Modified Snacks Reduce LDL Cholesterol

Batya Swift Yasgur MA, LSW

January 28, 2022

A new, randomized crossover study shows that individuals who ate specifically formulated snacks high in certain ingredients including fiber, phytosterols, and antioxidants reduced their LDL cholesterol, even in the absence of other dietary or lifestyle changes.

Investigators randomized 54 adults to receive either the specially formulated snacks made by Step One Foods or control snacks from the grocery store that were similar in calories and packaging.

Participants were instructed to consume the snacks twice a day as a substitute for something they were already eating and to make no other changes in diet or lifestyle. None of the patients were receiving statin drugs either before or during the study period.

After the first 4 weeks, a 4-week washout period ensued, and then the original control group crossed over to receive the specially formulated snacks, while the experimental group now received the control snacks.

LDL cholesterol levels fell by almost 9% and total cholesterol (TC) by 5% in those receiving treatment foods compared with those receiving control foods.

"What you eat is very important, and you can eat foods that will lower your cholesterol," lead author Stephen I. Kopecky, MD, consultant, Division of Preventive Cardiology, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, told | Medscape Cardiology.

"Based on our study findings, this type of 'food-as-medicine' approach expands the options for medical professionals and patients, [as] many patients are either unwilling or unable to take statins drugs and may be able to manage their hyperlipidemia with realistic food-based interventions," said Kopecky, who is the director of the Mayo Clinic's Statin Intolerance Clinic.

The study was published online January 26 in The Journal of Nutrition.

At-Risk Population

Statin drugs are commonly used to treat hyperlipidemia, but many individuals are either unable or unwilling to take them, "leaving a large patient population at increased risk of cardiovascular events," the authors write.

Specific dietary components, including soluble fiber and daily plant sterol intake, have been shown to reduce LDL cholesterol. Some research has also suggested that alpha-linolenic acid (ALA) "may have hypolipidemic effects on very low-density lipoproteins," thereby inhibiting atherosclerosis, and that antioxidants may "confer benefits through anti-inflammatory effects, autonomic adrenergic response modulation, and endothelial function modification."

They note that the vegan portfolio diet delivered high concentrations of fiber and plant sterols, with a 17% reduction in LDL cholesterol when combined with the National Cholesterol Education Program Step II approach, but user compliance on that diet was "poor."

In this study, the researchers gave participants foods containing meaningful quantities of the relevant ingredients. These snacks included oatmeal, pancakes, cranberry bars, chocolate bars, smoothies, and granola, with all products interchangeable in terms of the nutrients of interest.

Each serving contained a minimum of:

  • 5 g fiber (containing ≥ 2g soluble, viscous fiber)

  • 1 g ALA

  • 1 g phytosterols

  • 1800 mmol antioxidants

All products were formulated from whole food ingredients "documented to positively effect cardiovascular health," such as walnuts, almonds, oats, and berries, and all were enriched with plant sterols. The calorie count per serving ranged from 110 to 190 kcal.

Control products were similar items from the supermarket, matched for calorie content as well as preparation requirements.

Participants were instructed not to change their diets or activity levels during the intervention periods. "We did not want them to make any modifications that might affect the results of the study," Kopecky explained.

The primary outcome was the impact of the intervention on fasting LDL cholesterol. Secondary outcomes included the impact of the intervention on circulating TC, triglycerides, HDL cholesterol, fasting glucose, insulin, high-sensitivity C-reactive protein (hsCRP), and the effects of the single-nucleotide polymorphisms (SNPs) CYP7A1 and APOE on outcome.

The researchers measured participants' serum lipids at baseline and at the end of each phase, with results compared using the analysis of variance (ANOVA) model.

Healthy Options

The study included 54 nonsmoking individuals (18 men and 36 women, mean age, 49 ± 12 years; mean LDL cholesterol, 131 ± 32.1 mg/dL; mean TC, 219 ± 36.7 mg/dL; mean triglycerides, 156 ± 82.4 mg/dL) who were candidates for statins but either unwilling to take these agents or intolerant to them.

The treatment and the control groups were both highly compliant (95.0% and 96.5% compliance, respectively; P = .914), as determined by serum 18:3n-3 fatty acid concentration assessment.

When the researchers compared endpoint results, they found that LDL cholesterol was reduced by a mean of 8.8% ± 1.69 in the intervention group compared with the control group (P < .0001), with some participants experiencing LDL cholesterol reductions of more than 20%.

Total cholesterol was reduced by a mean of 5.08% ± 1.12 in the intervention group compared with the control group (P < .0001), but there were no significant differences between the groups in HDL cholesterol, triglycerides, serum glucose, insulin, and hsCRP concentrations.

The presence of SNPs did not affect outcomes (P ≥ .230).

"In this country, 57% of the calories we consume daily come from ultra-processed food — that means food that's ready to eat and comes in a wrapper — and approximately 74% of Americans go to vending machines daily," Kopecky observed.

"The products we provided were obviously processed food, but they were processed foods that gave people healthy options. We are trying to make it easy for people to eat food that is healthy and will lower cholesterol," he said.

"For every 1% that we can lower our LDL cholesterol, we lower the risk of a heart attack or cardiac death by 1% in five years. So, if you do this on a big level you are, on a national level, potentially significantly changing the cost of care in this country by having less cardiac disease, which is the number 1 killer."

Moreover, "an 11% reduction [in LDL cholesterol] is what we normally use to decide on the adequacy of a treatment response to statins," Kopecky added.

Favorable Changes

Commenting for | Medscape Cardiology, Kim Allan Williams, Sr, MD, professor and chief of the Division of Cardiology, Rush University Medical Center, Chicago, Illinois, who was not involved with the study, added that there was no reduction in CRP, unlike the finding in the portfolio diet, "since animal-laden diets are inflammatory and generally do not lower CRP, as shown in the EVADE trial."

Also commenting for | Medscape Cardiology, Kenneth Feingold, MD, professor of medicine (emeritus), University of California San Francisco, said it is "well known that dietary fiber, particularly soluble fiber and dietary phytosterols, decrease LDL cholesterol levels."

Feingold, who was not involved with the study, raised the question of the cost of the product and whether it would be covered by insurance. And the products might add as much as an extra 380 calories daily if added to the diet without decreasing the intake of other foods. "Obviously, over an extended period of time, this could lead to significant weight gain in susceptible individuals."

Also commenting for | Medscape Cardiology, Tamanna Singh, MD, clinical cardiologist and a member of the Sports Cardiology Center in the Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute, Cleveland Clinic, Ohio, said that "while the reductions [in LDL cholesterol levels] were not as robust as statin therapy, this study further confirms that plant-based nutrients, such as these four components, make favorable changes to lipid profiles in the long term."

Singh, who is a member of the ACC Prevention of Cardiovascular Disease Council and was not involved with the study, suggested that "concomitant dietary changes with more aggressive cholesterol reduction with medical therapy as warranted would yield the best results."

Kopecky added, "Often, patients refuse to take statins because they are intolerant — for example, because of muscle aches — and don't like to take them. Those are the patients who were included in this study, the patients who said, 'I don't want to take this [a statin]. Do you have another option?"

J Nutr. Published online January 16, 2022. Abstract

Primary funding for the study came from the province of Manitoba, Canada, via government grant support. Step One Foods supplied all foods used in the trial and additional monetary funding not covered by governmental support. The California Walnut Board contributed walnuts for manufacture of the intervention foods. Kopecky consults to Prime Therapeutics and receives research support through Tru Health. The other authors' disclosures are listed on the original paper. Feingold, Williams, and Singh report no relevant financial relationships. 

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