- Email: [email protected]
Muscling in on salbutamol
1094
POLYUNSATURATED FATTY ACIDS IN HUMAN MILK
change the strength of respiratory muscles, ventilatory endurance, or exercise tolerance in healthy individuals.s concentrations did not
in animals have shown convincingly that the duration of action of salbutamol (achieved by prolonging infusion) induced the same anabolic effects as clenbuterol6 in the rat. Thus, unless the pattern of salbutamol metabolites in blood and/or urine can be shown to reliably distinguish the sustained-release preparation for normal salbutamol, serious consideration should be given to adding this drug to the list of banned substances for athletes.
However,
Mean (SEM) wt% total fatty acids shown *Data for 1992, tp < 0 05 vs both other groups, tp < 0 05 both other groups, §p < 0 05 vs both other groups
and the data provided by the Department of Health in 19772 do not represent the present composition of human milk in the UK. We have found that the proportion of linoleic acid in human milk has increased strikingly from 1977 to 1992 (table), which is in line with changes in dietary fatty acid intakes.3 Breastmilk from vegetarian mothers contains the highest proportion of linoleic acid and the lowest proportion ofDHA.4 Infants born to vegetarian mothers have lower proportions of DHA in their tissues.4 Infants born to vegan mothers and then breastfed have DHA concentrations in their erythrocytes that are only a third of those in infants breastfed by mothers with an omnivore diet. This trend might be viewed with some concern because of the growing popularity of vegetarianism. However, the growth and development of vegan children seems normal.5 Yet, there might be subtle functional changes. It is worth emphasising that in animals impaired visual function has only been noted when there has been extreme depletion of DHA from tissues. The variations in brain DHA reported by Farquharson might, therefore, be within the normal physiological range. Department of Nutrition and Dietetics, King’s College London,
T. A. B. SANDERS SHEELA REDDY
London W8 7AH, UK 1. Sanders
TAB, Naismith DJ. A comparison of the influence of breast-feeding and
bottle-feeding on the fatty add composition of erythrocytes. Br J Nutr 1979; 41: 619-23. 2. Department of Health and Social Security. Report on health and social subject, no 12: the composition of mature human milk. London: HM Stationery Office, 1977. 3. British Nutrition Foundation. Unsaturated fatty acids: nutrition and physiological significance. London: Chapman & Hall, 1992. 4. Sanders TAB, Reddy S. The influence of a vegetarian diet on the fatty add composition of human milk and the essential fatty add status of the infant. J Pediatr 1992; 120: S71-S77. 5. Sanders TAB, Manning J. The growth and development of vegan children. J Hum Nutr Diet 1992; 5: 11-21.
Muscling
in
on
salbutamol
SIR,-In your Aug 15 editorial you comment on the controversy the Barcelona Olympics about the use of the &bgr;2-adrenergic agonist clenbuterol to enhance muscle mass and function. Although at
there is a considerable amount of evidence that such agents can increase rapidly lean body mass and reverse muscle wasting in several animal models of human illness,l no published information is available for man. We have shown in sedentary, healthy male volunteers (n 6) that daily oral administration of a slow-release preparation of salbutamol (Volmax, Glaxo), a &bgr;2 -adrenergic agonist used in the treatment of asthma, causes substantial increases within 1-3 weeks in quadriceps (10-27%, median 14%) and hamstring muscle strength (13-48%, median 18%), as well as in static maximum inspiratory mouth pressure (6-26%, median 8%); these variables remained unchanged in the strength-matched placebo groUp.2,3 These results suggest that &bgr;2-adrenergic agonists can alter skeletal muscle function in man, but will they also improve skeletal muscle function in catabolic conditions? These effects of salbutamol on muscle function are probably dependent on the duration of action of the drug. Indeed, salbutamol, like most (32-adrenergic agonists, has a short plasma half-life, and, in contrast to clenbuterol, has never been reported to induce physiological or functional changes in skeletal muscles of laboratory animals. Freeman et a14 have shown that although 5 mg nebulised salbutamol kept exercise-induced asthma to a minimum in patients with mild asthma, it had little effect on the cardiorespiratory responses to progressive maximum exercise. Furthermore, acute infusion of salbutamol at therapeutic =
our tests
Department of Physiological Sciences, University of Manchester, Manchester M13 9PT, UK, Department of Geriatric Medicine, and North Western Injury Research Centre, University of Manchester
LUCIE MARTINEAU MICHAEL A. HORAN NANCY J. ROTHWELL RODERICK A. LITTLE
Yang YT, McElligott MA. Multiple actions of &bgr;-adrenergic agonists on skeletal muscle and adipose tissue. Biochem J 1989; 261: 1-10. 2. Martineau L, Horan MA, Little RA, Rothwell NJ. Effect of salbutamol on skeletal muscle functional capacity in man. Proc Nutr Soc 1991; 50: 237A. 3. Martineau L, Horan MA, Little RA, Rothwell NJ. Salbutamol, a &bgr;2-adrenergic agonist, increases skeletal muscle strength in young men. Clin Sci (in press). 4. Freeman W, Packe GE, Cayton RM. Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma. Thorax 1989; 44: 942-47. 5. Violante B, Pellegrino B, Vinay C, Sellen R, Ghinamo G. Failure of aminophylline 1.
and salbutamol to improve respiratory muscle function and exercise tolerance in healthy patients. Respiration 1989; 55: 227-36. 6. Choo JJ, Horan MA, Little RA, Rothwell NJ. Anabolic effects of clenbuterol on skeletal muscle are mediated by &bgr;2-adrenoceptor. Am J Physiol 1992; 263: E50-56.
Breastfeeding and HIV SIR,-Mr Dunn and colleagues’ estimates of the risk of transmission of HIV via breastfeeding (Sept 5, p 585) are worryingly high and raise many important questions. Is it valid to extrapolate these estimates to developing countries? The risk of transmission through breastfeeding probably differs between traditional societies in which breastfeeding is the norm and industrialised societies where bottle-feeding predominates. In my experience the frequency of problems such as sore nipples and engorgement is much higher among women in industrialised than in traditional societies. Such problems could facilitate transmission of HIV. The summary estimate of the additional risk of HIV-1 transmission through breastfeeding from a mother infected prenatally is based on six studies, only two of which were in women from traditional societies (Haiti and Zaire). Fewer breast-fed than bottle-fed babies of Haitian HIV-seropositive mothers became infected. The Zairean study is inconclusive because only 10 mothers bottle-fed their babies. Dunn and colleagues’ summary estimate of 29% risk of transmission from a breastfeeding mother infected postnatally is based on four small studies, the largest of which is from Zambia. It is assumed that the 19 women investigated were not infected during their pregnancy because they were seronegative at the time of delivery. However, the frequency of HIV infection was very high at the time of the study so these women may have become infected during their pregnancy but seroconverted afterwards. Sexual intercourse during pregnancy is not taboo in Zambia, and pregnant women could be especially vulnerable to infection with HIV because of increased vascularity of the vagina and uterus. Therefore it cannot be assumed that the seropositive babies in this study were infected through breastfeeding. Without this study the summary estimate would be higher, but the confidence interval much wider. Mathematical models that include variables such as HIV seroprevalence in women of reproductive age in a particular area, infant mortality, fertility and breastfeeding rates, and child mortality due to HIV, can be designed to calculate expected seroprevalence rates in children for specified risks of transmission via breastfeeding. Many seroprevalence surveys are now underway in African countries and their results need to be examined to see if they are consistent with Dunn’s estimates of the risk of transmission via breastfeeding. As Dunn et al emphasise, where infant mortality from infectious diseases is high, overall child mortality will increase if breastfeeding is discouraged, even where HIV seroprevalence rates are high, so it is important to continue to promote breastfeeding. However, what
POLYUNSATURATED FATTY ACIDS IN HUMAN MILK
change the strength of respiratory muscles, ventilatory endurance, or exercise tolerance in healthy individuals.s concentrations did not
in animals have shown convincingly that the duration of action of salbutamol (achieved by prolonging infusion) induced the same anabolic effects as clenbuterol6 in the rat. Thus, unless the pattern of salbutamol metabolites in blood and/or urine can be shown to reliably distinguish the sustained-release preparation for normal salbutamol, serious consideration should be given to adding this drug to the list of banned substances for athletes.
However,
Mean (SEM) wt% total fatty acids shown *Data for 1992, tp < 0 05 vs both other groups, tp < 0 05 both other groups, §p < 0 05 vs both other groups
and the data provided by the Department of Health in 19772 do not represent the present composition of human milk in the UK. We have found that the proportion of linoleic acid in human milk has increased strikingly from 1977 to 1992 (table), which is in line with changes in dietary fatty acid intakes.3 Breastmilk from vegetarian mothers contains the highest proportion of linoleic acid and the lowest proportion ofDHA.4 Infants born to vegetarian mothers have lower proportions of DHA in their tissues.4 Infants born to vegan mothers and then breastfed have DHA concentrations in their erythrocytes that are only a third of those in infants breastfed by mothers with an omnivore diet. This trend might be viewed with some concern because of the growing popularity of vegetarianism. However, the growth and development of vegan children seems normal.5 Yet, there might be subtle functional changes. It is worth emphasising that in animals impaired visual function has only been noted when there has been extreme depletion of DHA from tissues. The variations in brain DHA reported by Farquharson might, therefore, be within the normal physiological range. Department of Nutrition and Dietetics, King’s College London,
T. A. B. SANDERS SHEELA REDDY
London W8 7AH, UK 1. Sanders
TAB, Naismith DJ. A comparison of the influence of breast-feeding and
bottle-feeding on the fatty add composition of erythrocytes. Br J Nutr 1979; 41: 619-23. 2. Department of Health and Social Security. Report on health and social subject, no 12: the composition of mature human milk. London: HM Stationery Office, 1977. 3. British Nutrition Foundation. Unsaturated fatty acids: nutrition and physiological significance. London: Chapman & Hall, 1992. 4. Sanders TAB, Reddy S. The influence of a vegetarian diet on the fatty add composition of human milk and the essential fatty add status of the infant. J Pediatr 1992; 120: S71-S77. 5. Sanders TAB, Manning J. The growth and development of vegan children. J Hum Nutr Diet 1992; 5: 11-21.
Muscling
in
on
salbutamol
SIR,-In your Aug 15 editorial you comment on the controversy the Barcelona Olympics about the use of the &bgr;2-adrenergic agonist clenbuterol to enhance muscle mass and function. Although at
there is a considerable amount of evidence that such agents can increase rapidly lean body mass and reverse muscle wasting in several animal models of human illness,l no published information is available for man. We have shown in sedentary, healthy male volunteers (n 6) that daily oral administration of a slow-release preparation of salbutamol (Volmax, Glaxo), a &bgr;2 -adrenergic agonist used in the treatment of asthma, causes substantial increases within 1-3 weeks in quadriceps (10-27%, median 14%) and hamstring muscle strength (13-48%, median 18%), as well as in static maximum inspiratory mouth pressure (6-26%, median 8%); these variables remained unchanged in the strength-matched placebo groUp.2,3 These results suggest that &bgr;2-adrenergic agonists can alter skeletal muscle function in man, but will they also improve skeletal muscle function in catabolic conditions? These effects of salbutamol on muscle function are probably dependent on the duration of action of the drug. Indeed, salbutamol, like most (32-adrenergic agonists, has a short plasma half-life, and, in contrast to clenbuterol, has never been reported to induce physiological or functional changes in skeletal muscles of laboratory animals. Freeman et a14 have shown that although 5 mg nebulised salbutamol kept exercise-induced asthma to a minimum in patients with mild asthma, it had little effect on the cardiorespiratory responses to progressive maximum exercise. Furthermore, acute infusion of salbutamol at therapeutic =
our tests
Department of Physiological Sciences, University of Manchester, Manchester M13 9PT, UK, Department of Geriatric Medicine, and North Western Injury Research Centre, University of Manchester
LUCIE MARTINEAU MICHAEL A. HORAN NANCY J. ROTHWELL RODERICK A. LITTLE
Yang YT, McElligott MA. Multiple actions of &bgr;-adrenergic agonists on skeletal muscle and adipose tissue. Biochem J 1989; 261: 1-10. 2. Martineau L, Horan MA, Little RA, Rothwell NJ. Effect of salbutamol on skeletal muscle functional capacity in man. Proc Nutr Soc 1991; 50: 237A. 3. Martineau L, Horan MA, Little RA, Rothwell NJ. Salbutamol, a &bgr;2-adrenergic agonist, increases skeletal muscle strength in young men. Clin Sci (in press). 4. Freeman W, Packe GE, Cayton RM. Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma. Thorax 1989; 44: 942-47. 5. Violante B, Pellegrino B, Vinay C, Sellen R, Ghinamo G. Failure of aminophylline 1.
and salbutamol to improve respiratory muscle function and exercise tolerance in healthy patients. Respiration 1989; 55: 227-36. 6. Choo JJ, Horan MA, Little RA, Rothwell NJ. Anabolic effects of clenbuterol on skeletal muscle are mediated by &bgr;2-adrenoceptor. Am J Physiol 1992; 263: E50-56.
Breastfeeding and HIV SIR,-Mr Dunn and colleagues’ estimates of the risk of transmission of HIV via breastfeeding (Sept 5, p 585) are worryingly high and raise many important questions. Is it valid to extrapolate these estimates to developing countries? The risk of transmission through breastfeeding probably differs between traditional societies in which breastfeeding is the norm and industrialised societies where bottle-feeding predominates. In my experience the frequency of problems such as sore nipples and engorgement is much higher among women in industrialised than in traditional societies. Such problems could facilitate transmission of HIV. The summary estimate of the additional risk of HIV-1 transmission through breastfeeding from a mother infected prenatally is based on six studies, only two of which were in women from traditional societies (Haiti and Zaire). Fewer breast-fed than bottle-fed babies of Haitian HIV-seropositive mothers became infected. The Zairean study is inconclusive because only 10 mothers bottle-fed their babies. Dunn and colleagues’ summary estimate of 29% risk of transmission from a breastfeeding mother infected postnatally is based on four small studies, the largest of which is from Zambia. It is assumed that the 19 women investigated were not infected during their pregnancy because they were seronegative at the time of delivery. However, the frequency of HIV infection was very high at the time of the study so these women may have become infected during their pregnancy but seroconverted afterwards. Sexual intercourse during pregnancy is not taboo in Zambia, and pregnant women could be especially vulnerable to infection with HIV because of increased vascularity of the vagina and uterus. Therefore it cannot be assumed that the seropositive babies in this study were infected through breastfeeding. Without this study the summary estimate would be higher, but the confidence interval much wider. Mathematical models that include variables such as HIV seroprevalence in women of reproductive age in a particular area, infant mortality, fertility and breastfeeding rates, and child mortality due to HIV, can be designed to calculate expected seroprevalence rates in children for specified risks of transmission via breastfeeding. Many seroprevalence surveys are now underway in African countries and their results need to be examined to see if they are consistent with Dunn’s estimates of the risk of transmission via breastfeeding. As Dunn et al emphasise, where infant mortality from infectious diseases is high, overall child mortality will increase if breastfeeding is discouraged, even where HIV seroprevalence rates are high, so it is important to continue to promote breastfeeding. However, what