Table 2.
Summary of the included studies’ results of outcomes related to molecular output and related biomarkers.
| Authors (Year) | Main Results | Biomarkers and Outcomes |
|---|---|---|
| Alonso-Pedrero, Lucia at al., 2020 [32] | Higher consumption of UPF (>3 servings/d) presented higher risk of having shorter telomeres in an elderly Spanish population. | Participants with >3 servings/day of UPF consumption: higher short telomere risk (p = 0.032), higher family history of CVD (p = 0.045), and diabetes and dyslipidemia prevalence (p = 0.014); higher consumption of fats, SFAs, sodium, sugar-sweetened beverages (SSBs), fast food, and processed meat (p < 0.001), PUFAs (p = 0.011), dietary cholesterol (p = 0.008); less adherence to the MedDiet (p < 0.001). |
| Baba, Yoshitake et al., 2020 [33] | Intake of 336.4 mg of Green Tea Catechins (GTC) promoted working memory in adults. | GTC: significantly lower commission errors on the CPT (p = 0.004), after a single dose; significantly lower correct response time on the 4-part CPT (FPCPT) (p = 0.012). |
| Fernández-Real, José Manuel et al., 2012 [34] | Consumption of MedDiet + VOO for 2 years increased (serum osteocalcin) and (P1NP), indicating bone-protective effects. | MedDiet + VOO: TOC concentrations increased (p = 0.007), P1NP levels increased (p < 0.01); consumption of olives: positively associated with both baseline total osteocalcin (p = 0.02) and 2 year (osteocalcin) (p = 0.04). |
| Fortin, A. et al., 2018 [35] | MedDiet and low-fat diet in patients with T1D and MetS could help with weight loss, with no significant changes in anthropometric and metabolic parameters between regimens. | BMI, WC, weight, and triglycerides: decreased overtime with both diets (p < 0.05). |
| Fretts, Amanda M. et al., 2016 [36] | Processed meat, but not unprocessed red meat consumption, was linked to a shorter LTL. | Processed meat: inverse correlation with LTL (p = 0.009), after adjustment for potential mediators, including SBP, LDL-C, fibrinogen, and BMI. |
| García-Calzón, Sonia at al., 2015 [37] | Diet, through proinflammatory or anti-inflammatory pathways, could be a fundamental predictor of telomere length. | DII score 3: inverse significant association with TL (p = 0.001) |
| González-Guardia, Lorena et al., 2015 [38] | MedDiet + CoQ promotes urine metabolites excretion, reducing oxidative stress. Metabolites excreted after SFA diet are linked to increased oxidative stress. | MedDiet + CoQ: higher hippurate urine levels and reduced phenylacetylglycine levels (p < 0.05); inversely related to Nrf2 and thioredoxin (Trx) (p = 0.004), superoxide dismutase 1 (SOD-1) (p = 0.03) and gp91phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase gene expression (p = 0.039); SFA diet: phenylacetylglycine excretion was negatively related to CoQ (p = 0.039) and positively correlated with isoprostane urinary levels (p = 0.013). |
| Gu, Yian et al., 2015 [39] | Among whites, greater adherence to a MedDiet was significantly connected with longer LTL. In addition, eating a diet rich in vegetables and poor in meat, dairy, or cereal might contribute to longer LTL. | MedDiet adherence: higher LTL in whites (p-trend = 0.02); consumption of vegetables and cereals: increased LTL (p = 0.002 and p = 0.003); consumption of reduced dairy and meat intake: increased LTL (p = 0.05 and p = 0.004). |
| Guallar-Castillón, Pilar et al., 2012 [40] | SEAD may prevent myocardial infarction by lowering inflammation markers and reducing triglycerides, insulin, insulin resistance, and SBP. | Higher SEAD adherence: lower plasma CRP, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), urine albumin, and SBP (p-trend < 0.001), triglycerides (p-trend = 0.012), urine albumin/creatinine ratio (p-trend < 0.034). |
| Gutierrez-Mariscal, Francisco M. et al., 2012 [41] | MedDiet protects DNA from oxidative damage and CoQ supplementation enhances this protection, lowering p53 activation. On the other hand, SFA diet potentiate oxidative stress and p53 stabilization. | Med + CoQ diet: increase of fasting plasma (CoQ) and postprandial (2 h) plasma [CoQ] (p < 0.001 and p = 0.018); decrease of plasma (8-OHdG) (p < 0.0001) and after postprandial period (p = 0.026), of p53 postprandial levels (p < 0.05), of nuclear p-p53 (Ser20) postprandial levels (p = 0.0013), of NM-p53 postprandial (p < 0.05) and of CM-p53 postprandial levels (p = 0.046); MedDiet: decrease of CM-p53 postprandial levels (p = 0.043) and increase of mdm2 mRNA levels (p < 0.05); SFA diet: higher fasting plasma concentrations of TC (p < 0.001), LDL-C (p = 0.013), ApoB (p = 0.017), Apolipoprotein A1 (ApoA1) (p = 0.002) and p53 mRNA levels (p = 0.047); |
| Gutierrez-Mariscal, Francisco M. et al., 2014 [42] | In comparison to the harmful activity of an SFA diet, which initiates the p53-dependent DNA repair mechanism, the MedDiet diet and MedDiet + CoQ10 have beneficial effects on DNA damage. | Med + CoQ: lower mRNA Gadd45a, mRNA Gadd45b, mRNA Ogg1, nuclear APE-1/Ref-1 protein level, mRNA DNA polβ, and mRNA XPC (p = 0.044, p = 0.027, p = 0.048, p = 0.038, p = 0.041 and p = 0.019, respectively). |
| Hernáez, Álvaro et al., 2020 [43] | The MedDiet improved atherothrombosis biomarkers (HDL, fibrinogen, and Non-esterified fatty acids (NEFA) levels) in high cardiovascular risk individuals. | Adherence to MedDiet: increased activity of platelet activating factor acetylhydrolase (PAF-AH) in HDLs (adjusted difference: +7.5% (0.17; 14.8) and HDL-bound 𝛼1-antitrypsin levels (adjusted difference: −6.1% [−11.8; −0.29]; reduced fibrinogen (adjusted difference: −9.5% (−18.3; −0.60) and NEFA concentrations (adjusted difference: −16.7% (−31.7; −1.74)). |
| Becerra-Tomás, Nerea et al., 2021 [44] | In older adults with MetS, increased total fruit consumption is linked with lower WC, plasma glucose and LDL-C levels, as well as higher SBP and DBP. Total and natural fruit juice consumption was associated with reduced WC and glucose levels. | Higher total fruit consumption: significantly reduction in WC and glucose (p = 0.01) and LDL-C (p < 0.01); significantly increase DBP (p < 0.01); higher total fruit juice consumption: significantly reduces WC and glucose (p < 0.01); higher consumption of orange fruits (increase in SBP and DBP (p < 0.01)); green fruits (decrease in glucose (p = 0.01) and increase in HDL-C (p = 0.01)); red/purple fruits (decrease in glucose (p = 0.01)); white fruits (decrease in BMI and WC (p < 0.01)). |
| Jalilpiran, Yahya et al., 2020 [45] | Inverse correlation between the DASH and MedDiet patterns and several cardiovascular risk factors. | Greater adherence to MedDiet: lower WC, triacylglycerol, hs-CRP, fibrinogen, and higher HDL-C (p < 0.05); lower DBP (p = 0.01) and fibrinogen levels (p < 0.001); Greater adherence to DASH: lower fibrinogen (p < 0.05); reduced risk of high DBP (p < 0.001), insulin levels (p = 0.001), hs-CRP (p = 0.009), and fibrinogen (p < 0.001). |
| Kanerva, Noora et al., 2014 [46] | Lower hs-CRP levels are due to the Baltic Sea diet. | BSDS: inverse association with hs-CRP (p < 0.01), contributed mainly by high intake of Nordic fruits and cereals, low intake of red and processed meat, and moderate intake of alcohol (p < 0.05). |
| Khalatbari-Soltani, Saman et al., 2020 [47] | Adherence to the MedDiet decreased hepatic steatosis risk based on the FLI, in addition to the existing evidence of reducing CVD risk. When different parameters for determining the NAFLD score were used, no connection was found. | Adherence to MedDiet: lower risk of hepatic steatosis based on FLI (p-trend < 0.006), after adjustment for BMI (p-trend = 0.031) and after adjustment of BMI and WC (p-trend = 0.034). |
| Kondo, Keiko et al., 2014 [48] | Treatment with a high-fiber, low-fat diet for 8 weeks effectively improved periodontal disease markers and metabolic profiles, at least in part, by mechanisms effects other than caloric restriction. | High-fiber, low-fat diet: significantly reduced probe depth (PD), Clinical attachment loss (CAL), bleeding on probing (BOP), and Gingival crevicular fluid (GCF) (p < 0.005), and showed improvement of BW, HbA1c (p < 0.0001), and hs-CRP (p = 0.038). |
| Martens, Remy J. H. et al., 2020 [49] | 24 h urinary sodium excretion (UNaE) was not connected with the examined cardiac biomarkers; lower 24 h urinary potassium excretion (UKE) was nonlinearly linked with higher hs-cTnT and NT-proBNP. | Diets rich in Potassium: lower hs-cTnT (p = 0.023) and NT-proBNP (p = 0.005). |
| Martínez-Lapiscina, Elena H. et al., 2014 [50] | The preventive impact of MedDiet may be larger for patients with a favorable genetic profile because it regulates the effect of genetic risk factors on cognition. | MedDiet: beneficial effect in CLU gene rs11136000 variant carrying the T minor allele in MMSE test (p < 0.001) and CDT score (p = 0.001), in CR1 gene rs3818361 variant without the A minor risk allele in MMSE test (p = 0.001) and CDT score (p = 0.006); in PICALM rs3851179 polymorphism with at least one T minor allele in CDT score (p = 0.005); and in non-APOE4 carriers in MMSE test (p = 0.007) and CDT (p < 0.001) |
| Mofrad, Manije D. et al., 2019 [51] | Higher EDI was associated with lower risk of being overweight or obese, as well as having LDL-C levels. However, in elderly men, there was no significant association between EDI and other CVD risk factors. | Highest tertile of EDI: higher consumption of fruits, vegetables, fish, olive oil, bread, cereal, and dairy products (p < 0.05); EDI: associated with higher intakes of carbohydrates, SFA, PUFAs, monounsaturated fatty acids (MUFAs), cholesterol, folate vitamin B1, vitamin B6, vitamin A, vitamin C, potassium, and magnesium (p < 0.05); Higher EDI: lower weight, BMI, WC, serum insulin, HOMA-IR, fibrinogen, ALT, AST, and DBP (p < 0.05); higher fasting blood sugar (FBS), HDL-C, TC levels, and quantitative insulin sensitivity check index (QUICKI) (p < 0.05). |
| Mujica-Parodi, Lilianne R. et al., 2020 [52] | Destabilization of brain networks may be an early sign of hypometabolism, which is linked to dementia. Dietary interventions that result in ketone utilization increase available energy and, as a result, may have the potential to protect the aging brain. | KD: decreased destabilization of brain network (DBN) (p < 0.001); higher amplitude for low-frequency fluctuations (ALFF) (p < 0.001); cognitive acuity: declined with age (p < 0.001); network switching: inverse association with ALFF (p < 0.001). |
| Neth, Bryan J. et al., 2020 [53] | MMKD may help prevent cognitive decline in adults at risk of Alzheimer’s disease (AD) risk, by improving cerebral spinal fluid (CSF) AD biomarker profile, peripheral lipid and glucose metabolism, cerebral perfusion and cerebral ketone body uptake. | MMKD: higher fasting ketone body levels (p = 0.008), mainly in subjective memory complaints (SMC) group (p = 0.015); reduced very low-density lipoprotein cholesterol (VLDL-C) levels and triglycerides (p = 0.02); increased CSF Aβ42 (p = 0.04) and decreased tau levels in mild cognitive impairment (MCI) group (p = 0.007); increased cerebral perfusion, mainly in MCI group (p < 0.05) and cerebral ketone body uptake (11C-acetoacetate (p = 0.02); AHAD: decreased tau levels in MCI group (p = 0.02). |
| Paoli, Antonio et al., 2011 [54] | The KEMEPHY diet resulted in weight and WC loss, as well as improvements in cardiovascular risk markers. | KEMEPHY diet: reduction in BMI, BW, % fat mass, WC, TC, LDL-C, triglycerides, and blood glucose (p < 0.0001); increase in HDL-C (p < 0.0001). |
| Bhanpuri, Nasir H. et al., 2018 [55] | After a year, CCI improved the majority of biomarkers of CVD risk in T2D patients. The increase in LDL-C seems to be restricted to the large LDL subfraction. LDL particle size increased, while total LDL-P and ApoB remain unchanged, and inflammation and BP decreased. | Decrease in weight, ApoB/ApoA1 ratio, triglycerides, triglycerides/HDL-C ratio, large very low-density lipoprotein particle (VLDL-P), small LDL-P, BP, hs-CRP, white blood count (WBC), 10-year Atherosclerotic cardiovascular disease (ASCVD) risk score, antihypertensive medication (AHM) use (p < 0.001); increase in ApoA1, LDL-C, HDL-C, LDL-P size, and large HDL-P (p < 0.001). |
| Schönknecht, Yannik B. et al., 2020 [56] | A high-energy meal caused hyperglycemia, hyperlipemia, and a decrease in antioxidant markers, whereas the MedDiet had a positive effect on glycemic, insulinemic, and lipemic responses. | WDHC: increased glucose (p = 0.002) and insulin levels (p < 0.001), compared with other meals WDHF: increased triglycerides levels and higher NEFA (p < 0.001), compared with other meals MedDiet: higher vitamin C levels (p < 0.001), compared with other meals. |
| Song, Xiaoling et al., 2016 [57] | Moderate weight loss had little effect on systemic inflammation in relatively healthy adults. A lower dietary fat and higher carbohydrate content had little impact on systemic inflammation measures but significantly reduced adiponectin concentrations when compared to a moderate-fat diet. | Low-calorie, low-fat,(LCLF) diet: greater reductions in weight, fat mass and fasting leptin levels (p < 0.001), compared to other diets; reduced adiponectin (p = 0.008), compared to low-fat diets; adiponectin: tend to increase with weight loss (p = 0.051). |
| Tiainen, A-MK. et al., 2012 [58] | Fat intake is inversely associated with LTL whereas vegetable intakes were positively associated with LTL. | Vegetable intake: positive association with LTL (p = 0.05) in women, after adjustments. Total fat, SFAs, and butter intake: inverse correlation with LTL (p = 0.04, p = 0.01 and p = 0.04). |
| Uusitupa, M. et al., 2013 [59] | Healthy Nordic diet improved lipid profile and reduced low-grade inflammation. | Healthy Nordic diet: lower non-HDL-C (p = 0.04), LDL-C/HDL-C ratio (p = 0.046), ApoB/ApoA1 ratio (p = 0.025); control diet: increased interleukin-1 receptor antagonist (IL-1 Ra) (p = 0.00053), related with saturated fats and magnesium+ intake (p = 0.049 and p = 0.012). |
| Yousefi, Reyhaneh et al., 2020 [60] | When combined with a calorie-restricted diet, daily consumption of 300 mg GSE improved LDL-C, HDL-C, visceral adiposity index (VAI), and atherogenic index of plasma (AIP) and helps to ameliorate some CVD risk factors in obese or overweight individuals. | GSE: significantly increase in HDL-C and HDL-C/LDL-C at w 12 (p = 0.01 and 0.003, respectively) and significantly decrease in LDL-C (p = 0.04), compared to placebo; significantly decreased VAI, AIP, TC and triglycerides compared to baseline (p =0.04, p = 0.02, p =0.01 and p = 0.02, respectively). |
| Yubero-Serrano, Elena M. et al., 2012 [61] | The anti-inflammatory effect of a MedDiet rich in olive oil and exogenous CoQ supplementation has an additive effect in aged men and women, regulating the inflammatory response and ER stress, indicating that a MedDiet + CoQ is helpful for healthy aging. | Med + CoQ: higher fasting plasma (CoQ) (p < 0.001) and plasma CoQ levels compared with the Med and SFA diets (p = 0.018 and p = 0.032), increase in IkB-α mRNA levels compared with the SFA diet (p = 0.028), decrease in IKK-β, p65 and IL-1β mRNA levels compared with the other diets (p = 0.010; p = 0.008 and p = 0.012; p = 0.011). MedDiet: lower p65, IKK-β, MMP-9 and IL-1β mRNA levels compared with the SFA diet (p = 0.033, p = 0.034; p = 0.034; p = 0.029), higher levels of IkB-α mRNA (p = 0.018). SFA diet: higher MMP-9 (p = 0.008 and p = 0.032), IL-1b (p = 0.017), JNK-1 (p = 0.037), sXBP-1 (p = 0.033 and p = 0.008), CRT (p = 0.031) and BiP/Grp78 (p = 0.021) mRNA levels compared with Med and Med + CoQ diets. |
| Boccardi, Virginia et al., 2013 [62] | Lower telomere shortening and higher Peripheral blood mononuclear cells (PBMCs) TA may play a role in lifespan and, more importantly, health span in populations consuming traditional MedDiet. | LTL: shorter with age (p < 0.001) and positive correlation with TA (p = 0.028), higher in women (p < 0.001) and differ according to smoking status (p < 0.001); negatively correlated with IS (p < 0.001) and nitrotyrosine (p = 0.011). PBMC TA: negatively correlated with both inflammation score (IS) (p = 0.048) and nitrotyrosine levels (p = 0.022); MDS ≥ 6: longer TL (p = 0.003) and higher TA (p = 0.013); lower plasmatic levels of CRP (p = 0.018), IL-6 (p = 0.010), TNF-α (p = 0.021) and nitrotyrosine (p = 0.009); IS: positively correlated with nitrotyrosine levels (p < 0.001). |
| Bonaccio, Marialaura et al., 2021 [63] | Higher levels of UPF were linked to increased risk of CVD and all-cause mortality, partly due to its high dietary content of sugar. | Intake of UPF: lower adherence to the MedDiet and intake of fiber (p < 0.001); higher energy intake, fat, sugar, dietary cholesterol, and Na+ (p < 0.001); increased risks of CVD mortality (HR: 1.58; 95% CI: 1.23, 2.03), death from ischemic heart disease (IHD)/cerebrovascular disease (HR: 1.52; 95% CI: 1.10, 2.09), and all-cause mortality (HR: 1.26; 95% CI: 1.09, 1.46). |
| Cassidy, Aedín et al., 2010 [64] | LTL, which is a putative biomarker of chronic disease risk, is associated with body composition and dietary factors. | Fiber intake (cereal fiber and whole grains) and vitamin D: higher LTL (p = 0.006, p = 0.01 and p = 0.01); LTL: inversely correlated with age (p < 0.0001), BMI (p = 0.005), WC (p = 0.009), weight (p = 0.004) and linoleic acid (p = 0.0009) and total fat intake (p = 0.003), including MUFAs and PUFAs (p = 0.006 and p = 0.0008). |
| Chou, Yi-Chun et al., 2019 [65] | In older adults, a high-quality diet containing a variety of vegetables was linked to a lower incidence of cognitive decline. | High diet quality with high vegetable diversity: lower risk of global cognitive decline (p-trend = 0.03) and of decline of attention domain (p-trend = 0.049); lower risk of global cognitive decline (p-trend = 0.03) in elders. |
| Crous-Bou, Marta et al., 2014 [66] | Longer telomeres were associated with greater adherence to the MedDiet. These results further support the benefits of adhering to this diet in terms of promoting health and longevity. | MedDiet score: proportional with TL (p = 0.016); higher in women with lower BMI (p = 0.01), who smoked less, had higher intake of total energy, were more physically active; higher with vegetables, fruits, grains, fish, nuts, and total fat intake, as well as lower meat intake (p < 0.001); TL: longer in younger women (p < 0.001); shorter in women who smoked more (p = 0.02); LTL: longer with AHEI (p = 0.02). |
| do Rosario, Vinicius A. et al., 2020 [67] | In overweight older individuals, fruit-based anthocyanins attenuated the potential negative postprandial effects of a HFHE challenge on vascular and microvascular function, as well as inflammation biomarkers. | Anthocyanin: higher postprandial flow mediated dilation (FMD) and post-occlusive reactive hyperaemia maximum perfusion (PORHmax) (p < 0.05), after 2 h; lower CRP (p < 0.05) and trend to lower IL-6 (p = 0.075), after 4 h. |