Extremely Limited Synthesis of Long Chain Polyunsaturates in Adults: Implications for their Dietary Essentiality and use as Supplements
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 Aug;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: By way of introduction, early nutrition research was very concerned with determining what were the essential nutrients for human health and survival. By definition, an essential nutrient is one that is
- Required by the body for survival
- Can’t be made by the body
It’s a bit more complicated than that and there are some nutrients which are defined as conditionally essential (glutamine is one) but this covers the basics.
Vitamins and minerals are essential, about half of the amino acids are essential and, as early research fought to determine, it turns out that some fatty acids are essential. These are called, generally, the EFAs and, as we now know there are two of them.
Due to methodological issues that I won’t detail, 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. I’d note 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 (n-3,w-3) for ALA and omega-6 (n-6, 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 essential.
ALA is metabolized to EPA (you don’t want to know the full name) 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.
Now, for the most part, I’m not going to talk much about the LA->AA pathway. 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) 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.
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).
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 stance.
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. You need to be taking preformed EPA/DHA (in either capsule or liquid form). This was one of the changes I made to the second edition of the Rapid Fat Loss Handbook (the first edition allowed for flax to substitute for fish oil).