Summary

1. Diets dominated by rapidly absorbed carbohydrates produce chronically high levels of insulin.

2. Excess Insulin signalling alone can explain obesity, inflammation and insulin resistance progressing to diabetes.

• Across modern societies most people are experiencing chronically high levels of insulin from diets dominated by rapidly absorbed carbohydrates
• Recently Insulin itself has been found to directly increase inflammation throughout the body and diet driven insulin excess may be the precipitating cause of Type 2 Diabetes.
• Inflammation is the most important risk factor for the main killers: heart disease, stroke, cancer and brain degeneration.
• No decrease in the epidemic of obesity and diabetes can occur without specifically addressing the route cause—chronically high levels of insulin from diets dominated by rapidly absorbed carbohydrates

High insulin levels (from diet) cause:

Diabetes

Obesity

Inflammation

 It is important to reduce high insulin levels simply by avoiding rapidly absorbed carbohydrates that spike blood glucose 

• Recently Insulin itself has been found to directly increase inflammation throughout the body and diet driven insulin excess may be the precipitating cause of Type 2 Diabetes

The Insulin Tsunami

• Across modern societies most people are experiencing chronically high levels of insulin from diets dominated by rapidly absorbed carbohydrates
• Insulin is the hormone that directs food into fat stores and high levels of insulin and glucose will constantly syphon calories into fat stores and stimulate increased food consumption for energy needs.
• Recently Insulin itself has been found to directly increase inflammation throughout the body and diet driven insulin excess may be the precipitating cause of Type 2 Diabetes.
• Inflammation is the most important risk factor for heart disease, stroke, cancer, etc.

• No decrease in the epidemic of obesity and diabetes can occur without specifically addressing the route cause—chronically high levels of insulin from diets dominated by rapidly absorbed carbohydrates

Insulin is a vital hormone regulating many more processes than just blood glucose levels such as growth and development but once we are fully grown insulin continues to drive ever increasing waistlines, metabolic disturbances and age related diseases.  Even small amounts, such as 50 grams of rapidly digested carbohydrates spike glucose levels and produce large increases in insulin secretion that not only produce insidious weight gain but a cell signaling pattern that increases our risk of age related diseases. Unfortunately rapidly digestible carbohydrates have become the staple foods of modern societies and it requires a great deal of effort and commitment to avoid them. 50-60% of all calories consumed in the Western Diet are high glycemic starches and sweeteners such as flour, potatoes, rice, corn syrup, corn flour and sugar.

Self-Eating (Autophagy) an ancient process involved in repair & aging, switches on while fasting and is exquisitely sensitive to dietary glucose abundance.

The tools of the “blind watchmaker” (Richard Dawkins on evolution) are serendipity and improvisation.  The first lesson in order to uncover the secrets of biology is to recognize the untidiness of it all, where mechanisms for doing one thing are borrowed to do another and the process repeated ad infinitum; if it works after a fashion, at least to get to the point of sexual maturity then all the better but after that he could care less, however after maturity the human condition involves 70 years or so of decline and unraveling the idiosyncrasies of the blind watchmaker may turn up some benefits to our fragile existence.

This is how I view the evolution of autophagy over a billion years:  A process that worked to preserve the life of single celled organisms when dormant and starved of nutrients has evolved to become a complex and lethally indispensable process for the existence of any form of multicellular animals. Funny that autophagy is unknown to most doctors, its discovery is so new, but its untidiness and improvisation is evident from the numerous overlapping functions it fulfills.  While fasting it provides glucose and fatty acids for energy and amino-acids for assembly of vital new proteins but simultaneously fasting likely improves autophagy’s other improvised roles; it detoxifies cells and stops them gumming up, regulates recycling, healing, repair, cell turnover, immunity and inflammation.  The exciting thing for us is that this vital process is eminently amenable to regulation through lifestyle choices such as exercise and nutrition.  Differentiating between fasting and feasting is critical to survival and a barometer of this switch is the level of glucose in blood and extra-cellular fluid, just 10 grams: a tiny amount compared to energy demands which, if supplied by glucose alone could vary between 0.5 grams per minute at rest to 5 grams per minute while running (clearly 5g per minute form a pool of 10g would be rapidly unsustainable). This delicate sensitivity of blood glucose to feeding argues that glucose is a barometer of energy status and not our primary energy source, this role is  reserved for fatty acids of which we carry hundreds of thousands of Calories in our 10-20% plus body fat. The molecular signaling pathway of this pivotal role of blood glucose is becoming clearer; simply restricting blood glucose reverses the ratio of insulin to glucagon that controls the activation of mTOR that in turn regulates autophagy and numerous other things that influence aging and age related diseases that are now the commonest causes of death and disability,

Never underestimate the difficulty of changing false beliefs by facts.  Henry Rosovsky

Fallacies are not just crazy ideas and usually have at least some element of plausibility, “detoxification” sounds like a good thing right, so an industry of snake oil salesmen thrive on nothing more than word association to convince impressionable and naïve people to spend valuable vacation time in detox centers and consume concoctions supposed to clean the liver and digestive tract in a similar fashion to a colonoscopy preparation regime: make no mistake about it those who use the term “detox” in serious conversation are either naïve or unscrupulous and often both.  On the other hand detoxification is a complex and vital process to the health of individual cells and the body as a whole but it’s not something that we can go away one weekend a month for or indulge in the occasional chemically induced episode of diarrhea.  Before we throw the baby out with the bathwater, there are ways to enhance the body’s natural detoxification processes but first we have to better define the biological processes involving detoxifying functions.

Autophagy (self-eating):  At the cellular level substantial amounts of potentially toxic proteins are constantly produced and need to be broken down and recycled in order to prevent cell stress and dysfunction which can ultimately lead to premature cell death and degenerative conditions like dementia.  Sophisticated systems have evolved (autophagy and ubiquitin/proteasome machinery) to recycle not only proteins, but mobilize fats and carbohydrates for energy use during times of fasting.  For instance this is accomplished during sleep where brain cells switch energy resources to the task of clearing a backlog of protein fragments generated during periods of consciousness and we now know that sleep deprivation can cause increased neuronal cell death.  The link between fasting and cell detoxification may explain the beneficial effects of calorie restriction on longevity but also suggests that the sensing mechanisms of fasting, such as lower glucose levels, enhance cellular detoxifying via autophagy as well.  Abundant glucose dramatically increases insulin secretion and the insulin signaling system suppresses autophagy as does high amino acid levels from high protein consumption.

Liver Function:  At the whole body level the liver is the main organ of detoxification of enormous amounts of endogenously produced waste products as well as potentially harmful substances absorbed from what we eat.  Fat soluble waste is excreted into the gut as bile and water soluble waste via the kidneys as urine. The role of water in urine excretion is self-evident but the role of the bile and digestive tract is detoxification is not so widely appreciated.  One of the many remarkable functions of fiber is the enhancement of removal of fat soluble excretory products in bile.

Take Home Message!  Eat low glycemic high fiber foods:  Foods that produce low levels of glucose and only moderate amounts of protein are good for cellular detoxification and high fiber foods are good for liver and gut function.

What to eat and avoid?

Harmful Foods-Minimize these 

Over 70% of calories consumed by children and adults alike are quickly digested carbohydrates resulting in large increases in blood glucose that prompts insulin secretion resulting in fat deposition, stops energy production from fat and increases food consumption and hunger.  Long term effects of frequent spikes of high blood sugar are cell damage and inflammation, hypertension, metabolic syndrome that can lead to serious problems later in life such as heart attacks, strokes, cancer and dementia.

• Sugar, High Fructose Corn syrup, all caloric sweeteners including honey and agave syrup, sweets & candies. Use low calorie sugar substitutes if necessary
• All Juices, even orange juice, eat the fruit instead, sodas, energy drinks, gatorade, powerade, grape juice, cranberry juice, etc. Also avoid cocktail drink mixes like margarita and sweet and sour mix.
• White flour, bread, pasta, cakes, cookies, biscuits, etc.
• Potatoes, white rice, corn flour products, chips, etc.

Beneficial Foods-Instead Choose to Eat High Fiber, Low Glycemic Foods

Carbohydrates can be roughly categorized by the speed of their digestion into simple sugars; the faster the worse for health and slower the better, with fiber on the most beneficial end of the spectrum, which also minimize the amount of simple sugars obtained from your diet. Low glycemic food choices, vast, varied and enjoyable include many foods that were previously stigmatized like eggs, dairy and meat.  Calorie counting is unnecessary if high fiber plant foods are the bulk of your diet as they are satiating and suppress hunger due to slow digestion and low insulin response, in addition they contain thousands of phytonutrients which protect against stress, inflammation and cell damage. 

• Unlimited consumption of salads, leafy green vegetables, whole fruits, and nuts.
• Moderation but not overindulgence in all sorts of interesting foods, including meat, fish, cheese, butter, eggs, olive oil, rape seed/canola oil, herbs and spices. These are what make foods enjoyable and they are mostly nonfattening and nutritionally beneficial
• Peas, lentils, legumes and beans are high in protein and fiber good in moderation as they still contain digestible carbohydrates.
• Whole grains, while much better than refined flour are still high glycemic carbohydrates and counteract ketogenesis if you are trying to lose weight or reverse hypertension and metabolic syndrome. Oat bran and oat germ are an inexpensive alternative, as are wheat bran and wheat germ.
• Drink: water or tea (green tea), coffee, diet drinks if necessary. Again avoid drinks with any sugar, HFCS, or any other calorie containing syrup.
• Alcohol: Fine in moderation: red wine may have particular benefits.
• Supplements most are unnecessary and could even be harmful other than a source of omega3 and vitamin D such as in fish liver oils.

Influence of Diet on Voluntary Physical Activity?

Explanations of how high glycemic foods as well as fiber deficiency can directly influence physical activity and exercise habits and lead to a vicious cycle of increased obesity and inactivity. 

 Physical activity is very important to health and longevity and to a certain extent exercise can help lose weight from fat stores but few of us have the time, dedication or body strength needed to lose weight by exercise alone: consider that an hour of fast running consumes around 1000 Calories and 10 kg of fat contains 90,000 Calories.  Nevertheless, many regard lack of exercise the main reason for rising obesity rates in children and adults alike but evidence suggests the type of foods we eat can suppress spontaneous activity and the natural desire for playful exercise.  These same foods fail to satisfy hunger and therefore lead to a vicious circle of overeating and inactivity.

In other pages of this blog we describe how high glycemic carbohydrates (sugar, flour, potatoes, rice, etc.) make up 60% or more of our staple foods and after every meal, day after day year after year, elevate blood glucose 2-3 fold and insulin levels more than 10 fold. There are numerous detrimental biological consequences of such changes and amongst them is an avoidance of physical activity.  This notion is supported by a recent study whereby laboratory animals were fed either a high glycemic or low glycemic diet.  Voluntary physical activity was 45% higher for the Low Glycemic fed mice after 38 weeks of feeding. The authors concluded that dietary composition can affect physical activity level (1) in addition body composition was changed by the type of food not energy intake and the high-GI diet caused a pre-diabetic condition which other studies suggest affect up to 30% of adolescents in the USA (2).

Basic science research has revealed some of  the biological mechanisms whereby physical activity can be suppressed by the type of food we eat:    Most people will be familiar with the overwhelming lack of energy and need for rest that occurs with illness for example a bout of “flu”.  Inflammatory cytokines, produced by activated immune cells, induce “sickness behaviour” (1) (3) which is essentially avoidance of physical activity.  Inflammation is associated with depressive symptoms, anxiety and invokes fatigue and reduced movement (3), anti-inflammatory compounds can block/reverse many of these changes (3).  A much milder form of sickness behavior may be brought about by low grade inflammation associated with high levels of blood glucose (and fructose) after meals containing large amounts of high glycemic starches and sugars documented by increased levels of markers of inflammation in these situations (5).  A more recent study has shown increased intestinal wall permeability in obese individuals associated with inflammation and its reversal with a low glycemic high fiber diet  (6).  Several other possible interactions exist such as the suppression of mitochondrial biosynthesis with high levels of insulin brought about by high glucose may directly decrease exercise tolerance.  High glucose also increases stress by increasing production of reactive oxygen molecules and widespread glycation of proteins results in serious impairment of cell function (7).

Although the science may seem complicated the take home message is simple: avoid high glycemic foods and eat much more fiber.  The sad reality is that trying to follow such a lifestyle choice is very difficult as just the opposite, high glycemic low fiber foods dominate our food culture and supermarkets.

1. Inflammatory modulation of exercise salience: using hormesis to return to a healthy lifestyle. Alistair V Nunn, Geoffrey W Guy, James S Brodie, Jimmy D Bell. s.l. : Nutrition & Metabolism , Vols. 2010, 7:87.

2. The Prevalence of the Metabolic Syndrome Among a Racially/Ethnically Diverse Group of U.S. Eighth-Grade Adolescents and Associations With Fasting Insulin and Homeostasis Model Assessment of Insulin Resistance Levels. R. Jago, T. Baranowski, J. Buse, S. Edelstein, P. Galassetti, J. Harrell, F. Kaufman, B. Linder, and T. Pham. s.l. : Diabetes Care, Vols. 31:2020–2025, 2008.

3. Inactivation of the cerebral NFkappaB pathway inhibits interleukin-1beta-induced sickness behavior and c-Fos expression in various brain nuclei. Nadjar A, Bluthe RM, May MJ, Dantzer R, Parnet P. s.l. : Neuropsychopharmacology , Vols. 2005, 30:1492-1499.

4. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Miller AH, Maletic V, Raison CL:. s.l. : Biol Psychiatry, Vols. 2009, 65:732-741.

5. High–glycemic index carbohydrate increases nuclear factor- B activation in mononuclear cells of young, lean healthy subjects. Scott Dickinson, Dale P Hancock, Peter Petocz, Antonio Ceriello and Jennie Brand-Miller. s.l. : Am J Clin Nutr, Vols. 2008;87:1188 –93. http://www.ajcn.org/cgi/content/full/87/5/1188.

6. Xiao, et al. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome. s.l. : FEMS Microbiology Ecology, Volume 87, Issue 2, pages 357–367, February 2014.

7. Dicarbonyls linked to damage in the powerhouse: glycation of mitochondrial proteins and oxidative stress. N Rabbani, P Thornalley. s.l. : Biochem Soc Trans., Vols. 2008 October ; 36(Pt 5): 1045–1050. doi:10.1042/BST0361045.

Higher consumption of dietary fiber has been associated with lower risk of death from all causes as well as cardio-vascular diseases such as heart attack and stroke.  A recent analysis of most of the published population studies on fiber and cardio-vascular diseases was published in the British Medical Journal and here is a link to the original paper: Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ 2014.

Figure 2 from the paper is shown below and illustrates relative risk (RR) of a heart attack (CHD) with varying degrees of fiber consumption from all sources.  Note that less than 20 grams a day is associated with increased risk (10 gms a day corresponds to a RR of around 1.3 means a 30% increased risk of a heart attack or similar event).  To put this into perspective a RR of 1.3 is of the same order found to be  associated with raised LDL cholesterol and taking Statins reduces the risk of coronary heart disease by around 10 to 20% i.e. RR 1.1 to 1.2.  It is interesting to note that food consumption studies reveal that the majority of UK and US people consume around 10 grams of fiber a day, much less than the recommended 30 grams a day.

Risk reduction from heart disease with increasing consumption of fiber

The study found a dose response relationship between fiber intake and cardio-vascular disease where each 7 gm increase decreased risk by about 9%.  They projected a possible 40 to 50% reduction in risk with fiber intake of 60 to 70 grams per day.

1. How can one consume 70 plus grams of fiber a day?
2. Is there a downside?

A fascinating study by Jenkins et al 2002 sheds some light on these questions, and the original paper can be accessed here: The Garden of Eden: plant based diets and the genetic drive to conserve cholesterol and its implications for heart disease in the 21st century.  

Three diets were compared in the study and one of them was a plant based diet containing 145 grams of fiber per day.  This diet was intended to mimic that which our ancestors the great apes might have consumed between 5 and 10 million years ago, however all the food was purchased at a local supermarket.  The following extract from the study goes a long way to answer the two questions:

It consisted of large amounts of leafy vegetables, nuts (almonds and hazelnuts), and fruit, some tropical, but all purchased in local grocery stores. Theoretically, all these foods could be eaten raw but the majority of vegetables were eaten cooked. The diet was effectively devoid of any significant amount of starch. The major feature of the Simian diet was the large volume and the length of time spent eating. Considerable pressure had to be brought to bear on the subjects to ensure they ate all their food and did not lose weight. The foods were palatable but the volume (5.5 kg/d for a 70-kg man) was excessive. At the end of the 2-week diet periods of weight maintenance, LDL-cholesterol was  reduced on the Simian diet by 33%, on the Neolithic diet by 23% and on the therapeutic diet by 7%.  Analysis of the diet for components, which might alter cholesterol metabolism, showed that the Simian diet provided approximately 1 g of plant sterols daily, 145 g of fiber and 92 g of vegetable protein and on an average, over 70 g almonds or hazelnuts per day. 

The study gives support to several purported benefits of high fiber diets:

1. There was no downside for consuming a relatively massive amount of 145 grams of fiber per day.
2. On the contrary fiber consumption was a powerful limiting factor regarding total calorie intake: Considerable pressure had to be brought to bear on the subjects to ensure they ate all their food and did not lose weight. 
3. The high fiber Simian diet quickly and dramatically improved subjects’ cholesterol profiles

For those wishing to control their weight there is a warning sign from the study in that whole grain cereals are regarded as the obvious source of fiber but they are also the major source of high glycemic starch in our diet and attempts at eating more whole grains to maximize fiber consumption runs the risk of weight gain with high blood sugar and insulin levels.  For instance whole wheat contains 61% starch as well as 12% fiber and in order to get 48 gms of fiber from this source one would have to simultaneously consume 244 gms starch and 56 gms protein, an extra 1200 calories.  In order to achieve adequate fiber without weight gain there is a need to replace whole wheat flour used in staples like bread, pasta, cakes and cookies with low carb/high fiber formulations (www.fiberflour.org).

ATP synthase is a most amazing molecular machine found in mitochondria that produces ATP, the cell’s most important energy carrier, its main component rotates at 300 cycles per second driven by a cascade of 1,000 hydrogen ions to produce a hundred ATP molecules a second.

I want to use the life cycle of this molecular machine, which makes life as we know possible, to illustrate the importance of obligatory recycling of living material and the influence of lifestyle decisions on those processes.  ATP synthase has a half life of around 40 hours, therefore no ATP synthase exist in your body for longer than 5 days. This means that every living cell has to dismantle and rebuild all of its ATP synthase within 5 days and in order to maintain a stable energy supply without excessive accumulation of waste material, the production of new ATP synthase must be matched with the recycling of old:  this is a hugely expensive undertaking in terms of energy and resources for the organism and clearly must be necessary for survival.  The reason for such a high turnover of all proteins in the body is that they become damaged and dysfunctional quite rapidly. Specific identification and removal of dysfunctional proteins is complex and highly regulated, carried out in proteosomes and a process called autophagy. Deficiencies in autophagy are thought to be responsible for many degenerative conditions such as dementia, Parkinson’s, and aging in general.  A lethal childhood condition Batten Disease, is caused by inadequate dismantling and therefore intracellular build up of dysfunctional ATP synthase proteins.

So how do lifestyle decisions affect protein synthesis and autophagy? Diet and Exercise!

Nutritional factors have a major controlling influence on autophagy; high levels of amino acids and glucose suppress autophagy and fasting particularly starvation powerfully activates it. The main pathway to suppress autophagy is through a master-controller (mTOR) that is controlled amongst other factors by insulin and glucagon, note that these hormones are regulated primarily by blood glucose levels and to a lesser degree amino-acids.  Simply put glucose and amino-acids suppress autophagy while low levels of both enhance it.  Many of the health benefits of calorie restriction are though to be due to activation of autophagy.  However enhancement of autophagy may also be achieved by  specific avoidance of raised glucose and excessive protein intake without the difficulties associated with generalized calorie restriction.

On the synthesis side diet; acting through insulin and glucagon, as well as exercise and other environmental circumstances have a controlling influence on  muscle and mitochondrial biosynthesis acting through the master-controller transcription factor (PGC1alpha), as seen in the figure below from this linked reference.

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