The Biochemistry of VOCs: What Our Breath Reveals About Health

When we breathe, we don’t just exchange oxygen and carbon dioxide. Each exhaled breath carries a complex mixture of volatile organic compounds (VOCs)—tiny molecules produced by our body’s metabolic processes. These VOCs can act as biochemical fingerprints, reflecting the state of our health and even signalling the onset of disease. At Breath Diagnostics, we are working to harness this information to develop non-invasive tools for early detection, monitoring, and personalized treatment.

Where Do VOCs Come From?

First, we need to distinguish between endogenic and exogenic VOCs. Endogenic means, the VOCs are generated within the human body, whereas exogenic molecules originate from outside the human body and are absorbed via inhalation or food intake. Endogenous VOCs are mainly used for disease detection and primarily originate from the biochemistry of our cells. They are produced in metabolic cycles, by enzymatic reactions, or through oxidative stress. Let’s look at a few of the key biochemical pathways:

1. The Citric Acid Cycle (Krebs Cycle)

The citric acid cycle is central to energy production. Disturbances in this cycle can lead to the accumulation of intermediate metabolites, some of which become VOCs.

• Acetone: Produced when fatty acids are broken down for energy, especially in fasting, diabetes, or ketogenic states. Elevated breath acetone is a marker of altered glucose metabolism.

• Isoprene: Originating from lipolysis in skeletal muscle and thus can change during physical activity or cardiovascular stress.

2. Amino Acid Metabolism

Proteins are constantly being broken down and rebuilt in the body. VOCs emerge from these processes:

• Ammonia: Released during amino acid deamination. High levels in breath may point to liver dysfunction or urea cycle disorders. However, bacteria in the mouth can lead to result distortion, making nasal sampling preferably.

• Sulfur-containing compounds (dimethyl sulfide, hydrogen sulfide, methanethiol): Derived from methionine and cysteine metabolism. These are often linked to liver disease, gut microbiota activity, or even oral health.

3. Oxidative Stress and Lipid Peroxidation

When reactive oxygen species (ROS) damage cell membranes, volatile hydrocarbons and aldehydes are produced.

• Alkanes (ethane, pentane): Indicators of lipid peroxidation and oxidative stress, associated with conditions such as asthma, cancer, and inflammatory diseases.

• Aldehydes (formaldehyde, acetaldehyde): Can reflect mitochondrial dysfunction, chronic inflammation, or toxic exposures.

4. Microbiome Contributions

Not all VOCs come directly from our own cells. The gut and oral microbiota contribute distinct VOCs through fermentation and anaerobic metabolism.

• Short-chain fatty acids (butyrate, propionate, acetate): Volatile products of gut microbial metabolism, linked to digestive health and metabolic balance.

• Nitrogenous VOCs: Produced by bacterial activity in the mouth and gut, often influencing breath odor but also serving as potential disease biomarkers.

What Do These VOCs Tell Us?

Each class of VOC provides unique insight into processes in our body. Changes in VOC profiles may indicate metabolic shifts, organ dysfunction, infection, or even cancer. Unlike blood tests, breath analysis captures these biochemical changes in real time and without needles.

At Breath Diagnostics, we aim to transform the knowledge of biochemical VOC origins into practical diagnostic tools, focusing on VOCs indicating pulmonary diseases and dysfunctions. Breath is more than just air—it is a window into human biochemistry. By decoding the VOC signatures hidden within, we bring science one step closer to making non-invasive diagnostics a daily reality.

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