Addiction Neurobehavioral Model of Obesity

April 30, 2019

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 a 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 acumbens, 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 the 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 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 acumbens 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 drug 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 resistant to aversive foot shocks.

Opioid circuitry in both the nucleus acumbens 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 nucleus Activation of nucleus Activation of nucleus Activation of 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 results 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 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 a grazing behavior.  Unfortunately, the brain’s perception of nutrient value is distorted by synthetic flavors.  The patient ends up overconsuming manufactured carbohydrate and manufactured fat in a combination that is highly obesogenic.

Food palatability (engineering and variety) stimulate appetite, reduce satiety, and promote 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 the 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-Branchey, 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 blood stream 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