Could a Vitamin Deficiency Be the Hidden Cause of Hypermobile Syndrome?

By Kelley Herring

When we think of joint flexibility, images of dancers and gymnasts often come to mind—individuals who can bend and twist their bodies into seemingly impossible positions.

But for some, there’s a darker side to hypermobility that goes beyond impressive physical feats. For those with hypermobile Ehlers-Danlos syndrome (EDS), this condition is a gateway to a host of debilitating symptoms, from chronic pain and fatigue to digestive issues and mental health challenges.

Recent groundbreaking research from Tulane University has uncovered a genetic link to this perplexing syndrome, opening new avenues for diagnosis and nutritional therapies that could change the lives of millions ¹.

Understanding Hypermobile Ehlers-Danlos Syndrome

Hypermobile Ehlers-Danlos syndrome is one of the 13 recognized subtypes of Ehlers-Danlos syndrome, a group of connective tissue disorders that affect collagen production.

Collagen is a vital protein that provides strength and elasticity to connective tissues throughout the body, including skin, ligaments, tendons, blood vessels, and internal organs ².

The symptoms of hypermobile EDS can vary widely but often include joint hypermobility, frequent joint dislocations and subluxations, chronic pain, soft and velvety skin, and a range of systemic issues such as gastrointestinal disorders, cardiovascular problems, and autonomic dysfunction.

The disorder can also lead to significant emotional and psychological distress, as individuals struggle with chronic pain and the unpredictability of their symptoms ³.

The Genetic Puzzle: MTHFR Gene and Folate Deficiency

Despite its prevalence, hypermobile EDS has been the only subtype without a known genetic marker—until now. Researchers at Tulane University School of Medicine have linked hypermobility to a deficiency in folate, the natural form of vitamin B9, caused by a variation in the MTHFR gene ⁴.

Here’s how it works: The MTHFR gene variant impairs the body’s ability to metabolize folate, leading to an accumulation of unmetabolized folate in the bloodstream. This deficiency disrupts the binding of key proteins to collagen in the extracellular matrix, resulting in overly elastic connective tissue ⁵.

Imagine your body as a construction site, where collagen is the scaffolding that holds everything together, keeping your joints, skin, and tissues strong and stable. The MTHFR gene is like the project manager in charge of supplying the right materials—in this case, active folate—to keep that scaffolding sturdy.

But when the MTHFR gene has a variant, it’s like the project manager getting the wrong blueprints or materials, leading to a mix-up in the supply chain. Instead of providing the right type of folate, it sends out incomplete or unmetabolized folate, which piles up on-site and clogs the system. Without the right materials, the scaffolding—your collagen—doesn’t bind properly and becomes overly stretchy, making your connective tissues as wobbly as a rubber band instead of being firm and supportive.

So, you can see how crucial those “raw starting materials”—the foods in your diet—are!

The implications of EDS are not restricted to wobbly joints. In fact, the condition is linked to a number of seemingly unrelated issues such as chronic fatigue, thin tooth enamel, dizziness, digestive troubles, migraines, anxiety, and depression. For women, the risks extend to reproductive health issues, including endometriosis and uterine fibroids ⁶.

A Breakthrough in Diagnosis and Treatment

Dr. Gregory Bix, director of the Tulane University Clinical Neuroscience Research Center, says:

“Millions of people likely have this condition, and until now, we’ve had no known cause to treat”

The traditional method for diagnosing hypermobility—using the Beighton score to measure the flexibility of the spine, fingers, and limbs—has been controversial and insufficient ⁷.

Now, with the ability to test for elevated folate levels and the MTHFR genetic variant, medical professionals can more accurately diagnose hypermobility and hypermobile EDS, offering patients a clearer path to effective treatment ⁸.

Folate, Folic Acid, and Methylated Folate

Folate, folic acid, and methylated folate are all forms of vitamin B9, but they differ in their structure and how the body processes them:

• Folate: This is the natural form of vitamin B9 found in foods like leafy greens and liver. It exists in a polyglutamate form, which the body converts into the active form, 5-methyltetrahydrofolate (5-MTHF), through a multi-step process. Whole food supplements often offer this form ⁹.
• Folic Acid: This is the synthetic form of vitamin B9 commonly used in supplements and food fortification. Folic acid is not biologically active and requires conversion in the liver to be used by the body. This synthetic form has been associated with numerous risks—especially for those with MTHFR gene mutations—including masking vitamin B12 deficiency and increasing the risk of certain cancers ¹⁰. It’s best to avoid this form.
• Methylated Folate (L-methylfolate or 5-MTHF): This is the active form of folate that the body can use directly. Methylated folate bypasses the need for conversion, making it especially important for individuals with MTHFR gene mutations who have difficulty converting folic acid into its active form. While methylated folate is widely available as a supplement, it should be taken with caution, as excessive intake can lead to imbalances in the methylation cycle, potentially resulting in neurological or cardiovascular issues ¹¹.

Food Sources of Folate

The good news is that eating foods that are naturally rich in methylated folate can help manage this condition naturally—without taking expensive supplements or being exposed to the accompanying risks. Here are some of the richest sources of folate from both plant-based and animal-based sources, along with their serving sizes and amounts:

Paleo-Friendly Plant-Based Sources

1. Spinach: 1 cup, cooked – 263 mcg
2. Asparagus: 1 cup, cooked – 262 mcg
3. Brussels Sprouts: 1 cup, cooked – 156 mcg
4. Broccoli: 1 cup, cooked – 168 mcg
5. Avocado: 1 whole – 90 mcg
6. Lettuce (Romaine): 1 cup, shredded – 64 mcg
7. Beets: 1 cup, cooked – 136 mcg
8. Oranges: 1 large – 55 mcg
9. Papaya: 1 cup, cubed – 53 mcg
10. Bananas: 1 medium – 24 mcg

Animal-Based Sources

1. Liver (Beef, Chicken, Turkey): 3 ounces, cooked – 215 mcg
2. Eggs: 1 large – 22 mcg
3. Crab: 3 ounces, cooked – 65 mcg
4. Salmon: 3 ounces, cooked – 30 mcg
5. Lamb: 3 ounces, cooked – 12 mcg
6. Poultry (Chicken, Turkey): 3 ounces, cooked – 12 mcg
7. Pork: 3 ounces, cooked – 8 mcg
8. Clams: 3 ounces, cooked – 84 mcg
9. Shrimp: 3 ounces, cooked – 14 mcg ¹².

High Octane Nutrition: Plant-Based vs. Animal-Based Folate

While both plant-based and animal-based foods offer folate, the bioavailability—or how well your body absorbs and utilizes this nutrient—can vary significantly depending on its source.

Plant-based folates are predominantly found in the form of polyglutamates, which must undergo conversion in the digestive tract before they can be absorbed.

This conversion process can be inefficient, particularly in those with compromised digestive health. In contrast, animal-based sources such as liver provide folate in a more bioavailable form—often as monoglutamates or methylated folate—that the body can more readily absorb and utilize ¹³.

This principle extends to many nutrients—from iron to omega-3 fatty acids—where animal-based sources often come up with better bioavailability, making them preferable to plant-based sources ¹⁴.

Clinical Impact and Future Directions

At Tulane’s Hypermobility and Ehlers-Danlos Clinic—the only clinic in the U.S. focused on fascia disorders—patients with hypermobility are showing promising improvements after treatment with methylated folate.

Reports from the clinic indicate reductions in pain, brain fog, allergies, and gastrointestinal issues.

Dr. Jacques Courseault, medical director of the Tulane Fascia Institute and Treatment Center, says:

“We’ve discovered something in medicine that can help not just a small group of people, but potentially many across the world. This is real, it’s been vetted out well, and clinically we’re noticing a difference” ¹⁵.

As we uncover more about the intricate connections between our genes, nutrients, and overall health, we move closer to personalized medicine that can address the root causes of complex disorders.

The optimal blood level of folate to counteract symptoms, particularly in individuals with hypermobile Ehlers-Danlos syndrome (EDS) and an MTHFR genetic variant, is generally considered to be within the normal reference range of 5 to 16 nanograms per milliliter (ng/mL) ¹⁶.

The Importance of Nutrient-Dense Diets for Methylation

Just as our ancestors relied on nutrient-rich diets to maintain their health, modern science is revealing the profound impact that vitamins like folate have on our genetic expression and overall well-being.

If you’re following an animal-based ketogenic diet and want to ensure adequate intake of methylated folate, it’s essential to focus on specific nutrient-dense animal foods.

Here’s a rundown of the high-octane animal foods that will ensure you’re getting the nutrients you need:

1. Liver (Beef, Chicken, or Turkey):
– Serving: 4 ounces per week
– Benefits: Liver is one of the richest natural sources of methylated folate, providing approximately 215 mcg per 3-ounce serving. Including liver in your diet once a week can significantly contribute to your folate intake

2. Egg Yolks:
– Serving: 3-4 large eggs per day
– Benefits: Egg yolks contain around 22 mcg of folate per egg, along with essential fats that support a ketogenic diet. Regular consumption of egg yolks helps boost your folate levels while providing quality fat and protein

3. Bone Marrow:
– Serving: 2-3 tablespoons per day
– Benefits: Bone marrow offers a unique nutrient profile, including small amounts of folate, and is rich in fat, making it ideal for a zero-carb keto diet. It’s also excellent for supporting overall joint and connective tissue health ¹⁷.

4. Kidneys (Lamb, Beef, or Pork):
– Serving: 3 ounces, 2 times per week
– Benefits: Kidneys are a nutrient-dense organ meat, providing a good source of bioavailable folate. They can be a valuable addition to a zero-carb diet, offering around 100 mcg of folate per serving

5. Bone Broth (from Grass-Fed Animals):
– Serving: 1-2 cups per day
– Benefits: Bone broth made from grass-fed animals provides a range of essential nutrients, including gelatin and collagen, which support gut health and the absorption of nutrients like folate. While not a direct source of folate, it enhances overall nutrient bioavailability ¹⁸.

6. Poultry (Chicken, Turkey):
– Serving: 4-6 ounces, 3-4 times per week
– Benefits: Poultry provides modest amounts of folate and is an excellent source of protein. Consuming dark meat, like thighs and drumsticks, can also provide additional fat needed for a ketogenic diet

Don’t miss out on the fantastic articles by Kelley Herring and other trusted sources on our US Wellness Meats Discover Blog!

References

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