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)

The Real Facts about Metabolically Healthy Obesity

One of great paradoxes of our obesity epidemic is that many obese individuals appear to be quite healthy. This makes the true believers in the Holy Grail of BMI as the standard for good health quite livid. They know in their hearts that obesity is a mortal sin. Early this year the Centers for Disease Control (CDC) published another in a long series of articles demonstrating that being overweight significantly decreases your likelihood of dying compared to being “normal weight” (1). Immediately Harvard Medical School went on a rampage crying foul. So you can imagine the delight of the weight-loss experts when a new meta-analysis demonstrated that “there is no healthy pattern of increased weight” (2). Take that, you silly scientists at the CDC. Unfortunately, this article represents another case of a meta-analysis creating meta-confusion.

When you state that someone is metabolically healthy obese, it means just that—they are healthy. So how can you look at someone and say they are healthy? You have to look for accepted signs of health, not whether or not they fit into designer clothing. Fortunately, there is a health ranking of obese individuals that is not based on their actual weight. It is called the Edmonton Obesity Staging System (EOSS). Obviously to be included in this ranking system, an individual has to be obese (BMI > 30). But now they are ranked in terms of health as shown below:

Stage 0: Normal blood pressure, blood glucose, and blood lipid levels and no physical or psychological impairment to being obese.

Stage 1: Existence of subclinical risk, such as borderline hypertension, impaired fasting glucose, elevated liver enzymes, mild physical symptoms, and mild impairment of well-being.

Stage 2: Established chronic disease (hypertension, type 2 diabetes, sleep apnea, osteoarthritis, etc.) and moderate limitations in physical and psychological well-being.

Stage 3: Established end-organ damage (heart attack, stroke, heart failure, etc.) and significant physical and psychological impairment.

Stage 4: Essentially the walking dead.

My definition of a healthy obese individual is someone who has an EOSS Stage 0 ranking.

So using these EOSS definitions and the NHANES III data from 1988-1994, how many people with excess weight are actually healthy using the standard definitions of excess weight: Overweight being a BMI of 25-30, Grade 1 Obesity having a BMI between 30-35, Grade 2 Obesity having a BMI between 35-40, and Grade 3 Obesity having a BMI > 40?

Overweight Obese 1 Obese 2 Obese 3
U.S. Population 50M 23M 10M 6M
Stage 0 15% 8% 5% 5%
Stage 1 28% 19% 17% 10%
Stage 2 47% 59% 64% 67%
Stage 3 10% 14% 14% 14%

The total number of overweight and obese Americans falling within the four rankings of EOSS accounted for nearly 90 million Americans. You can also see that there is great heterogeneity within each category of excess weight, but between 5 to 8% of obese patients are quite healthy regardless of their weight.

If you have an EOSS Stage 0 ranking regardless of your weight, you are healthy. Obviously, the more things wrong with you health-wise regardless of your weight, the more likely you are to going to have even more health problems in the future.

And here is the problem with the article that generated so much glee at Harvard Medical School—the researchers didn’t distinguish between truly healthy obese (EOSS Stage 0) and not-so-healthy obese (EOSS Stage 1). In fact, 9 of the 12 studies they included for their meta-analysis defined being “healthy” as not having metabolic syndrome (2). To have metabolic syndrome requires having three very different unhealthy factors. The other 3 studies included defined “healthy” as having two or less risk factors for metabolic syndrome. This means someone with hypertension, elevated blood glucose, or elevated triglycerides would be considered “healthy” in this meta-analysis (2). I guess I come from the old school, in that I wouldn’t consider such people healthy.

Now if you go back to the earlier study published by the CDC, these researchers used a very simple clinical end point that can’t be fudged (1). This end point is called death. Their data clearly points out that overweight people had a significantly a lower death rate than normal-weight people. That’s a hard fact. And the Grade 1 Obese individuals have about the same death rate as normal-weight individuals. If the CDC had used the EOSS system instead of relying on BMI, then it is likely that every grade of obese person with an EOSS Stage 0 would be living longer than normal-weight individuals.

Another recent study has indicated that metabolically healthy obesity (again using mixed patient populations) may be a transitory stage (4). However that study also used a combination of EOSS Stage 0 and Stage 1 patients within their definition of “metabolically healthy obese”. When you separate the truly healthy obese (EOSS Stage 0) from the not-so-healthy (EOSS Stage 1), you find that EOSS Stage 0 patients (regardless of their levels of obesity) maintain their health over a long time period (more than 16 years) as shown below (3).

Obesity-chart

The EOSS Stage 1 individuals in all weight classes become progressively less healthy with time. So if you combine the truly healthy obese (EOSS Stage 0) with not so healthy obese (EOSS Stage 1), then you might come to the wrong conclusion that the concept of metabolically healthy obesity doesn’t exist (2,4).

So what’s the real linkage between weight and mortality? It depends on your levels of cellular inflammation as I explained in my book Toxic Fat, published in 2008. And the less cellular inflammation you have at any weight, the healthier you are. The best measure of your levels of cellular inflammation is the AA/EPA ratio. It should be between 1.5 and 3. The average AA/EPA ratio for Americans is about 19 (5). As you reduce cellular inflammation, the severities of all forms of chronic disease are reduced regardless of your weight.

References

  1. Flegal KM, Kit BK, Orpana H, and Graubard BI. “Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis.” JAMA 309:71-82 (2013)
  2. Kramer CK, Zinman B, and Renakeran R. “Are metabolically healthy overweight and obesity benign conditions?” Annals of Internal Medicine 159: 758-769 (2013)
  3. Padwal RS, Pajewshi NM, Allison DB, and Sarma AM. “Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity.” Can Med Assoc Journal 183:E1059-E1065 (2011)
  4. Appleton SL, Seaborn CJ, Visvanathan R, Hill CL, Gill TK, Taylor AW, and Adams RJ. “Diabetes and cardiovascular disease outcome in the metabolically healthy obese phenotype.” Diabetes Care 36:2388-294 (2013)
  5. 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)

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.

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)

Put Statins in the Drinking Water? I Think Not.

Put Statins in the Drinking Water?  I Think Not.

It is amazing that only after the patent expiration of the best-selling statin drug of all time (i.e. Lipitor) that the FDA finally admitted that maybe the drug class that many physicians wanted to put into the drinking water might have some problems after all (1). In particular, the FDA issued a warning that use of statins increases the risk of memory loss and diabetes. The FDA said the risk of diabetes is “small;” however, they were playing fast and loose with the data. This is because the weaker the statin, the less the side-effect profile. The stronger (and better selling) the statin, the greater the side effects are (like diabetes and memory loss). You would think that after having Americans spend more than $50 billion in statin sales that the FDA would have asked these safety questions earlier.

How could statins cause memory loss and diabetes? It has been known for nearly 20 years that statins are the only drug that increase the levels of arachidonic acid (AA) by stimulating the enzyme delta 5-desaturase (2-4). This means greater cellular inflammation that leads to insulin resistance (thus increasing diabetes) and disturbances in signaling mechanisms in nerve cells (thus decreasing memory). I guarantee that no physician knows these facts because the drug companies had no reason to lose a potential sale to disclose that information. Apparently the FDA agreed with the drug companies, since that relevant information was never mentioned in any of the side-effect profiles until now.

The drug industry developed a great marketing pitch for statins: “If your cholesterol is high, you are going to die”. Unfortunately, the data never supported that spiffy slogan. Epidemiological studies do indicate that if your cholesterol levels are high and you are less than 50 years of age, then there is an increased risk for mortality. After age 50, that risk of increased mortality with high cholesterol disappears (5).

Furthermore, keep in mind that statins were not the first drugs to lower cholesterol. There were many other drugs before the statins, but they had the unfortunate side-effect of increasing mortality. It was only with use of the first statin drugs that decreased mortality was finally shown in those having had a prior heart attack. This is called secondary prevention trial. Aspirin and fish oil are also effective in secondary prevention trials, but neither of those interventions reduces cholesterol (6). However, in primary prevention trials (done with people with no history of heart attacks), statins aren’t very good. This is estimated by looking at a number known as “number needed to treat” or NNT. This number indicates how many people have to take a drug to prevent a single heart attack. With the newest statins, the NNT is usually 2 percent. That means you have to treat 100 people to prevent two heart attacks. Unfortunately you have no idea who those two people are, which means the other 98 people will have a lifetime of side effects. One of those side effects is developing diabetes, which occurs in about 1 percent of the patients (forget the other side effects, such as memory loss, muscle fatigue, etc). Who that one person is out of 100 who will develop diabetes is also unknown. Therefore your chances of reducing a heart attack are significantly cut by the likelihood of increasing your chances of developing diabetes. Some wonder drug!

Finally, defenders of statins for the primary prevention of heart disease point to the recent JUPITER trial (7). This clinical trial used people that had normal levels of LDL cholesterol, but very high levels of C-reactive protein (CRP). These people were already inflamed. It should be noted that the drug company that markets the statin drug used in the study funded this particular study. In fact, the government had no interest in the trial. Maybe government officials knew from previous statin trials that in people with normal LDL cholesterol levels and normal levels of CRP that statins had absolutely no benefit in reducing future heart attacks (8). Nonetheless in this small subsection of the population (more than 80 percent of the screened patients were rejected), there was a reduction in first-time heart attacks. But since the patients were highly inflamed to begin with, this means that aspirin or fish oil would probably have given the same result had the same population been tested (9,10). In fact, the JELIS study in Japan confirmed this hypothesis (11). Using the same number of patients, with high cholesterol and lows levels of inflammation (as measured by the AA/EPA ratio), it was demonstrated that those patients given more EPA to lower the AA/EPA ratio had significant reduction in future cardiovascular events. I will make a leap of faith that if the population in the JELIS study was as inflamed as that in the JUPITER study, the results with omega-3 fatty acids would have been even more dramatic.

Lost in all this marketing hype is what actually causes LDL cholesterol to increase in the first place. The answer was known in the 1970s. It’s high levels of insulin (12). This is because insulin activates the same enzyme that statins inhibit. Call me crazy, but it seems to make more sense to lower insulin by the diet rather than taking statins for a lifetime if your goal is to live longer. The best way to lower insulin is the anti-inflammatory Zone Diet coupled with enough fish oil to reduce the AA/EPA ratio to the in the Japanese population range. That’s just good science, not good marketing.

References

  1. Harris G. “Safety alerts cite cholesterol drugs’ side effects.” New York Times, Feb 28. (2012)
  2. Hrboticky N, Tang L, Zimmer B, Lux I, Weber PC. “Lovastatin increases arachidonic acid levels and stimulates thromboxane synthesis in human liver and monocytic cell lines. J Clin Invest 93: 195-203 (1994)
  3. Rise P, Pazzucconi F, Sirtori CR, and Galli C. “Statins enhance arachidonic acid synthesis in hypercholesterolemic patients.”
  4. Nutr Metab Cardiovasc Dis 11:88-94 (2001)
  5. Rise P, Ghezzi S, and Galli C. “Relative potencies of statins in reducing cholesterol synthesis and enhancing linoleic acid metabolism.” Eur J Pharmacol 467:73-75 (2003)
  6. Anderson KM, Castelli WP, and Levy D. “Cholesterol and mortality. 30 years of follow-up from the Framingham study.” JAMA 1987 257:2176-2180 (1987)
  7. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, and Zanchetti A. “Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.” Lancet 373:1849-1860 (2009)
  8. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. “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)
  9. Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, and Lau J. “n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review.” Am J Clin Nutr 84:5-17 (2006)
  10. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, and Glynn RJ. “Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.” N Engl J Med 359:2195-2207 (2008)
  11. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, and Gotto AM. “Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.” N Engl J Med 344:1959-1965 (2001)
  12. 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)
  13. Lakshmanan MR, Nepokroeff CM, Ness GC, Dugan RE, and; Porter JW. “Stimulation by insulin of rat liver hydroxy-β-methylglutaryl coenzyme A reductase and cholesterol-synthesizing activities.” Biochem Biophys Res Commun 50:704-710 (1973)

Hard times are ahead

Last month was a red-letter month for the future of mankind as the world population passed 7 billion. Unfortunately, this fact dovetails with recent research that indicates it is likely that one-half of all Americans will be diabetic by 2050 (1).

The combination of these two trends does not bode well for the future. To begin with, how are we going to feed all these people? Most of the arable land on the planet is already under cultivation. Furthermore, urbanization is destroying prime cropland at a rapid pace.

Added to these facts is that the diversity of most of the world’s calories is rapidly decreasing. Currently the five top sources of calories in the world are corn, soybeans, wheat, rice and potatoes (as well as its kissin’ cousin cassava, which is incredibly poor in protein and nutrients). The first two crops (corn and soy) are rich sources of omega-6 fatty acids. In addition, corn, wheat, and rice provide extremely high-glycemic carbohydrates that can be easily refined to last forever and make thus a wide variety of processed foods. (Potatoes and cassava tend to decompose rapidly and can’t be easily refined, except perhaps as potato chips). As a consequence, omega-6 fatty acids and refined carbohydrates are now the cheapest form of calories in the world. In fact, it is estimated that they are 400 times less expensive per calorie than fresh fruits and vegetables.

So how can you feed this growing population of more than 7 billion people? The answer is easy—produce even more refined carbohydrates and omega-6 fatty acids.

Unfortunately, feeding the growing population of the world with cheap omega-6 fatty acids and refined carbohydrates is exactly the best way to increase cellular inflammation and drive the development of diabetes (2). It is estimated that by 2050 diabetes will be the primary non-infectious disease on the planet. This is equally bad news as it is also the most expensive chronic disease to treat on a long-term basis.

Today, more than 26 percent of all Americans older than 65 has diabetes. If the estimates of increased diabetes are correct (1), then it is likely that the number of Americans older than 65 in 2050 with diabetes may be greater than 50 percent. The current level of diabetes is the primary reason why our health-care expenses are spiraling out of control. If you double number of older Americans with diabetes by 2050, there is no way the current health-care system, as we know it can possibly survive. Add to the fact that once you have diabetes, you are 2-4 times more likely to develop heart disease and Alzheimer’s. It is not a very pleasant picture of the future of health care in America.

What can you do about it? On a global basis, not much unless you would like to see an apocalyptic event that reduces the population from 7 billion to a more manageable 1-2 billion individuals. Of course, this is highly unlikely. However, on the individual basis there is a lot you can do to protect yourself in the future. Simply take control of your future by focusing on managing cellular inflammation for a lifetime by following an anti-inflammatory diet. This may be your only real health security in times of increasing demands on the planet’s resources to produce food. There is no question that we have other troubles brewing like climate change, decreasing water supplies, and decreasing cheap energy, all of which will also impact the cost of food, driving more individuals toward inexpensive sources of calories no matter what the health consequences. But the rise of diabetes will occur first.

Old folks like myself will probably be OK, but the future generations will take the brunt of trouble brewing ahead.

References

  1. Boyle JP , Thompson TJ, Gregg EW, Barker LE, and Williamson DF. “Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence.” Population Health Metrics 8:29 (2010)
  2. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)

Changing gene expression

I have often stated that the real power of the Zone Diet is to change gene expression, especially the expression of anti-inflammatory genes. What I never realized is how rapid gene expression could occur. Now, new research from Norway gives me the answer (1). It takes about 24 hours!

This pilot study is on the effect of diet on gene expression in healthy obese individuals. Interestingly, when the researchers calculated the estimated daily calorie requirements for these subjects necessary to maintain their weight, they were surprised that they were already eating 250 fewer calories per day than predicted to maintain their current weight. So much for the “fact” that obese individuals are fat because they eat more calories than they need to maintain their weight. In fact, this observation was confirmed in an earlier study in which the number of calories consumed by obese and lean individuals did not vary, but the obese individuals consumed fewer meals consisting of larger servings (2).

So what the Norwegian researchers did was simply maintain the same number of calories the subjects were already eating and change the macronutrient balance to be very close to the Zone Diet (30 percent carbohydrates, 30 percent protein, and 40 percent fat). Then the subjects consumed six meals containing about 460 calories evenly spaced throughout the day so that the total calories consumed at any one time was moderate. Just making those two simple dietary changes resulted in more than an eight-pound weight loss in 28 days. The levels of body fat didn’t change since the number of calories consumed was exactly the same as they were previously consuming. However, it appears that evenly spacing the meals and reducing the calorie size of the meals resulted in less insulin production and therefore less retained water.

Then they looked to see if they could find any changes in gene expression in both the fat cells and the blood with the dietary changes. Amazingly they found dramatic changes in only 24 hours. Of the 16,000 genes they could identify, about 60 percent remained unchanged in their expression, but 40 percent were either turned on (i.e., up-regulated) or turned down (i.e., down-regulated). Interestingly, the changes seen in the first 24 hours were held constant throughout the 28 days of the experiment.

Upon further analysis, the up-regulated genes corresponded to those that had anti-inflammatory properties, and the down-regulated genes were those associated with chronic disease conditions, such as diabetes and heart disease. Furthermore, since these changes in gene expression occurred within 24 hours of the dietary change, they could not be attributed to any change in body weight and fat loss.

Fortunately, I had the opportunity to have dinner with the lead author of the study to discuss her work while I was in Europe last week. She told me that she has expanded the number of subjects in several new trials, and the results remain the same. I also found out that she has been following my work for many years.

This type of study only confirms the power of genetic analysis to demonstrate how a highly structured diet with the correct macronutrient content can rapidly alter genetic expression and hence controls your future health. But the door swings both ways. An unbalanced diet will have just the opposite genetic effects. While I have always been impressed by the power of the Zone Diet, this new experimental data takes my respect for the Zone Diet to a new level of awe, even by me.

References

  1. Brattbakk H-R, Arbo I, Aagaard S, Lindseth I, de Soysa AK, Langaas M, Kulseng B, Lindberg, and Johansen B. “Balanced caloric macronutrient composition down regulates immunological gene expression in human blood cells-adipose tissue diverges.” OMICS 15: doi:1089/omi.2010.0124 (2011)
  2. Berg C, Lappas G, Wolk A, Strandhagen E, Toren K, Rosengren A, Rosengren A, Thelle D, and Lissner L. “Eating patterns and portion size associated with obesity in a Swedish population.” Appetite 52: 21-26 (2009)

If you’re fat, you may be OK

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.

Zone diet validation studies

Weight Loss

Any diet that restricts calories will result in equivalent weight loss. However, the same doesn’t hold true as to what the source of that weight loss is. Weight loss from either dehydration (such as ketogenic diets) or cannibalization of muscle and organ mass (such as low-protein diets) has no health benefits. Only when the weight loss source is from stored fat do you gain any health benefits. Here the Zone diet has been shown to be superior to all other diets in burning fat faster (1-4). It has been demonstrated that if a person has a high initial insulin response to a glucose challenge, then the Zone diet is also superior in weight loss (5,6). A recent study from the New England Journal of Medicine indicates that a diet composition similar to the Zone diet is superior to other compositions in preventing the regain of lost weight (7). This is probably caused by the increased satiety induced by the Zone diet compared to other diets (1,8,9).

Reduction of cellular inflammation

There is total agreement in the research literature that the Zone diet is superior in reducing cellular inflammation (10-12). Since cellular inflammation is the driving force for chronic disease, then this should be the ultimate goal of any diet. Call me crazy for thinking otherwise.

Heart disease

It is ironic that the Ornish diet is still considered one of the best diets for heart disease, since the published data indicates that twice as many people had fatal heart attacks on the Ornish diet compared to a control diet (13). This is definitely the case of don’t confuse me with the facts. On the other hand, diets with the same balance of protein, carbohydrate and fat as the Zone diet has have been shown to be superior in reducing cardiovascular risk factors, such as cholesterol and fasting insulin (14,15).

Diabetes

The first publication validating the benefits of the Zone diet in treating diabetes appeared in 1998 (16). Since that time there have been several other studies indicating the superiority of the Zone diet composition for reducing blood glucose levels (17-20). In 2005, the Joslin Diabetes Research Center at Harvard Medical School announced its new dietary guidelines for treating obesity and diabetes. These dietary guidelines were essentially identical to the Zone diet. Studies done at the Joslin Diabetes Research Center following those dietary guidelines confirm the efficacy of the Zone diet to reduce diabetic risk factors (21). If the Zone diet isn’t recommended for individuals with diabetes, then someone should tell Harvard.

Ease of use

The Zone diet simply requires balancing one-third of your plate with low-fat protein with the other two-thirds coming from fruits and vegetables (i.e. colorful carbohydrates). Then you add a dash (that’s a small amount) of heart-healthy monounsaturated fats. The Zone diet is based on a bell-shaped curve balancing low-fat protein and low-glycemic-index carbohydrates, not a particular magic number. If you balance the plate as described above using your hand and your eye, it will approximate 40 percent of the calories as carbohydrates, 30 percent of calories as protein, and 30 percent of the calories as fat. Furthermore, it was found in a recent Stanford University study that the Zone diet provided greater amounts of micronutrients on a calorie-restricted program than any other diet (22).

Eventually all dietary theories have to be analyzed in the crucible of experimentation to determine their validity. So far in the past 13 years since I wrote my first book, my concepts of anti-inflammatory nutrition still seem to be at the cutting edge.

References

  1. Skov AR, Toubro S, Ronn B, Holm L, and Astrup A. “Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity.” Int J Obes Relat Metab Disord 23: 528-536 (1999)
  2. Layman DK, Boileau RA, Erickson DJ, Painter JE, Shiue H, Sather C, and Christou DD. “A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women.” J Nutr 133: 411-417 (2003)
  3. Fontani G, Corradeschi F, Felici A, Alfatti F, Bugarini R, Fiaschi AI, Cerretani D, Montorfano G, Rizzo AM, and Berra B. “Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with omega-3 polyunsaturated fatty acids.” Eur J Clin Invest 35: 499-507 (2005)
  4. 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)
  5. 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: a randomized trial.” JAMA 297: 2092-2102 (2007)
  6. Pittas AG, Das SK, Hajduk CL, Golden J, Saltzman E, Stark PC, Greenberg AS, and Roberts SB. “A low-glycemic-load diet facilitates greater weight loss in overweight adults with high insulin secretion but not in overweight adults with low insulin secretion in the CALERIE Trial.” Diabetes Care 28: 2939-2941 (2005)
  7. 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)
  8. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, Roberts SB, Agus MS, Swain JF, Larson CL, and Eckert EA. “Dietary high-glycemic-index foods, overeating, and obesity.” Pediatrics 103: E26 (1999)
  9. Agus MS, Swain JF, Larson CL, Eckert EA, and Ludwig DS. “Dietary composition and physiologic adaptations to energy restriction.” Am J Clin Nutr 71: 901-907 (2000)
  10. 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)
  11. 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)
  12. 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)
  13. Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, and Brand RJ, “Intensive lifestyle changes for reversal of coronary heart disease.” JAMA 280: 2001-2007 (1998)
  14. Wolfe BM and Piche LA. “Replacement of carbohydrate by protein in a conventional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects.” Clin Invest Med 22: 140-1488 (1999)
  15. Dumesnil JG, Turgeon J, Tremblay A, Poirier P, Gilbert M, Gagnon L, St-Pierre S, Garneau C, Lemieux I, Pascot A, Bergeron J, and Despres JP. “Effect of a low-glycaemic index, low-fat, high-protein diet on the atherogenic metabolic risk profile of abdominally obese men.” Br J Nutr 86:557-568 (2001)
  16. Markovic TP, Campbell LV, Balasubramanian S, Jenkins AB, Fleury AC, Simons LA, and Chisholm DJ. “Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with or without type 2 diabetes.” Diabetes Care 21: 695-700 (1998)
  17. Layman DK, Shiue H, Sather C, Erickson DJ, and Baum J. “Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss.” J Nutr 133: 405-410 (2003)
  18. Gannon MC, Nuttall FQ, Saeed A, Jordan K, and Hoover H. “An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes.” Am J Clin Nutr 78: 734-741 (2003)
  19. Nuttall FQ, Gannon MC, Saeed A, Jordan K, and Hoover H. “The metabolic response of subjects with type 2 diabetes to a high-protein, weight-maintenance diet.” J Clin Endocrinol Metab 2003 88: 3577-3583 (2003)
  20. Gannon MC and Nuttall FQ. “Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition.” Nutr Metab (Lond) 3: 16 (2006)
  21. Hamdy O and Carver C. “The Why WAIT program: improving clinical outcomes through weight management in type 2 diabetes.” Curr Diab Rep 8: 413-420 (2008)
  22. Gardner CD, Kim S, Bersamin A, Dopler-Nelson M, Otten J, Oelrich B, and Cherin R. “Micronutrient quality of weight-loss diets that focus on macronutrients: results from the A TO Z study.” Am J Clin Nutr 92: 304-312 (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.

Ease off the fats during pregnancy

Obesity remains one of the primary headlines every day. But what you probably don’t know is the fastest growing segment of the obesity epidemic is children less than 4 years old. Approximately 20 percent are obese (1). Even more disturbing is the growth of obesity in children under the age of six months (2). You can’t blame school lunch programs for this youngest group, since they are too young to go to school, and you can’t blame lack of exercise since they can’t walk yet.

Frankly, no child wants to be obese. In fact, their quality of life is similar to that of a child undergoing chemotherapy (3). Yet we are constantly reminded that they are obese because they lack personal responsibility, and they only have to “eat less and exercise more”. The fact that such interventions don’t seem to work is simply a minor detail (4-6).

As I mentioned in an earlier blog, the culprit may be fetal programming in the womb that is causing epigenetic changes in the fetus before birth. This has already been demonstrated in pregnant rats that were fed a high-fat diet from the first day of pregnancy (7). These rats were genetically bred to be obesity resistant so that extra fat in their diet didn’t increase the body weight of the mothers during pregnancy. However, the offspring of those mothers fed the high-fat diet had blood sugar levels that were nearly twice as high as compared to offspring coming from the pregnant rats being fed a normal-fat diet. This is an indication that they were born with insulin resistance.

When researchers looked for epigenetic markers that might distinguish the two groups of offspring, sure enough they found chemical markers in the genes that regulate glucose metabolism. Since these epigenetic markers on the genes are not easily removed, the offspring with them would face a lifetime of dietary challenge to counteract their new genetic pre-disposition to obesity and diabetes.

So let’s come back to the growing childhood obesity problem in the very young. It may be due to fetal programming caused by high levels of both saturated and omega-6 fatty acids in the prenatal diet. Both types of fatty acids will cause increased cellular inflammation that can affect gene expression. If that occurs in the fetus, then that may be enough to genetically alter their future for a lifetime, including a far greater risk of obesity and diabetes.

References

  1. Anderson SE and Whitaker RC. “Prevalence of Obesity Among US Preschool Children in Different Racial and Ethnic Groups.” Arch Pediatric Adolescent Med 163: 344-348 (2009)
  2. Kim J, Peterson KE, Scanlon KS, Fitzmaurice GM, Must A, Oaken E, Rifas-Shiman SL, Rich-Edwards JW, and Gillman MW. “Trends in overweight from 1980 through 2001 among preschool-aged children enrolled in a health maintenance organization.” Obesity 14: 1107-1112 (2006)
  3. Schwimmer JB, Burwinkle TM, and Varni JW. “Health-related quality of life of severely obese children and adolescents.” JAMA 289: 1813-1819 (2003)
  4. McGovern L, Johnson JN, Paulo R, Hettinger A, Singhal V, Kamath C, Erwin PJ, and Montori VM. “Clinical review: treatment of pediatric obesity: a systematic review and meta-analysis of randomized trials.” J Clin Endocrinol Metab 93: 4600-4605 (2008)
  5. Kamath CC, Vickers KS, Ehrlich A, McGovern L, Johnson J, Singhal V, Paulo R, Hettinger A, Erwin PJ, and Montori VM. “Clinical review: behavioral interventions to prevent childhood obesity: a systematic review and meta-analyses of randomized trials.” J Clin Endocrinol Metab 93: 4606-4615 (2008)
  6. Shaw K, Gennat H, O’Rourke P, and Del Mar C. “Exercise for overweight or obesity.” Cochrane Database Syst Rev 2006: CD003817 (2006)
  7. Strakovsky RS, Zhang X, Zhou D, and Pan YX. “Gestational high-fat diet programs hepatic phosphoenolpyruvate carboxykinase gene expression and histone modification in neonatal offspring rats.” J Physiol 589: 2707-2717 (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.