Other fatty acids

3.2.1 Monounsaturated fatty acids (MUFAs)

MUFAs can be synthesized by humans and generally represent a large part of diet fatty acids. Used as an energy fuel, they are also esterified in all lipid types, especially in triglycerides of adipose tissue, maintaining their fluid state at body temperature. Quantitatively, oleic acid (18:1 n-9) is the prominent MUFA.

Its very long chain derivatives (especially those with 24 C) are important in brain structures, such as myelin (BOURREet al., 1976a, b).

It is difficult to study the effect of a total deficiency in oleic acid, since all fats used in animal or human nutrition contain it in variable amounts. This problem was experimentally bypassed in the rat by using diets containing oleic acid-free synthetic lipids. The signs observed during gestation-lactation persist during adult life in animals maintained on deficient diet, though there was no worsening in the alterations of cell membranes but a slight correction. The body, and espe-cially the liver, has not a sufficient synthesis capacity to ensure a normal com-position in oleic acid of membranes in some organs. Despite many gaps in knowledge, oleic acid could be considered as essential during the period of gestation and lactation, at least in the rat (BOURREet al., 1997).

As for polyunsaturated fatty acids, it is likely that oleic acid modulates the activity of enzymes, receptors or transporters through its incorporation into membrane phospholipids. It acts on lung glucocorticoid receptors (VISCARDIand MAX, 1993), benzodiazepin receptors (WITTand NIELSEN, 1994) and signal trans-duction (CHENand MURAKAMI, 1994). It also modulates toxin effects on neuro-blastomas (JOURDONet al., 1989) or expression of some genes (ANTRAS-FERRY et al., 1994).

Concerning cardiovascular diseases, it is noteworthy that palmitoleic acid (16:1 n-7), whose plasma level is normally very low, is considered as a marker of atherogenic risk (CAMBIENet al., 1988). There are controversies about the role of oleic acid in the control of plasma lipoprotein concentration. Although endoge-nous oleic acid stimulates hepatic synthesis and secretion of lipoproteins in vitro (LEGRANDet al., 1997), the replacement of saturated fatty acids for oleic acid in the diet decreases cholesterolemia (GORDONand KRAMER, 1995).

In conclusion, the neutrality of oleic acid is an advantage and justifies its consumption (table 16).

3.2.2 Saturated fatty acids (SFAs)

SFAs are synthesized by humans, especially in the liver, the brain and the adipose tissue. Together with dietary SFAs, they are constituents of phospholi-pids (rich in stearic acid 18:0), sphingoliphospholi-pids and triglycerides. They cover a large part of energy expenditure. They are partially converted into monounsatu-rated fatty acids. In addition, some very long chain SFAs play an important role in the myelin of some nervous membranes (BOURREet al., 1976a, b).

Many epidemiological studies, among which the Seven Countries Study (KEYSet al., 1984), have shown that saturated fat excess was a risk factor stron-gly associated with coronary death. However, it is necessary to study each SFA.

For example, it has been shown that stearic acid does not induce hypercholes-terolemia (GRUNDY, 1994), whereas lauric and myristic acids do (KROMHOUTet al., 1995), the latter being considered as the most powerful (KRIS-ETHERTONand DIETSCHY, 1997). Stearic, palmitic (16:0) and myristic (14:0) acids follow different metabolic pathways, so that they cannot be considered as a whole (HUGHESet al., 1996). For example, it has been recently shown that myristic acid is more rapidly oxidized in vitro than palmitic acid (RIOUXet al., 2000). Moreover, myris-tic and palmimyris-tic acids play an important role in cellular functions by acylating some proteins (CASEY, 1995).

Precise roles of short chain fatty acids (from 4 to 10 carbons) have been little studied in the context of hypercholesterolemia, but recent research works confirm that they are neutral (NICOLISI, 1997; NICOLISIand ROGERS, 1997). They are better absorbed than other fatty acids, using portal route. They are propo-sed in cases of fat malabsorption, which has little interest in the general healthy population.

Finally, butyric acid (4:0), provided by dietary fiber fermentation, is an inhibi-tor of tumor cell proliferation, in vitro and in vivo. It induces apoptosis (program-med cell death) in malignant cells, for example in the colon (BARTRAM et al., 1995; HAGUEet al., 1996). Butyric acid also acts as an antiproliferating factor for vascular smooth muscle cells (RANGANNAet al., 1995).

In conclusion, the evolution of knowledge leads to consider the different saturated fatty acids independently, and to limit their intake to about 8% of energy intake, or 25% of total fatty acids (table 16).

3.2.3 Transfatty acids and conjugated fatty acids

The occurrence of trans fatty acids is normally low in natural products and they do not express known physiological roles. Some industrial processes induce their presence in foods. Several studies have shown that they increase plasma LDL-cholesterol and lipoprotein (a) and thus increase cardiovascular risk (FELDMAN et al., 1996). Although margarine content in trans fatty acids has decreased in France during past years, it is advisable that an upper consump-tion limit be proposed in the future.

Conjugated fatty acids (with conjugated double bonds) are principally for-med in the rumen and are present in milk products and some meats. The major conjugated fatty acids are the CLAs (conjugated linoleic acids), mixture of various molecules derived from linoleic acid and claimed as having anti-carcino-genic properties in various species or models (IPet al., 1994). The 9-cis 11-trans isomer, or rumenic acid, could be the most important, since it is the only one that is incorporated into membrane phospholipids (BELURY and KEMPA -STECZKO, 1997). Biological activity of these compounds is currently under study in the areas of carcinogenesis, diabetes, obesity and cardiovascular diseases.

3.3 Cholesterol

Hypercholesterolemia is a risk factor among others for cardiovascular diseases (BERENSON et al., 1998). Cardiovascular morbidity and mortality

increase with cholesterol plasma level, especially with LDL-cholesterol. On the contrary, cholesterol increase in HDLs (high density lipoproteins) plays a protec-tive role. The relationship between cholesterolemia and incidence of cardiovas-cular events was evidenced by numerous epidemiological studies, with variable degrees of significance (KEYS et al., 1957; KANNEL, 1988). Statistical relation-ships between plasma cholesterol and cardiovascular risk led to the use of plasma cholesterol as a marker or a “witness” of this risk. Beneficial effects of reducing plasma cholesterol using synthesis inhibitors (statins) have demonstra-ted that hypercholesterolemia was not only a marker, but also a true risk factor (SHEPERD et al., 1995; SACKS et al., 1996). However, this concept could be questioned by the discovery of “pleiotropic” effects of statins, independently from their effects on cholesterol synthesis. Normal plasma cholesterol level increases from 20 years of age, around 0.1 g·L^–1every ten years above the thre-shold of 2 g·L^–1. It decreases at extreme ages (above 75 or 80 years), so that the relationship between cholesterolemia and cardiovascular disease disap-pears in the elderly. It is necessary to exclude from possible recommendations all those who could not benefit from cholesterol reduction. The same is true for children, whose cholesterolemia is low. The reduction of plasma cholesterol in the general population is one of the goals of the national cholesterol education program in the United States, directed to moderately hypercholestrolemic sub-jects with associated risk factors.

Two considerations suppress the justification of interventions to reduce plasma cholesterol in some age classes: the physiological increase in plasma cholesterol leads to consider as normal the levels of about 2.3-2.5 g·L^–1around the fifties; the disappearance of the relationship between cholesterolemia and cardiovascular events in the elderly.

Proposing a recommendation to reduce plasma cholesterol indistinctly is seriously questionable for several reasons:

– Endogenous cholesterol biosynthesis is very active and contributes for a major part to plasma cholesterol levels. In healthy people, this synthesis is regulated in many tissues, especially the liver where it is intensively activa-ted by decreasing intakes or increasing catabolism.

– Cholesterol level is poorly influenced by exogenous cholesterol (CONNOR and CONNOR, 1995). A drastic reduction of dietary supply, associated with a modification of dietary fatty acid profile (replacement by mono or polyun-saturated acids for polyun-saturated ones) allows at best to reach a 10-15%

decrease of total plasma cholesterol.

– Reduction of exogenous cholesterol to obtain this decrease is only sustai-nable with difficulty over a long period for people having a moderate risk (MONNIERet al., 1997). Indeed, the exogenous supply modifies plasma cholesterol only when it ranges from 100 to 300 mg·d^–1 (CONNOR and CONNOR, 1995), amount provided by a single egg yolk. The probabilities that the general population follow such a strict diet for a hypothetical bene-fit appear to be rather modest.

The recommendations in this chapter for the repartition of fatty acids, bet-ween saturated, monounsaturated and polyunsaturated, put people in condi-tions of almost optimal nutritional control, and an additional reduction of cholesterol supply below 200-300 mg·d^–1cannot significantly influence the

vas-cular risk. Recommendations to reduce exogenous cholesterol are justified only for hypercholesterolemic people.

4 - ANCs FOR CARBOHYDRATES

National (DUPIN et al., 1992) and international advisory boards (FAO/WHO, 1998) agree that carbohydrates obtained from a variety of food sources should be the major contributor to covering human energy needs (50-55% of daily energy). First, this recommendation is the arithmetic result of those established for other nutrients. It is universally recommended to reduce lipid intakes to 30-35% of energy needs, there is no argument for increasing the contribution of proteins to energy supplies, and the ingestion of alcohol is unjustified from an energy standpoint. Secondly and at the present time, no constituent indispen-sable for growth and maintenance needs and that the organism cannot synthe-size has been identified among carbohydrates. Thus, a carbohydrate-poor diet (Eskimos) leads to no specific deficiency (SZEPESI, 1996).

Carbohydrates exert a number of physiological effects and are very impor-tant for the health and well being of humans. The potential risks from high car-bohydrate supplies involve only special situations and have no effect on current recommendations.