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Phytohemagglutinin (Plant Lectins): Dangers + Potential Uses

Written by Joe Cohen, BS | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Joe Cohen, BS | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Phytohemagglutinin or PHA is a lectin or plant protein found mostly in red kidney beans. In medicine, it is used to trace the shape of brain cells and test cellular immunity. While PHA could help reduce cancer and increase weight loss, high amounts of this lectin are very toxic to humans. Read more to learn about the dangers and potential uses of PHA.

What is Phytohemagglutinin?

Phytohemagglutinin is a lectin, a sugar-binding protein, found in many raw legumes eaten worldwide. Lectins are one of the main causes of food sensitivity [1].

PHA causes blood cells (red and white) to lump together, which makes them easier to find and kill when infected [2].

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 [3].

It also used to fight against HIV as it activates dormant HIV-1 cells, which alerts the immune system to destroy them [4].

Lectins like PHA are mostly found in legumes. PHA is found in the highest concentrations in raw red and white kidney beans, but also in the raw common bean and broad bean (Phaseolus vulgaris and vicia faba) in lower amounts [5, 6, 7].

While small amounts of PHA might be helpful, PHA is ultimately 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 [8].

PHA Components

The unpurified protein form of the lectin phytohemagglutinin is PHA-P [9].

PHA-P consists of two closely related lectins, called leucoagglutinin L, PHA-L, and E, PHA-E. The letters E and L indicate these proteins group together either red blood cells or white blood cells — leukocytes [9].

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 [11].

PHA is mostly found in beans of various bean plants. Different species of bean plants have differing amounts of PHA, with red kidney beans having the most [12].

PHA is also found in the roots of bean plants [13].

Bean Lectins

PHA or lectins, in general, are found in the following legumes:

  • Red and White Kidney Beans [14, 15]
  • Green beans [16]
  • Fava beans [R]
  • Black beans [17]
  • Pinto Beans [18]
  • Jack Beans [19]
  • Navy Beans [20]
  • Spotted Beans [12]
  • Soybeans [21]
  • Mung Beans [22]
  • Chickpeas [23]

How It Works

In general Phytohemagglutinin (PHA) binds to specific sugars such as mannose, N-acetyl glucosamine, and galactose to increase cell-signaling and clotting [9, 1, 24].

It can cause white blood cell to divide and accumulate, which increases cell immunity. In fact, it selectively causes white blood cells to divide, not affecting other cells. This may 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 [27].

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 damages gut health by:

  • Binding to stomach cells and stopping them from secreting the stomach acid needed for digestion [28, 29]
  • Increasing bacteria which stick to the walls of the small intestine and reducing nutrient absorption [30]
  • Disrupting enzyme balance in the small intestine, which could also decrease nutrient digestion and absorption [31]
  • Binding directly to the small intestine and damaging cells [31]

On the other hand, PHA helps to reduce cancer by:

  • Causing white blood cells to release IL-4 and IL-13, small proteins (cytokines) which activate the immune response and reduce the spreading of cancer cells [32]
  • Stopping DNA mutations (the addition of Thymidine into DNA), which prevents cancer cells from growing [33, 34]
  • Cutting apart cancer cells, causing cell death [35, 33]

It causes immune cell division by:

  • Making dormant white blood cells create new DNA and divide [36, 37, 38]

It increases immune response by:

  • Helping cells recognize pathogens and activate the immune system (via Toll-like receptors binding) [39]

On the other hand, PHA can also lower immune response, by:

  • Reducing the body’s production of antibodies [40]
  • Stopping thyroid hormones from entering cells and causing an inflammatory response [41]
  • Making foreign cells lose any receptors on their membrane that could alert the immune system and cause a response [42]

It increases weight loss by:

  • Lowering insulin levels, which increases fat burning and reduces body fats without causing muscle or protein loss [43]
  • Binding to a bile-producing hormone, which increases digestion and suppresses hunger [44]

PHA could potentially cause sugar intolerance by:

  • Lowering blood insulin levels and preventing the breakdown of sugar [45]

Phytohemagglutinin and T-cell activation

T-cells can be activated by lectins, like phytohemagglutinin (PHA) [46]. This is what happens during the process:

  1. PHA binds to the surface of T-cells (via receptors on IL-6 T-cells) [47, 48].
  2. This can trigger the reactions needed to activate T-cells (calcium inside the cell rises) [49].
  3. Activated T-cells boost cell immunity and signal other cells to target infected dormant white blood cells, like those infected by HIV [50, 51].
  4. PHA also activates a cell-communication protein (Ras) that signals for T-cell growth and activation [52, 53].

Not all T-cell activation is beneficial, however. On the contrary.

T-cells are divided into 2 types — Th1 or Th2 (T helper type 1 or 2) — based on the proteins they produce (cytokines). In non-allergenic 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 [54, 55, 55].

Th2 cytokines (IL-4, IL-5, IL-6, and IL-13) gather antibody-making and other white blood cells, which causes and increases inflammation [56].

Dangers of Phytohemagglutinin

Eating raw kidney beans is highly not recommended, as only 4 to 5 beans contain a toxic amount of Phytohemagglutinin (PHA). PHA is mostly destroyed during cooking — especially when using a pressure cooker, as the pressure can further and more quickly increase the temperature — making fully boiled beans safe enough to eat [14].

1) Damages the Digestive System

Excessive amounts of PHA can cause prolonged and severe food poisoning symptoms such as nausea, vomiting, diarrhea, and stomach pain, as seen in 50 UK patients [57].

Too much PHA can also cause inflammation of the stomach and intestine [58].

It can reduce liver function and even cause liver damage, according to rat studies [59].

2) May Cause Muscle Loss

When healthy rats were fed diets with large amounts of kidney bean lectins for 10 days, they experienced muscle loss. However, rats fed with low-lectin diets showed no muscle loss [45].

Rats fed an egg white and raw kidney bean diet also experienced muscle loss [60].

Healthy rats experienced bone muscle and heart muscle loss after they were fed raw red kidney bean and egg white diets [61].

3) May Cause Nutrient Deficiency

In the long term, PHA can reduce the absorption of nutrients, electrolytes, and water in the small intestine. In rats, it did this by increasing bacterial growth inside of the intestine [6].

PHA also reduced water and electrolyte absorption in the small intestines of rats by causing abnormally short, dense villi — finger-like structures needed to absorb nutrients — to grow. These structures are too dense, less can be exposed to the food in the intestine, and as a result, fewer nutrients are absorbed [62].

4) May Cause Arthritis

Arthritis is autoimmune, and people with arthritis produce antibodies with specific sugars (N-acetyl glucosamine exposed). While wheat gluten more commonly binds to this sugar and triggers arthritis, PHA is also able to bind to it and worsen inflammation [63, 1].

5) May Cause Autoimmune Disease

PHA can damage the intestines and reduce nutrient intake in humans. This may cause poor gut health — including leaky gut — linked to autoimmune disease [64, 65].

When the gut is leaky, gut bacteria and their toxins can escape through the gut and into the body, increasing inflammation and damage. Also, food-derived antigens (proteins or partially digested proteins) can pass through the gut and increase autoimmune responses [R, R].

Dietary lectins look exactly like foreign proteins to the immune system, which activates an attack. The body is not able to discriminate the lectins from harmful bacteria, leading to inflammation and constant flare-ups [66].

Lectins like PHA also force the thyroid and pancreas to display antigens, another autoimmune attack trigger [63].

Lectins also increase an inflammatory a cytokine that is found in large amounts in people with autoimmune diseases (TNF-alpha), which explains why people with food sensitivities can only feel worse when they eat lectins [67].

6) May Cause Anemia

PHA can make the red blood cells group together. The body recognizes these clots as infected and removes them from the body. This lowers the total cell count and causes anemia. Ingesting too much PHA can cause severe symptoms. It caused extreme weight loss, swelling, bloody diarrhea, and anemia in dogs and anemia and death in guinea pigs [12].

Heart attack and death might have also been caused by PHA in dogs [2].

Health Benefits of Phytohemagglutinin

While Phytohemagglutinin is dangerous, it also has some benefits:

1) May Combat Cancer

In multiple studies, Phytohemagglutinin (PHA) reduced cancer and tumor growth in mice [68, 69, 70].

Eating soaked, cooked, and dried black and navy beans also reduced colon cancer in rats. PHA prevented tumor growth in mice when combined with Fluorouracil, a chemotherapy drug [20, 33].

In a cell study, PHA physically destroyed white blood cancer cells from the thymus. A lectin found in broad beans caused colon cancer cells to become harmless gland-like cells, which can slow colon cancer, in another cell study [35, 71].

Spotted beans stopped leukemia and immune cancer cells from dividing [12].

2) Reduces Overactive Immune Response

Lowering immune system activity can be helpful in reducing sensitivity or rejection of foreign cells after vaccination, blood donation, or organ transplants. Phytohemagglutinin (PHA) stopped an overactive immune response in these situations by reducing the body’s production of antibodies. This is still in an experimental phase, however [40].

Blood Donation

PHA reduced the immune response and the production of antibodies in mice and rats injected with foreign red blood cells and antigens. It had the same effect in rats injected with typhoid bacteria (reduction of antibodies) [40, 72].

PHA reduced the blood-clotting response in rabbits to sheep cells (SRBC). This contributes to PHA’s ability to lower immune response, as a large number of clots can alert the immune system to attack [2, 73].

Vaccination

PHA also reduced any autoimmune response in guinea pigs to a protein used to test for tuberculosis infection (tuberculin) after previous vaccination [2].

PHA boosts the body’s immune response to parasites or fungi (by binding to Toll-like receptors) in response to vaccines [39].

Organ Donation

PHA prevented the rejection of donor spleen stem cells in mice. It did this by making the cells revert to an immature state and lose any foreign receptors on their membrane [41].

PHA reduced the immune response of dogs with kidney transplants. It also prolonged the life of skin transplants in rabbits [40, 40].

It can also be used to detect transplant organ rejection [74, 75].

3) May Help With Diabetes

Kidney bean lectins slowed starch digestion in 7 healthy subjects, leading to less sugar being taken up by the gut [76].

In very old reports dating back to the 1920s, patients 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 is destroyed by the hot water [77].

In early experiments, bean pod extracts were investigated as insulin substitutes. Bean pod extracts injected into rabbits kept blood sugar levels stable [77].

More recently, eating canned Pinto, Black and Dark Red Kidney Beans kept blood sugar levels stable in 17 Type 2 Diabetes patients. This is most likely due to the other compounds in the beans, such as fiber and enzymes (alpha-amylase) [78].

In rabbits, bean extract decreased blood sugar levels and improved sugar tolerance by 18.5 %. Bean pod tea similarly reduced blood sugar levels in rats [R, R].

The common bean pod reduces the absorption of sugar in the gut and keeps blood sugar stable [79].

4) Increases Weight Loss

A Phytohemagglutinin-rich diet reduced insulin levels but kept glucose levels stable in young rats, which reduced their weight [45].

Obese rats fed PHA from red kidney bean-rich diets and lost weight and had low insulin levels. In fact, low insulin helps to increase fat burning [43].

Lectins also cause an increase in adiponectin, a protein that decreases sugar levels and boosts fat breakdown [67].

Phytohemagglutinin Scientific Uses

Phytohemagglutinin (PHA) may be beneficial for science, especially when it comes to preserving embryo and stem cells. It may also be used in farming to reduce fungi, as opposed to using synthetic compounds.

1) Promotes 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) [80, 81].

Low concentrations 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 [82, 83].

PHA improved development and intact removal of mouse stem cells from half-embryos in a cell study. This means that an embryo split in half could be used for both delivering a baby and collecting stem cells [84].

2) May Be Antifungal

The spotted bean prevented the increase of fungi that are unhealthy for plants, which means it could be used to naturally prevent fungus in farming (as a fungicide). It could possibly also be used to control pests [85] [12].

3) Other Uses

  • In neuroscience to visually trace the shape of neurons (PHA-L) [86, 87, 88]
  • To increase genetic material used for a procedure that analyzes a person’s genetic code to better detect abnormalities [89, 90]

Phytohemagglutinin Test

Phytohemagglutinin (PHA) can also be used to test immune function, responsiveness, and defects, as it activates white blood cells [91].

PHA is injected into the skin and the skin is observed for inflammation or reddening. It is one of the best tests for testing immunity as it does not require previous exposure. This makes it convenient to use in children and infants [3, 92].

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 [93]
  • Immune deficiency [93]
  • Leprosy [94]
  • Connective tissue diseases [92]
  • Cancer [95, 96]
  • Skin Rashes [97]
  • Surgical Patients [98]

This test has also been thoroughly researched and used in animals [92, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108].

Side Effects & Precautions

When injected into the skin, phytohemagglutinin (PHA) can cause:

  • Swelling at the injection site or in the injection limb [109, 2]
  • Long-term overactive immune response (seen in bird studies) [109]

Ingesting the spotted bean can cause [12]:

  • excessive urination
  • reduced blood sugar
  • reduced blood pressure

Too much PHA can be toxic. It caused nausea, vomiting, and diarrhea in humans. It can trigger leaky gut and health complications from it, such as food sensitivity, autoimmune response, and inflammation [8].

The PHA skin test can be done on infants and children, but pregnant women should not ingest or use PHA since safety has not been determined [3].

Lectin Sensitivity Predispositions

A person’s ability to tolerate lectins could be related to their blood type, although the relationship is not as straightforward as usually 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 — resulting in clotting and damage [110].

This may be due to variations in the coating of cells, as well as exposure to viruses. Viruses can destroy a part of the protective coating. This way, more common exposure to viruses or bacteria may, in fact, trigger lectin sensitivity in some people [110].

Phytohemagglutinin and Gliadin

Phytohemagglutinin (PHA) and Gliadin, a protein found in wheat, may both trigger celiac disease [111].

Gliadin contains a lectin-like substance which binds to intestinal walls (like PHA) and activates gluten intolerance symptoms such as diarrhea and bloating [112, 113].

This can cause permanent damage to the intestine and prevent the absorption of nutrients [114].

Gliadin activates a protein that increases immune reaction to infections (NF kappa beta). Cancer, inflammatory, and autoimmune diseases are linked to an overabundance of these activated proteins [115].

Gliadin causes celiac disease by:

  • Causing immune (T) cells to enter the gut walls, trigger inflammation and an autoimmune response [114, 116]
  • 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 [114]
  • Prevents toxins from being removed or degraded properly [114]
  • 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 [114]

Drug Interactions

Nicotine reduced the effects of phytohemagglutinin (PHA) on human white blood cells [117].

PHA enhanced the action of a chemotherapy drug 5-FU to reduce tumor growth [33].

Azathioprine and PHA together reduced the immune response in dogs with kidney transplants better than each alone [2].

Limitations and Caveats

There are few studies available that examine the interaction between phytohemagglutinin (PHA) and other drugs.

There are also more cell and animal studies than human studies, of which few are valuable. One review of 11 human trials about PHA and weight loss stated that the quality of the available studies was too low to draw any conclusions [118].

While PHA can help embryo development in cells, one study did not find any effect [119].

One study also claimed that PHA was not a good method for measuring cell immunity [120].

Supplementation

Dosage

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 [14].

Combination With Other Substances

When mixed with immune-boosting sugars (polysaccharides) from the Milk Vetch plant, phytohemagglutinin (PHA) from red kidney beans increased immune response and immune cell division in rats [99].

When used with alpha-ketoglutaric acid (AKG) in rats, PHA stimulated the bowel, protected the kidneys, and caused weight loss [121].

User Experiences

Few (if any) users speak positively about their experience with phytohemagglutinin.

There are 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 claims 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 to feel better after vomiting.

In general, the public is very cautious about accidentally ingesting raw or half-cooked beans because of PHA.

If You Have Food Sensitivities

I recommend following my lectin avoidance diet, named as such because I think that lectins are the single major trigger of autoimmune disease. However, they are not the only trigger. And this diet is not a one-size-fits-all regimen. It may not suit EVERYONE’s needs, but it’s a good template from which to build a personalized diet.

If you suffer from food sensitivities, the Lectin Avoidance Diet helps you figure out which foods are inflammatory, and which are less inflammatory for you.

About the Author

Joe Cohen, BS

Joe Cohen, BS

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.
Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

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