Phytohemagglutinin or PHA is a lectin or plant protein found mostly in red kidney beans. In medicine, it is mainly used to test cellular immunity. Although preliminary research suggests PHA could help with diabetes, weight loss, and overactive immune response, high amounts of this lectin are very toxic. Read below to learn about the dangers and potential uses of PHA.
What Is Phytohemagglutinin?
Phytohemagglutinin (PHA) is a lectin, a sugar-binding protein, found in many raw legumes eaten worldwide. Lectins are one of the main causes of food sensitivity .
PHA causes blood cells (red and white) to clump together, which makes them easier to find and kill when infected .
PHA is most known for the PHA skin test. It’s a simple way to measure immunity, as PHA increases white blood cell count, amplifying the immune response .
It is also used to fight HIV as it activates dormant HIV-1 cells, which alerts the immune system to destroy them .
Lectins like PHA are mostly found in legumes. PHA is found at the highest concentrations in raw beans, especially red and white kidney beans. Lower amounts are found in common beans (Phaseolus vulgaris) and broad beans (Vicia faba) [5, 6, 7].
PHA is a toxin to animals with single-stomach digestive systems like humans. PHA poisoning can occur from eating just 4 or 5 raw beans, causing severe nausea, vomiting, and diarrhea .
The unpurified protein form of the PHA lectin is PHA-P .
PHA-P consists of two closely related lectins: PHA-L, and PHA-E. The letters E and L indicate these proteins group either red blood cells (‘E’ for erythrocytes) or white blood cells (‘L’ for leukocytes) together .
The mucus form is PHA-M, which can be used to increase white blood cells [9, 10].
While these forms are the most common, PHA from red kidney beans can be divided into a family of 5 lectins .
PHA is mostly found in beans of various legumes. Different species have different amounts of PHA, with red kidney beans having the most. Although at lower levels, PHA is also found in the roots of bean plants [12, 13].
PHA or lectins, in general, are found in the following legumes:
- Red and white kidney beans 
- Green beans 
- Fava or broad beans 
- Black beans 
- Pinto beans 
- Jack beans 
- Navy beans 
- Spotted beans 
- Soybeans 
- Mung beans 
- Chickpeas 
How It Works
In general, phytohemagglutinin (PHA) binds to specific sugars such as mannose, N-acetyl glucosamine, and galactose to promote cell signaling and blood clotting [9, 1, 24].
It can cause white blood cells to divide and accumulate, which increases cell immunity. Because it only stimulates the division of white blood cells but not other cells, it has been suggested to protect against cancer. PHA-L is better at increasing white blood cells than PHA-E [25, 26, 9].
PHA’s ability to group cells is controlled by its proteins, while its ability to break down starch is controlled by its sugar component .
Although these effects can have some benefits, they are more often the cause of gut problems. PHA can bind to and inactivate stomach and gut cells, as well as digestive enzymes.
PHA may damage the gut by:
- Binding to stomach cells and stopping them from secreting the stomach acid needed for digestion [28, 29]
- Causing the overgrowth of harmful bacteria that stick to the walls of the small intestine and reduce nutrient absorption 
- Disrupting enzyme balance in the small intestine, which can also decrease nutrient digestion and absorption 
- Binding directly to the small intestine and damaging cells 
PHA has a dual role in the immune system. On the one hand, it stimulates the immune response by:
- Promoting white blood cell multiplication [31, 32, 33]
- Helping immune cells recognize pathogens and activate the immune system 
On the other hand, PHA can also lower it by:
- Reducing antibody production 
- Preventing thyroid hormones from entering cells and causing inflammation 
- Making foreign cells lose any receptors on their membrane that could alert the immune system and cause a response 
It may cause weight loss by:
- Lowering insulin levels, which promotes fat burning without causing muscle loss 
- Stimulating the release of a bile-producing hormone (cholecystokinin), which increases digestion and suppresses hunger 
PHA could potentially cause sugar intolerance by lowering blood insulin levels and preventing sugar breakdown 
Finally, PHA may help reduce cancer by:
- Causing white blood cells to release the pro-inflammatory cytokines IL-4 and IL-13, which activates the immune response and reduces the spread of cancer cells 
- Reducing DNA mutations, which prevents cancer cells from growing [42, 43]
- Killing cancer cells, thus blocking tumor growth [44, 42]
Phytohemagglutinin and T Cell activation
T cells can be activated by PHA and other lectins. The process goes as follows :
- PHA binds to receptors on the surface of IL-6 T cells [46, 47].
- This triggers a spike of calcium levels inside T cells, which serves as a stimulus to activate them .
- Activated T cells boost cell immunity and signal other cells to target infected dormant white blood cells, such as those infected by HIV [49, 50].
- PHA also activates a protein that signals for T cell growth and activation (Ras) [51, 52].
Not all T cell activation is beneficial, however. Quite the contrary.
T cells are divided into 2 types, Th1 or Th2, based on the cytokines they produce. In non-allergic situations, Th2 responses are capable of healing wounds. But in people who are sensitive, high Th2 cytokine levels cause food sensitivities, allergic inflammation, and asthma [53, 54].
Th2 cytokines (IL-4, IL-5, IL-6, and IL-13) gather B cells and other white blood cells, which triggers and worsens inflammation .
Dangers of Phytohemagglutinin
Eating raw kidney beans is highly not recommended, as toxic PHA levels can be achieved by eating as few as 4-5 beans. PHA is mostly destroyed during cooking (especially when using a pressure cooker), making fully boiled beans safe to eat .
1) May Damage the Digestive System
Ingesting high amounts of PHA can cause prolonged and severe food poisoning symptoms such as nausea, vomiting, diarrhea, and stomach pain, as seen in a case series of 50 people .
PHA can also cause inflammation of the stomach and intestine .
In rats, it reduced liver function and even caused liver damage .
2) May Cause Muscle Loss
Rats fed diets with high amounts of kidney bean lectins (above 27 mg/day) for 10 days experienced muscle loss .
A diet consisting of raw kidney beans and egg white also caused muscle loss in rats [60, 61].
3) May Cause Nutrient Deficiency
In the long term, PHA can reduce the absorption of nutrients, electrolytes, and water in the small intestine. One way in which it did so was by causing bacterial overgrowth in the gut .
PHA also reduced water and electrolyte absorption in the small bowels by altering the shape of the finger-like structures on the lining that absorb nutrients (villi). Because the villi were too short and dense, the surface available for nutrient uptake was smaller .
4) May Cause Autoimmune Diseases
By damaging the intestines, PHA reduces gut health and can cause “leaky gut”. This condition is associated with autoimmune diseases because the gut bacteria, their toxins, and food-derived antigens can enter the blood and trigger the autoimmune response [63, 64].
The body recognizes dietary lectins as foreign proteins indistinguishable from those of harmful bacteria, which activates the immune system and causes inflammation and constant flare-ups .
Lectins such as PHA also stimulate antigens on cell types that don’t normally display them, such as pancreatic islet and thyroid cells, thus stimulating autoimmune attacks in these tissues .
Arthritis is an autoimmune disease characterized by the production of antibodies with specific sugars (N-acetyl glucosamine) exposed. Although wheat gluten is a more common trigger food because it binds to these sugars, PHA may also bind to them and worsen inflammation [66, 1].
Lectins greatly increase the production of a pro-inflammatory cytokine (TNF-alpha), suggesting it can be used as a marker of response and adherence to a diet low in lectins .
5) May Cause Anemia
PHA can make red blood cells clump together. The body recognizes these clots as infectious particles and removes them, which lowers the total red blood cell count and causes anemia. Ingesting too much PHA has been reported to cause anemia, bloody diarrhea, extreme weight loss, swelling, heart attack, and even death in animal studies [12, 2].
Although high PHA levels are very toxic, preliminary research suggests that lower levels may have some beneficial health effects.
The following purported benefits are only supported by limited, low-quality clinical studies. There is insufficient evidence to support the use of PHA for any of the below-listed uses. Remember to speak with a doctor before taking PHA and never use it as a replacement for approved medical therapies.
Kidney bean lectins slowed starch digestion in a small trial on 7 healthy people, leading to less sugar being absorbed in the gut .
In very old reports dating back to the 1920s, people receiving 1 cup of bean pod tea every morning saw their blood sugar levels drop by 10% within 4 hours. Sugar tolerance also improved after drinking the tea. It’s uncertain, however, if PHA was destroyed by the hot water .
Back in the first half of the 20th century, bean pod extracts were investigated as insulin substitutes. When injected into rabbits, they kept their blood sugar levels stable .
More recently, eating canned pinto, black and dark red kidney beans kept blood sugar levels stable in 17 type 2 diabetes patients, most likely due to other compounds in the beans, such as fiber and inhibitors of carbohydrate-digesting enzymes (alpha-amylase) .
In rabbits, bean extract decreased blood sugar levels and improved sugar tolerance by 18.5%. Similarly, bean pod tea reduced blood sugar levels in rats .
Because the evidence comes from small or very old clinical trials and animal research, we cannot conclude for certain that PHA helps with diabetes until further research in humans is conducted.
Animal and Cell Research (Lack of Evidence)
No clinical evidence supports the use of PHA for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies should not be interpreted as supportive of any health benefit.
1) Reducing Overactive Immune Response
Lowering the immune response can be helpful to relieve inflammatory and autoimmune conditions or to prevent the rejection of foreign cells after vaccination, blood donation, or organ transplants. PHA may help with all these conditions by reducing the production of antibodies, although the experiments are still at the animal stage .
PHA reduced the immune response and production of antibodies in mice and rats injected with foreign red blood cells and antigens, such as the microbe that causes typhoid fever (Salmonella enterica subsp. enterica) [35, 71].
PHA also reduced the blood-clotting response in rabbits injected sheep cells. This contributes to its ability to lower immune response, since blood clots alert the immune system to attack [2, 72].
PHA also reduced the autoimmune response to a protein used to test for tuberculosis infection (tuberculin) after vaccination in guinea pigs .
PHA acts by boosting the immune response to parasites or fungi (by binding to Toll-like receptors) in response to vaccines .
PHA prevented the rejection of donor spleen stem cells in mice. It did so by making the cells revert to an immature state and lose any foreign receptors on their membrane .
PHA reduced the immune response of dogs with kidney transplants and prolonged the life of skin transplants in rabbits .
Low amounts have been used to monitor transplant organ rejection in humans and animals [73, 74].
2) Weight Loss
A PHA-rich diet reduced insulin levels but kept glucose levels stable in young rats, ultimately reducing their weight .
Obese rats fed PHA from red kidney bean-rich diets lost weight, possibly because it lowered insulin and helped burn fat .
Lectins also increase the production of adiponectin, a protein that lowers sugar levels and boosts fat breakdown .
Below, we will discuss some preliminary research on PHA’s potential anticancer effects. It’s still in the animal and cell stage and further clinical studies have yet to determine if this amino acid may be useful in cancer therapies.
Do not under any circumstances attempt to replace conventional cancer therapies with PHA or any other supplements. If you want to use it as a supportive measure, talk to your doctor to avoid any unexpected interactions.
PHA reduced tumor growth in multiple mice studies. In one of them, it enhanced the effects of the chemotherapeutic drug fluorouracil [75, 76, 77, 42].
Similarly, eating soaked, cooked, and dried black and navy beans reduced colon cancer in rats .
In cell-based studies, PHA killed and slowed the growth of leukemia, lymph, and colon cancer cells [44, 78, 12].
PHA has several applications in science, such as to preserve embryos and stem cells, serving as a non-synthetic pesticide, and to better trace brain cells in imaging studies.
1) Embryo Development
PHA promoted the development of embryos after fertilization in a cell study (mixed-cell pig embryos). These can be used to study cell genetics, but may also be useful for in vitro fertilization (IVF) [79, 80].
Low amounts of PHA taken from white kidney beans also promoted embryo development in mice cells. PHA improved the growth and survival of ovarian cells taken from goats after 6 days of exposure. However, it failed to do so in a similar study with ovarian cells from cows [81, 82, 83].
PHA improved the development and intact removal of mouse stem cells from half-embryos in a cell study. This implies that an embryo split in half could be used for both delivering a baby and collecting stem cells .
Spotted bean PHA has been shown to kill and inhibit fungi that are pathogenic to plants, suggesting its potential use as a fungicide. Another study found PHA toxic to grain aphids, suggesting it may also serve for pest control [85, 12].
PHA-L can be used In neuroscience to visually trace the shape of brain cells in electron microscopy imaging studies [86, 87, 88].
PHA can also be used to test immune function, responsiveness, and defects, as it activates white blood cells .
PHA is injected into the skin, which is checked for inflammation or reddening. It is one of the best tests for testing immunity, as it doesn’t require previous exposure. This makes it convenient to use in children and infants [3, 90].
The PHA test can be useful for detecting the immune response in patients with:
- Louis-Bar syndrome, a disease that causes poor coordination and small, dilated blood vessels 
- Immune deficiency 
- Leprosy 
- Connective tissue diseases 
- Cancer [93, 94]
- Skin rashes 
- Surgical patients 
This test has also been thoroughly researched and used in animals [90, 97, 98, 99, 100, 101].
Side Effects & Precautions
This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects.
Call your doctor for medical advice about side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.
Too much PHA can be toxic. It has been reported to cause nausea, vomiting, and diarrhea. It can trigger “leaky gut” and health complications derived from it, such as food sensitivity, autoimmune response, and inflammation .
Ingesting raw spotted bean can cause :
- Excessive urination
- Reduced blood sugar
- Reduced blood pressure
When injected into the skin, phytohemagglutinin (PHA) can cause:
- Swelling at the injection site or in the injection limb [102, 2]
- Long-term overactive immune response (seen in bird studies) 
The PHA skin test can be done on infants and children, but pregnant women should not ingest or use PHA due to the lack of safety data .
Lectin Sensitivity Predisposition
A person’s ability to tolerate lectins may be related to their blood type, although the relationship is not as straightforward as sometimes presented. Lectins like PHA are similar to foreign blood antigens (like blood from a person with type A would be to a person with type B) resulting in clotting and damage .
This may be due to variations in the coating of cells, as well as exposure to viruses and bacteria that damage it. This suggests that repeated infections with bacteria and viruses may cause lectin sensitivity .
Phytohemagglutinin and Gliadin
PHA and gliadin, a protein found in wheat, may both trigger celiac disease .
Gliadin contains a lectin-like substance that binds to intestinal walls (like PHA) and triggers gluten intolerance symptoms such as diarrhea and bloating [105, 106].
This can cause permanent damage to the intestine and prevent the absorption of nutrients .
Gliadin activates a protein that increases the immune response to infections (NF-kB). Cancer, inflammatory, and autoimmune diseases are linked to an overabundance of these activated proteins .
Gliadin causes celiac disease by [107, 109]:
- Causing T cells to enter the gut walls, triggering inflammation and an autoimmune response
- Releasing a protein that breaks down the cell connections in the small intestine, which allows gliadin to slip through, bind to immune cells, and cause inflammation
- Preventing toxins from being removed or broken down properly
- Degrading the villi finger-like structures of the small intestine and increasing growth in the grooves between them, which reduces the surface needed for nutrient absorption
Supplement/Herb/Nutrient-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
Nicotine reduced the effects of phytohemagglutinin (PHA) on human white blood cells .
PHA enhanced the action of a chemotherapy drug 5-FU to reduce tumor growth .
Azathioprine and PHA together reduced the immune response in dogs with kidney transplants better than each alone .
Limitations and Caveats
Most of the potential benefits of PHA have only been tested in animal and cell-based studies or in small, low-quality studies in humans. Larger, better-quality clinical trials are needed to validate their preliminary results.
The potential drug interactions of PHA have also been insufficiently investigated.
If you have been exposed to PHA and experience poisoning, contact a poison control center near you (call 1-800-222-1222).
The unit used to measure the toxicity of phytohemagglutinin (PHA) is the hemagglutinating unit or hau. When fully cooked, a single red kidney bean contains a safe amount for people who are not sensitive: 200 to 400 hau. A single raw kidney bean, on the other hand, contains 20,000 to 70,000 hau, which is toxic .
Combination With Other Substances
When mixed with immune-boosting sugars (polysaccharides) from astragalus or milkvetch, phytohemagglutinin (PHA) from red kidney beans increased immune response and immune cell division in rats .
When used with alpha-ketoglutaric acid (AKG) in rats, PHA stimulated the bowel, protected the kidneys, and caused weight loss .
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Few (if any) users spoke positively about their experience with phytohemagglutinin.
For instance, there were many negative reviews describing the symptoms of PHA poisoning.
Many users did not know that half-cooked beans can be toxic, so the side effects of PHA-poisoning caught them by surprise.
One user complained of several hours of severe diarrhea after eating raw kidney beans.
Another claimed that eating a tin of improperly-cooked red kidney beans gave them a tingling sensation all over their body and weakness in half of their facial muscles. They also complained of pain.
Another user ate hummus and, within 30 minutes, experienced nausea and about 2 hours of vomiting, stomach cramps, and gas.
Another warned others to avoid beans altogether, as they get headaches, terrible gas and bloating for 8-10 hours no matter what bean they eat. They stated that they are not allergic.
One user ate a black bean burger and experienced nausea and headaches just 4 hours after. They claimed feeling better after vomiting.
In general, most people are very cautious about accidentally ingesting raw or half-cooked beans because of PHA.