Cautionary paper concerning B12 with folic acid supplementation

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circular
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Cautionary paper concerning B12 with folic acid supplementation

Postby circular » Wed Oct 24, 2018 8:02 pm

Folic acid and vitamin-B12 supplementation and the risk of cancer: long-term follow-up of the B-vitamins for the Prevention Of Osteoporotic Fractures (B-PROOF) trial

This may interest some who take B12 and folic acid or folate to help lower homocysteine, but I wonder if the results would have been different if the subjects used folate instead?
Results: Allocation to B-vitamins was associated with a higher risk of overall cancer (171 [13.6%] vs. 143 [11.3%]), HR 1.25; 95%CI 1.00-1.53, p=0.05). B-vitamins were significantly associated with a higher risk of colorectal cancer (43[3.4%] vs. 25[2.0%]), HR 1.77; 95%CI 1.08-2.90, p=0.02). Conclusion: Folic acid and vitamin-B12 supplementation was associated with an increased risk of colorectal cancer. Impact: Our findings suggest that folic acid and vitamin-B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin-B12 [and folate and B12] are needed to evaluate whether folic acid [and/or folate] and vitamin B12 supplementation should be limited to patients with a known indication such as a proven deficiency.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Cautionary paper concerning B12 with folic acid supplementation

Postby NF52 » Thu Oct 25, 2018 2:13 pm

circular wrote:Folic acid and vitamin-B12 supplementation and the risk of cancer: long-term follow-up of the B-vitamins for the Prevention Of Osteoporotic Fractures (B-PROOF) trial

This may interest some who take B12 and folic acid or folate to help lower homocysteine, but I wonder if the results would have been different if the subjects used folate instead?

It seems likely that dietary folate produces different results, as least based on this study of the link between folic acid vs. natural sources of folate on risk of prostrate cancer:
Among the 643 men who were randomly assigned to placebo or supplementation with folic acid, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval [CI] = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). contrast, baseline dietary folate intake and plasma folate in nonmultivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses. These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid–containing supplements vs natural sources of folate.

As the Editors noted:
Folate metabolism may have a complex role in prostate cancer; the effects of folic acid–containing supplements on the risk of prostate cancer may be different those of natural dietary sources...
Given the small number of prostate cancers in this study, the estimates of prostate cancer risk in the placebo and folic acid groups should be interpreted with caution.
Folic Acid and Risk of Prostate Cancer: Results From a Randomized Clinical Trial

An article published in 2007 article came to a similar conclusion about the risks of folic acid as the recent study. This is from a 3-year follow-up in a
double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma....incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation...CONCLUSIONS:
Folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.
Folic acid for the prevention of colorectal adenomas: a randomized clinical trial.

None of these studies addressed ApoE 4 as a variable. So my personal, non-randomized take-away: people with a history of familial colorectal cancer and/or previous polyps (hand raised twice) probably should keep having those colonoscopies as recommended--and maybe focus on natural folate sources.
4/4 and still an optimist!

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Re: Cautionary paper concerning B12 with folic acid supplementation

Postby Julie G » Thu Oct 25, 2018 4:58 pm

Here’s a nice overview of the difference between folic acid and folate that addresses the mechanism by which the former can lead to cancer.

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Re: Cautionary paper concerning B12 with folic acid supplementation

Postby circular » Mon Nov 12, 2018 8:12 am

Thanks for the links Julie. I haven't taken any time to delve into this, but I just happened to come across the ConsumerLab report again. They state vis the paper linked in the OP that:
The researchers noted that most other studies with folate alone have not shown associations with higher cancer risk, but studies with folate and B12 have.

Hmmmm ...
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Cautionary paper concerning B12 with folic acid supplementation

Postby aphorist » Mon Nov 12, 2018 9:01 am

Unmetabolized folic acid results in a reduction of natural killer cells [1]. NK kill cancer cells


[1] Troen, A., Mitchell, B., Sorensen, B., Wener, M., Johnston, A., & Wood, B. et al. (2006). Unmetabolized Folic Acid in Plasma Is Associated with Reduced Natural Killer Cell Cytotoxicity among Postmenopausal Women. The Journal Of Nutrition, 136(1), 189-194. doi:10.1093/jn/136.1.189


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