IngredientsThe pancreatic alpha-amylase inhibitor isoform 1 (alpha-AI 1), also known as phaseolamin, is a constituent protein of the common white and kidney beans (Phaseolus vulgaris L.). Phaseolamin is a glycoprotein found mainly in white and red kidney beans and is a known amylase inhibitor, the principal protein responsible for the inhibition of starch breakdown. The compound belongs to the broader family of legume lectins and is classified as a proteinaceous enzyme inhibitor. Its systematic biochemical designation, assigned at the time of its isolation and characterization, is the Phaseolus vulgaris alpha-amylase inhibitor isoform 1 (α-AI1).
Kidney beans, Phaseolus vulgaris, contain a proteinaceous inhibitor of alpha-amylase, which was named phaseolamin. Phaseolus vulgaris L. (family Fabaceae) is the common bean species encompassing a wide variety of cultivars, including white kidney beans, navy beans, pinto beans, and red kidney beans, all of which may contain alpha-amylase inhibitors. P. vulgaris is not the only source of phaseolamin, but it is also widely considered safe. Commercial supplement preparations are predominantly derived from white kidney bean (also called white cannellini bean) varieties, as these are favored for their relatively high alpha-amylase inhibitory activity and lower phytohemagglutinin content compared with red kidney beans.
The pancreatic alpha-amylase inhibitor isoform 1 (alpha-AI 1), also known as phaseolamin, is a constituent protein of the common white and kidney beans. Next to it, there are two other isoforms and an alpha-amylase inhibitor-like protein (alpha-AI 2, alpha-AI 3, and alpha-AIL, respectively). The most widely distributed in the plant is the alpha-AI 1, which represents about one tenth of the total seed protein content. Of the three alpha-amylase inhibitor isoforms (Alpha-AI1, Alpha-AI2, and Alpha-AIL), Alpha-AI1 shows bioactivity in humans.
The structural distinction between isoforms is pharmacologically important. Between α-AI1 and α-AI2, only the former shows inhibitory activity against mammalian amylases. This has been explained in terms of inhibitor structural properties. There is a 78% homology in amino acid sequence between them and both undergo post-translational cleavage, yet α-AI2 has no inhibitory effect on mammalian amylases. The differences in the sequence between the two therefore have a significant effect on the inhibitory activity.
Proteolytic activation of α-AI1 includes the removal of the signal peptide and the proteolytic scission into α and β subunits. Dimerization then leads to αβ dimers that associate in pairs to form the heterotetramer α2β2, the active α-AI molecule. Polypeptides present between 50–35 kDa, 35–25 kDa, and 15–10 kDa correspond, respectively, to phaseolin, phytohemagglutinin, and αAI-1 (alpha-amylase inhibitor-1) subunits in commercial phaseolamin preparations.
Two hairpin loops are responsible for the stability of an α-AI1–porcine pancreatic amylase (PPA) complex, through the formation of fifteen hydrogen bonds with PPA in the active site cleft. Each variety of P. vulgaris produces an alpha-AI type 1 with a fairly different primary structure; nevertheless, all the enzymes show the same inhibitory activity on animal amylases.
This enzyme was first discovered in 1945, and was characterized and named "phaseolamin" in 1975. Since then, phaseolamin was tested for its efficacy as a starch blocker and purified extracts were used as human dietary supplements with anti-hyperglycaemic and anti-obesity purposes. The 1975 characterization was carried out by Marshall and Lauda, who purified the inhibitor to homogeneity by conventional protein fractionation methods involving heat treatment, dialysis, and chromatography on DEAE-cellulose, Sephadex G-100, and CM-cellulose.
The principal commercial form is a dried aqueous extract from the common white bean P. vulgaris, produced from non-GMO whole kidney beans and certified as gluten free. It is used as a dietary supplement — odorless and tasteless — in various forms, including powders, tablets, and capsules.
The most extensively studied proprietary form, Phase 2® (Pharmachem Laboratories, Kearny, NJ, USA), has been marketed under several names. This starch blocker was previously named Phaseolamin 2250, because 1 g of the product blocked 2,250 starch calories. Phase 2 is also marketed under the brand names Glucosanol, Glycolite, PhaseLite, and Starchlite, and consists of Phaseolus vulgaris extract and Gum Arabic.
Standardization of potency is conducted by measuring alpha-amylase inhibiting units. Each lot of Phase 2 has at least 3,000 alpha-amylase-inhibiting units (AAIU) per gram when tested at a pH 6.8 using potato starch as substrate and pancreatin as enzyme source. A proprietary manufacturing process results in increased stability in acidic conditions of the stomach and duodenum. In vitro, Phase 2 maintains its alpha-amylase inhibitory activity after being exposed to acidic conditions mimicking those of the gastrointestinal tract, compared to generic extracts.
Phase 2® is prepared using thermal processing conditions to substantially inactivate hemagglutinating activity (HA) and trypsin-inhibiting activity (TIA) while preserving substantial α-amylase-inhibiting activity. Production lots are routinely assayed to assure compliance with the established product specifications and standardized to contain less than 3,400 HA units/g and less than 40 TIA units/mg. This thermal processing step is an important quality-control distinction, as the efficacy and safety of amylase inhibitor extracts depend on the processing and extraction techniques used.
Bean pods (Phaseolus vulgaris) are among the most widely used traditional remedies against diabetes mellitus, with historical knowledge summarized and compared to recent study results. The common bean has been cultivated and consumed across multiple continents and has a long history in folk medicine distinct from its culinary use.
Hot aqueous extract of common bean pods — referred to as "bean pod tea" — is famous in folk medicine mostly for its antidiabetic, but also anti-obesity, antioxidant, and other properties. This preparation tradition is documented in multiple ethnobotanical traditions in Europe, Asia, and the Americas. Phaseolus vulgaris was used as an indigenous plant in Unani and Ayurvedic medicine in India.
Phaseolus vulgaris L. has been described in folk medicine for use in treating acne, bladder conditions, burns, cardiac complaints, as a carminative, depurative, diabetes, diarrhoea, as a diuretic, for dropsy, dysentery, itch, kidney complaints, rheumatism, sciatica, and tenesmus. These wide-ranging historical uses reflect the diverse phytochemical content of the whole bean beyond the alpha-amylase inhibitor fraction alone.
Reports dating from the first half of the 20th century as well as recent publications show contradictory results. It seems that Phaseolus preparations should not be considered the first choice in phytopharmaceutical treatment of diabetes or lead structure research. To be effective, fairly high doses of aqueous extracts need to be given. Because of their fiber content and an α-amylase inhibitory effect, beans might be more useful as food components in preventing or ameliorating type 2 diabetes.
It is important to note that the traditional use of bean pods and the modern supplemental use of concentrated, standardized phaseolamin extract represent distinct preparations. Traditional decoctions of the whole pod are not equivalent in composition or potency to purified protein extracts. The traditional preparations were not specifically seeking to isolate phaseolamin; rather, phaseolamin was later identified as one of several potentially active constituents within Phaseolus vulgaris.
White kidney bean extract contains glycoprotein inhibitors collectively known as phaseolamin, which act as competitive inhibitors of α-amylase by physically occupying the enzyme's active site. Phaseolamin is specific for animal alpha-amylases, having no inhibitory activity towards the corresponding plant, bacterial, and fungal enzymes, or any other hydrolytic enzyme tested. This selectivity for animal (including human and porcine) alpha-amylases is what makes phaseolamin relevant as a dietary supplement; it does not suppress the amylase activity of the microorganisms in the gut.
The biochemistry of inhibition proceeds as follows. The digestion of starch, the main source of carbohydrates in the human diet, begins when food is chewed and mixed with saliva containing α-amylase that randomly hydrolyzes the α(1-4) glycosidic bonds of starch. Because α-amylase cannot cleave the terminal glucosidic bonds and branch points of starch, digestion in the mouth is incomplete; the average chain length is generally reduced from several thousand to less than eight glucose units. Pancreatic amylase then continues this process in the small intestine. Phaseolamin, when present, forms a tight complex with both salivary and pancreatic alpha-amylase, blocking this cascade.
Measurement of the stoichiometry of inhibition showed that a 1:1 complex of alpha-amylase and inhibitor is formed. Optimal inhibitory activity is expressed during preincubation of enzyme and inhibitor at pH 5.5 and 37°C.
Consumption of the alpha-amylase inhibitor causes marginal intraluminal alpha-amylase activity facilitated by the inhibitor's appropriate structural, physico-chemical, and functional properties. As a result, there is decreased postprandial plasma hyperglycaemia and insulin levels, increased resistance of starch to digestion, and increased activity of colorectal bacteria.
Phaseolamin is commonly recognized as a starch blocker, a compound which slows down the digestion of complex carbohydrates, and thus gastric emptying as well, due to the inhibition of α-amylase enzymatic activity. Undigested starch passing into the colon is then subject to bacterial fermentation, which may alter short-chain fatty acid production and the composition of the gut microbiota.
In addition to the primary alpha-amylase inhibitory mechanism, commercial extracts also contain phytohemagglutinin (PHA), a lectin that may have appetite-modulating effects. Phytohemagglutinin is a lectin that binds to receptors on the intestinal lining and may suppress appetite by influencing the release of certain hormones, including decreasing ghrelin. However, this effect is associated specifically with the PHA component rather than with phaseolamin itself. Phaseolamin does not affect gut hormone-mediated appetite modulation because it blocks amylase in the digestion of complex carbohydrates (starch).
The three common bean lectin compounds — phytohemagglutinin (PHA), arcelins, and α-AI (α-AI1, α-AI2, and α-AIL) — have an amino acid sequence homology of about 50–90%. Despite this structural kinship, they have substantially different biological activities. The phaseolamin fraction (α-AI1) is responsible for enzyme inhibition, while the PHA fraction has lectin activity that may affect gut cells independently. Quality commercial extracts are processed to minimize PHA content while retaining α-AI1 activity.
Multiple systematic reviews and meta-analyses have evaluated the evidence for phaseolamin-containing white kidney bean extract (WKBE) on body weight and body composition.
A 2018 systematic review and meta-analysis published in Foods (Udani, Tan, and Molina) selected eleven studies that met inclusion criteria, and found that Phaseolus vulgaris supplementation showed an average effect on weight loss difference of −1.08 kg, and the average effect on body fat reduction was also statistically significant.
A systematic review and meta-analysis of randomized clinical trials of WKBE showed a significant reduction in body fat, however, failed to show significant effects on weight loss. The distinction between effects on fat mass specifically versus total body weight reflects the heterogeneity across trials and the challenge of disentangling changes in lean mass from total weight.
One well-characterized randomized, double-blind, placebo-controlled trial (Jäger et al., 2024; Scientific Reports; NCT02930668) enrolled overweight and moderately obese participants. This study examined the impact of a proprietary aqueous extract from whole dried white kidney beans standardized by its alpha-amylase inhibitor activity (Phase 2 WKBE) on weight management. In a randomized, double-blind, placebo-controlled fashion, 81 participants completed the study and ingested either a high dose of Phase 2 (1000 mg, WKBE HIGH), a low dose (700 mg, WKBE LOW), or a matching placebo (microcrystalline cellulose) three times a day, 30 min before meals, for 12 weeks during a calorie-restricted diet. In a dose-dependent manner, Phase 2 significantly reduced body weight, fat mass, BMI, waist, hip, and — in the WKBE HIGH group — thigh circumference.
A randomized, double-blinded, placebo-controlled study in obese volunteers examined a Phaseolus vulgaris cultivar from Southwestern China. The extract or placebo was given at 2,400 mg per day before each daily meal for 35 consecutive days, and each subject's body weight, fat mass, BMI, blood biochemical parameters, skinfold fat thickness, and waist/hip circumferences were monitored and analyzed. Subjects receiving the extract had significant reduction of body weight, BMI, fat mass, adipose tissue thickness, and waist/hip/thigh circumferences while maintaining lean body mass compared to subjects receiving placebo.
A review of multiple human studies found that several human studies, typically conducted in overweight or obese individuals, explored the effect of WKBE on weight loss and other body composition measurements, with supplement doses typically ranging from 445 to 3,000 mg/d, study durations ranging from 28 to 84 days, and sample sizes ranging from 10 to 120 participants. The majority of studies were randomised, double-blind placebo-controlled trials (RCTs), with some setting a daily calorie intake for participants or complementing with a multi-component weight-loss program. The average weight loss from the human studies discussed was 2.6 kg and ranged from 1.8 to 3.5 kg.
The weight and fat-loss evidence is moderate. The overall body of RCT evidence demonstrates statistically significant effects in many trials, but clinically the magnitudes are modest, and the quality of individual trials is variable. Clinical and preclinical evidence supports the potential of white kidney bean as a nutraceutical for metabolic health, demonstrating consistent reductions in body fat mass, glycemic excursion, and overall weight. Nevertheless, significant limitations persist, including heterogeneity in trial designs, absence of dose standardization, and inadequate long-term safety assessments. Furthermore, the majority of positive trials used a specific proprietary extract; results may not generalize to all commercial preparations.
Consumption of the alpha-amylase inhibitor causes marginal intraluminal alpha-amylase activity facilitated by the inhibitor's appropriate structural, physico-chemical, and functional properties. As a result there is decreased postprandial plasma hyperglycaemia and insulin levels, increased resistance of starch to digestion, and increased activity of colorectal bacteria.
The addition of 3,000 mg of powdered WKBE to butter reduced the glycemic index of white bread by 34% when compared with no WKBE, but this was not evident at the lower dose. This suggests that the glycemic index-lowering effect is dose-dependent and may vary with the food matrix.
Studies show that purified P. vulgaris extract supplementation reduces postprandial glucose, insulin, C-peptide excursions, appetite, and suppressed ghrelin secretion in healthy human subjects.
The extracts are potential ingredients in foods for increased carbohydrate tolerance in diabetics, decreased energy intake for reducing obesity, and for increased resistant starch. Regular consumption of Phaseolus vulgaris extract is also considered beneficial to prevention of diabetes and is inversely associated with the risk of type 2 diabetes.
An early double-blind clinical investigation found that 1,500 mg of Phase 2 administered over the course of 8 weeks showed potential usefulness in the treatment of obesity and hypertriglyceridemia in a study population of 27 obese adults.
An animal study directly examining metabolic syndrome used phaseolamin-containing extract. The efficacy of a per os repeated treatment with P. vulgaris extract (500 mg/kg) was compared with metformin (100 mg/kg) and atorvastatin (10 mg/kg) in a model of metabolic syndrome evoked by prolonged high-fat diet (HFD; week 1 to week 19) in C57BL/6 mice. Bean extract and compounds administration started after metabolic syndrome establishment at week 11. P. vulgaris extract reduced body weight over time and effectively lowered glycaemia, triglycerides, and cholesterol. On week 19, bean extract normalized the HFD-evoked tolerance to glucose and insulin. These preclinical findings are supportive but should not be directly extrapolated to human dosing.
An in vitro assay showed that a commercial phaseolamin sample inhibited α-amylase activity by 99%. This maximal in vitro inhibition has not been replicated at the same magnitude in vivo in humans, as the inhibitor must survive gastric acid and proteolytic digestion before reaching its site of action in the small intestine. Since phaseolamin was first tested for its efficacy as a starch blocker, some results were not as expected, probably because of insufficient inhibitory activity on human alpha-amylase in certain preparations.
The glycemic evidence is preliminary to moderate. There is mechanistically plausible and some clinically demonstrated reduction in postprandial glycemia, but rigorous, large-scale RCTs focused on glycemic outcomes (particularly in people with type 2 diabetes) are limited in number and quality. The evidence does not currently support phaseolamin as a stand-alone antidiabetic treatment.
Preclinical studies provide mechanistic insights. Rodents fed a high-fat diet supplemented with WKBE demonstrated lower LDL cholesterol, reduced serum triglycerides, and improved hepatic lipid metabolism. Histological investigations also showed reduced lipid accumulation in the adipose tissue and liver, consistent with decreased fat storage. These studies confirm that WKBE reduces lipid absorption, enhances lipid catabolism, and mitigates fat deposition. Both human and preclinical studies provide evidence of WKBE's role in ameliorating lipid profiles, modulating lipid metabolism, and contributing to its overall anti-obesity effects.
Regular intake of Phaseolus vulgaris containing soluble fibers and resistant starch has been reported to decrease the body's glycemic index, reduce low-density lipoprotein (LDL), increase high-density lipoprotein (HDL) levels, and positively influence risk factors for metabolic syndrome, thereby reducing the risk of cardiovascular disease, obesity, and diabetes. However, it should be noted that these lipid effects in human studies are associated with consumption of whole bean preparations rich in fiber, resistant starch, and multiple bioactives, not necessarily with isolated phaseolamin alone. The independent lipid-modulating contribution of phaseolamin as distinct from fiber and other bean constituents has not been clearly delineated in human clinical trials.
Evidence for direct lipid-lowering effects attributable specifically to phaseolamin is weak to preliminary. Preclinical rodent data are supportive, and human observational or multi-component-intervention data are suggestive, but well-controlled trials isolating phaseolamin's contribution to lipid outcomes in humans are lacking.
Increased resistance of starch to digestion and increased activity of colorectal bacteria have been reported as downstream consequences of α-amylase inhibition. When phaseolamin prevents starch from being broken down in the small intestine, a greater proportion of dietary starch reaches the colon as a substrate for microbial fermentation. This is analogous to the behavior of dietary fiber and resistant starch and may result in shifts in the composition of the gut microbiome. A prolonged treatment with a standardized extract of P. vulgaris containing phaseolamin has been demonstrated to significantly reduce several pathological features related to a metabolic syndrome-like condition induced in mice by high-fat diet. Research into the specific microbial taxa affected, and whether these changes are clinically beneficial in humans, is ongoing and the current evidence is largely preclinical.
Evidence for gut microbiota modulation is preliminary and largely preclinical. Human studies specifically examining phaseolamin's effects on gut microbiota composition and diversity are limited in number and scale.
Phaseolamin is available as a dietary supplement in various forms, including powders, tablets, and capsules.
The following dosages have been reported specifically within cited clinical studies:
These figures represent dosages employed in research settings and are not recommendations. Formulation potency varies considerably between commercial products; standardization to alpha-amylase inhibitory units (AAIU) per gram is the relevant quality metric.
The FDA issued a Generally Recognized as Safe (GRAS) notice to Pharmachem Laboratories for its Phase 2 Carb Controller® white kidney bean extract. The FDA notice stated: "Based on the information provided by Pharmachem, as well as other information available to FDA, the agency has no questions at this time regarding Pharmachem's conclusion that white kidney bean extract is GRAS under the intended conditions of use." The notification resulted from a dossier of information submitted by Pharmachem regarding the composition, safety, and clinical human evidence demonstrating that Phase 2 is a safe addition to foods and beverages.
In the United States, dietary supplements, including those containing white kidney bean extracts, are regulated by the Food and Drug Administration (FDA). FDA regulatory standards mandate accurate labeling and safety for these supplements.
Previous toxicological studies in rats showed no mortality or significant toxicity following oral (gavage) administration of single doses up to 5 g/kg body weight or multiple doses (90 days) up to 1 g/kg bw/day of the Phase 2 extract alone.
The no-observed-effect level (NOEL) seen in the 4-week rat study was equivalent to the highest Blockal dose tested (2 g/kg bw/day), which provided 1,112 mg/kg/day of Phase 2 white kidney bean extract. The results of these studies support and are consistent with the safety of the marketed dietary supplement Blockal, and indirectly, the safety of its main ingredient, Phase 2 Starch Neutralizer (Phaseolamin 2250), a standardized extract derived from the common white kidney bean.
The rats treated with 100, 500, and 1,500 mg/kg of the commercial phaseolamin sample did not show physical signs of extract-induced toxicity, and there were no treatment-related deaths. Additionally, there were no symptoms of starch accumulation in the intestinal tract, such as diarrhea.
Safety trials establish a maximum daily intake of up to 6–10 g for a 70 kg adult, although most supplements recommend lower doses. Animal studies corroborate these findings, reporting no adverse effects at substantially higher relative doses.
Most animal and human studies indicate that white kidney bean extract is well tolerated, with no adverse effects at commonly administered doses.
Raw Phaseolus vulgaris beans contain phytohemagglutinins (PHAs), lectins that can cause toxicity if the beans are consumed raw or undercooked. Phytohemagglutinins, a class of lectins present at high levels in raw common beans, may affect animal growth by interfering with the digestion and absorption of nutrients in the gastrointestinal tract. Raw white kidney beans may contain 20,000–70,000 HA units per gram compared to 200–400 HA units in cooked beans. Colored beans, particularly large-seeded kidney beans, have high levels of PHAs; small white navy beans are reported to have negligible levels of these lectins. Red kidney beans have about three times the amount present in white kidney beans.
Standardized commercial extracts are processed specifically to reduce PHA content. Phase 2® is prepared using thermal processing conditions to substantially inactivate hemagglutinating activity and trypsin-inhibiting activity while preserving substantial α-amylase-inhibiting activity. Production lots are standardized to contain less than 3,400 HA units/g. A commercial phaseolamin sample exhibited low hemagglutination activity with 8 HU/50 μL for human type A+ erythrocytes and 4 HU/50 μL for human type B+, AB+, and O+ erythrocytes.
Other white kidney bean compounds that might be present in small amounts in commercial extracts include trypsin and chymotrypsin blockers, which can block the protein-digesting enzymes trypsin and chymotrypsin. Commercial standardized extracts are tested and limited for trypsin inhibitor activity (TIA), as noted in subchronic toxicity specifications above.
A key safety and efficacy consideration is the variability among commercial products. The efficacy and safety of the amylase inhibitor extracts depend on the processing and extraction techniques used. Products that have not been properly thermally processed may retain higher levels of PHAs and trypsin inhibitors. The potency of α-amylase inhibitory activity also varies substantially across commercial preparations, which affects both efficacy and the reliability of applying research findings to a given product.
Because phaseolamin causes undigested starch to enter the colon, increased bacterial fermentation of this substrate may produce gas and cause bloating or flatulence in some individuals. This mechanism is analogous to that of dietary fiber. These effects have generally been described as mild in human trials at commonly studied doses, though systematic reporting of adverse events has been inconsistent across trials.
Health conditions that Phaseolamin may help support.
Phaseolamin is an alpha-amylase inhibitor derived from white kidney beans (Phaseolus vulgaris) that blocks starch digestion, reducing carbohydrate caloric absorption. A 35-day RCT in obese subjects showed 2.24 kg weight loss with Phaseolus vulgaris extract versus 0.29 kg with placebo. A 2024 double-blind RCT confirmed weight and fat loss with standardized extract over 12 weeks.
Body systems that Phaseolamin may help support.
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