Short-Term Medical Benefits and Adverse Effects of Weight Loss

  1. F. Xavier Pi-Sunyer, MD
  1. From St. Luke's-Roosevelt Hospital Center and Columbia University College of Physicians and Surgeons, New York, New York. Requests for Reprints: F. Xavier Pi-Sunyer, MD, Obesity Research Center, St. Luke's-Roosevelt Hospital Center, 111 Amsterdam Avenue, New York, NY 10025. Grant Support: In part by grants P30-DK26687, DK40414, and R55-DK35911 from the National Institutes of Health.
     
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    Abstract

    Weight loss reduces many of the health hazards associated with obesity including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, sleep apnea, hypoxemia and hypercarbia, and osteoarthritis. Potential adverse effects of weight loss include a greater risk for gallstone formation and cholecystitis, excessive loss of lean body mass, water and electrolyte problems, mild liver dysfunction, and elevated uric acid levels. Less consequential problems such as diarrhea, constipation, hair loss, and cold intolerance may also occur. The short-term adverse effects are not severe enough to contraindicate weight loss, nor do they outweigh its short-term benefits.

    Obesity is associated with a number of health hazards including insulin resistance with hyperinsulinemia, diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, stroke, gallbladder disease, and cancer. Other adverse health conditions include respiratory insufficiency, sleep apnea, heart failure, gout, and osteoarthritis. These conditions generally improve as weight loss continues.

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    Short-Term Benefits of Weight Loss

    Insulin Resistance and Diabetes Mellitus

    Obesity leads to insulin resistance, that is, a diminished biological response to the hormone in insulin-sensitive tissues. This resistance is characterized by an elevation of circulating insulin [1] and by a diminished ability to oxidize and store glucose [2-4]. In obese persons who develop diabetes mellitus, the insulin resistance is the same or increased and is accompanied by an impairment of insulin secretion [5]. Although insulin levels in obese persons may be higher than those in normal persons, they are not high enough to maintain normal glucose tolerance because hepatic glucose production is increased and insulin-mediated glucose uptake is decreased, thus resulting in hyperglycemia.

    With weight loss, insulin sensitivity increases, insulin secretion by the islet cells improves, hepatic glucose production decreases, and glucose disposal improves [6].

    Blood glucose levels decrease in both normoglycemic and hyperglycemic persons who receive hypocaloric diets [7-9]. In patients with non–insulin-dependent diabetes mellitus, serum glucose levels improve within days after starting a weight loss program and can do so with both conventional low-calorie diets (LCDs), ranging from 1200 to 1500 calories per day [10, 11], and very-low-calorie diets (VLCDs), ranging from 300 to 800 calories per day [7-9, 12]. For example, Henry and colleagues [8] showed that the average fasting blood glucose levels in persons with type 2 diabetes decreased from 290 mg/dL to 110 mg/dL in 3 days in response to a 300-kcal diet. Similarly, Bogardus and coworkers [13] showed that plasma glucose improved from 167 mg/dL to 133 mg/dL in response to a diet containing 450 kcal/m2 per day. Medication (oral agents or insulin) can be greatly reduced or eliminated in such cases [12, 14]. An improvement in carbohydrate metabolism occurs before any substantial change in body composition [8], so that much of the early effect on blood glucose levels is probably the direct result of the lowered caloric intake. Over the longer term, as weight loss is maintained and insulin sensitivity improves [15-17], an improvement in prevailing blood glucose levels is shown by a decrease in the levels of glycated hemoglobin [17]. Kirschner and associates [18] reported that, after a 23-kg weight loss (22% of initial body weight), all patients taking oral agents and 82% of patients taking insulin were able to discontinue medication. Similar results were reported by Fitz and colleagues [19], with weight losses of 9.3 kg.

    Hypertension

    Hypertension improves with weight loss in overweight persons [20]. A significant decrease in systolic blood pressure in 81% of patients and in diastolic pressure in 62% of patients who lost weight using VLCDs has been reported [21]. The Framingham study, a prospective, epidemiologic study of a typical American town, showed that blood pressure decreased with weight loss. In men, a 15% decrease in weight was associated with a 10% decrease in systolic blood pressure [22]. Others have confirmed these findings [7, 23]. In the Evans County longitudinal study, obese persons who joined a weight-reduction program and who lost an average of 8 kg had an average decrease of 18 mm Hg in their systolic and 13 mm Hg in their diastolic blood pressures [24]. This effect can occur in the absence of sodium restriction [25]. It is important to note that a significant short-term effect on blood pressure can occur even if ideal weight is not reached. A decrease of 10% to 30% of body weight in patients who are 30% to 82% (mean, 67.2%) above calculated ideal weight has been reported to decrease diastolic blood pressure by 15 mm Hg [23]. Use of a VLCD for 12 weeks has been shown to result in an average weight loss of 22 kg. Reisin and associates [20] reported that patients receiving a diet of 800 to 1200 kcal who averaged a weight loss of 10.5 kg but did not reach normal weight nevertheless showed decreases in both systolic and diastolic pressures of about 20 mm Hg. In about three quarters of these patients, blood pressure returned to normal. Similar results were found by Ramsay and coworkers [26]. MacMahon and colleagues [27] reported a 1-mm Hg decrease in systolic and diastolic blood pressure per kg of weight loss among a group of obese women. Eliahou and associates [28] also reported that two thirds of their obese, hypertensive patients who stayed on their program reverted to normal blood pressure, although they lost an average of only half of their excess weight. The Third Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure found the data relating weight loss to decreased blood pressure so compelling that it recommended weight reduction as an important goal for obese, hypertensive patients [29].

    Dyslipidemia

    Obesity is often associated with an elevation of serum triglycerides [30] and a decrease in high-density lipoprotein (HDL) cholesterol [31, 32]. Total and low-density lipoprotein (LDL) cholesterol are sometimes elevated [33] but are often normal [34]. The ratio of LDL to HDL cholesterol is usually elevated, however, resulting in a greater atherogenic risk [30, 35]. All these values generally improve with weight loss [18, 36-40]. The triglyceride elevation is often due to an enhanced free fatty acid flux to the liver, which, combined with hyperinsulinemia, causes excess production of very-low-density lipoprotein (VLDL) in the liver [41]. As weight loss supervenes, both free fatty acid flux and hyperinsulinemia decrease, causing a decrease in VLDL production. Also, weight loss results in an enhancement of lipoprotein lipase activity at the adipose tissue level, increasing triglyceride clearance [42] and thus improving VLDL lipid levels. Often, fasting levels that may be as high as 1000 to 1500 mg/dL will return to normal levels (<250 mg/dL) with hypocaloric dietary treatment alone.

    Weight loss has been repeatedly reported to increase HDL cholesterol levels [39, 43, 44]. Even rather small weight losses of 5% to 10% of initial weight will have this result [39, 45].

    Pulmonary Function

    Obesity can be associated with mild to severe respiratory functional impairment [46]. Increasing obesity is associated with decreasing oxygen saturation [47], resulting in two primary disorders: obesity-hyperventilation syndrome and sleep apnea [48, 49]. The former is associated with hypoxemia and hypercarbia, which can be exacerbated by a marked depression in both hypoxic and hypercapnic respiratory drives [50]. Patients with hypoxemia and sleep apnea improve quickly with weight reduction [51, 52]. A disturbance of ventilation-perfusion is common in obese persons [49]. This disturbance can lead to hypoxic pulmonary vasoconstriction and higher pulmonary artery pressure [51, 53]. The increased cardiac output and compensatory left ventricular hypertrophy seen in more severely obese patients [54] can result in heart failure [53, 54]. These conditions also ameliorate with weight loss; the degree of improvement depends on the length of time the condition has been present and the degree of intrinsic heart disease. With significant weight loss, essentially normal pulmonary function and pulmonary artery pressure can be achieved, and cardiac function can be normalized.

    Other Benefits

    Because the risks attending general surgical procedures are greater in severely obese patients [55], it is often of benefit to reduce a patient's weight and to allow diuresis of excess water before attempting a major elective procedure such as an orthopedic operation or cholecystectomy. A 5% to 10% reduction in body weight or a 5-unit change in body mass index (BMI) can reduce the duration of hospitalization and the incidence of postoperative complications [55-57].

    Low back pain [58] and osteoarthritis of the knee [59] are both more common in obese persons. The pain and disability, however, improve with weight loss. The degree of improvement varies with the amount of structural damage but can be essentially complete.

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    Adverse Effects of Weight Loss

    Several adverse effects of weight loss have been documented. These effects have been associated more often with VLCDs than with LCDs, probably because of the more radical caloric deficits of the former.

    Gallstones

    Obese patients have a greater risk for gallstones than do persons of normal weight [60], probably because they produce bile with a higher saturation of cholesterol than do lean controls matched for age, sex, and serum lipid levels [61, 62]. In obese persons, biliary cholesterol secretion is greatly increased, yet bile salt secretion remains relatively constant. As a result, bile becomes supersaturated with cholesterol, and nucleation can begin. The nucleation process is abetted by the fact that obese patients have larger, less contractile gallbladders, allowing for a larger and more stagnant reservoir for the supersaturated bile [63]. In addition, increasing age, higher triglyceride levels, and preexisting silent gallstones all increase the risk for symptomatic gallstones and cholecystitis [64].

    A higher risk for gallstone formation has been noted in obese persons. The lithogenicity of bile, which is elevated in obese persons [61], is increased further during weight loss [62]. Three quarters of severely obese patients who underwent gastric surgery for their obesity and who lost large amounts of weight showed the presence of gallstones by oral cholecystography an average of 12 months later [65]. Obese patients placed on 1000-kcal, 40% fat diets for 8 weeks were found to have reduced outputs of cholesterol, bile acids, and phospholipids as well as a reduced bile acid pool size and a reduced synthesis and fecal excretion of cholesterol. However, relatively higher amounts of cholesterol than bile acids and phospholipids were secreted into the bile, resulting in an increase in the lithogenic index for cholesterol crystallization [61]. Two later studies using VLCDs that contained little fat found that gallstones or sludge formed in about 25% of patients [66, 67]. Yang and colleagues [68] recently reported a 7% incidence of gallstones among patients receiving a VLCD for 12 weeks. The reasons for these discrepancies are unclear. A recent report of a 1200-kcal, 30% fat diet showed no increased gallstone formation during a period of 16 weeks [69]. The Nurses Health Study, a longitudinal prospective evaluation, showed that the BMI-adjusted relative risk for cholecystectomy or unremoved gallstones was 1.27 to 1.66 for those losing 4.0 to 9.9 kg and 1.57 to 2.4 (average, 1.97) for those losing 10 kg or more in the previous 2 years [70].

    Whatever the risks for gallstone formation during weight loss, the bile has a lower lithogenic index after weight loss than it did when the patient was heavier [61]; however, more studies of the separate effects of caloric deficit and of fat calorie deficit are needed. Although an enhanced risk of gallstone formation exists during the period of weight loss, this risk is reduced after a lower weight is achieved.

    Protein Balance

    Weight loss results in a loss not only of fat but also of a significant amount of protein and water. A healthy or appropriate ratio of fat-to-lean body mass loss has not been established. A ratio of about 75% fat to 25% lean body mass has been generally considered reasonable and safe after the period of early diuresis [71]; however, a wide difference appears to exist among dieters with regard to this ratio. Some have lost significantly more lean body mass in research studies [72], yet these persons are difficult to identify using the laboratory tests available in the normal clinical setting. For this reason, more liberal diets are thought to be safer; more calorically stringent VLCDs should be given for only short periods (12 to 16 weeks) if at all [73, 74].

    The earlier VLCDs used in the 1970s contained protein of low biological value [75] and were associated with several cases of cardiac arrhythmias [76]. Some of these patients did not respond to anti-arrhythmia therapy and subsequently died [77]. More recent diets have included protein of high biological quality. Since the introduction of these higher-quality proteins, few untoward cardiac effects have occurred [73, 74]. No direct cause-effect relation has ever been proven, and some physicians have suggested that other mechanisms (such as electrolyte abnormalities) might be responsible. Whatever the cause for the intractable arrhythmias, cardiac side effects have not recently been associated disproportionately with VLCDs, suggesting that the newer formulations are significantly safer. Nevertheless, an electrocardiogram should be done for each person who is to undergo a diet less than 800 kcal. Any arrhythmia or QTc interval abnormality noted during such an evaluation should be considered a contraindication to a VLCD. Although some controversy exists regarding screening criteria for QTc interval abnormalities, a QTc interval of more than 0.44 should generally be considered a warning to the clinician [78]. A patient with such an interval should not be placed on a VLCD without a cardiologist's approval. If such a sign occurs during the VLCD, a careful check for potential electrolyte abnormalities should be done, and the diet should be liberalized or stopped.

    Water and Electrolyte Problems

    Another adverse effect is that of water and electrolyte problems. Weight reduction, particularly in heavier persons, results in considerable diuresis. Although this loss of primarily excess water is beneficial, it can be accompanied by an inordinate loss of sodium and potassium [79]. These minerals must be replaced accordingly and in daily amounts sufficient to maintain normal levels in the blood and tissues. Under usual circumstances, a total intake of 2 to 25 g of sodium and 3 to 4 g of potassium is adequate. Without such replacement, deficiencies of these two important ions can occur, with potential adverse effects on the heart and other cellular functions. Magnesium, calcium, and phosphorus can also be lost during diuresis [80]. Appropriate supplementation of these minerals is necessary if patients are on unbalanced diets of fewer than 1200 calories. Recommended dietary allowances should be met so that the patient receives 350 mg of magnesium, 1200 mg of calcium, and 800 mg of phosphorus. These minerals are usually sufficient and may be given in food or as dietary supplements.

    Liver Dysfunction

    A substantial proportion of obese persons have elevations in serum transaminase levels, which are thought to be caused by the pressure on hepatocytes and bile canaliculi created by or secondary to a fatty liver. Such elevations may continue or worsen during a hypocaloric diet because of the rapid mobilization of fat from adipose stores to the liver [81]. Other parameters, such as alkaline phosphatase levels, may also increase. These liver function results usually normalize, however, as weight loss continues.

    Other Adverse Effects

    Persons who undergo weight loss tend to develop an elevation in their uric acid levels that generally peaks at 1 to 2 weeks [82]. This increase is due in part to cell breakdown and in part to urate and ketone competition for tubular reabsorption at the kidney tubule. A low intake of carbohydrate abets this problem, so that it can often be resolved by increasing the carbohydrate intake. Uric acid levels rarely become high enough to require medical treatment [83].

    Because a catabolic state may lead to some loss of immunologic activity, patients with infections or who develop infection during their hypocaloric diet should be given a more liberalized diet.

    Other untoward side effects of VLCDs are less severe. Because many VLCDs contain low levels of dietary fiber, constipation often occurs. In some patients, paradoxically, diarrhea can occur, particularly in patients receiving liquid formula preparations. Such diarrhea is generally not serious enough to cause fluid or electrolyte imbalances and tends to improve with time on the diet. Hypotension, hair loss, and cold intolerance may also occur [73].

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    Summary

    The short-term benefits of weight loss for persons who have an associated medical condition such as diabetes, hypertension, or dyslipidemia have been well documented in the literature. The adverse effects of weight loss are more prevalent with VLCDs [84]; however, these effects are not severe enough to contraindicate weight loss. The long-term riskbenefit ratio of weight loss requires further review.

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    1. Ann Intern Med October 1, 1993 vol. 119 no. 7 Part 2 722-726
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