The Truth About Weight Loss and Emerging Innovation Opportunities
Editor’s Note: This article is from FreeS Fund, and VCBeat has obtained permission to republish it.
How to Scientifically Control Weight Is a Hot Social Topic. While weight-loss myths may be exciting, any goal setting should be based on scientific rationality.
In this issue of the FreeS Fund Report, we examine a wide range of weight-loss-related topics from an interdisciplinary perspective spanning technology, healthcare, and consumer sectors.Authoritative papers, clinical trial reports, and related books, and summarize the viewpoints and insights therein, with the aim of helping everyone gain a better understanding of body weight and their own bodies.
Surprisingly, we have found that many truths about weight loss are counterintuitive:
● As people age, it becomes increasingly difficult to lose weight. In adulthood, the number of adipocytes (fat cells) in the human body remains relatively stable; however, their volume can fluctuate significantly, with individual fat cells capable of expanding up to 1,000 times in size. In this sense, obesity may have no upper limit.
● In principle, uncontrolled appetite is one of the triggers for obesity; however, if we engage in dietary restriction or physical exercise,Instead, it may increase appetite.. However, in the long term, lifestyle modifications remain beneficial, promoting greater physical and mental well-being.
● "Miracle weight-loss drugs" primarily promote weight loss by suppressing appetite and regulating gastric emptying.But "miracle drugs" are not suitable for everyone., as the factors contributing to obesity vary, the efficacy of treatment also differs. After discontinuation of the medication, there may be signs of gradual weight regain; adjunctive dietary and exercise modifications can help sustain the weight loss achieved during pharmacotherapy.
● For patients with severe obesity,SurgeryThe effects are relatively pronounced and offer the best durability, but safety varies among individuals, and there may be other long-term adverse effects.
For individuals, the weight loss journey is often long, lonely, and fraught with anxiety and confusion. You need not harshly blame yourself for obesity by attributing it to a lack of willpower, as everyone’s absorption and metabolic rates differ. While striving to maintain optimal physical and mental well-being,We should also accept and embrace the diversity of aesthetics.. Because weight control has never been about seeking others' approval or conforming to a one-size-fits-all standard,but rather a response to and safeguarding of one’s own physical and mental well-being.
As people age, their basal metabolic rate generally declines, leading to reduced energy expenditure and weight gain.Basal metabolism refers to the rate of energy metabolism when the human body is awake and in a state of extreme rest, unaffected by muscle activity, ambient temperature, food intake, or mental stress. If your current weight has increased slightly compared to when you were younger, there may be no need for excessive anxiety.
Whether weight intervention is truly necessary depends on the answers to the following questions: from the perspective of medical health,Is your weight truly in the obese range, and does this condition genuinely have a negative impact on your health?
Obesity has clearly defined medical criteria. The widely accepted diagnostic indicator isBMI (Body Mass Index). BMI = weight (kg) divided by the square of height (m). According to the body mass index thresholds established by the World Health Organization (WHO), individuals with a BMI greater than 24 but less than 28 are classified as overweight, while those with a BMI of 28 or higher are classified as obese.
However, we should not focus solely on body weight but also pay attention to body fat percentage, which refers to the amount of fat in the human body. This is because weight is influenced not only by fat but also by muscle mass; therefore, individuals with a BMI indicating overweight may simply be more muscular.
Fat is the primary energy storage substance in the human body., is essential for sustaining life; only excessive accumulation leads to obesity.
Adipocytes can be broadly classified into three types:Brown Adipose Tissue, White Adipose Tissue, and Beige Adipose Tissue. Brown and beige adipose tissues are primarily distributed on both sides of the neck, as well as in the shoulders and upper arms. When we feel cold, these types of fat generate heat to help the body resist the cold. White adipose tissue is mainly located in the chest, around visceral organs, and subcutaneously, with its primary function being energy storage.
The number of fat cells in humans is relatively low during early childhood, after which they undergo rapid proliferation, stabilizing at approximately 30 billion after puberty. Each adipocyte contains triglycerides, which are central to the development of obesity. In adulthood, the number of fat cells in the human body remains largely stable.However, adipose tissue volume can vary significantly, with the volume of a single adipocyte increasing by up to 1,000-fold.From this perspective, obesity may have no upper limit.
People pay such close attention to obesity because it is not only a disease in itself but can also lead to cardiovascular and cerebrovascular diseases, hyperglycemia, and other conditions.Other disease risks.
1. From a Physiological Perspective: Unveiling the Pathological Mechanisms of Obesity
A paper published in《Biomolecules》The paper “Obesity–An Update on the Basic Pathophysiology and Review of Recent Therapeutic Advances” summarizes the scientific achievements of academic research on the mechanisms of obesity to date.
The authors stated: “The pathophysiological mechanisms of these metabolic disorders are at differentThe Intersection of Highly Specialized Medical Fields, such as genetics, cell and molecular biology, endocrinology, etc. (We) can now only reveal (the underlying mechanisms) through ‘omics’ technologies, which may be the closest approach to precision medicine.”
Human energy balance is influenced and regulated by the central nervous system, adipose tissue, and multiple organs and systems, including the gastrointestinal tract, liver, and pancreas.
The appetite control center in the human body is primarily located in the arcuate nucleus (ARC) of the hypothalamus, which contains two types of neurons that regulate appetite: AgRP neurons stimulate appetite, while POMC neurons suppress it. Ghrelin, secreted by the gastrointestinal tract, acts on specific neurons in the hypothalamus,Appetite; whereas leptin, secreted by adipose tissue, acts on another specific type of neuron in the hypothalamus,Appetite Suppression. Leptin and ghrelin are always in a state of offense and defense.
Therefore, the weight loss measures we adopt in our daily lives,What are some appetite suppressants?
Published in《Cardiovascular Research》The paper “New therapies for obesity” explores fourThe Impact of Different Weight Loss Interventions on Appetite, Including Low-Calorie Diets, Aerobic Exercise, Pharmacotherapy, and Bariatric Surgery:
● Low-calorie diets increase appetite.Low-calorie diets tend to create an energy deficit, leading to increased hunger and, consequently, heightened appetite.
● Aerobic exercise maintains or increases appetite.In individuals with obesity, the subjective sensation of appetite is temporarily suppressed during exercise, yet energy intake is minimally affected. Specifically, during aerobic exercise performed in a fasted state, hunger increases slightly, followed by enhanced postprandial satiety, but without a significant increase in energy intake.
● Pharmacological treatment may reduce appetite.The mechanisms of certain anti-obesity medications primarily follow two approaches: one is to attenuate appetite signals to counteract the desire to eat, and the other is to amplify satiety signals to improve impaired feelings of fullness.
● Bariatric surgery reduces appetite.Gastrectomy or gastrointestinal bypass surgery reduces ghrelin levels, leading to decreased appetite and subsequently reduced food intake.
The authors of “New therapies for obesity” argue that obesity may be viewed as a disorder of appetite regulation, with increased hunger or reduced satiety as its primary symptoms. Merely throughLifestyle interventions are ineffective in reducing hunger or increasing satiety.. Whether through a low-calorie diet or exercise, the ultimate effect is directed towardAppetite StimulationCompared to the feedback loops that control energy consumption,The feedback loops regulating long-term energy intake may play a more potent role.
Shifting the focus back to the individual, absorption and metabolic rates vary from person to person, meaning that suitable weight-loss strategies differ accordingly. In the following sections, we will elaborate in detail on the advantages and disadvantages of various approaches—including low-calorie diets, aerobic exercise, pharmacological interventions, and bariatric surgery—as well as the populations for whom each is most appropriate.
2. From an evolutionary perspective, obesity is a mismatch disease
In his book *The Story of the Human Body*, Daniel Lieberman, Professor of Human Evolutionary Biology at Harvard University in the United States, examines human health and disease from an evolutionary perspective and proposes"Mismatch Diseases"concept.
In his view,Many human traits are adapted to the environments in which we evolved, but not to the modern environments we have created through culture.An increasing number of mismatch diseases, including obesity and diabetes, are the result of our bodies’ maladaptation or insufficient adaptation to these new environments.
If we look back at the history of human development, the hunter-gatherer era lasted for more than 200,000 years, the agricultural era for nearly 10,000 years, and the industrial era for roughly two hundred years. Many of our anatomical structures and physiological functions remain adaptations to the environment of the hunter-gatherer era.
In that era, our ancestors relied on foraging for fruits and hunting to survive, frequently facing periodic food shortages. Only those genes that enabled rapid and efficient extraction of sufficient nutrients from limited food sources and their subsequent storage were likely to be passed down. This also madeHumans have evolved a preference for energy-dense foods and the ability to efficiently store fat. Meanwhile, avoiding unnecessary energy expenditure has also become an instinct.
However, in the past few centuries, and particularly in recent decades, human labor and lifestyles have undergone dramatic changes within a relatively short period.The pressure on humans to find food and ensure reproduction has decreased sharply, yet traits such as human anatomical structure and physiological functions have not had sufficient time to evolve to adapt to this rapid change.
Nowadays, acquiring food no longer requires traversing mountains and hills, or even enduring the toil of “hoeing grain under the midday sun.” By simply ordering takeout from home, food is delivered right to our hands. Meanwhile, food supply has increased significantly; foods are more calorie-dense, more finely processed, and easier to digest, break down, and absorb. However, due to the conveniences brought by technology, our energy expenditure levels have become progressively lower, leading to a severe imbalance in caloric equilibrium. As Lieberman stated,Humanity is gradually sinking into a quagmire of increasingly prevalent mismatch diseases.
As mentioned above, the current mainstream weight management strategies are primarily categorized into four types: low-calorie diet, aerobic exercise, pharmacological treatment, and bariatric surgery. Let us explore these in detail.Characteristics and Key Considerations of the Four Approaches.
1. Diet: The Debate Over Fat and Sugar
A counterintuitive truth is thatA low-fat diet alone is not as effective in controlling body weight as people might imagine,Indiscriminately avoiding beneficial and essential dietary fat intake may instead have negative consequences. Americans have already learned this lesson through trial and error.
In 1955, U.S. President Eisenhower suffered a sudden heart attack. Following his first myocardial infarction, his medical team provided lifestyle modification recommendations, with a key directive being a diet low in fat and cholesterol but high in carbohydrates.
At that time,Heart disease is a prevalent condition in the United States.。Regarding the causes of heart disease, two major schools of thought have proposed hypotheses. One school, led by British physiologist John Yudkin, posits thatCarbohydratesis the primary cause of heart disease, while Professor Ancel Keys of the University of Minnesota in the United States believed thatFatis the primary cause of heart disease.
Ancel Keys claimed that he began in 1958，A survey was conducted across seven countries—Italy, Greece, Yugoslavia, Finland, the Netherlands, Japan, and the United States—known as the "Seven Countries Study." The results showed that in these countries, as fat intake increased, so did the number of deaths from heart disease.
Subsequently, Ancel Keys’ conclusions were adopted by U.S. public health authorities. In 1980, the U.S. government issued the Dietary Guidelines for Americans for the first time. The guidelines recommended a low-fat diet for Americans, with daily fat intake not exceeding 30% of total energy intake.
Surprisingly, over the following two decades, obesity and heart disease rates among U.S. residents surged dramatically. In stark contrast, President Eisenhower, who strictly adhered to “low-fat” dietary recommendations, underwent cholecystectomy and developed diabetes and stroke within 14 years after his first heart attack, ultimately succumbing to a fatal myocardial infarction.
These anomalies have begun to attract increasing attention from researchers. According to a review by Katherine Pett and other scholars, a reanalysis of the data from the Seven Countries Study conducted in 1999 revealed thatSugar Has a Stronger Association with Heart Disease Than Saturated Fat, which proves that the culprit is sugar, not saturated fat. Additionally, critics argue that the research conducted by KeysOriginally launched in 22 countriesThe data from the Seven Countries Study that was ultimately presented was carefully selected by him, while other data that could not verify his hypothesis were deliberately concealed.
In 2010, the American Society for Nutrition stated that there was no clear evidence linking dietary fat intake to coronary heart disease and cardiovascular disease.The 2016 edition of the Dietary Guidelines for Americans further removed restrictions on cholesterol and the proportion of energy derived from fat.
Excessive Sugar IntakeThe harms of weight gain are becoming increasingly recognized. According to the 2016 Global Burden of Disease Risk Study published in The Lancet, the “summary exposure value” for sugar-sweetened beverages—taking into account both the level of exposure by risk category and the severity of their impact on disease burden—increased by 40% between 1990 and 2016.Sugar-Sweetened BeveragesRisks to the cardiovascular and metabolic systems include:Obesity, Type 2 Diabetes, Hypertension, and Cardiometabolic Diseasesdeath caused by.
According to the World Health Organization (WHO) recommendations, added sugar intake should ideally be limited to less than 10% of total daily energy intake, which translates to 50 grams, with a further reduction to 25 grams being preferable. For children, this limit should be even lower; for those aged 4–5 years, it is best kept below 16 grams.
The Controversy Surrounding Sugar and Fat,Raise Awareness of the Importance of Diet to Health, so if the goal is weight loss, what is a reasonable approach?
First, control energy intake.
“Expert Consensus on Medical Nutrition Therapy for Overweight and Obesity in China (2016 Edition)” mentions that one method of calorie-restricted balanced diet is to reduce daily caloric intake by approximately 500 kcal based on current consumption. To compensate for this deficit, the body will utilize stored glycogen and fat.
Second, adjust the dietary structure.
A widely recognized dietary pattern is known as"Mediterranean Diet"。In our previous report, “VCBeat Report 25: Food Investment Insights from China’s Dietary Structure,” we noted that the “Mediterranean Diet Pyramid” was jointly introduced in 1993 by Oldways, the Harvard T.H. Chan School of Public Health, and the World Health Organization, drawing primarily on dietary patterns observed in Greece and Southern Italy during the 1960s. This dietary pattern is considered to reduce the risk of heart disease, depression, and dementia.
Specifically, the Mediterranean diet has the following characteristics:
● Consume whole grains, fruits, vegetables, olive oil, and nuts daily
● Consume fish and seafood at least twice a week
● Consume dairy products, eggs, and poultry in moderation
● Limit consumption of red meat and sugary foods
● Drink plenty of water and consume alcohol (wine) in moderation
● Cooking method: Primarily sous-vide
● Daily Lifestyle: Dining with family and friends, taking afternoon naps, and engaging in regular exercise
Summary
The impact of fat and sugar on the body is not absolute; the key lies in proper portion control. Many individuals with obesity indeed need to adjust their dietary patterns, which involves both controlling energy intake and optimizing their diet composition.
Exercise: Understanding the Significance of Exercise from the Perspective of Underlying Physiological Mechanisms
Having discussed diet, let us now turn to exercise. Just as dietary adjustments must adhere to the principle of "compatibility,"Although exercise may seem “counterintuitive,” it can be understood as a therapeutic intervention; in other words, individuals must increase energy expenditure through physical activity to restore physiological equilibrium.
"Returning to the fundamentals, we can enhance athletic performance by understanding biomechanical and exercise physiological systems."
See FirstBiomechanical SystemThe human body has three major energy-supplying systems: the phosphagen (ATP-CP) system, the glycolytic system, and the aerobic system.
Phosphagen (ATP-CP) System:It can provide high-intensity energy in a short period without the need for oxygen. When we engage in activities requiring explosive power or high intensity, such as sprinting, long jump, shot put, and weightlifting, the phosphocreatine system supplies energy to the muscles. However, this burst of energy typically lasts no more than ten seconds.
Glycolytic System:It refers to the process of energy regeneration through the breakdown of carbohydrates (glycogen and blood glucose), which still occurs without oxygen involvement. Although the reaction time of the glycolytic system is slower than that of the phosphagen system, it can sustain activity for 2 to 3 minutes. In events such as the 800-meter run, energy is primarily supplied by the glycolytic system.
Aerobic System:It refers to the process of generating energy using carbohydrates, fats, and a small amount of protein. It is the primary source of energy during rest and low-intensity activities, such as jogging, long-distance cycling, and swimming. The metabolic pathways of the aerobic system are longer, but they produce more energy, soLow-Intensity Activities Burn More Fat。
FromPrinciples of Exercise PhysiologyEnergy sources vary across different types of physical activity. In daily life, whether at rest or in motion, all three major energy systems contribute to ATP production; however, due to their differing capacities, exercise intensity and duration are the primary determinants of each system’s relative contribution.
Do not blindly follow fitness trends. Choose exercises that better suit your physical condition to more effectively address issues or achieve your goals.For instance, if your primary goal is fat loss, you should prioritize aerobic exercise with anaerobic exercise as a supplement. Conversely, if your goal is body shaping, you should focus primarily on anaerobic exercise.
However,The impact of exercise on weight control is not as significant as that of dietary changes.As the saying goes:“70% diet, 30% exercise.”For instance, the energy intake from a single 600-milliliter bottle of carbonated beverage requires an adult to walk briskly for 8,500 steps to expend. Upon recognizing the difficulty of energy expenditure, we may develop a greater sense of reverence toward diet and exercise.
《New therapies for obesity》Data show that a daily caloric deficit of 500 kcal combined with 150 minutes of weekly exercise can lead to a 2%–5% body weight reduction over one year. With the addition of comprehensive meal-based caloric control and structured training, a 10% weight loss within a year may be achievable. Of course, this success is limited to a small minority.
The reality is,Weight Regain After Lifestyle Intervention Is a High-Probability Event。《New therapies for obesity》It is noted that relying solely on consistent exercise leads to a weight loss plateau after one year; from a five-year perspective, approximately 80% of the previously lost weight is likely to be regained. Only about 10%–25% of individuals are able to maintain a weight loss of more than 10% in the long term.
Why is this?
First, from the perspective of energy metabolism,Basal metabolic rate decreases during exercise.，Moreover, the magnitude of the decline in basal metabolic rate is far greater than that of the decrease in the proportion of fat mass to total body weight.Basal metabolic rate is the primary form of energy expenditure in the human body.。This is also referred to as “metabolic adaptation.”
A paper published in《Current Biology》the article “Energy compensation and adiposity in humans” mentions,Exercise can lower basal metabolic rate, thereby reducing the fat-burning effects of physical activity. This phenomenon is most pronounced in individuals with obesity and older adults, with the greatest impact observed in those with obesity.This is also why we often hear complaints that “exercise actually makes you gain weight.” Although it’s frustrating, the fact remains thatThe level of obesity determines individual differences in compensatory mechanisms.
Metabolic adaptation also brings another effect, even ifWeight Regain in Individuals Undergoing Weight Loss, the basal metabolic rate will remain at a low level for an extended period of time,Subsequent weight loss may be more challenging.
“There are two possibilities for this compensatory effect,One possibility is that exercise increases appetite, leading to greater food intake; another possibility is that exercise reduces energy expenditure in other areas of the body, such as resting metabolic rate, thereby lowering the overall energy cost of physical activity.”As noted by the authors of “Energy compensation and adiposity in humans,” weight regain is highly likely to occur in the long term.
Therefore, from the perspective of physiological mechanisms,For most individuals, weight changes achieved solely through lifestyle interventions have relatively limited medium- to long-term effects.
Does this mean we can simply rest on our laurels? Certainly not!
On the basis of adjusting weight loss expectations,It remains necessary to develop targeted, personalized exercise plans.Alternatively, a better approach is to choose a “competitive” sport in which you have relative proficiency, such as adversarial ball games (soccer, basketball, baseball), or aerobic exercises that involve persistent self-challenge (long-distance running, swimming, yoga), allowing dopamine to help you overcome laziness. In addition, we can leverage various technological devices to enhance workout effectiveness.
Although exercise alone may not yield dramatic weight-loss results in the long run, health is not synonymous with low body weight.Maintaining a balanced diet and regular exercise will help you become happier and stronger.
Summary
Whether through dietary adjustments or fitness training, weight-loss plans that rely solely on lifestyle changes are mostly effective only for short-term weight control, with a high probability of long-term rebound. However, in the long run, lifestyle modifications remain beneficial, promoting both physical and mental well-being.
Medications: Miracles Do Not Necessarily Occur in Everyone
As previously mentioned, obesity can be regarded as a disorder of appetite regulation, which can be managed through pharmacological appetite suppression. For a long time, pharmacotherapy received limited acceptance in mainstream medical practice due to concerns regarding efficacy and adverse effects. With deepening understanding of the peripheral and central signals and mechanisms involved in weight management and maintenance, it has become possible to develop more effective and safer anti-obesity medications.
In the field of weight-loss medications, the most popular ones currently areSemaglutideSemaglutide, the original research product developed by the Danish biopharmaceutical company Novo Nordisk, is a human glucagon-like peptide-1 (GLP-1) analog that can be used for diabetes and obesity care.
GLP-1 is a gut hormone secreted by the human intestine that enhances satiety, exerting effects on the body through multiple mechanisms, including appetite suppression, acceleration of gastric emptying, and blood glucose regulation. Physiological GLP-1 secretion peaks after meals, inducing a sense of fullness in the brain.GLP-1 drugs were originally used to promote insulin secretion for the treatment of diabetes, and were later applied to the treatment of obesity, showing significant efficacy.
Although it sounds “miraculous,” such remarkable efficacy does not necessarily occur in everyone.
Published in《Obesity》A study in the magazine roughly categorized obese individuals into four subtypes: brain-hunger obesity, emotional-hunger obesity, gut-hunger obesity, and slow-burn obesity.
Based on the experimental results,GLP-1 receptor agonists, such as semaglutide, may achieve significant weight loss effects in individuals with gut-driven hunger obesity.In other words, before using such medications, it is advisable to first determine whether you have gut hunger-type obesity.A typical manifestation of this type of obesity is feeling full after eating a normal portion size, but soon experiencing hunger again.
If not, your obesity may fall into the following category:
● Brain hunger type: requires greater food intake to achieve satiety.
● Emotionally driven hunger, which requires eating to alleviate anxiety and depression.
● Slow-burning type, with a relatively slow metabolism.
For these three groups, the weight-loss effects of GLP-1 medications may be less than satisfactory.
It should also be pointed out that a significant drawback of this class of weight-loss drugs lies inDiscontinuing the medication may lead to a rebound, with the speed of recurrence varying from person to person.
《The Lancet》 journals《eClinicalMedicine》An article examining the efficacy of GLP-1 receptor agonists noted that although these medications produce significant weight loss, maintaining that weight after discontinuation poses considerable challenges for patients with obesity. Within one year of stopping treatment, participants typically regained more than two-thirds of their previously lost weight. The good news is that individuals who engaged in exercise during GLP-1 therapy did not exhibit a significant tendency toward weight rebound after discontinuation.
So，Even with pharmacological weight loss, lifestyle modifications remain essential to sustain weight reduction or minimize the degree of weight regain.
Of course, one issue that cannot be overlooked isPotential Side Effects of Medications. Some news reports have already documented adverse reactions experienced by certain individuals undergoing treatment with “weight-loss injections,” including dizziness, tachycardia, fatigue, mild hypoglycemia, and facial skin sagging.
Summary
“Miracle Weight-Loss Drugs” primarily promote weight loss by suppressing appetite and regulating gastric emptying. However, they are not suitable for everyone, and their efficacy varies depending on the underlying causes of obesity. After discontinuation, there may be signs of gradual weight regain; combining medication with dietary and exercise modifications is more likely to sustain the weight-loss benefits.
Bariatric Surgery: Significant Efficacy, Prominent Drawbacks
Bariatric surgery is directly associated with appetite suppression.Compared with dietary adjustments, exercise, and medication, the weight-loss effects of surgery are more straightforward.
Bariatric surgery primarily follows two approaches:1. Gastrectomy，This is achieved by resecting 80% of the stomach to reduce gastric volume and restrict food intake. Meanwhile, since the resected portion includes the fundic tissue responsible for ghrelin production, ghrelin levels decrease, leading to reduced appetite.2. Gastrointestinal Bypass Surgery，This involves altering the pathway of food through the digestive tract. Postoperatively, after entering the stomach, food can only pass through the upper portion, bypassing the lower stomach and a segment of the small intestine. This reduces nutrient absorption, lowers ghrelin levels, and simultaneously stimulates intestinal secretion of GLP-1.
However, although these two typesThe effects of bariatric surgery are significant, yet the development of the weight-loss surgery industry remains constrained; currently, such procedures are only suitable for a subset of individuals with severe obesity.
First, the current supply of medical resources cannot fully meet market demand. Second, surgery is inherently invasive and carries risks of intraoperative and postoperative complications; thus, only a minority of individuals are willing to undergo such major interventions solely for weight loss. Furthermore, surgery may have long-term consequences, such as altering digestive and absorptive pathways, which may require patients to take high-dose multivitamins and trace element supplements on a long-term basis.
Summary
For patients with severe obesity, surgical intervention yields more direct and sustained results; however, the majority of individuals do not need to undergo surgery.
As the domestic market for weight loss and weight management continues to expand year by year, numerous potential opportunities have emerged. In this report, we focus exclusively on analyzing the innovation opportunities in two specific segments: sugar substitutes and weight-loss medications.
1. Sweeteners and DGI Foods
As previously mentioned,Excessive Sugar Intake Is a Major Cause of Weight Gain. When people consume excessive amounts of sugar, any excess beyond what is required for physiological functions is stored in the body as fat.
In the early stages, people reduced their intake of natural sugars such as sucrose, maltose, and fructose by using sugar substitutes.May represent a relatively cost-effective weight loss strategy.
What Has Been the Trajectory of Our Sugar Consumption?
The first generation of sweeteners is represented by sucrose.Sucrose is primarily derived from sugar beets and sugarcane, with a history spanning thousands of years.
Second-generation sweeteners are primarily high-fructose corn syrup,It offers a higher sweetness-to-cost ratio than sucrose. In the early days, most leading beverage brands, including Coca-Cola and PepsiCo, primarily used high-fructose corn syrup (HFCS). In 1984, HFCS surpassed sucrose for the first time to become the second-generation primary sweetener.
However, excessive fructose intake increases the liver's metabolic burden, and any unmetabolized portion is converted into visceral fat. Therefore, if a medical checkup indicates fatty liver disease, it is advisable to assess whether daily fructose consumption is excessive.
Third-generation sweeteners are primarily high-intensity artificial sweeteners.These sweeteners have significantly reduced calorie content and maintain a high sweetness-to-cost ratio, but researchers' concerns about their safety have never ceased. Currently, the formulations of most sugar-free beverages on the market rely on synthetic high-intensity sweeteners, such as the well-knownAspartame, Sucralose, supplemented with a small amount of natural low-intensity sweeteners.
Fourth-generation sweeteners are primarily natural sweeteners.Natural sweeteners are primarily extracted from natural sources or produced through microbial fermentation, making them healthier than artificial synthetic sweeteners. With theSynthetic BiologyBreakthrough applications in the field of sugar substitutes are emerging continuously, with an increasing number of natural high-intensity sweeteners appearing on the market. Consequently, natural sweeteners are steadily capturing market share from artificial synthetic sweeteners.
There are three typical representatives of natural high-intensity sweeteners: brazzein, thaumatin, and steviol glycosides.
● Brazilian Sweet: It exhibits extremely high sweetness, reaching thousands of times that of sucrose. Upon entering the human body, it is converted into amino acids before being absorbed and metabolized, thereby eliciting no glycemic response and lacking the bitter aftertaste associated with some earlier artificial sweeteners.
● Thaumatin: It has a sweet and refreshing taste, no off-flavors, and a long-lasting effect. Furthermore, thaumatin exhibits good processing stability; it remains stable during pasteurization and in baked goods, and is unaffected by common preservatives.
● Stevia: High sweetness, low calorie content, stable physical properties, and a high sweetness-to-cost ratio, with a slight bitter and licorice-like aftertaste. Its sweetness is 200–450 times that of sucrose, while its caloric value is only 1/300 that of sucrose.
PeakRui Capital'sWaterdrop FarmIt is a synthetic biology company dedicated to manufacturing high-value proteins, with its main products including brazzein and thaumatin.
In actual production, sweeteners are more commonly used in combination to enhance sweetness and reduce costs; mitigate off-flavors and improve flavor profile; and enhance and ensure product stability. Promising directions for the future includeThis involves blending high-potency natural sweeteners with low-potency natural sweeteners,to achieve an evolutionary direction that is both healthy and palatable.
The “Healthy China Action (2019–2030)” proposes advocating that food producers and operators use natural sweetening substances and sweeteners permitted under food safety standards to replace sucrose, and encourages urban populations with high sugar intake to reduce consumption of sucrose-containing beverages and sweets, opting instead for beverages and foods produced using natural sweetening substances and sweeteners as substitutes for sucrose.
Driven by the demand for “both great taste and health,”The sugar-free market in China is also expanding at an accelerating pace.According to estimates by Zheshang Securities Research Institute, if benchmarked against the levels of developed countries, China’s domestic sugar substitute market (covering only beverages and baked goods) is expected to reach nearly RMB 14 billion in scale by 2030, with a compound annual growth rate of approximately 30% over the decade.
In addition to controlling sugar intake, we also need to pay attention to another concept—the Glycemic Index (GI). The GI indicates the speed and magnitude of blood glucose fluctuations after consuming carbohydrate-rich foods. Generally, a higher GI value signifies greater blood glucose fluctuation and a faster rise in blood sugar levels. Conversely, a lower GI value indicates smaller blood glucose fluctuations and a slower rise in blood sugar levels.
● Low-GI Foods: GI value below 55, for example: whole-grain bread, apples, oats.
● Medium-GI Foods: GI values range from 55 to 70, for example: rice noodles, sweet potatoes, and brown rice.
● High-GI Foods: GI value higher than 70, for example: noodles, steamed buns, pumpkin.
Choosing low-GI foods can bring many health benefits, such as slowing the rise in blood sugar, reducing fat accumulation, and prolonging satiety.
In the field of energy-control foods, invested by FreeS FundMethuselahThe company has developed a comprehensive medical nutrition food portfolio—a rarity in the industry—that encompasses foods for special medical purposes (FSMP), low-glycemic index (low-GI) products, and energy-controlled weight management solutions. Its products have entered more than 700 Grade A tertiary hospitals and served over 10 million patients. Meanwhile, it brings health-focused foods, designed for scientifically managed blood sugar and energy intake under medical nutrition guidance, to a broader consumer base, establishing itself as a representative brand amid the new wave of professionalization and technological advancement in the food industry.
For more on innovation opportunities in the food sector, we provided a detailed discussion in “What Will Humans Eat in the Future? | VCBeat Report 27.” Please click the link to read.
2. Weight-Loss Drugs: Beyond Efficacy, Safety and Adherence Are Key Focus Areas for Future R&D
According to Pfizer’s projections, the U.S. market size for GLP-1 drugs in the fields of type 2 diabetes and obesity is expected to reach by 2030$90 billion，poised to replace PD-1/L1 inhibitors as"The World's Top-Selling Drug". Among these, the market for type 2 diabetes medications accounts for approximately $35–40 billion, while the weight-loss medication market accounts for approximately $50–55 billion.
"Given that weight-loss drugs possess certain consumer product attributes, specialized formulations tailored to the needs of specific populations can stand out in a competitive market."And its pharmaceutical properties seem to dictate that this hundred-billion-dollar market may be “carved up” by the serious healthcare industry.
The Core Industry Chain of Weight-Loss Drugs Is a “Smile Curve”。Currently, the majority of profits remain concentrated among leading pharmaceutical companies that hold key patents and dominate sales channels. In the short term, pharmaceutical and active pharmaceutical ingredient (API) manufacturers with first-mover advantages will enjoy a certain window of opportunity. However, in the medium to long term, competition in the weight-loss drug market is expected to intensify rapidly as approximately 100 related global pipelines advance.
As a representative of GLP-1 drugs,Novo NordiskThe semaglutide developed has achieved commercial success. Novo Nordisk’s 2023 financial report shows that sales of Wegovy (the brand name for its semaglutide product) surged by 406% to reach $4.6 billion, far outpacing competitors in the global GLP-1 market.
Ranked alongside Novo Nordisk asLilly, One of the “GLP-1 Duo”, developed another GLP-1 drug, tirzepatide. On November 8, 2023, after tirzepatide was approved for weight management, it generated $176 million in revenue for Eli Lilly in less than two months.
Multinational pharmaceutical giant RocheIt is also ramping up its investments in the weight-loss drug sector. In late 2023, Roche announced the acquisition of Carmot Therapeutics, a manufacturer of obesity treatments, for $3.1 billion. Through this deal, Roche will gain access to a portfolio of anti-obesity and diabetes drugs based on GLP-1 (glucagon-like peptide-1) agonists.
Interestingly, five years before this deal was reached, Eli Lilly acquired the GLP-1 program from Chugai Pharmaceutical, a subsidiary of Roche in Japan, for an upfront payment of $50 million. In just five short years,Roche reacquired GLP-1 drugs at a 60x premium,This clearly demonstrates the booming market for new weight-loss drugs.
Currently,As a highly esteemed class of weight-loss medications, once the core issue of efficacy has been addressed, safety and adherence have become the primary focuses in the research and development of GLP-1 receptor agonists.Medication adherence means that patients take their medications at the prescribed dose, frequency, and time.
The subsequent research and development directions for weight-loss drugs mainly encompass three aspects:
1. How to Extend the Duration of Drug Efficacy. For instance, reducing the dosing frequency from once weekly to once monthly, a lower administration frequency often leads to improved patient adherence.
Second, how to make medication more convenient. For instance, in addition to injectables, the development of oral formulations can serve a broader population of overweight individuals. Compared with injectables, oral formulations also facilitate better medication adherence. This may be one of the reasons why the research and development of small-molecule weight-loss drugs is so vigorous.
Third, continuously improve functionality.For instance, when GLP-1 receptor agonists are used alone for weight loss, patients may experience muscle loss. Consequently, some pharmaceutical companies are exploring combination therapies that pair GLP-1 agents with other drugs to enable consumers to gain muscle mass while losing weight.
“The King of Medicine,” Sun Simiao, once wrote in Essential Formulas Worth a Thousand Gold: “Eliminate potential ailments before they arise, treat diseases before they manifest, and provide medical care before any symptoms appear.” From ancient times to the present,“The Superior Physician Treats Disease Before It Arises”All are used to describe superb medical skills. As technology penetrates deeper and becomes more widespread in the medical field, how to diagnose and intervene earlier, prevent diseases before they occur, eliminate them before they develop, and cure them before they become severe,It is gradually transforming from a distant goal into an attainable reality.
Just as when weight issues become a disease—Previously,Exercise or dietary adjustments can serve as an effective intervention.When interventions extend beyond the realm of serious medicine and expand into the consumer goods sector, related startups may also shift their mindset. Building on medical or technological foundations, they can place greater emphasis on product development and specific application scenarios. For instance, improving the taste of sugar substitutes and foods for special medical purposes (FSMP) can help people control energy intake; reducing the complexity of using wearable devices can enable monitoring of more physiological indicators, allowing individuals to observe changes in their bodies more intuitively and accurately.
Not Just Weight Control,When extended to the broader biopharmaceutical industry, the principle that “the finest physicians prevent disease before it arises” remains equally applicable.An individual’s health status typically transitions from healthy to sub-healthy, and eventually to diseased, through a gradual process. Therefore, it is entirely feasible to adopt more proactive preventive measures. For instance, most patients with liver cirrhosis or liver cancer seek medical attention only after the onset of severe symptoms, at which stage diagnosis and cure are often exceedingly difficult. If highly accessible early screening enables detection and diagnosis at the stage of non-alcoholic steatohepatitis (NASH), or even in the pre-parenchymal pathological changes phase, the difficulty of achieving a cure may be reduced, thereby effectively alleviating the medical burden on families and society.
Consequently, we anticipate the following trends may emerge in the fields of healthcare and pharmaceutical R&D:
First,Earlier diagnosis and disease definition will become increasingly important., which may require leveraging more new computational, measurement, and regulation technologies to digitize physiological indicators for more precise recording and more effective prediction.
Secondly,Against the backdrop of shifting disease diagnosis to an earlier stage, we can adopt a wider range of intervention measures., rather than being limited to serious medical care.
Returning to life itself, in terms of specific methods for weight control, whether you choose to adjust your lifestyle, try weight-loss medications, or undergo surgery, the ultimate weight loss results vary from person to person. After all, everyone’s rates of absorption and metabolism are different.Select a scientific approach that suits you.。
As stated in the book The Story of the Human Body: “If the rich and complex evolutionary history of the human species has taught us one most valuable lesson, it is that culture does not allow us to transcend our own biological constraints… The world is not perfect, and neither are our bodies.”But it is the only body we have, and it deserves to be enjoyed, nurtured, and protected.”
Every unique you deserves to have itA healthier and more vibrant physique.