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Trigonelline the unknown alkaloid in coffee

Trigonelline is a naturally occurring compound found in coffee. It's named after fenugreek seeds (Trigonella foenum-graecum), where it was first discovered, but it's also present in significant amounts in coffee beans.


Trigonelline has several potential health benefits. It's been studied for its potential neuroprotective effects, which could make it beneficial in the treatment of neurodegenerative diseases. It may also have antibacterial and antiviral properties.  Trigonelline has been shown to have antioxidant properties. It can scavenge free radicals and reduce oxidative stress, which are key factors in many diseases. The antioxidant activity of trigonelline is believed to be due to its ability to donate hydrogen to free radicals, thereby neutralizing them and preventing them from causing cellular damage. This makes trigonelline a potentially useful compound in the prevention and treatment of diseases associated with oxidative stress, such as cardiovascular disease, cancer, and neurodegenerative disorders1.

In coffee, trigonelline contributes to flavor, particularly in the roasting process. As coffee beans are roasted, trigonelline breaks down and forms various products that contribute to the flavor and aroma of coffee. It's particularly important in the formation of the "roasty" flavor that's characteristic of darker roasts.


Trigonelline has been found to have neuroprotective effects.


Alzheimer's Disease: Trigonelline has been shown to have potential benefits in the treatment of Alzheimer's disease. It can inhibit the formation of beta-amyloid plaques, which are a hallmark of Alzheimer's disease. This effect is thought to be due to its antioxidant properties, which help to protect brain cells from damage. It can also inhibit acetylcholinesterase, an enzyme that breaks down the neurotransmitter acetylcholine, which is important for memory and learning. By inhibiting this enzyme, trigonelline can potentially improve cognitive function in Alzheimer's patients 1.

  • Parkinson's Disease: In a study on rats, trigonelline was found to protect dopaminergic neurons in the substantia nigra, a part of the brain that is affected in Parkinson's disease. This effect was thought to be due to its anti-inflammatory and antioxidant properties. Trigonelline was also found to improve motor function in these rats 2.

  • Neuroinflammation: Trigonelline has been shown to have anti-inflammatory effects in the brain. It can inhibit the activation of microglia, which are immune cells in the brain that can cause inflammation and damage to neurons when they are overactivated. By inhibiting microglial activation, trigonelline can potentially protect neurons from damage 3.

  • Oxidative Stress: Trigonelline has strong antioxidant properties, which can protect neurons from oxidative stress. Oxidative stress is a condition where there is an imbalance between the production of free radicals and the body's ability to counteract their harmful effects. It is a major cause of neuronal damage in various neurological disorders. By neutralizing free radicals, trigonelline can protect neurons from oxidative damage 4.


Trigonelline has also been studied for its potential antidiabetic effects. Research suggests that it may have several mechanisms of action that could be beneficial for managing diabetes.

  • Improvement of glucose tolerance: Trigonelline has been shown to improve glucose tolerance, which could help to control blood sugar levels in people with diabetes.

  • Stimulation of insulin secretion: Some studies suggest that trigonelline may stimulate the secretion of insulin, the hormone that regulates blood sugar levels. This could potentially help to reduce blood sugar levels in people with diabetes.

  • Inhibition of α-glucosidase and α-amylase: Trigonelline may inhibit the activity of α-glucosidase and α-amylase, enzymes that break down carbohydrates into sugars. By inhibiting these enzymes, trigonelline could potentially slow down the absorption of sugars from the diet, helping to control blood sugar levels.

  • Antioxidant effects: Trigonelline has been shown to have antioxidant effects, which could potentially help to protect against the oxidative stress that is often associated with diabetes.

  • Anti-inflammatory effects: Inflammation is thought to play a role in the development of diabetes, and trigonelline has been shown to have anti-inflammatory effects.


However, while these potential effects are promising, more research is needed to fully understand the potential benefits and risks of trigonelline for people with diabetes. It's also important to note that while trigonelline may have potential benefits for diabetes management, it should not be used as a substitute for conventional diabetes treatment unless under the supervision of a healthcare provider.


Trigonelline has also been studied for its potential neuroprotective effects. In the context of Parkinson's disease, it has been found that trigonelline can inhibit neuroinflammation, which is a key factor in the progression of this disease.


A study titled "Trigonelline mitigates lipopolysaccharide-induced neuroinflammation" found that trigonelline can inhibit the production of pro-inflammatory cytokines and enhance the production of anti-inflammatory cytokines in the brain. This can potentially slow down the progression of Parkinson's disease.


Another study titled "Trigonelline: A plant alkaloid with therapeutic potential for diabetes and central nervous system disease" also highlighted the potential of trigonelline in treating central nervous system diseases like Parkinson's. The study suggested that trigonelline can modulate several signaling pathways in the brain, which can help in the management of Parkinson's disease.

However, more research is needed to fully understand the potential of trigonelline in treating Parkinson's disease and other neurodegenerative disorders. It's important to note that while these studies show promise, they do not constitute medical advice and anyone considering using trigonelline for these purposes should consult with a healthcare provider.

Here are the sources for your reference:

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