Christina Applegate has been candid about her struggles with multiple sclerosis (MS). But in a recent episode of her podcast MesSy, she revealed one of the most debilitating aspects of her condition: severe gastrointestinal symptoms that have landed her in the hospital dozens of times.
The Dead to Me actress shared that she has been hospitalized “upwards of 30 times” due to extreme pain, vomiting and diarrhea, which she believes are connected to her MS—despite doctors initially dismissing the link. We spoke to healthcare professionals to learn more about her experience and living with MS.
Christina Applegate’s latest MS health update
During the March 18 episode of MesSy, which she co-hosts with fellow MS warrior Jamie-Lynn Sigler, Applegate, 53, responded to listener emails. One listener, Kelly, described experiencing severe vomiting and diarrhea daily that her family didn’t understand. Applegate related to the experience, explaining that it has been a persistent issue for her since she was diagnosed with multiple sclerosis in 2021.
“This is really important because for three years, since I was diagnosed, I’ve been in the hospital upwards of 30 times from throwing up and diarrhea and pain that is unimaginable,” she shared. “They’ve done every test known to man on me, put so much radiation into my body from CT scans to everything else. And literally, just in the last month, I have figured it out.”
Applegate went on to explain what she believes could be happening in her body, saying, “Talk to your doctor about motility issues, okay? Because one of the things with MS is that it slows down our organs—not, like, completely, but there is a slowing of the function of your organs.”
The link between Applegate’s MS and gastrointestinal symptoms
The former Married with Children star noted that she has started seeing a pattern in her symptoms, describing what she calls “The Fight Club” happening in her body. “If I have to poop, I puke. And when I puke, I get all the pain, and then all the things happen,” she explained. “So there’s, like, this really horrible argument.”
Applegate’s neurologist initially told her that gastrointestinal issues aren’t a common MS symptom. However, she pointed out that others with the disease have had similar experiences. “It’s interesting because now Kelly has it, too, since the day she was diagnosed,” she said. “So I’m sorry [but] there’s gotta be a correlation here.” ,
Applegate emphasized that she is pushing for more answers. She told listeners she plans to bring up the issue with her medical team during a scheduled colonoscopy. “I know you guys are saying that I’m crazy, and I’m coming in here for no reason. And now I’m seeing a pattern.”
The science behind it
Gastrointestinal symptoms, including nausea, vomiting and bowel dysfunction, are not uncommon in people with MS. Research has shown this condition can affect the autonomic nervous system, which controls involuntary bodily functions such as digestion.
“A study published in the journal Multiple Sclerosis International showed that 65.6 percent of patients with MS endorsed at least one persistent GI symptom,” says Claudia Cometa, PharmD, founder of Peace Advocacy Group. “The potential causes [can relate to the] disease process itself where the signals between the brain and the digestive system are disrupted, as well as side effects of the medications used to treat MS.”
Christina Applegate on the pain of living with MS
GI symptoms are the only issues Applegate deals with in relation to her MS diagnosis. During a November 2024 episode of MeSsy, Applegate described living with MS as “a full-time job.” She shared that her most debilitating symptom is nerve pain in her feet. This feeling she associated with fire or a vice grip, making even walking or standing overwhelming.
“I lay in bed screaming” because of the pain, Applegate said. “It’s something that’s with me 24/7.” Applegate also said that while she may look healthy, much of her experience lies beneath the surface. “I can’t even pick up my phone sometimes, ’cause now it’s traveled into my hands,” she detailed.
Despite these challenges, Applegate maintained her characteristic humor, attributing her reality to the “beauty of the invisible disease.” “I just lay in bed all the time. I mean, I worked for almost 50 years, so I’m like, I’m kind of okay with it,” she laughed.
Christina Applegate experienced first MS symptom on Dead to Me set
While filming the pilot for Dead to Me, Applegate noticed her first symptom—difficulty maintaining her balance. In a December 2024 episode of MeSsy, Applegate revealed that she fell during a scene involving running across a field, reflecting later that it was an early sign of MS.
“I remember falling that day,” Applegate told Dead to Me creator Liz Feldman. “Hi, first sign of MS! So, not to bring everybody down, but there it was.” Feldman also recalled moments of imbalance during long filming hours, initially attributing them to fatigue. “It was very hard to figure it out because, you know, I remember one time, it was really late at night. We’d been shooting [for] probably 14 or 15 hours … It seemed completely reasonable that anybody would be collapsing.”
Despite her subsequent diagnosis and declining mobility, Applegate completed the series. “I wish I had paid attention,” she shared with the New York Times in 2022. “But who was I to know?” Applegate’s long-time friend, actress Selma Blair, who also has MS, was another to spot the first signs.
“I was sitting in Selma’s living room, our children playing, and I told Selma I’d been having this weird tingling in my feet,” Applegate recalled to British Vogue in 2023. “She said, ‘You must get tested for MS.’ [Even my doctor doubted it] but there it was. In essence, because of her, I’m going to have a better quality of life.”
When Applegate was first diagnosed, she took to social media: “Hi friends. A few months ago I was diagnosed with MS,” the tweet read. “It’s been a strange journey. But I have been so supported by people that I know who also have this condition. It’s been a tough road. But as we all know, the road keeps going. Unless some a—— blocks it.”
What is multiple sclerosis (MS)?
“Multiple sclerosis can be thought of as a neurological condition because of how its symptoms manifest, but at its core, it is an autoimmune condition,” explains Thomas Pontinen, MD, LCP-C, Co-founder and physician at Midwest Anesthesia and Pain Specialists. “The immune system malfunctions and attacks the myelin, a protective layer that forms around nerve fibers in the brain and the spinal cord.” This leads to communication disruptions between the brain and the rest of the body.
Additional reporting by Alexandra Pollock
