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Crohns Sufferers - Should You Take Folic Acid?

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Folic acid is one of the 2 important B vitamins in Crohn’s disease. Its deficiency can cause anemia, lead to homocysteine accumulation and worsen the symptoms of Crohn’s disease. This article discusses the causes of folate deficiency and how it can be treated. Besides merely serving as a dietary supplement, folic acid has other applications in the treatment of Crohn’s disease. In what other ways can folic acid help? Read on to find out.

Crohn’s Disease as a Deficiency State

The major presentation of Crohn’s disease is the inflammation of the gastrointestinal tract. Although any part of the alimentary canal can be affected, the most common site of inflammation in Crohn’s disease patients is the terminal (end of the) ileum.

The inflammation that characterizes Crohn’s disease is really a reaction mounted by the body’s immune system.

However, Crohn’s disease is not an autoimmune disease as it was once believed. Rather, it is caused by an impaired immune system. Specifically, Crohn’s disease arises from the impairment of innate immunity. Therefore, it is a kind of immune deficiency disease.

Nutritional deficiency is another common aspect of Crohn’s disease. Because the gastrointestinal tract is the site of absorption for all macronutrients and micronutrients, the absorption of essential minerals and vitamins are affected by Crohn’s disease.

Depending on the site of inflammation, Crohn’s disease can cause certain nutritional deficiencies.

For example, vitamin B12 is absorbed in the part of the small intestine known as terminal ileum. Therefore, vitamin B12 deficiency is common among Crohn’s disease patients and certain among those with damage to the terminal ileum.

In addition, folic acid is absorbed in the jejunum and ileum of the small intestine. Therefore, folate deficiency is also common among Crohn’s disease patients.

Folate Deficiency

Folic acid or vitamin B9 is one of the most important vitamins needed to maintain optimal health. It is obtained from diet or supplements.

Folic acid is essential for red blood cell formation, for protecting genetic materials such as DNA and for preventing birth defects during pregnancy. An optimal folate level is also required to prevent anemia.

Signs of Folate Deficiency
  • Weakness
  • Weight loss
  • Loss of appetite
  • Headache
  • Irregular heartbeat
  • Irritability
  • Behavioral disorders including depression
  • Megaloblastic and macrocytic anemia

All the biochemical processes dependent on folic acid are affected by folate deficiency.

In most cases, folic acid and vitamin B12 have overlapping roles. Since both folate and vitamin B12 deficiencies are common among Crohn’s disease patients, long-term supplementation of either or both vitamins may be required.

For example, both folic acid and vitamin B12 are needed in the transmethylation reactions involved in the production of neurotransmitters such as dopamine, serotonin, and epinephrine.

Therefore, folate deficiency triggered by Crohn’s disease may cause depression and cognitive impairment.

In addition, both vitamins are needed for the utilization of homocysteine, a toxic intermediate of amino acid syntheses.

The accumulation of homocysteine during folate and/or vitamin B12 deficiency can cause neurological and cardiovascular damage in Crohn’s disease patients.

Folate Deficiency and Crohn’s Disease

There are 3 possible causes of folate deficiency in people living with Crohn’s disease. These causes are malnutrition, malabsorption and increased folate utilization in the body.


Malnutrition is an important consideration in Crohn’s disease especially in patients who have had the disease for a long while.

One possible way malnutrition can cause folate deficiency is poor diet. Eating a diet poor in folic acid can cause folate deficiency even in healthy people. For Crohn’s disease patients, a diet low in folic acid can cause severe folate deficiency.

In addition, the damage to the gastrointestinal tract due to Crohn’s disease can make swallowing difficult and cause diarrhea too. Loss of appetite is another common complaint among people living with Crohn’s disease.

When eating is difficult, there is a high chance that malnutrition can occur. Folate deficiency can, therefore, result even though the patient’s diet is rich in folic acid.


Malabsorption is also very common among Crohn’s disease patients. Because folic acid is absorbed in the small intestine, its absorption is severely impaired by inflammation and damage to that part of the digestive tract.

Folate deficiency due to malabsorption of folic acid has been reported in Crohn’s disease patients with damaged duodenum, jejunum, and ileum.

In one study, folate deficiency was most associated with damage to the proximal end (duodenum and jejunum) of the small intestine rather than the distal end (terminal ileum). This shows that unlike vitamin B12 absorption, folic acid is mostly absorbed in the first sections of the small intestine.

Increased Requirement

Studies show that inflammation increases the body’s need for folate. Therefore, diseases with inflammatory components can cause folate deficiency simply by raising the utilization of folic acid in the body.

Folate deficiency caused by increased utilization of folic acid has been reported for rheumatoid arthritis patients and suspected in Crohn’s disease patients.

This increased need for folate is believed to be caused by the increased production of pro-inflammatory immune cells such as granulocytes. As the body responds to injuries such as the one sustained in the gastrointestinal tract in Crohn’s disease, immune cells cause inflammation at the site of injury.

Because folate is needed for the release and functioning of these immune cells, the body uses up its store of folic acid and, therefore, needs more from dietary and supplemental sources.

At least one study has confirmed the occurrence of folate deficiency in Crohn’s disease patients with normal dietary folate intake and folic acid absorption but increased folate utilization.

Treatment for Crohn’s Disease

Treatment options for Crohn’s disease may also cause Crohn’s disease.

For example, surgical removal of part of the small intestinal may reduce the absorption of folic acid from the gastrointestinal tract. A similar effect is observed with vitamin B12 deficiency and removal of part of the ileum.

Besides surgery, some drugs used in the management of Crohn’s disease can also cause folate deficiency.

Sulfasalazine and methotrexate are the 2 drugs commonly used by Crohn’s disease patients that can also cause folate deficiency. These drugs are used to control inflammation and especially recommended for people suffering from rheumatoid arthritis, ulcerative colitis, and Crohn’s disease.

The 2 drugs act by inhibiting some of the enzymes needed for folic acid synthesis. One such enzyme is dihydrofolate reductase. By inhibiting these enzymes, these drugs block the production of nucleic acids and prevent the rapid cell division.

Therefore, health experts advise that Crohn’s disease patients take 1 mg of a folic acid supplement daily.

Homocysteine and Crohn’s Disease

A number of studies have established that the folic acid deficiency caused by Crohn’s disease can lead to the accumulation of homocysteine in the body especially when vitamin B12 deficiency is also present.

In one study, 52% of patients with Crohn’s disease were found to have abnormally high levels of this toxic compound in their blood.

Homocysteine does not only cause damage in the nervous and cardiovascular systems, but there is also solid evidence that this toxic intermediate is present in high levels in the mucosal membrane of the colon in patients with Crohn’s disease.

Clearly, homocysteine in the mucosal surface of the gastrointestinal tract is a source of concern. Because it raises harmful free radicals, high levels of homocysteine in the injured and exposed mucosal layer of the gastrointestinal tract can only worsen the inflammation and other symptoms of Crohn’s disease.

Therefore, folic acid supplementation is essential for Crohn’s disease patients in order to effectively lower homocysteine levels in the body.

Studies on Folic Acid and Crohn’s Disease

Folate Absorption in Crohn’s Disease

A 1994 study published in the journal, Digestion, investigated the prevalence of impaired folate absorption among Crohn’s disease patients. The study involved 100 patients and 20 healthy controls. Each of the participants took an oral folate absorption test.

The results of the study showed that 25 of the patients with Crohn’s disease had abnormal folate absorption as evidenced by post-test serum folate levels that were incomparable to their oral folate intakes. Out of these 25 patients, 9 showed no increase in serum folate levels.

The researchers found no correlation between the severity and extent of Crohn’s disease and the reduction in folate absorption.

They concluded that increasing dietary folate intake may help raise serum folate levels in those patients with impaired folate absorption.

However, 10% of patients with no measurable change in post-test serum folate levels may need to receive folate supplementation through the parenteral route (injection).

Folic Acid as an Anti-inflammatory Agent

In a 2010 study published in the European Journal of Internal Medicine, a group of researchers investigated the effects of vitamin B12 and folic acid on inflammation in a group of patients with inflammatory bowel disease.

The study involved 45 patients with Crohn’s disease, 93 patients with ulcerative colitis and 53 healthy subjects (control group).

The results showed that

  • vitamin B12 level was 18% higher in the control group than among patients with Crohn’s disease
  • the folic acid level was 20% higher in the control group than among Crohn’s disease patients
  • the folic acid deficiency was more common than vitamin B12 deficiency

In their conclusion, the researchers stated that the ability of folic acid and vitamin B12 to lower homocysteine levels is responsible for the anti-inflammatory effect in patients with Crohn’s disease.

Folic Acid and Methotrexate

A 2012 study published in the journal, Digestive and Liver Disease, assessed the efficacy and side effects of methotrexate in the treatment of inflammatory bowel disease.

The study involved 89 patients with Crohn’s disease and 23 patients with ulcerative colitis.

The results showed that methotrexate was effective for 34% of patients with Crohn’s disease and partially effective for 26% of the patients. More importantly, 44% of these patients experienced side effects and 3 out of 4 of those with these side effects had to discontinue methotrexate.

Lastly, the study showed these severe side effects were 5 times more common in Crohn’s disease patients who did not take folic acid compared to those who combined methotrexate with folic acid.

The study showed that folic acid supplementation is not only useful for preventing/treating folate deficiency in the management of Crohn’s disease but also for reducing the side effects of first-line drugs such as methotrexate.

By reducing the side effects of methotrexate, folic acid can help ensure patients with Crohn’s disease keep taking their medications.

Concerns about the potential toxicity of methotrexate may mandate adding folic acid to the medications used in the treatment of Crohn’s disease. In a 2011 study published in the Journal of Clinical Gastroenterology, the researchers identified the most common side effects of methotrexate in the treatment of Crohn’s disease as nausea (22% of patients) and elevated liver enzymes (10%).

Folic Acid vs. Folinic Acid

A 2009 study published in The British Journal of Dermatology compared the efficacies of folic acid and folinic acid supplement in reducing the side effects of methotrexate.

The study found that folic acid was just as effective as folinic acid in spite of the cost difference between the 2 supplements.

Folinic acid or leucovorin or citrovorum factor is folic acid vitamers. It also has the same activity as folic acid. However, it is a more expensive supplement. Unlike folic acid, folinic acid does not require the enzyme, dihydrofolate reductase, to be converted to its active form.

Therefore, methotrexate (a dihydrofolate reductase inhibitor) should not reduce its efficacy.

However, this study found both supplements to be equally effective for lowering the elevated liver enzymes and relieving other hepatic side effects associated with methotrexate therapy.





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