Brief description of patient problem/setting (summarize the case very briefly):

Patient is a 37 y/o male with a PMHx of HLD, Anemia, Vitamin D deficiency, and a brain hemorrhage in 2019 who presented in the outpatient family-medicine setting. He is also noticeably obese with a BMI of 35.5. He presented for a follow-up regarding elevated liver function tests, hypertriglyceridemia, and low HDL’s which were detected on his annual bloodwork. He admitted that his diet typically consists of greasy and fatty foods such as pizza, fried chicken, and burgers. His bloodwork also revealed increased levels of Ferritin in the setting of Anemia, he expressed that Thalassemia runs in his family and was advised to refrain from taking ferrous sulfate until further evaluation was conducted on the etiology of his anemia. He denied fatigue, abdominal pain, jaundice, or any other acute complaints.

Search Question: Clearly state the question (including outcomes or criteria to be tracked)

In adults with elevated triglyceride levels and low HDL’s, how does a Mediterranean diet compared to a low-fat diet affect triglyceride reduction and HDL levels ?

Question Type: What kind of question is this? (boxes now checkable in Word)

☐Prevalence                          ☐Screening                ☐Diagnosis

☐Prognosis                             X Treatment                ☐Harms

Assuming that the highest level of evidence to answer your question will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)? 

Please explain your choices. 

If there were no available meta-analyses or systematic reviews to answer this clinical question I would then turn to randomized controlled trials that compare dietary interventions such as the mediterranean diet versus a low-fat or other heart-healthy diet. I think RCT’s would be a particularly strong choice because they set up a more direct comparison between interventions while ensuring that confounding is kept to a minimum through randomization. Especially in this PICO they would be extremely useful when looking to determine whether one dietary pattern is more effective than another in lowering triglyceride levels and improving HDL’s. If RCT’s were not available, I would then consider prospective cohort studies because they allow patients to be followed over time to assess how adherence to different dietary patterns affects triglycerides, HDL’s, liver enzymes, weight and other cardiometabolic outcomes. Dietary interventions often require longer periods of follow-ups to assess the degree of sustainability, real-world adherence, and long-term benefit. Another reasonable choice would be retrospective cohort studies, these studies can help with identifying patterns between dietary counseling, lifestyle habits, and lipid levels amongst broader populations. I especially think they would be helpful in including patients that have comorbidities, poor baseline diets, and other facts that are not well represented in RCT’s.

PICO search terms:

P	I	C	O
Hypertriglyceridemia	Mediterranean diet	Low-fat diet	Triglyceride reduction
Elevated triglycerides	Mediterranean dietary pattern	Reduced-fat diet	HDL improvement
Adults with hyperlipidemia		Fat-restricted diet	Lipid panel improvement
Dyslipidemia			Lower serum triglycerides
Adults with abnormal lipid panel
Adults with high triglycerides

Search tools and strategy used:

I used 3 different databases, and these include: Cochrane Library, Pubmed, & the American Journal of Medicine. With my PICO question in mind, I came up with search terms such as “Dyslipidemia, Hypertriglyceridemia, and Elevated triglycerides” to represent the population. For intervention I used “Mediterranean Diet” and for comparison I consistently used “Low-fat diet”. Finally for the outcome I tried to use terms that would include both triglycerides and HDL’s as these were the abnormal lab values that my patient presented with and were key to my PICO question. With each database I generally tried to use specifiers to keep the results to less than 200 to make it easier to find suitable sources. I also used filters such as within the last 10 years, Adults, systematic reviews & meta-analysis all to ensure I was finding the most recent and credible data. I did include one source that was outside the 10-year range but contained highly valuable information. I sifted through the results section of each database by looking at the abstracts to quickly determine what was relevant. I also prioritized studies that directly compared the two dietary patterns and reported whether or not triglycerides and HDL’s had changed. Overall, this strategy led to me to find some valuable information that I was able to interpret and synthesize into a concise clinical bottom line.

Database	Search Terms Used	Number of Results	Filters/Limiters Applied
Pubmed	Hypertriglyceridemia AND Mediterranean diet OR Low-fat diet AND Triglycerides	173	Within last 10 years, Full text, Meta-analysis, Randomized Controlled Trial, Systematic Review, English, Adult 19+ years
Cochrane Library	Dyslipidemia AND Mediterranean diet OR Low-fat diet AND lipid panel improvement	8	In the last 10 years
American Journal of Medicine	Adults AND Mediterranean diet OR Low-fat diet AND Triglycerides OR HDL	30	Research article

Results found:

1. Mylavarapu, Maneeth, et al. “Mediterranean Diet versus Low-Fat Diet on Cardiovascular Disease (CVD) Risk Factors and Outcomes: A Systematic Review of RCTs.” Medicine, vol. 105, no. 11, 13 Mar. 2026, p. e47971, https://doi.org/10.1097/md.0000000000047971.

Accessed 18 Mar. 2026.

1. Study Type: Systematic Review
2. Abstract:

1. Background: The Mediterranean diet (MD) and low-fat diet (LFD) were well-known dietary interventions for cardiovascular disease prevention. However, there is an ongoing debate about the relative efficacy of improving cardiovascular (CV) risk factors and clinical outcomes between the 2. This systematic review aims to evaluate and summarize findings from randomized controlled trials (RCTs) that directly compare the MD and LFD concerning CV risk factors and clinical outcomes.
2. Methods: Per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a comprehensive literature search was conducted across PubMed, Google Scholar, SCOPUS, Science Direct, and RCTs that compared MD and LFD in adults, and reported data on CV risk factors or clinical outcomes were included.
3. Results: Our systematic review includes 11 RCTs with 5942 participants. MD significantly reduced the formation of procoagulant and prothrombotic microvesicles. Studies have also reported that MD has resulted in greater reductions in total cholesterol, cholesterol-high-density lipoproteins ratios, insulin levels, blood glucose levels, leukocyte count, and body mass index compared to LFD.
4. Conclusions: MD demonstrates superior efficacy over LFD in improving CV risk factors and outcomes. These findings could support the preferential recommendation of MD over LFD for the secondary prevention of cardiovascular diseases. Further research should explore the long-term adherence and implementation of these dietary interventions in diverse populations.
5. Keywords: cardiovascular risk factors, dietary inflammatory index, low-fat diet, Mediterranean diet, randomized control trials, systematic review
6. Key Points:

• This is a systematic review of randomized controlled trials comparing the Mediterranean diet with a low-fat diet in adults, mainly focused on cardiovascular risk factors and outcomes. A total of 11 RCTs with 5942 participants were included.
• It was determined that the Mediterranean diet generally produced more favorable improvements in cardiovascular risk factors than the low-fat diet. Across the included studies, the Mediterranean diet was associated with greater reductions in total cholesterol, triglycerides, cholesterol/HDL ratio, insulin levels, blood glucose, leukocyte count, and body mass index.
• While the main outcome of interest was standard lipid outcomes, some studies in the review also found benefits of the Mediterranean diet on inflammatory and vascular markers, such as reductions in procoagulant and prothrombotic microvesicles, as well as improvements in dietary inflammatory index and other markers of cardiometabolic health.
• Regarding more clinically important cardiovascular outcomes such as heart attacks, stroke, and heart failure, the evidence was more limited because only 2 studies specifically reported major cardiovascular events. One of these showed that the Mediterranean diet reduced major cardiovascular events compared with the low-fat diet in patients with established coronary artery disease, while another found no significant difference between the 2 diets. Overall, the review suggests that the Mediterranean diet may be more effective than a low-fat diet for improving cardiovascular risk factors, although evidence on hard outcomes remains more limited.

4. Why I chose this study:

• I chose this study because it directly addresses my PICO question in how it compares the Mediterranean diet with a low-fat diet. The evidence proposed by this study is also of a high-level considering that it is a systematic review of randomized controlled trials. Furthermore, evidence was collected from 11 different RCT’s with 5942 participants which further adds to credibility of the findings. Many of the outcomes that were included in this study are directly applicable to my patient’s presentation such as the triglycerides, HDL’s, and other cardiovascular risk factors. Beyond these parameters I found considerable value in the broader context of the study as it addressed cardiometabolic and cardiovascular effects which are useful in making recommendations and counseling patients with dyslipidemia.

5. Link to study:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12991705

2. Rees, Karen, et al. “Mediterranean-Style Diet for the Primary and Secondary Prevention of Cardiovascular Disease.” Cochrane Database of Systematic Reviews, vol. 3, no. 3, 13 Mar. 2019, https://doi.org/10.1002/14651858.cd009825.pub3

1. Study type: Systematic Review
2. Abstract:

1. Background: The Seven Countries study in the 1960s showed that populations in the Mediterranean region experienced lower coronary heart disease (CHD) mortality probably as a result of different dietary patterns. Later observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on cardiovascular disease (CVD) risk factors, but clinical trial evidence is more limited.
2. Objective: To determine the effectiveness of a Mediterranean‐style diet for the primary and secondary prevention of CVD.
3. Methods: They searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9); MEDLINE (Ovid, 1946 to 25 September 2018); Embase (Ovid, 1980 to 2018 week 39); Web of Science Core Collection (Thomson Reuters, 1900 to 26 September 2018); DARE Issue 2 of 4, 2015 (Cochrane Library ); HTA Issue 4 of 4, 2016 (Cochrane Library ); NHS EED Issue 2 of 4, 2015 (Cochrane Library). They searched trial registers and applied no language restrictions.

They selected randomised controlled trials (RCTs) in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). Both of the following key components were required to reach our definition of a Mediterranean‐style diet: high monounsaturated/saturated fat ratio (use of olive oil as main cooking ingredient and/or consumption of other traditional foods high in monounsaturated fats such as tree nuts) and a high intake of plant‐based foods, including fruits, vegetables and legumes. Additional components included: low to moderate red wine consumption; high consumption of whole grains and cereals; low consumption of meat and meat products and increased consumption of fish; moderate consumption of milk and dairy products. The intervention could be dietary advice, provision of relevant foods, or both. The comparison group received either no intervention, minimal intervention, usual care or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow‐up periods of three months or more defined as the intervention period plus post intervention follow‐up.

4. Results:

In this substantive review update, 30 RCTs (49 papers) (12,461 participants randomised) and seven ongoing trials met our inclusion criteria. The majority of trials contributed to primary prevention: comparisons 1 (nine trials) and 2 (13 trials). Secondary prevention trials were included for comparison 3 (two trials) and comparison 4 (four trials plus an additional two trials that were excluded from the main analyses due to published concerns regarding the reliability of the data).

Two trials reported on adverse events where these were absent or minor (low‐ to moderate‐quality evidence). No trials reported on costs or health‐related quality of life.

Primary prevention

The included studies for comparison 1 did not report on clinical endpoints (CVD mortality, total mortality or non‐fatal endpoints such as myocardial infarction or stroke). The PREDIMED trial (included in comparison 2) was retracted and re‐analysed following concerns regarding randomisation at two of 11 sites. Low‐quality evidence shows little or no effect of the PREDIMED (7747 randomised) intervention (advice to follow a Mediterranean diet plus supplemental extra‐virgin olive oil or tree nuts) compared to a low‐fat diet on CVD mortality (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.50 to 1.32) or total mortality (HR 1.0, 95% CI 0.81 to 1.24) over 4.8 years. There was, however, a reduction in the number of strokes with the PREDIMED intervention (HR 0.60, 95% CI 0.45 to 0.80), a decrease from 24/1000 to 14/1000 (95% CI 11 to 19), moderate‐quality evidence). For CVD risk factors for comparison 1 there was low‐quality evidence for a possible small reduction in total cholesterol (‐0.16 mmol/L, 95% CI ‐0.32 to 0.00) and moderate‐quality evidence for a reduction in systolic (‐2.99 mmHg (95% CI ‐3.45 to ‐2.53) and diastolic blood pressure (‐2.0 mmHg, 95% CI ‐2.29 to ‐1.71), with low or very low‐quality evidence of little or no effect on LDL or HDL cholesterol or triglycerides. For comparison 2 there was moderate‐quality evidence of a possible small reduction in LDL cholesterol (‐0.15 mmol/L, 95% CI ‐0.27 to ‐0.02) and triglycerides (‐0.09 mmol/L, 95% CI ‐0.16 to ‐0.01) with moderate or low‐quality evidence of little or no effect on total or HDL cholesterol or blood pressure.

Secondary prevention

For secondary prevention, the Lyon Diet Heart Study (comparison 3) examined the effect of advice to follow a Mediterranean diet and supplemental canola margarine compared to usual care in 605 CHD patients over 46 months and there was low‐quality evidence of a reduction in adjusted estimates for CVD mortality (HR 0.35, 95% CI 0.15 to 0.82) and total mortality (HR 0.44, 95% CI 0.21 to 0.92) with the intervention. Only one small trial (101 participants) provided unadjusted estimates for composite clinical endpoints for comparison 4 (very low‐quality evidence of uncertain effect). For comparison 3 there was low‐quality evidence of little or no effect of a Mediterranean‐style diet on lipid levels and very low‐quality evidence for blood pressure. Similarly, for comparison 4 where only two trials contributed to the analyses there was low or very low‐quality evidence of little or no effect of the intervention on lipid levels or blood pressure.

5. Conclusion: Despite the relatively large number of studies included in this review, there is still some uncertainty regarding the effects of a Mediterranean‐style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention. The quality of evidence for the modest benefits on CVD risk factors in primary prevention is low or moderate, with a small number of studies reporting minimal harms. There is a paucity of evidence for secondary prevention. The ongoing studies may provide more certainty in the future.
6. Key points:

1. This study is a systematic review of RCT’s that studied the effects of consuming a mediterranean diet in both the primary and secondary prevention of cardiovascular disease. Included in this review were 30 RCT’s with a total of 12,461 participants.
2. For primary prevention it was determined that when the mediterranean-style diet was compared with other dietary interventions such as low-fat diets there was a small and modest reduction in triglycerides and LDL cholesterol. In terms of HDL cholesterol there was little or no effect. Benefits were also found in terms of blood pressure and total cholesterol in certain comparisons.
3. Similar to the last study there were broader outcomes addressed by this study. For example, it found a reduction in stroke with the Mediterranean diet compared with a low-fat diet but little to no effect on total mortality, CV mortality, or myocardial infarction. In terms of secondary prevention, there was some evidence of reduced cardiovascular and total mortality, but the available studies were fewer in quantity, and the overall quality of that evidence was limited.
4. Overall, this review suggests that a Mediterranean diet may provide modest benefit for some cardiovascular risk factors and this includes a small reduction in triglycerides. However, the overall evidence remains mostly uncertain because of the differences between the studies and a lack of strong evidence on major clinical outcomes.
5. Why I chose this study:

• Like my previous choice this study contains high-level evidence being that it is a systematic review of randomized controlled trials. It was provided pooled estimates and quality ratings which are helpful in determining the strength and reliability of the evidence. What also made me choose it is the fact that it helps to answer my PICO question directly, this is because it examined outcomes such as triglycerides, HDL, LDL, and other lipid-related risk factors. I was also inclined to choose this study because of the fact that it compares the Mediterranean-style diet with low-fat diets of course, but it also compared it to minimal intervention or usual care. Overall, it provided me with solid evidence that the Mediterranean diet does offer benefit, but this benefit is mostly modest as opposed to dramatic, this is helpful when considering how to counsel patients on their diet.

5. Link to study: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009825.pub3/full?highlightAbstract=secondari%7Cstyl%7Cdisease%7Cfor%7Cdiseas%7Ccardiovascular%7Cprimari%7Cthe%7Csecondary%7Cmediterranean%7Cprevent%7Cfour%7Cof%7Cstyle%7Cdiet%7Cprevention%7Cprimary
   

3. Nordmann, Alain J., et al. “Meta-Analysis Comparing Mediterranean to Low-Fat Diets for Modification of Cardiovascular Risk Factors.” The American Journal of Medicine, vol. 124, no. 9, Sept. 2011, pp. 841-851.e2, https://doi.org/10.1016/j.amjmed.2011.04.024.

1. Study Type: Meta-analysis of RCT’s
2. Abstract:

1. Background: Evidence from individual trials comparing Mediterranean to low-fat diets to modify cardiovascular risk factors remains preliminary.
2. Objective: To identify randomized controlled trials comparing Mediterranean to low-fat diets in overweight/obese individuals, with a minimum follow-up of 6 months, reporting intention-to-treat data on cardiovascular risk factors.
3. Methods: They searched the electronic databases MEDLINE, EMBASE, Biosis, Web of Science (all from their inception to January 2011), and the Cochrane Central Register of Controlled Trials using the terms “diets, fat restricted [Mesh]“ and “Mediterranean diets.” We restricted the search to articles indexed as clinical trial (publication type) and those that included the root random in their titles or abstracts. We also searched reference lists of identified articles, clinical trial registries of ongoing or planned trials, recently published editorials and reviews on the topic, and we contacted experts in the field for further eligible trials. No language restrictions were imposed.

Study Selection and Quality Assessment

Two authors (KS, AN) independently assessed trial eligibility and quality. Eligible trials had to compare Mediterranean with low-fat diets in either overweight/obese patients with at least one additional cardiovascular risk factor (primary prevention) or patients with established coronary artery disease (secondary prevention); to have a randomized controlled design and a minimum follow-up of 6 months; and to report intention-to-treat data on changes of body weight, blood pressure, and lipid values. We included trials where Mediterranean diets were defined as diets with moderate fat intake (where the main sources of added fat were olive oil and nuts), rich in vegetables, and low in red meat (with poultry and fish replacing beef and lamb).12 Low-fat diets were defined as diets aiming at an energy intake with ≤30% of calories from fat.13 We evaluated the quality of trials according to concealment of treatment allocation; blinding of patients, caregivers, and clinical outcome assessors; full description of losses to follow-up and withdrawals; the proportion of patients with complete clinical follow-up; and trials not stopping early for benefit.14,15

Outcomes and Data Extraction

Two authors (KS, AN) independently extracted published trial data and additional data provided by the original investigators. We considered the following cardiovascular risk factors baseline and 2 years of follow-up as outcomes of interest: mean differences in body weight, body mass index, waist circumference, systolic and diastolic blood pressure, total high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein (hs-CRP), fasting plasma glucose, and serum insulin between. In addition, we extracted any clinical outcome data when available.

Statistical Analysis

We pooled treatment effects and calculated weighted mean differences for all risk factors between patients randomized to Mediterranean and low-fat diets by using a random-effects model.16 Because we could not obtain standard deviations for the differences of the means of risk factors from one trial,17 we first calculated the standard errors by dividing the differences of the means by the percentage points of the t-distributions corresponding to the P-values given, and then calculated the standard deviations by multiplying the standard errors by the square roots of the number of observations.

We investigated the presence of publication bias by means of funnel plots.18 We tested for heterogeneity with the Cochran Q test and measured inconsistency (I2; the percentage of total variance across studies that is due to heterogeneity rather than chance) of treatment effects across all cardiovascular risk factors of interest.19,20 We conducted sensitivity analyses to examine treatment effects according to quality components of included trials; primary versus secondary prevention trials, trials with balanced versus trials with unbalanced co-interventions, and trials with restriction of daily calorie intake versus trials without restriction of daily calorie intake. We used Stata 10.1 (StataCorp LP, College Station, Tex) for data analysis.

4. Results: Seven RCTs were included in the review (3,650 patients). All trials had an open design. Allocation concealment was adequate in five trials. Blinding assessment for all outcomes was adequate in two trials. Follow-up ranged from two to four years (where reported). Most trials had rates of loss to follow up less than 10%. No trial was stopped early for benefit. Compared with low-fat diets, Mediterranean diets were associated with a significant reduction in body weight (WMD -2.24kg, 95% CI -3.85 to -0.63; six RCTs), body mass index (WMD -0.56 kg/m2, 95% CI -1.01 to -0.11; six RCTs), systolic blood pressure (WMD -1.70mmHg, 95% CI -3.35 to -0.05; six RCTs), diastolic blood pressure (WMD -1.47mmHg, 95% CI -2.14 to -0.81; six RCTs), and total cholesterol (WMD -7.35mg/dL, 95% CI-10.32 to -4.39; six RCTs) at two years follow-up. Substantial heterogeneity was observed for these outcomes (Ι² ranged from 60% to 97%). Sensitivity analyses did not materially alter the results. There was no evidence of publication bias.
5. Conclusions & Relevance: Mediterranean diets appeared to be more effective than low-fat diets in inducing clinically relevant long-term changes in cardiovascular risk factors.
6. Key Points:

1. This is yet another systematic review and meta-analysis of RCT’s comparing a mediterranean diet to a low-fat diet in obese adults who were found to have increased cardiovascular risks. There were 7 RCT’s with 3,650 participants and they were tracked over the span of about 2 years.
2. This study also found that the mediterranean diet demonstrated more favorable improvements in several outcomes such as body weight, BMI, systolic and diastolic blood pressure, fasting glucose, and total cholesterol.
3. The main outcomes from this study that were most relevant to my question were that the mediterranean diet produced more favorable changes in triglyceride levels. However, there were no statistical differences in HDL cholesterol between the Mediterranean and low-fat diet groups.
4. Overall, this study suggests that the Mediterranean diet may in fact be more effective than a low-fat diet for improving multiple cardiometabolic risk factors including triglyceride levels. The evidence for HDL improvement was not significant and there was limited evidence on actual clinical outcomes.
5. Why I chose this study:

• I chose this study because like the others the evidence is from a considerably high level being that it is a meta-analysis of RCT’s. All of the included RCT’s also directly compared a Mediterranean diet with a low-fat diet. The participants in the study were all obese which is even more aligned with the patient I encountered who was also obese. The study examined several cardiometabolic outcomes including triglycerides and HDL cholesterol which were the core of my PICO question. Another important element from this study was the fact that it assessed outcomes over a period of about 2 years which is significant since dietary recommendations are meant to inspire sustained and progressive changes. Even though this is an older study I still chose it because of the fact that it included RCT’s with long-term follow-up. Nutritional research that includes large head-to-head trials are not as frequently conducted and the length of time participants were followed offers a different perspective when compared to short-term diet studies.

5. Link to study: https://www.amjmed.com/article/S0002-9343(11)00410-4/fulltext

What is the clinical “bottom line” derived from these articles in answer to your question?

Overall, the collection of evidence from these three studies suggests that a Mediterranean diet is associated with an inconsistent advantage when it comes to improving triglyceride levels and boosting HDL’s. However, the evidence does suggest that a mediterranean diet is at least comparable to and in some cases modestly better than a low-fat diet for improving cardiometabolic risk factors. For example, the 2011 meta-analysis by Nordmann et al. found that triglyceride values improved more favorably in those consuming a mediterranean diet, but the same effect was not fully observed in terms of HDL levels. The 2019 Cochrane review by Rees et al. found that in primary prevention the Mediterranean diet was associated with only a small reduction in triglycerides with little to no effects on HDL levels. In terms of secondary prevention, the evidence for lipid changes was practically unremarkable. Finally, the 2026 systematic review by Mylavarapu et al. did show some greater reductions in triglycerides observed in the Mediterranean diet group but no clear benefit for HDL improvement. It did demonstrate however that the Mediterranean diet tends to produce better overall cardiovascular risk factor improvements as compared to a low-fat diet.

Ultimately these studies provide support to the idea that in adults with dyslipidemia can benefit from consuming a Mediterranean diet as a reasonable and evidence-based alternative to a low-fat diet. The data shows that there is some modest benefit for triglycerides and cardiometabolic health, but it also consistently shows that any improvement in HDL’s is limited in terms of evidence.