When triglycerides are high
As a cardiologist and cholesterol specialist, I am often asked what to do when triglycerides are high. Most of us understand what LDL cholesterol (aka “bad cholesterol”) is, but are high triglycerides bad? And what makes them go up? Elevated triglyceride levels are quite common, affecting more than one-fourth of American adults. Labeled as a “risk enhancing feature” by the American Heart Association, let’s explore how high triglycerides increase the risk for heart disease and what we can do about them.
What are triglycerides? What are optimal levels?
Triglycerides are fat that circulates in lipoproteins (cholesterol vehicles) in your blood. They are composed of three fatty acids attached to a (glycerol) backbone.
Triglyceride levels can be measured with a blood test - they are part of the standard lipid panel you get with your doctor. Other lipid parameters in this blood test include total cholesterol, HDL cholesterol, and LDL cholesterol. I’ve written about the standard lipid panel before and how to interpret it, so read this first if you’re just getting started and then come back here.
Normal levels of triglycerides are less than 150 mg/dL, with optimal likely less than 100 mg/dL. Anything above 150 mg/dL is considered elevated.
Levels greater than 500 mg/dL (and definitely >1000 mg/dL) are considered severely elevated and require very specialized low-fat dietary guidance by a registered dietician and medical treatment due to the risk of pancreatitis. What we’ll be discussing today are moderately elevated levels, which are lower than 500 mg/dL.
Why triglycerides increase
Hypertriglyceridemia, or elevated triglycerides in the blood, results from an imbalance in the production of triglyceride-rich lipoproteins and their removal. Stick with me here, because this is the key to understanding what makes them go up!
There are two main lipoproteins that carry the majority of our triglycerides - VLDL (made in the liver) and chylomicrons (from our intestines). Thus, we see elevated triglycerides most commonly from
increased production of VLDL particles in your liver and/or
increased dietary fat intake, leading to increased intestinal chylomicrons
Importantly, particularly at more moderate levels of hypertriglyceridemia, VLDL overproduction predominates, while increased chylomicrons are the primary source at higher levels of triglycerides. So, given that VLDL overproduction is the issue for most people with moderately elevated triglycerides, the key questions is - what causes the liver to make too much VLDL?
Both genetic predisposition and acquired conditions can cause elevated levels of triglycerides. In cases where triglycerides are moderately or severely elevated, it’s typically a combination of both.
1.Insulin resistance
Insulin is a hormone responsible for shuttling glucose from the blood and into the cells where it can be used for energy. In cases of insulin resistance, the body doesn’t respond properly to insulin, leading to higher blood glucose levels over time. In addition to stimulating glucose uptake by muscle and fat cells, insulin is also responsible for suppressing glucose production in the liver and inhibiting lipolysis (breakdown of triglycerides) in fat cells (adipocytes). When the adipose tissue no longer responds to insulin, triglycerides break down in fat cells and are released as excess free fatty acids into the bloodstream. These fatty acids head to the liver, which then stimulates the assembly and secretion of VLDL, resulting in an excess of VLDL and viola - hypertriglyceridemia.
2.Genes
Some people are genetically more prone to have elevated levels of triglycerides than others. When triglycerides are moderately elevated, typically this is due to the additive effects of several different genes that affect triglyceride metabolism. There are also several inherited conditions resulting from a single genetic condition that dramatically effects triglyceride levels such as familial combined hyperlipidemia (FCH) and familial chylomicronemia syndrome (FCS) to name a few.
3.Medications
Certain medications can cause elevated triglyceride levels. These medications include corticosteroids, beta-blockers, some diuretics like hydrochlorothiazide and chlorthalidone, antiretroviral regimens, oral estrogens, tamoxifen, some anti-depressants, and some anti-psychotic drugs
Triglycerides and heart disease risk
Elevated LDL-cholesterol is the primary target for cholesterol lowering because it robustly increases heart disease risk. That said, elevated triglyceride levels are an independent risk factor for cardiovascular disease. Individuals with high triglycerides have a higher risk of coronary artery disease than those with normal or low levels. Research has demonstrated that despite the use of statin therapy, heart and stroke risk remains high in patients with elevated triglycerides despite adequately treated LDL cholesterol levels. We also know that lowering triglycerides with purified, high dose EPA in those with a recent heart attack (and optimal LDL cholesterol levels), reduces risk of further events.
Mendelian randomization studies (which group people based on genes of interest) indicate that high triglycerides likely contribute to atherosclerosis because of the increased number of remnant cholesterol particles.
Remnant cholesterol particles (intermediate-density lipoprotein, chylomicron remnants, and VLDL remnants) are formed when an enzyme breaks down the triglycerides from VLDL and chylomicrons, leaving a very cholesterol rich, atherogenic particle. Under normal circumstances, these particles contribute very little to the circulating amount of atherogenic lipoproteins - typically it’s mainly LDL particles. However, when insulin resistance is at play or there are otherwise a large number of VLDL particles, these remnants increase in number and become delivery vehicles for cholesterol into the artery wall. Hence, it’s the creation of these atherogenic remnant particles, not necessarily triglycerides themselves, that create this elevated risk.
How triglycerides can be reduced
Unless triglycerides are very high (> 500 mg/dL), guidelines recommend lifestyle changes as the first line treatment for elevated triglycerides. Secondary causes should also be ruled out. Since elevated levels of VLDL and insulin resistance are the primary drivers for more moderate levels of elevated triglycerides, targeting these causes will lower triglycerides. Dietary interventions can lower triglycerides by 20-25%.
1. Minimize added sugar/refined grains
Eating foods that contain simple sugars can increase your triglyceride levels and worsen insulin resistance. Simple sugars, particularly fructose, also directly stimulates triglyceride synthesis in the liver. Refined grains include white bread, white rice, white pasta, pastries, crackers, and muffins. These should be replaced with whole grains that are high in fiber. Added sugar should also be limited.
2. Increase heart-healthy fats and protein
Consuming more omega-3 polyunsaturated fatty acids (PUFAs) — especially EPA and DHA — can help lower triglyceride levels by 3-45% depending on baseline triglycerides. These long chain omega-3s are found in fatty fish such as salmon, while plant based individuals can obtain EPA and DHA from algae oil. A small amount of ALA (a short chain omega-3) gets covered into EPA and DHA, and this can be found in hemp seeds, pumpkin seeds, chia seeds, walnuts, and flax seeds.
Increasing other sources of healthy fats such as nuts, seeds, and avocados can also be beneficial, as is increasing sources of lean protein. In one study, replacing 10% of calories from carbohydrates with 10% of calories from unsaturated fat lowers triglycerides by 10 mg/dL, while replacing 10% of calories from carbs with 10% of calories from protein lowers triglycerides by 16 mg/dL
3. Decrease alcohol consumption
Just one ounce of alcohol per day causes a 5-10% increase in triglycerides. Alcohol consumption should be limited to no more than one drink per day if you're a woman or two drinks per day if you're a man.
4. Regular aerobic and resistance exercise
Regular aerobic exercise increases the breakdown of fatty acids as well as triglycerides. Both resistance and aerobic exercise have been shown to decrease triglycerides, and they also result in a lower spike in triglycerides after meals - which has been associated with increased heart disease risk. At least 150 to 300 minutes of aerobic exercise per week is recommended.
5. Weight loss if above ideal body weight
A major step to lowering triglyceride level is losing weight if body weight is above ideal. Losing just 5-10% of body weight can improve several cardiometabolic risk factors if present, and typically lowers triglycerides around 20%, but can lower them by as as much as 70%.
6. Consider Time Restricted Eating (TRE) / Intermittent Fasting (IF)
There is also some evidence that time restricted eating (eating food only during a specific window typically from 8 to 10 hours) as well as intermittent fasting (typically alternative day 24 hour fasts) may also be beneficial. I reviewed this topic in detail here. While the science is still not conclusive, it appears that various forms of fasting can result in weight loss that is comparable to continuous energy restriction and also may be easier to stick with. There is also some evidence that there may be cardiometabolic benefits, such as reduced triglycerides, above and beyond just the weight loss alone.
The skinny on triglycerides
Elevated triglycerides, while not *the* primary target for cholesterol lowering, remains an important measure of our risk for cardiovascular disease. Closely linked with metabolic syndrome and the characteristic dyslipidemia that accompanies it, hypertriglyceridemia is often an important clue of underlying metabolic dysfunction. If LDL cholesterol is at goal, but triglycerides are not, this is an important next target for cardiovascular risk reduction. Lifestyle therapy is usually the first line therapy and can be quite effective.
