Head to head
Methotrexate against Mycophenolic acid
Two old immunosuppressants patients are frequently moved between. Both are prescription drugs with decades of use and defined monitoring requirements, which is the part that does not appear in any supplement comparison of immune modulators.
Column A
MethotrexateMethotrexate, folate antimetabolite and anti-inflammatory
The best available test of whether suppressing chronic inflammation extends life. In a large human cardiovascular trial it did not reduce events, and in mouse lifespan testing it did not extend lifespan.
Column B
Mycophenolic acidMycophenolic acid, inosine monophosphate dehydrogenase inhibitor
A transplant immunosuppressant tested on the logic that rapamycin's lifespan effect might come from immune suppression. It did not extend mouse lifespan in either sex, which argues that rapamycin works some other way.
Side by side, on the facts we can check
| Attribute | Methotrexate | Mycophenolic acid |
|---|---|---|
| Category | Immune | Immune |
| FDA status | FDA-approved for rheumatoid arthritis, psoriasis, and several cancers. Not approved for cardiovascular prevention or any ageing indication. | FDA-approved as mycophenolate mofetil and mycophenolate sodium for prophylaxis of organ rejection. Carries boxed warnings for embryofetal toxicity, malignancy and serious infection. No ageing indication. |
| Half-life | Three to ten hours at low doses, longer at high doses and in renal impairment, which is the main determinant of its toxicity. | Roughly 16 to 18 hours for mycophenolic acid after administration as mycophenolate mofetil, with enterohepatic recirculation producing a secondary peak. |
| Molecular weight | 454.4 Da. A small molecule, not a peptide. | 320.3 Da for mycophenolic acid. A small molecule, not a peptide. |
| Mechanism | At high oncology doses it inhibits dihydrofolate reductase, starving cells of reduced folate needed for DNA synthesis, which is a cytotoxic effect. At the low weekly doses used in rheumatoid arthritis the mechanism is different and centres on inhibition of aminoimidazole carboxamide ribonucleotide transformylase, causing adenosine accumulation, which is anti-inflammatory. It also promotes intracellular folate depletion and affects methylation. The two dose ranges are effectively different drugs and should not be conflated. | A reversible inhibitor of inosine monophosphate dehydrogenase, the rate-limiting enzyme in de novo guanosine nucleotide synthesis. T and B lymphocytes depend on the de novo pathway because they lack an effective salvage pathway, so inhibiting it suppresses lymphocyte proliferation with relative selectivity. That selectivity is the basis of its transplant use and also the reason it is a clean probe: it suppresses immunity without touching the nutrient-sensing pathways rapamycin acts on. |
| Human studies cited | 0 | 0 |
| Legal status, US | FDA-approved, prescription only | FDA-approved, prescription only |
Frequently asked questions
What is the difference between Methotrexate and Mycophenolic acid?
Methotrexate: The best available test of whether suppressing chronic inflammation extends life. In a large human cardiovascular trial it did not reduce events, and in mouse lifespan testing it did not extend lifespan. Mycophenolic acid: A transplant immunosuppressant tested on the logic that rapamycin's lifespan effect might come from immune suppression. It did not extend mouse lifespan in either sex, which argues that rapamycin works some other way.
Which has stronger research evidence, Methotrexate or Mycophenolic acid?
This database does not grade compounds. It counts what was run in people: 0 of the 1 studies cited on the Methotrexate profile were human work, against 0 of 1 for Mycophenolic acid. Those counts are of our own citation lists and understate any larger literature, and neither is a recommendation.
Are Methotrexate and Mycophenolic acid FDA-approved?
Methotrexate: FDA-approved for rheumatoid arthritis, psoriasis, and several cancers. Not approved for cardiovascular prevention or any ageing indication.. Mycophenolic acid: FDA-approved as mycophenolate mofetil and mycophenolate sodium for prophylaxis of organ rejection. Carries boxed warnings for embryofetal toxicity, malignancy and serious infection. No ageing indication..
Reviewed Sep 2026. This page sets two published records side by side. It is educational, it is not medical advice, and it contains no dosing protocols or recommendations for personal use.