6 Metabolic Health Can Be Improved But It Is Hard

Sabine Zempleni

What Many Think Weight Loss Should Look Like

The NCDs hypertension, CVD and T2D are multifactorial diseases that develop over a long time. Interestingly, they all seem to have one metabolic origin in common: Obesity and systemic chronic inflammation.

Drugs are available to treat and manage T2D and CVD successfully; hypertension due to obesity is often drug resistant. The best treatment for all three would be a healthy lifestyle and weight loss.

Losing weight will reduce the chronic systemic inflammation and slows the disease progression. After weight loss is achieved blood pressure will often return to normal, blood lipids will improve and insulin resistance can improve to the point of reversal.

Before we even look at the scientific data for weight loss and metabolic improvement, you should wrap your head around what weight loss even means. Most of us would probably conjure up a picture like the one to the left (thanks to Instagram browsing).

For many desired weight loss is defined as reaching a toned, thin body for women and a body with visible, larger muscles for men.

Most people will not reach this ideal because their genes and life circumstances will not allow them to. Others will reach this ideal briefly, but will return over the next years back to their old weight. A study following participants from the TV show The Biggest Loser demonstrated this very clearly. All but one study participant regained at least some of the lost weight within 6 years.

The point I’m making here is that as health professionals we are not defining weight loss that way. Make sure that this is the weight loss you are talking about in the context of metabolic improvement:

  • Slow weight loss. Metabolic improvement can be seen with a weight loss of only 5 % of the body weight.
  • Weight loss, no matter how much, needs to be maintained.
  • The focus should be on an increasingly healthy lifestyle not on looks.


As usual, recall what you already know. If not review:


You Will Learn:

  • Substantial weight loss is possible, but maintenance of the lower weight is elusive.
  • Obesity alters the regulation of body weight profoundly.
  • Bariatric surgery can help jump-start weight loss in severely obese patients. Maintenance is difficult as well.
  • Exercising and ongoing behavior therapy show promise in countering biology.
  • Prevention of obesity is easier than weight loss.



Substantial Weight Loss Is Possible, But Maintenance of the Lower Weight Is Elusive For Most

Losing 5% weight to improve or restore metabolic health? Sounds easy enough? Initial weight loss might be reasonably easy but the maintenance of the lower weight is extremely difficult.

The graph below shows the development of average weight in seven long-term weight-loss studies. During the 6 months of active weight loss the participants showed a weight loss between 5 and 15 % of the starting weight. This weight loss is enough to improve metabolic health. But, with exception of one study weight was gained back during the next 3 to 5 years.



During the initial weight loss phase the degree of adherence to the diet (or exercise program) is the key to faster weight loss. Based on the scientific evidence it looks like it is less important what type of diet is chosen, but that the adherence to the diet is high.

Very consistently—no matter what diet—the adherence to the diet starts waning around the 6 to 9 months mark.

Individuals on low-carb diets tend to start eating more carbohydrates. Individuals on low fat, high carbohydrate diets tend to eat more fat and less carbohydrates. Habitual eating habits that caused the weight gain in the first place sneak back into the dietary pattern. The faster the adherence wanes the faster the weight is regained. In average, people regain weight at a rate of 1 – 2 kg per year. This regain is faster right after the weight loss and then slows down somewhat.

Scientists wondered what exactly happens at this tipping point. A NIH working group reviewed the evidence of weight regain in 2015 and came to the conclusion that “One explanation for the declining adherence is that the perceived costs of adherence gradually exceed the perceived benefits. Initially, the positive consequences of weight loss (e.g., sense of accomplishment; better fit of clothes) outweigh the cognitive and physical effort needed to lose weight. Later, when the goal is to maintain lost weight, the positive feedback is less compared to the effort required to keep adhering to the same regimen. Thus, the benefits no longer seem to justify the costs.”

Behavioral approaches can be used to change this cost-benefit ratio. These strategies include:

  • Peer support
  • Maximizing motivation
  • Reduction of boredom
  • Easy access to healthy meals
  • Increasing self-regulating skills

The figure below shows that professional guidance during the weight maintenance phase attenuates weight regain better than self-help. Studies with long-term behavioral interventions during the weight maintenance phase show better results, but are still far from perfect. Success varies tremendously between individuals and despite ongoing behavioral intervention many people still regain weight over time.


While we cannot predict who will be successful and who will regain weight, studies identified two traits that seem to make continued maintenance of the lower weight more likely:

  • People who show a faster and larger weight loss tend to do better at maintaining the lower weight.
  • Highly motivated people are more successful maintaining the weight loss.


Does Food Addiction Exist?

For starters, the term “addiction” is inappropriate in this context. Addiction is a debilitating, chronic, relapsing brain disease. Overeating is not.

Eating is a pleasant experience and naturally triggers the pleasure center in our brain releasing dopamine and opioids. As part of the hedonic pathway this feel good response is a survival mechanism. Eat a lot when palatable food is available to prepare for times of food shortages. True substance addiction taps into the same system but destroys feedback loops and regulation.

At this point scientists are fairly sure that humans don’t get truly addicted to specific foods. Animal experiments showed an overshooting response of the hedonic pathway to high sugar and fat intake. For humans the results are less clear and need to be researched in more depth.


Losing weight looks different for each individual person. However, if individuals want to succeed then it is crucial to acknowledge that it won’t be a steep steady decline in weight all the time. There will be periods of slow weight loss while for other periods there might be a weight plateau. Vacations, holiday seasons, birthday parties, or phases of stress might even trigger some regain of weight. The patient record below shows an example of successful weight loss and maintenance. This is what real long-term weight loss looks like.




Obesity Alters The Regulation of Body Weight Profoundly

In its simplest form weight regulation is a feedback loop between the brain and the body periphery. The periphery signals the status of energy stores and energy balance. When energy stores decrease the brain increases the efficiency of energy use, triggers a preference for palatable foods, and decreases satiety.

The Biggest Loser study looked at the RMR of participants after 6 years. To their surprise the researchers found that after 6 years the RMR was in average 500 kcal/d lower than expected. There was a large individual variation between study subjects though (292 – 706 kcal/d).

At the same time metabolic changes increase the driver to eat after weight loss.



The key to energy homeostasis are the hormones leptin and ghrelin.

As you already know Leptin is secreted by the adipose tissue and the amount of leptin secreted is proportional to the size of the adipose tissue. Leptin’s major function is to signal the status of the adipose tissue to other organs. Losing adipose tissue decreases leptin secretion. This signal is picked up by the brain and hunger increases.

Ghrelin is secreted by the stomach and does the opposite. A full stomach decreases ghrelin secretion and induces satiety. An empty stomach increases ghrelin secretion and the feeling of hunger.

Here is the problem. If someone becomes obese, the signaling of those hormones does not work as intended anymore. Gaining weight increases leptin blood levels initially. This should induce less hunger and increased satiety and restore the energy homeostasis.

However, if leptin blood levels are permanently high leptin resistance develops. The brain starts ignoring the high levels of leptin. If your brain stops listening, then it becomes harder for people to know when they are hungry and when they are full.

When weight is lost the adipose tissue produces less leptin. The brain interprets those lower leptin levels not as a good thing—keep in mind the brain lost track of the adipose tissue status a while ago—but as dangerous starvation. The brain starts energy conservation measures. We start craving more energy rich foods and eating will not induce satiety as easily. Energy use becomes super efficient and less energy is needed to maintain the existing adipose tissue stores. The RMR decreases.

The consequence  is a gap between the reduced energy needs and the increased food intake due to increased hunger. Weight is gained back.


Are all macro-nutrient calories equal?

A calorie is a calorie independent of the macro-nutrient delivering it. But, protein, carbohydrates and fats impact satiety differently and therefore contribute to the regulation of the energy intake differently.

Protein induces longer satiety and a high-protein diet seems to help weight loss and maintenance. We just need to keep in mind that protein does not equal meat. Plant-based proteins such as legumes are healthy and work as well.

Digestible carbohydrates such as sugars and starches trigger a more short-term satiety. Fiber is a different story though. It increases food volume and decreases energy density. This leads to increased satiety after a meal. If the fiber is combined with a high water content—for example in fruits and vegetables—the effect is even greater.

For fat the situation is paradoxical. High amounts of dietary fat induce a strong satiety response—her comes the catch—once the fat reaches the intestine. On the other hand people who eat a high fat diet tend to overeat energy. Scientists think the reason for this paradox is that the satiety response is so delayed that the palatability of fatty foods initially stimulate over-consumption of energy. Since a gram of fat has over double the kcals (9 kcal/g) than carbohydrates or protein (4 kcal/g) overeating is easy.



Bariatric Surgery Can Help Jump-Start Weight Loss in Severely Obese Patients. Maintenance is Difficult As Well.

Bariatric surgery is becoming common as a treatment option for obesity especially in severely obese individuals with chronic diseases.

During bariatric surgery part of the stomach is either tied off or removed creating a small stomach pocket or a bypass is created that directs food directly into the duodenum.

After bariatric surgery patients need to learn how to eat small portions of food and as a consequence they lose large amounts of weight rapidly. The weight loss can vary individually though as the graph below shows.


As you see not everybody has success. In somw patient weight is re-gained slowly after the initial weight drop. Stomach and intestines expand over time again allowing the patient to eat more and absorb more calories.

While bariatric surgery was invented to help severely obese patients to lose weight rapidly and hopefully maintain some of the weight loss, studies tracking some of those patients had a surprise in store. So far unexplained, bariatric surgery induces beneficial changes in hunger and satiety regulation as well as beneficial effects on glucose metabolism and insulin sensitivity.


Especially after the type of bariatric surgery that bypasses most of the stomach, ghrelin secretion decreases and PYY, another hunger hormone, increases. leaving bariatric surgery patients less hungry and allowing them to experience better satiety after a meal.

The incretin GLP-1, secreted by the pancreas and gut during digestion,  is involved in the blood glucose management. Increased GLP-1 results in more effective insulin secretion and better blood glucose regulation. This is thought to be the key to the immediate improvements of T2D after the surgery.

Bile acids emulsify fat but they also provide feedback about incoming fat to the metabolism and modify the gut microbiome. Increased secretion of bile acids is discussed to have positive metabolic effects.

Overall, bariatric surgery is an good option to jump start weight loss and metabolic improvements for metabolically unhealthy, obese people. Since bariatric surgery is a highly invasive surgery it will have the same dangers as any surgery. Obese individuals are especially vulnerable to complications during surgery and often have delayed woubd healing. The benefits need to outweigh the dangers.

Bariatric surgery will not magically fix all problems. The patient will still need to learn healthy eating, portion control and an active lifestyle.

Problem behaviors influencing appetite and unhealthy eating decisions are still kicking in after the novelty wears off. Behavioral intervention can help improve adherence and motivation.


Exercising And Ongoing Behavior Therapy Show Promise in Countering Biology

Bariatric surgery is able to counter biology to a certain degree. Positive changes in hunger and satiety will make it easier to lose and maintain weight. Considering the major downsides of the surgery this should not be an option for overweight and moderately obese, metabolically healthy individuals. The question is if there are other strategies to counter biology.



Regular exercise is a promising contender. So far we thought that weight loss is mostly mediated by healthier eating aided by an increased RMR when muscle mass increases. The physical exercise was thought to improve cardiovascular health and insulin resistance and aid dietary intervention.

Lately though evidence emerged that exercising also changes the energy regulation feedback loop. The research is still brand new but here are a few ideas that are proposed:

  • People who exercise during weight loss have better adherence to dietary interventions. It is not clear why.
  • Exercising affects appetite, food choices and overall intake.
  • Exercise results in a more inefficient energy use—the muscle converts more energy into heat—increasing energy need.

Sounds amazing? These study results will be very frustrating for 50% of the American population. The additional beneficial effects of exercise are only seen in so-called exercise responders. Here is the frustrating part: Responders are more likely to be male.

Behavioral strategies also show promise. Research is looking into how the rewarding effect of palatable foods and cravings during weight loss can be countered. This includes modifying memories related to food, learning how to delay instant gratification, and improving impulse control.



Prevention of Obesity Is Easier Than Weight Loss


The weight loss and regain evidence makes it clear that once a person is obese it is very difficult to lose weight and maintain this weight loss. While we need to find better approaches to help obese people to improve their metabolic health the best approach would be to prevent obesity all-together.

Recently, an expert committee selected by the American Medical Association, in collaboration with the Department of Health and Human Services’ Health Resources and Service Administration and the CDC, produced a series of recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity.

Four specific target behaviors were identified that are supported by consistent scientific evidence. These key target behaviors consist of :

  1. Consuming at least five servings of fruits or vegetables each day
  2.  Limiting screen time (TV, computer, and video games) to two hours or less per day
  3. Engaging in at least one hour of physical activity per day
  4. Consuming almost no sugary beverages

This approach is called the 5–2–1-0 intervention and is readily actionable. The message is easy to remember and reasonably easy to implement. Messaging has been adopted widely in regional initiatives, either directly or in a slightly modified form. It will be interesting to see how effective this and other prevention strategies will be.

It should be clear by now that the obesity pandemic cannot be brushed of as being healthy at any weigh. On the flip side weight bias and discrimination are unacceptable and health professionals need to learn how to address weight in a productive way. Based on this first module it should also be clear that the main emphasis needs be on obesity prevention and supporting families to make a healthy, active lifestyle the norm.

In the followong modules you will explore how lifestyle decisions starting before can put a child on a healthy or unhealthy trajectory in life.


Interested In More Information?

Fothergill E, Guo J, Howard L, et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016;24(8):1612-1619. doi:10.1002/oby.21538

MacLean PS, Wing RR, Davidson T, et al. NIH working group report: Innovative research to improve maintenance of weight loss. Obesity (Silver Spring). 2015;23(1):7-15. doi:10.1002/oby.20967



Editors: Nicole Legler, Gabi Ziegler

NUTR251 Contributors:

  • Spring 2020: Allison Aden, Grace Neville, Grant Young, Caroline Leibel, Kristine Krager, Dylan Fruhling, Kalen Codr, Rawan AL Jabri, Kristine Krager, Amelia Johnson
  • Fall 2020: Morgan McCain, Megan Appelt, Miles Judson




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Nutrition Through the Life Cycle Copyright © 2020 by Sabine Zempleni is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, except where otherwise noted.

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