There has been an intentional, unlabeled increase in manufacturing fructose, which is having an impact on weight and leading to the obesity epidemic. Soda drinkers in particular are consuming more fructose than people realize.

Manufactured high-fructose corn syrup contains a ratio of 55:45 fructose to glucose. High-fructose corn syrup was invented in the early 1970s and began to replace regular sugar in prepared foods around 1975. The onset of the obesity epidemic coincides with the use of HFCS. Current sweetened beverages made with HFCS have a fructose-to-glucose ratio of approximately 60:40, containing 50% more fructose than glucose. According to the National Institute of Health, “Several major brands appear to be produced with HFCS that is 65% fructose. Finally, the sugar profile analyses detected forms of sugar that were inconsistent with what was listed on the food labels.”

https://www.ncbi.nlm.nih.gov/pubmed/20948525

The intentional and unlabeled increase in fructose seems strange. Sugar content varied widely from amounts stated on labels; on average, the drinks had 18% more fructose than expected. HFCS is supposed to be 55% fructose, as compared to the 50% in table sugar.

Most foods and drinks are supposed to be using HFCS that is 42% fructose, but many sodas and drinks were using HFCS with a far higher content. Beverages that contained 65% fructose were Coke, Pepsi, and Sprite. Beverages that contained 60% fructose were Dr. Pepper, Gatorade, and Arizona Iced Tea.

Americans drink about 50 gallons of soda every year (containing 34 pounds of sugar), and soda drinkers are consuming far more fructose than anyone realized. Fructose specifically activates the reward center. Could it be the sugar-sweetened beverage companies know that the reward system is activated by fructose, creating more compulsion to purchase? The incidental side effect is excessive fat accumulation in the liver, and our epidemic of NAFLD, metabolic syndrome, prediabetes, and type 2 diabetes. Could the priming of the opioid epidemic also be associated?

Weight loss is clearly of primary concern to Americans, but the healthcare industry doesn’t seem to have a good solution. America doesn’t have a healthcare system; we have a sick maintenance cabal.

Between 1989 and 2016, the average American gained 29 pounds and spent more than $1 trillion on weight loss products. In 2016 alone, chronic diseases driven by the risk factors of being overweight or obese accounted for $480.7 billion in direct health care costs in the U.S., with an additional $1.24 trillion in indirect costs due to lost economic productivity. The total cost of chronic diseases due to obesity and overweight was $1.72 trillion, equivalent to 9.3 percent of the U.S. gross domestic product (GDP). Obesity as a risk factor is by far the greatest contributor to the burden of chronic diseases in the U.S., accounting for 47.1 percent of the total cost of chronic diseases nationwide.

Obesity has become such a significant independent disease that over the past 20 years, a completely new sub-specialty of obesity medicine has developed. Obesity affects more than one-third of the population, but less than 2 percent of obese individuals in the United States are actively treated, and of those treated, less than 10 percent manage to maintain weight loss.

Despite the fact that widespread obesity is a relatively new disease, associated with multiple reversible lifestyle factors, most of the clinical research funding and physician education has been geared towards medication management rather than lifestyle intervention. Using this standard of care approach, only 1 in 167 patients maintains weight loss.

Recommending dietary changes, as well as not prescribing medications, both erode profit margins for Big Food and Big Pharma. There is no money for them in a healthy population; all the money is in sick care.

Counting calories often fails. Instead, focus on eating real food.
What is a calorie?

A calorie in physics is the energy required to raise the temperature of 1 gram of water to 1 °C. The calorie you see on a food package, however, is actually a kilocalorie, or 1,000 calories, the amount of energy needed to raise the temperature of 1 kilogram of water 1 degree Celsius. The original method used to determine calories in a given food directly measured the energy it produced. The food was placed in a bomb calorimeter, a sealed container surrounded by water. The food was completely burned and the resulting rise in water temperature was measured.

What is a nutritional calorie?

Calories in food and calories as measured in physics are not the same. Nutritional calories exclude non-digestible components, such as dietary fiber and artificial sweeteners, both of which could be burned in a bomb calorimeter to generate heat. Many of these components humans can’t digest, such as cellulose, are the primary energy source for other species. Human calories are dependent upon the body’s ability to catabolize them, which usually involves enzymatic action rather than a high-temperature oxidation reaction.

Food labeling

Food labeling information is based upon food component calorie estimation, calculated by adding up the calories provided by the energy-containing nutrients: protein, carbohydrate, fat, and alcohol. Because carbohydrates contain some fiber that is not digested and utilized by the body, the fiber component is usually subtracted from the total carbohydrate before calculating the calories. The Atwater system uses the average values of 4 Kcal/g for protein, 4 Kcal/g for carbohydrates, 9 Kcal/g for fat, and 7 Kcal/g for alcohol.

http://www.nal.usda.gov/fnic/foodcomp/

http://www.nat.uiuc.edu

These nutritional calories are the energy available in food, which our body can use for chemical reactions or store in reserve as fat or glycogen, We count the calorie value that the body can extract from the food eating but ignore the interaction of that food as a signaling molecule, the non-digestible components, and the thermic energy consumed in breaking the food down for consumption.

There occurs a paradox in nutritional science where a high-calorie consumption of one food substrate causes weight gain, while the same calorie value of another substrate seems to cause weight loss, leading some to suggest that calories don’t count.

The laws of physics are not broken, however — calories do matter with respect to energy balance. Whether fat, protein, or carbohydrate, a surplus of calories will lead to weight gain. The relevance is the quality of the calorie and the body’s response to those specific nutrients as signaling molecules beyond the direct caloric value. The body’s ability to convert the food substrate into usable energy is based upon a highly complex process, starting with a mechanical breakdown of food as well as chemical and enzymatic processes throughout the gut that are significantly affected by the individual microbiome. The body is not static, and how it utilizes a nutrient and the extraction of energy associated with that nutrient changes continuously. The real issue in obesity and type 2 diabetes management is how the body utilizes the nutrients presented, and if that specific approach works for that specific individual, in that specific time.

Food as a nutrient and as programming:

Food should be viewed as both a source of nutrient energy (globally translated as calories), but also as a set of instructions to the body, a program directing the body to a specific action. Food is not completely degraded to its elemental parts during digestion; it maintains components of integrity, which then programs the cells. A corrupted program can lead to outcomes such as obesity or diabetes or even an autoimmune state. These instructions are not interpreted just by the body, but also the gut microbiome, which can independently translate the instruction set and create its own programming subroutine, which then affects the body. Conventional nutritional advice ignores the instructional programming code carried in the food we consume, but these instructional programs cannot be ignored.

Focusing on feeling deprived only increases desirability.

It’s easier to track not eating sugars and artificial sugars than actually counting their calories. Tracking and reliving the calories of carbohydrates you didn’t eat stimulates ghrelin, the hunger hormone.

Instead of calories, focus on real food.

It’s easier to track pounds of steak, fish, shrimp, or chicken than calories. It’s not what you didn’t eat; it’s what you did eat and who you are that matters. You are a person that doesn’t eat sugars (artificial or natural), you don’t fall prey to the big processed food manufacturers, and you know the truth about vegetable oil.

Focus on feeding windows and time-restricted feeding.

It’s easier to track the hours of healthy eating than calories. If you know that you will only eat in a limited time window of 6 to 8 hours per day, the rest of your time becomes available for real activity.

A calorie is a calorie only if it is incinerated in a bomb calorimeter, and the heat is given off is measured. Biologically derived calories from different foods have entirely different metabolic effects on the human body. Equal calorie portions of sugar, alcohol, meat or olive oil have widely differing effects on hormonal systems such as insulin, and satiety signals such as cholecystokinin or peptide YY. It is irrelevant how many calories a portion of food on a plate contains. What matters is how our body responds to the ingestion and absorption of those calories, how they are metabolized, and the resulting level of satiety (fullness).

The current caloric reduction strategies promoted for weight loss are ineffective. Using the standard calorie reduction approach produces a probability of attaining a normal weight at 1 in 167, generating a greater than 99% failure rate.

Fildes A et al. Probability of an Obese Person Attaining Normal Body Weight: Cohort Study Using Electronic Health Records. Am J Public Health. 2015;105: e54–e59

It is wrongly assumed that excessive caloric intake is the root cause of obesity. A calorie of food energy has different metabolic fates depending upon the hormonal stimulation. That same calorie may be used to generate body heat or stored as body fat. Obesity is a disease of failed energy partitioning, not one of total energy intake. The primary driver of this partitioning is the hormone insulin, which is specifically a fat storage growth hormone.

Focusing on calories in and calories out produces an inherent bias against high-fat food, which may actually protect against obesity and related diseases. The simplistic calorie focus results in a dietary guideline supportive of replacing fat with starch and sugar, which promotes insulin resistance.

It is our hope that shifting focus away from calories and emphasizing a dietary pattern that focuses on food quality rather than quantity will reduce obesity, related diseases and cardiovascular risk.

Malhotra A, DiNicolantonio JJ, Capewell S. It is time to stop counting calories, and time instead to promote dietary changes that substantially and rapidly reduce cardiovascular morbidity and mortality. Open Heart 2015;2(1) DOI: 10.1136/openhrt-2015-000273[published Online First: Epub Date]|.

Snacking will make you fat because of the chronic high insulin from the constant feeding.

There have been two major changes in our dietary habits since the 1970s, prior to the onset of the obesity epidemic. The change to a high-carbohydrate, low-fat diet has been well documented and has played an important role in causing obesity. However, the increase in meal frequency plays an equal if the not larger role and has been largely ignored. In the 1970s, the average number of eating opportunities was three – breakfast, lunch and dinner. By 2005, that number had almost doubled. Now we eat breakfast, snack, lunch, snack, dinner, and snack — and each of these contains refined carbohydrates more often than not.

Cameron JD. 6 meals per day do not result in greater weight loss. Br J Nutr. 2010 Apr;103(8):1098-101

Popkin BM. Does hunger and satiety drive eat anymore? Am J Clin Nutr 2010;91:1342–7

Tracking calories to determine that you are eating less is self-deception, and even if you did meticulously track calories, you would be off by as much as 20-50 percent. Even if you were absolutely perfect at tracking the actual calories, your calculations wouldn’t account for the bio-availability of nutrients, the effect of anti-nutrients from vegetables, or the thermic effect of food. Your resting metabolic calorie requirement changes from day to day, hour to hour, and season to season. Your gut microbiome, which determines nutrient absorption, changes continuously and interacts with your enteric nervous system and central nervous system.

Some people assume that their workout equipment which provides “calories burned” is actually accurate, but it’s not. Many people also reward themselves with a snack for exercising, which is a bad idea.

Instead of calorie counting:

Practice Hara Hachi bu, Confucian teaching, that instructs people to eat until they are 80 percent full. “Eat until you are eight parts (out of ten) full” or “belly 80 percent full.”

Simple changes to your eating patterns or the environment will dramatically increase the joy of food.

First, eat more slowly. Eating faster results in eating more. Slow down to allow your body to respond to cues, which tell us we are no longer hungry. You have a hormone called leptin that lets you know you are full, but if you wolf down your food, it doesn’t have enough time to work. Therefore, you should focus on food. Turn off the TV and the computer. If you’re going to eat, just eat.
Second, use small plates and tall, narrow glasses.
Third, cut out all the snacks. People eat from boredom or they eat from chemical signaling. Most of this chemical signaling can be eliminated when you remove artificial flavors, refined sugars, and industrial seed oils.

You probably have the mantra “breakfast is the most important meal of the day” stuck in your head. This was a baseless marketing phrase created in 1944 by General Foods to sell more cereal. John Harvey Kellogg of the Kellogg’s cereal company, a deeply religious Seventh Day Adventist, believed that cereal would improve Americans’ health and keep them from masturbating and desiring sex. Before the invention of cereal (to reduce masturbation), breakfast was not as standard or routine. Kellogg might actually have been half right — breakfast didn’t improve health, but increasing feeding frequency with processed cereal foods results in more insulin resistance and worsened male impotence.

Cut out breakfast, unless it is one of your two meals of the day and it falls inside your eating window. Regular breakfast consumption increases weight and insulin resistance by adding unnecessary calories to diets. https://doi.org/10.1136/bmj.l42

Eliminate vegetable oil.

One of the easiest substitutions you can make is eliminating vegetable oil and replacing it with real fat. Real fat tastes better, makes your food more flavorful, and carries fat-soluble vitamins.

Bottom line:

If you are eating real food, then your willpower is better spent somewhere other than calorie counting and calorie restriction. Remember, you are retraining your body to know when it’s actually full and to know what real hunger is. Your goal is to eat only when truly hungry.

Eliminating breakfast and restricting food to a 6 to 8 hour period of a given day makes this simple. Get rid of artificial flavorings, artificial and refined sugars, and refined foods. Healthy fat makes you satiated for a longtime. Satiety and the nutrient density of food is the ultimate test.

It’s not what you didn’t eat; it’s what you did eat and who you are that matters. It’s more about how your body responded to the food you did eat.

Reframe who you are:

You are a person that doesn’t eat sugars (artificial or natural), you don’t fall prey to the big processed food manufacturers, and you know the truth about vegetable oil.

There are some misconceptions about food and what to eat and not eat. The truth is that food is medicine and information for your body. Food is for real hunger, not boredom. Each patient is unique and any advice will need to be medically tailored.

Hara Hachi bu (腹八分目) is a Japanese phrase that translates to, “Eat until you are eight parts (out of ten) full” or “belly 80 percent full.”  You can make simple changes in everyday habits to learn to eat until you are only 80 percent full.

First, eat more slowly. Eating faster results in eating more.  Slow down to allow your body to respond to cues, which tell us we are no longer hungry. You should also focus on food.  Turn off the TV and the computer.  If you’re going to eat, just eat.  You’ll eat more slowly, consume less, and savor the food more.

Second, use small dishes.  Choose to eat on smaller plates and use tall, narrow glasses. You’re likely to eat significantly less without even thinking about it. Ten minutes before eating a meal, drink a large glass of cold water with lemon, and do so again 10 minutes after finishing a meal. Don’t snack, and don’t have anything in the house that you should not eat.

There are more steps you can take to make yourself healthier:

Step Step Step: Walk for 10 minutes after every time you eat or drink anything, even if it’s just water.

Step 1: Stop all vegetable oils — no canola, corn, soybean oil, Crisco, or margarine. Vegetable oils are also called industrial seed oils and were originally industrial waste products. Look at all food labels, and do not eat food with any vegetable oils listed. Do not use any spray-on oil. Instead, eat healthy oils and fats such as olive oil, coconut oil, butter, avocado, and duck fat.

Step 2: Eliminate all sugars and artificial sweeteners, or anything that is sweet on your tongue. Eliminate all refined sugars (juices, soda, diet soda, candy, chips).

Step 3: Sleep well and get at least 7 hours of uninterrupted sleep every night. Do not use your TV, phone, or computer in bed.

Step 4: Supplement with 4-6 grams of Krill or Fish Oil per day. Consider adding minerals like magnesium and salts as well. Ketone supplements may also play a role.

Step 5: Decide if you need a Cleanse Protocol or the Live Health Protocol. The purpose of either is NO vegetable oils, NO refined carbohydrates, and getting restorative sleep.

Cleanse Protocol: If you are starting out and are uncertain if specific foods may be contributing to your inflammation, or if you have weight to lose and are stuck, the cleanse protocol may be appropriate. You should only eat twice a day. During this time, you can eat as much beef, chicken, or fish as you like, and you can add butter and spices. That’s it for the next 4 weeks, then re-add one item per week that you might be sensitive to, as long as it still fits under the Live Health Protocol. Drink only water.

Live Health Protocol: This protocol helps you to live healthily and reduce your pain and inflammation. You should eat real food, such as meat (beef, pork, chicken, and fish), whole real eggs, green leafy vegetables, and seeds and tree nuts (almonds, macadamia). Drink only water, coffee, and unsweetened tea.

• Don’t eat fake industrial foods, carbohydrates or sugars (grains, cereals, grits, oatmeal, rice, rice cakes, pasta, potatoes, bread), fruits, or nuts from the soil (peanuts, cashews). Don’t drink soda, juice, diet soda, or creamers in coffee.

Bonus points:
Eat one to two tbsp of psyllium fiber dissolved in warm water 30 minutes before bed.
The ultimate health supplement is to skip one meal per day and eat only twice a day, in a short 6 to 8-hour feeding window.
No caffeine after 3 p.m.

Am I on the right track?
Some patients need immediate feedback, and this can be done by measuring ketones as a marker of fat loss.

Don’t make this complicated.  Eat the same thing every day for the first few weeks, and choose between 4-5 different meals.  You should feel full after the meal.  Don’t snack. It’s a process that will take a few weeks to learn.

Don’t think of this as not having something, look at what you can have and eat until you are satisfied.

The more vegetable oil and sugar you eat, the worse your pain and inflammation will be. You may have to increase your salt intake if you feel fatigued or get muscle cramps. Medications may have to be adjusted.

It’s about reducing your sugar intake and increasing protein and healthy fats, and the rest will take care of itself.

It’s a way of living, not a diet.  This is a process: you will fail a few times, but each time you fail you learn. Don’t try, just do.
For more information

Reversediabetes.md

 

Reverse Diabetes MD Presentation | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

Using an addiction model for obesity may be a more accurate way to view it. Obesity is more complicated than the simple calories in and calories out model.  Obesity is more than eat less, move more.

Obesity is affected by an underlying neuropsychological and neuroendocrine response system, which hijacks the endorphin system, resulting in a substance use-like disorder. Obesity will not be solved by the “eat less, move more” mantra when the hardwired response is a dopaminergic reward system.  No amount of habit formation can steer the patient away from a dopamine flux; this is an itch that demands to be scratched.  The treatment requires extinguishing cues, providing satiety, and temporarily substituting other behaviors.

The pathophysiology of the problem is as follows:

Obesity is not the problem; obesity is the result of the maladaptive behavior reinforced by engineered food. Obesity is just the most visible sign of the underlying issues.

Food activates two distinct systems: nutrient set points and the endorphin system.

The human brain has homeostatic set points for food and liquid consumption that are nutrient-based.  The reward system is activated through highly nutrient-dense foods, which promote primitive species survival by rapid fat storage.  This reward system activation of the primitive endorphin system occurs by dopamine production in the nucleus acumens, similar but not exactly the same as other addictive substances.

The neuropsychology of eating behavior is that some foods (those high in fat, sugar, and salt when combined with flavor enhancers) have an abuse potential similar to manufactured and concentrated substances like cocaine, alcohol, and opiates.

Compulsive overeating is a more classically recognized addiction disorder. Dopamine is the recognized neurotransmitter for classic substance abuse disorders and in the regulation of food reward and the hedonic aspects of appetite.

The classic addiction model does not completely explain obesity, however. We agree with the Nature article that analyzed the food addiction model as it relates to obesity stated that the model is “misleading”, with supporting evidence described as “inconsistent and weak.”

Obesity and the brain: how convincing is the addiction model? Nature Rev. Neurosci. 13, 279–286 (2012).

According to the Yale Food Addiction Scale, not all obese individuals exhibit food addiction

Using the Yale Food Addiction Scale criteria for substance dependence to food consumption, 25% to 37.5% of obese individuals meet the criteria.  This is 200-300% greater in obese versus lean groups.  There is a 500% greater rate of food addiction observed in obese people with binge-eating disorder.

Meule, A. How prevalent is “food addiction”? Front. Psychiatry 2, 61 (2011).

Davis, C. et al. Evidence that ‘food addiction’ is a valid phenotype of obesity. Appetite 57, 711–717 (2011).

Gearhardt, A. N. et al. An examination of the food addiction construct in obese patients with binge eating disorder. Int. J. Eat. Disord. 30 Aug 2011 (doi:10.1002/eat.20957).

The more likely mechanism is the overconsumption of food. Overconsumption of food is akin to goal‐directed drug-taking; it is under the control of the ventral striatal and prefrontal control and becomes habitual and compulsive driven predominantly by the dorsal striatum, with loss of executive control.

Acute administration of the drug of abuse produces a rise in acumens dopamine. Then, sensitization of the mesolimbic dopaminergic systems leads to an enhanced salience and consequent motivation towards drug‐related cues. Development of addiction is associated with a decrease in striatal D2 receptors, linked to a reward deficiency syndrome, where greater levels of drugs are taken to produce the same level of reward.

Rodents exposed to high‐sugar, high‐fat, and a combination of high‐sugar high‐fat diets develop behaviors that resemble addiction, such as binge eating, compulsive food‐seeking, and withdrawal symptoms.

Using sugar addiction models, an opiate‐mediated withdrawal syndrome has been demonstrated.

Compulsive food‐seeking is resistant to aversive foot shocks.

Opioid circuitry in both the nucleus acumens and the ventral palladium mediate taste-reactivity responses to palatable events.

Activation of mu opioid receptors in the ventral striatum and amygdala causes hyperphagia

Glycemic Index & Brain Function

Activation of the nucleus after high GI meal

 

It’s the hyperpalatable foods that produce an addiction‐like syndrome.

Animals presented with either high‐sugar or high‐fat diets eat excessively but do not gain weight as they offset the increased intake by eating less chow.

It is only the high fat and sugar combination that causes weight gain.

We believe that the obese patients’ relationship to food is more similar to a behavioral addiction like pathological gambling than a classic substance addiction, but there is no clear-cut withdrawal mechanism.  According to the National Institute of Health, there is a “harmful use that is maladaptive but does not meet the criteria for dependence.”

The refeeding cycle is driven by external cues, anticipatory clues, pancreatic training, and loss of fat metabolism adaptation.  Specific nutrients do cause an endorphin activation and a neurochemical effect in the brain.

The role of Big Food to increase food production results in depletion of micronutrients:

Megafarms use monocropping, which depletes the soil of beneficial microelements in order to maximize production.

By 1967, American corn farms were growing nearly three times as much corn as it had thirty years earlier.  The mono-cropped surplus was shared with livestock to increase production; the average dairy cow now produces more than 70 pounds of milk per day, and the top-performing Holsteins produce two hundred pounds per day, a 1,200 percent increase over the 1948 average.

Similarly, a typical potato farmer produced about 63 sacks of potatoes for every acre in the 1930s, but by the mid-1960s, it was up to two hundred sacks.

However, reduced micronutrients result in bland food. Maximizing food quantity came at the cost of nutrient density and food began to get blander. The solution to high production bland food was post-production processing with the addition of engineered flavoring to simulate taste.

The field of flavor engineering combines organic chemistry with engineering, neuroscience, psychography, psychophysics, ethnography, demography, molecular biology, finance, botany, economics, and physiology to produce flavors that specifically increase cravings.

Eating is a behavior-driven by an expectation of pleasure; we crave flavors. Hyperpalatable (tasty), highly processed foods are designed by food manufacturers to activate the reward system and increase food consumption.  The constant signaling barrage promotes grazing behavior.  Unfortunately, the brain’s perception of the nutrient value is distorted by synthetic flavors.  The patient ends up overconsuming manufactured carbohydrates and manufactured fat in a combination that is highly obesogenic.

Food palatability (engineering and variety) stimulate appetite, reduces satiety, and promotes excessive energy intake. Increased variety and palatability also cause weight gain in animal models. Food combinations high in sugar, fat, and flavor are hyperpalatable. Highly palatable meals were 44% larger than the average meal, which can cause activation of hedonic motivational pathways. Over time, consumption of a highly palatable diet may lead to reductions in brain reward response capacity.

Processed food contains primarily polyunsaturated fatty acids (PUFA) Omega-6 vegetable oils. Rancidity in vegetable oils is difficult for the human palate to discern, and therefore shelf stability of processed foods can be prolonged. The standard American diet has a greater than 20:1 ratio of unhealthy Omega-6 to healthy Omega-3. This distorted ratio is associated with many neuropsychiatric dysfunctions, including profound anxiety. Restoring a healthy ratio of 4:1 (even by supplementing Omega 3) seems to reduce this profound anxiety.

 

Buydens-Branches, L., & Branchey, M. (2007). Long-chain n-3 polyunsaturated fatty acids decrease feelings of anger in substance abusers. Psychiatry Research, 157(1-3), 95–104. doi:10.1016/j.psychres.2007.01.004

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225526/

Sucrose (table sugar) is a disaccharide made of 50% fructose and 50% glucose, and it is metabolized primarily in the small intestine releasing equal parts glucose and fructose. Glucose causes insulin release and is rapidly cleared from the bloodstream by insulin-dependent channels. However, fructose is independent of insulin and is rapidly taken up by the liver by a first-pass effect, and is preferentially stored as fat.

Glucose and Fructose have different effects on the addiction centers in the brain. Fructose produced activation in the brain’s ‘reward circuit,’ and increased the desire for food. Glucose, meanwhile, does not directly activate the reward center.

American College of Neuropsychopharmacology. “Fructose and glucose: Brain reward circuits respond differently to two kinds of sugar.” ScienceDaily. ScienceDaily, 10 December 2014. www.sciencedaily.com/releases/2014/12/141210080734.htm

In contrast, high-fructose corn syrup contains a ratio of 55:45 fructose to glucose. High-fructose corn syrup was invented in the early 1970s and began to replace regular sugar in prepared foods around 1975. The onset of the obesity epidemic coincides with the use of HFCS. Current sweetened beverages made with HFCS have a fructose-to-glucose ratio of approximately 60:40, containing 50% more fructose than glucose.

According to Science Daily, “Several major brands appear to be produced with HFCS that is 65% fructose. Finally, the sugar profile analyses detected forms of sugar that were inconsistent with what was listed on the food labels.”

https://www.ncbi.nlm.nih.gov/pubmed/20948525

University of Southern California – Health Sciences. “Soda consumers may be drinking more fructose than labels reveal.” ScienceDaily. ScienceDaily, 4 June 2014.

The intentional and unlabeled increase in fructose seems strange. Sugar content varied widely from amounts stated on labels, on average, the drinks had 18% more fructose than expected. HFCS is supposed to be 55% fructose, as compared to the 50% in table sugar.  Most foods and drinks are supposed to be using HFCS that is 42% fructose.

Beverages that contain 65% fructose were Coke, Pepsi, and Sprite. Beverages that contain 60% fructose were Dr. Pepper, Gatorade, and Arizona Iced Tea.

http://goranlab.com/pdf/Ventura%20Obesity%202010-sugary%20beverages.pdf

Americans drink about 50 gallons of soda every year (containing 34 pounds of sugar), but soda drinkers are consuming far more fructose than anyone realized.  Fructose specifically activates the reward center. Could it be the sugar-sweetened beverage companies know that the reward system is activated by fructose, creating more compulsion to purchase?

The incidental side effect is excessive fat accumulation in the liver, and our epidemic of NAFLD, Metabolic Syndrome, Prediabetes, Type 2 Diabetes.  Could the priming of the opioid epidemic  also be associated?

Treatment from an addiction approach:
Extinguishing the precedent cues
Temporal substitution
Satiety

Effects on the Neuroendocrine systems:
Reducing Neuroinflammation by augmenting Omega 3
Improving insulin resistance by emptying the liver
Time-limited feeding

References:

Pro v Con Reviews: Is Food Addictive?  Is food addiction a valid and useful concept? H. Ziauddeen  P. C. Fletcher. 12 October 2012 https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X.2012.01046.x

http://goranlab.com/pdf/Ventura%20Obesity%202010-sugary%20beverages.pdf

 

Why Treat Obesity and Prediabetes | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

It’s important to treat obesity and prediabetes before diabetes can develop because obesity is the leading indicator in developing diabetes. Data from the National Health and Nutrition Examination Survey reveals that only 12.2 percent of American adults are metabolically healthy.  Eighty-six million adults in the U.S. have prediabetes (HbA1c ranging from 5.7–6.4%), and up to 70 percent of these individuals will eventually develop diabetes.  Obesity is the main factor in the progression of prediabetes to diabetes.

Almost all patients who present to our clinics have significant issues associated with pain, which is one of the hallmarks of metabolic inflammation.  The vast majority of patients who present to our clinics are also overweight, and when we evaluate their biochemical markers, they have prediabetes and metabolic inflammation.  Pre-diabetes is known to be a condition that precedes type 2 diabetes (T2D).  The changes in immune cells’ concentration and function can cause an increased migration of these inflammatory cells to already inflamed tissue. There is also upregulation of cytokines. This immune activation begins during the pre-diabetic state.

The HbA1c has a significant tendency to miss cases of diabetes.  When compared to the oral glucose-tolerance test (OGTT), HbA1c will under-diagnose diabetes in 73 percent of adults.  HbA1c has a sensitivity of 26.93 percent and specificity of 99.39 percent.

The 2019 American Diabetes Association Standards of Medical Care in Diabetes recommends at least yearly screening for those with high risk of prediabetes, stating that patients with “A1C 5.7−6.4% (39−47 mmol/mol)…are ideal candidates for diabetes prevention efforts” as well as that “lifestyle/behavioral therapy featuring an individualized reduced calorie meal plan is highly effective in preventing type 2 diabetes and improving other cardiometabolic markers (such as blood pressure, lipids, and inflammation). ”

• Weight loss utilizing coaching, dietary change, self-efficacy, and increased physical activity can help as well. The recommendation is to “achieve and maintain 7% loss of initial body weight and increase moderate-intensity physical activity (such as brisk walking) to at least 150 min/week.” Additionally, “Metformin therapy for prevention of type 2 diabetes should be considered in those with prediabetes, especially for those with BMI ≥35 kg/m2, those aged <60 years, and women with prior gestational diabetes mellitus.”

They further state that “Prediabetes is associated with heightened cardiovascular risk; therefore, screening for and treatment of modifiable risk factors for cardiovascular disease is suggested.”

Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes—2019; American Diabetes Association. Diabetes Care 2019 Jan; 42(Supplement 1): S29-S33. https://doi.org/10.2337/dc19-S003

Type 2 diabetes is characterized by both peripheral insulin resistance and inadequate insulin production. Insulin resistance has been associated with elevated levels of free fatty acids and proinflammatory cytokines in plasma and leads to decreased glucose transport into muscle cells.

For Type 2 Diabetes to occur, both insulin resistance and inadequate insulin secretion must co-exist. For example, overweight individuals may have insulin resistance, but diabetes only develops in those who cannot increase insulin secretion sufficiently to compensate for their insulin resistance. Unfortunately, this period of prediabetes permits significant tissue damage.

Increased cardiovascular risk begins prior to the development of persistent hyperglycemia, due to insulin resistance (Stern, 1996; Haffner and D’Agostino, 1999).  Macrovascular damage has already occurred with the onset of insulin resistance, while microvascular damage increases with the onset of hyperglycemia.  The United Kingdom Prospective Diabetes Study (UKPDS) analyzed more than 4,000 type 2 diabetes patients who were aggressively treated and followed for up to 15 years. Those in the intensely treated group had a significantly lower rate of progression of microvascular complications than patients receiving standard care. Rates of macrovascular disease were only reduced in the metformin-monotherapy arm, where the risk of myocardial infarction was significantly decreased.

In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, there was a 66 percent increase in mortality per 1 percent increase in HbA1c, with the best outcome for patients maintaining HbA1c below 6.0.

 

Early intervention in the atherogenic prediabetic state, while HbA1c remains in the prediabetic range (5.7-6.4%),  reduces the 200-400 percentage of increased risk of cardiovascular events and plaque formation.  This intervention is cost-effective, low-risk, and disease-modifying if using both lifestyle modification and metformin.  Delaying early intervention (when HbA1c  > 6.5) increases the glycocalyx and endothelial damage and irreversible diabetes-specific microvascular complications.  We readily acknowledge that overly rigorous blood glucose control may have a negative outcome if multiple hypoglycemic agents are used in addition to metformin.  However, the ability to tolerate metformin is excellent if dose escalation is done slowly.

Our early intervention is geared towards lifestyle modification and metformin monotherapy, using the following lifestyle modifications: reducing gastrointestinal permeability from gluten and gliadin, thus reducing the inflammatory load
reducing carbohydrate loading to reduce insulin resistance and fat deposition in the liver, specifical fructose
restoring an appropriate Omega 6:3 ratio by removing industrial seed oils and supplementing with omega-3 fish oil
improving insulin sensitivity by reducing insulin release, using time-restricted feeding, and reducing the overall glycemic load

Metformin

• Metformin has historically been considered a pharmaceutical first-line agent in the treatment of type 2 diabetes, with a very low side effect profile, except for individuals with renal compromise.  Despite the extensive use of metformin, its mechanism of action remains unclear. The following are possibilities when considering how metformin works:
• antibiotic, changing the gut microbiome ratio to a lower proinflammatory load
• effect on the mTOR pathway, which may independently reduce neuropathic pain and is associated with cancer suppression as well as life-lengthening
• change in vagal tone, reducing sympathetic tone and cortisol secretion
• enhances insulin sensitivity at the receptor and lower blood level of insulin
• reduces the formation of advanced glycation end-products
• inhibits the liver’s ability to release glucose into the bloodstream
• inhibits the mitochondrial respiratory chain in the liver, leading to activation of AMPK, enhancing insulin sensitivity (via effects on fat metabolism) and lowering AMP, thus reducing the expression of gluconeogenic enzymes
• inhibition of fructose-1,6-bisphosphatase by AMP in the liver

The longer we can delay progression to Type 2 Diabetes, even if using oral hypoglycemics, the more cost effective it is. The following is a cost analysis of early intervention with metformin, compared to delay in treatment until insulin supplementation is required due to B-cell fatigue, assuming similar lifestyle management:

• The average wholesale cost of generic Metformin is less than $0.05/tablet 1,000 mg, making a 30-day supply $6.00 per month. https://www.goodrx.com/metformin?dosage=1000mg&form=tablet&label_override=metformin&quantity=60
• For an average wholesale insulin cost, a combination of both long-acting and short-acting insulin is prescribed.

Long-acting insulin, Lantus, costs $431/month, and the short-acting insulin, Humalog, costs $533/month, for a combined cost of  $964/month excluding injection supplies.

https://www.goodrx.com/insulins

Someone could pay for 160 months of metformin therapy for the same cost as 1 month of insulin therapy.

Metformin continues to reduce the likelihood of developing type 2 diabetes among those at high risk for it over 15 years, particularly among those with higher baseline glycemia.  Metformin prevents diabetes, which is important because diabetes leads to vision loss, renal failure, amputations, and heart disease.

Preventing or delaying or reducing the risk for diabetes is, is in and of itself, important. Metformin is cheap and well-tolerated with a powerful effect.

Diabetes prevention seen at 15 Years, regardless of analytic method.

Long-term Effects of Metformin on Diabetes Prevention: Identification of Subgroups That Benefited Most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Prevention Program Research Group. Diabetes Care Apr 2019, 42 (4) 601-608; DOI: 10.2337/dc18-1970

Reversion to normal glucose regulation with reversal of insulin resistance, using early intervention prevents progression of prediabetes to diabetes.  Normalized glucose regulation is an indicator of disease modification, with measurable reduced all-cause mortality.  Our goal is to reduce metabolic inflammation and avoid the preventable complications of insulin resistance.

References for additional reading:

Prevalence of optimal metabolic health is remarkably low among U.S. adults, with one in eight Americans achieving optimal levels of the five traditional cardiometabolic risk factors without medication.

Joana Araújo, Jianwen Cai, and June Stevens. Metabolic Syndrome and Related Disorders. Feb 2019. http://doi.org/10.1089/met.2018.0105

ENDO 2019: The Endocrine Society Annual Meeting.

https://www.endocrine.org/news-room/2019/endo-2019—a1c-test-misses-many-cases-of-diabetes

Prescrire Int. 2014 Nov;23(154):269-72.  https://www.ncbi.nlm.nih.gov/pubmed/25954799

N Engl J Med 2008; 358:2545-2559 https://www.nejm.org/doi/full/10.1056/nejmoa0802743

“Patients allocated metformin, compared with the conventional group, had risk reductions of 32% (95% CI 13-47, p=0.002) for any diabetes-related endpoint, 42% for diabetes-related death (9-63, p=0.017), and 36% for all-cause mortality (9-55, p=0.011).”

Lancet. 1998 Sep 12;352(9131):854-65.  https://www.ncbi.nlm.nih.gov/pubmed/9742977

“The increased risk of adverse cardiovascular outcomes associated with type 2 diabetes does not begin at the diagnostic cutoff for plasma glucose (or HbA1c) at which the condition is diagnosed. Rather, there appears to be a continuum of increased microvascular and macrovascular risk that extends to levels of glycaemia well below these cutoffs. While it seems reasonable to hypothesize that correction of prediabetic dysglycemia might also reduce the future risk of adverse cardiovascular outcomes, further evidence from clinical trials is needed to demonstrate improved long-term outcomes in this setting.”

Hopper I, Billah B, Skiba M, Krum H. Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomized controlled clinical trials. Eur J Cardiovasc Prev Rehabil. 2011;18:813–823. [PubMed]

Metformin to be considered in IGT, IFG, HbA1c of 5.7–6.4 %, especially in BMI >35 kg/m², age <60 years or prior GDM

American Diabetes Association Standards of medical care in diabetes—2014. Diabetes Care. 2015;38(Suppl 1):S31–S33.

“As most individuals with prediabetes will eventually go on to develop type 2 diabetes, the large number of people with prediabetes worldwide implies a reservoir of new type 2 diabetes cases to come. Optimizing the management of prediabetes, with the aim of delaying diabetes onset for as long as possible, is therefore an urgent global clinical priority.”

“In the Diabetes Prevention Study (DPS), for example, no patient who achieved at least four of the five lifestyle goals (weight reduction, total fat intake, saturated fat intake, fibre intake, exercise) went on to develop diabetes during the period of follow-up.”

Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes Care 2012;35:723–730

“The Diabetes Prevention Program (DPP), a randomized controlled clinical trial, demonstrated that compared with the placebo intervention (placebo), the intensive lifestyle intervention (lifestyle) reduced the incidence of type 2 diabetes by 58%, and the metformin intervention (metformin) reduced the incidence of type 2 diabetes by 31% over 2.8 years”

Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012;35:731–737

Balk EM, Earley A, Raman G, Avendano EA, Pittas AG, Remington PL. Combined diet and physical activity promotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the Community Preventive Services Task Force. Ann Intern Med 2015;163:437–451

Knowler WC, Barrett-Connor E, Fowler SE, et al.; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403

About GGT (Oracle of Death or The final common Pathway) | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

Excess processed foods and carbohydrates can also lead to increased liver damage. GGT isn’t something that people consider when considering health risks, but it could be referred to as the “oracle of death” or “the final common pathway” because of how it predicts liver damage and subsequent disease. Gamma-glutamyl transferase (GGT) is an enzyme found in high concentrations in the liver, and it is elevated in diseases that cause damage to the liver.

GGT is a transferase that catalyzes the transfer of gamma-glutamyl functional groups from molecules such as glutathione (GSH) to an acceptor that may be any amino acid, a peptide, or water. GSH removes free radical toxins and provides natural protection against harmful oxidative stress. The normal biologic role of GGT is to reconstitute glutathione, the body’s master antioxidant.

GGT is the only enzyme of the GSH cycle located on the outer surface of the plasma membrane. It breaks down extracellular GSH and provides cysteine, the rate-limiting substrate, for intracellular de novo synthesis of GSH. When GGT concentrations are above “low-normal” ranges, excess GGT can catabolize (degrade) GSH, causing critical depletion of this antioxidant.

When GSH is depleted, oxidative stress and damage start to occur.  This leads to lead to a cycle of the irreversible cell, tissue, and DNA damage, and severe impairment of organ function. Elevated GGT indicates that you are demanding more GSH, and there was not enough GSH in the system to deal with an oxidative insult. During oxidative stress, GGT gene expression is increased, an adaptation to stress.

If you consume excess carbohydrates, processed foods, vegetable oil, alcohol, or other liver toxins, the liver can become insulin resistant, resulting in a high insulin level. Elevated insulin is a metabolic switch that causes fat to accumulate in the liver. Hyperinsulinemia (excess insulin) drives insulin resistance, and insulin resistance encourages more hyperinsulinemia.

As fat accumulates in the liver, the liver becomes more insulin resistant and simultaneously undergoes more oxidative stress, depleting Glutathione, which is reflected by increasing GGT.

 

GGT data was originally collected by the smartest guys in the room (life insurance actuaries), and the original reason for measuring it was its ability to mark alcohol abuse in life insurance applicants. The life insurance industry collected this data for many years, resulting in biometric stratification of mortality risk, and it has now become central to the life insurance underwriting process for predicting all causes of death.

Palmier J., Dixon A., Lanzarth B. Leading Contributors to Mortality Risk in Life Insurance Applicants. Schaumburg, Ill, USA: Society of Actuaries; 2012. (Smalltalk Issue 38).

Palmier J., Lanzrath B. J. Laboratory and biometric predictors of cancer-related mortality in an insured population. Journal of Insurance Medicine. 2012;43(3):162–168

 

Traditionally, elevated GGT has been associated with liver dysfunction, most often alcohol overconsumption. Other drugs that can elevate GGT include barbiturates, phenytoin, anti-inflammatory drugs (including aspirin), St. John’s Wort, and kava.

We now believe that elevated GGT is an early warning sign of other health risks, such as atherosclerosis, stroke, type 2 diabetes, kidney disease, cancer, metabolic syndrome (MetS), and all-cause mortality.

GGT doesn’t have to be above levels considered normal by a laboratory in order to have increased risks. When GGT concentrations exceed the lowest 25% to 35% of normal population ranges, disease risks grow in proportion to increased GGT. This “dose-response” increase in GGT concentration, indicates a greater risk of future diseases and mortality, even when GGT levels are within “normal” ranges.

Even a higher end of normal GGT poses a significant increase in risk:

Normal low

• < 9 U/l for women
• < 14 U/l for men

Moderately high with increased risk

• 18 U/I for women
• 28 U/I for men

High levels of normal with significant increase in risk

• >36 U/L for women
• >56 U/L for men

According to the National Institute of Health, “GGT levels measured in the Framingham Offspring Study (FOS), only moderately elevated GGT, starting at levels just above population GGT medians, and often measured one or two decades in advance of disease endpoints or mortalities, established GGT as an early predictive marker of MetS, CVD, heart failure, and all-cause mortality.”

 

Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk

Gerald Koenig, Stephanie Seneff. Dis Markers. 2015; 2015: 818570. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620378/

GGT is predictive of future mortality. In the general population, about 21% of men and 15.6% of women have elevated GGT. Elevated GGT, even within normal laboratory ranges, presents significant additional risks.

Patients with a high end of normal  GGT have more than a 1.5-fold risk of dying from cardiovascular diseases in comparison to people with normal low levels of GGT.

All-cause mortality and elevated GGT in the upper fifth of the population levels results in a 2x higher risk for all-cause mortality, 1.7x  higher risk for cardiovascular death, and 2.3x higher risk for cancer and death. Liver cancer and elevated GGT in the upper fifth of the population levels (not even top 1%) results in 15 to 18 times higher risk hepatic cancer and death from liver cancer

Hazard ratios

According to Clinical Chemistry, “GGT above the reference category (GGT ≥9 U/L in women, ≥14 U/L in men) was significantly (P <0.001) associated with all-cause, cancer, hepatobiliary, and vascular mortalities.”

Gamma Glutamyltransferase and Long-Term Survival: Is It Just the Liver? Lili Kazemi-Shirazi et al. DOI: 10.1373/clinchem.2006.081620 Published April 2007. http://clinchem.aaccjnls.org/content/53/5/940

Elevated levels also result in increased risk for atherogenic dyslipidemia, a predictor of impending heart disease. Dyslipidemia is a reflection of insulin resistance, and when your liver becomes insulin resistant, it will tend to cause visceral fat accumulation in your organs.  Visceral fat accumulation is most noticeably seen as a larger waist than expected, or a “beer belly,” even a small one in women.  Many people are apparently slim, but they are TOFI (thin outside, fat inside).

Dyslipidemia is a combination of high LDL, low HDL, high triglyceride, high particle count of LDL

• LDL:HDL
  Triglyceride:HDL
  LDL-P
  Oxidized LDL
  GGT

 

Most idiopathic or essential hypertension (where they don’t know the cause of the high blood pressure) – is related to hyperinsulinemia with resulting vessel stiffness and thickness.  Reversing hypertension may be as simple as reducing insulin.

GGT correlates with atherosclerotic plaque formation in arteries, which is associated with an inflammatory disease, metainflammation.

GGT activity also co- locates with oxidized LDL in the atherosclerotic plaque, as seen below.

Circulating Markers of Liver Function and Cardiovascular Disease Risk.

Arterioscler Thromb Vasc Biol. 2015 Nov;35(11):2290-6. doi: 10.1161/ATVBAHA.115.305235. Epub 2015 May 14.

https://www.ncbi.nlm.nih.gov/pubmed/25977566

Risk for future diabetes:

If your BMI is low and you have a low GGT, you have a baseline risk of 1.0

If you have a low BMI below 25 and a high GGT (in the top quarter of the population), you have a 3x risk of diabetes within 3-5 years

If you have a moderate-high BMI greater than 30 and a high GGT (in the top quarter of the population), you have a 15x risk of diabetes within 3-5 years

If you have a high BMI greater than 35 and a high GGT (in the top quarter of the population), you have a 19x risk of diabetes within 3-5 years

Obesity is one factor that predicts future diabetes, but GGT may be more accurate. If you correct the obesity level for GGT, obesity doesn’t predict diabetes. GGT is more predictive of diabetes as it reflects liver insulin resistance and liver inflammation.

Our treatment protocols for elevated GGT encourage:

• Decompress the fat out of the liver by either time-restricted feeding or fasting
• Eliminate vegetable oil and supplement with fish or krill omega-3 oil
• Switch to natural fats, such as butter and tallow
• Eliminate processed foods, including refined grains and acellular carbohydrates
• Metformin to enhance insulin sensitivity in the liver
• Moderate to high coffee consumption has been universally shown to reduce GGT

Reverse Diabetes MD Presentation | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

It’s time to take a more detailed look at the root causes of obesity, prediabetes, and type 2 diabetes because of the implication for future public health. Reversing the obesity, prediabetes, and type 2 diabetes epidemic is today’s most important public health challenge.  Nearly 70% of population is insulin resistant, prediabetic, or frankly diabetic.

Kraft, J.R.:” Glucose Insulin Tolerance. A routine Clinical Laboratory Tool Enhancing Diabetes Detection”. In O.B. Hunter. Jr. (ed): Radio assay: Clinical Concepts. Skokie, IL. Professional Education Dept. G.D. Searie& Co., 1974. Pp 91-106

Using data from the National Health and Nutrition Examination Survey 2009-2016, less than 12.2% of the US population is now considered metabolically healthy.

“Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009-2016,” was published online Nov. 28 in the journal Metabolic Syndrome and Related Disorders.

Almost all the patients who present to our clinics are overweight, and when we evaluate their biochemical markers, they have prediabetes and metabolic inflammation.  Pre-diabetes is known to be a condition that precedes type 2 diabetes (T2D).  The changes in immune cells concentration and function can cause an increased migration of these inflammatory cells to already inflammed tissue. There is also upregulation of cytokines. This immune activation begins during the pre-diabetic state.

According to studies published in a cardiovascular and heart disease prevention journal in Europe, “The increased risk of adverse cardiovascular outcomes associated with type 2 diabetes does not begin at the diagnostic cutoff for plasma glucose (or HbA1c) at which the condition is diagnosed. Rather, there appears to be a continuum of increased microvascular and macrovascular risk that extends to levels of glycemia well below these cutoffs.”

Hopper I, Billah B, Skiba M, Krum H. Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomized controlled clinical trials. Eur J Cardiovasc Prev Rehabil. 2011;18:813–823. [PubMed]

A 2015 global survey carried out by Credit Suisse revealed a substantial level of misinformation that exists among doctors and nutritionists:

• 92% believed that fat consumption could lead to cardiovascular issues
• 87% believed that fat consumption could lead to obesity
• 54% of doctors and 40% of nutritionists thought that eating cholesterol-rich foods raised blood cholesterol
• 83% of doctors believed butter was worse than margarine
• 66% of doctors believed vegetable oils are beneficial to health.

Fat; The New Health Paradigm – Credit Suisse 2015

The fact that prescription medications are now the third most common cause of death globally after heart disease and cancer should be alarming. The Academy of Medical Royal Colleges and the BMJ provide a blueprint to reduce the harms of “too much medicine” as part of the Choosing Wisely campaign, with recommendations to educate the public to ask their medical professionals whether there are “simpler or safer options” to taking a medication.

Malhotra A, Maughan D, Ansell J, Lehman R, Henderson A, Gray M et al. Choosing Wisely in the UK: The Academy of Medical Royal Colleges’ initiative to reduce the harms of too much medicine BMJ 2015; 350 :h2308.

The root cause of obesity, prediabetes, and type 2 diabetes are embedded in the food environment. Legislative efforts to encourage less consumption of processed foods and sugary drinks will help significantly reduce the burden of diet-related disease, which now contributes to more disease and death globally than physical inactivity, smoking and alcohol combined.

Newton JN, Briggs AD, Murray CJ, Dicker D, Foreman KJ, Wang H, et al. Changes in health in England, with analysis by English regions and areas of deprivation, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015. doi:10.1016/S0140-6736(15)00195-6.

Processed foods labelled as “low-fat” or “proven to lower cholesterol” should be avoided. The flawed science behind the 1977 Dietary Guidelines promoted a reduction in fat consumption, which permitted an increase in carbohydrate consumption.  The shift from natural food containing animal products and fats resulted in an increase in processed food consumption rich in carbohydrates, processed grains, and industrial seed oils. In the United States between 1961-2011, 90% of the increased calorie intake has come from carbohydrates and polyunsaturated vegetable oils.

Select Committee on Nutrition and Human Needs. Dietary goals for the United States. First ed. Washington: U.S. Govt. Print. Off., February 1977.

CreditSuisse.Fat: The New Health Paradigm: Research Institute, 2015: 76

 

The rise in obesity following these guidelines suggest that they may be a root cause of the problem. Nutrition science was originally founded on human correlational studies, which are frequently flawed. But that science has also been corrupted by commercial influences. The undue influence of the food industry on official guideline bodies and politicians has posed a significant threat to public health. “Nutritional epidemiology is a scandal. It should just go to the waste bin,” claims professor John Ioannidis, professor of medicine, health research and policy, and statistics  at Stanford University School of Medicine and School of Humanities and Sciences.

Max Planck also said, “Science progresses one funeral at a time.” it took nearly 50 years from the first published scientific evidence linking smoking and lung cancer until effective regulation was introduced to curb tobacco consumption. Big tobacco companies adopted a strategy of denial, planting doubt, obfuscating, and even buying the loyalty of scientists. The recent similarities with big food and big pharma are uncanny.

Brownell KD, Warner KE. The perils of ignoring history: big tobacco played dirty and millions died. How similar is big food? Milbank Q 2009;87: 259–94.

The food industry has a fiduciary responsibility to produce profit for their shareholders. Unfortunately, the food industries’ downstream cost to public health is bankrupting most westernized societies. Unfortunately, academics, institutions and journals whose primary responsibility is to patients and scientific integrity have at times colluded with industry for financial gain.  It is incredulous to suggest that consuming 22 teaspoons of sugar daily falls within recommended guidelines. This is despite the known science that for optimum health there is no dietary or biological requirement for sugar to be consumed in the human diet.

Malhotra, A. (2013) The dietary advice on added sugar needs emergency surgery. BMJ, 346, f3199.

 

Evidence from multiple randomized controlled trials reveals that a higher-fat, lower-carbohydrate diet is superior to a low-fat diet for weight loss and cardiovascular disease risk reduction. A meta-analysis of 53 randomized controlled trials involving 68,128 participants conducted by the Harvard School of Public Health concluded that “when compared with dietary interventions of similar intensity, evidence from randomized controlled trials does not support low-fat diets over other dietary interventions for long-term weight loss. In weight loss trials, higher-fat weight loss interventions led to significantly greater weight loss than low-fat interventions.”

Sackner-Bernstein J, Kanter D, Kaul S. Dietary Intervention for Overweight and Obese Adults: Comparison of Low-Carbohydrate and Low-Fat Diets. A Meta-Analysis. PLoS One 2015;10(10):e0139817 DOI: 10.1371/journal.pone.0139817[published Online First: Epub Date]|.

Bazzano LA, Hu T, Reynolds K, et al. Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial Effects of Low-Carbohydrate and Low-Fat Diets. Ann. Intern. Med. 2014;161(5):309-18 DOI: 10.7326/M14-0180[published Online First: Epub Date]|.

Harcombe Z, Baker JS, Cooper SM, et al. Evidence from randomized controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart 2015;2(1) DOI: 10.1136/openhrt-2014-000196[published Online First: Epub Date]|.

 

The Women’s Health Initiative, one of the largest randomized controlled diet trials ever performed, used 48,835 post-menopausal women, with a mean follow-up period of 8.1 years, randomized to either a standard western diet or a low-fat, calorie-reduced diet with increased exercise.   The authors had postulated that a low-fat, calorie-reduced diet with increased exercise would reduce cardiovascular disease. The intervention achieved an 8.2% energy decrease in total fat intake and a 2.9% energy decrease in the saturated fat intake but did not reduce risk of CHD or stroke. The reduction in dietary fat and total daily calories (361 calories/day reduction) failed to produce any significant weight loss over the duration of the study, thus rejecting the hypothesis that the low-fat diet is either beneficial for cardiovascular disease or weight loss.

Howard BV, Van Horn L, Hsia J, et al. Low-fat dietary pattern and risk of cardiovascular disease: The Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):655-66 doi: 10.1001/jama.295.6.655[published Online First: Epub Date]|.

By contrast, consumption of fat induces satiation and when compared to the other macronutrients such as protein and carbohydrates,  fat has the least impact on blood glucose and insulin production. Excessive insulin production and subsequent insulin resistance is the precursor to type 2 diabetes.  A meta-analysis of the evidence available prior to the 1977 US change in dietary guidelines did not support the dietary fat restrictions. Despite the lack of scientific consensus, these guidelines advised to limit total fat to 30% of calorie intake and saturated fat to 10% of calorie intake, creating the low-fat craze and a national experiment on diet-induced metabolic dysfunction.

Harcombe Z, Baker JS, Cooper SM, et al. Evidence from randomized controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart 2015;2(1) doi: 10.1136/openhrt-2014-000196[published Online First: Epub Date]|.

 

Thirty years later, in 2014, a meta-analysis of 76 studies with over 600,000 participants from 18 countries concluded that “Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.”

Chowdhury R, Warnakula S, Kunutsor S, et al. Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis. Ann. Intern. Med. 2014;160(6):398-406 doi: 10.7326/M13-1788[published Online First: Epub Date]|.

 

A study published in the BMJ (British Medical Journal) noted that “Saturated fat intake was not associated with all- cause mortality, CVD mortality, total CHD, ischemic stroke, or type 2 diabetes.”

de Souza RJ, Mente A, Maroleanu A, et al. Intake of saturated and trans unsaturated fatty acids and risk of all-cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ 2015;351 doi: 10.1136/bmj.h3978[published Online First: Epub Date]|.

 

Further, The American Journal of Clinical Nutrition found that “diets with cheese and meat as primary sources of saturated fatty acids cause higher HDL cholesterol and apo A-1 and, therefore, appear to be less atherogenic than is a low-fat, high- carbohydrate diet.”

Thorning TK, Raziani F, Bendsen NT, Astrup A, Tholstrup T, Raben A. Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers in overweight postmenopausal women: a randomized crossover trial. The American journal of clinical nutrition 2015 doi: 10.3945/ajcn.115.109116[published Online First: Epub Date]|.

 

Full-fat dairy may protect against obesity.  A 2014 study concluded: “Participants in the highest tertile of whole-fat dairy intakes (milk, cheese, yogurt) had significantly lower odds for being obese. “

Crichton GE, Alkerwi Aa. Whole-fat dairy food intake is inversely associated with obesity prevalence: findings from the Observation of Cardiovascular Risk Factors in Luxembourg study. Nutrition Research 2014;34(11):936-43 doi: 10.1016/j.nutres.2014.07.014[published Online First: Epub Date]|.

 

Cohort studies confirm that plasma saturated fatty acids from dairy sources such as cheese and yogurt are inversely related to the incidence of type 2 diabetes. By contrast, the plasma saturated fat palmitic acid, linked to the consumption of starch, sugar and alcohol, is strongly associated with the development of type 2 diabetes.

Mozaffarian D. Saturated fatty acids and type 2 diabetes: more evidence to re-invent dietary guidelines. Lancet Diabetes Endocrinol 2014;2:770–2

Natural, non-processed, non-refined food (meat, fish, eggs, nuts, seeds, olive, avocados) contains high levels of saturated fat. These natural foods are a portion of the ancestral human diet.  People have eaten as much as they want to of these foods without adverse health consequences since paleolithic times, until 1977 when the Dietary guidelines demonized saturated fat of omnipresent natural fat, driving people away from highly nourishing, wholesome and health-promoting foods.

Reducing dietary saturated fats does not reduce cardiovascular events and death. Improvements in cardiovascular outcomes are independent of direct cholesterol lowering. Dietary trials that provide abundant natural fats such as α-linoleic acid, polyphenols and Ω-3 fatty acids found in nuts, olive oil, oily fish and vegetables exert a positive health effect, likely by reducing inflammation, atherosclerosis and thrombosis.

Chakrabarti S, Freedman JE. Review: nutriceuticals as antithrombotic agents. Cardiovasc Ther 2010;28:227–35.

Interestingly, replacing saturated fat with Ω-6 containing vegetable oils (highly processed and refined industrial seed oil) does lower LDL cholesterol but does not actually improve cardiovascular mortality, and may actually increase mortality.

Veerman J Lennert. Dietary fats: a new look at old data challenges established wisdom BMJ 2016; 353 :i1512

Total and LDL cholesterol are a poor marker of cardiovascular health.  Cholesterol profile of elevated triglycerides and low HDL is a more predictive marker of cardiac risk and a reliable marker of insulin resistance. In fact, the QRISK calculator, used to estimate the 10-year risk of CVD, does NOT use LDL cholesterol, but uses total cholesterol/HDL ratio instead.

Preventing insulin resistance in young men would prevent 42% of myocardial infarctions, a larger reduction than correcting hypertension (36%), low high-density lipoprotein cholesterol (31%), body mass index (21%) or low-density lipoprotein cholesterol (16%).

Eddy D, Schlessinger L, Kahn R, Peskin B, Schiebinger R. Relationship of insulin resistance and related metabolic variables to coronary artery disease: a mathematical analysis. Diabetes Care. 2009;32(2):361–6.

 

Refined Carbohydrates:

Prediabetes and Type 2 diabetes are diseases of insulin resistance with initial excessive insulin production, which display the symptom of elevated blood glucose levels as the disease progresses. Treating the root cause of the disease, instead of the symptom, is the key. Eliminate all refined carbohydrates to reverse obesity, prediabetes, and type 2 diabetes.

Refined carbohydrates are known to increase blood glucose levels, increase requirements for medications and result in weight gain. It is disturbing that dietary guidelines prioritize the consumption of starchy carbohydrates for type 2 diabetics, to nearly 55% of their daily macronutrient consumption. Such diets will potentially lead to progressive worsening of disease with all its attendant complications, such as blindness, kidney failure, nerve damage, peripheral vascular disease, heart disease and stroke.

Added sugar has no nutritional value whatsoever. There are no biochemical reactions in the human body that require dietary fructose. No single study exists that demonstrates benefit associated with its consumption.

Credit Suisse – Sugar Consumption at a crossroads

Dietary carbohydrate restriction is the “single most effective intervention for reducing all of the features of the metabolic syndrome” according to Credit Suisse, and should be the first approach in diabetes management. A ketogenic diet (one that comprises less than 10 percent of calorie intake from carbohydrates) results in the greatest falls in HbA1C and reduction in the use of medications. These benefits accrue independently of weight loss.

Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 2015;31:1–13.

Sugar+veg oil+grain=obesity®PreDM®T2D

Dietary sugar is strongly associated with increased risk of type 2 diabetes, hypertension, and cardiovascular disease, independent of its calories or its effects on body weight.

Lustig RH: Sickeningly sweet: does sugar cause type 2 diabetes? YES. Can J Diab (in press).

Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Lustig RH, Mulligan K, Noworolski SM, Tai VW, Wen MJ, Erkin-Cakmak A, Gugliucci A, Schwarz JM. Obesity (Silver Spring). 2016 Feb;24(2):453-60. doi: 10.1002/oby.21371. Epub 2015 Oct 26.

Added sugar intake and cardiovascular diseases mortality among US adults. Yang Q, Zhang Z, Gregg EW, Flanders WD, Merritt R, Hu FB. JAMA Intern Med. 2014 Apr;174(4):516-24. doi: 10.1001/jamainternmed.2013.13563.

 

Vegetable Oil:

Despite at least 2-3 million years of human history, only since 1917 have industrial seed oils been a significant part of the human diet, with a major uptick in consumption in the late 1970s. Linoleic acid (the Ω-6 fat in these vegetable oils) is extremely susceptible to oxidation, making foods rancid, but also oxidizing in the body. Linoleic acid, in non-processed whole food (seeds, nuts, fish, and eggs), coexists with vitamins, minerals, and antioxidants, protecting this highly susceptible polyunsaturated fat.

Free Radic Biol Med. 2001 Dec 1;31(11):1388-95. The stomach as a bioreactor: dietary lipid peroxidation in the gastric fluid and the effects of plant derived antioxidants. Kanner J, Lapidot T.

Curr Atheroscler Rep. 2009 Nov;11(6):403-10. Impact of circulating esterified eicosanoids and other oxylipins on endothelial function. Shearer GC, Newman JW.

A meta-analysis including almost 10,000 patients confirmed that high intake of Ω-6 oils (from vegetable oils/margarines) increases the risk of death and heart disease compared to saturated fat plus trans fat. Human research data suggest that we should remove these vegetable oils from our food supply for optimal health.

29.BMJ. 2013 Feb 4;346:e8707. doi: 10.1136/bmj.e8707. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. Ramsden CE1, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR.

Older data was confounded by the inclusion of Ω- 3 polyunsaturated fatty acid intake. This misrepresented the health benefits of Ω–6. Other studies, such as the Anti-Coronary Club trial, confirm that Ω–6 PUFA increases death and coronary heart disease compared to animal fat.

Christakis G, Rinzler SH, Archer M t al. Effect of the anti-coronary club program on coronary heart disease. Risk-factor status. JAMA 1966;198:597–604

The LA Veterans trial found that cancer mortality increases with the consumption of Ω–6 rich vegetable oils.

Pearce ML, Dayton S. Incidence of cancer in men on a diet high in polyunsaturated fat. Lancet 1971;1:464-7.

Animal studies have also found that Ω–6 PUFA promotes the growth of experimentally induced cancers, whereas Ω–3 inhibits their growth. Ω–6 rich vegetable oil ( such as sunflower and corn oil), is linked to the increased risk of death, coronary heart disease, and cancer in humans as well as the growth of cancer in animal models.

Am J Epidemiol. 1998 Feb 15;147(4):342-52. Adipose tissue Ω–3 and Ω–6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer. Simonsen N1, van’t Veer P, Strain JJ, Martin- Moreno JM, Huttunen JK, Navajas JF, Martin BC, Thamm M, Kardinaal AF, Kok FJ, Kohlmeier L.

Cancer Res. 1988 Dec 1;48(23):6642-7. Effect of different levels of Ω–3 and Ω–6 fatty acids on azoxymethane-induced colon carcinogenesis in F344 rats. Reddy BS, Sugie S.

 

Why eat less, move more fails:

A calorie is a calorie only if it is incinerated in a bomb calorimeter, and the heat given off measured. Biologically derived calories from different foods have entirely different metabolic effects on the human body.  Equal calorie portions of sugar, alcohol, meat or olive oil have widely differing effects on hormonal systems, including insulin and satiety signals such as cholecystokinin or peptide YY. It is irrelevant how many calories a portion of food on a plate contains. What matters is how our body responds to taking in and absorbing those calories, how they are metabolized, and the resulting level of satiety.

The current caloric reduction strategies promoted for weight loss are ineffective. Using the standard calorie reduction approach produces a probability of attaining a normal weight at 1 in 167, generating a greater than 99% failure rate.

Fildes A et al. Probability of an Obese Person Attaining Normal Body Weight: Cohort Study Using Electronic Health Records. Am J Public Health. 2015;105: e54–e59

It is wrongly assumed that excessive caloric intake is the root cause of obesity. A calorie of food energy has different metabolic fates depending upon the hormonal stimulation. That same calorie may be used to generate body heat or stored as body fat. Obesity is a disease of failed energy partitioning, not one of total energy intake. The primary driver of this partitioning is the hormone insulin.  Insulin is specifically a fat storage growth hormone.

Focusing on calories in and calories out produces an inherent bias against high-fat food, which may be protective against obesity and related diseases.  The simplistic calorie focus results in a dietary guideline supportive of starch and sugar replacement of fat, which promotes insulin resistance.

It is our hope that shifting focus away from calories and emphasizing a dietary pattern that focuses on food quality rather than quantity will reduce obesity, related diseases, and cardiovascular risk.

Malhotra A, DiNicolantonio JJ, Capewell S. It is time to stop counting calories, and time instead to promote dietary changes that substantially and rapidly reduce cardiovascular morbidity and mortality. Open Heart 2015;2(1) doi: 10.1136/openhrt-2015-000273[published Online First: Epub Date]|.

Yo-yo dieting with rapid weight loss and regain from fad dieting is detrimental to health. Such ‘weight cycling’ contributes to hypertension, insulin resistance and dyslipidemia, resulting in increased mortality risk and worse cardiovascular outcomes.

Mann T, Tomiyama AJ, Westling E, et al. Medicare’s search for effective obesity treatments: diets are not the answer. Am Psychol 2007;62:220–33.

LC + exercise ¹ health

In the Action for Health in Diabetes trial,  no cardiovascular benefits were found on a low-calorie diet combined with increased physical activity in type 2 diabetic patients.

(Despite the significant weight loss even up to the maximum follow-up of 13.5 years, no health benefits could be found. )

Wing RR, Bolin P, Brancati FL, et al. Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. NEngl J Med 2013;369:145–54.

 

Exercise is not the solution:

It is widely accepted amongst the public and media that consuming more calories than we burn is the cause of the obesity epidemic, and therefore the solution is to just do more exercise.

Food and beverage companies have pushed this physical activity message to exonerate themselves. The very companies promoting processed and highly refined foods linked to the obesity epidemic have sponsored major sporting events.  This association of ultra-processed food and soft drinks with sport is troubling. Celebrity endorsements give the wrong message, particularly to children.

Regular physical activity does have beneficial health effects, but weight loss is not one of them. In fact, there has been little change in our levels of physical activity in the past three decades, while the levels of obesity have increased.

Luke A, Cooper RS. Physical activity does not influence obesity risk: time to clarify the public health message. Int J Epidemiol 2013;42:1831–6.

It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet . A Malhotra, T Noakes, S Phinney Br J Sports Med bjsports- 2015-094911Published Online First: 22 April 2015 doi:10.1136/bjsports-2015- 094911

 

The time spent not eating, is more important than the time spent eating. Snacking will make you fat.  It’s the chronic high insulin from the constant feeding.

There have been two major changes in our dietary habits since the 1970s, prior to the onset of the obesity epidemic. The change to a high-carbohydrate, low-fat diet has been well documented and has played an important role in causing obesity. However, the increase in meal frequency plays an equal if not larger role and has been largely ignored. In the 1970s, the average number of eating opportunities was three – breakfast, lunch and dinner. By 2005, that number had almost doubled. Now we eat breakfast, snack, lunch, snack, dinner and snack — and more often than not, each of these contains refined carbohydrates.

Cameron JD. 6 meals per day does not result in greater weight loss. Br J Nutr. 2010 Apr;103(8):1098-101

Popkin BM. Does hunger and satiety drive eating anymore? Am J Clin Nutr 2010;91:1342–7

 

Eating nearly continuously from the moment we arise to the moment we go to sleep becomes an opportunity to store food energy without a chance to burn it. Eating six times a day does not result in weight loss but tends to increase overall consumption of food.  Snacks are produced for convenience and shelf stability and are filled with refined carbohydrates and often supplemented with Ω–6 vegetable oil.  The hyper-processing of food contributes to a high glycemic index, and the grazing pattern of behavior results in a chronically elevated level of insulin, the fat storage hormone.

Reducing the frequency of our meals and eliminating snacking are simple ideas that were practiced widely before the obesity epidemic.

 

Additional references for RCT’s comparing low carb and low fat for weight loss

• Shai I, et al. Weight loss with a low-carbohydrate, mediterranean, or low-fat diet. N Engl J Med 2008;359(3);229–41.
• Gardner CD, et al. Comparison of the Atkins, Zone, Ornish, and learn Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women. The A to Z Weight Loss Study: A Randomized Trial. JAMA. 2007;297:969–977.
• Brehm BJ, et al. A Randomized Trial Comparing a Very Low Carbohydrate Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women. J Clin Endocrinol Metab 2003;88:1617–1623.
• Samaha FF, et al. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. N Engl J Med 2003;348:2074–81.
• Sondike SB, et al. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr. 2003 Mar;142(3):253–8.
• Aude YW, et al. The National Cholesterol Education Program Diet vs a Diet Lower in Carbohydrates and Higher in Protein and Monounsaturated Fat. A Randomized Trial. Arch Intern Med. 2004;164:2141–2146.
• Volek JS, et al. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutrition & Metabolism 2004, 1:13.
• Yancy WS Jr, et al. A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia. A Randomized, Controlled Trial. Ann Intern Med. 2004;140:769–777.
• Nichols-Richardsson SM, et al. Perceived Hunger Is Lower and Weight Loss Is Greater in Overweight Premenopausal Women Consuming a Low-Carbohydrate/High- Protein vs High-Carbohydrate/Low-Fat Diet. J Am Diet Assoc. 2005;105:1433–1437.
• Krebs NF, et al. Efficacy and Safety of a High Protein, Low Carbohydrate Diet for Weight Loss in Severely Obese Adolescents. J Pediatr 2010;157:252-8.
• Summer SS, et al. Adiponectin Changes in Relation to the Macronutrient Composition of a Weight-Loss Diet. Obesity (Silver Spring). 2011 Mar 31. [Epub ahead of print]
• Daly ME, et al. Short-term effects of severe dietary carbohydrate-restriction advice in Type 2 diabetes–a randomized controlled trial. Diabet Med. 2006 Jan;23(1):15–20.
• Westman EC, et al. The effect of a low-carbohydrate, ketogenic diet versus a low- glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr. Metab (Lond.)2008 Dec 19;5:36.
• Halyburton AK, et al. Low- and high-carbohydrate weight-loss diets have similar effects on mood but not cognitive performance. Am J Clin Nutr 2007;86:580–7.
• Dyson PA, et al. A low-carbohydrate diet is more effective in reducing body weight than healthy eating in both diabetic and non-diabetic subjects. Diabet Med. 2007 Dec;24(12): 1430-5.
• Keogh JB, et al. Effects of weight loss from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk in subjects with abdominal obesity. Am J Clin Nutr 2008;87:567–76.
• Volek JS, et al. Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet. Lipids 2009;44:297–309.
• Partsalaki I, et al. Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese children and adolescents. J Pediatr Endocrinol Metab. 2012;25(7-8):697-704.

Dr. Padda explains how he has developed a program to reverse diabetes and how the diabetes industry is profiting from the African-American community.

Click Play to Listen:

Time Restricted Feeding | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

Time-restricted feeding.

Time-restricted feeding can help people move into a healthier lifestyle and reverse insulin resistance as well as maintain a healthy weight. Most people eat from the time they wake up until the time they go to bed; typically, they eat three main meals, multiple snacks, and often soda in between.  This pattern leads to chronic high insulin production, which fatigues the insulin receptors.  In addition, insulin is a fat storage hormone, and elevated insulin levels lead to fat accumulation in the liver, creating metabolic inflammation.

Your metabolism exists in two states – the “fed” (insulin high) state and the “fasted” (insulin low) state. Either we are storing food energy (increasing storage), or we are burning stored energy (decreasing storage or fat lysis).  If we start eating the minute we roll out of bed and do not stop until we go to sleep, we spend almost all our time in the fed state. Over time, we gain weight, because we have not allowed our body time to burn stored food energy.

Time-restricted feeding shortens the time window that a patient eats, shortening the “fed” state and lengthening the “fasted” state.  This reduces the total amount of insulin produced for the day.  Insulin is a fat-storage hormone, and a high level of insulin production leads to insulin resistance.  Time-restricted feeding is considered a type of fasting and has extraordinary benefits, including weight and body fat loss, lowered blood insulin and sugar levels, and a reversal of type 2 diabetes. Other possible benefits include improved mental clarity and concentration, a reduction in the risk of Alzheimer’s disease, activating of cellular cleansing by stimulating autophagy, and reduction of inflammation.

Time-restricted feeding is a type of fasting; it is not starvation.  Starvation is the involuntary absence of food for a long time, leading to severe suffering or even death. Starvation is not deliberate or controlled.  Fasting is the voluntary withholding of food. It’s done by someone who is not underweight and thus has enough stored body fat to live off. When done right, intermittent fasting should not cause suffering.  Food is easily available, but you choose not to eat it. You may begin a fast at any time of your choosing, and you may end a fast at will, too. You can start or stop a fast for any reason or no reason at all.  Any time that you are not eating, you are intermittently fasting. For example, you may fast between dinner and breakfast the next day, a period of approximately 12-14 hours. In that sense, intermittent fasting should be considered a part of everyday life.

The mere presence of insulin increases fat storage, and the absence of insulin permits lipolysis or fat usage as energy.

Lifestyle changes are key to managing obesity and Type 2 Diabetes, but by themselves don’t always control blood glucose levels. Bariatric surgery (gastric band or bypass) is effective but has significant risk. Drugs often manage the symptoms and may stave off complications, but don’t reverse the disease.

Time-restricted feeding has the potential to fill this gap in obesity and diabetes care by providing calorie restriction and the hormonal benefits of bariatric surgery without invasive surgery. Time-restricted feeding is defined as the controlled and voluntary abstinence from all calorie-containing food and drinks for a specified period of time.  During the fasting periods, patients are allowed to drink unlimited amounts of very-low-calorie fluids such as water, coffee, tea, and even bone broth. A general multivitamin supplement is encouraged to provide adequate micronutrients.

Metabolic flexibility:

Time-restricted feeding, or meal-timing strategy, reduces swings in hunger and alters fat and carbohydrate burning patterns, which may help with losing weight and improving insulin sensitivity.  It does not necessarily affect how many total calories patients burn but reduces the daily hunger swings and increases fat burning at night. It improves metabolic flexibility, which is the body’s ability to switch between burning carbs and burning fats.  Metabolic flexibility is the ease with which the body transitions between two different and opposing states, “fed” and “fasted,” without cravings or hunger pangs.

During feeding, insulin is elevated, which signals your body to store excess calories as fat. In the presence of insulin, the burning of fat is halted, while the body burns glucose instead.  In the fasted state, insulin is low (while glucagon and growth hormone increase), so the body mobilizes stored body fat from your fat cells and burns this fat for energy (instead of glucose).  You can only burn stored body fat while in the fasted state, and you can only store more body fat while in the fed state.

Most overweight patients live in a constant fed state, and rarely in a fasted state.  They continually burn glucose rather than fat at the cellular level. They have insulin resistance, caused by chronically high insulin levels, which promote fat storage and suppress fat mobilization.

When overweight “sugar burners” stops eating for even a few hours, they quickly run out of glucose from their last meal, instead of transitioning to the fasted state and burning stored body fat.  This causes acute brain signals of hunger and cravings for immediate sugar.  They spend most of the day trapped in a cycle of eating every few hours, spiking glucose, and then becoming hungry when blood sugar drops.  They may even develop low blood sugar and feel jittery; this is called reactive hypoglycemia.  This is a big clue that a patient lacks metabolic flexibility.

Fat-adapted energy use:

Your metabolic flexibility is determined by your mitochondria, the tiny energy factories inside the cells.  The mitochondria can burn both glucose (sugar) or fat for fuel, and over time they will develop a preference for one over the other; “sugar burners” have increased the pathways in the mitochondria that burn glucose and decreased pathways for burning fat.  As you become more metabolically flexible, the fat burning pathways will predominate, and you will become “fat adapted.”

Becoming fat adapted takes time and practice, and your body has to do a number of things to slowly up-regulate (or increase) your fat-burning pathways.  This includes improving insulin sensitivity to lower insulin and promote fat mobilization into free fatty acids and upregulating the fat-burning pathways at the cellular level (in the mitochondria).

Ways to improve fat adaptation include:

• Low-carbohydrate diets: A low-carb, high-fat (LCHF) diet improves the body’s ability to utilize fat for energy rather than glucose, as there is more fat and less glucose, even in the fed state.
• Exercise: High-intensity exercise depletes glucose and glycogen rapidly, forcing the body to switch to fat for fuel. Exercise also improves insulin sensitivity.
• Caloric restriction: Eating fewer calories also equals less glucose available for fuel, forcing the body to rely on stored body fat for fuel.
• Intermittent fasting forces the body to spend more time in the fasted state, giving the body more “practice” at burning fat.
• Supplementation: Ketone supplementation may be useful when first starting out. Ketones are breakdown products of fat, and when you first start out, ketones can reduce your hunger and provide energy for your mitochondria.

Patient education and engagement is the key to remission and curtailing the use of pharmacological interventions.  Morrison et al, also found that more frequent interactions with a provider led to markedly rapid reductions in serum glucose, HbA1C, and low-density lipoprotein cholesterol levels, followed up with the treating physician on average every 2 weeks.

How to do time-restricted feeding:

Our protocol can reverse obesity and Type 2 Diabetes (in individuals who still have the capacity to produce some insulin) by resensitizing the insulin receptor and restoring normal cyclical insulin production.  We restore the normal ebb and flow pattern of insulin, so the receptors are re-sensitized, and the constant high level of circulating insulin is reduced, reducing the fat storage action of insulin.

Time-restricted feeding is a type of intermittent fasting that limits your food intake to a certain number of hours each day.  An example of time-restricted eating is if you choose to eat all your food for the day in an 8-hour period, such as from 11 a.m. to 7 p.m., providing an 8-hour feeding window.  The remaining 16 hours are the fasting period, during which no calories are consumed.  This same schedule would be repeated every day.

Restricting feed times to a shorter window each day, starting at 8 hours/day and reducing by 1 hour per week down to 4-6 hours/day is highly effective in reversing diabetes and weight loss.  Medications must be clinically adjusted to prevent unintentionally low glucose levels or changes in blood pressure, which can be life-threatening.  To have success with this technique, cravings should be prevented.  Satiety is the key; you should not be hungry, or this will not be sustainable.  Food choice drives satiety.

Steps to success

Step 1

Before you start a time-restricted feeding schedule, you should talk to your doctor or health care provider. Get medical advice from a professional who is aligned with your health goals.

You may have medical conditions that need close monitoring. Likewise, you may be on medications that may need to be adjusted. It is important to have a strong understanding of your medical history and the medications you take prior to initiating a fasting program. Please talk to your doctor or healthcare provider.

Step 2

Stop all sugars, including all artificial sweeteners. Many sugars and processed carbs just aren’t satiating. Stop all sugar and artificial sugar sweetened beverages. Before you start your protocol, you should eliminate sugars and processed carbohydrates.

Stop all sources of vegetable oil and replace with healthy natural oil and real butter.  Replacing industrial seed oil with real oils is easy if you are not eating processed foods.  It even makes the food taste better.

Stop all processed foods.  Processed foods are engineered to make you eat again and again and again, every 2-3 hours.

Step 3

Focus on protein and healthy fats. Focus on getting meals that are rich in protein and healthy fats. Eat all types of meat like beef, fish, chicken, eggs, lamb, and seafood. Yogurt and cheeses are also nutritious and filling. Fill up on low-sugar vegetables like olives, peppers, cucumbers, and avocado, and eat as many green leafy vegetables as you please.  This approach will help you get better adapted to fat metabolism and may make fasting easier to adopt.

Step 4

Start slow.   This metainflammation didn’t happen in one day, and it won’t go away in a day. Consider a liberal 8-hour eating window on your first day to see how it feels. Eat as you please during your 8-hour time frame and see how your body and appetite feel during the remaining hours of the day.

Then, slowly narrow your eating window. As you feel more comfortable assessing your hunger and understanding the nature of hunger pangs, you can slowly decrease your daily feeding window. Consider decreasing by one hour a week, until you reach a 4-hour window.

Things to think about:

If you haven’t made adjustments to your diet beforehand to include more satiating foods filled with protein, healthy fat and fiber, you may notice hunger pangs. If you are experiencing hunger pangs, consider drinking some hot tea, coffee, water or seltzer. This will fill your stomach up and give you enough time to realize that maybe you really aren’t as hungry as you initially thought.  Some people use lemon in seltzer water.

This should be a fun experience, not a miserable experience.  If you are having a miserable experience, something has been overlooked.  Remember that time-restricted feeding is a  great way to limit snacking. Eating satiating real food during your eating window will restore and realign your hormone system.

Patients can reverse their diseases without the worry of side effects and financial burden of many pharmaceuticals, as well as the unknown long-term risks and uncertainty of surgery, all by means of time-restricted feeding.

Some practical tips:

• Don’t use time restricted feeding as an excuse to eat junk food when you are eating—continue to avoid processed foods.
• When you first start time-restricted feeding, you might have to supplement with a fast-mimicking substance like a ketone supplement.
• Check with your doctor before starting time-restricted feeding, especially if you are diabetic and on diabetes medications!
• You can generally take any vitamins or supplements you want while fasting as long as they don’t have calories, but you don’t need any supplements as you will be eating plenty of nutrient-dense foods every day. You may have to increase salt intake.
• You don’t have to worry about losing muscle from lack of protein during your fast, as long as you eat adequate protein at the meals before and after fasting. A LCHF (low-carb, high-fat) diet pairs nicely with intermittent fasting, as both improve fat adaptation a great deal.
• Exercising with time restricted feeding, either cardio or lifting weights (lifting weights is better), is acceptable. You will not lose muscle while fasting as long as you are exercising regularly.
• Drink plenty of water and non-caloric beverages while fasting; coffee and tea in the morning make fasting considerably more enjoyable in addition to health and fat-burning benefits and are highly recommended. You may have to increase salt intake.
• Skipping your morning meal gives your body more time to burn fat for energy. Hunger is lowest in the morning, so it may be easiest to skip it and break your fast later in the day.

Time-restricted feeding has many benefits but remains controversial. Diabetes medications will need to be adjusted. Discuss any changes in medication and relevant lifestyle changes with your doctor.  People who should not use time-restricted feeding include those who are underweight or have eating disorders, pregnant or breastfeeding women, and children under the age of 18.

Need more help? We have more to offer.

Additional references:

Suleiman Furmli, Rami Elmasry, Megan Ramos, Jason Fung. Therapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulin. BMJ Case Reports, 2018; bcr-2017-221854 DOI: 10.1136/bcr-2017-221854

Morrison F , Shubina M , Turchin A . Encounter frequency and serum glucose level, blood pressure, and cholesterol level control in patients with diabetes mellitus. Arch Intern Med 2011;171:1542–50.doi:10.1001/archinternmed.2011.400

Duke S-AS , Colagiuri S , Colagiuri R . Cochrane Metabolic and Endocrine Disorders Group. Individual patient education for people with type 2 diabetes mellitus. Cochrane Database Syst Rev 2009;22.doi:10.1002/14651858.CD005268.pub2

Brethauer SA , Aminian A , Romero-Talamás H , et al . Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg 2013;258:1.doi:10.1097/SLA.0b013e3182a5034b

Pucher PH , Lord AC , Sodergren MH , et al . Reversal to normal anatomy after failed gastric bypass: systematic review of indications, techniques, and outcomes. Surg Obes Relat Dis 2016;12:1351–6.doi:10.1016/j.soard.2016.01.030

Shoar S , Nguyen T , Ona MA , et al . Roux-en-Y gastric bypass reversal: a systematic review. Surg Obes Relat Dis 2016;12:1366–72.doi:10.1016/j.soard.2016.02.023

The University of Alabama at Birmingham. “Time-restricted feeding study shows promise in helping people shed body fat.” ScienceDaily. ScienceDaily, 6 January 2017. www.sciencedaily.com/releases/2017/01/170106113820.htm

Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss? K. A. Varady. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X.2011.00873.x

Moro, T., Tinsley, G., Bianco, A., Marcolin, G., Pacelli, Q. F., Battaglia, G., … Paoli, A. (2016). Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. Journal of translational medicine, 14(1), 290. doi:10.1186/s12967-016-1044-0. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064803/

Gabel, K., Hoddy, K. K., Haggerty, N., Song, J., Kroeger, C. M., Trepanowski, J. F., … Varady, K. A. (2018). Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: A pilot study. Nutrition and healthy aging, 4(4), 345–353. doi:10.3233/NHA-170036. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004924/