Medical research related to low-carbohydrate diets

Low-carbohydrate diets became a major weight loss and health maintenance trend during the late 1990s and early 2000s. While their popularity has waned recently from its peak, they still remain popular. This diet trend has stirred major controversies in the medical and nutritional sciences communities and, as yet, there is not a general consensus on their efficacy or safety. The majority of the medical community remains generally opposed to these diets for long term health despite several studies reporting positive results in both weight loss and improvement in health indicators.

This article summarizes a sampling of the studies that exist related to this diet trend. It is not a complete listing of all relevant research. For general information about low-carbohydrate diets see the main article.

Synopsis
Because of the substantial controversy regarding low-carbohydrate diets, and even disagreements in interpreting the results of specific studies, it is currently difficult to objectively summarize the research in a way that reflects scientific consensus. It is at least important to recognize that, despite the characterization by some that the general concept of low-carbohydrate dieting for health was invented by Dr. Atkins in the 1970s, in reality the general concept has existed as a diet recommendation since the nineteenth century.

Although there has been some research done throughout the twentieth century, most directly relevant scientific studies have occurred in the 1990s and early 2000s and, as such, are relatively new and the results are still debated in the medical community. Supporters and opponents of low-carbohydrate diets frequently cite many articles (some times the same articles) as supporting their positions. It is worth noting that one of the fundamental criticisms of those who advocate the low-carbohydrate diets has been the lack of long-term studies evaluating their health risks. However, in 2006, Halton et al. published a 20-year study regarding the risk of coronary heart disease, one of the principle concerns, for practitioners of low-carbohydrate diets (the study concluded that for the group studied, at worst, there was no increased risk of heart disease and "when vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease").

Specific Studies
The following is not a complete list of all relevant research but a selected list of articles demonstrating some of the breadth of scientific knowledge available on this subject.

Journal of the American Medical Association: 1926
Lieb et al., 1926 conducted a case study of Dr. Vilhjalmur Stefansson, an anthropologist and explorer who lived with the Inuit eating a diet consisting almost entirely of meat, fish, and fat. A research team studied Stefansson's health looking for signs that his "unusual" diet had adversely affected his health. The team was unable to find any health problems in Stefansson and noted that the Inuit themselves also were quite healthy.

The Lancet: 1956
Kekwick and Pawan, 1956 conducted a study of subjects consuming 1000-calorie diets, some 90% protein, some 90% fat, and some 90% carbohydrates. Those on the high fat diet lost the most, the high protein dieters lost somewhat less, and the high carbohydrate dieters actually gained weight on average.

Kekwick and Pawan noted irregularities in their study (patients not fully complying with the parameters of the study). As such the validity of the conclusions has to be questioned.

Annals of Internal Medicine: 1965
A study conducted in 1965 at the Oakland (California) Naval Hospital used a diet of 1000 calories per day, high in fat and limiting carbohydrates to 10 grams (40 calories) daily. Over a ten-day period, subjects on this diet lost more body fat than did a group who fasted completely (Benoit et. al. 1965). Some advocates of low-carbohydrate diets have termed this the metabolic advantage of such diets.

American Journal of Clinical Nutrition: 1997
Holt et al., 1997 performed a study of glucose and insulin responses for test subjects to a variety of foods, both high- and low-carbohydrate. The conclusions state the following.
 * Our study was undertaken to test the hypothesis that the postprandial insulin response was not necessarily proportional to the blood glucose response and that nutrients other than carbohydrate influence the overall level of insulinemia ... The results of this study confirm and also challenge some of our basic assumptions about the relation between food intake and insulinemia. Within each food group, there was a wide range of insulin responses, despite similarities in nutrient composition ... As observed in previous studies, consumption of protein or fat with carbohydrate increases insulin secretion compared with the insulinogenic effect of these nutrients alone (22, 30-32) ... However, some protein and fat-rich foods (eggs, beef, fish, lentils, cheese, cake, and doughnuts) induced as much insulin secretion as did some carbohydrate-rich foods (eg, beef was equal to brown rice and fish was equal to grain bread).

This study challenges the general assertion that only carbohydrates significantly impact insulin production.

The authors describe their work as "preliminary" and so the results should be judged with caution.

New England Journal of Medicine: 2003
Two important NEJM studies from this year are mentioned here. Samaha et al., 2003 completed a study of 132 obese subjects comparing the efficacy of low-carbohydrate and low-fat diets. The conclusions of the article state the following.
 * Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed.

Foster et al., 2003 performed a similar study 63 obese men. Their conclusion was the following.
 * The low-carbohydrate diet produced a greater weight loss (absolute difference, approximately 4 percent) than did the conventional diet for the first six months, but the differences were not significant at one year. The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease. Adherence was poor and attrition was high in both groups. Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate, high-protein, high-fat diets.

In essence these studies showed that, setting aside their short-term nature and some safety questions, the low-carbohydrate diet was at least somewhat more effective in weight loss and in improvement of other health issues in an important demographic.

Journal of the American Medical Association: 2003
Bravata et al., 2003 conducted a literature search study of low-carbohydrate diet studies conducted between 1966 and 2003. The paper stated the following conclusion.
 * There is insufficient evidence to make recommendations for or against the use of low-carbohydrate diets, particularly among participants older than age 50 years, for use longer than 90 days, or for diets of 20 g/d or less of carbohydrates. Among the published studies, participant weight loss while using low-carbohydrate diets was principally associated with decreased caloric intake and increased diet duration but not with reduced carbohydrate content.

The study determined that carbohydrate reduction did not significantly contribute more to weight loss than simply reducing calories. It is worth noting that the article does state that
 * Low-carbohydrate diets had no significant adverse effect on serum lipid, fasting serum glucose, and fasting serum insulin levels, or blood pressure.

Journal of Child Neurology: 2003
Evangeliou et al., 2003 completed a 6-month study of 30 autistic children following a low-carbohydrate, ketogenic diet. The paper stated the following conclusions.
 * Of the remaining group who adhered to the diet, 18 of 30 children (60%) [the rest did not complete the study], improvement was recorded in several parameters and in accordance with the Childhood Autism Rating Scale. Significant improvement (> 12 units of the Childhood Autism Rating Scale) was recorded in two patients (pre-Scale: 35.00 +/- 1.41[mean +/- SD]), average improvement (> 8-12 units) in eight patients (pre-Scale: 41.88 +/- 3.14[mean +/- SD]), and minor improvement (2-8 units) in eight patients (pre-Scale: 45.25 +/- 2.76 [mean +/- SD]).

The authors state clearly that the study was limited and the results are preliminary.

Journal of the American Academy of Neurology: 2003
Kossoff et al., 2003 conducted a small study of six epileptic patients studying the effects of the Atkins diet. The abstract states the following.


 * The ketogenic diet is effective for treating seizures in children with epilepsy. The Atkins diet can also induce a ketotic state, but has fewer protein and caloric restrictions, and has been used safely by millions of people worldwide for weight reduction. Six patients, aged 7 to 52 years, were started on the Atkins diet for the treatment of intractable focal and multifocal epilepsy. Five patients maintained moderate to large ketosis for periods of 6 weeks to 24 months; three patients had seizure reduction and were able to reduce antiepileptic medications. This provides preliminary evidence that the Atkins diet may have a role as therapy for patients with medically resistant epilepsy.

In a 2004 Lancet article, Dr. Kossoff also stated that
 * The ketogenic diet is a high-fat, adequate protein, low carbohydrate diet that has been used for the treatment of intractable childhood epilepsy since the 1920s ... Although less commonly used in later decades because of the increased availability of anticonvulsants, the ketogenic diet has re-emerged as a therapeutic option.

Annals of Internal Medicine: 2004
Two significant studies can be found in the Annals of Internal Medicine in 2004. Yancy et al., 2004 completed a study of 120 overweight, high-lipid-count subjects comparing the efficacy of low-carbohydrate and low-fat diets. The conclusions of the article state the following.
 * Compared with a low-fat diet, a low-carbohydrate diet program had better participant retention and greater weight loss. During active weight loss, serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low-carbohydrate diet than with the low-fat diet.

Stern et al., 2004 conducted a one-year study of 132 obese adults. The conclusions state the following.
 *  Participants on a low-carbohydrate diet had more favorable overall outcomes at 1 year than did those on a conventional diet. Weight loss was similar between groups, but effects on atherogenic dyslipidemia and glycemic control were still more favorable with a low-carbohydrate diet after adjustment for differences in weight loss.

Nutrition Journal: 2004
Feinman and Fine, 2004 present an argument refuting the "calorie is a calorie" principle cited by some as an argument against the weight-loss benefits of low-carbohydrate diets. The "calorie is a calorie" argument, loosely speaking, states that the laws of thermodynamics imply that calories ingested from any source are burned at the same rate in the body (meaning that, for the purposes of weight loss, all sources of calories are the same).

The paper refutes this (the argument is omitted here) stating the following in the conclusion.
 * Thus, ironically the dictum that a "calorie is a calorie" violates the second law of thermodynamics, as a matter of principle.

The authors' point is that while some have argued that there is no point in comparing the effectiveness of diets based on the sources of calories (proteins, fats, or carbohydrates), the arguments in favor of this viewpoint are not supported by science. This paper is not directly based on any clinical studies but rather is a discussion of basic scientific theory related to this subject.

American Journal of Epidemiology: 2005
Ma et al., 2005 completed a one-year study of 572 healthy adults monitoring their diet and physical activity. The study concluded the following.
 * In conclusion, results from our study suggest that daily dietary glycemic index is independently and positively associated with BMI [Body Mass Index]. This finding is consistent with the hypothesis that with increased glycemic index, more insulin is produced and more fat is stored, suggesting that type of carbohydrate may be related to body weight. Our data did not support the current public trend of lowering total carbohydrate intake for weight loss or of lowering glycemic load for weight loss, as suggested by other researchers.

This study refutes the suggestion that total carbohydrate consumption directly correlates with weight loss but does support the notion that the glycemic index of foods consumed correlates with weight loss. The study does not specifically distinguish between nutritive and non-nutritive carbohydrate consumption nor is it clear that any of the diets was ketogenic (a key factor for most low-carbohydrate diets).

Journal of Nutrition and Metabolism: 2005
Yancy et al., 2005 completed a study of 28 overweight subjects with type 2 diabetes. The conclusion of the study was the following.
 * The LCKD [low carbohydrate, ketogenic diet] improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication.

The article lends support to the argument that low carbohydrate diets can be at least a partial remedy for some forms of diabetes (and may lend support to the argument that some forms of diabetes may in fact be caused by high carbohydrate diets).

New England Journal of Medicine: 2006
Halton et al., 2006 completed a study analyzing the long-term (20 years) health effects of low-carbohydrate diets. The study was limited to women and followed 82,802 subjects. Based on questionnaires, the study determined the correlation between the carbohydrate intake and coronary heart disease risk.

The conclusion in the article states the following.
 * Our findings suggest that diets lower in carbohydrate and higher in protein and fat are not associated with increased risk of coronary heart disease in women. When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease.

This study refutes the argument that low-carbohydrate diets necessarily cause heart disease, at least in women. Perhaps more significantly, it suggests that the low-carbohydrate diet can be part of a healthy, long-term lifestyle.

Notably, this article answers the one concern raised in the conclusions by Samaha et al., 2003 (mentioned above).

International Journal of Cancer, 2006
Bravi et al., 2006 completed a study of 2301 subjects, 767 with renal cell carcinoma (cancer of the kidneys), analyzing the effects of various types of foods on the risk of developing the cancer. The authors of the paper concluded the following.
 * A significant direct trend in risk was found for bread (OR = 1.94 for the highest versus the lowest intake quintile), and a modest excess of risk was observed for pasta and rice (OR = 1.29), and milk and yoghurt (OR = 1.27). Poultry (OR = 0.74), processed meat (OR = 0.64) and vegetables (OR = 0.65) were inversely associated with RCC [renal cell carcinoma] risk.

This, in effect, says that bread consumption raised the risk of the cancer by 94% whereas the consumption of poultry and vegetables decreased the risk of the cancer by 26% and 35%, respectively.

Meta-analytic summaries
Meta-analysis is a method to succinctly summarize and combine the results from multiple individual studies. The following meta-analyses of low carbohydrate diets are limited to randomized controlled trials that directly compare low carbohydrate diets to other diets. Some of the studies listed above are randomized controlled trials and are included in these meta-analyses.

A meta-analysis of randomized controlled trials by the Cochrane Collaboration in 2002 concluded that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people.

A more recent meta-analysis that included randomized controlled trials published after the Cochrane review  found that "low-carbohydrate, non-energy-restricted diets appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year. However, potential favorable changes in triglyceride and high-density lipoprotein cholesterol values should be weighed against potential unfavorable changes in low-density lipoprotein cholesterol values when low-carbohydrate diets to induce weight loss are considered." Although studies from Stanford University and Duke University were not meta-analytic, their results favored the low-carbohydrate approach, as opposed to the aforementioned study which questions which is better.