Effect of Flax in Yogurt on Blood Cyanide Levels

Official title

A Randomized, Controlled, Cross-over Trial Examining the Effect of Flaxseed on Blood Cyanide Levels in Healthy Adults

Overview

A randomized, controlled, cross-over post-prandial trial in healthy human volunteers will be conducted at the IH Asper Institute to determine the effect whole ground flaxseed, roasted then ground whole flaxseed, whole intact flaxseed and flaxseed hulls mixed into yogurt on blood cyanide levels.

Detailed description

Participants will receive yogurt containing the following flaxseed products in a random order:

1. 40 g ground flaxseed, untreated; 2. 40 g ground flaxseed, roasted before grinding; 3. 40 g intact whole flaxseed; 4. 28 g flaxseed hulls; 5. 0 g flaxseed.

Venous blood will be collected at the following time points: 0 (before consumption of test product), 15, 30, 45, 60, 75, 90, 120, 150, 180 min.

Urine will be collected prior to consumption of test product and 180 min.

Primary endpoints: 1) Peak blood level of cyanide and incremental area under the curve (iAUC) for cyanide in blood over a 3h postprandial period. Secondary endpoint: 1) cyanogenic glycoside and thiocyanate concentrations in plasma and urine over a 3h postprandial period.

Tertiary endpoints: 1) metabolic profile in plasma and urine over 3 h postprandial period.

Interventions

• Dietary supplement 0 g Flax
  175 g yogurt with no flax product
• Dietary supplement 40 g whole ground flaxseed
  175 g yogurt with 40 g whole ground flaxseed
• Dietary supplement 40 g roasted then ground whole flaxseed
  175 g yogurt with 40 g roasted then ground whole flaxseed
• Dietary supplement 40 g of whole intact flaxseeds
  175 g yogurt with 40 g of whole intact flaxseeds
• Dietary supplement 28 g flax hulls
  175 g yogurt with 28 g flax hulls

Primary outcome measures

• Peak blood level of cyanide [Time frame: 180 minutes]
• iAUC blood cyanide [Time frame: 180 min]

Secondary outcome measures (1)

• Cyanogenic glycoside and thiocyanate concentrations in plasma and urine [Time frame: 180 minutes]

Eligibility criteria

Inclusion criteria

• Generally healthy adult, 18 years or older;
• Willing to provide informed consent;
• Willing/able to comply with the requirements of the study.

Exclusion criteria

• Pregnant or lactating;
• Medical history of disease that is currently under treatment;
• Active treatment for any type of cancer within 1 year prior to study start;
• Presence of a gastrointestinal disorder, daily use of any stomach acid-lowering medications or laxatives (including fibre supplements) within the past month or antibiotic use within the past 6 weeks;
• Plasma concentration of vitamin B12 < 148 pmol/L;
• Complete blood count outside normal range;
• Medical history of liver disease or liver dysfunction (defined as plasma AST or ALT ≥3 times the upper limit of normal (ULN));
• Fasting blood glucose ≥6.1 mmol/L and/or HbA1c ≥6.0%;
• Fasting plasma total cholesterol >7.8 mmol/L;
• Fasting plasma HDL <0.9 mmol/L;
• Fasting plasma LDL >5.0 mmol/L;
• Fasting plasma triglycerides >2.3 mmol/L;
• Systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg;
• Major surgery within the last 3 months;
• Smoking, use of tobacco, vape or cannabis (within the last week);
• Allergies to flaxseed or yogurt;
• Aversion or unwillingness to eat study foods;
• Participation in another clinical trial, current or in the past 4 weeks

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Prevention

Study locations

Canada · 1 center

• I. H. Asper Clinical Research Institute — Winnipeg

Publications

• Abraham K, Buhrke T, Lampen A. Bioavailability of cyanide after consumption of a single meal of foods containing high levels of cyanogenic glycosides: a crossover study in humans. Arch Toxicol. 2016 Mar;90(3):559-74. doi: 10.1007/s00204-015-1479-8. Epub 2015 Feb 24. PMID 25708890
• Agbor-Egbe T, Lape Mbome I. The effects of processing techniques in reducing cyanogen levels during the production of some Cameroonian cassava foods. Journal of Food Composition and Analysis. 2006 Jun;19(4):354-63.
• Carlsson L, Mlingi N, Juma A, Ronquist G, Rosling H. Metabolic fates in humans of linamarin in cassava flour ingested as stiff porridge. Food Chem Toxicol. 1999 Apr;37(4):307-12. doi: 10.1016/s0278-6915(99)00015-0. PMID 10418947
• Cressey P, Reeve J. Metabolism of cyanogenic glycosides: A review. Food Chem Toxicol. 2019 Mar;125:225-232. doi: 10.1016/j.fct.2019.01.002. Epub 2019 Jan 4. PMID 30615957
• Cressey P, Saunders D, Aupaau F. Evaluation of food safety risks associated with foods containing cyanogenic glycosides. New Zealand Food Safety Technical Paper No: 2022/29. 2022 Nov.
• Diaz-Rueda P, Morales de Los Rios L, Romero LC, Garcia I. Old poisons, new signaling molecules: the case of hydrogen cyanide. J Exp Bot. 2023 Oct 13;74(19):6040-6051. doi: 10.1093/jxb/erad317. PMID 37586035
• EFSA Panel on Contaminants in the Food Chain (CONTAM); Schrenk D, Bignami M, Bodin L, Chipman JK, Del Mazo J, Grasl-Kraupp B, Hogstrand C, Hoogenboom LR, Leblanc JC, Nebbia CS, Nielsen E, Ntzani E, Petersen A, Sand S, Vleminckx C, Wallace H, Benford D, Brimer L, Mancini FR, Metzler M, Viviani B, Altieri A, Arcella D, Steinkellner H, Schwerdtle T. Evaluation of the health risks related to the prese PMID 32626287
• Gleadow RM, Moller BL. Cyanogenic glycosides: synthesis, physiology, and phenotypic plasticity. Annu Rev Plant Biol. 2014;65:155-85. doi: 10.1146/annurev-arplant-050213-040027. Epub 2014 Feb 24. PMID 24579992

Identifiers

NCT: NCT06491095 · 4030/4687

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗