Extremely Limited Synthesis of Long Chain Polyunsaturates in Adults: Implications for Their Dietary Essentiality and Use as Supplements
Title and Abstract
Plourde M, Cunnane SC. Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Appl Physiol Nutr Metab. (2007) 32(4):619-34.
There is considerable interest in the potential impact of several polyunsaturated fatty acids (PUFAs) in mitigating the significant morbidity and mortality caused by degenerative diseases of the cardiovascular system and brain. Despite this interest, confusion surrounds the extent of conversion in humans of the parent PUFA, linoleic acid or alpha-linolenic acid (ALA), to their respective long-chain PUFA products. As a result, there is uncertainty about the potential benefits of ALA versus eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Some of the confusion arises because although mammals have the necessary enzymes to make the long-chain PUFA from the parent PUFA, in vivo studies in humans show that asymptotically equal to 5% of ALA is converted to EPA and <0.5% of ALA is converted to DHA. Because the capacity of this pathway is very low in healthy, nonvegetarian humans, even large amounts of dietary ALA have a negligible effect on plasma DHA, an effect paralleled in the omega6 PUFA by a negligible effect of dietary linoleic acid on plasma arachidonic acid. Despite this inefficient conversion, there are potential roles in human health for ALA and EPA that could be independent of their metabolism to DHA through the desaturation – chain elongation pathway.
My Comments
In many, if not all, of my books, I tend to highly recommend that people take some form of preformed fish oils on a daily basis. For various reasons, either related to people not liking to swallow pills, or occasional vegetarian concerns, a question I often get is whether or not flaxseed oil can take the place of preformed fish oils in the diet. As well, there is often a great deal of confusion on various Internet forums as to whether or not flax oil is an appropriate source of the essential fatty acids.
In general, the short answer is no.
The long answer is the subject of today’s research review.
By way of further introduction, early nutrition research was very concerned with determining what were the essential nutrients for human health and survival. Now, an essential nutrient is defined by the following two characteristics:
- The nutrient is required by the body for survival
- The nutrient can’t be made in the body
The topic of essential vs. inessential nutrients is actually a touch more complicated than that but I’ll spare you the details here.
Things like water and air (not often though of as nutrients, mind you) are essential for life. So are the myriad vitamins and minerals. About 8 of the 20 amino acids found in protein foods are essential. Carbohydrates, strictly speaking are not essential, a topic I discuss in Nutrient Metabolism Overview. And while early research fought to determine exactly what was going on, it turns out that some fatty acid are essential. These are called, in general the essential fatty acids (EFA’s) and, as we now know, there are two of them.
Due to methodological issues that I won’t detail here, determining what fatty acids were actually essential was actually a fairly difficult problem in the early part of the 20th century. In early research, it was thought that there were three EFAs, alpha-linoleic acid (ALA, not to be confused with alpha-lipoic acid, an insulin sensitizer), linolenic acid (LA), and arachidonic acid (AA). When it was found that rats could make AA out of LA, it was dropped, leaving two EFAs. It’s worth mentioning that, at one point, it was thought that LA was the only EFA but, as we now know, both ALA and LA are essential fatty acids.
These two fatty acids are also often referred to by their chemical names (which have to do with their structure) which are omega-3 (often abbreviated as n-3 or w-3) for ALA and omega-6 (abbreviated as n-6 or w-6) for LA.
Now, both LA and ALA are metabolized in the body (this includes a variety of processes including oxidation in the liver) to other compounds, I’ll spare everyone the biochemical details.
LA is metabolized to gamma-linoleic acid and then eventually to arachidonic acid. As mentioned above, this is why AA was removed from the list of EFAs; since the body can synthesize it from LA, it’s not considered an essential nutrient.
Now, for the most part, I’m not going to talk much more about the LA to AA pathway. While LA is certainly essential, it’s thought that excessive amounts of LA/AA are detrimental to the body. AA has inflammatory characteristics and some research suggests that an excess intake of LA relative to ALA
The reason is that excess LA/AA is actually detrimental to the body. AA has inflammatory characteristics and excess LA (esp. in relation to ALA intake) is thought to be a harmful to the body. I’d note that studies show that the current ratio of LA:ALA is around 25:1. It’s thought that a ratio of 4:1 or lower would be better.
ALA is metabolized to EPA (eicosapentaenoic acid) which is further metabolized to DHA (same comment). EPA and DHA are more commonly referred to as the fish oils since they are found in high amounts in fatty fish.
Bottom line, most of us get way too much LA in the first place, unless you eat essentially a zero fat diet you get most of what you need, there’s no real need to make lots of AA from a health or survival standpoint.
Of more concern is the EPA/DHA issue which is what I want to discuss in more detail. Both are critical for things like optimal health, fat burning, etc. It looks like DHA may be even more important. Babies accumulate DHA in their brains and babies who either don’t receive sufficient DHA (from the diet) or have a rare genetic syndrome can end up with brain damage. DHA is present in large amounts in cellular membranes. Basically, sufficient DHA intake is critical.
Which brings us to the real topic of this week’s paper: Can the body convert ALA to EPA/DHA in sufficient amounts? Because, if it can, then using a source of ALA such as flaxseed oil is sufficient. If it can’t, then intake of preformed EPA/DHA via fish oils is going to be required.
Now it’s clear that the human body possesses the enzymatic machinery to convert ALA to EPA/DHA. But there is an issue of whether the conversion process can occur in sufficient amounts.
Without going into the ridiculous detail of this week’s paper, the short-answer is basically “No, it can’t.” Now, there are some methodological issues with the studies having to do with the amount (giving large amounts of ALA can cause an underestimation of true conversion) given and some other stuff but the bulk of the data points to the simple conclusion that the human body is simply terrible at converting ALA to EPA/DHA.
In fact, studies using flax oil supplementation show no change in DHA levels. None. It will raise EPA a bit but the conversion to DHA is essentially zero.
There are two odd exceptions to the above that I want to mention. The first is in vegans. Due to zero intake of animal foods, they have zero intake of DHA. But while they show lower levels of DHA, they don’t show deficiency symptoms. While more research needs to be done, presumably pathways of conversion/production of DHA are up-regulated under this situation.
The other is in extreme w-3 deficiency, where plasma DHA levels typically rise after ALA supplementation. This is just a classic feedback loop, and occurs for other nutrients as well (for example, absorption of certain minerals will increase the more deficient someone is). This probably explains why a lot of bodybuilders (eating nearly zero fat) did get something out of flaxseed oil during the 90’s, in a massive deficiency, they got better conversion. Once that deficiency is fixed, conversion rates drop into the toilet.
But beyond that, the overall impact of ALA supplementation plasma levels of EPA is small, for DHA essentially nil. And given the critical importance of both EPA/DHA on human health, fat loss and performance, the bottom line is that this makes ALA (via flaxseed oil or what have you) an insufficient replacement for preformed fish oils.
As a couple of final comments, I’d also note that supplementation of EPA doesn’t raise DHA levels either. Since all commercial fish oils I’ve ever seen contain both EPA/DHA, this is a fairly non-issue. But it is yet another reason why ALA by itself is insufficient. Not only is the conversion of ALA to EPA small, the conversion of EPA to DHA is simply nil, hence ALA won’t impact on the body’s DHA levels.
Having established that ALA intake is ineffective at increasing EPA/DHA levels, a final and related question to address is whether ALA has any effects above and beyond what EPA/DHA are doing. This week’s paper mentions one possibility which is a mild impact of ALA supplementation on cardiovascular disease. It also notes that EPA/DHA supplementation has a greater effect. Other researchers (not all agree) feel that the true EFAs are EPA/DHA, and that ALA is simply a parent compound that is not essential in its own right. Currently I tend to agree with this second position.
Summing Up
The body requires EPA/DHA for optimal function. This includes fat loss, prevention of a lot of diseases, controlling inflammation, etc. While the body has the machinery to convert alpha-linolenic acid (ALA, found in high quantities in flaxseed oil), the amount of that conversion is small for conversion to EPA and negligible for DHA. Hence I don’t feel that ALA/flax oil is an appropriate EFA source.
Rather, preformed fish oils need to be consumed daily. Individuals who consume a lot of fatty fish can use that as their source; failing that pills or liquid fish oils would be appropriate. Recently, foods are being fortified with higher levels of w-3 although, in my opinion, they aren’t cost effective. High w-3 eggs cost significantly more than regular eggs and stil don’t provide a significant amount of w-3s; it would be cheaper to buy normal eggs and take an w-3 supplement.
As a vegetarian, I’ve been looking into this matter for myself and my vegetarian daughter. Do you have any information on the effectiveness of non-fish (algae-derived) DHA supplementation?
Given that a tablespoon of flaxseed is about 12-14 grams, the average conversion rate still would provide plenty of EPA. So would an algae DHA supplement, along with flaxseed oil, be sufficient for EPA/DHA requirements?
I will be honest that I have not looked into the vegetarian derived supplements. But a molecule of DHA should be a molecule of DHA regardless of source. The same would go for EPA. So if they’ve found a way to drive EPA/DHA from non animal sources, I don’t see any reason why it wouldn’t be effective.