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.

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About Dr. Barry Sears

Dr. Barry Sears is a leading authority on the impact of the diet on hormonal response, genetic expression, and inflammation. A former research scientist at the Boston University School of Medicine and the Massachusetts Institute of Technology, Dr. Sears has dedicated his research efforts over the past 30 years to the study of lipids. He has published more than 30 scientific articles and holds 13 U.S. patents in the areas of intravenous drug delivery systems and hormonal regulation for the treatment of cardiovascular disease. He has also written 13 books, including the New York Times #1 best-seller "The Zone". These books have sold more than 5 million copies in the U.S. and have been translated into 22 different languages.

15 thoughts on “Try the team approach to nutrition

  1. It seems like the general recommendation on this site for fish oil is to start at 2.5 grams. I don’t really notice too much of a difference in how i feel until i get up to 7.5 grams. I’m 6’4” and 200lbs. I realize there are large individual differences for optimal fish oil intake but, in general, at what amount do you start to see fish oil affect adiponectin levels? …is that amount greater than the amount needed for fish oil’s countless other benefits?

    Also, there has been some debate lately about omega 3′s oxidation and it’s affect on the liver. would you possibly comment on that? maybe in a separate post?

    continued thanks. you have no idea how big an impact you have had on my life.

    • The animal data by Shulman indicated that about 30% of the diet as fish oil (menhadden oil) was sufficient. A rough calculation would indicate that this would correspond to about 10% of the total calories as EPA and DHA. For some consuming 2000 calories per day that would be about 2.5 grams per day as EPA and DHA. The next step is actually doing dose-response studies in humans, similar to those published last year in the American Journal of Clinical Nutrition on fish requirements in women with a high risk of breast cancer. That study indicated that about 7.5 grams of EPA and DHA per day was reasonable. At any levels of fish oil intake, and especially at those levels, one has to be concerned whether or not one has sufficient anti-oxidants to protect the omega-3 fatty acids from oxidizing. That’s why I always recommend taking at least 8,000 ORAC units per day for every 2.5 grams of supplemented EPA and DHA. 8,000 ORAC units is similar to eating 10 servings of vegetables and fruits per day. I take about 7.5 grams of EPA and DHA per day and eat about 10 servings of vegetables and fruits per day. That’s why I supplement my diet with extra polyphenols (about 16,000 ORAC units per day) to protect the omega-3 fatty acids from excessive oxidation.

  2. Dr. Sears, thanks for the additional information in your reply to Chris. Now I’m better understanding the recommendation of 1/2 cup Sea Health Plus daily.

  3. awesome, awesome information.

    In a typical day I eat almost exclusively fruits and vegetables as carb sources but at 7.5 grams it sounds like my body may not be reaping the full benefits of the oil I’m consuming. Makes me wonder if I’d be better off significantly upping my Sea Health plus intake and going with 5 grams of fish oil. I guess the only way to find out is to try.

    Is there any danger associated with your body oxidizing n-3′s or is it just wasteful? Or possibly some of both? If it can be harmful, are people that consume large amounts of refined carbohydrates and vegetable oils potentially doing more harm than good with n-3 supplementation?

    • As long as omega-3 fatty acids are completely oxidized to water and CO2 via the Krebs cycle, there is no problem as you are making ATP for chemical energy. It is when the omega-3 are oxidized to aldehydes and ketones that can cause chemical damage to the DNA that that is a problem. That type of oxidation occurs with free radical attack on the omega-3 fatty acids. That type of oxidation can be inhibited by the polyphenols. This is why I always suggest adding extra polyphenols to your diet when supplementing with EPA and DHA.

  4. About adiponectin, its very interesting scientific information regards Irvingia gabonensis, which can: combat leptin resistance, increase adiponectin levels, block carbs (alpha-amylase enzyme) and inhibit glycerol-3-phosphate (which stores body fat). For me its really impressive this plant against obesity. Any thought about it?

    • I read the two articles (one on a cell culture study and other on a clinical study) and found them interesting. I was a little perplexed that the compound seemed to down-regulate PPAR gamma while up-regulating adiponectin. Usually increased adiponectin levels will increase will increase PPAR gamma expression. Nonetheless, I suspect the underlying component may be some type of polyphenol compound that can have such potential systemic effects.

  5. I feel so much better when I’m taking the fish oil regularly, but the problem I have is that it takes me forever to work up to the amount I need (otherwise I spend all of my time in the bathroom), and if I forget for a couple of days, I have to start almost from scratch building up again.

  6. Dont forget that in addition to fruits and vegetables, herbs and spices are a rich source of polyphenols and natural cocoa powder (non-dutched) has the highest ORAC score of any food tested by the USDA, significantly more than blueberries, goji, or acai berries which are far more costly. The ORAC score for 10 grams of natural cocoa powder is approximately 8,000. One serving of Hershey’s natural cocoa powder (1 tablespoon) is 5 grams. Gram for gram spices such as dried oregano, cinnamon, paprika, black pepper also have a much higher ORAC score tha pomegrante juice, blueberries, sweet potatoes and many foods known as high powered antioxidants. And these are inexpensive nutrients easy to incorporate in the diet. That being said I still eat 7-10 servings of fruits and vege’s a day, but I also have a serving or two of natural cocoa powder every day and add dried oregano to lots of foods.

  7. The info regarding cocoa powder is appreciated. Is there also a high dose of caffeine in the cocoa? What are some good ways to use it? Also what does ORAC stand for? Thanks.

    • That’s why it is best to eat the chocolate in the morning so the caffeine effect will not keep you awake. I made that mistake several times before I put two and two together.

      ORAC stands for Oxygen Radical Absorption Capacity.

  8. Maybe the fish oil needs to be fermented.It wasn’t rendered until about 1850′s.For thousands of years it was fermented and not heated nor filtered.The romans wrote it was included in the Centurian rations to keep them healthy and fit for duty.Where do you find fermented cod liver oil?Try Green pasture Blue Ice Fermented Cod Liver Oil.Its the only source that I have found and You don’t have to worry about including more polyphenals as it is still in there because it hasn’t been scrubbed by man of all that was naturally present.Its not pleasant tasting at first but I got used to it pretty quick and really feel the effects by less pain and free range of motion returning after suffering arthritis for yrs.This isn’t a sears product but maybe the good doctor should investigated it and get back to all his subscribers.I am only a consumer but I have never found any other fish product that works as well.

    • The fermentation process used in making fish paste in ancient Roman times is still unknown. Actually fermented cod liver oil was first reported on in the medical literature in 1786 when the first cod livers were bought back from American to England. It was considered a miracle treatment for arthritis at the time. Unfortunately, today cod livers are grossly contaminated with PCBs and other fat-soluble toxins like dioxins and flame retardants. This means that any fermented cod liver oil today will also contain those same fat-soluble toxins. They can only be removed by molecular distillation. I will try to get a same of the fermented cod liver oil that you mentioned and have it analyzed for PCBs as we do for all lots of our high purity omega-3 oil products. Whatever the source of the EPA and DHA, you have to use enough to get a therapeutic effect.

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