The latest knowledge about the pathophysiology of obesity stems from the discovery of hormones and pathways important in appetite and weight regulation. Lifestyle modification is the first step in weight management. Lifestyle modification consists of a healthy diet, exercise, ensuring sleep quality, and stress mitigation. Up to now, dietary guidelines have been updated multiple times based on available scientific evidence. In popular culture, there are dozens of different diets targeted towards weight loss. Unfortunately, the general population leans towards a quick fix and rapid results, which is not necessarily sustainable in the long term. In addition, some of these diets may focus on weight loss and ignore overall health promotion.
One kilogram of fat contains 9000 kilocalories. To lose half a kilogram of fat per week, a person should achieve a 4500 kcal net deficit for a week, 642 kcal in one day. Net energy deficit is achieved by decreasing food intake (dieting) and increasing physical activity. For example, a 55-year old moderately active 136 kg woman needs 2600 kcal for her daily needs. For a person who consumes a 2600 kcal diet, creating a 642 kcal deficit will require a 25 percent reduction in daily energy intake if the individual does not increase physical activity. The patient needs to spend effort, time, and usually some extra money to reach the goal of losing 26 kg of fat in a year. The effort can be too much, and the time to achieve the target weight is too long for some individuals. Reaching ideal body weight might seem too slow for some individuals triggering giving up on lifestyle treatment. It is advisable to set realistic goals that can be achievable.
There is no single diet that can universally fit everyone for weight loss benefit. The initial dietary approach was based on achieving energy deficit by varying macronutrient composition. Unfortunately, the "calorie in calorie out "concept of weight regulation oversimplifies the physiologic process of appetite and weight regulation. Weight and appetite regulation are maintained by a complex interaction of hormonal and neuronal pathways. Adaptive physiologic mechanisms in place in the human body resist any change in weight from diet, exercise, or pharmacotherapy. Meaningful improvement in overall health outcomes requires at least 10% weight loss. A weight loss of 5 to 10% is associated with a reduced risk of diabetes mellitus and coronary artery disease. Therefore, at least 5% weight loss is recommended in obesity management as an initial goal, and achievement of 5% weight loss is considered a success when assessing response to therapy. Succesful diets have beneficial effects based not only on macronutrient composition aimed at creating negative energy balance but should also have salutary effects on satiety, appetite, and insulin resistance.
Issues of Concern
Mortality from cardiovascular causes has gone down with advances in science and technology in modern medical science. The rate of decline in cardiovascular mortality has unfortunately stagnated, but recently, rates are going up in 35 - 46-year-old males and females in the United States. This stagnation is primarily linked to rising obesity rates and unhealthy lifestyles, including unhealthy diet, lack of physical activity, chronic psychosocial stress, and poor sleep quality.
Western diet is typically rich in refined carbohydrates (mainly from refined grains), sugar, salt, animal fats, processed meats, food additives, and preservatives. It is also characterized by a lack of fibers, vitamins, antioxidants, and micronutrients, likely because of inadequate intake of fruits and vegetables. This dietary pattern accounts for high-caloric intake resulting in insulin resistance and weight gain. Western diet has been associated with elevated serum markers of inflammation. Kimmons and coworkers found that less than 10% of American adolescents or adults reported consuming the recommended amounts of fruits or vegetables. Adults preferred whole fruits and adolescents fruit juices, mainly orange juice. Herrick and coworkers reported that apples, apple juice, citrus juice, and bananas were responsible for almost half of total fruit consumption in American Youth. American adults and youth does not consume a variety and not enough amounts of fruits and vegetables.
Unfortunately, the wide availability of calorie-dense nutritionally poor processed foods, high prevalence of sedentary lifestyle, chronic psychosocial stress, and sleep deprivation create an obesogenic environment with the modern lifestyle. Genetic influences might also be responsible for food preferences. Chronic overnutrition on top of a sedentary lifestyle is the perfect recipe for weight gain, chronic inflammation, and metabolic disorders. The combination of chronic inflammation and metabolic disorders is known as metaflamation. Chronic low-grade inflammation contributes to the development of diseases such as obesity, type 2 diabetes mellitus, fatty liver, cardiovascular disease, and neurodegenerative disease such as Alzheimer disease.
Dietary Approach by Restriction of Macronutrients
There are three primary macronutrients, namely carbohydrates, fat, and protein. Carbohydrate yields 4 kilocalories (kcal) per gram, protein yields 4 kcal per gram, and fat provides 9 kcal per gram. Manipulation of macronutrient composition to aim for energy restriction as a dietary intervention has been studied extensively, and this kind of dietary intervention has been used for a long time. The varying composition of macronutrients, even in energy-matched diets, have different weight loss outcomes and overall health benefits. These different outcomes are likely secondary to differences in endocrine effects and changes in the gut microbiome that ultimately impact fat storage and body weight.
A low-fat diet has been traditionally advocated for the prevention of heart disease. Energy from fat amounts to 9 kcal per gram, which was the basis for considering fat as the energy-rich macronutrient. A low-fat diet was supposed to have energy restriction beneficial for weight loss. A low-fat diet consists of 20 to 25% of energy from fat, whereas a very low-fat diet contains 10 to 20 percent of energy from fat. The original promise of cardioprotective benefits from the low-fat diet also presumed weight loss as an added benefit.
A recent meta-analysis of trials comparing the efficacy of a low-fat diet to a low carbohydrate diet showed that a low-fat diet was less effective than a low carbohydrate diet in achieving sustainable long-term weight loss. When the low-fat diet was compared to the usual diet in non-weight-loss trials, a low-fat diet versus a high-fat diet led to similar weight loss. Evidence from randomized control trials shows that a low-fat diet is not superior to other dietary interventions for obesity. A very low-fat diet is challenging to sustain over the long term.
Low Carbohydrate Diet
The modern diet is very calorie-dense. It is also very high in refined carbohydrates, partly owing to the historical guidelines recommending a low-fat diet. Carbohydrate has earned an unpopular reputation of being unhealthy macronutrient. Historical data shows that during paleolithic times, our ancestors procured food by hunting and gathering; their primary energy source relied mainly on carbohydrates paradoxically. It is essential to know that it is high in fiber, low glycemic, and plant-based. The source of fat in the diet came from meat and fish.
A typical American diet has 45 to 65% of energy intake from carbohydrates. Therefore, a low carbohydrate diet can be defined as less than 45% dietary energy source from carbohydrates. There are varying definitions of low carbohydrate diets, which alludes to the fact that it is challenging to study outcomes of a low carbohydrate diet without a precise definition of a low carbohydrate diet. A low carbohydrate diet typically contains 52-150 grams of carbohydrates per day.
The presumed weight loss mechanism with a low carbohydrate diet relies on reduced secretion of insulin secondary to a low carbohydrate intake which stimulates lipolysis. Ketones are formed with a very low carbohydrate diet with carbohydrate restriction between 20 and 50 grams. When the body is faced with a low glucose supply, the first adaptive mechanism is gluconeogenesis. When gluconeogenesis reserve is exhausted, fat is broken down to fatty acid for oxidation. This rationale also forms the basis of a low-carb, high-fat diet. Nowadays, a low carbohydrate, healthy fat diet is trendy.
A low carbohydrate diet improves insulin sensitivity and benefits patients with diabetes, prediabetes, metabolic syndrome, overweight, and obesity. Long-term weight loss and health-promoting benefits of a low carbohydrate, high-fat diet have not been demonstrated. Long term sustainability of a low carbohydrate, high-fat diet is also questionable. There is an abundance of data showing health-promoting and weight loss benefits of a relatively higher carbohydrate, plant-based, low glycemic-high fiber diet, which would be sustainable on a long-term basis. A diet high in refined carbohydrates leads to frequent insulin spikes (secretory bursts), increased fat deposition, and lower satiety. A strict diet with low carbohydrates would also end up being poor in fibers and micronutrients. In addition, the higher fat content may also amount to increased intake of saturated fat with adverse cardiovascular outcomes.
A recent meta-analysis of randomized control trials demonstrated a more significant decrease in body weight, fat, and triglycerides with a low carbohydrate diet than a low-fat diet. The apparent increase in LDL was demonstrated with a low carbohydrate - high-fat diet, but overall health benefits outweigh the risk associated with the rise in LDL. A low carbohydrate diet leads to an increase in LDL due to large LDL particles size. Large LDL-C are particles not clearly associated with increased cardiovascular risk. The short-term benefits of a low-carb, high-fat diet in terms of weight loss are significant. On a short-term basis, a low carbohydrate diet improves glycemic control with favorable weight loss in type 2 diabetes mellitus, prediabetes, and metabolic syndrome. On the contrary, low fiber content and high fat in a low carbohydrate- high-fat diet may adversely impact bowel health and the gut microbiome.
The Mediterranean diet is based on a popular diet in the Mediterranean region, such as Italy and Greece. The Mediterranean diet is rich in fruits, vegetables, nuts, seeds, seafood, fish, and olive oil. The primary source of nutrients is plant-based, rich in fibers, lower in glycemic load, and high in antioxidants and micronutrients. In addition, it is lower in saturated fat and omega-6 polyunsaturated fatty acid (n-6 PUFA) and higher in monounsaturated fatty acids (MUFA) and omega-3 polyunsaturated fatty acid (n-3 PUFA).
The Mediterranean diet has been advocated for cardioprotective and health-promoting benefits, but numerous studies have also shown weight loss benefits. A recent meta-analysis demonstrated that the Mediterranean diet, when combined with energy restriction and physical activity, resulted in significant weight loss compared with the control diet. Meta-analysis of randomized controlled trials also demonstrated improved metabolic profile, resulting in reduced risk of developing type 2 diabetes mellitus and metabolic syndrome with a Mediterranean diet compared to the control diet. After 12 months, the traditional Mediterranean diet produced an average weight loss of 8.7 percent, and the low carbohydrate Mediterranean diet produced an average weight loss of 10%.
The Ornish Diet
The Ornish diet is named after Dr. Dean Ornish. Dr. Ornish created the diet in 1977. The Ornish diet is rich in complex carbohydrates, fiber, low-fat content, and extremely low in saturated fat. This diet emphasizes whole foods, plant-based whole grains, fruits, vegetables, legumes, and minimally processed foods. Based on the limited clinical trials available for the Ornish diet in obese subjects, the Ornish diet produced an average weight loss of 3.5% after six months and 3.2% after 12 months. The Ornish diet is typically practiced as a part of lifestyle intervention, including aerobic exercise, resistance training, flexibility activities such as yoga, and stress management.
The Atkins Diet
Dr. Robert Atkins originally promoted the Atkins diet. The Atkins diet is low in carbohydrates without any restriction on fat or protein content in the diet. Because of low carbohydrate and high protein and fat content, the Atkins diet leads to more satiety, improvement in glycemic control, improvement in triglycerides and HDL. A low carbohydrate diet is also associated with a rise in LDL. The Atkins diet is high in protein, where more than 20 to 35% of energy in the diet comes from protein. High protein content accounts for increased satiety effect and also heightens total energy expenditure. Dietary protein has a greater thermogenic effect than carbohydrates, accounting for increased total energy expenditure with a high protein diet.
The high protein content of the diet can lead to the browning of white adipose tissue. Vegetarian protein source leads to a more efficient thermogenic effect than protein from an animal source. The long-term benefits of a high protein diet combined with a high-fat diet should be weighed against the risk of increasing LDL and cardiovascular disease due to the higher intake of saturated fat. A high protein diet, especially from an animal source, results in potentially increased acid load to the kidney in the form of sulfates and phosphates, which can affect renal function. When protein is obtained from an animal source, the high protein diet leads to high saturated fat content. The Atkins diet produced clinically significant short-term and long-term weight loss in a meta-analysis of 10 clinical trials ranging from 3 to 24 months.
The Paleolithic Diet
The paleolithic diet refers to mimicking the dietary pattern of our ancestors before agriculture. It relates to diet during hunting and gathering lifestyle. There was no single paleolithic diet as it varied according to geographical region based on climate and food availability. This difference accounts for the varied composition of macronutrients and the source, whether from plant or animal sources. The paleolithic diet included the primary source of energy from plant-based food. It consisted of whole foods, fruits, nuts, seeds, legumes, vegetables, and protein and fat from meat and fish. The carbohydrate consumed was low glycemic and rich in high fiber content. The paleolithic diet did not have any food processing except heating of the food. The significant difference between the paleolithic diet and the modern diet is that the paleolithic diet did not include cereal grains, dairy, and ultra-processing of food. Paleolithic diet has gained considerable attention and popularity in current culture.
The paleolithic diet is rich in whole foods, fruits, fibers. The plant source provides phytochemicals, micronutrients, antioxidants, and fibers. The diet is high in protein (25 to 35% of energy), moderate in fat and carbohydrates, low glycemic, and minimally processed. Paleolithic diet improves insulin sensitivity, reduces the risk of cardiovascular disease, and helps achieve weight loss on a short- and long-term basis. The long-term sustainability of the paleolithic diet is questionable because of the high cost.
The Vegetarian Diet
The vegetarian diet is gaining popularity as a diet for overall health promotion. There are different versions of the vegetarian diet. A vegan diet includes only plant-based nutrients, excluding meat, fish, dairy, and eggs. Lacto – Ovo- Vegetarian provides for the provision of eggs and dairy along with a plant-based diet. Pescatarian diet allows the use of fish along with plant-based nutrients. A recent meta-analysis of 12 clinical trials shows that individuals assigned to a vegetarian diet lost more weight than those assigned to a nonvegetarian diet. Subgroup analysis of vegetarian subjects showed that subjects assigned to the vegan diet lost more weight than those assigned to the lacto-ovo-vegetarian diet. Significantly more weight loss was detected in subjects on an energy-restricted vegetarian diet versus those without any energy restriction in the diet.
Intermittent Fasting - Time-based Energy Restriction
Intermittent fasting is a dietary approach where there are timed periods of fasting without any restriction of a particular macronutrient. The overall rationale for weight loss based on intermittent fasting relies on broad caloric restriction. There are not many randomized controlled trials showing evidence of weight loss from intermittent fasting. Intermittent fasting could be alternate day fasting or time-restricted eating, where nutritional intake happens only during a fixed time window. Caloric restriction has a beneficial effect on weight reduction, increases insulin sensitivity, improves blood pressure control, and causes overall cardiovascular risk reduction. Insulin resistance manifests as elevated plasma insulin levels, which increases sodium and fluid retention, leading to increased blood pressure. Insulin resistance is also linked to endothelial dysfunction, which also contributes to hypertension.
The beneficial effect of intermittent fasting relies on a similar premise of caloric restriction. Intermittent fasting leads to better glucose control. Intermittent fasting may be more sustainable over a long period than caloric restriction alone. Intermittent fasting and caloric restriction also have the added benefit of reducing oxidative stress. It has the potential to slow the progression of neurodegenerative diseases like Alzheimer and Parkinson disease. Intermittent fasting may also have added beneficial effects from the optimization of circadian rhythm and ketogenesis. Disturbance in circadian rhythm, for example, from shift-work leads to metabolic disturbances increasing the risk of obesity, diabetes, metabolic syndrome, and cardiovascular disease.
Caloric restriction leads to decreased energy intake, decreased mitochondrial free radical production, and reduced oxidative stress. Caloric restriction also leads to reduced inflammatory markers. In a study of obese individuals with asthma, inflammatory markers such as TNF alpha and brain-derived neutrophilic factors were significantly reduced after caloric restriction. After 42 hours of fasting, glycogen stores become depleted, and fatty oxidation predominates, leading to ketosis. The ketogenic diet is also trendy, consisting of high fat intake, much of which comes from animal fat. Excessive animal fat intake can be associated with higher levels of trimethylamine N-oxide, which can be associated with higher cardiovascular risk from a ketogenic diet. Long-term weight loss benefits of the ketogenic diet are not consistent, and the diet is challenging to adhere to in the long term.
In a study of overweight men with type 2 diabetes, when subjected to caloric restriction and intermittent fasting, subjects lost 1% of body fat with a mean 6.5% weight loss after 12 weeks. Intermittent fasting leads to lowering blood pressure by decreasing sympathetic tone and increasing parasympathetic tone. Increasing parasympathetic tone also leads to reduced levels of inflammatory cytokines. Intermittent fasting also had a positive impact on lipid levels. In a study of nonobese individuals, subjects who fasted for 20 hours intervals then ate without restriction on alternate days showed increased insulin-mediated glucose uptake after two weeks.
Caloric restriction may change the pace of aging by modulating Sirtuin1 (SIRT1). Sirtuins are recently discovered molecules that may be important in aging. Sirtuins are a family of signaling proteins involved in metabolic regulation. SIRT1 is an enzyme located primarily in the cell nucleus that deacetylates transcription factors that contribute to cellular regulation (reaction to stressors, longevity).SIRT1 increases in response to caloric restriction. Upregulation of SIRT1 by caloric restriction contributes to increased insulin sensitivity and reduced inflammation, potentially through modulation of NF-k/TNF Alpha pathway(NK-Nuclear factor, TNF-Tumor necrosis factor.
PPAR-gamma (peroxisome proliferator-activated transcription factor receptor gamma) acts as a nuclear transcription factor that controls multiple genes connected to cell survival and response to metabolic alterations. One PPAR- gamma gene targets the aP2 gene and codes a protein that assists fat storage. SIRT1 can act as a repressor of PPAR gamma. Caloric restriction leads to activation of SIRT1 in adipose tissue, which reduces fat storage and probably resets hormonal levels to change the pace of aging. Mild caloric restriction with alteration of feeding frequency may improve compliance among subjects.
Diets Based on a Calorie Deficit
Low-calorie Diet and Very Low-calorie Diet
These diets are based on the concept of the "calories in-calories out model." Physiological adaptive mechanisms resist weight loss through decreasing energy expenditure when the dietary approach is purely based on negative energy deficit. A low-calorie diet consists of 1000 to 1500 kcal/day. A very low-calorie diet consists of less than 800 kcal/day. Low-calorie diets restrict carbohydrates or fat to create a negative energy deficit. A low-calorie diet may not be sustainable over the long term. A very low-calorie diet should not be recommended without medical supervision. A recent study demonstrated a more significant weight loss benefit from a very low-calorie diet when combined with behavioral programs over behavioral programs alone. A variation of a very low-calorie diet is known as a very low-calorie ketogenic diet (VLCKD). It consists of 600 to 800 kcal/ day and low carbohydrate (less than 30 to 50 grams per day) intake along with adequate protein intake (0.8 to 1.2gm/day/kg of ideal body weight ). It is used for a short period, followed by a transition to a low-calorie diet. A recent meta-analysis of a very-low-calorie ketogenic diet demonstrated improvement in weight, BMI, HbA1c, blood pressure, total cholesterol, and triglycerides over a short period. The weight loss benefit from VLCKD was demonstrable over two years. No changes in LDL and HDL were demonstrated as a result of VLCKD.
Meal replacements are used to create a negative energy deficit. People tend to overestimate or underestimate the calorie content of the food. Meal replacements can replace one or more meals. They are convenient. Multiple commercial products are available; additionally, their costs vary by product. A systemic review studying meal replacements demonstrated a mean weight loss of -2.2 to -6.13 kg compared with other diets involving support alone. Meal replacements are not successful in achieving long-term weight loss due to physiologic adaptations that decrease energy expenditure. These adaptations lead to a plateau effect in the weight loss trajectory.