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Meta-analysis study on fish oil effectiveness is fatally flawed

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One of the events in the food industry you never want to see is the making of sausage where sometimes good cuts of meat are combined with items you would never want to eat. 

The same is true of meta-analysis studies in medical research.  Meta-analysis means that you take a lot of different studies (some good, some not so good) using different patient populations, different inclusion criteria, different protocols, and different outcome criteria and mix them together to get a conclusion that often demonstrates a non-result.  The best example of this is the recent study in the Journal of the American Medical Association that combined a wide number of studies using fish oil supplements to come up with the conclusion that omega-3 fatty acids have no benefit (1).  So let’s take a look at this study in a little more detail.

First, it is always useful to look at the investigators.  In this case, the authors are from Greece (not exactly a hotspot of high-quality clinical research since Aristotle), and to my knowledge none of them has been involved in any actual cardiovascular intervention studies in the past, let alone any work with omega-3 fatty acids. (I believe a little background is a good foundation to build from, but then call me crazy.)

Second, the average dose used in these studies was 1.5 grams of omega-3 fatty acids per day.  Surprisingly, the American Heart Association recommends more than double this dose to reduce triglycerides, a known risk factor for heart disease (apparently not in Greece since the authors ignored this fact).  This would indicate the authors were making conclusions based on placebo doses of omega-3 fatty acids.  Usually a placebo dose gives placebo effects, which was confirmed in their meta-analysis.  Furthermore, just giving a dose of anything is meaningless unless it is reducing a measureable clinical parameter in the blood that has a relationship to the disease condition being studied.  For example, if I gave a statin dose that reduced LDL cholesterol levels from 250 mg/dl to 245 mg/dl, I wouldn’t expect any therapeutic benefits unless I gave enough statin drug to reduce the LDL cholesterol level to less than 130 mg/dl, if not much lower. 

So what is a good dose of omega-3 fatty acids?  As I have already mentioned, the American Heart Association recommends 3.4 grams of EPA and DHA per day to lower triglyceride levels.  However, I believe a better marker is the amount of omega-3 fatty acids needed to reduce the AA/EPA ratio to the levels found in the Japanese population, which has the lowest levels of cardiovascular events in the world.  Recent studies with healthy Americans indicate that would take between 5 and 7.5 grams of EPA and DHA per day (2).  Again, this indicates that the dose of omega-3 fatty acids in this meta-analysis was providing a placebo dose. 

Third, another problem with meta-analysis is conflicting protocols.  In this study, almost half the patients came from two just studies: The GISSI study and the JELIS study.  The GISSI study (more than 11,000 patients) indicated that omega-3 fatty acid supplementation on the foundation of a Mediterranean diet could reduce sudden cardiovascular death rate by 45% versus a placebo and reduced overall cardiovascular death by 20% (3).  This study was criticized because the care that all groups were receiving didn’t include statins (since they were not yet approved).  After all, the thinking for a typical cardiologist is that there is no reason to use omega-3 fatty acids if you can simply give a statin drug instead.

That faulty thinking was addressed by the JELIS study in which all the patients (about 18,000) were getting statins (4).  Unlike the GISSI study, the AA/EPA ratio was measured in these patients.  The initial AA/EPA ratio was 1.6 (a level requiring Americans to take about 5 to 7.5 grams of omega-3 fatty acids per day just to reach that starting point), and then even more EPA was added to the active group.  After 4 ½ years, those Japanese patients getting the statins and extra fish oil had another 20% reduction in cardiovascular events over and above those getting the statins and an equivalent amount of supplemented olive oil.  The take-home lesson from the JELIS study was that any physician who didn’t prescribe supplemental omega-3 fatty acids along with statins was simply practicing bad medicine. 

Meta-analysis studies are supposed to make up for potential shortcomings in small clinical trials (like the ones used to approve virtually all pharmaceutical drugs).  In the hands of unqualified researchers who have little understanding of the field or compound being studied, a meta-analysis can become an instrument for the mass confusion generated by this recent article in the Journal of American Medical Association. 

The bottom line is that you need adequate doses of natural compounds to generate a therapeutic effect.  The levels of these doses of natural compounds will always be far greater than with drugs, but also with far fewer side-effects.  If you give a placebo dose of a natural compound, then expect a placebo result.  But please don’t try to pass off such an obvious result as “science”.

References

  1. Rizos EC et al.  “Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events.”  JAMA 308: 1024-1038 (2012)
  2. Yee LD et al. “Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition.”  Amer J Clin Nutr 91: 1185-1194 (2010)
  3. GISSI-Prevenzione Investigators. “Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial.” Lancet 354: 447-455 (1999)
  4. Yokoyama M et al.  “Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomized open-label, blinded endpoint analysis.” Lancet 369: 1090-1098  (2007)   

What are the real differences between EPA and DHA?

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The first casualty of marketing is usually the truth. The reality is that the two key omega-3 fatty acids (EPA and DHA) do a lot of different things, and as a result the benefits of EPA and DHA are often very different. That’s why you need them both. But as to why, let me go into more detail.

Benefits of EPA

The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA is the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons. First, EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA (1). The more EPA you have in the diet, the less AA you produce. This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.)

DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane, you can’t make inflammatory eicosanoids. Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme, just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.

The various enzymes (COX and LOX) that make inflammatory eicosanoids can accommodate both AA and EPA, but again due to the greater spatial size of DHA, these enzymes will have difficulty-converting DHA into eicosanoids. This makes DHA a poor substrate for these key inflammatory enzymes. Thus DHA again has little effect on cellular inflammation, whereas EPA can have a powerful impact.

Finally, it is often assumed since there are not high levels of EPA in the brain, that it is not important for neurological function. Actually, it is key for reducing neuro-inflammation by competing against AA for access to the same enzymes needed to produce inflammatory eicosanoids. However, once EPA enters into the brain, it is rapidly oxidized (2,3). This is not the case with DHA (4). The only way to control cellular inflammation in the brain is to maintain high levels of EPA in the blood. This is why all the work on depression, ADHD, brain trauma, etc., has demonstrated that EPA is superior to DHA (5).

Benefits of DHA

At this point, you might think that DHA is useless. Just the opposite, because DHA can do a lot of different things than EPA and some of them even better.

First is in the area of omega-6 fatty acid metabolism. Whereas EPA is the inhibitor of the enzyme (D5D) that directly produces AA, DHA is an inhibitor of another key enzyme, delta-6-desaturase (D6D), that produces the first metabolite from linoleic acid known as gamma linolenic acid or GLA (6). However, this is not exactly an advantage. Even though reduction of GLA will eventually decrease AA production, it also has the more immediate effect of reducing the production of the next metabolite known as dihomo gamma linolenic acid or DGLA. This can be a disaster as a great number of powerful anti-inflammatory eicosanoids are derived from DGLA. This is why if you use high-dose DHA, it is essential to add back trace amounts of GLA to maintain sufficient levels of DGLA to continue to make anti-inflammatory eicosanoids.

In my opinion, the key benefit of DHA lies in its unique spatial characteristics. As mentioned earlier, the extra double bonds and length of DHA compared to EPA means it takes up a lot more space in the membrane. Although this increase in spatial volume makes DHA a poor substrate for phospholipase A2 as well as the COX and LOX enzymes, it does a great job of making membranes (especially those in the brain) a lot more fluid as the DHA sweeps out a much greater volume in the membrane than EPA. This increase in membrane fluidity is critical for synaptic vesicles and the retina of the eye because it allows receptors to rotate more effectively, thus increasing the transmission of signals from the surface of the membrane to the interior of the nerve cells. This is why DHA is a critical component of these parts of the nerves (7). On the other hand, the myelin membrane is essentially an insulator so that relatively little DHA is found in that part of the membrane.

This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes (8). Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes (9). In addition, these greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA. As a result DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery, thus reducing the likelihood of developing atherosclerotic lesions (10). Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.

Common Effects for Both EPA and DHA

Not surprisingly, there are some areas in which both EPA and DHA appear to be equally beneficial. For example, both are equally effective in reducing triglyceride levels (10). This is probably due to the relatively equivalent activation of the gene transcription factor (PPAR alpha) that causes the enhanced synthesis of the enzymes that oxidize fats in lipoprotein particles. There is also apparently equal activation of the anti-inflammatory gene transcription factor PPAR-gamma (11). Both seem to be equally effective in making powerful anti-inflammatory eicosanoids known as resolvins (12). Finally, although both have no effect on total cholesterol levels, DHA can increase the size of LDL particle to a greater extent than EPA can (10).

Summary

EPA and DHA do different things, so you need them both. If your goal is reducing cellular inflammation, then you probably need more EPA than DHA. How much more? Probably twice the levels, but you always cover your bets with omega-3 fatty acids by using both at the same time.

References

  1. Sears B. “The Zone.” Regan Books. New York, NY (1995)
  2. 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)
  3. 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)
  4. 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)
  5. Martins JG. “EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials.” J Am Coll Nutr 28:525-542 (2009)
  6. Sato M, Adan Y, Shibata K, Shoji Y, Sato H, and Imaizumi K. “Cloning of rat delta 6-desaturase and its regulation by dietary eicosapentaenoic or docosahexaenoic acid.” World Rev Nutr Diet 88:196-199 (2001)
  7. Stillwell W and Wassall SR. “Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids 126:1-27 (2003)
  8. Chapkin RS, McMurray DN, Davidson LA, Patil BS, Fan YY, and Lupton JR. “Bioactive dietary long-chain fatty acids: emerging mechanisms of action.” Br J Nutr 100:1152-1157 (2008)
  9. Li Q, Wang M, Tan L, Wang C, Ma J, Li N, Li Y, Xu G, and Li J. “Docosahexaenoic acid changes lipid composition and interleukin-2 receptor signaling in membrane rafts.” J Lipid Res 46:1904-1913 (2005)
  10. Mori TA, Burke V, Puddey IB, Watts GF, O’Neal DN, Best JD, and Beilin LJ. “Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men.” Am J Clin Nutr 71:1085-1094 (2000)
  11. Li H, Ruan XZ, Powis SH, Fernando R, Mon WY, Wheeler DC, Moorhead JF, and Varghese Z. “EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: evidence for a PPAR-gamma-dependent mechanism.” Kidney Int 67:867-874 (2005)
  12. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, and Moussignac RL. “Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals.” J Exp Med 1996:1025-1037

What is Cellular Inflammation?

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People (including virtually all physicians) are constantly confused what cellular inflammation is. So I decided to take the opportunity to explain the concept in more detail.

There are two types of inflammation. The first type is classical inflammation, which generates the inflammatory response we associate with pain such as, heat, redness, swelling, pain, and eventually loss of organ function. The other type is cellular inflammation, which is below the perception of pain. Cellular inflammation is the initiating cause of chronic disease because it disrupts hormonal signaling networks throughout the body.

Definition of Cellular Inflammation

The definition of cellular inflammation is increased activity of the gene transcription factor know as Nuclear Factor-kappaB (NF-κB). This is the gene transcription factor found in every cell, and it activates the inflammatory response of the innate immune system. Although the innate immune system is the most primitive part of our immune response, it has been resistant to study without recent breakthroughs in molecular biology. In fact, the 2011 Nobel Prize in Medicine was awarded for the earliest studies on the innate immune system and its implications in the development of chronic disease.

There are several extracellular events through which NF-κB can be activated by distinct mechanisms. These include microbial invasion recognized by toll-like receptors (TLR), generation of reactive oxygen species (ROS), cellular generation of inflammatory eicosanoids, and interaction with inflammatory cytokines via defined cell surface receptors. We also know that several of these initiating events are modulated by dietary factors. This also means that appropriate use of the diet can either turn on or turn off the activation of NF-κB. This new knowledge is the foundation of anti-inflammatory nutrition (1-3).

Understanding Cellular Inflammation

Although the innate immune system is exceptionally complex, it can be illustrated in a relatively simple diagram as shown below in Figure 1.

Figure 1. Simplified View of the Innate Immune System

Essential fatty acids are the most powerful modulators of NF-κB. In particular, the omega-6 fatty acid arachidonic acid (AA) activates NF-κB, whereas the omega-3 fatty acid eicosapentaenoic acid (EPA) does not (4). Recent work suggests that a subgroup of eicosanoids known as leukotrienes that are derived from AA may play a significant factor in NF-κB activation (5,6)

Extracellular inflammatory cytokines can also activate NF-κB by their interaction with specific receptors on the cell surface. The primary cytokine that activates NF-κB is tumor necrosis factor (TNF) (7). Toll-like receptors (TLR) are another starting point for the activation of NF-κB. In particular, TLR-4 is sensitive to dietary saturated fatty acids (8). The binding of saturated fatty acids to TLR-4 can be inhibited by omega-3 fatty acids such as EPA. Finally ROS either induced by ionizing radiation or by excess free radical formation are additional activators of NF-κB (9).

Anti-inflammatory Nutrition To Inhibit Cellular Inflammation

Anti-inflammatory nutrition is based on the ability of certain nutrients to reduce the activation of NF-κB.

The most effective way to lower the activation of NF-κB is to reduce the levels of AA in the target cell membrane thus reducing the formation of leukotrienes that can activate NF-κB. Having the patient follow an anti-inflammatory diet, such as the Zone Diet coupled with the simultaneous lowering omega-6 fatty acid intake are the primary dietary strategies to accomplish this goal (1-3).

Another effective dietary approach (and often easier for the patient to comply with) is the dietary supplementation with adequate levels of high-dose fish oil rich in omega-3 fatty acids, such as EPA and DHA. These omega-3 fatty acids taken at high enough levels will lower AA levels and increase EPA levels. This change of the AA/EPA ratio in the cell membrane will reduce the likelihood of the formation of inflammatory leukotrienes that can activate NF-κB. This is because leukotrienes derived from AA are pro-inflammatory, whereas those from EPA are non-inflammatory. The increased intake of omega-3 fatty acids is also a dietary approach that can activate the anti-inflammatory gene transcription factor PPAR-γ (10-12), decrease the formation of ROS (13) and decrease the binding of saturated fatty acids to TLR-4 (14). This illustrates the multi-functional roles that omega-3 fatty acids have in controlling cellular inflammation.

A third dietary approach is the adequate intake of dietary polyphenols. These are compounds that give fruits and vegetables their color. At high levels they are powerful anti-oxidants to reduce the generation of ROS (15). They can also inhibit the activation of NF-κB (16).

Finally, the least effective dietary strategy (but still useful) is the reduction of dietary saturated fat intake. This is because saturated fatty acids will cause the activation of the TLR-4 receptor in the cell membrane (8,14).

Obviously, the greater the number of these dietary strategies implemented by the patient, the greater the overall effect on reducing cellular inflammation.

Clinical Measurement of Cellular Inflammation

Since cellular inflammation is confined to the cell itself, there are few blood markers that can be used to directly measure the levels of systemic cellular inflammation in a cell. However, the AA/EPA ratio in the blood appears to be a precise and reproducible marker of the levels of the same ratio of these essential fatty acids in the cell membrane.

As described above, the leukotrienes derived from AA are powerful modulators of NF-κB. Thus a reduction in the AA/EPA ratio in the target cell membrane will lead to a reduced activation of NF-κB by decreased formation of inflammatory leukotrienes. The cell membrane is constantly being supplied by AA and EPA from the blood. Therefore the AA/EPA ratio in the blood becomes an excellent marker of the same ratio in the cell membrane (17). Currently the best and most reproducible marker of cellular inflammation is the AA/EPA ratio in the blood as it represents an upstream control point for the control of NF-κB activation.

The most commonly used diagnostic marker of inflammation is C-reactive protein (CRP). Unlike the AA/EPA ratio, CRP is a very distant downstream marker of past NF-κB activation. This is because one of inflammatory mediators expressed in the target cell is IL-6. It must eventually reach a high enough level in the blood to eventually interact with the liver or the fat cells to produce CRP. This makes CRP a more long-lived marker in the blood stream compared to the primary inflammatory gene products (IL-1, IL-6, TNF, and COX-2) released after the activation of NF-κB. As a consequence, CRP is easier to measure than the most immediate inflammatory products generated by NF-κB activation. However, easier doesn’t necessarily translate into better. In fact, an increase AA/EPA ratio in the target cell membrane often precedes any increase of C-reactive protein by several years. An elevated AA/EPA ratio indicates that NF-κB is at the tipping point and the cell is primed for increased genetic expression of a wide variety of inflammatory mediators. The measurement of CRP indicates that NF-κB has been activated for a considerable period of time and that cellular inflammation is now causing systemic damage.

Summary

I believe the future of medicine lies in the control of cellular inflammation. This is most effectively accomplished by the constant application of anti-inflammatory nutrition. The success of such dietary interventions can be measured clinically by the reduction of the AA/EPA ratio in the blood.

References

  1. Sears B. The Anti-Inflammation Zone. Regan Books. New York, NY (2005)
  2. Sears B. Toxic Fat. Thomas Nelson. Nashville, TN (2008)
  3. Sears B and Riccordi C. “Anti-inflammatory nutrition as a pharmacological approach to treat obesity.” J Obesity doi:10.1155/2011/431985 (2011)
  4. Camandola S, Leonarduzzi G,Musso T, Varesio L, Carini R, Scavazza A, Chiarpotto E, Baeuerle PA, and Poli G. “Nuclear factor kB is activated by arachidonic acid but not by eicosapentaenoic acid.” Biochem Biophys Res Commun 229:643-647 (1996)
  5. Sears DD, Miles PD, Chapman J, Ofrecio JM, Almazan F, Thapar D, and Miller YI. “12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice.” PLoS One 4:e7250 (2009)
  6. Chakrabarti SK, Cole BK, Wen Y, Keller SR, and Nadler JL. “12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes.” Obesity 17:1657-1663 (2009)
  7. Min JK, Kim YM, Kim SW, Kwon MC, Kong YY, Hwang IK, Won MH, Rho J, and Kwon YG. “TNF-related activation-induced cytokine enhances leukocyte adhesiveness: induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein kinase C-dependent NF-kappaB activation in endothelial cells.” J Immunol 175: 531-540 (2005)
  8. Kim JJ and Sears DD. “TLR4 and Insulin Resistance.” Gastroenterol Res Pract doi:10./2010/212563 (2010)
  9. Bubici C, Papa S, Dean K, and Franzoso G. “Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance.” Oncogene 25: 6731-6748 (2006)
  10. Li H, Ruan XZ, Powis SH, Fernando R, Mon WY, Wheeler DC, Moorhead JF, and Varghese Z. “EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Evidence for a PPAR-gamma-dependent mechanism.” Kidney Int 67: 867-874 (2005)
  11. Kawashima A, Harada T, Imada K, Yano T, and Mizuguchi K. “Eicosapentaenoic acid inhibits interleukin-6 production in interleukin-1beta-stimulated C6 glioma cells through peroxisome proliferator-activated receptor-gamma.” Prostaglandins LeukotEssent Fatty Acids 79: 59-65 (2008)
  12. Chambrier C, Bastard JP, Rieusset J, Chevillotte E, Bonnefont-Rousselot D, Therond P, Hainque B, Riou JP, Laville M, and Vidal H. “Eicosapentaenoic acid induces mRNA expression of peroxisome proliferator-activated receptor gamma.” Obes Res 10: 518-525 (2002)
  13. Mas E, Woodman RJ, Burke V, Puddey IB, Beilin LJ, Durand T, and Mori TA. “The omega-3 fatty acids EPA and DHA decrease plasma F(2)-isoprostanes.” Free Radic Res 44: 983-990 (2010)
  14. Lee JY, Plakidas A, Lee WH, Heikkinen A, Chanmugam P, Bray G, and Hwang DH. “Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids.” J Lipid Res 44: 479-486 (2003)
  15. Crispo JA, Ansell DR, Piche M, Eibl JK, Khaper N, Ross GM, and Tai TC. “Protective effects of polyphenolic compounds on oxidative stress-induced cytotoxicity in PC12 cells.” Can J Physiol Pharmacol 88: 429-438 (2010)
  16. Romier B, Van De Walle J, During A, Larondelle Y, and Schneider YJ. “Modulation of signaling nuclear factor-kappaB activation pathway by polyphenols in human intestinal Caco-2 cells.” Br J Nutr 100: 542-551 (2008)
  17. Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, Lehman A, Belury MA, and Clinton SK. “Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition.” Am J Clin Nutr 91: 1185-1194 (2010)

Meditation: Push-ups for the brain?

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Meditation has always been considered a “fringe” area of medicine. Although it has been around for thousands of years, it was never considered “high-tech”.

However, the development of new imaging technologies has finally given researchers the ability to ask some interesting questions about meditation and its effect on brain structure and cognitive performance.

When comparing brain wave patterns using old technologies like an EEG, it has been demonstrated that experienced meditators have higher levels of alpha waves (indicative of a relaxed brain) and lower levels of beta waves (indicative of focusing on intentional tasks or anxiety) during mediation (1). More recent imaging technology like the SPECT scan indicates that experienced meditators have improved cerebral blood flow (2). MRI technology has shown that experienced meditators have a greater density of grey matter in the brain (3), improved neural connections (4), and lower sensitivity to induced pain (5) when compared to matched control groups.

One of the problems with these types of studies has always been subject recruitment. The studies described above are simply various examples of case-control epidemiological studies. This type of study is often done in cancer epidemiology and is used to compare someone with cancer to a control without cancer to see if any differences are apparent (like if smoking is associated with lung cancer). The problem is that experienced meditators may already have different brain structures or improved neural networks and corresponding improved attention spans that attracted them to meditation in the first place. This is like comparing professional athletes to their fans watching them on TV and then looking for differences in fitness between the two groups.

Aware of these shortcomings, more recent, better controlled, shorter-term studies have taken either non-meditators or experienced meditators and put them into an intensive meditation program to be compared to equally matched subjects waiting to enter the same a program. Using a more tightly controlled group of subjects, it has been found that meditation does indeed have benefits in reducing sensitivity to pain (6), improving ability to modulate alpha waves that help reduce distractions (7), increasing brain grey matter (8), and increasing telomerase activity (9). The increased telomerase activity is usually associated with increased lifespan because when telomeres on the DNA become too short, the cell dies.

There are a lot of health benefits that stem from sitting in a comfortable chair thinking of nothing for at least 20 minutes a day. In fact, it is so easy that most people never get around to doing it.

So if you don’t have time to take at least 20 minutes a day to meditate, then consider taking high-dose fish oil. In as little as 35 days, you will see it also generates significant increases in the intensity of alpha waves, increased attention span, and improved mood (10) just like experienced meditators, who have spent years trying to reach the same goals. And if you maintain high levels of omega-3 fatty acids in your blood for a longer period of time, it appears that you get decreased telomere shortening that should help you live longer (11). And if you are worried about time, taking adequate levels of fish oil to get these benefits only takes 15 seconds a day.

Of course, if you were really smart, you would do both every day.

References

  1. Lagopoulos J, Xu J, Rasmussen I, Vik A, Malhi GS, Eliassen CF, Arntsen IE, Saether JG, Hollup S, Holen A, Davanger S, and Ellingsen O. “Increased theta and alpha EEG activity during nondirective meditation.” J Alt Complementary Medicine 15: 1187-1192 (2009)
  2. Newberg A, Alavi A, Baime M, Pourdehnad M, Santanna J, and d’Aquili E. “The measurement of regional cerebral blood flow during the complex cognitive task of meditation: a preliminary SPECT study.” Psychiatry Res 106: 113-122 (2001)
  3. Toga AW, Lepore N., Gaser C. The underlying anatomical correlates of long-term meditation: larger hippocampal and frontal volumes of gray matter. Neuroimage 45: 672-678 (2009)
  5. Luders E, Clark K, Narr KL, Toga AW. “Enhanced brain connectivity in long-term meditation practitioners [In Process Citation] Neuroimage 57: 1308-1316 (2011)
  7. Grant JA, Courtemanche J, Duerden EG, Duncan GH, and Rainville P. “Cortical thickness and pain sensitivity in zen meditators.” Emotion 10: 43-53 (2010)
  8. Zeidan F, Martucci KT, Kraft RA, Gordon NS, McHaffie JG, and Coghill RC. “Brain mechanisms supporting the modulation of pain by mindfulness meditation.” J Neuroscience 31: 5540-5548 (2011)
  9. Kerr CE, Jones SR, Wan Q, Pritchett DL, Wasserman RH, Wexler A, Villanueva JJ, Shaw JR, Lazar SW, Kaptchuk TJ, Littenberg R, Hamalainen MS, and Moore CI. “Effects of mindfulness meditation training on anticipatory alpha modulation in primary somatosensory cortex.” Brain Research Bulletin 85: 96-103 (2011)
  10. Holzel BK, Carmody J, Vangel M, Congleton C, Yerramsetti SM, Gard T, and Lazar SW. “Mindfulness practice leads to increases in regional brain gray matter density.” Psychiatry Research 191: 36-43 (2011)
  11. Jacobs TL, Epel ES, Lin J, Blackburn EH, Wolkowitz OM, Bridwell DA, Zanesco AP, Aichele SR, Sahdra BK, Maclean KA, King BG, Shaver PR, Rosenberg EL, Ferrer E,; Wallace BA, and Saron CD. “Intensive meditation training, immune cell telomerase activity, and psychological mediators.” Psychoneuroendocrinology 36: 664-681 (2011)
  12. Fontani G, Corradeschi F, Felici A, Alfatti F, Migliorini S, and Lodi L. “Cognitive and physiological effects of omega-3 polyunsaturated fatty acid supplementation in healthy subjects.” Eur J Clin Invest 35: 691-
  13. Farzaneh-Far R, Lin J, Epel ES, Harris WS, Blackburn EH, and Whooley MA. “Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease.” JAMA 303: 250-257 (2010)

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

If you’re fat, you may be OK

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It is well known from epidemiological studies that about 30 percent of obese individuals and 50 percent of overweight individuals are relatively healthy in terms of cardiometabolic risk factors (1). The same study also indicated that about 25 percent of normal-weight individuals have significant cardiometabolic risk. A follow-up study indicated individuals defined as “metabolically healthy obese” are not at any long-term risk of heart disease (2).

Is the world turning upside down?

I explained the reasons behind these paradoxical observations in my most recent book, “Toxic Fat,” published three years ago (3). It simply depends on what type of fat cells you have. If you have healthy fat cells (“good” fat), they will pull excess arachidionic acid out of the bloodstream and store it in the fat cells. This buried arachidonic acid can spread inflammation to other organs that ultimately results in the appearance of cardiometabolic risk factors. On the other hand, if you have “bad” fat (unhealthy or sick fat cells), they are not very effective in removing arachidonic acid from the bloodstream. Once this happens, circulating arachidonic acid can metastasize like a cancer to other organs. This begins a very slippery slope toward the early development of cardiometabolic diseases, such as diabetes and heart disease. Finally, you get to the stage of dying fat cells that are surrounded by inflammatory macrophages. Now you are in true trouble as the previously stored arachidonic acid is more rapidly released back into the bloodstream.

Now let's fast forward to a new article in the Journal of the American College of Cardiology (4) that simply confirms what I wrote about fat cell inflammation three years ago. As with the earlier epidemiological study, researchers found that about 30 percent of the obese subjects had little inflammation in their fat cells as indicated by the absence of inflammatory macrophages. This percentage of obese patients was essentially identical to that found in the earlier epidemiological study (1). When the arterial blood flow of the metabolically healthy obese was compared to lean subjects, the rates were virtually identical, whereas the arterial blood flow rates were much lower (that's bad) in the obese subjects who had significant fat cell inflammation.

Unfortunately, their characterization of inflamed fat cells was incorrect. What they were really looking at was dying fat cells. The fat cells of these so-called metabolically healthy obese subjects were already sick (i.e., bad fat) since there were metabolic markers (hyperinsulinemia, increased TG/HDL ratios, elevated blood glucose and increased CRP levels) that indicated that inflammation was already spreading to other organs (such as the liver, muscles and pancreas).

The best way to know if you have truly healthy fat cells (no matter how many you have) is to have a low AA/EPA ratio in the blood. This remains the best clinical marker of the true health of the adipose tissue. If you have healthy fat cells (good fat), then you can expect cellular inflammation in other organs will be reduced leading to a longer and better life no matter what your weight.

References

  1. Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, and Sowers MR. “The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population.” (NHANES 1999-2004) Arch Intern Med 168: 1617-1624 (2008)
  2. Wildman RP. “Healthy obesity.” Curr Opin Clin Nutr Metab Care 12: 438-443 (2009)
  3. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  4. Farb MG, Bigornia S, Mott M, Tanriverdi K, Morin KM, Freedman JE, Joseph L, Hess DT, Apovian CM, Vita JA, and Gokce N. “Reduced adipose tissue inflammation represents an intermediate cardiometabolic phenotype in obesity.” J Am Coll Cardiol 58: 232-237 (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.

What are we really entitled to?

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For the past year the future of the American economy has centered on the word “entitlement,” especially in terms of health care. But no one is quite certain about what the word means. Social Security is not really an entitlement because it is a forced savings program that promises you the money you put into an old-age fund will be given back to you when you need it, some time in your 60s. The fact that the government has been using that account as a piggy bank to fund itself without raising taxes and leaving behind government I.O.U.s in place of the funds is another matter. But you are definitely entitled to at least get back the money you put into it.

Medicare is a completely different matter. In this case, you put very little money into a fund (which is also heavily borrowed from by the government), and you expect to get a lot more back. In my view, you are entitled to get back the money you paid into Medicare, and anything more should be considered a gift from a rich uncle (Sam), who is no longer very rich.

In an attempt to resolve this problem, Congressman Paul Ryan came up with a plan that went nowhere but had at least some intellectual merit: You pay into the medical fund for old age, and you get back what you paid in (and a little more) at age 67. The most notable feature of this plan was getting an annual voucher for about $6,000 based on 2012 dollars to be applied for private health insurance premiums after age 67.

At the current Medicare tax rate, the only way to pay in more than $6,000 into proposed trust fund on an annual basis is if you make more than $200,000 per year. Since there aren’t too many Americans making that type of salary, it’s your rich uncle who must make up the difference. Even if you were making $200,000 per year for 40 years and only planned to live another 15 years after retirement, it is still a pretty good deal, as it is forced savings for health-care insurance in the future. Any overpayment on your part will only help those who are not lucky enough to make $200,000 a year for 40 years. Unfortunately, this proposal was politically dead on arrival

The real problem with any health-care entitlement program was pointed out in a well-reasoned article in the May 19th issue of The New Republic — you can’t cure chronic disease, you can only manage it (1). In addition, new research analyses of the current state of Americans in old age indicates that we aren’t doing a very good job of managing chronic diseases (2). Although Americans are living longer, the length of life with chronic disease and loss of functional mobility (i.e. independent living) have rapidly increased since 1998. We are living longer because the elderly are essentially on life support generated by increasingly more expensive drugs that only marginally extend the lives of the very sick. We are not going to cure heart disease, cancer, stroke, and definitely not Alzheimer’s. The best we can do is to help manage their outcomes. Unfortunately, these are also diseases of the elderly, and the cost of increasing each year of life after 65 has risen from about $50,000 in the 1970s to nearly $150,000 in the 1990s. This could possibly be justified if the rich uncle were still rich.

The solution according to the authors of the New Republic article is redirecting the money that we can spend to maximize expenditures on public health care (prevention and elongation of independent living) as opposed to “curing” elderly with chronic disease that usually results in the decreased quality of life (1). The primary beneficiaries of this shift in medical thinking should be children followed by working adults, with the lowest health-care priority going to those over age 80. It sounds harsh, but that is exactly how socialized medicine works in Europe.

So what do you do to protect yourself in the future, especially if you are nearing 65? My suggestion is to start aggressively reducing cellular inflammation by following an anti-inflammatory diet and lifestyle. That’s the only thing you are really entitled to and that will also be the only thing your “rich” uncle can realistically pay for in the future.

References

  1. Callahan D and Nuland S. “The quagmire: how American medicine is destroying itself.” The New Republic. May 19, 2011
  2. Crimmins EM and Beltran-Sanchez H. “Mortality and morbidity trends: is there compression of morbidity?” J Gerontol B Physchol Soc Sci 66: 75-86 (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.

The dangers of over-analyzing too much data in prostate study

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In the last week there has been a constant buzz about an online pre-publication of a new research article that suggests that high concentrations of omega-3 fatty acids promote aggressive prostate cancer (1). Well, that really isn’t the case, in spite of the press reports. That’s why you have to carefully read the article before jumping to conclusions.

Prostate cancer, like all cancers, is driven by cellular inflammation. The level of cellular inflammation is defined by the AA/EPA ratio of isolated serum phospholipids. When you analyze the data correctly in that article, you find that there was no difference in the AA/EPA ratio between the low-aggressive, high- aggressive, or control group. In fact, all the groups had the same elevated AA/EPA ratio of 18.8. Since I like to have individuals try to maintain an AA/EPA ratio of less than 3, all of these groups could be considered to be inflamed.

Not surprisingly, when you look at either EPA or AA levels separately in each group, they are identical. It’s only when you look at the DHA levels, do you see a small difference statistically, but it’s meaningless clinically. There was a 2.5 percent increase in the DHA levels in the high-aggressive group compared to the control group. In the paper, authors state their error in measuring DHA is ± 2.4 percent. Call me crazy, but I don’t see the big difference between the reported results and their error measurements. To further cloud the results, the authors also find that the levels of trans-fatty acids are lower in the aggressive prostate cancer patients than the controls. So I guess if you wanted to take their data at face value, DHA makes prostate cancer more aggressive and trans-fatty acids found in junk foods make prostate cancer less aggressive.

I believe this is simply a case of over-interpretation of massive amounts of collected data. If you get enough data points, you can always make some type of correlation, but that’s all it is. At some point you also have to allow common sense to enter the final analysis.

Nonetheless, let’s say their data might be correct. How could excess DHA increase the aggressiveness of any cancer? Well, it might decrease the levels of dihomo gamma linolenic acid (DGLA) as I have explained in many of my books (2-5). DGLA is the building block for a powerful group of anti-inflammatory eicosanoids, and its formation is inhibited by DHA. Depressing DGLA levels would reduce the body’s ability to hold back the inflammation that drives the tumor. Unfortunately, with all the data they accumulated, they forgot to publish the changes in the DGLA levels in the various groups. Oops.

So even if there were not any changes in the AA/EPA ratio between groups, a depression of DGLA levels in the aggressive prostate cancer group would easily explain the clinical observation. Unfortunately, that interpretation requires an extensive background in understanding eicosanoid biochemistry, which is not easily found in academic clinical-research centers.

This is not the first time that the potential benefits of DHA are in question. In the largest cardiovascular intervention study ever done, it was demonstrated that adding high levels of EPA to the diet of Japanese patients with high cholesterol levels (who already with a very low AA/EPA ratio of 1.6), dramatically decreased their likelihood of future cardiovascular events (6). This reduction was only correlated with increases in EPA levels as well as with a decrease in the AA/EPA ratio from an already low 1.6 to an even lower 0.8 (7). The levels of DHA in these patients had no significance for predicting future cardiovascular events.

Likewise other studies using DHA alone to treatment post-partum depression, improve neurological functioning of children or treating Alzheimer’s have also been found to be negative (8,9).

It’s not that DHA is bad, it just doesn’t do much to reduce cellular inflammation. DHA does a lot of other useful things, but reducing cellular inflammation in not one of them.

References

  1. Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, Thompson IM, King EB, Albanes D, and Kristal AR. “Serum phospholipid fatty acids and prostate cancer risk.” Amer J Epidem 173: doi 10:1093/aje/kwr9027 (2011)
  2. Sears, B. “The Zone.” Regan Books. New York, NY (1995)
  3. Sears, B. “The OmegaRx Zone.” Regan Books. New York, NY (2002)
  4. Sears, B. “The Anti-inflammation Zone.” Regan Books. New York, NY (2005)
  5. Sears, B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  6. Matsuzaki M, Yokoyama M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, and Matsuzawa Y. “Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease.” Circ J 73:1283-1290 (2009)
  7. Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, and Matsuzawa Y. “Relationships between Plasma Fatty Acid Composition and Coronary Artery Disease.” J Atheroscler Thromb 18:99-107 (2011)
  8. Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, and Ryan P. “Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial.” JAMA 304; 1675-1683 (2010)
  9. 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)

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

When is a diet not a diet?

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

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

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

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

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

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

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

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

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

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

References

  1. Layman DK, Evans EM, Erickson D, Seyler J, Weber J,; Bagshaw D, Griel A, Psota T, and Kris-Etherton P. “A moderate-protein diet produces sustained weight loss and long-term changes in body composition and blood lipids in obese adults.” J Nutr 139: 514-521 (2009)
  2. Larsen TM, Dalskov SM, van Baak M, Jebb SA, Papadaki A, Pfeiffer AF, Martinez JA, Handjieva-Darlenska T, Kunesova M, Pihlsgard M, Stender S; Holst C, Saris WH, and Astrup A. “Diets with high or low protein content and glycemic index for weight-loss maintenance.” N Engl J Med 363: 2102-2113 (2010)
  3. Pereira MA, Swain J, Goldfine AB, Rifai N, and Ludwig DS. “Effects of a low glycemic-load diet on resting energy expenditure and heart disease risk factors during weight loss.” JAMA 292: 2482-2490 (2004)
  4. Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, and Sears B. “Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets.” Am J Clin Nutr 83: 1055-1061 (2006)
  5. Pittas AG, Roberts SB, Das SK, Gilhooly CH, Saltzman E, Golden J, Stark PC, and Greenberg AS. “The effects of the dietary glycemic load on type 2 diabetes risk factors during weight loss.” Obesity 14: 2200-2209 (2006)

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

Breast cancer and inflammation

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

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

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

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

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

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

References

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

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

Coffee and diabetes: What’s the connection?

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

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

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

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

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

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

References

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

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

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

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

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

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

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