When most people think of Ehlers-Danlos Syndrome (EDS), they picture flexible joints, stretchy skin, or chronic musculoskeletal pain. But for many patients, the story goes far beyond connective tissue. In clinical practice, it’s not uncommon to see individuals with EDS struggling with fatigue, dizziness, brain fog, and restless legs — only to find that their ferritin levels are low or that they’re running short on vitamin B12.

So is there a real connection between EDS and nutritional deficiencies like low iron or B12? The answer isn’t simple, but research and clinical observation suggest the relationship is worth paying attention to.

One of the most important factors is the gut. People with hypermobile EDS and related hypermobility spectrum disorders often experience gastrointestinal challenges, including reflux, bloating, constipation, or slow motility. These symptoms may not just be uncomfortable; they can interfere with the absorption of critical nutrients. Reviews have highlighted that nutritional deficiencies in EDS often occur despite adequate dietary intake or even diligent oral supplementation, pointing toward malabsorption rather than simple dietary gaps (Ehlers-Danlos Society PDF).

Another layer comes from the autonomic nervous system. Dysautonomia, including conditions like POTS (postural orthostatic tachycardia syndrome), is common in EDS. Autonomic dysfunction can disrupt the natural balance of “rest and digest,” leaving the gut less efficient at nutrient absorption. A review on dysautonomia and EDS emphasized just how prevalent gastrointestinal symptoms are in this group, and suggested that limited intake, slow motility, and even bacterial overgrowth all play roles in nutritional deficiency risk (PMC article).

Some researchers also point to the higher rates of comorbid gastrointestinal disorders. Celiac disease, for instance, has been noted more often in patients with hypermobility syndromes, and when present, it directly interferes with absorption of iron, B12, and folate (Practical Gastroenterology review). Even in patients without celiac, overlaps with IBS, small-intestinal bacterial overgrowth, or other inflammatory conditions may compromise absorption further.

On a more experimental level, the genetics of EDS provide intriguing clues. A rare subtype of the condition, called spondylocheiro dysplasia EDS, involves a mutation in the ZIP13 transporter gene (SLC39A13). This protein helps move iron inside cells, particularly in the endoplasmic reticulum and Golgi, where collagen is processed. Research in both fruit flies and mammals has shown that when ZIP13 doesn’t work properly, collagen synthesis falters and iron handling becomes disordered (Nature Communications, 2024; eLife study). While this doesn’t apply to all EDS patients, it demonstrates a fascinating link between iron metabolism and connective tissue biology.

Of course, not every deficiency in EDS is caused by absorption or genetics. Fatigue, pain, and dietary restrictions often lead to narrower diets or “safe” foods that may lack micronutrient density. For some, this is enough to tip the balance toward chronic deficiency, even without clear gut dysfunction.

At this point, large-scale studies are limited, but there is active interest in the question. The Ehlers-Danlos Syndrome Research Foundation is running a project called Analysis of Micronutrient Tests for Nutritional Deficiencies in Patients with Ehlers-Danlos Syndrome, aimed at better understanding how widespread deficiencies like low ferritin and B12 really are (EDS Research Foundation). Early reports suggest that these deficiencies are common enough to warrant routine screening.

So what does this mean for patients and providers? For those living with EDS, persistent fatigue or brain fog may not just be “part of the condition.” Checking ferritin, B12, and other micronutrients could uncover treatable contributors to symptoms. For clinicians, maintaining a high index of suspicion for iron deficiency anemia or B12 deficiency in EDS patients — particularly those with gastrointestinal complaints — may help close a gap in care.

While the science isn’t conclusive, the overlap is clear: connective tissue disorders like EDS don’t exist in isolation. They ripple out into digestion, absorption, and nutritional health. Paying closer attention to this nutritional dimension could make a meaningful difference in how these patients feel day to day.