The news stunned and disturbed dietitians. On March 22, the Health and Human Services Office of Research Integrity announced that Eric T. Poehlman, PhD, engaged in scientific misconduct by fabricating and falsifying data.1

Poehlman’s case is particularly important to dietitians because his work is related to obesity and resting metabolic rate (RMR) in aging postmenopausal women. Much of what we know about these topics came from Poehlman’s work, and now much of the work is open to question—and some has been discounted entirely.

Data from the studies were published from 1992 to 2002 (see chart on page 17). Notices by Poehlman have appeared in the journals that originally published the articles (for example, Annals of Internal Medicine2). Poehlman takes complete responsibility for the scientific misconduct and has publicly exonerated his coauthors.

Problems for Researchers and Practitioners
The Office of Research Integrity uncovered solid evidence of misconduct. For example, it was discovered that some data in a longitudinal study of aging were falsified by reversing the original values for total energy expenditure with the follow-up values. In a longitudinal menopause study, Poehlman falsified thyroid hormone data; essentially, the longitudinal study was never conducted and original data for the 35 women were fabricated. Only three women were seen at follow-up.1

Poehlman published more than 200 articles. Although only 10 papers have been corrected or retracted, some editors are cautious about citing Poehlman articles, especially when he is listed as first author. Some topics have been studied by other researchers, so articles on the same subject are available that are not dependent on Poehlman’s work; though that is not the case in all areas.

A study by Toth and Poehlman reported that RMR in vegetarians was approximately 11% higher than in nonvegetarians.3 To date, there has not been another published study comparing RMR of vegetarians with that of nonvegetarians. Thus, there is no evidence to confirm or refute the Toth and Poehlman study’s findings.

Even when there is comparable research from other sources, the body of literature may be small. The effect of endurance training on metabolic rate in older individuals, for example, is the subject of two of the discredited Poehlman articles, but there is little published elsewhere on the topic. Practitioners are left wondering whom and what to trust.

Indeed, a case such as this tests our understanding of scientific integrity and brings the consequences of misconduct home to roost. The accompanying sidebar defines such misconduct and explains the difference between mere error or methodological imperfection and true misconduct.

Dietitians working in the areas of Poehlman’s studies must take a wait-and-see attitude. In the meantime, we should review our current knowledge of RMR in older adults, generally, and in post-menopausal women, specifically, and the potential effects of aging on body composition. The influence of endurance training by older individuals on metabolic rate, mentioned above, is also discussed.

Body Composition, RMR, and Aging
RMR decreases with age. Much of the decrease is associated with a decline in lean body mass, but changes in body composition do not account for the entire decrease. Subtle changes in metabolic processes—for example, declines in Na+-K+-ATPase activity—also contribute to the decline.4

Lean body mass, primarily as skeletal muscle, decreases with age. Nonmuscle protein losses are minimal. The involuntary decline in muscle mass is known as sarcopenia. Sarcopenia is different than wasting, a result of inadequate energy intake, or cachexia, where lean body mass is decreased while weight is maintained. Sarcopenia is likely due to reduced muscle protein synthesis and the inability of aging muscle to respond to anabolic stimuli such as diet and exercise.5

In young adults, nearly 60% of fat-free mass is muscle, but in older adults muscle as a percentage of fat-free mass declines to 45%. Muscle mass is associated with muscle strength and reduced muscle strength is a hallmark of aging.6 Many studies of muscle size and strength are performed in men; whether women’s muscles decline to the same degree is not fully known.

Recent studies in healthy older men suggest that aging muscles fail to respond to anabolic stimuli. The presence of cytokines (proteins that regulate immunological aspects of cell growth and function) or lower levels of hormones (such as growth hormone, testosterone, or other growth promoting hormones) may be the cause of sarcopenia, at least in men. The amount of an important contractile protein, myosin heavy chain (MHC), is significantly lower in older adults. The reduction in MHC synthesis may result in the atrophy of type 2 muscle fibers, a type of muscle fiber known to decrease in older men and women.6

Physical inactivity causes the decline of muscle mass in older adults. Studies have shown that resistance exercise can increase both the quantity and quality of muscle protein. It is important to note that resistance training cannot completely prevent the decline in muscle mass accompanying aging. However, resistance training does help maintain the structure and functionality of muscles. Strong, functional muscles help prevent falls, support activities of daily living, and prevent frailty.7

Similarly, aerobic exercise training has an effect on muscle mass. Short et al studied 78 untrained men and women between the ages of 19 and 87.8 Protein synthesis declined with age (approximately 4% to 5% each decade). An aerobic training program of four months of cycling (45 minutes, three to four days per week) enhanced muscle protein synthesis in subjects who exercised, compared with controls engaging in no aerobic training. The increase in protein synthesis with aerobic exercise occurred in all age groups. A decline in protein synthesis occurs with aging, but the decline can be attenuated with both aerobic and resistance exercise.

Body Composition and RMR in menopausal women
More studies on RMR and aging have been conducted in men than in women.4 The body of literature has always been fairly small in postmenopausal women and included some of the Poehlman articles that have now been retracted.

A question on the minds of many middle-aged women is: “Does menopause cause weight gain?” By itself, menopause is not associated with weight gain. However, studies have shown that an age-related decrease in RMR and a decrease in physical activity—even leisure activities—often results in weight gain around the time of menopause.9 In other words, weight gain at menopause is not inevitable but is frequently seen.

Not all women experience weight gain during the perimenopausal period. However, in most postmenopausal women, including weight-stable women, body composition changes. Lean tissue is lost from the legs and abdominal fat is increased. Women who are not physically active experience greater weight gain and larger increases in abdominal fat than physically active women.9

Hormonal changes occurring with menopause appear to favor the deposition of fat in visceral fat stores. However, the research results are mixed, probably because of the methods used to measure intra-abdominal fat. Waist-to-hip ratio (WHR) is often used as a measure of intra-abdominal fat. Studies that use CT scans or other precise methods are needed. There is also evidence that hormone replacement therapy (HRT) may protect against visceral fat deposits in obese and nonobese women.10 However, there are risks associated with HRT.

Regular exercise in postmenopausal women may protect against the accumulation of visceral fat, but the body of knowledge is sparse. Postmenopausal women are not studied as frequently and protocols combine both diet and exercise, making it difficult to determine the independent effects of each. Exercise for postmenopausal women is highly encouraged for many reasons, and emerging studies show that exercise can prevent either weight gain or abdominal weight gain in menopausal women.

Asikainen and colleagues reviewed 18 randomized controlled studies in early postmenopausal women (aged 50 to 65) to determine the effects of exercise on health.11 The studies included many markers of health-related fitness including body weight, percentage of body weight as fat, and muscle strength. Together the studies included more than 2,600 subjects.

The authors concluded that for postmenopausal women between the ages of 50 and 65, a daily exercise program equivalent to 30 minutes of moderate-intensity walking coupled with resistance training two times per week helped maintain body weight, increase muscle strength, and preserve bone mineral density.

Using data from the Third National Health and Nutrition Examination Survey, Holcomb et al report that in premenopausal Caucasian women an increased level of physical activity was associated with a decreased body mass index and a decreased WHR.12 Although intra-abdominal fat was not measured directly, the study suggests that exercise has an independent effect on abdominal fat accumulation.

Although it is generally accepted that women’s RMRs decline with age, some researchers argue that the decline is seen because women in Westernized countries are overwhelmingly sedentary. One hypothesis is that the same decline would not be observed if women consistently engaged in aerobic activity. Van Pelt and colleagues compared RMR in 65 healthy women who were weight stable.13 Twenty-five were pre-menopausal; of those 25 subjects, 12 were sedentary and 13 were distance runners between the ages of 21 and 35. The remaining subjects were postmenopausal and between the ages of 50 and 72. Fifteen were sedentary, 15 were distance runners, and 10 were endurance-trained swimmers.

The endurance-trained older women had a higher RMR than the sedentary older women, but there was no significant difference in RMR when the RMR of the older endurance-trained women were compared with younger endurance-trained women. Among sedentary women, RMR was approximately 10% lower in the older, postmenopausal women than the younger, premenopausal women. The results of this study support the hypothesis that the same decline in RMR seen in sedentary women as they age is not seen in women who consistently engage in aerobic activity. It should be noted that the RMR of the postmenopausal runners and swimmers was nearly identical—suggesting that the results of this study may be generalized to women engaging in endurance-trained activities other than running and swimming (eg, cycling).

Decline in RMR in Physically Active Men
If endurance-trained older women do not demonstrate the same decline in RMR that sedentary older women do, can the same be said for older men who engage in aerobic exercise? At least one study suggests that a similar response occurs in men. Van Pelt et al studied 137 healthy men who were weight stable.14 Seventy-one were young (aged 26 to 27); of those 71 subjects, 32 were sedentary. The remaining subjects were aged 62 to 63. Thirty-four were sedentary and 32 engaged in endurance exercise three times or more per week. Both the sedentary and endurance-trained older men had a lower RMR when compared with younger men in their respective exercise groups. In other words, older sedentary men had a lower RMR than younger sedentary men, and older men who exercised had a lower RMR than younger men who exercised.

When the exercise subgroup was studied further, it was noted that the decline in RMR with age was associated with the volume of exercise and energy intake. If the older men were able to maintain the same volume of endurance exercise and consume the same amount of energy (kilocalories per day) as the younger men, there was no difference between the RMR of older and younger exercisers. A decline in RMR among older, endurance-trained men is not inevitable but is often seen because it is difficult to maintain the same volume of training and same caloric intake as younger men.

Conclusion
The notification of scientific misconduct of a well-known researcher has caused dietitians to pause and reflect on the current body of literature in the areas of body composition, RMR, and aging. RMR decreases with age, and declining RMR over decades contributes to changes in body composition. Sarcopenia, the involuntary decline in muscle mass, is frequently seen in otherwise healthy older men and women. Resistance training and aerobic exercise have positive effects on muscle mass even in older individuals.

Maintaining physical activity—even leisure activities—is more difficult as people age. It is particularly difficult to maintain the same volume of exercise as individuals age. It is not inevitable that weight will be gained with aging, especially for women in the perimenopausal period, but it is frequently seen because of declines in physical activity. For older individuals, it is especially important to engage in 30 minutes of moderate intensity exercise daily and resistance training twice per week. There are many benefits to such an exercise program, including maintenance of body weight, increased muscle strength, and preservation of bone mineral density.

— Marie Dunford, PhD, RD, is the author of a consumer-oriented nutrition book, Nutrition Logic: Food First, Supplements Second, and the editor of a forthcoming book for professionals, Sports Nutrition: A Practice Manual for Professionals.

References
1. Findings of scientific misconduct. U.S. Department of Health and Human Services (DHHS). Notice number: NOT-OD-05-040, March 22, 2005. Available at: http://ori.hhs.gov/misconduct/cases/poehlman.shtml

2. Poehlman ET. Notice of retraction: Final resolution. Ann Intern Med. 2005;142(9):798.

3. Toth MJ, Poehlman ET. Sympathetic nervous system activity and resting metabolic rate in vegetarians. Metabolism. 1994;43(5):621-625.

4. Wilson MM, Morley JE. Invited review: Aging and energy balance. J Appl Physiol. 2003;95(4):1728-1736.

5. Roubenoff R, Castaneda C. Sarcopenia—Understanding the dynamics of aging muscle. JAMA. 2001;286(10):1230-1231.

6. Short KR, Nair KS. Muscle protein metabolism and the sarcopenia of aging. Int J Sport Nutr Exerc Metab. 2001;11:S119-S127.

7. Westerterp KR, Meijer EP. Physical activity and parameters of aging: A physiological perspective. J Gerontol A Biol Sci Med Sci. 2001;56(2):7-12.

8. Short KR, Vittone JL, Bigelow ML, et al. Age and aerobic exercise training effects on whole body and muscle protein metabolism. Am J Physiol Endocrinol Metab. 2004;286(1):E92-E101.

9. Astrup A. Physical activity and weight gain and fat distribution changes with menopause: Current evidence and research issues. Med Sci Sports Exerc. 1999;31(11Suppl):S564-S567.

10. Simkin-Silverman LR, Wing RR. Weight gain during menopause. Postgrad Med. 2000;108(3):47-50,53-54,56.

11. Asikainen TM, Kukkonen-Harjula K, Miilunpalo S. Exercise for health for early postmenopausal women: A systematic review of randomised controlled trials. Sports Med. 2004;34(11):753-778.

12. Holcomb CA, Heim DL, Loughin TM. Physical activity minimizes the association of body fatness with abdominal obesity in white, premenopausal women: Results from the Third National Health and Nutrition Examination Survey. J Am Diet Assoc. 2004;104(12):1859-1862.

13. van Pelt RE, Jones PP, Davy KP, et al. Regular exercise and the age-related decline in resting metabolic rate in women. J Clin Endocrinol Metab. 1997;82(10):3208-3212.

14. van Pelt RE, Dinneno FA, Seals DR, et al. Age-related decline in RMR in physically active men: Relation to exercise volume and energy intake. Am J Physiol Endocrinol Metab. 2001;281(3):E633-E639.