Prostate Health: How Genes, Diet, and Lifestyle Shape Your Risk

Key takeaways:
~ Oxidative stress, caused by an imbalance of reactive oxygen species (ROS), is a significant factor in the development of prostate cancer and benign prostate hyperplasia (BPH). It can damage cells, interfere with protein function, and harm DNA.
~ Diet and environmental toxins matter, increasing oxidative stress and inflammation in the prostate, contributing to prostate problems.
~ Genetic variants can increase the risk of BPH or prostate cancer, and some of these variants are related to how our bodies handle environmental toxins.
~ Understanding these genetic factors can help you know which environmental factors and dietary interactions are most important.
Members will see their genotype report below and the solutions in the Lifehacks section. Consider joining today. 

What causes prostate problems?

Prostate problems are common in men as they age, with conditions like benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer affecting millions of men. Your genetic variants, along with environmental factors, significantly influence your risk of developing prostate issues.

In this article, you’ll learn:

• What the prostate does and why problems occur
• The underlying causes of changes and inflammation in the prostate
• Risk factors, including genetic variants and how they combine with environment
• Diet, lifestyle, and supplements that can help prevent problems

Types of prostate problems:

Prostate problems are common in older men and can include:

Prostate-specific antigen (PSA) levels are used to screen for prostate issues. High PSA levels can indicate prostatitis, BPH, or prostate cancer. The name prostate-specific is a bit of a misnomer since women also produce PSA at lower levels.

Prostate cancer is one of the most common cancers in men. In the US and EU, it is the second most common cancer diagnosis — and the second highest cause of cancer-related deaths in males. (Lung cancer is #1.) Currently, 1 in 8 men can expect to be diagnosed with prostate cancer in their lifetime, but the good news is that the 5-year survival rate is 99% when caught early.[ref][ref]

What does the prostate do?

The prostate is a gland in the male reproductive system that surrounds the urethra just below the bladder. It secretes a part of the fluid that becomes semen and protects sperm. Additionally, it acts as a muscle that is important in controlling urination. When the prostate is enlarged, it can press on the bladder and decrease urine flow through the urethra.

Oxidative stress at the heart of prostate cancer and BPH:

One of the most critical molecular pathways in the development of prostate cancer involves a complex interaction between oxidative stress, chronic inflammation, and androgen receptor (AR) driven signaling. Additionally, it has been suggested that oxidative stress is essential for the formation of the aggressive phenotype in addition to being fundamental to prostate cancer growth.

What is oxidative stress?
Oxidative stress is the state in a cell when reactive oxygen species (ROS) are higher than normal. Reactive oxygen species are molecules with free radicals derived from oxygen through redox reactions. Examples of ROS include hydrogen peroxide, superoxide, and hydroxyl radicals. ROS at low levels has important signaling properties within a cell, but a higher levels, ROS is very detrimental.

Oxidative stress can cause vascular tissue damage, interfere with the way that proteins in cells are supposed to work, and cause damage to the nuclear DNA. Oxidative stress can also negatively impact stem cells and decrease a cell’s ability to repair the damage.[ref]

What causes oxidative stress in the prostate?

Oxidative stress increases in aging as well as through exposure to toxicants and dietary choices.

Let’s take a look at how diet and toxins increase susceptibility to prostate problems…

Oxidative stress from diet:
Omega-6 fats are found in large quantities in our modern diet (fried foods, mayo, chips, sauces, etc.).

The peroxidation of omega-6 fatty acids causes inflammation in the prostate. Men with BPH and high PSA levels have higher levels of these peroxidation metabolites. Our modern diet has a lot higher intake of omega-6 fats than humans have historically eaten. This is likely one of the reasons behind the increase in prostate problems since the 1950s.[ref][ref]

Why is the prostate so vulnerable?
Prostate cells turn over rapidly and have fewer DNA repair enzymes, thus leaving them vulnerable to damage from oxidative stress. This damage then leads to the activation of inflammatory pathways.[ref]

Decreased antioxidants:
In men with BPH, research shows they have a decrease in antioxidant defenses. In other words, the excess of ROS in the prostate can’t be countered by the body’s built-in antioxidant defenses.[ref] This could be due to a lack of micronutrients in the diet or due to continuing exposure to a toxicant that causes oxidative stress.

Age is an important factor:
One reason that aging is associated with oxidative stress is an increase in cellular senescence.

cellular senescence = increased inflammation in the prostate = BPH

Senescent cells are at the end of their cellular life and are unable to divide. This process is normal, and senescent cells are cleared out throughout life. But in older people, there is an increase in senescence above what can be easily cleared out. It is a problem because senescent cells give off inflammatory cytokines (which normally are the signal that causes the immune system to clear them out). An excess of senescent cells then leads to elevated inflammation, which is directly linked in research to the development of BPH.[ref]

Environmental toxins:

In addition to dietary causes and cellular senescence in aging, exposure to toxicants also increases oxidative stress in the prostate.

Here are examples from research studies on environmental factors:

• Farmers exposed to high levels of pesticides are at a fourfold increased risk of prostate cancer.[ref]
• Dioxins are persistent organic pollutants that increase the risk of prostate cancer.[ref]
• Phthalates are chemicals found in artificial fragrances (think air fresheners, laundry detergents, and shampoo) and plastics. Phthalates act as endocrine disruptors and are associated with oxidative stress in BPH and prostate cancer.[ref]
• Exposure to trace metals, such as cadmium, mercury, lead, or nickel, is also associated with prostate diseases.[ref]
• BPA, an estrogen mimic found in plastics, is linked to enlarged prostate and prostate cancer risk.[ref][ref]
• PFAS (Per- and polyfluoroalkyl substances) exposure increases the relative risk of prostate cancer (a little bit).[ref]

There’s a new environmental factor that research is showing to be a significant problem: microplastic and nanoplastic particles.

A 2024 study investigated prostate tumor tissue samples. The results showed that the tumors and tissue around the tumors contained microplastics primarily in the 20 to 50 μm size range, with polystyrene and PVC particles being the main types.[ref]

Another 2024 study of prostate tissue from men undergoing the TUR-P procedure (non-cancerous tissue) showed that 50% of the tissue samples contain microplastic particles.[ref]

Microplastics have also been found in semen and testicular samples. The particles have been shown to directly increase oxidative stress. Additionally, some microplastic particles may leach endocrine disruptors, such as BPA or BPS.[ref]

How do cells take care of oxidative stress?

Cells can respond to excess reactive oxygen species (ROS) with several built-in antioxidant defenses. Essentially, molecules that contain free oxygen are highly reactive.

ROS isn’t completely bad and is utilized by cells in specific ways for cell signaling. However, the level of ROS is tightly controlled in cells. Excess reactive oxygen species (ROS), termed oxidative stress, can lead to cell damage, including DNA damage or cell death.

Cells have multiple ways of controlling the level of ROS, including endogenous antioxidants such as glutathione, superoxide dismutases (SOD), and catalase. Genetic variants related to the ability to counteract oxidative stress increase the risk of BPH and prostate cancer.

One way cells control oxidative stress is through the Nrf2 pathway. Activation of Nrf2 calls up antioxidant response genes, including the glutathione transferase enzyme (GSTs). As part of Phase II detoxification, GSTs are the enzymes responsible for causing the reaction between glutathione and other substances, such as toxicants, to make them water-soluble and able to be easily excreted.[ref]

I’ll come back to these oxidative stress enzymes in the genetics section…

Related article: Nrf2 Pathway: Increasing the body’s ability to get rid of toxins

What causes prostate cancer?

Essentially, cancer is caused by out-of-control cell growth. Mutations or breaks in cellular DNA in specific genes are the driving factors in cancerous cells. The mutations occur either in genes that promote cancer (oncogenes) or in genes that stop cell growth. While mutations happen all the time during DNA replication, we have built-in DNA repair mechanisms that usually catch and correct the mutations. Excessive damage to DNA, such as from genotoxic substances, excess oxidative stress, or radiation, can result in cancer-causing mutations that replicate and result in tumors.[ref]

Commonly, mutations found in prostate cancer cells are in the TP53 (tumor protein p53) gene.[ref] TP53 is a tumor suppressor gene that keeps cells from dividing and growing uncontrolled. Mutations that prevent TP53 from working can then lead to cancer.

Hormones, testosterone, and the prostate:

Let’s dig into how and why hormones impact the prostate.

Androgen hormones are the steroid hormones responsible for male characteristics (lower voice, facial hair, muscle mass, Adam’s apple). Androgens include testosterone, dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA), and Dehydroepiandrosterone sulfate (DHEA-S). Women also produce these hormones, just at lower levels than men do. Likewise, men produce estrogen, just at much lower levels than women.

Prostate cancer is considered an androgen-dependent cancer, meaning that initial cancer cell proliferation and survival depend on the androgen hormones.

Estrogens, on the other hand, are protective against prostate cancer due to their anti-androgenic effects. Women produce estrogen mainly in the ovaries, but for men, estrogen is created through the conversion of androgen precursors by an enzyme called aromatase. The aromatase enzyme is encoded by the CYP19A1 gene (in the genotype report section), and aromatase is produced in the gonads and prostate.[ref]

Hormones in Cancer vs. BPH:
One difference between benign prostate hyperplasia (BPH) and prostate cancer is the production of aromatase (and thus estrogen) in the prostate cells. Researchers found that in BPH cells, aromatase was produced, creating estrogens from testosterone. But in the prostate cancer biopsies, very little aromatase was present, thus making no detectable estrogens.[ref]

One thing to note here is that circulating levels of androgens and estrogens don’t necessarily show what is happening in the prostate cells. Researchers are finding that the tissue-specific levels of androgens and aromatase in the prostate drive the difference between BPH and prostate cancer.[ref]

Lifehacks:

Everything presented here is for informational purposes only. Talk with your doctor if you have any medical questions or questions about interactions with supplements. Prostate cancer, or BPH, isn’t a DIY healthcare situation.

Dietary changes to prevent prostate problems:

Broccoli for everyone, more broccoli for GSTM1 null:
Broccoli, a cruciferous vegetable, has been the focus of several studies associated with GSTM1 null vs. present. Studies have suggested that those having a GSTM1 null genotype would benefit from eating additional servings of broccoli for the prevention of prostate cancer. Specifically, people with the GSTM1 present genotype may benefit from broccoli a few times a week, while those with the null genotype should add another serving or two during the week.[ref]

Lycopene, a carotenoid found in tomatoes, has been shown in several studies to decrease the relative risk of prostate cancer a little bit.[ref] A randomized clinical trial found that boosting tomato products and lycopene consumption decreased PSA levels by 1-8%. (not a lot!)[ref] But…. not all studies show that lycopene is beneficial, though. For example, in a Canadian study, tomato intake (juice, ketchup, and tomatoes) was shown in one study to increase the relative risk of prostate cancer by 50%, a surprising result to the authors.[ref].

Fat intake:
Some studies show that higher fat intake increases the risk of prostate cancer.[ref][ref] However, other studies show no risk increase.[ref][ref] Getting more specific, a diet with a lower ratio of omega-6 to omega-3 fatty acids has been shown to delay the progression of prostate cancer cell growth.[ref] Omega-6 fats are abundant in fried foods and packaged foods, so shifting to a diet of whole foods and avoiding omega-6 oils may be worth investigating.

Related article: Ancestral Diet: Omega-3 and Omega-6 Fatty Acids Impact the FADS1 gene

Protein and Meat:
A large meta-analysis in 2018 showed no increase in prostate cancer risk based on protein or animal protein intake.[ref] Likewise, dairy consumption does not influence prostate cancer risk, according to a large meta-analysis of over 26,000 cases.[ref]

Mediterranean Diet:
A Swedish study found no benefit from a Mediterranean-style diet for preventing prostate cancer.[ref]

Related article: Mediterranean Diet and Your Genes

Fish or fish oil for prevention:
High dietary intake of DHA and EPA, found in fish or marine oil, is associated with a decreased risk of a prostate cancer diagnosis.[ref]

Supplements for reducing oxidative stress in the prostate:

Quercetin:
A placebo-controlled clinical trial found that quercetin improved prostatitis scores in 67% of men.[ref]

Sulforaphane:
Derived from cruciferous vegetables, such as broccoli sprouts, sulforaphane has been shown in cell studies to decrease prostate cancer activity.[ref] This may be a supplement to consider if you carry the GSTM1 null variant and don’t want to eat a lot of broccoli a couple of times a week.[ref]

Related article: Sulforaphane, studies, bioactivation

Green tea:
A large study in Japan found that drinking five or more cups of green tea per day decreased the risk of prostate cancer by about 50%, compared to drinking only one cup of green tea per day.[ref] Green tea contains polyphonels that may help combat oxidative stress.

Coffee:
Another source of polyphenols in the diet is coffee. A meta-analysis shows that 3+ cups of coffee a day correlates with a small prostate cancer risk reduction.[ref]

Vitamin E:
The overall results on vitamin E for prostate cancer are mixed, with some studies showing a slight increase in prostate cancer risk when taking vitamin E.[ref] But, most studies use synthetic alpha-tocopherol as the supplemental form of vitamin E, which may be the cause of the slight increase in risk. Mixed tocopherols and tocotrienols may be the best option from natural sources of vitamin E. For example, in men with the GPX4 GG variant above, those with higher gamma-tocopherol levels were at a 3.5-fold decreased risk of mortality with prostate cancer. [ref]

Luteolin:
Cell studies show that luteolin inhibits prostate tumor growth.[ref][ref] Clinical trials are lacking here to know whether luteolin works in vivo for prostate cancer.

Related article: Luteolin Benefits: Anti-inflammatory and Neuroprotective

Fisetin:
Multiple studies show that fisetin, a dietary flavonol, can target prostate cancer cells.[ref][ref] At higher doses, fisetin also acts as a senolytic. Unfortunately, no clinical trials show the effects in vivo of low or high-dose fisetin.

Related article: Fisetin: Antioxidant and Senolytic 

Note: For people with slow COMT enzyme function, quercetin, luteolin, and fisetin may cause irritability or mood changes. You can read more here, and be alert  to the possibility of mood changes: COMT and Supplement interactions

Aspirin:
Research suggests that regular, long-term use of aspirin, a COX inhibitor, may reduce prostate cancer incidence and mortality. Some studies show a 20% reduction in mortality for regular aspirin users, but the research is based on surveys asking people to recall their aspirin usage rather than prospective trials.[ref][ref][ref][ref] The reason that aspirin may be effective is that prostate cancer tumor tissues have higher COX2 expression than BPH tissue.

Hormone-related supplements:

Berberine for PC or BPH: Berberine is a supplement commonly used for the prevention of insulin-related problems or to reduce cholesterol. Cell studies show that berberine may act as an aldo-keto reductase family 1 member C3 inhibitor, which may hold a lot of potential in prostate cancer.[ref] Other studies also show that berberine suppresses androgen receptor signaling.[ref] Animal studies show that berberine prevents BPH by acting on oxidative stress and androgen hormones.[ref][ref][ref]

Saw Palmetto (Serenoa repens) is a popular supplement for prostate problems, but its clinical trials have mixed results. Saw Palmetto contains oleic acid and lauric acid, which reduce the binding to the alpha1-adrenergic receptors. Let’s take a look at some of the clinical trials:

• A 2019 study looked at the safety and efficacy of Saw Palmetto supplements in a Chinese population. The results showed it was effective, safe, and well-tolerated for lower urinary tract symptoms and BPH.[ref]
• A 2000 study found no benefit from 12 weeks of Saw Palmetto (320 mg/day) in men with BPH.[ref]
• Alternatively, a 2010 study found 320mg/day of Saw Palmetto improved symptoms in men with BPH.[ref]
• Saw Palmetto, along with beta-sitosterol, has been shown in a clinical trial to reduce BPH symptoms and 5α-reductase after 12 weeks. The study participants took 500 mg of beta-sitosterol-enriched Saw Palmetto oil.[ref]

Reishi:
Reishi (Ganoderma Lucidum) is a mushroom extract that may help with BPH. In a randomized clinical trial using 6mg of Reishi extract a day, prostate symptom scores improved statistically compared to a placebo.[ref][ref]

Phytoestrogens:
Plant compounds that mimic estrogen have been studied for their effect on prostate cancer risk. Genistein is one of these phytoestrogens found in soy products. Clinical trials have shown little benefit for genistein supplementation, and high soy diets likewise don’t affect PSA levels.[ref]

Pumpkin Seed Extract:
A clinical trial (80+ participants; age 65+) found that pumpkin seed extract relieved lower urinary tract symptoms associated with BPH. Animal studies show that pumpkin seed inhibits testosterone-induced prostate growth. Pumpkin seeds contain sterols that are similar to beta-sitosterol as well as gamma-tocopherol.[ref]

Resveratrol:
A clinical trial using 1.5 g/day of resveratrol showed that it lowered androstenedione by 24% and DHEAS by 50%. However, it didn’t affect prostate size or PSA levels at 4 months.[ref]

Testosterone replacement therapy:
A study following over 5,000 older men for 4 years showed that TRT didn’t statistically increase the risk of prostate cancer.[ref] An earlier study also had similar findings of no increased risk of prostate cancer with TRT.[ref] Talk to your doctor, though, for advice on your specific situation.

Lifestyle changes:

Exercise:
A Canadian study found that strenuous physical activity is linked to a slightly reduced risk of prostate cancer in men ages 50 to 84.[ref] But a meta-analysis of 21 different cohort studies from multiple countries concluded no effect of physical activity on prostate cancer risk.[ref]

Avoiding phthalates:
Exposure to phthalates increases prostate cancer cell proliferation in cell studies.[ref] Phthalates are found in plastics and artificial fragrances.

Related article: Detoxifying Phthalates: Genes and Diet

Recap of your genetic variants:

Related Articles and Topics:

Testosterone: Genetic Variants that Impact Testosterone Levels

Genetic Causes of Male Infertility

Quercetin: Scientific Studies + Genetic Connections