IngredientsAnkaflavin is a naturally occurring polyketide secondary metabolite produced by fungi of the genus Monascus. Typical Monascus pigments, associated mainly with Monascus purpureus, include three subgroups differing in color: monascin and ankaflavin (yellow), rubropunctatin and monascorubrin (orange), and rubropunctamine and monascorubramine (red). Ankaflavin belongs to the yellow pigment subgroup and, structurally, to the azaphilone family of compounds. These azaphilones are a family of natural cyclic compounds that have at least one chiral center.
Ankaflavin has the molecular formula C23H30O5 and is classified as a yellow-colored pigment. Monascus pigments originate from medium-chain fatty acids such as octanoic acid, which are synthesized by the fatty acid metabolic pathway and bind to a chromophore structure through a transesterification reaction; the reduction of the orange pigment monascorubramine then gives rise to the yellow pigment ankaflavin.
Within the group of Monascus pigments, yellow and orange pigments are biosynthetically produced, whereas the red pigments are formed by the chemical reaction of orange Monascus pigments with compounds containing a free amino group. The biosynthetic pathway of ankaflavin involves polyketide synthase (PKS) enzyme clusters: the Mrpig A gene encodes a PKS and catalyzes biosynthesis of the key aromatic ring intermediate, while the Mrpig N gene encodes a FAD-dependent monooxygenase that catalyzes hydroxylation at the C-4 carbon, thus generating the key azaphilone scaffold.
Ankaflavin is most often studied in combination with, or compared to, its structural analogue monascin (molecular formula C21H26O5). The two compounds differ in the length of a side-chain aliphatic group, with ankaflavin possessing a longer alkyl moiety. Monascin and ankaflavin are azaphilone compounds with similar structures that exhibit multiple beneficial effects including anti-inflammation, anti-oxidation, anti-diabetes, immunomodulation, attenuation of Alzheimer's disease risk factor, and anti-tumorigenic effects.
The Monascus fungus has been identified in several species, but the most relevant species in the food industry are Monascus purpureus, Monascus ruber, and Monascus pilosus. The yellow pigments monascin and ankaflavin are constituent metabolites of M. purpureus, M. pilosus, and M. ruber. Research into strain-specific production has revealed differences: M. purpureus can produce monascin and ankaflavin in a correlated manner, whereas M. ruber produces monascin with minimum ankaflavin; M. purpureus is capable of producing citrinin but is unlikely to produce monacolin K, whereas M. ruber produces monacolin K but not citrinin.
Red yeast rice is a bright reddish-purple fermented rice which acquires its color from being cultivated with the mold Monascus purpureus. Red yeast rice is produced by cultivating the mold species Monascus purpureus on rice for 3–6 days at room temperature; the rice grains turn bright red at the core and reddish-purple on the outside. The fully cultured rice is then either sold as the dried grain, cooked and pasteurized to be sold as a wet paste, or dried and pulverized to be sold as a fine powder.
Beyond rice substrates, ankaflavin is also produced when M. purpureus is fermented on dioscorea (yam) root: Red mold dioscorea (RMD) is fermented M. purpureus in a dioscorea substrate, which can produce large quantities of the yellow pigments monascin and ankaflavin. The traditional method for the production of red yeast rice-related foods was solid-state culture; however, pigments are now industrially produced by simple extraction and concentration processes from red yeast rice proliferated by an aerated and agitated liquid-state culture method.
Red yeast rice with a high content of yellow Monascus pigments is marketed under the name Ankascin®, which has already been commercialized and approved by the US FDA as a new dietary ingredient (NDI). Ankascin 568-R Plus (Sunway Biotech Co., Ltd., Taiwan) contains an extract focusing on two compounds — ankaflavin and monascin — rather than the lovastatin-type monacolins normally found in red yeast rice; it was accepted by the US FDA as a new dietary ingredient in 2018. Ankascin 568-R is subjected to a patented extraction process that removes citrinin, a toxic by-product of the fermentation process. The product is available in capsule form; in one studied formulation, the treatment group received 500 mg of Ankascin 568 Plus per day, which included 110 mg of Ankascin 568-R.
In addition to its culinary use, red yeast rice has also been used in Chinese herbology and Traditional Chinese Medicine, possibly during the Tang dynasty around AD 800. Red yeast rice is described in the Chinese pharmacopoeia Ben Cao Gang Mu by Li Shizhen.
Red yeast rice, produced by the fermentation of cooked rice kernels with a Monascaceae mold, Monascus purpureus, has long been used to treat blood circulation stasis, indigestion, diarrhea, and limb weakness in East Asian countries.
Red yeast rice has been used to produce alcoholic beverages and various fermented foods in China and Korea since ancient times; it has also been used to produce tofuyo (Okinawan-style fermented tofu) in Japan since the 18th century. In traditional Chinese cooking, red yeast rice served as a natural red pigment, flavor enhancer, and food preservative — it colors and flavors meats such as char siu (barbecued pork) and Peking duck, and features in fermented products like red bean curd (tofuyo), rice vinegar, and rice wines.
During the Ming Dynasty, red yeast rice was described as "sweet in flavor and warm in property." The genus Monascus has been used for centuries in Asia as a source of pigment for coloring traditional foods, such as Peking duck.
Red pigments extracted and isolated from red yeast rice have been produced as natural pigments on an industrial scale since 1945. Since the carcinogenicity of synthetic red pigments was discovered, the consumption of natural pigments made by Monascus fungi has increased.
Ankaflavin itself, as a discrete isolated compound, is a product of modern analytical chemistry. The folk use of red yeast rice preparations encompassed the full complement of Monascus metabolites, of which ankaflavin was one component. No historical tradition identified ankaflavin specifically; attributing traditional therapeutic uses to the isolated compound is therefore an inference from the whole-food context.
There are six known Monascus pigments in three colors: orange (monascorubrin and rubropunctatin), yellow (ankaflavin and monascin), and red (monascorubramine and rubropunctamine). In total, twenty-five pigments have been isolated from red yeast rice, including rubropunctamine, rubropunctatin, monascorubramine, monascorubrin, monascin, and ankaflavin, as well as xanthomonasin A and B, monankarin A, monasfluore A and B, monapurones, monascopyridines, and others.
More than 101 chemical constituents have been isolated from red yeast rice, mainly consisting of monacolins, pigments, organic acids, sterols, decalin derivatives, flavonoids, polysaccharides, and other compounds.
Within this complex mixture, ankaflavin and monascin are singled out for contemporary functional food research. The Monascus yellow pigments, in particular monascin and ankaflavin, are the focus of current Monascus functional food research owing to their multiple health benefits. Monascin and ankaflavin act as activators of the PPARγ agonist/Nrf-2 pathway, which subsequently ameliorates metabolic syndrome.
One of the most characterized mechanisms of ankaflavin is its activity at the peroxisome proliferator-activated receptor gamma (PPARγ): ankaflavin (at a dose of 10 mg/kg bw in an animal model) exerted PPARγ agonist activity, thereby enhancing insulin sensitivity as indicated by hepatic GLUT2 translocation, PTP1B suppression, and glucose uptake, by downregulating blood glucose and upregulating pancreatic and duodenal homeobox-1 and Maf-A expression and increasing insulin secretion. The protective effects of ankaflavin against diabetes are mediated by the upregulation of the Nrf2 signaling pathway, which enhances antioxidant activity and serves as a PPARγ agonist to enhance insulin sensitivity.
Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed mice.
Ankaflavin and monascin exhibit an anti-obesity effect via the suppression of differentiation and lipogenesis. The anti-obesity effect of the yellow Monascus pigments is related to down-regulating the transcription factors C/EBPβ/PPARγ expression, inhibiting lipogenesis by increasing lipase activity, and suppressing Niemann-Pick C1 Like 1 (NPC1L1) protein expression associated with small intestine tissue lipid absorption.
Treatments with Monascus pigments including ankaflavin down-regulate the protein expression of inducible nitric oxide synthase (iNOS) and suppress the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Ankaflavin treatment was also found to reduce the production of inflammatory factors, such as TNF-α and IL-1β, in an animal diabetes model.
Ankaflavin elevates glutathione (GSH) levels in the liver and pancreas of methylglyoxal-induced rats; GSH may lower the methylglyoxal level, which attenuates the formation of advanced glycation end-products (AGEs) in the serum, kidney, liver, and pancreas.
Three active components of Monascus-fermented red yeast rice — monacolin K, monascorubrin, and ankaflavin — have documented antiproliferative effects against tumor cells. Ankaflavin from Monascus-fermented red rice has been shown to exhibit a selective cytotoxic effect and to induce cell death in HepG2 (hepatocellular carcinoma) cells. These azaphilone compounds demonstrate a range of biological activities that include anticancer and anti-inflammatory activities, as well as antidepressant, anti-osteoporosis, and anti-diabetic effects.
Monascin and ankaflavin, the yellow pigments produced by Monascus species, have been proven to possess hypolipidemic functions. In one study, equal dosages of monascin, ankaflavin, and monacolin K were orally administered to hamsters fed a high-cholesterol diet for 6 weeks. The results indicated that monascin and ankaflavin were similar to monacolin K in significantly reducing total cholesterol (TC), triglycerides (TG), and LDL-C levels in serum and lipid plaque in the heart aorta (p < 0.05).
Monascin and ankaflavin were found to reduce serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), and to reduce aortic lipid plaques, confirming hypolipidemic effects in animal models.
Monascin and ankaflavin not only possess pleiotropic bioactivities, but are also more potent than monacolin K in lowering lipid levels and have lower toxicity — a finding emerging from preclinical comparisons, not yet confirmed in humans.
The most cited clinical evidence for ankaflavin-containing preparations comes from a trial described in a review of Ankascin 568-R: In a clinical study, 57 qualified subjects were initially enrolled, with 40 subjects assigned to test and placebo groups. The dietary behavior and lifestyle of the subjects did not change during the study, and no clinical syndromes or discomfort were recorded. There were no differences in anthropometric measurements after eight weeks of intervention between the two groups. Total cholesterol and LDL-C levels in the treatment group (500 mg of Ankascin 568 Plus per day, including 110 mg of Ankascin 568-R) decreased significantly by 11.9% and 19.0%, respectively.
Evidence strength assessment: The available human evidence is limited to a small, single study (n = 40, 8-week duration) in subjects with metabolic syndrome. The trial shows promising lipid-lowering results, but the findings require replication in larger, independently conducted randomized controlled trials before firm conclusions can be drawn.
In a rat model using a high-fat, high-fructose diet, monascin improved blood glucose regulation and performed antioxidant and hypolipidemic effects, while ankaflavin performed anti-inflammatory and hypolipidemic effects. Oral administration of red mold dioscorea, monascin, and ankaflavin to high-fat/high-fructose-fed rats for 10 weeks showed that all three were able to prevent the development of metabolic disorder.
In a separate animal model of methylglyoxal-induced diabetes in Wistar rats: diabetes was induced by treating rats with MG (600 mg/kg bw) for 4 weeks. Ankaflavin (10 mg/kg bw) exerted PPARγ agonist activity, thereby enhancing insulin sensitivity via hepatic GLUT2 translocation, PTP1B suppression, and glucose uptake, and downregulating blood glucose. Ankaflavin treatment also reduced the production of inflammatory factors including TNF-α and IL-1β in this model.
Evidence strength assessment: Preclinical (animal) evidence for anti-diabetic and metabolic effects is substantial and mechanistically characterized. No dedicated human clinical trials specifically targeting glucose regulation with isolated ankaflavin or ankaflavin-dominant preparations were identified in the available literature.
Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice.
The yellow pigments monascin and ankaflavin of Monascus purpureus-fermented rice were proven to regulate ethanol-induced damage in HepG2 cells. In an animal study using C57BL/6J mice fed the Lieber–DeCarli liquid alcohol diet for 6 weeks, monascin and ankaflavin significantly reduced serum aspartate aminotransferase and alanine aminotransferase activity, as well as total liver cholesterol and triglyceride levels. Histopathological results indicated that monascin and ankaflavin prevented lipid accumulation in the liver.
Evidence strength assessment: Evidence is entirely preclinical (cell lines and mouse/rat models). No human trials on NASH or alcoholic liver disease with ankaflavin have been identified.
Monascin and ankaflavin are found to strongly inhibit differentiation and lipogenesis and stimulate lipolysis effects in a 3T3-L1 preadipocyte model. The anti-obesity effect of yellow Monascus pigments is related to down-regulating the transcription factors C/EBPβ/PPARγ expression, inhibiting lipogenesis by increasing lipase activity, and suppressing NPC1L1 protein expression associated with small intestine tissue lipid absorption.
Evidence strength assessment: The anti-obesity evidence for ankaflavin rests on cell culture studies and obese animal models. No human clinical trials on ankaflavin for obesity management have been identified in the available literature.
Ankaflavin from Monascus-fermented red rice exhibits a selective cytotoxic effect and induces cell death on HepG2 (hepatocellular carcinoma) cells, as reported in a study published in the Journal of Agricultural and Food Chemistry (Su et al., 2005).
In cytotoxicity comparisons across Monascus pigments, ankaflavin had an IC50 of 21.8 μM against tested cancer cell lines, compared with monascin (IC50 = 29.1 μM) and orange pigment-derived monaphilones (IC50 = 1.0–3.8 μM), indicating moderate cytotoxicity relative to other Monascus metabolites.
Several biological activities were associated with red yeast rice pigments in in vitro studies: antifungal, antiviral, antioxidant, cytotoxic, nematicidal, and anti-inflammatory. A red yeast rice fraction containing only red Monascus pigments was also associated with the induction of cellular senescence of highly proliferating HepG2 cancer cells.
Studies in rodents have reported reductions in the number of tumors, mean tumor volume, and tumor burden.
Evidence strength assessment: All anticancer evidence for ankaflavin is limited to in vitro (cell culture) and some animal studies. There are no human clinical trials. The cytotoxic activity in cell lines does not directly translate into established clinical anti-tumor efficacy. This area of research is preliminary and exploratory.
Monascus-fermented monascin and ankaflavin have been shown to improve memory and learning ability in amyloid-β protein intracerebroventricular-infused rats via the suppression of Alzheimer's disease risk factors. Monascin and ankaflavin are reported in a 2017 review to exhibit attenuation of Alzheimer's disease risk factors as one of their documented beneficial effects, though the evidence cited in that review is drawn from preclinical animal models.
Evidence strength assessment: Neuroprotective and Alzheimer's disease-related activity is supported only by animal experiments. No human trials exist. This remains a speculative and emerging area.
Comparative animal studies demonstrated that monascin and ankaflavin, given orally to hamsters fed a high-cholesterol diet for 6 weeks, were similar to monacolin K in significantly reducing lipid plaque in the heart aorta. Ankaflavin has been characterized as an active compound with anti-atherosclerotic activity, based on this and related animal research. No human trials targeting atherosclerosis endpoints with ankaflavin have been identified.
Among the secondary metabolites of red mold rice, the yellow pigments monascin and ankaflavin are proven as functional compounds for the prevention of cardiovascular disease, fatty liver, and lipogenesis. Both monascin and ankaflavin achieve anti-inflammatory effects by reducing inflammatory factor levels. Mechanistically, this occurs through iNOS suppression and reduction of TNF-α, IL-1β, and IL-6 in both cell culture and animal studies. This anti-inflammatory activity is consistently reported across multiple preclinical models but has not been specifically evaluated in human inflammatory disease trials.
Ankaflavin is not typically available as a standalone isolated supplement at the time of the available literature. It is most commonly delivered via standardized red yeast rice extracts. The following dosages appear in the primary research:
No universal consensus dosage for ankaflavin in humans has been established. The animal study dosages cannot be directly extrapolated to humans without pharmacokinetic bridging studies.
The primary safety concern associated with all Monascus-fermented products, including those containing ankaflavin, is co-production of the mycotoxin citrinin: Citrinin is a mycotoxin produced by fungi that is potentially carcinogenic and nephrotoxic — a substance that causes a decline in kidney function. Citrinin contamination is a concern in food safety and is one of the main issues limiting the use of M. purpureus fermentation products. Since citrinin content in Monascus-fermented products is still a safety concern, some researchers have attempted to reduce citrinin production; phosphate–ethanol extraction has been shown to be effective in the removal of citrinin.
Ankascin 568-R Plus contains an extract focusing on ankaflavin and monascin rather than the lovastatin-type monacolins normally found in red yeast rice, but many other red yeast rice preparations on the market do contain monacolin K. Products that are not specifically standardized to remove monacolins carry the risk of statin-like adverse effects, including myopathy.
The EFSA has noted a preclinical safety signal of relevance: In 3-day-old chicken embryos, incubation at 38.5°C for 9 days with the pigments monascorubrin, rubropunctatin, monascin, and ankaflavin — purified from the mycelium of M. purpureus — led to malformations and lethality. This finding is from an embryotoxicity model and its relevance to human exposure has not been established, but it is a documented caution identified in regulatory review.
Safety evaluation of M. purpureus-fermented red mould rice was assessed in albino rats. Acute and sub-chronic toxicity studies were conducted on both sexes of albino rats. Feeding acute doses of red mould rice at 0.5, 1.0, 2.5, and 5.0 g/kg body weight to rats did not cause any symptoms of toxicity or mortality. Testing confirmed that none of aflatoxin B1, B2, G1, and G2 is produced by Monascus sp. Ames testing showed that Monascus pigments do not act as carcinogens, and the pigments did no harm to rats that were fed them.
In the hamster comparison study referenced above, monascin and ankaflavin were found to have a more favorable side-effect profile with respect to creatinine phosphokinase (CPK/CK) elevation than monacolin K at the same dosages — a marker associated with myopathy risk. Monacolin K is a well-known hypolipidemic medication, but its side effect of myopathy is a concern. Monascin and ankaflavin have been proven to possess hypolipidemic functions without the same degree of CK elevation.
Ankascin®, a red yeast rice preparation standardized for yellow Monascus pigments including ankaflavin and monascin, has been approved by the US FDA as a new dietary ingredient (NDI). In the European Union, EFSA's safety assessment of red yeast rice has focused principally on monacolins. The EFSA Panel considered that the available preclinical data do not allow derivation of a safe intake for monacolins in red yeast rice; yellow pigment-specific safety data has not been the primary subject of EFSA opinions to date.
Ankaflavin is a well-characterized secondary metabolite of Monascus fermentation, structurally belonging to the azaphilone class of polyketides. Its mechanisms of action — including PPARγ/PPARα agonism, AMPK activation, Nrf2 induction, anti-inflammatory cytokine suppression, and anti-adipogenic transcription factor modulation — are robustly characterized at the molecular and preclinical level. The body of animal research is extensive, covering hypolipidemia, anti-obesity, anti-diabetes, anti-NASH, neuroprotection, and anticancer endpoints.
Clinical human evidence remains sparse. The most significant human data is a single, small (n = 40), 8-week, placebo-controlled trial using an Ankascin 568-R-containing product showing significant LDL-C and total cholesterol reduction in metabolic syndrome patients. This trial, while promising, is insufficient by itself to establish clinical efficacy. The field requires larger, independently replicated, multi-center randomized controlled trials to confirm preclinical findings in humans across the many proposed indications.
Health conditions that Ankaflavin may help support.
Body systems that Ankaflavin may help support.
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