- Click here for explanation of classification scheme.

1. To examine whether older individuals show a reduced energy expenditure and lipolytic rate in response to caffeine, a noncaloric pharmacological agent.

1. Healthy men, volunteers; young and old
2. Regularly consume moderate amounts of caffeinated substances (<4 cups coffee/d)
3. Not obese or underweight with stable weight within the past year
4. Able to do exercise
5. Not taking any medications
6. Give written consent.

1. Excessive caffeine drinkers (>4 cups coffee/d)
2. Disease history of CVD, abnormal resting or exercise EKG, cardiomyopathy, hypertension, diabetes mellitus, renal failure or liver disease excluded
3. Use of tobacco products within the previous 3 months
4. Weight instability (±2 kg) within the past year as assessed by health history questionnaire
5. Body weight that is 15% above or below ideal based on their age group according to the 1959 Metropolitan Life insurance weight tables
6. Exercise-limiting noncardiac disease (e.g., arthritis, peripheral vascular disease and cerebral vascular disease).

After 30 min rest: Norepinephrine (50 and 60 min), free fatty acid (FFA), kinetics (70, 80 and 90 min), and RMR (0-30 min), then subject administered either placebo or caffeine pill with 50 ml of tepid water. Following pill ingestion, 90 min of continuous of norepinephrine and FFA kinetics, and 3 15-min intervals of RMR.

On second inpatient visit: same procedures but received either placebo or caffeine pill not given in 1^st inpatient visit.

ANTHROPOMETRIC

• Ht measured? Yes, method not described
• Wt measured? Yes, method not described
• Fat-free mass and fat mass? Yes; Underwater weighing.

CLINICAL

• Monitored heart rate? Not mentioned
• Body temperature? Not mentioned.

Resting energy expenditure

• IC type: Ventilated hood
• Equipment of Calibration: Not mentioned; but stated “detailed description of IC was reported” in another published article
• Coefficient of variation using std gases: Not mentioned;
• Rest before measure: On first inpatient visit subjects were asked to be in bed by 10 p.m.; for infusion testing --rested 30 min before testing began
• Measurement length: Baseline: 0-30 min; during each infusion study (2): three 15-min interval measurements of RMR
• Steady state: Not provided;
• Fasting length: Instructed to abstain from all caffeine-containing beverages for 48 hrs before test
• Exercise restrictions: Measurements performed 36-48 hours after the last exercise session
• Room temp: Not mentioned
• No. of measures within the measurement period: Baseline: 1 measurement (0-30 min); during infusion testing: three 15-min interval measurements of RMR (x2)
• Were some measures eliminated? No
• Were a set of measurements averaged? Mean of 3 samples of plasma corrected for extraction recovery
• Coefficient of variation in subjects measures? Not mentioned
• Training of measurer? Not mentioned
• Subject training of measuring process? Yes, prior to first inpatient visit.

DIETARY

• After admitted on first evening, subjects consumed their dinner (~1,000 kcal, 55% CHO, 30% fat, 15% protein) at 6 pm.
• In addition, energy intake and caffeine consumption were determined from a 3-day food diary (2 weekdays and 1 weekend day)
• Intervening factor: Energy expended in leisure-time physical activity was assessed by the Minnesota Leisure Time Physical Activity Questionnaire.

Outcome(s) and other measures

1. Measured RMR [(VO₂, l/min), VCO₂ (l/min; ml/kg/min), VO_2peak, ventilation (l/min)].
2. Blood sampling: fasting plasma glucose, insulin, FFA, caffeine, noreinephrine (appearance and clearance rates)
3. Independent variables of weight, height, age, BMI, and fat-free mass, fat mass
4. Energy expended by the Minnesota Leisure Time Physical Activity Questionnaire.
5. Energy intake (kcal) and caffeine consumption
6. Overnight urinary urea nitrogen.

Blinding used: Yes

• N=20 healthy men, who regularly consumed moderate amounts of caffeinated substances (self-reported mean intake: Y=126±136 mg/d; O=160±44 mg/d).
• Divided as:
  N=10; younger men (19-26 y) (Y)
  N=10; older men (65-80 y) (O)
• Statistical tests: A 3x2 repeated measures analysis of variance (ANOVA) was used to test for the effects of caffeine ingestion, age group, and the time course of concentrations of palmitic acid, [¹⁴C]
• Palmitate, norepinephrine, and [³H] norepinephrine during the 2 infusion tests; student’s Pearson product-moment correlation coefficient;. Tukey’s post hoc comparisons ; P<0.05.

ANTHROPOMETRIC

Men (younger)	Mean±SD
Wt, kg	79±9
Ht, cm	179±9
Fat-free body mass (kg)	70±8
Fat mass (kg)	9±4
Body fat %	11±4*
Leisure time activity (kcal/d)	689±454*
Self-reported food intake (kcal/d)	2,954±688*
Fasting caffeine, ng/ml	90±101
Fasting glucose (mg/dl)	96±6

Men (older)	Mean±SD
Wt, kg	76±8
Ht, cm	172±8
Fat-free body mass	59±7
Fat mass	17±7
Body fat, %	22±7
Leisure time activity (kcal/d)	357±224
Self-reported food intake (kcal/d)	2,122±706
Fasting caffeine	125±39
Fasting glucose	99±7

• Respiratory exchange rates (RER) at rest and after caffeine and placebo were not significantly different within or between groups.

RMR

• Baseline RMR (kcal/min) was higher (16%, P<0.05) in the younger men compared with the older men.
• Caffeine ingestion significantly increased energy expenditure in Y and O men for energy expenditure (Y=11%, 1.38±0.15 to 1.52±0.22 kcal/min, , P<0.05; O=9.5%, 1.15±0.13 to 1.26±0.20 kcal/min, P<0.05), but no differences were noted between age groups, when expressed as an absolute change in metabolic rate (mean change over 90-180 min, kcal/min), total thermic response to caffeine (kcal/90-180 min, kcal/min), or percent increase over RMR.
• Results indicated that older men reported lower (P<0.05) levels of energy expended in physical activity and were less (P<0.05) aerobically fit (VO₂).

Plasma Caffeine

• Caffeine ingestion significantly (P<0.05) increased plasma caffeine levels in both younger and older men at min 120 (Y=5,738±3,878 vs. O=6,987±3.328 ng/ml), 150 Y=(6,899±1,231 vs. O=7,085±2,905 ng/ml) and 180 (Y=6,386±708 vs. O=7,128±866 ng/ml).
• There were no differences in plasma caffeine levels between the 2 groups except at 180 min when older men had 10% higher values (P<0.05).

Plasma Hormones

• After ingestion of caffeine, plasma concentrations of glucose and insulin (values average for 120, 150, and 180 min) were not significantly different from baseline values in both groups.

Plasma Norepinephrine

• Older subjects tended to have greater concentrations and lower clearance rates of norepinephrine at rest, but there were no significant differences at baseline for norepinephrine concentration, appearance or clearance (O=197±56 vs. Y=169±pg/ml, O=0.6±0.2 vs. Y=0.5±0.2 µg/min, and O=2.8±0.4 vs. Y=3.1±0.71/min, respectively).
• After caffeine ingestion, however, norepinephrine concentrations were significantly greater in older than younger men (O=211±52 vs. & + 168±37 pg/ml, P<0.05). Plasma norepinephrine clearance and appearance rates were not significantly different from baseline. There were no interactions between caffeine treatment and age group fro norepinephrine concentrations and kinetics.

FFA

• Not abstracted since not related to evidence analysis question.

• “The major findings of this study were 1) older healthy men showed a similar thermogenic response to caffeine ingestion, 2) younger men had a lower concentration and rate of appearance of fatty acids compared with older men at rest, 3) in response to caffeine ingestion, younger men show a greater increase in FFA concentration and appearance than older men, 4) despite the lower availability of FFA, younger men had higher rates of fat oxidation than older men.”
• “The present study examined the thermogenic response to a physiological dose of caffeine in younger and older men. We found that the magnitude of increase in energy expenditure was 10 and 12% over baseline in older and younger men, respectively. These results are in agreement with reported findings using similar doses of caffeine in younger subjects.”
• “Our study noted that FFA concentrations and appearance rates increased by 122 and 124% in the younger men, respectively. It is possible that after caffeine ingestion older men are less capable of increasing FFA availability (eg, plasma concentrations and rate of appearance) due to their already high resting levels (ie, ceiling effect). This finding is in contrast to that found after brief starvation and exercise and may be related to methodological differences (eg, age, body composition, and fitness level).”
• “Caffeine ingestion has been shown to increase plasma concentrations of epinephrine, which may partially explain the increase in lipolysis and metabolic effect observed in this study, Our results do not support a relationship between changes in norepinephrine kinetics and total body fat oxidation and increased metabolic rate after stimulation with caffeine in younger and older men.”
• “The older men showed no change in the plasma concentration of FFA or the rate of appearance of fatty acids after caffeine ingestion."
• "Although older men had a percentage of fat twice that of younger men, no significant relationships existed between the norepinephrine and FFA kinetic data and the level of adiposity.”
• “Our results confirm a blunted ability to mobilize fat in older individuals after a caffeine challenge as evidence by no change in the plasma concentration or rate of appearance of fatty acids after caffeine ingestion....These observed changes do not appear to be related to generalized sympathetic nervous system activity or the rate of fat oxidation.”

Government:

NIA,

Strengths

• Strict control for individual differences among subjects by employing a repeated measures design, using a placebo and caffeine condition tht was administered in a double-blind fashion.
• Measurement techniques were highly standardized to ensure optimal basal conditions.
• All subjects were introduced to the ventilated hood system the evening before measurements to reduce anxiety.

Weaknesses

• Small sample size of both younger and older men; no power calculation used;? type 2 error
• Results limited to nonobese men; excluded overweight and underweight men
• Study participants were volunteers (self-selection bias)
• Generalizability: Healthy men only within a restricted age range (younger and older); no women
• Method of obtaining height and weight not explained; measured or self-report?
• Lack of description of IC and calibration: Stated described in a previous paper.

NOTE: This paper presents the same data as that in an NIH-retracted paper, so this data was not considered in conclusion statment.