Thymulin

updated

Thymulin is a zinc-dependent nonapeptide hormone of the thymus, separate from thymalin and thymosin alpha-1. The human evidence is two small randomized trials from the 1980s: one positive for rheumatoid arthritis on global assessment, one negative in multiple sclerosis. The recent immune data are in mice, no trial shows a benefit in healthy people or for hair, and the only US label found is an unapproved homeopathic pellet.

Zinc-dependent thymic nonapeptide hormone

  • PubChem lists Thymulin as CID 71300623, C33H54N12O15, molecular weight 858.9, CAS 78922-62-0, a zinc-free peptide record. The sequence is pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn.
  • A 1985 paper states that thymulin's biological activity is strictly dependent on zinc in the molecule.
  • In two randomized, double-blind rheumatoid arthritis trials comparing 1, 5 and 10 mg a day of nonathymulin, the 5 mg dose gave clinical improvement by global assessment in 56% versus 17% on placebo (p less than 0.02). The abstract gives no patient numbers.
  • In a randomized pilot trial in 40 patients with multiple sclerosis, subcutaneous nonathymulin for 6 months did not differ from placebo on disability scores.
  • A July 2026 mouse paper reports that thymulin suppressed inflammatory cytokine production in myeloid cells and sensitized tumors to anti-PD-L1 therapy in an age-dependent manner. The authors' suggestion for older people is a hypothesis.
  • A PubMed search on 10 October 2026 found no trial of thymulin for hair and no trial in healthy people for immune function.

What is thymulin, and is it an approved drug?

Thymulin is a nine-residue peptide hormone made by thymic epithelial cells, and its activity depends on zinc. On 10 October 2026, openFDA Drugs@FDA queries for thymulin and for nonathymulin returned no match, and the one US label found is an unapproved homeopathic pellet.

PubChem lists Thymulin as CID 71300623, C33H54N12O15, molecular weight 858.9, CAS 78922-62-0, with synonyms that include circulating thymic factor and facteur thymique serique. A second record, Nonathymulin (INN), is CID 3085284 with the same formula and weight and CAS 63958-90-7. Its listed synonyms include Thymic factor and the sequence pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH. Neither record includes zinc in the formula.

A 1977 Journal of Biological Chemistry paper established the amino acid sequence of a circulating thymic factor (FTS, facteur thymique serique) isolated from pig serum as Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH, by Edman analysis on the intact peptide and after tryptic digestion, with the C-terminal residue found by carboxypeptidase A digestion. The PubMed text prints the N-terminal residue as less than Glu, which is the pyroglutamyl notation, and PubChem writes it pGlu. The authors prepared a synthetic peptide that they say showed the same biological activities as native pig circulating thymic factor. The native material studied was porcine.

A 1985 paper states that the biological activity depends on zinc in the molecule, and the PubChem records are zinc-free. No analytical record reviewed ties a vial sold as thymulin or zinc-thymulin to the zinc-bound molecule.

On 10 October 2026, openFDA Drugs@FDA queries for thymulin and for nonathymulin each returned no match, so no FDA drug application was found. DailyMed holds one label under the name Thymuline (nonathymulin), a sublingual pellet from Homeocare Laboratories, label effective 28 February 2019. Its marketing category is unapproved homeopathic, the active ingredient is listed as Thymulinum 9C and the stated purpose is immune support. The label gives no efficacy data and does not state how much thymulin a pellet holds, so it is not a thymulin dose. These sources say nothing about other regulators.

PubChem: thymulin and nonathymulin identity, name hazards

Chemical identity record

National Library of Medicine. PubChem compound record CID 71300623 (Thymulin), with CID 3085284 (Nonathymulin) and CID 16130571 (thymosin alpha-1) for comparison.

PubChem lists Thymulin as CID 71300623, C33H54N12O15, molecular weight 858.9, CAS 78922-62-0, with synonyms that include circulating thymic factor and facteur thymique serique. A second record, Nonathymulin (INN), is CID 3085284 with the same formula and weight and CAS 63958-90-7, with synonyms that include Thymic factor and the sequence pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH. Neither record includes zinc in the formula. The CID 3085284 synonym list also contains the word Thymalin, so a PubChem name search for thymalin returns this nonapeptide. The Khavinson group's papers describe Thymalin as an immunomodulatory drug containing a polypeptide extract of thymus, with the KE and EW dipeptides named as its active substances (PMID 37686182). Thymosin alpha-1 (thymalfasin) is a separate record, CID 16130571, C129H215N33O55, 3108.3 g/mol.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined nonapeptide; zinc-free peptide records
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Thymalin and thymulin are different things, and thymosin alpha-1 is a separate molecule. Neither PubChem thymulin record includes zinc.

Read the original source
1977 sequence paper: pig serum circulating thymic factor, synthetic peptide matched

Chemical identity record

Pleau JM et al. J Biol Chem. 1977;252(22):8045-7. PMID 914862.

A 1977 Journal of Biological Chemistry paper established the amino acid sequence of a circulating thymic factor (FTS, facteur thymique serique) isolated from pig serum as Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH, by Edman analysis on the intact peptide and after tryptic digestion, with the C-terminal residue found by carboxypeptidase A digestion. The PubMed text prints the N-terminal residue as less than Glu, which is the pyroglutamyl notation, and PubChem writes it pGlu. The authors prepared a synthetic peptide that they say showed the same biological activities as native pig circulating thymic factor.

Participants / model
Pig serum (isolation); synthetic peptide for bioactivity comparison
Treatment
Isolated and synthetic peptide
Follow-up
Not applicable
Study design
Original biochemical report
Funding
not stated in the source

The native material studied was porcine.

Read the original source
1985 paper: thymulin activity strictly dependent on zinc

Cell study

Dardenne M et al. Proc Natl Acad Sci U S A. 1985;82(20):7035-8. PMID 2413455.

A 1985 paper states that thymulin is a nonapeptide hormone produced by thymic epithelial cells and that its biological activity is strictly dependent on zinc in the molecule. Two monoclonal antibodies recognized only the zinc-coupled molecule, and other antibodies recognized a zinc-independent epitope, which the authors read as a zinc-specific conformation. A randomized trial published in 1993 in 27 patients with Crohn's disease in remission, who had decreased plasma zinc and active thymulin, found that 200 mg a day of zinc sulphate for 3 months raised plasma thymulin activity and zinc, while 60 mg a day and placebo did not (PMID 8364132).

Participants / model
Antibody work (species not stated in the abstract); 27 patients with Crohn's disease in remission (second study)
Treatment
Not applicable for the antibody work; oral zinc sulphate for the Crohn's trial
Follow-up
3 months for the Crohn's trial
Study design
Original antibody studies; the Crohn's trial is a randomized trial
Funding
not stated in the source

The Crohn's trial measured thymulin activity as an outcome of zinc supplementation, not a clinical immune outcome.

Read the original source
DailyMed Thymuline label: unapproved homeopathic pellet, effective 28 February 2019

Official label

DailyMed, U.S. National Library of Medicine. Thymuline (nonathymulin) pellet, Homeocare Laboratories, label effective 2019-02-28. Set ID 1c3a713d-b6bf-4a3c-b7e2-93a3d80412b3. openFDA Drugs@FDA queries for thymulin and nonathymulin run 10 October 2026.

On 2026-10-10 openFDA Drugs@FDA queries for thymulin and for nonathymulin each returned no match, so no FDA drug application was found. DailyMed holds one label under the name Thymuline (nonathymulin), a pellet from Homeocare Laboratories, label effective 2019-02-28. Its SPL data list the marketing category as unapproved homeopathic and the route as sublingual. The label gives the active ingredient as Thymulinum 9C and the purpose as immune support, gives no efficacy data and does not state how much thymulin a pellet holds.

Participants / model
Not a clinical population
Treatment
Sublingual homeopathic pellets (label); no approved drug found
Follow-up
Label effective 2019-02-28
Study design
Official NLM label and FDA records
Funding
not stated in the source

The label's pellet count and schedule are not reproduced here. The label does not state how much thymulin a pellet holds, so it is not presented as a thymulin dose.

Read the original source

Is thymulin the same as thymalin or thymosin alpha-1?

No. Thymulin is one defined nonapeptide. The Khavinson group describes Thymalin as a drug containing a polypeptide extract of thymus, and thymosin alpha-1 (thymalfasin) is a separate PubChem record, CID 16130571. A PubChem name search for thymalin returns the thymulin nonapeptide.

A PubChem name search for thymalin returns the thymulin nonapeptide, because the synonym list of the Nonathymulin record (CID 3085284) also contains the word Thymalin. The two are different things. The Khavinson group's papers describe Thymalin as an immunomodulatory drug containing a polypeptide extract of thymus, with the KE and EW dipeptides named as its active substances (PMID 37686182).

Thymosin alpha-1 (thymalfasin) is a separate record, CID 16130571, C129H215N33O55, 3108.3 g/mol. Thymalin and thymosin alpha-1 each have their own page on this site, and evidence for either does not carry over to thymulin.

PubChem: thymulin and nonathymulin identity, name hazards

Chemical identity record

National Library of Medicine. PubChem compound record CID 71300623 (Thymulin), with CID 3085284 (Nonathymulin) and CID 16130571 (thymosin alpha-1) for comparison.

PubChem lists Thymulin as CID 71300623, C33H54N12O15, molecular weight 858.9, CAS 78922-62-0, with synonyms that include circulating thymic factor and facteur thymique serique. A second record, Nonathymulin (INN), is CID 3085284 with the same formula and weight and CAS 63958-90-7, with synonyms that include Thymic factor and the sequence pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH. Neither record includes zinc in the formula. The CID 3085284 synonym list also contains the word Thymalin, so a PubChem name search for thymalin returns this nonapeptide. The Khavinson group's papers describe Thymalin as an immunomodulatory drug containing a polypeptide extract of thymus, with the KE and EW dipeptides named as its active substances (PMID 37686182). Thymosin alpha-1 (thymalfasin) is a separate record, CID 16130571, C129H215N33O55, 3108.3 g/mol.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined nonapeptide; zinc-free peptide records
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Thymalin and thymulin are different things, and thymosin alpha-1 is a separate molecule. Neither PubChem thymulin record includes zinc.

Read the original source

What did the human trials find?

Two small 1980s randomized trials exist. In two rheumatoid arthritis trials comparing 1, 5 and 10 mg a day of nonathymulin, the 5 mg dose gave clinical improvement by global assessment in 56% versus 17% on placebo, with no clear change in immunological parameters. In 40 patients with multiple sclerosis, subcutaneous nonathymulin did not differ from placebo.

Two randomized, double-blind, placebo-controlled trials tested nonathymulin, a synthetic thymic peptide hormone, in rheumatoid arthritis and compared 1, 5 and 10 mg a day. The 5 mg dose gave significant clinical improvement by global assessment of all patients who entered the trials (56% versus 17% on placebo, p less than 0.02) and by four objective parameters, with minimal adverse effects and no clear change in immunological parameters. The abstract does not state the number of patients, the route or the trial length. A 1984 letter from the same group is indexed without an abstract. The authors include Dardenne and Bach, who also wrote the 1970s papers that characterized the peptide, and no later randomized trial of thymulin in rheumatoid arthritis turned up in the searches.

In a randomized, double-blind, placebo-controlled pilot trial, 40 matched patients with evolutive multiple sclerosis and moderate disability received subcutaneous nonathymulin (called synthetic serum thymic factor in the abstract) or placebo for 6 months and were followed for another 6 months. There was no significant difference in Kurtzke disability scores, the Ambulation Index or the Functional Scale, and no significant side effects were recorded. The authors conclude it was not effective in evolutive, moderately disabled multiple sclerosis.

No trial gave thymulin to healthy people. A PubMed search on 10 October 2026 for thymulin, nonathymulin, serum thymic factor or circulating thymic factor with placebo, randomized or double-blind terms returned 14 records. The rheumatoid arthritis trials and the multiple sclerosis trial are the only ones that gave thymulin or nonathymulin to patients.

Rheumatoid arthritis trials, 1987: 5 mg dose improved global assessment, 56% versus 17%

Randomized controlled trial

Amor B et al. Ann Rheum Dis. 1987;46(7):549-54. PMID 3310925.

Two randomized, double-blind, placebo-controlled trials tested nonathymulin, a synthetic thymic peptide hormone, in rheumatoid arthritis and compared 1, 5 and 10 mg a day. The 5 mg dose gave significant clinical improvement by global assessment of all patients who entered the trials (56% versus 17% on placebo, p less than 0.02) and by four objective parameters, with minimal adverse effects and no clear change in immunological parameters.

Participants / model
Patients with rheumatoid arthritis
Treatment
Nonathymulin 1, 5 or 10 mg a day; route not stated in the abstract
Follow-up
not stated in the source
Study design
Two randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

The abstract does not state the number of patients, the route or the trial length. A 1984 letter from the same group is indexed without an abstract (PMID 6362675). The authors include Dardenne and Bach, who also wrote the 1970s papers that characterized the peptide. No later randomized trial of thymulin in rheumatoid arthritis turned up in the PubMed search.

Read the original source
Multiple sclerosis pilot trial: 40 patients, subcutaneous nonathymulin, no benefit

Randomized controlled trial

Roullet E et al. Acta Neurol Scand. 1989;80(6):575-8. PMID 2618585.

In a randomized, double-blind, placebo-controlled pilot trial, 40 matched patients with evolutive multiple sclerosis and moderate disability received subcutaneous nonathymulin (called synthetic serum thymic factor in the abstract) or placebo for 6 months and were followed another 6 months. There was no significant difference in the Kurtzke disability scores, Ambulation Index or Functional Scale, and no significant side effects were recorded. The authors conclude it was not effective in evolutive, moderately disabled multiple sclerosis.

Participants / model
40 patients with multiple sclerosis
Treatment
Subcutaneous nonathymulin or placebo
Follow-up
6 months of treatment, then 6 months of follow-up
Study design
Randomized, double-blind, placebo-controlled pilot trial
Funding
not stated in the source

A negative trial. The abstract gives no dose.

Read the original source
Searches, 10 October 2026: no hair trial, no healthy-people immune trial

PubMed search record

PubMed search run on 10 October 2026: thymulin AND (hair OR alopecia OR hair follicle OR hair growth), 4 records. A second PubMed search for thymulin terms with placebo, randomized or double-blind terms returned 14 records. ClinicalTrials.gov queries run the same day.

The hair search returned 4 records: a 1988 zinc deficiency review, the 2012 letter, the 1995 alopecia areata article, and a 2012 FOXN1 deficiency and thymic transplantation paper that is not about hair treatment. The search for (thymulin OR nonathymulin OR serum thymic factor OR circulating thymic factor) with placebo, randomized or double-blind terms returned 14 records, reviewed by title and by abstract where unclear. The rheumatoid arthritis trials and the multiple sclerosis trial are the only ones that gave thymulin or nonathymulin to patients. The rest were zinc supplementation studies, observational thymulin level studies, a 1981 mouse skin-graft paper on FTS and analogues, an erratum, a mouse homeopathy paper, and papers unrelated by title. ClinicalTrials.gov returned 1 record for the query thymulin, a zinc supplementation and oral polio vaccine study in infants, and 5 unrelated records for serum thymic factor; none lists thymulin as an intervention by title. In the records reviewed there is no trial of thymulin for hair, no trial in healthy people for immune function, and no human pharmacokinetics.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 2026-10-10
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

What do the mouse and rodent studies show?

A July 2026 mouse paper reports that thymulin suppressed inflammatory cytokine production in myeloid cells, enhanced antitumor T-cell immunity and sensitized tumors to anti-PD-L1 therapy in an age-dependent manner. A 2006 rodent review reports that dose changed the direction of the effect on pain.

A July 2026 Nature Communications paper reports that thymulin, a thymus-derived peptide that declines with age, suppressed pro-inflammatory cytokine production in myeloid cells by inhibiting NF-kB signaling, enhanced antitumor T-cell immunity, improved tumor control and survival, and sensitized tumors to anti-PD-L1 therapy in an age-dependent manner in the authors' mouse work. The authors suggest thymulin as a possible way to improve cancer immunotherapy in older people, which is a hypothesis. The record's competing-interests statement lists a consulting role for the senior author with Otsuka Pharmaceutical Factory.

The pattern in healthy people is less simple than a decline with age. A 2000 study of 93 healthy individuals found plasma thymulin rising to its highest level at age 5 to 10 years, falling from adolescence to a lowest value at age 36, and then staying steady until age 80 (PMID 10971509).

A 2006 review by the group that did the work reports that low doses (ng) of thymulin by intraplantar or intraperitoneal injection caused hyperalgesia with more proinflammatory mediators. Systemic injections of 1 to 25 micrograms of thymulin, or of an analogue peptide (PAT) that lacked the hyperalgesic effect, reduced inflammatory pain and cytokine levels after endotoxin injection. Intracerebroventricular thymulin reduced endotoxin-induced hyperalgesia dose-dependently. This is a review of animal work, the abstract does not name the rodent species, and PAT is an analogue, not thymulin.

July 2026 Nature Communications mouse paper, plus plasma thymulin by age in 93 healthy people

Animal study

Kanemaru H et al. Nat Commun. 2026;17(1). PMID 42481458.

A July 2026 Nature Communications paper reports that thymulin, a thymus-derived peptide that declines with age, suppressed pro-inflammatory cytokine production in myeloid cells by inhibiting NF-kB signaling, enhanced antitumor T-cell immunity, improved tumor control and survival, and sensitized tumors to anti-PD-L1 therapy in an age-dependent manner in the authors' mouse work. A 2000 study of 93 healthy individuals found plasma thymulin rising to its highest level at age 5 to 10 years, falling from adolescence to a lowest value at age 36, and then staying steady until age 80 (PMID 10971509).

Participants / model
Aged mice and mouse tumor models; plasma thymulin in 93 healthy individuals from birth to old age (second study)
Treatment
Thymulin administered in mice; no human dosing; blood sampling in the human study
Follow-up
not stated in the source
Study design
Original preclinical study; the human age study is observational
Funding
not stated in the source; the record's competing-interests statement lists a consulting role for the senior author with Otsuka Pharmaceutical Factory

The authors suggest thymulin as a possible way to improve cancer immunotherapy in older people, which is a hypothesis. The mouse route and dose are not given in the source record used for this page.

Read the original source
2006 review: low-dose thymulin hyperalgesia, higher systemic doses reduced inflammatory pain

Narrative review

Dardenne M et al. Ann N Y Acad Sci. 2006;1088:153-63. PMID 17192563.

A 2006 review by the group that did the work reports that low doses (ng) of thymulin by intraplantar or intraperitoneal injection caused hyperalgesia with more proinflammatory mediators. Systemic injections of 1 to 25 micrograms of thymulin, or of an analogue peptide (PAT) that lacked the hyperalgesic effect, reduced inflammatory pain and cytokine levels after endotoxin injection. Intracerebroventricular thymulin reduced endotoxin-induced hyperalgesia dose-dependently.

Participants / model
Rodents (species not named in the abstract)
Treatment
Thymulin or PAT by local, intraperitoneal, systemic or intracerebroventricular injection
Follow-up
not stated in the source
Study design
Narrative review of original animal studies
Funding
not stated in the source

This is a review of animal work, the abstract does not name the species, and PAT is an analogue, not thymulin.

Read the original source

Does thymulin support immune function and hair?

Not in people. Immune support is backed only by a 2026 mouse signal and an old rheumatoid arthritis result without a clear immunological change, and no benefit was shown in healthy people. The hair claim has no human treatment data, only an ex vivo hair follicle letter whose findings cannot be read from the record.

Sellers describe thymulin (zinc-thymulin, serum thymic factor, FTS) as supporting immune function and hair, and as a separate molecule from thymalin and thymosin alpha-1. The separation is correct. The immune claim is supported only as a 2026 mouse anti-inflammatory and immunotherapy-sensitizing signal and as an old rheumatoid arthritis result that was not accompanied by a clear immunological change. No benefit was shown in healthy people.

The hair claim traces to one research letter with no abstract. A 2012 letter in the Journal of Investigative Dermatology titled Thymic peptides differentially modulate human hair follicle growth is indexed in PubMed with no abstract. The indexing terms in Europe PMC's copy include circulating thymic factor (the MeSH term that covers thymulin), thymosin and thymosin beta-4, together with scalp, hair follicle and organ culture. The title says differentially, which implies the peptides did not all act the same way, but the record gives no detail on which peptide did what or by how much. A 1995 supplement article on the thymus in alopecia areata is also indexed with no abstract (PMID 7738381). The hair claim is therefore ex vivo human follicle culture at most, not a treatment result.

A PubMed search on 10 October 2026 for thymulin with hair, alopecia, hair follicle or hair growth returned 4 records: a 1988 zinc deficiency review, the 2012 letter, the 1995 alopecia areata article, and a 2012 FOXN1 deficiency and thymic transplantation paper that is not about hair treatment. ClinicalTrials.gov returned 1 record for the query thymulin, a zinc supplementation and oral polio vaccine study in infants, and 5 unrelated records for serum thymic factor; none lists thymulin as an intervention by title. In the records reviewed there is no trial of thymulin for hair, no trial in healthy people for immune function and no human pharmacokinetics.

2012 research letter, no abstract: ex vivo human hair follicle culture

Cell study

Meier N et al. J Invest Dermatol. 2012;132(5):1516-9. PMID 22402437.

The 2012 Journal of Investigative Dermatology research letter is indexed in PubMed with no abstract. The indexing terms in Europe PMC's copy include circulating thymic factor (the MeSH term that covers thymulin), thymosin and thymosin beta-4, with scalp, hair follicle and organ culture. The title says differentially, which implies the peptides did not all act the same way, but the record gives no detail on which peptide did what or by how much. A 1995 supplement article on the thymus in alopecia areata is also indexed with no abstract (PMID 7738381).

Participants / model
Human scalp hair follicles in organ culture (from indexing terms only)
Treatment
Peptides in culture; details not available
Follow-up
not stated in the source
Study design
Original research letter, no abstract
Funding
not stated in the source

The hair claim is ex vivo human follicle culture at most, not a treatment result. The findings cannot be read from the record.

Read the original source
Searches, 10 October 2026: no hair trial, no healthy-people immune trial

PubMed search record

PubMed search run on 10 October 2026: thymulin AND (hair OR alopecia OR hair follicle OR hair growth), 4 records. A second PubMed search for thymulin terms with placebo, randomized or double-blind terms returned 14 records. ClinicalTrials.gov queries run the same day.

The hair search returned 4 records: a 1988 zinc deficiency review, the 2012 letter, the 1995 alopecia areata article, and a 2012 FOXN1 deficiency and thymic transplantation paper that is not about hair treatment. The search for (thymulin OR nonathymulin OR serum thymic factor OR circulating thymic factor) with placebo, randomized or double-blind terms returned 14 records, reviewed by title and by abstract where unclear. The rheumatoid arthritis trials and the multiple sclerosis trial are the only ones that gave thymulin or nonathymulin to patients. The rest were zinc supplementation studies, observational thymulin level studies, a 1981 mouse skin-graft paper on FTS and analogues, an erratum, a mouse homeopathy paper, and papers unrelated by title. ClinicalTrials.gov returned 1 record for the query thymulin, a zinc supplementation and oral polio vaccine study in infants, and 5 unrelated records for serum thymic factor; none lists thymulin as an intervention by title. In the records reviewed there is no trial of thymulin for hair, no trial in healthy people for immune function, and no human pharmacokinetics.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 2026-10-10
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source
Rheumatoid arthritis trials, 1987: 5 mg dose improved global assessment, 56% versus 17%

Randomized controlled trial

Amor B et al. Ann Rheum Dis. 1987;46(7):549-54. PMID 3310925.

Two randomized, double-blind, placebo-controlled trials tested nonathymulin, a synthetic thymic peptide hormone, in rheumatoid arthritis and compared 1, 5 and 10 mg a day. The 5 mg dose gave significant clinical improvement by global assessment of all patients who entered the trials (56% versus 17% on placebo, p less than 0.02) and by four objective parameters, with minimal adverse effects and no clear change in immunological parameters.

Participants / model
Patients with rheumatoid arthritis
Treatment
Nonathymulin 1, 5 or 10 mg a day; route not stated in the abstract
Follow-up
not stated in the source
Study design
Two randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

The abstract does not state the number of patients, the route or the trial length. A 1984 letter from the same group is indexed without an abstract (PMID 6362675). The authors include Dardenne and Bach, who also wrote the 1970s papers that characterized the peptide. No later randomized trial of thymulin in rheumatoid arthritis turned up in the PubMed search.

Read the original source
July 2026 Nature Communications mouse paper, plus plasma thymulin by age in 93 healthy people

Animal study

Kanemaru H et al. Nat Commun. 2026;17(1). PMID 42481458.

A July 2026 Nature Communications paper reports that thymulin, a thymus-derived peptide that declines with age, suppressed pro-inflammatory cytokine production in myeloid cells by inhibiting NF-kB signaling, enhanced antitumor T-cell immunity, improved tumor control and survival, and sensitized tumors to anti-PD-L1 therapy in an age-dependent manner in the authors' mouse work. A 2000 study of 93 healthy individuals found plasma thymulin rising to its highest level at age 5 to 10 years, falling from adolescence to a lowest value at age 36, and then staying steady until age 80 (PMID 10971509).

Participants / model
Aged mice and mouse tumor models; plasma thymulin in 93 healthy individuals from birth to old age (second study)
Treatment
Thymulin administered in mice; no human dosing; blood sampling in the human study
Follow-up
not stated in the source
Study design
Original preclinical study; the human age study is observational
Funding
not stated in the source; the record's competing-interests statement lists a consulting role for the senior author with Otsuka Pharmaceutical Factory

The authors suggest thymulin as a possible way to improve cancer immunotherapy in older people, which is a hypothesis. The mouse route and dose are not given in the source record used for this page.

Read the original source

How is thymulin thought to work?

Thymulin is a nonapeptide hormone produced by thymic epithelial cells, and its activity is strictly dependent on zinc in the molecule. In mice it suppressed inflammatory cytokine production in myeloid cells by inhibiting NF-kB signaling. In the rheumatoid arthritis trials, clinical improvement came with no clear change in immunological parameters.

A 1985 paper states that thymulin is a nonapeptide hormone produced by thymic epithelial cells and that its biological activity is strictly dependent on zinc in the molecule. Two monoclonal antibodies recognized only the zinc-coupled molecule, and other antibodies recognized a zinc-independent epitope, which the authors read as a zinc-specific conformation. The abstract does not state the species.

A randomized trial published in 1993 in 27 patients with Crohn's disease in remission, who had decreased plasma zinc and active thymulin, found that 200 mg a day of zinc sulphate for 3 months raised plasma thymulin activity and zinc, while 60 mg a day and placebo did not (PMID 8364132). That trial measured thymulin activity as an outcome of zinc supplementation, not a clinical immune outcome.

In mice, thymulin suppressed pro-inflammatory cytokine production in myeloid cells by inhibiting NF-kB signaling. In the rheumatoid arthritis trials, clinical improvement came with no clear change in immunological parameters, so those trials do not show an immune mechanism in people.

1985 paper: thymulin activity strictly dependent on zinc

Cell study

Dardenne M et al. Proc Natl Acad Sci U S A. 1985;82(20):7035-8. PMID 2413455.

A 1985 paper states that thymulin is a nonapeptide hormone produced by thymic epithelial cells and that its biological activity is strictly dependent on zinc in the molecule. Two monoclonal antibodies recognized only the zinc-coupled molecule, and other antibodies recognized a zinc-independent epitope, which the authors read as a zinc-specific conformation. A randomized trial published in 1993 in 27 patients with Crohn's disease in remission, who had decreased plasma zinc and active thymulin, found that 200 mg a day of zinc sulphate for 3 months raised plasma thymulin activity and zinc, while 60 mg a day and placebo did not (PMID 8364132).

Participants / model
Antibody work (species not stated in the abstract); 27 patients with Crohn's disease in remission (second study)
Treatment
Not applicable for the antibody work; oral zinc sulphate for the Crohn's trial
Follow-up
3 months for the Crohn's trial
Study design
Original antibody studies; the Crohn's trial is a randomized trial
Funding
not stated in the source

The Crohn's trial measured thymulin activity as an outcome of zinc supplementation, not a clinical immune outcome.

Read the original source
July 2026 Nature Communications mouse paper, plus plasma thymulin by age in 93 healthy people

Animal study

Kanemaru H et al. Nat Commun. 2026;17(1). PMID 42481458.

A July 2026 Nature Communications paper reports that thymulin, a thymus-derived peptide that declines with age, suppressed pro-inflammatory cytokine production in myeloid cells by inhibiting NF-kB signaling, enhanced antitumor T-cell immunity, improved tumor control and survival, and sensitized tumors to anti-PD-L1 therapy in an age-dependent manner in the authors' mouse work. A 2000 study of 93 healthy individuals found plasma thymulin rising to its highest level at age 5 to 10 years, falling from adolescence to a lowest value at age 36, and then staying steady until age 80 (PMID 10971509).

Participants / model
Aged mice and mouse tumor models; plasma thymulin in 93 healthy individuals from birth to old age (second study)
Treatment
Thymulin administered in mice; no human dosing; blood sampling in the human study
Follow-up
not stated in the source
Study design
Original preclinical study; the human age study is observational
Funding
not stated in the source; the record's competing-interests statement lists a consulting role for the senior author with Otsuka Pharmaceutical Factory

The authors suggest thymulin as a possible way to improve cancer immunotherapy in older people, which is a hypothesis. The mouse route and dose are not given in the source record used for this page.

Read the original source
Rheumatoid arthritis trials, 1987: 5 mg dose improved global assessment, 56% versus 17%

Randomized controlled trial

Amor B et al. Ann Rheum Dis. 1987;46(7):549-54. PMID 3310925.

Two randomized, double-blind, placebo-controlled trials tested nonathymulin, a synthetic thymic peptide hormone, in rheumatoid arthritis and compared 1, 5 and 10 mg a day. The 5 mg dose gave significant clinical improvement by global assessment of all patients who entered the trials (56% versus 17% on placebo, p less than 0.02) and by four objective parameters, with minimal adverse effects and no clear change in immunological parameters.

Participants / model
Patients with rheumatoid arthritis
Treatment
Nonathymulin 1, 5 or 10 mg a day; route not stated in the abstract
Follow-up
not stated in the source
Study design
Two randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

The abstract does not state the number of patients, the route or the trial length. A 1984 letter from the same group is indexed without an abstract (PMID 6362675). The authors include Dardenne and Bach, who also wrote the 1970s papers that characterized the peptide. No later randomized trial of thymulin in rheumatoid arthritis turned up in the PubMed search.

Read the original source

What is known about the safety of thymulin?

Human safety data are limited to two 1980s rheumatoid arthritis trials, which reported minimal adverse effects, and a 40-patient multiple sclerosis trial that recorded no significant side effects. No human pharmacokinetics were found, and in rodents the dose changed the direction of the effect on pain.

The rheumatoid arthritis trial abstract reports minimal adverse effects at the doses compared, and the multiple sclerosis trial recorded no significant side effects over 6 months of subcutaneous nonathymulin. Neither abstract gives a full safety dataset, and the rheumatoid arthritis abstract does not state patient numbers.

No human pharmacokinetic study of thymulin was found in the PubMed search on 10 October 2026. A 2006 review of animal work reports that low doses (ng) caused hyperalgesia with more proinflammatory mediators in rodents, while systemic doses of 1 to 25 micrograms reduced inflammatory pain after endotoxin, so the dose changed the direction of the effect.

The only US label found is an unapproved homeopathic pellet that gives no efficacy data and does not state how much thymulin a pellet holds. Vials sold as thymulin or zinc-thymulin are not tied to the zinc-bound molecule by any analytical record reviewed, since the PubChem records are zinc-free, so the identity and activity of a given vial are not established.

Rheumatoid arthritis trials, 1987: 5 mg dose improved global assessment, 56% versus 17%

Randomized controlled trial

Amor B et al. Ann Rheum Dis. 1987;46(7):549-54. PMID 3310925.

Two randomized, double-blind, placebo-controlled trials tested nonathymulin, a synthetic thymic peptide hormone, in rheumatoid arthritis and compared 1, 5 and 10 mg a day. The 5 mg dose gave significant clinical improvement by global assessment of all patients who entered the trials (56% versus 17% on placebo, p less than 0.02) and by four objective parameters, with minimal adverse effects and no clear change in immunological parameters.

Participants / model
Patients with rheumatoid arthritis
Treatment
Nonathymulin 1, 5 or 10 mg a day; route not stated in the abstract
Follow-up
not stated in the source
Study design
Two randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

The abstract does not state the number of patients, the route or the trial length. A 1984 letter from the same group is indexed without an abstract (PMID 6362675). The authors include Dardenne and Bach, who also wrote the 1970s papers that characterized the peptide. No later randomized trial of thymulin in rheumatoid arthritis turned up in the PubMed search.

Read the original source
Multiple sclerosis pilot trial: 40 patients, subcutaneous nonathymulin, no benefit

Randomized controlled trial

Roullet E et al. Acta Neurol Scand. 1989;80(6):575-8. PMID 2618585.

In a randomized, double-blind, placebo-controlled pilot trial, 40 matched patients with evolutive multiple sclerosis and moderate disability received subcutaneous nonathymulin (called synthetic serum thymic factor in the abstract) or placebo for 6 months and were followed another 6 months. There was no significant difference in the Kurtzke disability scores, Ambulation Index or Functional Scale, and no significant side effects were recorded. The authors conclude it was not effective in evolutive, moderately disabled multiple sclerosis.

Participants / model
40 patients with multiple sclerosis
Treatment
Subcutaneous nonathymulin or placebo
Follow-up
6 months of treatment, then 6 months of follow-up
Study design
Randomized, double-blind, placebo-controlled pilot trial
Funding
not stated in the source

A negative trial. The abstract gives no dose.

Read the original source
2006 review: low-dose thymulin hyperalgesia, higher systemic doses reduced inflammatory pain

Narrative review

Dardenne M et al. Ann N Y Acad Sci. 2006;1088:153-63. PMID 17192563.

A 2006 review by the group that did the work reports that low doses (ng) of thymulin by intraplantar or intraperitoneal injection caused hyperalgesia with more proinflammatory mediators. Systemic injections of 1 to 25 micrograms of thymulin, or of an analogue peptide (PAT) that lacked the hyperalgesic effect, reduced inflammatory pain and cytokine levels after endotoxin injection. Intracerebroventricular thymulin reduced endotoxin-induced hyperalgesia dose-dependently.

Participants / model
Rodents (species not named in the abstract)
Treatment
Thymulin or PAT by local, intraperitoneal, systemic or intracerebroventricular injection
Follow-up
not stated in the source
Study design
Narrative review of original animal studies
Funding
not stated in the source

This is a review of animal work, the abstract does not name the species, and PAT is an analogue, not thymulin.

Read the original source
DailyMed Thymuline label: unapproved homeopathic pellet, effective 28 February 2019

Official label

DailyMed, U.S. National Library of Medicine. Thymuline (nonathymulin) pellet, Homeocare Laboratories, label effective 2019-02-28. Set ID 1c3a713d-b6bf-4a3c-b7e2-93a3d80412b3. openFDA Drugs@FDA queries for thymulin and nonathymulin run 10 October 2026.

On 2026-10-10 openFDA Drugs@FDA queries for thymulin and for nonathymulin each returned no match, so no FDA drug application was found. DailyMed holds one label under the name Thymuline (nonathymulin), a pellet from Homeocare Laboratories, label effective 2019-02-28. Its SPL data list the marketing category as unapproved homeopathic and the route as sublingual. The label gives the active ingredient as Thymulinum 9C and the purpose as immune support, gives no efficacy data and does not state how much thymulin a pellet holds.

Participants / model
Not a clinical population
Treatment
Sublingual homeopathic pellets (label); no approved drug found
Follow-up
Label effective 2019-02-28
Study design
Official NLM label and FDA records
Funding
not stated in the source

The label's pellet count and schedule are not reproduced here. The label does not state how much thymulin a pellet holds, so it is not presented as a thymulin dose.

Read the original source
PubChem: thymulin and nonathymulin identity, name hazards

Chemical identity record

National Library of Medicine. PubChem compound record CID 71300623 (Thymulin), with CID 3085284 (Nonathymulin) and CID 16130571 (thymosin alpha-1) for comparison.

PubChem lists Thymulin as CID 71300623, C33H54N12O15, molecular weight 858.9, CAS 78922-62-0, with synonyms that include circulating thymic factor and facteur thymique serique. A second record, Nonathymulin (INN), is CID 3085284 with the same formula and weight and CAS 63958-90-7, with synonyms that include Thymic factor and the sequence pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH. Neither record includes zinc in the formula. The CID 3085284 synonym list also contains the word Thymalin, so a PubChem name search for thymalin returns this nonapeptide. The Khavinson group's papers describe Thymalin as an immunomodulatory drug containing a polypeptide extract of thymus, with the KE and EW dipeptides named as its active substances (PMID 37686182). Thymosin alpha-1 (thymalfasin) is a separate record, CID 16130571, C129H215N33O55, 3108.3 g/mol.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined nonapeptide; zinc-free peptide records
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Thymalin and thymulin are different things, and thymosin alpha-1 is a separate molecule. Neither PubChem thymulin record includes zinc.

Read the original source
Searches, 10 October 2026: no hair trial, no healthy-people immune trial

PubMed search record

PubMed search run on 10 October 2026: thymulin AND (hair OR alopecia OR hair follicle OR hair growth), 4 records. A second PubMed search for thymulin terms with placebo, randomized or double-blind terms returned 14 records. ClinicalTrials.gov queries run the same day.

The hair search returned 4 records: a 1988 zinc deficiency review, the 2012 letter, the 1995 alopecia areata article, and a 2012 FOXN1 deficiency and thymic transplantation paper that is not about hair treatment. The search for (thymulin OR nonathymulin OR serum thymic factor OR circulating thymic factor) with placebo, randomized or double-blind terms returned 14 records, reviewed by title and by abstract where unclear. The rheumatoid arthritis trials and the multiple sclerosis trial are the only ones that gave thymulin or nonathymulin to patients. The rest were zinc supplementation studies, observational thymulin level studies, a 1981 mouse skin-graft paper on FTS and analogues, an erratum, a mouse homeopathy paper, and papers unrelated by title. ClinicalTrials.gov returned 1 record for the query thymulin, a zinc supplementation and oral polio vaccine study in infants, and 5 unrelated records for serum thymic factor; none lists thymulin as an intervention by title. In the records reviewed there is no trial of thymulin for hair, no trial in healthy people for immune function, and no human pharmacokinetics.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 2026-10-10
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

Why does thymulin sit in C tier?

Thymulin is a defined molecule with a primary-source sequence, a clear zinc-dependence story and two small 1980s randomized human trials, one positive and one negative. It stays at C because no regulator-approved product exists, no later randomized trial was found, and the recent immune data are in mice.

The rheumatoid arthritis abstract gives no patient numbers, route or trial length, the multiple sclerosis trial was negative, and the immune claim rests on a 2026 mouse signal with nothing in healthy people. The hair claim has no human treatment data.

The only US label is an unapproved homeopathic pellet, and no analytical record ties vials sold as thymulin to the zinc-bound molecule.

1977 sequence paper: pig serum circulating thymic factor, synthetic peptide matched

Chemical identity record

Pleau JM et al. J Biol Chem. 1977;252(22):8045-7. PMID 914862.

A 1977 Journal of Biological Chemistry paper established the amino acid sequence of a circulating thymic factor (FTS, facteur thymique serique) isolated from pig serum as Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH, by Edman analysis on the intact peptide and after tryptic digestion, with the C-terminal residue found by carboxypeptidase A digestion. The PubMed text prints the N-terminal residue as less than Glu, which is the pyroglutamyl notation, and PubChem writes it pGlu. The authors prepared a synthetic peptide that they say showed the same biological activities as native pig circulating thymic factor.

Participants / model
Pig serum (isolation); synthetic peptide for bioactivity comparison
Treatment
Isolated and synthetic peptide
Follow-up
Not applicable
Study design
Original biochemical report
Funding
not stated in the source

The native material studied was porcine.

Read the original source
1985 paper: thymulin activity strictly dependent on zinc

Cell study

Dardenne M et al. Proc Natl Acad Sci U S A. 1985;82(20):7035-8. PMID 2413455.

A 1985 paper states that thymulin is a nonapeptide hormone produced by thymic epithelial cells and that its biological activity is strictly dependent on zinc in the molecule. Two monoclonal antibodies recognized only the zinc-coupled molecule, and other antibodies recognized a zinc-independent epitope, which the authors read as a zinc-specific conformation. A randomized trial published in 1993 in 27 patients with Crohn's disease in remission, who had decreased plasma zinc and active thymulin, found that 200 mg a day of zinc sulphate for 3 months raised plasma thymulin activity and zinc, while 60 mg a day and placebo did not (PMID 8364132).

Participants / model
Antibody work (species not stated in the abstract); 27 patients with Crohn's disease in remission (second study)
Treatment
Not applicable for the antibody work; oral zinc sulphate for the Crohn's trial
Follow-up
3 months for the Crohn's trial
Study design
Original antibody studies; the Crohn's trial is a randomized trial
Funding
not stated in the source

The Crohn's trial measured thymulin activity as an outcome of zinc supplementation, not a clinical immune outcome.

Read the original source
Rheumatoid arthritis trials, 1987: 5 mg dose improved global assessment, 56% versus 17%

Randomized controlled trial

Amor B et al. Ann Rheum Dis. 1987;46(7):549-54. PMID 3310925.

Two randomized, double-blind, placebo-controlled trials tested nonathymulin, a synthetic thymic peptide hormone, in rheumatoid arthritis and compared 1, 5 and 10 mg a day. The 5 mg dose gave significant clinical improvement by global assessment of all patients who entered the trials (56% versus 17% on placebo, p less than 0.02) and by four objective parameters, with minimal adverse effects and no clear change in immunological parameters.

Participants / model
Patients with rheumatoid arthritis
Treatment
Nonathymulin 1, 5 or 10 mg a day; route not stated in the abstract
Follow-up
not stated in the source
Study design
Two randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

The abstract does not state the number of patients, the route or the trial length. A 1984 letter from the same group is indexed without an abstract (PMID 6362675). The authors include Dardenne and Bach, who also wrote the 1970s papers that characterized the peptide. No later randomized trial of thymulin in rheumatoid arthritis turned up in the PubMed search.

Read the original source
Multiple sclerosis pilot trial: 40 patients, subcutaneous nonathymulin, no benefit

Randomized controlled trial

Roullet E et al. Acta Neurol Scand. 1989;80(6):575-8. PMID 2618585.

In a randomized, double-blind, placebo-controlled pilot trial, 40 matched patients with evolutive multiple sclerosis and moderate disability received subcutaneous nonathymulin (called synthetic serum thymic factor in the abstract) or placebo for 6 months and were followed another 6 months. There was no significant difference in the Kurtzke disability scores, Ambulation Index or Functional Scale, and no significant side effects were recorded. The authors conclude it was not effective in evolutive, moderately disabled multiple sclerosis.

Participants / model
40 patients with multiple sclerosis
Treatment
Subcutaneous nonathymulin or placebo
Follow-up
6 months of treatment, then 6 months of follow-up
Study design
Randomized, double-blind, placebo-controlled pilot trial
Funding
not stated in the source

A negative trial. The abstract gives no dose.

Read the original source
July 2026 Nature Communications mouse paper, plus plasma thymulin by age in 93 healthy people

Animal study

Kanemaru H et al. Nat Commun. 2026;17(1). PMID 42481458.

A July 2026 Nature Communications paper reports that thymulin, a thymus-derived peptide that declines with age, suppressed pro-inflammatory cytokine production in myeloid cells by inhibiting NF-kB signaling, enhanced antitumor T-cell immunity, improved tumor control and survival, and sensitized tumors to anti-PD-L1 therapy in an age-dependent manner in the authors' mouse work. A 2000 study of 93 healthy individuals found plasma thymulin rising to its highest level at age 5 to 10 years, falling from adolescence to a lowest value at age 36, and then staying steady until age 80 (PMID 10971509).

Participants / model
Aged mice and mouse tumor models; plasma thymulin in 93 healthy individuals from birth to old age (second study)
Treatment
Thymulin administered in mice; no human dosing; blood sampling in the human study
Follow-up
not stated in the source
Study design
Original preclinical study; the human age study is observational
Funding
not stated in the source; the record's competing-interests statement lists a consulting role for the senior author with Otsuka Pharmaceutical Factory

The authors suggest thymulin as a possible way to improve cancer immunotherapy in older people, which is a hypothesis. The mouse route and dose are not given in the source record used for this page.

Read the original source
DailyMed Thymuline label: unapproved homeopathic pellet, effective 28 February 2019

Official label

DailyMed, U.S. National Library of Medicine. Thymuline (nonathymulin) pellet, Homeocare Laboratories, label effective 2019-02-28. Set ID 1c3a713d-b6bf-4a3c-b7e2-93a3d80412b3. openFDA Drugs@FDA queries for thymulin and nonathymulin run 10 October 2026.

On 2026-10-10 openFDA Drugs@FDA queries for thymulin and for nonathymulin each returned no match, so no FDA drug application was found. DailyMed holds one label under the name Thymuline (nonathymulin), a pellet from Homeocare Laboratories, label effective 2019-02-28. Its SPL data list the marketing category as unapproved homeopathic and the route as sublingual. The label gives the active ingredient as Thymulinum 9C and the purpose as immune support, gives no efficacy data and does not state how much thymulin a pellet holds.

Participants / model
Not a clinical population
Treatment
Sublingual homeopathic pellets (label); no approved drug found
Follow-up
Label effective 2019-02-28
Study design
Official NLM label and FDA records
Funding
not stated in the source

The label's pellet count and schedule are not reproduced here. The label does not state how much thymulin a pellet holds, so it is not presented as a thymulin dose.

Read the original source
Searches, 10 October 2026: no hair trial, no healthy-people immune trial

PubMed search record

PubMed search run on 10 October 2026: thymulin AND (hair OR alopecia OR hair follicle OR hair growth), 4 records. A second PubMed search for thymulin terms with placebo, randomized or double-blind terms returned 14 records. ClinicalTrials.gov queries run the same day.

The hair search returned 4 records: a 1988 zinc deficiency review, the 2012 letter, the 1995 alopecia areata article, and a 2012 FOXN1 deficiency and thymic transplantation paper that is not about hair treatment. The search for (thymulin OR nonathymulin OR serum thymic factor OR circulating thymic factor) with placebo, randomized or double-blind terms returned 14 records, reviewed by title and by abstract where unclear. The rheumatoid arthritis trials and the multiple sclerosis trial are the only ones that gave thymulin or nonathymulin to patients. The rest were zinc supplementation studies, observational thymulin level studies, a 1981 mouse skin-graft paper on FTS and analogues, an erratum, a mouse homeopathy paper, and papers unrelated by title. ClinicalTrials.gov returned 1 record for the query thymulin, a zinc supplementation and oral polio vaccine study in infants, and 5 unrelated records for serum thymic factor; none lists thymulin as an intervention by title. In the records reviewed there is no trial of thymulin for hair, no trial in healthy people for immune function, and no human pharmacokinetics.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 2026-10-10
Study design
Literature and registry searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

PubChem: thymulin and nonathymulin identity, name hazards

Chemical identity record

National Library of Medicine. PubChem compound record CID 71300623 (Thymulin), with CID 3085284 (Nonathymulin) and CID 16130571 (thymosin alpha-1) for comparison.

PubChem lists Thymulin as CID 71300623, C33H54N12O15, molecular weight 858.9, CAS 78922-62-0, with synonyms that include circulating thymic factor and facteur thymique serique. A second record, Nonathymulin (INN), is CID 3085284 with the same formula and weight and CAS 63958-90-7, with synonyms that include Thymic factor and the sequence pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH. Neither record includes zinc in the formula. The CID 3085284 synonym list also contains the word Thymalin, so a PubChem name search for thymalin returns this nonapeptide. The Khavinson group's papers describe Thymalin as an immunomodulatory drug containing a polypeptide extract of thymus, with the KE and EW dipeptides named as its active substances (PMID 37686182). Thymosin alpha-1 (thymalfasin) is a separate record, CID 16130571, C129H215N33O55, 3108.3 g/mol.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined nonapeptide; zinc-free peptide records
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Thymalin and thymulin are different things, and thymosin alpha-1 is a separate molecule. Neither PubChem thymulin record includes zinc.

Read the original source
1977 sequence paper: pig serum circulating thymic factor, synthetic peptide matched

Chemical identity record

Pleau JM et al. J Biol Chem. 1977;252(22):8045-7. PMID 914862.

A 1977 Journal of Biological Chemistry paper established the amino acid sequence of a circulating thymic factor (FTS, facteur thymique serique) isolated from pig serum as Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH, by Edman analysis on the intact peptide and after tryptic digestion, with the C-terminal residue found by carboxypeptidase A digestion. The PubMed text prints the N-terminal residue as less than Glu, which is the pyroglutamyl notation, and PubChem writes it pGlu. The authors prepared a synthetic peptide that they say showed the same biological activities as native pig circulating thymic factor.

Participants / model
Pig serum (isolation); synthetic peptide for bioactivity comparison
Treatment
Isolated and synthetic peptide
Follow-up
Not applicable
Study design
Original biochemical report
Funding
not stated in the source

The native material studied was porcine.

Read the original source
1985 paper: thymulin activity strictly dependent on zinc

Cell study

Dardenne M et al. Proc Natl Acad Sci U S A. 1985;82(20):7035-8. PMID 2413455.

A 1985 paper states that thymulin is a nonapeptide hormone produced by thymic epithelial cells and that its biological activity is strictly dependent on zinc in the molecule. Two monoclonal antibodies recognized only the zinc-coupled molecule, and other antibodies recognized a zinc-independent epitope, which the authors read as a zinc-specific conformation. A randomized trial published in 1993 in 27 patients with Crohn's disease in remission, who had decreased plasma zinc and active thymulin, found that 200 mg a day of zinc sulphate for 3 months raised plasma thymulin activity and zinc, while 60 mg a day and placebo did not (PMID 8364132).

Participants / model
Antibody work (species not stated in the abstract); 27 patients with Crohn's disease in remission (second study)
Treatment
Not applicable for the antibody work; oral zinc sulphate for the Crohn's trial
Follow-up
3 months for the Crohn's trial
Study design
Original antibody studies; the Crohn's trial is a randomized trial
Funding
not stated in the source

The Crohn's trial measured thymulin activity as an outcome of zinc supplementation, not a clinical immune outcome.

Read the original source
DailyMed Thymuline label: unapproved homeopathic pellet, effective 28 February 2019

Official label

DailyMed, U.S. National Library of Medicine. Thymuline (nonathymulin) pellet, Homeocare Laboratories, label effective 2019-02-28. Set ID 1c3a713d-b6bf-4a3c-b7e2-93a3d80412b3. openFDA Drugs@FDA queries for thymulin and nonathymulin run 10 October 2026.

On 2026-10-10 openFDA Drugs@FDA queries for thymulin and for nonathymulin each returned no match, so no FDA drug application was found. DailyMed holds one label under the name Thymuline (nonathymulin), a pellet from Homeocare Laboratories, label effective 2019-02-28. Its SPL data list the marketing category as unapproved homeopathic and the route as sublingual. The label gives the active ingredient as Thymulinum 9C and the purpose as immune support, gives no efficacy data and does not state how much thymulin a pellet holds.

Participants / model
Not a clinical population
Treatment
Sublingual homeopathic pellets (label); no approved drug found
Follow-up
Label effective 2019-02-28
Study design
Official NLM label and FDA records
Funding
not stated in the source

The label's pellet count and schedule are not reproduced here. The label does not state how much thymulin a pellet holds, so it is not presented as a thymulin dose.

Read the original source
Rheumatoid arthritis trials, 1987: 5 mg dose improved global assessment, 56% versus 17%

Randomized controlled trial

Amor B et al. Ann Rheum Dis. 1987;46(7):549-54. PMID 3310925.

Two randomized, double-blind, placebo-controlled trials tested nonathymulin, a synthetic thymic peptide hormone, in rheumatoid arthritis and compared 1, 5 and 10 mg a day. The 5 mg dose gave significant clinical improvement by global assessment of all patients who entered the trials (56% versus 17% on placebo, p less than 0.02) and by four objective parameters, with minimal adverse effects and no clear change in immunological parameters.

Participants / model
Patients with rheumatoid arthritis
Treatment
Nonathymulin 1, 5 or 10 mg a day; route not stated in the abstract
Follow-up
not stated in the source
Study design
Two randomized, double-blind, placebo-controlled trials
Funding
not stated in the source

The abstract does not state the number of patients, the route or the trial length. A 1984 letter from the same group is indexed without an abstract (PMID 6362675). The authors include Dardenne and Bach, who also wrote the 1970s papers that characterized the peptide. No later randomized trial of thymulin in rheumatoid arthritis turned up in the PubMed search.

Read the original source
Multiple sclerosis pilot trial: 40 patients, subcutaneous nonathymulin, no benefit

Randomized controlled trial

Roullet E et al. Acta Neurol Scand. 1989;80(6):575-8. PMID 2618585.

In a randomized, double-blind, placebo-controlled pilot trial, 40 matched patients with evolutive multiple sclerosis and moderate disability received subcutaneous nonathymulin (called synthetic serum thymic factor in the abstract) or placebo for 6 months and were followed another 6 months. There was no significant difference in the Kurtzke disability scores, Ambulation Index or Functional Scale, and no significant side effects were recorded. The authors conclude it was not effective in evolutive, moderately disabled multiple sclerosis.

Participants / model
40 patients with multiple sclerosis
Treatment
Subcutaneous nonathymulin or placebo
Follow-up
6 months of treatment, then 6 months of follow-up
Study design
Randomized, double-blind, placebo-controlled pilot trial
Funding
not stated in the source

A negative trial. The abstract gives no dose.

Read the original source
July 2026 Nature Communications mouse paper, plus plasma thymulin by age in 93 healthy people

Animal study

Kanemaru H et al. Nat Commun. 2026;17(1). PMID 42481458.

A July 2026 Nature Communications paper reports that thymulin, a thymus-derived peptide that declines with age, suppressed pro-inflammatory cytokine production in myeloid cells by inhibiting NF-kB signaling, enhanced antitumor T-cell immunity, improved tumor control and survival, and sensitized tumors to anti-PD-L1 therapy in an age-dependent manner in the authors' mouse work. A 2000 study of 93 healthy individuals found plasma thymulin rising to its highest level at age 5 to 10 years, falling from adolescence to a lowest value at age 36, and then staying steady until age 80 (PMID 10971509).

Participants / model
Aged mice and mouse tumor models; plasma thymulin in 93 healthy individuals from birth to old age (second study)
Treatment
Thymulin administered in mice; no human dosing; blood sampling in the human study
Follow-up
not stated in the source
Study design
Original preclinical study; the human age study is observational
Funding
not stated in the source; the record's competing-interests statement lists a consulting role for the senior author with Otsuka Pharmaceutical Factory

The authors suggest thymulin as a possible way to improve cancer immunotherapy in older people, which is a hypothesis. The mouse route and dose are not given in the source record used for this page.

Read the original source
2006 review: low-dose thymulin hyperalgesia, higher systemic doses reduced inflammatory pain

Narrative review

Dardenne M et al. Ann N Y Acad Sci. 2006;1088:153-63. PMID 17192563.

A 2006 review by the group that did the work reports that low doses (ng) of thymulin by intraplantar or intraperitoneal injection caused hyperalgesia with more proinflammatory mediators. Systemic injections of 1 to 25 micrograms of thymulin, or of an analogue peptide (PAT) that lacked the hyperalgesic effect, reduced inflammatory pain and cytokine levels after endotoxin injection. Intracerebroventricular thymulin reduced endotoxin-induced hyperalgesia dose-dependently.

Participants / model
Rodents (species not named in the abstract)
Treatment
Thymulin or PAT by local, intraperitoneal, systemic or intracerebroventricular injection
Follow-up
not stated in the source
Study design
Narrative review of original animal studies
Funding
not stated in the source

This is a review of animal work, the abstract does not name the species, and PAT is an analogue, not thymulin.

Read the original source
2012 research letter, no abstract: ex vivo human hair follicle culture

Cell study

Meier N et al. J Invest Dermatol. 2012;132(5):1516-9. PMID 22402437.

The 2012 Journal of Investigative Dermatology research letter is indexed in PubMed with no abstract. The indexing terms in Europe PMC's copy include circulating thymic factor (the MeSH term that covers thymulin), thymosin and thymosin beta-4, with scalp, hair follicle and organ culture. The title says differentially, which implies the peptides did not all act the same way, but the record gives no detail on which peptide did what or by how much. A 1995 supplement article on the thymus in alopecia areata is also indexed with no abstract (PMID 7738381).

Participants / model
Human scalp hair follicles in organ culture (from indexing terms only)
Treatment
Peptides in culture; details not available
Follow-up
not stated in the source
Study design
Original research letter, no abstract
Funding
not stated in the source

The hair claim is ex vivo human follicle culture at most, not a treatment result. The findings cannot be read from the record.

Read the original source

Why is Thymulin in C tier?

C fits a defined molecule with a primary-source sequence, a clear zinc-dependence story and two small randomized human trials from the 1980s, one positive and one negative. It stays at C because no regulator-approved product exists, the only US label is an unapproved homeopathic pellet, no later randomized trial was found, and the recent immune data are in mice.