Focusing on Folate

vitamin b9 in food, folate

Eat the Greens for Vitamin B9

Folate, aka vitamin B9, and its synthetic form, folic acid, are water soluble and essential; meaning we have to get it from food. Whereas vitamin B12 is only available from animal products, vitamin B9 is only naturally available from leafy vegetables.

Notice the word “naturally” since a lot of breakfast cereals and milk are fortified with folic acid. It’s better to eat your greens and beans instead of high glycemic cereals and milk, which also happens to be fortified with antibiotics and growth hormones.

Most of us don’t eat enough greens though so we will have to use a dietary supplement to get our B9, which means folic acid, the synthetic version of folate. Most high grade multivitamin supplements will contain at least the RDI of B9 but it will not be natural folate.

The main reason vitamin B9 is included in this section is that we must be smart about supplementing it. Why do we have to be smart about folic acid supplements? Cancer, cardiovascular disease and pregnancy are three good reasons; alcohol and Alzheimer’s are two others.

This vitamin is a two-edged sword where cancer is concerned.

On the plus side, because of the role it plays in the synthesis and repair of DNA, there is evidence that a deficiency of folic acid can cause damage to DNA thus opening the door to cancer. Specifically, individuals having a diet low in folate have an increased risk for breast, pancreatic and colon cancer.

The problem is that so far there are no clinical trials that prove conclusively that dietary B9 or supplemented folic acid reduces the risk of the types of cancers mentioned.

Feeding Cancer with Folic Acid

On the negative side, too much supplemented folic acid may actually contribute to tumor growth. A 2007 issue of JAMA, 297(21):2351-2359, reported on a randomized clinical trial in patients with a history of colorectal cancer.

While the article was titled, Folic acid for the Prevention of Colorectal Adenomas, it discovered an association between supplementation of 1000ug/day of folic acid, which is more than twice the RDA, with a “statistical trend for advanced colorectal lesions” plus a doubling of the risk for the presence of three or more colorectal adenomas.

An adenoma is a benign tumor but over time could become malignant cancer, at which time it would be labeled as an adenocarcinoma. In this study, folic acid supplementation was also related to an increased risk for cancers at other sites, mainly the prostate.

It is not so cut and dried however since human and animal studies on high-dose folic acid and cancer have not shown any conclusive results. It appears that more research is needed which is the usual cop-out when no one wants to foot the bill for clinical trials for supplements.

RDAs and DFEs: No Equality with Folate and Folic Acid

The recommended daily allowance (RDA) is a component of the recommended daily intakes developed by the Institute of Medicine of the National Academy of Sciences.

RDAs state the level of nutrients sufficient to meet the daily intake of 97-98% of healthy individuals in various age groups, sex and special situations such as pregnancy.

Because food sourced B9 and folic acid (the synthetic) are absorbed differently, the intakes are stated as “Dietary Folate Equivalents” of DFEs. Strange as it seems, the synthetic folic acid is more bioavailable than natural food sourced folate.

The ratio of supplemented folic acid and from fortified foods to natural food sourced folate is .6ug to 1ug; that is, .6 of synthetic folic acid is the same as 1 ug of folate.

The RDA/DFE Numbers

The RDA for DFEs of vitamin B9 start at 150 ug/day for children from 1 to 3 years old, then jumps to 200 ug/day from 4 to 8 years, 300 ug/day between 9 and 13 years and then cap out at 400 ug/day for 14 year olds and up through adult. Larger amounts are needed for pregnancy and breast feeding mothers; 600 ug and 500 ug respectively.

Breaking the Upper Limit

Having laid that foundation, here is where smart supplementation of folic acid comes in.

An adult that eats a bowl of fortified breakfast cereal with 2% milk gets about 200 ug of folic acid. Add to that a glass of orange juice and now we’re up to 260 ug. A couple of eggs with two slices of toast bring the total up to 360 ug.

Many people take a multivitamin with breakfast and most contain 50% of the RDA for folic acid (200 ug) and now we have consumed 560 ug which is 160 ug over the RDA. Throw in lunch and dinner and consuming 1000 ug of folic acid for the day is pretty easy to do.

1000 ug just happens to be the established upper limit of folic acid above which could trigger adverse health effects.

The embedded YouTube video below narrated by Dr. Jeffery Moss, DDS, CNS, DACBN, of Moss Nutrition is an excellent presentation of the benefits of folate and folic acid as well as the dangers of ingesting too much. Yes, it can actually cause cancer in some individuals for a surprising reason that Dr. Moss explains very well. It is a little under 7 minutes long and well worth the time to view it.

The Dangers

The good thing about B9 is that there is no health risk if it is consumed in food. Even the synthetic folic acid health risks from supplements and fortified food are low in that it is water soluble and excesses are expelled in urine. OK, so why do we care about upper limits or too much vitamin B6 whether from folate or folic acid?

The danger is twofold. One is interactions; the other is the risk of triggering a vitamin B12 deficiency. The first interaction has to do with alcohol.

Alcohol: Drinking and Supplementing go Together

When it comes to alcohol and folic acid, here’s the rule: high alcohol and low folate equals high cancer risk. The implication is pretty straightforward if we have more than a couple of alcoholic drinks a day we need to take in more dietary folate. Alcohol interferes with the absorption and metabolism of vitamin B9. How do we know?

A study published in a 1995 Journal of the National Cancer Institute, (vol. 87, No.4), Alcohol, low-methionine–low-folate diets, and risk of colon cancer in men, told us so. The study was conducted on 45,000 men and showed that relatively low folate intake coupled with a high alcohol intake resulted in a high rate of colon cancer.

There is a good news side to the study in that drinking alcoholic beverages while consuming 650 mcg or more of folate per day was not associated with an increased risk of colon cancer. So all you guys who like to booze it up, better start chasing that J-Beam with a shot of juiced spinach.

Not to overlook the ladies, two studies showed that increased folate intake may reduce the risk of breast cancer in women who regularly consume alcohol. This could be significant since even moderate alcohol intake has been associated with an increased risk of breast cancer in women.

A very large study done on 88,000 nurses was published in a 2001 issue of Epidemiology, (vol. 12, no. 4) titled, “Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women”.

It reported that folic acid (supplement) intake had no relation to breast cancer in women who drank less than one alcoholic drink per day.

However, when they kicked up the folic acid supplements to 600 mcg a day and kept doing the one-drink-a-day routine, they experienced half the risk of breast cancer than women who took less than 300 mcg of folic acid daily.

It looks like the same advice applies to women as well as men; if you drink alcohol, eat your greens, beans, and fortified foods.

Folic Acid, Pregnancy, and Birth Defects

Before moving on, here’s one more for the ladies. Becoming pregnant and taking in at least the minimum daily allowance of folate or folic acid is critical to avoid certain birth defects known as neural tube defects.

These are horrible defects that may involve the failure of part of the brain or skull to form (anencephaly) or possible failure of the backbone or spinal canal to close before birth (spina bifida). Both are potentially fatal but both are entirely preventable.

It is pretty clear that the development and growth of a fetus depend on proper cell division. It was stated earlier that folate is critical for DNA and RNA synthesis. The problem is that these defects occur between the 21st and 27th days after conception and the woman may not even know she is pregnant.

Before we started fortifying foods with folic acid, the risk of neural tube defects (NTD) in the U.S. was estimated to be one in 1000 pregnancies. Randomized clinical trials have shown a 60% to 100% reduction in NTD cases when women took folic acid supplements in addition to a varied diet of good folate sources for a month before and after conception.

The results of those and other studies pushed the U.S. Public health services to recommend that all women becoming pregnant take 400 mcg per day of folic acid to prevent NTD. It seems that the message for women concerning alcohol, pregnancy, and folic acid is clear; SUPPLEMENTATION IS A MUST.

Pregnancy and role of folic acid

Genetics, Liquor and Folic Acid

In at least two studies seen in Pub Med, individuals who inherit both genes for the C677T variant of the enzyme MTHFR (Methylenetetrahydrofolate reductase), polymorphism T/T, have been found to be at a decreased risk for colon cancer when folate intake is adequate.

However, when vitamin B9 intake is low and/or alcohol intake is high, individuals with the (T/T)genotype have been found to be at increased risk of colorectal cancer. In addition to colon cancer, the same gene variant is also associated with coronary atherosclerosis in patients at high risk for coronary artery disease.

Speaking of Heart Disease and Folic Acid

When it comes to cardiovascular disease, homocysteine is the word to remember. The results of more than 80 studies say even moderately high levels of homocysteine in the blood rise the risk of cardiovascular diseases. Homocysteine is an amino acid and it has been linked with heart and vascular disease. The problem is that while high levels of homocysteine have been linked to such conditions, lowering homocysteine levels don’t necessarily lower heart disease risk.

Nevertheless, it seems prudent to control our levels of this particular amino acid.

What does all this have to do with vitamin B? It has been shown that deficiencies of three B vitamins, folic acid (B9), pyridoxine (B6), or B12 (cyanocobalamin) can lead to high homocysteine levels.

A study was written up in Pub Med and published in a 2001 issue of Circulation (vol 103, no. 22) followed 1,980 Finnish men for ten years. It found that those who consumed the most dietary folate had a 55% lower risk of an acute coronary event when compared with those who consumed the least dietary folate.

Of the 3 vitamins mentioned that regulate homocysteine levels, folic acid has been shown to have the best effect in minimizing basal levels of homocysteine in the blood when there is no deficiency coexistence with vitamin B12 or vitamin B6. So we have one more reason to supplement with folic acid or eat our beans and greens.

Medicinal Interactions

The list of meds that may interact with B9 is fairly short and is itemized below without a lot of comment. It is included mainly for awareness.

  • NSAIDs: therapeutic doses of anti-inflammatories (aspirin, ibuprofen, etc) may interfere with folate metabolism.
  • Phenytoin, an anticonvulsant, can inhibit the intestinal absorption of folic acid. Ditto for long term use of Phenobarbital and Primidone;
  • cholesterol-lowering agents, cholestyramine and colestipol, may decrease the absorption of folic acid if taken together.
  • Methotrexate: taking folic acid with this drug may reduce its side effects. Often prescribed for rheumatoid arthritis or psoriasis;
  • Trimethoprim (an antibiotic), may depress folate levels.
  • pyrimethamine (an antimalarial), may have anti-folate activity.
  • triamterene (a blood pressure medication), and sulfasalazine (a treatment for ulcerative colitis) may both exhibit anti-folate activity.