Metabolic Effects of High-Protein, Low-Carbohydrate Diets Margo A. Denke, MD eight-losing diets appeal to the growing popu- Power Diet, and the Zone Diet are all variations on Wlation of overweight Americans. Fad diets this common theme. promise rapid weight loss, easy weight loss, limited Several diets promise that, as long as you restrict restrictions on portion sizes of favorite foods, and carbohydrates, you will lose weight and you can eat as above all an enhanced sense of well being. The pop- much food as you want. There may be a kernel of truth ularity of fad diets points out the honest promises of to this claim. For some patients, high-protein intake traditional weight loss diets. Traditional weight loss suppresses appetite.2 For other patients, ketosis from diets promise slow weight loss of 0.45 to 0.9 kg/week. carbohydrate restriction suppresses appetite. Restrict- The weight loss is nothing but easy, because portion ing carbohydrate eliminates some popular foods that sizes of nearly all foods except low-calorie “free are often consumed in excess such as bread, cereal, foods” must be continuously evaluated and tracked. soft drinks, french fries, and pizza. By simply exclud- Claiming an enhanced sense of well being is hardly ing carbohydrate foods, patients following the Atkins appropriate for a traditional diet—most patients report diet typically consume 500 fewer calories a day.3 dissatisfaction from the constant vigilance over di- etary intake. Through discipline and perseverance, HOW LOW-CARBOHYDRATE DIETS traditional weight loss programs try to teach a patient PRODUCE INITIALLY GREATER a new lifestyle of healthy eating. Unfortunately, 70% WEIGHT LOSS of successful weight losers return to their old habits Reducing caloric intake by 500 kcal/day should and within 2 years regain at least half of the weight result in a 0.45- to 0.9-kg weight loss each week. lost. These patients typically have little insight into the However, low-carbohydrate, high-protein diets typi- reasons why the weight was regained, and consider cally produce a 2- to 3-kg weight loss in the first week. themselves “failures” to traditional diet programs. This added weight loss is not due to the miracle of They become prime targets for diets promising rapid “switching the body’s metabolism over to burning fat and easy weight loss. stores.” It is due to a diet-induced diuresis. When carbohydrate intake is restricted, 2 metabolic pro- PROTOTYPES OF THE HIGH-PROTEIN, cesses occur, both of which simultaneously reduce LOW-CARBOHYDRATE DIETS total body water content. The first process is mobili- High-protein, low-carbohydrate diets have a long his- zation of glycogen stores in liver and muscle. Each tory of cyclic popularity. Greek Olympians ate high gram of glycogen is mobilized with approximately 2 g meat, low vegetable diets Ͼ2,000 years ago to improve of water. The liver stores approximately 100 g of athletic performance. Dr. William Harvey recommended glycogen and muscle has 400 g of glycogen. Mobili- a diet prohibiting sweet and starchy foods and permitting zation glycogen stores result in a weight loss of ap- ad lib consumption of meats for patients who needed proximately 1 kg. Patients notice this change as a diuresis. As the basic understanding of nutrition and reduction in symptoms of “bloating” and are very essential vitamins developed, these diets fell out of favor. pleased with the effect. The second process is gener- They regained popularity in the late 1960s and early ation of ketone bodies from catabolism of dietary and 1970s with the publication of the Atkins’ Diet, Stillman’s endogenous fat. Ketone bodies are filtered by the Diet, The Drinking Man’s Diet, the Scarsdale Diet, and kidney as nonreabsorbable anions.4 Their presence in the Air Force Diet. The American Medical Association renal lumenal fluids increase distal sodium delivery to strongly criticized these diets,1 leading to their submer- the lumen, and therefore increase renal sodium and gence on the popular diet trend. water loss. Resurgence of low carbohydrate diets has been In a study comparing an 800-calorie mixed diet with fueled by rising obesity and insulin resistance in the an 800-calorie low-carbohydrate, high fat diet,5 10-day general population. Although the Atkins’ Diet is the weight loss was 4.6 kg on the ketogenic diet and 2.8 kg prototype of the low carbohydrate diet, The Sugar on the mixed diet. Energy-nitrogen balanced studies doc- Busters Diet, Carbohydrate Addicts Diet, Protein umented that the difference in weight lost was all ac- counted for by losses in total body water. From the Division of Endocrinology and Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, LONG-TERM WEIGHT LOSS IS Texas. Manuscript received October 16, 2000; revised manuscript INFLUENCED BY CALORIC received and accepted February 6, 2001. Address for reprints: Margo A. Denke, MD, Center for Human RESTRICTION, NOT CARBOHYDRATE Nutrition, The University of Texas Southwestern Medical Center at RESTRICTION Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9052. The diuretic effect of low-carbohydrate intake is E-mail: [email protected]. limited to the first week of the diet. The remaining ©2001 by Excerpta Medica, Inc. All rights reserved. 0002-9149/01/$–see front matter 59 The American Journal of Cardiology Vol. 88 July 1, 2001 PII S0002-9149(01)01586-7 weight loss is a function of the laws of energy balance. Complications from exclusion of fruits, vegetables, Calories from any source determine the success of and grains: Because they exclude fruits, vegetables, additional weight loss. and grains, low-carbohydrate, high-protein diets are In the only published study of Atkins diet, pa- deficient in micronutrients. Children consuming low- tients following the diet reduced caloric intake by carbohydrate ketogenic diets have reduced intakes of 500 kcal/day. The average weight loss was 7.7 kg at calcium, magnesium, and iron.21 Two sailors follow- 8 weeks, which is no greater than that expected ing a low-carbohydrate, high-protein hypocaloric diet from caloric restriction alone.6 The ability of low during an extended voyage developed optic neuropa- 23 carbohydrate intake to generate ketones has been thy from thiamine deficiency. Although vitamin de- touted as a relative advantage for losing weight. ficiencies can be circumvented by supplemental mul- tivitamins, even supplemented low-carbohydrate diets However, this advantage was not confirmed in a will still be deficient in a growing number of impor- 1-month study comparing ketogenic with nonketo- 7 tant, biologically active phytochemicals present in genic hypocaloric diets. Most comparison studies fruits, vegetables, and grains. have evaluated the relative advantages of either a Complications from high-protein intake: Increasing low carbohydrate or low fat hypocaloric diets; some the protein content of a diet significantly increases studies found a slight 1- to 3-kg greater weight loss glomerular filtration rate.24,25 Increases in glomerular on a low-carbohydrate diet,8,9,10,11 others a slight filtration rate are likely explained by increased renal advantage with a high-carbohydrate diet,12 but most capillary permeability. Unfortunately, this compensa- studies have observed no statistical advantage of a tory response to the greater production of nitrogen is low-carbohydrate diet.13–18 The preponderance of insufficient to clear protein by-products, and blood evidence suggests that as long as caloric intake urea nitrogen levels increase. High protein diets sig- remains constant,19 there is no intrinsic advantage nificantly lower urinary pH by increasing titratable to cutting carbohydrate intake.20 acid concentrations.25,26 High protein intakes provide a greater uric acid load to the kidney. Despite in- creases in urinary uric acid excretion, increases in UNTOWARD METABOLIC EFFECTS serum uric acid are observed.6,26 Complications from ketosis: Eucaloric ketogenic di- ets have been prescribed as part of an antiepileptic UNTOWARD LONG-TERM EFFECTS regimen in children with refractory seizure disorders. Development of nephrolithiasis: Hypercalciuria is a Children following these ketogenic diets have higher risk factor for nephrolithiasis. High-protein diets in- rates of dehydration, constipation, and kidney stones. duce hypercalciuria by several different mechanisms. Other reported adverse effects include hyperlipidemia, High-protein diets increase glomerular filtration rate impaired neutrophil function, optic neuropathy, osteo- and decrease renal tubular reabsorption of calcium. porosis, and protein deficiency.21 The relation between dietary protein intake and cal- Because ketogenic diets effect the central nervous cium excretion (Table 1) is clearly linear.27 system, it has been suspected that ketogenic diets may The stone-forming propensity of the hypercalciuria alter cognitive function. In a randomized weight loss induced by high-protein diets is aggravated by other study comparing a ketogenic with a nonketogenic changes in urine composition. A high animal protein hypocaloric diet, subjects consuming the ketogenic diet reduces gastrointestinal alkali absorption, leading diet had impairments in higher order mental process- to reduced urinary citrate.28 Hyperuricemia and hyper- ing and flexibility than those following the nonketo- uricosuria are also associated with excess intake of genic diet.7 animal protein. Animal protein is a rich source of Complications from high saturated fat intake: De- sulfur-containing amino acids; amino acids have a spite the beneficial effects of weight loss, diets that greater propensity to lower urinary pH. promote liberal intake of high fat meats and dairy Adding a carbohydrate restriction to a high-protein products raise cholesterol levels. In a study 24 sub- diet exacerbates many of these parameters. Low-car- jects following the Atkins’-type 4-week induction bohydrate intake further reduces urinary pH by induc- diet, then 4 weeks maintenance diet,6 low-density ing ketosis. Limiting the intake of vegetables and fruits further reduces urinary citrate by reducing di- lipoprotein cholesterol levels increased significantly etary sources of alkali.