High cholesterol (hypercholesterolemia) is a known risk factor for heart disease; however, cholesterol has, in part, been over-villainized when it also serves beneficial roles for the human body. Utilizing functional testing is very helpful in better quantifying cardiovascular risk corresponding to cholesterol levels. If you have high cholesterol, lifestyle changes can help to improve your levels and magnify the effects of cholesterol-lowering medications. The American Heart Association (AHA) recommends focusing on heart-healthy dietary patterns in the prevention and management of all cardiovascular diseases. This article will emphasize several key points when optimizing cholesterol levels through diet.
What is Cholesterol
Cholesterol is a fat-like substance that is necessary for body function. This lipid molecule helps to maintain the structure of cell membranes and is the building block by which steroid hormones, bile acids, and vitamin D are made in the body. Our bodies make most of our cholesterol on their own, but some cholesterol also comes through diet.
Cholesterol is carried and transported through the body by carriers called lipoproteins, the most notorious being low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL’s primary function is to transport cholesterol to body tissues; it holds the potential to become oxidized, forms arterial plaques, and contribute to atherosclerosis - this is why LDL cholesterol is known as “bad cholesterol.” HDL’s primary function is to pick up cholesterol from peripheral cells and return it to the liver for recycling or excretion from the body - this is why HDL cholesterol is known as “good cholesterol.”
What Causes High Cholesterol
The human body naturally produces all the LDL cholesterol it needs, but certain lifestyle factors can influence how your body makes and eliminates cholesterol. Behaviors that can negatively impact cholesterol levels include eating an unhealthy diet, lack of physical activity, being overweight, and smoking.
Inheritance of specific genes can also cause higher levels of cholesterol. The most common of these genetic conditions is familial hypercholesterolemia, resulting from mutations in the LDL-receptor or ApoB-100 genes. Mutations of either gene ultimately result in reduced LDL clearance from circulation and high blood LDL cholesterol.
Familial dysbetalipoproteinemia is another genetic condition that results in high cholesterol and is caused by a mutation in ApoE, which supports the uptake of lipoproteins by the liver.
High cholesterol may be secondary to underlying medical conditions. Diabetes mellitus, both type 1 and type 2, is linked with lower levels of HDL cholesterol and higher levels of LDL cholesterol. One of insulin’s functions is to increase lipid uptake by cells by increasing the activity of an enzyme called lipoprotein lipase (LPL), which liberates fatty acids from certain lipoproteins. In type 1 diabetes and advanced-stage type 2 diabetes, insulin levels are low, and LPL activity decreases. This impairs the ability to break down cholesterol-carrying lipoproteins, translating to high LDL cholesterol levels and increased risk for atherosclerosis.
Chronic kidney disease (CKD) also causes down-regulation of LPL and the LDL-receptor, with a net effect of increasing LDL cholesterol and triglycerides. CKD also results in more small, dense LDL particles, which are more likely to contribute to atherosclerosis than larger LDL particles.
Thyroid hormones influence metabolism and how the body processes fats. In hypothyroidism, the thyroid makes too little thyroid hormone. In turn, metabolism slows down, fewer LDL receptors are synthesized, and cholesterol increases because LDL cholesterol cannot be effectively recycled and eliminated from the body.
Liver disease, no matter the cause, can decrease liver function. The liver serves many functions in the body, one of which is lipid metabolism. Liver disease can potentially impact cholesterol synthesis and elimination, negatively impacting lipid profiles.
Functional Medicine Labs to Test for High Cholesterol Patients
Advanced Lipid Panel
The advanced lipid panel is the best blood panel to diagnose high cholesterol and stratify cardiovascular risk. This panel includes the components of a basic lipid panel but also measures important subpopulations of lipoproteins and apolipoproteins (a protein component of lipoprotein) and calculates LDL and HDL lipoprotein particle number and size.
These additional markers are now understood to be better predictive markers for atherosclerotic and cardiovascular risk compared to the standard lipid panel. Fasting is not necessary for this panel; however, it may be recommended by your doctor in some instances when an accurate triglyceride level is essential for diagnostic purposes. (1, 3, 4)
Cholesterol Balance Test
Our total body cholesterol comes from both what we make in our cells and what we absorb from our gastrointestinal tract. The Cholesterol Balance Test measures markers of cholesterol production and gastrointestinal cholesterol absorption. The results of this test give practitioners powerful and personalized information on what physiologic mechanism is causing the elevated cholesterol levels so they can choose a therapy targeted to that specific pathway.
ApoE genotype testing aids in the diagnosis of familial dyslipidemia and in understanding the mechanisms behind an individual’s lipoprotein metabolism. ApoE2 and ApoE4 genes can increase LDL levels and the risk for heart disease. (2)
hsCRP & Homocysteine
High-sensitivity C-reactive protein (hsCRP) and homocysteine are two markers that are well researched as predictive markers of atherosclerosis and future cardiovascular events. These are both blood tests that can be easily ordered on their own or added to an advanced lipid panel. (5, 6)
CMP & HbA1C
To rule out secondary causes of high cholesterol, your doctor may order a comprehensive metabolic panel (CMP), which assesses blood sugar, kidney function, and liver function. Hemoglobin A1c (HbA1c) can be run with fasting blood sugar to screen for prediabetes and diabetes. A functional doctor will compare CMP and HbA1c values over time to look for trends in increasing blood sugar or decreasing kidney/liver values so that preventive interventions can be implemented before disease progression.
Comprehensive Thyroid Panel
A thyroid panel can rule out hypothyroidism. Hashimoto’s hypothyroidism is the autoimmune and most common form of hypothyroidism. Measuring thyroid peroxidase and thyroglobulin antibodies screens for thyroid autoimmunity, often present before overt hypothyroidism.
4 Evidence-Based Nutrition Hacks to Lower High Cholesterol
What you eat can affect your cholesterol levels. The best approach is not to rely on a single supplement or food type but rather to integrate a broader dietary approach that encompasses diverse food. Cholesterol-lowering diets should emphasize the reduction of saturated fats, trans fats, and refined sugars and incorporate more plant foods, fiber, and monounsaturated fats.
1. Add More Fruits and Vegetables to Your Plate
Fruits and vegetables are natural sources of fiber and phytosterols (consisting of sterols and stanols). Phytosterols have a very similar molecular structure to cholesterol, so they compete with and displace cholesterol in the intestines, resulting in reduced absorption and increased cholesterol excretion from the body. This meta-analysis found that eating up to 3 grams of plant sterols and stanols daily can lower LDL cholesterol by as much as 12%.
2. Focus on Soluble Fiber
It is well established that eating foods high in soluble fiber effectively lowers cholesterol levels. Soluble fiber dissolves into water, creates a gel-like substance, and slows the digestion of cholesterol-rich foods. It also binds cholesterol in the intestines, preventing reabsorption into the bloodstream, and aids in elimination from the body via feces. According to the National Lipid Association, eating just 5-10 grams of soluble fiber daily can lower total and LDL cholesterol by at least 5 to 11 points. Research also supports lower levels of inflammatory mediators correlated with fiber-rich diets. Foods high in soluble fiber include oats and other whole grains, legumes, fruits, and vegetables.
3. The Type of Fat Matters
There are different types of fat, depending on the biochemical composition of the lipid molecule. Saturated fats contain only single bonds because they are fully saturated with hydrogen atoms; they are typically solid at room temperature. Saturated fats naturally occur in meat and dairy products but are also found in some plant-based foods like coconut. Because saturated fats can increase LDL cholesterol, the AHA recommends reducing saturated fats to less than 6% of total daily calories if trying to lower cholesterol levels.
Trans fats, or partially hydrogenated oils, are not naturally found in foods but are created in the processing of foods to make them more solid. Trans fats are found in fried foods, baked goods, and other processed/packaged foods. Trans fats increase LDL cholesterol and lower HDL cholesterol. It is recommended that trans fats be eliminated from the diet to improve lipid profile and cardiovascular health.
Unsaturated fats contain double bonds in their chemical structure and are typically liquid at room temperature. Unsaturated fats are subcategorized into monounsaturated and polyunsaturated fats. Unsaturated fats are considered “healthy fats” because they can improve lipid profiles and hold anti-inflammatory properties. Sources of monounsaturated fats include olives, nuts, and avocados. Good sources of polyunsaturated fats include safflower and sunflower oil, flax seeds, walnuts, and fish.
Omega-3 and omega-6 fatty acids are two essential polyunsaturated fats, meaning they cannot be made by the body and must be eaten through diet. While both hold important functions for the body, when considering cholesterol-lowering and heart-healthy diets, omega-3 fatty acids, most commonly found in fatty fish, hold the most benefit. Supplementation with fish oil has been associated with improved blood vessel function, decreased plaque formation, and improvements in triglyceride, ApoB, and HDL cholesterol levels. (10)
4. Mediterranean Diet Plan
The Mediterranean diet is a heart-healthy eating plan based on the traditional cuisines of Mediterranean countries. It emphasizes incorporating plant foods, olive oil, and fish into the diet. Significant risk reduction in the development of cardiovascular disease has been proven when following the Mediterranean dietary guidelines.
The Seven Countries Study (SCS) was the first major study to investigate diet and lifestyle in relation to cardiovascular disease. It concluded that adherence to the Mediterranean diet is associated with a 29% lower cardiovascular mortality risk.
The HALE Project followed SCS with the objective to better understand how dietary patterns and lifestyle factors impact cardiovascular risk in combination and concluded that leading a healthful lifestyle in combination with a Mediterranean diet is associated with a 61% risk reduction from all cardiovascular diseases and a 64% lower rate of death due to coronary heart disease.
Specific to cholesterol levels, several studies have shown adherence to the Mediterranean diet results in improved lipid profiles, specifically improved HDL function, lower levels of total and LDL cholesterol, lower concentrations of ApoB, and improved markers of inflammation. Some of these results have been applied to individuals with familial hypercholesterolemia. (7, 8, 9)
If you suffer from high cholesterol, you are at higher risk for cardiovascular disease. Through specialty testing, you can better understand why your cholesterol is increased and how cholesterol composition and metabolism may contribute to your cardiovascular risk. Dietary interventions are proven effective at lowering cholesterol and improving cardiovascular function.
Lab Tests in This Article
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2. Mahley, R. W. (2016, June 9). Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. Journal of Molecular Medicine, 94(7), 739–746. https://doi.org/10.1007/s00109-016-1427-y
3. Jacobson, T. A., Ito, M. K., Maki, K. C., et al. (2015, March). National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 1—Full Report. Journal of Clinical Lipidology, 9(2), 129–169. https://doi.org/10.1016/j.jacl.2015.02.003
4. Lipoprotein (a) | CDC. (n.d.). Retrieved September 21, 2022, from https://www.cdc.gov/genomics/disease/lipoprotein_a.htm
5. Clearfield, M. B. (2005, September). C-Reactive Protein: A New Risk Assessment Tool for Cardiovascular Disease. Journal of Osteopathic Medicine, 105(5), 409–416. https://doi.org/10.7556/jaoa.2005.105.9.409
6. Refsum, H., Ueland, P. M., Nygård, O., & Vollset, S. E. (1998, February). Homocysteine and Cardiovascular Disease. Annual Review of Medicine, 49(1), 31–62. https://doi.org/10.1146/annurev.med.49.1.31
7. Hernáez, Á., Castañer, O., & Elosua, R., et al. (2017, February 14). Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals. Circulation, 135(7), 633–643. https://doi.org/10.1161/CIRCULATIONAHA.116.023712/-/DC1.
8. Antoniazzi, L., Arroyo-Olivares, R., & Bittencourt, M. S., et al. (2021, June 30). Adherence to a Mediterranean diet, dyslipidemia and inflammation in familial hypercholesterolemia. Nutr Metab Cardiovasc Dis, 31(7), 2014–2022. https://doi.org/10.1016/j.numecd.2021.04.006
9. Meslier, V., Laiola, M., & Roager, H. M., et al. (2020, July). Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut, 69(7), 1258–1268. https://doi.org/10.1136/gutjnl-2019-320438
10. Jain, A. P., Aggarwal, K. K., & Zhang, P.-Y. (2015). Omega-3 fatty acids and cardiovascular disease. Eur Rev Med Parmacol Sci, 19(3), 441–445. https://www.europeanreview.org/article/8446