In 2021, we are in no short supply of supplements that can support healthy cholesterol and improve lipid measurements.

Many are backed by stacks of research including mechanistic studies, human randomized controlled trials, and some even have thousands of years of historical use in Ayurvedic and Traditional Chinese Medicine.

It seems a lack of options is not the issue here. Rather, many clinicians are reluctant to or frustrated with incorporating supplements into a treatment plan, especially when it contradicts current guidelines.

Clinicians simply don’t always feel confident when to use what supplement for lipids, especially in relation to statins and other pharmaceuticals. 

In this post, you will not only learn about bergamot, a citrus fruit that within the last 10 years has grown in popularity with not only functional and integrative clinicians, but also with conventional medical doctors, desperate for other options apart from a traditional statin recommendation.

Most importantly, you will learn how to prioritize well-researched supplements such as bergamot, berberine, omega-3 fatty acids and niacin, and incorporate them into a structured lipid-lowering treatment plan.

But first, some introductions.

What is Bergamot?

Bergamot is a citrus fruit grown almost exclusively in the narrow Calabrian region in Italy and is a common flavoring found in Earl Grey tea. It has been used for generations as a drink by the local population to prevent heart disease, which caught the eye of researchers eager to discover its secrets.

Like all citrus fruits, bergamot is rich in not only vitamin C and fiber, but also bioactive molecules called polyphenols. Belonging to a large chemical family called flavonoids, polyphenols are found in a wide variety of foods and have considerable evidence showing improvements in cardiovascular disease, diabetes, and neurodegenerative disease.

Although not entirely understood, polyphenols accomplish this primarily through a reciprocal relationship with the gut microbiome, in which polyphenol metabolites not only modulate the composition of beneficial and harmful bacteria, but can also be absorbed and benefit other aspects of human health through interactions with cellular enzymatic processes.  

What makes bergamot unique is its high concentration of rare polyphenols not seen in other citrus fruits. These polyphenols not only activate anti-inflammatory antioxidant pathways, but also work at the level of the GI tract and liver to influence the enzyme activity involved in carb and fat metabolism, allowing for improvements in many cholesterol and lipid measurements.

In a 2019 systematic review 1 of the effect of bergamot on lipid profiles in humans, the authors concluded that doses of 500-1,500 mg of bergamot extract achieved significant decreases in total cholesterol, LDL cholesterol and triglycerides. Additional improvements in HDL levels were achieved in eight out of the 12 articles included in the review.

One of the most exciting applications of bergamot extract is in combination with statins, the main cholesterol-lowering therapy since the 1980s. While statins have a long history of use and several large clinical trials with excellent data on LDL reductions, they also come with a high probability of side effects including fatigue, muscle pain and weakness that make long-term adherence an issue for many patients.

The American Journal of Cardiology has recognized this fact, and in 2018 published an opinion article 2 outlining for the first time ever, recommendations on the use of nutraceuticals such as bergamot in statin-intolerant patients. Ultimately, the article concluded that nutraceuticals are a viable option for statin-intolerant patients, and can lower lipids as well as improve other measurements such as arterial stiffness, endothelial dysfunction and chronic inflammation.

Nutraceuticals for the Cardiovascular Patient

While no two patients or treatment approaches are the same, generally speaking, nutraceuticals for cardiometabolic health should be considered for either long-term support or as a targeted therapy.

Foundational support for cardiovascular health

  • Omega-3 fatty acids
    • Possibly the most well-known cardiovascular supplement, omega-3 supplementation benefits both cardiovascular and cognitive health.
  • Vitamin D3 with K2
    • Having a cooperative relationship, the fat-soluble vitamins D3 and K2 are critical for both cardiovascular and skeletal health, with vitamin D having many other roles including proper immune function. 
  • Magnesium
    • Magnesium is needed as a cofactor for over 500 enzymatic processes, including healthy heart and blood vessel functions. An estimated 70% of the population is deficient in this critical mineral. 
  • Probiotics
    • Healthy gut function is tied to all aspects of health, including  cardiovascular and cognitive function. Probiotics can lower inflammation of the GI tract, which in turn can lower systemic inflammation and cardiovascular disease risk. 

Targeted support for cardiovascular health

  • Bergamot
    • Recommended as the first choice for nutraceutical lipid support, bergamot lacks side effects commonly seen with niacin, does not deplete CoQ-10 as seen with red yeast rice, and has more comprehensive effects than plant sterols, which only impact LDL cholesterol. 
  • Berberine
    • Berberine is an alkaloid found in a variety of different medicinal plants and has a long history of use given its antimicrobial effects in the gut as well as its ability to improve blood sugar, insulin and lipids. Berberine is an excellent nutrient to combine with bergamot when elevated lipids are the primary concern. 
  • Niacin
    • Although falling out of favor due to side effects and the interpretation of two large clinical trials, niacin remains a strong choice for lipid control, as it impacts all lipid markers associated with cardiovascular risk. Clinicians should be aware of contraindications with niacin, including liver disease and gout.
  • Plant sterols
    • Sterols have a chemical structure that resembles cholesterol, but are poorly absorbed. When taken orally, sterols appear to compete with cholesterol-binding sites in the GI tract, increasing cholesterol excretion. 
  • Red yeast rice
    • Often called a "natural statin," red yeast rice contains the active ingredient monacolin K, which mirrors the drug lovastatin. However, because the natural occurring compound is comparable to a drug, regulations have been placed on the supplement that prevents the truthful labeling of the main active ingredient, making the effectiveness of common RYR supplements suspect. 
Putting it All Together

Having a framework is one thing, but seeing it integrated into the real world is where true understanding comes.  

Ready to dive deeper into this topic?

Watch the webinar,

. Dr. Shilpa Saxena, Chief Medical Officer at Forum Health and creator of the Group Visit Toolkit, breaks down the nuances of individualizing patient care while grappling with current guidelines, patient preferences and supplement claims.
STEVEN IMGRUND, MS, CNS

Steven Imgrund is a board-certified nutritionist. Steven developed his passion for nutrition and health working as personal trainer and health coach, specializing in weight loss and behavior change. Through working with hundreds of clients, Steven has seen the challenges with implementing long-term lifestyle and dietary habits. This experience has fueled his passion for functional medicine, and his desire to help health care practitioners use proven lifestyle and supplement strategies to safely address the root causes of their patients cardiometabolic issues. Steven received his Masters in Human Nutrition through Bridgeport University in 2018, and Certified Nutrition Specialist (CNS) certification in 2020.

 

References
  1. Lamiquiz-Moneo I, Giné-González J, Alisente S, et al. Effect of bergamot on lipid profile in humans: A systematic review. Critical Reviews in Food Science and Nutrition. 2019;60(18):3133-3143. doi:10.1080/10408398.2019.1677554
  2. Banach M, Patti AM, Giglio RV, et al. The Role of Nutraceuticals in Statin Intolerant Patients. Journal of the American College of Cardiology. 2018;72(1):96-118. doi:10.1016/j.jacc.2018.04.040