Here’s what happens when your body senses low serum folate levels

Your body is a communicator that uses a language of molecules to tell you what it needs.

Folate may be small, but its impact on our health is huge.

Folate is important in different ways, from the time we eat to how its biochemical pathways affects our gene expression.

When there’s a lack of folate in your body, it starts a chain reaction of signals that resonates far beyond what you can see.

That is to say, the body senses this as a deficiency, and takes steps to compensate. The body does this by producing more homocysteine.

And it also tries to conserve folate by recycling it from old red blood cells.

However, if folate levels are too low, the body may not be able to recycle enough folate.

In this blog post, we’ll explain what happens when your body senses low serum folate levels, and find out how it affects your health in many ways.

What is Serum Folate?

Serum folate is the amount of folate that is circulating in the blood.

When serum folate levels are low, the body senses this and takes steps to increase folate levels.

One way that the body does this is by increasing the absorption of folate from the diet. This is done by increasing the production of a protein called folate receptor alpha.

Folate receptor alpha helps to transport folate from the gut into the bloodstream.

A low serum folate level is caused by a number of factors, including:

  • Not getting enough folate in your diet
  • Not absorbing folate properly
  • Taking methotrexate
  • Having a liver or kidney disease

When the body senses low serum folate levels, it releases an amino acid called homocysteine, a by-product of folate metabolism.

When homocysteine levels are high, it can damage blood vessels and increase the risk of heart disease, stroke, and other health problems.

To prevent these problems, it is important to keep your serum folate levels in check.

The recommended daily intake of folate for adults is 400 micrograms (mcg), pregnant women need about 600 mcg, and breastfeeding moms need 500 mcg.

Consequences of having low serum folate levels

Here are some of the things that occurs when you have low serum folate levels in your body:

  • Decreased production of red blood cells
  • Megaloblastic anemia
  • Increased homocysteine levels
  • Increased risk of neural tube defects
  • Increased risk of pre-eclampsia

You may also experience these symptoms:

  • Fatigue
  • Shortness of breath
  • Pale skin
  • Lightheadedness
  • Depression
  • Difficulty concentrating
  • Tingling in the hands and feet
  • Mouth ulcers
  • Weight loss
  • Loss of appetite
  • Diarrhea

It’s important to note that these symptoms above are also related to other health conditions, so to be sure you’re having low folate levels, do some tests to find out.

What happens when your body senses low serum folate levels?

When you have low serum folate levels in your blood, different series of biochemical reactions and responses are triggered to increase folate uptake, redistribution, and recycling.

These processes help keep enough folate in the body for vital cellular functions, especially those related to DNA synthesis and cell division.

When the body senses low serum folate levels, it releases folate receptors. These receptors helps to absorb folate from the blood.

And if the body is still unable to get enough folate from the diet, it will start to break down its own stores of folate.

This leads to folate deficiency in red blood cells, causing megaloblastic anemia.

Now, our main focus is to know what exactly happens inside the body, so to get a clear picture, here’s an explanation for the biochemical processes (mechanisms):

1. Detection of low folate levels

The body senses low serum folate levels through a series of different mechanisms.

One such mechanism involves the Folate Receptor Alpha (FRĪ±) located on the surface of cells [1].

When folate levels are low, the receptor’s affinity for binding folate increases, promoting cellular uptake.

2. Cellular Signaling

The cells (both enterocytes and hepatocytes) that detects low serum folate levels initiate a signaling pathway [2].

One key signaling molecule involved is called “5-methyltetrahydrofolate”.

This molecule acts as a sensor and helps transmit the signal to other parts of the body. It is involved in the methionine-homocysteine cycle, that helps with DNA methylation.

Enterocytes and hepatocytes use vitamin B12-dependent enzyme methionine synthase to detect low serum folate levels, which triggers a signaling pathway known as the "methyl cycle."
3. Cellular folate uptake and transport

Folate enters the body through dietary sources, primarily in the form of folate derivatives.

Intestinal cells called enterocytes, absorbs folate through membrane transporters, such as the reduced folate carrier (RFC) and the proton-coupled folate transporter (PCFT) [3].

These transporters ensures folate’s passage across the intestinal epithelium and into the blood.

4. Folate circulation and distribution

Once absorbed, folate is transported in the bloodstream primarily as 5-methyltetrahydrofolate (5-MTHF), the biologically active form [4].

Folate is bound to plasma proteins, such as albumin, to prevent rapid renal excretion [5]. The liver stores and redistributes folate to various tissues as needed [6].

5. Intracellular folate pool

Inside cells, folate is polyglutamated by the enzyme folylpolyglutamate synthase (FPGS) [7].

Polyglutamation improves folate retention within cells and promotes its activation in various metabolic pathways [8].

6. Folate sensing and feedback mechanisms

Cells have regulatory mechanisms to sense folate levels and respond to deficiencies [9].

Dihydrofolate reductase (DHFR) is a key enzyme that helps with folate metabolism [10].

DHFR activity is modulated by folate availability [11]: When folate levels are low, cells increase DHFR activity to recycle and preserve folate.

7. Activation of folate-dependent pathways

In response to low folate levels, cells prioritize essential pathways that require folate-derived cofactors [12].

DNA synthesis and repair, critical for cell division and growth, are down-regulated to conserve folate for essential functions [13].

Methionine synthesis from homocysteine, needed for making protein and regulating epigenetics remains active [14].

8. Alteration of cellular processes

Cells adapt to low folate conditions by slowing down cell division and conserving resources [15].

Cells that divide quickly, such as those inside the bone marrow, have reduced growth rates, which affects the creation of red and white blood cells [16].

How can you prevent low serum folate levels?

The best way to prevent low serum folate levels is to eat a healthy diet that includes plenty of folate-rich foods.

Good sources of folate include:

  • Oranges
  • Kidney beans
  • Lentils
  • Grapefruit
  • Lettuce
  • Asparagus
  • Brussels
  • Sprouts

If you are unable to get enough folate from your diet, you may need to take a folate supplement.

And if you are concerned about your blood folate levels, run a test to check it.

Final Thoughts

Folate is important in the body’s communication system using molecules. It affects genes and vital functions a lot.

Folate keeps things balanced and functioning smoothly by triggering responses when its levels drop.

If it’s not enough, our body tries its best to make up for it, but that can cause problems like anemia, and your homocysteine levels may rise causing other health issues.

Knowing all this, you get folate by eating foods like oranges, beans, and greens leafys, and maybe taking supplements if needed.

By doing this and checking your folate levels regularly, your body will be in good shape.

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