Tag Archives: anti-inflammatory

Blame weight gain on the brain

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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.

How polyphenols make probiotics work better

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Probiotics in dietToday we hear a lot about probiotics, especially when popular yogurts are fortified with them. So what are they? The term probiotics is simply a synthesized word for live microorganisms (bacteria or yeast) that may have some health benefits. In the lower part of your gut, you have a virtual zoo of microorganisms. Some are beneficial; others are very harmful. In fact, it is estimated that you have 10 times as many microorganisms in the gut than the entire number of cells that constitute your body. Of the hundreds of different microorganisms in the gut, two usually stand out as probiotic stars: Lactobacillus and bifidobacterium.

It appears that selected strains of these particular microorganisms have anti-inflammatory properties, which inhibit the activity of nuclear factor-κB (NF-κB), the genetic “master switch” that turns on inflammation (1,2). Certain yeasts secrete a soluble factor that also inhibits NF-κB (3), and this may be the same mechanism that those “friendly” bacteria use to reduce inflammation.

But here’s the problem with probiotics — you have to get enough of the live organisms into the gut to provide any benefits. It’s easy to fortify them into some yogurt product that is kept at low temperature, but getting those bacteria to pass through the digestive system and reach the lower part of the large intestine is another story. It is estimated that 99.999 percent of the live probiotics are digested in the process.

So how can you enhance the biological action of those extremely few probiotics that actually make it alive to the lower intestine? The answer is polyphenols. Like probiotics, polyphenols also inhibit NF-κB (4,5). In fact, polyphenols are the primary agents that protect plants from microbial attack.

Unlike probiotics, polyphenols are more robust in their ability to reach the lower intestine. But like probiotics you have to take enough polyphenols to have a therapeutic effect in the gut. You will probably need at least 8,000 ORAC units per day to maintain adequate levels of polyphenols in the gut. That is approximately 10 servings of fruits and vegetables per day. But if you want to significantly reduce the existing inflammatory burden in the gut and the rest of body, you have to consume a lot more polyphenols. Supplementation with highly purified polyphenols becomes your only realistic alternative.

And here is where I think the real benefits of dietary polyphenols may reside. By reducing the inflammatory load in the gut, you can automatically reduce the anti-inflammatory load in the rest of the entire body. So before you take that next serving of probiotic-fortified yogurt, make sure you are taking adequate levels of polyphenols to make sure those probiotics actually deliver their marketing promises.

References

  1. Hegazy SK and El-Bedewy MM. “Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in ulcerative colitis.” World J Gastroenterol 16: 4145-4151 (2010)
  2. Bai AP, Ouyang Q, Xiao XR, and Li SF. “Probiotics modulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis.” Int J Clin Pract 60: 284-288 (2006)
  3. Sougioultzis S, Simeonidis S, Bhaskar KR, Chen X, Anton PM, Keates S, Pothoulakis C, and Kelly CP. “Saccharomyces boulardii produces a soluble anti-inflammatory factor that inhibits NF-kappaB-mediated IL-8 gene expression. Biochem Biophys Res Commun 343: 69-76 (2006)
  4. Romier B, Van De Walle J, During A, Larondelle Y, and Schneider YJ. “Modulation of signaling nuclear factor-kappaB activation pathway by polyphenols in human intestinal Caco-2 cells.” Br J Nutr 100: 542-551 (2008)
  5. Jung M, Triebel S, Anke T,Richling E, and Erkel G. “Influence of apple polyphenols on inflammatory gene expression.” Mol Nutr Food Res 53: 1263-1280 (2009)

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.

A short history of the human food supply

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The real goal of nutrition is the management of cellular inflammation. Increased cellular inflammation makes us fat, sick, and dumb (how about overweight, ill, and less intelligent). Strictly speaking, diets are defined by their macronutrient balance. This is because that balance determines the resulting hormonal responses. This doesn’t mean you can ignore the impact of various food ingredients on the generation of cellular inflammation.

This is why I categorize food ingredients into three major classes depending on when they were introduced into the human diet. The more ancient the food ingredients, the less damaging inflammatory impact they will have on turning genes off and on (i.e. gene expression). This is because the greater the period of time our genes have co-evolved with a given food ingredient, the more our body knows how to handle them. Unfortunately, human genes change slowly, but changes in our food supply can happen very rapidly.

With that as a background, let me describe the three major categories of food ingredients, especially in terms of their introduction to the human diet.

Paleolithic Ingredients

This category includes food ingredients that were available more than 10,000 years ago. Our best evidence is that humans first appeared as a new species in Southern Africa about 200,000 years ago (1). For the next 190,000 years, food ingredients of the human diet consisted of animal protein (grass-fed only), fish, animal and fish fats, fruits, vegetables, and nuts. I call these Paleolithic ingredients. This means for the first 95 percent of our existence as a species, these were the only food ingredients that genes were exposed to. As a result of 190,000 years of co-existence with our genes, these food ingredients have the least inflammatory potential on our genes.

Our best estimate of the macronutrient composition of the typical Paleolithic diet some 10-15,000 years ago was 25-28 percent protein, 40 percent carbohydrate, 32-35 percent fat with a very high intake of EPA and DHA (about 6 grams per day) and a 1:1 ratio of omega-6 to omega-3 fats (2). This is basically the composition of the anti inflammatory diet (3-5). If you use only Paleolithic ingredients, then you are almost forced to follow an anti inflammatory diet. The food ingredients are more restrictive, but the increased anti-inflammatory benefits are well worth it.

Mediterranean Ingredients

The second group of food ingredients represents those food choices that were available 2,000 years ago. We started playing Russian roulette with our genes 10,000 years ago as we started to introduce a wide variety of new food ingredients into the human diet. First and foremost was the introduction of grains, but not all at the same time. Wheat and barley were introduced about 10,000 years ago with rice and corn coming about 3,000 years later. Relative latecomers to the grain game were rye (about 5,000 years ago) and oats (about 3,000 years ago).

At almost the same time came the first real use of biotechnology. This was the discovery that if you fermented grains, you could produce alcohol. Alcohol is definitely not a food ingredient that our genes were prepared for (and frankly our genes still aren’t). I think it only took mankind about 10 years to learn how to produce alcohol, which probably makes the first appearance of beer occurring some 9,990 years ago. Wine was a relatively late arrival appearing about 4,000 years ago. With the domestication of animals (some 8,000 years ago) came the production of milk and dairy products. About 5,000 years ago, legumes (beans) were also introduced. Legumes tend to be rich in many anti-nutrients (such as lectins) that must be inactivated by fermentation or boiling. Needless to say, these anti-nutrients are not the best food ingredients to be exposed to.

I call this second group of food ingredients Mediterranean ingredients since they are the hallmark of what is commonly referred to as a “Mediterranean diet” (even though the diets as determined by macronutrient balance in different parts of the Mediterranean region are dramatically different). Those cultures in the Mediterranean region have had the time to genetically adapt to many of these new ingredients since all of these ingredients existed about 2,000 years ago.

Unfortunately, many others on the planet aren’t quite as fortunate. That’s why we have lactose intolerance, alcohol-related pathologies, celiac disease, and many adverse reactions to legumes that have not been properly detoxified. As a result these Mediterranean ingredients would have greater potential to induce increased levels of cellular inflammation than Paleolithic ingredients. However, at least they were better than the most recent group, which I term as, the “Do-You-Feel-Genetically-Lucky” group.

Do-You-Feel-Genetically-Lucky Ingredients

Unfortunately, these are the food ingredients that are currently playing havoc with our genes, especially our inflammatory genes. You eat these ingredients only at your own genetic risk. The first of these was refined sugar. Although first made 1,400 years ago, it didn’t experience a widespread introduction until about 300 years ago. With the advent of the Industrial Revolution came the production of refined grains. Products made from refined grains had a much longer shelf life, were easier to eat (especially important if you had poor teeth), and could be mass-produced (like breakfast cereals).

However, in my opinion the most dangerous food ingredient introduced in the past 200,000 years has been the widespread introduction of refined vegetable oils rich in omega-6 fatty acids. These are now the cheapest source of calories in the world. They have become ubiquitous in the American diet and are spreading worldwide like a virus. The reason for my concern is that omega-6 fatty acids are the building blocks for powerful inflammatory hormones known as eicosanoids. When increasing levels of omega-6 fatty acids in the diet were combined with the increased insulin generated by sugar and other refined carbohydrates, it spawned a massive increase in cellular inflammation worldwide in the past 40 years starting first in America (6). It is this Perfect Nutritional Storm that is rapidly destroying the fabric of the American health- care system.

The bottom line is that the macronutrient balance of the diet will generate incredibly powerful hormonal responses that can be your greatest ally or enemy in controlling cellular inflammation. Unless you feel incredibly lucky, try to stick with the food ingredients that give your genes the best chance to express themselves.

References

  1. Wells S. “The Journey of Man: A Genetic Odyssey.” Random House. New York, NY (2004)
  2. Kuipers RS, Luxwolda MF, Dijck-Brouwer DA, Eaton SB, Crawford MA, Cordain L, and Muskiet FA. “Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet.” Br J Nutr 104: 1666-1687 (2010)
  3. Sears, B. “The Zone.” Regan Books. New York, NY (1995)
  4. Sears, B. “The OmegaRx Zone.” Regan Books. New York, NY (2002)
  5. Sears, B. “The Anti-Inflammation Zone.” Regan Books. New York, NY (2005)
  6. 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.

Pass the polyphenols

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Considering that virtually nothing was written about the health benefits of polyphenols before 1995, it continues to amaze me the amount of health benefits this group of nutrients generates. This is primarily due to our growing understanding of how these phytochemicals interact with the most primitive parts of our immune system that have been conserved through millions of years of evolution.

Three new studies add to this growing knowledge. In the January 2011 issue of the American Journal of Clinical Nutrition, it was reported that eating one serving a week of blueberries could reduce the risk of developing hypertension by 10 percent (1). Since a serving size of fruit is defined as ½ cup, that serving size contains about 65 grams of blueberries. Put that into more precise molecular terms, this serving size would provide about 4,000 ORAC units or about the same amount of ORAC units as a glass of wine. The researchers speculated that there was a subclass of polyphenols (which includes delphinidins) that appear to be responsible for most of the effects. So if eating one serving of blueberries (½ cup) once a week is good for reducing the risk of hypertension, guess what the benefits of eating 1 cup of blueberries every day might be? The answer is probably a lot.

Speaking of red wine, in the second study in Biochemical and Biophysical Research Communications researchers found that giving high levels of isolated polyphenols from red wine demonstrated that exercise endurance in older rats could be significantly enhanced. Very good news for old folks like me. They hypothesized the effects may be directly related to “turning on” genes that increase the production of anti-oxidant enzymes (2). The only catch is that the amount of red wine polyphenols required to reach these benefits would equate to drinking about 20-30 glasses of red wine per day.

The final study in Medicine & Science in Sports and Exercise demonstrates that cherry juice rich in polyphenols reduces muscle damage induced by intensive exercise in trained athletes. This reduction in muscle damage was correlated with decreased levels of inflammatory cytokines (3). The reduction of cytokine expression is one of the known anti-inflammatory benefits of increased polyphenol intake.

Three pretty diverse studies, yet it makes perfect sense if you understand how polyphenols work. Polyphenols inhibit the overproduction of inflammatory compounds made by the most ancient part of the immune system that we share with plants. The only trick is taking enough of these polyphenols. To get about 8,000 ORAC units every day requires eating about a cup of blueberries (lots of carbohydrates) or two glasses of red wine (lots of alcohol), or half a bar of very dark chocolate (lots of fat) or 0.3 g of highly purified polyphenol powder in a small capsule (with no carbohydrates, no alcohol, and no saturated fat). And if you are taking extra high purity omega-3 oil, exercising harder, or have an inflammatory disease, you will probably need even more polyphenols. It doesn’t matter where the polyphenols come from as long as you get enough. That’s why you eat lots of colorful carbohydrates on an anti inflammatory diet.

References

  1. Cassidy A, O’Reilly EJ, Kay C, Sampson L, Franz M, Forman J, Curhan G, and Rimm EB. “Habitual intake of flavonoid subclasses and incident hypertension in adults.” Am J Clin Nutr 93: 338-347 (2011)
  2. Dal-Ros S, Zoll J, Lang AL, Auger C, Keller N, Bronner C, Geny B, Schini-Kerth VB. “Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: Role of NADPH oxidase.” Biochem Biophys Res Commun 404: 743-749 (2011)
  3. Bowtell JL, Sumners DP, Dyer A, Fox P, and Mileva KN. “Montmorency cherry juice reduces muscle damage caused by intensive strength exercise”. Med Sci Sports Exerc 43: online ahead of print doi: 10.1249/MSS.obo13e31820e5adc (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.

Coffee and diabetes: What’s the connection?

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One of the great controversies in nutrition is the role of coffee and human health. On the one hand, coffee is the primary source of polyphenols in the American diet because of the lack of consumption of fruits and vegetables. On the other hand, coffee is rich in caffeine, an alkaloid that acts as a stimulant on the central nervous system and is known to be an addictive agent (1). In fact, Roland Griffiths, professor of Behavioral Biology at the John Hopkins School of Medicine (and my old college roommate), says, “Caffeine is the world’s most widely used mood-altering drug.” So the question remains is caffeine good for you?

No one knows for sure, but one interesting point has been made that it appears the more coffee you drink, the lower your risk for developing diabetes (2). In fact, if you drink more than four cups of coffee per day, you decrease your risk of diabetes by 50 percent. This new research demonstrates that coffee increases the levels of sex hormone-binding globlin (SHBG) in the blood. As I pointed out in my book “The Anti-Aging Zone,” SHBG plays an important role in sequestering the levels of estrogen and testosterone in the blood so that levels of these unbound sex hormones that can interact with their receptors are tightly regulated (3). Usually as insulin resistance increases, the levels of SHBG decrease in the blood (4). This can lead to an over-stimulation of the receptors by the unbound sex hormones resulting in increased risk for breast and prostate cancer development.

What in the coffee actually causes the increase in SHBG is unknown, but what is known is that once you decaffeinate the coffee, all its benefits on the elevation of SHBG levels and any reduction in risk for diabetes disappear.

It is highly unlikely that caffeine by itself is beneficial for reducing type 2 diabetes, since there were no benefits related to drinking tea or to total daily caffeine intake (2). Perhaps some other compound that was also extracted with the caffeine may play a role in the reduction of type 2 diabetes.

So what really happens when you decaffeinate coffee? First, you soak the beans in water to remove the caffeine and flavors as well as the polyphenols. Then you treat the water with organic solvents (methylene chloride or ethyl acetate) to remove the caffeine (as well as many of the polyphenols and much of the flavor). Then (assuming you have removed all of the organic solvent), you add back the treated water extract to the beans to hopefully reabsorb some of the flavors back into them. Obviously, not all the flavors or polyphenols return since the resulting taste is far less robust than the original coffee bean.

So it seems to me that exploring what else has been extracted in addition to the caffeine may lead to new dietary treatments for diabetes. Whether that will be done is highly unlikely. Instead of waiting for such experiments, you might as well follow the best treatment for preventing diabetes, which is following the anti inflammatory diet for a lifetime. That is how you control cellular inflammation, which is the driving force for development of type 2 diabetes (5,6).

References

1. Juliano LM and Griffiths RR. “A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features.” Psychopharmacology 176: 1-29 (2004)

2. Goto A, Song Y, Chen BH, Manson JE, Buring JE, and Liu S. “Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women.” Diabetes 60: 269-275 (2011)

3. Sears B. “The Anti-Aging Zone.” Regan Books. New York, NY (1999)

4. Akin F, Bastemir M, and Alkis E. “Effect of insulin sensitivity on SHBG levels in premenopausal versus postmenopausal obese women.” Adv Ther 24: 1210-1220 (2007)

5. Sears B. “Anti-inflammatory diets for obesity and diabetes.” J Coll Amer Nutr 28: 482S-491S (2009)

6. Sears B. “The Anti-Inflammation Zone.” Regan Books. New York, NY (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.

Try the team approach to nutrition

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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

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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.

The secret of blueberries: It’s the dephinidins

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We continually hear about the benefits of fruits and vegetables for better health. There are a number of them. One is obviously their lower glycemic load that reduces insulin secretion. Another is their polyphenol content that gives fruits and vegetables their colors. Although virtually no research was conducted on polyphenols before 1995, since that time there has been a explosion of animal studies that have indicated their remarkable benefits as anti-oxidants and anti-inflammatory agents.

Upon deeper inspection, there is one group of polyphenols that seems to generate the most consistent health benefits. These are the delphinidins. Delphinidins are a subgroup of a family of polyphenols known as anthocyanidins. To make the story about delphinidins more intriguing, they are primarily found in blueberries. More specifically, the primary sources of delphinidins are the American blueberry, the Russian blueberry (i.e. bilberry), and the Patagonian blueberry (i.e. maqui berry). This is why the published clinical studies in humans seem to consistently involve blueberries. And the clinical data is impressive. Whether it is about reducing oxidized cholesterol or improving insulin resistance in patients with metabolic syndrome (1,2) or improving memory in patients with early dementia (3), the human data on the use of blueberries simply jumps out at you.

Since the active ingredient in each of these varieties of blueberries appears to be the delphinidins, then it is reasonable that the higher the levels of this particular polyphenol, the better the potential results. The Russian blueberry contains six times more delphinidins than American blueberries, and the Patagonia blueberry contains 14 times more delphinidins than the American blueberry. This probably reflects the harsher growing climates that other forms of blueberries are exposed to when compared to the American blueberry, which has become overly domesticated (making it richer in fructose and lower in delphinidins).

However, as with all natural products you have to take a therapeutic dose to get a therapeutic effect. You could measure this therapeutic threshold in terms of their anti-oxidative potential (measured in ORAC units) or the actual amounts of delphinidins themselves. It appears that for a blueberry extract to be effective requires that it provides at least 16,000 ORAC units per day. To put this in perspective, this level of ORAC units is equivalent to eating greater than 20-30 servings of vegetables on a daily basis.

But if the delphinidins are so important for the benefits of blueberries, isn’t it possible that the smaller amounts of the maqui berry might be even more beneficial because of its higher delphinidin concentration? That’s why we have several ongoing clinical trials to explore that potential. I will keep you informed as the results start coming in. Yet in the meantime, keep eating lots of those colorful carbohydrates just like your grandmother told you to eat.

References
1. Stull AJ, Cash KC, Johnson WD, Champagne CM, and Cefalu WT. “Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women.” J Nutr 140: 1764-1768 (2010)
2. Basu A, Du M, Leyva MJ, Sanchez K, Betts NM, Wu M, Aston CE, and Lyons TJ. “Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome.” J Nutr 140: 1582 1588 (2010)
3. Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqivst-Tymchuk R, Shukitt-Hale R, and Joseph JA. “Blueberry supplementation improves memory in older adults.” J Agric Food Chem 58: 3996-4000 (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.

Want to lose Weight? Eat like our Paleolithic ancestors

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A recent article appeared in the British Journal of Nutrition that gives an updated estimate of what diet (i.e. Paleolithic) our ancestors may have eaten during the time from their first appearance in Africa some 200,000 years ago until they started leaving Africa 100,000 years later (1). This is important because this type of diet until 10,000 years ago (with the advent of agriculture) was the nutritional foundation through which our genes evolved. Since our diet and gene expression are intimately tied together (2), understanding the dietary forces that molded how our genes respond to diet is important. This is particularly true since nutritional science has many conflicting interactions that make the study of a single nutrient often result in conflicting data. One such example is the study of insulin responses induced by the diet without studying the impact of fatty acid composition on insulin secretion and vice versa. This is why the study of Paleolithic nutrition provides a template to ask questions to optimize our current diet. In fact, I actually I stated this on page 99 of my first book, “The Zone” (3).

So what are the newest updates on the composition of the Paleolithic diet of our African ancestors? It appears the protein content was between 25 and 29 percent, the carbohydrates were about 40 percent and the total fat was about 30-36 percent. If that sounds familiar to the 30 percent protein, 40 percent carbohydrate, and 30 percent fat ratio in the anti inflammatory diet, it should. Essentially the newest estimate of the Paleolithic diet of our human ancestors in Africa is the anti inflammatory diet.

Equally important, it was estimated that the intake of long-chain omega-3 fatty acids (EPA and DHA) was about 6 grams per day. This is similar to my recommendations in “The OmegaRx Zone,” published in 2002 (4). The dietary ratio of arachidonic acid (AA) to EPA was also estimated in this article and was found to be about 2. Since the dietary intake of these fatty acids would be reflected in the blood, then we can assume the AA/EPA ratio in Paleolithic man was about 2. This AA/EPA ratio is again strikingly similar to the recommendations in my various books about what the best AA/EPA ratio should be for optimal control of the cellular inflammation, which leads to the acceleration of chronic disease (4-6).

When you follow the Paleolithic diet (a.k.a. the anti inflammatory diet), you find almost instantaneous changes in hormonal responses (7, 8) and improved glycemic control (8,9) before there is any weight loss. And if you continue to follow it, you not only lose weight, but also burn fat faster (11-14).

Was I just taking lucky guesses on my recommendations for the anti inflammatory diet over the past 15 years? I would like to think they were not lucky guesses, but based on insight coming from my background in drug delivery technology that strives for a therapeutic zone for optimal results. The lucky part was having the perseverance to stay true to those insights. On the other hand, it is always nice to get validation even 15 years after the fact.

References
1. Kuipers RS, Luxwolda MF, Dijck-Brouwer DJA, Eaton SB, Crawford, MA, Cordain L, and Muskiet FAJ. “Estimate macronutrient and fatty acid intakes from an East African paleolithic diet.” British J Nutr 104: 1666-1687 (2010)
2. Sears B and Ricordi C. “Anti-Inflammatory nutrition as a pharmacological approach to treat obesity.” J Obesity published online September 30, 2010. doi: 10.1155/2011/431985. (2010)
3. Sears B. “The Zone.” Regan Books. New York, NY (1995)
4. Sears B. “The OmegaRx Zone.” Regan Books. New York, NY (2002)
5. Sears B. “The Anti-Inflammation Zone.” Regan Books. New York, NY (2005)
6. Sears B. “Toxic Fat.” Nelson Publishing. Nashville, TN (2008)
7. 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)
8. Markovic TP, Jenkins AB, Campbell LV, Furler SM, Kragen EW, and Chisholm DJ. “The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM.” Diabetes Care 21: 687-694 (1998)
9. Lindberg S, Jonsson T, Granfeldt Y, Borgstrand E, Soffman J, Sjorstrom K, and Ahren B. “A Paleolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.” Diabetologia 50: 1795-1807 (2007)
10. Frassetto LA, Schloetter M, Mietus-Synder M, Morris RC, and Sebastian A. “Metabolic and physiologic improvements from consuming a Paleolithic, hunter-gatherer type diet.” Eur J Clin Nutr 63: 947-955 (2009)
11. Osterdahl M. Kocturk T. Koochek A, and Wandell PE. “Effects of a short-term intervention with a Paleolithic diet in healthy volunteers.” Eur J Clin Nutr 62: 682-685 (2008)
12. 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)
13. 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)
14. 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)

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.

A cash cow based on bad science

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There has been no more profitable class of drugs than the cholesterol-lowering statins. Their success is based on a very simple premise: High cholesterol levels mean certain cardiovascular death. While there has always been questioning of the cholesterol story at the fringes of academic research (1), now the cries are rising within the highest reaches of the academic research community that something is just not right.

Since no one wants to die, you would think that measurement of mortality would be the primary clinical end-point for any clinical trial of a statin drug. There is no question that for people who have already had a heart attack, taking a statin prolongs their life by reducing all-cause mortality. But what about the people who have never had a heart attack but have high cholesterol levels? There the answer is much more open.

One recent article has studied all the published studies with some 65,000 patients who had high cholesterol but no evidence of heart disease to see the effect that statin drugs have on their mortality (2). The answer was virtually none. In fact, in all the statin trials published since 2005, there has been a striking lack of benefits in populations that simply had high cholesterol levels but no evidence of any cardiovascular disease (3). This is true except for one trial that was funded by a drug company that makes a new powerful, statin and run by the individual who has the patent for measuring C-reactive protein as a marker for cardiovascular risk (3).

Here was a new premise: People who had normal levels of cholesterol and no heart disease but high levels of C-reactive protein also need even more powerful statins. The fact that C-reactive protein is an unreliable marker in cardiovascular patients because it changes so quickly was conveniently ignored (4). Nonetheless a successful trial would generate more sales for the drug company and more testing of C-reactive protein for everyone going to see a physician.

So when a careful analysis of this “highly-successful” trial was published this year, it was found that there were no benefits in reducing cardiovascular mortality between the active and placebo groups (3). As the cholesterol story appears to have a growing number of flaws in it, I predict it will become more commonplace to have drug companies and medical researchers continue to use sleight-of-hand statistical dodges to make it appear their “wonder” drugs are actually doing wonderful things, like reducing death from heart disease in those who have no evidence of heart disease.

Maybe it’s time to return to a better working hypothesis of what really drives heart disease—inflammation and to use anti-inflammatory diets to prevent the occurrence of cardiovascular disease (5,6).

References

1. Ravnshov U. The Cholesterol Myths. New Trends Publishing. Warsaw, IN (2002)
2. Ray KK, Seshasai SRK, Erqou, S, Sever P, Jukema JW, Ford I, and Sattar N. “Statins and all-cause mortality in high-risk primary prevention.” Arch Intern Med 170: 1-024-1031 (2010)
3. De Lorgeril M, Salen P, Abramson J, Dodin S, Hamazaki T, Kotucki W, Okuyama H, Pavy B, and Rabaeus M. “Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy.” Arch Intern Med 170 1032-1036 (2010)
4. Bogaty P, Brophy JM, Boyer L, Simard S, Joseph L, Bertrand F, and Dagenais GR. “Fluctuating inflammatory markers in patients with stable ischemic heart disease. Arch Intern Med 165: 221-226 (2005)

5. Sears B. “The Zone.” Regan Books. New York, NY (1995)
6. Sears B. “The Anti-Inflammation Zone.” Regan Books. New York, NY (2005)

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