Review Monounsaturated Oils Do Not All Have the Same Effect on Plasma Cholesterol

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Review Monounsaturated oils do not all have the same effect on plasma cholesterol

AS Truswell and N Choudhury Human Nutrition Unit, University of Sydney, Sydney, NSW 2006, Australia

Evidence assembled here indicates that when olive oil forms a major part of dietary fat in controlled human experiments, total and LDL-cholesterols are somewhat higher than when the same amount of fat is one of the modern predominantly monounsaturated oils: low erucic rapeseed or high oleic sun¯ower oil. Oils rich in monounsaturated fatty acids thus do not all have the same effect on plasma cholesterol. This phenomenon is explicable by consideration of the content of other fatty acids and the non-saponi®able fractions of the different monounsaturated oils. It helps to explain the discrepancy that has existed between the classic experiments (using olive oil), which found monounsaturated oils `neutral', and some of the more recent experiments which found them more cholesterol-lowering than carbohydrates. Four published meta-analyses are reviewed. The three which included most of the published experiments show that monounsaturated fatty acids (MUFA) have less plasma cholesterol-lowering effect than polyunsaturated fatty acids. Descriptors: monounsaturated fatty acids; plasma cholesterol; LDL and HDL; olive oil; canola oil; high-oleic sun¯ower oil

In the original human experiments on the effect of different (canola) and high-oleic sun¯ower and saf¯ower oils were fats and oils on plasma cholesterol (Ahrens et al, 1957; not then generally available. The rule that MUFAs have a Malmros & Wigand, 1957; Keys et al, 1957; Hegsted et al, neutral effect prevailed for 30 y and was re¯ected in 1965; Vergroesen & De Boer, 1971) and others all found authoritative dietary recommendations (for example, Amer- that oleic acid (18:1, o-9), the major monounsaturated fatty ican Heart Association, 1973; Joint Working Party, 1976). acid, had little or no plasma cholesterol-lowering effect But Mattson & Grundy (1985) reported that MUFA gave compared with linoleic acid (18:2, o-6), the predominant the same lowering of plasma LDL cholesterol as polyunsa- dietary polyunsaturated fatty acid, which gave consistently turated oil in metabolic ward experiments. Plasma total lower plasma cholesterols. Keys et al (1958) expressed the cholesterol was slightly lower on the polyunsaturated diet effect of oleic acid as neutral, not different in its effect on but this was because HDL cholesterol was a little lower. plasma cholesterol from an equivalent amount of carbo- The next year Grundy (1986) reported that MUFA oil was hydrate. They calculated that the coef®cient for monoun- not neutral compared to carbohydrate Ð plasma LDL and saturated fatty acids (MUFA) in the regression equation: total cholesterols were lower with MUFA oil compared to low-fat, high carbohydrate, and HDL cholesterol was D total cholesterol mg 100 ml higher. Grundy's MUFA rich oils were high-oleic saf¯ower 2:76 D sat 0:05 D mono 1:35 D poly 1:68 1 oil. This appeared to be another example of nutritionists was so small (and not statistically signi®cantly different changing their minds and advice. It was hard to understand from zero), that it is ignored in the usual form of Keys' how Keys and the other earlier investigators had all got it predictive equation (Keys et al, 1957; Anderson et al, wrong. One possible explanation is that Grundy et al (1986) 1957): used liquid formula diets (Hegsted & Nicolosi, 1990); D total cholesterol 2:74 D sat 1:31 D poly 2 another is that their mono and poly diets both had very high P/S ratios (3.0 and 7.5 respectively). They had how- In equations (1) and (2) D fat class is the change of fat class ever differentiated LDL, HDL and VLDL cholesterol. expressed as percent of total calorie intake. While their reports were being considered the oxidised All these researchers measured only total plasma LDL hypothesis for atherogenesis was proposed (Steinberg cholesterol and they used olive oil to represent predomi- et al, 1989) and the fact that in vitro MUFA are not liable to nantly MUFA oils, namely oils rich in 18:1 cis (Ahrens et autoxidation, but polyunsaturated fatty acids are (Pryor, al, 1957; Malmros & Wigand, 1957; Hegsted et al, 1965; 1994), added another reason for re-evaluation of the role of Vergroesen & De Boer, 1971; Keys et al, 1958). Olive oil MUFAs (Mattson, 1989). was the obvious oil to choose. Low erucic rapeseed oil In subsequent research some papers have supported Grundy's ®ndings (Wardlaw et al, 1991), others have not Correspondence: Prof AS Truswell. (Carmena et al, 1996; Dreon et al, 1990). Some experts Monounsaturated oils do not all have the same effect on plasma cholesterol AS Truswell and N Choudhury 313 Table 1 Regression equations for change of plasma total cholesterol acids were less in these). In the 63 papers reporting `solid (mmol/l) from meta-analyses food diets' blood total and LDL cholesterols were signi®- Satsa Monoa Polya Other cantly increased by saturated and decreased by polyunsaturated fatty acids; MUFA produced no signi®cant effect Keys et al, 1957b 0.071 0.001 70.037 (Table 1). There was no signi®cant difference in the small Mensink & Katan, 1992 0.039 70.003 70.015 positive effects of MUFA and polyunsaturates on HDL Hegsted et al, 1993c 0.053 70.003 70.031 0.0007 DCd Clarke et al, 1997 0.052 0.005 70.026 cholesterol. These three meta-analyses all reach substantial agree- a Change of fatty acid group as percentage of total dietary energy. ment (Table 1). The fourth meta-analysis (Gardner & b Coef®cients converted for mmol/l from original mg/dl. Kraemer, 1995) comes to different conclusions but it only c Equation for combined metabolic ward studies (coef®cients for ®eld studies were quite similar). included 14 papers, a minority sample of all the published d Change of dietary cholesterol in mg/MJ. human experiments. Gardner & Kraemer's (1995) results indicated no signi®cant differences in total LDL or HDL expressed opinions such as `we now know that diets high in cholesterol when oils high in MUFA or polyunsaturated MUFA are as effective as those rich in polyunsaturated fatty acids were compared. They did not publish a regres- fatty acids (PUFA) in lowering serum cholesterol but, in sion equation. Surprisingly they do not appear to have been contrast to the effect of n-6 PUFA, MUFA do not lower aware of the meta-analysis by Mensink & Katan (1987) HDL' (Ulbricht & Southgate, 1991). Of®cial recommenda- three years earlier in the same journal. tions are more cautious. For COMA in the UK `Substitution A possibility mentioned in discussion by a few authors of saturates by monounsaturates reduces plasma levels of (Hegsted et al, 1993; Gardner & Kraemer, 1995) is that total and LDL cholesterol to about the same extent as average samples of speci®c plant oils rich in MUFA might substitution by carbohydrates .... There is only inconsis- differ somewhat in their effect on plasma cholesterol. tent evidence that monounsaturates per se actively reduce While investigating the possibility that palmitic acid LDL cholesterol' (Department of Health, 1994). (16:0), and hence palmolein, may be less cholesterol- In a situation like this meta-analysis might be helpful. raising than myristic and lauric acids and oils rich in Four have now been published. They differ considerably in these (Hayes et al, 1991) we happened to compare in design and selection of studies. Mensink & Katan (1992) turn, in three separate sets of human experiments (21± 42 selected 27 trials published between 1972 and 1992 invol- subjects per experiment) plasma total, LDL and HDL ving 682 subjects. Their selection criteria looked for good cholesterol on palmolein against three MUFA rich oils: dietary control, descriptions that allowed calculation of canola, olive and high-oleic sun¯ower oils. Palmolein intake of fatty acid classes and good design. They con- contains more saturated and less MUFA (Table 3). We cluded that all fatty acids increase HDL cholesterol but the found that total and LDL cholesterols were lower on canola effect diminishes with increasing degree of unsaturation. oil than on palmolein (Truswell et al, 1992) and on high- The regression equation for LDL cholesterol showed a oleic sun¯ower oil than on palmolein (Choudhury et al, signi®cant negative (namely, lowering) coef®cient for 1997) as predicted by the Keys et al (1957) equation, but polyunsaturates, not for MUFA (Table 1). they were not lower on olive oil than on palmolein Hegsted et al (1993) included the whole literature, (Choudhury et al, 1995). HDL cholesterols averaged including early papers that only reported total cholesterol, 0.10mmol/l higher on palmolein than on each of the with a few exceptions: formula diets or very short experi- three MUFA oils. The same results of these three compar- mental periods. They separately analysed 50 papers report- isons have been reported by others (Table 2): lower ing metabolic ward experiments and 37 ®eld study cholesterols on canola cf. palmolein (Sundram et al, experiments, and focused on serum total cholesterol. In 1995) and on high oleic sun¯ower oil cf. palmolein regression equations for both sets of data, saturates had (Denke & Grundy, 1992; Noakes et al, 1996; Cater et al, positive and polyunsaturates negative coef®cients but again 1997) likewise the same plasma cholesterols on olive oil as the coef®cient for MUFA was not statistically signi®cantly on palmolein (Ng et al, 1992). By deduction plasma different from zero (Table 1). cholesterol should therefore be higher on olive oil than Clarke et al (1997) include 71 papers (5076 subjects) in on canola oil or on high-oleic sun¯ower oilÐand these their meta-analysis but analyse separately the eight papers results have recently been reported in direct comparisons that used formula diets (overall effect of saturated fatty (Lichtenstein et al, 1993; Perez-Jimenez et al, 1995) (Table

Table 2 Mean plasma cholesterols & LDL-cholesterols, mmol/l, in crossover paired comparisons of predominantly monounsaturated oils against another monounsaturated oil or against the more saturated palmolein

Monounsaturated oils n Palmolein Canola HOSO Olive

21 5.04 (3.22) 4.51 (2.81)a Truswell et al (1992) 23 4.54 (2.56) 4.44 (2.44) Sundram et al (1995) 14 5.17 (3.93) 4.44 (3.31)a Denke & Grundy (1992) 23 6.23 (4.18) 5.70 (3.77)a Noakes et al (1996) 42 5.50 (3.69) 5.12 (3.42)a Choudhury et al (1997) 9 5.79 (4.37) 5.22 (3.72)a Cater et al (1997) 33 5.05 (3.43) 5.10 (3.47) Ng et al (1992) 21 4.63 (3.41) 4.65 (3.33) Choudhury et al (1992) 15 5.03 (3.26)a 5.31 (3.42) Lichtenstein et al (1993) 21 3.95 (2.40)a 4.26 (2.64) Perez-Jimenez et al (1995) a Plasma cholesterol signi®cantly lower than on the oil being compared. Monounsaturated oils do not all have the same effect on plasma cholesterol AS Truswell and N Choudhury 314 Table 3 Lipids in predominantly monounsaturated oils

Canola Olive Low eruric rapeseed High oleic sun¯ower High oleic saf¯ower

18:1 cis (% total FAs) 76 63 80 73 Saturated fatty acids C12-16 (% total FAs) 14 7 7 8 Polyunsaturated fatty acids (% total FAs) 10 30 9 18 Squalene mg/100g 500 (small amount) 30 (small amount) Total phytosterols mg/100g 110 250 350 440

Note: Fatty acids percentages based on analyses for experiments in Table 2. Most range Æ 5% total FAs.

2). In animals too plasma LDLs were higher on olive oil or Keys' classic result. When 20% of energy as carbohydrates olive/saf¯ower (2:1) than on canola/palm oil (9:1) in guinea was replaced by olive oil there was no difference in plasma pigs; hepatic LDL receptors were more abundant on the total cholesterol. But HDL cholesterol was signi®cantly canola/palm oil diet (Fernandez et al, 1996). In rats olive higher on olive oil and triglycerides lower than on carbo- oil leads to higher concentrations of cholesterol in the liver hydrate. This is because in short term experiments HDL than diets with saturated or polyunsaturated fatty acids cholesterol tends to be lower when carbohydrate is sub- (Beynen, 1989). In cynomolgus monkeys a polyunsaturated stituted for any fat or oil (changing at more than 10% of fat diet increased the fractional catabolic rate of apo B dietary energy) (Truswell, 1994). In another experiment lipoprotein; this was not seen on a monounsaturated fat diet Mensink et al (1989) found that LDL-cholesterols, like (Brousseau et al, 1993). total cholesterols did not differ when olive oil was The relatively high plasma cholesterol with olive oil exchanged for carbohydrate. compared to other MUFA oils is consistent with the Does the realisation that olive oil gives somewhat higher unexpected ®nding that Cretan boys had similar plasma plasma cholesterols than other MUFA oils affect the cholesterols to boys in the USA and Holland, though their standing of the Mediterranean diet as a nutritional ideal? dietary fat was mainly olive oil (Aravanis et al, 1988a; Not fundamentally. There are 17 Mediterranean countries Mensink & Katan, 1989). Middle-aged men in Crete do not and many Mediterranean diets; olive oil is only one show low plasma cholesterol either nowadays; they aver- component of the traditional concept, along with plentiful aged 5.5 mmol/l in 1988 (Aravanis et al, 1988b). vegetables, fruit, high glycaemic index cereals, pulses and If olive oil usually gives higher plasma cholesterols than wine, more ®sh than red meat (Ferro-Luzzi & Sette, 1989). other MUFA oils this could explain the discrepancy Olive oil cannot explain the French paradox; the French between the results of Grundy's group and those of the nation only obtains 2% of dietary energy from this food earlier human experiments. (Ferro-Luzzi & Leclerq, 1997). Olive oil certainly gives The shorthand description that an oil is (predominantly) lower plasma cholesterol than butter (Ahrens et al, 1957), monounsaturated omits details of the fatty acid pattern that even if newer MUFA oils and polyunsaturated oils can can in¯uence plasma cholesterol levels (Table 3). Canola produce still lower cholesterols, and it is hypothesised that oil contains more polyunsaturated fatty acids than olive oil. the polyphenols in virgin olive oil may act in vivo as High-oleic sun¯ower oil contains only 4% saturates against protective antioxidants (Wiseman et al, 1996). Other 14% in olive oil while both contain about the same 10% of MUFA oils have negligible amounts of these polyphenols polyunsaturated fatty acids. High-oleic saf¯ower contains (Colquhoun et al, 1996), although they usually contain 8% saturates (less than olive oil) and 18% polyunsaturates more vitamin E than olive oil (Bauernfeind, 1980). (more than olive oil). Hence olive oil should tend, on Keys' formula, to give higher plasma cholesterols than the other three MUFA oils. Differences in the non-saponi®able lipids References (Table 3) between these oils probably work in the same direction. Olive oil contains much more squalene than other Ahrens EH Jr, Hirsch J, Insull W Jr, Tsaltas TT, Blomstrand R & Peterson ML (1957): The in¯uence of dietary fats on serum-lipid levels in man. vegetable oils, about 500 mg per 100 g (Perez-Jiminez et Lancet 1, 943±953. al, 1995; Miettinen & Vanhanen, 1994). Indeed squalene is American Heart Association (1973): Diet and coronary heart disease. used by food technologists to identify the presence of olive Statement for physicians and other health professionals developed by oil (Belitz & Grosch, 1987). Squalene is on the pathway of the Committee on Nutrition. 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