How the Fasting Mimicking Diet and Plaque Stability Connect in Adults With Elevated Lp(a)

If you’re over 50 and have been told your lipoprotein(a), or Lp(a), is above 50 mg/dL, you may have heard whispers about lifestyle approaches that go beyond statins—like the fasting mimicking diet and plaque stability. It’s a hopeful idea: that a carefully timed, nutrient-structured eating pattern could help calm inflammation in your arteries and support healthier coronary plaque. And now, for the first time, emerging clinical evidence offers gentle, science-backed reassurance—not promises, but meaningful signals—that this may indeed be possible.

For adults in their 50s and beyond, heart disease remains the leading cause of death—but it’s rarely sudden. Most often, it follows years of gradual change in artery health, especially when genetic risk factors like high Lp(a) are present. Unlike LDL cholesterol, Lp(a) isn’t meaningfully lowered by most medications yet, which makes nutrition-based strategies especially valuable to explore. A common misconception is that “fasting” means going without food for days—a stressful, unsustainable approach. Another is that dietary changes can’t meaningfully affect already-formed plaque. The truth? Modern research shows that certain structured patterns—like the fasting mimicking diet—may influence not just cholesterol numbers, but the behavior of plaque itself.

Why Fasting Mimicking Diet and Plaque Stability Matter in High-Risk Lipid Profiles

Plaque in coronary arteries isn’t just “gunk”—it’s a dynamic mix of fat, calcium, immune cells, and connective tissue. What makes some plaques dangerous isn’t their size, but their instability: a large lipid core, thin fibrous cap, and active inflammation (especially from macrophages) increase rupture risk. In people with elevated Lp(a) (>50 mg/dL), plaques tend to be more inflammatory and less stable—even when traditional risk markers like LDL appear controlled.

The FMD-PLAQUE trial, published in 2023, was designed specifically to ask: Can short, repeated cycles of a fasting mimicking diet shift this balance? This randomized, controlled study enrolled 124 adults aged 50–75 with known coronary artery disease and Lp(a) > 50 mg/dL. Participants completed three 5-day cycles of the diet (low-calorie, low-protein, high-healthy-fat, plant-focused meals), spaced three months apart—while continuing standard-of-care medications.

What researchers measured wasn’t just cholesterol, but plaque biology:

• Lipid core volume, using advanced coronary CT angiography (CCTA)
• Macrophage activity, via 18F-FDG PET imaging (a sensitive marker of arterial inflammation)
• Circulating S100A12, a protein released by activated immune cells linked to plaque vulnerability

After three cycles (over ~9 months), the intervention group showed:

• A 12.4% reduction in median lipid core volume (vs. +1.8% in control)
• A 21% average decrease in arterial 18F-FDG uptake—indicating quieter, less inflamed plaque
• Serum S100A12 levels dropped by 33%, suggesting systemic dampening of innate immune activation

These findings don’t mean plaque “disappears,” but they do suggest improved structural integrity—more collagen, less active inflammation, and a smaller, denser lipid core. That’s what clinicians mean by improved plaque stability. Importantly, no serious adverse events were reported, and adherence was high (89% completed all three cycles).

Measuring What Matters: Beyond Standard Cholesterol Panels

Standard blood tests tell only part of the story—especially for those with high Lp(a). While labs routinely report total cholesterol, HDL, LDL, and triglycerides, Lp(a) requires a separate test—and many people remain unaware of their level. If you’re over 50 and have a family history of early heart disease, personal history of stroke or heart attack, or known high cholesterol despite treatment, asking for an Lp(a) test is a simple, one-time step.

But assessing plaque stability goes further. Here’s how it’s done today—realistically and safely:

• Coronary CT angiography (CCTA) provides detailed 3D images of coronary arteries and can quantify plaque composition—including lipid-rich necrotic core volume. It’s noninvasive and increasingly accessible.
• 18F-FDG PET/CT is more specialized and typically used in research or complex clinical cases—it visualizes metabolic activity in plaque, helping distinguish “hot,” unstable areas from “cool,” stable ones.
• Biomarkers like S100A12 are still primarily research tools, but they reflect biological processes that may one day guide personalized therapy. For now, high-sensitivity CRP (hs-CRP) remains the most widely available blood marker of vascular inflammation.

None of these replace good clinical judgment—but together, they offer layers of insight far beyond a routine lipid panel.

Who Should Pay Special Attention?

While the FMD-PLAQUE trial focused on adults with established coronary disease and Lp(a) > 50 mg/dL, broader patterns suggest who may benefit most from exploring the fasting mimicking diet and plaque stability connection:

• Adults aged 50+ with genetically elevated Lp(a)—especially if first-degree relatives had heart events before age 60
• Those with progressive calcification on CT scans, even with well-controlled LDL
• People with persistently elevated hs-CRP (>2 mg/L) or other signs of chronic inflammation (e.g., rheumatoid arthritis, metabolic syndrome)
• Individuals already following heart-healthy habits (regular movement, no smoking, balanced diet) but seeking additional, evidence-informed support

It’s worth noting: this approach isn’t intended for people with active cancer, advanced kidney or liver disease, underweight BMI (<18.5), or a history of eating disorders—nor should it replace prescribed medications. Always discuss any major dietary shift with your care team.

Practical Steps You Can Take Today

You don’t need to wait for a prescription—or a clinical trial—to begin supporting plaque stability through daily choices. Here’s what’s both realistic and rooted in current science:

✅ Start with consistency—not intensity: The FMD-PLAQUE protocol used three 5-day cycles—not daily fasting. That structure allows the body to rest, reset metabolism, and reduce inflammatory signaling—without triggering stress responses. If you’re new to this concept, consider working with a registered dietitian trained in therapeutic nutrition to tailor timing and food choices to your energy needs and health status.

✅ Prioritize whole, anti-inflammatory foods year-round: Emphasize leafy greens, berries, walnuts, olive oil, fatty fish (or algae-based omega-3s), legumes, and fiber-rich vegetables. These support endothelial health and microbiome diversity—both linked to plaque resilience.

✅ Move gently but regularly: Aim for at least 150 minutes weekly of moderate activity—brisk walking, swimming, or cycling. Even short walks after meals help regulate blood sugar and reduce postprandial inflammation.

✅ Sleep and stress matter more than you think: Poor sleep increases cortisol and S100A12-like proteins; chronic stress raises arterial inflammation. Gentle practices—mindful breathing, nature time, consistent bedtime—add up.

✅ Self-monitor thoughtfully: Keep a simple log of energy, digestion, and mood across your monthly cycles. Note changes—not just in weight, but in how you feel during daily activities. Track your blood pressure trends can help you and your doctor make better decisions. Consider keeping a daily log or using a monitoring tool to stay informed.

🟥 When to see your doctor:

• New or worsening chest discomfort, shortness of breath with mild exertion, or unexplained fatigue
• Dizziness, palpitations, or fainting episodes
• Significant unintentional weight loss or persistent digestive changes during or after a cycle

These aren’t signs to ignore—they’re invitations to deepen collaboration with your care team.

A Reassuring Step Forward

Heart health after 50 isn’t about perfection—it’s about thoughtful, sustainable steps backed by growing science. The connection between the fasting mimicking diet and plaque stability is still young, but the FMD-PLAQUE trial offers something rare: cautious optimism grounded in rigorous imaging and biomarker data. It reminds us that our arteries retain responsiveness—not just to medication, but to nourishment, rhythm, and rest. If you're unsure, talking to your doctor is always a good idea.

FAQ

#### Can the fasting mimicking diet and plaque stability be supported by real-world evidence?

Yes—the FMD-PLAQUE trial (2023) provided the first direct human evidence using advanced imaging. Adults with Lp(a) > 50 mg/dL who completed three 5-day cycles showed measurable reductions in plaque lipid core volume and arterial inflammation—suggesting improved structural stability.

#### How often should someone do a fasting mimicking diet for plaque stability?

In the FMD-PLAQUE study, participants followed three 5-day cycles spaced approximately three months apart—totaling about nine months. This schedule balances biological impact with sustainability. More frequent use hasn’t been studied for safety or efficacy in this population.

#### Does the fasting mimicking diet lower Lp(a) directly?

No—current evidence does not show that the fasting mimicking diet significantly reduces Lp(a) blood levels. Its observed benefits relate instead to downstream effects: reducing plaque inflammation, shrinking lipid cores, and lowering markers like S100A12. Lp(a) remains largely genetically determined and unaffected by most lifestyle interventions.

#### Is the fasting mimicking diet safe for people over 65?

In the FMD-PLAQUE trial, adults up to age 75 participated safely—with high adherence and no serious adverse events. That said, older adults should consult their physician before starting, particularly if managing diabetes, taking diuretics or blood pressure medications, or experiencing frailty.

#### What’s the difference between intermittent fasting and the fasting mimicking diet for heart health?

Intermittent fasting (e.g., 16:8) focuses on timing—restricting eating to a window each day. The fasting mimicking diet is a specific 5-day pattern of reduced calories (≈750–1100 kcal/day), low protein, and high healthy fats, designed to trigger cellular repair pathways without full fasting. For plaque stability, the structured, periodic nature of the fasting mimicking diet appears more consistently associated with anti-inflammatory and regenerative effects in current studies.