Does adherence to ketogenic therapy increase your risk of developing cardiovascular disease?

In a word, no.

But that’s not the common message portrayed in the media. Why is there such a stark misconception about ketosis? In this article, we’ll look at the existing evidence pertaining to ketogenic therapy and its potential to impact heart health. We’ll look closely at the studies supposedly showing keto’s connection to heart disease and clarify our current understanding and knowledge gaps surrounding ketogenic therapies.

Evidence Ketogenic Therapies Cause Heart Disease (or Lack Thereof)

When we look for studies demonstrating a causal relationship between a ketogenic way of eating and cardiovascular events, we find that none exist. There are no intervention trials that have specifically looked at subjects on ketogenic therapy and found they have more heart disease, heart attacks, strokes, or cardiovascular-related events.

As a result, no one can say with certainty that nutritional ketosis increases cardiovascular events.

That said, we also don’t have evidence showing nutritional ketosis decreases cardiac events.

That means we have no peer-reviewed research looking at ketogenic therapy’s connection with heart health. This brings up an important question: without research-backed evidence, how can we make decisions when it comes to ketogenic therapy and its potential impacts on cardiovascular disease risk?

Navigating the Absence of Data

When we don’t have results from clinical outcome trials, we have to use what’s called “surrogate outcome data,” which are indicators believed to correlate with an elevated or diminished risk of heart disease.

Many researchers and conventional practitioners believe LDL cholesterol is the most important piece of surrogate data to gauge cardiovascular risk. In the general population, some studies show that reduced levels of LDL are associated with lower cardiovascular risk, whereas heightened levels can be associated with an increased likelihood of heart disease

That said, it’s important to remember that LDL is only one of many cardiovascular risk factors. that we should put into the context of an individual’s overall cardiovascular risk assessment.

Beyond LDL: A Comprehensive Evaluation of Heart Disease Risk

While LDL is traditionally the principal marker used to assess cardiovascular risk, other health markers play an equally pivotal role in indicating one’s heart health. These include metabolic markers like glucose, hemoglobin A1c, and insulin; markers of inflammation such as CRP; and more specific lipid markers such as ApoB and VLDL. These markers may signify metabolic damage, which has been shown to increase the likelihood of heart disease.

Reevaluation of Faulty Studies

Recent studies purport that eating more fat and fewer carbohydrates increases one’s risk of heart disease, stroke, or death.

Yet a significant limitation in these studies pertains to the way in which the researchers defined and formulated their “ketogenic” therapy. In these particular studies, participants were permitted to eat between 25% of calories to up to 40% of calories from carbohydrates if they were eating the study’s prescribed ketogenic therapy. 

Eating 25%-40% of your daily calories from carbohydrates does not align with the definition of nutritional ketosis. People actively pursuing or maintaining ketosis must keep their carbohydrate intake much lower than the participants in the study (usually around 5-10% of their total daily calories or below 30 grams of daily carbohydrates).

Because these studies did not have participants achieve nutritional ketosis, they do not accurately reflect the physiologic state of ketosis and cannot conclusively establish a link between ketosis and cardiac risk.

How Bias Skews Data

Bias is another factor that can skew research and results.

One example of a bias often seen in nutrition is that high-fat diets are dangerous for your health and low-fat diets are good for you. This belief began decades ago, and the commonly-believed message ever since is that eating low-fat is healthy.

Consequently, those who adhered to low-fat diets were more inclined towards health-conscious behaviors. Those who ate more fat were usually less inclined to develop healthy habits. This propagated an inherent bias that vilified dietary fat and exalted low-fat foods, the so-called “healthy user bias.”.

Around the same time that this low-fat craze hit its peak, red meat was demonized. Unfortunately, studies show that those who ate red meat also tended to smoke more, drink more, exercise less, and have other unhealthy habits. What resulted was that red meat was blamed for what tobacco, alcohol, a sedentary life, and other unhealthy habits were doing to the body.

While these biases developed decades ago, they still affect how we perceive and research fat, red meat, and carbohydrates in the health sphere today and influence what research is pursued and published.

How Ketogenic Therapies Affect Heart Health: Looking at Available Data

So how does adopting a ketogenic nutrition plan affect your heart health?

A recent publication from Virta Health focused on their one-year Continuous Care intervention with ketogenic therapy. While participants exhibited a 10% increase in LDL levels on average, the calculated cardiovascular risk over a decade decreased by 12%! Other markers, including ApoB, blood pressure, triglycerides, and VLDL, demonstrated stability or favorable changes, collectively contributing to a reduction in cardiovascular risk.

So their LDL went up, but their calculated heart disease risk went down!

This apparent paradox underscores the complex interplay of multiple metabolic parameters in influencing cardiovascular risk.

A Special Note on Hyper-Responders

While most people starting a high-fat ketogenic therapy see little change in their LDL levels, there is a specific group of people, so-called “hyper-responders,” whose LDL goes up substantially when they begin their ketogenic therapy.

What’s especially interesting is that hyper-responders who have the greatest increase in LDL levels tend to be lean, active, and metabolically healthy. Engineer and citizen scientist Dave Feldman, along with cardiologist and researcher Dr. Matt Boudoff, are currently studying hyper-responders with CT angiograms and extensive blood and genetic testing in the hope to better understanding the factors influencing this distinctive response.

What Does It All Mean?

This analysis underscores the absence of definitive outcome studies pertaining to ketogenic therapies and their effects on cardiovascular health and highlights the inherent limitations of observational data.

But where does that leave us? How do you, as an individual or a clinician, know what to do regarding nutritional ketosis, LDL, and cardiovascular disease risk?

Many see two ways to approach this question:

1. The first is that since no outcome data exists on those in nutritional ketosis, this population should be treated just like everybody else. Even though they are metabolically different, and their dietary makeup is drastically different from the general population, many physicians prefer to take a cautionary approach until more definite data exist. For these practitioners, the standard medical guidelines still apply.

2. The other approach is that since this population is clearly physiologically unique, they should be treated differently. This approach suggests this population should have its own guidelines that reflect the community’s metabolic health and unique physiology.

At this point, we can’t say which of the above two approaches is most helpful. Which option you and your practitioner choose will depend on your individual context.

Unfortunately, busy medical facilities tend to use mainstream medical guidelines that lock patients into cookie-cutter, non-personalized treatments that ignore the history, challenges, and successes of the individual.

That’s a trap we hope to avoid here at Metabolic Mind. By continuing to discuss the unique physiologic state of nutritional ketosis and the benefits it can have on a person’s health, we hope to educate and inform you of new potential treatments that you can discuss with your medical team.

Wrapping It Up

So does nutritional ketosis increase cardiovascular risk?

The answer is: we don’t know, at least not from the concrete outcome studies we have right now. There are no outcome studies to demonstrate either an increased or decreased incidence. And when it comes to surrogate data studies, there is no consistent evidence to indicate an increased risk.

The current evidence does not support the assumption that nutritional ketosis increases cardiovascular risk. Changing this mindset is crucial so that clinicians might be more willing to try nutritional ketosis as a therapeutic medical intervention, especially for those who have tried multiple different interventions for their type-2 diabetes, Alzheimer’s Disease, psychiatric condition, or other health issues.

Sources

• Tune, Jonathan D., et al. “Cardiovascular Consequences of Metabolic Syndrome.” Translational Research: The Journal of Laboratory and Clinical Medicine. (2017).

• Halsey, Grace. “Ketogenic Diet Associated with Increased Serum Lipids, 2-fold Greater Risk of MACE.” Patient Care Online. (2023).

• UBC Faculty of Medicine Communications. “Popular keto diet may be linked to higher risk of heart disease, cardiac events.” (2023).

• Hallberg, Sarah J., et al. “Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study.” Diabetes Therapy. (2018).

• Bhanpuri, Nasir H., et al. “Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study.” Cardiovascular Diabetology. (2018).