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From the Townsend Letter
August / September 2018

Diet and Risk of Prostate Cancer Recurrence
by Jacob Schor, ND, FABNO
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Prostate cancer is the most common non-skin malignancy and the third leading cause of cancer death among men in the United States. The American Cancer Society estimated that in 2017, 161,360 men would be diagnosed with, and 26,730 would die from, prostate cancer. The majority of these men, about 92%, were diagnosed with low-grade, localized disease. Globally prostate cancer incidence varies 60-fold suggesting that lifestyle and dietary factors may have a large impact.1

We frequently see these men in practice at some point after diagnosis when they come seeking advice on how to reduce risk of recurrence. In the last ten years or so significant strides have been made that suggest a number of dietary characteristics are associated with significant impacts on recurrence risk. This article will review some of the more significant data that should now inform the advice we give to patients who have been diagnosed with prostate cancer.

Eggs and Chicken
In 2010, a paper by Erin Richman was among the first to catch our attention. Richman prospectively tracked consumption of processed and unprocessed red meat, fish, poultry, and eggs to see whether risk of prostate cancer recurrence or progression was affected by eating these foods. Her initial assumption was that processed and red meat, then assumed to increase initial diagnosis, would be the culprits that increased risk of recurrence as well. Chicken and eggs were tracked only because it was thought they were safe and would have no effect. Richman and colleagues followed 1,294 men diagnosed with prostate cancer for an average of 2 years. Though a short trial, their data added up to 2,610 person-years during which time 127 events occurred, defined as either prostate cancer death, metastasis, elevated prostate-specific antigen (PSA) or secondary treatment.

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The results surprised us (and we assume Richman et al as well). Men who ate the most eggs or poultry with skin were at double the risk of recurrence or progression during the trial compared to men who ate smaller amounts. For eggs, comparing the highest and lowest quartiles of consumption, or an average of 5.5 eggs per week against, 0.4 eggs, the hazard ratio was 2.02 [95% CI: 1.10, 3.72; P for trend = 0.05]. Comparing highest and lowest quartiles of poultry consumption yielded a non-significant hazard ratio of 1.55. A comparison, though, between the upper and lower tertiles of those eating poultry with skin on yielded a statistically significant hazard ratio of 2.26. (95% CI: 1.36, 3.76; P for trend = 0.003). Men with higher prognostic risk and a high poultry intake had a four-fold increase in risk compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Eating processed or unprocessed red meat, fish, or skinless poultry was not associated with prostate cancer recurrence or progression; it was only consumption of eggs and poultry with skin that significantly increased risk.
BioDisruptThis was not what we would have guessed, and our focus on shifting men away from eating red meat and processed meat suddenly seemed trivial compared to reducing consumption of eggs and chicken skin.2
Erin Richman has gone on, in the years since, to author a number of important research studies on the impact diet and lifestyle have on prostate cancer recurrence. During the intervening years she has gotten married, and her recent work is published under her married name, Erin L. Van Blarigan
Richman's chicken and egg study was something of a turning point. Prior to its publication, we had scant data about primary prevention and assumed that after diagnosis we should tell men pretty much the same things we told them before they were diagnosed. We typically suggested that a, "… diet low in fat, high in vegetables and fruits, …. avoiding high energy intake, excessive meat, excessive dairy products and calcium intake, … [would be] possibly effective in preventing PC."3
The factors that cause prostate cancer do not necessarily promote recurrence or progression.
Richman's chicken and egg results were important because men with prostate cancer in their attempts to follow a ‘healthier diet' often decrease red meat and increase egg and poultry consumption to compensate for a reduction in protein. Richman turned what we thought was a smart plan into a dumb plan.
It is worth noting that eggs and poultry do not increase risk of getting prostate cancer.4 Harvard researchers Willard, Giovannucci, Liu et al (who would later mentor Richman) had suggested that different factors promote prostate cancer progression after diagnosis in contrast to those that initiate the cancer. Still other factors may increase how aggressive the cancer is. [The same Giovannucci paper reported that increased levels of alpha-linolenic acid were associated with higher risk of prostate progression, a troubling thought for adherents of the Budwig diet] 5
Erin's 2010 paper was not the first to associate poultry with prostate cancer. A 2001 paper by Michaud et al reported an association between poultry skin and metastatic prostate cancer risk.6 The American Institute of Cancer Research suggested a possible association between total poultry and prostate cancer in their 2007 report.7
So how have we explained this link between chicken, eggs and prostate cancer? In hindsight it seems obvious. With the chicken, it's probably the heterocyclic amines, the same family of chemicals blamed for why high meat consumption increases prostate cancer risk.8 Cooked poultry skin contains more heterocyclic amines (HCA) than any other type of cooked meat; crispy chicken skin contains more HCA than barbecued beef or even fried bacon. Eggs contain the highest amount of choline of any food; choline, it seems, strongly promotes prostate cancer growth. There is a risk of being perceived as racist for quoting Bogen and Keating, who suggested in 2001 that African American men were at higher risk of prostate cancer simply because of their higher chicken consumption:

[Heterocyclic amine]...intakes were estimated to be greatest for African American males, who were estimated to consume approximately 2- and approximately 3-fold more [heterocyclic amines] than white males.... This difference...may at least partly explain why prostate cancer (PC) kills approximately 2-fold more African American than white men….9

Eating eggs raises serum choline levels. Johansson et al reported in 2009 that high plasma choline is associated with greater risk of prostate cancer.10 Prostate cancer cells take up far more choline than healthy prostate cells.11 In fact, radio-labeled choline is used for PET scan imaging of prostate tumors rather than the radioactive glucose used in standard PET scans.12 Prostate cancers eat up choline with a passion. Erin, as Richman, reported in 2012 that dietary choline was correlated with risk of prostate cancer death.13

Van Blarigan was lead author of a 2015 study that compared consumption of saturated fat versus vegetable fats after prostate cancer diagnosis with the risk of dying from prostate cancer. This was a prospective study (n=926) of men diagnosed with prostate cancer from the Physicians' Health Study. During follow-up, 333 deaths (56 prostate cancer deaths) occurred. Even slight shifts in type of fat and percentage of calories sourced from fats and carbohydrates made significant differences. Men who obtained five percent more of their daily calories from saturated fat and five percent less of their daily calories from carbohydrate after diagnosis had a 1.8-fold increased risk of all-cause mortality (HR 1.81; 95 % CI 1.20, 2.74; p= 0.005) and a 2.8-fold increased risk of prostate cancer-specific mortality (HR 2.78; 95 % CI 1.01, 7.64; p= 0.05). Men who obtained ten percent more of their daily calories from vegetable fats and ten percent less of their daily calories from carbohydrates had a 33 % lower risk of all-cause mortality (HR 0.67; 95 % CI 0.47, 0.96; p=0.03). Saturated fat intake may increase risk of death, and vegetable fat intake may lower risk of death.14

Milk and Dairy Foods
The paper that alerted me to the name change was published in January 2018.15 Erin Van Blarigan and colleagues had conducted a prospective study comparing consumption of dairy foods with prostate cancer recurrence, following 1,334 men with non-metastatic prostate cancer who were part of the CAPSURE cohort. The men were followed for a mean of eight years starting about two years after diagnosis.
Men who consumed more than four servings of whole milk per week compared to those who consumed 0-3 servings per month had a 73% increased risk of recurrence of prostate cancer (HR: 1.73; 95%CI: 1.00, 2.98; p=0.04). Higher body mass index (BMI) tended to worsen the association (p=0.01). For men with a BMI ≥27, making the same comparison of >4 servings/week versus 0-3 servings/month of whole milk, tripled risk of reoccurrence (HR: 2.96; 95%CI: 1.58, 5.54; p≤ 0.001). Whole milk consumption was not associated with increased risk in men with BMI of less than 27.
There is little new about the idea that milk might be a problem. A number (but not all) studies published over the years have suggested that dairy products increase risk of prostate cancer.16-24
Yet data about dairy consumption after diagnosis has been limited. The authors of this current study, Van Blarigan and her coauthors, reported in 2012 that among the 3,918 men in the Health Professionals Follow-up Study, those who consumed whole milk more than four times per week after diagnosis had double the risk of dying from prostate cancer and a 51% increased risk of prostate cancer recurrence compared to those drinking whole milk less than three times per month.25
These same authors also analyzed data from the 926 men in the Physicians Health Study and reported in 2015 that consuming more than three servings a day of dairy products was associated with a 2.4-fold increased risk of prostate cancer specific mortality compared to men consuming less than one serving per day.26
A 2017 Swedish study by Downer et al, looked at dairy consumption among 230 men diagnosed with localized prostate cancer. Drinking 3 or more servings per day of high fat milk increased prostate cancer mortality 6.1-fold over men who drank less than 1 serving per day.27
The bottom line is that consuming dairy, in particular whole milk, puts men at greater risk of recurrence. We should assume that men who have chosen a wait and watch approach rather than treatment, should be even more concerned about dairy consumption. This current study suggests that we may be able to segregate those most at risk by BMI.
Several possible mechanisms have been suggested why milk is a problem:

•    High calcium intake decreases vitamin D28;
•    Milk proteins increase igf-129;
•    Fluctuating phosphorous levels modify vitamin D concentration30;
•    Elevated saturated fat may modulate immune responses.31

As mentioned, Erin and her colleagues have already reported that saturated fat intake is associated with increased risk of prostate cancer mortality; and now this data, that whole milk has a greater effect, suggests that the fat content of whole milk increases risk.32 This clearly should raise concern about other high-fat dairy products such as half & half, cream, butter, and especially that glorious triple-cream brie sold at Costco.
Several other earlier studies have looked at whole milk and prostate cancer recurrence. Pettersson et al reported that men who had the highest whole milk intake (>4 servings/week) had about a two-fold increased risk of prostate cancer mortality (HR: 2.15; 95%CI: 1.28, 3.60; P-trend) compared to men with low intake (0-3 servings /month). In their study there was no association between total dairy consumption and risk of lethal prostate cancer, biochemical or clinical recurrence.33
We should add whole milk and probably other high-fat dairy products to our lists of foods that men with a history of prostate cancer should avoid. I've often joked about how patients lump all foods found in the dairy case of the grocery store into one category so that when you tell them to avoid "dairy foods," they ask if that "means eggs?" My response has been, "Do cows lay eggs?" In a way though these people are right. For men who have had prostate cancer, both eggs and dairy increase risk dramatically.

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