DeltaGold® (Annatto Tocotrienols — American River Nutrition)

Bixa orellana
Evidence Level
Limited
3 Clinical Trials
6 Documented Benefits
2/5 Evidence Score

DeltaGold is a branded annatto seed extract from American River Nutrition that supplies tocotrienols, members of the vitamin E family, at about 90% delta-tocotrienol and 10% gamma-tocotrienol. Human research on this material is small, from two research groups. A 12-week placebo-controlled trial in 89 postmenopausal women with low bone mass, funded by the maker, found lower bone resorption and oxidative DNA damage markers; bone density was not measured. A placebo-controlled trial in 71 adults with fatty liver found larger falls in liver enzymes, a fatty liver index, triglycerides, an oxidative stress marker and an insulin resistance score; a 48-week trial found similar liver fat changes with alpha-tocopherol. Two glucose trials from the same Pakistani group do not name their product source. Pooled tocotrienol trials from all sources found no significant change in total or LDL cholesterol.

Studied Dose DeltaGold 70 at 430 or 860 mg/day (300 or 600 mg tocotrienol) for 12 weeks; annatto delta-tocotrienol 300 mg twice daily for 12 to 48 weeks; 250 or 300 mg/day for 12 to 24 weeks in glucose trials of unstated source.
Active Compound Tocotrienols from annatto seed (Bixa orellana), about 90% delta-tocotrienol and 10% gamma-tocotrienol; the DeltaGold 70 extract used in the bone marker trial is 70% tocotrienol.

Benefits

Lower bone resorption markers in postmenopausal women

In a 12-week placebo-controlled trial in 89 postmenopausal women with low bone mass, DeltaGold 70 at 300 or 600 mg/day tocotrienol lowered urinary NTX, a bone resorption marker, plus serum sRANKL and the sRANKL/OPG ratio, and raised the BALP/NTX ratio. OPG and urinary calcium did not change and the doses did not differ. Bone density was not measured. The maker funded the study.

Lower oxidative stress markers versus placebo in two trials

In the 12-week trial in postmenopausal women, urinary 8-OHdG, a marker of oxidative DNA damage, fell with tocotrienol versus placebo. In a placebo-controlled trial of annatto delta-tocotrienol in adults with fatty liver, serum malondialdehyde, a lipid peroxidation marker, fell more than with placebo at 12 and 24 weeks. Both are lab markers, not clinical outcomes.

Lower insulin resistance score versus placebo over 24 weeks

In a placebo-controlled trial in 71 adults with fatty liver given annatto delta-tocotrienol 300 mg twice daily, HOMA-IR, an insulin resistance score and a primary endpoint, fell more than with placebo at 24 weeks (mean difference -0.37). In a later 48-week trial, HOMA-IR improved to a similar degree with delta-tocotrienol and with alpha-tocopherol.

Blood sugar markers in delta-tocotrienol trials of unstated source

Two placebo-controlled trials from one research group, 300 mg/day for 12 weeks in 77 adults with prediabetes and 250 mg/day for 24 weeks in 110 adults with type 2 diabetes on oral glucose-lowering drugs, reported larger falls in fasting glucose, HbA1c, insulin and HOMA-IR than placebo. The abstracts do not name the product source, so these are not confirmed DeltaGold results.

Triglycerides fell more than with placebo over 12 weeks

In the placebo-controlled trial of annatto delta-tocotrienol in 71 adults with fatty liver, triglycerides fell more than with placebo at 12 weeks (-0.24 versus -0.12 mmol/L, p<0.001), a measure outside the trial's stated outcomes; total and LDL cholesterol were not reported. Pooled trials of tocotrienols from any source found no significant change in total or LDL cholesterol.

Lower liver enzymes and liver fat index versus placebo

In a small placebo-controlled pilot trial in 71 adults with fatty liver, annatto delta-tocotrienol 300 mg twice daily lowered ALT, AST and the fatty liver index (a score from body mass index, waist size, triglycerides and GGT) more than placebo at 12 and 24 weeks. Ultrasound fat grade did not differ at 12 weeks and improved more at 24 weeks (p=0.047). Over 48 weeks, liver fat changes matched alpha-tocopherol.

Mechanism of action

1

Delta- and Gamma-Tocotrienol Forms

Natural vitamin E includes four tocopherols and four tocotrienols, and the body retains alpha-tocopherol preferentially while metabolizing the other forms. A 48-week trial in adults with fatty liver compared delta-tocotrienol with alpha-tocopherol and found similar changes in liver fat and insulin resistance, with larger falls in body weight and some inflammatory markers on delta-tocotrienol.

2

HMG-CoA Reductase Modulation

Tocotrienols are reported to lower the activity of HMG-CoA reductase, the cholesterol-synthesis enzyme that statins block, through a post-transcriptional route. In people, pooled tocotrienol trials found no significant change in total or LDL cholesterol, so this mechanism has not translated into a demonstrated cholesterol effect.

3

Inflammation and MicroRNA Markers

In the annatto delta-tocotrienol trial in adults with fatty liver, hs-CRP fell more than with placebo. In a type 2 diabetes trial of delta-tocotrienol of unstated source, hs-CRP, TNF-alpha and IL-6 fell and several circulating microRNAs changed versus placebo. These are blood markers, not clinical outcomes.

4

Oxidative Stress Markers

In placebo-controlled trials of the annatto material, urinary 8-OHdG and serum malondialdehyde fell more than with placebo. Claims that tocotrienols are stronger antioxidants than tocopherols in people are not established by the studies cited here.

5

Membrane and Phospholipid Changes

In a serum metabolomics analysis of the postmenopausal trial, 600 mg/day for 12 weeks raised serum tocotrienols and lysophospholipids and lowered acylcarnitines compared with baseline. The authors propose that tocotrienols are built into cell membranes and alter phospholipid metabolism; this is an interpretation, not a measured health outcome.

Clinical trials

1
DeltaGold 70 for 12 Weeks and Bone Turnover Markers in 89 Postmenopausal Women
PubMed

Randomized, double-blind, placebo-controlled trial (NCT02058420) run by Texas Tech University Health Sciences Center; olive oil placebo versus DeltaGold 70 at 430 or 860 mg/day (300 or 600 mg tocotrienol). American River Nutrition supplied the product and funded the study. Safety and quality-of-life results from the same trial appeared in BMC Complement Altern Med in 2018 and a serum metabolomics analysis in Front Nutr in 2021. (Shen et al. 2018, Osteoporos Int)

89 postmenopausal women with osteopenia (mean age 59.7 years); 87 completed.

Versus placebo, urinary NTX, serum sRANKL, the sRANKL/OPG ratio and urinary 8-OHdG (an oxidative DNA damage marker) fell and the BALP/NTX ratio rose; serum BALP fell only marginally, and OPG and urinary calcium did not change. The two doses did not differ. Bone density and fractures were not measured. Safety blood tests (aminotransferases, alkaline phosphatase, bilirubin and kidney markers) did not change, no treatment-related adverse events were reported, and quality of life and physical activity did not differ between groups.

2
Annatto Delta-Tocotrienol 300 mg Twice Daily in 71 Adults With Fatty Liver
PubMed

Randomized, double-blind, placebo-controlled trial at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan (SLCTR/2015/023), with a sucrose placebo; primary endpoints were fatty liver index and HOMA-IR. A 2018 report in Turk J Gastroenterol with the same 35 versus 36 randomization gave 12-week results and named the capsules as annatto extract from American River Nutrition (90% delta, 10% gamma), donated by a US tocotrienol researcher; that report lists funding from the institute and Pakistan's Higher Education Commission. (Pervez et al. 2020, Complement Ther Med)

71 adults with ultrasound-confirmed fatty liver, a fatty liver index of 60 or more and raised ALT; 64 completed the 12-week report.

At 24 weeks, versus placebo, the fatty liver index fell (mean difference -8.52), as did the HOMA-IR insulin resistance score (-0.37), hs-CRP (-0.61), malondialdehyde, a lipid peroxidation marker (-0.91), ALT (-8.86) and AST (-6.6), and ultrasound steatosis grade improved more (p=0.047). In the 12-week report, triglycerides and body weight also fell more than with placebo, but ultrasound grade did not yet differ. No adverse events were reported.

3
Annatto Delta-Tocotrienol Versus Alpha-Tocopherol for 48 Weeks in 100 Adults With Fatty Liver
PubMed

Randomized, double-blind, active-controlled trial with no placebo group (SLCTR/2019/038): delta-tocotrienol 300 mg or alpha-tocopherol 268 mg twice daily. Primary endpoints were fatty liver index, liver-to-spleen attenuation ratio on CT and HOMA-IR; malondialdehyde was a secondary endpoint. A companion microRNA paper from the same trial (Int J Mol Sci 2022) thanks American River Nutrition for the study supplements and reports university funding. (Pervez et al. 2022, Complement Ther Med)

100 adults with fatty liver (50 per group), analyzed by intention to treat.

All three primary endpoints improved from baseline in both groups with no significant difference between them. Body weight, IL-6, TNF-alpha, leptin and cytokeratin-18 fell more, and adiponectin rose more, with delta-tocotrienol. No adverse events were reported. Without a placebo group, the shared improvements cannot be credited to either supplement.

Side effects and drug interactions

Common Potential side effects

In the 12-week trial of 300 or 600 mg/day tocotrienol from DeltaGold 70 in 87 postmenopausal women who completed it, liver and kidney function tests did not change and no treatment-related adverse events were reported. The maker funded that study.
No adverse events were reported in trials of annatto delta-tocotrienol 300 mg twice daily for 12 to 24 weeks against placebo or for 48 weeks against alpha-tocopherol. These trials were small, and no study cited here followed people for longer than 48 weeks.
Vitamin E can inhibit platelet aggregation, and the US upper limit for supplemental vitamin E (1,000 mg a day for adults) is based on bleeding risk. That limit is defined for alpha-tocopherol, not tocotrienols, and no study cited here measured bleeding with DeltaGold.
Rare allergic reactions to annatto, including a published case of anaphylaxis to annatto food dye, have been reported. Whether the tocotrienol extract carries the same risk has not been studied.

Important Drug interactions

Anticoagulants and antiplatelet drugs. NIH notes that large doses of vitamin E taken with medicines such as warfarin can increase bleeding risk. No study cited here tested DeltaGold with these drugs; ask a prescriber before combining them.
Statins. No trial cited here tested DeltaGold with a statin, and the pooled analysis of 15 tocotrienol trials cited here found no significant change in total or LDL cholesterol, so an added cholesterol-lowering effect is not supported. NIH also notes that an antioxidant combination including vitamin E blunted the rise in HDL cholesterol in people taking simvastatin with niacin. Do not adjust a statin without your prescriber.
Glucose-lowering medicines. In a 24-week trial of delta-tocotrienol of unstated source in adults with type 2 diabetes who were taking oral glucose-lowering drugs, fasting glucose and HbA1c fell more than with placebo, so an added effect is possible. Anyone on these medicines should speak with their prescriber first.
Chemotherapy and radiotherapy. NIH notes that oncologists generally advise against antioxidant supplements during these treatments because they might reduce their effectiveness. Ask the treating team before use.
Pregnancy and breastfeeding. No study cited here tested DeltaGold in pregnant or breastfeeding women.
Surgery. Because vitamin E can inhibit platelet aggregation, tell your surgeon if you take it.

Frequently asked questions about DeltaGold® (Annatto Tocotrienols — American River Nutrition)

What is DeltaGold used for?

DeltaGold is sold as a source of annatto tocotrienols, mainly delta-tocotrienol. Placebo-controlled trials of this material have measured bone turnover markers in postmenopausal women and liver, oxidative stress and insulin resistance markers in adults with fatty liver. These are small trials of lab markers; none measured fractures, bone density or long-term health outcomes, and a supplement is not a treatment for any disease.

Is DeltaGold safe, and does it have side effects?

In the trials cited here, 300 to 600 mg/day of tocotrienol for 12 weeks did not change liver or kidney function tests in postmenopausal women, and no treatment-related adverse events were reported there or in trials of 300 mg twice daily lasting up to 48 weeks. These studies were small and short, and one was funded by the maker. Vitamin E can inhibit platelet aggregation, so people on blood thinners, people facing surgery, and pregnant or breastfeeding women should talk with a clinician first.

Does DeltaGold lower cholesterol?

No trial cited here shows that. A pooled analysis of 15 tocotrienol trials from any source found no significant change in total or LDL cholesterol, while HDL rose slightly. In one placebo-controlled trial of the annatto material in adults with fatty liver, triglycerides fell more than with placebo at 12 weeks (0.24 versus 0.12 mmol/L, p<0.001), but triglycerides were not one of that trial's stated outcomes and total and LDL cholesterol were not reported. An older rice bran tocotrienol study that reported large cholesterol drops compared results with baseline rather than with a placebo group.

How is DeltaGold different from palm or rice bran tocotrienols?

DeltaGold comes from annatto seed and is mostly delta-tocotrienol with some gamma-tocotrienol, while the palm tocotrienol blend discussed in one trial report also contains alpha-tocopherol. Palm and rice bran tocotrienol products are different materials, so their trials, such as a 1-year palm tocotrienol liver trial and a rice bran cholesterol study, do not show what DeltaGold does. Only trials that used the annatto extract are counted as evidence for it on this page.

What is DeltaGold?

DeltaGold is a branded annatto seed extract from American River Nutrition that supplies tocotrienols, members of the vitamin E family, at about 90% delta-tocotrienol and 10% gamma-tocotrienol. Human research on this material is small, from two research groups.

What is the recommended dosage of DeltaGold?

The clinically studied dose is DeltaGold 70 at 430 or 860 mg/day (300 or 600 mg tocotrienol) for 12 weeks; annatto delta-tocotrienol 300 mg twice daily for 12 to 48 weeks; 250 or 300 mg/day for 12 to 24 weeks in glucose trials of unstated source. Always follow the product label and check with a healthcare provider for personal advice.

Does DeltaGold interact with any medications?

Possible interactions include: Anticoagulants and antiplatelet drugs. NIH notes that large doses of vitamin E taken with medicines such as warfarin can increase bleeding risk. No study cited here tested DeltaGold with these drugs; ask a prescriber before combining them. Statins. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for DeltaGold?

NutraSmarts rates the evidence for DeltaGold as Limited (2 out of 5). It is backed by 3 study summaries and 15 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(15 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. 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: Randomized, double-blind, placebo-controlled trial in 89 postmenopausal women with osteopenia (87 completed): annatto tocotrienol (70% purity, 90% delta and 10% gamma) at 430 or 860 mg/day for 12 weeks lowered urinary NTX, serum sRANKL, the sRANKL/OPG ratio and urinary 8-OHdG and raised the BALP/NTX ratio versus placebo. Serum BALP fell only marginally, OPG and urinary calcium did not change, and the doses did not differ. Bone density and fractures were not measured.
  2. Shen CL, Wang S, Yang S, Tomison MD, Abbasi M, Hao L, Scott S, Khan MS, Romero AW, Felton CK, Mo H. A 12-week evaluation of annatto tocotrienol supplementation for postmenopausal women: safety, quality of life, body composition, physical activity, and nutrient intake. BMC Complement Altern Med. 2018;18(1):198. doi: 10.1186/s12906-018-2263-0.PubMedUsed to support: Same trial as the Osteoporos Int report, naming the product as DeltaGold 70 (300 or 600 mg tocotrienol a day). Liver and kidney function did not change, no treatment-related adverse events were reported, and serum delta-tocotrienol rose. Quality of life, body composition, physical activity and nutrient intake did not differ between groups. The paper states that American River Nutrition supplied the product and funded the study.
  3. Shen CL, Mo H, Dunn DM, Watkins BA. Tocotrienol Supplementation Led to Higher Serum Levels of Lysophospholipids but Lower Acylcarnitines in Postmenopausal Women: A Randomized Double-Blinded Placebo-Controlled Clinical Trial. Front Nutr. 2021;8:766711. doi: 10.3389/fnut.2021.766711.PubMedUsed to support: Serum metabolomics analysis of the same 12-week trial, comparing placebo with 600 mg/day tocotrienol (90% delta, 10% gamma): 48 serum biochemicals rose and 65 fell in the tocotrienol group compared with baseline, including higher tocotrienols and lysophospholipids and lower acylcarnitines. The authors propose membrane incorporation and changes in phospholipid metabolism.
  4. Pervez MA, Khan DA, Ijaz A, Khan S. Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease. Turk J Gastroenterol. 2018;29(2):170-176. doi: 10.5152/tjg.2018.17297.PubMedUsed to support: Randomized, double-blind, placebo-controlled pilot trial in 71 adults with fatty liver and raised ALT (64 completed): delta-tocotrienol 300 mg twice daily for 12 weeks, from annatto extract (90% delta, 10% gamma) made by American River Nutrition per the full text, lowered aminotransferases, hs-CRP, malondialdehyde, triglycerides and fatty liver index more than placebo but did not improve ultrasound steatosis grade. No adverse effects were reported. Funded by the Armed Forces Institute of Pathology and the Higher Education Commission of Pakistan.
  5. Pervez MA, Khan DA, Slehria AUR, Ijaz A. Delta-tocotrienol supplementation improves biochemical markers of hepatocellular injury and steatosis in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled trial. Complement Ther Med. 2020;52:102494. doi: 10.1016/j.ctim.2020.102494.PubMedUsed to support: Randomized, double-blind, placebo-controlled trial in 71 adults with fatty liver (35 versus 36, the same randomization as the 2018 12-week report): delta-tocotrienol 300 mg twice daily for 24 weeks reduced fatty liver index, HOMA-IR, hs-CRP, malondialdehyde, ALT and AST versus placebo, and ultrasound steatosis improved more (p=0.047). No adverse events were reported.
  6. Pervez MA, Khan DA, Mirza SA, Slehria AUR, Nisar U, Aamir M. Comparison of delta-tocotrienol and alpha-tocopherol effects on hepatic steatosis and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: A randomized double-blind active-controlled trial. Complement Ther Med. 2022;70:102866. doi: 10.1016/j.ctim.2022.102866.PubMedUsed to support: Randomized, double-blind, active-controlled trial in 100 adults with fatty liver: delta-tocotrienol 300 mg or alpha-tocopherol 268 mg twice daily for 48 weeks. Fatty liver index, liver-to-spleen ratio, HOMA-IR and malondialdehyde improved in both groups with no significant difference between them; body weight, IL-6, TNF-alpha, leptin and cytokeratin-18 fell more and adiponectin rose more with delta-tocotrienol. No placebo group. No adverse events were reported.
  7. Pervez MA, Khan DA, Gilani STA, Fatima S, Ijaz A, Nida S. Hepato-Protective Effects of Delta-Tocotrienol and Alpha-Tocopherol in Patients with Non-Alcoholic Fatty Liver Disease: Regulation of Circulating MicroRNA Expression. Int J Mol Sci. 2022;24(1):79. doi: 10.3390/ijms24010079.PubMedUsed to support: Circulating microRNA analysis of the 48-week trial of delta-tocotrienol 300 mg versus alpha-tocopherol 268 mg twice daily in 100 adults with fatty liver (no placebo group): both lowered the six microRNAs measured, and delta-tocotrienol lowered miRNA-375 and miRNA-34a more. The full text thanks American River Nutrition for providing the study supplements and lists a National University of Medical Sciences grant.
  8. Suleman F, Khan DA, Pervez MA, Aamir M. Effects of delta-tocotrienol supplementation on glycaemic control in individuals with prediabetes: A randomized controlled study. J Pak Med Assoc. 2022;72(1):4-7. doi: 10.47391/JPMA.966.PubMedUsed to support: Randomized placebo-controlled trial in 77 adults with prediabetes (40 versus 37): delta-tocotrienol 300 mg once daily for 12 weeks gave significantly greater falls in fasting glucose, HbA1c, insulin and HOMA-IR than placebo. The abstract and trial registration do not name the product source. Small, single-center trial.
  9. Mahjabeen W, Khan DA, Mirza SA, Pervez MA. Effects of delta-tocotrienol supplementation on Glycemic Control, oxidative stress, inflammatory biomarkers and miRNA expression in type 2 diabetes mellitus: A randomized control trial. Phytother Res. 2021;35(7):3968-3976. doi: 10.1002/ptr.7113.PubMedUsed to support: Randomized placebo-controlled trial in 110 adults with type 2 diabetes taking oral glucose-lowering drugs: delta-tocotrienol 250 mg a day for 24 weeks reduced plasma glucose, insulin, HOMA-IR, HbA1c, malondialdehyde, hs-CRP, TNF-alpha and IL-6 versus a cellulose placebo and changed several circulating microRNAs. The abstract does not name the product source.
  10. Qureshi AA, Khan DA, Silswal N, Saleem S, Qureshi N. Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of Tocotrienols in Healthy Fed Humans. J Clin Exp Cardiolog. 2016;7(4):434. doi: 10.4172/2155-9880.1000434.PubMedUsed to support: Open-label pharmacokinetic study in 6 healthy fed adults given single doses of 750 or 1000 mg of annatto tocotrienols (DeltaGold softgels supplied by American River Nutrition): plasma delta-tocotrienol peaked in about 3 to 4 hours with a half-life of under 3 hours, and no subject reported adverse effects. No control group and no health outcomes.
  11. Zuo S, Wang G, Han Q, Xiao H, O Santos H, Avelar Rodriguez D, Khani V, Tang J. The effects of tocotrienol supplementation on lipid profile: A meta-analysis of randomized controlled trials. Complement Ther Med. 2020;52:102450. doi: 10.1016/j.ctim.2020.102450.PubMedUsed to support: Meta-analysis of 15 randomized trials (20 arms) of tocotrienols from any source: HDL cholesterol rose significantly (0.146 mmol/L), while total cholesterol (0.010 mmol/L), LDL cholesterol (0.095 mmol/L) and triglycerides (-0.112 mmol/L) did not change significantly overall; triglycerides fell significantly only in arms dosing 200 mg/day or more (-0.177 mmol/L). Not specific to annatto or DeltaGold.
  12. Qureshi AA, Sami SA, Salser WA, Khan FA. Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans. Atherosclerosis. 2002;161(1):199-207. doi: 10.1016/s0021-9150(01)00619-0.PubMedUsed to support: Rice bran tocotrienol-rich fraction (a different material from DeltaGold) at 25 to 200 mg/day on an AHA Step-1 diet in 90 adults with high cholesterol: 100 mg/day gave the largest falls in total cholesterol (20%), LDL (25%), apolipoprotein B (14%) and triglycerides (12%) compared with baseline values. The authors attribute the effect to lower HMG-CoA reductase activity.
  13. Magosso E, Ansari MA, Gopalan Y, Shuaib IL, Wong JW, Khan NA, Abu Bakar MR, Ng BH, Yuen KH. Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial. Nutr J. 2013;12(1):166. doi: 10.1186/1475-2891-12-166.PubMedUsed to support: Randomized placebo-controlled trial of a palm tocotrienol blend (a different material from DeltaGold), 200 mg twice daily for 1 year in 87 adults with high cholesterol and ultrasound-confirmed fatty liver: normalization of the hepatic echogenic response was more frequent than with placebo (intention to treat p=0.039). No adverse events were reported.
  14. Office of Dietary Supplements, National Institutes of Health. Vitamin E: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements. 2026;Updated October 19, 2026..SourceUsed to support: Government fact sheet (not PubMed-indexed): vitamin E occurs as four tocopherols and four tocotrienols and the liver preferentially keeps alpha-tocopherol; vitamin E can inhibit platelet aggregation and large doses with anticoagulants or antiplatelet drugs such as warfarin can increase bleeding risk; the adult upper limit for supplemental alpha-tocopherol is 1,000 mg a day, set on bleeding risk; oncologists generally advise against antioxidant supplements during chemotherapy or radiotherapy.
  15. 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 of anaphylaxis after eating a food containing annatto dye, confirmed by skin testing. A single case of a reaction to the food color, not the tocotrienol extract.