High Levels of Folate

From Supplements and

Fortification Are Not
Associated with
Increased Risk of
Colorectal Cancer

Presenters:
Tiffany Craig
Elizabeth Potter
Source:
Stevens VL, McCullough ML, Sun Juzhong, Jacobs EJ, Campbell PT, Gapstur SM. High Levels of
Folate From Supplements and Fortification Are Not Associated With Increased Risk of
Colorectal Cancer. Gastroenterology. 2011;141:98-105. doi:10.1053/j.gastro.2011.04.004

Whats the deal with folate?

Reminder:

1-C metabolism
Methionine cycle
Substrate methylation
Neurotransmitter methylation

Cell proliferation
DNA synthesis, methylation, and repair, OH MY!

Folate forms:
Folic acid supplements/fortification (85% absorption)
Folate inherent in food (50% absorption)

US food supply fortification fully implemented in 1998

Background Previous Studies

Conflicting evidence of high folate supplementation

and carcinogenesis (colorectal)

Risk, PRO fortification:

Meta-analysis of prospective studies (2005)Sanjoaquin MA et al
Pooled analysis 13 primary prospective studies (2010)Kim D-H et al
Both reported higher total folate intake associated with a
reduced risk of colon cancer
Risk, CON fortification:
Randomized clinical trail (2007)Cole BF et al
Men and women with history of colorectal adenomas
Increased risk of more advanced lesions in FA supplement
group
Exposure was prior to food supply fortification

Study Purpose
Unanswered

questions driving research

Evaluation of high folate and increased risk

of colorectal cancer
Impact of folate chemical form

Investigate

the association between high

folic acid intake and colorectal cancer
risk

Solely in the post-fortification era

Prospective epidemiologic study

Approach and Methods

Prospective cohort study 1999-2007

CPS-II Nutrition Cohort Pop.

Americans, age 50-74, 43,512 men, 56,011 women

Exclusions: BMI <18.5 or > 50, history of cancer (other than
nonmelanoma skin cancer)

FFQ administered in 1999

End of study: 2007, colorectal cancer diagnosis, or death

2002 and 2006 follow-up

Folate consumption categorized

Natural folate, dietary folate, folic acid

DFE calculation: folate + 1.7 * FA (heightened bioavilability)

Results
Total

folate consumption was statistically

significantly inversely associated with
colorectal cancer risk in men and women

RR Q5 vs Q1 0.81, P = 0.47

*Significant from 1999 FFQ to 2007 follow up

Conclusions

High intake of both natural and synthetic folate was

associated with a reduced risk of colorectal cancer

Total folate all forms, all sources are the best measure for
nutrient exposure

No evidence of increased risk of colorectal cancer was

observed for the highest levels of folate or folic acid intake
(>1200 DFE/day)

Is this legit?

Large sample
Prospective in nature
Categorized/differentiated folate form

BUT

Lacks diversity(98% white)

Cohort pop healthier than normal

Abbreviated follow up time (8 years)

Breadth and accuracy of FFQ

Modest at best- correlation between folate intakes and

erythrocyte folate level (0.47 dietary folate)

Exposure minimal relative to lifespan opportunity for

future research!

Dietary patterns assumed unchanged for 8 years

Opportunity for the future

Prospective study
Individuals born post-1998 (16 years now!)
Followed for health implications
Ensure representative sample pop.
Investigate B12 status?

Question for YOU:

Considering this study, would you recommend folic acid
fortified foods and/or supplements to an elderly patient
with no history of polyps considering the confounding risk
of masking a B12 deficiency?
Considering what you know about folic acid
bioavailability, would you support folate fortification if is
was coupled with B12 fortification as well?

Source
1.

Stevens VL, McCullough ML, Sun Juzhong, Jacobs EJ, Campbell PT, Gapstur SM. High
Levels of Folate From Supplements and Fortification Are Not Associated With
Increased Risk of Colorectal Cancer. Gastroenterology. 2011;141:98-105.
doi:10.1053/j.gastro.2011.04.004