A Gene Essential for Blood Fat Removal & Its Impact on Blood Pressure (APOE)

Exercise

Multiple studies show that exercise training may lower blood pressure, both in the first few hours after exercise and in the long term. Exercise guidelines often recommend aerobic exercise most days of the week (at least 150 min/week of moderate activity or 75 min/week of vigorous activity) supplemented with dynamic resistance exercise twice weekly [R].

A meta-analysis of 51 studies found that aerobic exercises such as jogging, running, and biking increased “good” cholesterol (HDL-cholesterol) levels by 4.6% and decreased “bad” cholesterol (LDL-cholesterol) by 5%. This suggests that exercise may lower the risk of atherosclerosis in individuals with apoE4 isoforms (i.e., in those that can’t effectively clear cholesterol) [R].

Indeed, in mice lacking apoE (comparable to the ineffective apoE4 isoform), exercise prevented the development of atherosclerosis, suggesting that it may also lower blood pressure. One study found that exercise may be particularly beneficial for lowering blood pressure in hypertensive individuals carrying apoE3 or apoE4 isoforms [R, R]. 

Meta-analyses estimated blood pressure reductions of 12.26 mmHg (systolic) and 6.12 mmHg (diastolic) from aerobic exercise. The combination of moderate- with high-intensity aerobic exercise (interval training) further enhanced the blood pressure-lowering effects of exercise training [R, R, R].

As for resistance training, a single bout lowered blood pressure by up to 8.2 mmHg (systolic) and 4.1 mmHg (diastolic) within the first hours after exercise, while continuous resistance training lowered it by 4-5 mmHg (systolic) and 1.7-5 (diastolic). However, resistance training should be used with caution because it increases blood pressure during exercise [R, R, R, R].

Exercise modalities such as aquatic exercise, stretching, brisk walking, and tai chi have all been proven effective at lowering blood pressure [R, R, R, R].

In all cases, exercise was more effective in hypertensive people than in those with normal blood pressure values.

Exercise may help lower blood pressure by reducing cholesterol and preventing atherosclerosis progression — particularly in those carrying APOE risk variants.

Mediterranean Diet

Mediterranean diets are well-known to help lower cholesterol and decrease the risk of heart diseases such as atherosclerosis [R, R, R, R].

A meta-analysis of 30 clinical trials found that adherence to a Mediterranean diet helps prevent heart disease by lowering systolic (by ~3 mmHg) and diastolic (by ~2 mmHg) blood pressure in people with normal values. In those with hypertension, this diet lowered systolic blood pressure by 1.44 mmHg and diastolic blood pressure by 0.7 mmHg [R, R].

When compared to other diets, the Mediterranean diet is especially effective at lowering diastolic blood pressure. A meta-analysis found it only effective for this purpose, while another one ranked it third in terms of diastolic pressure-lowering effect (after the DASH and Paleolithic diets) [R, R].

Extra-Virgin Olive Oil

A major component of Mediterranean diets is olive oil. Oleocanthal, a compound found in extra-virgin olive oil, may promote apoE activity [R].

Several meta-analyses found that extra-virgin olive oil in particular may lower systolic but not diastolic blood pressure. The antioxidant polyphenols in extra-virgin olive oil may reduce oxidative damage to the blood vessels and enhance the production of the blood vessel-widening molecule nitric oxide [R, R, R].

In a small study of people with high blood pressure, a diet rich in extra-virgin olive oil reduced the need for blood pressure-lowering medication [R].

Fatty Fish/Omega-3

Fish are also major Mediterranean diet components. Fatty fish such as salmon, tuna, mackerel, herrings, and sardines are rich in omega-3 fatty acids.

In one study, atherosclerosis-related dysfunction was reduced in mice lacking apoE (comparable to the ineffective apoE4 isoform) that were supplemented with omega-3-rich fish oil [R].

High blood levels of omega-3 fatty acids, especially docosahexaenoic acid (DHA), were associated with a reduced incidence of elevated blood pressure events in a meta-analysis of 8 observational studies [R].

Meta-analyses show that supplementation with omega-3 fatty acids from fish oil (EPA + DHA) significantly reduces both systolic (by 2.5-5.5 mmHg) and diastolic (by 1.5-3.5 mmHg) blood pressure, as well as the levels of the inflammatory marker CRP (by ~0.5 mg/L). The effects are more pronounced in people with moderate, untreated hypertension [R, R].

A Mediterranean diet rich in extra-virgin olive oil and fatty fish (omega-3s) may lower blood pressure by promoting apoE activity, lowering cholesterol, and preventing atherosclerosis progression.

Melatonin

Studies have shown that melatonin may increase apoE production and prevent atherosclerosis progression, suggesting that it may also lower blood pressure in individuals carrying APOE risk variants [R, R, R].

A meta-analysis of 7 studies involving people with nocturnal hypertension found that supplementation with controlled-release (but not fast-release) melatonin lowered systolic (by 6.1 mmHg) and diastolic (by 3.5 mmHg) blood pressure. Another meta-analysis of 8 studies and 743 people with metabolic disorders also found melatonin effective at lowering blood pressure  [R, R].

Like sleep, blood pressure has circadian rhythmicity. It increases in the morning and decreases at night. Melatonin shows the opposite pattern, indicating that it may have a role in lowering blood pressure at night. In line with this, activation of the melatonin receptors MT1 and MT2 widens the blood vessels [R].

Melatonin may lower blood pressure by increasing apoE production and preventing atherosclerosis progression.