Keto Diet for Heart Failure? What Clinicians, Patients Need to Know

Word is spreading among patients with heart failure (HF) that going on a ketogenic diet could aid their health, even though the evidence supporting benefit over risk is still in the early stages. A new review article, recently published online in JACC: Heart Failure, is making the case that HF specialists should be aware of what the literature does—and doesn’t—say, and be prepared to guide their patients along the way if they choose to pursue this path.

There are some scientific underpinnings behind the idea that a ketogenic diet, originally created to treat epilepsy but now seen by many as a tool for weight loss and glycemic control, could be beneficial in heart failure.

“The failing heart increases oxidation of ketone bodies to meet its energy demands, so it is conceivable that the ketogenic diet could aid the failing heart by boosting the supply of ketone bodies. Moreover, the ketogenic diet could ameliorate HF by improving overall metabolic health, including body weight, lipid profile, glycemic control, and blood pressure,” the paper notes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a mainstay of HF therapy, also increase the liver’s production of ketones, which some say may explain some of their cardioprotective effects.

“Patients and physicians alike really kind of recognize some of these evolving concepts,” senior author W.H. Wilson Tang, MD (Cleveland Clinic, OH), told TCTMD. Their review is meant to clarify how a ketogenic diet might work in heart failure, with an exploration of mechanisms as well as possible pitfalls, he said. “These are the things that patients come and ask us all the time: ‘Doctor, should I be on a ketogenic diet?’”

Some data suggest the eating pattern can increase both LDL cholesterol and adverse cardiovascular events. Still, grocery stores are filled with products labeled as keto, Tang pointed out. On this backdrop, the co-authors thought it was important to dig into whether a ketogenic diet could play a role in HF management.

Indeed, the concept is not without controversy.

Salvatore Carbone, PhD (Virginia Commonwealth University, Richmond), whose work focuses on dietary interventions in heart failure, said that while the idea of ketogenic diets for patients with this disease is “highly provocative” due to the many unknowns, there is a plausible mechanism supporting it.

“The evidence for ketone bodies to be potentially beneficial in heart failure exists,” he commented to TCTMD. That said, giving an infusion of these molecules isn’t the same thing as trying to achieve ketosis through diet, for which data are lacking, Carbone stressed.

He emphasized that the current knowledge gaps are noteworthy. “I think the question is: is the ketogenic diet safe in heart failure? We don't know. Is it effective? We don't know. Could it be beneficial? Maybe, due to the effect of ketone bodies, but we the evidence is really zero,” said Carbone.

Amanda Vest, MBBS, MPH (Tufts Medicine, Boston, MA), director of the advanced HF program at her center, called the new paper “timely.”

Patients with heart failure and obesity often ask about ketogenic diets, for which “there are a few tantalizing pieces of literature suggesting potential benefits, but currently insufficient human studies for fully informed recommendations,” Vest said in an email to TCTMD. Given that the risks of a ketogenic diet depend on each patient’s comorbidities and medical situation, she cautioned, clinicians must focus on the “right diet, for the right patient, at the right time.”

Patients come and ask us all the time: ‘Doctor, should I be on a ketogenic diet?’ W.H. Wilson Tang

In the review, which was led by Nandan Kodur, BS (Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH), the authors explain that a ketogenic diet is “a carbohydrate-restricted diet that increases endogenous production of ketone bodies and induces ketosis,” defined as a beta-hydroxybutyrate level ≥ 0.5 mmol/L. This can take several forms, from the classical ketogenic diet to a modified or medium-chain-triglyceride ketogenic diet, modified Atkins diet, or low-glycemic-index treatment. All of these variations have different distributions of fat, protein, and carbohydrate.

Importantly, the paper also offers practical advice, said Tang. If a patient with HF is asking whether a ketogenic diet is a good fit, “what do I tell them? What do I monitor? How do I instruct them to monitor [ketosis]? What are the things that we should avoid? Who are the people [for whom] we definitely should not do that?”

Among the proposed risks to metabolic health, the paper notes, are the fact that a ketogenic diet can increase levels of LDL cholesterol and the metabolite trimethylamine N-oxide (TMAO); deprive patients of nutrients found in foods like whole grains, legumes, and fruits; and be so restrictive that it’s not sustainable. For all of these concerns, the review lists counterpoints and suggestions for how to adjust the diet’s components.

The biggest worry, said Tang, is the potential for dehydration and electrolyte imbalances, and specifically the complication of ketoacidosis.

Future research will have to pin down whether persistent ketosis in the body is a good thing—or not—for patients with heart failure, and whether it may be good for some people but not others. “There's a lot of promising signs that there are some subsets of patients [where] the availability of ketones and ketone esters and ketone bodies may be actually potentially helpful. We just have to be more rigorous in our investigation,” he urged.

In the meantime, Tang added, it’s a “balancing act” between widespread enthusiasm among the public and the reality that HF patients need to be watched carefully if attempting a ketogenic diet.

For clinicians, the review outlines what’s required. This includes medical supervision (eg, monthly appointments to monitor health and progress, educating patients about staying hydrated and recognizing signs of ketoacidosis, and reintroducing carbohydrates gradually after the diet is stopped), medication-dosage adjustments (eg, altering amounts of glucose-lowering and antihypertensive drugs and discouraging use of SGLT2 inhibitors), and blood-ketone monitoring (eg, using an at-home meter at the same time each day and ensuring sustained ketosis).

And for people with heart failure considering this option, the message is clear, Tang said: “Don't do it at home on your own.”

Possibility for Harm

Speaking to how little is understood about diet in heart failure, Carbone noted that it’s not even known if losing weight will lower mortality in this setting. In fact, Vest pointed out, “for patients with heart failure without obesity, we have data suggesting that significant weight loss is associated with lower survival, especially for patients who lose skeletal muscle mass.”

Carbone called attention to other risks, particularly the rise in LDL cholesterol often seen on patients eating a keto diet. One reason for this rise is that ketogenic diets typically include a lot of saturated fat from animal sources. The review suggests that alternate sources, like olive oil and nuts, could be ingested instead to prevent the LDL increase. “That’s a great idea, but we don't have the data to support that yet,” he said.

Additionally, ketogenic diets can be high in sodium, Carbone noted. And perhaps even more crucial, there’s the worry that patients might avoid taking an SGLT2 inhibitor—a therapy with known benefits and contraindicated in those undergoing ketogenic diet—because they’d rather take a dietary route for managing their heart failure.

And it’s not as if a ketogenic diet is the only option, he added. “Most well-controlled studies using ketogenic diet have not shown [it] to be superior to caloric restriction in terms of cardiometabolic risk factors. Ketogenic diet improves body weight and so does caloric restriction. Ketogenic diet improves hemoglobin A1c and so does caloric restriction. The advantage of ketogenic diet is that you see effects more rapidly, but there is a plateau and adherence is extremely hard to achieve in the long term.”

We need to keep the same rigor for diet that we keep with medications, especially in highly complex clinical populations. Salvatore Carbone

Despite his reservations, Carbone agreed that the concept is worthy of further study. “We need to keep the same rigor for diet that we keep with medications, especially in highly complex clinical populations. If somebody's healthy [and has] zero problems, probably you're fine with doing a ketogenic diet for 3 months: the risk for side effects is extremely low,” he said. “In patients with heart failure, just 3 months could cause a hospitalization, which could lead to an increased risk of death to be honest.

“So right now, I would never recommend a ketogenic diet in my patients with heart failure,” Carbone continued. “If there are data that come out suggesting that it could be beneficial in [a few] years, I will be the first one to start recommending it. But I think we need the data [and for now] we need to be cautious about recommending it—in fact, we shouldn’t.”

Vest stressed an individualized approach. If a patient with heart failure wants to try a modified ketogenic diet with healthier fats, isn’t at risk for ketoacidosis or severe hypoglycemia, and has an elevated body weight, it might be a reasonable short-term strategy for weight loss—with the caveat that there needs to be close monitoring. However, “pending further studies on ketosis specifically as a treatment for [heart failure with reduced ejection fraction], I would not currently recommend this dietary pattern for patients with normal or low body weight for concern of the adverse consequences of rapid weight loss for patients with heart failure,” she added.

Looking ahead, she said, it would make sense to do a randomized trial of a dietary intervention that produces mild ketosis in patients who have heart failure with preserved ejection fraction and obesity, but who aren’t at risk of ketosis-related side effects.

“This is the group of patients where weight loss is most likely to be beneficial and where current heart failure therapies are often insufficient to resolve symptoms,” said Vest, adding that participants need to be advised on dietary quality and healthy fat choices. “I would also be interested to see measures of diuresis in such a study: whether it is due to the ketosis or the lower carbohydrate ingestion, there have been anecdotes that a ketogenic dietary patten may help augment diuresis in some individuals.”

The review, too, specifies the need for additional study. “Given the mixed findings in animal studies, lack of clinical trials, and broad adoption of SGLT2 inhibitors across the spectrum of HF, more research is needed to demonstrate the safety and incremental clinical benefits of the ketogenic diet—and this will hopefully settle the debate of whether adopting the ketogenic diet to ameliorate HF is fact or fiction,” its authors conclude.