Over 95% of Americans have detectable unmetabolized FOLIC ACID (UMFA) in their blood.

In Canada, 40% of the population has high FOLATE levels.

Why is this important?

Weren't we told that more Folate is good?

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Folate, (a B vitamin), plays an essential role in our biology, in DNA synthesis, repair, and methylation.

However, increasing studies have raised concerns about the potential risks associated with excessive intake of its synthetic form, folic acid.

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So, how do natural folate & synthetic folic acid differ, and

Are there health consequences of overconsumption?

Understanding Folate and Folic Acid

Folate, also known as vitamin B9, is essential for our bodies. It is important for:

• DNA repair,
• DNA synthesis,
• Methylation.

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However, there’s a distinction we need to make:

• Folate: The natural form found in foods
• Folic Acid: The synthetic form used in supplements and fortified foods

While both serve similar functions, their impact on our health can differ significantly.

Specifically, the body processes these forms differently, which is at the root of the potential problems associated with folic acid.

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Why High Folic Acid Is Becoming a Problem

Folic acid has been identified as potentially problematic due to several factors:

1. Limited Metabolism: The human body has a limited capacity to convert folic acid into its active form. This is due to the enzyme dihydrofolate reductase (DHFR), which is responsible for this conversion, having limited activity in humans.
2. Unmetabolized Folic Acid (UMFA): Due to the limited conversion capacity, excess folic acid intake can lead to the accumulation of unmetabolized folic acid in the bloodstream.
3. Widespread Exposure: In North America, a combination of food fortification and voluntary supplementation has led to chronic exposure to high levels of folic acid.
4. Bioavailability: Folic acid is more bioavailable than natural folate, which can lead to easier overconsumption.

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The Prevalence of High Folate Levels

In North America, the combination of food fortification and supplementation has led to a startling increase in folate levels:

• Up to 35% of the US population takes folic acid supplements
• 5% exceed the upper limit of folate intake
• Over 95% of Americans have detectable unmetabolized folic acid (UMFA) in their blood
• In Canada, 40% of the population has high folate levels

Health Impacts of Excess Folate

Out of balance folate levels, for example, from high folic acid intake have been associated with various health issues:

Health Concerns in Adults:

• Cancer risk: Excess folate intake has been associated with increased cancer risk, although the mechanisms are not fully understood. One study found a 20% increase in cancer incidence in individuals with high folate intake.
• Immune function: High folate levels may disrupt immune function.
• Neurodevelopmental issues: Some studies suggest a link between excess folate and neurodevelopmental problems. An increase in autism risk is seen in children whose mothers had high folate levels during pregnancy.
• Overall mortality: There is potential for excess folate to impact overall mortality.

Pregnancy and Birth Outcomes:

• Increased risk of gestational diabetes mellitus (GDM), especially when combined with vitamin B12 imbalance.
• Potential for decreased birth length and low birth weight with high folic acid doses.
• Mixed effects on oral clefts and congenital heart defects, with some studies showing protective effects of high doses for heart defects.

Disease Risk in Offspring:

• Insulin resistance in children, particularly observed in populations where high folic acid doses are prescribed during pregnancy
• Altered DNA methylation of regions regulating insulin-like growth factor 2 in infants, potentially influencing susceptibility to chronic diseases.

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What about Natural Folate?

Natural folate may not have the same issues as folic acid:

1. Natural folates are less bioavailable and stable compared to folic acid, which limits the potential for overconsumption.
2. Natural folates are biologically active forms that do not require activation by DHFR, unlike folic acid.
3. Natural folate intake is constrained by the limited amount present in food sources, reducing the risk of excess intake.

However, more research is needed to fully understand the comparative effects of natural folate versus folic acid at high intake levels.

The B12-Folate Connection

The relationship between vitamin B12 and folate is also important for understanding the potential risks of excess folate intake.

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So, how do B12 and Folate interact?

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Metabolic Interdependence:

• Vitamin B12 and folate are both essential for the one-carbon metabolism cycle, which is critical for DNA synthesis & methylation reactions.
• B12 acts as a cofactor for the enzyme methionine synthase, which converts homocysteine to methionine using 5-methyltetrahydrofolate (the active form of folate) as a methyl donor.

Masking of B12 Deficiency:

• High folate intake, for example, from folic acid supplementation, can mask the hematological signs of vitamin B12 deficiency.
• This masking effect can delay the diagnosis of B12 deficiency, potentially leading to neurological damage.

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Getting Folate from Real Food

Given the potential risks associated with excessive folic acid intake, focusing on natural folate sources can be a sound approach.

Foods rich in natural folate include:

• Leafy greens (spinach, kale, lettuce)
• Legumes (lentils, beans)
• Asparagus
• Avocados
• Brussels sprouts
• Broccoli

Not only do they provide natural folate, they also come with a side of other nutrients & fiber.

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Measuring Folate in Serum

Serum folate measurement can provide information about an individual’s recent folate intake & status:

• Short-term indicator: Serum folate reflects recent dietary intake and absorption (e.g., over the past few days to weeks).
• Normal range: Generally, 2-20 ng/mL (4.5-45.3 nmol/L) is considered normal, though ranges may vary slightly between laboratories.
• Deficiency detection: Levels below 3 ng/mL (6.8 nmol/L) often indicate folate deficiency.
• Excess detection: Levels above 20 ng/mL (45.3 nmol/L) may suggest excessive intake, often from supplements.

Actionable insights:

1. Low levels: Can indicate need for dietary changes or supplementation.
2. High levels: Can suggest over-supplementation or potential B12 deficiency masking.
3. Fluctuations: Can help assess absorption issues or adherence to supplementation.
4. Complementary testing: Can be paired with RBC folate for a view of long-term status.

Balanced supplementation of both folate and B12 can be considered, if you are supplementing one, consider supplementing the other.

Monitoring B12 status alongside folate intake is essential, particularly in populations at risk of B12 deficiency (e.g., vegetarians, older adults).

In conclusion, while folate is undeniably important for our health, the source, amount, and overall nutrient status matter.

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Choose whole foods & measure your folate levels next time you get a blood test.

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Disclaimer

This information is not medical advice nor is it lifestyle advice. This content and other content on this website is for informational and educational purposes only and is not intended to be a substitute for lifestyle advice, medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical or health condition.

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References

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• Moussa HN, Hosseini Nasab S, Haidar ZA, Blackwell SC, Sibai BM. Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks. Future Sci OA. 2016 Apr 21;2(2):FSO116.
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• Imbard, Apolline, et al. “Neural Tube Defects, Folic Acid and Methylation.” International Journal of Environmental Research and Public Health, vol. 10, no. 9, 2013, pp. 4352-4389.
• Maruvada, Padma, et al. “Knowledge Gaps in Understanding the Metabolic and Clinical Effects of Excess Folates/Folic Acid: A Summary, and Perspectives, from an NIH Workshop.” The American Journal of Clinical Nutrition, vol. 112, no. 5, 2020, pp. 1390-1403.
• Pannia, Emanuela, et al. “Maternal Folic Acid Supplementation Programs Offspring Lipid Metabolism in a Sex-Specific Manner.” Nutrients, vol. 11, no. 11, 2019, p. 2746.
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