Annatto (Bixa orellana)

Bixa orellana
Evidence Level
Preliminary
6 Clinical Trials
6 Documented Benefits
1/5 Evidence Score

Annatto is the red-orange seed of the achiote shrub (Bixa orellana), used as a spice and natural food color in cheese, butter and snacks. Its color comes from two carotenoids: fat-soluble bixin and its water-dispersible relative norbixin. In the US, annatto extract made from the seed is a listed color additive exempt from certification for foods and drugs, and in the EU it is additive E160b, with acceptable daily intakes set for bixin and norbixin. The seed also contains delta- and gamma-tocotrienols and geranylgeraniol, which are sold as separate concentrated extracts; their research does not describe whole annatto. Human studies of the seed or its color extracts are few and small: an 8-week egg trial found no lipid changes versus egg whites, and short trials from one research group measured lab oxidation markers. Allergic reactions, including rare anaphylaxis, have been reported.

Studied Dose No established supplement dose. Human studies used food-color amounts: ground annatto at about 1.2 mg bixin/kg a day for 8 weeks, color extracts at 0.05 mg carotenoid/kg a day for 7 days, and single meals with 1.2 mg/kg bixin or 0.06 mg/kg norbixin.
Active Compound Bixin (fat-soluble) and norbixin (water-dispersible) apocarotenoids from the seed coat; the seed also contains delta- and gamma-tocotrienols and geranylgeraniol.

Benefits

Blood lipids in healthy adults eating annatto-enriched eggs

In an 8-week randomized trial, 105 healthy adults ate two eggs, two eggs with ground annatto, or two egg whites daily. Triglycerides, LDL and HDL cholesterol, apolipoproteins and lipoprotein particle measures did not change over time or differ between groups, so the trial shows no lipid effect, favorable or unfavorable.

Fullness ratings after eight weeks of annatto-enriched eggs

In a second report from the same 105-person egg trial, the hunger hormone ghrelin and satiety ratings did not differ between groups. Only within the annatto egg group did satisfaction and fullness ratings rise after 8 weeks. Without a between-group difference, this does not show that annatto affects appetite.

Blood oxidation markers after one high-calorie meal

In a crossover study of 12 healthy adults, a high-fat, high-carbohydrate meal eaten with a small dose of norbixin was followed by lower blood markers of inflammation and lipid oxidation over the next 1 to 2 hours than the same meal without it; bixin had a partial effect on lipid oxidation. One small study from one research group, a single meal and short-term lab markers only.

Lab-tested LDL and red blood cell oxidation over seven days

In a 16-person crossover, 7 days of annatto color extract capsules at a food-color dose left routine blood tests and most oxidation markers unchanged versus placebo, with LDL oxidation changes short of significance. A companion placebo-controlled report from the same group found red blood cells resisted lab-induced damage and lipid oxidation better after bixin or norbixin. Short-term lab markers at food-color doses, not health outcomes.

Absorption of bixin and norbixin from annatto food color

After 7 volunteers swallowed a single dose of commercial annatto color containing 16 mg of bixin, both bixin and norbixin appeared in the blood. Bixin was generally gone within 8 hours and norbixin within 24 hours, with wide differences between people, so the pigments do not appear to linger in the blood after one dose.

Lipid and oxidation markers in animal studies

In laboratory animal work, bixin at 10 to 100 mg/kg reduced artery lesions and oxidation markers in cholesterol-fed rabbits and lowered glucose and lipids in diabetic rats, while norbixin at a high dose raised lipids and acted as a pro-oxidant in rats. These doses far exceed food use, and none of this has been tested in people.

Mechanism of action

1

Two pigments with different solubility

Bixin is an oil-soluble apocarotenoid and norbixin is its water-dispersible form, obtained when the seed color is extracted with alkali. In a human absorption study, both appeared in plasma after one dose of bixin-based color, with norbixin persisting longer, and in rats the two had opposite effects on lipids and oxidation.

2

Antioxidant chemistry studied mainly in the lab

Like other carotenoids, bixin and norbixin have long chains of conjugated double bonds that can react with oxidants. Reduced lipid oxidation has been measured in rabbits and in short human studies of lab markers, but no study has shown a lasting antioxidant effect in people eating annatto.

3

Effects on drug-metabolizing liver enzymes in cells

In a human liver cell line, bixin raised expression of the genes for the enzymes CYP1A1 and CYP1A2, which help clear some medicines, while norbixin did not. Earlier rat work cited by the same authors found similar enzyme induction with annatto. Whether dietary amounts do this in people is untested.

4

Residual seed protein as an allergy trigger

Annatto color is a carotenoid extract, but in one allergy case the patient had IgE antibodies to a protein of about 50 kD found in the dye, pointing to leftover seed protein, not the pigment, as the likely cause of the reaction.

Clinical trials

1
Annatto-Enriched Eggs for 8 Weeks in 105 Healthy Adults (EGGANT, Two Reports)
PubMed

Parallel randomized trial in Colombia comparing two eggs a day, two eggs with ground annatto, or two egg whites for 8 weeks, measuring blood lipids, with satiety results from the same trial published separately in Foods in 2024 (Galvis et al. 2023, Nutrients)

105 healthy adult men and women who completed the trial (109 randomized); annatto dosed at the equivalent of 1.2 mg bixin per kg body weight a day.

No significant changes over time or between groups in triglycerides, LDL or HDL cholesterol, apolipoproteins or lipoprotein subfractions. In the satiety report, ghrelin and satiety ratings did not differ between groups; only within the annatto egg group did satisfaction and fullness ratings rise (Hedges g 0.43 and 0.38). Egg whites as control could not be fully masked.

2
Annatto Color Extracts for 7 Days and Oxidation Markers in 16 Adults (Crossover)
PubMed

Randomized, double-blind, placebo-controlled Latin square crossover of daily capsules of bixin-rich annatto powder, norbixin powder, lycopene or placebo (0.05 mg carotenoid per kg) for 7 days each, measuring ex vivo LDL oxidation and blood markers; red cell results at the same dose and duration were published separately by the same group in Nutr Res in 2020 (Conte et al. 2019, J Nutr Metab)

16 healthy young adults (8 men, 8 women), each taking all four treatments.

No treatment changed routine blood chemistry or most oxidative stress markers. Versus placebo, the bixin-rich powder lowered the ex vivo LDL oxidation rate and nitric oxide metabolites only at p < 0.1, short of the usual significance threshold. The companion paper reports higher lab-tested red cell membrane resistance and less red cell lipid peroxidation after bixin or norbixin versus placebo (P < .05). Lab markers at food-color doses, not health outcomes.

3
Bixin or Norbixin With One High-Calorie Meal in 12 Adults (Crossover)
PubMed

Randomized controlled crossover in which a high-fat, high-carbohydrate meal was eaten with no carotenoid (placebo), with bixin 1.2 mg/kg, or with norbixin 0.06 mg/kg, with blood sampled over 4 hours (Roehrs et al. 2017, Food Res Int)

12 healthy adults (6 men, 6 women).

According to the abstract, the norbixin meal lowered postprandial IL-1, IL-6, TNF-alpha and lipid oxidation at 60 to 120 minutes, while bixin only partly prevented the rise in lipid oxidation; neither changed routine blood chemistry. A single-meal study of short-term blood markers from one research group; longer use was not tested.

4
Single Dose of Annatto Food Color: Bixin and Norbixin in Plasma (7 Volunteers)
PubMed

Uncontrolled absorption study after one dose of 1 mL commercial annatto food color (16 mg cis-bixin in soybean oil) (Levy et al. 1997, Analyst)

7 volunteers.

Both bixin and norbixin were detected in plasma, with norbixin at higher levels than bixin over 2 to 8 hours. Bixin was generally cleared by 8 hours and norbixin by 24 hours, with considerable variation between individuals. No control group and no health outcomes.

5
Bixin in Cholesterol-Fed Rabbits (Animal Study, Not a Human Trial)
PubMed

60-day study in rabbits on a 0.5% cholesterol diet given bixin at 10, 30 or 100 mg/kg, compared with untreated cholesterol-fed rabbits and a statin group (Somacal et al. 2015, Mol Cell Biochem)

Rabbits; no people.

Bixin reduced aortic lesion extent by up to 55% and was accompanied by 60% lower lipid peroxidation, 37% lower non-HDL cholesterol, 41% lower triglycerides and higher HDL cholesterol versus untreated cholesterol-fed rabbits. Doses were far above food-color intake, and the result has not been tested in people.

6
Bixin Versus Norbixin in Diabetic Rats (Animal Study, Not a Human Trial)
PubMed

30-day study in chemically induced diabetic rats given bixin or norbixin at 10 or 100 mg/kg, with metformin and insulin comparison groups (Roehrs et al. 2014, Int J Endocrinol)

Rats; no people.

Bixin lowered blood glucose, LDL cholesterol and triglycerides and reduced oxidation markers. Norbixin changed most measures little, and at 100 mg/kg it raised LDL cholesterol and triglycerides and acted as a pro-oxidant. The two main annatto pigments behaved differently, so results for one cannot be assumed for the other.

Side effects and drug interactions

Common Potential side effects

Allergic reactions to annatto have been reported, including hives, swelling and, rarely, anaphylaxis with a sharp drop in blood pressure after eating an annatto-colored cereal. Leftover seed protein in the color is a suspected trigger. People who have reacted to annatto-colored foods should avoid it.
In an older oral challenge study of 56 people with chronic hives, annatto extract at the amount found in 25 g of butter triggered a reaction in 26%, a rate higher than any of the synthetic food dyes tested in the same series (9% to 17%).
As a food color, EFSA has set acceptable daily intakes of 6 mg bixin and 0.3 mg norbixin per kg body weight per day; estimated norbixin intake reached its limit only at high intake levels in toddlers in one country.
Short human studies at food-color doses (7 days to 8 weeks) reported no changes in routine blood chemistry or blood lipids. Long-term safety of annatto at supplement doses has not been studied.
Concentrated tocotrienol and geranylgeraniol extracts from annatto are different products with their own dose and safety data; a 90-day rat study of concentrated annatto geranylgeraniol found forestomach effects at all doses tested and liver effects at the higher doses.

Important Drug interactions

No human drug-interaction studies of annatto seed or its color extracts were found.
In cell studies, bixin increased CYP1A1 and CYP1A2 gene expression, enzymes that help clear some medicines; the relevance of dietary or supplement intake is unknown. People on medicines with a narrow dosing range should ask a pharmacist before using concentrated annatto products.
Concentrated annatto tocotrienol or geranylgeraniol supplements carry their own interaction cautions; check those products separately.

Frequently asked questions about Annatto (Bixa orellana)

Is annatto the same as an annatto tocotrienol or geranylgeraniol supplement?

No. Those are concentrated extracts of compounds from the seed, sold as separate products and studied at doses far above what annatto color supplies. Their trial results describe the concentrated extract, not annatto seed or the food color, which contributes mainly bixin and norbixin.

Why does annatto appear on so many food labels?

Annatto extract is a natural color used in cheese, butter, cereals and snacks. In the US it is a listed color additive exempt from certification, and the label of the color additive itself must state that the color comes from annatto seed. In the EU it appears as E160b.

Can annatto cause a reaction in sensitive people?

Yes, though it appears to be uncommon. Case reports describe hives, swelling and rarely anaphylaxis after annatto-colored foods, and an older challenge study found reactions in about a quarter of people with chronic hives. Anyone with a suspected reaction should see an allergist.

What have human studies of annatto measured?

Only a handful of small studies exist. An 8-week egg trial in 105 adults found no lipid changes versus egg whites, and short studies from one research group measured lab oxidation markers after single meals or 7 days of color extract capsules. None tested a health outcome.

What is Annatto?

Annatto is the red-orange seed of the achiote shrub (Bixa orellana), used as a spice and natural food color in cheese, butter and snacks. Its color comes from two carotenoids: fat-soluble bixin and its water-dispersible relative norbixin.

What is Annatto used for?

Annatto is researched primarily for Antioxidant. In an 8-week randomized trial, 105 healthy adults ate two eggs, two eggs with ground annatto, or two egg whites daily. Triglycerides, LDL and HDL cholesterol, apolipoproteins and lipoprotein particle measures did not change over time or dif…

What is the recommended dosage of Annatto?

No established supplement dose. Human studies used food-color amounts: ground annatto at about 1.2 mg bixin/kg a day for 8 weeks, color extracts at 0.05 mg carotenoid/kg a day for 7 days, and single meals with 1.2 mg/kg bixin or 0.06 mg/kg norbixin. Always follow the product label and check with a healthcare provider for personal advice.

Is Annatto safe, and does it have side effects?

Side effects and cautions reported for Annatto include: Allergic reactions to annatto have been reported, including hives, swelling and, rarely, anaphylaxis with a sharp drop in blood pressure after eating an annatto-colored cereal. Leftover seed protein in the color is a suspected trigger. It may also interact with some medications. Annatto is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Annatto interact with any medications?

Possible interactions include: No human drug-interaction studies of annatto seed or its color extracts were found. In cell studies, bixin increased CYP1A1 and CYP1A2 gene expression, enzymes that help clear some medicines; the relevance of dietary or supplement intake is unknown. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Annatto?

NutraSmarts rates the evidence for Annatto as Preliminary (1 out of 5). It is backed by 6 study summaries and 16 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(16 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Galvis Y, Pineda K, Zapata J, Aristizabal J, Estrada A, Fernandez ML, Barona-Acevedo J. Consumption of Eggs Alone or Enriched with Annatto (Bixa orellana L.) Does Not Increase Cardiovascular Risk in Healthy Adults-A Randomized Clinical Trial, the Eggant Study. Nutrients. 2023;15(2):369. doi: 10.3390/nu15020369.PubMedUsed to support: Parallel randomized trial in Colombia (EGGANT): 105 healthy adults ate two eggs, two eggs with annatto powder (a store-bought ground annatto, dosed at the equivalent of 1.2 mg bixin per kg body weight), or two egg whites daily for 8 weeks. Plasma triglycerides, LDL and HDL cholesterol, apolipoproteins A1 and B and lipoprotein subfractions did not change over time or differ between groups.
  2. Galvis-Pérez Y, Pineda K, Zapata J, Aristizabal J, Estrada A, Fernández ML, Barona-Acevedo J. Annatto-Enriched Egg Improves the Perception of Satiety in Healthy Adults-Randomized Clinical Trial: EGGANT Study. Foods. 2024;13(5):731. doi: 10.3390/foods13050731.PubMedUsed to support: Second report of the same 105-person EGGANT trial. Ghrelin, body measurements and visual analog satiety scores showed no significant differences between groups or over time in the repeated measures analysis. Within the egg plus annatto group only, effect sizes for satisfaction and fullness ratings rose after 8 weeks (Hedges g 0.431 and 0.384). Egg whites were the control, and the authors note the control could not be fully masked.
  3. Conte L, Somacal S, Nichelle SM, Rampelotto C, Robalo SS, Roehrs M, Emanuelli T. Short-Term Bixin Supplementation of Healthy Subjects Decreases the Susceptibility of LDL to Cu(2+)-Induced Oxidation Ex Vivo. J Nutr Metab. 2019;2019:9407069. doi: 10.1155/2019/9407069.PubMedUsed to support: Randomized, double-blind, placebo-controlled Latin square crossover in 16 healthy young adults: one capsule a day for 7 days of a food-grade annatto powder (30% bixin), a norbixin powder made from an alkaline annatto extract (42% norbixin), lycopene or starch placebo, each at 0.05 mg carotenoid per kg body weight. No treatment changed routine blood chemistry or most oxidative stress markers. Versus placebo, the bixin powder lowered the ex vivo LDL oxidation rate and nitric oxide metabolites only at p < 0.1.
  4. Beni AA, Rodrigues RF, Conte L, Costa IF, Delalibera ÉA, Roehrs M, Rampelotto C, Emanuelli T, Somacal S. Dietary supplementation with annatto food-coloring extracts increases the resistance of human erythrocytes to hemolysis. Nutr Res. 2020;76:71-81. doi: 10.1016/j.nutres.2020.02.003.PubMedUsed to support: Test-tube work plus an ex vivo arm from the same research group, in which healthy volunteers took bixin or norbixin capsules (0.05 mg/kg body weight a day) or placebo for 7 days, the same dose and duration as the 2019 crossover. Blood was collected after each 7-day treatment, with placebo as the comparison. Their red blood cells, challenged in the lab, showed higher membrane resistance to breaking (P < .05), more so with bixin, and were protected from lipid peroxidation with an improved redox state (P < .05). An ex vivo lab marker, not a health outcome.
  5. Roehrs M, Conte L, da Silva DT, Duarte T, Maurer LH, de Carvalho JAM, Moresco RN, Somacal S, Emanuelli T. Annatto carotenoids attenuate oxidative stress and inflammatory response after high-calorie meal in healthy subjects. Food Res Int. 2017;100(Pt 1):771-779. doi: 10.1016/j.foodres.2017.08.005.PubMedUsed to support: Randomized controlled crossover in 12 healthy adults (6 men, 6 women): a single high-fat, high-carbohydrate meal with no carotenoid (placebo), with 1.2 mg/kg bixin, or with 0.06 mg/kg norbixin, with blood drawn over 4 hours. Per the abstract, the norbixin meal lowered postprandial IL-1, IL-6, TNF-alpha and lipid oxidation at 60 to 120 minutes, the bixin meal only partly prevented lipid oxidation, and neither changed routine blood chemistry. Figures are from the abstract.
  6. Levy LW, Regalado E, Navarrete S, Watkins RH. Bixin and norbixin in human plasma: determination and study of the absorption of a single dose of Annatto food color. Analyst. 1997;122(9):977-80. doi: 10.1039/a701304c.PubMedUsed to support: Seven volunteers swallowed 1 mL of a commercial annatto food color (16 mg cis-bixin in soybean oil). Bixin and norbixin appeared in plasma, with norbixin levels higher than bixin; bixin was generally cleared by 8 hours and norbixin by 24 hours, with large differences between people. No control group; an absorption study.
  7. Somacal S, Figueiredo CG, Quatrin A, Ruviaro AR, Conte L, Augusti PR, Roehrs M, Denardin IT, Kasten J, da Veiga ML, Duarte MM, Emanuelli T. The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects. Mol Cell Biochem. 2015;403(1-2):243-53. doi: 10.1007/s11010-015-2354-x.PubMedUsed to support: Animal study, not a human trial. Rabbits on a 0.5% cholesterol diet given bixin (10, 30 or 100 mg/kg) for 60 days had smaller aortic lesions (up to 55%), lower lipid peroxidation, non-HDL cholesterol and triglycerides, and higher HDL cholesterol than untreated cholesterol-fed rabbits. Doses far above food-color intake.
  8. Roehrs M, Figueiredo CG, Zanchi MM, Bochi GV, Moresco RN, Quatrin A, Somacal S, Conte L, Emanuelli T. Bixin and norbixin have opposite effects on glycemia, lipidemia, and oxidative stress in streptozotocin-induced diabetic rats. Int J Endocrinol. 2014;2014:839095. doi: 10.1155/2014/839095.PubMedUsed to support: Animal study, not a human trial. In chemically induced diabetic rats treated for 30 days, bixin (10 or 100 mg/kg) lowered blood glucose, LDL cholesterol and triglycerides and reduced oxidation markers, while norbixin changed most measures little and at 100 mg/kg raised LDL cholesterol and triglycerides and acted as a pro-oxidant.
  9. Nish WA, Whisman BA, Goetz DW, Ramirez DA. Anaphylaxis to annatto dye: a case report. Ann Allergy. 1991;66(2):129-31..PubMedUsed to support: Case report: hives, swelling and severe low blood pressure within 20 minutes of eating milk and a cereal colored with annatto. Skin testing was strongly positive to annatto dye and negative to milk, wheat and corn, and the patient had IgE to one of two protein bands near 50 kD in the dye, suggesting residual seed protein as the trigger. The authors call annatto a potential rare cause of anaphylaxis.
  10. Mikkelsen H, Larsen JC, Tarding F. Hypersensitivity reactions to food colours with special reference to the natural colour annatto extract (butter colour). Arch Toxicol Suppl. 1978;(1):141-3. doi: 10.1007/978-3-642-66896-8_16.PubMedUsed to support: Oral challenge series: 56 patients with chronic urticaria or angioedema on an elimination diet were given annatto extract at the amount used in 25 g of butter, and 26% reacted, on average about 4 hours after intake. Reaction rates to synthetic dyes in the same series ranged from 9% to 17%. A selected patient group, not the general population.
  11. EFSA Panel on Food Additives and Flavourings (EFSA FAF Panel), Younes M, Castle L, Engel KH, Fowler P, Frutos Fernandez MJ, Fürst P, Gürtler R, Gundert-Remy U, Husøy T, Mennes W, Moldeus P, Oskarsson A, Shah R, Waalkens-Berendsen I, Wölfle D, Crebelli R, Leblanc JC, Tard A, Aquilina G. Safety of annatto E and the exposure to the annatto colouring principles bixin and norbixin (E 160b) when used as a food additive. EFSA J. 2019;17(3):e05626. doi: 10.2903/j.efsa.2019.5626.PubMedUsed to support: EU food additive opinion on annatto (E 160b). Restates that EFSA's 2016 opinion set an acceptable daily intake of 6 mg bixin and 0.3 mg norbixin per kg body weight per day. Bixin exposure estimates stayed below its ADI; for norbixin the ADI was reached at the high (95th percentile) level for toddlers in one country's refined scenario, which the panel judged not a health concern given likely overestimation.
  12. Shen CL, Yang S, Tomison MD, Romero AW, Felton CK, Mo H. Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial. Osteoporos Int. 2018;29(4):881-891. doi: 10.1007/s00198-017-4356-x.PubMedUsed to support: Concentrated tocotrienol extract, not whole annatto seed (labeled for context). 89 postmenopausal women with low bone density took 430 or 860 mg/day of an annatto seed tocotrienol extract (70% purity; 90% delta, 10% gamma) or olive oil placebo for 12 weeks; bone resorption and oxidative stress markers fell versus placebo. Shows the seed's tocotrienols can be concentrated into a separate product; it is not evidence for eating annatto or its color.
  13. Preece K, Glávits R, Foster JR, Murbach T, Endres JR, Hirka G, Vértesi A, Béres E, Szakonyiné IP. A toxicological evaluation of geranylgeraniol. Regul Toxicol Pharmacol. 2021;124:104975. doi: 10.1016/j.yrtph.2021.104975.PubMedUsed to support: Concentrated geranylgeraniol, not whole annatto seed (labeled for context). Describes geranylgeraniol as a compound found in annatto seeds and tested a distilled annatto oil of about 80% trans-geranylgeraniol: no genotoxicity in lab tests, while a 90-day rat study at 725 to 2900 mg/kg/day found forestomach effects at all doses and liver effects at the two higher doses.
  14. Zegarra L, Vaisberg A, Loza C, Aguirre RL, Campos M, Fernandez I, Talla O, Villegas L. Double-blind randomized placebo-controlled study of Bixa orellana in patients with lower urinary tract symptoms associated to benign prostatic hyperplasia. Int Braz J Urol. 2007;33(4):493-500; discussion 501. doi: 10.1590/s1677-55382007000400006.PubMedUsed to support: Leaf, not seed (labeled for context). 136 men with moderate urinary symptoms from an enlarged prostate took dried Bixa orellana leaf powder (250 mg three times daily) or placebo for 12 months. Symptom scores, urine flow and residual urine did not differ from placebo, and adverse effects were similar between groups. The full text identifies the material as lyophilized leaves.
  15. Matuo MC, de Oliveira Takamoto RT, Kikuchi IS, de Jesus Andreoli Pinto T. Effect of bixin and norbixin on the expression of cytochrome P450 in HepG2 cell line. Cell Biol Int. 2013;37(8):843-8. doi: 10.1002/cbin.10108.PubMedUsed to support: Cell study, not a human trial. In a human liver cancer cell line, bixin raised expression of the drug-metabolizing genes CYP1A1 and CYP1A2 but not CYP2B6, 2C9, 2E1 or 3A4, and norbixin had no inducing effect. The abstract notes earlier rat work in which annatto raised CYP1A and CYP2B activity. Whether food or supplement intake changes drug levels in people is untested.
  16. US Food and Drug Administration (Electronic Code of Federal Regulations, accessed 2026). 21 CFR 73.30 Annatto extract; 21 CFR 73.1030 Annatto extract (drugs). Code of Federal Regulations, Title 21, Part 73. 2026;21 CFR 73.30 and 73.1030 (current eCFR text).SourceUsed to support: Not PubMed-indexed; official US regulation read at ecfr.gov. Annatto extract, prepared from annatto seed (Bixa orellana L.), is a listed color additive exempt from certification that may color foods generally (73.30) and drugs generally (73.1030) in amounts consistent with good manufacturing practice; the label of the color additive and of color mixtures made from it must state that the color is derived from annatto seed. Use in foods with standards of identity requires that added color be authorized. Arsenic and lead limits apply.