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The Androgen-Deprivation Patient

This patient may have advanced PrCa with or without metastasis and is on constant or intermittent medically induced chemical castration with ADT. 

Androgen deprivation therapy (ADT), also known as hormone therapy, is a form of chemical castration and is one of the common treatments for advanced prostate cancer. The types of ADT include luteinizing hormone-releasing hormone (LHRH) agonists, which prevent the pituitary gland from secreting the luteinizing hormone (LH) due to the presence of high levels of LHRH.

LHRH agonist drugs include leuprolide (Lupron), goserelin (Zoladex), and triptorelin (Trelstar).

Another method of chemical castration in patients with advanced prostate cancer is LHRH antagonists, which prevent LH secretion by blocking the release of LHRH. LHRH antagonist drugs include degarelix (Firmagon).

Other categories of ADT (and chemical castration) include androgen synthesis inhibitors.

Androgen synthesis inhibitors work by preventing the production of androgens by all tissues, including the adrenal glands, by inhibiting the CYP17 enzyme responsible for producing testosterone. Androgen synthesis inhibitors include abiraterone (Zytiga) and ketoconazole.

Lastly, yet another form of medically induced castration is antiandrogens. Antiandrogens work by blocking the androgen receptors from the binding of androgens and include, apalutamide (Erleada), bicalutamide (Casodex), enzalutamide (Xtandi), and darolutamide (Nubeqa)

Despite the mechanism of action, hormone therapy for advanced prostate cancer induces chemical castration, which comes along with unwanted side effects. ADT’s adverse events include hot flashes in about 60% of men, metabolic syndrome, cardiovascular events, anemia, memory, and cognitive decline, and osteosporosis.¹¹ Other adverse events from antiandrogens include hypertension, fluid retention, and hypokalemia.¹²

The nutraceutical recommendations for the ADT patient include ingredients that mitigate cognitive decline, improve physical energy, support bone health, and lower the frequency of hot flushes. Nutraceutical recommendations to minimize adverse effects from ADT are the following:

• Brain function and cognition: acetyl-L-carnitine, lion’s mane, ashwagandha
• Improve physical energy: ashwagandha or any other adaptogenic botanicals and cordyceps
• Hot flushes and night sweats: black cohosh
• Bone health: vitamin K2, boron, and black cohosh

The therapeutic goal for patients on ADT is to support medical treatments with natural and lifestyle practices to mitigate disease progression while minimizing adverse events from ADT for the patient to sustain quality of life.

Nutraceutical Recommendations for Prostate Cancer Patients with Scientific Support

Selenium seems protective for PrCa in most studies. One of those landmark studies was the Nutritional Prevention of Cancer (NPC) study. Participants received selenium in the form of selenized yeast at 200 mcg/day. Researchers here looked at the effects of selenized yeast on skin cancer and noticed a 65% reduction of prostate cancer in the group on selenium from the yeast compared to placebo as a secondary study outcome.¹³

Shortly after the publication of the NPC results in the late 1990s, I began working with prostate cancer patients and remembered selenium being a favorable hot topic for PrCa at urological conferences. The enthusiasm for the mineral died down after the results of the SELECT study was published.

The SELECT trial (SELenium and Vitamin E Cancer Prevention Trial) ended early in 2008 when no benefit for prostate cancer prevention with the use of either vitamin E or selenium.¹⁴

Later reports from SELECT demonstrated that selenium supplementation increased the risk of high-grade prostate cancer (by 91%) among men with a high baseline toenail selenium concentration only in the arm for selenomethionine, not the group taking both vitamin E and selenium. There were no adverse events in the group taking both vitamin E and selenium, suggesting possible synergistic activity between the two nutrients.¹⁵

The use of selenomethionine (SeMet) instead of selenized yeast in SELECT was controversial as the choice to use SeMet was for logistical reasons, i.e., batch-to-batch variability in selenized yeast, etc., not due to evidence that L-selenomethionine is the superior form of selenium for prostate cancer.¹⁶ Besides, the NPC trial showing a significant risk reduction in PrCa used selenized yeast, not L-selenomethionine.¹³

While L-selenomethionine is the predominant form of selenium in selenized yeast, the yeast contains numerous other mineral forms—also includes selenocysteine and methyl selenocysteine—with varying chemopreventive properties.¹⁶

When comparing the selenized yeast form of selenium to selenomethionine in a small group of men with prostate cancer, one study suggests that SeMet does not decrease oxidative stress and therefore doesn’t protect cells or prevent cancer compared to selenium from selenized yeast.¹⁷

Recommendation: 200 mcg of selenium in the form of selenized yeast.

Vitamin E is a nutrient I frequently use with patients with PrCa but mainly in mixed tocopherol. Gamma tocopherol is the most prevalent form of vitamin E in the diet, whereas alpha-tocopherol, found in dietary supplements, is the most biologically available form.¹⁸ Numerous studies looking at gamma-tocopherol vitamin E have shown an inverse association with prostate cancer risk.¹⁹

Alpha-tocopherol supplementation has shown up to a 40% decrease in development and mortality in men consuming 50 International Units (IU) compared to placebo—a result that was sustained two years after the study ended.²⁰

Interestingly, higher concentrations of plasma gamma-tocopherol were associated with a statistically significantly lower risk of developing prostate cancer. Studies show protective associations between selenium and alpha-tocopherol concentrations and subsequent prostate cancer only in the presence of higher concentrations of gamma-tocopherol.²¹

The SELECT trial found no protective effect from vitamin E in the form of alpha-tocopherol at 400 IU a day, taken alone or in combination with selenium. Further published SELECT research showed an increased risk of prostate cancer in the vitamin E, alpha-tocopherol arm but not in the combination intervention.

Three flaws from SELECT as it relates to vitamin E and PrCa:

1. They used a synthetic, unnatural version of the vitamin in dl-alpha-tocopherol, not a natural mixed tocopherol version.
2. Gamma tocopherol (in combination with alpha-tocopherol) seems to be essential in protecting against prostate cancer. 
3. The dose in alpha-tocopherol vitamin E in SELECT was eight times higher than that from the ATBC study, 400 IU vs. 50 IU, respectively. Such a high dose of a substandard form of vitamin E in alpha-tocopherol may potentially promote prostate cancer.

Recommendation: 400 IU of vitamin E, mixed tocopherol with higher gamma-tocopherol.  

Zinc. The human prostate contains one of the highest amounts of zinc of all tissues in the body. Zinc continuously decreases in the prostate in early to late cancer cells. One study shows supplemental zinc intake was associated with a reduced risk of clinically relevant advanced PrCa.²²

Another Swedish study looked at men with high zinc intake and showed lower PrCa specific mortality, especially in men with localized tumors.²³

Too high zinc consumption of over 100 mg/day may significantly increase the risk of being diagnosed with advanced prostate cancer. In one cohort, approximately 32% of the total zinc intake was from dietary supplements, representing the largest zinc source. So, while there is no evidence of causation in higher amounts of zinc causing PrCa, there is a correlation.²⁴

Recommendation: 15 to 30 mg of zinc daily.

Vitamin D. Numerous studies on prostate cancer patients with the lowest pre-diagnostic 25(OH)D levels show a significantly greater risk of prostate cancer-specific mortality.²⁵

Although some studies show no benefit of vitamin D on prostate cancer,²⁶ in one non-randomized, small human study, vitamin D(3) supplementation at 4000 IU/d, revealed a decrease in serum levels of prostate-specific antigen (PSA) or the rate of progression of PrCa. The study concluded that patients with low-risk prostate cancer under active surveillance might benefit from vitamin D(3) supplementation at 4000 IU/d.²⁷

Recommendation: I recommend a reasonable dosage of vitamin D3, between 2000 IU and 4000 IU a day, or an amount necessary to get serum levels to 40 to 60 ng/ml. Though the benefits of vitamin D and PrCa are not definitive, vitamin D may prevent fatal cancer of all types.²⁸

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