Perfect cholesterol numbers don't guarantee a healthy heart. This counterintuitive reality has emerged from recent research on carnivore and ketogenic dieters, challenging fundamental assumptions about cardiovascular health.

A groundbreaking study has sent shockwaves through the low-carb community. The KETO-CTA trial, examining plaque formation in lean, metabolically healthy ketogenic dieters, revealed something unexpected: despite favorable lipid profiles, some participants showed progression of arterial plaque.

This finding presents a metabolic paradox. If high cholesterol doesn't cause heart disease in these individuals, what does?

The answer may lie not in cholesterol at all, but in a phenomenon called "insulin suppression" – a metabolic state unique to strict carnivore diets that could increase cardiovascular risk through an entirely different mechanism.

The Lean Mass Hyper-Responder Phenomenon

To understand this paradox, we must first understand Lean Mass Hyper-Responders (LMHRs). These individuals show dramatic increases in LDL cholesterol when following very low-carbohydrate diets, with LDL-C ≥200 mg/dL, HDL-C ≥80 mg/dL, and triglycerides ≤70 mg/dL – a profile that defies conventional cardiovascular risk assessment.

The LMHR phenomenon typically occurs in lean, metabolically healthy individuals who are highly fat-adapted. Their cholesterol numbers would terrify conventional cardiologists, yet these people often show excellent health markers otherwise.

This profile has led many to believe they're immune to cardiovascular disease. The recent KETO-CTA trial suggests otherwise.

When researchers compared plaque progression in LMHRs to similar individuals eating standard American diets, they found something surprising: both groups showed similar rates of plaque formation. This contradicted the hypothesis that the "perfect" metabolic profile of LMHRs would protect against atherosclerosis.

Beyond Insulin Resistance

To understand what's happening, we need to distinguish between three metabolic states: insulin sensitivity, insulin resistance, and insulin suppression.

Insulin sensitivity represents optimal metabolism – cells respond efficiently to insulin, blood sugar regulation works smoothly, and metabolic health thrives. This state typically features moderate insulin levels that respond appropriately to food intake.

Insulin resistance occurs when cells become unresponsive to insulin signals. The pancreas compensates by producing more insulin, leading to chronically elevated insulin levels (hyperinsulinemia). This state drives many modern diseases, including type 2 diabetes and cardiovascular disease.

But there's a third state that's rarely discussed: insulin suppression.

Insulin suppression occurs when insulin production itself is inhibited. Unlike insulin resistance, where insulin levels are high but ineffective, insulin suppression features abnormally low insulin levels. This state commonly develops in strict carnivore dieters who consume virtually no carbohydrates.

Why does this happen? The answer involves a crucial gut hormone called GLP-1.

The Missing GLP-1 Signal

GLP-1 (glucagon-like peptide-1) is a hormone produced in the intestines that plays multiple roles in metabolism. It stimulates insulin release, reduces glucagon secretion, slows gastric emptying, and helps regulate appetite.

Here's the critical point: carbohydrates are necessary to trigger significant GLP-1 production.

In a carnivore diet completely devoid of carbohydrates, GLP-1 signaling becomes severely diminished. Without this signal, insulin release is minimal – even when blood glucose rises from protein conversion (gluconeogenesis).

The result? Chronically low insulin levels, abnormally high glucagon levels, and difficulty clearing blood sugar – a pattern that mimics some aspects of diabetes despite the absence of dietary carbohydrates.

This metabolic state explains why some LMHRs develop rising blood sugars and A1C levels over time, despite consuming zero carbs.

The Plaque Connection

How does insulin suppression contribute to plaque formation? The mechanism appears to involve several factors:

1. Inadequate blood sugar regulation. Without sufficient insulin response, blood glucose levels may rise and fluctuate more than expected, especially after protein-rich meals. This glycemic variability can promote vascular inflammation.

2. Hormonal imbalance. The extremely high glucagon-to-insulin ratio creates a metabolic environment that may promote inflammation and lipid dysregulation at the cellular level.

3. Reduced metabolic flexibility. The body becomes highly adapted to fat metabolism but loses some ability to handle glucose efficiently when it does appear.

The KETO-CTA trial found that in lean, metabolically healthy people on ketogenic diets, baseline plaque was associated with plaque progression. Interestingly, neither total exposure nor changes in baseline levels of ApoB and LDL-C were associated with changes in plaque – suggesting factors beyond cholesterol are at work.

This finding aligns with the insulin suppression hypothesis. The problem isn't cholesterol – it's the metabolic environment created by extreme carbohydrate restriction in genetically susceptible individuals.

The Genetic Component

Not everyone on a carnivore diet develops insulin suppression to the same degree. Genetic factors play a significant role in determining individual responses.

Those from "diabesogenic" genetic backgrounds – people genetically predisposed to develop type 2 diabetes when consuming high-carbohydrate diets – appear particularly vulnerable to the negative effects of insulin suppression when following strict carnivore diets.

These individuals often show rising blood sugars, increasing A1C levels (typically in the 5.7-5.9 range), and signs of vascular inflammation despite consuming zero carbohydrates.

The genetic predisposition toward vascular inflammation, combined with the metabolic effects of insulin suppression, creates the perfect storm for plaque formation – even with "perfect" cholesterol numbers.

Strategic Carbohydrate Inclusion

The solution to this paradox isn't returning to a high-carbohydrate diet. Rather, it involves strategic carbohydrate inclusion – just enough to stimulate GLP-1 production and maintain insulin signaling without triggering insulin resistance.

For most people, this means incorporating a small amount of carbohydrates into an otherwise low-carb diet. The optimal amount varies by individual, but often ranges from 30-50 grams of carbohydrates daily.

Good options include:

1. Berries and low-glycemic fruits, which provide carbohydrates along with beneficial polyphenols and antioxidants

2. Small amounts of starchy vegetables like sweet potatoes or winter squash

3. Modest servings of properly prepared legumes for those who tolerate them

4. High-fat dairy products like full-fat yogurt or kefir, which contain some lactose (milk sugar)

The timing of carbohydrate consumption also matters. Including carbohydrates with protein-rich meals can help optimize the insulin response to protein and improve overall glucose metabolism.

Monitoring and Personalization

How can you tell if you're experiencing insulin suppression? Several markers provide clues:

1. Rising fasting blood glucose despite strict carbohydrate restriction

2. Increasing A1C levels over time

3. Extremely high LDL and total cholesterol (the LMHR pattern)

4. Symptoms like reduced exercise performance, fatigue, or hormonal changes

5. Low fasting insulin levels combined with elevated blood glucose

The most effective approach involves personalized monitoring. Regular blood tests can track glucose, A1C, insulin, and lipid markers. Continuous glucose monitors provide valuable insights into glucose variability throughout the day.

For those concerned about cardiovascular risk, coronary calcium scans and CIMT (Carotid Intima-Media Thickness) tests can monitor arterial health over time.

The Therapeutic Paradox

Here lies another paradox: strict carnivore diets can be powerful therapeutic tools for metabolic healing, particularly for those with insulin resistance, obesity, or inflammatory conditions.

The rapid improvements many experience when first adopting a carnivore diet are real and significant. These diets eliminate problematic foods, reduce inflammation, and can dramatically improve insulin sensitivity in the short term.

However, what works as a therapeutic intervention may not be optimal as a lifelong strategy. The metabolic environment that facilitates rapid healing may create different challenges when maintained indefinitely.

This explains why many long-term carnivore dieters eventually reintroduce small amounts of carbohydrates – not because they "failed" at carnivore, but because they're optimizing for long-term metabolic health.

Beyond Dogma

The carnivore paradox highlights the importance of moving beyond dietary dogma. Human physiology is complex and individualized. What works for one person may not work for another, and what works in the short term may not be optimal long-term.

The goal isn't adherence to a particular dietary label but optimizing metabolic health. For most people, this means finding the right balance – enough carbohydrate restriction to maintain insulin sensitivity, but not so much that it leads to insulin suppression.

This balanced approach acknowledges the benefits of carbohydrate restriction while respecting the body's need for certain metabolic signals that only carbohydrates can efficiently provide.

The emerging science suggests that metabolic flexibility – the ability to efficiently use both fat and glucose for fuel – may be more important for long-term health than rigid adherence to any particular macronutrient ratio.

The Path Forward

For those following carnivore or very low-carb diets, these findings don't necessarily mean abandoning your approach. Rather, they suggest considering strategic modifications based on your individual response.

If you're thriving on a strict carnivore diet with stable blood sugar, energy, and hormones, you may be among those who tolerate this approach well long-term.

However, if you're experiencing rising blood sugars, increasing A1C, fatigue, or hormonal issues despite strict adherence, consider experimenting with small amounts of carbohydrates to stimulate GLP-1 and insulin signaling.

The goal is finding your personal metabolic sweet spot – where insulin sensitivity is optimized without triggering either insulin resistance or insulin suppression.

This balanced approach may offer the best of both worlds: the metabolic advantages of fat-adaptation combined with the hormonal benefits of appropriate carbohydrate signaling.

In the end, the carnivore paradox teaches us something profound about human metabolism: extremes rarely tell the whole story. The path to optimal health often lies not in rigid adherence to a particular dietary dogma, but in understanding the unique needs of your own metabolism and responding accordingly.