Meta Information
ID:klotho
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Interactions
Target id:
/condition/active-cancer
Target name:
Active Cancer
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
The role of Klotho in cancer is complex and not fully understood; it may act as a tumor suppressor or promoter depending on the cancer type and context.
Actionable advice:
This should be strictly avoided with a current diagnosis of cancer due to unpredictable and potentially harmful effects.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
No-data / genuinely uncertain: Klotho's role in cancer is context-dependent (tumor-suppressor in some models, permissive in others), and there are no human safety data for exogenous Klotho in active malignancy. Marked unvalidatable.
Action type:
avoid
Target id:
/class/chemotherapy-radiation
Target name:
Cytotoxic Cancer Therapies (Chemotherapy & Radiation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Klotho's cellular protective and anti-apoptotic mechanisms could theoretically interfere with the efficacy of therapies designed to kill rapidly dividing cancer cells.
Actionable advice:
This should be strictly avoided during active cancer treatment to prevent reducing therapeutic efficacy.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: Klotho has anti-apoptotic/cytoprotective actions that could theoretically blunt therapies designed to kill rapidly dividing cells. Theoretical, experimental protein - low certainty.
Label source:
Class inference
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
The effects of administering exogenous Klotho protein or gene therapy on fetal development are unknown and could be harmful.
Actionable advice:
This should be strictly avoided during pregnancy due to unknown risks to the developing fetus.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
No data: effects of exogenous Klotho protein/gene therapy on fetal development are unknown. Precautionary; marked unvalidatable.
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
It is unknown if exogenous Klotho is excreted in breast milk or what its effects on a nursing infant would be.
Actionable advice:
It should be avoided completely while breastfeeding due to unknown risks to the infant.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
No data: it is unknown whether exogenous Klotho is excreted in breast milk or its infant effects. Precautionary; marked unvalidatable.
Action type:
avoid
Target id:
/intervention/calcitriol
Target name:
Active Vitamin D (Calcitriol)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Klotho's primary function is to suppress active Vitamin D (1,25-dihydroxyvitamin D) synthesis to control phosphate levels; administering active Vitamin D directly opposes this core mechanism.
Actionable advice:
Co-administration should be avoided, as it directly counteracts Klotho's physiological function and can lead to mineral imbalances.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Established Klotho biology: Klotho suppresses 1-alpha-hydroxylase and active vitamin D (1,25-(OH)2D) synthesis to control phosphate; co-administering calcitriol works against this and risks mineral dysregulation (hypercalcemia/hyperphosphatemia). Mechanistic.
Label source:
Class inference
Action type:
avoid
Target id:
/biomarker/serum-phosphate
Target name:
Serum Phosphate
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
null
Description:
Klotho is a master regulator of phosphate homeostasis, primarily by increasing its excretion in the urine. Therapy requires monitoring to prevent hypophosphatemia or other imbalances.
Actionable advice:
Regularly monitor serum phosphate levels before and during Klotho therapy.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Established Klotho biology: as a co-receptor for FGF23, Klotho promotes urinary phosphate excretion, so phosphate monitoring is warranted to detect hypophosphatemia during therapy. Mechanistic monitoring rationale.
Label source:
Class inference
Action type:
monitor
Target id:
/biomarker/serum-calcium
Target name:
Serum Calcium
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
null
Description:
Klotho increases calcium reabsorption in the kidneys. Therapy requires monitoring to prevent hypercalcemia, especially if combined with other agents affecting calcium.
Actionable advice:
Regularly monitor serum calcium levels before and during Klotho therapy.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Established Klotho biology: Klotho increases renal calcium reabsorption (TRPV5), so calcium monitoring is warranted to detect hypercalcemia, especially with other calcium-raising agents. Mechanistic monitoring rationale.
Label source:
Class inference
Action type:
monitor
Target id:
/class/thiazide-diuretics
Target name:
Thiazide Diuretics
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Both Klotho and thiazide diuretics increase calcium reabsorption in the kidneys, which can lead to an additive effect and an increased risk of hypercalcemia (abnormally high calcium levels).
Actionable advice:
This is best used with caution, and it is a good idea to monitor serum calcium levels very closely if used together.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: both Klotho (TRPV5) and thiazides increase renal calcium reabsorption, so the combination could be additive and raise hypercalcemia risk. Mechanistic, experimental protein.
Label source:
Class inference
Action type:
monitor
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Klotho has been shown to improve insulin sensitivity and glucose metabolism, which may potentiate the effects of glucose-lowering drugs and increase the risk of hypoglycemia.
Actionable advice:
Blood glucose is best monitored closely, especially upon initiation of Klotho, and being prepared to adjust medication doses is a good idea.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: Klotho improves insulin sensitivity/glucose metabolism in models, so it could potentiate glucose-lowering drugs and add to hypoglycemia risk. Theoretical, monitor glucose.
Label source:
Class inference
Action type:
adjust_with_prescriber
Target id:
/class/anticholinergic-medications
Target name:
Anticholinergic Medications
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
null
Description:
Anticholinergic drugs are known to impair cognitive function, which would directly oppose the potential pro-cognitive and neuroprotective benefits observed with Klotho in preclinical studies.
Actionable advice:
Concurrent use of strong anticholinergic medications is best avoided if cognitive enhancement is a goal.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Theoretical/low-confidence: anticholinergics can impair cognition, which would oppose Klotho's proposed pro-cognitive/neuroprotective effects. Speculative functional antagonism, not demonstrated.
Label source:
Class inference
Action type:
avoid
Target id:
/dietary/high-phosphate-foods
Target name:
High-Phosphate Foods (Processed Foods, Sodas)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
null
Description:
A high dietary phosphate load places stress on the FGF23-Klotho system, counteracting the intended benefit of maintaining healthy phosphate balance.
Actionable advice:
Foods with high phosphate additives (e.g., colas, processed meats and cheeses) are best avoided to support Klotho's function.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: a high dietary phosphate load stresses the FGF23-Klotho axis and counteracts the goal of maintaining phosphate balance; moderating phosphate intake is consistent with therapy. Mechanistic.
Label source:
Class inference
Action type:
avoid
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
null
Description:
Klotho levels are naturally deficient in chronic kidney disease (CKD), and this deficiency contributes to the disease's progression. Klotho replacement is a potential therapeutic strategy for CKD.
Actionable advice:
Klotho therapy may be beneficial for this condition, but requires careful dose selection and monitoring by a specialist.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Established biology: Klotho is deficient in CKD and its loss contributes to CKD-mineral-bone disorder and progression, so Klotho repletion is mechanistically rational in renal impairment (still experimental). Mechanistic.
Label source:
Class inference
Action type:
monitor
Target id:
/intervention/vitamin-k2
Target name:
Vitamin K2
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
null
Description:
Both Klotho and Vitamin K2 are critical for preventing vascular calcification, but they act through different pathways. Their combined action may offer superior cardiovascular protection.
Actionable advice:
Consider co-supplementation with Vitamin K2 for potentially enhanced cardiovascular benefits.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: Klotho and vitamin K2 both oppose vascular calcification via different pathways (phosphate handling vs matrix-Gla-protein carboxylation), so combined use may be complementary. Plausible, unstudied.
Label source:
Class inference
Action type:
informational_none
Target id:
/class/ghrps-ghrhs
Target name:
Growth Hormone Secretagogues
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
null
Description:
Klotho signaling is known to suppress the growth hormone/IGF-1 axis, which is a proposed mechanism for its longevity effects. This action may counteract therapies designed to boost GH levels.
Actionable advice:
It is worth being aware that Klotho may reduce the effectiveness of growth hormone-releasing peptides and hormones.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: Klotho signaling suppresses the GH/IGF-1 axis (a proposed longevity mechanism), which could partially oppose GH-secretagogues (GHRPs/GHRH analogs). Mechanistic, opposing directions.
Label source:
Class inference
Action type:
informational_none
Target id:
/biomarker/igf-1
Target name:
Insulin-like Growth Factor 1
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
null
Description:
Because Klotho can suppress the GH/IGF-1 axis, monitoring IGF-1 levels can serve as a biomarker to assess the systemic biological activity of the therapy.
Actionable advice:
Periodically monitor IGF-1 levels to help gauge the systemic impact of Klotho therapy.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic monitoring rationale: because Klotho suppresses the GH/IGF-1 axis, IGF-1 can serve as a pharmacodynamic readout of systemic Klotho activity. Mechanistic.
Label source:
Class inference
Action type:
monitor
Target id:
/class/immunosuppressants
Target name:
Calcineurin Inhibitors
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
null
Description:
Calcineurin inhibitors like tacrolimus are nephrotoxic and are known to suppress endogenous Klotho expression. Exogenous Klotho may help mitigate this kidney damage.
Actionable advice:
Klotho may be renoprotective when using these drugs, but requires close monitoring of kidney function.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: calcineurin inhibitors (tacrolimus/cyclosporine) are nephrotoxic and suppress endogenous Klotho, so exogenous Klotho might mitigate that injury - a complementary, theoretical benefit. Experimental.
Label source:
Class inference
Action type:
monitor
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Klotho may promote vasodilation and have modest blood pressure-lowering effects, potentially increasing the risk of hypotension when combined with other blood pressure medications.
Actionable advice:
It is a good idea to check blood pressure, especially when starting Klotho therapy or adjusting antihypertensive doses.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: Klotho may promote vasodilation and modestly lower blood pressure, so additive hypotension with antihypertensives is conceivable. Low-certainty, monitor BP.
Label source:
Class inference
Action type:
monitor
Target id:
/intervention/vitamin-d
Target name:
Vitamin D (High Dose)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
High-dose Vitamin D supplementation increases calcium and phosphate absorption, which can work against Klotho's primary goal of maintaining mineral balance, potentially increasing hypercalcemia risk.
Actionable advice:
Standard doses of Vitamin D are generally best, and it is worth monitoring serum calcium and phosphate levels if higher doses are required.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: high-dose vitamin D raises calcium/phosphate absorption, which can work against Klotho's role in maintaining mineral balance; monitor calcium/phosphate if combined. Mechanistic.
Label source:
Class inference
Action type:
monitor