Pass the polyphenols

Considering that virtually nothing was written about the health benefits of polyphenols before 1995, it continues to amaze me the amount of health benefits this group of nutrients generates. This is primarily due to our growing understanding of how these phytochemicals interact with the most primitive parts of our immune system that have been conserved through millions of years of evolution.

Three new studies add to this growing knowledge. In the January 2011 issue of the American Journal of Clinical Nutrition, it was reported that eating one serving a week of blueberries could reduce the risk of developing hypertension by 10 percent (1). Since a serving size of fruit is defined as ½ cup, that serving size contains about 65 grams of blueberries. Put that into more precise molecular terms, this serving size would provide about 4,000 ORAC units or about the same amount of ORAC units as a glass of wine. The researchers speculated that there was a subclass of polyphenols (which includes delphinidins) that appear to be responsible for most of the effects. So if eating one serving of blueberries (½ cup) once a week is good for reducing the risk of hypertension, guess what the benefits of eating 1 cup of blueberries every day might be? The answer is probably a lot.

Speaking of red wine, in the second study in Biochemical and Biophysical Research Communications researchers found that giving high levels of isolated polyphenols from red wine demonstrated that exercise endurance in older rats could be significantly enhanced. Very good news for old folks like me. They hypothesized the effects may be directly related to “turning on” genes that increase the production of anti-oxidant enzymes (2). The only catch is that the amount of red wine polyphenols required to reach these benefits would equate to drinking about 20-30 glasses of red wine per day.

The final study in Medicine & Science in Sports and Exercise demonstrates that cherry juice rich in polyphenols reduces muscle damage induced by intensive exercise in trained athletes. This reduction in muscle damage was correlated with decreased levels of inflammatory cytokines (3). The reduction of cytokine expression is one of the known anti-inflammatory benefits of increased polyphenol intake.

Three pretty diverse studies, yet it makes perfect sense if you understand how polyphenols work. Polyphenols inhibit the overproduction of inflammatory compounds made by the most ancient part of the immune system that we share with plants. The only trick is taking enough of these polyphenols. To get about 8,000 ORAC units every day requires eating about a cup of blueberries (lots of carbohydrates) or two glasses of red wine (lots of alcohol), or half a bar of very dark chocolate (lots of fat) or 0.3 g of highly purified polyphenol powder in a small capsule (with no carbohydrates, no alcohol, and no saturated fat). And if you are taking extra high purity omega-3 oil, exercising harder, or have an inflammatory disease, you will probably need even more polyphenols. It doesn’t matter where the polyphenols come from as long as you get enough. That’s why you eat lots of colorful carbohydrates on an anti inflammatory diet.


  1. Cassidy A, O’Reilly EJ, Kay C, Sampson L, Franz M, Forman J, Curhan G, and Rimm EB. “Habitual intake of flavonoid subclasses and incident hypertension in adults.” Am J Clin Nutr 93: 338-347 (2011)
  2. Dal-Ros S, Zoll J, Lang AL, Auger C, Keller N, Bronner C, Geny B, Schini-Kerth VB. “Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: Role of NADPH oxidase.” Biochem Biophys Res Commun 404: 743-749 (2011)
  3. Bowtell JL, Sumners DP, Dyer A, Fox P, and Mileva KN. “Montmorency cherry juice reduces muscle damage caused by intensive strength exercise”. Med Sci Sports Exerc 43: online ahead of print doi: 10.1249/MSS.obo13e31820e5adc (2011)

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

Coffee and diabetes: What’s the connection?

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

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

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

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

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

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


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

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

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

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

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

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

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

Try the team approach to nutrition

One of the problems with nutrition is that it is too complex for simple thinking. Unlike drugs, which are designed to inhibit a particular target enzyme, nutrients often work in combinations like a team operating at the genetic level. When you try to apply drug-like thinking (i.e. one compound has to do all the work) to nutrient research, then the results are often underwhelming. Nowhere is this clearer than when we look at how nutrients interact to control body weight.

Weight gain can be best understood as a defect in both metabolism (the conversion of dietary energy into chemical energy) and storage (the stockpiling of excess dietary intake). This involves a four-way conversation between the brain, the gut, the liver and the adipose tissue. The only way these various organs can communicate with each other is via hormones. The gut sends signals to the brain when to stop eating. If the brain receives those signals loud and clear, your desire for food decreases (i.e. satiety). Finally, the food that has been ingested is either converted by the liver into suitable metabolites that can either be used for generating chemical energy (i.e. ATP) or stored (primarily in the fat cells) for future use. When it all works together, it runs smoothly. When it doesn’t work well, you end up gaining more body fat accelerating the pathway toward chronic disease.

One of the key hormones in this complex communication process is adiponectin. Apidonectin is an anti-inflammatory hormone made by the fat cells that is essential for reducing insulin resistance and preventing lipotoxicity (1). In other words, it is at the center of this complex hormonal communication system to help keep body weight in check and slow the development of chronic disease. Great, but how do you increase adiponectin?

First, there is no drug that can do it, but there are nutrients that can. One approach is to consume more omega-3 fatty acids (1). High levels of omega-3 fatty acids activate a genetic transcription factor that causes the increased production of adiponectin. But it takes a lot of high purity omega-3 oil to turn on that gene transcription factor. Now there appears to be another way: Taking polyphenols (2). The polyphenols don’t increase the activity of the genetic transcription factor, but they do facilitate the assembly of adiponectin into its most active form. Of course, if you don’t have enough omega-3 fatty acids in the diet, you can’t produce the necessary adiponectin building blocks to be assembled. When you combine the two (high purity omega-3 oil and polyphenols), then you don’t need to use as much of either one for the desired end result (3).

That’s how nutrition really works. You have to use a team nutrient approach to alter genetic expression. A lot more complicated than giving a single drug, but of course without the inherent side effects.


  1. Sears B. “Toxic Fat.” Thomas Nelson. Nashville, TN (2008)
  2. Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, and Shulman GI. “Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice.” Diabetes 55: 924-928 (2006)
  3. Wang Q, Liu M, Liu X, Dong LQ, Glickman RD, Slage TJ, Zhou Z, and Liu F. “Up-regulation of adiponectin by resveratrol.” J Biol Chem 286: 60-66 (2011)
  4. Shirai N and Suzuki H. “Effects of simultaneous intakes of fish oil and green tea extracts on plasma, glucose, insulin, C-peptide, and adiponectin and on liver lipid concentrations in mice fed low- and high-fat diets.” Ann Nutr Metab 52: 241-249 (2008)

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

The secret of blueberries: It’s the dephinidins

We continually hear about the benefits of fruits and vegetables for better health. There are a number of them. One is obviously their lower glycemic load that reduces insulin secretion. Another is their polyphenol content that gives fruits and vegetables their colors. Although virtually no research was conducted on polyphenols before 1995, since that time there has been a explosion of animal studies that have indicated their remarkable benefits as anti-oxidants and anti-inflammatory agents.

Upon deeper inspection, there is one group of polyphenols that seems to generate the most consistent health benefits. These are the delphinidins. Delphinidins are a subgroup of a family of polyphenols known as anthocyanidins. To make the story about delphinidins more intriguing, they are primarily found in blueberries. More specifically, the primary sources of delphinidins are the American blueberry, the Russian blueberry (i.e. bilberry), and the Patagonian blueberry (i.e. maqui berry). This is why the published clinical studies in humans seem to consistently involve blueberries. And the clinical data is impressive. Whether it is about reducing oxidized cholesterol or improving insulin resistance in patients with metabolic syndrome (1,2) or improving memory in patients with early dementia (3), the human data on the use of blueberries simply jumps out at you.

Since the active ingredient in each of these varieties of blueberries appears to be the delphinidins, then it is reasonable that the higher the levels of this particular polyphenol, the better the potential results. The Russian blueberry contains six times more delphinidins than American blueberries, and the Patagonia blueberry contains 14 times more delphinidins than the American blueberry. This probably reflects the harsher growing climates that other forms of blueberries are exposed to when compared to the American blueberry, which has become overly domesticated (making it richer in fructose and lower in delphinidins).

However, as with all natural products you have to take a therapeutic dose to get a therapeutic effect. You could measure this therapeutic threshold in terms of their anti-oxidative potential (measured in ORAC units) or the actual amounts of delphinidins themselves. It appears that for a blueberry extract to be effective requires that it provides at least 16,000 ORAC units per day. To put this in perspective, this level of ORAC units is equivalent to eating greater than 20-30 servings of vegetables on a daily basis.

But if the delphinidins are so important for the benefits of blueberries, isn’t it possible that the smaller amounts of the maqui berry might be even more beneficial because of its higher delphinidin concentration? That’s why we have several ongoing clinical trials to explore that potential. I will keep you informed as the results start coming in. Yet in the meantime, keep eating lots of those colorful carbohydrates just like your grandmother told you to eat.

1. Stull AJ, Cash KC, Johnson WD, Champagne CM, and Cefalu WT. “Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women.” J Nutr 140: 1764-1768 (2010)
2. Basu A, Du M, Leyva MJ, Sanchez K, Betts NM, Wu M, Aston CE, and Lyons TJ. “Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome.” J Nutr 140: 1582 1588 (2010)
3. Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqivst-Tymchuk R, Shukitt-Hale R, and Joseph JA. “Blueberry supplementation improves memory in older adults.” J Agric Food Chem 58: 3996-4000 (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.

Aspirin…not just for heart disease

As I pointed in my first book, “The Zone,” more than 15 years ago, aspirin remains a wonder drug because of its ability to reduce inflammation (1). The medical community now uses aspirin for the prevention of strokes and heart attacks, but a recent study may extend its anti-inflammatory benefits to cancer survivors.

A study pre-published online from The Lancet examined various clinical trials comparing the long-term mortality of those individuals who used aspirin or didn’t (2). This meta-analysis study indicated that relatively low-dose aspirin (about 75 mg or a baby aspirin a day) reduced cancer deaths in various long-term cancer survivors by about 20 percent. So should all of us be taking a baby aspirin daily? Possibly, but aspirin does have side effects, especially in terms of bleeding.

But one thing you can do with total safety is to boost your intake of fruits and vegetables. It turns out that fruits and vegetables contain salicylates, the group of compounds that represents the major active ingredient in aspirin. In addition, fruits and vegetables also contain other anti-inflammatory polyphenols (the chemicals that give plants their color). Since plants don’t have access to the local pharmacy to protect themselves from microbial invasion, they have to synthesize their own “drugs”. By consuming fruits and vegetables, we are constantly visiting our “food” pharmacy. Their defense mechanisms now become our nutritional allies in silencing inflammatory gene expression that is turned on when certain food components (such as omega-6 and saturated fats) fool the most primitive part of the immune system (the innate immune system) to think it is under microbial attack.

Most of the inflammation that drives cardiovascular disease and cancer starts with this type of cellular inflammation induced by our diet (3). It’s taken new breakthroughs in molecular biology to finally understand that what’s good for the plant is also going to be great for us if we want to live a longer and better life.

1. Sears B. “The Zone.” Regan Books. New York, NY (1995)
2. Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, and Meade TW. “Effects of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials.” Lancet, Early Online Publication, 7 December (2010)
3. Sears B. “The Anti-Inflammation Zone.” Regan Books. New York, NY (2005)

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

Omega-3 fatty acids may reduce breast cancer risk

The list just keeps growing for the benefits of omega-3 fatty acids and overall health. The newest to the list is breast cancer. A study just published in the journal of Cancer Epidemiology, Biomarkers & Prevention surveyed approximately 35,000 postmenopausal women, ages 50 to 76, for their use of various specialty supplements (1). The 24-page summary took into account past and present use of supplements as well as frequency (days/week) and duration (year). Individuals taking high purity omega-3 oil had a 32 percent reduced risk of developing breast cancer, whereas other supplements typically taken to reduce menopausal symptoms (e.g., black cohosh, dong quai, soy, or St. John’s wort) had no association. Although further research needs to be conducted, this again adds to the growing body of evidence on the benefits of omega-3s for disease prevention.

Of this survey didn’t answer the question about if they had taken more, would they have seen even better results? This is because cancer like all chronic diseases is driven by silent inflammation coming from increasing levels of Toxic Fat (i.e., arachidonic acid). High purity omega-3 oil dilutes Toxic Fat, but only a strict anti inflammatory diet can actually reduce Toxic Fat. Follow an anti-inflammatory program consisting of a strict anti inflammatory diet, ultra-refined high purity omega-3 oil concentrates and anti-inflammatory polyphenols to reduce the driving force for virtually all chronic disease.
1. Brasky TM, Lampe JW, Potter JD, Patterson RE, White E. Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) Cohort. Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1696-708.

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.

Like you needed a reason to eat chocolate …

You couldn’t walk into a pharmacy like CVS or Walgreen’s over the past few weeks without getting bombarded with the pastel colors of Easter eggs and chocolate candy displays. Come the day after Easter all this candy will be on sale, and even if you don’t celebrate Easter, you might be apt to pick some up on your next trip in. It doesn’t take much for us to justify indulging in our favorite treats. When a research study comes along promoting the benefits of green tea, red wine, or even chocolate, people automatically use it as an excuse to jump on the bandwagon and indulge more.

A recent study published in the European Heart Journal may make you inclined to run out and take advantage of these Easter sales (1), but proceed with caution. The study looked at 19,357 individuals over eight years who were free of myocardial infarction, stroke, not taking anti-hypertensive medications and their dietary intake of chocolate. What they found was that individuals who consumed chocolate had a lower risk of heart attacks and strokes, which they believed was due to the effects of the chocolate on lowering blood pressure (1).

How much chocolate were they consuming exactly? About one small square a week. The authors believe that a group of polyphenols, called flavonols found in cocoa, may be what lowered people’s blood pressure (2). Unfortunately, you won’t be able to find much of this group of flavonols among the Easter candy selections. Generally the more flavonols, the more bitter the chocolate, so the darker the better.

Just remember chocolate is a calorically dense food and high in saturated fat, so if you do consume, consume in moderation!

1. Buijsse B, C Weikert, D Drogan, M Bergmann, H Boeing. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur Heart J March 30, 2010.
2. Chocolate ‘can cut blood pressure and help heart’. Available at: Accessed: March 30, 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.