EE: Smoking and Nicotine (2013)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • To determine the thermic effect of smoking multiple cigarettes with markedly differing nicotine yields.


  • Steady state: Not defined.
Inclusion Criteria:
  1. Understand and give written consent
  2. Men in good health, age 18-65 yrs
  3. Smoke cigarettes regularly for at least 1 year.
Exclusion Criteria:
  1. Refusal to consent
  2. Not meeting inclusion criteria
  3. Diseases in subjects that were excluded: cardiopulmonary disease, diabetes mellitus, or thyroid disease
  4. Medications excluded: antihistamine, decongestants, or sedative.
Description of Study Protocol:

Three treatments were imposed for each subject:

  1. BASELINE: No smoking
  2. LOW: Smoking 6 low-nicotine (0.8mg nicotine) cigarettes
  3. HIGH: Smoking 6 high-nicotine (1.74mg nicotine) cigarettes.

The sequence in which the protocols were performed was randomized.


  • Ht, Wt, body fat%.


  • Monitored heart rate? Not addressed
  • Body temperature? No
  • Medications administered? No.

Resting energy expenditure

  • IC type: Sensormedics 2900 Z open system
  • Coefficient of variation using std gases: Yes or No
  • Measurement length: 30 minutes for baseline; For following 2 hours, 20-minute period alternating with 10-minute period of sitting with or without smoking
  • Steady state: Not addressed
  • Fasting length: 12 hours
  • Exercise restrictions XX hr prior to test? 12 hours
  • No. of measures within the measurement period: 1 in 30 minutes and 6 in 2 hrs
  • Were some measures eliminated? No
  • Were a set of measurements averaged? No
  • Coefficient of variation in subjects measures? Not addressed
  • Training of measurer? Not addressed
  • Subject training of measuring process? Not addressed.


  • Subjects were not eating before and during the measurement.
  • Cigarettes
    • High-nicotine: 2R1F yielding 1.74 mg nicotine and 22.0mg CO per cigarette
    • Low-nicotine: 1R4F yielding 0.8mg nicotine and 11.6 mg CO per cigarette.

Intervening factor: Smoking intensity was assessed—exhaled CO was measured after smoking the first 2 cigarettes and then after each of the four remaining cigarettes.

Data Collection Summary:

Outcome(s) and other measures

  1. Measured RMR [(VO2, l/min), VCO2 (l/min; ml/kg/min), RQ, ventilation (l/min)].
  2. Expired CO (ppm).

Blinding used: No.

Description of Actual Data Sample:
  • N=16 men aged 41±11 years.

Statistical tests

  • One-way ANOVA to test for differences in energy expenditure during the 30 minutes daily baseline measurements across the 3 protocols.
  • Repeated-measures multivariate ANOVA to test for the effects of the smoking treatments.
Summary of Results:

Descriptive characteristics, Mean±SD

  • Wt, kg: 80.9±16.7
  • Ht, cm: 177.7±8.0
  • Body fat %: 19.5±5.0
  • Pack-yrs: 28.5±18.5.

Expired CO was similar for both HIGH and LOW cigarettes throughout the two protocols. This suggests that LOW cigarettes were smoked more aggressively, because the CO yield of HIGH cigarettes (2R1F) was twice that of LOW cigarettes (1R4F), 22.0 vs. 11.6 mg nicotine per cigarette, respectively.

During the resting baseline treatment (protocol 1), no significant change in RMR was detected across the 2-hour (plus initial 30-minutes) measurement period.

No significant differences across treatments in the 30-minute daily baseline RMR during protocol 1, 2, and 3.

Smoking significantly increased RMR by 6.8% above the resting baseline level. The effect was the same for both HIGH and LOW cigarettes.

With consumptions of more cigarettes, the peak increase for HIGH treatment was 9.3%, significantly greater than the peak of 5.9% for the LOW.

Average over 2 hours, the HIGH treatment significantly increased RMR by 6.9% and the LOW treatment significantly increased RMR by 5.2%.

Author Conclusion:

“The initial increase in RMR of 6.8% as a result of smoking 2 cigarettes is consistent with previous reports. After smoking 3 cigarettes, the change in RMR is essentially the same for both HIGH and LOW cigarettes. These finding support our hypothesis but conflict with findings previously reported by Perkins et al, who found nearly double the response when administering a 30 ug/kg dose of nicotine vs 15 ug/kg.”

“We attribute our findings to the aggressive smoking of the LOW cigarettes. Expired CO data indicate that the LOW cigarette, because of its low CO yield, was smoked nearly twice as aggressively as the HIGH cigarette."

“The data imply that after smoking 3 cigarettes, a similar blood nicotine level may have been achieved with either the HIGH or LOW cigarette despite the large difference in nicotine yield. However, there are no blood nicotine values available to document this.”

“It was concluded that, initially, the nicotine yield of cigarettes is not an important influence on the thermic of smoking. But over a longer period and after multiple cigarettes, the nicotine yield may become and important influence factors.”

Funding Source:
University/Hospital: University of Louisville
Reviewer Comments:


  • Well-designed study with appropriate statistics.
  • Smoking intensity was measured on both HIGH and LOW protocol to assess if it has any impacts on RMR
  • Results and conclusions are consistent with data.
  • Randomizations of the sequence of treatments were performed.
  • Controlled for food intake, exercise, and measurement procedures.


  • Limitations of the study was not fully addressed.
  • Would increase generalizability if included female smokers as well.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? N/A
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? N/A
  1.3. Were the target population and setting specified? N/A
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? N/A
  2.2. Were criteria applied equally to all study groups? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? N/A
  2.4. Were the subjects/patients a representative sample of the relevant population? N/A
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? No
  7.1. Were primary and secondary endpoints described and relevant to the question? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? N/A
  7.5. Was the measurement of effect at an appropriate level of precision? N/A
  7.6. Were other factors accounted for (measured) that could affect outcomes? N/A
  7.7. Were the measurements conducted consistently across groups? N/A
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? N/A
  8.2. Were correct statistical tests used and assumptions of test not violated? N/A
  8.3. Were statistics reported with levels of significance and/or confidence intervals? N/A
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  8.6. Was clinical significance as well as statistical significance reported? N/A
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? N/A
  9.2. Are biases and study limitations identified and discussed? N/A
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? N/A
  10.2. Was the study free from apparent conflict of interest? N/A