Chronic Inflammation and Yoga: Combating the Fiery Killer

by Ram

Red Leaves by Melina Meza

Ever experienced an unexplained excruciating pain in the joints, ankles, knees that lasted for some time and then subsided? Or, maybe when you bent your fingers to hold some object, you experienced a burning pain in your fingers so painful that you were unable to straighten them for some time. Or, for some of us who do yoga regularly, we may have experienced pain, burning, numbness, or tingling in the buttock, hip, low back, knees, etc. Notice how this pain subsides when you are advised by your physician to take non-steroidal anti-inflammatory drugs like ibuprofen, or for some of us who have been living with this chronic agonizing pain, relief comes from those powerful anti-inflammatory steroid medications.

So, what is inflammation, why does it occur, and what are the best safe and natural options to curb this disorder? Let’s start by defining the term: From the Latin term "inflammo" (meaning setting alight or igniting), inflammation is part of the body's immune/defense response, the body's attempt at self-protection. The objective of inflammation is to remove damaged cells, harmful irritants, or toxic pathogens and begin the healing process.

When something harmful or irritating affects a part of our body, there is a biological response to try to remove it. This response takes the form of inflammation for the body to heal itself. While inflammation is not infection, an infection itself caused by bacteria, virus or fungus can trigger an inflammation process. Thus, you may appreciate the fact that inflammation in a true sense is beneficial when, for example, you develop a viral infection or if your back sustains a blow and the injured tissues need care and protection. The classical signs of acute inflammation are pain, heat, redness and fluid accumulation (swelling). Inflammation may also be associated with symptoms including: fever, chills, fatigue/loss of energy, muscle aches, headaches and loss of appetite.

Chain of Events that Occur during the Inflammation Process. Just as every country maintains an army, air force and naval units to defend itself from enemy forces, our body too has an excellent defense system (aka immune system) characterized by an arsenal of molecules. Acute inflammation is the initial response of the body to harmful stimuli and is characterized by the release of (a) specialized chemicals that create a conducive atmosphere for the defense molecules (pro-inflammatory molecules) to act and (b) specialized defense molecules/cells that fight the invaders. You may have heard from your physician or other sources terms including but not limited to: leukocytes, macrophages, dendritic cells, mast cells, bradykinin, histamine, and TNF. All these constitute our defense/immune system that is akin to a country’s defense system, with several layers of defenses of increasing specificity that culminate in the removal of pathogens and promote healing of any damaged tissue. Thus, in a perfect world or perfect body, the inflammatory process occurs just as it should, releasing defense/pro-inflammatory molecules when needed and then turning them off when the threat has been sufficiently addressed.

Negative Aspect of the Inflammation Process. Imagine if the defense forces take on their own country and its citizens! Similarly, chronic inflammation is characterized by a defense response that is aberrant, out of control and is not completely turned off or extinguished. Just like a slow-burning fire that does not ebb, in chronic inflammation the defense/pro-inflammatory molecules continue to be present in the body even when they are not needed. With the inflammation switch refusing to turn off, the body operates as if it is always under attack. Inflammation draws on our body’s energy and resources and having a constant, low-grade flow of powerful pro-inflammatory molecules can result in bodily damage with time. Furthermore, once this system goes out of control, it self-perpetuates and quickly spirals into disease in areas such as blood vessels (atherosclerosis), pancreatic tissue (diabetes), bones and joints (arthritis), digestive system (lactose and gluten intolerance), limbs, muscles and nerves (fibromyalgia), fat tissue (obesity), throat (thyroid issues)—just for starters. Sounds like the body going haywire in its own defense, with the immune system failing to distinguish between what is foreign and what is our own self, and making the body vulnerable to attacks from its own defense team.

Causes of Chronic Inflammation. As an aging researcher, I have learned that aging is one of the biggest risk factors for chronic inflammation because as we age, our bodies are less able to disarm the inflammatory process. Couple the aging process with a genetic predisposition, hypertension, or even smoking and it fuels the flames. In addition, stress (both physical and mental), environment, poor foods (sugary, processed, or fast food), high blood-insulin levels (type-2 diabetes), hormonal imbalance (estrogen and menopause) and obesity (leptin, adiponectin and other dietary hormone imbalance) are just a few of the factors that promote chronic inflammation.

Treatment for Chronic Inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) that include drugs like aspirin, ibuprofen, and naproxen, reduce the level of certain chemicals called prostaglandins that are involved in inflammation. Treatment with NSAIDs can lead to less swelling and less pain. However, extended use of NSAIDS can cause intestinal bleeding and serious damage to the stomach, liver and kidneys. Commonly referred to as steroids, glucocorticoids work to calm an overactive immune system and to decrease the level of inflammation in the body. People with multiple sclerosis, rheumatoid arthritis, lupus and other chronic inflammatory diseases are frequently prescribed these steroids to calm the inflammatory response. The problem is that these come with their own baggage of side effects and extended use of steroids can trigger osteoporosis, glaucoma, weight gain, high blood pressure and a lowered resistance to infections. Finally, a nutritious diet is the basis for good health. Vitamins D, E and C and folic acid have powerful anti-inflammatory actions, and foods high in omega 3s&6s, fruits, vegetables, fermented foods and unrefined carbohydrates may help to reduce the body's inflammatory response.

Yoga as an Anti-Inflammatory Therapy. There’s also good news for those of us who have a regular yoga practice. Several studies now report that a regular yoga practice (a) brings down the levels of stress hormones that promote inflammation (b) lowers the levels of a number of pro-inflammatory molecules in the body and brings down inflammation that is beneficial in conditions like arthritis, (c) reduces a subset of pro-inflammatory molecules called cytokines thereby relieving severe pain seen in diseases like fibromyalgia, and (d) inhibits inflammation that in turn weakens and even kills cancerous cells in people with cancer. See Stress, Inflammation and Yoga Practice to read one of the original studies.

In a study that confirms nearly all of the above observations, researchers at Ohio State University in Columbus divided 50 women with an average age of 41 into two groups: new to yoga and experts. The researchers than subjected these women to a battery of stress-inducing tasks, including holding their feet in extremely cold water or solving difficult math problems without the aid of a paper and pencil. Blood samples were taken several times before, during and after the stressful activities and measured for the levels of several pro inflammatory molecules. The research team found that women who were new to yoga had higher levels of nearly all the pro-inflammatory molecules tested and a much greater inflammatory response to the stressful tasks than women who were experts - suggesting that yoga may help to tune down the stress responses. See Adiponectin, leptin, and yoga practice.

Yoga’s beneficial effects on inflammation are not confined just to people with inflammatory conditions. Remember, I wrote a previous post about caregivers and how yoga could help these Karma yogis. Turns out that caregivers who exhibit high levels of stress-associated inflammation and who often don't have the time or energy to bring on a little relief from the stress of taking care of a loved one will benefit from a yoga practice even if it is for a brief period daily as it lowers stress-associated inflammation. In a study published in the  journal Psychoneuroendocrinology, researchers found that caregivers who participated in a yoga practice experienced a change in the response of 68 anti-inflammatory genes, leading to a global decrease in inflammation.

After writing this article in one sitting I am experiencing an unexplained burning pain in my fingers. So, guess what? It’s time for me to roll out the mat and do a few yoga stretches. What a cheap and effective therapy for combating inflammation!

Okay. Back to Aging.

by Brad

Okay. It’s been a while, as I’ve been busy with writing NIH grants and papers, as well as traveling. So it's time to get back to one of the central points of this blog: what is aging? It turns out this is no more clear than trying to define yoga. When I joined the Buck Institute for Research on Aging some 11 years ago, I was surprised and a little chagrined to discover how unsettled and wide open this central question of aging biology was.

This was not my original field of study, but as a chemist and structural biologist working at a major teaching university, I saw a prime opportunity to make a career shift by joining the Buck Institute and using my skill to elucidate molecular mechanisms of aging. But I had no idea how many competing theories existed on this subject, ranging from rather oblique terms like ”antagonistic pleotrophy” to more familiar ones—at least to a chemist—like “entropy” and “free radical damage.” So the other day when there was some news coverage in the New York Times of a breakthrough in aging research (see NY Times article here), I saw this as a chance to tackle this subject. The article, titled “In Body’s Shield Against Cancer, a Culprit in Aging May Lurk,” came out of the Mayo Clinic and looked at the role of senescent cells in aging (see original research here).

When cells reach a point of pathological state, either through telomere shortening or some other aberration or damage, a sequence of events are put into place that either sends these cells into a cell death pathway, or into a state of senescence, a kind of limbo non-dividing state. One reason this occurs is to avoid the formation of a cancerous cell, which the organism obviously wants to avoid. Cells that become senescent were usually thought of as sequestered cells that no longer posed a problem to the organism, but were also no longer productive. However, what this new study showed is that these senescent cells appear to have more damaging effects on neighboring cells and tissues, possibly through a secreted inflammatory signal.

Manzanita by Brad Gibson

By constructing a mutant mouse strain where the researchers could target and kill these senescent cells without harming the healthy cells, researchers found that it had a significant beneficial effect on the health of the mice, and that they lived longer. There is a lot of follow-up work to be done to confirm these studies in “normal mice” as well as in humans. In any case, the data are highly intriguing. It is also worth pointing out that when asked whether this would cure aging, the scientists were much more cautious, as they clearly understood that this is probably only one of many mechanisms that are contributing to aging. Nonetheless, it is interesting to see how inflammation comes up repeatedly as a cause or at least a driver of many age-related disease, from Alzheimer’s disease to diabetes.

One question that I would like to get back to is: what can we do as individuals to influence this process? What are the conditions that lead to cellular senescence versus cell death, for example, and what are the physiological and environmental determinants that cause as a cell to enter this critical state in the first place? If we knew the answers to these questions and as well other questions of this type, we might be able to critically examine how we can influence are own rate of aging. This question is related but separate from how we can reduce and/or cope with various age-related losses and pathologies as they emerge. Both questions will be critical to answer to reach an understanding on the practice of healthy aging.  How yoga might be a part of that practice is what we are trying to address here….

What is a Yoga Practice?

by Brad

A year or so ago I was talking with a colleague about a genomics study he was planning that was going to look at exercise and aging. Previously, he and his colleagues had shown that resistance exercise training had a significant effect on the genes that were transcribed in muscle tissue, and that the older people undergoing this training had gene transcription profiles that resembled much younger people. This time around they were planning a more nuanced study and would look at several exercise regimens, including yoga. I remembered asking him what type of yoga practice they planned to use, and was met with a slightly confused look. He wasn’t sure, but thought it was a “standard practice” involving some stretching and aerobic components. When I inquired further about whether it was Iyengar style or one of those high-energy aerobic practices (like Ashtanga Vinyasa), I realized that our discussion had reached a dead end. He had no idea what I was talking about.

Photo from Yoga: The Poetry of the Body by Yee and Zolotow

So when I ran across another article today on Yoga for Back Pain that was mentioned in the Science Times section of this weeks NY Times (see here), I decided to take a little closer look at what the actual practice was. I also looked back at the Ornish and Blackburn study I discussed a couple weeks ago (see here), as well as a few other studies I had run across. I was interested in seeing how well the practice was described and whether it made in sense.

I was surprised to find that the most high profile of these studies, the 2008 Ornish and Blackburn study (see here), had the least detail. What they described as yoga for stress management consisted of “gentle yoga-based stretching, breathing, meditation, imagery, and progressive relaxation techniques 60 min/day, 6 days/week”. In contrast, a study published this summer by Dr. Fishman on osteoporosis and yoga (see here ) was considerably more comprehensive, listing all 10 yoga poses by both Anglicized and Indian names, e.g., “Upward and Downward Dog poses (Adho Mukha Svanasana and Urdhva Mukha Svanasana),” as well providing an appendix of 13 figures illustrating each poses. It should be pointed out that the lead author of this study was extremely familiar with yoga, having practiced it in India for three before attending medical school.

Another group that was fairly thorough in their description was Sherman et al. which just appeared on-line a couple days ago (see here) in their study of chronic low back pain, where they describe a viniyoga practice consisting of 5-11 poses (with pictorial diagrams referenced from earlier 2005 paper by this same group (see here). Interestingly, these authors also provided the credential for the teachers as “instructors with at least 500 hours of viniyoga training, 5 years of teaching experience, and familiarity with the selected postures and who were briefed by our yoga consultant.” This paper also gave a defense of their yoga style (viniyoga), as “a therapeutically oriented style of yoga that emphasizes safety and is relatively easy to learn.” 

Iyengar-style yoga was used in another study examining stress and inflammation by Kiecolt-Glaser, et al (see here) because it ”emphasizes the use of props to help students achieve precise postures safely and comfortably according to their particular body types and need”. In this latter study, the 12 poses and timing of each were well described and was constant, and apparently selected “based on their purported relationship to immune function and/or restorative effects.”

Obviously not everyone is going to agree with what is a good or best yoga practice for stress, back pain, osteoporosis or whatever. But what is clear is that these studies need to provide a through description of the regimen (time, poses, teacher qualifications) and their overall rationale, so that if someone wanted to reproduce this study or compare it with another, they shouldn’t be in the dark as to what the yoga practice was. In the end, it’s you who is going to have to decide on what to believe, as the standards for comparing these practices, pose sequences, and yoga styles are confusing at best. Maybe Nina and Baxter can comment on this, as I’m not an expert.

FRIDAY Q&A

Q: I'm wondering to what extent, and at what rate, we should expect to be able to increase our flexibility as we continue to age. I've made significant progress over the years, and have generally learned how to be mindful enough not to overdo. However, every so often I overstretch without realizing it - whether it's my back trying to get a fuller forward bend, or my Achilles tendon while pushing the envelope. I'm in my 50s and have been doing regular yoga for about 5 years. It's made an immense difference in my core strength and balance and flexibility and I'm much less injury prone now. And yet, every so often, it's my yoga practice that puts me out of commission.

A: Baxter and I discussed your question, and he agrees with me that there is no fixed extent or rate for increasing flexibility as we age, as this will differ from person to person. His advice is to maximize the effectiveness of your stretches while minimizing potential injury by holding your stretches longer rather than pushing harder. He mentioned that it takes at least 45 seconds to get your muscle to fully release. And my kinesiology teacher taught me that in order to change the resting length of the muscle (the length the muscle returns to after stretching), you need to stretch it for 90 seconds. So I use a timing of 90 seconds for many of my stretches. --Nina

Q: Does yoga have any good stretches for a 60 year old stiff person?

A: Yoga has a very large number of poses that allow you to stretch a very wide variety of muscles, no matter how stiff you are. So the first question to ask yourself is: where exactly am I stiff? Some of us are stiff all over and some of us are flexible all over, but it turns out that many of us are flexible in some areas and stiff in others. Identifying which areas you need to stretch will help you chose the poses that will be most helpful to you. That being said, there are a couple of poses that we highly recommend for their versatility. Downward-Facing Dog pose is especially wonderful because it stretches your legs, hips, shoulders and arms, all at the same time.

If this pose is too demanding, you can do an easy variation, Half Dog pose (also called Right Angle pose). With your hands at shoulder-height on the wall or resting on the surface of a table, walk back so your hips are directly over your feet and your arms are parallel to the floor.

Baxter recommend that you warm up for these poses with some dynamic movement, such as swinging your arms above your head or moving your legs around in your hip joints. --Nina

Q: How would one go about investigating the effects of yoga on aging scientifically?

A: This question is intriguing and so important that Brad will devote an entire post to the subject sometime soon.

Q: Just curious about how autoimmune diseases are related to aging? Some seem to be inflammatory conditions I think, and that makes me wonder about allergies, yoga and aging.

A: This is a very big and complicated question! And there’s no quick, simple answer, as the mechanisms behind many of these diseases (not to mention aging itself) are not fully understood. But Baxter says, “Not all autoimmune diseases are created equal.” Different autoimmune diseases arise at different stages in life, so not all are related to aging. Also, not all are related to inflammatory conditions. So that’s why we’ve decided that on this blog we’ll discuss the autoimmune diseases associated with aging individually, over time. Is there any particular disease that concerns you?

We are going to try to do a Q&A every Friday, so keep the questions coming. You can leave a question in a comment or you can email a comment to us at the address shown under "Contact Us" in the right-hand column.

Alcohol intake increases LDL cholesterol, in some people

Occasionally I get emails from people experiencing odd fluctuations in health markers, and trying to figure out what is causing those fluctuations. Spikes in LDL cholesterol without any change in diet seem to be a common occurrence, especially in men.

LDL cholesterol is a reflection of many things. It is one of the least useful measures in standard lipid profiles, as a predictor of future health problems. Nevertheless, if one’s diet is not changing, whether it is high or low in fat, significant fluctuations in LDL cholesterol may signal a change in inflammatory status. Generally speaking, the more systemic inflammation, the higher is the measured LDL cholesterol.

Corella and colleagues (2001) looked into alcohol consumption and its effect on LDL cholesterol, as part of the Framingham Offspring Study. They split the data into three genotypes, which are allele combinations. Alleles are genes variations; that is, they are variations in the sections of DNA that have been identified as coding for observable traits. The table below summarizes what they have found. Take a look at the last two columns on the right.

As you can see, for men with the E2 genotype, alcohol consumption significantly decreases LDL cholesterol. For men with the E4 genotype, alcohol consumption significantly increases LDL cholesterol. No significant effects were observed in women. The figure below illustrates the magnitude of the effects observed in men.

On average, alcohol consumption was moderate, around 15 g per day, and did not vary significantly based on genotype. This is important. Otherwise one could argue that a particular genotype predisposed individuals to drink more, which would be a major confounder in this study. Other confounders were also ruled out through multivariate controls - e.g., fat and calorie intake, and smoking.

Alcohol consumption in moderation seems, on average, to be beneficial. But for some individuals, particularly men with a certain genotype, it may be advisable to completely abstain from alcohol consumption. Who are those folks? They are the ones for whom LDL cholesterol goes up significantly following moderate alcohol consumption.

Low omega-6 to omega-3 ratio: Grain-fed meats or industrial vegetable oils?

Just a little note on the use of language. Clearly there is no such a thing as grain-fed or grass-fed beef, because one does not feed beef anything. One feeds cattle grain or grass, and then the resulting beef is said to be “grain-fed” or “grass-fed”. It is a manner of speaking that facilitates discourse, which is why it is used here.

To compensate for this digression, let me show you a graph, which pretty much summarizes the "punch line" of this post. The graph below shows the omega-6 fat contents of 1 lb (454 g) of grain-fed beef and 1 tablespoon (roughly 14 g) of a typical industrial vegetable oil (safflower oil). As you can see, there is a lot more omega-6 in the much smaller amount of industrial vegetable oil. A gram-for-gram comparison would practically make the beef content bar disappear.

It has been estimated that our Paleolithic ancestors consumed a diet with an omega-6 to omega-3 ratio of about 1. While other estimates exist, the general consensus seems to be that that ratio was not much greater than 5. Western diets, in contrast, typically have omega-6 to omega-3 ratios of between 15 and 40. In some cases, the ratio is even higher.

Omega-6 fats are essential fats, meaning that they must be part of one’s diet. Fats make up about 60 percent of our brain. About 20 percent is made up of omega-6 and omega-3 fats. The primary omega-6 fat found in our brain is arachidonic acid, which is either synthesized by our body based on linoleic acid from plant foods or obtained directly from animal foods such as meat and eggs. The predominant omega-3 fat found in our brain is docosahexaenoic acid (DHA), of which certain types of fish and algae are rich sources.

Inflammation is an important process in the human body, without which wounds would never heal. Incidentally, muscle gain would not occur without inflammation either. Strength training causes muscle damage and inflammation, after which recovery leads to muscle gain. Omega-6 fats play an important role in inflammation. Generally, they are pro-inflammatory.

Too much inflammation, particularly in a chronic fashion, is believed to be very detrimental to our health. A very high omega-6 to omega-3 ratio seems to cause excessive and chronic inflammation. The reason is that omega-3 fats are generally anti-inflammatory, counteracting the pro-inflammatory action of omega-6 fats. Over time, a very high omega-6 to omega-3 ratio is believed to cause a number of Western diseases. Among them are cardiovascular complications, cancer, and various autoimmune diseases.

So, should you worry about too much omega-6 from grain-fed meats?

If you think that the answer is “yes”, consider this. Apparently the (arguably) longest-living group in the world, the non-Westernized Okinawans, consume plenty of pork. Pork is a staple of their traditional diet. It is true that the average cut will have an omega-6 to omega-3 ratio of more than 7, which is not very favorable. Pork in general, whether grain-fed or not, is relatively high in omega-6 fats. As a side note, pork is not a good source of linoleic acid (found in plants), even though it is a rich source of arachidonic acid, the omega-6 fat synthesized from linoleic acid by various animals.

It is difficult to estimate the exact amounts of omega-6 and omega-3 fats from grain-fed cuts of meat; different sources provide different estimates. Here are some reasonable estimates based on various sources, including Nutritiondata.com. A typical 100 g portion of grain-fed pork should contain about 690 mg of omega-6 fats, and 120 mg of omega-3 fats. A typical 100 g portion of grain-fed beef should have about 234 mg of omega-6 fats, and 12 mg of omega-3 fats. It does not take that much omega-3 to counterbalance the omega-6 obtained from grain-fed pork or beef, even if one eats a lot of them. Two softgels of fish oil will normally contain about 720 mg of omega-3 fats (they will also come with 280 mg of omega-6 fats). Three sardines will have over 2 g of omega-3 fats, and less than 200 mg of omega-6 fats.

Industrial vegetable oils (made from, e.g., safflower seeds, soybean, and sunflower seeds) are very, very rich sources of omega-6 fats, in the form of linoleic acid. There is a lot more omega-6 in them than in grain-fed meats. One tablespoon of safflower oil contains over 10 g of omega-6 fats, in the form of linoleic acid, and virtually zero omega-3 fats. About 2 kg (4.4 lbs) of grain-fed pork, and 5 kg (11 lbs) of grain-fed beef will give you that much omega-6; but they will also come with omega-3.

How much fish oil does one need to neutralize 10 g of pure omega-6 fats? A lot! And there is a problem. Excessive fish oil consumption may be toxic to the liver.

If you cook with industrial vegetable oils rich in linoleic acid (this excludes olive and coconut oils), or eat out a lot in restaurants that use them (the vast majority), you will probably be consuming significantly more than 10 g of omega-6 fats per day. The likely negative health effects of eating grain-fed meats pales in comparison with the likely negative health effects of this much omega-6 fats from industrial vegetable oils.

You should reduce as much as possible your consumption of industrial vegetable oils rich in linoleic acid, as well as other products that use them (e.g., margarine). Keep in mind that industrial vegetable oils are in many, many industrialized foods; even canned sardines, if they are canned with soybean oil.

It is also advisable to couple this with moderate consumption of fish rich in omega-3, such as sardines and salmon. (See this post for a sardine recipe.) Taking large doses of fish oil every day may not be such a good idea.

Should you also consume only grass-fed meat? Do it if you can. But, if you cannot, maybe you shouldn’t worry too much about it. This also applies to eggs, dairy, and other animal products.

References:

Elliott, W.H., & Elliott, D.C. (2009). Biochemistry and molecular biology. New York: NY: Oxford University Press.

Ramsden, C.E., Faurot, K.R., Carrera-Bastos, P., Cordain, L., De Lorgeril, M., & Sperling (2009). Dietary fat quality and coronary heart disease prevention: A unified theory based on evolutionary, historical, global, and modern perspectives. Current Treatment Options in Cardiovascular Medicine, 11(4), 289-301.

Schmidt, M.A. (1997). Smart fats: How dietary fats and oils affect mental, physical and emotional intelligence. Berkeley, CA: North Atlantic Books.

Adiponectin and tumor necrosis factor-alpha levels after a high saturated fat meal

This is one of those interesting studies where the authors start with some pre-conceived assumptions and end up concluding something else, some way toward the opposite of what they assumed.

My final interpretation of the study results is a bit different though. It suggests that the results are actually the opposite of what the authors originally assumed.

The authors of the study (Poppitt et al., 2008; full reference at the end of this post) start by stating that since “… dietary fat is associated with increased lipid storage, weight gain, and obesity …” it is important to study the effect of dietary fat intake on the blood levels of certain substances that are associated with lipid disorders, weight gain and obesity.

In short, the authors start from the assumption that dietary fat is bad. By the way, this type of indictment of all fats is not very common these days. Usually saturated fat is the target.

Since dietary fat is assumed to be bad for us, that justifies the authors’ goal of studying the effect of dietary fat on certain hormones associated with bad health, including the body fat-secreted hormones adiponectin and tumor necrosis factor-alpha. Low levels of serum adiponectin, and elevated levels of tumor necrosis factor-alpha, are associated with various health complications.

In the study, a high-fat test meal with approximately 59 g of fat (71% of energy as fat) was given at breakfast on two occasions to 18 healthy and lean men. These men had, on average, 23 years of age, a 31-inch waist, and a body mass index of 22.9. In other words, they were young and fit.

Two fatty meal variations were used, one with a lot more saturated fat than the other. Their ratio of saturated:unsaturated fatty acids was 71:29 for the high saturated fat meal, and 55:45 for the other. The table below provides a more detailed picture of the fat composition of the meals. The authors refer to these meals as instances of “acute intake of dietary lipid”.

Lunch, snack and dinner meals were also served to the participants. Those meals were nearly fat-free, with 1 to 3 g of fat only; apparently to help the participants “recover” from the high fat meal. They included plenty of refined grains (e.g., pasta) and fruit juices. Way to go; give these folks refined carbohydrates and sugars galore to help them recover from the “damage” done by the high fat meal!

Blood samples were collected at 0 (baseline), 1, 3, and 6 h for the measurement of various substances, including the body fat hormones adiponectin and tumor necrosis factor-alpha levels.

The figure below shows the variation in adiponectin levels at several times after the meal. The black circles are for the high saturated fat group, and the white circles for the other group. Adiponectin levels do not really start at the same level for both groups, which makes the graph a bit unclear; to better interpret the graph it may be a good idea to simply ignore the first (white) circle at the zero mark on the vertical axis. Also, no hormone levels were negative, of course; the zero on the vertical axis represents a reference value.

As we can see from the figure above, adiponectin levels go up for both groups after the fatty meal, and end up higher than they started for both groups; more for the high saturated fat than for the low saturated fat group. They are at very similar levels at the 24 h mark, but the levels at 24 h for the high saturated fat group appear to be a lot higher than they were right after the fatty meal. (The start point for the high saturated fat group being the first black circle from the left on the graph.) None of the differences are reported as significant. This is not surprising, given the small sample.

The figure below shows the variation in tumor necrosis factor-alpha levels at several times after the meal. This is an even more interesting one, because it suggests a possible negative effect of the low fat meals.

In terms of tumor necrosis factor-alpha levels, the figure above suggests that both groups end up higher than they started, by about the same amount, which is not very good. (With tumor necrosis factor-alpha, unlike adiponectin, the less you have the better - so to speak, the hormone has important functions.) Again, none of the differences, with the exception of one, are reported as significant. The exception is the tumor necrosis factor-alpha level at 6 h for the low saturated fat group, which is significantly lower. But that difference disappears at the 10 h mark, never to be seen again.

Interestingly, note that tumor necrosis factor-alpha levels go up very clearly after the additional meals, which were low fat meals rich in refined carbohydrate and sugars. The variation in adiponectin is not as clearly associated with the additional meals. The points at which those meals were served are indicated by the arrows at the top of the graph; first arrow from left for lunch, second for a snack, and third arrow for dinner.

The conclusion by the authors of the study was that there is “… no evidence from this study of lean, healthy male subjects that the adipose hormone adiponectin is sensitive to acute intake of dietary lipid or to an increase in fatty acid saturation.” They do acknowledge the reduction in tumor necrosis factor-alpha up until the start of the low fat meals, and say that the “mechanism leading to the decrease in TNF-alpha on the high SFA:USFA treatment in our trial is unknown to us.”

My interpretation of this study is that, at least for young and lean men:

- There is some evidence that dietary saturated fat intake leads to increased levels of circulating adiponectin and decreased levels of tumor necrosis factor-alpha in the first few hours after a meal rich in saturated fat; with plenty of palmitic acid in it, by the way, of which animal fat is a great source. These are desirable and health-promoting hormonal responses.

- These is some evidence that meals high in refined carbohydrates and sugars increase levels of circulating tumor necrosis factor-alpha in the hours following the meals. Elevated levels of tumor necrosis factor-alpha are not good news; something that I guess is implied by the name of the hormone.

- There is some evidence that dietary saturated fat intake leads to an increase in adiponectin levels 24 h after a high fat meal, even when it is followed by low fat meals high in refined carbohydrates and sugars. This suggests a protective effect, which is in line with the hypothesis that adiponectin is not only a health marker by also a health-promoting hormone.

Due to the small sample used, none of the conclusions above is based on statistically significant results. More research is needed in the future, with larger samples. I am not sure it will happen though. This study’s findings were obviously accidental, and saturated fat phobia is still widespread.

Adiponectin is highly correlated with body weight, particularly weight associated with body fat mass. So, if you were able to achieve weight loss through a low carbohydrate diet involving a high consumption of saturated fat, there is absolutely no need to change that based on the results of this study.

Plus, saturated fat has the added benefit that it increases HDL cholesterol, the “good” cholesterol.

Reference:

Poppitt, S.D. et al. (2008). Postprandial response of adiponectin, interleukin-6, tumor necrosis factor-α, and C-reactive protein to a high-fat dietary load. Nutrition, 24(4), 322-329.

Adiponectin, inflammation, diabetes, and heart disease

Humans, like many animals, evolved to be episodic eaters and spend most of their time fasting. Body fat is the main store of energy in the human body. Excess dietary carbohydrates and fat are stored as body fat, in specialized cells known as adipocytes. Excess dietary protein is not normally stored as body fat.

Adipocytes can be seen as being part of a very important and distributed endocrine organ, being responsible for the release of many different hormones into the bloodstream. One of these hormones is adiponectin. Other important hormones secreted by body fat tissue are leptin and tumor necrosis factor-alpha.

Among hormones, adiponectin is particularly interesting because it is negatively correlated with body fat mass. That is, unlike other hormones such as leptin and tumor necrosis factor-alpha, a decrease in body fat mass (a well known health marker) is associated with an increase in adiponectin. This has led some researchers to speculate that adiponectin is a causative factor that promotes health, in addition to being a health marker.

Jung and colleagues (2008; full reference at the end of this post) studied 78 obese individuals (41 females) who participated in an exercise program during 12 weeks. The exercise program involved mostly low intensity aerobic activities, such as brisk walking. The individuals also took an appetite suppressant, with the goal of reducing their calorie intake by about 500 kcal per day.

The table below (click on it to enlarge) shows various measurements for the participants before and after the 12-week intervention.

From the table above we can say that there were significant reductions in weight, body mass index (BMI), waist and hip circumference, waist-to-hip ratio (WHR), total body fat, and total fasting cholesterol and triglycerides. However, the participants were still obese at the end of the intervention, with an average body fat percentage of 35.5.

The table below shows the concentrations of various hormones secreted by body fat tissue, as well as other types of tissue, before and after the 12-week intervention. These hormones are all believed to be health indicators and/or health causes.

We see from the table above that the hormonal changes were all significant (all at the P < .001 level except one, at the P < .05 level), and all indicative of health improvements. The serum concentrations of all hormones decreased, with two exceptions – adiponectin and interleukin-10, which increased. Interleukin-10 is an anti-inflammatory hormone produced by white blood cells. The most significant increase of the two was by far in adiponectin (P = .001, versus P = .041 for interleukin-10).

One of the most promising effects of adiponectin seems to be an increase in insulin sensitivity. This effect appears to be unrelated to any effects on insulin secretion. That is, adiponectin seems to act directly on various cells, including muscle cells, increasing their ability to clear glucose from the blood. This effect seems to be one of the underlying, and previously unknown, reasons why loss of body fat improves health in those who suffer from diabetes type 2.

Increased serum adiponectin has been found to be significantly associated with: decreased body fat and particularly visceral fat, decreased risk of developing diabetes type 2, decreased blood pressure, and decreased fasting triglycerides.

Adiponectin appears to also have anti-inflammatory and athero-protective properties.

On average, women have higher levels of serum adiponectin than men.

According to Giannessi and colleagues (2007) administration of adiponectin in mice has shown positive results. Since research on adiponectin is new, it will probably be some time until related drugs are developed. Giannessi and colleagues also note that fish oil and vanadium salts may increase the synthesis and release of adiponectin.

So far it seems that the most effective way of increasing adiponectin levels is weight loss, particularly through body fat loss. Even as new drugs are developed, this will likely remain the most natural and safe way of increasing adiponectin levels.

All of this helps in the identification of missing links between body fat loss and health improvement. It seems that losing body fat has an effect similar to that of supplementation; it increases the blood concentration of a health-promoting substance - adiponectin!

References:

Giannessi, D., Maltinti, M., & Del Ry, S. (2007). Adiponectin circulating levels: A new emerging biomarker of cardiovascular risk. Pharmacological Research, 56(6), 459-467.

Gil-Campos, M., Cañete, R., & Gil, A. (2004). Adiponectin, the missing link in insulin resistance and obesity. Clinical Nutrition, 23(5), 963-974.

Jung, S.H. et al. (2008). Effect of weight loss on some serum cytokines in human obesity: increase in IL-10 after weight loss. The Journal of Nutritional Biochemistry, 19(6), 371-375.

Body fat and disease: How much body fat can I lose in one day?

Body fat is not an inert deposit of energy. It can be seen as a distributed endocrine organ. Body fat cells, or adipocytes, secrete a number of different hormones into the bloodstream. Major hormones secreted by adipose tissue are adiponectin and leptin.

Estrogen is also secreted by body fat, which is one of the reasons why obesity is associated with infertility. (Yes, abnormally high levels of estrogen can reduce fertility in both men and women.) Moreover, body fat secretes tumor necrosis factor-alpha, a hormone that is associated with generalized inflammation and a number of diseases, including cancer, when in excess.

The reduction in circulating tumor necrosis factor-alpha and other pro-inflammatory hormones as one loses weight is one reason why non-obese people usually experience fewer illness symptoms than those who are obese in any given year, other things being equal. For example, the non-obese will have fewer illness episodes that require full rest during the flu season. In those who are obese, the inflammatory response accompanying an illness (which is necessary for recovery) will often be exaggerated.

The exaggerated inflammatory response to illness often seen in the obese is one indication that obesity in an unnatural state for humans. It is reasonable to assume that it was non-adaptive for our Paleolithic ancestors to be unable to perform daily activities because of an illness. The adaptive response would be physical discomfort, but not to the extent that one would require full rest for a few days to fully recover.

Inflammation markers such as C-reactive protein are positively correlated with body fat. As body fat increases, so does inflammation throughout the body. Lipid metabolism is negatively affected by excessive body fat, and so is glucose metabolism. Obesity is associated with leptin and insulin resistance, which are precursors of diabetes type 2.

Some body fat is necessary for survival; that is normally called essential body fat. The table below (from Wikipedia) shows various levels of body fat, including essential levels. Also shown are body fat levels found in athletes, as well as fit, “not so fit” (indicated as "Acceptable"), and obese individuals. Women normally have higher healthy levels of body fat than men.

If one is obese, losing body fat becomes a very high priority for health reasons.

There are many ways in which body fat can be measured.

When one loses body fat through fasting, the number of adipocytes is not actually reduced. It is the amount of fat stored in adipocytes that is reduced.

How much body fat can a person lose in one day?

Let us consider a man, John, whose weight is 170 lbs (77 kg), and whose body fat percentage is 30 percent. John carries around 51 lbs (23 kg) of body fat. Standing up is, for John, a form of resistance exercise. So is climbing stairs.

During a 24-hour fast, John’s basal metabolic rate is estimated at about 2,550 kcal/day. This is the number of calories John would spend doing nothing the whole day. It can vary a lot for different individuals; here it is calculated as 15 times John’s weight in lbs.

The 2,550 kcal/day is likely an overestimation for John, because the body adjusts its metabolic rate downwards during a fast, leading to fewer calories being burned.

Typically women have lower basal metabolic rates than men of equal weight.

For the sake of discussion, we expect each gram of John’s body fat to contribute about 8 kcals of energy, assuming a rate of conversion of body fat to calories of about 90 percent.

Thus during a 24-hour fast John burns about 318 g of fat, or about 0.7 lbs. In reality, the actual amount may be lower (e.g., 0.35 lbs), because of the body's own down-regulation of its basal metabolic rate during a fast. This down-regulation varies widely across different individuals, and is generally small.

Many people think that this is not much for the effort. The reality is that body fat loss is a long term game, and cannot be achieved through fasting alone; this is a discussion for another post.

It is worth noting that intermittent fasting (e.g., one 24-hour fast per week) has many other health benefits, even if no overall calorie restriction occurs. That is, intermittent fasting is associated with health benefits even if one fasts every other day, and eats twice one's normal intake on the non-fasting days.

Some of the calories being burned during John's 24-hour fast will be from glucose, mostly from John’s glycogen reserves in the liver if he is at rest. Muscle glycogen stores, which store more glucose substrate (i.e., material for production of glucose) than liver glycogen, are mobilized primarily through anaerobic exercise.

Very few muscle-derived calories end up being used through the protein and glycogen breakdown pathways in a 24-hour fast. John’s liver glycogen reserves, plus the body’s own self-regulation, will largely spare muscle tissue.

The idea that one has to eat every few hours to avoid losing muscle tissue is complete nonsense. Muscle buildup and loss happen all the time through amino acid turnover.

Net muscle gain occurs when the balance is tipped in favor of buildup, to which resistance exercise and the right hormonal balance (including elevated levels of insulin) contribute.

One of the best ways to lose muscle tissue is lack of use. If John's arm were immobilized in a cast, he would lose muscle tissue in that arm even if he ate every 30 minutes.

Longer fasts (e.g., lasting multiple days, with only water being consumed) will invariably lead to some (possibly significant) muscle breakdown, as muscle is the main store of glucose-generating substrate in the human body.

In a 24-hour fast (a relatively short fast), the body will adjust its metabolism so that most of its energy needs are met by fat and related byproducts. This includes ketones, which are produced by the liver based on dietary and body fat.

How come some people can easily lose 2 or 3 pounds of weight in one day?

Well, it is not body fat that is being lost, or muscle. It is water, which may account for as much as 75 percent of one’s body weight.

References:

Elliott, W.H., & Elliott, D.C. (2009). Biochemistry and molecular biology. New York: NY: Oxford University Press.

Fleck, S.J., & Kraemer, W.J. (2004). Designing resistance training programs. Champaign, IL: Human Kinetics.

Large, V., Peroni, O., Letexier, D., Ray, H., & Beylot, M. (2004). Metabolism of lipids in human white adipocyte. Diabetes & Metabolism, 30(4), 294-309.

Intermittent fasting and reduced inflammation

A recent post on the Primal Wisdom blog led me to do go back to some of the research on an approach to dieting that I tried myself, with some positive results. The approach is known as intermittent fasting (IF). I also found an excellent blog post by Dr. Michael Eades on IF (see here).

Typically IF involves fasting every other day. On the non-fasting days, food and water consumption is not restricted in any way. On fasting days, only water is consumed. Variations of this approach usually involve replacing water with juice, and having an eating window of only a few hours within longer periods – e.g., fasting 19 hours and then eating during a window of 5 hours, for each period of 24 hours.

IF is different from calorie restriction (CR), in that in the latter total daily calorie intake is restricted to a somewhat fixed amount, below one’s basal metabolic rate (the number of calories needed to maintain one’s current weight). In CR the calorie restriction is not normally achieved through fasting, but through careful portion size control and selection of foods based on calorie content. Having said that, some prominent CR practitioners also practice IF.

One interesting aspect of IF studies is that often they do not involve any calorie reduction in the participants' diet; that is, individuals consume the same amount of calories that they would if they were not fasting at all. In other words, they consume 2X outside their fasting window; where X would be their normal caloric consumption without fasting.

Yet, the benefits of IF are still achieved. For example, during Ramadan, the levels of inflammation markers and factors, such as C-reactive protein (CRP) and homocysteine, go down, and remain low for several weeks after IF is interrupted. These inflammation markers and factors are known to be strongly associated with heart disease.

In fact, animal studies suggest that virtually identical benefits can be obtained through IF in terms of increased lifespan and disease resistance, as those normally associated with CR. Again, this is somewhat surprising because often IF does not involve any reduction in calories consumed.

Fasting promotes increased levels of growth hormone in humans. A decline in growth hormone levels is associated with aging. Thus, increased circulating growth hormones may be one of the mechanisms by which IF may affect lifespan.

There have been some reports of IF being associated with negative effects on health, but I suspect that they are associated with gorging on refined carbohydrates and sugars during the eating window. Refined carbohydrates and sugars promote inflammation, and IF reduces inflammation. It is conceivable that a very high consumption of refined carbohydrates and sugars during the eating window may completely negate the benefits of IF, particularly if one is doing a half-hearted version of IF to start with.

A combination of IF and a diet low in refined carbohydrates and sugars probably makes sense in terms of our evolved physiology. Our Stone Age ancestors had to fast on a regular basis, based on the availability of food – there were no refrigerators or grocery stores during the vast majority of our evolutionary history as a species. When food was available, it was consumed to satiety. In other words, our Stone Age ancestors practiced IF, against their will. Because of that, this is the state in which our body evolved to operate optimally.

If you watch enough episodes of the TV show Survivorman, you will probably notice that it is very unlikely that our Stone Age ancestors had access to enough calories to survive on plant foods only, assuming that they faced problems similar to those in the show.

Our digestive tract has evolved over millions of years from a mostly vegetarian diet, practiced by our Australopithecine ancestors, to a primarily carnivorous diet, adopted by human ancestors as far back as Homo erectus, and probably Homo habilis. Given that, only the recent invention of refined carbohydrates and sugars has given us access to enough dense carbohydrate sources of calories.

So, a combination of IF and a diet low in (or devoid of) refined carbohydrates and sugars makes evolutionary sense, and is probably why so many people who adopt Paleolithic diets see so many improvements in health markers such as inflammation markers, blood pressure, and HDL cholesterol.