Meta Information
ID:spermidine
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-10T18:33:02.330114Z
Model
Gemini 3.1 Pro (High)
Interactions
Target id:
/intervention/methionine-restriction
Target name:
Methionine Restriction
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
This diet reduces the body's spermidine precursor; supplementation directly compensates for this effect.
Actionable advice:
May be particularly beneficial.
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: methionine restriction lowers polyamine (spermidine) precursors while inducing autophagy; spermidine supplementation could complement or partly offset these effects. Plausible, unstudied combination.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/dasatinib-quercetin
Target name:
Dasatinib and Quercetin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine's autophagy effects may complement the senolytic action of this combination for cellular rejuvenation.
Actionable advice:
This is best used under medical supervision.
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: spermidine is an established inducer of autophagy, and the senolytic dasatinib+quercetin combination is reported to engage overlapping autophagy/longevity pathways, so an additive or complementary effect is plausible. This is mechanism-based reasoning; the specific combination has not been studied in humans.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/intermittent-fasting
Target name:
Intermittent Fasting
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine induces autophagy, a key process also activated by fasting, potentially amplifying cellular renewal.
Actionable advice:
May enhance fasting-related 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: spermidine is an established inducer of autophagy, and intermittent fasting is reported to engage overlapping autophagy/longevity pathways, so an additive or complementary effect is plausible. This is mechanism-based reasoning; the specific combination has not been studied in humans.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/trehalose
Target name:
Trehalose
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both are potent inducers of cellular autophagy, potentially leading to a strong synergistic effect.
Actionable advice:
No specific action 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: spermidine is an established inducer of autophagy, and trehalose is reported to engage overlapping autophagy/longevity pathways, so an additive or complementary effect is plausible. This is mechanism-based reasoning; the specific combination has not been studied in humans.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/urolithin-a
Target name:
Urolithin A
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine (autophagy) and Urolithin A (mitophagy) offer complementary cellular cleanup mechanisms for enhanced benefit.
Actionable advice:
No specific action 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: spermidine is an established inducer of autophagy, and urolithin A (a mitophagy inducer) is reported to engage overlapping autophagy/longevity pathways, so an additive or complementary effect is plausible. This is mechanism-based reasoning; the specific combination has not been studied in humans.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/fisetin
Target name:
Fisetin
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both promote autophagy and have senolytic properties, potentially enhancing cellular health and rejuvenation.
Actionable advice:
No specific action 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: spermidine is an established inducer of autophagy, and the senolytic flavonoid fisetin is reported to engage overlapping autophagy/longevity pathways, so an additive or complementary effect is plausible. This is mechanism-based reasoning; the specific combination has not been studied in humans.
Label source:
Class inference
Action type:
informational_none
Target id:
/class/mtor-inhibitors
Target name:
mTOR Inhibitors
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both substances promote cellular autophagy, potentially enhancing cellular cleanup and anti-aging effects.
Actionable advice:
It is important to talk to a specialist about this combination.
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: spermidine is an established inducer of autophagy, and mTOR inhibitors (rapamycin) is reported to engage overlapping autophagy/longevity pathways, so an additive or complementary effect is plausible. This is mechanism-based reasoning; the specific combination has not been studied in humans.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/resveratrol
Target name:
Resveratrol
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both compounds may activate autophagy, potentially leading to enhanced cellular health and longevity benefits.
Actionable advice:
No specific action required.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Resveratrol and calorie restriction also activate sirtuin-1 (SIRT1), an NAD+-dependent protein deacetylase that improves mitochondrial function and increases cellular antioxidant capacity, leading to improved cardiovascular function and possible antiaging effects (112944, 117137).
Label source:
Action type:
informational_none
Target id:
/intervention/egcg-green-tea
Target name:
Egcg
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both compounds are known to induce autophagy, potentially leading to enhanced cellular health benefits.
Actionable advice:
No specific action 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: spermidine is an established inducer of autophagy, and EGCG / green tea catechins is reported to engage overlapping autophagy/longevity pathways, so an additive or complementary effect is plausible. This is mechanism-based reasoning; the specific combination has not been studied in humans.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/lithium
Target name:
Lithium Orotate
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both lithium and spermidine are known to induce cellular autophagy, potentially enhancing cellular cleanup.
Actionable advice:
No specific action required.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Lithium is uniformly distributed in body water; there is only a small difference between extracellular and intracellular levels.
Label source:
Action type:
informational_none
Target id:
/intervention/metformin
Target name:
Metformin
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both may activate cellular autophagy pathways, potentially enhancing cellular renewal and metabolic benefits.
Actionable advice:
Blood glucose is best monitored if combining.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Intervention: Consider the benefits and risks of concomitant use with metformin hydrochloride.
Label source:
Action type:
monitor
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine may also lower blood pressure, potentially increasing the risk of hypotension when combined.
Actionable advice:
Blood pressure should be monitored closely.
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: spermidine has shown blood-pressure-lowering/cardioprotective effects in preclinical studies, so an additive hypotensive effect with ACE inhibitors is theoretically possible. Not demonstrated clinically.
Label source:
Class inference
Action type:
monitor
Target id:
/intervention/amlodipine
Target name:
Amlodipine
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine may also lower blood pressure, potentially increasing the risk of hypotension when combined.
Actionable advice:
Blood pressure should be monitored closely.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(5.3)
o NORVASC is indicated for the treatment of hypertension, to
lower blood pressure.
Label source:
Action type:
monitor
Target id:
/class/arbs
Target name:
Angiotensin Receptor Blockers (ARBs)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine may also lower blood pressure, potentially increasing the risk of hypotension when combined.
Actionable advice:
Blood pressure should be monitored closely.
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: spermidine's preclinical blood-pressure-lowering effect could add to that of ARBs; theoretical, not clinically demonstrated.
Label source:
Class inference
Action type:
monitor
Target id:
/intervention/metoprolol
Target name:
Metoprolol
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine may also lower blood pressure, potentially increasing the risk of hypotension when combined.
Actionable advice:
Blood pressure should be monitored closely.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In addition, TOPROL-XL administered at a dose of 50 mg once daily lowered blood pressure 24-hours post-dosing in placebo-controlled studies.
Label source:
Action type:
monitor
Target id:
/intervention/nebivolol
Target name:
Nebivolol
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Spermidine may also lower blood pressure, potentially increasing the risk of hypotension when combined.
Actionable advice:
Blood pressure should be monitored closely.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The effect on vital signs (e.g., pulse and blood pressure) was approximately the sum of the effects of sildenafil and nebivolol.
Label source:
Action type:
monitor
Target id:
/class/statins
Target name:
Statins
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Statins may increase cellular uptake of polyamines, potentially enhancing the effects of spermidine.
Actionable advice:
No specific action 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: a proposed interaction whereby statins alter polyamine uptake and could modulate spermidine's effects; speculative and not established.
Label source:
Class inference
Action type:
informational_none