Apolipoprotein B is a large protein that serves as the backbone of LDL and other lipoproteins. It can help determine your risk of heart disease and some studies suggest it may even be a better predictor than the commonly-measured LDL cholesterol (the “bad” cholesterol). Read on to learn more about apolipoprotein B, what causes abnormal levels, and how to improve yours.
What is Apolipoprotein B?
Apolipoproteins are the building blocks of lipoproteins such as high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Lipoproteins bind fats and cholesterols and shuttle them around the blood.
Apolipoprotein B (ApoB) serves as the structural backbone of three important lipoproteins [1]:
- Very-low-density lipoprotein (VLDL)
- Intermediate-density lipoprotein (IDL)
- Low-density lipoprotein (LDL)
There are two types of apoB. One (ApoB48) is made in the gut as a part of compounds called chylomicrons. The other (ApoB100) is made in the liver and gets released into the blood in the form of VLDL. VLDL loses fats called triglycerides to form IDL and eventually LDL [2, 3].
Apolipoprotein B helps LDL bind to receptors on cells and deliver cholesterol. It’s also necessary for liver cells to bind LDL and remove it from the blood [1].
Each molecule of VLDL, IDL, and LDL contains exactly one molecule of apoB. This makes apoB a measure of total non-HDL lipoproteins in circulation. In other words, apoB is a measure of lipoprotein carrying “bad” cholesterol [2, 3].
ApoB-containing lipoproteins are the main contributors to the hardening of the arteries (atherosclerosis) and heart disease [1].
Role in the Immune System
Studies suggest that ApoB may help defend the body against bad bacteria such as Staphylococcus aureus by interfering with a process called quorum sensing. Quorum sensing is how bacteria “talk” to each other to coordinate the necessary actions for survival [4].
Apolipoprotein B Test
Testing ApoB is not part of routine practice, but doctors will use ApoB to help determine your risk of heart disease if you have a family history of heart disease or other heart disease risk factors (i.e. high cholesterol and triglycerides). It is also used to diagnose genetic diseases that cause extremely low or high ApoB levels.
Normal Levels
The normal range for apolipoprotein B is generally below 120 mg/dL (milligrams per deciliter), or 1.2 g/L (grams per liter), and optimally below 90 mg/dL (0.9 g/L). Ranges may vary slightly between laboratories.
Some labs may report a slightly different range for men and women. Men tend to have slightly higher levels on average [5].
Some labs also report a lower limit of the normal range, which is generally around 40 – 50 mg/dL (0.4 – 0.5 g/L).
Low Apolipoprotein B Levels
Causes
ApoB levels can decrease in conditions that affect lipoprotein production in the liver.
Causes shown below are commonly associated with low ApoB levels. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret your ApoB level, taking into account your medical history, symptoms, and other test results.
1) Liver Disease
Most of ApoB is produced in the liver. That’s why apoB levels decrease in liver disease [6].
A study found that ApoB levels were reduced by 25% in 74 patients with chronic liver failure compared to 82 healthy subjects [7].
In another study, liver malfunction induced by hepatitis B decreased apoB levels in 148 people [8].
In a study of 213 people, 25% of people with chronic hepatitis C had low ApoB levels. Only 5% of healthy controls had low levels. Lower apoB levels were also linked to a higher viral load [9].
2) Malnutrition
ApoB levels can decrease with protein malnutrition [10, 11]. This type of malnutrition is usually due to an underlying health issue (e.g. protein wasting enteropathies).
Dietary protein deficiency is rare in Western countries. They usually happen with starvation.
3) Hyperthyroidism
People with hyperthyroidism can have lower apoB levels. That happens because of an increased breakdown of LDL particles [12].
Two studies found lower ApoB levels in 48 hyperthyroid patients, which increased as their thyroid function improved after therapy [13, 14].
4) Medication
Many drugs used to lower cholesterol can decrease ApoB levels, including:
- Statins (Lipitor and Zocor) [15]
- Fibrates such as gemfibrozil (Lopid) [16]
- Bile acid sequestrants including cholestyramine (Questran) and colestipol (Colestid) [17, 18]
- Ezetimibe (Zetia) [18]
- PCSK9 monoclonal antibodies such as alirocumab (Praluent) and evolocumab (Repatha) [19]
- Mipomersen (Kynamro), used to treat familial hypercholesterolemia (genetically high cholesterol) [20]
Selective estrogen receptor modulators (SERMS) such as Raloxifene (Evista), used to treat and prevent osteoporosis in postmenopausal women can also decrease ApoB [21].
5) Genetic Disorders
Familial hypobetalipoproteinemia is a disease in which low ApoB levels are caused by mutations in the ApoB gene and other related genes. There are over 60 mutations that can cause this disease [22, 23, 24, 25].
Abetalipoproteinemia is another disease in which ApoB levels are undetectable [26].
Although deficiency of apoB may lower the risk of heart disease, it can result in debilitating neurological complications, fatty liver, and liver cancer. That’s why early discovery and appropriate treatment and follow up are essential [26].
Health Effects of Low Apolipoprotein B Levels
May Increase The Risk of Infections
Research suggests that apolipoprotein B may help defend the body against microbes [4]. Lower would in theory, therefore, increase the risk of infections.
There is one study with 40 people with severe injuries that showed that those with low ApoB levels had an increased risk of infection compared to those with higher levels [27].
However, additional studies that would support this finding are needed.
Increasing Apolipoprotein B
Apolipoprotein B levels can be low due to an underlying health issue. The most important thing is to work with your doctor to find out what’s causing your low ApoB levels and to treat any underlying conditions.
Studies suggest that alcohol decreases ApoB levels, likely due to its effect on the liver. Reducing alcohol consumption may help raise ApoB levels by improving liver health.
In a study of 16 people, those who drank alcohol saw a decrease in their LDL-apoB levels [28].
In a study of 18 alcoholics, ApoB levels increased by 24% after they stopped drinking [29].
High Apolipoprotein B Levels
High levels of ApoB correspond to higher levels of “bad” cholesterol (LDL and VLDL cholesterol) and are associated with a higher risk of heart disease.
Causes
Causes listed below are commonly associated with high apolipoprotein B levels. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret your results, taking into account your medical history, symptoms, and other test results.
1) High-Fat Diet and Sugar
A study of 53 people found that increasing calories from saturated fat from 8% to 18% increased ApoB levels by 9.5% [30].
Similarly, in a study of 40 people, those who ate more saturated fat had higher ApoB levels than those who ate less (15% vs 5% of calories) [31].
Data suggests that over 13% of the U.S. population consumes 25% or more of energy from added sugars. A study showed that eating 25% calories from fructose and high-fructose corn syrup increased ApoB levels in 48 people after only 2 weeks [32].
In almost 25k people, those who had higher intakes of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar, and sugar-sweetened beverages) had higher ApoB levels [33].
In a study of 13 people who ate up to 3 large eggs a day, ApoB levels increased 0.93 mg/dL per 100 mg of cholesterol consumed [34].
2) Insulin Resistance and Diabetes
Insulin resistance is when the body no longer responds to the hormone insulin. This causes glucose to stay in the blood, raising blood sugar levels.
Insulin decreases ApoB production by promoting apoB breakdown and clearance in the liver. However, when cells become insulin resistant, ApoB is cleared less efficiently and blood levels increase [35].
In an observational study of 15 people, those with insulin resistance had 35% higher ApoB levels than those without the condition [36].
An observational study of more than 700 people found that ApoB levels were 15% higher in people with diabetes than in healthy people [37].
In another observational study of 1,500 people, diabetics had higher ApoB levels than non-diabetics. ApoB levels were then tested again after three months. Increases in ApoB levels were directly linked to increases in blood sugar levels [38].
3) Being Overweight/Obese
Higher ApoB was linked to higher BMI in an observational study of almost 25k people [33].
Similarly, in 298 people with diabetes, higher BMI was associated with higher ApoB levels [39].
The same was shown in a study of 76 men and 115 women [40].
However, one study failed to find a link between ApoB and BMI in 476 young Cherokee adults [41].
A study of 35 obese people found that a 12% weight loss resulted in 17% lower ApoB levels over 16 weeks [42].
Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of obesity and metabolic syndrome.
In an observational study of 22k people, those with non-alcoholic fatty liver disease (NAFLD) had 18% higher ApoB levels [43].
4) Hypothyroidism
In an observational study of more than 200 people, those with hypothyroidism had 35% higher ApoB levels than those with normal thyroid function [44].
Another observational study of more than 400 people found that those who were hypothyroid had elevated ApoB levels [45].
ApoB levels decreased by 27% in 19 people with hypothyroidism after treatment improved their thyroid function [14].
5) Kidney Disease
In an observational study of 30 people, those with chronic kidney disease had 30% higher ApoB levels. This was due to less ApoB being removed from circulation [46].
Nephrotic syndrome is a kidney disorder that causes the body to release too much protein in the urine. Nephrotic syndrome causes more apoB to be made by the liver and less removed from circulation [47].
6) Medication
Various drugs can increase apoB levels, including:
- Androgens/anabolic steroids [48]
- Chemotherapy drugs including doxorubicin (Adriamycin, Doxil, Lipodox) and paclitaxel (Taxol, Abraxane) [49]
- Carbamazepine (Tegretol, Carbatrol, Epitol), used to treat seizures and nerve pain [50, 51]
- Cyclosporine (Neoral, Sandimmune, Gengraf) and tacrolimus (Prograf, Protopic, Astagraf XL), drugs used to suppress the immune system and prevent organ rejection after transplants [52]
- Infliximab (Remicade), a drug used to treat autoimmune disease [53]
- Protease inhibitors used to treat HIV [54]
7) Pregnancy
ApoB levels are normally increased during pregnancy [55].
8) Menopause
Sex hormones influence ApoB levels.
In an observational study of 1.6k women, ApoB levels were higher in postmenopausal than in premenopausal women [5].
In another observational study of 37 women, postmenopausal women had higher ApoB levels than premenopausal women [56].
9) Lack of Sleep and Sleep Disorders
In an observational study of 7.3k people, sleeping less than 6 hours a night was associated with a 75% increased risk of high ApoB levels compared to sleeping seven to eight hours [57].
In another study with over 8.5k people, sleeping less than 6 hours increased the odds of having high ApoB by 1.8 times in women. The association was not significant in men [58].
In 570 women with suspected obstructive sleep apnea, ApoB levels increased with apnea severity, but only in non-obese subjects and those < 55 years of age [59].
Sleep may affect ApoB by increasing insulin resistance. A lack of sleep and lower sleep quality have been linked to higher insulin resistance [60].
10) Growth Hormone Deficiency
In an observational study of 25 people, individuals with growth hormone deficiency had 25% higher ApoB levels than healthy controls [61].
Treatment of growth hormone deficiency increases the removal of ApoB from circulation [62].
11) Genetic Disorders
ApoB levels are high in inherited genetic disorders such as familial hypercholesterolemia and hyperlipidemia [63, 64].
Associations
1) Smoking
In an observational study of over 24k men and 35k women, current smokers had higher levels of ApoB than non-smokers [65].
In another study of almost 25k people, ApoB was linked to smoking [33].
Similarly, in 600 people, ApoB levels were higher in current cigarette smokers than non-smokers. The association was significant for men but not women [66].
In addition, in over 250 men, those who smoked over 20 cigarettes/day had about 12 mg/dL higher ApoB levels than non-smokers [67].
However, a study of over 10k adolescents and adults failed to show any significant effect of smoking on ApoB levels [68].
It’s possible that people who smoke also tend to have a less healthy diet that would affect ApoB levels.
2) Drinking Coffee
In an observational study of 77 people, drinking more than two cups a day of coffee was linked to higher ApoB levels. Less than two cups a day showed no association with ApoB levels [69].
In 42 people with high cholesterol, 8 cups a day of boiled coffee, but not filtered coffee or tea, increased ApoB levels [70].
Further, in 180 men who drank coffee, ApoB increased in those who changed to decaf. This suggests that a coffee component other than caffeine is responsible for the effect [71].
However, in a study of 119 healthy students, neither filtered nor decaffeinated coffee had an effect on ApoB [72].
Health Effects of High Apolipoprotein B Levels
1) Heart Disease
VLDL, IDL, and LDL molecules contribute to the hardening of the arteries and heart disease because they can lodge in blood vessel walls and help build up plaques. Because ApoB levels are a marker of how many of these molecules are in the blood, they can reveal your risk of heart disease [1].
Many observational studies show that high apoB levels are strongly linked to an increased risk of heart disease. Research suggests that ApoB may even be a better measure of heart disease risk than traditional risk factors LDL-C, total cholesterol, and triglycerides [73, 74, 75, 76, 77, 78, 79, 80].
2) Diabetes
One observational study tested apoB and blood sugar levels of more than 600 healthy people at baseline and then 10 years later. High ApoB levels increased the risk of developing type 2 diabetes over the 10-year period [81].
High ApoB levels were associated with higher HbA1c levels (a measure of 3-month average glucose levels) in an observational study of over 400 people. Women with high ApoB levels at baseline had increased HbA1c levels after 1 to 2 years [82].
3) Cancer
Higher ApoB levels were linked to an increased risk of lung and colorectal cancer in an observational study of 5.2k people, with a follow up of over 15 years. However, higher apoB levels were associated with a decreased risk of breast cancer in women [83].
4) Memory Decline and Alzheimer’s
People with depression often have issues with brain function including memory. In an observational study of 180 people, higher ApoB levels were associated with worse memory scores in those with depression [84].
An observational study of 56 people found that those with Alzheimer’s disease had 26% higher ApoB levels than those without the disease [85].
In animals, too much ApoB promotes memory decline and brain cell damage [86].
Decreasing Apolipoprotein B
The most important thing is to work with your doctor to find out what’s causing your high ApoB levels and to treat any underlying conditions.
In addition, work with your doctor on a strategy to decrease your ApoB levels. In general, lifestyle and dietary changes that lower bad and increase good cholesterol will also decrease your ApoB levels.
Discuss the lifestyle changes listed below with your doctor. None of these strategies should ever be done in place of what your doctor recommends or prescribes!
1) Eat a Healthy, Balanced Diet
Mediterranean Diet
A Mediterranean diet is high in olive oil, leafy greens, legumes, and nuts and fruits. Foods eaten in moderation include fish, meat, and dairy.
A study of 70 people found that eating a Mediterranean diet for 4 weeks decreased ApoB levels by 10% [87].
Another study of 551 people at high risk of heart disease found that the Mediterranean diet reduced ApoB levels by 4.4% compared to a low-fat diet [88].
More Fish
Eating oily fish (2.8 oz, or 80 g, a day) such as salmon and herring for 8 weeks reduced ApoB levels in 126 people [89].
In a study of 20 people, a diet that included fish at least two times a week reduced ApoB levels by 23% over 24 weeks compared to a typical Western diet [90].
More Nuts
A meta-analysis of 61 studies and 2.5k people concluded that eating nuts decreased ApoB levels by an average of 3.7 mg/dL [91].
A study of nearly 200 people found that eating 43 g of walnuts a day for 8 weeks decreased ApoB by 7 mg/dL [92].
In an observational study of 9.6 people, those who ate nuts more than 4 times a week had half the risk of having high ApoB levels compared to those who never ate nuts [93].
A meta-analysis of six studies and 250 people found that hazelnuts decreased ApoB levels [94].
More Soluble Fiber
A diet high in soluble fiber decreased ApoB levels over 6 weeks in a study of 44 people [95].
Soluble fiber is found in vegetables, fruits, beans, and oats.
Less Fructose
Fructose is found in most fruits and high-fructose corn syrup is found in sodas, cereals, juices, and baked goods.
Eating > 25% calories from fructose and high-fructose corn syrup increased ApoB levels in 48 people [32].
In almost 25k people, those who had higher intakes of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar, and sugar-sweetened beverages) had higher ApoB levels [33].
Less Fried and Roasted Foods/Saturated Fats
Compounds in fried and roasted foods called advanced glycation endproducts (AGEs) are able to raise ApoB levels. When 26 people consumed diets low in AGEs, their ApoB levels decreased by 25% [96].
Alternatives to frying and roasting include boiling, poaching, stewing, or steaming your food.
Consuming 18% of calories from saturated increased ApoB levels by 9.5% compared to eating 8% of calories from saturated fat (53 total people) [30].
People who ate 15% of calories from saturated fat had higher ApoB levels after three weeks than those who ate 5% of calories from saturated fat (40 total people) [31].
Unsaturated Fats/Vegetable Oils
An 8-week study of 16 men found that eating 39% of calories as fat from diets rich in safflower and canola oils reduced ApoB levels by as much as 24% compared to a typical American diet [97].
2) Exercise
An observational study of over 100 people found that those who engaged in 30 – 60 minutes of moderate exercise five days per week had 14% lower ApoB levels than those who didn’t exercise at all [98].
Resistance exercise decreased ApoB levels by 50 mg/dL over 3 months in 52 people with type 2 diabetes [99].
Studies suggest both resistance and endurance exercise are helpful [100, 101].
3) Lose Weight
A study of 35 obese people found that a 12% weight loss resulted in 17% lower ApoB levels over 16 weeks [42+].
In 9 people with non-alcoholic fatty liver disease, a low-fat diet caused weight loss and decreased ApoB levels [102].
4) Get Enough Sleep
Sleeping less than 6 hours a night is associated with higher ApoB levels [57, 58].
5) Drink Less Coffee and Quit Smoking
Drinking lots of coffee (over 2 cups/day) is linked to higher ApoB levels. The same effect has been observed with decaf [69].
In addition, several studies found higher ApoB levels in smokers [65, 33, 66, 67].
It’s not certain that these relationships are causal, but not smoking and not overindulging in coffee will certainly be good for your health.
6) Supplements
Discuss the following foods and supplements with your doctor. Research has shown they may help decrease cholesterol levels:
- Fiber, including beta glucans and glucomannan [103, 104]
- Plant sterols [105]
- Red yeast rice [106]
- Omega-3s [107]
- Berberine [108]
- Probiotic products that contain Lactobacillus strains [109, 110]
- Vitamin C [111, 112]
Remember, always speak to your doctor before taking any supplements, because they may interfere with your health condition or your treatment/medications!
Genetics
Low ApoB Levels
Familial hypobetalipoproteinemia, familial combined hypolipidemia, and abetalipoproteinemia are genetic disorders that result in low or undetectable levels of ApoB. Mutations in the following genes can cause these disorders [113, 23, 24]:
The following SNPs are associated with decreased ApoB levels [114]:
High ApoB Levels
Familial hypercholesterolemia and hyperlipidemia are genetic disorders that result in high ApoB levels. Mutations in the following genes can cause these disorders [63, 64]:
The following SNPs are associated with increased ApoB levels [115, 114, 116]:
