Tag Archives: omega-3

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.

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.

How to get depressed quickly

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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.

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.

Breast cancer and inflammation

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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.

Another good reason to eat your fruits and vegetables

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Your grandmother always told you, you couldn’t leave the table until you ate all your vegetables. She was giving you the essence of reducing your chances of dying from cardiovascular disease.

The trouble with testing any dietary hypothesis (even Grandma’s advice on vegetables) is the complexity of understanding nutrition. Unlike drugs, which are based on linear thinking (one drug affects one enzyme and that treats you), nutrition is based on non-linear thinking. That means nutrition is more like a three-dimensional chess match. Whenever you change one component (i.e. amount of fat) in the diet, there will be unintended changes as something else is automatically changed as a consequence (like either an increase in dietary protein or carbohydrate to make up the difference of the reduction of dietary fat). This secondary dietary change may totally obscure what you are trying to study. This explains why so many dietary studies appear to produce such wishy-washy results. To try to get around this constant dilemma, investigators often do extremely large epidemiological studies, using people who are initially disease-free and ask how an exposure to some dietary variable affects the development of a particular disease or more importantly death from a particular disease. These are called prospective cohort studies.

As you might imagine, there are very few of these studies since they require a very large number of subjects, and if the outcome is death, then they have to be followed for a very long time. This also means that these studies are extremely expensive. In a soon-to-be-published article in the European Heart Journal is a massive prospective cohort study (with more than 300,000 subjects and based upon an average of eight years of follow-up) that suggested if you ate more fruits and vegetables, your likelihood of dying of heart disease was reduced by 22 percent (1).

How much is more fruits and vegetables? It is about eight servings per day, and it appeared to be a dose-response effect. For each serving of fruits or vegetables, the risk of death from heart disease goes down by 4 percent. Bottom line, the more fruits and vegetables you eat, the greater the reduction in cardiovascular death.

Since you have to eat, why not eat right if your goal is reducing the risk of death from heart disease. If you are eating more fruits and vegetables, then something must be removed from the diet if the calories are to remain constant. The most logical choice would be reducing grains and starches as you increase fruits and vegetables. In the process, you reduce the glycemic load of the diet and reduce production of insulin. This will not only reduce your risk of dying from heart disease, but also help you lose excess body fat (2)

Notice that I keep emphasizing the words death and dying. The prevailing “wisdom” in the cardiovascular community is that it doesn’t matter what you eat as long as you reduce cholesterol levels. And since increased fruits and vegetables consumption has little impact on cholesterol levels, we are told that if you really want to reduce the risk of dying from heart disease, it’s imperative that you must take a statin drug for the rest of your life. Unfortunately, the research data doesn’t support such optimism. For example, if subjects are studied who have no heart disease (these are called primary prevention studies), then taking statin drugs has no impact on reducing their all-cause mortality (3). In other words, any reduction in cardiovascular death was offset by increases of death from other causes. Not such a good deal if your goal is reducing death whatever the cause. Another group of researchers came to the conclusion after analyzing a number of published trials using statin drugs for the primary prevention of developing heart disease, that there was no compelling reason for their use (4). Since the vast majority of the people taking statin drugs have no established heart disease, this would mean the continued prescription of these drugs comes close to health-care fraud.

But what if you already have heart disease? What is the best way to reduce the risk of dying from it? To answer that question, you undertake secondary prevention studies using death (it’s very easy to measure) as your clinical endpoint. In secondary prevention studies, statins will reduce cardiovascular mortality by about 20 percent in people who already have established heart disease. But if you really want to reduce the likelihood of dying from existing heart disease (like by 70 percent), then you not only have to have the patients increase their intake of fruits and vegetables, but also remove much of the omega-6 fatty acids from the diet and replace them with omega-3 fats (5).

If you do both of these dietary changes (replace grains and starches with more fruits and vegetables as well as replace omega-6 fats with omega-3 fats), then you are essentially following the anti inflammatory diet. That’s how you live longer whether you have heart disease or not.

References

1. Crowe FL, Roddam AW, Key TJ, et al. “Fruit and vegetable intake and mortality form ischaemic heart disease.” Eur Heart Journal 32: doi 10.1093 (2011)

2. Sears B. “The Zone.” Regan Books. New York, NY (1995)

3. Ray KK, Seshsai SRK, Erqou S, Sever P, Jukema JW, Ford I, and Sattar NS. “Statins and all-cause morality in high-risk primary prevention.” Arch Intern Med 170: 1024-1031 (2010)

4. Taylor F, Ward K, Moore THM, Burke M, Davey-Smith G, Casas JP, and Ebrahim S. “Statins for the primary prevention of cardiovascular disease.” The Cochrane Library Issue 1 (2011)

5. de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P, and Delaye J. “Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.” Lancet 343: 1454-1459 (1994)

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.

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.

Weight loss or fat loss? It makes a difference

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With the New Year comes the guaranteed resolution for most people to lose weight. Invariably that resolution is usually abandoned some time in February. Part of the reason is that we really don’t know what we are talking about when it comes to weight loss. Weight loss is composed of three separate components: water loss, muscle loss, and fat loss. If you restrict calories, you are going to lose weight. What that weight loss might consist of (water, muscle, or fat) is a very different question.

There are no health benefits to water loss (i.e. dehydration) or muscle loss (i.e. protein deprivation), but there is something magical about fat loss. If you can lose excess body fat, then you are virtually guaranteed to lower blood sugar levels, blood lipid levels, and blood pressure. Not surprisingly, drugs used to reduce blood sugar, blood lipids and blood pressure are the biggest sellers in the country.

Considering the continuing outcry to reverse our obesity epidemic, no one seems to bother to measure fat loss in any clinical trials. This is why you see a lot of research studies published stating it doesn’t matter what diet you follow because if you restrict calories, you will lose weight. I agree with that statement. But if you want better health (not to mention looking better in a swimsuit), then you want to make sure that you are losing fat at the fastest possible rate while conserving muscle mass at the same time. The published clinical studies that have looked at fat loss make it very clear that the anti inflammatory diet is the best dietary strategy to burn fat faster (1-3).

If the moderate-carbohydrate anti inflammatory diet is good, then shouldn’t an even lower-carbohydrate diet like the Atkins diet be better? Not so fast. The published studies comparing the anti inflammatory diet to the Atkins diet make it clear that there are no benefits to consuming a lower-carbohydrate diet that generates ketosis, but there are plenty of negative consequences, such as increased cellular inflammation and decreased capacity for exercise (4,5).

But losing weight is relatively easy compared to keeping it off. That’s why the recent DIOGENES study is so important (6). This study makes it very clear that if you want to keep lost weight off, then your best choice is maintaining a diet that has at least 25 percent of the calories coming from protein, and about 40 percent of the calories coming from low-glycemic carbohydrates. That’s the anti inflammatory diet.

So if your New Year’s resolution is to lose weight (and really lose fat) and keep it off, then the anti inflammatory diet should be your only choice.

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. 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. White AM, Johnston CS, Swan PD, Tjonn SL, and Sears B. “Blood ketones are directly related to fatigue and perceived effort during exercise in overweight adults adhering to low-carbohydrate diets for weight loss: a pilot study.” J Am
Diet Assoc 107:1792-1796 (2007)
6. 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)

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.