Why doesn’t exercise and diet reduce heart disease for diabetics?

That’s a good question after the June 24 issue of the New England Journal of Medicine reported on the failure of long-term diet and exercise to reduce heart disease in diabetics1. It had been known from earlier and shorter studies that diet and exercise in diabetics appeared to generate a decreased risk of cardiovascular disease. This is important since heart disease remains the number-one killer of Americans, and people with diabetes are two to four times more likely to develop heart disease. Since diabetes is becoming epidemic, this would suggest that heart disease should soon begin to escalate. But for exercise and diet have any benefits in any condition, they have to been continued forever. That is the motivation for this 13-year study that started with the best of intentions. However, last year the study was terminated at 10 years since it was clear that there were no cardiovascular benefits. Now that the study details have been published, it is clear why it failed.

First, all of the success of diet and exercise started to evaporate after the first year. Remember, the people who enter these studies are highly motivated with a terrible future awaiting them. So why would they seemingly throw away all the initial benefits of weight loss and reduction of blood sugar? Part of the reason can be explained by why most diet program fail: Willpower can only take you so far if your hormones are working against you. The end result is you are constantly hungry and always tired.

The amount of calories the subjects of this study consumed was low (between 1,200 and 1,800 calories per day), but the diet was a high-carbohydrate diet (that induces low blood sugar due to hyperinsulinemia). The diet was coupled with lots of exercise (that also lowers blood sugar). This is an almost surefire prescription to be constantly hungry and tired. As a result, compliance wanes.

On the other hand, if you are never hungry, then compliance is better. That was the case with another 13-year study of diabetic patients who had gastric bypass surgery. For these patients, there was a significant reduction in cardiovascular events2. The reason is probably hormonal. If you lose weight by diet and exercise, your levels of the hunger hormone ghrelin increases with no change in the levels of your satiety hormone, PYY. Just the opposite happens with gastric bypass surgery. Ghrelin doesn’t change, but PYY increases3. The result is that you are not hungry, and therefor your lifestyle compliance improves.

Of course, giving every diabetic gastric bypass surgery makes little sense. Giving them new, more powerful diabetic drugs with equally powerful side effects (like heart attacks) also makes no sense.

There may be third way: Functional foods that can increase PYY levels. But these have to be tasty (like pasta and rice) and convenient (only 90 seconds to make) since you have to take them the rest of your life. That’s the project I have been working on for the past six years. These new Zone meals may be the answer, as they appear to reduce hunger without causing fatigue while eating the foods you like to eat. Zone meals are low-tech medicine with potentially high-tech results and are coming soon.

References

  1. Wing RR et al. “Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.” NEJM DOI:10.1056/NEJMoa 1212914 (2013)
  2. Romeo S et al. “Cardiovascular events after bariatric surgery in obese subjects with type 2 diabetes.” Diabetes Care 35: 3613-2617 (2012)
  3. Olivan B et al. “Effect of weight loss by diet or gastric bypass surgery on peptide YY3-36 (PYY) levels.” Ann Surg 249: 948-953 (2009)

Zone diet validation studies

Weight Loss

Any diet that restricts calories will result in equivalent weight loss. However, the same doesn’t hold true as to what the source of that weight loss is. Weight loss from either dehydration (such as ketogenic diets) or cannibalization of muscle and organ mass (such as low-protein diets) has no health benefits. Only when the weight loss source is from stored fat do you gain any health benefits. Here the Zone diet has been shown to be superior to all other diets in burning fat faster (1-4). It has been demonstrated that if a person has a high initial insulin response to a glucose challenge, then the Zone diet is also superior in weight loss (5,6). A recent study from the New England Journal of Medicine indicates that a diet composition similar to the Zone diet is superior to other compositions in preventing the regain of lost weight (7). This is probably caused by the increased satiety induced by the Zone diet compared to other diets (1,8,9).

Reduction of cellular inflammation

There is total agreement in the research literature that the Zone diet is superior in reducing cellular inflammation (10-12). Since cellular inflammation is the driving force for chronic disease, then this should be the ultimate goal of any diet. Call me crazy for thinking otherwise.

Heart disease

It is ironic that the Ornish diet is still considered one of the best diets for heart disease, since the published data indicates that twice as many people had fatal heart attacks on the Ornish diet compared to a control diet (13). This is definitely the case of don’t confuse me with the facts. On the other hand, diets with the same balance of protein, carbohydrate and fat as the Zone diet has have been shown to be superior in reducing cardiovascular risk factors, such as cholesterol and fasting insulin (14,15).

Diabetes

The first publication validating the benefits of the Zone diet in treating diabetes appeared in 1998 (16). Since that time there have been several other studies indicating the superiority of the Zone diet composition for reducing blood glucose levels (17-20). In 2005, the Joslin Diabetes Research Center at Harvard Medical School announced its new dietary guidelines for treating obesity and diabetes. These dietary guidelines were essentially identical to the Zone diet. Studies done at the Joslin Diabetes Research Center following those dietary guidelines confirm the efficacy of the Zone diet to reduce diabetic risk factors (21). If the Zone diet isn’t recommended for individuals with diabetes, then someone should tell Harvard.

Ease of use

The Zone diet simply requires balancing one-third of your plate with low-fat protein with the other two-thirds coming from fruits and vegetables (i.e. colorful carbohydrates). Then you add a dash (that’s a small amount) of heart-healthy monounsaturated fats. The Zone diet is based on a bell-shaped curve balancing low-fat protein and low-glycemic-index carbohydrates, not a particular magic number. If you balance the plate as described above using your hand and your eye, it will approximate 40 percent of the calories as carbohydrates, 30 percent of calories as protein, and 30 percent of the calories as fat. Furthermore, it was found in a recent Stanford University study that the Zone diet provided greater amounts of micronutrients on a calorie-restricted program than any other diet (22).

Eventually all dietary theories have to be analyzed in the crucible of experimentation to determine their validity. So far in the past 13 years since I wrote my first book, my concepts of anti-inflammatory nutrition still seem to be at the cutting edge.

References

  1. Skov AR, Toubro S, Ronn B, Holm L, and Astrup A. “Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity.” Int J Obes Relat Metab Disord 23: 528-536 (1999)
  2. Layman DK, Boileau RA, Erickson DJ, Painter JE, Shiue H, Sather C, and Christou DD. “A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women.” J Nutr 133: 411-417 (2003)
  3. Fontani G, Corradeschi F, Felici A, Alfatti F, Bugarini R, Fiaschi AI, Cerretani D, Montorfano G, Rizzo AM, and Berra B. “Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with omega-3 polyunsaturated fatty acids.” Eur J Clin Invest 35: 499-507 (2005)
  4. Layman DK, Evans EM, Erickson D, Seyler J, Weber J, Bagshaw D, Griel A, Psota T, and Kris-Etherton P. “A moderate-protein diet produces sustained weight loss and long-term changes in body composition and blood lipids in obese adults.” J Nutr 139: 514-521 (2009)
  5. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, and Ludwig DS. “Effects of a low-glycemic-load vs low-fat diet in obese young adults: a randomized trial.” JAMA 297: 2092-2102 (2007)
  6. Pittas AG, Das SK, Hajduk CL, Golden J, Saltzman E, Stark PC, Greenberg AS, and Roberts SB. “A low-glycemic-load diet facilitates greater weight loss in overweight adults with high insulin secretion but not in overweight adults with low insulin secretion in the CALERIE Trial.” Diabetes Care 28: 2939-2941 (2005)
  7. Larsen TM, Dalskov SM, van Baak M, Jebb SA, Papadaki A, Pfeiffer AF, Martinez JA, Handjieva-Darlenska T, Kunesova M, Pihlsgard M, Stender S, Holst C, Saris WH, and Astrup A. “Diets with high or low protein content and glycemic index for weight-loss maintenance.” N Engl J Med 363: 2102-2113 (2010)
  8. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, Roberts SB, Agus MS, Swain JF, Larson CL, and Eckert EA. “Dietary high-glycemic-index foods, overeating, and obesity.” Pediatrics 103: E26 (1999)
  9. Agus MS, Swain JF, Larson CL, Eckert EA, and Ludwig DS. “Dietary composition and physiologic adaptations to energy restriction.” Am J Clin Nutr 71: 901-907 (2000)
  10. Pereira MA, Swain J, Goldfine AB, Rifai N, and Ludwig DS. “Effects of a low-glycemic-load diet on resting energy expenditure and heart disease risk factors during weight loss.” JAMA 292: 2482-2490 (2004)
  11. Pittas AG, Roberts SB, Das SK, Gilhooly CH, Saltzman E, Golden J, Stark PC, and Greenberg AS. “The effects of the dietary glycemic load on type 2 diabetes risk factors during weight loss.” Obesity 14: 2200-2209 (2006)
  12. Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, and Sears B. “Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets.” Am J Clin Nutr 83: 1055-1061 (2006)
  13. Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, and Brand RJ, “Intensive lifestyle changes for reversal of coronary heart disease.” JAMA 280: 2001-2007 (1998)
  14. Wolfe BM and Piche LA. “Replacement of carbohydrate by protein in a conventional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects.” Clin Invest Med 22: 140-1488 (1999)
  15. Dumesnil JG, Turgeon J, Tremblay A, Poirier P, Gilbert M, Gagnon L, St-Pierre S, Garneau C, Lemieux I, Pascot A, Bergeron J, and Despres JP. “Effect of a low-glycaemic index, low-fat, high-protein diet on the atherogenic metabolic risk profile of abdominally obese men.” Br J Nutr 86:557-568 (2001)
  16. Markovic TP, Campbell LV, Balasubramanian S, Jenkins AB, Fleury AC, Simons LA, and Chisholm DJ. “Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with or without type 2 diabetes.” Diabetes Care 21: 695-700 (1998)
  17. Layman DK, Shiue H, Sather C, Erickson DJ, and Baum J. “Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss.” J Nutr 133: 405-410 (2003)
  18. Gannon MC, Nuttall FQ, Saeed A, Jordan K, and Hoover H. “An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes.” Am J Clin Nutr 78: 734-741 (2003)
  19. Nuttall FQ, Gannon MC, Saeed A, Jordan K, and Hoover H. “The metabolic response of subjects with type 2 diabetes to a high-protein, weight-maintenance diet.” J Clin Endocrinol Metab 2003 88: 3577-3583 (2003)
  20. Gannon MC and Nuttall FQ. “Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition.” Nutr Metab (Lond) 3: 16 (2006)
  21. Hamdy O and Carver C. “The Why WAIT program: improving clinical outcomes through weight management in type 2 diabetes.” Curr Diab Rep 8: 413-420 (2008)
  22. Gardner CD, Kim S, Bersamin A, Dopler-Nelson M, Otten J, Oelrich B, and Cherin R. “Micronutrient quality of weight-loss diets that focus on macronutrients: results from the A TO Z study.” Am J Clin Nutr 92: 304-312 (2010)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

No excuses, eat your breakfast

Everyone knows that breakfast should be the most important meal of the day. Unfortunately, no one seems to have time to consume a real breakfast. If they do, then it’s usually a high-carbohydrate quasi-dessert that is so portable that they can eat it in the car. Although our world is becoming time-compressed, our biological rhythms are not. While you sleep, your body is literally digesting itself to provide energy for the brain. Much of this energy comes from digesting muscle mass to make glucose as the supplies of stored carbohydrate in the liver are rapidly depleted during the night forcing the body to start digesting muscle to supply enough glucose to the brain. Rebuilding lost muscle mass demands protein replenishment upon waking, and you aren’t going to get achieve that goal by eating a typical breakfast cereal and definitely not by drinking a cup of coffee as a stimulant.

It has been known for some time there is a strong relationship between skipping breakfast and obesity and subsequent establishment of poor dietary habits (1,2). Furthermore, the higher the protein content of the breakfast, the greater the satiety. That increase in satiety is correlated with increased PYY (the satiety hormone) levels in the blood (3). It was also demonstrated more than 10 years ago that giving a higher-protein breakfast meal to overweight adolescents resulted in significant appetite suppression. This lack of hunger is correlated with dramatic changes in the levels of insulin and glucagon in the blood (4).

Now a new study pre-published electronically indicates that a high-protein breakfast also dramatically alters brain function (5). Overweight adolescents who normally skipped breakfast were either given nothing for breakfast, a carbohydrate-rich breakfast, or a protein-rich breakfast for six days. On the seventh day of each breakfast cycle, they had a fMRI scan of their brains while being shown pictures of various palatable foods on a screen. After consuming the higher-protein breakfast for six days, there was far less activation in the regions of brain associated with food motivation and reward when shown the pictures of highly desirable foods.

One surprising observation from this study is the primary reason given by the overweight adolescent subjects for skipping breakfast was not that they were trying to lose weight, but they just lacked the time or were not feeling hungry upon waking. The lack of time in the morning is understandable because adolescents don’t get enough sleep anyway. However, the lack of hunger is probably due to the rise of hormonal levels early in the morning to rouse someone out of sleep. This acts like a powerful stimulant (and if you need more, then drink coffee). But the lack of breakfast means eating more snacks with higher calories throughout the day. Bottom line, even if you aren’t hungry at breakfast, just eat it anyway. But make sure it has adequate levels of protein if you want to lose weight.

References

  1. Deshmukh-Taskar PR, Nicklas TA, O’Neil CE, Keast DR, Radcliffe JD, and Cho S.
    “The relationship of breakfast skipping and type of breakfast consumption with nutrient intake and weight status in children and adolescents: the National Health and Nutrition Examination Survey 1999-2006.” J Am Diet Assoc 110: 869-878 (2010)
  2. Sjoberg A, Hallberg L, Hoglund D, and Hulthen L. “Meal pattern, food choice, nutrient intake and lifestyle factors in The Goteborg Adolescence Study.” Eur J Clin Nutr 57: 1569-1578 (2003)
  3. Leidy HJ and Racki EM. “The addition of a protein-rich breakfast and its effects on acute appetite control and food intake in ‘breakfast-skipping’ adolescents.” Int J Obes 34: 1125-1133 (2010)
  4. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, and Roberts SB.
    “High glycemic-index foods, overeating, and obesity.” Pediatrics 103: E26 (1999)
  5. Leidy HJ, Lepping RJ, Savage CR, and Harris CT. “Neural responses to visual food stimuli after a normal vs. higher-protein breakfast in breakfast-skipping teens.” Obesity doi 10.1038./oby.2011.108 (2011)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

Mythologies in treatment of childhood obesity

childhood obesityWe all know that obese children tend to be inactive. This leads to the “obvious” conclusion that the solution to childhood obesity is simply more exercise. But what if that conclusion is totally wrong?

There is no mistaking that obesity and lack of physical activity are linked. But which comes first? The answer appears to be obesity (1). A study published online in the Archives of Disease in Childhood followed young children over a four-year period carefully measuring their physical activity with accelerometers to measure physical activity for seven consecutive days as well as their percentage of body fat using DEXA scans. What they found was that physical inactivity was not related to the increased accumulation of body fat, rather they found that increased body fat was the cause of decreasing physical activity. This is also the situation with adults (2-5).

So why do so many researchers believe that inactivity leads to fatness? Because it just has to be the answer. This belief persists in spite of numerous studies that demonstrate that increased physical activity has little impact on reducing childhood obesity (6). This is a classic case of don't confuse me with the facts, since in my heart I know I am right.

This is not to say that exercise has no benefits in obese children. In fact, the same authors had published an earlier study indicating that while intense exercise had little impact on fat loss, there is a significant benefit in reducing insulin resistance (7).

The implications of this study in children are immense. In essence, increasing public expenditures to increase physical activity will not address the childhood obesity epidemic no matter how much money you throw at the problem. Instead you have to focus on reducing calorie intake. However, this decrease in calorie consumption is not going to be accomplished by increased willpower, but by increasing satiety (lack of hunger) in obese children.

As I pointed out in my most recent book, “Toxic Fat,” if you want to increase satiety, you must reduce cellular inflammation in the brain (8). That is best accomplished by a combination of an anti-inflammatory diet coupled with high-dose fish oil.

Of course, as an alternative, you could always consider gastric bypass surgery.

References

  1. Metcalf BS, Hosking J, Jeffery AN, Voss LD, Henley W, and Wilkin TJ. “Fatness leads to inactivity, but inactivity does not lead to fatness.” Arch Dis Chil doi:10.1136/adc.2009.175927
  2. Bak H, Petersen L, and Sorensen TI. “Physical activity in relation to development and maintenance of obesity in men with and without juvenile onset obesity.” Int J Obes Relate Metabl Disord 28: 99-104 (2004)
  3. Petersen L, Schnorhr, and Sorensen TI. “Longitudinal study of the long-term relation between physical activity and obesity in adults.” Int J Obes Relate Metabl Disord 28: 105-112 (2004)
  4. Mortensen LH, Siegler Ic, Barefoot JC, Gronbaek M, and Sorensen TI. “Prospective associations between sedentary lifestyle and BMI in midlife.” Obesity 14: 1462-1471 (2006)
  5. Ekelund U, Brage S, Besson H, Sharp S, and Wareham NJ. “Time spent being sedentary and weight gain in healthy adults.” Am J Clin Nutr 88: 612-617 (2008)
  6. Wareham NJ, van Sluijs EM, and Ekelund U. “Physical activity and obesity prevention: a review of the current evidence.” Proc Nutr Soc 64: 229-247 (2005)
  7. Metcalf BS, Voss LD, Hosking J, Jeffery AN, and Wilkin TJ. “Physical activity at the government-recommended level and obesity-related outcomes.” Arch Dis Child93: 772-777 (2008)
  8. Sears B. “Toxic Fat”. Thomas Nelson. Nashville, TN (2008)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

Blame weight gain on the brain

Many people claim they are addicted to food. That may not be too far from the truth.

Over millions of years of evolution, our brains have adapted to provide us a reward for successfully ingesting food. The hormone dopamine appears to be the key link in this reward process. But to complete the circuit, dopamine has to interact with its receptor. It has been known for many years that the ability of dopamine to combine with one of its receptors (the D2 dopamine receptor) is compromised in obese individuals compared to normal-weight individuals (1). This led to the hypothesis that obese individuals overeat as a way to compensate for the reduction in the dopamine reward circuits just as individuals with addictive behaviors (drugs, alcohol, gambling, etc.) do when their dopamine levels are low. It is also known that food restriction up-regulates the number of D2 receptors (2). This likely completes the reward circuit.

This effect of increasing D2 receptors is confirmed in obese patients who have undergone gastric bypass surgery that results in calorie restriction (3). This may explain why gastric bypass surgery is currently the only proven long-term solution of obesity. More recent studies with functional magnetic resonance imaging (fMRI) have indicated that unlike women with a stable weight where the mere visual image of palatable food increases the reward activity in the brain, that response is highly reduced in women who have gained weight in the past six months (4). This suggests that the dopamine reward circuits are compromised in women with recent weight gain, thus prompting a further increased risk for overeating in those individuals to increase dopamine output.

So does this mean that the obese patient with a disrupted dopamine reward system has no hope of overcoming these powerful neurological deficits? Not necessarily. There are a number of dietary interventions to increase the levels of dopamine and its receptors. The first is calorie restriction, which is only possible if you aren’t hungry. The usual culprit that triggers constant hunger is a disruption of hormonal communication of hunger and satiety signals in the brain. It has been shown that following a strict Zone diet can quickly restore the desired balance that leads to greater satiety (5-7). The probable mechanism is the reduction of cellular inflammation by an anti-inflammatory diet (8-10).

Another dietary intervention is high-dose fish oil that has been demonstrated to both increase dopamine and dopamine receptors in animals (11,12). This would explain why high-dose fish oil has been found useful in the treatment of ADHD, a condition characterized by low dopamine levels (13). Finally, high-dose fish oil can reduce the synthesis of endocannabinoids in the brain that are powerful stimulators of hunger (14).

I often say that if you are fat, it may not be your fault. The blame can be placed on your genes and recent changes in the human food supply that are changing their expression, especially in the dopamine reward system. However, once you know what causes the problem, you have the potential to correct it. If you are apparently addicted to food, the answer may very well lie in an anti-inflammatory diet coupled with high-dose fish oil.

References

  1. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, and Fowler JS. “Brain dopamine and obesity.” Lancet 357: 354-357 (2001)
  2. Thanos PK, Michaelides M, Piyis YK, Wang GJ, and Volkow ND. “Food restriction markedly increases dopamine D2 receptor (D2R) in a rat model of obesity as assessed with in-vivo muPET imaging and in-vitro autoradiography.” Synapse 62: 50-61 (2008)
  3. Steele KE, Prokopowicz GP, Schweitzer MA, Magunsuon TH, Lidor AO, Kuwabawa H, Kumar A, Brasic J, and Wong DF. “Alterations of central dopamine receptors before and after gastric bypass surgery.” Obes Surg 20: 369-374 (2010)
  4. Stice E, Yokum S, Blum K, and Bohon C. “Weight gain is associated with reduced striatal response to palatable food.” J Neurosci 30 :13105-13109 (2010)
  5. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, and Roberts SB. “High glycemic-index foods, overeating, and obesity.” Pediatrics 103: E26 (1999)
  6. Agus MS, Swain JF, Larson CL, Eckert EA, and Ludwig DS. “Dietary composition and physiologic adaptations to energy restriction.” Am J Clin Nutr 71: 901-7 (2000)
  7. Jonsson T, Granfeldt Y, Erlanson-Albertsson C, Ahren B, and Lindeberg S. “A paleolithic diet is more satiating per calorie than a mediterranean-like diet in individuals with ischemic heart disease.” Nutr Metab 7:85 (2010)
  8. Pereira MA, Swain J, Goldfine AB, Rifai N, and Ludwig DS. “Effects of a low glycemic-load diet on resting energy expenditure and heart disease risk factors during weight loss.” JAMA 292: 2482-2490 (2004)
  9. Pittas AG, Roberts SB, Das SK, Gilhooly CH, Saltzman E, Golden J, Stark PC, and Greenberg AS. “The effects of the dietary glycemic load on type 2 diabetes risk factors during weight loss.” Obesity 14: 2200-2209 (2006)
  10. Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, and Sears B. “Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets.” Am J Clin Nutr 83: 1055-1061 (2006)
  11. Chalon S, Delion-Vancassel S, Belzung C, Guilloteau D, Leguisquet AM, Besnard JC, and Durand G. “Dietary fish oil affects monoaminergic neurotransmission and behavior in rats.“ J Nutr 128: 2512-2519 (1998)
  12. Chalon S. “Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Essent Fatty Acids 75: 259-269 (2006)
  13. Sorgi PJ, Hallowell EM, Hutchins HL, and Sears B. “Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.” Nutr J 6: 16 (2007)
  14. Watanabe S, Doshi M, and Hamazaki T. “n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonylglycerol level in mice.” Prostaglandin Leukot Essent Fatty Acids 69:51–59 (2003)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

Try the team approach to nutrition

One of the problems with nutrition is that it is too complex for simple thinking. Unlike drugs, which are designed to inhibit a particular target enzyme, nutrients often work in combinations like a team operating at the genetic level. When you try to apply drug-like thinking (i.e. one compound has to do all the work) to nutrient research, then the results are often underwhelming. Nowhere is this clearer than when we look at how nutrients interact to control body weight.

Weight gain can be best understood as a defect in both metabolism (the conversion of dietary energy into chemical energy) and storage (the stockpiling of excess dietary intake). This involves a four-way conversation between the brain, the gut, the liver and the adipose tissue. The only way these various organs can communicate with each other is via hormones. The gut sends signals to the brain when to stop eating. If the brain receives those signals loud and clear, your desire for food decreases (i.e. satiety). Finally, the food that has been ingested is either converted by the liver into suitable metabolites that can either be used for generating chemical energy (i.e. ATP) or stored (primarily in the fat cells) for future use. When it all works together, it runs smoothly. When it doesn’t work well, you end up gaining more body fat accelerating the pathway toward chronic disease.

One of the key hormones in this complex communication process is adiponectin. Apidonectin is an anti-inflammatory hormone made by the fat cells that is essential for reducing insulin resistance and preventing lipotoxicity (1). In other words, it is at the center of this complex hormonal communication system to help keep body weight in check and slow the development of chronic disease. Great, but how do you increase adiponectin?

First, there is no drug that can do it, but there are nutrients that can. One approach is to consume more omega-3 fatty acids (1). High levels of omega-3 fatty acids activate a genetic transcription factor that causes the increased production of adiponectin. But it takes a lot of high purity omega-3 oil to turn on that gene transcription factor. Now there appears to be another way: Taking polyphenols (2). The polyphenols don’t increase the activity of the genetic transcription factor, but they do facilitate the assembly of adiponectin into its most active form. Of course, if you don’t have enough omega-3 fatty acids in the diet, you can’t produce the necessary adiponectin building blocks to be assembled. When you combine the two (high purity omega-3 oil and polyphenols), then you don’t need to use as much of either one for the desired end result (3).

That’s how nutrition really works. You have to use a team nutrient approach to alter genetic expression. A lot more complicated than giving a single drug, but of course without the inherent side effects.

References

  1. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  2. Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, and Shulman GI. “Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice.” Diabetes 55: 924-928 (2006)
  3. Wang Q, Liu M, Liu X, Dong LQ, Glickman RD, Slage TJ, Zhou Z, and Liu F. “Up-regulation of adiponectin by resveratrol.” J Biol Chem 286: 60-66 (2011)
  4. Shirai N and Suzuki H. “Effects of simultaneous intakes of fish oil and green tea extracts on plasma, glucose, insulin, C-peptide, and adiponectin and on liver lipid concentrations in mice fed low- and high-fat diets.” Ann Nutr Metab 52: 241-249 (2008)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

Increased satiety: The real secret to weight loss

Satiety is defined as lack of hunger. If you aren’t hungry, then cutting back calories is easy. Unfortunately, Americans seem to be hungrier than ever. This is not caused by a lack of willpower but due to hormonal imbalances in the hypothalamus that tell the brain to either seek more food or spend time on more productive activities. So the real question is not what is the best diet for weight loss, but what is the best diet for satiety?

the anti inflammatory diet has been clinically shown to burn fat faster than standard, recommended diets (1-3) as well as decreasing hunger compared to standard, recommended diets (4,5). But then whoever said that standard, recommended diets (like the USDA Food Pyramid) are good? A better comparison might be the anti inflammatory diet versus a Mediterranean diet.

I have often said that the anti inflammatory diet should be considered as the evolution of the Mediterranean diet because of its enhanced hormonal control. So where is the data for my contention?

The first randomized controlled research appeared in 2007 using patients with existing heart disease (6). In this study, while both groups lost weight, it was only the group on a Paleolithic diet that had any benefits in glucose reduction. So what’s a Paleolithic diet? In this study it was one that supplied 40 percent of the calories as low-glycemic-load carbohydrates, 28 percent of the calories as low-fat protein, and 28 percent from fat (the remaining calories came from alcohol, which didn’t exist in Paleolithic times). That sounds exactly like the anti inflammatory diet to me, so I will simply call it that. On the other hand, the Mediterranean diet was lower in protein (20 percent) and higher in carbohydrates (50 percent) as well as containing far more cereals and dairy products than the anti inflammatory diet.

The interesting thing that came out of this initial study was that patients on the anti inflammatory diet were apparently eating fewer calories, but with greater satiety. So they repeated the study again with another set of cardiovascular patients, except they measured leptin levels this time. The results were exactly the same (7), that is the anti inflammatory diet was more satiating per calorie, and there was also a greater reduction in leptin levels. This makes perfect sense since improved glycemic control seen in the first comparison study (6) would have been a consequence of reducing insulin resistance. The decrease in the leptin levels in the second study (7) would have been a consequence of the reduction of leptin resistance. The most likely cause of this hormone resistance would be the anti-inflammatory benefits of the anti inflammatory diet because it decreases cellular inflammation. It’s cellular inflammation that disrupts hormonal signaling efficiency and causes hormone resistance.

So here we have two randomized controlled studies (6,7) that indicate the superiority of the anti inflammatory diet compared to Mediterranean diet relative to reducing hormone resistance as well providing greater satiety with fewer calories, just as demonstrated in earlier studies when the anti inflammatory diet was compared to standard recommended diets (4,5). It is increased satiety that is ultimately how you lose weight and keep it off. The anti inflammatory diet appears the easiest way to reach that goal.

References

1. Layman DK, Boileau RA, Erickson DJ, Painter JE, Shiue H, Sather C, and Christou DD. “A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women.” J Nutr 133: 411-417 (2003)

2. Lasker DA, Evans EM, and Layman DK, “Moderate-carbohydrate, moderate-protein weight-loss diet reduces cardiovascular disease risk compared to high-carbohydrate, low-protein diet in obese adults. A randomized clinical trial.” Nutrition and Metabolism 5: 30 (2008)

3. Fontani G, Corradeschi F, Felici A, Alfatti F, Bugarini R, Fiaschi AI, Cerretani D, Montorfano G, Rizzo AM and Berra B. “Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with omega-3 polyunsaturated fatty acids.” Eur J Clin Invest 35: 499-507 (2005)

4. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, and Roberts SB. “High glycemic-index foods, overeating, and obesity.” Pediatrics 103:e26 (1999)

5. Agus MSD, Swain JF, Larson CL, Eckert E, and Ludwig DS. “Dietary composition and physiological adaptations to energy restriction.” Am J Clin Nutr 71: 901-907 (2000)

6. Lindberg S, Jonsson T, Granfeldt Y, Borgstrand E, Soffman J, Sjostrom K and Ahren B. “A Paleolithic diet improves glucose tolerance more than a Mediterrean-like diet in individuals with ischaemic heart disease.” Diabetologia 50: 1795-1807 (2007)

7. Jonsson T, Granfeldt Y, Erlanson-Albertsson, Ahren B, and Lindeber S. “A Paleolithic diet is more satiating per calorie than a Mediterrean-like diet in individuals with ischemic heart disease.” Nutrition & Metabolism 7:85 (2010)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

Does living longer mean living poorly?

America has the highest health-care costs in the world. But are we really living better as a consequence of this massive cost? The January 2011 issue of the Journals of Gerontology says maybe not (1). There is no question that Americans are living longer, but our years of disease-free and functional living are declining faster. In particular, the chances of someone age 65 reaching age 85 have doubled from (from 20 percent to 40 percent), but a longer life is coming with more chronic disease and an increasing inability to function normally. In other words, the number of healthy years we can expect to have has actually decreased over the last decade.

So where are all our health-care dollars going? They appear to be keeping us alive. We are delaying death at the price of decreased quality of life as we age. As the lead author stated, “Longer life is what we want. But we’re going to have to pay for it with more treatment of diseases and accommodations for disability.” Since 40 percent of our health-care costs come after age 65, we can expect that Medicare costs will rise even faster than expected as an increasingly sicker baby-boomer population begins to enter Medicare starting this year.

But what about all the news we hear about “anti-aging” research where we can just inject “youth hormones,” like growth hormone, to reverse the aging process? It turns out that there may be trouble brewing in that area also. These hormones are growth factors. This means they turn on DNA synthesis that leads to a shortening of telomeres at the end of a DNA strand. When these telomeres become short enough, any future DNA turnover stops, and the cell dies. This has been demonstrated to occur in mice in which you can increase the levels of growth hormone. When you do so, the animals die prematurely, and there appears to be an acceleration of aging in many organs, including the brain (2).

This potential side effect of increased growth hormone is further confirmed in another recent study (3). This particular study demonstrated that giving mice inhibitors of the release of growth hormone increased their longevity. What was unique in this study was that they used specially bred mice that age prematurely. So if you want to speed up the aging process by taking growth hormone injections, you might look great in the process, but don’t count on an extended lifetime.

Of course, there is another way of looking better and living a longer, healthier life: Calorie restriction without hunger or deprivation. This is the foundation of the anti inflammatory diet. By maintaining the appropriate balance of protein to carbohydrate at every meal and snack, you are able to maintain satiety (i.e. absence of hunger). If you aren’t hungry, then you don’t eat as many calories. This automatically slows down the aging process as long as you are getting adequate protein and supplying necessary micronutrients (4). Not surprisingly, this is also how you squeeze out more quality years as you age.

References
1. Crimmins EM and Beltran-Sanchez H. “Mortality and morbidity trends: Is there a compression of morbidity?” Journals of Gerontology Series B 66B: 75-86 (2011)
2. Bartke A. “Can growth hormone accelerate aging?” Neuroendocrinology 78: 210-216 (2003)
3. Banks WA, Morely JE, Farr SA, Price TO, Ercal N, Vidaurre I, and Schally AV. “Effect of a growth hormone-releasing hormone antagonist on teleomerase activity, oxidative, stress, longevity, and aging in mice.” Proc Nat Acad Sci USA 107: 22272-22277 (2010)
4. Sears B. “The Anti-Aging Zone.” Regan Books. New York, NY (1999)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

Eat your breakfast

You’ve probably heard it a billion times. “Don’t skip breakfast!” But most Americans, adults and children, are not heeding this advice. There are a bunch of reasons why you should eat breakfast within one hour of waking. And it’s even better if the meal is Zone balanced – the correct amount of lean protein, low-glycemic carbohydrates and a dash of monounsaturated fat.

After sleeping a full night, your blood sugar level is low, and you are in a catabolic state. This means that body has been using up stored energy in the liver as well as beginning to cannibalize your muscle for energy. If you skip breakfast, your blood sugar stays low and cannibalization of your muscle will continue. This is a stress situation, and the body releases more cortisol as a response. This creates insulin resistance that increases insulin levels further, driving down blood sugar even more. No wonder by mid-morning you are incredibly hungry.

The whole basis of the anti inflammatory diet is to keep your insulin in a zone, not too high and not too low. This will stabilize blood sugar and prevent continuing muscle degradation for energy. Eating a Zone breakfast can help keep your insulin stabilized, provide the necessary protein to start rebuilding muscle mass and increase the levels of glycogen in the liver. This is called anabolism. It is this continued balance of catabolism and anabolism that we call metabolism. As long as the two phases of metabolism are balanced, so are your weight and your mood. This is why breakfast is so critically important for your alertness, productivity, increased cognition and memory, satiety, and weight control because it starts your day out on a high note as opposed to digging a deeper hormonal hole that you try to crawl out during the rest of the day. A balanced Zone breakfast is also the easiest way to keep your sugar cravings under control during the day. In other words, you will not need the constant trips to the vending machine or your secret stash of candy to artificially maintain blood sugar levels.

Still not convinced? Then give your kids breakfast. Research shows a link between regular breakfast consumption and improvement in academic performance and psychosocial functioning as well as cognition among children. Eating a breakfast every day will be the best way to protect any child against becoming overweight. Make that a Zone breakfast balanced in protein, low glycemic-load carbohyrates, and monounsaturated fat, and you have the ideal pediatric weight-loss program as obese children are less hungry at their next meal as demonstrated at Harvard Medical School more than a decade ago.2 This finding at Harvard was also confirmed by a research study in the Journal of the American Dietetic Association on breakfast consumption among children that found the prevalence of obesity to be higher in those who regularly skipped breakfast.3 Evidence also suggests that breakfast consumption may improve cognitive function related to memory, test grades, and school attendance.4 Want the smartest and leanness kid in the school? It’s easy — feed them a Zone breakfast every day. While you are at it, make each of their meals a Zone meal and give them plenty of EPA and DHA at the same time.

[1] Affenito S. “Breakfast: A Missed Opportunity.” Journal of the American Dietetic Association 107:565-69 (2007)

2 Ludwig DS et al, “High glycemic index foods, overeating, and obesity.” Pediatrics 103: e26 (1999)

3 Deshmukh-Taskar P et al. “The relationship of breakfast skipping and type of breakfast consumption with nutrient intake and weight status in children and adolescents: The National Health and Nutrition Examination Survey 1999-2006.” Journal of American Dietetic Association 110:869-78 (2010)

4 Rampersaud G et al. “Breakfast habits, nutritional status, body weight, and academic performance in children and adolescents.” Journal of American Dietetic Association 105: 843-60 (2005)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.

Give your second brain a chance

Most people think of the brain as the primary organ that does all of the information processing for the body. Actually, you have a second brain that is just as important. This second brain is your gastrointestinal (GI) tract that constantly senses dietary input and sends the resulting information to the brain to tell it when it can switch from seeking food to other activities, such as building cathedrals. This is why biological urges always overwhelm cognitive urges. Controlling these biological urges is not a matter of willpower but an integrated hormonal balancing mechanism. Try holding your breath for 25 minutes. It simply can’t be done not due to a lack of willpower, but because after about two minutes, the body’s need for a continual supply of oxygen overwhelms any other desire or course of action. The same is true of eating. It’s not a matter of willpower that controls appetite, but continual hormonal communication from the second brain as to whether or not there are adequate calories in the pipeline that can be ultimately converted to chemical energy to keep the body going.

There are hundreds of hormones released from your second brain to relay information on the body’s current food status. Two of the most important are PYY and GLP-1. These hormones are released from L-cells deep in the lower part of the GI tract. PYY is released in response to protein (1,2), and GLP-1 is released in response to carbohydrate (3). Both hormones are important because they also regulate satiety.

Both of these hormones are significantly increased after gastric bypass surgery (4,5), and this may account for the dramatic long-term benefits of the surgery on both weight loss and diabetes (6-8). The secret of the success of gastric bypass surgery may lie in the re-routing of the GI tract, which now brings a lot more protein and carbohydrate to their receptors found in L-cells that are located in the most distant parts of the GI tract. Apparently in obese individuals, much of the ingested protein and carbohydrate is broken down and absorbed much higher up in the GI tract. As a result, a relatively small amount of these macronutrients are sensed by the L-cells resulting in limited amounts of PYY and GLP-1 released from the GI tract to suppress hunger. As a consequence, obese individuals are constantly hungry.

This also begins to explain many of the seemingly contradictory reports on the benefit of low glycemic-load diets, like the Zone Diet, for weight loss (9, 10). The end result is to state that all diets are equally effective in weight loss since a “calorie is a calorie”, and if you restrict calories, the weight loss is identical. Of course, this simple thinking neglects genetic diversity. One study done by Harvard Medical School indicated that in genetically identical rats, weight gain is strongly correlated to the glycemic load of the diet (11). Based on this study, Harvard later conducted a clinical experiment putting overweight individuals on iso-caloric diets with differing glycemic loads for 18 months (12). If you just looked at the changes in weight, both diets were equally effective, indicating again that a “calorie is a calorie”. However, if the two groups are broken into high-initial-insulin responders versus low-initial-insulin responders, you find a very different picture emerging. For the high-insulin responders, their weight loss and long-term weight maintenance was considerably better on the low glycemic-load diet, just as it was with genetically identical rats. So this means that for those with a high initial insulin response to carbohydrates, a low glycemic-load diet, like the Zone Diet, would be their most appropriate choice, indicating a “calorie is not a calorie,” especially when you take into account genetics.

So how does this all science tie together in the real world? My hypothesis is that the fast insulin responders are simply digesting the protein and carbohydrate in a meal and absorbing it at a faster rate. This means carbohydrates enter into the bloodstream at a faster rate (i.e. high glycemic index) and fewer macronutrients (both protein and carbohydrate) are able to reach the lower part of the GI tract where the L-cells are located. This means that less PYY and GLP-1 will be secreted. As a result, there is less satiety, and they are likely to consume more calories. A low glycemic-load diet delays the absorption of carbohydrates, so that more GLP-1 is released from the L-cells. But you also have to slow down the absorption of protein so more PYY can be released. The type of protein that is broken down at the slowest rate is casein coming from milk. Other proteins, such a whey and soy, are rapidly broken down and absorbed in the upper regions of the GI track ensuring very little protein will ultimately reach the L-cells, causing an increase in PYY secretion.

So the ideal diet for those overweight individuals with a high initial insulin response may not only be a low glycemic-load diet (i.e. Zone Diet), but also a diet rich in casein. That’s why I am excited by the new generation of Zone Foods. They have a low glycemic load (similar to fruits) and are also rich in casein. The combination of the two factors may result in increased satiety because the delayed digestion and absorption means more of the initial carbohydrate and protein in the meal is reaching the L-cells, thus potentially releasing more GLP-1 and PYY.

If you aren’t hungry, then cutting back on calories is much easier, especially if you have a high initial insulin response to meals. This is the science behind the new Zone Foods. The science is complex, but the actual execution of that science is not, as long as you like to eat Zone bread, Zone pasta, and Zone pizza.

References

1. Batterham RL; Heffron H; Kapoor S; Chivers JE; Chandarana K; Herzog H; Le Roux CW; Thomas EL; Bell JD; Withers DJ Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab 4: 223-233 (2006)

2. Karra E; Chandarana K; Batterham RL. “The role of peptide YY in appetite regulation and obesity.” J Physiol 587: 19-25 (2009)

3. Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, and Egan JM. “Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1.” Proc Natl Acad Sci U S A 104: 15069-15074 (2007)

4. Holdstock C; Zethelius B, Sundbom M, Karlsson FA, and Eden Engstrom B. “Postprandial changes in gut regulatory peptides in gastric bypass patients.” Int J Obes (Lond) 32: 1640-1646 (2008)

5. Morinigo R, Moize V, Musri M, Lacy AM, Navarro S, Marin JL, Delgado S, Casamitjana R, and Vidal J. “Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects.” J Clin Endocrinol Metab 91: 1735-1740 (2006)

6. Laferrere B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, Lee H, and Yapp K. “Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes.” J Clin Endocrinol Metab 93: 2479-2485 (2008)

7. le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, Lonroth H, Fandriks L, Ghatei MA; Bloom SR. “Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg 246: 780-785 (2007)

8. White S, Brooks E, Jurikova L, and Stubbs RS. “Long-term outcomes after gastric bypass.” Obes Surg 15: 155-163 (2005)

9. Dansinger ML, Gleason JA, Griffith JL, Selker HP, and Schaefer EJ “Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial.” JAMA 293: 43-53 (2005)

10. Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, and King AC. “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 297: 969-977 (2007)

11. Pawlak DB, Kushner JA, and Ludwig DS. “Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals.” Lancet 364: 778-785 (2004)

12. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, and Ludwig DS. “Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial.” JAMA 297: 2092-2102 (2007)

Nothing contained in this blog is intended to be instructional for medial diagnosis or treatment. If you have a medical concern or issue, please consult your personal physician immediately.