Diabetes isn’t just about bloods sugar, it’s systemic inflammation, incessant cravings-driven eating. It’s obesity.

And it’s impacting our nation in ways most are completely unaware of.

From our children’s exposure to the US dietary regulations in our public schools and the rise in ADD (Attention Deficit Disorder), to behavioural issues in the prison system where most inmates emerge severely diabetic.

We are generating a massive problem of staggering social dysfunction most clearly evident in our nation’s urban areas. As a nation, we are failing.

And Dr. Gurpreet Padda is right in the middle of it. Based in St. Louis, MO, The Padda Institute is highly regarded as one of the best pain centers in St. Louis.

Does Meat Really Heal? Many anecdotal reports have been released claiming that the carnivore diet – which basically consists of eating a diet restricted to meat (usually red fatty meat)–has alleviated the symptoms of autoimmune disease, depression and caused weight loss and improved health. Despite these anecdotal, is there any scientific evidence to support these claims? In this article, we will examine some of the effects of this diet on some conditions.

1. What is the effect of the carnivore diet on obesity?

When you are on the carnivore diet, your intake of processed carbohydrates and sugar is completely cut off. Thesesimple sugars are the leading cause of weight gain. In the absence of these carbohydrates, your body burns fat for fuelin a process known as ketosis. This results in weight loss and the eradication of obesity. Obesity is a leading cause of chronic illnesses such as T2DM, Cardiovascular diseases and Fatty Liver disease among others.

2. What effect does the Carnivore Diet have on autoimmune diseases?

Studies have shown that excess intake of sugary foods and processed carbohydrates increases systemic levels of inflammation in the body, which can increase the risk for cancer and autoimmune diseases. Eliminating sugar intake through the meat diet can therefore theoretically decrease levels of inflammation in the body.

But does the meat diet directly decrease levels of inflammation in the body? The carnivore diet sends the body into a metabolic state called ‘ketosis,’burns fat for energy instead of using glucose. Compared to glucose metabolism which produces large amounts of free oxygen radicals, contributing to inflammation, ketotic metabolism has been shown to produce far fewer free radicals.

In fact studies have shown that ketosis decreases inflammationand reactive radicals in animal models of multiple sclerosis, an autoimmune condition that affects the brain. It also decreases markers of liver inflammation in people with non-alcoholic fatty liver disease. Since the ketogenic diet has also been shown to produce anti-inflammatory effects by directly inhibiting pro-inflammatory immune pathways in the body, it is assumed that the carnivore diet does the same, short of scientific tests being carried out. With this in mind, it can be concluded that the carnivore diet can in fact guard against inflammation and ameliorate symptoms of autoimmune disease.

3. Does the Carnivore diet have any cancer fighting properties?

Not enough studies have been done on the carnivore diet but emerging evidence suggests that the ketogenic diet may decrease the risk of cancer through its anti-inflammatory properties. Because they basically act in the same way, the same can be deduced of the carnivore diet. Carcinogenesis (the development of cancer) has been related to hyperinsulinemia, hyperglycemia, and chronic inflammation. The ketogenic diet is hypothesized to decrease risk of cancer by decreasing levels of insulin and glucose in the body and also by decreasing systemic levels of inflammation.

Initially, it was thought that cancer cells use a lot of glucose for energy, thus starving them of glucose would stop their growth. Unfortunately, this theory was disproved because normal cells too need energy, and there is no way of starving the cancer cells and feeding the normal ones.

However, there is an indirect link between cancer risk and sugar. Eating lots of sugar over time can cause you to gain weight, and scientific evidence shows that being overweight or obese increases the risk of 13 different types of cancer. In fact, obesity is the single biggest preventable cause of cancer after smoking. The carnivore diet can thus reduce the risk of obesity and thereby reduce the risk of cancer.

In addition, a study published in 2019 suggested there could be something else going on. Researchers found that people who drank more sugary drinks had a slightly increased risk of cancer, regardless of body weight. The study took weight in to account, but there are still lots of answered questions. More studies will be needed to investigate this.

But what of the studies that show a correlation between red meat and cancer? There is one major flaw in the way these studies are interpreted.  These studies are epidemiologic. This means that causal effects cannot be implied. In other words, just because there is a correlation between meat consumption and cancer does not mean that meat consumption itself causes cancer.

4. The Carnivore Diet and cognitive functioning…

Although there is limited evidence on the neuroprotective effects of the carnivore diet specifically, there is much evidence on the neuroprotective of the ketogenic diet, which the carnivore diet closely resembles. Data suggests that the ketogenic diet has anti-inflammatory effects on the brain and holds neuro-protective benefits.

The ketogenic diet was initially designed to manage children suffering from seizures. Studies show that as many as half of patients that are started on the ketogenic diet have fewer seizures after starting the diet. In children with specific genetic epilepsies or epilepsy syndromes, studies have shown up to 90% of patients achieve seizure freedom on the ketogenic diet.

Because inflammation is thought to play an important role in epilepsy and seizures, the ketogenic diet, and therefore the carnivore diet may decrease seizure occurrence through its anti-inflammatory effects. The anti-inflammatory mechanisms of the ketogenic diet involve reduced mitochondrial production of pro-inflammatory molecules and reduced production of excess excitatory neurotransmitter glutamate, which can cause neuronal damage (a.k.a“glutamate excitotoxicity”).

Inflammation is thought to play a role in the development of other neurological diseases such as autism (increasingly associated with maternal inflammation), Alzheimer’s Disease, and Parkinson’s Disease, as well as cognitive dysfunction in people with diabetes and obesity. Thus, decreasing inflammation, potentially through the carnivore diet, may improve symptoms related to neurological dysfunction associated with inflammatory processes.

5. What is the effect of the Carnivore diet on depression?

From anecdotal reports, the carnivore diet has shown neurological and psychological effects beyond the treatment of seizures and chronic pain. Several people on the carnivore diet report benefits such as increased alertness, energy, mood and concentration.

Moreover, inflammation can contribute to depression, and depression itself can promote inflammation. The ketogenic diet may improve mood and ameliorate depression symptoms through its anti-inflammatory properties.

6. So, does meat heal?

It is clear that the carnivore diet has marked positive effects on the conditions we set out to explore. This is mainly due to its cutting off of sugars and carbohydrates. It can be said that getting on a carnivore diet is likely to bring about improved health outcomes.

It is important to note that there is not a ‘one-size-fit all’ when it comes to diet. Every individual has a different body, genetics, digestive system and immune system, which all of play a role in the body’s reaction to food. However, one “take home” is that everyone should cut down on sugar and processed carbohydrates because these are known to cause weight gain, pro-inflammatory states, and health problems.

References:

1. Neurogal (2018): Does Meat Really Heal? Show me the Evidence for the Carnivore Diet. Retrieved from https://neurogal.com/neuro-blog/2018/12/7/does-meat-really-heal-show-me-the-evidence-for-the-carnivore-diet

2. Cancer Research UK (2017): Sugar and cancer – what you need to know. Retrieved from https://scienceblog.cancerresearchuk.org/2017/05/15/sugar-and-cancer-what-you-need-to-know/

3. The BMJ (2019): Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort. Retrieved from https://www.bmj.com/content/366/bmj.l2408

Dr. Padda untangles the roots of our current opiate epidemic, obesity epidemic and diabetes epidemic, which are currently in the process of crippling our economy. He discusses hopeful solutions for the future, including how to prevent the eminent devastation of our physical, emotional and financial health as a nation. This is an inspiring and powerful conversation that we should all be thinking about as we visualize a sustainable future for humanity.  

Obesity has become rampant in recent times. It is said to affect almost 50% of the American population. It has been credited with being a leading cause of chronic illness and ill health. The carnivore diet has become very popular as the new way to lose weight, maintain a healthy lifestyle and ward off diseases. A major proponent of this diet is its ability to melt away the fat. How effective is it in the management of obesity? Do its effects last? In this article we will explore the role this diet can play in the curbing of obesity.

1. What is obesity?

Obesity is a complex disease involving an excessive amount of body fat. Obesity isn’t just a cosmetic concern. It is a medical problem that increases your risk of other diseases and health problems, such as heart disease, diabetes, high blood pressure and certain cancers. There are many reasons why some people have difficulty avoiding obesity. Usually, obesity results from a combination of inherited factors, combined with the environment and personal diet and exercise choices.

2. What is the Carnivore diet?

The Carnivore Diet is a restrictive diet that only includes meat, fish, and other animal foods like eggs and certain dairy products. It excludes all other foods, including fruits, vegetables, legumes, grains, nuts, and seeds. Its proponents also recommend eliminating or limiting dairy intake to foods that are low in lactose — a sugar found in milk and dairy products — such as butter and hard cheeses.

A good number of people who have adopted the carnivore diet report faster weight loss, improved mental clarity, healthier digestion, and even improved athletic performance. Some have also reported remarkable relief from debilitating chronic health problems where conventional means did not succeed.

1. What does one eat on the carnivore diet?

This is what you are likely to eat if you are on the carnivore diet:

–Below is the Green List that is, food you should be eating all the time with an emphasis on fattier cuts of meat to take in enough calories:

• Meat: beef, chicken, turkey, organ meats, lamb, pork, etc.
• Fish: salmon, mackerel, sardines, crab, lobster, tilapia, herring, etc.
• Other animal products: eggs, lard, bone marrow, bone broth, etc.
• Low-lactose dairy (in small amounts): heavy cream, hard cheese, butter, etc.
• Water

Generally, salt, pepper, and seasonings with no carbs are allowed.

– Below is the RED list of what you should NOT be eating:

• Vegetables: broccoli, cauliflower, potatoes, green beans, peppers, etc.

• Fruits: apples, berries, bananas, kiwi, oranges, etc.
• High-lactose dairy: milk, yogurt, soft cheese, etc.
• Legumes: beans, lentils, etc.
• Nuts and seeds: almonds, pumpkin seeds, sunflower seeds, pistachios, etc.
• Grains: rice, wheat, bread, quinoa, pasta, etc.
• Alcohol: beer, wine, liquor, etc.
• Sugars: table sugar, maple syrup, brown sugar, etc.
• Beverages other than water: soda, coffee, tea, fruit juice, etc.

While some people incorporate some of these foods, a true Carnivore Diet does not permit them:

• Milk
• Yogurt
• Cheese

Coffee and tea: These may be plant-based, but some people keep these in the diet.

The carnivore diet can be considered to be a fad. Is there evidence that any traditional populations practiced the carnivore culture?

3. What effect might the carnivore diet have on obesity?

When on a carnivore diet, all you consume is meat, meat and more meat…Occasionally you could have some eggs and cheese and maybe a cup of coffee. What about this diet at a glance could help in combating obesity?

How does the carnivore diet work?

1. Cutting out sugar and carbohydrates

The absence of sugar and carbohydrates cause rapid and sustained fat loss without the need to count calories. Carbohydrates are hard to store and actually harmful if left to circulate in your system too long, so your body always wants to use them up first.

Your body releases insulin to shuttle blood sugar into muscles. To make sure the sugar gets used up first, insulin also tells your fat cells to store any fat you consume and to not release stored body fat for hours afterwards. If you eat a lot of easily-absorbed carbohydrates, your body releases a ton of insulin in response. Excess insulin can then remove too much sugar from your blood stream, resulting in hypoglycemia. The quickest way to restore blood sugar levels is to eat more carbs, which puts people on the carb roller coaster to weight gain.

The carnivore does away with all this by totally eliminating sugar and carbohydrates from your diet.

2. Eating a lot of protein suppresses appetite

One way that protein controls appetite is through the amino acid phenylalanine. Consumed protein is broken down into amino acids so it can be absorbed by the body. Multiple studies have shown how phenylalanine suppresses appetite and even improves mood and helps you burn stored fat. One study found that phenylalanine increases the release of an intestinal hormone called cholecystokinin in humans. This hormone signals the brain to feel satiated after eating and causes a reduction in subsequent food intake. A mouse study found that a single dose of phenylalanine caused an increase in another satiety hormone called GLP-1, it reduced levels of the hunger-hormone ghrelin.

3. Increase in dopamine

Protein foods are made from the building blocks of amino acids (including tyrosine), which are essential to the production of dopamine. It has therefore been suggested that upping protein intake may also boost dopamine production without increasing appetite. Dopamine is considered the reward-hormone and increasing its levels in your brain is helpful for making your weight loss diet less unpleasant.

4. The carnivore diet “imposes” time restricted eating

The carnivore diet tends to make people naturally adopt time-restricted eating patterns. Studies show that eating at night is a common cause of obesity. Junk food actually causes you to prefer late-night eating. Sugar and fat together, act as a trigger that cements the unhealthy habit of late-night eating. Worse yet, your body runs on an internal clock called circadian rhythms. These do more than set your sleep and wake times; they also determine your digestion and energy usage times. We’re meant to eat during the day and sleep at night. When you eat at night, your body doesn’t want to process those calories and instead they sit and cause metabolic dysfunction.

Protein does not seem to trigger a desire for late-night eating so the carnivore diet also helps curb that unhealthy practice. Late-night eating also reduces the quality of your sleep and poor sleep leads to poor eating the next day. Reduced sleep also increases stress and anxiety, so removing late-night eating not only improves weight loss, but helps your mood and overall feeling of well-being.

5. Does the carnivore diet stave off obesity?

There is a link between the Carnivore diet and sustained weight loss. In the absence of carbohydrates, fat can be kept off for long periods of time. The question becomes how safe it is to do the carnivore diet long term. More studies on this need to be carried out but in the meantime, this diet is one of the best in keeping obesity, and its associated diseases at bay.

References

1. Mayo Clinic (2019): Retrieved from https://www.mayoclinic.org/diseases-conditions/obesity/symptoms-causes/syc-20375742

2. NCBI (1994):L-phenylalanine releases cholecystokinin (CCK) and is associated with reduced food intake in humans: evidence for a physiological role of CCK in control of eating. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/8201963

3. NCBI (2012):The Carnivore Connection Hypothesis: Revisited, Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253466/

4. Lolo (2018):Carnivore Diet: Fad or the Future? Retrieved from http://unity.lolofit.com/blog/posts/carnivore-diet-fad-or-miracle-diet

5. Healthline (2019):All You Need to Know About the Carnivore (All-Meat) Diet. Retrieved from https://www.healthline.com/nutrition/carnivore-diet

Sugar has been vilified over the years with claims of its disastrous effects on our health. Are these claims true? Does taken a soda a day guarantee one ill health? What of the effects of excess sugar on obesity? In this article, we will explore these claims and determine whether indeed excessive sugar intake leads to obesity.

1. What is obesity?

Obesity rates have skyrocketed over the past century. In 1962, 46 percent of adults in the U.S. were considered overweight or obese. By 2010,that figure had jumped to 75 percent.

So, what exactly is obesity……

Obesity is a complex disease involving an excessive amount of body fat. Obesity isn’t just a cosmetic concern. It is a medical problem that increases your risk of other diseases and health problems, such as heart disease, diabetes, high blood pressure and certain cancers.

Obesity is diagnosed when your body mass index (BMI) is 30 or higher. To determine your body mass index, divide your weight in pounds by your height in inches squared and multiply by 703. Or divide your weight in kilograms by your height in meters squared.

BMI	Weight status
Below 18.5	Underweight
18.5-24.9	Normal
25.0-29.9	Overweight
30.0 and higher	Obesity

For most people, BMI provides a reasonable estimate of body fat. However, BMI doesn’t directly measure body fat, so some people, such as muscular athletes, may have a BMI in the obesity category even though they don’t have excess body fat.

2. Sugar and obesity

Obesity is a complex problem with multiple causes. But among the likely suspects, sugar is a top favorite. As sugar consumption has increased, so too has the size of our waistlines.

Added sugars are a controversial and hotly debated topic. Consumption of added sugars has been implicated in increased risk of a variety of chronic diseases including obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease (NAFLD) as well as cognitive decline and even some cancers. Support for these putative associations has been challenged, however, on a variety of fronts.

The sugars in your diet can be eithernaturally occurring or added. Naturally occurring sugars are found naturally in foods such as fruit (fructose) and milk (lactose). Added sugars are sugars and syrups put in foods during preparation or processing, or added at the table.

Numerous dietary and lifestyle habits can lead to weight gain and cause you to put on excess body fat.Consuming a diet high in added sugars, such as those found in sweetened beverages, candy, baked goods, and sugary cereals, is a contributing factor in weight gain and chronic health conditions, including obesity, heart disease, and diabetes.

Many people consume more sugar than they realize. It’s important to be aware of how much sugar you consume because our bodies don’t need sugar to function properly. Added sugars contribute zero nutrients but many added calories, which can lead to extra pounds or even obesity, thereby reducing impacting our health.

The ways in which added sugar intake leads to weight gain and increased body fat are complex and involve many factors.

3. Some ways why added sugar is fattening….

1. It is high in empty calories
   Added sugars are sweeteners added to foods and beverages to improve taste. Common types of added sugar include fructose, corn syrup, cane sugar, and agave.Excess sugar may cause you to pack on weight because it’s high in calories while offering few other nutrients.Though using small amounts of added sugar is unlikely to cause weight gain, regularly indulging in foods high in added sugars may cause you to gain excess body fat quicker and more drastically.
   2. Impacts blood sugar and hormone levels

   It’s well known that eating sugary foods significantly raises your blood sugar levels.Though enjoying a sweet food infrequently isn’t likely to harm health, daily consumption of large amounts of added sugar can lead to chronically elevated blood sugar levels.

   Prolonged elevated blood sugar — known as hyperglycemia — can cause serious harm to your body, by causing insulin resistance and resulting including weight gain.

   3. May lead to overeating

   Foods high in added sugars tend to be less filling. Eating foods rich in carbs — particularly refined carbs high in added sugars — yet low in protein can negatively impact fullness and may lead to weight gain by causing you to eat more at subsequent meals throughout the day or overeat at any one particular seating.

   Animal studies indicate that fructose impacts signaling systems in your hypothalamus, increasing levels of hunger-stimulating neuropeptides — molecules that communicate with one another, influencing brain activity — while decreasing fullness signals. Additionally, your body is predisposed to crave sweetness. In fact, research shows that sugar consumption is driven by the pleasure derived from the sweet taste of sugary drinks and foods.

   4. Linked to obesity and chronic disease

   Numerous studies have linked high intake of added sugars to weight gain and chronic conditions, such as obesity, heart disease, and diabetes.This effect has been observed both in adults and in children. Recently, a review of 30 studies in more than 242,000 adults and children found a significant link between sugar-sweetened beverages and obesity.

   4. What are some of the health problems associated with obesity?

   People with obesity are more likely to develop a number of potentially serious health problems, including:

   • Heart disease and strokes. Obesity makes you more likely to have high blood pressure and abnormal cholesterol levels, which are risk factors for heart disease and strokes.
   • Type 2 diabetes. Obesity can affect the way your body uses insulin to control blood sugar levels. This raises your risk of insulin resistance and diabetes.
   • Certain cancers. Obesity may increase your risk of cancer of the uterus, cervix, endometrium, ovary, breast, colon, rectum, esophagus, liver, gallbladder, pancreas, kidney and prostate.
   • Digestive problems. Obesity increases the likelihood that you’ll develop heartburn, gallbladder disease and liver problems.
   • Gynecological and sexual problems. Obesity may cause infertility and irregular periods in women. Obesity also can cause erectile dysfunction in men.
   • Sleep apnea. People with obesity are more likely to have sleep apnea, a potentially serious disorder in which breathing repeatedly stops and starts during sleep.
   • Osteoarthritis. Obesity increases the stress placed on weight-bearing joints, in addition to promoting inflammation within the body. These factors may lead to complications such as osteoarthritis.

   5. How can obesity affect your quality of life?

   People who are obese often find themselves struggling with some issues that might diminish their overall quality of life. Some of these issues might include:

   • Depression
   • Disability
   • Sexual problems
   • Shame and guilt
   • Social isolation
   • Lower work achievement

   6. How can you keep yourself from getting obese?
   

   Whether you’re at risk of obesity, currently overweight or at a healthy weight, you can take steps to prevent unhealthy weight gain and related health problems.

   • Exercise regularly. You need to get 150 to 300 minutes of moderate-intensity activity a week to prevent weight gain. Moderately intense physical activities include fast walking and swimming.
   • Follow a healthy-eating plan. Focus on low-calorie, nutrient-dense foods, such as fruits, vegetables and whole grains. Avoid saturated fat and limit sweets and alcohol. Eat three regular meals a day with limited snacking. You can still enjoy small amounts of high-fat, high-calorie foods as an infrequent treat.
   • Know and avoid the food traps that cause you to eat. Identify situations that trigger out-of-control eating. Try keeping a journal and write down what you eat, how much you eat, when you eat, how you’re feeling and how hungry you are, stay in control of your eating behaviors.
   • Monitor your weight regularly. People who weigh themselves at least once a week are more successful in keeping off excess pounds.
   • Be consistent. Sticking to your healthy-weight plan all the time
     

     7. So, is sugar friend or foe?

     Interfering with your hormones, increasing hunger, and displacing healthy foods are just a few of the ways that added sugars can lead to weight gain.Aside from causing you to put on excess body fat, eating too much added sugar can significantly increase your risk of chronic conditions, such as obesity, heart disease, and diabetes. It is thus wise to consume added sugars with caution because a stitch in time save nine.

     References

     1. Endocrineweb(2018):Insulin Resistance Causes and Symptoms, Retrieved from

     https://www.endocrineweb.com/conditions/type-2-diabetes/insulin-resistance-causes-symptoms

     2. Healthline (2019):6 Ways Added Sugar Is Fattening. Retrieved from

     https://www.healthline.com/nutrition/does-sugar-make-you-fat#section1

     3. American Heart Association (2018): Added Sugars. Retrieved from

     https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/sugar/added-sugars

     4. NCBI (2016): Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding. Retrieved from

     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133084/

     5. John Hopkins Medicine (2019): Obesity, Sugar and Heart Health. Retrieved from

     https://www.hopkinsmedicine.org/health/wellness-and-prevention/obesity-sugar-and-heart-health

     6. Mayo Clinic: Retrieved from

     https://www.mayoclinic.org/diseases-conditions/obesity/symptoms-causes/syc-20375742

Given that obesity and associated disorder type II diabetes mellitus have reached epidemic proportions worldwide, the development of efficient prevention and therapeutic interventions is a global public health interest. There is now a large body of evidence suggesting that the micro-organisms colonizing the human gut, known as gut microbiota, play a central role in human physiology and metabolism. Understanding how gut microbiota affects and regulates key metabolic functions such as glucose regulation and insulin resistance is an important health issue. We will highlight how prebiotic/probiotic interventions affect these bacterial processes and are now considered as promising approaches to treat obese and diabetic patients.

1. The gut microbiota of an obese person…

Obesity is a chronic, complex, and multifactorial disease representing the fifth leading cause of death in the world and accounting for almost 3.4 million deaths each year. Low-grade inflammation is the hallmark of metabolic disorders such as obesity, type 2 diabetes and nonalcoholic fatty liver disease.

Microbiota is now recognized as a real functional “organ” due to its immense impact on human health and has become the subject of intensive research over recent years. The vast majority of microbes reside in the intestinal tract, where they influence host physiology by playing fundamentally important roles in digestion, nutrition, immune regulation, and metabolism.

Gut microbiota composition and activity can fluctuate over time and depend on different factors including genetics, sex, age, health status, and drug/antibiotic consumption. Over the last decade, a large number of publications have reported a prominent role of microbiota in metabolic diseases.

Notably, accumulated evidence suggests an association between a dysregulated gut microbiome and obesity, glycemic control impairment, and therefore T2DM pathophysiology.

2. Obesity, Diabetes, and Dysbiosis

The preservation a normal and healthy gut microbiota plays a critical role in maintaining good health. Alterations of both composition and function of the microbiota, termed dysbiosis, are common features of several pathologies including metabolic diseases such as obesity and T2DM.

A number of preclinical and clinical studies have attempted to describe the differences between gut microbiota in obese, compared to lean individuals and have reported that obesity is related to lower microbial diversity and greater depletion. In early obesity, microbiota studies report that an increase of body weight is associated with a microbiota shift.

Although T2DM is generally considered as an attribute to obesity, some studies have correlated glycemic control impairment and insulin resistance to specific gut microbiota composition. Furthermore, antidiabetic drugs liraglutide and metformin have been recently shown to significantly lower body weight and improve glucose metabolism while considerably modifying the composition of gut microbiota.

Liraglutide decreased obesity-related microbial phenotypes and increased lean-related phenotypes while metformin modifies the intestinal microbiota composition by inducing the growth of several bacteria.

There is proof that gut microbiota is involved in the beneficial glucose-lowering effects of antidiabetic agents and that it is a promising therapeutic target in T2DM and the glycemic control impairment context.

3. How can Gut Microbiota be moderated?

Through several mechanisms, gut bacteria influence the chronic low grade inflammation that culminates in insulin resistance and the increase in fat deposits and body weight gain, characteristic of obese individuals.

With the acknowledgement of these obesity and inflammation induction mechanisms, several strategies to block or attenuate them are being developed and tested, in order to benefit obese and type 2 diabetic patients. We will look at these mechanisms and the effect they have:

3.1. Antibiotic Therapy

The use of broad spectrum antibiotic therapy greatly modifies the gut microbiota profile although the prevalence of surviving bacteria and the benefits for the host have not been determined, as the concept of a “healthy” gut microbiota is still under investigation.

The main mechanism suggested by antibiotic administration is a reduction in circulating LPS levels, which lessens inflammation and improves the insulin resistance induced by obesity in the liver, muscle, and adipose tissue. Improved intestinal function has also been noted as a benefit of the administration of antibiotics.

However, even with this striking metabolic improvement in antibiotic therapy experiments, it seems that translating this strategy to humans is not the best option, as there are complex issues such as antibiotic resistance in chronic administration panels and evidence that indicates a relationship between chronic low-dose antibiotic therapy and body weight gain.

3.2. Probiotics

Probiotics are live microorganisms that can be consumed through fermented foods or supplements. More and more studies show that the balance or imbalance of bacteria in your digestive system is linked to overall health and disease. Probiotics promote a healthy balance of gut bacteria and have been linked to a wide range of health benefits.

As obesity is a key cause of diabetes, probiotics can help with weight loss through a number of different mechanisms. An example is that some probiotics prevent the absorption of dietary fat in the intestine.The fat is then excreted through feces rather than stored in the body. Probiotics may also help you feel fuller for longer, burn more calories and store less fat. This is partly caused by increasing levels of certain hormones, such as GLP-1.

Probiotics may also help with weight loss directly. In one study, dieting women who took Lactobacillus rhamnosus for 3 months lost 50% more weight than women who didn’t take a probiotic. Another study of 210 people found that taking even low doses of Lactobacillus gasseri for 12 weeks resulted in an 8.5%.

It is however important to note that not all probiotics aid in weight loss. Some studies have found certain probiotics, such as Lactobacillus acidophilus, can even lead to weight gain.

3.3. Prebiotics

Prebiotics are classified as the non-digestible food ingredients that probiotics can feed off. They are used in the gut to increase populations of healthy bacteria, aid digestion and enhance the production of valuable vitamins. Galactooligosaccharides (GOS) are the most advanced form of prebiotics which belong to a group of particular nutrient fibers that feed and encourage the growth of good bacteria in the gut.

The major source of prebiotics is dietary fibre. They occur naturally in fruits and vegetables, but you can also take them in the form of nutritional supplements.

3.4. Bariatric Surgery

Bariatric surgery is an important method in the treatment of obesity. It is quite effective in achieving and protecting weight loss. This effectiveness of obesity treatment after bariatric surgery is not only related to food consumption. The altered microbiota after bariatric surgery has an impact on its effectiveness. Malabsorption status after bariatric surgery, changes in the metabolism of bile acids, changes in gastric pH, and changes in the metabolism of hormones lead to gut microbiota changes. Changes in microbiota also affect energy homeostasis. Because of these reasons, body weight loss is achieved after bariatric surgery.

4. What role will gut microbiota play in the treatment of T2DM in the future?

It is becoming increasingly clear that gut microbiota has profound impact on general health and well-being. Notably, it is now well-established that imbalanced gut microbiota is linked to host glycemic control impairment and T2DM development. Although the precise role of gut microbiota remains incompletely understood, further investigation is likely to be very helpful in the treatment and control of obesity, and resultant Type 2 Diabetes.

Current treatments of this complex chronic disease are far from being ideal since in a majority of patients, T2DM remains poorly controlled in the long run. Using pre/probiotics to control blood glucose has been considered for a long time, and the discovery of the key roles of gut bacteria in T2DM has boosted research efforts in this field.

A better understanding of how gut microbiota impacts general health will help in outlining new treatment strategies. These strategies will help in identifying probiotic strains with antidiabetic activities, or nutritional interventions that can increase helpful microbiota in the gut.

References:

1. Hindawi (2013): Influence of Gut Microbiota on Subclinical Inflammation and Insulin Resistance. Retrieved from https://www.hindawi.com/journals/mi/2013/986734/2. Frontiers in Endrocrinology (2019): Impact of Gut Microbiota on Host Glycemic Control. Retrieved from https://www.frontiersin.org/articles/10.3389/fendo.2019.00029/full

3. NCBI (2019): The effects of bariatric surgery on gut microbiota in patients with obesity: a review of the literature. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343052/

4. Bimuno(2018) : Prebiotics. Retrieved from https://www.bimuno.com/prebiotics

5. Healthline (2016): 8 Health Benefits of Probiotics. Retrieved from https://www.healthline.com/nutrition/8-health-benefits-of-probiotics

“…from a thermodynamic perspective, it is clear that obesity is generally the consequence of small cumulative imbalances of energy intake and expenditure.”

2017, Obesity Pathogenesis: An Endocrine Society Scientific Statement

calories in > calories out

We overeat

Too much food, too little physical activity

Overeating

(Energy in > Energy out)

Obesity and the obesity epidemic

1880s: Max Rubner demonstrates the laws of thermodynamics holds true for living organisms and establishes the isodynamic law of calories

1890s: Atwater and Benedict show thermodynamics holds true for humans and pioneer the science of calorimetry

1900s: von Noorden declares caloric imbalance as the cause of obesity

“The ingestion of a quantity of food greater than that required by the body leads to an accumulation of fat, and to obesity, should the disproportion be continued over a considerable period.”

Louis Newburgh’s revelation:

“All obese persons are alike in one fundamental respect—they literally overeat.”*

Therefore…

Obesity is caused by either a “perverted appetite” (eating too much) or “lessened outflow of energy” (insufficient expenditure).

Why don’t obese people compensate by eating less or exercising more, which, after all, are under conscious control, too? Because they suffer, says Newburgh, from various human weaknesses such as overindulgence and ignorance.”

Focus of attention? Full-Body Energy Balance

 

Energy Imbalance? How Much?

“Weight management is all about balance— balancing the number of calories you consume with the number of calories your body uses or `burns off.’”

The Centers for Disease Control

20 lbs/decade?

2 lbs/year

1 lb of fat ~ 3500 kcal

(2 * 3500 kcal)/365 days

19.2 Kcal/day

 

The average American consumes about 2700 kcal/day

Are we really talking about a .007 positive energy imbalance causing 2/3 of all healthcare expenditure in the United States????

The average American is now 30 pounds heavier than in 1960 — an average weight gain of .53 pounds per year.

5 kcal/day or a .002 positive energy imbalance

There are no stranger phenomena than the maintenance of constant body weight under marked variation in bodily activity and food consumption.

Eugene Du Bois, Basal Metabolism in Health and Disease, 1936

Eating less doesn’t work

Weight loss achieved in trials of calorie-restricted diets is “so small as to be clinically insignificant.”

Cochrane Collaboration, 2002

Exercising more doesn’t work

“It is reasonable to assume that persons with relatively high daily energy expenditures would be less likely to gain weight over time, compared with those who have low energy expenditures. So far, data to support this hypothesis are not particularly compelling.”

AHA/ACSM 2007, Physical activity guidelines

The fatal flaw with the energy balance hypothesis?

Remember this?

“The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories expended.”

The World Health Organization

an analogy? Wealth?

“The fundamental cause of wealth is a money imbalance between dollars earned and dollars spent.”

The World Economic Forum

dollars in > dollars out

The Alternative Hypothesis

Obesity is a disorder of excess fat accumulation

(Not energy balance, not over-eating, not sedentary behavior)

Gluttony and sloth are compensatory effects; they are not causes

German/Austrian hypothesis, pre-World War II

Gustav von Bergmann (1908), Julius Bauer

A hormonal/regulatory hypothesis

“Like a malignant tumor or like the fetus, the uterus or the breasts of a pregnant woman, the abnormal lipophilic tissue seizes on foodstuffs, even in the case of undernutrition. It maintains its stock and may increase it independent of the requirements of the organism. A sort of anarchy exists; the adipose tissue lives for itself and does not fit into the precisely regulated management of the whole organism… a lipomatous subject may die of starvation and still remain lipomatous.” Bauer, Archives of Internal Medicine, 1941.

“The effect after meals of withdrawing from the circulation even a little more fat than usual might well account both for the delayed sense of satiety and for the frequently abnormal taste for carbohydrate encountered in obese persons… A slight tendency in this direction would have a profound effect on the course of time.”

Russell Wilder, Mayo Clinic,1938

The hormonal/regulatory hypothesis

“…now more or less fully accepted, chiefly in Germany, by a number of leading investigators of metabolic diseases…”

Hugo Rony, Obesity and Leanness, 1940

“The current energy theory of obesity, which considers only an imbalance between intake of food and expenditure of energy, is unsatisfactory.”

“It is the distribution of energy in the body too which counts, not alone the rough imbalance between its intake and output.”

“The adipose tissue is not merely a passive storing place for reserve fat, but a living and active part of the body, with its own physiologic and pathologic processes.”

“An increased appetite with a subsequent imbalance between intake and output of energy is the consequence of the abnormal anlage rather than the cause of obesity.”

Bauer (1941)

The alternative hypothesis is another victim of World War II.

Insulin is “the principal regulator of fat metabolism.”

Rosalyn Yalow, Solomon Berson, 1965

Frayn, K.N. 2010. Metabolic Regulation: A Human Perspective, 3rd edition

Suppression of fat mobilization

The release of fatty acids from fat cells “requires only the negative stimulus of insulin deficiency.”

 

When insulin is secreted or chronically elevated, fat accumulates in the fat tissue.

When insulin levels drop, fat escapes from the fat tissue and the fat depots shrink.

We secrete insulin primarily in response to the carbohydrates in our diet.

“Carbohydrate is driving insulin is driving fat.”

George Cahill, 2005

 

“The most striking finding is that adipose tissue is exquisitely sensitive to the inhibitory effect of insulin on FFA release….”

“…insulin regulation of plasma FFA turnover/ oxidation is maximally manifest at low physiological plasma insulin concentrations….”

Bonadonna et al. 1990. Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans. Am. J. Physiol. 259:E736-750.

Refined grains, starches and sugars

Dysregulation of insulin signaling

Metabolic Dysfunction: Excess fat accumulation, obesity, and the obesity epidemic, metal inflammation, pain, cellular degradation

So why does dieting fail…  statistically, only 1:167 patients succeed

“All diets that result in weight loss do so on one basis and one basis only: they reduce total calorie intake.”

Textbook of Obesity, 2012

Diets that work?

Insulin reduction?

Calorie restriction (with carbohydrate restriction)

Carbohydrate restriction (without calorie restriction — i.e., LCHF/Leto)

Intermittent Fasting (TRF)

Fasting…

Raymond Greene, The Practice of Endocrinology, 1951

Foods to be avoided:

1. Bread and everything else made with flour…
2. Cereals, including breakfast cereals and milk puddings
3. Potatoes and all other white root vegetables
4. Foods containing much sugar
5. All the sweets…

You can eat as much as you like of the following foods:

1. Meat, fish, birds
2. All green vegetables
3. Eggs, dried or fresh
4. Cheese
5. Fruit…except bananas and grapes

The AMA trivializes this science as a debate about fad diets.

“fat is mobilized when insulin secretion diminishes” and yet low carbohydrate diets are “bizarre concepts of nutrition that should not be promoted to the public as if they were established scientific principles.”

JAMA, June 4, 1973. Vol 224, No 10.

Despite it being an essential response to infection and tissue injury, inflammation has also been associated with several pathological processes. Excessive acute inflammation causes tissue damage and non-resolving inflammation leads to chronic tissue malfunction, suggesting a delicate balance between the rapid and effective response to distresses in tissue homeostasis and the collateral damage on tissue function.

As a cluster, obesity, raised fasting plasma glucose, high cholesterol and hypertension comprise the metabolic syndrome.

Obesity is characterized by a low-grade chronic state of inflammation in which the level of pro-inflammatory cytokines such as TNF-α, IL-6, and CRP are increased. It is a state in which there is an over-accumulation of subcutaneous and/or abdominal adipose tissue.

This adipose tissue is no longer considered inert and mainly devoted to storing energy; it is emerging as an active tissue in the regulation of physiological and pathological processes, including immunity and inflammation. Adipose tissue is also implicated in the development of chronic metabolic diseases such as type 2 diabetes mellitus or cardiovascular disease.

Obesity can therefore be caused by inflammatory and metabolic diseases. Diet or dietary patterns as well play critical roles in obesity and other pathophysiological conditions. It is therefore recommended for one to have a healthy diet and other nutrients that are generally considered to be beneficial.

An explanation why motivation is reduced with metainflammation and a possible explanation why many patients with diabetes develop chronic pain pathologies with anhedonia, reflections on the addiction model of obesity.

The brain’s dopamine system, which drives motivation, is directly affected by chronic, low-grade inflammation. If your brain perceives that it is fighting off an infection or healing a wound, your brain recalibrates your motivation to do other things, so you don’t use up too much of your energy. This immune system mechanism regulates the use of energy resources during times of acute stress was likely adaptive in our ancestral environments, but the same mechanism to conserve energy for the immune system could become maladaptive when many people are less physically active and may have low-grade inflammation due to factors such as chronic stress, obesity, metabolic syndrome, or chronic pain.

Inflammatory cytokines have been shown to have a direct effect on mesolimbic dopamine (DA) that is associated with a reduced willingness to expend effort for reward. “the metabolic demands of chronic low-grade inflammation induce a reduction of striatal DA that in turn leads to a steeper effort-discounting curve because of reduced perceived ability (can’t) versus preference (won’t) for reward” ultimately contributing to motivational impairments

Michael T. Treadway, Jessica A. Cooper, Andrew H. Miller. Can’t or Won’t? Immunometabolic Constraints on Dopaminergic Drive. Trends in Cognitive Sciences, 2019; 23 (5): 435 DOI: 10.1016/j.tics.2019.03.003