What if gluten sensitivity doesn’t exist?

How can I possibility make that statement?  Two recent best-selling diet books have maintained that gluten makes us fat and dumb (1,2). Billions of dollars are spent on gluten-free (but carbohydrate-rich) food products.  And people feel better when they don’t eat bread.

Before explaining my statement, let me make two things very clear.  First, I am not a big believer in bread.  In 1997, in a Time magazine interview I said, “If all the bread left the face of the earth, we would have a much healthier planet.” (3)  I stand by that statement.

Second, gluten “sensitivity” is not celiac disease.  Celiac disease is a clinically proven autoimmune response to the proteins in gluten (4).  I know since my wife has severe celiac disease.

However gluten sensitivity is different.  Most of the people who pretend to be experts in gluten sensitivity usually have no background in gastrointestinal research.  After all, why try to back up your claims with real research that is very difficult to do?  So it came as a great initial salvation to those people when a real expert from Australia published a paper indicating that gluten sensitivity may exist but with no clues to the mechanism (5).  In this study subjects with irritable bowel syndrome (IBS) and no evidence of celiac disease were put on a gluten-free diet for six weeks and then either challenged daily with muffins and bread either containing gluten (16 grams per day) or without gluten.  Even though both groups were on a gluten-free diet, they were both having more symptoms, although the group getting the extra gluten had more symptoms of IBS, including being more fatigued than the control group (5).

gluten-chart-0

What was also strange about the results of this study was there were no differences in the intestinal inflammation or any increase in the permeability of the intestinal wall in either group.  This caused the researchers to ponder if they had been too simplistic in their experimental design.   So they went back to do another experiment in which a diet that was far more rigorous in reducing other potential food allergens, such as FODMAPs, which stand for Fermentable, Oligo-, Di-, Monosaccharides And Polyols.  These are poorly absorbed short-chain carbohydrates, which means that many of these dietary carbohydrates reach the colon where the trillions of bacteria are waiting to begin fermenting them. FODMAPs are found in foods, such as those containing free fructose (found in apples, cherries, pears, asparagus, artichokes, etc.), foods that can be easily broken down into free fructose (such as high-fructose corn syrup and table sugar), free lactose (found in milk, yogurt, soft cheeses, etc.), polymers of fructose known as fructans (found in peaches, artichokes Brussels sprouts, fennel, onion, wheat, barley, and rye), polymers of galactose known as galactans (found in legumes, chickpeas, lentils, etc.) and polyols (found in apricot, avocado, blackberries, plums, cauliflower, mushrooms, snow peas, etc.).  This is a lot more complex dietary undertaking than putting all of your bets on gluten (6).

So when the researchers repeated their experiment and removed many of the FODMAPs from the diet of the sufferers with “gluten sensitivity” and then added back bread and muffins consisting of either high gluten (16 grams per day), low gluten (2 grams per day), or a placebo, they got a very different response as shown below (7).

gluten-chart

Now you get a very different picture than the earlier study in which the researchers had not removed many of the FODMAPs from the diets of their subjects.  Furthermore, there was no increase in fatigue in those getting the gluten compared to the placebo, even though more than half of the subjects had the genetic susceptibility marker for celiac disease (DQ2 or DQ8 positive HLA), and a quarter of them had anti-bodies to gliadin (one of the proteins in the overall family of protein collectively called gluten).

These new results with the low-FODMAPs diet led the researchers to conclude:  In a placebo-controlled, cross-over rechallenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with non-celiac gluten sensitivity placed on diets low in FODMAPs.  That’s a mouthful, but in essence the benefits of a gluten-free diet may not be the removal of gluten but the removal of various FODMAPs found in the wheat, rye, and barley that just happen to also contain gluten.

What remains unknown is whether it is the FODMAPs or a unique bacteria composition in the guts of the “gluten-sensitive” people interacting with the FODMAPs that can cause the problems that lead to IBS and the designation of being “gluten-sensitive”.

However one thing is certain: This new research will not stop the continuing flow of “gluten-free” products rich in carbohydrates coming from the food industry and more popular diet books “discovering” the real reason we are getting fatter and dumber.  Maybe I was on the right track in 1997 when I stated that bread removal is not such a bad idea for mankind.  That’s because I also believe that it is increased diet-induced inflammation, not simply gluten, that is the real cause of our growing epidemics of obesity, type 2 diabetes, and Alzhemier’s.

References

1.  Davis W.  Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. Rodale Books.  Erasmus, PA (2011)

  1.  Perlmutter D.  Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar-Your Brain’s Silent Killers. Little, Brown and Company.  New York, NY (2013)
  2.  Ratnesar R.  “Against the grain.”  Time. December 15, 1997 (1997)
  3. Fasano A. Gluten Freedom: The Nation’s Leading Expert Offers the Essential Guide to a Healthy, Gluten-Free Lifestyle. Wiley.  New York, NY (2014)
  4. Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, and Gibson PR.  “Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.”  Am J Gastroenterol 106:508-514 (2011)
  5. Gibson PR and Shepherd SJ.  “Food choice as a key management strategy for functional gastrointestinal symptoms.” Am J Gastroenterol 107:657-666 (2012)
  6. Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, and Gibson PR.  “No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.” Gastroenterology 145:320-328 (2013)

Trying to Make Science Out of Sausage

Epidemiology is the study of associations and not causality. It essentially began in 1854 when John Snow noticed that there seemed to be a higher concentration of cholera patients in a certain area in London during one of its many cholera epidemics in the 19th century. That’s an association. The real breakthrough for John Snow was to remove the pump handle on the suspected water source and then observe a significant reduction in the cases of cholera in that area. That’s called an intervention study based on epidemiology. Now in the 21st century we seem very reticent to do any type of intervention studies and rely more on epidemiology to guide our medical decisions. This is made even more confusing with the introduction of meta-analysis into the picture. Meta-analysis is taking a large number of studies (often done under very different conditions), pretending they are all valid and then coming up with a conclusion. When you do a meta-analysis on epidemiology studies, it’s like trying to separate a piece of filet mignon from intestines used to make sausage.

This month an article from the Annals of Internal Medicine suggested that there is no relationship of any type of fatty acid with heart disease (1). Well, if there is no association of any type of fatty acid with heart disease, why not just eat lard instead of salmon? If this sounds a little fishy to you (pardon the pun), it does to me too. As I stated earlier, the problem with meta-analysis is that good studies are added to bad ones. Here’s a dirty secret about medical research. There are a lot of bad studies that get published. Usually if you can’t get the funds to do original research, then you write a review paper, and if you can’t write a review paper, then you do a meta-analysis of all published studies and pretend it’s original research. The media might buy that, but I don’t.

The irony of this study is that one of the authors had actually published a good article using good controls in the same journal a year earlier indicating that the higher the levels of omega-3 fatty acids in the blood, the less heart disease death and the greater the longevity of the individuals (2). Maybe he forgot that article when publishing this new sausage publication (1).

That notwithstanding, the problem with these types of published studies is that they miss the point of what causes heart disease in the first place. It is not fatty acids or cholesterol, but inflammation. The best way to measure inflammation is the ratio of AA to EPA in the blood. This was first reported in the New England Journal of Medicine some 25 years ago (3). High-dose fish oil in healthy volunteers (5 grams of EPA and DHA per day) reduced the AA/EPA ratio from 21 to 2.5 within six weeks. During that time many of the additional markers of cellular inflammation also dropped. When they stopped the omega-3 fatty acid supplementation, the AA/EPA ratio gradually returned to its initial high level with a corresponding increase in the depressed inflammatory proteins to their initial levels. A very nice intervention study.

Then there is the disturbing fact that Japanese males have essentially the same LDL cholesterol levels as Americans, but Americans have 3.5 times the age-adjusted death rate. In fact, the LDL cholesterol levels of the Japanese having been rising since 1980, whereas American’s LDL cholesterol levels have been dropping. In addition, Japanese males in the study were about 7 times more likely to smoke than Americans. Let’s see, rising LDL cholesterol levels coupled with more smoking, but they have 72% fewer deaths from heart disease (4). Maybe the AA/EPA ratio as a marker of inflammation might be a key? The AA/EPA ratio of the Japanese in that study was 2.6, whereas the Americans were 11.1. Actually the Americans in this study were less inflamed than the general American population that has an AA/EPA ratio of 20 (5). But even in the above study, the Japanese AA/EPA ratio was 76% lower than the Americans (4). Let’s see, the Japanese had 76% lower inflammation and 72% lower mortality from heart disease compared to the Americans even through their LDL cholesterol levels were the same and they smoked like chimneys. If I was a betting man, I would put my money on doing an intervention study to see what the effect on heart disease would be if I lowered the AA/EPA ratio. That’s exactly what the Japanese did with the JELIS trial that was one of the largest cardiovascular trials ever undertaken with some 18,000 subjects (6). All of them had high cholesterol, so all of them were put on statins. The average AA/EPA ratio of these subjects was 1.6 compared to the 20 in Americans (5,6). Half the subjects were then given more omega-3 fatty acids. If the meta-analysis study recently published was valid (1), then these extra omega-3 fatty acids would have no benefit especially since everyone was getting a statin. Actually, just the reverse occurred after 3 ½ years. Those who lowered their AA/EPA ratio had 20% fewer cardiovascular events compared to those that didn’t see a change in the placebo group. Further sub-group analysis indicated that the change in the AA/EPA ratio was the overriding factor (7) behind these cardiovascular benefits. This is a complicated way of saying that if you lower inflammation, you lower cardiovascular risk.

So the next time you read about a meta-analysis study on the lack of effect of fatty acids on heart disease, ask to see a real intervention trial that lowers the levels of inflammation. When you do, then you see a very different picture of the role of fatty acids in heart disease than you do by reading more sausage studies (1,8). And if you do an intervention trial with omega-3 fatty acids, make sure that you lower the AA/EPA ratio to the level found in the Japanese. Based on published dose-response studies, this will take a minimum of 5 grams of EPA and DHA per day (9). Up to this point in time, no such cardiovascular studies have been conducted with that level of omega-3 fatty acids. If you are not using at least that level of omega-3 fatty acids to study cardiovascular disease, then you are probably using a placebo dose and should expect placebo results.

References

  1. Chowdhury R et al. “Association of dietary, circulating, and supplement fatty acids coronary risk.” Ann Intern Med 160:396-406 (2014)
  2. Mozaffarian D et al. “Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults.” Ann Intern Med 158:515-525 (2013)
  3. Enders S et al. “The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells.” New Engl J Med 320:265-271 (1989)
  4. Sekikawa A et al. “Serum levels of marine-derive n-3 fatty acids in Icelanders, Japanese, Koreans and Americans.” Prostglandins Leukot Essent Fatty Acids 87:11-16 (2012)
  5. Harris WS et al. “Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: observations from 160,000 patients.” Prostaglandins Leukot Essent Fatty Acids 88:257-263 (2013)
  6. Yokoyama M et al. “Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.” Lancet 369:1090-1098 (2007)
  7. Matsuzaki M et al. “Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease.” Circ J 73:1283-1290 (2009)
  8. Rizos EC et al. “Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis.” JAMA 308:1024-1033 (2012)
  9. 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.” Am J Clin Nutr 91:1184-1194 (2010)

Practical hints for helping to manage brain trauma

Since the recent story on CNN (“He’s going to be better than he was before,” Jan. 18, 2014,) about the extraordinary recovery of Grant Virgin from severe brain trauma, I have gotten a lot of requests for information. Since I have been doing this protocol for more than seven years after first working with Dr. Julian Bailes on the equally remarkable recovery of Randal McCloy Jr. (the sole survivor of the Sago mine disaster in 2006) and others (1,2), I can offer some broad guidelines. Make no mistake, each case is different, but these guidelines will considerably help your decision-making process.

What Type of Fish Oil to Use

Purity

When is comes to treating brain trauma, purity and potency of the omega-3 product count. All fish and all fish-oil products are contaminated with various toxins. The most important is polychlorinated biphenyls or PCBs. These are known neurotoxins. It makes little sense giving someone a fish-oil product that is rich in PCBs. One of the dirty secrets of the fish-oil manufacturing industry is that it is extremely difficult to remove PCBs from a final product. In fact, it is so difficult, the industry tries to ignore it. Making a statement that a fish-oil product is free from PCBs is an outright lie. It is equally ridiculous to state that the PCBs levels in its products are lower than the international standards. Those international PCB standards (90 parts per billion or ppb) are so lax that virtually any fish-oil product in the supermarket is going to exceed them. Of course, if you want to heal the brain, then I would recommend looking for the purest fish oil you can find. If you are even considering using fish oil, make sure that the levels of total PCBs are less than 5 ppb. This is 18 times lower than the international standard. Using this more rigorous criterion of purity, your choices become very limited. Furthermore, PCB levels will vary from lot to lot. So you want to make sure that the lot you are actually using contains less than 5 ppb. Go to the product’s website or call the manufacturer. If the manufacturers can’t supply that data, it means they don’t know. If they said it is pure, then they mean it might pass the very lax international standards. Here’s a good rule about fish oils: Trust but always verify. PCB testing is expensive but so is saving a brain. Of course, if you don’t care about potential PCB accumulation in the brain, then use the cheapest fish-oil product you can find.

Potency

You are going to have to use a lot of fish oil to put out the inflammation in the brain and to rebuild it. Therefore, the potency of the fish oil counts. I would never recommend any fish-oil product containing any less than 60% EPA and DHA. Usually the higher the potency of the fish oil, the higher the purity, but not always. Removal of PCBs is very different than increasing omega-3 fatty acid potency. I have tested many high-potency fish oils that also have high PCB levels. Likewise, the omega-3 fatty acids levels will vary from lot to lot. Before you use any omega-3 fatty-acid product, ask for the potency of that particular lot. If company representatives can’t provide it or say it meets their standards, then it means they don’t really know.

The fish oil needs to contain both EPA and DHA. EPA puts out the inflammation in the brain, and DHA helps rebuild the brain. You need both. I usually recommend a 2:1 ratio of EPA to DHA as that is the ratio I have used for several years with great success.

Omega-3 fatty acids are prone to oxidation, which leads to rancidity. The rancidity comes from breakdown products of the fatty acids into aldehydes and ketones that can cause damage to the DNA. That’s why there is an international rancidity standard (called total oxidation or TOTOX) that governs all edible oil trading in the world. Before you use any fish oil product, ask for the TOTOX levels of the finished product (not the raw materials). If it is less than 26 meq/kg (the upper limit for an edible oil), then it is OK to use. If not, don’t even consider it.

Amounts

Even if you if you have a high-quality fish-oil product, you are going to need a lot for brain injuries. This will usually be in the range of 10-15 grams of EPA and DHA per day. That’s why you need the high-purity and high-potency fish oil. Because of the high amounts, it will have to be given in a liquid format. Why the high doses? Because you have to put out the fire in the brain before you can rebuild it.

The levels of fish oil needed are based on testing, not guessing. The best test for the levels of fish oil required is the ratio of two fatty acids in the blood. One is arachidonic acid (AA), and the other is EPA. Why this is important is because AA causes inflammation, and EPA reverses inflammation. You measure the levels of AA and EPA using a simple finger-stick blood test. The AA/EPA ratio is not a standard clinical test, but it has been in medical research for nearly 30 years, starting first at Harvard Medical School (3). The AA/EPA ratio will tell you how much a pure fish oil product you need as you want the AA/EPA ratio to be in the range of 1.5 to 3. If the AA/EPA ratio is higher than 3, you will need more fish oil. If AA/EPA is less than 1.5, you will need less fish oil. Maintaining the AA/EPA between 1.5 and 3 addresses the largest concern of using high-dose fish oil, which is potential bleeding. I chose an AA/EPA ratio of 1.5 as my lower limit since that is what it is in the Japanese population, and they don’t bleed to death (4-11).

The most inexpensive test for the AA/EPA ratio can be found at www.zonediagnostics.com.

Why drugs don’t work, and fish oil does

With severe brain trauma, the usual response of the physician is “we just have to wait”. The reason why is because there are no drugs that can cross the blood-brain barrier to put out the inflammation in the brain. That is not true with omega-3 fatty acids. They can easily enter the brain if there are high enough levels in the blood. What is the correct level in the blood? The AA/EPA ratio will tell you. Not only should the AA/EPA ratio be between 1.5 and 3, but also the EPA levels should be greater than 4% of the total fatty acids in the blood.

What Else?

When using high levels of fish oil even if it is pure and potent, you still have to emulsify it to reduce the size of oil droplets for better absorption. One of the best methods to emulsify liquid fish oil is to mix it with either a seaweed or an aloe vera product to reduce the size of the oil droplets to increase the absorption into the blood.

You also have to provide extra anti-oxidant protection to protect the omega-3 fatty acids from oxidation. The best way is using polyphenols to be mixed with the fish oil before administration. Adding extra virgin olive oil is a good choice. Adding highly purified polyphenol extracts to the liquid fish oil is a better choice.

What to expect

Each case is different. Based on my experience if you are using the correct amount of omega-3 fatty acids, you should see the beginnings of a response within 60 days. In Grant’s case, it was two days. If you do, then continue the same level of fish oil since putting out the inflammatory fire is only the first step of the process. The next step is rebuilding the brain. I would suggest monitoring the AA/EPA ratio every 30 days for the first 60 days and then every 60 days thereafter to make sure you are giving the right amount of fish oil.

Most importantly, this is not a Mr. Wizard home experiment. You should always be working with your physicians, not against them. They will also need education in the use and safety of high-dose fish oil, but this short summary is a good start.

Don’t expect any reimbursement from your insurance company for the use of the fish oil or AA/EPA testing. It may seem expensive, but compared to the human suffering of not trying to rebuild the brain, the costs of both the fish oil and AA/EPA testing are minor. I would also consider using flexible- spending health-care accounts if you have access to them to lower the overall cost, since they are based on pre-tax income.

Taking fish oil and following an anti-inflammatory diet is key

One of the reasons for Grant Virgin’s rapid progress was the fact that he was already taking moderate doses of fish oil for a medical condition. This meant he already had some reserve capacity in the body and the brain to reduce the inflammatory burden caused by a hit-and-run accident. You never know when brain trauma will occur. Maintaining a relatively low AA/EPA ratio in the blood is your best insurance policy for protection against future brain trauma if it does strike. You don’t have to be as aggressive as in the treatment phase, but aim for keeping the AA/EPA ratio between 5 and 10 in the blood. For comparison, the average American has an AA/EPA ratio of 20 (12). When dealing with brain trauma, an ounce of prevention is worth pounds of cure.

Finally, to accelerate the healing and rebuilding of the brain, you want to be following an anti-inflammatory diet (13-15). An anti-inflammatory diet is one that reduces the production of AA that drives inflammation in the brain. The less AA you have in the blood, the less AA gets into the brain. Try to keep the AA level in the blood to less than 9% of the total fatty acids. This takes more work than simply giving fish oil, but the more you reduce the levels of AA in the blood, the less high-dose fish you will need to maintain the AA/EPA ratio required to accelerate the healing and rebuilding process in the brain.

References

  1. Roberts L, Bailes J, Dedhia H, Zikos A, Singh A, McDowell D, Failinger C, Biundo R, Petrick J, and Carpenter J. “Surviving a mine explosion.” J Am Coll Surg 207:276-283 (2008)
  2. Sears B, Bailes J, and Asselin B. “Therapeutic use of high-dose omega-3 fatty acids to treat comatose patients with severe brain injury.” PhamaNutrition 1: 86-89 (2013)
  3. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaefer EJ, Wolff SM, and Dinarello CA. “The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells.” N Engl J Med 320:265-271 (1989)
  4. Swails WS, Bell SJ, Bistrian BR, Lewis EJ, Pfister D, Forse RA, Kelly S, Blackburn GL. “Fish-oil-containing diet and platelet aggregation.” Nutrition 9:211-217 (1993)
  5. Parkinson AJ, Cruz AL, Heyward WL, Bulkow LR, Hall D, Barstaed L, and Connor WE. “Elevated concentrations of plasma omega-3 polyunsaturated fatty acids among Alaskan Eskimos”. Am J Clin Nutr 59:384-388 (1994)
  6. Eritsland J, Arnesen H, Seljeflot I, andKierulf P. “Long-term effects of n-3 polyunsaturated fatty acids on haemostatic variables and bleeding episodes in patients with coronary artery disease.” Blood Coagul Fibrinolysis 6:17-22 (1995)
  7. Watson PD, Joy PS, Nkonde C, Hessen SE, and Karalis DG.
    Comparison of bleeding complications with omega-3 fatty acids + aspirin + clopidogrel–versus–aspirin + clopidogrel in patients with cardiovascular disease. Am J Cardiol 104:1052-1054 (2009)
  8. Salisbury AC, Harris WS, Amin AP, Reid KJ, O’Keefe JH, and Spertus JA.
    “Relation between red blood cell omega-3 fatty acid index and bleeding during acute myocardial infarction.” Am J Cardiol 109:13-18 (2012)
  9. Larson MK, Ashmore JH, Harris KA, Vogelaar JL, Pottala JV, Sprehe M, and Harris WS. “Effects of omega-3 acid ethyl esters and aspirin, alone and in combination, on platelet function in healthy subjects.” Thromb Haemost 100:634-641 (2008)
  10. Harris WS. “Expert opinion: omega-3 fatty acids and bleeding-cause for concern?” Am J Cardiol 99:44C-46C (2007)
  11. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S,Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, and Shirato K. “Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.” Lancet 369: 1090-1098 (2007)
  12. Harris WS, Pottala JV, Varvel SA, Borowski JJ, Ward JN, and McConnell JP. “Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: observations from 160,000 patients.” Prostaglandins Leukot Essent Fatty Acids 88:257-263 (2013)
  13. Sears B. The Zone. Regan Books. New York, NY (1995)
  14. Sears B. The OmegaRx Zone. Regan Books. New York, NY (2002)
  15. Sears B. The Anti-inflammation Zone. Regan Books. New York, NY (2005)

More Cholesterol Madness

This week the American Heart Association announced a doubling down on its bet on cholesterol and heart disease.  It certainly wasn’t because there was a sudden epidemic of heart disease, because death rates have been falling since 1970 (20 years before statins were introduced).  Nor has there been any new clinical data showing the benefits of lowering cholesterol levels. Although for the last 20 years the use of statins has been said to be the end of the scourge of heart disease, it still remains the number-one killer of Americans.

Furthermore, these newest guidelines essentially recommend that not only should more Americans be put on statins, but they should also start at the highest dose possible.  In actuality, this “dose” is where the toxic effects begin to appear.  What are the toxic effects?  They include muscle weakness, reduction in cardiovascular fitness, increased diabetes, and memory loss.  Whatever happened to the Hippocratic oath of doing the patient no harm?

    All of this might be justified if there were any indication that cholesterol is the driving force behind heart disease.  Unfortunately, the facts simply don’t support the hype.  Remember, before statins arrived in 1994, saturated fat was the villain in heart disease, not cholesterol (1).  Yet in 2010, Harvard Medical School published epidemiological studies that made the connection between saturated fat and heart disease very tenuous at best (2).

So what if cholesterol is not the cause of heart disease?

Actually, there is another drug that also reduces mortality from heart disease, yet doesn’t lower cholesterol.  It’s called an aspirin.  What aspirin does do is to reduce inflammation.

The inflammation versus cholesterol battle for what causes heart disease has been raging for decades.  What gave the cholesterol boys the upper hand was it is easy to measure blood cholesterol.  With the advent of statins, it was simple for doctors to repeat the drug company mantra to their patients, “If your cholesterol levels are high, you are going to die”.  Great marketing, but poor science.

Just to illustrate the importance of reducing inflammation versus LDL cholesterol on mortality from heart disease, we can look at the heart disease mortality rates in 2004 both Japan and the United States (3).  The Japanese had a death rate from heart disease that was 71% lower than Americans, although their LDL cholesterol levels were virtually the same.  What was different between the two populations were their levels of inflammation as measured by the AA/EPA ratio.  The Japanese levels of inflammation were 76% lower than Americans.  These changes are shown in the following figure.

Figure 1.  Per Cent Differences Between Japanese and Americans

Cholseterol-Madness-Figure-1

Even without advanced statistics, I think you can see there is a much better correlation between the reduction of the AA/EPA ratio between the Japanese and Americans relative to the reduction in mortality from heart disease than there is between differences in LDL cholesterol levels in Japanese and Americans relative to mortality from heart disease.

    The only way to explain this new madness for lowering cholesterol is it is a last-gasp effort of the cardiologists, who have spent their entire careers on the cholesterol bandwagon and will defend their faith to the death.  Unfortunately, it may be their patients who will have to pay the ultimate price for not being told the real enemy is inflammation.

 

References

1.  American Heart Association.  “Dietary guidelines for healthy American adults.  A statement for physicians and health professionals by the Nutrition Committee, American Heart Association.”  Circulation 77: 721-724A (1988)

2.  Siri-Tarino PW, Sun Q, Hu FB, and Krauss RM.  “Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.”  Am J Clin Nutr 91:535-546 (2010)

3.  Sekikawa A, Steingrimosdotir L, Ueshima H, Shin C, Curb JD, Evans RW, Hauksottir AM, Kadota A, Choo J, Masaki K, Thorsson B, Launer LJ, Farcia ME, Maegawa H, Willco BJ, Eirksdottir G, Fujyoshi A, Miura K, Harris TB, Kuller LH, and Gudnason V.  “Serum levels of marine-derived n-3 fatty acids in Icelanders, Japanes, Korean, and Americans.”  Prostaglandins Leukotrienes and Essential Fatty Acid 87:11-16 (2007)

YWikipedia: Y (named wye plural wyes) is the twenty-fifth letter in the ISO basic Latin alphabet (next to last letter) and represents either a vowel or a consonant in English.

Anti-aging made easy

Anti-aging diets have been around since the 15th century, starting with the books written by Luigi Cornaro. Although I addressed the history of Luigi in my book The Anti-Aging Zone written more than a decade ago, it bears repeating. Finding himself near death at age 35, Luigi Cornaro went on a strict calorie-restricted diet consisting primarily of an egg yolk, some vegetable soup, small amounts of locally grown fruits and vegetables, a very small amount of coarse, unrefined bread and about three glasses of red wine per day. He wrote his first anti-aging book (The Sure and Certain Method of Attaining a Long and Healthful Life) at age 83 and his third book at age 95. He finally died at age 99. At the end of his life he was still mentally sharp and physically active.

Isn’t that what anti-aging is supposed to be? Living a long and full life. But do you have to embark on such a restrictive diet? Can’t you just take a pill or alter a gene? In the Aug. 29th issue of Cell Reports, there is an article that suggests it might be possible to alter such a gene (1). The gene in question mTOR expresses two proteins mTORC1 and mTORC2. mTOR is shorthand for “mammalian target of rapamycin”. Rapamycin is an antibiotic isolated from the soil of Easter Island and is also a powerful immune suppressor. It has been demonstrated that the earlier you give rapamycin to mice, the more you slow their aging process (2,3). In this study researchers genetically reduced the activity of mTOR gene by 75% so it was like giving rapamycin at birth. As might be expected, there was an even greater increase in overall lifespan of the mice corresponding to adding another 16 years of life to humans. These genetically altered mice also appeared to maintain their cognitive skills to a greater extent than the controls, but on the down side they also had less muscle mass and bone density. More ominously, the genetically altered mice also appeared to be more susceptible to infections in old age, suggesting that their immune systems were compromised.

OK so you get some tradeoffs by inhibiting mTOR gene expression: A longer life with greater frailty and decreased immune function as you age. Obviously, you don’t want anyone tinkering with your genes because no one knows the outcome. However, you can tweak gene expression using diet.

One way to reduce mTOR activity is to simply reduce the levels of the amino acid leucine in your diet. This is because leucine stimulates mTOR. If you stimulate mTOR, then you build bigger and stronger muscles. That’s why body builders use a lot isolated dairy protein powders that are rich in leucine as well as eat a lot of egg whites (an even richer source of leucine). On the other hand, vegans don’t eat dairy or eggs and therefore get very little dietary leucine, and their lack of muscles show it. Unfortunately, one of the biggest problems with aging is lack of muscle mass and a less than optimal immune system. So just turning down mTOR activity is probably not sufficient for healthy aging. On the other hand, calorie restriction (like that of Luigi Cornaro) stimulates another gene known as SIRT1 that causes the increased expression of the “enzyme of life” (AMP kinase) that controls metabolism and slows the aging process. You can also stimulate SIRT1 by consuming lots of polyphenols. Can’t you just fine-tune both mTOR and AMP kinase and maximize your quality of life as you age?

Of course you can by having a dietary program consisting of consuming small (but not excessive) amounts of leucine in the blood throughout the day. You can do this by eating no more high-quality protein than you can fit on the palm of your hand. This is about 3 ounces for women and 4 ounces for men. This will activate the mTOR that is necessary to build and maintain muscle and bone. By consuming large amounts of non-starchy vegetables, you are consuming polyphenols that stimulate AMP kinase. By doing both, you are constantly balancing mTOR and AMP kinase but without the rigid calorie restriction undertaken by Luigi Cornaro nearly 500 years ago. You are still restricting calories, but now in the range of 1,200 to 1,500 calories per day compared to the estimated 600 calories per day that Luigi was consuming.

Just to cover your bets since you would be consuming more leucine than Luigi did, you need to counter balance that with more polyphenols most likely by supplementation. Consuming one to two glasses of red wine per day is one way to get extra polyphenols. A better way is to use purified extracts rich in polyphenols, but without the alcohol. Finally for good measure, you want to take at least 2.5 grams of EPA and DHA as that level has been shown to increase the levels of telomeres that further decrease the rate of aging (4).

But isn’t that the Zone Diet? Of course it is, and that’s why I wrote The Anti-Aging Zone more than a decade ago. It was true then, and it is still true today.

References

  1. Wu JJ, Chen EB, Wang JJ, Cao L, Narayan N, Fergusson MM, Rovira II, Allen M, Springer DA, Lago CU, Zhang S, DuBois W, Ward T, deCabo R, Garilova O, Mock B, and Finkel T. “Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression.” Cell Reports 4:1-8 (2013)
  2. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA,Fernandez E, and Miller RA. “Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.” Nature 460: 395-395 (2009)
  3. Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R; Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, and Strong R. “Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice.” J Gerontol A Biol Sci Med Sci 66:191-201 (2011)
  4. Kiecolt-Glaser JK. Epel ES. Belury MA. Andridge R, Lin J, Glaser R, Malarkey WB, Hwang BS, and Blackburn E. “Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial.” Brain Behav Immun 28:16-24 (2013)

Omega-3 fatty acids and prostate cancer? Oh, really?

There was a recent publication suggesting that higher levels of omega-3 fatty acids are associated with a greater risk of prostate cancer 1. Of course, the immediate media response was to indicate that taking fish oil supplements is dangerous. Of course, let’s not forget, then, that eating fish must also be dangerous.

Before letting the media focus on sound bites, a realistic first step might be to analyze the data and use some common sense to see if it justifies the headlines.

Everyone in the cancer field agrees that inflammation drives cancers. I believe the best marker for inflammation is the AA/EPA ratio as I have outlined in my various books for more than a decade. The reason is simple: As the AA/EPA ratio decreases, you make fewer inflammatory hormones (i.e. eicosanoids coming from AA) and more anti-inflammatory hormones (i.e. resolvins coming from EPA). Bottom line, this means less inflammation in the body. So let’s look at the fatty acid data as percent of the total fatty acids that was presented in this article that were associated with no development of prostate cancer, total prostate cancer incidence, and breaking of the total cancer group into either low-grade or high-grade cancer 1.

Non-cancer Cancer Low-grade cancer High-grade cancer
EPA 0.6% 0.7% 0.7% 0.7%
AA 11.4% 11.2%   11.2%   11.3%  
AA/EPA 19 16 16 16

Having decades of experience of doing fatty acid analyses, I can tell that these numbers are clinically insignificant. What does that mean? The numbers are basically the same. They might be statistically significant, but the differences definitely are not clinically relevant.

I have been very consistent over the years in stating that to have an impact on reducing inflammation, you have to have EPA levels greater than 4% of the total fatty acids, AA levels less than 9% of the total fatty acids and an AA/EPA ratio between 1.5 and 3. As you can see, the subjects in this article were nowhere close to those parameters. In fact, I would say all the subjects in this trial were identical relative to AA, EPA and the AA/EPA ratio. In other words, the analysis is meaningless.

Is there any population in the world that may have the ranges that I recommend? The answer is the Japanese population. Their levels of EPA are about 3% of total fatty acids, and they have an AA/EPA ratio of about 1.6 2. The JELIS study was a long-term study (3 ½ years) of 18,000 Japanese with high cholesterol levels given extra omega-3 fatty acids to lower their AA/EPA an even lower ratio. With this lower AA/EPA ratio (now 0.8), their cardiovascular events were reduced by 20% with no increase in any type of cancer. Likewise, high levels of omega-3 fatty acids have been used as prescription drugs for the treatment of elevated triglyceride levels with absolutely no reports of any increase in any type of cancer.

This is where common sense hopefully comes into play. If the conclusion of the article was correct that higher levels of omega-3 fatty acids increase prostate cancer, then the Japanese male population should be decimated with prostate cancer. So what are the facts? The Japanese have one of lowest rates of prostate cancer incidence in the world. In fact, their rate of prostate cancer incidence is 10 times lower than the United States 3. More importantly, the mortality from prostate cancer is also about 5 times less in Japan than in the United States 4. I emphasize the word mortality since prostate cancer is usually very slow growing so that males usually die with prostate cancer, not because of it. This is why the recent recommendation is to dramatically reduce the screening for prostate cancer because the harm of treatment usually outweighs the benefits of detection.

Common sense (and a little understanding of the biochemistry of inflammation) says that if you reduce inflammation (determined by your AA/EPA ratio), then your likelihood of living longer is greatly increased. The best way to reduce AA is to follow a strict Zone Diet. The best way to increase EPA is to take adequate levels of purified omega-3 fatty acids rich in EPA. It is obvious the subjects of this study were doing neither.

References

  1. Brasky TM, Darke AK, Song X, Tangen CM, Goodma PJ, Thompson IM, Meyskens FL, Goodman GE, Minasian LM, Parnes HL, Klein EA, and Kristal AR. “Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial.” J Nat Cancer Inst DOIL10.109393 (2013)
  2. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, and Shirato K. ” Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.” Lancet 367:1090-1098 (2007)
  3. Haas GP, Delongchamps N, Brawley OW, Wang CY, and de la Roza G. “The worldwide epidemiology of prostate cancer: perspectives from autopsy studies.” Can J Urol 15: 3866-3871 (2008)
  4. Marugame T and Mizuno S. “Comparison of Prostate Cancer Mortality in Five Countries: France, Italy, Japan, UK and USA from the WHO Mortality Database (1960–2000).” Jpn J Clin Oncol 35: 690–691 (2005)

Why doesn’t exercise and diet reduce heart disease for diabetics?

That’s a good question after the June 24 issue of the New England Journal of Medicine reported on the failure of long-term diet and exercise to reduce heart disease in diabetics1. It had been known from earlier and shorter studies that diet and exercise in diabetics appeared to generate a decreased risk of cardiovascular disease. This is important since heart disease remains the number-one killer of Americans, and people with diabetes are two to four times more likely to develop heart disease. Since diabetes is becoming epidemic, this would suggest that heart disease should soon begin to escalate. But for exercise and diet have any benefits in any condition, they have to been continued forever. That is the motivation for this 13-year study that started with the best of intentions. However, last year the study was terminated at 10 years since it was clear that there were no cardiovascular benefits. Now that the study details have been published, it is clear why it failed.

First, all of the success of diet and exercise started to evaporate after the first year. Remember, the people who enter these studies are highly motivated with a terrible future awaiting them. So why would they seemingly throw away all the initial benefits of weight loss and reduction of blood sugar? Part of the reason can be explained by why most diet program fail: Willpower can only take you so far if your hormones are working against you. The end result is you are constantly hungry and always tired.

The amount of calories the subjects of this study consumed was low (between 1,200 and 1,800 calories per day), but the diet was a high-carbohydrate diet (that induces low blood sugar due to hyperinsulinemia). The diet was coupled with lots of exercise (that also lowers blood sugar). This is an almost surefire prescription to be constantly hungry and tired. As a result, compliance wanes.

On the other hand, if you are never hungry, then compliance is better. That was the case with another 13-year study of diabetic patients who had gastric bypass surgery. For these patients, there was a significant reduction in cardiovascular events2. The reason is probably hormonal. If you lose weight by diet and exercise, your levels of the hunger hormone ghrelin increases with no change in the levels of your satiety hormone, PYY. Just the opposite happens with gastric bypass surgery. Ghrelin doesn’t change, but PYY increases3. The result is that you are not hungry, and therefor your lifestyle compliance improves.

Of course, giving every diabetic gastric bypass surgery makes little sense. Giving them new, more powerful diabetic drugs with equally powerful side effects (like heart attacks) also makes no sense.

There may be third way: Functional foods that can increase PYY levels. But these have to be tasty (like pasta and rice) and convenient (only 90 seconds to make) since you have to take them the rest of your life. That’s the project I have been working on for the past six years. These new Zone meals may be the answer, as they appear to reduce hunger without causing fatigue while eating the foods you like to eat. Zone meals are low-tech medicine with potentially high-tech results and are coming soon.

References

  1. Wing RR et al. “Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.” NEJM DOI:10.1056/NEJMoa 1212914 (2013)
  2. Romeo S et al. “Cardiovascular events after bariatric surgery in obese subjects with type 2 diabetes.” Diabetes Care 35: 3613-2617 (2012)
  3. Olivan B et al. “Effect of weight loss by diet or gastric bypass surgery on peptide YY3-36 (PYY) levels.” Ann Surg 249: 948-953 (2009)

Good Diet, Bad Study

As the creator of the Zone Diet, I am a strong believer in the Mediterranean diet as a lifetime dietary program for good health. In fact, the Zone Diet can be considered to be the evolution of the Mediterranean diet as it provides even greater anti-inflammatory benefits. That being said, this week’s New England Journal of Medicine contained an article on using the Mediterranean diet with high-risk cardiovascular patients that got great press based on some really poor science1. Let’s get to the bad science first.

The researchers compared two “Mediterranean” diets (one with extra nuts and the other with extra olive oil) to a low-fat diet. Unfortunately, they were unable to get the subjects to follow a low-fat diet. If you are a follower of Dean Ornish, then a low-fat diet means less than 10% of your calories coming from fat. Using that definition of a low-fat diet, you have to throw out one-third of the subjects because they couldn’t reduce their fat intake below 37% of total calories. In fact, at the end of this five-year study, the percentages of protein, carbohydrate, and fat in the diets of all three groups were approximately the same. As a result, you are left with a study with two groups of subjects being compared to another group of subjects who really didn’t change their diet that much.

Even Dean Ornish pointed this out in his rebuttal blog in the Huffington Post to this study2. He wrote that if people had followed his low-fat diet, then the results would have been much different. Well, actually when high-risk cardiovascular patients did follow his diet in a study done 15 years ago, those on his low-fat diet had twice the deaths compared to those in the control group3. So maybe it’s a good thing that the low-fat group couldn’t follow the prescribed low-fat diet.

The reason for adverse effects of a low-fat, low-protein, very high-carbohydrate diet for cardiovascular patients is quite clear. Those subjects following his high-carbohydrate, low-fat, and low-protein diet developed insulin resistance as evidenced by a significant increase in their triglyceride-to-HDL ratio3. If you already have had a heart attack, then an increase in insulin resistance and the accompanying increase in inflammation are almost certain to push you over the edge.

If you really dig deeper into the supplemental material (Table S7 to be exact) of this article (as most journalists neglected to do), you are remarkably unimpressed by the changes in the diet over a five-year period except that the people who got free olive oil and free nuts were consuming more free olive oil and free nuts than those who were not getting free food.

Now, back to the clinical results — a strange brew of stroke, heart attack, and death. Usually when you include a lot of different clinical end points as your primary goal, it means you are not very confident about seeing any real striking clinical benefit. Stroke is primarily associated with high blood pressure, whereas heart attack is associated with the rupture of small vulnerable plaques leading to blockage of the coronary arteries. I personally like death as a clinical end point since you can’t cheat on its definition, thus making it harder to manipulate your statistics to prove your point.

So let’s look at the individual clinical endpoints. There was a reduction in strokes that was statistically significant. Unfortunately, there was no statistically significant reduction in either heart attacks or death. For such a large study, these clinical results are not too impressive. Maybe if the researchers had actually gotten the low-fat group to reduce their fat intake to less than 10% of calories (instead of going from 39% to 37% of calories), there might have been more deaths in that group, which would have made the other two Mediterranean diet groups look better.

Virtually every cardiovascular researcher knows that fatty acid composition of the plasma is an important factor in the prediction of future cardiovascular events. Unfortunately, the authors of the New England Journal of Medicine article apparently didn’t think so. Obviously, they measured one fatty acid (alpha linolenic acid) in Figure 5S (again buried deep in the supplemental material), but somehow forgot to report the other 34 fatty acids also found in the plasma. Two of the most important of these unreported fatty acids would have included arachidonic acid (AA) and eicosapentaenoic (EPA). The AA/EPA ratio in the blood is the best marker of cellular inflammation that drives heart disease4. You would think inclusion of information on this ratio (or at least providing the fatty acid levels) would be important since a far larger JELIS study demonstrated that the lowering of the AA/EPA ratio resulted in a significant reduction of cardiovascular events5.

In contrast to this poorly executed study, there exists a far more powerful study conducted nearly 20 years ago on the benefits of a stricter Mediterranean diet. This is was the Lyon Diet Heart Study6. The primary clinical difference between this new study and older Lyon Diet Heart Study is that the Lyon Diet Heart Study generated a 65% reduction in overall cardiovascular mortality, a complete reduction in cardiac sudden death, and 44% reduction in all-cause mortality6,7. Those are clinical end points to get excited about. On the other hand, this New England Journal of Medicine article showed no impact on mortality. The only striking difference between the two groups in the Lyon Diet Heart Study was the restriction of omega-6 fatty acids in the experimental group. You find omega-6 fatty acids in vegetable oils like corn, safflower, and sunflower oils. They accomplished this dietary change by giving the subjects in the experimental groups margarines rich in omega-3 fats and trans fats. Although there was a dramatic decrease in death between the two groups in the Lyon Diet Heart Study, there were no differences in weight, BMI, blood pressure, cholesterol (good and bad), and blood lipids between the two groups. In other words, all the usual suspects in heart disease were eliminated. The only differences between the two groups were in the fatty acids, both linoleic acid and the AA/EPA ratio. If you again go back to bowels of the recent New England Journal article (in supplemental Table S7), you find out that the levels of linoleic acid (an omega-6 fatty acid) as analyzed from dietary records of the subjects was between 5 and 6% in both of the Mediterranean diets. In the Lyon Diet Heart Study, the investigators were able to reduce to the linoleic levels to 3.6%, which is similar to levels found in the Japanese (actually Okinawans), who have the lowest cardiovascular mortality in the developed world (8). The subjects in the control group of the Lyon Diet Heart Study had a nearly 50% higher level of linoleic acid in their blood compared to the experimental group8. However, those subjects following the “Mediterranean” diets in the new study had even higher levels of linoleic acid than those in the control group of the Lyon Diet Heart Study. That is the most likely reason there wasn’t any change in cardiovascular mortality or overall mortality in the New England Journal of Medicine study. Unlike this more “modern” study, the Lyon researchers further demonstrated that the AA/EPA ratio was reduced by some 30% (from 9 to 6.2) in the active group compared to the control group, and this resulted in a 65% reduction of cardiovascular death.

Bottom line, unless you dramatically reduce omega-6 intake by reducing your consumption of vegetable oils (such as corn, soy and safflower oils), you will not get clear-cut clinical results (like reduction in death) no matter how much hype the media give to the research.

As I said earlier, the Zone Diet can be considered to be the evolution of the Mediterranean diet because it represents a superior dietary program to control inflammation, the true underlying cause of heart disease. This is because the Zone Diet dramatically reduces white carbohydrates (pasta, bread, rice, and potatoes) and replaces them with increased amounts of colorful carbohydrates (vegetables and fruits). Unlike the New England Journal of Medicine article where the subjects were consuming about 5 servings a day of vegetables and fruits, the Zone Diet recommends 10 servings per day. Rather than keeping the linoleic acid content at 6% of the calories (the American Heart Association recommends 10-15%) or even at the 3.6% level as in the Lyon Diet Heart Study, the Zone Diet recommends fewer than 2% of total calories should consist of linoleic acid. Like the JELIS study, the Zone Diet recommends extra supplemental of omega-3 fatty acids to reduce the AA/EPA ratio to 1.5 or less.

Although the jury may still be out on the Mediterranean diet (especially after this poorly executed study) for the primary prevention of heart disease, the data from secondary prevention studies (5-7) strongly suggest that the Zone Diet may be the dietary approach you want to follow if reducing mortality is your personal clinical end point.

References

  1. Estuch R et al. “Primary prevention of cardiovascular disease with a Mediterranean diet.” N Engl J Med 368: doi10.1056/NEJMoa1200303 (2013)
  2. Ornish D. “Does a Mediterranean diet really beat a low-fat for health?” HuffPost Healthy Living Feb 25 (2013)
  3. Ornish D et al. “Intensive lifestyle changes for reversal of coronary heart disease.” JAMA 280: 2001-2007 (1998)
  4. Sears B. The Anti-Inflammation Zone. Regan Books. New York, NY (2005)
  5. 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)
  6. de Lorgeril et al. “Mediterranean alpha-linolenic-rich diet in secondary prevention of coronary heart disease.” Lancet 343: 1454-1459 (1994)
  7. de Lorgeril et al. “Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction.” Circulation 99: 779-785 (1999)
  8. Kagawa Y et al. “Eicosapolyenoic acids of serum lipids of Japanese islanders with low incidence of cardiovascular disease.” J Nutr Sci Vitaminol 28: 441-453 (1982)

Harvard explains why people regain weight with the Atkins diet

A study from Harvard Medical School explains that even though people can lose weight on a ketogenic diet, all lost weight usually rapidly returns.

Ketogenic diets have been recommended for decades for rapid weight loss. The most famous is the Atkins diet. Ketogenic diets are based on high-protein and very low-carbohydrate intake. For the past 40 years such diets have been routinely used in America for weight loss, yet America remains in the midst of a growing epidemic of obesity. While ketogenic diets can induce initial weight loss, all lost weight usually rapidly returns, resulting in more weight (and even more fat) than when the person started the ketogenic diet.

For many years it was thought that such weight regain was due to poor dietary compliance. Now Harvard Medical School in an article in the June 27, 2012, issue of the Journal of the American Medical Association shows the reason for weight regain is more ominous than simple dietary non-compliance. In carefully controlled studies Harvard researchers demonstrated that on a ketogenic diet the levels of the hormone cortisol increase by 18%, and the levels of active thyroid hormone (T3) control metabolism decrease by 12% (1).

The effect of increased cortisol is to cause rapid fat accumulation, as any patient who has ever used prescription cortisol-like drugs knows. It also causes depression of the immune system, loss of memory, and thinning of the skin. These are also hallmarks of the acceleration of the aging process. Furthermore, the lowering of the active form of the thyroid hormone slows down the metabolism, making even seemingly small increases in calorie intake result in increased body fat accumulation. Besides setting you up to regain all the lost weight, the Atkins diet apparently also increases the rate of aging.

However, many people seem willing to continue to try such ketogenic diets in hopes of losing weight quickly. Yet highly controlled studies I published in the world’s most prestigious nutrition journal in world more than six years ago demonstrated that is simply not a true statement (2). In this study either a ketogenic diet (the Atkins diet) or a non-ketogenic diet (the Zone Diet) were compared in obese individuals. For the first six weeks all meals for both groups were prepared in a metabolic kitchen at Arizona State University (in essence treating subjects like lab rats). Both diets contained an equal number of calories.

When it came to weight loss, the subjects following the Zone Diet actually lost slightly more weight than as those on the ketogenic diet during the initial six-week period as shown in Figure 1.

Figure 1. Weight Loss (Zone Diet in open circles, Atkins diet in black squares)

Relative to fat loss on the non-ketogenic Zone Diet, their loss of body fat was again superior to the Atkins diet as shown in Figure 2. Fat loss is far more important than weight loss since all the health benefits from weight loss come from the loss of excess body fat; not from the loss of retained water or loss of muscle mass.

Figure 2. Fat Loss (Zone Diet in open circles, Atkins diet in black squares)

When the subjects continued on the respective diets for another four weeks (but now preparing meals on their own), those subjects on the non-ketogenic Zone Diet continued to lose even more weight and body fat, whereas those on the ketogenic Atkins diet did not. They had reached a plateau. The new research from Harvard Medical explains why.

One of the major problems in following a calorie-restricted diet is lack of energy. In this same study, the subjects on the Zone Diet demonstrated improved daily energy compared to those on the Atkins diet. In another publication using the same subjects, we also demonstrated that those subjects following the Zone Diet had greater performance in endurance testing compared to those following the ketogenic Atkins diet (3).

Figure 3. Energy levels (Zone Diet in open circles, Atkins diet in black squares)

For the past 40 years, ketogenic diets (like the Atkins diet) have failed to treat obesity in America. That is why one relies upon science, not hype, to determine which is the best diet to lose weight (and really body fat), keep it off, and increase energy. Continuing research from Harvard Medical School since 1999 demonstrates that the Zone Diet is the best dietary program to accomplish both goals (1,4-7). And the one thing Harvard will always tell you is that they are never wrong.

References

  1. Ebbeling CB, Swain JF, Feldman HA, Wong WA, Hachey DL, Garcia-Logo E, and Ludwig DD. “Effects of dietary composition on energy expenditure during weight loss maintenance.” JAMA 307: 267-2634 (2012)
  2. Johnston, C.S., Tjonn, S., Swan, P.D., 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)
  3. White AM, Johnston CS, Swan PD, Tjonn SL, and Sears B. “Blood ketones are directly related to fatigue and perceived effort during exercise in overweight adults adhering to low-carbohydrate diets for weight loss: A pilot study.” J Am Diet Assoc 107: 1792-1796 (2007)
  4. Ludwig, DS, Majzoub AJ, Al-Zahrani A, Dallal GE, Blanco I, and Roberts SB. “High glycemic index foods, overeating, and obesity.” Pediatrics 103: e26 (1999)
  5. Agus MSD, Swain JF, Larson CL, Eckert EA, and Ludwig DS. “Dietary composition and physiologic adaptations to energy restriction.” Am J Clin Nutr 71:901–907 (2000)
  6. Pereira MA, Swain J, Goldfine AB, Rifai N, and Ludwig DS. “Effect of low-glycemic diet on resting energy expenditure and heart disease risk factors during weight loss.” JAMA. 292: 2482-2490 (2004)
  7. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, and Ludwig DS. “Effects of a low–glycemic load vs. low-fat diet in obese young adults”. JAMA 297: 2092-2102 (2007)

Meta-analysis study on fish oil effectiveness is fatally flawed

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)
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