What is metabolism?
When metabolism is mentioned, most people think of "fast metabolism" or "slow metabolism" in relation to weight loss. However, metabolism is a much broader concept.
Metabolism is the sum of all the chemical processes our body performs to sustain life. Converting the food we eat into energy, controlling blood sugar, storing or using fats for energy, protein synthesis, hormone production, and cell renewal are all parts of this system.
Therefore, it is not accurate to evaluate metabolic health solely based on weight. Disruption of metabolic balance can certainly lead to weight gain or difficulty losing weight. However, weight problems are only one of the visible consequences of metabolic disorders. Impairments in metabolic health can affect many systems, from blood sugar control and insulin sensitivity to liver and vascular health and energy production, and can have much broader long-term health consequences.
For example, a person of normal weight may have insulin resistance, fatty liver, or high visceral fat. In the long term, this person is at a very high risk of developing many health problems. Conversely, an overweight person may have blood sugar, blood pressure, and lipid levels that remain within normal limits for a long time. This is called “metabolic healthy obesity,” but we know that this condition also brings health problems in the long term [1]. Therefore, it is not correct to judge whether a person is 'healthy' or 'unhealthy' simply by looking at their weight or only at test results.
That's why I don't consider simply looking at the number on the scale sufficient when evaluating my patients. The real question is how well the body is managing the energy it receives.
What is Metabolic Health?
A healthy metabolic system requires different organs to work together in harmony. Insulin must be able to perform its function when needed, muscle tissue must be able to use glucose effectively, the liver must not store excessive fat, fat tissue must not grow uncontrollably, and blood vessels must not be chronically exposed to high glucose, insulin, and inflammation.
Metabolic imbalance doesn't usually happen overnight. Years of imbalances eventually lead to irreversible damage.
For example, even when blood sugar levels are still within normal limits, the body may start producing more and more insulin to maintain that normal level. This is called compensatory hyperinsulinemia. When the tissues' response to insulin begins to decrease, the beta cells of the pancreas compensate for this by secreting more insulin for a while. Therefore, someone who only monitors their blood sugar levels, even someone with normal fasting blood sugar and HbA1c values, may not notice this early change in metabolic balance. This is because in some people, the first noticeable change is not in blood sugar, but in the increase in insulin demand. Unfortunately, many doctors I know don't even check or know their patients' insulin levels. Yet, this is one of the parameters that can give us the first clue about metabolic health.
Insulin is also a powerful anabolic hormone. It suppresses lipolysis in adipose tissue, that is, the breakdown of stored fat into free fatty acids and their release into circulation, and is one of the signals that supports energy storage. Therefore, persistently high insulin levels, especially when accompanied by energy surplus and insulin resistance, become part of a metabolic environment that makes fat mobilization difficult. Over time, an increase in waist circumference, visceral fat accumulation, high triglycerides, and weight problems may be added to the picture. The underlying mechanisms of insulin resistance are particularly closely related to energy metabolism in the liver, muscle, and adipose tissue.[2]
For me, a good metabolic assessment means trying to detect the path to disease as early as possible, rather than identifying it after it has manifested.
Mitochondria: The Cellular Dimension of Metabolism
It's impossible to discuss metabolic health without mentioning mitochondria. Mitochondria are a vital part of our cells' energy production system. They convert energy from glucose and fatty acids into ATP, a form of energy the cell can use. But their role isn't limited to energy production. They also function as a kind of control and communication center within the cell. They contribute to the generation of different signals depending on whether the cell has sufficient energy, whether energy demand has increased, whether oxidative stress is occurring, or whether the cell is damaged.
During energy production, molecules called reactive oxygen species (ROS) are naturally produced. Their production in certain amounts is normal and even part of cellular signaling. However, when their production exceeds the cell's antioxidant defense capacity, oxidative stress can occur, and over time, proteins, cell membranes, and DNA can be damaged. Mitochondria are both important production sites for these molecules and play a role in how the cell manages its oxidative balance.
Mitochondria also play a role in initiating controlled cell death, or apoptosis, when a cell is severely damaged. Furthermore, they are directly linked to numerous metabolic processes, such as how the cell uses glucose and fatty acids, when to increase or decrease energy production, and how to respond to nutrient surplus or energy deficiency.
Therefore, mitochondrial health should not be considered simply in terms of "producing more energy." Besides energy production, mitochondria play a crucial role in controlling oxidative stress, responding to cellular damage, and adapting metabolism to changing conditions.
One of the key characteristics of a healthy metabolism. metabolic flexibilitySimply put, it is the body's ability to switch fuel according to its needs. It needs to be able to use glucose efficiently after eating and increase fat utilization during fasting. This flexibility decreases in insulin resistance and obesity. [3]
Impairments in mitochondrial function are also associated with insulin resistance, aging, and certain metabolic diseases. However, not every metabolic problem is caused by "malfunctioning mitochondria." Mitochondrial dysfunction can sometimes be the cause, and sometimes the result of a metabolic disease.
Therefore, instead of looking for a single vitamin or supplement that "boosts mitochondria," exercise, muscle mass, sleep, nutrition, glucose control, and overall metabolic status should be considered together.
How can we measure metabolic health?
Unfortunately, there is no single blood test that indicates metabolic health. However, examining the different elements that make up metabolic health piece by piece and putting them together like a jigsaw puzzle gives us a very good idea. Let's look at them one by one:
I prefer to think of it more like a jigsaw puzzle. Each test gives us a different piece. When we put the pieces together, we can understand a person's metabolic state much better.
1. Glucose and Insulin Metabolism
One of the first areas I assess is glucose-insulin balance. This is related to metabolism and is the best indicator of how well the body can use the energy it receives. Tests that can be used here include:
- Fasting glucose
- HbA1c
- Fasting insulin
- HOMA-IR
- Oral glucose tolerance test if needed.
- If necessary, insulin measurements can be taken during glucose loading in patients.
2. Looking at Cholesterol and Beyond
A standard lipid panel measures total cholesterol, LDL cholesterol (LDL-C), HDL cholesterol, and triglycerides. These are all important parameters, but they don't always provide sufficient information, especially when we want to assess cardiovascular risk in more detail.
For example, LDL-C, commonly referred to as "bad cholesterol," actually measures not the number of LDL particles in the blood, but the total amount of cholesterol carried within these particles. This is an important distinction because lipoprotein particles containing ApoB, which can enter and accumulate in the vessel walls, play a role in the development of atherosclerosis. Therefore, even if two people have the same LDL-C value, the number of circulating atherogenic particles and the associated cardiovascular risks can be very different. For this reason... ApoB I also prefer to include this measurement in the evaluation. I would even like to point out that I am the first physician to start performing this test in Cyprus. This test is quite important for me because, since each atherogenic LDL, IDL, and VLDL residual particle carries one ApoB molecule, ApoB provides different and more significant information than LDL-C about the total number of circulating atherogenic particles. A significant discrepancy between LDL-C and ApoB can be seen, especially in the presence of insulin resistance, high triglycerides, metabolic syndrome, or diabetes.
In addition Lp(a) It is a completely different and important risk factor. Lp(a) levels are largely genetically determined and, when high, can increase the risk of atherosclerotic cardiovascular disease independently of LDL-C. Therefore, measuring Lp(a) at least once in adulthood can help to better understand a person's inherited cardiovascular risk.
However, LDL-C, ApoB, or Lp(a) do not directly indicate the size of plaque already present in the vessels. They provide information about the risk of developing and progressing atherosclerosis. When we want to see the existing atherosclerotic burden, however... coronary artery calcium score (CAC) or, in suitable patients, imaging methods such as coronary CT angiography should be used.
High triglycerides, low HDL, and abdominal fat are common conditions, especially in people with insulin resistance. In the definition of metabolic syndrome, waist circumference, triglycerides, HDL, blood pressure, and fasting glucose are evaluated together.[4]
3. Waist Circumference and Visceral Fat
Two people may have the same weight and even BMI, but their metabolic risks can be completely different. One of the important reasons for this is where the fat is stored. Visceral fat, which accumulates in the abdomen, around the organs, is metabolically more important than subcutaneous fat tissue. Therefore, waist circumference, although it seems simple, is a very valuable measurement and is considered an important part of cardiometabolic risk assessment.[5]
This also explains why BMI alone isn't sufficient. A person with high muscle mass may have a high BMI. On the other hand, a person with a normal BMI may have low muscle mass and high visceral fat. Therefore, our goal should not be just lower weight, but better body composition.
4. Liver
The liver is one of the central organs of metabolic health. Liver enzymes such as ALT, AST, and GGT help in its assessment. However, normal liver enzyme levels do not completely rule out fatty liver disease or an ongoing liver problem. This is because enzymes like ALT, AST, and GGT do not directly measure the amount of fat accumulated in the liver or the overall health of the liver; rather, they indicate enzymes released into the bloodstream as a result of damage or stress to liver cells. The liver also has a very strong regenerative and functional reserve capacity. Despite damage, it can regenerate itself and maintain its function for a long time. Therefore, despite ongoing fatty liver disease or chronic liver disease, enzyme levels may return to normal over time or remain within normal limits throughout the disease. Thus, it is not correct to conclude that "liver enzymes are normal, therefore there is no problem with the liver." In high-risk patients, ultrasound or, if necessary, more advanced imaging methods may be considered. Fatty liver disease can sometimes be one of the first visible signs of a metabolic disorder.
The good news is that the benefits of these new generation metabolic drugs, popularly known as "weight loss injections," are not limited to weight loss alone. Studies with semaglutide and tirzepatide have shown a significant reduction in fatty liver disease, and in MASH patients, significant improvements in liver inflammation and disease activity. In fact, semaglutide, in its Wegovy form, has received FDA approval for the treatment of MASH patients with moderate to severe liver fibrosis who have not yet developed cirrhosis. Results with tirzepatide are also quite strong; however, it does not yet have FDA approval for the treatment of MASH. Studies with retatrutide, which has not yet received FDA approval, are also showing quite remarkable results in terms of fatty liver disease. Therefore, these new generation drugs are becoming increasingly important in the treatment of fatty liver disease, especially when associated with obesity, insulin resistance, and other metabolic problems.
5. Inflammation
Obesity is not simply the storage of excess energy as fat. Visceral adipose tissue, in particular, is a highly biologically active tissue. Fat cells and the immune cells within this tissue produce various inflammatory signals such as IL-6 and TNF-α. As the amount of visceral fat increases, this low-grade inflammatory environment becomes more pronounced and, over time, contributes to insulin resistance, impaired vascular function, and other metabolic problems.
Therefore, examining inflammation markers in metabolic assessment is a useful approach. hs-CRPCRP is one of the parameters we can use to assess low-level systemic inflammation. However, it is important to remember that CRP is not specific. A high value can be caused by many different reasons besides metabolic inflammation, ranging from infections and rheumatological diseases to a recent illness and intense physical exercise.
Neutrophil/Lymphocyte Ratio (NLR), which can be calculated from a routine complete blood count, is another simple parameter that can be added to the assessment. NLR is calculated by dividing the number of neutrophils in the blood by the number of lymphocytes and provides indirect information about the balance between inflammatory activity and stress response in the immune system. High NLR values have been associated with obesity, insulin resistance, metabolic syndrome, and cardiovascular disease. However, NLR alone is not a specific test indicating metabolic inflammation; infection, certain medications, smoking, stress, and many acute or chronic diseases can alter NLR values.
6. Kidney, Uric Acid and Blood Pressure
Metabolic health cannot be considered separately from the cardiovascular system, kidneys, and vascular system. Therefore, it should be evaluated as follows:
- Creatinine and eGFR
- Albumin/creatinine ratio in urine, if necessary.
- Uric acid
- Blood pressure
Parameters such as these should also be included. The aim is to detect the effects of metabolic disorders on other organs as early as possible.
7. Body Composition and Muscle Mass
It is important to know not only how many kilograms you weigh, but also why that weight was gained. Muscle tissue is a highly metabolically active tissue and plays a major role in glucose utilization via insulin.[2] Therefore, I do not find it correct to look only at total weight loss, especially in weight loss programs. For example, of two patients who lose 10 kilograms, one may lose mainly fat while the other may also lose a significant amount of muscle. The results on the scale may look similar, but the metabolic results are not the same. Therefore, it is valuable for patients to monitor their body fat percentage, visceral fat, and muscle mass along with their waist circumference. Even if these measurements cannot be made, it is important to pay attention to protein intake and exercise levels, especially in weight loss programs, to ensure that a significant amount of weight loss does not come from muscle.
The Relationship Between Metabolic Health and Weight
Weight and metabolic health are closely related, but they are not the same thing. In particular, as visceral fat increases, the likelihood of developing insulin resistance, fatty liver disease, hypertension, and lipid disorders also increases. However, it's important not to forget the other side of the relationship. Metabolic, hormonal, or neuroendocrine problems can affect a person's appetite, energy expenditure, fat storage, and weight loss capacity. Therefore, I don't find it sufficient to simply tell a patient who has been dieting for years and repeatedly gaining weight to "eat less and exercise more."
Obesity: Not a Willpower Problem, but a Biological Disease.
Obesity is one of the world's most important health problems today. According to a large-scale Lancet analysis evaluating 2022 data, the total number of children, adolescents and adults living with obesity in the world exceeds one billion. [6]
However, the importance of obesity is not solely determined by the number on the scale. Long-term obesity is associated with an increased risk of type 2 diabetes, hypertension, cardiovascular diseases, sleep apnea, fatty liver disease, joint diseases, and some types of cancer. More importantly, it is no longer scientifically sufficient to view obesity solely as a result of overeating.
Obesity is not simply a matter of "not being able to control one's appetite" or a lack of willpower. It is a chronic disease with a real biological basis, involving hormonal, metabolic, genetic, and neurological mechanisms that regulate appetite, satiety, energy expenditure, and fat storage. Just as high blood pressure is considered a disease and needs to be treated, obesity should be viewed as such.
"I'm on a diet but I can't lose weight." I often hear the phrase, "Sometimes the energy intake is more than expected." This should not be ignored. There are controlled studies showing that ultra-processed foods, in particular, can lead people to consume more calories without realizing it. [7] Therefore, it is important to understand whether patients who say, "I can't lose weight even though I'm dieting," are actually following a proper diet.
But sometimes, that's exactly how the story goes. The patient creates a calorie deficit, exercises, and is very careful, but weight loss is very inefficient. Factors behind or aggravating weight problems may include: genetic predisposition, insulin resistance, polycystic ovary syndrome, certain thyroid disorders, rarer endocrine diseases such as Cushing's syndrome, sleep disorders and sleep apnea, menopause, low muscle mass, certain antidepressant and antipsychotic medications, corticosteroids, and stress.
Genetics are more important than we think. Body weight has a very strong hereditary component, and numerous genes have been identified that play a role in appetite regulation.
Therefore, it is sometimes impossible to expect two people following the same diet to achieve the same results.
Appetite isn't simply caused by an empty stomach. There's a complex, constantly evolving communication network between our gut and our brain. gut-brain axis We give it a name. When we eat, the levels of various hormones such as GLP-1, PYY, CCK, and ghrelin change in the gastrointestinal system. The expansion of the stomach, the nutrients reaching the intestines, blood sugar, fatty acids, and other metabolic signals send information to the brain.
The vagus nerve is one of the important pathways in this communication network. In addition, hormones, the immune system, and certain metabolites produced by the gut microbiota also contribute to communication between the gut and the brain. [8]
The brain then processes this information in different centers, including the hypothalamus and reward systems. Ultimately, this influences thoughts:
- Am I hungry?
- How much should I eat?
- When did I feel full?
- How strong is my urge to crave food?
- Should I have dessert after dinner?
Therefore, appetite is not simply a behavior controlled by willpower. How different parts of our body communicate with each other directly affects our eating habits.
Why does the body resist weight loss?
I think this is one of the least discussed topics in weight management. When you lose weight, your body doesn't always accept the new weight immediately. Controlled studies have shown that after weight loss, some hormones that regulate hunger change in a way that supports weight gain, and these changes can continue for at least a year. [9]
In other words, after losing weight, a person may feel hungrier, less full, and become more interested in food. This doesn't mean the person has "lost willpower." The body is trying to regain the energy it lost. This is why some people lose 10 kilos, gain it back a few months later, diet again, lose weight again, and remain in the same cycle for years. Successful weight management should answer not only the question of "How do we lose weight?" but also "How do we maintain the weight loss without constantly fighting against the body?"
Weight Loss Injections: How GLP-1 Treatments Changed Weight Control?
One of the most significant advances in obesity treatment in recent years has been the introduction of GLP-1-based medications. GLP-1 is actually a naturally produced gut hormone. It is secreted after meals and sends various signals to the pancreas, gastrointestinal system, and brain. It increases glucose-dependent insulin secretion, regulates glucagon secretion, slows gastric emptying, and affects the appetite centers in the brain.
Drugs like semaglutide target the GLP-1 receptor. Tirzepatide, on the other hand, acts through both GLP-1 and GLP-1 receptors. The important aspect of these drugs is not just that they "suppress appetite".
They can alter the biological balance between hunger, satiety, and the thought of food, something many patients struggle with for years. That's why some patients say something quite similar to me after starting treatment: "This is the first time I'm not constantly thinking about food." There is a physiological explanation for this.
For more detailed information about the use and effects of slimming injections, Slimming Injections (Ozempic and Mounjaro) Visit our department.
Peptide Therapies: Which peptides are beneficial for weight loss or body composition?
Peptides have gained considerable attention in recent years in the fields of weight management, metabolic health, and body composition. Essentially, peptides are small structures formed by the arrangement of amino acids in specific sequences. Our bodies naturally produce numerous peptides, some of which function as hormones or signaling molecules. Many processes, such as appetite, blood sugar control, insulin secretion, the growth hormone system, digestion, and energy metabolism, are influenced by these signals.
Therefore, some peptides or peptide-structured drugs can have very powerful effects on weight control. The best-known examples are semaglutide, which targets the GLP-1 system, and tirzepatide, which targets both the GLP-1 and GIP systems. The effects of these drugs on weight loss and metabolic health have been demonstrated in large clinical trials. Newer molecules like retatrutide aim to achieve even more diverse results by targeting multiple metabolic receptors simultaneously.
In terms of body composition, the issue isn't limited to weight loss alone. When losing weight, we aim to minimize fat tissue while preserving muscle mass. Therefore, peptides like tesamorelin, which affect the growth hormone axis, or molecules like CJC-1295, ipamorelin, and similar compounds, are gaining traction in this area. However, there's an important distinction here: the fact that a molecule has a specific biological mechanism doesn't mean it's proven to be effective and safe for fat loss or muscle gain in healthy individuals. For example, while tesamorelin has clinical data and an approved use for reducing visceral fat in a specific patient group, the level of evidence for many other peptides marketed for body composition purposes is much more limited.
MOTS-c is a rather interesting peptide of mitochondrial origin; there is strong experimental evidence that it can affect cellular energy use, glucose metabolism, and response to metabolic stress, and therefore it is being investigated in terms of insulin sensitivity, exercise capacity, and body composition. However, clinical data for MOTS-c in humans are still quite limited, and it is not an approved treatment for weight loss or metabolic health; therefore, it is more accurate to consider it as a promising but experimental peptide at this stage.
Therefore, I find it more appropriate to approach peptide therapies by asking, "What metabolic problem are we trying to solve in this person?" rather than "Which peptide does what?". In one person, the primary problem might be excessive appetite and insulin resistance, while in another, visceral fat, low muscle mass, or the risk of muscle loss during weight loss might be the main issues. The treatment should be chosen accordingly. Peptides can be useful tools in the right patient, but they are not a substitute for proper nutrition, resistance training, adequate protein intake, sleep, and addressing hormonal and metabolic problems.
To access more comprehensive information about peptide therapies 'Peptide Therapies' You can visit our department.
Natural Approaches to Weight Loss
Weight control doesn't always require medication. In addition to diet and exercise, it's possible to benefit from some natural products that can support appetite control, satiety, gut health, and glucose metabolism. For example, soluble fibers like psyllium husk help prolong the feeling of fullness by retaining water in the stomach and intestines, and can also reduce post-meal blood sugar spikes. Probiotics and prebiotics can support metabolic health through the gut microbiota, while chromium Supplements can help with glucose metabolism and appetite, especially in some individuals with deficiencies. For those experiencing increased eating behavior due to stress, some herbal ingredients like Relora® may be considered. However, not all of these products have the same level of evidence, and none should be considered a powerful weight-loss treatment on its own.
I see these types of supplements more as parts of a comprehensive strategy. Especially during GLP-1-based weight loss treatments, proper fiber intake, maintaining gut health, sufficient protein, muscle mass support, and certain nutraceuticals selected according to the individual's needs help complement the treatment. More importantly, maintaining these habits established during medication after treatment can help with the long-term management of appetite and metabolic health. We don't have comprehensive scientific data to definitively say that this prevents weight regain after discontinuing the medication, but creating a sustainable nutrition, exercise, and metabolic health program instead of solely relying on injections is a much more sensible approach for long-term success.
From fiber to gut microbiota, from natural ingredients used in appetite control to nutraceuticals that can support metabolic health, let's examine this topic in more detail. “Natural Approaches to Weight Loss" You can visit our department.
***
All information presented here is for general informational and educational purposes only. This content is not intended to diagnose any disease, provide personalized medical assessments, or initiate, modify, or discontinue any treatment.
The information provided does not replace a doctor's examination, personal medical evaluation, or professional healthcare. Because health conditions and treatment needs vary from person to person, it is recommended that you consult your own doctor or relevant healthcare professional before starting any medication, supplement, treatment, or medical practice, or making any changes to your current treatment.
Because medical information and scientific data can change over time, the information presented here should not be assumed to be applicable to every individual or every clinical situation.
I wish you healthy days,
Dr. Ahmet Özyiğit, MD, MSc, PgDip, FAAMM, ABAARM
Longevity Physician
Elite Research and Surgical Hospital
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