Folate

Folate, also known as vitamin B9, is a water-soluble vitamin that is essential for the proper functioning of the human body. It plays several important roles, including:

  1. DNA synthesis: Folate is required for the production and maintenance of new cells, including the synthesis of DNA, RNA, and proteins.
  2. Red blood cell production: Folate is necessary for the production of red blood cells, which carry oxygen throughout the body.
  3. Neural tube development: Folate is crucial for the development of the neural tube in a developing fetus, which later becomes the brain and spinal cord.
  4. Homocysteine metabolism: Folate helps to convert the amino acid homocysteine into methionine, which is used in many important biochemical reactions in the body.
  5. Immune system function: Folate is important for the proper functioning of the immune system.
  6. Mental health: Folate deficiency has been linked to an increased risk of depression, and supplementation may help to improve symptoms in some people.

Folate is found naturally in many foods, including leafy green vegetables, fruits, and beans. It is also added to many fortified foods, such as bread, pasta, and cereal. Supplementation may be necessary in some cases, particularly for pregnant women or people with certain medical conditions.

Folate deficiency

Folate deficiency is a global health problem that can have serious consequences, including anemia, birth defects, and cognitive impairment which incurs costs to families and the economy. The prevalence of folate deficiency varies widely depending on the population and geographic region. Due to these differences, some groups are more affected by folate deficiency than others:

  1. Global prevalence: According to the World Health Organization (WHO), an estimated 17% of the global population is at risk of folate deficiency, with the highest prevalence in low- and middle-income countries (1).
  2. Age and sex: Folate deficiency is more common among certain age and sex groups. Women of childbearing age are at particular risk due to the increased demand for folate during pregnancy. Older adults are also at higher risk due to decreased absorption of folate from food and the increased likelihood of taking medications that interfere with folate metabolism (2).
  3. Health conditions: Certain health conditions can increase the risk of folate deficiency, including gastrointestinal disorders that interfere with nutrient absorption, liver disease, and alcoholism (3).
  4. Geographic location: The prevalence of folate deficiency can vary depending on the geographic region. In developed countries, folate deficiency is less common due to the widespread fortification of food with folic acid. However, in some low-income countries, folate deficiency is still a major public health concern (4).

It’s important to note that while some groups are more susceptible to folate deficiency, anyone can become deficient in this important nutrient if their dietary intake is inadequate.

Folate (B9) and aging

Folate is involved in many essential body functions, and its deficiency can have a wide range of effects on the body, including the hallmarks of aging. Let’s take a look at how folate can impact each of these processes, which are considered to be the hallmarks of aging:

  1. Genomic instability: Folate plays a key role in DNA synthesis and repair, and a deficiency in folate can lead to errors in DNA replication and repair, increasing the risk of genomic instability and mutations (1). Studies have shown that folate deficiency is associated with an increased risk of DNA damage and chromosomal abnormalities (2).
  2. Telomere attrition: Folate is involved in the synthesis and maintenance of DNA, including telomeres, which are the protective caps at the ends of chromosomes. A deficiency in folate can accelerate telomere shortening, leading to premature aging and an increased risk of age-related diseases (3). Studies have suggested that folate supplementation may help to preserve telomere length and slow down telomere attrition (4).
  3. Epigenetic alterations: Folate is involved in DNA methylation, which is an important epigenetic mechanism that regulates gene expression. Folate deficiency can lead to changes in DNA methylation patterns, which can contribute to the development of diseases such as cancer (5). Studies have shown that folate supplementation can reverse DNA methylation changes and reduce the risk of cancer (6).
  4. Loss of proteostasis: Folate is involved in the synthesis of new proteins, which are essential for maintaining proteostasis. A deficiency in folate can lead to a loss of proteostasis and an increased risk of protein-misfolding diseases (7). Studies have suggested that folate supplementation may help to maintain proteostasis and reduce the risk of protein misfolding diseases (8).
  5. Dysregulated nutrient sensing: Folate deficiency can impact nutrient sensing pathways, such as mTOR, which is involved in cell growth and metabolism. A deficiency in folate can dysregulate these pathways, leading to cellular dysfunction (9). Studies have shown that folate supplementation can improve nutrient-sensing pathways and reduce the risk of metabolic diseases (10).
  6. Mitochondrial dysfunction: Folate is involved in the synthesis of new mitochondria, which are the energy-producing organelles in cells. A deficiency in folate can lead to mitochondrial dysfunction and an increased risk of metabolic diseases (11). Studies have suggested that folate supplementation may improve mitochondrial function and reduce the risk of metabolic diseases (12).
  7. Cellular senescence: Folate deficiency can lead to cellular senescence, a state in which cells stop dividing and undergo changes that can contribute to aging and disease (13). Studies have shown that folate supplementation can reduce the rate of cellular senescence and improve cellular function (14).
  8. Stem cell exhaustion: Folate is important for the production and maintenance of stem cells, which can differentiate into many different cell types. A deficiency in folate can lead to stem cell exhaustion, impairing tissue regeneration and repair (15). Studies have suggested that folate supplementation may improve stem cell function and promote tissue repair (16).
  9. Altered intercellular communications: Folate is involved in the synthesis of DNA and RNA, which are essential for communication between cells. A deficiency in folate can impair intercellular communication, leading to disease (17). Studies have shown that folate supplementation can improve intercellular communication and reduce the risk of disease (18).

Folate and DNA

Folate is involved in the process of homologous recombination, which is one mechanism for repairing DNA breaks. Folate helps to supply the nucleotides necessary for DNA synthesis and repair, and it is also involved in the methylation of DNA, which can help to regulate gene expression and repair damaged DNA (19). Studies have suggested that folate supplementation may improve DNA repair mechanisms and reduce the risk of DNA damage-induced diseases, such as cancer (20). For example, a study on women with breast cancer found that high dietary folate intake was associated with a lower risk of recurrence (21). However, some studies have also suggested that high doses of folate supplementation may have adverse effects, such as promoting the growth of existing cancer cells (22). Therefore, it is important to ensure that folate supplementation is appropriate and within recommended doses(23).

Folate supplementation

Folate supplements are available in various forms, including oral tablets, capsules, and liquid drops, as well as injectable and intravenous (IV) formulations. Sublingual (under the tongue) forms of folate supplements are also available, although less common.

Oral supplements are the most commonly used form of folate supplementation and are generally effective in improving folate status. However, absorption of oral supplements can be affected by factors such as gastrointestinal health and other dietary components, which can reduce their effectiveness. Some oral supplements also contain folic acid, which requires conversion to its active form, 5-methyltetrahydrofolate (5-MTHF), before it can be utilized by the body.

Injectable and IV forms of folate are available for people who have difficulty absorbing oral supplements, such as those with gastrointestinal disorders. These forms of folate bypass the digestive system and are delivered directly into the bloodstream, making them more effective for some people.

Sublingual forms of folate are not as widely available and their effectiveness is not well-established. However, some studies suggest that sublingual forms may be more effective than oral supplements in certain populations, such as people with gastrointestinal disorders or those who are unable to absorb oral supplements.

It’s important to note that the effectiveness of folate supplementation can vary depending on individual factors such as age, sex, health status, and dietary intake.

Interactions with other micronutrients

Folate interacts with a variety of other micronutrients that can affect health, including vitamin B12, vitamin B6, and choline. Here are some examples of how folate interacts with these micronutrients:

  1. Vitamin B12: Folate and vitamin B12 are closely linked in several metabolic pathways. Both are involved in the synthesis of DNA and red blood cells, and folate is required for the activation of vitamin B12. Inadequate intake of either folate or vitamin B12 can lead to anemia and neurological problems, and deficiencies of these nutrients are common among older adults.
  2. Vitamin B6: Folate and vitamin B6 are also involved in many similar metabolic pathways. Both are required for the metabolism of amino acids and the synthesis of neurotransmitters, and deficiencies of either nutrient can lead to neurological problems, such as depression and confusion.
  3. Choline: Choline is a nutrient that is important for brain function and is a precursor to the neurotransmitter acetylcholine. Folate and choline have been shown to interact in several ways, including in the regulation of gene expression and the prevention of birth defects. Adequate intake of both folate and choline is important for optimal brain function and development.

It’s important to note that interactions between nutrients can be complex and vary depending on a person’s individual needs and health status.

Supplementing together

It can be beneficial to supplement folate with vitamin B12, vitamin B6, and choline to promote optimal health. Here are some ways that these nutrients work together and studies that support their combined use:

  1. Folate and vitamin B12: As I mentioned earlier, folate and vitamin B12 are closely linked in several metabolic pathways, and deficiencies of these nutrients can lead to anemia and neurological problems. Studies have shown that supplementing with both folate and vitamin B12 can improve cognitive function, reduce the risk of dementia, and decrease levels of homocysteine, a marker of cardiovascular disease (1, 2).
  2. Folate and vitamin B6: Folate and vitamin B6 are both involved in the metabolism of amino acids and the synthesis of neurotransmitters, and deficiencies of these nutrients can lead to neurological problems. Studies have shown that supplementing with both folate and vitamin B6 can improve mood and cognitive function and reduce the risk of cardiovascular disease (3, 4).
  3. Folate and choline: Folate and choline have been shown to interact in several ways, including in the regulation of gene expression and the prevention of birth defects. Studies have shown that supplementing with both folate and choline can improve cognitive function, reduce the risk of neural tube defects, and improve liver function (5, 6).

It’s important to note that while supplementing with these nutrients can be beneficial, it’s always best to obtain nutrients from a balanced diet whenever possible.

Dietary sources of folate

Supplementation is not the only way to gain folate. It can be argued that dietary sources of folate are even more important. Let’s have a look at common dietary sources of folate per 100 grams, along with the percentage of recommended daily intake (RDI) for adults:

FoodFolate (mcg/100g)% RDI for Adults
Lentils, cooked18145%
Spinach, cooked14637%
Asparagus, cooked14937%
Chickpeas, cooked14135%
Black-eyed peas, cooked13133%
Broccoli, cooked6316%
Brussels sprouts, cooked6115%
Avocado, raw8120%
Papaya, raw379%
Oranges, raw308%
Strawberries, raw246%

The recommended daily intake of folate for adults is 400 micrograms (mcg) per day. Keep in mind that the actual amount of folate you need may vary depending on your age, sex, and other factors, so it’s always best to consult with a healthcare professional or registered dietitian to determine your individual nutrient needs.

Folate bioavailability

The body extracts folate from dietary sources and oral supplements through a process of digestion and absorption in the small intestine. Here are the general steps involved in this process:

  1. Digestion: Food sources of folate are first broken down in the stomach and small intestine by digestive enzymes.
  2. Absorption: Folate is absorbed in the upper small intestine, where it is transported across the intestinal lining and into the bloodstream.
  3. Conversion: Once in the bloodstream, folate is transported to the liver, where it is converted to its active form, 5-methyltetrahydrofolate (5-MTHF).
  4. Transport and storage: 5-MTHF is then transported to other tissues throughout the body, where it is used in a variety of metabolic processes. Excess folate is stored in the liver and other tissues for future use.

What gets in the way of the absorption of folate

There are several health conditions and disorders that can decrease the bioavailability of folate in food sources and supplements, including:

  1. Gastrointestinal disorders: Certain gastrointestinal disorders, such as inflammatory bowel disease, celiac disease, and short bowel syndrome, can interfere with the absorption of folate and other nutrients from food and supplements.
  2. Alcoholism: Chronic alcohol consumption can interfere with folate absorption and metabolism, leading to folate deficiency.
  3. Medications: Certain medications, such as antacids, proton pump inhibitors, and some antibiotics, can interfere with folate absorption.
  4. Genetic factors: Some individuals may have genetic variations that impair the body’s ability to metabolize folate, leading to decreased bioavailability.

Folate (B9) summary

Folate is important for maintaining good health, it can slow down aging when in adequate supply, and there are strategies for optimizing folate intake:

Importance of folate for health: Folate is a B-vitamin that is essential for DNA synthesis, red blood cell production, and nervous system function. Adequate folate intake is particularly important for women of childbearing age to prevent birth defects and for older adults to prevent anemia and cognitive decline.

Impact of folate on biomarkers: Folate deficiency can lead to elevated levels of homocysteine, an amino acid that is associated with an increased risk of cardiovascular disease. Adequate folate intake can help to reduce homocysteine levels and improve cardiovascular health. Folate may also play a role in preventing certain cancers and neurological disorders.

Strategies for optimizing folate intake: To optimize folate intake, it’s important to consume a balanced diet that includes a variety of folate-rich foods, such as leafy green vegetables, legumes, and fortified grains. To enhance the absorption of folate, it’s helpful to consume foods that are high in vitamin C, such as citrus fruits and berries, and to avoid excessive alcohol consumption, which can interfere with folate absorption. For individuals who may have difficulty meeting their folate needs through diet alone, supplements can be a convenient and effective way to ensure adequate intake.

In addition by supplementing together folate with other micronutrients such as B12, B6, and Choline it is possible to maximize the benefit.

As always – the key is moderation. Please talk to a specialist to expand your options and to look after yourself.

References

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