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. 2024 Dec 4;387:e078386. doi: 10.1136/bmj-2023-078386

Table 6.

Sensitivity analysis. Values are hazard ratio (95% CI)* unless stated otherwise

Models† Chocolate consumption levels P trend‡ Per serving/week
0 or <1 serving/month 1 serving/month to <1 serving/week 1-4 servings/week ≥5 servings/week
Total chocolate§
Case/person years 4517/1 298 191 8387/2 094 735 5307/1 263 381 651/1 72 868
Baseline chocolate 1 1.00 (0.96 to 1.03) 1.00 (0.96 to 1.04) 0.92 (0.85 to 0.99) 0.14 0.99 (0.98 to 1.00)
Most recently updated chocolate 1 1.00 (0.97 to 1.04) 0.99 (0.95 to 1.03) 0.90 (0.84 to 0.96) 0.003 0.99 (0.98 to 1.00)
Adjustment factors:
 Time varying BMI 1 1.01 (0.97 to 1.05) 1.00 (0.96 to 1.04) 0.88 (0.81 to 0.96) 0.01 0.99 (0.97 to 1.00)
 Flavan-3-ols-rich food 1 1.04 (1.00 to 1.08) 1.03 (0.99 to 1.07) 0.90 (0.82 to 0.98) 0.05 0.99 (0.98 to 1.00)
 Food predicting T2D 1 1.02 (0.98 to 1.06) 1.01 (0.97 to 1.06) 0.91 (0.84 to 1.00) 0.11 0.99 (0.98 to 1.00)
 Epicatechin intake 1 1.03 (0.99 to 1.07) 1.02 (0.98 to 1.07) 0.90 (0.83 to 0.99) 0.07 0.99 (0.98 to 1.00)
 Saturated fat intake 1 1.03 (0.99 to 1.06) 1.01 (0.96 to 1.05) 0.88 (0.81 to 0.96) 0.01 0.98 (0.97 to 1.00)
Dark chocolate
Case/person years 2391/592 412 1473/398 618 776/226 516 131/52 802
Baseline chocolate 1 0.99 (0.92 to 1.06) 0.91 (0.84 to 0.99) 0.90 (0.75 to 1.07) 0.03 0.98 (0.96 to 1.00)
Most recently updated chocolate 1 0.96 (0.89 to 1.03) 0.93 (0.86 to 1.01) 0.75 (0.63 to 0.90) 0.001 0.97 (0.95 to 0.99)
Adjustment factors:
 Time varying BMI 1 0.96 (0.89 to 1.02) 0.94 (0.86 to 1.02) 0.80 (0.67 to 0.96) 0.01 0.97 (0.95 to 0.99)
 Flavan-3-ols rich food 1 0.95 (0.89 to 1.02) 0.92 (0.84 to 1.00) 0.78 (0.65 to 0.93) 0.003 0.97 (0.94 to 0.99)
 Food predicting T2D 1 0.95 (0.89 to 1.02) 0.93 (0.85 to 1.01) 0.82 (0.68 to 0.98) 0.01 0.97 (0.95 to 0.99)
 Epicatechin intake 1 0.96 (0.90 to 1.03) 0.95 (0.87 to 1.04) 0.86 (0.71 to 1.04) 0.09 0.98 (0.95 to 1.00)
 Saturated fat intake 1 0.95 (0.89 to 1.01) 0.91 (0.84 to 1.00) 0.77 (0.64 to 0.93) 0.002 0.96 (0.94 to 0.99)
Milk chocolate¶
Case/person years 1525/476 596 1909/494 537 1168/260 942 169/38 275
Baseline chocolate 1 0.97 (0.90 to 1.04) 0.99 (0.91 to 1.07) 0.88 (0.74 to 1.04) 0.35 0.99 (0.97 to 1.01)
Most recently updated chocolate 1 0.94 (0.87 to 1.01) 0.98 (0.91 to 1.07) 0.96 (0.81 to 1.14) 0.91 0.99 (0.97 to 1.01)
Adjustment factors:
 Time varying BMI 1 0.97 (0.90 to 1.04) 0.99 (0.91 to 1.08) 0.93 (0.79 to 1.11) 0.70 0.99 (0.97 to 1.01)
 Flavan-3-ols rich food 1 0.98 (0.91 to 1.05) 1.00 (0.92 to 1.09) 0.95 (0.80 to 1.13) 0.84 0.99 (0.97 to 1.01)
 Food predicting T2D 1 0.97 (0.90 to 1.04) 1.00 (0.92 to 1.09) 0.99 (0.83 to 1.18) 0.82 0.99 (0.97 to 1.02)
 Epicatechin intake 1 0.97 (0.90 to 1.04) 0.99 (0.91 to 1.08) 0.95 (0.80 to 1.13) 0.85 0.99 (0.97 to 1.01)
 Saturated fat intake 1 0.96 (0.89 to 1.03) 0.98 (0.90 to 1.07) 0.92 (0.78 to 1.10) 0.56 0.98 (0.96 to 1.01)

Data from three cohorts were combined to run the analysis. Fully adjusted models adjusted for age, calendar year, ethnicity (white, African American, Asian, and others), smoking status (never, former, current (1-14, 15-24, or ≥25 cigarettes/day), or missing), alcohol intake (g/day: 0, 0.1-4.9, 5.0-14.9, and ≥15.0 in women, 0, 0.1-4.9, 5.0-14.9, 15.0-29.9, and ≥30.0 in men, or missing), family history of diabetes (yes/no), menopausal status and postmenopausal hormone use (premenopausal, postmenopausal (never, former, or current hormone use), or missing, for women), use of oral contraceptives (yes, no, NHSII only), physical activity (<3, 3.0-8.9, 9.0-17.9, 18.0-26.9, ≥27.0 MET-h/week, or missing), baseline BMI (<21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9, 30.0-32.9, 33.0-34.9, ≥35.0, or missing), multivitamin use (yes/no), baseline hypertension, baseline hypercholesterolemia, total energy intake, alternative health eating index (five groups), total chocolate intake before baseline (as cumulative averages for 1980-2002 (NHS), 1991-2003 (NHSII), 1986-2002 (HPFS)), and study origin (NHS, NHSII, HPFS).

Adjustment of time varying BMI: Comparing with fully adjusted model, instead of adjusting for baseline BMI, adjusted for time varying BMI (<21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9, 30.0-32.9, 33.0-34.9, ≥35.0, or missing).

Adjustment of flavan-3-ols-rich foods: Comparing with fully adjusted model, instead of adjusting for alternative health eating index, adjusted for consumption of food and drinks high in flavan-3-ols, including tea, red wine, apples, pears, blueberries, bananas, and peppers (continuous, servings/day).

Adjustment of food predicting T2D: Comparing with fully adjusted model, instead of adjusting for alternative health eating index, adjusted for consumption of red and processed meat, fruit and vegetables, sugar sweetened beverages, whole grains (fifths).

Adjustment of epicatechin intake: Comparing with fully adjusted model, further adjusting for epicatechin intake (continuous, mg/day).

Adjustment of saturated fat intake: Comparing with fully adjusted model, further adjusting for saturated fat intake (as percentage of total energy intake, five groups).

BMI=body mass index; CI=confidence interval; NHS=Nurses’ Health Study; NHSII=Nurses’ Health Study II; HPFS=Health Professionals Follow-up Study; MET-h=metabolic equivalents task per hour; T2D=type 2 diabetes.

*

Calculated using Cox proportional hazards models.

Calculated using median levels of chocolate consumption categories as continuous predictor in the model.

§

For total chocolate, baseline years were 1986 for NHS, 1991 for NHSII, and 1986 for HPFS.

For dark and milk chocolate, baseline years were 2006 for NHS, 2007 for NHSII, and 2006 for HPFS.

Baseline chocolate: Comparing with fully adjusted model instead of using time dependent intake, use baseline chocolate intake.

Most recently updated chocolate: Comparing with fully adjusted model instead of using cumulatively averaged intake, use most recently updated chocolate intake.