Everybody hiccups, especially often as children. The mysterious physiological phenomenon is surrounded by plenty of folklore. Hiccups are an excuse to eat spoonfuls of sugar and try to swallow water upside down. Of course, none of these “remedies” work, as hiccups are simply jerky contractions in the diaphragm. Hiccups can be caused by taking in too much food or alcohol — a Korean adage says that hiccups happen to food thieves who eat quickly to hide the evidence. Little else is known about the cause of hiccups, despite the serious consequences that chronic hiccups can have: insomnia, exhaustion, and even death (1). Hiccupping is a minimally studied subject, often treated as a bizarre, perhaps vestigial function. There are only speculations as to why we hiccup at all.
Physiology of Hiccups
During normal breathing at rest, inspiration (breathing in) occurs after the contraction of the main thoracic inspiratory muscles, including the diaphragm. This contraction results in a vacuum in the lung cavity, creating negative pressure and drawing air into the lungs. The upper airway and glottis, the vocal cords that make the “uh-oh” sound, dilate to open the airway and allow air to enter. During expiration, the expiratory pulmonary muscles contract, including the stomach, and air is pushed out in exhalation.
Hiccups start with the activation of the hiccup central pattern generator in the brainstem, which regulates normal cardiac and respiratory function. The signal causes a sudden powerful contraction of the inspiratory muscles, resulting in rapid inspiration. This is followed by the reclosure of the glottis that makes the characteristic onomatopoeic hiccup sound (2).
Fetuses often hiccup in the womb, particularly towards the end of gestation. Similar fetal breathing movements prepare the fetus for breathing air after birth, so there are speculations that hiccups are a method of preparation for breathing outside the womb (3). Studies have shown that fetus hiccupping is greatly reduced between 24 and 26 weeks, while breathing movements increase in the same period of time (4). Hiccups are common in newborn babies but disappear in childhood except as occasional bouts.
There are several hypotheses for why we hiccup. It could be a result of a reflex arc stimulated from the spinal cord, brainstem, and the hypothalamus. Others have proposed that hiccups are a form of epilepsy. However, the majority of patients with chronic hiccups are not epileptic, and diazepam, a major anti-epilepsy drug, can actually trigger hiccups (5). Hiccups could also be the result of a “glottis closure complex” related to swallowing, which would make sense considering hiccups are often related to swallowing too quickly while eating or drinking (6). There are several other hypotheses that focus on the errors that could occur in the neural pathway connecting the hypothalamus to the muscles involved in breathing.
The Phylogenetic Hypothesis
Straus et al. propose that hiccups originate from our amphibian ancestors (2). The first air-breathers constantly switched between breathing in air and water, much as modern amphibians and lungfish do. The neural mechanism for this frequent change still remains in the form of hiccups. Diaphragms evolved long after the emergence on land, so the primitive air-breathers used cheek muscles to breathe, similar to animals that still exist like lungfish and amphibians. These organisms breathe by pumping water over their gills or sucking air into sack-like lungs with positive pressure.
The new phylogenetic hypothesis proposes that the neural pathways that allowed the switch between gill and lung breathing is conserved in mammals today. Frogs evolved from primitive air-breathers, and are born as gill-breathing tadpoles that metamorphose into the air-breathing adult state. The frequency of gill breathing in tadpoles is reduced by exposure to increased CO2 concentration from the air or water, which also reduces hiccups in humans. One effective remedy for hiccups is to breathe in and out of a paper bag, which is also used to treat hyperventilation. The CO2 builds up in the bag as one breathes the same air in a small space, increasing CO2 concentration in the air. The exposure to increased CO2 concentration reduces hiccups in humans and gill breathing in tadpoles, both of which are triggered by neuronal signals originating from the same area of the brainstem.
There are other physiological similarities between tadpole gill ventilation and hiccups, including a similar central pattern generator in the brainstem, glottal closure, and contraction of inspiratory muscles. The neurological pattern is a very simple, primitive signal from the brainstem, which controls breathing, metabolism, and other “basic” functions of the body. It is a signal easily replicable in more primitive animals, such as amphibians. In tadpoles, the glottis is closed during gill breathing as water enters the gill cavity, since without the glottal closure, the lung would be flooded by the water. Similarly, the human glottis closes at hiccup, which makes the characteristic hiccup noise. The inspiratory muscles that move air in and out of the lungs contract in both mammals and tadpoles.
The observable similarities between breathing during tadpole metamorphosis and hiccups in mammals suggest that hiccups arise from ancient gill-breathers developing primitive lungs to breathe air. Straus et al. even propose that the hiccup neural pathway is maintained to aid suckling, which involves rapid cheek aspiration and closure of the glottis to help the infant swallow the milk properly and not into the lungs. The prevalence of hiccups in healthy adults and children suggests that hiccups are not from neurological damage, which many hypotheses propose as the cause of hiccups. This is a fresh way to look at the evolutionary origins of a trait ubiquitous in mammals, well supported by the wealth of species intermediate between gill and lung breathing, which make it possible to study the transition from gill breathing to full air breathing.
There is no prevailing theory for the cause of hiccups. Straus et al.’s proposal could be considered more viable, as many other hypotheses treat hiccups as a malady. However, hiccups are common in humans, and most of us who hiccup do not have epilepsy. Straus et al. provide plenty of phylogenetic evidence for how hiccups might be a vestigial function from our gill-breathing days. This also reminds us that we have many vestigial or nonfunctional organs and functions, like the appendix, simply because of our evolutionary history. At least we do not have to get surgery to stop hiccups.
1. D. A. McFarling, J. O. Susac. Neurology 29, 797-801 (1979).
2. Straus et al. BioEssays 25, 182-188 (2003).
3. A. M. Dunn. The Lancet 2, 505 (1977).
4. M. Pillai, D. James. Arch. Dis. Child. 65, 1072-1075 (1990).
5. S. Launos et al. Eur. Respir. J. 6, 563-575 (1993).
6. J. J. Askenasy. Eur. Neurol. 32, 159-163 (1992).
7. D.F. Thompson, J.P. Landry. The Annals of Pharmacotherapy 31, 367-369 (1997).