When Statins Are Not an Option, Part 1: Leverage Nutrition First

Hyperlipidemia is a common health condition affecting 94 million Americans¹ and nearly 2 out of 3 Medicare recipients.² Although HMG-CoA reductase inhibitors (statins) are highly effective in lowering low-density lipoprotein cholesterol (LDL-C), statin intolerance and/or refusal to take statin medications affects about 1 in 3 statin-eligible patients, creating a large cohort of individuals with hyperlipidemia at persistently increased risk of cardiovascular events.

Although other pharmacologic options are available, attending to lifestyle fundamentals becomes critical in this pharma-reluctant group.

A healthy lifestyle, especially diet, is foundational to reducing cardiovascular disease risk, and all lipid management guidelines emphasize nutrition as a cornerstone of attaining LDL-C control.³ But optimizing nutrition goes far beyond instructing patients to reduce dietary cholesterol intake. First, most of the cholesterol encountered in the digestive tract comes from bile, not food and, second, nutrition affects multiple biochemical pathways affecting LDL-C levels in complex and interdependent ways. Fortunately, targeted nutrition interventions can yield marked LDL-C reductions and should be integral to the care of statin intolerant and statin unwilling patients.

Fiber, sterols. Dietary fiber and plant sterols, as found in all whole plant-based foods, modulate intestinal absorption of both biliary and dietary cholesterol; ensuring adequate intake of these compounds can significantly impact cholesterol levels. Increasing viscus fiber intake by as little as 5 grams per day can reduce circulating LDL-C by close to 5%⁴ while consuming 2 grams of plant sterols per day in divided doses can yield up to 10% LDL-C reductions.⁵

First, most of the cholesterol encountered in the digestive tract comes from bile, not food and, second, nutrition affects multiple biochemical pathways affecting LDL-C levels in complex and interdependent ways.

Insulin. Insulin stimulates HMG-CoA reductase, driving LDL-C production and increasing circulating LDL-C levels. Therefore, strategies that reduce circulating insulin levels such as avoiding highly processed carbohydrates and favoring complex unprocessed ones, can also positively impact cholesterol control. For example, following the DASH diet, which is high in complex carbohydrate content, can lead to LDL-C reductions of close to 10%. Layering on higher intakes of plant protein (at the expense of simple carbohydrate content) can result in even greater LDL-C improvements.⁶

Saturated fats. Finally, saturated fats downregulate LDL-C receptor function making LDL-C elevations worse, sometimes strikingly so. Patients who follow a ketogenic diet may see large spikes in LDL-C⁷ as a result. Conversely, replacing 5% of saturated fats with equal amounts of monounsaturated and/or polyunsaturated ones is associated with as much as 10% LDL-C drops.

Net result. Taken together, strategic dietary change alone can yield substantial LDL-C improvements. This was demonstrated by the Portfolio Diet⁸ study which relied on daily consumption of 35 grams of soy protein, 2 grams of plant sterols, 18 grams of soluble fiber, as well as unsaturated fats coming from nuts and seeds. Study participants who strictly followed this protocol saw nearly 30% LDL-C reductions, on average, in as little as 2 weeks.

The Portfolio Diet study relied on daily consumption of 35 grams of soy protein, 2 grams of plant sterols, 18 grams of soluble fiber, as well as unsaturated fats coming from nuts and seeds. Study participants who strictly followed this protocol saw nearly 30% LDL-C reductions, on average, in as little as 2 weeks.

However, as this regimen can be difficult to maintain outside of a highly controlled environment, other investigators have looked at mimicking tenets of the Portfolio diet in 2 ready-to-eat daily snacks made from whole food ingredients (Step One Foods®)⁹ that deliver consistent, clinically meaningful levels of fiber, unsaturated fats, and plant sterols in every serving. A randomized controlled clinical trial using this dosed food approach performed in a free-living population documented 9% average LDL-C reductions in 30 days,¹⁰ with some subjects experiencing nearly 40% LDL-C drops in that amount of time.

All patients with hyperlipidemia can benefit from dietary interventions that support LDL-C lowering, but a dosed food-based option (the efficacy of which can be objectively assessed after 4 weeks) may be especially applicable for patients who are statin intolerant or statin unwilling. Not every patient will respond to a structured dietary intervention. In those who fail to show meaningful improvements in LDL-C control, the null result can be utilized as the springboard for discussing previously rejected pharmaceutical options.

Key Takeaways

• The specific components of a patient's diet impact multiple biochemical pathways involved in LDL-C regulation and targeted nutrition interventions can yield marked and rapid cholesterol improvements.

• Ensuring patients consume adequate amounts fiber, unsaturated fats and plant sterols is critical to ensuring success of any lipid management plan (with or without statins).

References

1. Virani SS, Alonso A, Benjamin EJ, et al on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2020 Update: a report from the American Heart Association. Circulation. 2020;141:e139–e596. doi:10.1161/CIR.0000000000000757

2. Dong I, Klodas E. Healthcare cost implications of utilizing a dietary intervention to lower LDL cholesterol: proof of concept actuarial analysis. Curr Cardiol Rep. 2020;22(11):138. doi:10.1007/s11886-020-01397-9

3. Kirkpatrick CV, Sikand G, Petersen KS, et al. Nutrition interventions for adults with dyslipidemia: A Clinical Perspective from the National Lipid Association. Clin Lipidol. Published online June 2, 2023. doi:10.1016/j.jacl.2023.05.099

4. Ghavami A, Ziaei R, Talebi S, et al. Soluble fiber supplementation and serumlipid profile: a systematic review and dose-response meta-analysis of randomized controlled trials. Adv Nutr. 2023;14(3):465-474. doi:10.1016/j.advnut.2023.01.005

5. Gylling H, Plat J, Turley S, et al, for the European Atherosclerosis Society Consensus Panel on Phytosterols. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atheroscler. 2014;232(2):346-360. doi:10.1016/j.atherosclerosis.2013.11.043

6. Appel LJ, Sacks FM, Carey VJ, et al. Effects of protein, monounsaturated fat and carboyhydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA. 2005;294(19):2455-2464. doi:10.1001/jama.294.19.2455

7. Noain JS, Minupuri A, Kulkarni A, Zheng S. Significant impact of the ketogenic diet on low-density lipoprotein cholesterol levels. Cureus. 2020;12(7):e9418. doi: 10.7759/cureus.9418

8. Jenkins DA, Kendall CWC, Marchie A, et al. Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants. Am J Clin Nutr. 2005;81(2):380-387. doi: 10.1093/ajcn.81.2.380.

9. Step One Foods https://www.steponefoods.com/

10. Kopecky SL, Alias S, Klodas E, Jones PJH. Reduction in serum LDL cholesterol using a nutrient compendium in hyperlipidemic adults unable or unwilling to use statin therapy: a double-blind randomized crossover clinical trial. J Nutr. 2022;152(2):458-465. doi: 10.1093/jn/nxab375

Elizabeth Klodas MD, is a preventive cardiologist and founder and chief medical officer of Step One Foods, based in Minneapolis, Minnesota. Step One Foods helps people reduce their dependence on pharmaceuticals for treating health issues that could be solved by food.

Klodas completed her cardiology fellowships with both the Mayo Graduate School and Johns Hopkins School of Medicine, and founded Preventive Cardiology Clinic, in Edina, MN, where she continues to see patients. She served as the founding editor of Cardiosmart.org (patient education website of the American College of Cardiology [ACC]). She remains involved in clinical research and patient education and is an active member of ACC’s Nutrition Workgroup. Klodas is the author of Slay the Giant: The Power of Prevention in Treating Heart Disease.