Where does fat go?

Many years ago I saw a great cartoon of farmer harvesting bales of fat on a tractor with the caption reading, “That’s where they grow fat”. Now let’s fast forward to our current obesity epidemic. The fastest and most popular (although costly) way to lose fat is to simply suck it out of the body. Plastic surgeons have been doing this for the past 40 years. Yet for some reason their patients keep coming back every 12 months needing a new liposuction touch-up, like taking your car in for an oil lube and tire change at your local garage. Maybe these patients simply have no willpower to keep the fat off.

Now a new study in an online pre-publication article (1) indicates liposuction recipients may not be so “weak-willed” after all. After one year compared to a control group (who were promised discount prices for their liposuction if they would agree to wait for the outcome of the study), the females who had liposuction had no change in their body weight or their percentage of body fat 12 months after the operation. All the fat that had been removed by liposuction had returned. More ominously, the new fat appeared in the wrong places. Initially, it was taken from the hips, and 12 months later it reappeared on the abdomen. In essence, the liposuction had transformed the patients from a pear shape (with few long-term cardiovascular consequences) to an apple shape (with greater long-term cardiovascular consequences). While there was no short-term deterioration in their metabolic markers suggestive of future diabetes or heart disease, the change in the body shape is still an ominous predictor for their future health.

Why the body would grow new fat cells in different parts of the body is still a mystery. But it does indicate the body’s ability to defend itself against rapid fat loss. Fat loss must be a slow, continuous process to avoid activating these “fat-defending” systems. It is impossible to lose more than one pound of fat per week. You can lose a lot more weight, but that difference in weight loss primarily comes from either water loss or loss of muscle mass. This is why you see large of amounts of weight loss during the first week or two of any quick weight-loss diet (primarily water loss) followed by a much slower weight loss (now consisting of fat loss but at a much slower rate).

This is also why it is much easier to lose a lot of weight on shows like “The Biggest Loser” but very difficult to lose the last 10-15 pounds of excess weight (which is usually stored body fat). Apparently, it is only through the slow, steady loss of body fat that there isn’t any activation of the hormonal signals that activate the formation of new fat cells in other parts of the body to restore fat levels. Liposuction is rapid fat loss, and hence those hormonal signals are activated, which leads to the increased production of new fat cells in different parts of the body. People don’t like to hear this, but unfortunately it is the truth.

What drives fat gain is cellular inflammation that creates insulin resistance, as I explain in my book “Toxic Fat” (2). To lose excess body fat, you must first reduce cellular inflammation. That can only be done by an anti-inflammatory diet. There is no secret about it. What you must do is eat adequate protein at every meal, primarily eat colorful vegetables as carbohydrate choices, and avoid the intake of excess omega-6 (i.e., vegetable oils) fats and saturated fats by primarily using monounsaturated and omega-3 fats. You have to do this for a lifetime. Of course, if you do, then you will become thinner, healthier, and smarter.

The alternative is to turn yourself from a pear into an apple with liposuction.

References

  1. Hernandex TL, Kittelson JM, Law CK, Ketch LL, Stob NR, Linstrom RC, Scherziner A, Stamm ER, and Eckel RH. “Fat redistribution following section lepectomy: defense of body fat and patterns of restoration.” Obesity doi:1038/oby.2011.64
  2. 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.

The fallacy of using DHA alone for brain trauma

I am constantly amazed by the lack of understanding by neurologists of basic essential fatty acid biochemistry in the treatment of brain trauma and concussions. They often blindly believe that the only omega-3 fatty acid that has any impact in the treatment of concussions is DHA alone. Their blind faith is based on the observation that you find a lot of DHA in the brain and little EPA. This obviously means that EPA must not be important for brain function. This is similar to stating the world is flat because it appears that way to the naked eye.

I have mentioned many times in my books that EPA and DHA have different functions, and that’s why you need both of these essential omega-3 fatty acids (1-4). This is especially true for the brain. EPA produces most of the anti-inflammatory properties of omega-3 fatty acids since it’s structurally similar to arachidonic acid (AA) as they both contain 20 carbon atoms with approximately the same spatial configuration. As a result, EPA can inhibit the enzymes that would otherwise produce pro-inflammatory eicosanoids from AA. It is AA that generates the inflammation caused by brain trauma. DHA, on the other hand, is primarily a structural component of neural tissue. They do different jobs, and that’s why you need both in combination.

So why isn’t there as much EPA in the brain compared to DHA? The reason is simple. EPA enters the brain just as quickly as DHA, but it is rapidly oxidized, whereas DHA is sent off to long-term storage in neural tissue (5-7). The lifetime of DHA in the human brain is measured in years, whereas the lifetime of the EPA is measured in days. So obviously when you kill an animal and look at the brain, you are not going to find very much EPA.

What complicates the issue is that if you only treat a concussion with DHA, some of the DHA will be converted to EPA. This gives the appearance that DHA is working to reduce inflammation. Since brain trauma and concussions generate inflammation in the brain, doesn’t it make more sense to provide as much EPA as possible to reduce the inflammation as opposed to supplementing only with DHA and hoping some fraction of it will be converted to EPA?

To answer that question, it is useful to look at two recent studies that used the same protocol to study inflammation induced by a concussion injury (8,9). The same total amount of omega-3 fatty acids was used to treat the animals after the concussion injury. One experiment used a 2:1 ratio of EPA to DHA, and the other experiment used only DHA. If the DHA was so important, then the animals treated with the DHA alone should have demonstrated three times the reduction of neuro-inflammation compared to the group that received omega-3 fatty acids containing only one-third as much DHA.

In fact, just the opposite was the case. The 2:1 EPA/DHA group demonstrated greater benefits compared to the DHA-alone group in reducing neuro-inflammation induced by a concussion. Why? EPA is a far more powerful anti-inflammatory agent than DHA. This is why in both studies the AA/EPA ratio was used as the marker of inflammation induced by the concussion injury. Since the AA/EPA ratio was decreased in both studies, this meant that some of the pure DHA was converted to EPA providing at least some anti-inflammatory actions. Thus giving 100 percent DHA is not exactly the most efficient way to decrease neuro-inflammation induced by a concussion injury. This is further emphasized by a recent study that indicated that 1 gram of DHA per day for an 18-month period had no impact in the cognitive improvement of Alzheimer’s patients (10), even though Alzheimer’s is known to be a neuro-inflammatory disease (11).

Does this mean that DHA is not important for brain repair? Of course not. This is because you need both EPA and DHA for optimal repair of brain damage after a concussion. You need the EPA to reduce the neuro-inflammation, and you need the DHA to help rebuild new neurons. But to give DHA alone without additional EPA to maximally reduce neuro-inflammation caused by concussions simply makes no sense.

References

  1. Sears B. “The Zone.” Regan Books. New York, NY (1995)
  2. Sears B. “The OmegaRx Zone.” Regan Books. New York, NY (2002)
  3. Sears B. “The Anti-inflammation Zone.” Regan Books. New York, NY (2005)
  4. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  5. Chen CT, Liu Z, and Bazinet RP. “Rapid de-esterification and loss of eicosapentaenoic acid from rat brain phospholipids: an intracerebroventricular study.” J Neurochem 116: 363-373 (2011)
  6. Chen CT, Liu Z, Ouellet M, Calon F, and Bazinet RP. “Rapid beta-oxidation of eicosapentaenoic acid in mouse brain: an in situ study. “Prostaglandins Leukot Essent Fatty Acids 80: 157-163 (2009)
  7. Umhau JC, Zhou W, Carson RE, Rapoport SI, Polozova A, Demar J, Hussein N, Bhattacharjee AK, Ma K, Esposito G, Majchrzak S, Herscovitch P, Eckelman WC, Kurdziel KA, and Salem N. “Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography.” J Lipid Res 50: 1259-1268 (2009)
  8. Mills JD, Bailes JE, Sedney CL, Hutchins H, and Sears B. “Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model.” J Neurosurg 114: 77-84 (2011)
  9. Bailes JE and Mills JD. “Docosahexaenoic acid reduces traumatic axonal injury in a rodent head injury model.” J Neurotrauma 27: 1617-1624 (2010)
  10. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR, Weiner M, Shinto L, and Aisen PS. “Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial.” JAMA 304: 1903-1911 (2010)
  11. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR,McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL,Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, and Wyss-Coray T. “Inflammation and Alzheimer’s disease.” Neurobiol Aging 21: 383-421 (2000)

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.

Obesity starts in the womb

A new study from Harvard Medical School strongly suggests that childhood obesity begins in the mother’s womb (1). Specifically, the lower the EPA and DHA concentrations in either the mother’s diet or her umbilical cord attached to the fetus, the more likely the child will develop obesity by age 3.

It is well known from animal experiments that omega-6 fatty acids make the offspring fat, and omega-3 fatty acids make the offspring thin (2-4). This new study now confirms the same thing is happening in humans (1).

It has been demonstrated in animal models that it only takes three to four generations of a high omega-6 fatty acid intake to increase obesity in the offspring (5,6). I believe one of the driving forces for the increase in childhood obesity has been the dramatic increase in omega-6 fatty acids over the past 100 years (7). However, much of that omega-6 fatty acid increase has come from the massive increase in soybean oil consumption that started in the early 1970s. That 40-year period only represents about two generations of humans, which means it is quite likely there will be higher childhood obesity rates coming with the next generations as long as omega-6 fatty acid consumption stays elevated.

At the molecular level, the problem really starts when these excess omega-6 fatty acids are activated by ever-increasing insulin levels caused by refined carbohydrate consumption to create increased cellular inflammation. In my book “Toxic Fat“ I describe some of the political decisions and their metabolic consequences that have led to the epidemic increase of cellular inflammation that has resulted in the rapid deterioration of American health (8).

The bottom line is that this dramatic increase in omega-6 fatty acids in the diet of American mothers is causing trans-generation changes in our children due to fetal programming. This occurs in the womb and results in the final tuning of the genetic code of the fetus by changing the gene expression of the unborn child. This is called epigenetic programming and begins to explain why each succeeding generation of Americans is getting fatter and fatter (9).

Even more ominous warnings are animal studies that indicate the “reward” response (increased dopamine levels) induced by consuming junk food experienced by the mother can also be transferred to the next generation by fetal programming (10).

So what can you do about this growing genetic disaster? If you are contemplating having a child, then beginning to cut back on omega-6 fatty acids and eating more omega-3 fatty acids is a good starting point. The benefits include having a thinner and smarter child. If you already have children whose gene expression has already been altered by fetal programming, then you have to control their diet for a lifetime to prevent reverting to that altered gene expression. It’s not a pretty picture. Although you can’t escape the dietary consequences of fetal programming, you can minimize the damage by treating food as drug to manage increased cellular inflammation that is making us fatter, sicker and dumber.

References

  1. Donahue, SMA, Rifas-Shiman SL, Gold DR, Jouni ZE, Gillman MW, and Oken E. “Prenatal fatty acid status and child adiposity at age 3y.” Amer J Clin Nutr 93: 780-788 (2011)
  2. Gaillard D, Negrel R, Lagarde M and Ailhaud G. “Requirement and role of arachidonic acid in the differentiation of pre-adipose cells.” Biochem J 257: 389-397 (1989)
  3. Kim HK, Della-Fera M, Lin J, and Baile CA. “Docosahexaenoic acid inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 pre-adipocytes.” J Nutr 136: 2965-2969 (2006)
  4. Massiera F, Saint-Marc P, Seydoux J, Murata T, Kobayashi T, Narumiya S, Guesnet P, Amri EZ, Negrel R, and Ailhaud G. “Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern?” J Lipid Res 44: 271-279 (2003)
  5. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, and Rawlings RR. “Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century.” Am J Clin Nutr 93: 950-962 (2011)
  6. Hanbauer I, Rivero-Covelo I, Maloku E, Baca A, Hu Q, Hibbeln JR, and Davis JM. “The Decrease of n-3 Fatty Acid Energy Percentage in an Equicaloric Diet Fed to B6C3Fe Mice for Three Generations Elicits Obesity.” Cardiovasc Psychiatry Neurol: 2009, Article ID.867041 (2009)
  7. Massiera F, Barbry P, Guesnet P, Joly A, Luquet S, Moreilhon-Brest C, Mohsen-Kanson T, Amri EZ, and Ailhaud G. “A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations.” J Lipid Res 51: 2352-2361 (2010)
  8. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  9. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies J, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, and Hanson MA. “Epigenetic gene promoter methylation at birth is associated with child’s later adiposity.” Diabetes 60: 1528-1534 (2011)
  10. Ong ZY and Muhlhausler BS. “Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring.” FASEB J 25: S1530-6860 (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.

Fetal programming: Gene transformation gone wild (Part II)

In part 1 of this blog, I discussed how dietary changes can alter gene expression and how those epigenetic changes can be mediated from one generation to the next by fetal programming. This is very clear from animal studies. One of the most frightening studies was published a few years ago (1). In this study, genetically identical mice were split into two colonies. For the next three generations they were fed exactly the same number of calories with exactly the same balance of protein, carbohydrate, and fat. The only difference was that one group had a diet rich in omega-6 fatty acids and low in omega-3 fatty acids, and the other had a better balance of omega-3 to omega-6 fatty acids. After three generations the mice fed the high omega-6 fatty acid diet were grossly obese.

In addition, the mice with high omega-6 fatty acids had fatty livers and enlarged hearts and kidneys, all indicative of major metabolic disturbances.

This also happens with the brain. It has been demonstrated that removing omega-3 fatty acids and replacing them with omega-6 fatty acids over three generations makes animals a lot dumber, probably due to significant reductions in neurotransmitters, like serotonin and dopamine (2-5). Not only are they dumber, but their offspring also show a strong preference for junk food. (6)

How could this happen in such a short period of time? The answer is fetal programming induced by increased cellular inflammation. If this cellular inflammation is maintained by an inflammatory diet, there will be a constant driving force to maintain these epigenetic effects from one generation to other.

The next question is how long does this epigenetic programming have to be continued until it becomes a permanent part of the gene structure. One indication might be found in the development of lactose intolerance in those populations who have been exposed to dairy products for thousands of years. Seventy percent of the world’s population can’t digest these dietary products because they have lost the ability to maintain the necessary enzyme production after weaning from mother’s breast milk. Those who have been constantly exposed to dairy products after weaning have developed an epigenetic programming that seems to be permanent.

These epigenetic changes in humans may take place in only one generation. This is the suggestion of a new article to be published in Diabetes that indicates more than 25 percent of the explanation for childhood obesity could be predicted by prenatal epigenetic changes at birth (7).

As long as our epidemic of cellular inflammation continues to be fueled by the Perfect Nutrition Storm, we can expect our children to continue to become fatter, sicker, and dumber (8).

References

  1. Hanbauer I, Rivero-Covelo I, Maloku E, Baca A, Hu Q, Hibbeln JR, and Davis JM. “The Decrease of n-3 Fatty Acid Energy Percentage in an Equicaloric Diet Fed to B6C3Fe Mice for Three Generations Elicits Obesity.” Cardiovasc Psychiatry Neurol: 2009, Article ID.867041 (2009)
  2. 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)
  3. Zimmer L, Delpal S, Guilloteau D, Aioun J, Durand G, and Chalon S. “Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex.” Neurosci Lett 284: 25-28 (2000)
  4. Moriguchi T, Greiner RS, and Salem N. “Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration.” J Neurochem 75: 2563-2573 (2000)
  5. Chalon S. “Omega-3 fatty acids and monoamine neurotransmission.” Prostaglandins Leukot Essent Fatty Acids 75: 259-269 (2006)
  6. Ong ZY and Muhlhausler BS. “Maternal “junk-food” feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring.” FASEB J 25: S1530-6860 (2011)
  7. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies J, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, and Hanson MA. “Epigenetic gene promoter methylation at birth is associated with child’s later adiposity.” Diabetes 60: doi: 10.2337/db10-0979 (2011)
  8. Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, and Hanson MA. “Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease.” Pediatr Res 61: 5R-10R (2007)

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

Fish oil and fat loss

I have often said, “It takes fat to burn fat”. As I describe in my book “Toxic Fat,” increased cellular inflammation in the fat cells turns them into “fat traps” (1). This means that fat cells become increasingly compromised in their ability to release stored fat for conversion into chemical energy needed to allow you to move around and survive. As a result, you get fatter, and you are constantly tired and hungry.

One of the best ways to reduce cellular inflammation in the fat cells is by increasing your intake of omega-3 fatty acids. This was demonstrated in a recent article that indicated supplementing a calorie-restricted diet with 1.5 grams of EPA and DHA per day resulted in more than two pounds of additional weight loss compared to the control group in a eight-week period (2).

How omega-3 fatty acids help to ”burn fat faster” is most likely related to their ability to reduce cellular inflammation in the fat cells (3,4) and to increase the levels of adiponectin (5). Both mechanisms will help relax a “fat trap” that has been activated by cellular inflammation.

However, there is a cautionary note. This is because omega-3 fatty acids are very prone to oxidation once they enter the body. This is especially true relative to the enhanced oxidation of the LDL particles (6-9).

This means that to get the full benefits any fish oil supplementation, you have to increase your intake of polyphenols to protect the omega-3 fatty acids from oxidation. How much? I recommend at least 8,000 additional ORAC units for every 2.5 grams of EPA and DHA that you add to your diet. That's about 10 servings per day of fruits and vegetables, which should be no problem if you are following the Zone diet. If not, then consider taking a good polyphenol supplement.

Once you add both extra fish oil and polyphenols to a calorie-restricted diet, you will burn fat faster without any concern about increased oxidation in the body that can lead to accelerated aging.

References

  1. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  2. Thorsdottir I, Tomasson H, Gunnarsdottir I, Gisladottir E, Kiely M, Parra MD, Bandarra NM, Schaafsma G, and Martinez JA. “Randomized trial of weight-loss diets for young adults varying in fish and fish oil content.” Int J Obes 31: 1560-1566 (2007)
  3. Huber J, Loffler M, Bilban M, Reimers M, Kadl A, Todoric J, Zeyda M, Geyeregger R, Schreiner M, Weichhart T, Leitinger N, Waldhausl W, and Stulnig TM. “Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids.” Int J Obes 31: 1004-1013 (2007)
  4. Todoric J, Loffler M, Huber J, Bilban M, Reimers M, Kadl A, Zeyda M, Waldhausl W, and Stulnig TM. “Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids.” Diabetologia 49: 2109-2119 (2006)
  5. Krebs JD, Browning LM, McLean NK, Rothwell JL, Mishra GD, Moore CS, and Jebb SA. “Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women.” Int J Obes 30: 1535-1544 (2006)
  6. Pedersen H, Petersen M, Major-Pedersen A, Jensen T, Nielsen NS, Lauridsen ST, and Marckmann P. “Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes.” Eur J Clin Nutr 57: 713-720 (2003)
  7. Turini ME, Crozier GL, Donnet-Hughes A, and Richelle MA. “Short-term fish oil supplementation improved innate immunity, but increased ex vivo oxidation of LDL in man–a pilot study.” Eur J Nutr 40: 56-65 (2001)
  8. Stalenhoef AF, de Graaf J, Wittekoek ME, Bredie SJ, Demacker PN, and Kastelein JJ. “The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low-density lipoprotein heterogeneity and oxidizability in patients with hypertriglyceridemia.” Atherosclerosis 153: 129-138 (2000)
  9. Finnegan YE. Minihane AM, Leigh-Firbank EC, Kew S, Meijer GW, Muggli R, Calder PC, and Williams CM. “Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects.” Am J Clin Nutr 77: 783-795 (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.

Omega-3 fatty acids and blood pressure

Blood Pressure CuffIt was recognized many years ago that fish oil has a dose-dependent effect on lowering blood pressure (1). So how does it do it? There are a lot of different ways.

The first is the ability of the omega-3 fatty acids in fish oil to alter the levels of a group of hormones known as eicosanoids (2,3). These are the hormones that cause blood vessels to contract, thereby increasing the pressure needed to pump blood through the arteries. The omega-3 fatty acids, especially eicosapentaenoic acid (EPA), inhibit both the synthesis and release of the omega-6 fatty acid arachidonic acid (AA) that is the molecular building block necessary to produce those eicosanoids that cause constriction of blood vessels.

The second way that fish oil helps reduce blood pressure is to accelerate weight loss. When you lose excess weight, blood pressure invariably decreases. A recent trial has indicated that when you add fish oil to a calorie-restricted diet, there is greater weight loss (4). This study was followed by an additional trial that indicated when adding fish oil to a weight-reduction diet, there was a further effect on lowering blood pressure (5). So how does fish oil help you lose excess weight? The answer lies in the ability of the omega-3 fatty acids in fish oil to reduce cellular inflammation in the fat cells (6). It's that cellular inflammation that makes you fat and keeps you fat. Reducing that cellular inflammation in the fat cells is the key to weight loss.

Finally another cause of increased blood pressure is increased stress. It was shown in 2003 that high levels of fish oil reduce the rise of blood pressure induced by mental stress (7).

Of course, the best way to reduce blood pressure is to follow an anti-inflammatory diet rich in omega-3 fatty acids. That means a diet rich in fruits and vegetables with adequate levels of low-fat protein and low levels of omega-6 and saturated fats. It's also commonly known as the Zone diet.

References:

  1. Morris MC, Sacks F, and Rosner B. “Does fish oil lower blood pressure? A meta-analysis of controlled trials.” Circulation 88: 523-533 (1993)
  2. Sears B. “The Zone.” Regan Books. New York, NY (1995)
  3. Sears B. “The OmegaRx Zone.” Regan Books. New York, NY (2002)
  4. Thorsdottir I, Tomasson H, Gunnarsdottir I, Gisladottir E, Kiely M, Parra MD, Bandarra NM, Schaafsma G, and Martinez JA. “Randomized trial of weight-loss diets for young adults varying in fish and fish oil content.” Int J Obes 31: 1560-1566 (2007)
  5. Ramel A, Martinez JA, Kiely M, Bandarra NM, and Thorsdottir I. “Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European young adults during energy restriction.” Nutrition 26: 168-174 (2010)
  6. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  7. Delarue J, Matzinger O, Binnert C, Schneiter P, Chiolero R, and Tappy L. “Fish oil prevents the adrenal activation elicited by mental stress in healthy men.” Diabetes Metab 29: 289-295 (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.

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.

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.

Pass the polyphenols

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.