G6PD is an enzyme your body produces to protect red blood cells from damage. Its full name is glucose-6-phosphate dehydrogenase, and it plays a critical role in keeping red blood cells intact and functional. When someone refers to “G6PD,” they’re usually talking about G6PD deficiency, a genetic condition affecting more than 400 million people worldwide that makes red blood cells vulnerable to breaking apart under certain stresses.
What the G6PD Enzyme Does
Every cell in your body faces a constant low-level threat from unstable molecules called reactive oxygen species, which are natural byproducts of metabolism. Most cells have multiple ways to neutralize these molecules, but red blood cells are uniquely vulnerable because they rely almost entirely on one pathway for defense. G6PD is the gatekeeper of that pathway.
The enzyme kicks off a chain reaction that ultimately produces a protective molecule called NADPH. NADPH, in turn, keeps another molecule (glutathione) in its active form. Active glutathione converts hydrogen peroxide, a harmful byproduct, into plain water. Think of it as a conveyor belt: G6PD starts the belt, NADPH keeps it moving, and glutathione does the actual cleanup. Without enough G6PD, the entire defense system stalls, and red blood cells are left exposed to oxidative damage.
What Happens When G6PD Is Deficient
When someone doesn’t produce enough G6PD, their red blood cells can’t regenerate glutathione fast enough under stress. Reactive oxygen species accumulate and begin attacking hemoglobin (the protein that carries oxygen) and the cell membrane itself. Damaged hemoglobin clumps into visible deposits called Heinz bodies, and the membrane stiffens and loses its flexibility. Red blood cells normally squeeze through tiny capillaries by deforming like a rubber ball. Stiffened cells can’t do this, and the spleen filters them out and destroys them.
This premature destruction of red blood cells is called hemolysis. A sudden wave of hemolysis, known as a hemolytic crisis, causes symptoms that can range from mild to severe: fatigue, pale or yellowish skin (jaundice), dark or tea-colored urine, rapid heartbeat, and shortness of breath. In newborns, G6PD deficiency is a recognized cause of severe jaundice that may need treatment.
Most people with G6PD deficiency feel perfectly fine day to day. Problems arise only when a trigger overwhelms the limited defenses of their red blood cells.
Why It Runs in Families
The gene that codes for G6PD sits on the X chromosome. Males have one X chromosome (inherited from their mother) and one Y chromosome, so a single mutated copy of the gene is enough to cause full deficiency. Females have two X chromosomes, meaning they’d need mutations on both copies to be fully deficient. A woman who carries one mutated copy is a carrier and typically has a mix of normal and deficient red blood cells, because each cell randomly shuts off one of its two X chromosomes early in development. This mosaic pattern means some female carriers have mild symptoms, others have none, and a small number have significant deficiency depending on which X chromosome happens to be active in more of their cells.
One important inheritance detail: fathers cannot pass G6PD deficiency to their sons, because sons inherit their single X chromosome from their mother.
Who Is Most Affected
G6PD deficiency is the most common enzyme deficiency in the world, with prevalence reaching 25% in some populations. It is most frequent among people of African, Mediterranean, Middle Eastern, and Southeast Asian descent. Among Black Africans, prevalence in males reaches roughly 15%. In parts of the Middle East, rates among Arab, Kurdish, and Turkoman populations range from about 6% to 9%.
This geographic pattern isn’t random. The same regions with high G6PD deficiency rates overlap heavily with areas where malaria has historically been common. Research on populations in sub-Saharan Africa found that the most widespread African variant of the deficiency (called G6PD A-) cut the risk of malaria infection by more than half in males and by roughly 89% in females who carried two copies. The deficient red blood cells appear to be a less hospitable environment for the malaria parasite. Genetic analysis suggests this variant arose from a single African ancestor roughly 6,000 to 7,500 years ago, around the time slash-and-burn agriculture was expanding mosquito habitat and human population density, creating ideal conditions for malaria to spread. In evolutionary terms, the survival advantage against malaria kept the gene variant circulating at high frequencies despite the downside of hemolytic risk.
Common Triggers
Fava Beans
The connection between G6PD deficiency and fava beans is so well known that the condition is sometimes called favism. Fava beans contain compounds called vicine and convicine, which break down into molecules that generate a burst of free radicals during digestion. In someone with normal G6PD levels, the antioxidant system handles this easily. In someone who is deficient, the free radicals overwhelm the red blood cells and trigger hemolysis. Not every G6PD-deficient person reacts to fava beans, and the severity varies, but they are one of the most reliable dietary triggers.
Infections
Bacterial and viral infections are actually the most common trigger of hemolytic episodes. Infections ramp up the body’s production of reactive oxygen species as part of the immune response, and G6PD-deficient red blood cells can’t keep up.
Medications
Certain drugs generate oxidative stress in red blood cells and are considered unsafe for people with G6PD deficiency. The highest-risk medications include primaquine (an antimalarial), dapsone (used for skin conditions and leprosy), nitrofurantoin (a common urinary tract infection antibiotic), methylene blue (used in some diagnostic procedures), and rasburicase (used for high uric acid levels). Several sulfonamide antibiotics are also on the avoidance list. If you have G6PD deficiency, making sure every prescribing provider knows your status is one of the most important things you can do.
How G6PD Deficiency Is Classified
The World Health Organization updated its classification system in 2022, simplifying it into clearer categories based on how much enzyme activity a person has and what symptoms they experience:
- Class A: Less than 20% of normal enzyme activity, associated with chronic hemolytic anemia (ongoing red blood cell destruction even without triggers).
- Class B: Less than 45% of normal activity. This is where most common G6PD variants fall. People in this class are at risk for newborn jaundice and acute hemolytic episodes triggered by medications, fava beans, or infections, but don’t have chronic anemia between episodes.
- Class C: Greater than 60% of normal activity. No hemolysis. Clinically insignificant.
- Class U: Uncertain clinical significance, meaning not enough data exists yet to classify the variant.
Most people diagnosed with G6PD deficiency fall into Class B. They live normal lives and only experience problems when exposed to a known trigger.
Testing and Diagnosis
G6PD deficiency is diagnosed with a blood test that measures enzyme activity. Normal activity centers around 11.5 international units per gram of hemoglobin, with a typical range of 6.9 to 16.3. The WHO defines severity thresholds as percentages of the normal median: below 10% is severe deficiency, 10% to under 30% is moderate, and 30% to under 60% is mild. The standard cutoff for clinically significant deficiency is 30% of normal activity.
Timing matters. During or immediately after a hemolytic episode, the body ramps up production of young red blood cells (reticulocytes), which naturally have higher G6PD activity than older cells. Testing during this period can give a falsely normal result, masking the deficiency. For an accurate reading, testing should happen when the person is in a stable state, well after any acute episode has resolved.
In many countries with high prevalence, newborn screening programs routinely test for G6PD deficiency, particularly because severe newborn jaundice is one of the earliest and most preventable complications. For adults, testing is often prompted by an unexplained hemolytic episode or is done before prescribing a high-risk medication like primaquine.
Living With G6PD Deficiency
For the vast majority of people with this condition, management is straightforward: know your triggers and avoid them. That means being aware of which medications are unsafe, being cautious with fava beans, and understanding that infections can sometimes set off a hemolytic episode that isn’t entirely preventable. Carrying a medical alert card or wearing a medical ID bracelet can help ensure you aren’t given a contraindicated medication in an emergency.
During a hemolytic crisis, treatment is supportive. Mild episodes resolve on their own once the trigger is removed, as the body replaces the destroyed red blood cells within a few weeks. Severe episodes, particularly those involving very dark urine, extreme fatigue, or rapid heart rate, may require a blood transfusion to stabilize oxygen delivery while the body recovers. The small minority of people with Class A deficiency (chronic hemolytic anemia) may need ongoing monitoring and, in some cases, supplementation with folic acid to support continuous red blood cell production.