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CETP and Your Response to the Mediterranean Diet

The Mediterranean diet is a heart healthy eating pattern that emphasizes vegetables, fruits, legumes, whole grains, nuts, seeds, extra virgin olive oil, and regular fish intake while limiting red meat and sweets. This pattern is rich in fiber, antioxidants, and healthy fats, which support better cholesterol levels, improved insulin sensitivity, and overall metabolic health.

One reason people respond differently to the same diet is genetic variation. The CETP gene influences how cholesterol and triglycerides move between blood lipoproteins, affecting levels of HDL and LDL cholesterol. A common variant in CETP, called rs3764261, is linked to how strongly blood lipids respond to a Mediterranean eating pattern. Below we describe what each genotype may mean for your lipid response and give practical diet, supplement, lifestyle, and testing suggestions to help you get the most benefit from a Mediterranean style of eating.

How CETP affects lipid metabolism in plain language

  • CETP produces a protein that moves cholesterol and triglycerides between particles in your blood.
  • Changes in CETP activity can alter HDL levels and how quickly cholesterol is removed from tissues and returned to the liver.
  • Some CETP variants are associated with larger increases in HDL and greater drops in triglycerides when people follow a Mediterranean diet.

Practical eating and lifestyle guidance

No matter your genotype, focusing on a Mediterranean pattern will support heart and metabolic health. Below are key components to emphasize and small changes you can apply right away.

  • Make plants the core of most meals: vegetables, fruits, legumes, and whole grains.
  • Use extra virgin olive oil as your main fat. Aim for a few tablespoons daily across meals and salads.
  • Include nuts and seeds several times per week for healthy unsaturated fats and plant sterols.
  • Eat fatty fish like salmon, sardines, mackerel, or trout at least twice weekly for omega 3s.
  • Limit red and processed meats. Choose poultry, fish, legumes, and plant proteins instead.
  • Prefer whole fruit to fruit juice and fiber rich carbohydrates to refined grains.
  • Minimize added sugar and highly processed snacks and desserts.
  • Stay physically active, aim for strength training plus aerobic movement, and prioritize sleep and stress management.

Supplements and other considerations

Supplements can support heart health in some situations. Discuss any supplements with your healthcare provider before starting.

  • Omega 3 fish oil: may help reduce triglycerides and support cardiovascular health when diet is not enough.
  • Viscous fibers: psyllium or oat beta glucan can help lower LDL cholesterol when used consistently.
  • Magnesium: supports metabolic health and sleep in people with low dietary intake.
  • Plant sterols: can modestly reduce LDL when taken as directed.
  • Vitamin D: check levels and supplement only if deficient based on your provider's advice.

Monitoring and tests to consider

  • Fasting or non fasting lipid panel: total cholesterol, HDL, LDL, triglycerides to track response to diet.
  • Non HDL cholesterol and ApoB if available for more detailed risk assessment.
  • HbA1c or fasting glucose if you are monitoring insulin sensitivity or have risk factors for diabetes.
  • Work with your healthcare provider to set testing frequency based on baseline risk and changes you make.

Genetic interpretations for rs3764261

2 effect alleles (AA)

You carry two copies of the effect allele. This genotype is associated with more favorable changes in blood lipids when following a Mediterranean diet. Specifically, people with AA often see larger increases in HDL, the so called good cholesterol, and greater reductions in triglycerides.

Why this matters: CETP encodes a protein that shuttles cholesterol and triglycerides between lipoproteins. With the AA genotype, the way CETP interacts with diet appears to boost reverse cholesterol transport and improve triglyceride handling when the diet is rich in extra virgin olive oil, nuts, seeds, fish, vegetables, legumes, and whole grains.

Practical tips:

  • Prioritize consistent intake of extra virgin olive oil and mixed nuts to support HDL increases.
  • Include fatty fish twice weekly to further reduce triglycerides.
  • Combine dietary changes with regular aerobic and resistance exercise to enhance lipid improvements.
  • Monitor lipids periodically to document improvements and adjust as needed with your healthcare provider.
1 effect allele (AC)

You carry one copy of the effect allele. This genotype is associated with favorable changes in HDL and triglycerides when following a Mediterranean diet, though effects may be more moderate compared to two effect alleles.

Why this matters: Your CETP variant can interact with unsaturated fats and plant bioactives to support healthier lipid transfer between particles and improve reverse cholesterol transport. This can help increase HDL and lower triglycerides when you consistently follow a Mediterranean pattern.

Practical tips:

  • Emphasize olive oil, nuts, seeds, legumes, and whole grains as staples.
  • Aim for at least two servings of fatty fish each week for omega 3 support.
  • Add high fiber foods and viscous fiber sources if LDL lowering is also a goal.
  • Track lipids with your provider to measure progress and tailor recommendations.
0 effect alleles (CC)

You carry two copies of the non effect allele. The CC genotype is associated with typical CETP activity and a standard lipid response to a Mediterranean diet. You may not see the enhanced HDL increases or triglyceride reductions observed with some CETP effect allele carriers, but you can still achieve meaningful improvements in cholesterol and metabolic health.

Practical tips:

  • Follow the Mediterranean pattern with olive oil, nuts, seeds, fatty fish, legumes, and abundant vegetables to support lipid health.
  • Focus on weight management, regular exercise, and limiting refined carbs and added sugars to maximize benefits.
  • Consider viscous fiber and plant sterols for LDL lowering if needed after discussing with your provider.
  • Check lipids regularly and work with your healthcare professional to decide if additional interventions are appropriate.

Final notes and important disclaimer

PlexusDx provides genetic information to help you understand potential predispositions and how lifestyle may interact with your genes. This content is educational and does not provide medical advice. Always consult with your healthcare provider before making changes to diet, starting supplements, or altering medications. Your provider can interpret these findings in the context of your overall health, family history, and medical needs.