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Can a Folic Acid Deficiency Make You Unhappy?

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Folic acid is one of the most popular B vitamins. It serves diverse roles in the body and it is absolutely essential to metabolism. Available studies indicate that the health benefits of folic acid may include the relief of depressive symptoms. How effective is folic acid in the treatment of depression? Can it be used alone or along with standard antidepressants? How exactly does folic acid for depression work? Read on to find out.

Depression is a strange illness that affects feelings of self-worth and can cause low moods, anger, restlessness, and thoughts of self-harm or suicide. Typically, depression is caused by irregular brain patterns, which can be triggered by a number of causes. Research has found that many individuals with depression also have low folic acid levels in the body.

Researchers believe that adding more folic acid to the diet can help prevent depression and lessen depressive symptoms once a diagnosis of depression is received. Additionally, a few studies have found that taking folic acid supplements in addition to traditional antidepressants increases the effectiveness of the medication.

Read on to learn more about the connection between folic acid and depression and how you can use folic acid to lessen depressive symptoms and prevent depression.

Does Folic Acid for Depression Work?

The first question to answer about if folic acid helps depression is what forms of depression it can help with. Numerous studies have found that in many cases, a low level of folic acid in the body can sometimes cause depressive symptoms to worsen. Many individuals with depression also have low folic acid levels, which suggests that folic acid might be able to boost mood and prevent depression in some cases. Other studies support the use of folic acid supplements alongside traditional antidepressants. These studies have found that adding more folic acid to the diet makes antidepressants more effective.

However, adding folic acid to the diet, while healthy and beneficial for individuals with any form of depression, is not enough to completely cure depression alone. Stopping treatments prescribed by a doctor without proper monitoring can increase depression and even lead to thoughts of suicide. It is imperative to always work with qualified health professionals to treat mental health issues safely and effectively.

If you suspect you have moderate to severe depression, don’t wait to get help. Contact a qualified healthcare provider today to help reverse your low mood and prevent severe injury or death.


Signs of Minor Depression
  • Continued feelings of sadness most of the time
  • Lack of interest in activities
  • Insomnia
  • Low energy
  • Guilty feelings
  • Sudden weight loss or weigh gain


Signs of Major Depression


  • Any of the symptoms of minor depression
  • Constant negative thinking
  • Lack of focus
  • Irritability
  • Restlessness
  • Morbid thoughts
  • Thoughts of self-harm or suicide
  • Sudden weight loss or weight gain
  • Lashing out at friends or family
  • Constant fatigue
  • Trouble sleeping


When to Seek Help

If you have ever had thoughts of self-harm or suicide, your depression has progressed beyond the point of simple diet changes and natural remedies. If you have thoughts of self-harm or suicide, professional intervention is necessary. Don’t feel ashamed to contact a qualified health professional right away and get the help you deserve.

What is Folic Acid?

Folic acid is a B vitamin also known as folate or vitamin B9.  Like all B vitamins, it is essential to a long list of metabolic functions in the body.

This vitamin is needed by the body to synthesize, utilize and repair DNA. It is also useful for promoting rapid cell growth and division, and can as well act as a co-factor in some biological reactions. Folic acid is also essential for the functioning of the nervous system.

Dietary sources of folic acid include spinach, collard greens, turnip greens, asparagus, broccoli, grape fruit, oranges, straw berries, celery, brussel sprouts, cauliflower, beets, corn, carrots and okra. The vitamin is also commonly added to fortified cereals and bread.

Folic acid itself is biologically inactive, but in the body it is converted to dihydrofolic acid, which is further converted to tetrahydrofolate and other derivatives which are metabolically active.

The conversion of folic acid to its biologically active forms depends on the action of the enzyme, dihydrofolate reductase, in the liver.

Because the body utilizes vitamin B9 in diverse ways, folic acid deficiency can cause very serious complications. Some of the signs of this deficiency are seizures, vascular changes, depression, cognitive impairment and movement abnormalities.

Vitamin B9 supplements are available to treat folic acid deficiency. To prevent this deficiency, experts recommend the following:

  • For adults (14 years and above), the recommended daily intake of folic acid is 400 micrograms. The daily intake for breastfeeding women is 500 micrograms and pregnant women should take 600 microgram.

However, doses higher than these are required to treat depression.

  • The upper limit for daily folic acid intake is 800 micrograms for adolescents but adults are allowed a maximal daily dose of 1000 micrograms.

Very high doses of folic acid (more than 1000 micrograms daily) may cause seizures, stomach discomfort, insomnia, skin problems, diarrhea, cramps, bloating and rash.

Folic acid is used as a supplement in the treatment of depression. In this role, it is used to improve patients’ response to standard antidepressant. The recommended dosage of the vitamin for this use is 200 - 500 micrograms per day.

Natural Sources of Folic Acid

Folic acid is found naturally in many sources (it is also called folate). The most common place to find folic acid is in grains, vegetables, beans, and fruit. Folic acid is often added to processed foods because it is such an important nutrient. However, your body must convert folic acid back to folate for it to be used by the body. If your body naturally has trouble converting folic acid to folate, you could be deficient in folic acid even if you consume foods that are high in folic acid. Deficiencies are often caused by conditions like celiac disease, liver disease, alcohol consumption, eating disorders, kidney problems, and pregnancy.

For individuals with folic acid conversion difficulties, it is recommended to consume more than the USDA recommended consumption of folic acid, which is 400 mcg per day. Taking folic acid that comes in the form of l-methylfolate is also better for individuals with folic acid deficiencies.

How do you know if you are deficient in folic acid? You can take a blood test for the most accurate answer, but there are also a few signs that you might be deficient, which include:

Signs of a Folic Acid Deficiency
  • Getting sick often
  • Anemia
  • Low energy
  • Digestion issues
  • Irritability
  • Grey hair at a young age
  • Pale skin
  • Canker sores

Using Folic Acid for Depression

A considerable number of scientific studies suggests that depression is associated with folate deficiency. In addition, folate deficiency in depressed patients can also reduce the effectiveness of antidepressant drugs.

The importance of folate in depression can be traced to the role of the vitamin in transmethylation reactions. A transmethylation reaction involves the transfer of a methyl group from one compound to another. Such methyl transfers are necessary for the formation of certain neurotransmitters.

The relationship between folate and depression is also supported by observations that a common genetic variant of an enzyme that reduces a person’s ability to convert folic acid to L-methyl folate (which is its active metabolite), is more common in patients with depression.

This means that the genetic anomaly would affect transmethylation reactions and, by extension, neurotransmitter syntheses.

Furthermore, because low levels of folate disrupt transmethylation reactions, it can lead to the accumulation of homocysteine along with the disruption of neurotransmitters, phospholipids, myelin, and receptors.

Homocysteine is a toxic intermediate of amino acid syntheses and it is an amino acid not used in making proteins. It is formed from methionine and converted to its homologue, cysteine. Both the conversion and recycling of homocysteine back to methionine require B vitamins such as folic acid.

When low folate levels promote the accumulation of homocysteine, the toxic intermediate increases oxidative stress especially in the bones, heart and the central nervous system.

In the brain, homocysteine is responsible for kinds of neurological damage that can cause depression.

Regarding the effect of folate on standard antidepressants, there is now conclusive proof that low folate levels cause poor response to antidepressant treatments. Other studies suggest that a high level of folate can be used for better treatment outcomes.

Study 1

In a study published in the American Journal of Psychiatry, a group of researchers gave fluoxetine to 213 patients who were suffering from major depressive disorders. The researchers measured the blood levels of folate in each member of the study group.

At the end of eight weeks on fluoxetine, the patients with lower folate levels showed the least signs of improvement on the drug therapy.

Study 2

In a 2005 study published in the Journal of Psychopharmacology, researchers found that individuals with major depression are commonly low in folate and vitamin B12. The researchers also found that populations who typically have diets rich in folate are less likely to suffer from depressive disorders and other mood disorders. The researchers said there was “significant evidence” that increasing folate intake could help reduce incidences of depression.

Study 3

A study published in 2007 in the Journal of Psychiatry and Neuroscience backed the evidence from the other two studies. In this study, researchers reviewed data going back to the 1960s that supported the use of folate and folic acid to reduce depressive symptoms. According to this study, about one-third of individuals with depression are also low in folate and folic acid.

The researchers suggested that individuals with low levels of folic acid take up to 2 mg of folic acid daily to make up for poor absorption and the lack of folic acid in the diet. The researchers also suggested that even individuals who get folic acid through processed foods and natural foods can still benefit from the supplementation of folic acid and folate to help reduce the likelihood that they become clinically depressed.

In summary, folic acid supplementation helps to relieve depression, and is also effective in the treatment of depression when used with standard antidepressant drugs.

Folic Acid Improves Effectiveness of Antidepressants

Once absorbed, folic acid becomes metabolically active after it is being converted to dihydrofolate and then to tetrahydrofolate through a series of enzymatic reactions.

The first reaction is catalyzed by the enzyme, dihydrofolate reductase. The tetrahydrofolate is thereafter converted to the biologically active L-methyl folate by the enzyme, methylenetetrahydrofolate reductase.

L-methyl folate acts as an important regulator of a critical co-factor for trimonoamine neurotransmitter syntheses. This critical co-factor is known as tetrahydrobiopterin.

Tetrahydrobiopterin helps in the conversion of phenylalanine to tyrosine and in the hydroxylation of tyrosine and tryptophan, which are the important steps involved in the syntheses of monoamine neurotransmitters.

Therefore l-methyl folate can increase the production of one or more of the three monoamines (trimonoamine) neurotransmitters:

  • Dopamine
  • Norepinephrine
  • Serotonin

Like other neurotransmitters, these neurotransmitters are endogenous chemicals that transmit signals across synapses between nerve cells. However, the three monoamine neurotransmitters are important in the regulation of mood.

By augmenting the syntheses of trimonoamine neurotransmitters through the enhancement of tetrahydrobiopterin, L-methyl folate is able to boost the antidepressant effects of standard antidepressants.

Studies have shown that low serum folate levels and low cerebrospinal fluid levels of L-methyl folate may be related to depression in some patients.

Since L-methyl folate indirectly controls monoamine levels, a low level of L-methyl folate could impair the actions of the enzymes involved in the syntheses of trimonoamine neurotransmitters. This causes monoamine deficiency, which most experts believe is responsible for depression.

L-methyl folate is also believed to be involved in monoamine neurotransmitter metabolism.

In this role, it promotes the synthesis of tetrahydrobiopterin enzymatic cofactor, modulates the enzymes that break down monoamine neurotransmitters, and contribute to the actions of monoamine transporters and neurotransmitter receptors.

Studies on Folic Acid and Depression

In a 1980 study published in the journal, Psychosomatics, the link between folic acid deficiency and depression was explored. The study consisted of 48 patients that were divided into three groups: depressed patients, psychiatrically ill patients (but not depressed) and medically ill patients.

All the patients were hospitalized and given a standard diet with no drugs and vitamins for one week.

At the end of the week, depressed patients had significantly lower serum folic acid level than the patients in the other two groups.

The results also showed that the patients with lower serum folic acid levels scored higher in the Hamilton Rating Scale, the clinical standard for measuring the severity of depression.

In another study published in the journal, Psychological Medicine in 2004, the relationship between low folic acid, vitamin B12 and homocysteine as possible predictors for depression was demonstrated.

For this study, 412 persons aged 60 to 64 years where randomly recruited from a large community. They all underwent psychiatric and physical assessments and were also given brain MRI (magnetic resonance imaging) scans.

The subjects were assessed and checked for various depressive symptoms using the PRIME-MD PATIENT HEALTH questionnaire. Folic acid, serum, vitamin B12, folic acid, homocysteine and creatinine levels were also measured in the blood samples taken from the study participants.

The results of the study showed that the participants who had the lowest homocysteine levels also had fewer depressive symptoms even after adjusting for creatinine, folic acid and B12 levels.

On the other hand, the participants with the lowest levels of folic acid had the highest numbers of depressive symptoms even after adjusting for other causes of depression.   

The results also showed that vitamins B12 levels did not have any significance on depressive symptoms.

In a 1989 study published in the Journal of Affective Disorders, the link between folate deficiency and tetrahydrobiopterin was demonstrated.

The researchers measured the biopterin and neopterin levels in the participants. Neopterin is the product of the breakdown of guanine triphosphate and its measurement is taken as an indication of oxidative stress mounted by the immune system.

Biopterin, on the other hand, is the product of the breakdown of tetrahydropterin.

The average neopterin-biopterin ratio was higher in the 76 patients than in the 61 controls involved in this study. In female patients, biopterin levels were considerably lower than in controls.

In the control group there was a significant correlation between the molar concentration of biopterin and neopterin, but there were no such correlations found in the patients. These data show that tetrahydrobiopterin biosynthesis is reduced in this group.

A significant positive correlation was found between urinary biopterin and plasma folate levels.

This study suggests that folate deficiency can impair the synthesis of tetrahydrobiopterin, a cofactor that essential to the production of monoamine neurotransmitters.

In another 1989 study published in the journal, Acta Psychiatrica Scandinavica, the levels of serum folate were measured in patients with major depressive orders and normal controls. Red blood cell folate concentrations were also measured in different subgroups of the participants.

The results showed that the patients with major depressive disorders had lower serum and red blood cell folate concentrations than the normal controls.

Lower serum folate concentrations were also related with increased severity of depression.

How to Use Folic Acid to Reduce Mild Depression

If you have moderate to severe depression, consult with your doctor about using folic acid supplements in conjunction with your prescription medication. If you are not taking medication and have mild depression or suffer from frequent low moods but do not meet the criterion for clinical depression, you can experiment with adding more folic acid to your diet to protect your mental health. Research suggests that it is safe to take up to 2 mcg of folic acid daily without any major side effects or health risks.

However, eating folic acid is not enough to prevent and reverse depression on its own. In conjunction with folic acid supplements, take the following steps to protect your mental health and improve your day-to-day mood:

Eat Real Food

Sugar and processed foods provide quick energy, but lack the vitamins and nutrients that keep your body and mind healthy long-term. Avoid starchy carbs, sugar, processed foods, and processed grains. Replace them with vegetables, high-quality proteins, fruit, and whole grains.

Eat B12

B12 is also necessary to protect mental health. Vitamin B12 is a “brain vitamin” and is used for processes in the brain that affect mood and mental health. Vitamin B12 can be found in many natural foods, including seafood and dairy.

Get Enough Vitamin D

Vitamin D is a hormone that is essential for many of the body’s processes, but it is also important for mental health. There is a lot of truth to the concept of the sun making you happy and feel good. Seasonal Affective Disorder is a form of low-lying depression that is directly caused by lack of sunlight. Get more sun as often as you can, or supplement with vitamin D3 supplements.

Eat Omega 3

Omega 3 fats are some of the healthiest fats you can eat and are necessary to maintain brain health. Without the right balance of fats, your brain suffers and your mental health is in danger.


Exercise is essential for fighting low mood and depression. Studies have found that regular exercise stimulates positive thinking and helps prevent depression and can even reverse mild forms of depression.


Although sleep can be difficult when suffering from depression and low mood, it is important to try to get as much as possible. Eight to nine hours of sleep per day are ideal for most adults, and a lack of sleep can lead to an increase in depression and low mood.

Other Vitamins that Fight Depression

In conjunction with folic acid, these vitamins have been shown to improve mental health and fight depression:


GABA is a neurotransmitter that is involved in stress relief. Low GABA levels are linked to feelings of anxiety and depression. GABA is often included in supplements for depression and low mood. Studies have found that natural GABA is most effective at relieving anxiety and depression, but there is some evidence that also suggests that supplements can also have a positive effect. However, GABA should never be used alone to treat depression, as there is not enough evidence to suggest that it is powerful enough to fight depression on its own.


Inositol is a compound that helps transmit serotonin and other neurotransmitters. Inositol is commonly found in grains and meat. Individuals with chronic depression and bipolar disorder have been shown to have low levels of inositol. A few studies have found that taking high doses of inositol can help reduce feelings of anxiety and depression. However, there is little evidence to support the use of taking inositol alone to fight depression as the supplement has not been proven effective when taken alone.


Saffron is commonly used as an expensive spice made from crocus stigmas. Recent studies from India have examined saffron’s potential to work as a supplement to treat depression. These studies found that saffron can be effective in fighting moderate and mild depression and reversing the symptoms of mild depression. However, since saffron is the most expensive spice in the world, taking saffron as a supplement is likely too expensive for the average person.


SAMe is a naturally-occurring compound that works to make neurotransmitters more effective, including the transmission of dopamine and serotonin, the “feel good” chemicals. SAMe has been available in supplement form since 1998. Studies have found that individuals with low mood and depression as well as other mood disorders commonly have lower levels of SAMe naturally. In 2002, a study found that taking SAMe supplements was more effective than taking placebo to relieve symptoms of depression and was just about as effective as tricyclics in treating the symptoms of depression.

St. John’s Wort

St. John’s wort is an herbal remedy that has been used to treat low moods for hundreds of years.  This supplement is one of the most popular herbal supplements in the world. The plant is the most studied natural remedy for depression in the world, and results are generally favorable. St. John’s Wort is able to relieve feelings of depression for mild and moderate depression, but not severe depression. Interestingly enough, the same study that found that St. John’s Wort was not effective in treating severe depression also found that Zoloft (sertraline) was also not effective in treating severe depression.

Folic Acid Extremely Helpful for Depression

Studies suggest that in many cases, folic acid is a missing ingredient in mental health. Although folic acid is by no means the only treatment for depression, or the best treatment for depression, enough scientific evidence supports the use of folic acid as a boost for mental health and a supplement that is likely to help prevent and lesson the symptoms of existing depression.

For individuals who struggle with depressive symptoms, or for those who have a family history of depression, adding additional folic acid to the diet will only help prevent depression and lesson existing symptoms.





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