Monday, July 28, 2008

The Folic Acid/Cancer Link

Recently, we have received several inquiries from concerned clients because their doctors told them to stop taking the B-vitamin, folic acid, due to a suggested link to cancer. We think this is misinformed and potentially damaging advice. Last summer, we commented on this same issue. However, the misinformation is still circulating, so we are bringing you up to date on the latest research.

One client was recently told to stop taking her multivitamin/mineral because it contained folic acid (all do). Folate, which is what folic acid is broken down into, is critical because it promotes healthy cell production, especially during and after cancer treatment. Folate is very difficult to get in food unless it is fortified in grains. Even with fortification, sometimes it is not enough. Supplementation is essential because cancer patients are often nutrient depleted and dependent.

The most cutting-edge research has shown that the issue with folic acid and cancer has more to do with our impaired ability to absorb folic acid into folate than it does with taking too much of it. The research from 2008 alone backs this.

Genetics
The July, 2008 issue of Nutrigenetics and Nutrigenomics, which studies how nutrients affect our genes, is a journal that is years ahead of the curve. Their study on folic acid confirmed that in Caucasians especially, high folate intake was associated with a reduced risk of colorectal cancer, which goes against a JAMA study from last summer that said folic acid increased risk. The NAN researchers suggest that genetic polymorphisms (defects) that impact folic acid from being absorbed properly is the reason for a higher colon cancer risk. We have said for years that one-quarter of the human population has the inability to break down folic acid into absorbable folate. However, the only way to know for sure is to get a genetic test for folate metabolism (these are becoming more common now). If a polymorphism is discovered, one would need to address taking a folate source that can bypass this genetic defect (we have recommended one, Metagenics ActiFolate, for years).

Childhood Leukemia
Folic acid is shunted through several biochemical pathways in the body, and scientists already knew that inadequate amounts of the vitamin - due to low dietary supply or poor performance by enzymes that metabolize it - leads to defects in the way DNA is replicated in the cells.

And while the U.S. now assures adequate folic acid in the diet by supplementing flour and corn products, the new findings may help explain the historically high level of childhood leukemia in California in general and among Hispanic populations in particular.

Hispanic Americans have historically had the highest U.S. rates of newborns with neural tube defects and similarly higher-than-normal rates of childhood leukemia. While use of folic acid supplements before and during pregnancy is increasing among this high-risk group, its use still lags somewhat, and should be increased to avert childhood diseases.

Future studies need to suggest methods to exploit folic acid biochemical pathways to treat leukemia. March 27, Proceedings of the National Academy of Sciences

Bladder Cancer

DNA hypomethylation through impaired folate pathways is associated with increased risk of developing bladder cancer, and this association is independent of smoking and the other assessed risk factors.
The Lancet Oncology , Volume 9 , Issue 4


Folate Depends on Other B-Vitamins as Well

Folate is required for biological methylation and nucleotide synthesis, aberrations of which are thought to be the mechanisms that enhance colorectal carcinogenesis produced by folate inadequacy. These functions of folate also depend on the availability of other B-vitamins, including B2, B6 and B12. The study investigated whether combined dietary restriction of these vitamins amplifies aberrations in the epigenetic and genetic integrity of the p53 gene that is induced by folate depletion alone. The results indicate that inadequacies of other B-vitamins may amplify aberrations of the p53 gene induced by folate depletion alone, implying that concurrent inadequacies in several of these vitamins may have added tumorigenic potential beyond that observed with isolated folate depletion. International Journal Cancer August 2008

Folic Acid Fortification Helps the Folate Genetic Defect
The MTHFR 677C>T polymorphism (defect) was associated with significant differences in serum folate and homocysteine concentrations in the US population before folic acid fortification. The effect of this defect was reduced by moderate daily folic acid intake. American Journal Clinical Nutrition July, 2008

Male Fertility
A new study has identified a possible link between men's intake of folate and reduced chromosomal abnormalities in sperm. The study, published in the March journal Human Reproduction, is claimed to be the first indication that paternal diet may play a role after conception.

Memory Loss
The importance of B-vitamins cannot be underestimated for preventing memory loss, especially in the elderly. What's most important to understand is that just taking folic acid is not good enough for 25% of the human population because of a genetic abnormalities. For these individuals, all three folates (folic acid, L 5-methyl tetrahydrofolate, and 5-formyl tetrahydrolfolate) must be taken. The form of B-12 should always be methylcobalamin.
Nutritional Concepts eNewsletter June 2008

Activated Folate Sources that Bypass the Genetic Absorption Impairment
"Administration of a physiological dose of [6S]-5-methyltetrahydrofolate with L-ascorbic acid significantly improved the measured serum folate response in folate saturated healthy men," wrote the researchers, led by Professor Ann Van Loey, in the European Journal of Clinical Nutrition 7/07.

Scientists at the University of Bonn in Germany reported last year that the folic acid derivative, [6S]-5-methyltetrahydrofolate ([6S]-5-MTHF), is even more bioavailable when given as supplements than folic acid, and could be an alternative for the primary prevention of neural tube defects. American Journal of Clinical Nutrition, Vol. 84, pp. 156-161

Other notable data from 2008:
  • Dana-Farber Cancer Institute recommends B12 (at least 400 mcg); and folic acid 1 mg daily to patients with multiple myeloma to manage symptoms associated with peripheral neuropathy. Clinical Journal of Oncology Nursing April 2008
  • There is no strong support for an association between prostate cancer risk and circulating concentrations of folate. Cancer Epidemiology Biomarkers & Prevention, 2/2008
  • Folate depletion continues to be a risk factor for fetal growth restriction. Pre and postnatal supplementation may be beneficial. American Journal of Clinical Nutrition 7/08
  • The risk of pre-eclampsia, which affects two to three per cent of all pregnancies, may be reduced by 63% with multivitamin supplements that contain folic acid, suggests a new study amongst 2,951 pregnant women that appears in the American Journal of Obstetrics and Gynecology. 2/08
  • Women who took folic acid supplements for at least a year before pregnancy cut their chances for very early pre-term births -- 20 to 28 weeks into the pregnancy -- by 70 percent compared to other women. Society for Maternal-Fetal Medicine 2/08
  • The dramatic decline in cardiovascular events in the United States since 1950 may be partly attributable in part to voluntary fortification of the food supply with vitamin B6 and folic acid. American Journal of Clinical Nutrition 11/07
  • Simultaneous supplementation of riboflavin and folic acid increased the response to low-dose folate in the double-blind randomized placebo-controlled intervention study (the FAB2 Study) involving 98 healthy people and 106 patients with colorectal polyps.

    The study, published in the journal Cancer Epidemiology, Biomarkers & Prevention, adds to the controversial subject of folate and colorectal cancer, with some studies reporting that the B-vitamin may in fact increase the risk of the disease. On the other hand, other studies have reported protective benefits from folate for colorectal cancer. The new study focused on measuring increases in certain markers as a result of different supplementation regimes.
  • Supplementation with folic acid alone produced significant, dose-dependent increases in 5-methyltetrahydrofolate (MTHF), the reduced form of folate, in the mucosal layer of the colon. MTHF levels also increased in red blood cells and plasma. Simultaneous supplementation with riboflavin enhanced the response to low-dose folate in people with polyps.

    The data adds to an ever-growing body of science linking B-vitamin intake to reduced risk of certain cancers, including vitamin B6 and colorectal cancer (J. Nutr., Vol. 137, pp. 1808-1814), folate and breast cancer (Am. J. Clin. Nutr., Vol. 86, pp. 434-443), and folate, B6 and B12 and pancreatic cancer (Cancer Research, Vol. 67, Issue 11).

  • Folic acid has been proven to help the following issues:
    1. reduction of depression
    2. mood highs and lows
    3. periodontal disease
    4. pernicious anemia
    5. hearing loss
    6. reduction of dementia and Alzheimer’s disease

    Advances in Womens Health, 3/07

  • If anyone needed further support for benefits of folic acid fortification, a new study shows that the incidence of neural tube defects in Canada has dropped by 46 per cent since the advent of folic acid addition to flours. New England Journal of Medicine 7/07
  • Supplementation with vitamin C may increase the uptake of a folic acid derivative, suggests new research from Belgium.
Conclusion
As with the Vitamin E and Vitamin A "scares" of the last few years, the "danger of folic acid and cancer" is just that - a scare tactic based upon misinformation and poor research understanding and techniques.

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