/potassium intake. Limitations: Salt doses describe the experiment, not dosing advice; a test dose can perturb a clearance measurement. Evidence access: Primary abstract Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1649725/ · DOI 10.1042/cs0810059

evidence_access

Primary abstract

experimental_model

200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively.

limitations

Not a recommendation to change salt intake; lithium clearance was not a universally pure proximal-tubule marker.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Sodium intake changes the setting for a drug interaction.

primary_references

Indomethacin increases renal lithium reabsorption in man. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2494594/

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively. · source_derived_draft · unverified_draft

## lithium-sodium-renal-context Sodium intake changes the setting for a drug interaction. Indomethacin increased fractional lithium reabsorption on both high- and low-sodium diets in seven volunteers. Model: 200 versus 40 mmol/day sodium; reabsorption 71 to 75% and 75 to 81%, respectively. Limitations: Not a recommendation to change salt intake; lithium clearance was not a universally pure proximal-tubule marker. Evidence access: Primary abstract Indomethacin increases renal lithium reabsorption in man. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2494594/