New solution or simply admitting failure?

SurgeryLast week the International Diabetes Federation (IDF) announced that gastric bypass surgery is a cost-effective treatment for type 2 diabetes. This marks the first time in modern medicine that cutting out normal tissue is now considered good medicine. It also indicates the pathetic state of medical science for the treatment of diabetes.

Make no mistake: Type 2 diabetes is now a pandemic, affecting approximately 300 million people worldwide. This is projected to increase to some 450 million people worldwide by 2030. Since diabetes is one of the most costly chronic disease conditions, it is the most likely to break the financial backbone of health-care systems in every advanced country.

The typical gastric bypass surgery costs from $15,000 to $24,000. Just for argument's sake, let's assume it is $20,000 for each surgery. Since some 26 million people in the United States have type 2 diabetes, then a mere $520 billion dollars spent on gastric bypass surgery would solve our growing epidemic. Obviously we don't have that type of money floating in the health-care system.

Furthermore, the 10-year failure rate is relatively high for this type of surgery (1). For example, 20 percent of patients who were initially obese (BMI >50 percent) could not maintain their long-term BMI below 35 percent (the definition of morbidly obese). This failure rate rises to 58 percent for those whose initial BMI was greater than 50.

The key feature as to why gastric bypass surgery works is the almost immediate suppression of hunger, mediated by improved release of hormones from the gut (i.e. PYY) that go directly to the brain to tell the patient to stop eating. Over time it would appear that this initial enhancement of PYY release is being compromised. As a result, those patients regain the lost weight.

So maybe gastric bypass is not the best long-term solution (and definitely not a cost-effective one in those patients that regain much of their lost weight) for solving the current epidemic of diabetes. So what's the alternative? One solution would be an anti-inflammatory diet that supplies adequate protein to stimulate PYY release as well as control the levels of cellular inflammation in the pancreas, the underlying reason why insufficient insulin levels are secreted in the first place (2).

Call me crazy, but this dietary approach appears far more cost-effective.

References

  1. Christou NV, Look D, and MacLean LD. “Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years.” Ann Surg 244: 734-740 (2006)
  2. Donath MY,Boni-Schnetzler M, Ellingsgaard H, and Ehses JA. “Islet inflammation impairs the pancreatic beta-cell in type 2 diabetes.” Physiology 24: 325-331 (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.

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.

What is the Mediterranean diet?

The mediterranean dietToday we continually hear about the health benefits of following a Mediterranean diet. For example, a recent analysis of more than 50 published studies indicated that a Mediterranean diet would lead to a 30-percent reduction in metabolic syndrome (1). Since metabolic syndrome can be considered pre-diabetes, the public health implications are enormous. However, are we talking about the Spanish Mediterranean diet or the Italian, or the Moroccan, the Egyptian or the Lebanese versions? Here is the basic problem with all diets: Trying to define them correctly.

In order to compare one diet to another, each diet must ultimately be defined by its balance of the macronutrients (protein, carbohydrate and fat). This is because the macronutrient balance determines hormonal responses generated by that diet (2).

A Mediterranean diet can be considered to contain approximately 50 percent of the calories as carbohydrates, 20 percent of the calories as protein and 30 percent of the calories as fat. This is a higher protein-to-carbohydrate balance than is found in the usually recommended “healthy” diets for weight loss and cardiovascular health. As a result, this difference in the balance of the protein-to-carbohydrate ratio will generate different hormonal responses between the two types of diets, especially in terms of reducing insulin responses and controlling cellular inflammation.

This is important since it is excess insulin that makes you fat and keeps you fat, and it's cellular inflammation that makes you sick. Since insulin levels are determined by the protein-to-carbohydrate ratio, would more protein and less carbohydrate generate an even better response? Of course it would. That is why the Zone diet contains 40 percent of the calories as carbohydrates, 30 percent of the calories as protein, and 30 percent of the calories as fat. This improved protein-to-carbohydrate balance means lower insulin levels and less cellular inflammation.

Why stop there? Let's just continue reducing the carbohydrates. Now you get low-carbohydrate diets, like the Atkins diet. Unlike the Zone diet, carbohydrates are no longer the primary macronutrient in a true low-carbohydrate diet. Now the primary macronutrient is fat. Using these low-carbohydrate diets creates some real problems by generating an abnormal metabolic state known as ketosis. This occurs when you don't have enough carbohydrates (fewer than 20 percent of total calories) in the diet to metabolize fat completely to carbon dioxide and water. When that happens, your blood vessels lose their elastic nature, (3) increasing the risk of a heart attack (4). This is probably a consequence of lowering insulin too much as well as increasing inflammatory mediators (3). If you are trying to lose weight, increasing the likelihood of a heart attack is not a good idea. So it seems you need some carbohydrates, but not too few if your goal is to lose weight safely.

That's why people (as well as physicians and diet editors) get confused when they read articles in the New England Journal of Medicine talking about low-carbohydrate diets for weight loss when such diets actually contain 40 percent carbohydrates (5). To be correct, they should use the term “the Zone diet” instead of a “low-carbohydrate diet” to be correct. Despite the poor dietary description used in this article, the “low-carbohydrate” (aka the Zone) diet generated greater weight loss after two years, a greater reduction in the total cholesterol-to-HDL cholesterol (a marker of future cardiovascular risk), a greater decrease in triglycerides and a greater decrease in inflammatory markers when compared to a Mediterranean diet or the always-recommended low-fat diet (5). That's why you do controlled clinical trials instead of guessing what the best might be.

So if you want to lose weight and reduce your future heart disease risk, it seems prudent to follow the Zone diet and make most of your carbohydrates colorful ones (i.e., fruits and vegetables) and add olive oil and nuts for fat instead of using vegetable oils and saturated fats just as I recommended more than 15 years ago (2). Just call it the Mediterranean Zone diet. Now everyone is not only happy, but also they are finally using the proper diet terminology.

References

  1. Kastorini C-M, Milionis HJ, Esposito K, Giuglian D, Goudevnos JA, and Panagiotakos DB. “The effect of Mediterranean diet on metabolic syndrome and its components.” J Am Coll Cardiol 57: 1299-1313 (2011)
  2. Sears B. “The Zone.” Regan Books. New York, NY (1995)
  3. Buscemi S, Verga S, Tranchina MR, Cottone S, and Cerasola G. “Effects of hypocaloric very-low-carbohydrate diet vs. Mediterranean diet on endothelial function in obese women.” Eur J Clin Invest 39: 339-347 (2009)
  4. Yeboah J, Crouse JR, Hsu FC, Burke GL, and Herrington DM. “Brachial flow-mediated dilation predicts incident cardiovascular events in older adults.” J Am Coll Cardio 51: 997-1002 (2008)
  5. Shai I, Schwarzfuchs D, Henkin Y, Shahaar DR, Witkow S, Greenberg I, Golan R, Fraser D, boltin A, Vardi H, Tangi-Roxental O, Zuk-Ramot R, Sarusi B, Fricner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fielder GM, Bluher M, Stumvoll M and Stamper MJ. “Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.” N Engl J Med 359: 229-241 (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.

What’s the story on chocolate?

chocolate and polyphenolsChocolate is big business, generating about $50 billion in annual worldwide sales. But is it good medicine? Before I get to that answer, let me give you some background on the manufacturing of chocolate.

The first use of chocolate appears to be about 3,000 years ago in Central Mexico to produce an intensely bitter drink called xocolatl. Today, we still get the raw material for chocolate from the seeds of the cocoa tree. However, now they are fermented and roasted prior to extracting the raw cocoa beans from their pods. The raw cocoa mass is then ground and heated to produce what is called chocolate liquor.

This chocolate liquid is exceptionally bitter because it is rich in polyphenols. This is what you get when you buy unsweetened baker’s chocolate. Keep in mind that even with the extreme bitterness of unsweetened baker’s chocolate, the total polyphenol content is only about 5 percent of the total mass (the rest is cocoa butter). This means that purified chocolate polyphenols are about 20 times bitterer than the taste of unsweetened baker’s chocolate.

The chocolate liquor can also be further refined. The most common way is to remove the fat portion (i.e., cocoa butter) from the chocolate liquor by simple pressing. What remains is the cocoa powder that retains all of the polyphenols but in a dry form that can be ground to a powder. The isolated cocoa butter is the base for making white chocolate. Although it is free of any of the beneficial polyphenols, it still retains the excellent mouth feel of the cocoa butter. Add some extra sugar, and it is a great-tasting snack that has absolutely no health benefits.

You can always add more sugar to the cocoa liquor to sweeten the chocolate taste. That’s the ”dark chocolate” that dominates the market today. Of course in the process, you dilute out the polyphenols, which give chocolate all of its health benefits, not to mention increasing calories and increasing insulin levels because of the added sugar. That’s why eating dark chocolate will not help you lose weight. When you add more sugar and milk to the dark chocolate, the bitter taste (and the health benefits) is even reduced further. Now you have a milk chocolate candy bar.

Now what about the health benefits of the chocolate polyphenols before you start diluting them out with added sugar? Here the research data are clear. If you consume enough chocolate polyphenols, you will reduce blood pressure (1). This is probably due to the increase of nitric oxide production and its beneficial effects on relaxing the endothelial cells that line the blood vessels (2). How much is enough? Over a two-week period about 500 mg of polyphenols per day (this is the amount found in a typical 100-gram bar of unsweetened baker’s chocolate) can significantly reduce blood pressure by about 4 mm Hg (3). If you are willing to consume smaller amounts of very dark chocolate (providing 30 mg of polyphenols per day) for a much longer period of time, there is an improvement in endothelial cell relaxation, but without a reduction of blood pressure (4). Therefore, the blood pressure benefits of chocolate consumption appear to be dose-related. There is also evidence of chocolate polyphenols having some anti-inflammatory properties (5).

Considering these benefits, should chocolate be considered a “super fruit”? To answer that question, a recent publication compared the ORAC (Oxygen Radical Absorption Capacity) values of unsweetened cocoa to similar-size servings of other fruit powders from “super fruits,” such as blueberries, pomegranate and acai berries (6). The ORAC value is a measure of the ability of the dried fruit to quench free radicals. The cocoa powder had a significantly higher ORAC value per serving than the other fruit powders. Before you get too excited, keep in mind that the typical cocoa powder in the supermarket has been treated with alkali (i.e. Dutch-treated) to remove much of the bitterness of the polyphenols and in the process remove most of their health benefits (6).

So if you want the health benefits of chocolate, just make it bitter (i.e. unsweetened baker’s chocolate) and eat a lot of it (about 100 grams per day). You won’t lose any weight, but your blood pressure will come down a bit. Now if you want some real anti-inflammatory benefits, eat the chocolate, take 2.5 grams of EPA and DHA and follow an anti-inflammatory diet. Now you have a far more powerful dietary approach for reducing cellular inflammation and its clinical consequences, such as elevated blood pressure.

References

1. Ried K, Sullivan T, Fakler P, Frank OR, and Stocks NP. “Does chocolate reduce blood pressure? A meta-analysis.” BMC Med 8:39 (2010)

2. Taubert D, Roesen R, Lehmann C, Jung N, and Schomig E. “Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial.” JAMA 298: 49-60 (2007)

3. Grassi D, Lippi C, Necozione S, Desideri G, and Ferri C. “Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons.” Am J Clin Nutr 81: 611-614 (2005)

4. Engler MB, Engler MM, Chen CY, Malloy MJ, Browne A, Chiu EY, Kwak HK, Milbury P, Paul SM,Blumberg J, and Mietus-Snyder ML. “Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults.” J Am Coll Nutr 23: 197-204 (2004)

5. Selmi C, Cocchi CA, Lanfredini M, Keen CL, and Gershwin ME. “Chocolate at heart: The anti-inflammatory impact of cocoa flavanols.” Mol Nutr Food Res 52:1340-8 (2008)

6. Crozier SJ, Preston MG, Hurst JW, Payne JM, Mann J, Hainly L, and Miller DL. “Caco seeds are a super fruit,” Chemistry Central Journal 5:5 (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.

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.

How polyphenols make probiotics work better

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

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.

How to get depressed quickly

Your grandmother always said that high purity omega-3 oil was “brain food”. Now we are discovering more of the molecular mechanisms that are making grandma’s wisdom from yesteryear into today’s molecular biology breakthroughs.

The newest study that validates grandma’s wisdom will be reported in an upcoming issue of Nature Neuroscience and demonstrates the devastating impact that a lifetime diet that is deficient in omega-3 fatty acids can have on mood and impaired emotional behavior (1).

What enables the brain to make new connections is the endocannabinoid pathway that controls remodeling (i.e. plasticity) of neurons. In particular, the endocannabinoids must interact with their receptors to initiate neuronal remodeling. Without the adequate dietary intake of omega-3 fatty acids, the animals became far more depressed than their genetically identical cousins. The effect of the omega-3 fatty acid deficiency was not a general effect, but localized in the pre-frontal cortex, the area of the brain that is implicated in emotional rewards. Both EPA and DHA were depressed in the pre-frontal cortex. In addition, the levels of arachidonic acid (AA) were significantly increased in the same brain region thereby increasing the extent of neuro-inflammation. An earlier study indicated that it only takes one generation of deficiency of omega-3 fatty acids to increase depression and aggression in rats (2).

This study also helps to explain why high doses of omega-3 fatty acids improve depression in various clinical studies (3-6).

I suspect the mechanism may be the following. The depressed levels of DHA would decrease the fluidity of the neural membrane. This would make it more difficult for the activated endocannabinoid receptor to transmit its signal to the interior of the neuron necessary for the initiation of new neural synthesis. The depression of EPA as well as the increase in AA in the pre-frontal cortex would increase the levels of neuro-inflammation in the brain that would further inhibit the signaling mechanisms necessary to initiate the remodeling of neural tissue.

But to be effective, you must take a therapeutic dose of omega-3 fatty acids. That can be best determined by the AA/EPA ratio in the blood (7). This is because the brain doesn’t make these long-chain fatty acids, but it can readily take them up from the blood.

As usual your grandmother was correct when she called high purity omega-3 oil “brain food”. Her wisdom was in line with epidemiological studies that indicate lowered fish consumption is strongly associated with increased depression (8).

References

  1. Lafourcade M, Larrieu T, Mato S, Duffaud A, Sepers M, Matias I, De Smedt-Peyrusse V, Labrousse VF, Bretillon L, Matute C, Rodriquez-Puertas R, Laye S, and Manzoni OJ. “Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions.” Nature Neuroscience doi: 10:1038/nn.2736 (2011)
  2. De Mar JC, Ma K, Bell JM, Igarashi M, Greenstein D, and Rapoport SI. “One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats.” J Lipid Res 47: 172-180 (2006)
  3. Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G, Negroni M, Berra B, Politi P, and Rizzo AM. “Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial.” J Am Coll Nutr 29: 55-64 (2010)
  4. da Silva TM, Munhoz RP, Alvarez C, Naliwaiko K, Kiss A, Andreatini R, and Ferraz AC. “Depression in Parkinson’s disease: a double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation.” J Affect Disord 111: 351-359 (2008)
  5. Stahl LA, Begg DP, Weisinger RS, and Sinclair AJ. “The role of omega-3 fatty acids in mood disorders. Curr Opin Investig Drugs 9: 57-64 (2008)
  6. Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, and Marangell LB. “Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial.” Arch Gen Psychiatry 56: 407-412 (1999)
  7. Adams PB, Lawson S, Sanigorski A, and Sinclair AJ. “Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.” Lipids 31: S157-161 (1996)
  8. Hibbeln JR. “Fish consumption and major depression.” Lancet 351: 1213 (1998)

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.

When is a diet not a diet?

One of the major problems in nutrition is the lack of rigor in describing diets. The first problem is that the root of the word diet comes from the ancient Greek phrase “way of life”. A diet is not a short-term plan to fit into a swimsuit, but rather it is a way of life to reach a lifetime goal, like a longer and better life. If your goal is less grand like simply to lose weight, then to lose that weight and keep it off, you had better maintain that diet for the rest of your life. From that perspective, a diet like the Grapefruit diet doesn’t make much sense.

The second problem is the lack of precision in defining a diet. My definition of a diet is based on the macronutrient balance that ultimately determines hormonal responses. From this perspective, there are really only four diets based on the glycemic load, assuming that each diet contains the same number of calories.

Diet Common Name
Very low glycemic-load diet Ketogenic (i.e. Atkins diet)
Low glycemic-load diet Non-ketogenic (i.e. Zone Diet)
High glycemic-load diet American Heart (or Diabetes or Cancer, etc.) Association diet
Very high glycemic-load diet Strict vegetarian (i.e. Ornish diet)

Assuming these diets have an equal number of calories, you can then rank them in terms of the total amount of calories coming from protein, carbohydrates and fat as shown below:

Diet Macronutrient Composition
Very low glycemic-load diet 30% P, 10% C, and 60% F
Low glycemic-load diet 30% P, 40% C, and 30% F
High glycemic-load diet 15% P, 55% C, and 30% F
Very high glycemic-load diet 10% P, 80% C, and 10% F

You can see that depending on the macronutrient composition of the diet you choose to follow, it will generate very different hormonal responses. A ketogenic diet will induce increased cortisol levels that make you fat and keep you fat. High-glycemic diets induce excess insulin levels that make you fat and keep you fat. It’s only a low-glycemic diet that has been shown to burn fat faster (1) as well as maintain weight loss most effectively (2).

That’s why unless you define a diet carefully in terms of macronutrient balance, you can’t ever undertake any meaningful nutritional research to validate whether or not it achieves its stated goal. This is why most diet studies produce such conflicting results.

The wild card is which food ingredients you choose for a particular diet. This is where much of the confusion emerges as people throw around arbitrary terms like a Paleolithic diet or a Mediterranean diet. What the heck is a Mediterranean diet? Is it the diet from Morocco, Lebanon, Italy, or Spain? What you can do, however, is to review the food ingredients found in these diets.

For example, Paleolithic food ingredients would consist only of fruits, vegetables, nuts, grass-fed beef, eggs, and fish. A pretty limited group of foods to choose from, but it was all that was available to man 10,000 years ago. Mediterranean food ingredients include all of those in the Paleolithic group but now adding whole grains, alcohol, legumes, and dairy products. These were the dietary choices available about 2,000 years ago — a more diverse number of food choices for a particular diet, but now with a greater potential for generating inflammatory responses. Finally, there are the “Do-You-Feel-Lucky” food ingredients. This includes very recent additions to the human diet, such as sugar, refined carbohydrates and vegetable oils. These are food ingredients that make processed foods possible. However, they carry with them the greatest potential to increase cellular inflammation. Remember, it is increased cellular inflammation that makes you fat, sick, and dumb.

So if you want to be correct about the use of the word diet, then you should use the right terms. It could be an anti inflammatory diet using only Paleolithic food ingredients (i.e. a Paleo Zone Diet), or an anti inflammatory diet using only Mediterranean food ingredients (i.e. a Mediterranean Zone Diet), or even an anti inflammatory diet using the “Do-You-Feel-Lucky” food ingredients. This designation includes the most recent additions (sugar, refined carbohydrates, and vegetable oils) that have the greatest impact on inducing cellular inflammation, regardless of the macronutrient balance. Ultimately important are the hormonal responses of the macronutrient balance of the diet (especially after avoiding the worst offenders in the “Do-You-Feel-Lucky” group). The more restrictive your choices for food ingredients for any diet, the better the hormonal outcome for that particular diet. In particular, the primary clinical outcome for the anti inflammatory diet is the life-long management of cellular inflammation. And for that clinical parameter, the clinical research has found the anti inflammatory diet to be the clear winner regardless of the food ingredients selected (3-5).

References

  1. 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)
  2. 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)
  3. 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)
  4. 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)
  5. 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)

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.

Breast cancer and inflammation

Breast cancer is probably the greatest fear women have, even though they are 10 times more likely to die from heart disease. Yet both diseases are driven by cellular inflammation.

Cellular inflammation occurs when the most primitive part of your immune system (the innate immune system) is activated. The key player in the innate immune system is a gene transcription protein known as nuclear factor-kappaB (NF-κB). Once activated, NF-κB moves into the cell’s nucleus and causes the expression of a wide variety of pro-inflammatory mediators that accelerate the growth of the tumor. A recent publication in Cancer Research has demonstrated that complete inhibition of the NF-κB in the breast tissue prevents the development of breast cancer in animal models (1).

Of course, there is one slight problem with this approach. If you inhibit NF-κB too much, you make yourself a sitting target for microbial invasion. So the question is what activates the NF-κB in the first place? The answer is the diet, and specifically how the diet increases the levels of arachidonic acid, as I described in my most recent book, “Toxic Fat” (2). As the levels of arachidonic acid increase in the cell, there is an increased formation of inflammatory compounds (i.e. leukotrienes) that activate NF-κB (3).

So what might the best approach be for reducing the risk of breast cancer? The obvious answer is to decrease the levels of arachidonic acid in the breast tissue. The best way would be to follow a strict anti inflammatory diet to reduce the formation of arachidonic acid in the first place (4).

Unfortunately, most women (and men) are not willing to take that step. That being the case, then what other dietary approach can be used? I would suggest that supplementing the diet with high-purity omega-3 fatty acid concentrates rich in EPA and DHA is the one approach that everyone can follow. This is especially true since it takes only 15 seconds a day. The benefits of this approach was recently demonstrated in another article published last year in the American Journal of Clinical Nutrition that demonstrated supplementation with purified omega-3 concentrates can dramatically increase the levels of omega-3 fatty acids in the breast tissue of women who have a high-risk potential of developing breast cancer (5).

Of course, if you not only take high-purity omega-3 fatty acid concentrates, but also follow the anti inflammatory diet, then you will have done every possible dietary intervention to reduce the activation of NF-κB in the target tissue for breast cancer (not to mention also reducing the risk for heart disease). Of course, there are some side effects to this dietary approach: You become thinner, smarter and happier in the process.

References

  1. Liu M, Sakamaki T, Casimiro MC, Willmarth NE, Quong AA, Ju X, Ojeifo J, Jiao X, Yeow WS, Katiyar S, Shirley LA, Joyce D, Lisanti MP, Albanese C, and Pestell RG. “The canonical NF-kappaB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion.” Cancer Res 24: 10464-10473 (2010)
  2. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN. (2008)
  3. Sanchez-Galan E, Gomez-Hernandez A, Vidal C, Martin-Ventura JL, Blanco-Colio LM, Munoz-Garcia B. Ortega L, Egido J, and Tunon J. “Leukotriene B4 enhances the activity of nuclear factor-kappaB pathway through BLT1 and BLT2 receptors in atherosclerosis.” Cardiovasc Res 81: 216-225 (2009)
  4. Sears B. “The Zone.” Regan Books. New York, NY (1995)
  5. Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, Lehman A, Belury MA, and Clinton SK. “Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition.” Am J Clin Nutr 91:1185–1194 (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.