Another new wrinkle in the cholesterol story

One of the great marketing successes of the pharmaceutical industry has been the linkage between LDL cholesterol levels and heart disease. In essence, the message, “if your LDL cholesterol is high, you are going to die,” is powerful. Unfortunately, the data state otherwise.

It was known in the mid 1990s that oxidized LDL was the primary suspect in the development of atherosclerotic lesions; not natural, non-oxidized LDL. But it was also at this time that the first statin studies began to appear, and that gave the pharmaceutical industry a patented drug to “prevent” heart disease (2). It was such a good story to tell and an even better one to sell. Unfortunately, as I pointed out in an earlier blog, it has never held up well against unbiased scrutiny, especially in patients with high cholesterol levels but without any heart disease.

Part of the reason lies in the data. Shown below is the correlation of LDL cholesterol to heart disease

You can see from this data that there is a higher percentage of cardiovascular disease patients with high LDL cholesterol levels compared with very low levels, but not that much. This explains why about half the people who die from heart disease have normal LDL cholesterol levels (less than 130 mg/dl). It also means that high LDL cholesterol is not a very good predictor of heart disease.

On the other hand, a very different picture emerges if you look at the levels of oxidized LDL levels as shown below.

Even without a background in statistics you can see a very striking relationship in the prediction of heart disease with increasing levels of oxidized LDL levels.

So why don’t physicians use oxidized LDL levels as an indicator of heart disease risk? First, the test is much more difficult to do than a simple cholesterol test. Second, it ruins a great story that is easy to communicate to the patient. Third, the best way of reducing oxidized LDL levels is natural anti-oxidants, such as polyphenols, that have no patent protection (3,4). Reducing LDL cholesterol is simple. Just take a statin drug for the rest of your life. Reducing oxidized LDL cholesterol requires having plenty of antioxidants in your diet with polyphenols the most powerful.

Now there is another new entry into the LDL story. This is “super-sticky” LDL. In an online pre-publication, it was demonstrated that this new type of LDL particle may be even worse than oxidized cholesterol in promoting the development of heart disease (5). This “super-sticky” LDL comes from the formation of advanced glycosylation end products (AGEs). I described this formation of protein-carbohydrate linkages as an integral part of the aging process in my book, “The Anti-Aging Zone,” published more than a decade ago (6).

The best way to reduce the production of “super-sticky” LDL is to reduce blood sugar levels. This helps explain why individuals with diabetes are two to three times more likely to develop heart disease. The best way to reduce elevated blood sugar is the Zone diet. That’s why the latest dietary recommendations for the treatment of diabetes by the Joslin Diabetes Research Center at Harvard Medical School are essentially identical to the Zone diet.

Heart disease remains the number-one cause of death in America. Unfortunately, it is more complex than “taking a statin a day to keep death away”.

References

  1. Maor I and Aviram M. “Oxidized low-density lipoprotein leads to macrophage accumulation of unesterified cholesterol as a result of lysosomal trapping of the lipoprotein hydrolyzed cholesterol ester.” J Lipid Res 35: 803-819 (1994)
  2. Simvastatin Study Group. “Randomized trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).” Lancet 344: 1383-1389 (1994)
  3. Shafiee M, Carbonneau MA, Urban N, Descomps B, and Leger CL. “Grape and grape seed extract capacities at protecting LDL against oxidation generated by Cu2+, AAPH or SIN-1 and at decreasing superoxide THP-1 cell production.” Free Radic Res 37: 573-584 (2003) (ISSN: 1071-5762)
  4. Chen CY, Yi L, Jin X, Mi MT, Zhang T, Ling WH, and Yu B. “Delphinidin attenuates stress injury induced by oxidized low-density lipoprotein in human umbilical vein endothelial cells.” Chem Biol Interact 183: 105-112 (2010)
  5. Rabbani N, Godfrey L, Xue M, Shaheen F, Geoffrion M, Milne R, and Thornalley PJ. “Glycation of LDL by methylglyoxal increases arterial atherogenicity.” Diabetes 60 doi:10.2337/db09-1455 (2011)
  6. Sears B. “The Anti-Aging Zone.” Regan Press. New York, NY (1999)

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

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.

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.

Fetal programming: Gene transformation gone wild (Part I)

Normally genes change very slowly through mutation. Most mutations are harmful and hence provide no survival advantage to the organism. This is why there is a less than a 2 percent difference between our genes and those of a chimpanzee, even though we became a separate species more than six million years ago. What distinguishes mankind is not the number of genes (corn has twice as many genes as humans), but the speed at which our genes can be turned on and off. This is because of the presence of gene transcription factors that can be activated or inhibited by nutrients. The effect of nutrients on gene expression is known as nutrigenomics.

Because of mankind’s rapid gene switching abilities, gene expression can be influenced significantly by the diet. Due to the speed at which new food ingredients are being introduced into the human diet, these types of nutrigenomic interactions can create radical changes in gene expression in a very short period of time. Normally what a person eats should only affect their gene expression during their lifetime. But is it possible that these changes in genetic expression can be transferred to the next generation?

We can see how genetic engineering (i.e. cross-breeding) can rapidly change the size and shape of dogs, flowers, vegetables and fruits. The genes in each of these species don’t change, but changes in gene expression induced by crossbreeding can persist from one generation to the next, especially if they are constantly reinforced. This is known as epigenetics.

Somehow we don’t think this type of epigenetic change can happen to us, but it does as a result of fetal programming. The prenatal period in the womb is the time that a child’s genes are most susceptible to epigenetic programming. Epigenetic programming can be amplified by the ongoing dietary effects on gene transcription factors (i.e. nutrigenomics) taking place in the mother. The result is the imprinting of epigenetic changes on the genes of the developing fetus that can alter the metabolic future of the child (1).

Examples of how this type of epigenetic programming influences future metabolic effects has been demonstrated under the conditions of famine, which generate increased obesity and cardiovascular disease in the next generation (2). This is also true of children who were exposed to excess calories or elevated levels of glucose while they were developing in the womb (3,4). Likewise hypertension (i.e. pre-eclampsia) during pregnancy increases the risk of stroke as adults if the fetus is exposed to the high blood pressure in the womb (5) as well as the increased risk of adult obesity if the fetus is exposed to gestational diabetes in the mother (6).

Bottom line: The dietary and metabolic environment the fetus is exposed to in the womb can echo through the rest of his or her life. In part II of this blog, I will explore how the Perfect Nutritional Storm, described in my book “Toxic Fat” (7) has been making Americans fatter, sicker and dumber for the last three generations.

References

  1. Kussman M, Krause L, and Siffert W. “Nutrigenomics: where are we with genetic and epigenic markers for disposition and susceptibility?” Nutrition Rev 68: S38-S47 (2010)
  2. Painter RC, Roseboom TJ, and Bleker OP. “Prenatal exposure to the Dutch famine and disease in later life.” Reprod Toxicol 20: 345-352 (2005)
  3. Singhal A. “Early nutrition and long-term cardiovascular health.” Nutrition Rev 64: S44-S49 (2006)
  4. Boney CM, Verma A, Tucker R, and Bovh BR. “Metabolic syndrome in childhood: associated with birth weight, maternal obesity, and gestational diabetes mellitus.” Pediatrics 115: e290-e296 (2005)
  5. Kajantie E, Eriksson JG, Osmond C, Thornburg K, and Barker DJP. “Pre-eclampsia is associated with increased risk of stroke in the adult offspring.” Stroke 40: 1176-1180 (2009)
  6. Lawlor DA, Pichtenstein P, and Langstrom N. “Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood.” Circulation 123: 258-265 (2011)
  7. 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.

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.

New solution or simply admitting failure?

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

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

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

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

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

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

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

References

  1. Christou NV, Look D, and MacLean LD. “Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years.” Ann Surg 244: 734-740 (2006)
  2. Donath MY,Boni-Schnetzler M, Ellingsgaard H, and Ehses JA. “Islet inflammation impairs the pancreatic beta-cell in type 2 diabetes.” Physiology 24: 325-331 (2009)

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

What is the Mediterranean diet?

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

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

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

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

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

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

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

References

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

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

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.