Folate: Part 2

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:


– 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)


Folate DRIs

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)

Folate Sources to Meet RDA

– 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

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