Alpha-glucosidase ihibitors (AGIs) are what are we are going to dicuss about. These are a class of oral antidiabetic medicines. Those are used primarily to manage after-meal blood glucose levels with type 2 diabetes. There are acarbose, a widly used AGI, miglitol, and voglibose.

Mechanism of Actions

These drugs slow down carbohydrate digestion and absorption. Therefore, blood sugar levels rise slowly after meals. So, they helps to prevent rapid spikes. AGIs acts as competitive and non-competitive inhibitors to certain enzymes, alpha-amylse in the pancreas and alpha-glucosidare in the small intesine. These digesting enzymes play crucial roles in breaking down complex carbohydrate like starch. Alpha-amylse breaks down starch into much more simple molecules; maltose, maltotriose, and dextrin. And alpha-glucosidase which acts in the small intestine makes oligosaccharide and tri- or di-saccharides into mono-forms like glucose. These broke-down carbohydrates are good for absoprtion. By inhibiting these enzymes, AGIs slow the breakdown of complex carbohydrates, leading to a more gradual rise in blood glucose levels post-meal. Delayed glucose absorption benefits overall glycemic control when used alongside other diabetic meds or dietary interventions.

AGI containing foods

Where do we find alpha-glucosidase inhibitors (AGIs)? Do we have to rely on the market or pharmacies? Not necessarily. AGIs can also be found naturally in certain foods. These foods not only mimic the action of medications but also help slow carbohydrate digestion and absorption, supporting healthy blood sugar levels.

Bitter Melon

Bitter melon, despite its name, is not sweet and has a distinct bitter taste. A cup of bitter melon cooked or fermented can interferes the absorption of monosaccharides in the gut. This unique fruit is a powerful addition to an anti-diabetic diet due to its bioactive compounds, particularly charantin, which plays a significant role in blood sugar management.

In a study conducted on rats, a bitter melon diet influenced blood glucose and superoxide dismutase (SOD) levels (1). The groups given bitter melon, both fresh and fermented, showed significantly reduced fasting and postprandial blood glucose levels compared to the control group. However, the reductions were not as pronounced as those in the group treated with acarbose, a pharmaceutical alpha-glucosidase inhibitor. Interestingly, fermented bitter melon was found to be more effective than fresh bitter melon in lowering blood glucose.

Additionally, bitter melon contains phenolic compounds such as 5-hydroxymethyl-2-furfural (5-HMF), which demonstrate strong alpha-glucosidase inhibitory activity (2). Remarkably, this study also showed that even heat-treated bitter melon retains its anti-hyperglycemic properties. This means that cooking or processing bitter melon does not diminish its ability to lower blood sugar levels, making it a versatile ingredient for managing diabetes naturally.

1) J Nutr Metab. 2020 Feb 28:2020:6369873. doi: 10.1155/2020/6369873. eCollection 2020. Probiotics Fermented Bitter Melon Juice as Promising Complementary Agent for Diabetes Type 2: Study on Animal Model
Laksmi Hartajanie 1 2, S Fatimah-Muis 1, K Heri-Nugroho Hs 1, Ign Riwanto 1, M Sulchan 1

2) J Food Sci. 2021 Jul;86(7):3109-3121. doi: 10.1111/1750-3841.15798. Epub 2021 Jun 19. Thermal treatment enhances the α-glucosidase inhibitory activity of bitter melon (Momordica charantia) by increasing the free form of phenolic compounds and the contents of Maillard reaction products
Hsin-Jung Hsieh 1, Jer-An Lin 2, Kai-Ting Chen 1, Kuan-Chen Cheng 3 4 5 6, Chang-Wei Hsieh 1 6

Berries (e.g., blueberries, blackberries, strawberries)

Berries such as blueberries and blackcurrants contain phenolic compounds that inhibit alpha-amylase and alpha-glucosidase enzymes. These phenolics, through hydrogen bonding, bind to the active sites of the enzymes, reducing the space available for sugars to bind. This mechanism acts as a competitive and mixed-type inhibition.

In studies, groups treated with extracts of oat bran, blueberry, and blackcurrant powder showed increased alpha-amylase and alpha-glucosidase inhibitory activities (3). The magic lies in anthocyanidins, a type of phenolic compound. These findings suggest that blueberries and blackcurrants might be potential sources of anti-diabetic activity.

Various fruit by-products are rich in polyphenolic compounds, antioxidants, and alpha-glucosidase inhibitors (4). Among these, mango peel has shown the highest anti-diabetic activity. Other beneficial peels include those from litchi, banana, jackfruit, pineapple, and papaya. It is well-known that fruit peels often contain more beneficial compounds than the flesh. While eating them raw may be difficult, cooking or preparing clean, organic fruit peels can make them easier to consume and provide these health benefits

3) Food Research International Volume 138, Part A, December 2020, 109756
Food Research International. The effects of bioactive compounds from blueberry and blackcurrant powders on the inhibitory activities of oat bran pastes against α-amylase and α-glucosidase linked to type 2 diabetes. Xiaodan Hui et al.

4) J Food Sci Technol. 2021 May;58(5):1715-1726. doi: 10.1007/s13197-020-04681-2. Epub 2020 Aug 8. Fruit by-products: the potential natural sources of antioxidants and α-glucosidase inhibitors. Md Rakibul Islam 1, Ahmed Redwan Haque 1, Md Raihan Kabir 1, Md Mehedi Hasan 1, Khursheda Jahan Khushe 1, S M Kamrul Hasan 1

Cinnamon and tea

Cinnamon is a standout herb with remarkable alpha-glucosidase inhibitory properties. All types of cinnamon exhibit activity similar to acarbose, a pharmaceutical AGI. Taking a single dose of raw cinnamon before a meal can prevent postprandial (after-meal) hyperglycemia, particularly for those with type 2 diabetes (5). Cinnamon can be consumed as a powder, extract, or tea. Among the different varieties, Ceylon cinnamon stands out as the best overall option. While there are slight differences between cinnamon types, most significantly reduce starch breakdown and possess anti-hyperglycemic properties.

Other herbal teas are also effective. Some teas contain catechins, compounds that may inhibit alpha-glucosidase and help regulate blood sugar levels. Regular consumption of these teas may help prevent or manage type 2 diabetes naturally.

5) Plant Foods for Human Nutrition Article. Cinnamon Shows Antidiabetic Properties that Are Species-Specific: Effects on Enzyme Activity Inhibition and Starch Digestion.
Published: 01 August 2019
Volume 74, pages 544–552, (2019)
Nicholas J. Hayward, Gordon J. McDougall, Sara Farag, J. William Allwood, Ceri Austin, Fiona Campbell, Graham Horgan & Viren Ranawana

Side effects

What are the possible side effects of AGIs? The most common issues are gastrointestinal troubles, including bloating, abdominal discomfort, and diarrhea. These occur because undigested carbohydrates, due to alpha-glucosidase inhibition, act as osmotic agents. This means they draw water into the gut, potentially leading to diarrhea. In some cases, these drugs increases AST/ALT, too.

Fortunately, AGIs are not hypoglycemic agents. They do not stimulate insulin production or lower blood sugar below normal levels. However, consuming high amounts of AGIs, either through food extracts or medications like acarbose or miglitol, can cause hypoglycemia in people with type 2 diabetes who are on additional medications. If you are a patient, it’s important to follow your prescribed treatment plan and consult your doctor before making any changes.