Does Pterostilbene Increase LDL Cholesterol?

Some people worry that pterostilbene increases LDL cholesterol and that this is a bad thing.  

A study done in 2014 found that people who took pterostilbene supplements had an increase in LDL cholesterol (R). 

However, we have several reservations about this study, and how it’s interpreted:  

1. LDL levels are often measured indirectly, by subtracting the HDL and VLDL levels from total cholesterol levels. It remains to be seen whether LDL levels actually increased in this study (if so, by how much), or if total cholesterol increased, or if other components decreased that make up cholesterol (e.g., VLDL). 

Ideally, LDL is measured directly (and compared to total cholesterol and HDL cholesterol ratios) to get a better interpretation regarding how much LDL actually increased. 

2. Another more recent study found that LDL levels were not increased in normal healthy people that took 50 mg of pterostilbene per day. In healthy people who took 100 mg of pterostilbene, LDL levels were somewhat increased, but total cholesterol levels also differed significantly in participants making interpretations difficult (NOVOS contains only 50 mg of pterostilbene). While LDL levels increased overweight people who took pterostilbene, LDL levels also increased in the control (placebo) group (R). According to the researchers: 

“Subjects in the NRPT 1X (nicotinamide riboside + 50 mg of pterostilbene) group with normal BMI (18–25) showed no significant increases in LDL cholesterol. 

Subjects in the NRPT 2X (nicotinamide riboside + 100 mg of pterostilbene) group with normal BMI did show increases in LDL cholesterol. 

Subjects in the overweight category (BMI 25-32) showed increases in LDL cholesterol in both the NRPT 1X and NRPT 2X groups. However, overweight subjects in the placebo group also showed a significant increase. 

Overall, these findings suggest a small but significant increase in cholesterol may occur at the normal dose of NRPT, at least for people with a higher than normal BMI.”

3. Some scientists speculate that if pterostilbene does increase LDL, it does this via interaction with the PCSK9 signaling pathway and via epigenetic effects, which might be actually protective for the heart and blood vessels (R). According to the researchers: 

“The cardioprotective benefits of pterostilbene in LDL-C (LDL-cholesterol) lowering were mediated through the PCSK9/HNF1α/SREBP2/LDLR signaling pathway by mechanisms that involve inhibiting HNF1α/SREBP2/HIF1α/Nrf2 transcription factors, decreasing the secretion of PCSK9, upregulating epigenetic control of miR-335 and miR-6825, and increasing LDLR (LDL-receptor) expression, suggesting pterostilbene’s future clinical use in association with other drugs targeting PCSK9.”

4. LDL is often considered as the “bad” cholesterol, but it’s not that straightforward. Some studies show that too low of LDL levels could actually increase the risk of Parkinson’s disease for example (R). Also, negative effects of LDL depend not only on LDL levels but also whether the LDL is oxidized, glycated, and/or smaller in size — all of which are unhealthy attributes.

5. Various studies show that pterostilbene improves many other biomarkers of cardiovascular health. For example, in the same study that demonstrated that pterostilbene increased LDL cholesterol levels, it was found that pterostilbene also reduced blood pressure. High blood pressure is an important risk factor for heart disease and stroke. Other studies in animals show that pterostilbene prevents hypertrophy and improves vascular function (R), improves endothelial function by inhibiting the effects of oxidized (dangerous) LDL (R,R), and so on.

6. Various studies show that pterostilbene impacts many other important aging mechanisms and diseases in a beneficial way. For example, studies in mammals show that pterostilbene could reduce inflammation (R), reduce the risk of Alzheimer’s (R), diabetes (R), slow aging, and mitigate various other aging-related diseases (R,R,R). So if you look at the bigger picture, it seems that pterostilbene has more advantages than disadvantages. 

7. In the end, we need to look at the most important health outcome: lifespan extension. Each ingredient will have positive, neutral and negative effects. It’s the sum of all these effects that leads to lifespan extension or not. We see that pterostilbene could extend lifespan, or mitigate aging, regardless of the impact it may have on LDL (R).

To make a long story short, it’s important to see how LDL is measured (directly or indirectly), to look at other cardiovascular effects pterostilbene can have (like reducing oxidized cholesterol, improving endothelial health, or reducing blood pressure), and at other beneficial effects pterostilbene can have on various aging mechanisms (e.g. inflammation), aging diseases (e.g. Alzheimer’s or diabetes) or aging (lifespan) itself.