Sunday, May 15, 2011

Omega-3 Fatty Acids for Muscle Growth: Promising Potential

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Can omega-3 fatty acids boost muscle growth? Well, let's just say that I'm very excited to report about the results from two new studies that sought to answer that question. The results? I will tell you all about in this article.

I don't have time to keep up with the going-on's in the forums, and I don't know if the weight training community has taken note of these studies yet. I hope they will, because these findings are - by far - the most interesting thing I have come across in a long time.

First, I'd like to do a brief review on omega-3 (n-3) fats and how they work. And since we're on the topic, let's also do a quick no-BS review on what they are actually good for.

(This article is somewhat long and I wrote the n-3 health and fat loss review since I thought I'd give myself a refresher course on the topic. I don't talk about the new studies mentioned in the introduction until the latter 2/3 of this review. If you don't give a damn about the effects of n-3 intake on health and fat loss, feel free to skip the first part of the article and go to "Omega-3 Fatty Acids and Leucine Resistance.").


Omega-3 Fatty Acids and Your Cell Membranes 


Since most people's eyes glaze over when someone starts talking cell biology, imagine your cell as an avocado. Picture the avocado with myriads of pins buried in it.





This is your cell. The pins are membrane proteins, some of which are nutrient transporters for glucose, amino acids, and so forth. The dark skin and the edible green flesh is the plasma membrane, which consists of two thin layers made of fatty acids. N-3 supplementation has the potential of altering this part of the cell. Generally speaking, plasma membranes with a higher % EPA and DHA enrichment are healthier; they have the potential of modulating signals in between the white pins/plasma proteins and the avocado core. The "avocado core" is the cell interior, which react in response to signals from the cell exterior.

Pins: are called integral membrane proteins."Integral membrane protein" is a catch-all term for proteins that shuttle nutrients or signals to the cell itself, or the avocado core if you will. Included in these are glucose transporter type 4 (GLUT4) and amino acid transporters, for example. Pretend these pins had the ability to move up and down through the skin and flesh of the avocado. The word for this is translocation, or protein targeting depending on how fancy you want to get.

Skin and edible part: this is the cell membrane, also called the lipid bilayer, or the phospolipid bilayer. A large part of these layers consists of fatty acids and their structure is highly dependent on the fat composition of your diet. This is where n-3 fatty acids exert their effect; by their incorporation into lipid bilayers, n-3 acids can modulate signals between the pins to the cell itself. In particular, it is the omega-3 series members docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that facilitates these processes. When I talk about "n-3 supplementation/intake", it is often in specific reference to EPA and DHA, and not ALA.

Avocado core: cell interior, where transcription (i.e. muscle protein synthesis) takes place based on feedback from the cell exterior and pins.

Obviously, this is a vastly simplified version of the cell, but I've found the avocado analogy somewhat helpful in dumbing down the cell and its workings.

The fact that n-3 is incorporated into the plasma membrane of all your cells - be it brain cells, muscle cells, and so forth - explains how these fatty acid can have so diverse effects on human physiology and health. Let's take a look at what they do.


Omega-3 Fatty Acids: Effects on Health 

Controlled studies have clearly established the positive influence of n-3 intake on cardiovascular health. The role of n-3 as a modulator of inflammation is also well recognized and the fact that omega-3 fats down-regulate genes involved in chronic inflammation makes it likely that n-3 intake can reduce the risk of atherosclerosis.

Dietary epidemiology have also shown a link between n-3 and mentally debilitating disorders such as Alzheimer's and depression. Furthermore, n-3 may affect the development of many facets tied to brain function, such as intelligence, vision and mood. For example, infants who do not get enough n-3 from their mothers during pregnancy might be at risk for developing vision and nerve problems.

Other epidemiological trials have suggested a protective effect of n-3 on cancer and tumour growth; in particular, prostate, breast and colon cancer.


Omega-3 Fatty Acids: Effects on Body Composition


Freedom from disease and a sharper mind is all good and well, but what what about biomakers related to body composition? Results from studies on n-3 intake and insulin sensitivity are mixed. In summary, people with poor insulin sensitivity (obese) usually see an improvement with n-3, while lean subjects see no or only modest improvements. Keep in mind that "lean" in a clinical context is 15-20% body fat for males and around 25% body fat for females.

What about n-3 and fat loss? I have not seen a single study which shows that adding n-3 alone will generate fat loss in lean subjects, but overweight/obese subjects sometimes see a small - but clinically significant - effect of n-3 supplementation. There are some exceptions to this, i.e. some studies do show a clinically significant fat loss effect in lean subjects, but the sample size and diet design is extremely poor - such as in this widely cited study by Couet, et al.

In combination with exercise, n-3 has been shown to accelerate fat loss in a few studies, but once again the effect is limited to obese subjects.

However, I'll note that it's a profound flaw to look at the effects of n-3 and fat loss in lean subjects and conclude that there is no benefit. Why? Because the effect of n-3 on fat metabolism and adipose tissue is not acute. It takes approximately 4-6 weeks of n-3 supplementation to change the fatty acid composition of the cell membrane, and controlled interventions on n-3 supplementation and fat loss have never been longer than 12 weeks in duration. In the case of Brilla, et al., who looked at fat loss in lean subjects, it was 10 weeks.

The implication of this is that the study, or studies, on n-3 intake and fat loss in lean subjects might be too short in duration to show a clinically significant effect. The n-3 supplements simply didn't "kick in", if you will, until the passing of several weeks. Furthermore, any greater weight loss, as a percentage of body weight, is always harder to spot in lean subjects in comparison to obese subjects, unless you have a large sample size (Brilla, et al., used only 8 subjects in the fish oil + exercise group). 

In conclusion, there simply aren't any good trials on n-3 supplementation and their role in fat loss yet. Oh sure, there are studies looking at fish intake and so forth, but I'm talking controlled interventions without a bunch of variables (fish protein, outpatient trials with poor control, etc.).


Omega-3 Fatty Acids: What We Know So Far


In summary of a vast area of research on n-3 and health, the scientific evidence is indisputable for a positive effect on cardiovascular health and chronic inflammation. These are things you can measure and track, and find a clinically significant effect on within 12 weeks; i.e. improved blood lipids and lower TNF-a (tumor necrosis factor-alpha, an inflammatory marker).

Furthermore, research is also highly suggestive of a positive effect of n-3 on brain function and several disease processes, ranging from cancer to the metabolic syndrome. Keep in mind that it's impossible to provide hard data on these aspects of human health. You can't put people in a lab, give some of them some fish oil pills, and look at who got Alzheimer's or cancer 8 weeks later.

Instead you look at things like fish consumption in thousands of individuals, sometimes over several years, and compare the disease trends relative to fish or seafood consumption. When you do this, you often see positive associations between n-3 saturation of the phospholipid membranes and greater health.

This positive association seems independent of other factors that affect health; meaning that, in an imaginary scenario where we compare two people with the exact same stats, such as body fat percentage and lifestyle habits, with the exception of n-3 intake or fish intake, the person with a higher n-3 intake will be healthier.

A striking example of this, is the fact that fat Eskimos have significantly lower rates of Diabetes Type 2 compared to equally fat Americans (3.3% vs 7.7%). Not a completely valid comparison, due to the inherent problems of dietary epidemiology, but it illustrates the point I'm trying to make, as these health trends are seen across the board in many different populations.

It's safe to say that n-3 is good for us. The Western diet contains too little omega-3 relative to omega-6 fats for optimal health, and our low n-3 intake might certainly be an independent factor influencing the disease trend amongst Westerners compared to other populations with high n-3 intake (e.g. Eskimos, etc.).

Now finally, what about those new studies on n-3 and muscle protein synthesis? 



I saw that Michael Rennie, a hot shot in protein research, was among the authors so I very was excited to read it. The results were very interesting.

This study was carried out on older adults, aged 65 and above. The elderly population is a high-priority group in protein research and there are probably more studies looking at optimizing protein intake for the elderly than there are studies looking at how to make young guys or athletes ripped and swole. How come?

As we age, we encounter a phenomenon called "anabolic resistance". This is a catch-all term for an overall crappier response to weight training and dietary protein.

A fancier sounding word for anabolic resistance is "sarcopenia". But this is just a made-up word that researchers use to get funding for studies. Sarcopenia sounds better than anabolic resistance, I guess.

In terms of dietary protein, "leucine resistance" describes the phenomenon in regards to how the response to feeding is altered. The amino acid leucine is the primary amino acid responsible for triggering muscle protein synthesis. Elderly folks need higher concentrations of leucine to get the same response as young folks. Various feeding strategies that overcomes this problem include:

1. "Protein pulse feeding", which means eating infrequent meals higher in protein and leucine (in contrast to frequent meals). There is a threshold level of leucine needed to consume in each sitting to maximize muscle protein synthesis and this threshold is raised with aging. Larger meals cause leucine to hit that threshold, which triggers muscle protein synthesis. Leucine resistance is similar to insulin resistance in the sense that more leucine and insulin is required to trigger the same response.

2. Supplementing with whey protein or amino acids (EAA, BCAA or leucine). There are many practical advantages of this strategy, i.e. the hassle-free process of drinking whey protein or taking free-form amino acids.

3. Simply eating enough high-quality protein in each meal. This might seem like a no-brainer for us, but with aging comes a loss of appetite. When was the last time you saw a 70-year chew down a big steak? Achieving a high leucine concentration in the blood is mainly about eating enough protein. In the case of elderly folks, faster protein sources - such as well-chewed meat or whey protein - is preferable. This is first and foremost due to absorption kinetics; i.e. leucine concentrations will rise fast and the threshold will be easily reached with 20-30 g protein.  

So that's that. As a side-note, I detest faux diet gurus who cite studies on protein supplements for the elderly to sell leucine supplements. It makes zero sense for a young guy on a high-protein diet.

(Context is crucial. The supplement industry flourishes because no one cares to read or question their claims. Here's some advice: take a second or two to actually read and reflect on studies that are cited in order to validate a claim ("Leucine increases muscle protein synthesis by 537%!"). If it sounds too good to be true, it is too good to be true.)

Anyway, so this one study I mentioned earlier showed that 8 weeks of n-3 supplementation lead to a significant increase in muscle protein synthesis in response to feeding. The same experiment was repeated with younger subjects and the results were released a few weeks ago. 

Below, I'll do a detailed review of the newly released second study and talk a about the results.


Omega-3 Fatty Acids and Muscle Protein Synthesis


Here's the study I'm going to talk about now:

"Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperaminoacidemia-hyperinsulinemia in healthy young and middle aged men and women."


Introduction

...we have recently demonstrated that LCn-3PUFA supplementation (4 g·d-1 of Lovaza®) in older adults (≥65 y) significantly increased the rate of muscle protein synthesis during hyperinsulinemia-hyperaminoacidemia, most likely because of greater activation of the mTOR-p70s6k signalling pathway


This is in reference to the first study on a group of elderly subjects that I mentioned earlier. There have also been other studies, prior to that one, which suggested that n-3 supplementation spared muscle mass when added to a tube feeding formula during cancer treatment

...feed enriched in menhaden oil, a fish oil rich in EPA and DHA, doubled the insulinstimulated
non-oxidative whole-body disposal of amino acids (a marker of increased whole-body
protein synthesis) and increased the activation of the mTOR-p70s6k signalling pathway in
muscle of young and still growing steers...

Furthermore, animal studies have also hinted at an anabolic effect of n-3 enriched feedings. Based on the aforementioned studies, the researchers speculate that the mechanism by which n-3 can increase muscle growth is via activation of the mTOR-p70s6k signalling pathway in response to feeding. The exact mechanism is unknown.

The mTOR-p70s6k signalling pathway is commonly used as a marker for muscle anabolism and protein synthesis, and by measuring the phospholyration rate (activity) of p70s6k, you can get an idea of the anabolic rate in the muscle.

For example, in the study I reviewed in "Fasted Training Boosts Muscle Growth", they found that p70s6k increased more after fasted training. Though they did not measure muscle protein synthesis, it is reasonable to assume that MPS increased in concert with p70s6k. (Keep in mind that this does not necessarily mean that fasted training is superior to fed-state training. Measurements were made during a fairly narrow time-period. Read the article for my thoughts on the topic).

The purpose of the present study therefore was to determine the effect of LCn-3PUFA supplementation for 8 weeks on indices of muscle protein anabolism in human muscle in young/middle aged adults.

Examining the activity of the mTOR-p70s6k signalling pathway and muscle protein synthesis (MPS) in response to n-3 supplementation was the purpose of this study.


Method

Nine healthy individuals (5 men and 4 women; age: 39.7 ± 1.7 y; BMI 25.9 ± 1.0 kg/m2; body fat determined by dual X-ray absorptiometry: 25 ± 3 %; means ± SEM) participated in this study.

Note that "young" in a clinical context is not necessarily young as we tend to think of it. The average participant was almost 40-years old. Clinical standards are somewhat different than those used in everyday speech. For example, "lean" usually means 15-20% body fat, "high protein" tends to be used liberally and for almost any diet regimen with >0.8 g protein/kg (FDA standard), and a 30 g protein meal is considered a "high protein meal", and so forth. 

After obtaining baseline values for anabolic signalling pathways (mTOR-p70s6k) and muscle protein synthesis, the participants were given 4 g n-3/day for 8 weeks.

8 weeks of dietary supplementation with 4 g·d-1 of Lovaza® (GlaxoSmithKline, Research Triangle Park, North Carolina, USA) containing 1.86 and 1.50 g·d-1, respectively of the ethylesters of eicosapentaenoic acid [EPA; 20:5n-3] and docosahexaenoic acid [DHA; 22:6n-3]).


It should be noted that the addition of 4 g n-3/day was the only intervention made in this study. Participants were instructed to not change their usual diet and activity pattern for these 8 weeks.


Important: Note that the n-3 dose totalled 1.86 g EPA and 1.5 g DHA, which is a lot higher than what you will get from your average fish oil supplement. 

Looking at the n-3 supplement I'm using, the 3 g/day I've been taking only gives me a total of 0.54 g EPA and 0.36 g DHA (and 0.15 g ALA). That's really bad. Take a look at yours. A good n-3 brand should contain no more than 50% filler, but this one I'm taking is 65% filler ( in stark contrast to Lovaza, pharma-grade n-3, with only 15% filler). I haven't noticed this until now and will be more stringent with my n-3 intake. More information on good n-3 supplements at the end of the article. Let's carry on with the study review now.


Infusion Protocol


First, a brief description of the procedure on the day when the results were obtained. I'd normally skip this tedious section in my study reviews, but there are some crucial details here that will become important later on  in the article.

All participants ate a standardized meal at 8 PM on the day prior. A 6-8 AM the following morning,  they arrived at the laboratory, where they were infused with tracers for four hours.

Without going into technical detail, tracer infusion is a technique for tracking the passage of nutrients, i.e. amino acids and glucose, through the body. This is always done prior to infusion of amino acids; e.g. you can see how much of the amino acids that ended up in muscle if you infuse tracers, followed by amino acids, and lastly take a muscle biopsy (and that's exactly what they did here).

After fours hours of tracer infusion, participants were then infused with a mixture of amino acids and insulin for  three hours. The amino acid dose was determined to 105 mg/kg lean mass, which with these participants in mind amounts to ~5-6 g amino acids/hour.

A one-time "priming dose" of 35 mg/kg lean mass, or ~2 g amino acids, was given prior to the 3-hour infusion; this is often done in order to stabilize blood concentrations prior to steady-state infusions of this kind.

Important: Adding the aforementioned numbers together, 17-20 g amino acids were infused over a 3-hour period. This might seem like a fairly trivial amount, but the the amino acid mixture, Travasol 10%, was of a very high quality. 20 g of it yields 1.4 g leucine, 3.8 g BCAA (leucine, isoleucine, valine) or 13 g EAA (BCAA + 5 essential amino acids). I'll discuss the implications of this later on.

During the infusion protocol, blood samples were taken with regular intervals. Three muscle tissue samples were obtained, one prior to the amino acid infusion, and two towards the end. Based on these values, the researchers were able to obtain relevant data points for comparison against the ones obtained 8 weeks prior (the same procedure was performed before the n-3 intervention).





I just treated myself to an n-3-intervention. I don't eat a lot of fish, but when I do it's usually salmon with cottage cheese. I find that the salty salmon fits nicely with the cool creamy cottage cheese. Perhaps you would like it too.



Results


After these 8 weeks of 4 g n-3/day, EPA and DHA enrichment of the cell membranes had increased dramatically. This confirmed that compliance was good and that the n-3 supplementation was effective. For those interested in some raw numbers:

EPA: 0.66% vs 2.57%

DHA: 1.91% vs 4.05% 

Values are expressed as percentage of the total fatty acid composition of the phospholid membrane. It's interesting to note that n-3's displaced n-6 and monounsaturated fatty acids (MUFA) in the membrane. These were significantly lower (~50% vs 46% and ~8% vs 6%) after 8 weeks. Saturated fatty acid composition remained stable at 36-38% (increase by ~2%, not statistically significant).

What did this result in? Let's start with some health markers:

As expected, the concentration of inflammatory markers in plasma was low in this healthy
cohort of subjects and there were no differences (all P ≥ 0.33) before and after LCn-3PUFA
supplementation in the plasma concentrations of CRP (0.61 [0.39, 1.03] vs. 0.73 [0.17, 1.23]
mg·l-1, respectively), TNF-α (0.30 ± 0.02 vs. 0.31 ± 0.02 pg·ml-1, respectively) and IL-6 (1.49 [1.05, 3.25] vs. 1.34 [0.98, 1.47] pg·ml-1, respectively).
LCn-3PUFA supplementation had no effect on whole-body glucose kinetics.

These results are not all that surprising. Recall what I said earlier about n-3 supplementation and metabolic status. Overweight and obese people often see meaningful improvements in these markers with n-3 supplementation, but in these normal weight subjects, n-3 supplementation did not do much in terms of reducing inflammation or altering glucose tolerance.

Glucose rate of disappearance, which shows glucose tolerance but can also be seen as a rough marker for insulin sensitivity, was unchanged. Then again, 8 weeks might also have been too short of a time to see any significant improvements in this area.

The basal muscle protein FSR (calculated by using the muscle free phenylalanine enrichment
as the precursor enrichment) was not different before and after LCn-3PUFA supplementation...

Basal muscle protein FSR (fractional protein synthesis rate) denotes muscle protein synthesis (MPS) in the fasted state. I will use MPS instead of FSR to avoid confusion, and it's basically the same thing.

Why "fractional synthesis rate" you ask? Muscle protein is made out of three fractions; 2/3 myofibrillar protein and 1/3 sarcoplasmic and mithocondrial protein (around 15% of total muscle volume each).

Without derailing the topic too much, I'll note that an increase in MPS usually mean that synthesis in all these fractions increase equally in proportion to their volume. Weight training tends to increase synthesis of myofibrillar protein slightly more, relatively speaking, while endurance training increases mithocondrial protein synthesis specifically.

Anyway, MPS in the fasted state was unchanged, which is to be expected. Meaningful changes in MPS are always seen in response to feeding. For example, weight training boosts MPS in response to amino acids in the blood (via pre-workout and/or post-workout meals), but does not alter basal FSR, assuming concentrations of amino acids in the blood are not elevated.

Basal MPS is only altered in some disease states (the severe kind, burn injury, sepsis, etc.) and - of some modest interest - with anabolic steroids. Steroids exert their effect by boosting basal MPS much more than MPS in response to feeding, which I find somewhat interesting. It also appears that sleep deprivation has the potential of lowering basal MPS.

Once again, I find myself ranting like a mad man and going off-topic, so let's proceed with the study review now.

Insulin and amino acid infusion led to a marked increase in the muscle protein FSR (P < 0.001) and the anabolic response (i.e., the increase from basal values) was ~50% greater after LCn-3PUFA supplementation (0.042 ± 0.005 %·h-1 vs. 0.027 ± 0.005 %·h-1; P = 0.01). Consequently, the muscle protein FSR during insulin and amino acid infusion was significantly greater (P < 0.01) after than before LCn-3PUFA supplementation.

Important: Now this is the interesting part. In response to the amino acid infusion, MPS was dramatically increased after 8 weeks of n-3 supplementation. Some raw numbers below.

MPS before n-3 (FSR % / hr)

Basal: 0.037
Amino acids: 0.062 (+68%)

MPS after n-3 (FSR % / hr)

Basal: 0.042
Amino acids: 0.083 (+98%)

These numbers were estimated from a graph when they were not reported in the text. As you can see, the increase in MPS was ~50% greater post-n-3 supplementation (+ 68% vs +98%) in response to the 20-gram amino acid infusion. I'm pointing this out specifically to differentiate it from a +50% absolute increase (i.e. +118%), which it could easily be mistaken for from the quote.

A 98% absolute increase in MPS in response to such a modest amount of amino acids is unheard of. Let me give you some data points to provide some perspective on MPS in response to feeding and training:

Typical MPS increase in response to 20 g amino acids: +50-70%. See MPS values pre-n-3 supplementation.  Bohe, et al., used a similar dose and saw an increase of +57%. Similar values (+51%) were obtained after consumption of ~20 g beef protein.

Maximal MPS noted after high-protein meals or amino acid intake: +88-100%. Bohe, et al., for example, saw an increase of 88% in response to ~50 g amino acids infused over 3 hours. Other studies, such as this one, showed a ~100% maximal increase in response to 10 g EAA (~25 g mixed amino acids).

Maximal MPS noted after weight training and high-protein meals or amino acid intake: +170-200%. These values denote the highest absolute increase in MPS seen within 36 hours following weight training. Some data points are available in this text for those interested.

Important: The key point here is that MPS increased much more in response to feeding after n-3 supplementation, and that this increase is on par with the maximal increase seen after intakes of much higher doses of amino acids. The 20 g amino acids gave a boost in MPS that was comparable with a boost that would normally only been seen after intakes of 25-50 g protein.

...mTORSer2448 and p70s6kThr389 concentrations increased by ~50%

The activity (phospholyration rate) of anabolic signalling pathways increased similarly as MPS.

Very, very interesting. Now let's see what the researchers said about these results in the discussion that followed.



Discussion



These data compliment and extend the results we recently obtained in older adults and demonstrate that LCn-3PUFA supplementation not only alleviates the muscle protein anabolic resistance associated with old age but can actually boost the anabolic response to nutritional stimuli in healthy muscle from young and middle-aged adults.

I should note that the results from the prior study on older adults were even more impressive, relatively speaking. The increase in MPS in response to amino acids were ~120% greater after n-3 supplementation (vs ~50% greater for this sample.).

...the effect was probably mediated via one or more alternative pathway(s), which have yet to be determined (but may include e.g., Rheb or vps34).

Rheb is a cell membrane protein and vps34 can roughly be described as a nutrient sensor. Both of these are involved in activation of the anabolic cascade that follows amino acid sensing outside the cell.

Furthermore, weight training also activates these anabolic triggers, which has the effect of increasing MPS more than normally, i.e. the cell takes up more amino acids from the same amino acid dose if Rheb/vps34 expression is increased from weight training. The speculation above revolves around whether n-3 supplementation has the potential to alter Rheb/vps34 expression.

Considering the observed changes in skeletal muscle phospholipid composition, it is also possible that LCn-3PUFA supplementation modulated key substrates along the anabolic signalling cascades by affecting membrane lipid composition and/or fluidity.

Another potential mechanism, albeit very poorly and unprofessionally formulated in my opinion. Amino acids do not simply diffuse and move through the cell membrane; "fluidity" should not affect uptake of amino acids in that sense.

However, n-3 enrichment of the membrane has the potential of affecting nutrient transport via modulation of the integral plasma proteins. Go back and read about the avocado if you don't follow. Look at the white pins. Some of them are amino acid transporters.

I believe one potential mechanism for the increase in MPS post-n-3-supplementation is altered amino acid transporter expression. Amino acid transporters  are in contact with the cell membrane, and can translocate to the membrane surface in response to amino acids in the blood plasma. It's possible that an n-3 enriched membrane sensitizes, increases, or somehow alters transporters such as System-L, which is primarily responsible for uptake of leucine.

(Interesting side-note: paradoxically, transporters also increase during amino acid deprivation; i.e. starvation - presumably for transporting amino acids out of the cell interior, or to allow rapid resynthesis of muscle protein once amino acids become available again.).

A second hypothesis of mine, albeit somewhat remote and vague, is that increased blood flow supplementation might have something to with it. I do not have enough insight into hemodynamics to provide an informed opinion, but perhaps n-3 supplementation affected blood flow in such a way that hyperaminoacidemia occurred faster.

However, this would only alter the temporal pattern of MPS, and not the absolute rate. That might be a desirable effect for the elderly population, but not necessarily great for younger folks.

It is unlikely that the beneficial effect of LCn-3PUFA on muscle protein synthesis was related to their antiinflammatory properties because our subjects were young and healthy and we did not detect any treatment-induced changes in inflammatory cytokine concentrations in plasma – most likely because the concentrations were very low to begin with.

One hypothesis was that MPS could be negatively affected by inflammation. Since these subjects were healthy, there was no meaningful relationship between MPS and these markers. However, low-grade inflammation is often present in metabolically challenged individuals and there are studies which suggest that MPS is impaired in these cases.

Lowering inflammation, i.e. via n-3 supplementation, might be beneficial for restoring MPS in inflammatory states, such as obesity or illness. I don't think any human studies have confirmed this as far as obesity goes, e.g. lowered inflammation with n-3 and seen increases in MPS, but it's a theory.

Lowered inflammation with n-3-enriched tube feeding was posed as a possible mechanism for greater muscle retention in an earlier study on n-3 and cancer (a highly inflammatory disease state.).

...we infused amino acids and insulin at rates close to those used to achieve the half-maximal amino acid induced increase in muscle protein synthesis...

This is in reference to the choice of the amino acid dose to achieve a 50% increase in MPS, which is typical of that dose, based the response seen in other studies. This was done to avoid the "ceiling effect".

The "ceiling effect" is also referred to as the "muscle full" phenomenon and denotes the point where MPS falls back to basal values. In the Average Joe, this ceiling is reached in the third hour in response to an infusion rate of 10 g amino acids/hour, which amounts to about 2 g leucine total. After that, MPS becomes refractionary. A logical response. Had MPS not fallen back to basal values, we'd all look like Ronnie Coleman times ten.

Simply put, there is a limit to how much amino acids the muscles require for maintaining normal function, and they will not take up more aminos than what is required for muscle homeostasis.

We made our measurements of muscle protein synthesis during a 3-h infusion of insulin, amino acids and glucose because the rate of muscle protein synthesis rises quickly (within <30 min) in response to increased amino acid availability but then returns to basal values after ~2.5-3.0 h.

Important: This is a crucial aspect of this study that might make the results less than fully applicable. In fact, I think the researchers have made a critical error here.

It seems that they choose the amino acid infusion rate (105 mg/kg/hour) based on the assumption that MPS becomes refractionary in the third hour, regardless of the infusion rate, which is not the case at all. Bohe et al., showed that the refractionary response occurred in response to an infusion rate of 162 mg/kg/hour. Meaning that they had no grounds for limiting themselves to a 3-h infusion.

But why is this important then? Because the short time-period vastly limits the conclusion that can ultimately be drawn from the results. For example, recall that MPS increased by 68% in response to amino acids pre-n-3 supplementation. After n-3-supplementation, the same dose caused a 98% increase.

However, nothing can be said about the temporal pattern during these 3 hours. What if MPS would have become refractionary in the 4th hour after the second experiment, whilst remaining elevated after the first experiment?

We can only say that the absolute increase in MPS was greater within the narrow time-period of the study protocol. However, recall what I said about the "muscle full" scenario. It might be that n-3-supplementation simply increases the rapidity of amino acid uptake for any given dose; e.g. by altering amino acid transporter expression, which would then result in greater MPS within a shorter time-period.

However, once "muscle full" is achieved (after the absorption of ~2 g leucine), it should theoretically become refractionary. In contrast, sans n-3-supplementation the absorption would be slower, resulting in lower MPS that becomes refractionary at a later stage.

The key question here, which in my opinion remains unanswered, is whether n-3-supplementation has the potential of increasing the absolute capacity for MPS in response to a fixed amount of amino acids; similar to what weight training does. There is some indication that this might be the case:

There was a trend for an increase in the RNA-to-DNA ratio, the cell capacity for protein synthesis, but the difference did not reach statistical significance (P = 0.13).

Important: If this is the case, n-3-intake would be one of the most important dietary components for body composition. I am not much for hyperbole, but this is a very exciting study - even if it's limited by its short infusion protocol.

Therefore, we assume that the increase in the anabolic response after LCn-3PUFA supplementation was due to an increase in the magnitude of the anabolic response. However, we cannot rule out the possibility that the effect was due to an increase in the duration of the anabolic effect of nutritional stimuli.

Yes, as I noted before, they cannot say much about the temporal pattern. I'm disappointed in Rennie for his lack of critical reflection around the short infusion protocol, which was chosen based on erroneous assumptions in regards to the refractionary state. Then again, even the best make mistakes.

This study could have been vastly improved if they had chosen the infusion rate (162 mg/kg/hr) required to reach a "muscle full" scenario within three hours and used a 4-hr infusion protocol. They would then compare MPS pre- vs post-n-3-supplementation. Had they then seen that MPS was higher post-n-3-supplementation, their conclusion...

In summary, we have shown that LCn-3PUFA supplementation in healthy 25 - 45 y old individuals increases mTOR signalling and the anabolic response of muscle protein synthesis to hyperinsulinemia-hyperaminoacidemia, which resulted in increased muscle cell size (protein-to- DNA ratio) and protein concentration.

...would have been a lot more valid.

The specific mechanism(s) by which LCn-3PUFA act on the muscle protein synthesis process remain mostly unknown.

And the mechanism by which omega-3 fatty acids affects muscle protein synthesis remains shrouded in mystery.





Here's the reason I don't eat much fish. I have nothing against fish, but there is no protein source I would rather choose over roast beef. Perhaps one day we might also uncover the anabolic potential of roast beef. But until then, I'll make sure to supplement my fat intake with EPA and DHA. I suggest you do so too, if you don't eat fatty fish on a regular basis.



Final Thoughts and Recommendations


Even though the conclusions that can be drawn based on this study are somewhat limited due to the infusion protocol, I find the results promising enough to make changes to my own diet. Consequently, I will personally increase my daily n-3 intake to achieve a similar EPA/DHA saturation of the plasma membranes. I will also make this a mandatory part of the diet templates for my clients.

This means that I recommend an intake of 2 g EPA and 1.5 g DHA per day, and it means that you should pay closer attention to the EPA/DHA amounts you get from your fish oil supplement.

As I mentioned earlier, a 1-gram fish oil capsule does not yield high amounts of EPA and DHA, as most of it is filler. The 3 grams of fish oil I have been taking up until now yields a trivial amount of 0.18 EPA/0.12 DHA per capsule. I'd need about 10 of those capsules to reach the amounts required.

Which fish oil supplements contain satisfactory amounts of EPA/DHA? I don't feel like chewing on 10 of those capsules, so I will explore other alternatives. I've looked around for a bit and have found these high-EPA/DHA-brands:

NutraSea Original Liquid.

Cost of daily dose required (3 tsp/15 ml liquid) to reach 2 g EPA/1.5 g DHA:  $0.99. (500 mL bottle.)

Ultra Omega-3

Cost of daily dose required (4 softgels) to reach 2 g EPA/1.5 g DHA: $0.44. (180 g softgels.)

Swedish readers: "Omega-3 Forte" from Pharbio seems to be the best choice. You will need 6 softgels to meet the EPA/DHA-requirements. Daily cost: 9.4 SEK. You can order Omega-3 Forte from Svenskt Kosttillskott

The aforementioned brands are good and affordable alternatives for meeting the daily EPA/DHA requirements. Softgels are always cheaper, but some people can't stand fish oil capsules, in which case a liquid solution might be a more attractive alternative. So that's that.

If you eat fatty fish on a regular basis, a stringent EPA/DHA-protocol might not be required. You can check the EPA and DHA content of fish here. Example: your average store-bought salmon yields 0.7 g EPA and 1.4 g DHA per 100 g. Do the calculations based on your average weekly intake. Keep in mind that the amounts can vary depending on the breeding of the fish, e.g. farm-raised vs wild salmon.

Read more about supplements you might actually find useful in this article.

---

Where have you been? 

Some readers might wonder why there haven't been any updates for more than a month. I blame this partly on my new laptop crashing. I bought it for myself as a Christmas present, but it came with an unfortunate defect in the HDD which caused my laptop to crash.

The process of sending it back and forth to repairs took about three weeks, during which I had to used my old laptop (which is ridiculously slow). When I write, I always work with several tabs open, since I need to do frequent fact-checking for the studies I cite, and so forth. I couldn't stand doing that on my sluggish old laptop. My work and motivation suffered.

Once I received my new laptop in return again, I had fallen out of the groove of writing and just got lazy and complacent. But I'm back on track now, it seems. Hopefully, you won't have to wait another 5 weeks for the next update.

I hope you found today's article interesting. I apologize for the ranting, the technical detail, and the length of the study review. I think the results are truly interesting, and perhaps revolutionary as far as supplements goes. I was eager to give you the full scoop without dumbing it down too much.

If you enjoyed the article, or any other article on my site for that matter, perhaps you might consider a donation in show of support of my writings and the time I put into them.

That's all for today, folks.

74 comments:

cubby said...

One question I'm left with is this: Since fish oil may increase the maximum rate of MPS, does that mean proper supplementation may actually ever-so-slightly raise your maximum muscular potential? Or is it more likely to just quicken your journey to your maximum potential?

Anonymous said...

I love smoked salmon. Sometimes I treat myself to a spread similar to the one you pictured sens the cottage cheese. I spray it down with some lemon for flavor. Delicious!

Anonymous said...

Hi martin. How many teaspoons of cod liver oil do you think they would be necessary daily. I'm not talking about a suplement, just plain cod liver oil

Jose

Anonymous said...

glad your back martin i've been checking the site almost daily to see if its been updated haha

Anonymous said...

Meh. I think the more important take-home message is the ratio of n-6 to n-3 in your diet. It's not about maxing out on n-3, but rather limiting n-6 and keeping that ratio low.

That being said, if you choose grass-fed ruminants for your protein, eat occasional fish, and kick the processed foods and vegetable oils, you should be on your way to a good n-6/n-3 ratio.

Ahmed said...

This is some really great research Martin! Yeah, you take long to write articles, but there aren't many other sites who put out such researched and lengthy articles.

I'd say 1 great article in 5 weeks is better than 5 shitty ones.

OptimumNutrition said...

Martin,

Excellent article

In terms of supplementation, what are you views on rancidity ? Do fish oil capsules oxidise and go rancid ?

Regarding general health, is the priority not to attain a better omega3/6 ratio. In other words, would lowering omega 6 intake essentially be the same as raising omega 3 ?

Also, anti-inflammatories have been shown to blunt training adaptations. NSAIDs can block satellite cell proliferation http://jap.physiology.org/content/107/5/1600.short. I don't think omega3's work in the same way as NSAIDs. However, could high dose omega3's inhibit adaptations by preventing the acute inflammatory response ?

julianne said...

That was really interesting - thanks.
A really inexpensive, high concentrate, high purity omega 3 capsule in New Zealand is Nutralife Omega Science Here is a link - http://www.healthpost.co.nz/Product/NLOMS/Omega-Science-Omega-3-Concentrate
It has 500mg EPA+DHA per 1 gram capsule. If you try the fish oil inside - it is clean and fresh (indicating low or no oxidation)

I have also put together a resource on omega 3 and 6 in meat, oils, nuts, seeds, fish and seafood here:
http://paleozonenutrition.wordpress.com/2011/05/10/omega-6-and-3-in-nuts-oils-meat-and-fish-tools-to-get-it-right/

Manveet said...

IIRC Lyle Macdonald has been recommending 3g of EPA/DHA for a long time. I've been taking that dose for literally years. Usually turns out to be 10 fish oil caps a day.

Matthew Robert said...

Martin,

Do you believe PUFA's play a role in skin problems like acne, dermatitis, and eczema. I have been looking for information on this and have yet to find anything conrete. I know skin problems, and health markers aren't exactly an issue you care to put much thought into, but it would be much appreciated to pick your brain on this issue. Thanks you very much. - Matthew Robert

Vajid said...

Hey Martin,

Thanks for the article! I recently bought the Nutrasea fish oil and the lemon flavour tastes pretty good!

Quick question: If you miss a day's dose of fish oil for whatever reason, should you just continue on with your normal dosage the next day, or double your dosage to make up for the day you missed?

Lolo said...

Martin,

Well, there is a problem for me to take that much n-3: I smell like shit when I do it.

Is it just me and is there something I can do about?
(beside using a perfume LOL)

Philip said...

Anybody know where to get affordable high-quality/high-concentration fish oil capsules in Germany?

Anonymous said...

Martin,

Was wondering what effects the Lean Gains program might have on a young male (22 years old) with low testosterone (371-435). I suspect this is from low carbing for too long for skin issues... as I definitely have a huge libdo boost when I eat in 15/55/30 ratios for protein, carbs, and fats. Basically a Paleo high carb with yams, potatoes, rice, coconut oil, butter, meats and fish. I havent been measured since starting Lean Gains 2 weeks ago.. hoping it will help... low carb made me skinny fat and its definitely a result of my hormone status.

Anonymous said...

Thanks for the well researched article!

Fredrik Gyllensten said...

Fantastic article, Martin! :) Very interesting results.

Anonymous said...

Has anyone used OmegaVia? It looks to be the best one out there, and relatively cheap as well.

http://www.omegavia.com/

Edward said...

Martin,

Have you read anything on CLA Conjugated linoleic acids)? If so do you think it would be worth while taken in conjuction with Omega-3's?

Thanks Eddy

Garrison Brems said...

http://www.strongerfasterhealthier.com/product/1

This is the best fish oil product out there in my opinion and the EPA and DHA dosages are roughly what Martin recommends.

Garrison Brems said...

http://www.strongerfasterhealthier.com/product/1

This is the best fish oil product in my opinion and it has the proper dosage of EPA and DHA.

it is a little expensive but worth it. It is better than taking 10 huge pills a day.

Anonymous said...

That was a great read Martin! By the way - if you for example eat 100g or 200g of samon, how much omega 3 acids do you get then?

Cheers

Ian M. said...

Hi Martin, a fantastic review as usual. Like several of the commentators, I can't help but wonder if it wasn't the absolute increase in the o3 in the membranes that elicited the MPS effects, or the relative change in the o3/o9 ratio, which is certain to have it's own effects on cellular signaling. Did the authors of the paper test the 3/9 ratios? Regardless could you comment? If indeed a similar effect could be garnered by cutting out o6 (seed oils, etc), supplementation With o3s may not be as critical....

Benjamin said...

Does it matter if fish oil is consumed in the post-prandial versus the post-absorptive state?

My gut is telling me half of the dose would go well with the tail-end of intra workout aminos, and the other half would go well with the last feeding of the day. Then again, my gut could certainly be entirely wrong.

Kujo said...

Very interesting article.

There's been some studies about fish oil doses over 1.3 grams of combined EPA/DHA having negative effects on the immune system, like the one discussed on Alan's site => http://www.alanaragon.com/fish-oil.html

I've reduced my dosage to that range within the last year.

My current favorite liquid brand is is this one => http://www.iherb.com/Nature-s-Answer-Liquid-Omega-3-Deep-Sea-Fish-Oil-EPA-DHA-Natural-Orange-Flavor-16-fl-oz-480-ml/7908?at=0

I still believe as long as you have a healthy overall diet, and limit n-6's, the fish oil dosages you mention in this article are fine.

I may start to increase my dosage to the recommended range like I used to.

Anonymous said...

Nice article. I plan to give the Ultra the Omega-3 a try. Minor correction -- if you take 4 pills of Ultra Omega-3 that will be 2 grams of EPA and 1 gram of DHA.

Daniel said...

good break down.

I definitely think epa/dha and also Vit D are extremley valuable supplements...Most people view them as general health supps...but, I've gotten much better body comp results when i have taken these compounds over extended periods vs not taking them...

btw anti-inflamatory compounds definitely affect fat loss in the obese...look at the ECA stack studies done on healthy and obese subjects testing the effectiveness of aspirin in the stack...The aspirin only affected the results of the obese...not exactly relevant to us, but it is somewhat interesting, none the less...

sLs said...

did you see this study
http://www.ncbi.nlm.nih.gov/pubmed/21063431

normal fish oil is better than ethyl ester epa/dha

they used ethyl ester - what'd happened if they use normal fish oil?
even better results?

Alex said...

Great Martin i been thinking alot about the most beneficial dosage of omega 3s in my diet. Happy that your back !!

Anonymous said...

I have already read various sources,to know that my regular DHA/EPA intake doesnt cut it as far as having any serious effects,at least the ones im looking for.

Yout article gives me a renewed incentive to try and look for better brands next time.

Although I dont remember coming across any so far... :(

Tim- said...

I take 2-4 tablespoons of Carlson omega 3 fish oil daily. been taking it for 2 years.

I have noticed many benefits. I'm an endurance athlete training 20-30 hours a week so my primary use is for inflammation control, and improving my aerobic energy metabolism.

Anonymous said...

Hey Martin, you mention that Steroids boosts the basal MPS more than the post-exercise MPS. Would a steroid user then be benifiting from following a "broscience" protocol and have more protein spread throughout the day rather than a fasted state with a feeding window?

Risto said...

Martin, how do you keep up with all the studies? (Not in terms of time, but how do you make sure that you don't miss any important studies?)

I haven't personally ever supplemented with fish oil, but I eat natural fish (which is probably somewhat contaminated, true) every day. Do you think I'm fine by doing so?

d said...

Great article. Very comprehensive and well thought out.

My only question is, who sponsored the Lovaza study?

Roland Homoki said...

Hey Martin,

thank you for the article!
Here is an other Omega3: http://www.puritan.com/omega-3-products-128/triple-strength-omega-3-fish-oil-1360-mg-034888?NewPage=1
In Denmark I have to pay a toll as it comes from the US, but it's a very cheap place.

Timmypectorals said...

Great article Martin, thanks very much again for the time and effort to write it all up for us!

I have found a great source of high EPA and DHA for those in Europe and especially the uk:

http://www.myprotein.com/uk/products/omega_3_liquid

dirt cheap, works out at about £0.20 per day to get about 2g EPA and 1.25g DHA

Sean said...

Martin,

This may be a bit out of left field, but what brand and type of cottage cheese is that in the picture? It looks pretty appetizing.

TomTom said...

A very interesting read, Martin. You can tell when someone is a real expert and your study critique and analysis is truly one of a kind. A joy to read.

Anonymous said...

just wanted to share this with you and your readers thought it might interest some people
http://www.ncbi.nlm.nih.gov/pubmed/16051710?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

roy said...

well im def bumping my epa+dha intake after this. thanks for the great info!

Rick Leigh said...

Thanks again for another great read Martin, but just out of interest, how would you incorporate fish oil supplements into your diet if you were training fasted? Would you take them pre training to induce the effect or post training to maintain the fasted state?
Thanks, RIck

Ben said...

"Ultra Omega-3

Cost of daily dose required (4 softgels) to reach 2 g EPA/1.5 g DHA: $0.44. (180 g softgels.)"

Martin,

I think the math is slightly off here. While 4 softgels would be enough for 2g EPA, it would only amount to 1g DHA. You would need 6 softgels to get 1.5g DHA. that would make the cost $0.67 per serving.

Steffen said...

@ Philip and everyone else who comes from Germany:

Here you can find a very cheap option, how to get your daily amount of fish oil:

http://www.myprotein.com/de/products/omega-3-1000-mg

they have a 6000 capsules pack, which lasts for about 1000 days

Terry said...

@Steffen

Holy crap, that's awesome! That's a 2.8-year supply, coming in at less than 20 euro cent per day, so something like $0.30!

Kazkoks said...

Very interesting, another great article, btw., a good source of omega 3 is Linseed (flax). About 20grams of linseed got 3.5grams of omega 3.

Martin Bernardino said...

Martin,
Thanks for validating our daily use of these supps with this thorough breakdown.

My friend's dad had/has access to free samples of Omacor and, later, Lovaza. I couldn't believe him when he told me how much each pill costs.

Keep up the writing! -M

Anonymous said...

Love your work in general Martin, but my iq is 137 and after reading this article, I still couldn't tell you what this study means.

Anonymous said...

Theres talk being spreaded over the net about Omega 3 Fish Oil interfering with muscle grwoth since its anti inflammatory.

Is there any truth in this at all?

muscle size said...

Awesome post bro!
Fish oil is truly a staple to my everyday supplement routine. It truly benefits anyone trying to live a healthier life.

Anonymous said...

Are there any risks from EPA/DHA when supplementing at the recommended level?

/Tommy

Michael said...

Hey Martin,

I think this aspect of the study (and your commentary) is most important for all us readers:

"Important: The key point here is that MPS increased much more in response to feeding after n-3 supplementation, and that this increase is on par with the maximal increase seen after intakes of much higher doses of amino acids. The 20g amino acids gave a boost in MPS that was comparable with a boost that would normally only been seen after intakes of 25-50 g protein."

So the awesome MPS response in the test subjects was based on a fairly limited protein diet. But will the benefits of Omega3 supplementation really help someone already on a high-protein diet? Or is there some maximum rate of MPS we can achieve, and the high protein diet is already fulfilling that level without the Omega3's?

If the benefits will stack on top of eachother, I'll start downing these every morning. Look forward to your response!

Anonymous said...

Glad to hear it...especially since we have a lot of people touting that it blunts muscle adaptation because of it's anti-inflammatory properties. I am more inclined to believe this article, though.

Anonymous said...

15ml of NutraSea = 120 calories, according to the nutrition info on the label. If I count those cals towards daily limits, it's somewhat significant, particularly on deficit days. What do you recommend if fat loss is the goal?

Pandadude said...

Does this study really relate to bodybuilding when the subjects weren't training?
Omega 3's are anti-inflammatory and have shown to decrease adaption to training while omega 6 supplementation causes a better adaptive response and more muscle hypertrophy.
2g fish oil might not be enough in humans to have a seriously negative effect, but I don't see it being beneficial for gaining muscle (at least not on training days). Thoughts?

Anonymous said...

"as I definitely have a huge libdo boost when I eat in 15/55/30 ratios for protein, carbs, and fats. Basically a Paleo high carb with yams, potatoes, rice, coconut oil, butter, meats and fish. I havent been measured since starting Lean Gains 2 weeks ago.. hoping it will help... low carb made me skinny fat and its definitely a result of my hormone status."
anybody else with IF experience regarding a higher carb intake on nontraining days for longer periods?
Any comments by Martin, I know he prefers the high protein, at least in part because of hunger suppression. Personally, I have too noticed a higher libido with a lower protein, higher carb composition on nontraining days. And increased strengths in the following workout days.

Dany said...

In Sweden there is a product called Friggs Omega 3 which you can buy in a general supermarket. 15ml contains 2,4g EPA and 1,5g DHA. It cost around 70 SEK for 150 ml.

amrn65 said...

Salmon and cottage cheese....hmmmmm....sounds yummy. I will try it!

Tom said...

Hi Martin

As Ben Said:

"Ultra Omega-3

Cost of daily dose required (4 softgels) to reach 2 g EPA/1.5 g DHA: $0.44. (180 g softgels.)"

Martin,

I think the math is slightly off here. While 4 softgels would be enough for 2g EPA, it would only amount to 1g DHA. You would need 6 softgels to get 1.5g DHA. that would make the cost $0.67 per serving.

Would you suggest taking 6 to hit the DHA target and in the process going over the EPA target or 4 as you suggested in the article that would enable you to hit the EPA target and be slightly under the DHA?

Gary said...

NOW also has a Super EPA fish oil that offers a ratio of 1.5 to 1 EPA to DHA ratio. Which is close to the 1.33 to 1 ratio suggested.

It comes from fish oils also and you only need to take 3 to get the 2g EPA and 1.5g DHA (actually it gets you 1.44g DHA, but close enough for me).

Bodybuilding has a buy 2 get 1 free deal going on as of writing this and that gets the price to come down to about 22 cents per serving which is amazing. Normally for the highest price per serving it is 34 cents per serving which is still really cheap.

NOW Super EPA

P.S. I added Martin's Bodybuilding affiliate link to that so he can get the commission, which he deserves for doing all this work.

Gary said...

Just noticed that the serving size I posted is wrong. It is 2 pills per serving instead of 1. So you will have to double the cost per serving that I posted above.

quinnGoes said...

I don't know about you guys, but I'm NOT eating any more fish oil pills, and plan to limit even omega-3 even from fatty fish. Why? Because PUFAs are extremely unstable and susceptible to oxidation, Omega-3's even more so than Omega-6's. I think that Omega-3's are waaay too "fad"-ish, and it will likely be realized they are not the healthy substance we have been led to believe. Have you seen or heard of how when someone takes a lot of Omega-3, their skin becomes weak and easily bruised? Omega-3's have an anti inflammatory action in the short run, thus many studies have confirmed their benefit over a short run, but the mechanisms by which the inflammation is being reduced likely will turn out to be very harmful in the long run. I will be sticking with the plan of limiting PUFAs, as much as reasonable, by eating lots of red meat (rumens have the means to process PUFA's into saturated fats for us) and its fat. And coconut oil.

What do you guys think of this?:

Omega 3 oils are even more immuno-suppressive than the omega 6
oils. The first effect on the immune system from increased consumption
of omega 3 PUFAs is the suppression of prostaglandin synthesis; this
is because the more highly unsaturated long chain fats of the omega 3
oils interfere with the conversion of omega 6 oils into
prostaglandins. Since the omega 3 oils suppress the production of all
prostaglandins (both good and bad), they decrease the prostaglandin 2
series, those that are pro-inflammatory, and are associated with so
many pathological conditions. In the short term, therefore, omega 3
supplementation can actually decrease symptoms of arthritis,
allergies, and many types of headaches. The action of EPA, DHA, and
ALA is very much like aspirin in this regard.

In addition to the anti-inflammatory effects by virtue of
prostaglandin inhibition, there is another way that omega 3 fatty
acids are directly anti-inflammatory. Anti-inflammatory? Sounds good
doesn’t it? Look closer; the direct anti-inflammatory effects of omega
3 fatty acids do not result from the fatty acids themselves but from
the oxidized derivatives of these oils. You see, the omega 3 oils
rapidly destroy Vitamin E, after which they are themselves highly
oxidized. Research has shown that ...

IT IS THE OXIDIZED OMEGA 3 FATTY ACIDS
THAT HAVE THE ANTI-INFLAMMATORY EFFECTS.

The obvious problem here is that these anti-inflammatory effects
are short-lived, while the oxidative free radical damage that ensues
has devastating long term consequences. In experiments that last only
weeks to months, seemingly beneficial anti-inflammatory effects can be
documented. However, in these short-term studies there is no time for
the experimental subjects to show the immuno-suppressive damage, lipid
peroxidative damage, light sensitizing damage, anti-mitochondrial
effects, depressed aerobic energy production, lipofuscin age pigment
production, liver damage, brain damage, and metastatic cancer that
result from long-term intake of fish oils and other sources of omega
free fatty acids.

Nephron Exp Nephrol. 2004; 97(4):e136-45. Oxidized omega-3 fatty acids
inhibit pro-inflammatory responses in glomerular cells and endothelial
cells. Chaudhary, et al.

Redox Rep. 2002; 7(6):369-78. Inhibition of leukocyte-endothelial
interactions by oxidized omega 3 fatty acids. A novel mechanism for
the anti-inflammatory effects of omega 3 fatty acids in fish oil.
Sethi S.

AndyTexas said...

Martin,
I've been on your leangain's diet and I am getting accustomed to it already. I am following the workout routine you recommended but I just need your input on how to tweek it to suit my daily routine.

I am an active duty US military, Monday, Wednesday and Friday, we do group sprints and do pushups for an hour (its like an intense cardio session). The nutrition of these days are the "NON Workout Days " of the leangains nutrition guide.

Tuesday, Thursday and Saturday are the LeanGains workout routine and following the "Workout Nutrition" guide.

I'm getting lean but I'm not getting the strength and muscle gains (I am pretty sure its from the sprints and cardio session we have to do 3x a week). Can you recommend me a Nutrition guide for my specific workout load?
Thank you for sharing your knowledge thru your site so EVERYONE can benefit from. Keep up the good work.

Aj
US Active military

Th3pwn3r said...

Martin where are the updates?! Anyhow, I stopped by here because I'm watching the MLG Starcraft2 tournament that's going on live right now and wondered if you were doing the same. NERD!

Joe B said...

Interesting information; another common point people make about how often you eat is about the amount of nutrients that can be properly digested in that sitting; example - i have heard from several "experts" the maximum protein per meal that can be properly leveraged is 32 to 50 grams. Any thoughts?

Marcus said...

Good article. Might have missed it, but does the article state how/when it's best to take omega-3 supplements? All at once, spread out during the feeding phase? Before or after meals, before bed, or what?

/Marcus

Dani said...

So Im injured:(

I have patellar tendinitis. Same goes for my elbows and also bursitis in the both of my back shoulders and right front shoulder.

Some of these injures I have had for 6years.

The knees are just annoying because I cant work out, run or do any kind of normal workout movement without pain.

From my experience with my elbows and right front shoulder I can tell that it will probably never heal. Its very frustrating of course and also depressing. The doc´s just prescribe some anti- inflammatory meds´ that doesn't help at all. Sometimes I feel like an old man and Im only 28.

Do have any information to hand out.

Is there something that I can do to go back to normal?

Dani said...

I forgot to ask a Q about norepinephrine.

It seems that my norepinephrine levels go up before bedtime. Is there a way of fasting so it will go on in the morning instead while Im getting up from bed or perhaps during lunchtime while I need to use that extra energy.

It would help me with focus in school and such.

AOPRinciple said...

Martin,
I just discovered the site recently and am excited to implement your suggestions into my training regimen. It seems like you highly encourage lifters to incorporate squats and deadlifts into any program designed to increase strength and mass. I would like to make optimal use of both lifts while avoiding overtraining. Do you generally recommend these two lifts done on separate days?

I can't decide whether to insert the deadlift into a "leg day", since there is so much overlap between the two exercises, or into a "back day", for obvious reasons. Will I give my lower back and hamstrings enough recovery time if I squat and deadlift heavy on separate days during a week? It's frustrating trying to come up with a good compromise... Thanks!

-Dave

Anonymous said...

Sorry, can someone just answer me this question:

Does Leangains actually have a training program /routine on his website? Or is he waiting to release his book? If he does have a recommended program I could someone please link me?

Thanks

Anonymous said...

Does the timing of the n-3 supplementation matter?

From your article: "But why is this important then? Because the short time-period vastly limits the conclusion that can ultimately be drawn from the results. For example, recall that MPS increased by 68% in response to amino acids pre-n-3 supplementation. After n-3-supplementation, the same dose caused a 98% increase."

It seems from this, that it would be best to take your n-3 supplementation before taking your amino acids.

That leads me to the question: Since the leangains protocol says to drink aminos before fasted training, would it be worth it to break the fast by taking the n-3 supplmentation pre amino-acid supplementation?

Anonymous said...

Hi,

I know this is an older post, but since I'm trying to introduce LeanGains into my kife I just stumbled about it.

Besides the fact that I have some trouble with all the healthy food I'd need (due to financial reasons) (even without using LeanGains) there is another great source for omega 3 which is simply flax-seed-oil. My Wife used to take about 1 big spoon of ot and was able to drop weight even without doing any exercises or something like that. There are some Studies that say that omega-3 is better transported into cells and can be used for the natural job that "fat" is intented for and thus kicking "bad storage" food out… (Dr. Servan Schreiber wrote some things about that)

Just my 2 Cent, I'm going to figure out how to integrate LeanGains into a poor Mans (Students…) life ^^

Thanks for all your great work,
M

Anonymous said...

Hi Martin,

I know it's an old post but hopefully this registers as I question whether my balances are right.

I currently take 25g of ground flaxzeed daily, namely this

http://www.amazon.co.uk/Granovita-Organic-Ground-Flaxseed-450g/dp/B0013GAOSI/ref=sr_1_3?ie=UTF8&qid=1335019981&sr=8-3

I eat tuna or salmon 4/6 times a week.

I also use 25g of sunflower seeds and 25g of pumpkin seeds daily.

Do you think I am ok or is my ratio off?

Thankyou.

Trainer Troy said...

Hemp seed oil has a good ratio of 3,6,9 fats. 3:1:1 it tastes like grassy olive oil ( not too bad) and is unadulterated. I would be interested to know if anyone can figure out the dose required to hit the targets Martin is suggesting?

Anonymous said...

"Values are expressed as percentage of the total fatty acid composition of the phospholid membrane. It's interesting to note that n-3's displaced n-6 and monounsaturated fatty acids (MUFA) in the membrane. These were significantly lower (~50% vs 46% and ~8% vs 6%) after 8 weeks. Saturated fatty acid composition remained stable at 36-38% (increase by ~2%, not statistically significant)."

So bi-lipid layers with saturated fats didn't change composition at all? Does omega 3 fatty acid supplementation effect saturated fat composition in membranes at all? Can someone confirm this please?

Thanks

vidsan said...

Try cured salmon with avocado slices and scrambled eggs. You can leave it at that, or put it on a sandwhich with mayo and/or mustard.




My name is Martin Berkhan and I work as a nutritional consultant, magazine writer and personal trainer.

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