Table 1.
Clinical intervention studies demonstrating interindividual variability in bioavailability of plant food bioactives
| Bioactives/food rich in bioactives | Study products | Study type | Nb volunteers | Volunteers | Objectives | Results | Reference |
|---|---|---|---|---|---|---|---|
| Carotenoids | Watermelon juice providing 20 mg lycopene, 2.5 mg b‐carotene (Treatment 1) or 40 mg lycopene + 5 mg b‐caroten (Treatment 2) or Tomato juice providing 18 mg lycopene + 0.6 mg b‐carotene (Treatment 3) Daily intake of each treatment for 3 weeks | Chronic parrallel study | N = 10 for Treatment 1 N = 23 for treatment 2 N = 12 for treatment 3 | Healthy non‐smokers | Use of cluster analysis to examine individual temporal response of plasma carotenoids and provide basis for classifying subjects as strong or weak responders | Various carotenoids can produce various plasma responses for a given subject. Individual responsiveness was associated with genetic variants of the carotenoid metabolizing enzyme b‐caroten 15,15′ monoxygenase 1. | 41 |
| Lutein | Meal 1: providing lutein as a supplement (15 mg) Meal 2: providing the same amount of lutein as tomato puree | Acute cross‐over study | N = 39 | Healthy non‐obese, non‐smoker men | Characterization of the interindividual variability in lutein bioavailability by measuring lutein in plasma chylomicrons sampled over 8h postprandially and identification of SNPs involved | The CV of the postprandial lutein response was 75% after lutein supplement and 137% after tomato puree consumption. Most of this variance was explained by 29 SNPs in 15 genes related to both lutein and chylomicron metabolism. | 29 |
| Lycopene | Test meal containing 100 g tomato puree providing l9.7 mg all‐trans Lycopene | Acute study | N = 39 | Healthy non‐obese, non‐smoker men | Characterization of the interindividual variability in lycopene bioavailability by measuring lycopene in plasma chylomicrons sampled over 8h postprandially and identification of SNPs involved | The CV of the postprandial concentrations of lycopen in plasma chylomicrons was of 70%. 72% of this variance was explained by 28 SNPs in 16 genes involved in lycopen and lipid metabolism. | 28 |
| Cocoa flavanols | 5.3 and 10.7 mg total Cocoa Flavanols (CF)/kg BW | Acute parralel study | N = 20 young (25–35 yrs) N = 20 elderly (65–80 yrs) | Healthy men | Follow‐up of concentrations in total structurally‐related EC metabolites (SREM) and of individual metabolites in blood and urine over 24 h | The interindividual variations in total SREM were 38 and 39% in AUC (0–6 h) and Cmax, respectively without effect of age. Small differences observed between young and elderly for some specific metabolites. | 34 |
| Orange juice ‐ Flavanones | 400 mL fresh, homogenized and pasteurized orange juice | Acute cross‐over study | N = 18 | Healthy subjects (20–50 yrs) | Effect of orange juice processing on flavanone bioavailability as measured in 24 h urine | High excretors (N = 4), medium excretors (N = 7) and low excretors (N = 7) had mean flavanone excretion values of 15, 9, and 3% respectively after fresh juice intake. Type of food processing had an impact in high excretors but not in medium and low excretors | 40 |
| Hop prenylflavonoids ‐ 8 prenylnaringenin | 3 hop‐derived supplements per day for 5 days | Short‐term study | N = 50 | Healthy post‐menopausal women (46–74 yrs) | Examine the extent of interindividual variation in urinary excretion of hop‐derived prenylflavonoids | Subjects were classified into poor (60%), moderate (25%) and strong (15%) 8‐prenylnaringenin (8‐PN) producers based on urinary excretion and in vitro microbial bioactivation capacity (convertion of isoxanthohumol to 8‐PN). | 27 |
| Soy Isoflavones | Soymilk challenge (240 ml twice daily for 3.5 days) | Short‐term study | N = 159 (89 from USA and 70 from Australia) | Healthy adults | Follow‐up of urinary excretion of S‐equol (24h urine) to identify equol producers and search for association between equol producer status and dietary factors | The observed overall frequency of equol producer is 29.6% without any significant difference between USA and australian participants. Subtle effects of some dietary factors (PUFAs, maltose, VitA, Vit E). | 36 |
| Soy Isoflavones | Soy protein bar (containing 38 mg Daidzein) per day on 3 consecutive days | Short‐term study | N = 91 Korean American (KA) and N = 222 Caucasian American (CA) | Healthy Women and girls | Use a soy challenge test to confirm results from observational studies suggesting that the prevalence of equol producers is higher in Asian than in Western populations | Prevalence of Equol‐producer phenotype higher in KA (51%) than in CA (36%), of ODMA‐producer phenotype lower in KA (84%) than in CA (92%). No differences in dietary habits between equol and non‐equol producers. | 38 |
| Soy Isoflavones | Soymilk challenge (250 ml twice daily) on 3 consecutive days | Short‐term study | N = 41 including 29 vegetarians and 12 nonvegetarians | Healthy adults | Comparison of the frequency of equol producers in the two dietary patterns | The frequency of equol producers was higher in vegetarians (59%) than in nonvegetarians adults (25%). | 37 |
| Lignans‐ enterolactone | Purified secoisolariciresinol diglucoside (SDG) (1,31 micromol/kg BW) | Acute study | N = 12 | Healthy men and women | Pharmacokinetics study of enterolignans (enterodiol (END), enterolactone (ENL)) in volunteers after consumption of their plant precursor | Substantial variation observed among subjects in plasma concentration and urinary excretion of enterolignans: In 5 subjects AUC of ENL was twice that of END; in other 5 subjects AUC of ENL was only 1–2 times that of END; In 2 subjects AUC of END exceeded that of ENL. No differences between men and women. | 32 |
| Rapsberries‐Ellagitannins | 300 g rapsberries | Acute study | N = 10 | Healthy subjects (25–48 yrs) | Follow‐up of plasma (24h kinetics) and urine (48h kinetics) concentrations of ellagic acid and its microbial metabolites urolithins | Large interindividual variation in timing, quantity and type of urolithins‐O‐glucuronides excreted in urine. One subject produced no urolithins, whereas the other nine excreted quantities ranging from 1.3 to 44 μmol. Only one subject produced urolithin B‐glucuronide. | 31 |
| Walnuts and pomegranate extract ‐Ellagitannins | Two interventions: 1. 30 g walnuts per day for 3 days; 2. pomegranate extract 0.9g per day for 3 days | Short‐term study | 1. N = 20 2. N = 49 | 1. Healthy subjects (21–55 yrs) 2. Healthy, overweight subjects (40‐65 yrs) | Characterization of the interindividual variability in urolithin production assessed by measuring derivatives in 24 h urine; Analysis of fecal microbiota composition | Three metabotypes identified: metabotype A subjects (1. 65%; 2. 60%) excreted only urolithin A metabolites, metabotype B subjects (1. 20%; 2. 30%) in addition to UA also excreted urolithin B and isourolithin A, metabotype 0 subjects (1. 15%; 2. 10%) did not excrete urolithins. Higher level of Gordonibacter were found in metabotype A individuals. Metabotype B prevailed in overweight‐obese versus normoweight subjects. | 35 |
| Standard broccoli and high‐glucosinolate broccoli | 3 test meals (150 ml): broccoli soup, super broccoli soup, or water | Acute study | N = 16 | Healthy subjects | Investigate the impact of GSTM1 genotypes on sulphoraphane metabolism and excretion | Significant increase in plasma AUC and urinary excretion of total sulforaphane metabolites observed in GSTM1‐null subjects compared with the GSTM1‐positive subjects. | 30 |
| broccoli‐ Isothiocyanates | Test meal consisting in 2.5 g broccoli/kg BW with pasta | Acute study | N = 114 | Healthy subjects (18–50 yrs) | Investigate the effect of GSTM1 genotypes on sulforaphane metabolism and excretion | 62% of GSTM1 null individuals had high ITC excretion whereas only 39% of individuals with the GSTM present genotype were high ITC excretors. | 39 |
| broccoli‐ glucosinolates | Standardized meal containing 200 g cooked broccoli | Acute study | N = 23 | Healthy subjects | Examine the association between glucosinolate metabolism and gut bacterial community composition | Differences in gut microbiota composition contribute to observed variation in glucosinolate metabolism in low‐ (N = 5) vs high‐ITC excreters (N = 5). | 33 |
BW, body weight; CV, coefficient of variation; SNP, single nucleotide polymorphism; CF, cocoa flavanols; EC, epicatechin; PUFA, poly‐unsaturated fatty acids; ODMA, O‐desmethylangolensin, AUC, area under the curve; Cmax, peak plasma concentration; GSTM1, glutathione S‐transferase M1; ITC, isothiocyanate.