We all know the warning cry: high cholesterol levels can increase your risk of heart disease. But there’s a quieter warning for men only: high cholesterol levels are linked with aggressive prostate cancer (PCa).

That’s the message of a June 2023 paper by Liu, et al. published in the International Journal of Cancer.^[i] The article is a sequel to their earlier finding of this connection, based on data from the Health Professionals Follow-up Study (HPFS). The more recent publication now adds 568 more PCa cases to their total pool, and compares the total cholesterol levels (HDL and LDL combined) of 1260 men newly diagnosed with prostate cancer between 1993 and 2004, and 1328 controls.

What they discovered was an increased risk of higher-grade (Gleason ≥4 + 3) PCa among men with the highest total blood cholesterol levels (≥200 mg/d) vs. those with the lowest levels. It would appear that high total cholesterol is like an armed robber brandishing a gun and demanding your wallet of prostate health.

What’s the biology behind the threat?

I’ve previously blogged about the demographic observations of a cholesterol-prostate connection. For this blog, I want to take a closer look at the biology of PCa cells their need for cholesterol. A European biotechnology science team did a deep dive into the cellular chemistry of how normal prostate cells and PCa cells utilize cholesterol. According to these researchers,

The prostate is a gland in the male reproductive system which has the main purpose of secreting prostatic fluid which supports spermatozoa during fertilization. Prostate exhibits a unique metabolism adapted to meet the demands of its function; production of prostatic fluid, mostly consisting of citrate, zinc, kallikrein enzymes and cholesterol.^[ii]

Cholesterol is key component for building healthy cells. It is “essential for cell cycle progression and differentiation.”^[iii] The organ that manufactures 80% of your cholesterol is the liver, in a process called biosynthesis, and delivers it into blood circulation for all the body’s cells that need it. Healthy prostate cells benefit from supply source, but what you may not know is that prostate cells themselves also biosynthesize cholesterol. There are molecular signaling pathways that regulate how much cholesterol the prostate can manufacture.

The problem with PCa cells is that they are like hyperactive kids with uncontrollable energy. Not only do they uptake and store circulating cholesterol to meet the needs of building their rapidly duplicating cells, they biochemically downregulate the biosynthesis signaling pathways. It’s like a steam engine with a defective governor that no longer controls the flow of steam, and the engine begins to rev to insane speeds—think of a runaway locomotive!

Rye, et al. write:

In prostate cancer cell-lines, elevated activity of the cholesterol synthesis pathway supports cancer growth and aggressiveness. This has led to the general view that increased cholesterol synthesis in prostate cancer cells contributes to cellular accumulation of cholesterol and prostate cancer growth. A diet high in fat and cholesterol increase the risk of prostate cancer, while statins directly targeting the cholesterol synthesis pathway are associated with improved clinical outcome.^[iv]

The clue to discouraging the association between cholesterol and aggressive PCa cells lies in the above quote. In my update blog on The 3 Worst Things You Can do to Your Prostate, I note the importance of maintaining healthy cholesterol levels, but I also summarize recent conflicting evidence on the impact of statins use on PCa. I encourage you to revisit that blog.

In the meantime, there is wide agreement that both dietary cholesterol and PCa’s own self-manufacture of this fatty substance pose a threat to prostate health. Don’t let a diagnosis of PCa be the evidence, like a smoking gun, that cholesterol was one of the factors behind it. No matter what, high cholesterol is a dangerous culprit. Take the steps you need to avoid becoming its victim.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Liu H, Shui IM, Keum N, Shen X et al. Plasma total cholesterol concentration and risk of higher-grade prostate cancer: A nested case-control study and a dose-response meta-analysis. Int J Cancer. 2023 Jun 12.
[ii] Škara L, Hu?ek Turkovi? A, Pezelj I et al. Prostate Cancer-Focus on Cholesterol. Cancers (Basel). 2021 Sep 19;13(18):4696.
[iii] Liu, ibid.
[iv] Rye MB, Bertilsson H, Andersen MK, Rise K et al. Cholesterol synthesis pathway genes in prostate cancer are transcriptionally downregulated when tissue confounding is minimized. BMC Cancer. 2018 Apr 27;18(1):478.