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The Long History of Essential Fatty Acids but Belated Knowledge about Linoleate Deficiency per se: A Paradox

University of Toronto Department of Nutritional Sciences Toronto, Ontario M5S 3E2 Canada

Dear Sir,

Ralph Holman's recent historical perspective on salient steps in progress towards understanding the metabolism, biochemistry and clinical significance of polyunsaturates (Holman 1998 ) stimulated me to comment on one of the enduring paradoxes in this field. On the one hand, it is clear that there are two classes of polyunsaturates and that provision of both in an appropriate ratio is necessary for normal development. As Holman remarked, it took some effort to prove that these fatty acids are necessary for humans as well as other mammals. Throughout the period from their discovery to the present, linoleate and the long chain (n-6) polyunsaturates have received the most attention and have not faced the same skepticism about their nutritional importance as the (n-3) polyunsaturates. On the other hand, despite the lengthy and rich history of research in this field, the paradox is that deficiency of linoleate alone has only recently been reported (Cunnane and Anderson 1997 ). The feeding of fat-free or essential fatty acid (EFA) deficient diets containing various types of saturated fatty acids has been reported on many occasions, but this has always involved deficiency of all unsaturated fatty acids including not only (n-6) and (n-3) polyunsaturates but also monounsaturates. Despite an extensive review of the literature and discussions with many researchers in the field including Ralph Holman about this subject, it appears that the effects of feeding a complete diet excluding only (n-6) polyunsaturates but including a source of (n-3) polyunsaturates and oleate was not reported until 1997 (Cunnane and Anderson 1997 ). Two reports have addressed the impact of -linolenate (18:3n-3) on growth and development in rats otherwise fed a fat-free diet (Bourre et al. 1990 , Hansen and Jensen 1983 ). The diets they used were still missing oleate, which cannot be synthesized in adequate amounts to sustain normal body oleate levels without an additional dietary oleate source (Bourre et al. 1997 ).

As a result of not having adequately studied linoleate deficiency per se, it appears to have been assumed that 1) EFA deficiency and linoleate deficiency are synonymous and 2)that linoleate requirements can be determined using EFA deficient diets that lack nutrients other than linoleate, i.e. that are also deficient in -linolenate. I think that both these assumptions are wrong, and as a result, for many years, we may have overestimated the requirement for linoleate.

Despite losing body content of (n-6) polyunsaturates relative to baseline levels, over 80 d linoleate deficient rats grew the same as those consuming 2% of energy as linoleate and had few dermal lesions (Cunnane and Anderson 1997 ). This contrasts with the more severe grow impairment and scaliness of the skin of EFA deficient rats and supports previous work suggesting that as little as 0.4% of energy as linoleate is probably sufficient if -linolenate is present in the diet (Bourre et al 1990 ), which is not the case in EFA deficiency. Despite the competitive interaction between linoleate and -linolenate as reviewed by Holman (1998) , they have similar and relatively high rates of ß-oxidation. Thus a dual deficiency of linoleate and -linolenate would probably cause a more rapid depletion of both fatty acids from body stores than either linoleate or -linolenate deficiency alone. It would require more linoleate to correct the deficiency symptoms than if -linolenate was present in the diet, thereby overestimating the dietary requirement for linoleate alone. The slower depletion of (n-3) polyunsaturates from body stores when linoleate is present in the diet may explain why it has been hard to induce clear and consistent deficiency symptoms of (n-3) polyunsaturates. Coincidentally, when -linolenate is added to EFA deficient diets, linoleate deficiency is also harder to induce (Bourre et al. 1990 , Cunnane and Anderson 1997 , Hansen and Jensen 1983 ).

Linoleate is always present in diets deficient in (n-3) polyunsaturates because suitable natural oils exist that contain linoleate with only traces of -linolenate, thereby avoiding the expense and effort needed to prepare and feed diets containing specific free fatty acids. However, for linoleate deficiency studies, no such natural oils exist so that purified -linolenate and oleate must be combined with a dietary source of long chain saturates to provide all fatty acid types excluding (n-6) polyunsaturates. This additional effort is necessary in order to belatedly establish the true symptoms of linoleate deficiency per se and it dietary requirements. Hence, paradoxically, although a dietary requirement for linoleate became widely accepted long before that of -linolenate, knowledge of the effects of linoleate deficiency per se and, more importantly, its true requirement, appears to lag well behind that of the (n-3) polyunsaturates.

Manuscript received September 5, 1998. Initial review completed November 5, 1998. Revision accepted November 5, 1998.

REFERENCES

1. Bourre J. M., Dumont O. L., Clement M. E., Durand G.A.. Endogenous synthesis cannot compensate for absence of dietary oleic acid in rats. J. Nutr. 1997;127:488-493.[Abstract/Free Full Text]

2. Bourre J. M., Piciotti M.., Dumont O., Pascal G., Durand G.. Dietary linoleic acid and polyunsaturated fatty acids in rat brain and other organsMinimal requirements of linoleic acid. Lipids 1990;25:465-472.[Medline]

3. Cunnane S. C., Anderson M. J.. Pure linoleate deficiency in the ratInfluence on growth, accumulation of n-6 polyunsaturates, and [1-¹⁴C]-linoleate oxidation. J. Lipid Res. 1997;38:805-812.[Abstract]

4. Hansen H. S., Jensen B.. Urinary prostaglandin E₂ and vasopressin excretion in essential fatty acid deficient ratsEffect of linolenic acid supplementation. Lipids 1983;18:682-690.[Medline]

5. Holman R. T.. The slow discovery of the importance of omega 3 essential fatty acids in human health. J. Nutr. 1998;128:427S-433S.

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