excessive vomiting Archives

Cyclic Vomiting Syndrome and Mitochondrial Dysfunction: Research and Treatments

Published on December 7, 2021

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Cyclic vomiting syndrome (CVS) is a debilitating disease characterized by episodes of severe nausea and persistent vomiting interspersed with periods of wellness. CVS affects about 2 percent of school-aged children, and also affects adults, although in adults it is often not recognized. Getting a diagnosis can be challenging, and sometimes takes a long time. Episodes of CVS can be extremely debilitating, and are sometimes difficult to treat and require hospitalization.

My daughter has suffered from this disease for 10 years, since she was 2 years old (see her story here). Her episodes were somewhat predictable when she was younger, but have changed and become less predictable, and more difficult to manage with medication, as she gets older. Although we try to avoid triggers such as stress and fatigue, being a pre-teen girl, she likes to have sleepovers with her friends and stay up chatting all night. Unlike other pre-teen girls, however, she suffers the aftereffects of the sleepovers sometimes by vomiting for 24 hours or more.

What Causes Cyclic Vomiting Syndrome?

Although it has long been thought to be related to migraines, many sources state that the cause of cyclic vomiting syndrome is not known. Mechanisms that may be involved include episodic dysautonomia (malfunction of the autonomic nervous system that can result in a variety of symptoms), mitochondrial DNA mutations that cause deficits in cellular energy production, and heightened stress response that causes vomiting. However, there is mounting evidence for the role of mitochondrial dysfunction in the pathogenesis of this disease, a fact that is not often understood by the average practicing gastroenterologist. The connection to mitochondrial dysfunction has important implications for effective treatment of cyclic vomiting syndrome.

Mitochondrial Dysfunction, Cyclic Vomiting and Other Conditions

Mitochondria are small organelles within the cell responsible for energy production and other critical functions. Because of these crucial functions, Dr. Richard Boles, Director of the Metabolic and Mitochondrial Disorders Clinic at Children’s Hospital Los Angeles, explains that “30 years or so ago, many scientists couldn’t believe that mitochondrial disease could exist, because how does the organism survive?” However, mitochondrial dysfunction plays a role in many diseases, including CVS, and according to Dr. Boles:

“these are partial defects. Mitochondrial dysfunction doesn’t really cause anything, what it does is predisposes towards seemingly everything. It’s one of many risk factors in multifactorial disease. It can predispose towards epilepsy, chronic fatigue, and even autism, but it doesn’t do it alone. It does it in combination with other factors, which is why in a family with a single mutation going through the family, everyone in the family is affected in a different way. Because it predisposes for disease throughout the entire system.”

DNA mutations that affect mitochondrial function can occur in the DNA that is found in the nucleus of the cell (genomic DNA), or they can occur in the DNA that is found within the mitochondria themselves. Mitochondrial DNA is inherited differently than nuclear DNA. Most people are familiar with the inheritance of nuclear DNA, in which we have two copies of every gene, and we inherit one copy from each of our parents. However, mitochondrial DNA is inherited exclusively through the mother; therefore, mutations that affect the mitochondrial DNA can be traced through the maternal lineage of a family.

A possible relationship between cyclic vomiting syndrome and mitochondrial dysfunction was suggested by the finding that in some families, CVS was maternally inherited. Mitochondrial DNA mutations and deletions have been reported in patients with CVS, and disease manifestations of mitochondrial dysfunction have been found in the maternal relatives of patients with CVS. In other words, conditions such as migraines, irritable bowel syndrome, depression, and hypothyroidism, are often found in the maternal relatives of patients with CVS.

Mitochondrial DNA mutations don’t cause CVS directly, in the way that a DNA mutation causes cystic fibrosis, for example. In some patients, mitochondrial dysfunction plays a greater role in the causation of their disease, and in other patients, it may be less of a factor. Dr. Boles explains: “In some cases it’s a clear mitochondrial disorder, they have multiple other manifestations and it drives the disease. However, in most patients, it is one of many factors in disease pathogenesis.” Patients with classical mitochondrial disorders have disease manifestations such as muscle weakness, neurological problems, autism, developmental delays, gastrointestinal disorders, and autonomic dysfunction. Some patients with CVS have these other disease manifestations, and some have only CVS symptoms.

Treatment for Cyclic Vomiting Syndrome and Mitochondrial Dysfunction

As with many diseases, understanding as least some of the cause of CVS has allowed for the development of treatments tailored towards fixing the root cause. Co-enzyme Q10 and L-carnitine are two dietary supplements that have been used to treat a wide variety of conditions. Both supplements may be able to assist the mitochondria with energy production and thus, help compensate for mitochondrial dysfunction. A retrospective chart review study found that using these two supplements, along with a dietary protocol of fasting avoidance (having three meals and three snacks per day), was able to decrease the occurrence of, or completely resolve, the CVS episodes in some patients. In those patients who didn’t respond to treatment with supplements alone, the addition of amitriptyline or cyproheptadine, two medications that have been used for prevention of CVS episodes, helped to resolve or decrease the episodes. Treatment with the cofactors alone was well tolerated with no side effects, and treatment with cofactors plus amitriptyline or cyproheptadine was tolerated by most patients. Therefore effective treatment for prevention of CVS episodes does exist, although it may not be widely employed by most gastroenterologists.

My daughter is currently trying to treat her CVS with the combination of co-enzyme Q10 and L-carnitine. So far she hasn’t experienced any side-effects, and over the next few months we will see if she experiences a decrease or even a complete cessation of her episodes. My hope for her is that she won’t have to choose between missing out on a fun night with her friends, and being able to be functional for the rest of the weekend. Maybe she can be like every other teenager and go to a sleepover, and just be grumpy the next day, instead of spending the next day vomiting and lying on the bathroom floor in pain.

Dr. Richard Boles, MD: Dr. Boles completed medical school at UCLA, a pediatric residency at Harbor-UCLA, and a genetics fellowship at Yale. He is board certified in Pediatrics, Clinical Genetics and Clinical Biochemical Genetics. His current positions include Associate Professor of Pediatrics at the Keck School of Medicine at USC, an attending physician in Medical Genetics at Children’s Hospital Los Angeles, and Medical Director of Courtagen Life Sciences. Dr. Boles practices the “bedside to bench to bedside” model of a physician-scientist, combining an active clinical practice in metabolic and mitochondrial disorders with clinical diagnostics (DNA testing) and research. Dr. Boles’ clinical and research focus is on polymorphisms (common genetic changes) in the DNA of genes involved in energy metabolism, and their effects on the development of common functional disorders. Examples include migraine, depression, cyclic vomiting syndrome, complex regional pain syndrome, autism and SIDS. He has 50 published papers on mitochondrial disease.

Postscript: Using this advice, we were able to manage my daughter’s vomiting. Here is the follow-up story.

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This article was first published on January 28, 2014.

Cyclic Vomiting Syndrome

by Philippa Bridge-Cook, PhD

Published on November 26, 2013

12924 views

Before I even wake up fully, my ears register the sound of my twelve year old daughter throwing up. It is such a familiar middle of the night sound for me that it has ceased to be alarming. She has been throwing up on a regular basis since she was 2 years old, in episodes that come and go, usually lasting one to two days. The vomiting that comes with these episodes is violent, frequent, and often accompanied by severe abdominal pain. Without medication, she will vomit every 10 to 15 minutes for hours; luckily, for the last few years, we’ve sometimes been able to successfully treat these episodes with medication.

Sometimes her episodes last longer, like one recent very bad episode where she was sick for 6 days on and off. At times during that episode the vomiting was controlled by medication, but not always. When her medication didn’t work, she would lie on the bathroom floor and moan, and say “Mommy, help me,” or worse, “Mommy, I can’t live.” We have been told that the medications we give her—prescription Zofran, over the counter dimenhydrinate (Dramamine), and Tylenol and Advil—are the only options, and that there’s nothing else we can do. But when I see her suffering, I have to believe that there must be something more that can be done, because nobody should suffer like that, especially not a child.

When she was younger, the episodes would come every month or two. She is my oldest child, and for a long time I assumed she was just very susceptible to getting stomach flu, and that she was severely affected every time she got a stomach virus. As my other two children got older, and I realized how unusual the severity of her vomiting was, and the frequency of her episodes increased, I started to suspect it was something bigger than just stomach flu. I mentioned my concerns to her doctor, and he agreed, and suggested it might be cyclic vomiting syndrome.

Cyclic vomiting syndrome, or CVS, is a poorly understood, and under recognized disorder. Although it was originally thought to be a pediatric disorder, it is now known that it can occur in all ages, and that it is more common than previously thought. It is characterized by episodes of severe nausea and vomiting that alternate with periods with no symptoms. Some patients with CVS have symptoms in addition to nausea and vomiting during episodes such as headache, dizziness, fever, sensitivity to light, and diarrhea. For each individual with CVS, the episodes are similar to each other: they generally start at the same time of day, include the same symptoms, and last the same length of time. For my daughter, she always started vomiting in the middle of the night or early in the morning, it lasted about a day, and occurred every month or two. As she gets older, everything about her episodes has become less predictable. They have sometimes lasted longer, or clustered in groups where she can have one episode per week for three weeks, then nothing for three months. CVS is thought to be a part of the migraine spectrum, and sometimes patients are able to identify things that trigger episodes such as certain foods, illnesses, cyclical hormone changes, stress, or fatigue.

Cyclic vomiting syndrome is difficult to diagnose, because there is no specific test for the disorder. Therefore, it must be diagnosed by excluding all other possible reasons for the vomiting and other symptoms. My daughter was referred to a gastroenterologist and an endocrinologist. In addition to her episodes of vomiting, she is very small for her age. After a workup by both doctors, they couldn’t find any reason for her vomiting or her small size. Her gastroenterologist was reluctant to offer any diagnosis at all, even when I asked about CVS.

Because there is no physiological defect that with CVS can be measured by the medical tests we have currently, many times patients are told that their problems must be “in their head,” or just caused by anxiety, depression, or other mental health problems. Similar attitudes are faced by patients with many other functional disorders, which are diseases where no specific defects can be observed by medical tests. Functional disorders include fibromyalgia, irritable bowel syndrome, migraines, chronic fatigue syndrome, complex regional pain syndrome, and restless legs syndrome. It is short-sighted and insulting to patients to conclude that their problems are not real just because current diagnostic tests can’t detect a defect, and in many cases disbelief or dismissal by medical professionals leads to long diagnostic delays, during which time the patient suffers needlessly without treatment.

My daughter was faced with a version of this attitude, when for a time her gastroenterologist seemed to question repeatedly whether she might have anorexia or bulimia. The concern is legitimate, and it is important to rule out the possibility; however, the issue seemed to come up over and over again for us despite our answers. My daughter was asked if she ever didn’t eat because she was worried about getting fat, and she looked very surprised, because she’s worried about the exact opposite—she would love to be bigger. Clearly she doesn’t have bulimia, when she is waking up in the middle of the night and vomiting in her bed, and writhing in pain on the bathroom floor. Sometimes it gets very frustrating when doctors don’t seem to listen to and hear the answers that they are being given, because they have other ideas that conflict with what you are saying.

We were lucky, because my daughter’s pediatrician mentioned CVS as a possibility very early on. Otherwise I don’t think we would have any idea what her diagnosis might be, because her gastroenterologist was content to just rule things out based on test results, and not offer any opinion on what the problem actually is. It has been beneficial for us to have what we think is a likely possibility for a diagnosis, because it has allowed us to figure out strategies for helping her, including trying to avoid her triggers. The medication that was prescribed by her pediatrician is very useful for helping to manage her episodes when they do happen, although it isn’t as much of a complete solution as I would like, and I am still searching for additional treatments that may help. However, her episodes are less debilitating than they used to be thanks to the medication, and overall she is thriving despite her illness: in between episodes she is a happy, healthy twelve year old who loves figure skating, soccer, Glee, and texting her friends.

excessive vomiting