Gastroenterology
Volume 136, Issue 5 , Pages 1490-1492, May 2009

High- or Low-Carbohydrate Diets: Which Is Better for Weight Loss, Insulin Resistance, and Fatty Livers?

  • Guenther Boden

      Affiliations

    • Corresponding Author InformationReprint requests Address requests for reprints to: Guenther Boden, MD, Division of Endocrinology, Diabetes and Metabolism, and the Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania

Division of Endocrinology, Diabetes and Metabolism and Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania

published online 23 March 2009.

Article Outline

 

See “Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction,” by Kirk E, Reeds DN, Finck BN, et al, on page 1552.

The recent increase in obesity and the health problems associated with it has grown into a huge public health burden.1 A plethora of diets continue to be promoted to help with weight reduction.2 Many of these are either low-carbohydrate (LC) or high-carbohydrate (HC) diets.2, 3 There is continuing debate as to which of these 2 dietary approaches is best with respect to weight loss, reduction in cardiovascular risk including blood pressure and lipid levels, and for patients with diabetes, improvement of blood glucose control.

The manuscript by Kirk et al4 in this issue of Gastroenterology addresses some of these issues. These authors studied 22 obese (body mass index, 36.5 ± 0.8) men and women, 14 of whom had impaired glucose tolerance; none had overt diabetes. These volunteers were admitted to the General Clinical Research Center (GCRC) at Washington University Medical Center and were randomized to either an HC (carbohydrate ≥180 g/d) or a LC (carbohydrate ≤60 g/d) diet. After 48 hours on these diets, patients were discharged from the GCRC and told to continue on their HC or LC diets at home until they reached a 7% weight loss, which occurred after about 6 weeks. At that time, their caloric intake was adjusted to maintain weight. After approximately 4 weeks on this new weight-maintaining diet, all subjects were readmitted to the GCRC, where the clamps and body composition analyses were repeated.

What were the findings and what can we learn from them? Let us first look at weight loss. Both groups lost about 2 kg during the initial 48 hours in the controlled environment of the GCRC, where their energy intake was around 1100 kcal/d. Their prehospitalization energy intake is not known, but probably was ≥3000 kcal/d based on a study with similarly obese subjects where energy intake was measured.5 Thus, assuming no change in energy expenditure, their estimated caloric deficit was approximately 4000 kcal/48 h (∼3,000 − 1100 kcal/d × 2 days).

More important than this initial weight loss, which was mostly a loss of body water,6 was the weight loss which occurred during the first 6 or so weeks during which both LC and HC groups lost about 7 kg or 5,250 g of fat (∼75% of the weight loss was from fat). On average, therefore, they lost about 125 g of fat per day (5250 g/42 days), which translates into an energy deficit of approximately 1000 kcal/d. This suggests that once out of the hospital, their average daily energy intake increased considerably, to perhaps as much as 2000 kcal/d. Interestingly, weight loss was similar in the LC and the HC group after 48 hours and after nearly 11 weeks. Some studies have reported greater weight loss for several months with LC than HC diets.6, 7, 8, 9, 10, 11, 12 However, these differences disappeared during longer follow-up.8, 10 Moreover, a meta-analysis of several such studies came to the conclusion that there were no impressive differences in the effects on weight loss between these diets.11 Thus, the study by Kirk et al supports the concept that, over longer periods of time, the macronutrient composition of a calorie restricted diet is not very important for weight loss, which depends primarily on the balance of calories ingested versus calories expended.12

Kirk et al also found that insulin's effect to suppress hepatic glucose production (reflecting hepatic insulin sensitivity) improved more in the LC than the HC group, both after 48 hours and after about 11 weeks. By contrast, insulin stimulation of glucose uptake (reflecting peripheral, mostly skeletal muscle insulin sensitivity), improved only after about 11 weeks of dieting. What may explain the beneficial effect of the LC diet on the improvement in insulin sensitivity and why was it seen first in the liver and only later in the periphery? With respect to the first question, less insulin is secreted and needed to metabolize fatty acids or amino acids than glucose.13 A practical application of this is the calculation of insulin requirement by insulin pump users that is based exclusively on the carbohydrate contents of meals. Also, 63% of the subjects in Kirk et al's study were glucose intolerant, that is, they had insufficient insulin secretion and, therefore, can be anticipated to cope better with a less insulin-requiring, low LC diet than a more insulin-requiring, HC diet. Better glycemic control improves insulin resistance, perhaps by decreasing glucose toxicity.14 With respect to the second question, the liver is known to be several times more sensitive to insulin than skeletal muscle.15 Therefore, changes in insulin action can be detected first in the liver, particularly if these changes are small, which was the case in the current study for both hepatic and peripheral insulin sensitivity.

Perhaps the most interesting observation made by Kirk et al was that the LC diet decreased the excessive intrahepatic triglyceride (IHTG) content of these obese subjects within 48 hours by 30% (compared with about 10% in the HC group) and that both the LC and HC calorie restricted diets reduced IHTG content by about 40% after approximately 11 weeks. The cause for the rapid clearance of IHTG with the LC diet is not known. One factor might be the early improvement of hepatic insulin sensitivity which was also about 3 times greater in the LC compared with the HC group. Several studies have shown that insulin resistance is an essential requirement for accumulation of hepatic fat (reviewed in reference Angulo16). Insulin-resistance–driven hyperinsulinemia has been shown to markedly stimulate de novo lipogenesis17 by up-regulating the expression of the sterol regulatory element binding protein-1c in the liver, which is followed by the activation of key lipogenic enzymes including fatty acid synthase and acetyl CoA carboxylase.18, 19, 20 Whatever the reason, the dramatic effect of LC diets on IHTG merits further investigation in view of the clinical importance of hepatic steatosis, which can advance to steatohepatitis and cirrhosis,16 and because of our very limited pharmaceutical armamentarium to combat this problem.21

In summary, for nondiabetic individuals who desire weight loss, long-term compliance with a calorie-restricted diet is important. There is presently no convincing evidence that, over the long term, LC calorie-restricted diets are better than HC calorie restricted diets. Similarly, to mobilize fat from fatty livers in individuals with nonalcoholic fatty liver disease, reduction of excessive nutrient intake is most important. Thus, any calorie-restricted diet, whether LC or HC to which individuals are able to adhere for years rather than weeks, should be effective to improve weight, insulin resistance, and cardiovascular risk factors.22 By contrast, for glycemic control in diabetic patients, LC diets are better than HC diets.

Back to Article Outline

References 

  1. Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity among US adults, 1999–2000. JAMA. 2002;288:1723–1727
  2. Freedman MR, King J, Kennedy E. Popular diets: a scientific review. Obes Res. 2001;9(Suppl 1):1S–40S
  3. Atkins RC. Dr. Atkins' new diet revolution. New York: Avon Books; 1992;
  4. Kirk E, Reeds DN, Finck BN, et al. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology. 2009;136:1552–1560
  5. Boden G, Sargrad K, Homko C, et al. Effect of a low-carbohydrate diet on appetite, blood glucose levels and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med. 2005;142:403–411
  6. Yang M-U, Van Itallie TB. Composition of weight lost during short-term weight reduction (Metabolic responses of obese subjects to starvation and low-calorie ketogenic and nonketogenic diets). J Clin Invest. 1976;58:722–730
  7. Samaha FF, Iqbal N, Seshadri P, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003;348:2074–2081
  8. Foster GD, Wyatt HR, Hill JO, et al. Randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003;348:2082–2090
  9. Brehm BJ, Seeley RJ, Daniels SR, et al. A randomized trial comparing very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. 2003;88:1617–1623
  10. Stern L, Iqbal N, Seshadri P, et al. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med. 2004;140:778–785
  11. Malik VS, Hu FB. Popular weight-loss diets; from evidence to practice. Nat Clin Pract Cardiovasc Med. 2007;4:34–41
  12. Kinsell LW, Gunning B, Michaels GD, et al. Calories do count. Metabolism. 1964;13:195–204
  13. Fajans SS, Floyd JC, Knopf RF, et al. Effect of amino acids and protein on insulin secretion in man. Rec Prog Horm Res. 1967;23:617–656
  14. Boden G, Ruiz J, Kim C-J, et al. Effects of prolonged glucose infusion on insulin secretion, clearance, and action in normal subjects. Am J Physiol. 1996;270:E251–E258
  15. Rizza RA, Mandarino LJ, Gerich JE. Dose-response characteristics for effects of insulin on production and utilization of glucose in man. Am J Physiol. 1981;240:E630
  16. Angulo PA. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–1231
  17. Tamura S, Shimomura I. Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease. J Clin Invest. 2005;115:1139–1142
  18. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114:147–152
  19. Shimomura I, Matsuda M, Hammer RE, et al. Decreased IRS-2 and increased SREBP-1 lead to mixed insulin resistance and sensitivity in livers and lipodystrophic and ob/ob mice. Mol Cell. 2000;6:77–86
  20. Koo SH, Dutcher AK, Towle HC. Glucose and insulin function through two distinct transcription factors to stimulate expression of lipogenic enzyme genes in liver. J Biol Chem. 2001;276:9437–9554
  21. Boden G, Zhang M. Recent findings concerning thiazolidinediones in the treatment of diabetes. Expert Opin Investig Drugs. 2006;15:243–250
  22. Fontana L, Meyer TE, Klein S, et al. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A. 2004;101:6659–6663

 Conflicts of interest The author discloses no conflicts.

 Funding Supported by National Institutes of Health grants R01-DK58895, HL-0733267, and R01-DK066003 and a grant from the Groff Foundation.

PII: S0016-5085(09)00451-X

doi:10.1053/j.gastro.2009.03.019

Refers to article:

  • Editorial Accompanies Article Dietary Fat and Carbohydrates Differentially Alter Insulin Sensitivity During Caloric Restriction , 27 January 2009

    Erik Kirk, Dominic N. Reeds, Brian N. Finck, Mitra S. Mayurranjan, Bruce W. Patterson, Samuel Klein
    Gastroenterology May 2009 (Vol. 136, Issue 5, Pages 1552-1560)

Gastroenterology
Volume 136, Issue 5 , Pages 1490-1492, May 2009

Article Tools