Prostaglandins are powerful hormones that have a variety of diverse functions in the human body, most notably controlling the immune response. However, in excess, they can cause chronic disorders and diseases, including migraines, painful menstruation, and cancer. Read on to see how prostaglandins affect your health.
What Are Prostaglandins?
Prostaglandins are hormones involved in many diverse roles in the body, principally the acute immune reaction and inflammation [R].
Unlike most hormones, prostaglandins are not made by glands and then released into the bloodstream. They are made in multiple different tissues and exert their effects locally. They have potent effects, but are short-lived and quickly cleared from the body [R].
Prostaglandins were first isolated from semen by Swedish pharmacologist Ulf Svante von Euler in 1935. The name prostaglandins is derived from the fact that they were originally thought to be produced by the prostate gland (they are actually produced in the seminal vesicles, among many other types of tissues).
Prostaglandins only affect the cells they are made by and the cells in the surrounding area. They have diverse effects on the body, including:
- increasing/decreasing inflammation, and contributing to the signs of acute inflammation, such as redness, heat, swelling, and pain
- constricting or dilating blood vessels
- inducing labor
- increasing the production of mucus
While the body produces many types of prostaglandins, there are four primary types:
|Type of Prostaglandin||Function|
|Prostaglandin E2 (PGE2)|
|Prostaglandin D2 (PGD2)|
|Prostaglandin F2α (PGF2α)|
Prostaglandins are made from a fatty acid called arachidonic acid. When this fatty acid is released from cells, it is converted into prostaglandin H2 (PGH2, the precursor to all four of the primary prostaglandins) by either one of two enzymes [R, R]:
- cyclooxygenase-1 (COX-1). This enzyme maintains basal (minimal) levels of prostaglandins, that are needed for gut protection.
- cyclooxygenase-2 (COX-2) . This enzyme increases prostaglandin levels during acute inflammation such as infection or injury.
Prostaglandins help increase the concentration of cAMP, calcium ions, and activate G proteins inside the cells, all of which are involved in the transfer of energy and inflammatory signaling processes. These pathways are vital to initiate a defense response against foreign invaders that enter the body [R].
Health Benefits of High Prostaglandin Levels
1) Prostaglandins Protect the Gut and Help Against Ulcers
Patients with ulcers have lower levels of PGE2 in their gut than healthy patients [R].
In one study (SB-RCT) of 34 healthy volunteers, prostaglandin prevented NSAID-induced gut damage (measured as the number of small-intestinal lesions) in [R].
In a study of 11 patients with unmanageable ulcers, PGE2 administration completely healed the ulcers in seven patients within four to 14 weeks [R].
2) Prostaglandins Protect the Heart
Estrogen significantly decreased infarct size in rabbits, but this positive effect was blocked with either a COX-2 or a PGI2 receptor inhibitor [R].
In a DB-RCT of 11 patients with heart failure, 4-week PGE1 therapy improved heart health compared to placebo [R].
In mice, PGD2 protected against heart injury by activating Nrf2, an important master-regulator of antioxidant enzymes [R].
3) Prostaglandins Induce Labor
Prostaglandins induce uterine contractions and play a critical role in causing pregnant woman to go into labor [R].
Prostaglandins given locally can also help with stillbirths and hemorrhages during pregnancy. C-sections for delivering stillborns or surgery to deal with postpartum hemorrhages may be avoided with the use of prostaglandins [R].
In a study involving 50 patients who had either a faulty abortion or had been diagnosed with fetal death, 47 of them were able to successfully expel the products of conception with PGE2 [R].
4) Prostaglandins (PGE2) Can Calm Allergies
In a double-blind crossover study of 8 subjects with asthma, inhaling PGE2 decreased the response to allergens [R].
PGE2 also protected against allergic lung inflammation in mice [R].
5) PGE2 and PGF2α May Improve Sperm Function
When exposed to low levels of PGE2 and PGF2α, the motility and function of human sperm cells were improved [R].
Low doses of PGF2α at insemination improve conception rates in cattle [R].
Negative Effects of High Prostaglandin Levels
1) Prostaglandins (PGD2) Can Increase Allergies
Prostaglandins can both promote or suppress allergic inflammation, depending on many different factors.
For example, depending on the context, PGD2 can either increase or decrease inflammation in allergies [R].
In a study of 199 subjects, higher levels of PGD2 have been detected in those with severe asthma [R].
Similarly, levels of the PGD2 were higher in the urine in both humans and mice with food allergies [R].
However, in another study, mice without PGD2 had more severe food allergies [R].
Administration of a synthetic prostaglandin increased Th17 cells in mice with allergic inflammation. Th17 cells are proinflammatory T- cells that are major contributors to allergic responses [R].
2) High PGE2 Levels May Decrease the Ability to Fight Cancer
Prostaglandins can suppress the immune response. High levels of PGE2, in particular, have been linked to cancer.
One study found that PGE2 levels were significantly higher in esophageal cancer patients. Moreover, PGE2 levels were higher in tumor tissue compared to healthy tissue [R].
Similarly, higher levels of a PGE-metabolite (an indicator of PGE production) were found in head and neck cancer patients whose disease progressed or spread after treatment [R].
Also, in a population-based study, 153 gastric cancer patients had higher urinary PGE2 compared to 153 controls [R].
A high level of prostaglandin PGE2 injected into the portal vein (the vein that carries blood from the gut to the liver) of rats decreased immune cell count and increased the spread of liver cancer [R].
3) High Prostaglandins May Contribute To Inflammation-Related Pain
Blocking both PGE2 and PGI2 action relieves inflammatory pain in rats [R].
4) High Prostaglandins May Cause Migraines and Headaches
In another study (DB-RCT) with 11 healthy subjects, all subjects reported a headache after receiving PGE2 while no subjects reported a headache on placebo [R].
In 64 children with migraines, urinary PGF2a levels were significantly higher during a headache than during non-headache periods [R].
5) High Prostaglandin Levels Cause Menstrual Cramps
High levels of prostaglandins can cause intense period pain for menstruating women and also play a primary role in the mechanism of menstrual disorders, including abnormally heavy blood flow [R, R, R].
In a dose-escalating study with 24 women, higher doses of a PGF2a receptor blocker decreased menstrual pain [R].
6) High PGE2 Levels May Play a Part in Osteogenesis Imperfecta
PGE2 activates the renewal of bone [R].
Oteogenesis imperfecta is an inherited disorder characterized by bone fragility and low bone mass.
Children with osteogenesis imperfecta have higher levels of PGE2 compared to healthy children. In a study of 16 children given biophosphates (drugs have been shown to increase bone mineral density) PGE2 levels were reduced [R].
7) High PGE2 Levels Are Linked to Celiac Disease
Biopsies (surgical removal of tissue) of the gut of Celiac patients revealed elevated PGE2 levels [R].
8) High PGE2 Levels are Linked to ALS
One study found that PGE2 levels were two to 10 times higher in amyotrophic lateral sclerosis (ALS) patients compared to controls [R].
9) High PGE2 Levels May Play a Role in Reflux Esophagitis
Reflux esophagitis is inflammation of the esophagus caused by acid reflux.
Low PGE2 levels are thought to protect the esophagus while high levels lead to inflammation.
A study found increased production of PGE2 in 10 children with reflux esophagitis [R].
In 14 healthy volunteers, PGE2 levels in the esophagus increased after acid infusion and correlated with the heartburn intensity [R].
10) High PGE2 Levels May Play a Role in Deformity of Nails and Fingers
Evidence strongly suggests that PGE2 is involved in the development of in the deformity of the nails and fingers, referred to as nail clubbing or digital clubbing [R].
11) High PGD2 Levels May Play a Role in Male Pattern Baldness
In five men with male pattern baldness, bald skin had increased PGD2 levels compared to skin with hair on it [R].
12) High PGE2 Levels are Linked to Depression
In a study of 30 depressed patients, all but one of them had increased PGE2 levels [R].
13) High PGE2 Levels are Linked to Alzheimer’s Disease
PGE2 levels were five times higher in the brains of seven Alzheimer’s patients compared to seven healthy individuals of the same age [R].
Another study found that PGE2 levels were higher in 33 patients with mild memory loss and Alzheimer’s disease compared to 35 healthy individuals [R].
Microglia are the main immune cells of the brain and their ability to clear amyloid-beta plaques becomes impaired in Alzheimer’s disease. In a mouse model of Alzheimer’s, mice whose microglia were missing PGE2 receptors had improved clearance of plaques, reduced brain inflammation, and less deficits in memory [R].
13) High PGD2 Levels are Linked to Kidney Failure
Higher PGD2 levels were found in 17 patients with kidney failure compared to 34 patients with healthy kidney function. Levels of an enzyme needed to make PGD2 (PGD synthase) were 35 times high in kidney failure patients [R].
14) High PGE2 Levels are Linked to Schizophrenia
In 40 patient with schizophrenia, PGE2 levels were significantly higher than in 38 non-schizophrenic individuals. Schizophrenic patients with higher PGE2 levels had more feelings of guilt and hallucinatory behaviors [R].
Ways to Decrease Prostaglandin Levels
Herbs and Supplements That Decrease Prostaglandins
Another study found that 500 ml of black tea for one month decreased PGF2α levels in healthy volunteers [R].
2) Licorice and Peony (shakuyaku-kanzo-to)
Dysmenorrhea (painful periods) involves intense menstrual cramps. The primary cause for this is the abnormally high amount of prostaglandins in the menstrual fluids which hyperactivates the uterine muscle. By reducing prostaglandins, the intense pain and cramps subside [R].
In a cell study, an herbal medicine consisting of licorice and peony that was traditionally used to treat menstrual cramps reduced prostaglandins levels by 50% [R].
Chamomile extract blocked the production of prostaglandin E2 in immune cells in response to bacterial toxins. Chamomile selectively blocks the COX-2 enzyme, which reduces the risk of ulcers [R].
5) Nettle Leaf
Nettle leaf (Urtica dioica) extract reduced COX-2 levels in dog cartilage cells [R].
Curcumin reduced an enzyme that is needed to make PGE2 (prostaglandin E2 synthase-1) in blood cells [R].
7) White Willow Bark
White willow bark inhibits COX-1 and COX-2, and prevents the production and activation of prostaglandins [R].
Rosehip extract reduced COX-2 levels in dog cartilage cells [R].
9) EPA and DHA (Omega 3’s)
10) Beta-sitosterol and Campesterol
Beta-sitosterol and campesterol are compounds found in plants that protect against heart diseases and cancer.
In a study of immune cells, PGE2 and PGI2 levels were decreased by 68% and 67% when exposed to beta-sitosterol and 55% and 52% when exposed to campesterol [R].
11) Rosmarinic Acid
Rosmarinic acid is found in herbs such as rosemary.
Rosmarinic acid lowered PGE2 production in rat chondrocytes (cartilage cells) [R].
Resveratrol decreased PGE2 (and COX-2) in human joint cells (fibroblast-like synoviocytes) [R].
Drugs That Decrease Prostaglandins
1) Nonsteroidal Anti-Inflammatories (NSAIDs)
Nonsteroidal anti-inflammatory drugs (NSAIDs), are a popular choice for reducing prostaglandin production. Examples of popular NSAIDs include ibuprofen and aspirin. However, side effects can involve damage to the gut, high blood pressure, and excessive platelet production (this can increase blood clotting), which are all regulated by prostaglandins [R].
Selective COX-2 inhibitors (coxibs) are a new class of NSAIDs that only inhibit COX-2, instead of traditional NSAIDs that inhibit both COX-1 and COX-2 enzymes. Since COX-1 produces prostaglandins that protect the gut, coxibs lower the risk of ulcers. Examples include etoricoxib and celecoxib. However, they are associated with an increased risk of heart damage [R].
Corticosteroids are steroids used to reduce inflammatory symptoms in a variety of conditions including asthma and arthritis.
Corticosteroids blocked the production of PGE2 and PGF2α in human skin cells [R].
3) Mepacrine (quinacrine)
Mepacrine is a drug used to treat rheumatoid arthritis, giardiasis (infection with the protozoan giardia), and malaria.
Mepacrine prevents arachidonic acid from being released from the cells and converted to prostaglandins [R].
Health Benefits of Low Prostaglandins Levels
1) Low Prostaglandin Levels Are Associated with Less Inflammation
Because prostaglandins are produced in response to injury or infection in order to increase inflammatory immune response, low levels of prostaglandins are linked to lower inflammation in the body [R].
Negative Effects of Low Prostaglandin Levels
1) Low Prostaglandin Levels Allow Damage to the Gut
Prostaglandins prevent excessive stomach acid secretion and increase mucus and bicarbonate secretion. Low levels of prostaglandins make the gut more vulnerable to damage from toxins and infections [R].
2) Low Prostaglandin Levels Cause Heart Rhythm Disturbances
Low PGE2 and PGF2α levels caused irregularities in rat heart rhythms [R].
3) Low Levels of PGE May Play a Role in Some Autoimmune Diseases
Low levels of PGE1 may be involved in autoimmune diseases by activating B-cells (these produce autoantibodies) and reducing T-cell function [R].
Borage oil, an oil derived from the Borago officinalis seed, contains gamma-linoleic acid that can increase PGE levels. PGE, in turn, limits the production of the TNF-alpha, a cytokine. The constant production and release of this cytokine is what drives the self-destructing behavior of rheumatoid arthritis. By limiting TNF-alpha joint damage may be reduced [R].
4) Low Prostaglandin Levels May Play a Role in Diabetic Retinopathy and Neuropathy
Diabetic retinopathy is a condition in which high blood sugar levels damage the blood vessels in the retina.
Levels of PGE1, PGE2, and PGF2α were all lower in human retina cells from patients with diabetic retinopathy compared to retina cells from healthy patients [R].
Diabetic neuropathy is a group of nerve disorders caused by diabetes.
Ten days of daily PGE1 injections improved neuron function in 77 patients with diabetic neuropathy, compared to 42 controls [R].
Ways to Increase Prostaglandins
1) Sleep Loss (not recommended)
Three days of sleep deprivation increased PGE2 in 24 subjects. This was associated with more pain (e.g. headaches, stomach pain) and physical discomfort [R].
2) EPA and DHA (Omega-3s)
3) Gamma-linolenic Acid
4) L. reuteri
The probiotic L. reuteri stimulated the production of PGE2 by the gingival (gum) cells. This may hasten the resolution of gum inflammation [R].
Estrogen increased PGI2 in rabbits, which protected their hearts against damage after a heart attack [R].