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The Effects of Different Food Fats on Serum Cholesterol Concentration in Man
Abstract
• Total and beta lipoprotein serum cholesterol responses to changes in dietary fats are reported from 4 series of controlled experiments lasting from three to 6 months each, with maintenance for periods of two to 4 weeks in each case on different kinds and amounts of fats. From 16 to 28 men were used in each experiment, the subjects being selected schizophrenics maintained under rigidly standardized conditions in a special metabolic research unit of the Hastings State Hospital. The experiments were designed to eliminate time trends and to cover both directions of change from one fat to another.
• The diets used conformed to ordinary American foods and menus and were constant and adequate in calories, proteins, vitamins and minerals, the fats being isocalorically substituted for carbohydrates and covering the range of about 9 to 41% of total calories from total fats. The fats studied were: mixed fats in an average American diet both at low-fat (9 to 16% of calories) and high-fat (35 to 41% of calories) levels, olive oil, cottonseed oil, hydrogenated coconut oil, corn oil, sunflower seed oil and sardine oil.
• The low-fat diets consistently produced a fall in the serum cholesterol concentration from the control (ordinary U. S. diet) level. Fifty grams daily of olive oil or cottonseed oil introduced into the low-fat diets also produced a significant fall but less marked than the low-fat diet alone.
• At 50 gm daily of experimental fat, there was no significant difference between olive oil and cottonseed oil in the cholesterol response. Cottonseed oil at 100 gm daily produced a slightly lower cholesterol concentration than did olive oil fed at the same level. The basic low-fat diet also tended to produce a lower cholesterol concentration than 100 gm of olive oil daily. A much more marked depression of serum cholesterol concentration was produced by 100 gm daily of corn oil. Sunflower seed oil and sardine oil also produced significant cholesterol concentration depressions but were less effective than corn oil. Coconut oil, 100 gm daily, produced no significant change in the serum cholesterol compared with the control diet with the same total fat supplied in mixed form. The serum cholesterol values on 100 gm of butterfat daily were somewhat higher than on the control diet equal in total fat content.
• The changes in the total cholesterol concentration were accounted for, within the limits of error, by the cholesterol in the beta lipoprotein fraction.
• The serum cholesterol responses to the various fats corresponded roughly to the principle that saturated fats promote higher cholesterol levels than polyunsaturated fats but neither degree of saturation (iodine value) nor content of linoleic acid fully explained the results. Coconut oil is less cholesterol-promoting than would be predicted from the theories that degree of saturation or the content of essential fatty acids is the controlling factor. Sardine oil is considerably less cholesterol-depressing than would be expected if degree of unsaturation is the major factor. And corn oil caused greater depression of serum cholesterol than would be expected from either the essential fatty acid or the degree of unsaturation theories.
... In 1957, Keys published two important papers, one in the Journal of Nutrition (Anderson, Keys & Grande, 1957) and the other in Lancet (Keys, Anderson, Grande, 1957) on controlled feeding studies using schizophrenic patients from the Hastings State Hospital, businessmen in Minnesota, and Japanese coalminers in Shime, Japan. These were relatively small, short-term feeding studies with the number of subjects ranging from 16 to 66. ...
... In 1957, Keys published two important papers, one in the Journal of Nutrition (Anderson, Keys & Grande, 1957) and the other in Lancet (Keys, Anderson, Grande, 1957) on controlled feeding studies using schizophrenic patients from the Hastings State Hospital, businessmen in Minnesota, and Japanese coalminers in Shime, Japan. These were relatively small, short-term feeding studies with the number of subjects ranging from 16 to 66. ...
Coconut oil has been adversely affected by the current dietary guidelines that advocate a lowering of total fat and the replacement of saturated fat with polyunsaturated fat. This recommendation has its origins in the saturated fat-cholesterol-heart disease hypothesis that Ancel Keys first proposed in 1957. This hypothesis became an official recommendation with the publication of the Dietary Guidelines for Americans in 1980 and has been adopted by many other countries and international agencies. The dietary recommendations also warn against coconut oil. Recently, the American Heart Association re-issued this warning in its 2017 Presidential Advisory. However, a critical review of the experiments that Keys conducted has revealed experimental errors and biases that cast serious doubt on the correctness of his hypothesis and the warnings against coconut oil. Further, the recommendation to decrease saturated fat recommendation effectively means an increase in unsaturated fat in the diet. The actual result has been an increase in omega-6 fats and a high omega-6 to omega-3 fat ratio. This unhealthy ratio has been linked to heart disease, the very disease that the AHA wants to target, as well as cancer and inflammatory diseases. Defective experiments have led to defective guidelines. This first paper in this series of papers will present these errors and biases and address the points raised by the AHA.
... Conclusions have varied regarding the effect of dietary fat of animal origin on the one hand and of a plant origin on the other. Human studies (Kinsell et al., 1953;Ahrens et al., 1954;Beveridge et al., 1956;Bronte-Stewart et al., 1956;and Anderson et al., 1957) have shown that low serum cholesterol levels are obtained by feeding certain vegetable oils. Fisher and Leveille (1957) reported that, in a short term experiment with laying hens, blood cholesterol levels were found to be decreased by 20 percent of dietary linseed, sunflower and soybean oils, but not by tallow. ...
... It has been shown in work with chicks that the depressing effect of a vegetable fat (corn oil) on serum cholesterol levels is neither due completely to the high content of unsaturated fatty acids nor to the amount of "essential" fatty acids, but to a third unknown factor "X" present in corn germ and crude corn oil (Jones et al., 1956). Anderson et al. (1957) showed that corn oil caused greater depressions of serum cholesterol than would be expected from either the effect of "essential" fatty acids or the degree of unsaturation. The fact that egg yolk cholesterol does not respond to soybean oil as does serum cholesterol should not be considered as disagreement between the two sets of data. ...
SEVERAL dietary components have been shown to affect serum cholesterol concentrations in a wide variety of species. Conclusions
have varied regarding the effect of dietary fat of animal origin on the one hand and of a plant origin on the other. Human
studies (Kinsell et al., 1953; Ahrens et al., 1954; Beveridge et al., 1956; Bronte-Stewart et al., 1956; and Anderson et al., 1957) have shown that low serum cholesterol levels are obtained by feeding certain vegetable oils.
Fisher and Leveille (1957) reported that, in a short term experiment with laying hens, blood cholesterol levels were found
to be decreased by 20 percent of dietary linseed, sunflower and soybean oils, but not by tallow. The effect of these fats
on fatty acid composition of eggs was studied by the same workers, and it was observed that the cholesterol content of egg
fat was essentially unchanged by alterations in the fatty . . .
... Interestingly, several studies of CSO were conducted in 1950-1960. [37][38][39] Several studies evaluated the effects of CSO provided as tube-feeding formulas on serum cholesterol and triglyceride levels. 40,41 In the past decade, there has been renewed interest in CSO because of greater availability 42 and possibly because of its fatty acid profile. ...
Context
Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils.
Objectives
To conduct a systematic review of randomized controlled trials (RCTs) examining effects of CSO on markers of lipid metabolism and evaluate lipid and lipoprotein effects of incorporating CSO into a healthy dietary pattern using regression equations.
Data Sources
A systematic search was conducted for RCTs comparing CSO with a non-CSO comparator in any population.
Data Analyses
The Katan regression equation was used to predict lipid/lipoprotein changes when incorporating CSO into a US-style healthy eating pattern at 25 to 100% of the total oil allowance (ie, 27 g/2000 kcal) compared with average American intake (NHANES 2017 to 2020 pre-COVID pandemic).
Results
In total, 3 eligible publications (n = 2 trials), with 58 participants that provided 44% and 30% of total energy as CSO, were included. Fasting low-density lipoprotein cholesterol (LDL-C; ≈ –7.7 mg/dL) and triglycerides (≈ –7.5 mg/dL) were lower after 5 days of a CSO-enriched diet vs olive oil (OO). In a 56-day trial, CSO lowered total cholesterol (TC; ≈ –14.8 mg/dL), LDL-C (≈ –14.0 mg/dL), and non–high-density lipoprotein cholesterol (≈ –14.2 mg/dL) vs OO. Postprandially, angiopoietin-like protein-3, -4, and -8 concentrations decreased with CSO and increased with OO intake. Compared with average American intake, a healthy eating pattern with 27 g of CSO was estimated to lower TC (–8.1 mg/dL) and LDL-C (–7.3 mg/dL) levels, with minimal reduction in high-density lipoprotein cholesterol (–1.1 mg/dL). Compared with the healthy eating pattern, incorporating 27 g of CSO was predicted to increase TC and LDL-C levels by 2.4 mg/dL.
Conclusion
Limited high-quality research suggests CSO may improve lipid/lipoprotein levels compared with OO. Cholesterol predictive equations suggest CSO can be incorporated into a healthy dietary pattern without significantly affecting lipids/lipoproteins.
... The subsequent feeding of the same formula diet with coconut oil, raised the level of serum cholesterol although not to the levels previous to the intake of the linoleate rich diet. It was noted that the effect on the increment of serum cholesterol by coconut oil was less pronounced than anticipated based on its saturation (Anderson et al., 1957). In two publications, a cross-sectional study of pre-and post-menopausal women, Feranil et al. (2011) found that a high coconut oil intake related to high HDL in 1,121 premenopausal women but not in the 718 post-menopausal women. ...
Coconut oil has a multitude of health benefits. Most of the predictions and the interpretations of the nutritional quality of coconut oil are based on the fatty acid composition of coconut oil. This book details the well-established chemistry of the main compounds such as free fatty acids, triglycerides and all other lipid forms as well as the most recently investigated chemistry of the minor compounds such as phenolic fraction of coconut oil. In addition, the recent findings related to the antioxidants present in coconut oils extracted under different conditions, the antioxidant properties as well as health benefits related to both main and minor components of coconut oil are also summarized.
... Ancel Keys, past head of the Department of Hygiene at Minnesota University conducted a series of dietary experiments in the 1950s on long-term hospitalised male patients [40]. The results of these experiments, showing changes in TC of groups of men on "controlled" diets, have been influential in the current belief that saturated fat increases TC so these will now be discussed in some detail. ...
The lipid hypothesis of coronary heart disease proposes that a high total cholesterol level has a causative role in coronary heart disease (CHD), specifically in the development of atherosclerosis. It forms the basis for formulating target levels of serum cholesterol and hence the widespread use of statins for lowering cholesterol. An extension of the lipid hypothesis is the diet/heart hypothesis of coronary heart disease. This theory combines two ideas—that saturated fat raises cholesterol levels, and that a reduced saturated fat intake will lower cholesterol levels, thereby inhibiting the development of atherosclerosis and manifestations of CHD. Those who make diet recommenda-tions or prescribe medication to reduce cholesterol may be unaware of the underpinning science. The original research behind these recommendations has given us "healthy heart" guidelines and preventive measures we assume to be true. While the lipid and diet/heart hypotheses are often presented as fact, they remain inadequately proven theories that have little agreement from ex-perts. Historical perspectives can help us understand the basis of current-day beliefs. In the lipid hypothesis case, research from the 1950s and 60s was instrumental in its formation. This early work should not be considered irrelevant, outdated or obsolete because current recommenda-tions from national heart associations in many countries continue to be shaped by these studies. This paper examines evidence used to formulate the lipid hypothesis and, subsequently, the diet/ heart hypothesis. By critically evaluating steps in the formation of the theory, inconsistencies, mistakes and alternate explanations become apparent and cast doubt on its validity.
... After World War II several studies were conducted to determine the etiology of chronic cardiovascular diseases, in response to the special interest in the effect of dietary fats on dyslipidemias (Gofman et al., 1950). A strong association was found which led to an For the exclusive use of Amanda M. Baviera intensive search aimed at determining which families within the fats were mostly involved in nutritional-origin blood lipid profile changes, as well as distinguishing important differences in the level of unsaturation of fatty acids (Anderson et al., 1957). From that time and for the next 20 years a large number of studies that associated certain specific lipid components with atheroma development and subsequent cardiovascular mortality were published (McGandy et al., 1967;Keys, 1968). ...
It has been recognized that one major risk factor present in current lifestyle that contributes to the development of metabolic dysfunctions like obesity, type II diabetes mellitus and other associated diseases is the long-term ingestion of high-fat diets. However, the relationship between high-fat diet and the mechanisms involved in the pathogenesis of these metabolic disorders has been subject of extensive studies and seems to involve a broad range of physiological changes that affects several tissues. Initial investigations to comprehend these changes showed that the central feature of insulin-resistant state installation in obese animals is the chronic low-grade inflammation promoted by a pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), synthesized and released by white adipose tissue. After that, new areas of research have been arising in the understanding of several other alterations that explain the relationship between the high-fat diet ingestion and various pathologies. In this way, lipid accumulation and mitochondrial dysfunction in skeletal muscle, changes in the gut microbiota and impairment in hypothalamic and hippocampus neuronal remodeling have been pointed as new candidates to the development of metabolic disturbances as a consequence of high-fat diet ingestion. In this chapter will be described the most recent scientific evidence about the mechanisms of the changes promoted by a high-fat diet in the development of metabolic disorders.
... holesterol and triglyceride levels. Keys and Hegstead are among many who have investigated the above fats by correlating fatty acids composition with serum cholesterol level in humans. The approximate "atherogencity values" assigned to the common fatty acids in the diet are: 3 for 12:0 and 14:0, 1 for 16:0, -0.7 for 18:2w6, and 0 for 18:0 and 18:1. (3,32,18). These values are part of the basis for many of the early health benefits claimed for vegetable oils with a high polyunsaturated Isaturated fatty acid ratio (piS). More recently, oils with a high oleic acid content were reported to have cholesterol lowering properties similar to the high linoleic acid oils but with the added benef ...
... The effect of diet on serum cholesterol has been widely studied in humans, chickens, rats and other animals. Relationships between saturated and unsaturated fats and blood serum cholesterol levels in humans have been reported by Ahrens et al. (1957), Beveridge et al. (1956), Anderson et al. (1957) and numerous others. These investigators have suggested a link between the intake of animal fats and hypercholesteremia. ...
Egg yolk cholesterol was measured on a total of 67 hens from a closed population of White Leghorns. Three eggs per hen were
analysed to arrive at the mean cholesterol level for each hen. Milligrams percent of egg yolk cholesterol was determined for
each egg according to the method described by Abell (1952). This method was modified by using the color reagent of Zlatkis
et al. (1953).
Egg yolk cholesterol level ranged from a low of 921.4 mgs.% to a high of 1755.6 mgs.% with the parental population mean being
1268.8 mgs.%. A significant negative correlation was observed between rate of production and egg yolk cholesterol level with
a significant positive correlation between hatch of fertile eggs and egg yolk cholesterol. Rate of production and hatchability
accounted for approximately 16% of the variance in egg yolk cholesterol.
Eight-tenths of a standard deviation on each side of the population mean was used to truncate this population into low, medium
and high egg yolk cholesterol dams, and to establish selection intensities. Egg yolk cholesterol level was determined on a
random sample of 137 progency from the parent dams. A highly significant difference of 71.45 mgs.% of cholesterol was found
between the mean egg yolk cholesterol level of the progency from the low cholesterol dams and the progeny produced from the
high cholesterol dams, indicating separation of the populations after one generation of selection. The heritability of yolk
cholesterol level based on intrasire regression of offspring on dam was 0.24.
... The importance of blood lipids in general and cholesterol in particular in the pathogenesis of atherosclerosis has led to a search for dietary regimens to control hypercholesterolaemia. Dietary fish oils are effective in lowering serum cholesterol (Bronte-Stewart, Antonis, Eales & Brock, 1956; Anderson, Keys & Grande, 1957; Ahrens, Insull, Hirsch, Stoffel, Peterson, Farquhar, Miller & Thompson, 1959;DeGroot & Reed, 1959). In studies using chickens Wood (1960) demonstrated that vitamin A was the active hypocholesterolaemic factor in fish oils. ...
1. The interrelationship between cholesterol and vitamin A metabolism has been studied in rats.
2. The effect of cholesterol feeding in increasing the liver storage of cholesterol w-as enhanced during vitamin A deficiency.
3. This effect was due to an increased rate of absorption of cholesterol and not due to a decreased turnover rate.
4. Feeding of high levels of vitamin A markedly depressed the cholesterol absorption; however, its turnover was unaffected.
A practical consideration in feeding human beings, either for experimental, therapeutic, or preventive care hinges on the acceptability of a food pattern. These authors have evolved their practical food pattern from a series of quantitative diet tests and determinations of serum cholesterol. In all cases, menu patterns have been made up with foods commonly available in the market. This practical food pattern can be adapted to the various levels of animal fats and vegetable oils as prescribed by the physician.
Ancel Keys, whose life spanned over 100 years (1904–2004), made a wealth of seminal scientific and public health contributions. As a physiologist, nutritionist, and public health scientist, he has left his mark on the 20th century by exploring different areas of physiology and nutrition, as well as by contributing to the understanding of basic public health issues. Among his major achievements one can mention in chronological order: studying adaptation to very high altitude, developing the K ration to enable the US military to survive with light but dense food, dissecting the physiology of starvation and nutritional rehabilitation to optimize recovery of functions, uncovering the link between serum cholesterol and heart disease, coordinating the first multi‐country epidemiological longitudinal study in nutrition and health, coining the word “body mass index” (BMI), which he showed to be the best body weight index to predict body fat, and promoting the Mediterranean diet for a healthy life style. This review examines the historical events and scientific intrigues that have surrounded Ancel Keys's major classical studies that have ensured him a central place in the history of medical science.
Processed foods have been part of the human diet from the very earliest times. Recently, processed foods have come under scrutiny, particularly the category ultraprocessed foods as defined in the NOVA classification of foods. The basic tenet behind this renewed concern about ultraprocessed foods is that it is processing per se, which matters in diet and health, not nutrients or foods. Notwithstanding this, the literature on ultraprocessed foods is almost entirely focused around nutrients and obesity. However, not all studies have found positive links between obesity and ultraprocessed food intake. The category, ultraprocessed foods, is large, accounting for approximately 60% of energy intake and 90% of added sugar intake. The advocates of the NOVA system advise that the intakes of these foods should be avoided, but the scientific basis for this advice is very weak. Thus, a reduction in ultraprocessed foods has been advocated covering 16 foods to reduce US intakes of added sugar. However, when US food consumption data are examined on a food-by-food basis, only 6 of these 16 foods are associated with high added sugar intakes. Data from the United States, United Kingdom, Canada, and Brazil fail to show a relationship between percent energy from ultraprocessed foods and the intakes of fats, saturated fatty acids, or sodium. There is a positive association between ultraprocessed food intake and the intake of added sugar. A negative correlation with dietary fiber is found. This is not surprising, because almost all added sugar is found in the category, ultraprocessed foods, while the majority of dietary fiber is excluded. When compared with the scientific literature, there is little scientific basis for limiting the use of infant foods, fat spreads, or commercially prepared breads in the present diet.
Despite more than a century of research, cardiovascular disease (CVD) and coronary heart disease (CHD) are the leading causes of death in the developing world. Since the early days of CVD research, the underlying cause and putative prevention strategies remain elusive. This chapter discusses the history of the lipid hypothesis, from the initial observations of Anitschkow and Chalatow to the industrious work of Gofman and the further studies of Ancel Keys, who endeavoured to discover the role of cholesterol and saturated fat in CVD. The Seven Countries Study identified diet, saturated fat, and cholesterol as the underlying causes of CVD development. This chapter delivers an overview of the early research that formed the “lipid hypothesis,” which led to the development of modern treatment and prevention strategies for CVD.
The investigation was undertaken to develop a diet suitable for studying the effects of nutritional factors on cholesteremia in the rat.
A high level of hydrogenated coconut oil in the diet had little effect on serum cholesterol, but it enhanced essential fatty acid deficiency.
Exclusion of pyridoxine from the diet caused a slight elevation of serum cholesterol concentration and a severe growth inhibition.
Feeding of cholesterol led to an appreciable elevation in serum cholesterol concentration and enhancement of essential fatty acid deficiency. The further addition of cholic acid to this diet caused a still greater rise in serum cholesterol concentration. The relative proportions of cholesterol and cholic acid in the diet determined the serum cholesterol concentration obtained, with cholic acid exerting the greater hypercholesteremic effect. Corn oil added to this diet at a level of 1% reduced the accumulation of serum cholesterol.
There was a considerable elevation of serum cholesterol concentration when thiouracil was also included in the diet, however, thiouracil caused a severe growth depression and the inclusion of 1% of corn oil in the diet containing thiouracil was without effect on the serum cholesterol concentration.
The effects of these dietary changes on serum lipid phosphorus and liver lipid concentrations were also studied.
A diet containing 25% of hydrogenated coconut oil, 1% of cholesterol and 0.5% of cholic acid was selected as suitable for the study of nutritional factors affecting serum cholesterol concentration in the rat.
Lingcod liver oil unsaponifiable material was separated into three main fractions by means of an aluminum oxide column. Major components of the three fractions were vitamin A, cholesterol, and glyceryl ethers, respectively. These fractions were given as dietary supplements to cholesterol-fed chicks and the effect of the supplements on the hypercholesterolemia induced by the cholesterol feeding was investigated. The fraction containing vitamin A prevented the hypercholesterolemia. Crystalline vitamin A acetate produced a similar effect when it was added as a dietary supplement. It was concluded that vitamin A was probably the hypocholesterolemic agent in lingcod liver oil although other compounds in the oil may also exert some influence on the control of the serum cholesterol concentrations in the chicks.
Dietary experiments in which food was supplied in the form of a homogeneous liquid formula ration of definitely known composition have been performed on 171 subjects (159 men and 12 women, university students).During an initial period of 8 days all subjects ate the same ration and then groups of 8 to 12 individuals were given rations varying in respect of the fat moiety for a further 8 days. Plasma cholesterol analyses were performed at day 0, 4, 8, 12, and 16.The results obtained were interpreted as indicating that: firstly, there is no simple relationship between the hypocholesterolemic effect of an oil and degree of unsaturation; secondly, sitosterol or something closely associated with this sterol in the unsaponifiable matter accounts for a large part of the hypocholesterolemic activity of corn oil; and thirdly, certain fatty acids of short chain length or some other substance in butterfat and coconut oil have a hypercholesterolemic effect.
An investigation was carried out into the effect of marine fish oils on the serum cholesterol levels in hypercholesterolemic chickens. The oils were fed at the 10% level in the diet. Lingcod liver oil and halibut liver oil prevented the hypercholesterolemic effect of supplementary cholesterol, whereas crude herring oil increased the hypercholesterolemia to the same extent as did corn oil and tallow. Ratfish liver oil, dogfish liver oil, and basking shark liver oil had less noticeable effects on the cholesterol levels. No clear explanation could be given for the observed behavior but there seemed to be a difference in the effects on serum cholesterol of liver oils from teleostei fish and from selachii fish, the former class of liver oils being much more potent in preventing the increase in serum cholesterol concentration in chickens caused by the addition of cholesterol to the diet.
Im Rahmen der Ernährung dient die Nahrung dem Aufbau und der Erhaltung des lebendigen Organismus. Wenn sie diese Aufgaben erfüllen soll, muß sie in der Lage sein, ausreichende Mengen aller jener Bausteine zu liefern, die der Organismus für sein Wachstum, seine Erhaltung und die unübersehbare Fülle seiner Leistungen benötigt.
This chapter discusses the chemical factors affecting potato chip quality and processing techniques. The chemical composition of the tubers, as well as that of the frying medium, greatly influences chip quality. Reducing sugars in the tubers react with amino acids and other compounds present and cause undesirably dark chips. Tubers of low specific gravity take up more fat during processing, slightly decreasing the yield and producing chips containing more oil or fat than desired. Thus, these two factors (reducing sugar content and specific gravity) are of great importance to chippers. The chapter presents tuber characteristics and chipping quality and discusses the types of fats used in chip manufacture. Processing techniques, which include the storage and conditioning of tubers, vary greatly. It provides excellent directions on how to store and handle the frying fat. The chemical and physical characteristics essential for chipping have been discussed. Important problems in chip industry include the production and maintenance of suitable tubers, the disposal of wastes from peeling, trimming, and washing operations, and the elimination of undesirable oils and odors that escape through the stacks used to carry away the vapors from the cookers.
"Only once in a great while does a book come along that really does the job in addressing a major medical issue. When this happens, all can be joyful. Readers will find ALL their favorite dietary puzzlements dealt with With consummate scholarship, clarity and brevity, Truswell sifts out the chaff and identifies the critical questions, the responsible investigators, and the key studies. So says Emeritus Professor Henry Blackburn from the University of Minnesota in the foreword to this remarkable concise book on the history of research on diet and heart disease. This was a theme of scientific, medical and public interest in the 20th Century, a century marked by the rise and fall of coronary heart disease as the major cause of death in the first world, followed by the rise of this cause of death in the developing world. There is obviously much to learn, and this book is an excellent starting point, tracing dietary factors and their role in heart disease one by one: fats, sugar, salt, alcohol, coffee, trans-fats, etc. Without an understanding of the role of diet and the changes that have been seen in the North American and NW European diet, the story of the decline in the heart disease death rate may have been very different.
In recent times much knowledge has been gathered on factors that play, or may play, a role in the etiology of atherosclerosis. Besides other studies, many investigations of the blood plasma constituents have been made to establish their possible relationship with atherosclerosis, and also to find the relation of these blood constituents, and of atherosclerosis, to such factors as diet, habits of life, race, and climate. In a similar way some of these techniques have been used for studies of pregnant women, and, less frequently, in cases of complicated pregnancy. Of the latter, only data on toxemia of pregnancy (pre-eclampsia, eclampsia) are considered here. The available data can be divided into the following main groups: (1) (a) Dietary factors suggested or proved to play a role in causing or preventing the disease in human beings, either by a deficiency or by excess of one or more substances. (b) Dietary measures causing the same or very similar disease in experimental animals, together with measures to prevent the development of the disease in these animals. (2) (a) Deviations from the normal of the blood plasma levels of a number of substances, whether normally present or not. This includes also reactions occurring in the blood or blood vessel walls the underlying abnormalities of which are not yet known. (b) Deviations from the normal amounts of substances excreted by the kidney, including data on substances present only in the diseased. (3) The influences of nondietary therapeutic measures. (4) Habits of life which can play a role in inducing or preventing both diseases. (5) Possible similarities in the clinical symptoms and the (anatomical) pathological findings in both diseases, and their course with time.
The first requirement in human nutrition is for an energy source; the metabolic fuels that provide this are carbohydrates, fats, protein, and alcohol. There is a need for some essential fatty acids and for relatively small amounts of vitamins and minerals. The gold standard method of measuring basal metabolic rate (BMR) and energy expenditure in an activity is by measurement of heat output from the body. At its simplest, energy intake should match energy expenditure and hence, assuming that body weight is within the desirable range, should be such that a constant body weight is achieved. The need for protein is not just for total protein, but for an intake of amino acids in the amounts required for body protein synthesis and turnover.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) methylesters (ME) were prepared from a squid-liver oil and their hypocholesterolemic activities examined with rats. The supplement of 0.3% EPA-ME to the diet containing 1.0%cholesteroland 4.0 %butter as lipids reduced a serum-cholesterol level markedly, whereas DHA-ME gave almost no effect on the serum-cholesterol level. Both EPA-ME and DHA-ME reduced the liver-cholesterol level as effectively as linoleic acid did. The supplement of small amounts of EPA-ME was also effective in lowering the serum-cholesterol level; a dose of 0.03 # EPA-ME suppressed by 60.7# the elevation of serum-cholesterol level. The relationship between elevated serum-cholesterol levels and the incidence of coronary artery diseases is well established1). In general, animal fats increase serum-cholesterol levels, whereas vegetable oils have a hypocholesterolemic effect in experimental animals and man. On the other hand, fish oils have been shown to reduce serum-cholesterol levels in man2"4) and animals57). Stansby8'9) has also revealed that fish oil rich in highly unsaturated fatty acids (HUFA) are possibly effective in preventing the heart diseases relating to atheriosclerosis in man. The hypocholesterolemic effects of fish oils have been supposed to be due to HUFA, especially eicosapentaenoic acid (EPA: 20:5co3)*4 and docosahexaenoic acid (DHA: 22:6o>3)10*11). Futher-more, several investigations have demonstrated that EPA is probably effective in preventing the formation of thrombi.1214) However, further detailed studies have not been carried out probably due to the difficulty in preparing large quantities of HUFA such as EPA and DHA for biological and clinical tests.
Background:
A cholesterol-lowering diet and several other dietary interventions have been suggested as a management approach either independently or as an adjuvant to drug therapy in children and adults with familial hypercholesterolaemia (FH). However, a consensus has yet to be reached on the most appropriate dietary treatment. Plant sterols are commonly used in FH although patients may know them by other names like phytosterols or stanols.
Objectives:
To examine whether a cholesterol-lowering diet is more effective in reducing ischaemic heart disease and lowering cholesterol than no dietary intervention in children and adults with familial hypercholesterolaemia. Further, to compare the efficacy of supplementing a cholesterol-lowering diet with either omega-3 fatty acids, soya proteins, plant sterols or plant stanols.
Search methods:
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register, which is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated with each new issue of The Cochrane Library), quarterly searches of MEDLINE and the prospective handsearching of one journal - Journal of Inherited Metabolic Disease. Most recent search of the Group's Inborn Errors of Metabolism Trials Register: 22 August 2013. We also searched PubMed to 05 February 2012.
Selection criteria:
Randomised controlled trials, both published and unpublished, where a cholesterol-lowering diet in children and adults with familial hypercholesterolaemia has been compared to other forms of dietary treatment or to no dietary intervention were included.
Data collection and analysis:
Two authors independently assessed the trial eligibility and risk of bias and one extracted the data, with independent verification of data extraction by a colleague.
Main results:
In the 2014 update of the review, 15 trials have been included, with a total of 453 participants across seven comparison groups. The included trials had either a low or unclear risk of bias for most of the parameters used for risk assessment. Only short-term outcomes could be assessed due to the short duration of follow up in the included trials. None of the primary outcomes, (incidence of ischaemic heart disease, number of deaths and age at death) were evaluated in any of the included trials. No significant differences were noted for the majority of secondary outcomes for any of the planned comparisons. However, a significant difference was found for the following comparisons and outcomes: for the comparison between plant sterols and cholesterol-lowering diet (in favour of plant sterols), total cholesterol levels, mean difference 0.30 mmol/l (95% confidence interval 0.12 to 0.48); decreased serum LDL cholesterol, mean difference -0.60 mmol/l (95% CI -0.89 to -0.31). Fasting serum HDL cholesterol levels were elevated, mean difference -0.04 mmol/l (95% CI -0.11 to 0.03) and serum triglyceride concentration was reduced, mean difference -0.03 mmol/l (95% CI -0.15 to -0.09), although these changes were not statistically significant. Similarly, guar gum when given as an add on therapy to bezafibrate reduced total cholesterol and LDL levels as compared to bezafibrate alone.
Authors' conclusions:
No conclusions can be made about the effectiveness of a cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, for the primary outcomes: evidence and incidence of ischaemic heart disease, number of deaths and age at death,due to the lack of data on these. Large, parallel, randomised controlled trials are needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, plant sterols or stanols, soya protein, dietary fibers to a cholesterol-lowering diet.
Gruppen von Ratten, die cholesterinfreies Futter mit 30 % Safflor- oder 30 % Kokosnussöl erhielten, wurde in den Magen (4-14C)Cholesterin gegeben. Der sich anschliessende Anstieg in der Radioaktivität des Aortencholesterins war bei der Kokosnussölgruppe wesentlich höher als bei den Saffloröltieren. Beide Gruppen verhielten sich nahezu identisch bezüglich des Plasmacholesteringehaltes, der Aktivität-Zeit-kurve des Plasmacholesterins, der Aortencholesterinkonzentration and der in vitro Cholesterinsynthese der Aorta aus Acetat. Es wurde daher der Schluss gezogen, dass bei gleicher Plasmacholesterinkonzentration Kokosnussfütterung im Vergleich zur Salorölfiitterüng zu einem schnellerem Transport des Cholesterins aus dem Plasma in die Aortenwand führt.
Schätzungsweise kam in der Safflorölgruppe fur etwa 3/4 des Cholesterins der Aortenwand Transport aus dem Plasma in Betracht. Fur die Kokosnussöltiere liess sich these Berechnung nicht durchführen.
Die Fettsäuren der Cholesterin-Ester and der Triglyzeride des Plasmas zeigten in ihrer Zusammensetzung eine ausgesprochene Tendenz zur Angleichung an die Zusammensetzung des verfütterten Fettes. Die Plasmaphospholipidfettsäuren wurden durch die Kost nur wenig beeinflusst.
The research concerns the effects of the content of fat in food on the plasma cholesterol (5 resp. 35 resz. 60% of the total fat calories consisted in fats which contain mostly saturated fatty acids). It had been continued over a long period on four subjects.
Using nutrition poor on fat the free and the total cholesterol in the plasma is more reduced than in normal mixed food. Nutrition rich on fats proves the plasma cholesterol in the serum as high or only transitorily higher than in normal food.
The lack of a regulable increase of cholesterol after doubling the supply of nutritional fats with high content of saturated fatty acids is contradictory to a common opinion, but the result of the above research corresponds with the experience of other authors to whom the proper attention was not paid.
Summary During storage of Cod-liver and cod-liver-oil at various temperatures (-20° C, -10° C, 0° C, room temperatures), the amount of total cholesterin decreased, where as in general the unsaponified substances increased, which could be ascertained statistically (“student's test”). From the results it can be concluded that in stored cod-liver and cod-liver-oil changes occur, which are caused by oxidation and which decrease the quality of the raw material and its useability for industrial purposes.
Studies on man under controlled condi tions in this laboratory have shown that the average response of the cholesterol concentration in the blood to alterations in the fats in the diet can be predicted with reasonable accuracy from informa tion on the proportions of saturated and polyunsaturated fatty acids in the diet be fore and after the change. (Keys et al., '57, a, b, '59; Anderson et al., '57). The prediction equation derived from these studies has given satisfactory agreement with experimental data obtained by others (Ahrens et al., '57; Malmros and Wigand, '57; Turpeinen et al., '60). Data used for these purposes involve the specification of the fatty acids in the diet in units of weight or proportion of total calories in the diet calculated from the weights. In general, the data used in deriving the prediction equation and test ing its accuracy were obtained from ex periments in which there were no great differences in the average chain lengths of the carbon atoms in the fatty acid mole cules, namely, the weights of the fats were at least roughly proportional to the number of fatty acid molecules. It is con ceivable, however, that the effects of the fatty acids on the cholesterol level are more strictly proportional to the number of molecules than to the gross weight of the fatty acids. If this were the case, dis crepancies would appear when compari son is made of the effects of fats differing considerably in the average chain lengths of the contained fatty acids. Ahrens et al. ('57), from observations with diets containing butter and coconut oil, concluded that saturated fatty acids with short carbon chains cause higher cholesterol concentrations in the serum than equal weights of long-chain fatty acids. Our own experiments with butyric acid in the diet indicated that, at the high est level it occurs in natural diets, this fatty acid has no remarkable effect (Keys,
The serum lipid response of eight dogs before and after surgical thyroidectomy to high fat diets with various degrees of unsaturation was studied. The serum lipids were separated into very low density, low density and high density lipoprotein categories by centrifugation and protein, cholesterol, phospho- lipid and triglycérides of each lipoprotein class measured. While thyroidectomy generally raises the levels of low density lipoproteins, the hypothyroid dogs dem onstrate a smaller or nonexistent increase of phospholipid in response to high fat diets compared to cholesterol increases regardless of degree of saturation. Triglycéridesactually in some cases decrease in the very low density and high density lipoproteins in response to high fat diets. High density lipoproteins are generally not very responsive to dietary fat increases. On the basis of these re sults it seems likely that there are changes in the relative proportions of lipid and protein components in circulating lipoproteins of hypothyroid dogs produced by high fat diets. J. Nutr. 102: 515-522, 1972.
An investigation was carried out into the effect of marine fish oils on the serum cholesterol levels in hypercholesterolemic chickens. The oils were fed at the 10% level in the diet. Lingcod liver oil and halibut liver oil prevented the hypercholesterolemic effect of supplementary cholesterol, whereas crude herring oil increased the hypercholesterolemia to the same extent as did corn oil and tallow. Ratfish liver oil, dogfish liver oil, and basking shark liver oil had less noticeable effects on the cholesterol levels. No clear explanation could be given for the observed behavior but there seemed to be a difference in the effects on serum cholesterol of liver oils from teleostei fish and from selachii fish, the former class of liver oils being much more potent in preventing the increase in serum cholesterol concentration in chickens caused by the addition of cholesterol to the diet.
The influence of a purified rat diet containing 20 or 33% of the saturated medium chain-length triglycerides (MCT) with and without linoleic acid supplements on growth, caloric requirements for weight maintenance and weight increase, fertility, lactation performance, and serum cholesterol levels was compared with that of similar diets containing lard, coconut oil, or no fat.
Among male rats maintained on diets containing 20% lard or 20% MCT and .09% linoleic acid for 18 months no differences were observed between the groups other than the depressed body weight and lowered serum cholesterol levels of the group fed MCT. When groups of male rats were kept at constant weight by the daily restricted feeding of diets containing lard, MCT, or coconut oil or no fat plus 2% linoleic acid, the weight-maintenance requirements of the group fed MCT were higher than of those on lard and coconut oil and even somewhat higher than the requirements of the animals fed the fat-free diet. The requirements for weight increase over those for maintenance were 0.9 g. per gram increase for all diets. Additional linoleic acid in the MCT diet decreased the weight and maintenance differences between groups fed MCT and lard.
The lactation performance of mothers on MCT plus .09% linoleic acid was poor. The second generation animals initially showed signs of more severe linoleic acid deficiency which however disaappeared without linoleic acid supplements.
Some cholesterol levels of animals on MCT were significantly below those of groups on lard. Addition of linoleic acid to the MCT diet did not change the results.
So far as the industry is concerned, the evidence indicating a relationship of dietary fat to heart disease presents some interesting challenges. Undoubedly it portends a change in the fat cousumption pattern toward a lowerper capita use coupled with a shift from solid fats toward a higher proportion of edible oils. Most important of all, however, is the growing recognition that fats and oils are nutritionally valuable foods, intimately related to health and well-being, and should by no means be regarded merely as a source of calories.
Although there are innumerable factors involved in the etiology of heart disease, dietary fat is an important one and fortunately is one that can be modified in whatever way proves desirable. Because the more saturated types of fats lead to higher serum cholesterol levels than do the polyunsaturated oils, and because cholesterol is somehow involved in the course of atherosclerotic heart disease, clinical tests are now in progress to determine whether prolonged use of a diet rich in these oils will lead to fewer heart attacks than does the usual American diet rich in saturated fats. So far, data are encouraging enough to merit recommendation of the modification in dietary fat to the coronary-prone individual and to justify development of new high-linoleate fat products by the industry.
Coconut oil has been one of the most widely used vegetable oils since the agricultural revolution. Only in recent years has
there been controversy over the desirability of its uso. Controversy has usually stemmed from observed disturbances of calcium
or cholesterol metabolism when hydrogenated coconut oil was fed, frequently with inadequate linoleate supplementation, to
experimental animals. Furthermore, in many of the studies involving cholesterol, entirely unphysiological amounts of cholesterol
have been included in the diet. It is contended here that the findings in such studies are the consequence of abnormal nutrition
rather than inherent defects in coconut oil. Evidence from epidemiological studies of arteriosclerosis in populations consuming
large amounts of coconut oil are cited to show that coconut oil in a natural diet is not disadvantageous and may even be of
advantage. The high level of medium chain fatty acids in coconut oil is discussed from the point of view that they may contribute
to beneficial effects on the part of coconut oil under some abnormal conditions.
The fatty acid composition of body lipids was determined by GLC for 14 species of saltwater fish, three species of freshwater
fish and four species of shellfish. In addition, liver lipids of two species and egg lipids of one species were analyzed for
comparison with the fish body lipids. The various species ranged from lean to fatty and contained from 0.7~15.5% oil in the
tissues. Certain major fatty acids were found to vary widely among the species, as follows: 1.6~8.0% myristic, 9.5~33.4% palmitic,
2.0~11.2% palmitoleic, 5.2~29.1% oleic, 0.7~10.5% eicosenoic, 5.0~21.5% eicosapentaenoic, 0.2~11.6% docosenoic and 5.9~26.2%
docosahexaenoic acids. Analyses of two separate mullet-oil samples illustrated the wide differences that are possible for
a single species caught during different seasons. Significant differences in the amt of particular fatty acids were found
in comparing freshwater-fish analyses with analyses for marine fish. Oysters and scallops showed large amt of pentaenoic and
hexaenoic acids in their oils.
We investigated the hypothesis that the hypocholesterolemic activity of corn oil and other unsaturated vegetable oils is related to effects of their nontriglyceride components on intestinal lipid absorption. To test this hypothesis, corn, sunflowerseed (sun) and soybean oils (soy) were separated chromatographically into their pure triglycerides (TGs) and 4 nonTG fractions. For each native oil, a 7-membered series was prepared: native oil, pure TGs, pure TGs plus each of the 4 nonTG fractions, and pure TGs plus all 4 nonTG fractions. Three groups of lymph duct-cannulated rats received continuous (9–10 d) intraduodenal infusions of oils with added cholesterol (equivalent to a diet containing 20% fat +0.4% cholesterol) in a randomized Latin Square design. Each oil was infused for 18 h before lymph was sampled. There were no significant differences in chylomicron TG, phospholipid (PL) and cholesterol (total, unesterified or esterified) transfer rates (μmole/h) or in relative chylomicron size (molar ratio of PL/TG) within any of the 3 series. Recovery of TG and cholesterol in chylomicrons, relative to the rates of infusion, averaged 91 and 99% (corn), 77 and 72% (sun) and 90 and 79% (soy). Our results indicate that, at the level present in these 3 oils, the nonTG components do not significantly influence chylomicron lipid composition or size, or the rate of intestinal secretion of lipid components.
Familial hypercholesterolaemia is an inherited disorder characterised by a raised blood cholesterol, and premature ischaemic heart disease. Changing diet is an important management option to reduce low-density lipoprotein cholesterol (the bad cholesterol) levels. Recently, certain lipid-lowering drugs have shown to be safe and effective for the treatment of children with familial hypercholesterolaemia. However, dietary management remains important either on its own or combined with drug therapy. Several strategies are used to modify diet. This review aimed to compare cholesterol-lowering dietary interventions either in combination with each other or alone. These interventions included adding omega-3 fatty acids or plant sterols or plant stanols or soya proteins to diet. Eleven studies were included in the review. All the studies were short term and the majority were cross-over in design. For most of the comparisons there was no significant difference in the various intervention strategies when compared to cholesterol-lowering diet. However, for total cholesterol levels when plant sterols were compared with a cholesterol-lowering diet, a significant benefit was obtained with plant sterols. However, before drawing any conclusions, methodological problems with pooling results from cross-over studies should be considered. There is an imminent need for long-term trials with parallel group design to assess the potential benefits and harms of a cholesterol-lowering diet.
Trends in consumption of animal products are discussed, including reasons for changes. Although consumption of some products has increased--notably that of broilers and beef--for other products, it has declined, i.e., total dairy products and eggs. Evidence shows that consumers desire a lower fat content in both meat and dairy products, although, in the case of meat, minimal levels are necessary for palatability. Overall, it is suggested that consumers are concerned with nutritional quality and are influenced by health-related concerns. The use of vegetable proteins as extenders and substitutes for animal proteins is reviewed, with the conclusion that they will continue to influence consumption of animal products.
The statistical correlation between elevated serum cholesterol levels and increased risk of coronary heart disease has channeled thinking towards regarding dietary fat and cholesterol as the principal causes of hypercholesteremia. Since 1909 there have been a number of changes in nutrient availability in the United States. Protein availability is unchanged but the ratio of animal to vegetable protein rose from 1.06 in 1909 to 2.37 in 1972. Fat availability has risen by 26% with the ratio of animal to vegetable fat falling from 4.88 in 1909 to 1.64 in 1972. A review of available data indicates that amount and type of protein may affect cholesteremia and atherosclerosis in experimental animals. Soy protein is less cholesteremic than casein but the extent of difference can be affected by the type of carbohydrate. In a semipurified, cholesterol-free diet, saturated fat exerts an atherogenic effect but unsaturated fat does not. No atherogenicity is evident when saturated fat is added to laboratory ration. In the semipurified diet, fructose is more atherogenic than glucose, and casein is more atherogenic then soy protein. The latter difference can be virtually eliminated if alfalfa replaces cellulose as the dietary fiber. The data suggest that all elements of the diet interact and can affect cholesteremia and atherosclerosis. These effects must be considered in the planning of dietary intervention trials.
This article reviews seven community-based programs for prevention of cardiovascular disease and their effects on blood cholesterol levels and saturated fat intake. In two programs, cholesterol levels were reduced more in the intervention area than in the reference area. In two other programs, cholesterol increased less in the intervention area than in the reference area. In one program, cholesterol levels initially fell in the intervention group and increased in the reference group; after the first 4 years, the levels also started to increase in the intervention group. The final two programs reduced cholesterol equally in both groups. Only two programs reported on the intake of saturated fats; in both, intake of saturated fat was reduced more in the intervention area than in the reference populations. In one program area, total intake of fat was reduced more than in the reference area. Published data do not allow us to draw conclusions regarding which components of the programs were most important. These studies show that the average blood cholesterol level can be affected in a general population.
The serum lipid response of eight dogs before and after surgical thyroidectomy to high fat diets with various degrees of unsaturation was studied. The serum lipids were separated into very low density, low density and high density lipoprotein categories by centrifugation and protein, cholesterol, phospholipid and triglycerides of each lipoprotein class measured. While thyroidectomy generally raises the levels of low density lipoproteins, the hypothyroid dogs demonstrate a smaller or nonexistent increase of phospholipid in response to high fat diets compared to cholesterol increases regardless of degree of saturation. Triglycerides actually in some cases decrease in the very low density and high density lipoproteins in response to high fat diets. High density lipoproteins are generally not very responsive to dietary fat increases. On the basis of these results it seems likely that there are changes in the relative proportions of lipid and protein components in circulating lipoproteins of hypothyroid dogs produced by high fat diets.
Reduction in saturated fat and cholesterol intakes, with an increase in polyunsaturated fats, has been recommended for American diets. Studies reported and reviewed here show that such a change will reduce serum lipids and hence presumably the risk of coronary heart disease.
1. Methods are described for the separation, by paper electrophoresis and by cold ethanol, of α- and β-lipoproteins in 0.1 ml. of serum, with subsequent analysis of cholesterol in the separated portions.
2. It is shown that both methods of separation yield separated fractions containing substantially the same amounts of cholesterol.
3. Detailed data are given on the errors of measurement for total cholesterol and for cholesterol in the separated lipoprotein fractions.
4. Studies are reported on the stability of cholesterol in stored serum and on paper electrophoresis strips. It is shown that simple drying on filter paper causes no change in cholesterol content and yields a product that is stable for many weeks at ordinary room temperature.
5. The sources of variability in human serum cholesterol values are examined and it is shown that spontaneous intraindividual variability is a much greater source of error than the errors of measurement with these methods.
1. Lipids exist in the blood serum as emulsions ("chylomicrons") and as solutions of lipoprotein containing proteins, cholesterol, and other lipids. Interest in relation to atherosclerosis is centered on the cholesterol and the beta lipoproteins which contain most of the cholesterol.
2. The diet influences the blood lipids in man and animals but great quantitative differences between species makes it essential to study man himself to discover the effects of the diet on the blood lipids in man.
3. The amount of lipid in the chylomicron form in the serum is practically independent of the concentration of cholesterol and lipoproteins in the serum. The correlation between the concentrations of alpha and beta lipoproteins is very low.
4. Experiments on man show that dietary cholesterol per Se, even in large amount, has no important influence on the serum cholesterol concentration but that the latter is markedly affected by the total fat content of the diet.
5. Calorie intake per se has little influence on the blood lipids. Such effect as it has may be secondary to fat metabolism differences commonly associated with differences in calorie intakes.
6. Studies on population samples of healthy men show a marked direct relationship between the content or proportion of fat in the diet on the one hand and the concentration of total cholesterol and of beta lipoproteins in the serum on the other. The effect of the diet tends to be greater in middle-aged men than in younger men.
7. The average concentration of cholesterol in the serum of men in areas where the diets are very high in fats (of the order of 40 per cent of calories), is 25 to 50 per cent greater than the average in areas where the diets are low in fats (of the order of 20 per cent, or less, of calories).
8. A significant effect of dietary fat level on the serum cholesterol concentration is evident in man in a few weeks on a changed diet. The effect tends to increase very slowly with time thereafter and it is most pronounced when comparison is made between populations habitually subsisting on different diets.
9. It is not known how the dietary fat intake exerts its controlling influence on the blood lipids of man but the mechanisms must be complex.
Three dietary experiments have been performed in which 36, 37, and 49 male medical students and staff members participated as experimental subjects. In each study, everyone consumed the same homogeneous formula diet for eight days at which time they were divided into five groups. One group was maintained on the original diet for a further eight days and the others were given diets varying in respect of the level and nature of the fat moiety. Protein supplied 16.9% of total calories in all experimental rations. In the first experiment, 37 subjects ingested a diet providing 58.5% of calories as corn oil. During the initial period the average of the individual percentage decreases in plasma cholesterol was 32.0 (P = < 0.01). Those continuing on corn oil displayed a further insignificant decrease. The others, receiving diets high in beef dripping, chicken fat, lard, and butter showed average individual percentage increases of 11.7 (P = > 0.05), 12.7 (P = > 0.05), 15.4 (P = < 0.01), and 28.8 (P = < 0.01), respectively. In the second experiment, 49 subjects consumed a fat-free diet for eight days. The average individual percentage decrease in plasma cholesterol was 22.2 (P = < 0.01). Those continuing on the fat-free diet showed little further change. Those ingesting 20 and 60% of calories as corn oil showed further percentage decreases of 6.9 (P = > 0.05) and 15.2 (P = < 0.01), respectively. By contrast, those receiving diets providing 20 and 60%, of calories as butterfat showed respectively percentage increases of 6.6 (P = > 0.05) and 21.7 (P = < 0.01). In the third experiment, 36 subjects ingested for eight days a diet in which butterfat provided 60% of calories. The plasma cholesterol level remained essentially constant, and did not change significantly in those continuing on this diet for a further eight days. The composition of the fat moiety in the remaining groups in terms of per cent calories derived from butter-fat and corn oil respectively was: 45: 15; 30: 30; 15: 45; and 0: 60. The averages of the individual percentage decreases in plasma cholesterol values were, respectively, 3.9, 15.9, 27.1, and 32.0. Except for the lowest of these values all the changes are highly significant (P = < 0.01). In addition to other conclusions that may be drawn from this work, these studies reveal that (1) there is a factor (or are factors) in certain animal fats that acts to elevate plasma cholesterol levels, and (2) there is a factor (or are factors) in corn oil that acts to depress plasma cholesterol levels.
A THEROSCLEROSIS is generally considered to be the major disease of this era. Its consequences in the coronary, cerebral, and peripheral arteries, in the form o£ ocelu- sive phenomena, are responsible for more death and disability than any other disease. In spite of much study and research there is still no agreement con- cerning the sequence of pathogenetic events, etiol- ogy, or treatment of atheroselerosis. The not-too- rare oceurrence of coronary artery ocelusions (almost always a consequence of atheroselerosis) in young men from 20 to 40 years of age testifies to the fallacy of the idea, still prevalent, that atheroselerosis is a problem of the aged or senile. For the male it is a 1 This work was supported (in part) by the Atomic Energy Commission and the United States Public Health Service. The authors wish to acknowledge with gratitude the gener- ous and invaluable advice and assistance given by Profs. Hardin B. Jones and John H. Lawrence. A THEROSCLEROSIS is generally considered to be the major disease of this era. Its consequences in the coronary, cerebral, and peripheral arteries, in the form o£ ocelu- sive phenomena, are responsible for more death and disability than any other disease. In spite of much study and research there is still no agreement con- cerning the sequence of pathogenetic events, etiol- ogy, or treatment of atheroselerosis. The not-too- rare oceurrence of coronary artery ocelusions (almost always a consequence of atheroselerosis) in young men from 20 to 40 years of age testifies to the fallacy of the idea, still prevalent, that atheroselerosis is a problem of the aged or senile. For the male it is a
A series of studies of cholesterol metabolism in the Cebus monkey were carried out in an attempt to understand the mechanisms responsible for the great differences in serum cholesterol
levels when different dietary fats were used. Three groups of monkeys, one fed diets including 45 per cent of calories as
corn oil, a second corn oil plus cholesterol (0.1 gm./100 calories), and a third lard plus cholesterol for 5 months (mean
serum cholesterol values were 237, 268, and 601 mg. per cent, respectively) were injected with emulsions of cholesterol-4-C14. The mean biological half-lives for the disappearance of serum radiocholesterol were 8.8, 8.4, and 6.6 days respectively.
Esterification of radiocholesterol as measured by equilibration of specific activities of serum-free cholesterol and total
cholesterol was delayed in the monkeys fed lard plus cholesterol. When cholesterol-4-C-14-stearate was given intravenously to a series of monkeys, an erratic non-exponential biological decay curve resulted. Specific
activity for free serum cholesterol was greater than that for total cholesterol within 1 hour after the injection.
After 7 months on experimental diets including corn oil with added cholesterol and lard with added cholesterol the levels
of lipides in most tissues were not different for the two dietary groups, nor were they appreciably elevated above previous
control figures for monkeys not fed cholesterol. Total lipide levels in the adrenals of monkeys fed corn oil were twice those
of monkeys fed lard.
Monkeys were fasted before and after intragastric administration of cholesterol-4-C14 in small formula meals including various fats and fatty acids. The disappearance of total cholesterol from the serum consisted
of a rapid followed by a slow exponential function. The type of fat and fatty acid appeared to influence the rate of disappearance
of radiocholesterol. There was a broad range of apparent activity of the different fats and fatty acids in promoting cholesterol
absorption.
Five apparently healthy male subjects were placed upon diets having the following characteristics:
(1) 100 to 180 mg. cholesterol per day and 10.9 to 18.9 per cent of the total calories in the form of fat.
(2) 900 to 980 mg. cholesterol daily and with the same proportions for fat.
(3) 100 to 180 mg. cholesterol per day and 34 to 46 per cent of the total calories in the form of vegetable fat.
(4) 210 to 300 mg. cholesterol per day and 34 to 46 per cent of the total calories in the form of animal fat.
The diet low in fat and in cholesterol led to a highly significant decrease in plasma cholesterol levels, whereas the addition of cholesterol in the form of egg yolk did not cause any change. When the proportion of dietary fat was increased in the form of vegetable fat, a significant increase occurred in plasma cholesterol levels, and these values were not further significantly increased by a substitution of animal fat for the vegetable fat. The results of this investigation indicate that, within the limits used here, dietary cholesterol has no effect on plasma cholesterol levels, whereas alterations in the level of dietary fat, whether of animal or vegetable origin, led to parallel changes in plasma cholesterol.
Three dietary experiments have been performed in which 36, 37, and 49 male medical students and staff members participated as experimental subjects. In each study, everyone consumed the same homogeneous formula diet for eight days at which time they were divided into five groups. One group was maintained on the original diet for a further eight days and the others were given diets varying in respect of the level and nature of the fat moiety. Protein supplied 16.9% of total calories in all experimental rations. In the first experiment, 37 subjects ingested a diet providing 58.5% of calories as corn oil. During the initial period the average of the individual percentage decreases in plasma cholesterol was 32.0 (P = < 0.01). Those continuing on corn oil displayed a further insignificant decrease. The others, receiving diets high in beef dripping, chicken fat, lard, and butter showed average individual percentage increases of 11.7 (P = > 0.05), 12.7 (P = > 0.05), 15.4 (P = < 0.01), and 28.8 (P = < 0.01), respectively. In the second experiment, 49 subjects consumed a fat-free diet for eight days. The average individual percentage decrease in plasma cholesterol was 22.2 (P = < 0.01). Those continuing on the fat-free diet showed little further change. Those ingesting 20 and 60% of calories as corn oil showed further percentage decreases of 6.9 (P = > 0.05) and 15.2 (P = < 0.01), respectively. By contrast, those receiving diets providing 20 and 60%, of calories as butterfat showed respectively percentage increases of 6.6 (P = > 0.05) and 21.7 (P = < 0.01). In the third experiment, 36 subjects ingested for eight days a diet in which butterfat provided 60% of calories. The plasma cholesterol level remained essentially constant, and did not change significantly in those continuing on this diet for a further eight days. The composition of the fat moiety in the remaining groups in terms of per cent calories derived from butter-fat and corn oil respectively was: 45: 15; 30: 30; 15: 45; and 0: 60. The averages of the individual percentage decreases in plasma cholesterol values were, respectively, 3.9, 15.9, 27.1, and 32.0. Except for the lowest of these values all the changes are highly significant (P = < 0.01). In addition to other conclusions that may be drawn from this work, these studies reveal that (1) there is a factor (or are factors) in certain animal fats that acts to elevate plasma cholesterol levels, and (2) there is a factor (or are factors) in corn oil that acts to depress plasma cholesterol levels.
Dietary experiments in the cholesterol-fed chick have demonstrated that a higher level of serum cholesterol is achieved when cottonseed oil is fed instead of corn oil. Reconstituting the distilled fatty acids of cottonseed oil, and adding a small amount of my-ristic acid so that the proportions of the major fatty acids in corn oil were observed, did not make cottonseed oil fatty acids behave like corn oil in restricting the rise in serum cholesterol. Comparison of the whole corn germ with expressed and solvent extracted corn oil revealed that it was a much more potent agent for limiting the hypercholesteremia and subsequent atherosclerosis than the more refined products. It seems unlikely that this difference between corn oil and cottonseed oil in the effect on the hypercholesteremic response of the cholesterol fed bird could be explained by a difference in fatty acid composition.
Groups of physically healthy, schizophrenic men were metabolically stabilized on a typical American diet and then were maintained at calorie equilibrium under rigid control in dietary experiments lasting 16 or more weeks.
The response of the total serum cholesterol to a change from a low- to a high-fat intake was the same in one group of men receiving 83 g of protein daily as in a matched group on the same diet except for the isocaloric substitution of an extra 47 g of skimmed milk protein for carbohydrate in the diet. The cholesterol in the beta-lipoprotein fraction in the serum behaved as did the total serum cholesterol.
Two groups of subjects were maintained on a low-protein intake (averaging 8.6 per cent of calories from proteins), were changed for four weeks to a high-protein intake (17.7 per cent protein calories) and then were changed back to the low-protein intake, all at a constant fat intake. There was no significant change in the serum cholesterol level in either group at any time.
An increase, maintained for eight weeks, of 1000 mg per day in the dietary cholesterol intake, had no significant effect on the serum level in these experiments.
1 An increase of blood serum cholesterol has been observed in rats subsisting on Purina chow diet when supplemented with butterfat, or sunflower seed oil. Animals on sunflower seed oil also showed increase of liver cholesterol. Rats on “fat-free” diet showed increase in serum cholesterol but no change in liver cholesterol. When Purina chow-butter diet was supplemented with cholesterol and propylthiouracil, an even greater increase in both serum and liver cholesterol was found. 2) Separation of serum protein fractions by paper electrophoresis revealed that most of the cholesterol was associated with albumin and alpha globulin fraction in the rat; whereas, in man, the greatest proportion of cholesterol is found in the beta globulin fraction. This same general distribution was observed in all dietary groups regardless of their serum cholesterol levels, although rats receiving butter-cholesterol-propylthiouracil diet showed a slight shift of cholesterol toward the beta globulin fraction. 3) No diets induced a demonstrable change in mast cell count on tissue of rat ear.
Five apparently healthy male subjects, aged 33 to 41 years, consumed alternately mixed “free-choice” diets and homogenized “formula” diets. The latter, whose composition was accurately known, varied both in cholesterol content and in the amount and type of fat. Blood samples were taken throughout the study and the plasma analyzed for total and free cholesterol and phospholipid.
Diets containing vegetable fat, comprising either 28.4 or 58.5% of total calories, with or without supplementary cholesterol, led to decreases of similar magnitude in plasma lipid levels relative to the levels found on the antecedent mixed “free-choice” diets. When animal fat, in the form of butter, was given to provide 58.5% of calories, there was an actual increase in lipid levels on the 4th and 7th days, followed by a return to a level slightly below that recorded at the beginning of this dietary period.
Under the conditions of this study, there was a highly significant statistical difference between the effects of vegetable fat and animal fat on the blood lipids. A hypothesis has been presented to explain why a high dietary level of vegetable fat in a non-vegetarian diet of mixed food-stuffs causes an increase in plasma lipids whereas it has no such effect when included in a homogenized simple formula diet as the sole source of fat.
In 3 healthy male physicians a reduction of dietary fat produced a significant fall in the serum cholesterol concentration. Subsequently, when a diet containing normal quantities of fat but very low in cholesterol was taken, a rise in serum cholesterol concentration occurred in all 3 subjects.
affectingthe level of plasma cholesterol in humans: Cañad A simplified of total
- J M R Beveridge
BEVERIDGE, J. M. R., W. F. CONNELLANDG. A. MAYER 1956 affectingthe level of plasma cholesterol in humans: Cañad.J. Biochem. and Physiol., 34: 441. A simplified of total J. Biol. Chem., 195: 357. cholesterolin serui i and demon on plant for animaloods in diet
Effect of the rice diet on the serum cholesterc 154 patients with hypertensive SWELL TREADWELL 195f and fattyacid in absorption 180: 124. fattyacids and : therosclerosis, et cetera. 1950 STARK,H.fractions of vascular disease
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