FACTORS INFLUENCING THE METABOLIC EFFECTS OF DIETARY FRUCTOSE*

MXCDO~S..D

Department of Physiology, Guy's Hospital Medical School, London SEI 9RT, Great Britain

(Received: 4 June, 1975)

ABSTRACT

Dietary fructose, either as such or in sucrose, raises the level of triglyceride in the fasting blood. Several factors can modify this response and among these are the sensitivity and sex of the consumer, the type of dietary fat accompanying the fructose, and whether the fructose is taken as such or in sucrose.

INTRODUCTION

The metabolic effects of fructose are different from those of glucose, notably in the response of the triglyceride level of fasting serum (Macdonald, 1966a). The tri- glyccridc in fasting blood is mainly endogenous trigiyceride and is a risk factor in coronary artery disease (Carlson & Bottiger, 1972). Patients with hypertrigiyceri- dacmia show a further rise in this lipid fraction when given additional fructose and especially sucrose (Nikkila & Keldd, 1972). It may therefore be of clinical interest to discuss some of the factors that can modify the metabolic response to dietary fructose--taken either as such, or in the disaccharide sucrose.

SEX OF THE CONSUMER

The first suggestion that the lipid response to sucrose was not the same for young women as for men was reported in 1964 (Beveridge et al., 1964). It was found that

* Based on a paper read at a symposium on 'Sugars in Nutrition' held at Nashville, Tenn., USA, in 1972.

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Fd. Chem. (1) (1976)---© Applied Science Publishers Ltd, England, 1976 Printed in Great Britain

88 IAN MACDONALD

a high sucrose diet raised the fasting serum triglyceride concentration in men but not in young women. This was confirmed soon after (Macdonald, 1965) and was taken a step further by the finding that the triglyceride response of post-menopausal women to dietary sucrose was similar to that of men (Macdonald, 1966b). In a more detailed study the component of sucrose responsible for the different effects on serum triglyceride levels was found to be fructose (Macdonald, 1966a).

It was obviously of interest to discover which hormone or hormones were responsible for the different lipid response of young women to fructose and to learn whether the difference lay in absorption or in metabolism. Some evidence to suggest that the difference did not lie in the processes of absorption was the fact that when fructose or glucose were given intravenously to non-human primates, a sex difference in the immediate triglyceride response was apparent (Jourdan, 1969).

The difference in the triglyceride response between males and young females to sucrose by mouth was found in monkeys and the rise in fasting levels of serum triglyceride in the males could be prevented by the administration of oestrogen. On the other hand, giving testosterone to the female animals did not result in any rise in triglyceride levels while on a high sucrose diet (Coltart & Macdonald, 1971). These findings would suggest that oestrogen prevents the increase in the triglyceride level in response to sucrose (and, presumably, fructose).

However, this finding is contrary to that found in pregnanacy where there is not only hypertriglyceridaemia but also hypervolaemia (Svanborg & Vikrot, 1965) and also to the finding of a rise in fasting triglyceride level during oral contraceptive therapy (Wynn et aL, 1966). A resolution to this apparent conflict has recently been suggested by the preliminary findings that in male rats, the lipid response to sucrose is affected not only by oestrogen and progesterone, but when the two hormones are given together to an animal, the triglyceride response in the liver seems to be opposite to that of either hormone given alone (Jeffreys & White, 1972).

Art augmentation effect is seen when the oral contraceptive is given to monkeys on a high sucrose diet. Under these circumstances the level of endogenous serum triglyceride rises more than when either hormone is given alone (Stovin & Macdonald, 1975).

It is for future research to decide where and how the sex hormones operate in dietary fructose-lipid metabolism. The administration of glycerol both acutely and chronically leads to a marked increase in serum triglyceride in men, but a much less marked response is seen in young women (Macdonald, 1970). As ~ glycerol phosphate is an intermediate in fructose metabolism these findings would suggest that the sex hormones interfere at this stage or later in the formation of the glycerol moiety of triglyceride. On the other hand, Nikkila & Kekki (1971) have shown that young women clear triglyceride from the serum more effectively. As the level of any constituent of the serum is a balance between input and output, it is possible that both factors could be playing a part.

METABOLIC EFFECTS OF DIETARY FRUCTOSE 89

TYPE OF DIETARY FAT ACCOMPANYING THE FRUCTOSE

Although it is frequently necessary, when studying the metabolic effects of a dietary constituent, to give that constituent in large quantifies---or remove it altogether--this is not usually comparable with the physiological levels of ingestion. Hence it would seem appropriate to study the effects of dietary fructose in con- junction with fat, especially as it is known that the nature of dietary fat can have profound effects on some aspects of cholesterol metabolism. Endogenous tri- glycerides are no exception and the increased serum concentration of this lipid fraction brought about by sucrose can be reversed, both in normal subjects (Macdonald, 1967) and in hyperlipidaemia (Antar et al., 1970). The fasting level of serum triglyceride, normally raised by a diet high in fructose, is substantially reduced when the fructose diet contains sunflower seed oil, although the fall is not so marked as in fructose-free diets (Macdonald, 1972). It seems, therefore, that the nature of the dietary fat could be a more important factor than the nature of the dietary carbohydrate, even possiblymalthough this has not been shown--in the so-called carbohydrate-induced hyperlipidaemia.

EFFECT OF DIETARY NITROGEN ACCOMPANYING THE FRUCTOSE

Although no experiments using dietary fructose with various forms of dietary protein have been carried out, this is not so with sucrose. A rise in endogenous serum triglyceride occurs in man in diets very high in sucrose, whether the protein is calcium caseinate, sodium caseinate, egg albumen or gelatin, but when an amino acid mixture replaces the protein the rise in fasting serum triglyceride levels is very much greater. It can be deduced that this response is in some way connected with fructose because, in the amino acid diet with the fructose replaced by glucose syrup, no such rise in serum trigiyceride occurs (Coles & Macdonald, 1972).

STATE OF INGESTED FRUCTOSE

The bulk of the fructose normally consumed by humans is in the disaccharide (with glucose) sucrose. Dietary fructose in the monosaccharide form occurs mainly in honey and fruit. It is therefore of interest to learn whether there are any metabolic differences which depend on whether fructose is consumed as a disaccharide with glucose or p e r se. Certainly the osmotic effects of fructose become apparent in adults when 70-100 g fructose are taken by mouth, whereas no osmotic conse- quences occur when the same amount of fructose is eaten in twice the amount of sucrose. Consistent with this is the finding in men that the serum fructose level is

90 IAN MACDONALD

significantly higher after ingesting sucrose than after equimolecular amounts of glucose and fructose (Macdonald & Turner, 1968). Any direct effect that fructose has on metabolism can presumably be modified according to whether it is consumed as such or in the form of sucrose.

OTHER FACTORS THAT MAY MODIFY THE METABOLIC EFFECTS OF DIETARY FRUCTOSE

It has been established that the frequency of eating can change the metabolic response (Fabry, 1967) and that the frequency of consuming sucrose affects the rate of increase of triglyceride in fasting serum (Macdonald et al., 1970), a rise that is probably due to fructose.

There is a marked individual variation in the metabolic response to fructose, and this applies not only to triglyceride levels but also to other metabolites such as uric acid (Heuckenkamp & Zollner, 1971) and lactate (Pereira & Jangaard, 1971). There is also a within-individual variation in the response to fructose, because endogenous hypertriglyceridaemia seems to be more frequent in middle-agcd than in young men.

Serum fructose levels after ingesting sucrose are higher in men with peripheral vascular disease than in aged-matched controls (Macdonald & Turner, 1971) although it is not known in this instance which is the cart and which the horse.

CONCLUSIONS

There are doubtless many as yet unknown factors that modify the metabolic response to fructose, but those that are known would suggest that not only is it important to know how the body responds to a single constituent of the diet, but it is of equal importance to learn in what way the other constituents of the diet and the nature of the consumer modify this response.

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