Table 2.
Percentage differences (95% CIs) in 34 validated metabolites according to coffee consumption among participants from the NHS and NHSII*
| HMDB ID | Metabolite | Super class | Screening stage: total coffee per cup increase | Validation stage: total coffee per cup increase | Pooled samples: caffeinated coffee per cup increase | Pooled samples: decaffeinated coffee per cup increase |
|---|---|---|---|---|---|---|
| HMDB00875 | Trigonelline | Alkaloids and derivatives | 43.5 (38.8, 48.4) | 46.4 (41.0, 52.0) | 43.4 (39.3, 47.5) | 17.6 (12.2, 23.3) |
| HMDB04400 | AAMU | Organic nitrogen compounds | 22.9 (18.1, 27.8) | 22.5 (17.1, 28.2) | 33.5 (29.4, 37.7) | −9.0 (−13.3, −4.5) |
| HMDB11621 | Cinnamoylglycine | Organic acids and derivatives | 20.4 (15.8, 25.2) | 17.2 (12.0, 22.6) | 17.0 (13.3, 20.9) | 10.4 (5.3, 15.8) |
| HMDB11103 | 1,7-dimethyluric acid | Organoheterocyclic compounds | 18.1 (13.4, 22.9) | 20.4 (15.0, 26.0) | 32.3 (28.3, 36.5) | −14.1 (−18.1, −9.9) |
| HMDB01847 | Caffeine | Organoheterocyclic compounds | 16.6 (12.1, 21.3) | 17.2 (12.0, 22.5) | 28.0 (24.1, 32.0) | −11.8 (−15.8, −7.6) |
| HMDB00779 | Phenyllactic acid | Phenylpropanoids and polyketides | 14.6 (9.9, 19.6) | 13.8 (8.5, 19.4) | 11.3 (7.5, 15.3) | 11.0 (5.6, 16.7) |
| HMDB13678 | 4-hydroxyhippuric acid | Benzenoids | 14.2 (9.5, 19.2) | 16.5 (11.1, 22.2) | 13.5 (9.7, 17.5) | 9.3 (4.0, 14.9) |
| HMDB00630 | Cytosine | Organoheterocyclic compounds | 11.4 (7.0, 16.0) | 11.0 (6.0, 16.4) | 12.3 (8.7, 16.1) | 2.2 (−2.5, 7.3) |
| HMDB01991 | 7-methylxanthine | Organoheterocyclic compounds | 10.6 (6.0, 15.4) | 10.5 (5.4, 15.8) | 15.3 (11.5, 19.3) | −4.3 (−8.9, 0.5) |
| HMDB00062 | l-carnitine | Organic nitrogen compounds | 6.3 (2.0, 10.7) | 5.3 (0.2, 10.7) | 6.6 (2.9, 10.3) | 2.3 (−2.7, 7.4) |
| HMDB06726 | C20:4 CE | Lipids and lipid-like molecules | 6.2 (1.9, 10.6) | 5.2 (0.3, 10.5) | 4.5 (1.0, 8.1) | 4.4 (−0.6, 9.6) |
| HMDB00918 | C18:1 CE | Lipids and lipid-like molecules | 6.1 (2.1, 10.3) | 9.2 (4.4, 14.4) | 5.3 (2.0, 8.8) | 6.0 (1.2, 11.0) |
| HMDB00610 | C18:2 CE | Lipids and lipid-like molecules | 6.0 (2.0, 10.2) | 10.7 (6.0, 15.7) | 5.6 (2.3, 9.0) | 7.5 (2.7, 12.4) |
| HMDB05377 | C50:2 TAG | Lipids and lipid-like molecules | −5.3 (−8.8, −1.6) | −6.9 (−10.8, −2.8) | −4.4 (−7.3, −1.3) | −5.8 (−9.9, −1.5) |
| HMDB07102 | C34:1 DAG | Lipids and lipid-like molecules | −5.5 (−9.1, −1.8) | −7.4 (−11.4, −3.3) | −5.9 (−8.8, −2.9) | −4.0 (−8.2, 0.4) |
| HMDB10497 | C50:6 TAG | Lipids and lipid-like molecules | −5.5 (−9.3, −1.7) | −7.0 (−11.2, −2.6) | −6.1 (−9.1, −2.9) | −2.3 (−6.8, 2.5) |
| HMDB10513 | C56:10 TAG | Lipids and lipid-like molecules | −5.6 (−9.3, −1.7) | −6.2 (−10.6, −1.6) | −6.9 (−9.9, −3.7) | 0.3 (−4.3, 5.2) |
| HMDB10471 | C50:5 TAG | Lipids and lipid-like molecules | −5.7 (−9.4, −1.9) | −7.2 (−11.3, −2.9) | −6.1 (−9.1, −3.0) | −2.8 (−7.3, 1.8) |
| HMDB05433 | C50:3 TAG | Lipids and lipid-like molecules | −5.7 (−9.3, −1.9) | −5.6 (−9.7, −1.4) | −4.6 (−7.6, −1.5) | −4.7 (−9.0, −0.3) |
| HMDB05369 | C52:2 TAG | Lipids and lipid-like molecules | −5.8 (−9.4, −2.1) | −7.0 (−11.0, −2.8) | −5.1 (−8.1, −2.1) | −5.6 (−9.7, −1.2) |
| HMDB10498 | C54:9 TAG | Lipids and lipid-like molecules | −5.8 (−9.5, −1.9) | −7.5 (−11.9, −2.9) | −7.6 (−10.7, −4.4) | 0.3 (−4.5, 5.2) |
| HMDB11526 | C22:6 LPE | Lipids and lipid-like molecules | −5.8 (−9.5, −2.0) | −4.7 (−9.1, −0.1) | −3.4 (−6.5, −0.2) | −5.5 (−9.9, −1.0) |
| HMDB07218 | C36:2 DAG | Lipids and lipid-like molecules | −5.9 (−9.5, −2.2) | −6.0 (−10.1, −1.7) | −5.3 (−8.2, −2.2) | −4.1 (−8.4, 0.4) |
| HMDB05435 | C50:4 TAG | Lipids and lipid-like molecules | −6.0 (−9.7, −2.2) | −5.7 (−9.9, −1.3) | −5.4 (−8.5, −2.3) | −3.3 (−7.8, 1.3) |
| HMDB05448 | C56:9 TAG | Lipids and lipid-like molecules | −6.2 (−9.8, −2.4) | −5.5 (−9.8, −1.0) | −6.6 (−9.6, −3.4) | −0.6 (−5.1, 4.2) |
| HMDB07103 | C34:2 DAG | Lipids and lipid-like molecules | −6.6 (−10.2, −3.0) | −7.7 (−11.6, −3.5) | −6.7 (−9.6, −3.7) | −4.1 (−8.4, 0.4) |
| HMDB07219 | C36:3 DAG | Lipids and lipid-like molecules | −6.6 (−10.2, −2.7) | −5.7 (−10.0, −1.2) | −6.4 (−9.4, −3.2) | −2.4 (−6.9, 2.3) |
| HMDB02183 | DHA | Lipids and lipid-like molecules | −6.6 (−10.1, −3.0) | −4.6 (−8.8, −0.2) | −5.5 (−8.4, −2.5) | −2.5 (−6.7, 2.0) |
| HMDB05384 | C52:3 TAG | Lipids and lipid-like molecules | −6.7 (−10.4, −2.9) | −6.2 (−10.4, −1.8) | −5.7 (−8.8, −2.5) | −4.9 (−9.3, −0.3) |
| HMDB05380 | C52:5 TAG | Lipids and lipid-like molecules | −6.8 (−10.5, −2.9) | −5.3 (−9.6, −0.8) | −6.4 (−9.5, −3.2) | −2.1 (−6.6, 2.7) |
| HMDB07132 | C34:3 DAG | Lipids and lipid-like molecules | −7.2 (−10.8, −3.4) | −7.3 (−11.5, −3.0) | −7.1 (−10.1, −4.0) | −3.5 (−7.9, 1.1) |
| HMDB10517 | C52:7 TAG | Lipids and lipid-like molecules | −7.5 (−11.1, −3.7) | −7.4 (−11.5, −3.1) | −7.7 (−10.6, −4.6) | −2.0 (−6.5, 2.6) |
| HMDB10518 | C54:8 TAG | Lipids and lipid-like molecules | −7.6 (−11.3, −3.8) | −6.9 (−11.1, −2.4) | −7.8 (−10.8, −4.7) | −1.4 (−6.0, 3.4) |
| HMDB05436 | C52:6 TAG | Lipids and lipid-like molecules | −8.3 (−11.8, −4.5) | −7.1 (−11.2, −2.7) | −7.9 (−10.9, −4.9) | −2.5 (−6.9, 2.2) |
DHA, docosahexaenoic acid; HMDB ID, Human Metabolome Database identifier.
Multivariate linear regression analysis was conducted to adjust for age at blood draw (continuous), fasting status (yes, no), race (White, non-White), study cohort, case-control status, cumulative average levels of BMI (<23.0, 23.0–24.9, 25.0–27.4, 27.5–29.9, ≥30.0 kg/m2), physical activity (<3.0, 3.0–8.9, 9.0–17.9, 18.0–26.9, ≥27.0 MET h/week), alcohol consumption (0, 0.1–4.9, 5.0–9.9, 10.0–14.9, ≥15.0 g/day), smoking status (never smoker; past smoker, <30 pack-years; past smoker, ≥30 pack-years; current smoker, <30 pack-years; current smoker, ≥30 pack-years), whole grains (quintiles), fruits (quintiles), vegetables (quintiles), polyunsaturated fat–to–saturated fat ratio (quintiles), fish (quintiles), red meat (quintiles), sugar-sweetened beverages (quintiles), total energy intake (quintiles), regular multivitamin use (yes, no), regular aspirin/nonsteroidal anti-inflammatory drug use (yes, no), hypertension (yes, no), hypercholesterolemia (yes, no), menopausal status (premenopausal, postmenopausal, unknown), and menopausal hormone therapy (never, past, current use).