Hydrogen is the most abundant element in the universe, and its presence in the human body is fundamental to both structure and function. It is a constituent of water, which makes up a majority of the body’s mass, and is structurally integrated into all organic molecules, including carbohydrates, fats, and proteins. Beyond this structural role, hydrogen primarily operates as a positively charged ion, or proton (\(\text{H}^+\)), which performs regulatory and energy-generating functions. A separate focus involves the use of the neutral molecule, diatomic hydrogen (\(\text{H}_2\)), for its potential therapeutic effects.
Driving Cellular Energy Production
The process of generating the body’s main energy currency, adenosine triphosphate (ATP), relies on the precise movement of hydrogen ions. This process, called oxidative phosphorylation, occurs within the mitochondria, the cell’s powerhouses. Hydrogen atoms are first harvested from the breakdown of food molecules and are carried to the inner mitochondrial membrane by specialized molecules, primarily NADH and \(\text{FADH}_2\).
These carriers release high-energy electrons, which are then passed down a series of protein complexes embedded in the inner membrane, known as the electron transport chain. As electrons move through this chain, they lose energy, which the protein complexes capture and use to pump hydrogen ions (\(\text{H}^+\)) from the inner compartment (matrix) into the outer compartment (intermembrane space). This active transport creates a high concentration of protons in the intermembrane space, establishing an electrochemical gradient called the proton motive force.
The strong motive force created by this \(\text{H}^+\) gradient represents potential energy, much like water held behind a dam. Hydrogen ions cannot diffuse freely back into the matrix because the inner membrane is impermeable to them. Instead, they flow back down their concentration gradient through a dedicated enzyme complex called ATP synthase, a process known as chemiosmosis. The mechanical energy from this flow of protons causes the ATP synthase enzyme to rotate, driving the synthesis of ATP from adenosine diphosphate (ADP) and inorganic phosphate.
Essential Role in Acid-Base Homeostasis
The concentration of hydrogen ions (\(\text{H}^+\)) in bodily fluids dictates the \(\text{pH}\) level, which measures acidity or alkalinity. The body must maintain the \(\text{pH}\) of arterial blood within a narrow range, typically between 7.35 and 7.45, because cellular enzymes and proteins function optimally within this window. Deviations outside this range can severely impair metabolic processes, resulting in acidemia (\(\text{pH}\) below 7.35) or alkalemia (\(\text{pH}\) above 7.45).
The body uses several buffering systems to prevent sudden, dramatic shifts in \(\text{pH}\) by rapidly binding or releasing hydrogen ions. The bicarbonate buffer system is the primary mechanism in the blood, consisting of carbonic acid (\(\text{H}_2\text{CO}_3\)) and the bicarbonate ion (\(\text{HCO}_3^-\)). When excess hydrogen ions are introduced, the bicarbonate ion acts as a base to neutralize them by forming carbonic acid, thereby stabilizing the \(\text{pH}\).
The regulation of this buffer system involves the coordinated action of the respiratory and renal systems. The lungs offer rapid control by adjusting the rate of breathing to manage the concentration of carbon dioxide (\(\text{CO}_2\)), which is in equilibrium with carbonic acid and, consequently, \(\text{H}^+\). If the blood becomes too acidic, increasing the breathing rate expels more \(\text{CO}_2\) and removes \(\text{H}^+\) from the system.
The kidneys provide slower but more sustained regulation by controlling the amount of bicarbonate and hydrogen ions in the body. They can excrete excess \(\text{H}^+\) into the urine or reabsorb \(\text{HCO}_3^-\) back into the bloodstream, effectively balancing the acid load produced by daily metabolism. This dual regulation ensures that the \(\text{H}^+\) concentration, and thus the \(\text{pH}\), remains within the necessary limits for life.
Molecular Hydrogen Therapy
A distinct application of hydrogen involves its use as a neutral molecule, diatomic hydrogen gas (\(\text{H}_2\)), often referred to as molecular hydrogen. This emerging therapeutic approach is separate from hydrogen’s fundamental roles as an ion in energy production or \(\text{pH}\) regulation. Molecular hydrogen is administered through inhalation or by drinking water in which the gas has been dissolved.
The proposed mechanism of action for molecular hydrogen is its function as a selective antioxidant. Unlike conventional antioxidants that neutralize a wide range of reactive oxygen species (ROS), \(\text{H}_2\) is hypothesized to selectively target and neutralize only the most harmful free radicals, such as the hydroxyl radical (\(\cdot\text{OH}\)). It is believed to spare other less reactive ROS, which are important signaling molecules in the cell.
Because of its small size, \(\text{H}_2\) can rapidly diffuse across cell membranes and into organelles like the mitochondria and the nucleus, where oxidative damage is common. This capability allows it to address oxidative stress at its source. Research into molecular hydrogen is ongoing, exploring its potential to reduce inflammation, provide neuroprotection, and improve cellular function in various disease models.
While preclinical studies have demonstrated promising results, the therapeutic use of molecular hydrogen remains a subject of continued investigation. The research aims to fully characterize its mechanisms, establish optimal delivery methods, and validate its efficacy through rigorous human clinical trials. The molecule’s safety profile and lack of toxic byproducts are considered advantages.