Arginine
Semi-essential amino acid that fuels T cells and feeds spermidine; reduced amyloid-beta in Alzheimer's mice.
Summary
Arginine is a semi-essential amino acid used for protein and nitric oxide synthesis and as a precursor for proline, creatine and (via ornithine and putrescine) spermidine. A 2025 study found arginine in drinking water reduced amyloid-beta buildup and inflammatory cytokines in Alzheimer's mouse models, and she links this to lower arginine in Alzheimer's brains, diet-related drops in CSF arginine in MCI, and T cell exhaustion. Her sucralose post describes a study where sucralose-driven gut microbiome changes lowered arginine and blunted cancer immunotherapy response, which arginine or citrulline reversed in mice. Arginine plus a Bifidobacterium probiotic increased putrescine and spermidine and improved endothelial function in a human study.
Takes powdered arginine (with AKG), calling it an amino acid that 'becomes more essential in aging' and may help prevent Alzheimer's and power T cells.From My Current Supplement Stack for Longevity
The evidence
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Human trial
In human studies (design not detailed), a specific Bifidobacterium animalis subsp. lactis yogurt plus arginine increased putrescine and spermidine levels and improved endothelial function.
Read the study Discussed in Spermidine and Healthspan -
Human trial
The probiotic Lactobacillus rhamnosus GG has been shown in clinical trials to enhance gut barrier function and specifically stimulate gut arginine metabolism.
Read the study Discussed in Arginine and Alzheimer's Prevention -
Human trial
In a 2021 controlled diet trial, people with mild cognitive impairment eating a high-saturated-fat, high-glycemic diet had a significant decrease in cerebrospinal fluid arginine.
Read the study Discussed in Arginine and Alzheimer's Prevention -
Human obs.
In melanoma patients on immune checkpoint inhibitors, higher sucralose intake (by food questionnaire) was linked to a 10% vs 57% response rate; in mice the sucralose-altered microbiome lowered arginine, and adding arginine or citrulline reversed the effect.
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Animal
In several Alzheimer's mouse models, arginine added to drinking water from an early age significantly reduced amyloid-beta accumulation and inflammatory cytokines, with no changes in normal mice.
Read the study Discussed in Arginine and Alzheimer's Prevention -
Animal
In animals, the probiotic Bifidobacterium lactis LKM512 plus arginine increased spermidine and was associated with improved longevity and protection from age-induced memory impairment.
Read the study Discussed in Spermidine and Healthspan
Doses used in studies
Amounts reported in the research, not dosing recommendations.
| Dose | Context |
|---|---|
| 2-30 g/day | Range of L-arginine doses used in studies |
| 12 g/day arginine alpha-ketoglutarate, split into 3 doses | Male athletes aged 30-50 |
Cautions
- Arginine can lower blood pressure; it may not be a good option if you already have low blood pressure, and talk with your doctor if on medications.
- A small percentage of study participants reported intestinal symptoms at high doses.
- With arginine plus AKG, check interactions with blood thinners, anticoagulants, erectile dysfunction drugs, nitrates and diabetes medications.
- No clinical trials yet show how much arginine is effective for Alzheimer's prevention.