1. Vitamin A and Prostate Cancer
Laura Simonitch
lsimonitch@kumc.edu
B.S. University of Nebraska-Lincoln
Dietetic Intern, MS Student
University of Kansas Medical Center

2. Introduction
 Vitamin A is a fat-soluble vitamin1
.
 Needed for vision, bone growth, reproduction, embryonic
development, and for differentiation of epithelial tissues1
.
 Retinoids2
 Studies evaluated:
 serum retinol concentrations
 β-carotene + retinyl palmitate supplementation
1. Trumbo P, et al. (2001)
2. Mahan L, et al. (2012)
RDA for males: 900 µg/d
RDA for females: 700 µg/d

3. Purpose
 Belief that supplements will benefit health
and decrease risk for chronic diseases like3,4
.
 Retinol’s role in growth, differentiation, and
apoptosis5
3. White E, et al. (2004)
4. Satia-Abouta J, et al. (2003)
5. Peehl DM, et al. (2003)

4. Research Question
 What is the relationship between vitamin A
and risk for prostate cancer?

5. Review of the Literature
6. Neuhouser M, et al. Dietary supplement use and prostate cancer
risk in the carotene and retinol efficacy trial. Cancer Epidemiol
Biomarkers Prev. 2009
7. Mondul A, et al. Serum Retinol and Risk of Prostate Cancer. Am J
Epidemiol. 2011
8. Schenk J, et al. Serum Retinol and Prostate Cancer Risk: a Nested
Case-Control Study in the Prostate, Lung, Colorectal, and Ovarian
Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev. 2009
PubMed search terms: “vitamin A AND prostate cancer”, randomized
controlled trials, published within the last 5 years, human
studies, English language, Cancer subject, and adults 19
years or older

6. Participants
Study Type of Study Design Inclusion Criteria
Neuhouser
M, et al.
(2009)
Randomized Controlled
Trial, double-blinded
placebo-controlled
Ages 45-69, smokers, history of at least 20 pack-
years of cigarette smoking who were current or
former smokers with exposure to asbestos within
last 15 years
Mondul A,
et al. (2011)
Randomized, double-
blind, placebo-controlled,
primary prevention trial
Males who smoke at least 5 cigarettes per day,
between 50-69 years old
Schenk J,
et al. (2009)
Nested case-control
study
Cases (prostate cancer ): n = 692; Controls
(matched controls): n = 844. Men randomized to the
screening arm of the PLCO trial who underwent
prostate cancer screening by serum prostate-
specific antigen (PSA) and digital rectal examination
(DRE) at entry and annually

7. Intervention
Study Inclusion Criteria Treatment
Group(s)/Regimen
Comparison
Group
Neuhouser
M, et al.
(2009)
Ages 45-69, smokers, history of at
least 20 pack-years of cigarette
smoking who were current or former
smokers with exposure to asbestos
within last 15 years
30 mg β-carotene + 25,000 IU
retinyl palmitate supplements
(CARET vitamins) taken daily,
n = 6,197
Placebo
n = 5,803
Mondul A,
et al.
(2011)
Males who smoke at least 5
cigarettes per day, between 50-69
years old
α-tocopherol supplement (50
mg/day), n = 480;
β-carotene supplement (20
mg/day), n = 531; α-
tocopherol + β-carotene
supplements, n = 498
Placebo
n = 532
Schenk J,
et al.
(2009)
Cases: n = 692; Controls: n = 844.
Men who underwent prostate cancer
screening by PSA and DRE at entry
and annually
None None

8. Results – Neuhouser M, et al.
 Men taking CARET vitamins + another dietary
supplement prostate cancer relative risk
of 1.52
 Declined to 0.75 post-intervention
 Findings were exclusively aggressive cancer
 Non-aggressive prostate cancer diagnosis,
taking CARET vitamins with no other
supplements 35% reduced risk of cancer

9. Results
 Clinical significance
 High-dose of β-carotene + retinyl palmitate,
with at least one other dietary supplement,
may increase risk for aggressive prostate
cancer
Neuhouser M, et al. (2009).

10. Results – Mondul A, et al.
 Serum retinol concentration: more direct
measure of retinol status
 Quintile 5 significantly more prone to develop
prostate cancer during follow-up period than
Quintile 1
Baseline Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5
Serum retinol
(µg/L)
<483 483-546 547-606 607-684 ≥685
BMI 25.6 26.1 26.3 26.5 26.8

11. Results
 Positive serum retinol-prostate cancer risk
association greatest in:
 placebo group, α-tocopherol-only groups, high
baseline serum α-tocopherol, high baseline
serum β-carotene, high total cholesterol
levels, high dietary retinol intake
 20% greater risk for men in highest retinol
quintile for cancer overall
Mondul A, et al. (2011)

12. Results – Schenk J, et al.
Serum retinol concentrations were not associated
with overall prostate cancer risk
Significant 42% reduction in aggressive
cancer risk for those with highest serum retinol
concentrations
Baseline Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5
Serum retinol
(µg/L)
27.4-54.7 54.8-64.3 64.4-72.8 72.9-85.3 85.4-262.6
BMI 27.8 27.9 27.3 26.9 26.9

13. Results
Show protective association between serum
retinol concentrations and risk of aggressive
prostate cancer
Only study to show inverse relationship in
aggressive disease
Schenk J, et al. (2009)

14. Limitations
 Participants in Neuhouser M, et al.’s study
took their own dietary supplements
 Smokers versus nonsmokers

15. Conclusions
 Mixed results…
 Retinol affected by CRBP9
 Reason why circulating retinol may increase
risk is unknown
9. Jerónimo C, et al. (2004)

16. Take Home Message
 Careful consideration if dietary supplement is
needed, especially if already at increased risk
for prostate cancer

17. References
1. Trumbo, P. et al. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron,
Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington D.C.: National Academy Press; 2001. Accessed
March 10, 2013.
2. Mahan L, Escott-Stump S, Raymond J. Krause’s Food and the Nutrition Care Process. Missouri: Elsevier Saunders; 2012.
3. White E, Patterson RE, Kristal AR, et al. Vitamins And Lifestyle Cohort Study: study design and characteristics of supplement
users. Am J Epidemiol 2004;159:83–93. Available at:
http://aje.oxfordjournals.org.proxy.kumc.edu:2048/content/159/1/83.full.pdf+html. Accessed on February 17, 2012.
4. Satia-Abouta J, Kristal AR, Patterson RE, Littman AJ, Stratton KL, White E. Dietary supplement use and medical conditions -
the VITAL study. Am J Prev Med 2003;24:43–51. Available at:
http://www.sciencedirect.com.proxy.kumc.edu:2048/science/article/pii/ S0749379702005718. Accessed February 17, 2013.
5. Peehl DM, Feldman D. The role of vitamin D and retinoids in controlling prostate cancer progression. Endocr Relat Cancer.
2003;10(2):131–140. Available at: http://erc.endocrinology-journals.org.proxy.kumc.edu:2048/content/10/2/131.long. Accessed
March 10, 2013.
6. Neuhouser M, et al. Dietary supplement use and prostate cancer risk in the carotene and retinol efficacy trial. Cancer
Epidemiol Biomarkers Prev. 2009;18(8): 2202-2206.
http://www.ncbi.nlm.nih.gov.proxy.kumc.edu:2048/pmc/articles/PMC2733330/pdf/nihms-137336.pdf. Accessed February 10,
2013.
7. Mondul A, et al. Serum Retinol and Risk of Prostate Cancer. Am J Epidemiol. 2011;173(7):813-821. Available at:
http://www.ncbi.nlm.nih.gov.proxy.kumc.edu:2048/pmc/articles/PMC3105279/pdf/kwq429.pdf. Accessed February 9,2013.
8. Schenk J, et al. Serum Retinol and Prostate Cancer Risk: a Nested Case-Control Study in the Prostate, Lung, Colorectal, and
Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev. 2009 April;18(4):1227-1231. Available at:
http://www.ncbi.nlm.nih.gov.proxy.kumc.edu:2048/pmc/articles/PMC2717001/pdf/nihms109783.pdf. Accessed February 9, 2013.
9. Jerónimo C, Henrique R, Oliveira J, et al. Aberrant cellular retinol binding protein 1 (CRBP1) gene
expression and promoter methylation in prostate cancer. J Clin Pathol 2004;57:872–6. Available at:
http://jcp.bmj.com.proxy.kumc.edu:2048/content/57/8/872.long. Accessed March 10, 2013.

18. Thank you!
Questions?
Laura Simonitch
lsimonitch@kumc.edu
B.S. University of Nebraska-Lincoln
Dietetic Intern, MS Student
University of Kansas Medical Center

19. Strengths
 Neuhouser M, et al: excellent follow-up
during and after trial
 Mondul A, et al: large cohort and incident
case sample size, measurement of serum
retinol for entire cohort at 2 points in time
(unlike most studies)
 Schenk J, et al: had standardized procedures
for prostate cancer screening, a large sample
size, high compliance with protocol

20. Sources of Vitamin A
 Sweet potatoes
 Carrots
 Dark, leafy greens
 Liver
 Beef

21. Prostate Cancer Diagnosis
 Digital Rectal Examination
 Prostate-Specific Antigen Blood Test
 Prostate Ultrasound and Biopsy
 Cystoscopy or Bladder Scope Test:
measures health of urethra and bladder
 CAT scan: x-rays to find swollen or enlarged
lymph nodes
 MRIs: radio waves to examine prostate and
nearby lymph nodes
 Prostate Cancer Health Center. WebMD website. Available at: http://www.webmd.com/prostate-
cancer/guide/prostate-cancer-diagnosis-tests. Accessed April 15, 2013.

22. Prostate Cancer Treatment
 Surgery
 Radiation
 Hormone Therapy
 Chemotherapy (for those who don’t respond
to hormone therapy)
 Cyrotherapy: freezing cancerous areas of the
prostate
 Prostate Cancer Health Center. WebMD website. Available at: http://www.webmd.com/prostate-
cancer/guide/prostate-cancer-treatment-care. Accessed April 15, 2013.

23. Statistics
 2nd leading cause of cancer death in
American men, behind lung cancer
 ~238,590 new cases of prostate cancer will
be diagnosed in 2013
 ~1 man in 6 will be diagnosed with prostate
cancer during his lifetime, and ~1 man in 36
will die from it
 Average age at the time of diagnosis is about
67
What are the key statistics about prostate cancer? American Cancer Society web site. Available at:
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics.
Accessed April 18, 2013.

24. Survival
 The relative 5-year survival rate is nearly
100%
 The relative 10-year survival rate is 98%
 The 15-year relative survival rate is 93%
American Cancer Society Web site. Survival rates for prostate cancer. Available at:
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-survival-rates. Accessed April 18,
Stage 5-year relative survival rate
Local ~100%
Regional ~100%
Distant 28%