Mediterranean diet adherence is associated with mitochondrial microproteins Humanin and SHMOOSE; potential role of the Humanin-Nox2 interaction in cardioprotection.

Vicinanza R, Cammisotto V, Wan J, Yen K, Violi F, Pignatelli P, Cohen P

Frontiers in nutrition10 Mar 2026

PMID41883858PMCIDPMC13008867DOI10.3389/fnut.2025.1727012PepBankPUB-41883858

Summary

BackgroundThe health benefits of the Mediterranean Diet (Med-Diet) have been demonstrated in observational studies and randomized controlled trials. Emerging evidence suggests that the biological effects of the Med-Diet may be mediated by the modulation of mitochondrial function. Human mitochondrial DNA (mtDNA) encodes microproteins, which have been shown to regulate aging, cardiometabolic functions, and neuroprotection.ObjectivesTo investigate Humanin and SHMOOSE (Small Human Mitochondrial ORF Over SErine tRNA), as potential mitochondrial biomarkers of Med-Diet adherence and their associations with markers of oxidative stress.MethodsCross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome. Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire. Oxidative stress was evaluated by measuring soluble Nox2-derived peptide (sNox2-dp) and plasma 8-iso-prostaglandin F2α (8-iso-PGF2α) using enzyme-linked immunosorbent assays (ELISA). Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.ResultsHigh Med-Diet adherence was observed in 20 patients (40.8%), while 29 patients (59.2%) had low-medium adherence. Patients with high adherence exhibited higher plasma levels of SHMOOSE (p = 0.046) and Humanin (p = 0.045). The analysis of the dietary components of the Med-Diet revealed higher levels of SHMOOSE with olive oil consumption (p = 0.020) and low intake of refined bread (p = 0.029), while Humanin positively correlated with olive oil (p = 0.0069), fish (p = 0.038), and legumes (p = 0.0282). Additionally, Humanin was inversely associated with sNox2-dp (p = 0.019), which remained significant after adjusting for sex and BMI (B = -0.010; β = -0.302; p = 0.040), and 8-iso-PGF2α (p = 0.049).ConclusionThis study indicates (i) a positive association between adherence to the Med-Diet and circulating levels of mitochondrial microproteins SHMOOSE and Humanin supporting their role as potential mediators of Med-Diet benefits; (ii) a putative crosstalk between Humanin signaling and Nox2 activity, suggesting a novel cardioprotective mechanism of the Med-Diet. Collectively, these findings support mitochondrial microproteins as promising biomarkers for tailoring nutritional strategies for healthy aging. Further studies are warranted to elucidate the underlying mechanisms and determine the causal nature of these associations.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

No result from this study comes from a test of the peptide.

Natural levels measured7

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01HumanEndogenous levelObservational studyOther
In adults with atrial fibrillation, plasma Humanin levels were higher in patients with high Mediterranean diet adherence than in those with low-medium adherence.
In plain wordsIn older adults with atrial fibrillation, closer Mediterranean diet adherence was linked to higher levels of the body's own Humanin.
Peptide
Humanin
Outcome
IncreaseHumanin level by Mediterranean diet adherence
Study
n = 49
Comparator
Low-medium adherence
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
Patients with high adherence exhibited higher plasma levels of SHMOOSE (p = 0.046) and Humanin (p = 0.045).
3 context sentences(design, population, supporting numbers)
Summary · context
Cross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome.
Summary · context
Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire.
Summary · context
Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4188385801
02HumanEndogenous levelObservational studyOther
In adults with atrial fibrillation, plasma Humanin correlated positively with olive oil consumption.
In plain wordsIn older adults with atrial fibrillation, more olive oil was linked to higher levels of the body's own Humanin.
Peptide
Humanin
Outcome
IncreaseHumanin correlation with olive oil intake
Study
n = 49
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
Humanin positively correlated with olive oil (p = 0.0069)
3 context sentences(design, population, supporting numbers)
Summary · context
Cross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome.
Summary · context
Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire.
Summary · context
Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4188385802
03HumanEndogenous levelObservational studyOther
In adults with atrial fibrillation, plasma Humanin correlated positively with fish consumption.
In plain wordsIn older adults with atrial fibrillation, more fish was linked to higher levels of the body's own Humanin.
Peptide
Humanin
Outcome
IncreaseHumanin correlation with fish intake
Study
n = 49
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
Humanin positively correlated with olive oil (p = 0.0069), fish (p = 0.038)
3 context sentences(design, population, supporting numbers)
Summary · context
Cross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome.
Summary · context
Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire.
Summary · context
Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4188385803
04HumanEndogenous levelObservational studyOther
In adults with atrial fibrillation, plasma Humanin correlated positively with legume consumption.
In plain wordsIn older adults with atrial fibrillation, more legumes were linked to higher levels of the body's own Humanin.
Peptide
Humanin
Outcome
IncreaseHumanin correlation with legume intake
Study
n = 49
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
Humanin positively correlated with olive oil (p = 0.0069), fish (p = 0.038), and legumes (p = 0.0282).
3 context sentences(design, population, supporting numbers)
Summary · context
Cross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome.
Summary · context
Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire.
Summary · context
Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4188385804
05HumanEndogenous levelObservational studyOther
In adults with atrial fibrillation, plasma Humanin was inversely associated with soluble Nox2-derived peptide.
In plain wordsIn older adults with atrial fibrillation, higher natural Humanin levels were linked to lower levels of an oxidative stress marker.
Peptide
Humanin
Outcome
DecreaseHumanin association with sNox2-dp
Study
n = 49
Outcome group
Oxidative stress · Cardiovascular
Source sentences
Summary
Humanin was inversely associated with sNox2-dp (p = 0.019)
3 context sentences(design, population, supporting numbers)
Summary · context
Cross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome.
Summary · context
Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire.
Summary · context
Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4188385805
06HumanEndogenous levelObservational studyOther
In adults with atrial fibrillation, the inverse association between plasma Humanin and soluble Nox2-derived peptide remained significant after adjusting for sex and BMI.
In plain wordsIn older adults with atrial fibrillation, the link between natural Humanin levels and lower oxidative stress remained after adjusting for sex and BMI.
Peptide
Humanin
Outcome
DecreaseHumanin association with sNox2-dp after adjustment for sex and BMI
Study
n = 49
Outcome group
Oxidative stress · Cardiovascular
Source sentences
Summary
Humanin was inversely associated with sNox2-dp (p = 0.019), which remained significant after adjusting for sex and BMI (B = -0.010; β = -0.302; p = 0.040)
3 context sentences(design, population, supporting numbers)
Summary · context
Cross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome.
Summary · context
Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire.
Summary · context
Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4188385806
07HumanEndogenous levelObservational studyOther
In adults with atrial fibrillation, plasma Humanin was inversely associated with plasma 8-iso-PGF2α.
In plain wordsIn older adults with atrial fibrillation, higher natural Humanin levels were linked to lower levels of an oxidative stress marker.
Peptide
Humanin
Outcome
DecreaseHumanin association with 8-iso-PGF2α
Study
n = 49
Outcome group
Oxidative stress · Cardiovascular
Source sentences
Summary
Humanin was inversely associated with sNox2-dp (p = 0.019), which remained significant after adjusting for sex and BMI (B = -0.010; β = -0.302; p = 0.040), and 8-iso-PGF2α (p = 0.049).
3 context sentences(design, population, supporting numbers)
Summary · context
Cross-sectional analysis of 49 patients (mean age 78.4 ± 8.7 years; 57% female) selected from an observational study of non-valvular atrial fibrillation (AF) conducted at the Atherothrombosis Center of Sapienza University of Rome.
Summary · context
Patients were categorized into low-medium (0-6) and high (7-9) adherence to the Med-Diet based on the 9-item Med-Diet questionnaire.
Summary · context
Circulating Humanin and SHMOOSE levels were measured using an in-house sandwich ELISA.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4188385807

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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