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

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.

Many people think that sugar is sugar, but there are different types and sugar comes in many forms. Compared with glucose, fructose plays a primary role in development of metainflammation, obesity, prediabetes, and type 2 diabetes

Fructose directly increases de novo lipogenesis, promotes dyslipidemia, decreases insulin sensitivity, increases visceral adiposity, and stimulates the reward center, similar to cocaine.

What is sugar?

Because glucose is the sugar that we most often talk about and measure in diabetics, most people assume that their regular table sugar is made of glucose. However, common table sugar is actually a disaccharide, made of two monosaccharides, fructose and glucose, bonded together in a 1:1 ratio.

High fructose corn syrup (HFCS) contains about 5% more fructose than glucose. HFCS is manufactured by hydrolyzing corn starch into glucose, which then is isomerized into fructose. Fructose is preferred by food and soft drink manufacturers because fructose exerts a significantly increased perception of sweetness and likely because its production is subsidized.  Glucose has a sweetness index of 74 compared to sucrose of 100 or fructose of 173.

According to the CDC, over 30 million Americans have diabetes, with 1 in every 4 not knowing their diagnosis. Fructose is more strongly linked to obesity and diabetes than glucose. There is no biochemical reaction in any eukaryotic organism that requires fructose.

Metabolism of glucose and fructose

Glucose can be utilized as an energy source by almost every cell in the body. Only the liver can metabolize fructose, and it will preferentially convert fructose into fat storage.  The body has the ability to handle a small amount of fructose at a time, without adverse health consequences. Fructose does come naturally from fruits, but the absorption is slow due to the large amount of fiber.  Unfortunately, removing the fiber by juicing or destroying the fiber, as done in a smoothie, dramatically increases the speed of absorption, overwhelming the liver and sending a fructose rush to the brain.

Glucose consumption normally causes insulin release from the pancreas. Insulin acts on surface cell receptors, which allow glucose absorption into the cell for energy use or converting it to fat inside the cell.  High levels of insulin, in the presence of high levels of glucose, cause a liver enzyme [phosphofructokinase PFK] to convert glucose to fructose, which is then quickly turned into fat storage and not used for energy production.  However, if you directly ingest fructose, it bypasses the enzyme gateway and insulin is not released, and it goes straight to fat storage.

The metabolism of fructose differs from that of glucose, with liver metabolism of fructose favoring de novo lipogenesis [fat production directly from fructose].  Additionally, fructose does not stimulate insulin secretion or leptin production. Insulin normally regulates the absorption of sugar into the cells, and leptin normally notifies brain receptors that you are full.  Because insulin and leptin act as key signals in the regulation of food intake and body weight, fructose consumption causes yet further hunger and additional weight gain.  The body is rapidly storing fat, and doesn’t know it’s full.

Insulin resistance from fructose and the beginning of metabolic inflammation

Fructose can also directly trigger insulin resistance. When mice are fed with excessive amounts of fructose, they produce carbohydrate responsive element-binding protein, or ChREBP, which blocks the liver from responding to the insulin.

Fructose is 20 times more likely to cause fatty liver (the key problem of insulin resistance) compared to glucose alone.  Fructose feeding studies, replacing glucose with a calorically equal amount of fructose, document  a 5x increase in de novo lipogenesis and an increased liver fat by 38% within eight days.

[The metabolism of ethanol (alcohol) is similar to that of fructose. Nearly 80% of the ingested ethanol is delivered to the liver, and metabolized to acetaldehyde, which also stimulates de novo lipogenesis.]

Fructose overfeeding can provoke insulin resistance. Healthy subjects overfed 1000 calories per day of fructose demonstrated a 25 percent worsening of their insulin sensitivity in seven days.

Fructose induces insulin resistance even at typical consumption doses, in less than eight weeks. Subjects were fed 25 percent of their daily calories as Kool-Aid sweetened with either glucose or fructose. The fructose group increased their insulin resistance, and could be clinically classified as pre-diabetic.  The glucose group did not.

Fructose engages in the Maillard reaction, or glycation seven times faster than glucose, and  a metabolite of fructose does it 250 times faster.  We commonly measure this as HgBA1C for glucose.  The measure for fructose is fructosamine.  This glycation effect makes the cell walls sticky, and the receptors not work.  This may explain why patients with high glycation levels require more pain medication, because their receptors simply don’t work.  It also is part of the explanation how insulin resistance occurs.

Fructose and addiction

Fructose stimulates the reward center of the brain while glucose does not.  Data suggests that the fructose molecule in sugar is what it makes it addictive.

 

• Glucose activates the cortex, the basal ganglia, and certain other parts, but not the limbic system.  Glucose results in a sensation of serotonin-induced happiness. By contrast, fructose stimulates the limbic system and is associated with increased dopamine release in the nucleus acumbens, similar to other addictive drugs (glucose does not stimulate the nucleus acumbens).  Fructose results in a sensation of dopamine-induced pleasure.

Agricultural subsidies

Governmental subsidies were initially a method to subsidize farmers during the Depression and the Dust Bowl in 1933.  We had a destitute population in the American southwest, dying of famine. Most of the the food and food manufacturers were in the Northeast.  By the time it took to transport food by rail to the Southwest, it would go rancid. They had to process it: remove the fiber from the  wheat, package it in 5 pound bags, ship it to the Southwest, and then bake it locally. The subsidy was designed to make it worthwhile for the American food industry to invest in a processing and distribution system for a famine-stricken population, which made sense through World War 2.

Unfortunately, President Nixon, concerned about re-election, knew that fluctuating food prices caused political unrest.  Nixon instituted a policy of maintaining low consumer prices for food by agricultural subsidy.  Until that point, our subsidies were actually designed to pay farmers to not grow certain crops and maintain inflated prices. This policy also allowed the soil to regain nutrient after crop harvest.  His agriculture secretary, Rusty Butz, changed farming operations so soil was no longer left fallow; there was no time to restore nutrient after a crop was harvested.  It also encouraged monocropping and megafarms.  Subsidies have created an agricultural farmer dependency on governmental support.  The massive overproduction of just a few grain items resulted in a huge surplus and difficulty in long-term storage.  Distributing this slowly rotting surplus was solved through the food stamp system, creating a consumer dependency on governmental support. Unfortunately, these processed staple items are carbohydrate-rich, but have had most of their fiber stripped and fat removed to prevent rancidity,  and lack much of the soil-derived micronutrients.

Governmental subsidies and import tariffs have resulted in corn being a much more economical sweetener than sugar–a trend that is not seen in other parts of the world.  The consumption of HFCS increased by more than 1000% between 1970 and 1990, far exceeding the changes in intake of any other food or food group. HFCS now represents more than 40% of caloric sweeteners added to foods and beverages, a daily average of 132 calories per person. The effect of governmental subsidy is most evident when you compare the same soft drink in the United States to one in Mexico; for example, Coke contains corn syrup as the sweetener in the United States while it contains cane sugar in Mexico.

The per capita consumption of high fructose corn syrup — the primary sweetener in soft drinks and other sweetened beverages — has increased from 38.2 pounds in 1980 to 868 pounds in 1998 (Chou et al., 2004). In 1942, annual U.S. production of soft drinks was 90 8 oz. servings per person; in 2000, it was 600 servings (Jacobson, 2005).

Other names for sugars:

Processed foods will most likely have sugars added. Unfortunately, they can go by any number of names. While this is an extensive list, it is not complete. The more naturally you can eat your foods, the better success you will have with creating a permanent weight loss solution.

Agave Syrup

Amasake

Any name ending in “ose” or “ol” or “syrup”

Barbados Sugar

Barley Malt

Blackstrap Molasses

Black Sugar

Brown Sugar

Cane Juice or Cane Juice Crystals

Cane Sugar

Caramel or Caramel Coloring

Castor Sugar

Confectioner’s Sugar

Corn Sweetener

Corn Syrup – a manufactured syrup of corn

starch, containing varying proportions of glucose

maltose, and dextrose

Corn Syrup Solids

Crystallized Cane Juice

D-mannose

Date Sugar

Demerara

Demerara Sugar

Dehydrated Cane Juice or Dehydrated Cane

Juice Crystals

Dextran

Dextrin

Dextrine

 

Dextrose (glucose) – a simple sugar made of

only one molecule

Erythritol

Evaporated Cane Juice

Evaporated Cane Juice Sugar

Florida crystals (a trademarked name)

White or Brown Sugars

Fructose – a simple sugar refined from fruit

Fruit Juice Concentrate

Galactose or Galatactose

Glucose or Glucose Syrup

Golden Syrup

Grape Sugar

Grape Juice or Grape Sweetener

High Fructose Corn Syrup (HFCS)

Honey

Hydrolysed or Hydrolyzed Starch

Hydrogenated Glucose Syrup

Hydrogenated Starch Hydrolysates (HSH)

Invert Sugar

Isomalt

Levulose

Lactitol or Lactital

Lactose – a simple sugar from milk

Malt

Malt Extract

Malt Syrup

Maltodextrin

Maltose

Malitol

Maple Syrup

Molasses

Monosaccharide

Muscovado

Organic Dehydrated Cane Juice

Organic Brown Sugar

Panocha

Polysaccharide

Powdered Sugar

Raw Cane Crystals

Raw Honey

Raw Sugar