New research illuminates how Mediterranean Diet adherence leads to health benefits

Olive oil, fish, legumes linked to increased levels of microproteins

How does what we eat translate into benefits such as neuroprotection or cardiovascular health? Recent findings by scientists in the US and Italy support a theory that the mitochondria inside our cells interact with components of the Mediterranean Diet to facilitate its multiple health-promoting effects.

What are mitochondria and what do they do? Often called the “powerhouses of the cell,” mitochondria are complex microscopic structures that convert nutrients into energy. (All human cells, except for red blood cells, have hundreds or thousands of mitochondria.) Among their many other functions, mitochondria release tiny proteins that act as molecular messengers. These messengers signal to the cell to dial up or down processes such as inflammation, metabolism, cell death, and more. Seven mitochondrial-derived microproteins (MDPs) have been identified; two of these, humanin and SHMOOSE, have been studied for their neuroprotective and antioxidative properties.

What was evaluated in this study? Researchers sought to learn if blood-plasma levels of MDPs humanin and SHMOOSE were associated with adherence to the Mediterranean Diet (MeDi). A cohort of 49 older adults (age > 60), participants in a large heart study, were grouped as high adherence (HA) or low/medium adherence (LA) to the MeDi, based on dietary questionnaires. Groups were balanced for age (mean 78), BMI (mean 31), and chronic health conditions. MeDi scores ranged from 0–9 points (1 point each): Olive oil: ≥1 Tbl/day; Fruit: ≥1 serv./day; Vegetable/salad: ≥1 serv./day; Both ≥1 fruit and ≥1 vegetable/day; Legumes: ≥2 serv./week; Fish: ≥3 serv./week; Wine: ≥1 glass/day; Red meat: <1 serv./day; Bread: <1 serv. white bread or rice/day, or ≥5 serv. whole-wheat bread/week.

Participants’ blood samples were analyzed for plasma levels of humanin and SHMOOSE.

What did the investigators find? Levels of humanin and SHMOOSE were significantly higher in participants in the HA group. Olive oil, fish, legumes, and low refined carbs were MeDi components with the strongest associations with MDP levels. SHMOOSE levels were higher in participants who consumed ≥1 Tbl olive oil/day and in those who consumed <1 serv. white bread/day. Humanin levels were higher in those who consumed ≥1 Tbl olive oil/day; fish ≥3x/week; or legumes ≥2x/week.

What do the links between MDPs and MeDi adherence mean? The associations between olive oil, fish, and legumes and higher circulating levels of humanin and SHMOOSE suggest that those MeDi foods positively affect mitochondrial function. Also, measuring humanin and SHMOOSE levels could be used as a marker of response to diets such as the MeDi. Further, confirming the links between MDPs and MeDi adherence can help scientists detail the role of mitochondria in the pathway from diet to health outcomes.

References: Vincinanza R, Cammisotto V, Wan J, et al. Mediterranean diet adherence is associated with mitochondrial microproteins Humanin and SHMOOSE; potential role of the Humanin-Nox2 interaction in cardioprotection. Front Nutr. 2026;12:1727012; Yen K, Miller B, Kumagai H, Silverstein A, Cohen P. Mitochondrial-derived microproteins: from discovery to function. Trends Genetics. 2025(41);2:132–145.