Folic Acid and Breast Cancer Risk
Folic acid, a synthetic form of a natural vitamin known as folate (or vitamin B9), appears to be causing problems for our health and several studies have demonstrated a link between folic acid and a higher breast cancer risk. I thought this was important enough to share with you, especially since a lot of us are taking multi-vitamins which contain folic acid.
The Difference Between Folate and Folic Acid
Folate is a B vitamin (vitamin B9) required by the body for DNA synthesis and methylation, DNA repair, cell division, and for the healthy development of the neural tube in the fetus in early pregnancy. Getting enough folate is crucial for growing and dividing cells because they are constantly replicating their DNA. Folate is available in our diet from things like asparagus, avocados, Brussels sprouts, and leafy greens such as lettuce, spinach, kale, etc.
Folic acid is a synthetic form of folate – if you are taking a B-complex vitamin supplement, more than likely it will include folic acid. Folic acid is also added to processed foods such as breakfast cereals, breads, white rice and white flour. Folic acid was thought, for many years, to be better absorbed than naturally-occurring folate. However, taking synthetic folic acid is not the same as getting natural folate from plant sources. What we are discovering is that the body processes natural folate and folic acid differently, and that natural folate plays a protective role, while synthetic folic acid may be causing health problems rather than solving them.
The Problem with Folic Acid
Mandatory fortification of food with folic acid has been in effect in the USA since 1998, and at somewhere around 87 countries have regulations on the matter in different stages of implementation. [1]
There are several problems associated with folic acid:
• In the digestive tract, the majority of folic acid is not converted to the active form of vitamin B9, 5-methyltetrahydrofolic acid, or 5-MTHF. The liver or other tissues need to do that job, and after taking a folic acid supplement, it can take some time for the body to convert all of it to the active form, 5-MTHF. [2], [3]
• Even a relatively small dose of folic acid, 200–400 mcg per day, can cause problems because it may not be completely metabolized before the next dose is taken. If you’re eating foods that are fortified with folic acid, the problem is amplified. Several studies have been published that show that excessive amounts of folic acid can remain unmetabolized and stay in the bloodstream, and this can cause health problems. [4], [5] Those problems include increased cancer risk (and particularly breast cancer) and rapid proliferation of pre-cancerous lesions. Another complicating factor is that among older people, high levels of folic acid can hide a vitamin B12 deficiency leading to anemia, dementia and cognitive impairment. [6]
• Despite all this, in 2015 the World Health Organization issued a statement that “high folic acid intake has not reliably been shown to be associated with negative health effects”. In 2016, in response to this statement, researchers at Tufts University in Boston, MA released a paper discussing several of the studies that have strongly implied that high levels of folic acid is not always safe, especially in the elderly. [7]
I share all of this with you to illustrate it’s a fairly contentious subject. The focus of this article, however, is to discuss how high folic acid levels might be contributing to breast cancer risk.
The Folic Acid Breast Cancer Link
A number of studies have investigated high folic acid levels and breast cancer risk.
A 2004 study [8] compared the breast cancer mortality rates between women who took folic acid during their pregnancy with women who did not. Over 3,000 women took part in the trial. Thirty years later, the women who followed their doctor’s recommendations to take folic acid during pregnancy were twice as likely to die from breast cancer.
That same year, 2004, Dr Y I Kim, a Canadian researcher, released a paper [9] stating “Over the past few years, the US population has been exposed to a significant increase in folate intake, for which essentially no data on safety exist. The potential cancer-promoting effect of folic acid supplementation needs to be considered in carefully monitoring the long-term effect of folic acid fortification on the vast majority of the US population, who are not at risk of NTDs [neural tube defects].”
The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial ran between 1993-2003 and included 25,400 women. A 2006 study [10] investigated findings from that trial, specifically women taking multi-vitamins. Researchers concluded that those who took multi-vitamins containing folic acid increased their risk of breast cancer by a whopping 20%.
Subsequent to these findings, the aforementioned Dr Y I Kim authored a paper published in Nutrition Reviews which concluded “Based on the lack of compelling supportive evidence, routine folic acid supplementation should not be recommended as a chemopreventive measure against breast cancer at present.” [11]
A 2010 Swedish study followed women for over 9 years. Researchers found that women who took multi-vitamin supplements were more likely to be diagnosed with breast cancer. [12]
A 2017 animal study [13] investigated the effects of a high folic acid diet on tumor progression in mice with breast cancer. The mice were fed either a high folic acid diet or a normal diet (the control group) during the period of initial tumor progression. The mice induced with breast tumors were found to highly express a cancer-specific folate receptor known as FRa. Around 20% of breast tumors overexpress FRa, which seems to participate in the transformation of more aggressive types of breast cancer, being most frequently expressed in triple negative (ER-/PR-/HER2-) and progesterone receptor negative (PR-) breast cancers. The mice in the high folic acid group developed significantly larger tumors than the control group. The high folic acid group also had activation of a gene known as STAT3, which promotes breast cancer growth and progression. Further experiments showed that STAT3 was activated by folic acid. Researchers concluded that their results could provide a new explanation for how folic acid promotes growth of existing tumors.
Folate (remember, the natural form) is required by the MTHFR gene to produce a key enzyme in folate metabolism which is intimately involved in DNA methylation (also discussed in my article Epigenetic Factors to Reduce Breast Cancer Risk – Part 1. A 2012 clinical trial [14] investigated 155 breast cancer patients and 155 healthy women to look at a possible association of folic acid concentrations and genetic variants in the MTHFR gene with breast cancer risk in patients with BRCA1 mutations. They found that lower folic acid concentrations were associated with a lower risk of breast cancer.
Dr Joel Fuhrman, a doctor and author who emphasizes the role of nutrition in healing, has also noted a link between high folic acid levels and breast cancer. In one of his newsletters, he states “A study investigating both food folate and synthetic folic acid found that only supplemental folic acid increased breast cancer risk. In other studies, women with low levels of food folate intake were more likely to be diagnosed with breast cancer. Not enough natural folate and too much folic acid both increase risk.” [15]
Let me reiterate that last statement. Not enough natural folate and too much folic acid both increase risk of breast cancer.
Bottom line, and my advice to you – avoid supplements that contain synthetic folic acid (vitamin B9) and eat your greens – the foods that contain natural folate.
One 2016 study [16] suggested that taking folic acid along with other B-vitamins, particularly vitamin B6, may help the body to make the conversion more efficient.
References:
[1] Folate and Its Impact on Cancer Risk – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132377/
[2] Folic Acid Metabolism in Human Subjects Revisited: Potential Implications for Proposed Mandatory Folic Acid Fortification in the Uk – https://www.ncbi.nlm.nih.gov/pubmed/17617936
[3] Folic Acid Handling by the Human Gut: Implications for Food Fortification and Supplementation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095662/
[4] Unmetabolized Folic Acid Prevalence Is Widespread in the Older Irish Population Despite the Lack of a Mandatory Fortification Program – https://www.ncbi.nlm.nih.gov/pubmed/22854405
[5] Folic Acid Causes Higher Prevalence of Detectable Unmetabolized Folic Acid in Serum than B-complex: a Randomized Trial – https://www.ncbi.nlm.nih.gov/pubmed/25943647
[6] Folate and Vitamin B-12 Status in Relation to Anemia, Macrocytosis, and Cognitive Impairment in Older Americans in the Age of Folic Acid Fortification – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828842/
[7] Excessive Folic Acid Intake and Relation to Adverse Health Outcome – https://www.ncbi.nlm.nih.gov/pubmed/27131640
[8] Taking Folate in Pregnancy and Risk of Maternal Breast Cancer – https://www.bmj.com/content/329/7479/1375
[9] Will Mandatory Folic Acid Fortification Prevent or Promote Cancer? – https://www.ncbi.nlm.nih.gov/pubmed/15531657
[10] Folate Intake, Alcohol Use, and Postmenopausal Breast Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial – https://www.ncbi.nlm.nih.gov/pubmed/16600944
[11] Does a High Folate Intake Increase the Risk of Breast Cancer? –
https://www.ncbi.nlm.nih.gov/pubmed/17063929
[12] Multivitamin Use and Breast Cancer Incidence in a Prospective Cohort of Swedish Women – https://www.ncbi.nlm.nih.gov/pubmed/20335555
[13] High Folic Acid Diet Enhances Tumour Growth in PyMT-induced Breast Cancer – https://www.nature.com/articles/bjc201711
[14] Folic Acid and Breast Cancer Risk – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518164/
[15] Dr Joel Fuhrmann, Position Paper: Folate – https://www.drfuhrman.com/get-started/position-papers/9/folate
[16] Folic Acid Causes Higher Prevalence of Detectable Unmetabolized Folic Acid in Serum than B-complex: a Randomized Trial – https://www.ncbi.nlm.nih.gov/pubmed/25943647
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