Research into the Dangers of Very Low Calorie Diets

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With the controversy surrounding the dangers of a particular very low calorie diet in low carb circles, I thought it would be a good idea to collect research on some of the dangers of very low calorie diets.

If you see any that are not listed here whether it is old or brand new, please share.

VLCD's, Starvation and Diabetes

Starvation diet and very-low-calorie diets may induce insulin resistance and overt diabetes mellitus

We have observed seven initially obese individuals who, during the course of a strenuous weight-reduction program, developed diabetes mellitus: non-insulin-dependent diabetes mellitus in five cases and insulin-dependent diabetes mellitus in two cases. None had any sign of prior diabetic symptoms. Although weight reduction is encouraged in obesity, crash diets without proper medical surveillance may have deleterious effects. This sequence of induction of diabetes has not previously been reported in the medical literature. The metabolic situation in extremely low-calorie diets may be comparable to that in starvation. An attempt is made to explain our observation concerning the induction of a diabetic state during such diets, on the basis of increased insulin resistance in states of starvation and anorexia nervosa, with a concomitant role in stress hormones.

Abstract: Koffler M, Kisch ES, Starvation diet and very-low-calorie diets may induce insulin resistance and overt diabetes mellitus. J Diabetes Complications. 1996 Mar-Apr;10(2):109-12.

VLCD's and Gastrointestinal Organs

Gastrointestinal and cardiac response to low-calorie semistarvation diets

Effects of low-calorie semistarvation diets on gastrointestinal and cardiac organ systems were studied. Male Sprague Dawley rats were divided into two groups, Group I, control (C) and Group II, semistarvation (SS), and maintained on a diet designed after low- calorie modified-fasting regimens in popular use. C animals consumed this diet ad libitum; SS animals received 23% of the total calories of C but the same ratio of calories from protein, carbohydrate, and fat and the same quantity and quality of all essential nutrients. Final weights of total body, heart, liver, and small intestine were lower in SS than in C animals. Protein depletion in SS compared with C animals was evident for heart, pancreas, and intestinal mucosa. Unless aggressively supplemented, low-calorie SS diets may deplete protein stores of the gastrointestinal organs of digestion and absorption and contribute to decrease in body nitrogen stores, specifically cardiac muscle.

Full Text:Young et al, Gastrointestinal and cardiac response to low-calorie semistarvation diets. Am J Clin Nutr. 1988 Jun;47(6):981-8

VLCD's, Heart and Sudden Death

Cardiovascular Complications of Weight Reduction Diets.

Weight reduction diets may reduce the severity of risk factors for coronary heart disease such as diabetes mellitus, hypertension, and dyslipidemia. Several case reports and small studies of patients receiving starvation diets have reported hypotension and sudden cardiac death. Myofibrillar damage was documented in 1 case. Very-low-calorie diets are generally safe and well-tolerated. However, low QRS voltage, QT interval prolongation, and both nonsustained ventricular arrhythmias and sudden cardiac death have been described in subjects treated with such diets. Orthostatic hypotension may complicate very-low-calorie protein diets because of sodium depletion and depressed sympathetic nervous system activity. Bariatric surgery is associated with disproportionately high mortality rates in both the perioperative and postoperative periods.

Abstract:Ahmed et al, Cardiovascular Complications of Weight Reduction Diets. AJMS, 321(4):280-284, April 2001.

Cardiac effects of starvation and semistarvation diets: safety and mechanisms of action

A major concern with the use of starvation or semistarvation diets for weight reduction in severely obese people has been the reports of sudden death due to ventricular arrhythmias. Obesity per se is associated with cardiovascular changes, including left ventricular hypertrophy and prolongation of the QT interval. With weight loss, the mass of the heart and left ventricle decrease, but some signs of left ventricular dysfunction remain. The effect of weight loss on the electrocardiogram abnormalities of obesity appears to depend upon diet duration and upon whether protein and mineral nutritional status is maintained. Copper, potassium, and magnesium deficiencies may play important roles in promoting an electrically unstable heart. Stress, by eliciting autonomic imbalance, may act upon an electrically unstable heart to provoke acute arrhythmias in a subset of the obese population with QT interval prolongation.

Full Text:Fisler, J S, Cardiac effects of starvation and semistarvation diets: safety and mechanisms of action, Am-J-Clin-Nutr. 1992 Jul; 56(1 Suppl): 230S-234S

Very low calorie diets and pre-fasting prolonged QT interval. A hidden potential danger.

The association of torsade de pointes and a prolonged electrocardiographic QT interval is well described. A prolonged QT interval may be congenital or acquired in several ways--by the use of anti-arrhythmic agents exemplified by quinidine, by the presence of hypocalcaemia or hypokalaemia, by the use of psychotropic drugs, and by the presence of intrinsic cardiac disease or bradycardias. Possibly less well appreciated is the potential for drastic weight loss to prolong the QT interval, as the present case report illustrates. A young woman weighing 244 pounds lost 24 pounds in two weeks with a consequent prolongation of QTc interval from pre-diet value of 0.57 seconds to 0.72 seconds at admission, when severely symptomatic paroxysms of torsade de pointes were recorded. Successful therapy with lignocaine and prompt re-feeding suppressed the arrhythmia and, three days later, the QTc was reduced to almost its pre-diet state. A (UK) DHSS report offers guidelines in the use of very low calorie diets. This case suggests that a pre-diet electrocardiogram should be carefully assessed for QT prolongation before initiation of dieting to achieve serious weight loss.

Abstract:BC Thwaites, M Bose, Very low calorie diets and pre-fasting prolonged QT interval. A hidden potential danger. West Indian Med J (1992) 41: 169-71.

Cardiac dysfunction in obese dieters: a potentially lethal complication of rapid, massive weight loss

During 1977 and 1978, 17 obese but otherwise healthy adult Americans died suddenly of ventricular arrhythmias during or shortly after completing rapid, massive weight reduction induced by very low-calorie diets consisting largely of collagen hydrolysates for 2 to 8 months. A reexamination of the data on these victims has disclosed a significant positive correlation (r = 0.824) between their prediet body mass index and their duration of survival on the very low-calorie diets. Since body mass index reflects degree of fatness, this observation indicates that the ability to defer the lethal effects of severe caloric restriction was a function of the proportion of body fat before dieting. During caloric reduction, the ratio of nitrogen loss to weight loss is inversely related to body fat content; accordingly, we suggest that the fattest dieters survived the longest because they were better able to conserve body (and myocardial) protein. Also, obese people have an enlarged lean body mass which may afford additional protection.

Full Text:Van Itallie TB, Yang MU., Cardiac dysfunction in obese dieters: a potentially lethal complication of rapid, massive weight loss, Am J Clin Nutr. 1984 May;39(5):695-702.

Sudden death associated with very low calorie weight reduction regimen

"We studied the cases of 17 individuals who died suddenly of ventricular arrhythmia after prolonged use (median 5 months) of very low calorie weight reduction regimens consisting entirely or largely of protein. The deaths appeared to be independent of type of medical supervision received during the diet, daily dosage of potassium supplementation, and biological quality of the protein product used. Factors common to all cases were marked obesity at the onset of dieting, prolonged use of extremely low calorie diets (approximately 300 to 400 kcal daily), and significant and rapid weight loss. Our review of available electrocardiograms and pathological specimens revealed a pattern of cardiac changes previously described in starvation. We conclude that use of very low calorie weight reduction regimens should be curtailed until further studies determine what modifications, if any, can insure their safety. "

Full Text:HE Sours et al, Sudden death associated with very low calorie weight reduction regimensAm. J. Clinical Nutrition, Apr 1981; 34: 453 - 461.

Sudden, Unexpected Death in Avid Dieters Using the Liquid-Protein-Modified-Fast Diet

SUMMARY Clinical and morphologic findings are described in 17 patients who died suddenly and unexpectedly during or shortly after use of the liquid-protein-modified-fast diet. Of the 17 patients, 16 were women, most were young (average age 37 years), and most lost a massive amount of weight (average 41 kg or 35% of their prediet weight) over a short period of time (average 5 months). Eight had one or more episodes of syncope. Multiple-lead ECGs were recorded in 10 patients. All had normal sinus rhythm; all had episodes of ventricular tachycardia; nine and possibly 10 patients had prolongation of the QT interval, unassociated with the recognized causes of QT interval prolongation in at least seven of the nine patients; and nine had diminished amplitude of the QRS complexes ("low voltage"). Histologic study of left ventricular myocardium in 14 patients disclosed attenuated myocardial fibers in 12, increased lipofuscin pigment in 11, and mononuclear-cell myocarditis in one. Similar histologic findings, however, also were found in 16 cachectic control subjects studied in similar fashion, but ECGs in them showed no prolongation of QT intervals or episodes of ventricular tachycardia. Thus, semistarvation, particularly in the face of antecedent obesity, is a cause of acquired QT interval prolongation, and repeated ECGs are recommended in patients on semistarvation diets for treatment of obesity.

Full Text:Isner et al, Unexpected Death in Avid Dieters Using the Liquid-Protein-Modified-Fast Diet, 60 (6): 1401. (1979)

VLCD's and Gallbladder

Similarity in Gallstone Formation from 900 kcal/day Diets Containing 16 g vs 30 g of Daily Fat (Evidence that Fat Restriction Is Not the Main Culprit of Cholelithiasis During Rapid Weight Reduction)

Diets containing essentially no fat, 1-2 g fatper day, have resulted in cholesterol gallstones.Greater fat may result in less gallbladder stasis. Dogallstones form with greater fat content? We studied 272 moderately obese subjects who had normalgallbladder ultrasonograms. The 900 kcal/day liquiddiets contained either 16 g fat (N = 94) or 30 g fat (N= 178) each day for 13 weeks. A second gallbladderultrasound was performed. Sixteen of 94 (17.0%) of the16-g fat group developed stones with a weight loss of 18(±7) kg and a body mass index (BMI) decrease of6 (±2) kg/m2. Twenty of 178 (11.2%) ofthe 30-g fat group developed stones (P = 0.18, no differencein stone formation) with similar weight loss of 20(±7) kg (P = 0.08) and BMI decrease of 7(±2) kg/m2 (P = 0.04). Substantial fatfor rapid weight-reducing diets resulted in gallstone formation. Sinceexperiments have shown that our higher fat diet,containing 10 g fat per meal, results in maximalgallbladder emptying, cholelithiasis from rapid weightloss may not be solely attributable to gallbladderstasis.

Abstract:Vezina et al, Similarity in gallstone formation from 900 kcal/day diets containing 16 g vs 30 g of daily fat: evidence that fat restriction is not the main culprit of cholelithiasis during rapid weight reduction. Dig Dis Sci. 1998 Mar;43(3):554-61.

Long-Term Weight Patterns and Risk for Cholecystectomy in Women

Background: Obesity and rapid weight loss in obese persons are known risk factors for gallstones. However, the effect of intentional, long-term, moderate weight changes on the risk for gallstones is unclear.

Objective: To study long-term weight patterns in a cohort of women and to examine the relation between weight pattern and risk for cholecystectomy.

Design: Prospective cohort study.

Setting: 11 U.S. states.

Participants: 47 153 female registered nurses who did not undergo cholecystectomy before 1988.

Measurements: Cholecystectomy between 1988 and 1994 (ascertained by patient self-report).

Results: During the exposure period (1972 to 1988), there was evidence of substantial variation in weight due to intentional weight loss during adulthood. Among cohort patients, 54.9% reported weight cycling with at least one episode of intentional weight loss associated with regain. Of the total cohort, 20.1% were light cyclers (5 to 9 lb of weight loss and gain), 18.8% were moderate cyclers (10 to 19 lb of weight loss and gain), and 16.0% were severe cyclers (≥ 20 lb of weight loss and gain). Net weight gain without cycling occurred in 29.3% of women; net weight loss without cycling was the least common pattern (4.6%). Only 11.1% of the cohort maintained weight within 5 lb over the 16-year period. In the study, 1751 women had undergone cholecystectomy between 1988 and 1994. Compared with weight maintainers, the relative risk for cholecystectomy (adjusted for body mass index, age, alcohol intake, fat intake, and smoking) was 1.20 (95% CI, 0.96 to 1.50) among light cyclers, 1.31 among moderate cyclers (CI, 1.05 to 1.64), and 1.68 among severe cyclers (CI, 1.34 to 2.10).

Conclusion: Weight cycling was highly prevalent in this large cohort of middle-aged women. The risk for cholecystectomy associated with weight cycling was substantial, independent of attained relative body weight.

Full Text:Syngal, S., Coakley, E. H., Willett, W. C., Byers, T., Williamson, D. F., Colditz, G. A. (1999). Long-Term Weight Patterns and Risk for Cholecystectomy in Women. ANN INTERN MED 130: 471-477

The role of gallbladder emptying in gallstone formation during diet-induced rapid weight loss

Obese persons are at risk for cholesterol gallstones because their bile is saturated with cholesterol. The risk increases during rapid weight loss by means of certain very-low-calorie diets or gastric bypass surgery. Gallstone risk factors during rapid weight loss include increased bile cholesterol saturation index and gallbladder stasis. Obese subjects were randomized to one of two low-calorie liquid diets for rapid weight loss: a 520-kcal diet with less than 2 g fat/d, and a 900-kcal diet with 30 g fat/d (including one 10-g fat meal to stimulate maximal gallbladder emptying). Bile and blood lipids, saturation index, leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity, and ultrasonographic gallbladder emptying were measured repeatedly during dietary treatment. Both diets produced comparable weight loss of 22%. Bile cholesterol saturation index increased during both diets (26%), but fell to 15% below prediet level after weight loss. Compared with subjects' maximal gallbladder emptying fraction of 66%, the 520-kcal diet provided poor gallbladder emptying (35%), whereas the 10-g fat meal of the 900-kcal diet provided maximal emptying. Gallstones developed in four of six 520-kcal subjects and none of seven 900-kcal subjects (P = .021), an unanticipated difference that resulted in premature study termination for ethical reasons. Blood lipids and HMG CoA reductase activity in mononuclear leukocytes fell at week 8 during both diets, but recovered while weight was still being lost. The findings suggest that gallstone risk during rapid weight loss may be reduced by maintenance of gallbladder emptying with a small amount of dietary fat. Ultimately, weight loss reduced bile cholesterol saturation and improved highdensity lipoprotein (HDL) levels.

Full Text:Gebhard, R. L., Prigge, W. F., Ansel, H. J., Schlasner, L., Ketover, S. R., Sande, D., Holtmeier, K. and Peterson, F. J. (1996), The role of gallbladder emptying in gallstone formation during diet-induced rapid weight loss. Hepatology, 24: 544-548. doi: 10.1002/hep.510240313

Gallbladder motility and gallstone formation in obese patients following very low calorie diets. Use it (fat) to lose it (well)

Dieting obese subjects are at risk of developing gallstones. A gallbladder motor dysfunction could have a pathogenetic role. The principal aim of this study was to evaluate the long term effects of two very low calorie diets differing in fat content on gallbladder emptying and gallstone formation in obese subjects.

DESIGN AND SUBJECTS: Gallbladder emptying in response to meals (breakfast, lunch and dinner) in two different diet regimens (3.0 vs 12.2 g of fat/d) was evaluated by ultrasonography in 32 gallstone-free obese patients on different days, before and during (at 45 d intervals) one or two 6-month weight reduction diets (for the first three months: 2.24 MJ (535.2 kcal), 3.0 g fat/d vs 2.415 MJ (577.0 kcal), 12.2g fat/d; for the second three months, the same low calorie diet of 4.194 MJ (1002 kcal)/d for both groups). In 10 subjects, bile analysis was also performed.

RESULTS: Twenty-two (69%) subjects concluded the study, eleven in each group, and a significant weight loss was achieved by all subjects. Gallstones (asymptomatic) developed in 6/11 (54.5%) (P < 0.01) of subjects following the lower fat diet, but in none with the higher fat regimen. In the dieters during the first three months (very low calorie phase) the higher fat meals always induced a significantly greater gallbladder emptying than the lower fat meals. The cholesterol saturation index initially increased significantly and then decreased, without difference between the two groups.

CONCLUSION: In the obese during rapid weight loss from a very low calorie diet, a relatively high fat intake could prevent gallstone formation, probably by maintaining an adequate gallbladder emptying, which could counterbalance lithogenic mechanisms acting during weight loss.

Full Text:Festi D, Gallbladder motility and gallstone formation in obese patients following very low calorie diets. Use it (fat) to lose it (well). Int J Obes Relat Metab Disord. 1998 Jun;22(6):592-600.

Obesity and risk of gallstone development on a 1200 kcal/d (5025 Kj/d) regular food diet.

OBJECTIVE: Previous studies report a greatly increased risk of gallstone formation in obese persons during periods of caloric restriction on very low calorie formula diets. The aim of the present study was to assess the risk of gallstone development in moderately obese patients losing weight on a prescribed 1200 kcal/d (5025 Kj/d) regular food diet.

DESIGN and SUBJECTS: A consecutive sample of 70 men and women (body mass index > 25 kg/m2) (mean +/- SD, 28.9 +/- 2.8 kg/m2) responding to an announcement of an outpatient weight loss program in a major metropolitan research and teaching hospital were enrolled in a meal replacement program which prescribed 1200 kcal/d (5025 Kj/d) consisting of regular foods with approximately 20 g/d fat (15% of kcal) for 16 weeks.

RESULTS: Participants who completed the study (n = 34) lost a mean of 5.1 +/- 3.6 kg (p < 0.001) (range, +2.7 kg to -12.5 kg; 6.7 +/- 5.0% of body weight, range +/-3.1% to -17.0%; 0.36 +/- 0.25 kg/week) with no clinically significant adverse effects. There were no discernible new gallstones as measured by ultrasonography during the study period. Liver enzyme blood concentrations did not change significantly after 16 weeks except for alkaline phosphatase, which decreased by 4.5 mu/l from a mean initial level of 72.7 mu/l (p < 0.05).

CONCLUSION: Weight loss over 16 weeks on a 1200 kcal/d (5025 Kj/d) regular food/approx 20 g/d fat (15% of kcal) diet was not accompanied by a high rate of gallstone formation in moderately obese persons.

Abstract:Heshka S., Spitz A., Nunez C., Fittante A. M., Heymsfield S. B. & Pi-Sunyer F. X. (1996) Obesity and risk of gallstone development on a 1200 kcal/d (5025 kJ/d) regular diet. Int. J. Obes. 20:450-454.

Relationship between rate of weight loss and gallstone formation

Speakers Notes: Weight loss is associated with an increased risk of gallstones because weight loss increases bile cholesterol supersaturation, enhances cholesterol crystal nucleation, and decreases gallbladder contractility [1]. The incidence of new gallstones is approximately 25%-35% in obese patients who experience rapid weight loss after treatment with a very-low-calorie, low-fat diet (<600 kcal/d; 1-3 g fat/d) [2,3] or gastric surgery [4]. This figure summarizes the data from 9 studies that evaluated the incidence of gallstones in obese patients undergoing weight loss. The risk of gallstone formation increased markedly when the rate of weight loss exceeded 1.5 kg (~1.5% of body weight) per week [5].

Slide:Weinsier et al, Relationship between rate of weight loss and gallstone formation, Am J Med 1995, 98.115

Gallstone formation in obese women treated by a low-calorie diet.

This study assessed the incidence of gallstone formation in 47 obese women who consumed a low-calorie diet (LCD) for the first 16 weeks of a 26-week weight loss program. The LCD consisted of four daily servings of a liquid diet combined with an evening meal of a pre-packaged dinner entrée and provided approximately 925 kcal/d. Six of the 47 patients (12.8%) displayed gallstones at week 17, as determined by sonography. Five patients were asymptomatic when followed for up to 48 weeks. The sixth, however, reported severe abdominal pain 30 weeks after beginning treatment and required a cholecystectomy. Patients who developed gallstones, as compared with those who did not, had significantly higher baseline triglyceride and total cholesterol levels and had a significantly greater rate of weight loss. Results of this study indicate that an increased risk of gallstones is not limited to very-low-calorie diets and that the incidence of this complication should be assessed in persons who consume popular over-the-counter meal replacement plans.

Abstract:Spirt et al. Gallstone formation in obese women treated by a low-calorie diet. Int J Obes Relat Metab Disord. 1995 Aug;19(8):593-5.

Contributions of Obesity and Weight Loss to Gallstone Disease

Objective: To examine the relation of obesity and weight loss to the formation of gallstones according to pertinent clinical and research issues.

Data Sources and Extraction: Original reports obtained through a MEDLINE search from 1966 to 1992 on gallstones plus obesity or reducing diets, supplemented by a manual search of bibliographies, a Current Contents title search from 1991 to 1992 on gallstones and gallbladder, and expert opinion. Only studies of humans were cited.

Data Synthesis: For women, but less so for men, obesity is a strong risk factor for gallstones, and this risk is increased during weight loss. Between 10% and 25% of obese men and women may develop gallstones within a few months of beginning a very low calorie diet, and perhaps one third of these will develop symptoms of gallstones. Persons with the highest body mass index before weight loss and those who lose weight most rapidly appear to be at the greatest risk for gallstones. Treatment with ursodeoxycholic acid (ursodiol) during weight loss dieting is the only proven prevention for the formation of gallstones. Issues to be resolved include how different diets affect the risk for developing gallstones, the identification of other risk factors for gallstone formation during weight loss, the effect of weight loss among people with preexisting gallstones, and the optimum means of preventing gallstones during weight loss.

Conclusions: During weight loss, particularly among the obese, an increased risk exists for symptomatic gallstone formation. This acute risk offers the opportunity to investigate the cause of gallstones and possibly to prevent them.

Full Text:Everhart JE, Contributions of Obesity and Weight Loss to Gallstone Disease. Ann Intern Med. 1993 Nov 15;119(10):1029-35.

A prospective study of hospitalization with gallstone disease among women: role of dietary factors, fasting period, and dieting.

BACKGROUND: Dietary risk factors for the development of gallstones have not been clearly established. We analyzed data from a population-based prospective study to determine dietary risk factors for hospitalization with gallstone disease.

METHODS: We evaluated the role of dietary constituents, fasting, and dieting on subsequent hospitalization with gallstone disease among 4,730 women, ages 25 to 74 years, who participated in the first follow-up of the first National Health and Nutrition Examination Survey. Baseline dietary variables were established through a 24-hour dietary recall and a medical history. Proportional hazards models were used to calculate the effects of dietary variables while controlling for baseline risk factors.

RESULTS: After an average of 10 years follow-up, gallstone disease was confirmed by hospital records among 216 women who denied gallstone disease at the baseline examination. The hazard rate of hospitalization with gallstone disease increased with increasing overnight fasting period and with dieting. Intake of fiber showed a small protective effect. The effect of energy intake was significant only among women younger than age 50 years at baseline. Results were not affected by adjustment for known risk factors for gallstone disease or other dietary factors.

CONCLUSION: A long overnight fasting period, dieting, and low fiber intake may increase the risk of hospitalization with gallstone disease.

Full Text:Sichieri et al, A prospective study of hospitalization with gallstone disease among women: role of dietary factors, fasting period, and dieting. Am J Public Health. 1991 Jul;81(7):880-4.

Gallbladder kinetics in obese patients: Effect of a regular meal and low-calorie meal

Gallbladder contractility has been studied in 21 obese patients >130% ideal weight) and 30 nonobese subjects before and at regular intervals after the administration of a regular solid-liquid meal, and after a low-calorie, low-fat meal used conventionally for weight-loss purposes (Modifast®). Gallbladder volume was determined by means of real-time ultrasonography, using a linear array scanner with a 3.5 MHz probe. In seven of the obese patients, gallbladder contractility was also evaluated after a 10-day regimen with Modifast. The obese group showed a statistically significant greater gallbladder fasting volume and blunted contractility than controls both after the ordinary and the low-calorie meal. The 10-day low-calorie regimen was associated with a statistically significant increment in fasting gallbladder volume, while the percent volume reduction after Modifast did not change. It is suggested that, in addition to metabolic factors, gallbladder hypocontractility in the obese may contribute to the high incidence of cholesterol gallstones noted in these patients. A low-calorie, low-fat diet augmenting gallbladder volume may favor bile stasis and therefore the likelihood of developing gallstones.

Abstract:Marzio L, Capone F, Neri M, Mezzetti A, De Angelis C, Cuccurullo F. Gallbladder kinetics in obese patients. Effect of a regular meal and low-calorie meal. Dig Dis Sci. 1988; 33:4-9.

VLCD's and the Liver

Hepatic effects of dietary weight loss in morbidly obese subjects.

This prospective study was carried out in order to evaluate the influence on liver morphology and function of a very-low-calorie formula diet. Fourty-one morbidly obese, non-alcoholic subjects had liver biopsy performed before and after a median weight loss of 34 kg. Fatty change improved (p less than 0.001), but 24% of the patients developed slight portal inflammation (p = 0.039) or slight portal fibrosis (p = 0.063). Patients developing portal fibrosis had a higher degree of fatty change at entry (p = 0.029), a more pronounced reduction of fatty change (p = 0.014) and a faster weight loss (p = 0.026). Liver biochemistry, which was of no individual diagnostic value, improved. It is concluded that morbidly obese subjects with a high degree of hepatic fatty change are at risk of developing portal inflammation and fibrosis when undergoing very fast dietary weight reductions.

Abstract:Anderson et al, Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol. 1991 Mar;12(2):224-9.

VLCD's and Maintaining Weight Loss

A 54-month evaluation of a popular very low calorie diet program

BACKGROUND. Thirty-three percent of the adult American population over the age of 20 is obese. Many attempts to treat this increasingly occurring problem have had poor results. Both achieving weight loss and maintaining weight loss are difficult; however, current treatments appear more effective in achieving weight loss than in maintaining weight loss. The current study followed a cohort of patients to analyze weight maintenance and predictors of weight maintenance in a 26-week, formula-based, very low calorie diet program.

METHODS. The study population consisted of a consecutive sample of 145 overweight patients who entered a very low calorie diet program and were contacted at 54 months after program entry.

RESULTS. For men, the average initial weight loss at program termination was 27.2 kg (22% of original weight) and for women, 19.3 kg (18.8% of original weight). At 54 months after program entry, the average maintained loss was 5.1 kg (4.3% of original weight), at a cost of $630 per kg of long-term weight loss. There was no significant difference in maintained weight loss between men and women. Twenty-six percent of patients maintained a medically significant weight loss of 10% of entry weight. Subjects who exercised regularly maintained an average of 9.6 kg compared with 1.3 kg for nonexercisers. Those who attended the program for a longer period, and exercised more, maintained their weight better. The 54-month weight loss was similar to that seen at 30 months but markedly less than that at 18 months.

CONCLUSIONS. Very low calorie diet programs have limited long-term success that may not justify the risk of adverse effects and high costs. Longer program attendance and continued exercise are associated with improved weight maintenance. Evaluation of dietary programs should be based on a sample of consecutive patients followed for a minimum of 2 years after program completion.

Full Text:Walsh MF, Flynn TJ. A 54-month evaluation of a popular very low calorie diet program. J Fam Pract. 1995;41:231-6

Long-term weight maintenance after an intensive weight-loss program.

Objective: This prospective study assessed long-term weight maintenance of patients completing an intensive very-low-calorie diet (VLCD) weight-loss program.

Method: Individuals who had completed the 12-week core education program and lost > or = 10 kg were recruited.

Results: Of 154 eligible subjects, follow-up weights were obtained at > or = 2 years in 112 subjects (72.7%, 72 women, 40 men). Subjects had an average initial body mass index of 37.3 kg/m2 and an average weight loss of 29.7 kg in five months. Six hundred and forty-five follow-up weights (median, five per subject) were obtained over two to seven years of follow-up from clinic visits (70%) and self-report by telephone or mail (30%). Subjects regained an average of 2.5% per month of their lost weight during the first two to three years of follow-up; however, their weight stabilized over the next four years. Subjects regained an average of 73.4% of their weight loss during the first three years. The average weight loss maintained for 112 subjects was 22.8% of initial weight loss after an average of 5.3 years of follow-up. When successful weight maintenance was defined as maintaining a weight loss of 5% or 10% of initial (pre-treatment) body weight, 40% were maintaining a 5% weight loss at five years and 25% were maintaining a weight loss of 10% at 7 years. Multiple regression analyses suggested that age had a significant (p=0.004) and positive effect on weight maintenance.

Conclusion: This study suggests that weight maintenance after an intensive VLCD program is improving but still needs intensive efforts to enable most individuals to maintain a substantial percentage of their weight loss long-term.

Full Text:Anderson JW, Vichitbandra S, Qian W, Kryscio RJ. Long-term weight maintenance after an intensive weight-loss program. Am J Coll Nutr 1999;18:620-7.

VLCD and Resting Metabolic Rate (RMR) and Thyroid

Energy-metabolism adaptation in obese adults on a very-low-calorie diet

In this study, six obese women received a very-low-calorie diet (VLCD) for 3 wk. At day 0, body composition was assessed with a bioelectric impedance analyzer. The evolution in lean body mass (LBM) during the VLCD was estimated from nitrogen balance, measuring urine and fecal losses and taking into account skin, nitrate, and menstrual losses to avoid underestimation bias that could explain the decreased ratio of resting metabolic rate (RMR) to LBM previously reported. RMR was measured at days 0, 3, 5, and 21. The RMR-LBM ratio declined significantly during the VLCD period and decreased faster during the first week; the day 3, day 5, and day 21 ratio values were 94%, 91%, and 82%, respectively, of the original. The RMR-LBM ratio decrease after 21 d of a VLCD was near that found in chronic undernutrition. Results of previous studies that did not find any drop in the RMR-LBM ratio in obese adults on VLCDs might be explained by their LBM- assessment methods.

Full Text:Fricker et al, Energy-metabolism adaptation in obese adults on a very-low-calorie diet. AJCN, 1991 Apr;53(4):826-30.

Effects of a very low calorie diet on weight, thyroid hormones and mood.

Changes in weight, thyroid hormones and mood were examined in 15 obese (113 kg) women over an 18-week period. After 4 weeks of a 1200 kcal/day diet, patients were randomly assigned to one of two dietary conditions: very low calorie diet (VLCD) (n = 8) or balanced deficit diet (BDD) (n = 7). VLCD patients consumed 400 kcal/day for 8 weeks and then gradually returned to a 1200 kcal/day diet. BDD patients consumed 1200 kcal/day for the entire 18 weeks. Differences in weight losses between the conditions were statistically significant only during the consumption of the VLCD. Serum T3 decreased by as much as 66 percent in VLCD patients during consumption of the 400 kcal/day diet, whereas rT3 increased by as much as 27 percent. T3 increased when patients were realimented with a 1000 kcal/day balanced diet but remained a significant 22 percent below baseline at the end of the study. BDD patients also showed marked reductions in T3, as great as 40 percent, so that the differences between the two conditions were not statistically significant. Multiple regression analyses, collapsing across conditions (n = 15), indicated that weight loss at week 12 and baseline T3 accounted for 63 percent of the variance in the change in T3 at week 12. Patients in both conditions showed improvements in mood. Changes in depression were not associated with changes in serum T3.

Abstract:Wadden et al, Effects of a very low calorie diet on weight, thyroid hormones and mood. Int J Obes. 1990 Mar;14(3):249-58.

Short and long term effects of a very low calorie diet on resting metabolic rate and body composition.

Short and long term effects of a protein sparing modified fast (PSMF) diet on resting metabolic rate (RMR) and body composition were investigated. During a period of 6 months on diet, RMR decreased significantly, both in absolute value and after correction for fat-free mass (FFM). Short term evaluation with this type of diet showed no decrease in RMR. The results from this study indicate that the fall in RMR associated with a PSMF diet (weight loss) is not due to an acute adaptation to the lower energy intake. Changes in FFM are important in the change in RMR, but other factors have to be involved.

Abstract: Vansant G., Van Gaal L., Van acker K. & DeLeeuw I. (1989) Short and long term effects of a very low calorie diet on RMR and body composition. Int. J. Obesity 13(Suppl.):87-89.

Sustained depression of the resting metabolic rate after massive weight loss

To assess potential long-term effects of weight loss on resting metabolic rate (RMR), the RMRs of seven obese women were measured by indirect calorimetry before weight loss, during a protein-sparing modified fast, and for 2 mo while at a stable reduced weight. Body composition was also determined at each interval. RMR significantly decreased 22% (p less than 0.01) with initiation of the modified fast. RMR values during the modified fast and during the maintenance diet at stable reduced weight were not different and all were significantly lower than the prediet RMR. Loss of lean tissue could not account for the decrease because changes in RMR per fat-free mass paralleled the total RMR reduction. A sustained decrement in RMR accompanied weight loss and persisted for greater than or equal to 8 wk despite increased caloric consumption and body weight stabilization.

Full Text:Elliot et al, Sustained depression of the resting metabolic rate after massive weight loss. Am J Clin Nutr. 1989 Jan;49(1):93-6.

Effect of a high-protein, very-low-calorie diet on resting metabolism, thyroid hormones, and energy expenditure of obese middle-aged women

A 4-6 mo study was conducted to examine effects of a very-low-calorie, high-protein diet and realimentation on energy expenditure, resting metabolic rate (RMR), and serum thyroid hormones of obese women aged 30- 54 yr. Fifteen healthy women, greater than or equal to 126% ideal body weight, were placed on the diet (420 kcal/day) and lost an average of 1.1 kg/wk until a predetermined goal weight was attained. RMR, triiodothyronine (T3), and reverse T3 decreased significantly (p less than 0.05). Thyroxine remained unchanged. Upon gradual realimentation onto solid foods, all metabolic parameters increased significantly within 5 wk toward pre-diet baseline values, but RMR (kcal/h) and T3 values remained significantly below pre-study values. Estimates of mean energy expenditure, utilizing a technique based on energy intake and body composition changes, averaged 1719 kcal/day during the diet period.

Full Text:Barrows K, Snook JT, Effect of a high-protein, very-low-calorie diet on resting metabolism, thyroid hormones, and energy expenditure of obese middle-aged women, Am J Clin Nutr. 1987 Feb;45(2):391-8.

Diminished energy requirements in reduced-obese patients.

In assessing the reasons for the frequent regaining of weight by reduced-obese patients, we examined retrospectively the seven-day energy intake requirements for weight maintenance of 26 obese patients (12 males, 14 females) at maximum weight (152.5 +/- 8.4 kg) and after weight loss (100.2 +/- 5.7 kg). These results were compared with those obtained in 26 age- and sex-matched control patients who had never been obese (62.6 +/- 2.3 kg). The obese and control subjects required comparable caloric intakes: 1432 +/- 32 kcal/m2/d vs 1341 +/- 33 kcal/m2/d, respectively. Following weight loss, the reduced-obese subjects required only 1021 +/- 32 kcal/m2/d, a 28% decrease (P less than 0.001) in requirements relative to their obese state and a 24% decrease relative to the control patients (P less than 0.001). The mean individual energy requirement of the reduced-obese subjects (2171 kcal/d) was less than that for the control subjects (2280 kcal/d) despite the fact that they still weighed 60% more than the controls. In order to maintain a reduced weight, some reduced-obese or even partially reduced patients must restrict their food intake to approximately 25% less than that anticipated on the basis of metabolic body size. The reasons why this finding is unlikely to be an artifactual consequence of changes in lean body mass or body water content are discussed. This finding has implications with regard to the pathophysiology and treatment of obesity in humans.

Abstract:Leibel RL, Hirsch J, Diminished energy requirements in reduced-obese patients. Metabolism. 1984 Feb;33(2):164-70


The Evolution of Very-Low-Calorie Diets: An Update and Meta-analysis

Objective: Very-low-calorie diets (VLCDs), providing <800 kcal/d, have been used since the 1970s to induce rapid weight loss. Previous reviews of the literature have disagreed concerning the relative efficacy of VLCDs vs. conventional low-calorie diets (LCDs) for achieving long-term weight loss.

Research Methods and Procedures: We sought to update findings on the clinical use, safety, and efficacy of VLCDs and to perform a meta-analysis of randomized trials that compared the long-term efficacy of LCDs and VLCDs. Original research articles were retrieved by a Medline search and from prior reviews of VLCDs. Trials were included only if they were randomized comparisons of LCDs and VLCDs and included a follow-up assessment at least 1 year after maximum weight loss. Data were abstracted by both authors regarding: duration of VLCD, total length of treatment, attrition, short- and long-term weight loss, changes in weight-related comorbidities, and adverse effects.

Results: Six randomized trials were found that met inclusion criteria. VLCDs, compared with LCDs, induced significantly greater short-term weight losses (16.1 ± 1.6% vs. 9.7 ± 2.4% of initial weight, respectively; p = 0.0001) but similar long-term losses (6.3 ± 3.2% vs. 5.0 ± 4.0%, respectively; p > 0.2). Attrition was similar with VLCD and LCD regimens.

Discussion: VLCDs did not produce greater long-term weight losses than LCDs. In the United States, the use of liquid meal replacements as part of a 1000 to 1500 kcal/d diet may provide an effective and less expensive alternative to VLCDs. In Europe, VLCDs are used with less intensive medical supervision than in the United States, which reduces the cost of this approach.

Full Text:Gilden Tsai A, Wadden TA. The evolution of very-low-calorie diets: an update and meta-analysis, Obesity (Silver Spring). 2006 Aug;14(8):1283-93.

Low and Very Low Calorie Diets

Summing up the safety, who, what, where, when?

Who? Very-low-calorie- diets can be prescribed for adults who are massively obese or moderately obese with a clearcut medical indication for slimming. A careful clinical and biological check-up is necessary, particularly to search for renal dysfunction, any sign of inflammatory or infectious process (which would result in a seriously negative nitrogen balance); hyperuricemia is not a contraindication but has to be treated. ECG abnormalities, particularly rhythm disorders and prolonged QT, call for a very close cardiological monitoring.

What? The diet should consist of proteins of good or, preferred, of excellent biological value: at least 55g for women of small or medium height and moderate obesity; 70g for men, and for tall or massivly obese women; 100g for massively obese men. For all subjects, 1.5 L water/d and supplementation of minerals, vitamins and trace elements according to RDA. A small amount of carbohydrates can be added in order to diminish ketosis provided it is not alloted to the detriment of the amount of protein lad.

Where? If there is no special risk factor, the diet can be followed in ambulatory condidtions without interrupting sedentary work. Not only must there be a previous check-up, there must also be a programmed follow-up.

When? A VLCD should not be followed longer then 4 wk. Because it has been shown that VLCD improved the mood, sometimes until euphoria, it is safe to warn the patient of the danger of prolonged use, to schedule a consultation at the end of the diet and to contact patients who do not show up. If necassary a second or third VLCD can be programmed but not without a free interval of at least 2 mo on a well balanced low calorie diet.

Severe vs moderate energy restriction with and without exercise in the treatment of obesity: efficiency of weight loss.

Thirty obese women were randomly assigned to either 40% [severe energy restriction (SER)] or 70% [moderate energy restriction (MER)] of their maintenance energy requirements and to no exercise, aerobic exercise (walking), or aerobic exercise plus circuit weight training. Body composition by hydrostatic weighing and energy expenditure by indirect calorimetry were measured at 0, 3, and 6 mo. In addition, we developed a deficit-efficiency factor (DEF), calculated as body energy loss/dietary energy deficit, to attempt to quantify the effectiveness of the weight-reduction interventions. Subjects in the SER group lost more weight (mean +/- SE: 15.1 +/- 1.4 vs 10.8 +/- 1.0 kg), fat (11.7 +/- 1.1 vs 8.3 +/- 0.6 kg), and fat-free mass (2.8 +/- 0.3 vs 1.8 +/- 0.3 kg) than the MER group (P < or = 0.05). However, the overall DEF was greatest in the MER group (0.80 +/- 0.07) compared with the SER group (0.52 +/- 0.05; P < or = 0.01). Exercise had no significant effect. This study demonstrates that MER may offer an advantage over SER because it produces a greater energy loss relative to energy deficit.

Full Text: Sweeney et al, Severe vs moderate energy restriction with and without exercise in the treatment of obesity: efficiency of weight loss, Am J Clin Nutr. 1993 Feb;57(2):127-34.

Controlled trial of the metabolic effects of a very-low-calorie diet: short- and long-term effects

Resting energy expenditure (REE), weight, and body composition were measured up to seven times in 13 obese women during a 24-wk study. Patients were randomly assigned to a very-low-calorie diet (VLCD, 500 kcal/d) or a balanced-deficit diet (BDD, 1200 kcal/d). After 8 wk of supplemented fasting, REE of the VLCD patients decreased by 17% whereas that of the BDD patients was virtually unchanged. REE of the VLCD patients increased during 12 subsequent weeks of realimentation such that differences in REE between the two groups were not statistically significant at week 24 (VLCD = -11%, BDD = -2%). Reductions in weight and fat-free mass (FFM) were 12.1% and 3.6% for the VLCD patients and 10.6% and 4.1% for the BDD patients, respectively. There were no significant differences between the groups in pre- to posttreatment changes in REE normalized to FFM. Results suggest that REE recovers partially after consumption of a VLCD. They also provide evidence of a possible metabolic advantage of weight loss by a more moderate restriction.

Full Text:Foster et al, Controlled trial of the metabolic effects of a very-low-calorie diet: short- and long-term effects. Am J Clin Nutr. 1990 Feb;51(2):167-72.

Psychological Risks of VLCD

Psychological Consequences of Food Restriction

A review of the literature and research on food restriction indicates that inhibiting food intake has consequences that may not have been anticipated by those attempting such restriction. Starvation and self-imposed dieting appear to result in eating binges once food is available and in psychological manifestations such as preoccupation with food and eating, increased emotional responsiveness and dysphoria, and distractibility. Caution is thus advisable in counseling clients to restrict their eating and diet to lose weight, as the negative sequelae may outweigh the benefits of restraining one's eating. Instead, healthful, balanced eating without specific food restrictions should be recommended as a long-term strategy to avoid the perils of restrictive dieting.

Abstract:Janet Polivy, Psychological Consequences of Food Restriction, J American Dietetic Association 9666):589-592 June 1996