M. Yannakoulia and N Scarmeas N Engl J Med 2024
Food consumption provides essential and non-essential nutrients to the human body, thereby promoting growth and health. Individual food choices and the potential modification of eating habits are complex issues, influenced by food availability and acceptability. Food availability depends on physical, political, and economic factors. From the myriad foods available or potentially available for consumption, selection is based on socioeconomic, cultural, and individual factors. Individual foods are components of diets; diets are characterized by their nutrient content, food groupings, and temporal consumption patterns.
The abundance of diets is continually expanding, and some diets have been extensively researched.
We reviewed the underlying rationale and components of the most recognized, scientifically explored, and widely promoted diets. We did not review diets for specific nutritional or metabolic deficiencies, nor many of the constructed dietary indices. This review does not aim to detail the clinical efficacy of each diet presented, although we briefly outline some of the well-known potential health effects and underlying mechanisms. While most (but not all) dietary modifications have been driven by the desire to control body weight, we considered important health effects independent of adiposity.
MEDITERRANEAN DIET Scientific research into the dietary patterns adopted by people in the Mediterranean region and the possible effects of these patterns on health began after World War II, led by two US-based scientists. Leland Allbaugh, field director of a survey on the island of Crete funded by the Rockefeller Foundation, described the Cretans' diet as "surprisingly good" and "extremely well adapted to their natural and economic resources, as well as their needs." This diet consisted of olives, cereals, pulses (edible seeds of legumes), fruit (the typical dessert after dinner), vegetables, and herbs, along with limited amounts of goat meat, milk, game, and fish. Bread (wholemeal, made from barley, wheat, or both) played a prominent role at every meal, and olive oil accounted for a relatively large proportion of energy intake.
The second scientific study to support the health-related attributes of the Mediterranean diet is the Seven Countries Study, led by Ancel Keys. The study's original design involved a comparison of diets and lifestyles across seven countries based on data from one or more cohorts of men in each country. All-cause mortality and coronary heart disease mortality rates were lower in the cohorts where olive oil was the primary dietary fat than in the cohorts from Northern Europe and the United States.
Today, the term Mediterranean diet is used to describe a dietary pattern characterized by a predominance of plant-based foods (fruits, vegetables, minimally processed grains, legumes, nuts, and seeds), with moderate amounts of dairy products, primarily fermented (e.g., cheese and yogurt); low to moderate amounts of fish and poultry; low amounts of red meat; and typically wine with meals. This diet has been the most researched, representing a potentially significant dietary modification for many health outcomes.
A comprehensive review of meta-analyses of observational studies and randomized controlled trials, with data from over 12,800,000 participants, suggested robust evidence for a protective association between adherence to the Mediterranean diet and the following health outcomes (out of the 37 examined): all-cause mortality, cardiovascular disease, coronary heart disease, myocardial infarction, cancer, neurodegenerative diseases, and diabetes. The beneficial effects of the Mediterranean diet may be mediated through multiple mechanisms, including reductions in blood lipids and markers of inflammatory and oxidative stress, improved insulin sensitivity, enhanced endothelial and antithrombotic function, and even a reduction in neurodegenerative changes in the brain.
Vegetarian diets have been adopted since antiquity for ethical or philosophical reasons and as part of religious commitments. Since the last decades of the 20th century, however, increasing attention has been paid to the health effects associated with vegetarian diets, as well as their ecological benefits (lower greenhouse gas emissions and reduced water and land use). Today, vegetarianism can encompass a variety of eating behaviors characterized by diverse attitudes, perceptions, motives, and also social and health dimensions. A vegetarian diet can be defined as any dietary pattern that excludes meat, meat products, and, to varying degrees, other animal products, while the term plant-based is broader and is used to characterize dietary patterns that are based primarily on non-animal foods but do not exclude animal products. The Mediterranean diet is an example of the latter. Fruits, vegetables, grains, nuts, seeds, and legumes make up an important part of vegetarian and plant-based diets.
A vegan diet is a strict form of vegetarianism, consisting solely of plant-based foods and excluding all foods and beverages derived wholly or partially from animals. In a lacto-vegetarian diet, dairy products are included, and in an ovo-vegetarian diet, eggs are permitted. The most common version of a vegetarian diet, lacto-ovo-vegetarianism, allows both dairy and eggs. Pescatarianism permits fish and seafood, as well as dairy and eggs. Finally, there are several variations of flexible dietary patterns, classified under the general term flexitarian diets, which are essentially vegetarian diets that include some animal products in varying amounts and combinations.
Given the multitude and multidimensionality of vegetarian dietary patterns, isolating a specific biological mechanism is quite challenging. Influences across multiple pathways have been invoked, including metabolic, inflammatory, and neurotransmitter pathways; the gut microbiota; and genome instability. Greater adherence to vegetarian diets has been linked to a reduced risk of cardiovascular disease, ischemic heart disease and death from ischemic heart disease, dyslipidemia, diabetes, certain cancers, and potentially, death from any cause. The associations between adherence to vegetarian diets and body composition, anthropometric markers, and weight-related measures have been debated.
The more restrictive the diet, the greater the risk of various nutrient deficiencies. Vegans are particularly susceptible to vitamin B12 deficiency, as vitamin B12 is found only in animal products, and lower intakes of other nutrients (including vitamin B2, niacin, iodine, zinc, calcium, potassium, and selenium) have also been reported. Nutritional supplementation or intermittent consumption of animal protein in low to moderate amounts (the flexitarian approach) can mitigate potential adverse health effects.
Low-Fat Diets: Because lipids and carbohydrates are the two macronutrients that contribute most to total energy intake in modern diets, balancing these macronutrients is the goal of various dietary modifications for successful weight management and other health outcomes. Low-fat diets for weight loss were already in use before being promoted by the medical community to reduce the risk of cardiovascular disease. During the 1980s, dietary fat was blamed for coronary heart disease and obesity. Low-fat diets, low-fat products, and the low-fat ideology became increasingly popular.
Aunque no existe una definición universal, cuando los lípidos contribuyen con menos del 30% de la ingesta total de energía, la dieta se considera baja en grasas. En las dietas muy bajas en grasas, el 15% o menos de la ingesta total de energía se deriva de los lípidos (por ejemplo, un plan de dieta de 2000 calorías incluiría <33 g de lípidos), dejando aproximadamente del 10 al 15% de proteínas y el 70% o más de carbohidratos. La dieta Ornish es un tipo de dieta vegetariana muy baja en grasas en la que los lípidos contribuyen con el 10% de las calorías diarias (relación de grasas poliinsaturadas a saturadas, >1) y en la que las personas comen lo que desean. La adecuación de nutrientes de las dietas bajas en grasas y muy bajas en grasas depende en gran medida de las elecciones individuales de alimentos. La adherencia a estas dietas puede ser un desafío, ya que no solo muchos alimentos de origen animal, sino también aceites vegetales y alimentos vegetales oleaginosos (por ejemplo, nueces y aguacates) deben restringirse. En tales casos, se puede considerar la suplementación con productos fortificados.
Low-fat diets have been evaluated in several well-designed studies and dietary interventions, including the Women's Health Initiative Dietary Modification Trial. The results of this trial provided evidence of lower breast cancer mortality among women advised to follow a low-fat diet (20% of calories from fat) compared to those who continued their usual diet, but the difference was small. Low-fat interventions appear to lead to weight loss compared to usual diet, but may be less effective than low-carbohydrate or other diets. Furthermore, low-fat diets may have a beneficial effect on several cardiometabolic factors, including blood lipids (particularly low-density lipoprotein [LDL] cholesterol, but with a controversial, lowering effect on high-density lipoprotein [HDL] cholesterol) and blood pressure, with reduced risks of myocardial infarction, diabetes, and death from any cause. However, the type of fat consumed may also matter. The literature on the biological mechanisms linking various fatty acids to cardiovascular disease and total lipid intake to obesity is extensive, and proposed mechanisms for the associations of low-fat diets with cancer have included immunological alterations, anti-inflammatory changes, and fatty acid-related reactive oxygen species production.
ATKINS, KETOGENIC, AND LOW-CARBOHYDRATE DIETS Since the late 19th century, there have been medical reports on the potential health effects of diets low or very low in carbohydrates and without restrictions on lipids, proteins, or total energy intake. The initial therapeutic focus was weight reduction and the management of drug-resistant epilepsy. However, the wider promotion of these ketone-inducing dietary patterns came after the publication of "The Atkins Diet Revolution" in 1972. Despite the popularity of these diets, several concerns were raised. The Food and Nutrition Council of the American Medical Association criticized the scientific evidence behind this approach and the potential harmful effects on health, primarily on the cardiovascular system.
However, in the 2000s, some randomized controlled trials showed that participants advised to follow the lowest carbohydrate diets (i.e., versions of the Atkins diet) experienced greater weight loss and greater improvements in some coronary heart disease risk factors than those assigned to higher carbohydrate diets. Although the superiority of this dietary modification was not found to persist in all studies during the follow-up or maintenance phase, and although adherence was variable, the scientific community subsequently began to explore the clinical potential of this diet more thoroughly.
El término cetogénico se usa para describir una variedad de dietas. Para la mayoría de las personas, el consumo de solo 20 a 50 g de carbohidratos por día conduce a la presencia de cetonas medibles en la orina. Estas dietas se conocen como dietas cetogénicas muy bajas en carbohidratos. Otra clasificación, utilizada principalmente en el manejo de la epilepsia resistente a los medicamentos, se basa en la relación de lípidos dietéticos con la suma de proteínas y carbohidratos dietéticos. En la versión clásica o más estricta, esta relación es de 4:1 (dietas en las que <5% de la energía se deriva de los carbohidratos), mientras que en la opción más relajada, la relación es de 1:1 (la dieta Atkins modificada, con aproximadamente el 10% de la energía proveniente de los carbohidratos), con varias opciones intermedias.
Diets containing higher amounts of carbohydrates (50 to 150 g per day) are still considered low-carbohydrate compared to typical consumption, but these diets may not induce the same metabolic changes as very low-carbohydrate diets. Practically speaking, any diet in which carbohydrates contribute less than 40 to 45% of total energy intake—a percentage assumed to represent average carbohydrate consumption—can be classified as low-carbohydrate. Several popular diets fall into this category. In the Zone Diet, 30% of calories come from protein, 30% from fat, and 40% from carbohydrates, and each meal must meet a protein-to-carbohydrate ratio of 0.75. The Zone Diet, along with the South Beach Diet and other low-carbohydrate diets, promotes the consumption of complex carbohydrates with the goal of reducing postprandial serum insulin concentrations.
Carbohydrate-restricted diets induce metabolic changes, to a greater or lesser extent, similar to those observed during starvation (e.g., changes in plasma levels of free fatty acids, insulin, glucose, and ketone bodies). Since a decrease in one macronutrient is always accompanied by a parallel increase in another, it is important to evaluate these diets considering not only their low carbohydrate content but also their high lipid or protein content, or both.
Evidence from long-term studies (i.e., >6 months) suggests that very low or low-carbohydrate diets result in weight loss that is equivalent to, but not better than, that achieved with other diets that have a higher carbohydrate content. On the other hand, randomized controlled trials have shown that low-carbohydrate ketogenic diets effectively reduce cardiovascular risk factors (blood glucose levels, glycated hemoglobin, and certain, but not all, blood lipids), especially in overweight or obese patients with type 2 diabetes.
Ketogenic diets have been reported to significantly reduce body weight and fat mass in cancer patients. There is growing interest in the potential effects of these diets on schizophrenia and mood disorders, as well as their role in cognitive function, Alzheimer's disease, and other dementias.
The anticonvulsant effect of the ketogenic diet occurs through a number of potential mechanisms that stabilize synaptic function and increase resistance to seizures. These mechanisms are not fully understood, but include the reduction of carbohydrates in the central nervous system and the inhibition of glycolysis, changes in neuronal excitability via ATP-sensitive potassium channels through alterations in mitochondrial function, inhibition of the mTOR pathway (mammalian target of rapamycin), and inhibition of excitatory glutamatergic synaptic transmission. Thus, low-carbohydrate ketogenic diets appear to reduce seizure frequency in children with drug-resistant epilepsy. The benefits in seizure control appear in the short and medium term and seem to be similar to the benefits of current antiepileptic drugs. Some efficacy in reducing seizures, although not as great, has been demonstrated with less restrictive forms of the ketogenic diet. Ketogenic diets may also reduce seizure frequency in adults with drug-resistant epilepsy, although the evidence is uncertain, and some promising results have been reported in adults with super-refractory status epilepticus. The most commonly reported adverse clinical effects of ketogenic diets include gastrointestinal symptoms, such as constipation, and dyslipidemia (potentially related to animal protein sources, which are often high in saturated fatty acids and fats).
LOW GLYCEMIC INDEX DIET The glycemic index, a ranking system that measures (on a scale of 1 to 100) the degree to which a particular food raises blood glucose levels, complements information about macronutrient composition. The glycemic index value of a food or meal depends not only on the nature of the carbohydrates included, but also on other dietary and non-dietary factors that affect nutrient digestibility or insulin secretion. In general, non-starchy vegetables, fruits, legumes, and whole grains induce low glycemic responses and are part of a low glycemic index diet. Meat, fish, poultry, eggs, and most dairy products also have a very low glycemic index. Low glycemic index diets can be a tool in the management of diabetes, as well as related cardiometabolic conditions and diseases, particularly in the context of glycemic dysfunction.
PALEOLITHIC DIET There was no single dietary regime adopted by all humans during the Stone Age. However, as isotope studies indicate, the staple foods in the hunter-gatherer diet were uncultivated plants (fruits, roots, and vegetables), some wild game, fish, and sometimes honey. This diet was very high in fiber and contained varying amounts of fat, with protein predominantly from animal sources. Most carbohydrates were derived from vegetables and fruits, with little contribution from grains and none from sugary foods or dairy products. The Paleolithic diet (or Paleo diet) has become a popular diet in the media. Various definitions of this diet have been used in both scientific and non-scientific literature, with lists of foods to be included (vegetables, fruits, lean meats, fish, nuts, and eggs) and excluded (grains or cereals, dairy products, legumes, added sugar and salt, and refined fats). The Paleolithic diet is generally considered a low-carbohydrate diet, but in some versions of it, carbohydrates account for up to 45% of total daily energy intake.
It has been suggested that the scarcity of high-glycemic and processed foods in the Paleolithic diet may beneficially affect insulin resistance and inflammatory mechanisms. This diet has been associated with improvements in insulin resistance and diabetes, dyslipidemia, hypertension, and inflammation, as well as body composition and weight-related measures. Evidence regarding the clinical efficacy of the Paleolithic diet is not as extensive as that for other diets, and any benefits remain a focus of ongoing research.
The DASH Diet: In the early 1990s, a randomized, multicenter clinical trial, Dietary Approaches to Stop Hypertension (DASH), was conducted to test the effect of dietary patterns on blood pressure control. Participants assigned to the trial diet for 8 weeks experienced greater reductions in blood pressure (on average, 5.5 mmHg systolic and 3.0 mmHg diastolic) than participants assigned to a control diet. Based on this evidence, the trial diet, called the DASH diet, was identified as an effective strategy for preventing and treating hypertension. The diet is rich in fruits and vegetables (five and four servings per day, respectively) and low-fat dairy products (two servings per day), and contains low amounts of saturated fat and cholesterol and relatively low levels of total lipids. With this diet, potassium, magnesium, and calcium levels are close to the 75th percentile of intake in the U.S. population, and the diet includes high amounts of fiber and protein. Basic and clinical research has linked alterations in these and other nutrients in the DASH diet to multiple physiological mechanisms that affect blood pressure control, glucose tolerance, inflammation, oxidative stress, fat absorption, and adipogenesis.
Since the original report, the DASH diet has been studied in relation to several disorders, in addition to hypertension. Greater adherence to this diet has been associated with a significant reduction in all-cause mortality, and the results of multiple observational studies have suggested associations with reductions in cancer incidence and cancer-related mortality. A comprehensive review of meta-analyses showed that, based on prospective cohort data for a total population of approximately 950,000 participants, greater adherence to the DASH diet was associated with a decrease in the incidence of cardiovascular disease, coronary heart disease, stroke, and metabolic diseases such as diabetes. Controlled trials showed decreases in diastolic and systolic blood pressure and in several metabolic measures, including insulin and glycated hemoglobin levels, and total and LDL cholesterol levels, as well as reductions in body weight. Modifications or improvements to the DASH diet have been proposed, such as the DASH-sodium diet, which combines the DASH diet with a low sodium intake, and the OmniHeart diet, in which a partial replacement of carbohydrates with protein (approximately half from plant sources) or with unsaturated fatty acids (predominantly monounsaturated) is advised.
The MIND diet (Mediterranean–DASH Intervention for Neurodegenerative Delay) is a dietary pattern designed to address the needs of a specific health outcome: cognitive function. Based on findings from previous research on nutrition and cognition or dementia, MIND combines features of the Mediterranean and DASH diets. It emphasizes the consumption of plant-based foods (whole grains, vegetables, beans, and nuts), with a unique focus on berries and leafy green vegetables. The diet restricts the consumption of red meat, as well as other foods high in total and saturated fat (fast food and fried foods, cheese, butter and margarine, and cakes and sweets), and olive oil is the primary oil in the diet. Fish is recommended more than once a week and poultry more than twice a week. MIND has shown some potential benefits with respect to cognitive outcomes and is being actively investigated in randomized clinical trials.
Intermittent fasting. Fasting (i.e., abstaining from food and caloric beverages for periods ranging from 12 hours to several weeks) has been practiced for centuries. Many religions recommend periods of fasting for believers (e.g., the Muslim Ramadan) as a mark of devotion, self-control, and denial of physical needs, as well as an opportunity for introspection. Clinical research has largely focused on fasting for its long-term effects on aging, metabolic dysfunction, and energy balance. Fasting is distinct from caloric restriction, in which energy intake is reduced by a certain percentage, usually 20 to 40 percent, while the frequency of meals is maintained.
Intermittent fasting has emerged as a less demanding alternative to continuous fasting. It's a general term that describes various regimens that include alternating periods of fasting or restricted eating with periods of normal or as-you-want eating.
The approaches used so far can be classified into two main types. For the first type, the reference period is the week. In alternate-day fasting, fasting is practiced every other day, with each fasting day followed by a day of unrestricted eating, while in modified alternate-day fasting, a very low-calorie diet is alternated with eating as desired. Fasting can be practiced for two consecutive or non-consecutive days, with normal eating for the remaining five days (the 5:2 diet). Other approaches include consecutive days of restricted eating (a very low-calorie diet for five days) followed by periods of unrestricted eating (for at least 10 days). In the second type of intermittent fasting, time-restricted eating, the day is the reference period, and eating takes place only during a specific period of the day (usually an 8- or 10-hour window).
When diet is modified to accommodate intermittent fasting, a metabolic shift occurs in fuel source utilization, from glucose to fatty acids and ketone bodies, resulting in increased energy efficiency and multiple effects on cellular and organ functions, including greater stress resistance. Evidence supporting the long-term effects and clinical benefits of intermittent fasting compared to continuous energy restriction is limited and debatable. However, some preliminary studies in humans and animals have found that intermittent fasting is associated with improvements in a wide range of health conditions, disorders, and cardiovascular health indicators, such as glucose regulation and diabetes, body composition indices, abdominal fat and obesity, dyslipidemia, hypertension, and inflammation. Because intermittent fasting is believed to have positive effects on energy metabolism, reduce the growth potential of cancer cells, and increase the susceptibility of cancer cells to treatment, the clinical effects of intermittent fasting on cancer initiation and progression are of interest. Similarly, due to preclinical evidence of the effects of intermittent fasting on neurodegenerative processes and other biological brain pathways, recent research is focusing on the possible effects on neuropsychiatric disorders.
Conclusions From a medical research perspective, a focus on elucidating the efficacy and biological mechanisms linking specific diets to various health outcomes is justifiable. An important requirement for such research is agreement on the definition of each diet. However, the wide variation in the diets that have been investigated makes standardization and evaluation difficult. Other challenges include the relatively limited evidence from randomized controlled trials, the reliance on single-blind dietary interventions, varying degrees of adherence, and other limitations inherent in this research, including dietary measurement errors, potential confounding factors, and the magnitude of the effect size, all of which have been widely discussed. Evidence is also limited for comparisons of one potentially healthy diet with another, although recent research has attempted such comparisons, primarily between constructed dietary indices.
Diets have been developed within different historical and cultural frameworks and for different populations and patient groups, posing challenges for clinical translation into daily practice. While the health effects and transferability of diets have been demonstrated for some ethnic groups and locations worldwide, adapting them to other cultures and underrepresented groups can be challenging. Recent advances in nutrient biomarkers, imaging techniques, and other diagnostic methods, as well as our understanding of the food microbiome and exposome, the interaction of these factors with the genome, and multi-omics approaches, could enable the construction of individualized profiles and more personalized application of diets for small groups or individuals.81 Potential adherence must also be considered. Adherence can decrease over time, and higher discontinuation rates have been reported for more restrictive dietary patterns.
Although many diets have been developed with the initial goal of controlling body weight, dietary composition also has important health effects that are independent of its effects on adiposity. A general review of the literature suggests that moderate-fat, plant-based diets, characterized by the consumption of vegetables, fruits, whole grains, pulses or legumes, nuts, and unsaturated fats, with low to moderate amounts of poultry and seafood and low amounts of red meat and sugar, may offer substantial health benefits. The Mediterranean diet may be one such option, at least for some population groups.
It is imperative to educate healthcare professionals about diets and their potential effects on disease. Advice on healthy eating should be integrated into clinical practice and taught in medical school curricula, and healthcare professionals should offer variations of plant-based diets that take into account individual preferences, cost, affordability, and cultural considerations.