Folate &

Adenoma (precancerous lesions) / colorectal cancer

- strong evidence: ^folate intake/blood folate assoc w/ 40-60% dec in risk of adenomas/colorectal cancer

• evidence from post fortification & multivitamin use for dec risk

- opposing evidence: folic acid facilitates adenoma transformation into colorectal cancer

• but: ^INCIDENCE may be due to ^screening, b/c there has been con't dec in colorectal cancer MORTALITY post-fortification

Folic Acid:

Treatment Measures

- Secondary trial (subjects w/ hx colorectal adenomas): given folic acid or placebo to test if folate could prevent colorectal adenomas from returning

- Result: ^adenomas for folic acid gr.--> WHY? ^folic acid may accelerate tumor growth if already predisposed

- Conclusion: folate def AND excess may contribute to carcinogenesis @ different stages of tumor development

Folate &

Colorectal Cancer Risk:

Prevention

- Animal models: dose-dependent protective effect

- Folic acid protective only BEFORE tumor established

- once foci established, ^folic acid ^growth rate

Low Folate Status

& Cancer Risk

- low folate = normal cells more susceptible to cancer  initiators leading to uracil misincorporation (^uracil incorporated into DNA)

• reduced T synthesis --> DNA bc unstable --> global hypomethylation = abnormal gene expression
• DNA repair (of misincorporated uracil) may leave nicks resulting in strand breaks & DNA instability
• hypomethylation = more genes turned on, including cancer promoting genes which ^risk

High Folate Status

& Cancer Risk

- high folate = est. cancer cells grow faster

• rapid rate of cell division & DNA synthesis

- some anti-cancer drugs target folate:

• methotrexate reduces DHF-->THF in thymidylate synthesis (impairing DNA synth)
• methotrexate struct similar to folic acid: binds DHF reductase more tight than folate to stop DNA synth

Alcohol &

Cancer Risk

- Alcohol ^cancer risk: interferes w/ folate metabolism

• inhibit folate absorption & uptake; ^renal excretion, ^folate requirements

- Evidence: ^breast cancer risk w/ alcohol consumption 

• 2-3 drink/d = 32%^
• >3 drinks/d = 46%^

Folic Acid Supplement:

Recommendations for >50yrs

- Hx colorectal adenomas or est. cancers (any): do NOT take folic acid

- Pt. who come for routine screening w/ no Hx

• no need to take supp. (can get from fortified food)
• advise: ^consumption natural food sources of folate (which are also ^ in fiber, LF)

RDA: 400 mcg DFE

UL: 1000 mcg folic acid --> can eat as much dietary folate as want!

• folic acid @ ^levels may delay dx of B12 def.
• UL set b/c ^folate may mask B12 def by correcting hematological abnormalities (appear to "fix" anemia parameters)

- Natural: 1 serving (~100mcg DFE) x 4 = RDA

• OJ, spinach, strawberries, beans

- Synthetic

• enriched cereal (~140mcg DFE) x 1.7 = 230mcg
• RTE cereal (~100mcg DFE) x 1.7 = 170mcg
• total = 400mcg = RDA
• *note: super-fortified prod or multiple servings may result in exceeding UL