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Reply to MF McCarty

Faculté de Médecine, Institut de Physiologie, Universite de Lausanne, Bugnon 7, 1005 Lausanne, Switzerland, E-mail: Eric.Jequier{at}physiol.unil.ch

Dear Sir:

I thank McCarty for his comments on my editorial (1). McCarty emphasizes a sex difference in the relation between daily alcohol energy intake and body weight: in men, there is no clear relation, whereas in women, moderate drinkers tend to be lighter than nondrinkers (2). The paradox that I mentioned, ie, an increased alcohol-induced energy intake without weight gain, is even more evident in women than in men because moderate alcohol intake seems to induce a decrease in body weight in women. If these large cross-sectional epidemiologic surveys (2) are correct, the only explanation for this finding is that a moderate alcohol intake increases energy expenditure in women more so than in men.

How can alcohol intake stimulate energy expenditure? McCarty mentions that cross-sectional studies also show that moderate drinkers are more insulin sensitive than nondrinkers (3, 4). He suggests that down-regulation of diurnal insulin secretion in moderate alcohol drinkers might disinhibit hepatic ketogenesis and gluconeogenesis, which are thermogenic processes. These metabolic explanations are unlikely to be true for the following reasons:

1. Ketogenesis is a moderately thermogenic pathway (5) and is more sensitive to the inhibitory action of insulin than muscle glucose uptake is sensitive to the stimulatory action of the hormone.
   
2. Gluconeogenesis is a highly thermogenic pathway but it is unlikely that it is stimulated in moderate alcohol consumers because alcohol inhibits gluconeogenesis (6).
   
3. Although cross-sectional epidemiologic surveys suggest that light-to-moderate alcohol intake is associated with enhanced insulin sensitivity (3, 4), metabolic studies in healthy volunteers show an alcohol-induced impairment in glucose metabolism caused by a decreased tissue sensitivity to insulin (7, 8).
   
4. McCarty's statement that "both clinical and animal research suggest that diminution of diurnal insulin secretion tends to promote leanness" raises the question of what comes first: low insulin secretion is more likely a consequence of an energy deficit (ie, from hypoenergetic diets or physical activity of long duration) than the cause of the energy deficit.
   

How can we solve the paradox in women of an increased alcohol-induced energy intake associated with a reduced body weight, if alcohol has only a moderate thermogenic effect? A recent paper by Levine et al (9) showed that nonexercise activity thermogenesis (NEAT) may play a major role in body weight regulation in response to chronic excesses in energy intake. This type of activity includes strolling around and movements of the limbs with little displacement of the body's center of gravity, ie, various types of activity referred to as fidgeting (10). Levine et al (9) clearly showed that a large portion of the variability in energy storage during an 8-wk overfeeding study in healthy volunteers was accounted for by changes in NEAT. If a moderate alcohol intake activates NEAT, this may be the most likely explanation of the above-cited paradox. Why this alcohol-induced increase in energy expenditure could be more important in women than in men remains to be elucidated.

REFERENCES

1. Jéquier E. Alcohol intake and body weight: a paradox. Am J Clin Nutr 1999;69:173–4.[Free Full Text]
2. Colditz GA, Giovannucci E, Rimm EB, et al. Alcohol intake in relation to diet and obesity in women and men. Am J Clin Nutr 1991;54:49–55.[Abstract/Free Full Text]
3. Facchini F, Chen YD, Reaven GM. Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity. Diabetes Care 1994;17:115–9.[Abstract]
4. Kiechl S, Willeit J, Poewe W, et al. Insulin sensitivity and regular alcohol consumption: large, prospective, cross sectional population study. BMJ 1996;313:1040–4.[Abstract/Free Full Text]
5. Flatt JP. The biochemistry of energy expenditure. In: Bray GA, ed. Recent advances in obesity research. Vol 2. London: Newman Publishing, 1978:211–28.
6. Siler SQ, Neese RA, Christiansen MP, Hellerstein MK. The inhibition of gluconeogenesis following alcohol in humans. Am J Physiol 1998;275:E897–907.
7. Shah JH. Alcohol decreases insulin sensitivity in healthy subjects. Alcohol Alcohol 1988;23:103–9.[Abstract/Free Full Text]
8. Avogaro A, Fontana P, Valerio A, et al. Alcohol impairs insulin sensitivity in normal subjects. Diabetes Res 1987;5:23–7.[Medline]
9. Levine JA, Eberhardt NL, Jensen MD. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science 1999; 283:212–4.[Abstract/Free Full Text]
10. Ravussin E, Lillioja S, Anderson T. Determinants of 24-hour energy expenditure in man: methods and results using a respiratory chamber. J Clin Invest 1986;78:1568–78.

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