Published Science

There has been much discussion of the conspicuous differences in (1) body size and shape, (2) efficiency of the gastro-intestinal tract and (3) behavioural biology between those mammals subsisting mainly on animal matter and those that graze or browse on grass and (e.g. Moir, 1968; Vallenas et al., 1971; Jolly, 1972; Jarman, 1974; Wilson, 1975; Janis, 1976; Clutton-Brock, 1977). The former have been labelled as “insectivores” or “carnivores”, according to the kind of animal matter consumed, thereby following taxonomic, and thus evolutionary, relationships; the latter are usually called “herbivores”, irrespective of the kind of plant matter eaten, even though the distinction between ruminating, refecting and other herbivores has been stressed in the wide debate. More precise subdivisions are necessary, therefore, although these gross categories still have a use, especially in correlative studies; the two extremes are best labelled, however, “faunivory” and “folivory”, respectively.

There has been much discussion of the conspicuous differences in (1) body size and shape, (2) efficiency of the gastro-intestinal tract and (3) behavioural biology between those mammals subsisting mainly on animal matter and those that graze or browse on grass and (e.g. Moir, 1968; Vallenas et al., 1971; Jolly, 1972; Jarman, 1974; Wilson, 1975; Janis, 1976; Clutton-Brock, 1977). The former have been labelled as “insectivores” or “carnivores”, according to the kind of animal matter consumed, thereby following taxonomic, and thus evolutionary, relationships; the latter are usually called “herbivores”, irrespective of the kind of plant matter eaten, even though the distinction between ruminating, refecting and other herbivores has been stressed in the wide debate. More precise subdivisions are necessary, therefore, although these gross categories still have a use, especially in correlative studies; the two extremes are best labelled, however, “faunivory” and “folivory”, respectively.

Of 27 Asians with a megaloblastic bone marrow, 22 (81%) had nutritional deficiency of vitamin B12 (NMA), while five (19%) had true pernicious anaemia (PA). All the patients were Hindu vegetarians except for a single Muslim who had PA. Dietary intakes of calories, protein, iron, vitamin B12 and folate were below the recommended level in both groups. The PA group had lower levels of serum B12 and higher levels of serum folate than the NMA group. Despite low levels of red cell folate (RCF) in the NMA patients, the abnormality in deoxyuridine (dU) suppression was always corrected by vitamin B12. The dU suppressed value showed a significant inverse relationship to the RCF level. Nutritional deficiency of vitamin B12 is the most common cause of megaloblastic anaemia in Hindu vegetarians but the incidence of true PA is higher than previously thought and may approximate to that of the white population.

Lacto-ovo, lacto, and vegan vegetarian diets were analyzed for calcium, phosphorus, magnesium, zinc, iron, and nitrogen at four calorie intake levels ranging from 1,700 to 2,800 kcal/day. Diets containing dairy products had a high calcium and phosphorus content, ranging from 1,279 to 1,755 mg calcium and 1,378 to 2,160 mg phosphorus for the four calorie levels, respectively, and vegan diets contained less calcium, ranging from 612 to 810 mg. The magnesium content of all three types of vegetarian diets was adequate or high, ranging from 366 to 560 mg/day. The zinc content was lower than that of the RDA (15 mg/day), and was particularly low at the 1,700 calorie intake levels of all diets. The iron content of these diets varied widely and ranged from 12.7 to 22.7 mg. This study has shown that vegetarian diets planned and presented at the higher calorie intake levels contain adequate amounts of minerals and trace elements, whereas this is not the case at the 1,700 calorie intake level. This observation is of importance as the mineral and trace element content of relatively low calorie vegetarian diets would not supply sufficient amounts of these nutrients. In addition, the bioavailability of minerals and trace elements from these diets remains to be determined.

Certain plants - notably soya bean and cassava - contain substances which can produce adverse physiological effects in human beings. People have in some instances learnt to deal with these effects by cooking and other forms of preparation.

To examine myc protein products in the wide variety of human tumor cells having alterations of the c-myc locus, we have prepared an antiserum against a synthetic peptide corresponding to the predicted C-terminal sequence of the human c-myc protein. This antiserum (anti-hu-myc 12C) specifically precipitated two proteins of 64 and 67 kilodaltons in quantities ranging from low levels in normal fibroblasts to 10-fold-higher levels in Epstein-Barr virus-immortalized and Burkitt's lymphoma cell lines, to 20- to 60-fold-higher levels in cell lines having amplified c-myc. The p64 and p67 proteins were found to be highly related by partial V8 proteolytic mapping, and both were demonstrated to be encoded by the c-myc oncogene, using hybrid-selected translation of myc-specific RNA. In addition, the p64 protein was specifically precipitated from cells transfected with a translocated c-myc gene. Both p64 and p67 were found to be nuclear phosphoproteins with extremely short half-lives. In tumor cell lines having alterations at the c-myc locus due to amplification or translocation, we observed a significant change in the expression of p64 relative to p67 when compared with normal or Epstein-Bar virus-immortalized cells.

In somatic cells the level of myc transcription is not restricted to particular cell types but correlates closely with the rate of cell division. Such transcription involves the use of two active myc promoters and produces two messenger RNA species that are differentially represented among the transcripts of different tissues. In apparent contrast to somatic cells, mitotically and meiotically dividing germ cells have veryfew myc transcripts and appear to proliferate, at least for a few divisions, in the absence of myc transcription. These results raise interesting questions regarding the role of the myc gene product in terminally differentiating cells, particularly of the germ line series.

In rats with diet-induced hypercholesterolemia, two concomitant changes began to occur within 1 week and persisted for 1 year: an increase in total plasma cholesterol and an increase in the number of mononuclear cells adhering to the aortic intima (up to values 50 times normal). Adherent cells were approximately 90% monocytes and approximately 10% lymphocytes. Adhesion was focal, with some preference for ostia of aortic branches; it was followed by migration into the subendothelial space. The subendothelial monocytes/macrophages progressively became foam cells, thus giving rise to microscopic "fatty streaks." Ultimately, typical atherosclerotic plaques were formed. Four possible mechanisms of increased cell adhesion are suggested. Endothelial changes were mild; myelin figures arising from the endothelial surface were seen by electron microscopy. Endothelial denudation was never observed, neither in light-microscopic preparations stained with AgNO3 nor by ultrastructure. Platelet participation was minimal. It is concluded that in this model atherosclerotic plaques are initiated by mononuclear cell adhesion and emigration; endothelial denudation is not a necessary step in their pathogenesis.

Mean fasting plasma total cholesterol, low-density lipoprotein cholesterol and total triglycerides were 6, 7, and 19% lower (NS) in 36 vegetarian males compared to 18 nonvegetarian males of similar age, weight, height, alcohol consumption, and physical activity levels. None of the participants smoked. Although the vegetarian subjects were characterized by widely differing egg consumption levels, no relationships were observed between dietary or egg cholesterol intakes and plasma lipid levels. Total fat intake, however, appeared to exert an important influence upon plasma lipid levels within the vegetarian group. Total mean cholesterol and triglyceride levels were 11 and 21% lower and mean high-density lipoprotein cholesterol levels were 14% higher in low-fat vegetarians (23 to 33% kcal from fat) compared to high-fat vegetarians (35 to 48% kcal from fat). The similarity in lipid profiles between vegetarians and nonvegetarians may be partially explained by the relatively high fat intake (36.6%, mean) in the vegetarian subpopulation, and by the careful matching of vegetarians to nonvegetarians.

A proportionate study was carried out of the causes of death of the 759 Vegetarian Society members whose deaths were recorded in Society records and whose death certificates could be traced. Compared to the general population, a lower proportion of deaths from respiratory diseases and from lung cancer was noted particularly in long-standing members, consistent with the evidence that vegetarians smoke less than the average. The proportion of deaths from colorectal cancer was slightly lower than in the general population but there was no reduction in the proportions of deaths from other diseases that have been linked with meat or fat consumption, such as cardiovascular diseases and breast cancer. The proportions of deaths from stomach cancer and from accidents and violence were greater than expected. The significance of the findings is discussed and also the possible limitations of the proportionate method of analysis in relation to studies of vegetarians.

We have indirectly assessed the role of free fatty acids (FFA) and of hepatic ketogenesis in the regulation of ketone body levels in euthyroid and hyperthyroid subjects. All studies were performed under controlled dietary conditions (35 and 45 kcal/kg body weight/day respectively for euthyroid and hyperthyroid subjects). In the post-absorptive state hyperthyroid patients had normal, glucagon levels and, in spite of increased insulinemia (p less than 0.02), elevated concentrations of blood glucose (p less than 0.01), glycerol (p less than 0.001) and ketone bodies (p less than 0.05). In the face of this hyperketonaemia, there was no significant increase of plasma FFA, suggesting possible increased hepatic conversion of FFA to ketone bodies. However, when FFA were acutely raised to high levels, the induced rise of ketone bodies was similar in hyperthyroid and euthyroid subjects. Oral propranolol administration to hyperthyroid patients in the post-absorptive state decreased the concentrations of glycerol (p less than 0.05) and ketone bodies (p less than 0.05) without altering insulin concentrations. Ketone bodies fell without any significant decrease of FFA suggesting a possible direct effect of propranolol administration on hepatic ketogenesis. However, the ketone body response to raised FFA levels was unaffected by propranolol. We have evidence in hyperthyroid patients of increased lipolysis and ketogenesis in spite of increased daily caloric intake. These results suggest that these metabolic abnormalities are not merely due to relative starvation. We have tentative evidence for modification of the intra-hepatic conversion of FFA to ketone bodies in the post-absorptive state but no supporting evidence when FFA levels were experimentally raised.

To study the metabolic effects of ketosis without weight loss, nine lean men were fed a eucaloric balanced diet (EBD) for one week providing 35-50 kcal/kg/d, 1.75 g of protein per kilogram per day and the remaining kilocalories as two-thirds carbohydrate (CHO) and one-third fat. This was followed by four weeks of a eucaloric ketogenic diet (EKD)--isocaloric and isonitrogenous with the EBD but providing less than 20 g CHO daily. Both diets were appropriately supplemented with minerals and vitamins. Weight and whole-body potassium estimated by potassium-40 counting (40K) did not vary significantly during the five-week study. Nitrogen balance (N-Bal) was regained after one week of the EKD. The fasting blood glucose remained lower during the EKD than during the control diet (4.4 mmol/L at EBD, 4.1 mmol/L at EKD-4, P less than 0.01). The fasting whole-body glucose oxidation rate determined by a 13C-glucose primed constant infusion technique fell from 0.71 mg/kg/min during the control diet to 0.50 mg/kg/min (P less than 0.01) during the fourth week of the EKD. The mean serum cholesterol level rose (from 159 to 208 mg/dL) during the EKD, while triglycerides fell from 107 to 79 mg/dL. No disturbance of hepatic or renal function was noted at EKD-4. These findings indicate that the ketotic state induced by the EKD was well tolerated in lean subjects; nitrogen balance was regained after brief adaptation, serum lipids were not pathologically elevated, and blood glucose oxidation at rest was measurably reduced while the subjects remained euglycemic.

To study the effect of chronic ketosis on exercise performance in endurance-trained humans, five well-trained cyclists were fed a eucaloric balanced diet (EBD) for one week providing 35-50 kcal/kg/d, 1.75 g protein/kg/d and the remainder of kilocalories as two-thirds carbohydrate (CHO) and one-third fat. This was followed by four weeks of a eucaloric ketogenic diet (EKD), isocaloric and isonitrogenous with the EBD but providing less than 20 g CHO daily. Both diets were appropriately supplemented to meet the recommended daily allowances for vitamins and minerals. Pedal ergometer testing of maximal oxygen uptake (VO2max) was unchanged between the control week (EBD-1) and week 3 of the ketogenic diet (EKD-3). The mean ergometer endurance time for continuous exercise to exhaustion (ENDUR) at 62%-64% of VO2max was 147 minutes at EBD-1 and 151 minutes at EKD-4. The ENDUR steady-state RQ dropped from 0.83 to 0.72 (P less than 0.01) from EBD-1 to EKD-4. In agreement with this were a three-fold drop in glucose oxidation (from 15.1 to 5.1 mg/kg/min, P less than 0.05) and a four-fold reduction in muscle glycogen use (0.61 to 0.13 mmol/kg/min, P less than 0.01). Neither clinical nor biochemical evidence of hypoglycemia was observed during ENDUR at EKD-4. These results indicate that aerobic endurance exercise by well-trained cyclists was not compromised by four weeks of ketosis. This was accomplished by a dramatic physiologic adaptation that conserved limited carbohydrate stores (both glucose and muscle glycogen) and made fat the predominant muscle substrate at this submaximal power level.

We studied plasma concentrations of TSH (basal and after TRH), thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3; rT3), free T4 and free T3 in thirty obese subjects, twenty patients with anorexia nervosa, fifteen malnourished subjects and twenty normal weight subjects. Total serum T4 values were similar for the four groups of subjects while serum free T4 values were slightly increased in anorexia nervosa and normal in the other groups. Serum total and free T3 levels were both significantly decreased in anorexia nervosa and malnutrition, and within normal limits in obesity. The mean serum rT3 level was increased in anorexia nervosa and malnutrition while was reduced in obesity. A delay in peak response of TSH to TRH stimulation (30' rather than 20') was noted in anorexia and malnourished patients. The results suggest that these alterations of serum iodothyronines are due to a different peripheral conversion of T4 to T3 according to nutritional status.

Previous studies in this Unit have shown that a high protein intake, given as meat, did not induce hypercalciuria, except for the initial and temporary increase in two subjects. In the present investigation the long-term effect of a high meat diet on calcium metabolism was studied for 78 to 132 days in four adult males and the short-term effect for 18 to 30 days in three subjects. Calcium and phosphorus balances and calcium absorption studies, using 47Ca as the tracer, were carried out. During the long-term high meat intake and during the short-term high meat studies, there was no significant change of the urinary or fecal calcium nor of the calcium balance. There was also no significant change of the intestinal absorption of calcium during the high meat intake. These long- and short-term studies have confirmed our previous results that a high protein intake, given as meat, does not lead to hypercalciuria and does not induce calcium loss.

Length and weight measurements obtained on 142 vegetarian and 229 nonvegetarian school children from a normative population were fitted to growth curves using the asymptotic nonlinear regression equation of Jenss and Bayley. All of the children were Caucasian and age ranged from a few weeks to 6 yr. The growth curves obtained for vegetarian children were from 0.5 to 1.0 kg and 1 to 2 cm lower, depending on age, sex, and diet, than were curves for reference populations of nonvegetarian children. Length was affected more than weight. Macrobiotic vegetarian children's curves were more depressed than those of the other vegetarian children, indicating that there was a good deal of heterogeneity in growth within vegetarians which was associated with dietary group characteristics. Measurements of females were more consistently affected than males, and their diets were also more far reaching with respect to animal food avoidances. The analysis of food records available provided evidence that energy intakes of the vegetarians were below recommended levels, whereas protein intakes did not appear to be limiting.

1. Non-haem iron absorption from a variety of vegetable meals was studied in parous Indian Women, using the erythrocyte utilization of radioactive Fe method.2. The studies were undertaken to establish whether Fe absorption could be correlatedwith the chemical composition of the foodstuff.3. Addition of the following organic acids commonly found in vegetables, improved the geometric mean Fe absorption from a basic rice meal as follows: from 0·028 to 0·085 with 1 g citric acid, from 0·031 to 0·081 with 15 mg ascorbic acid, from 0·048 to 0·095 with 1 g L-malic acid, from 0·041 to 0·096 with 1 g tartaric acid. The only exception was oxalic acid; the addition of 1 g calciumoxalate to cabbage (Brassica oleraceae) was associated with some depression in Fe absorption from 0·320 to 0·195.4. There was a marked inhibition of the geometric mean absorption when 500 mg tannic acid was added to a broccoli (Brassica oleraceae) meal (0·015 v. 0·297). Sodium phytate (2 g) caused a similar, though less profound inhibition (0·035 to 0·152).5. When 3 mg ferrous sulphate was added to different vegetables the geometric mean absorption varied widely. Vegetables of low Fe bioavailability were wheat germ (Triticum aestivum) 0·007, aubergine (Solanum melongena) 0·007, butter beans (Phaseolus lunatus) 0·012, spinach (Spinacea oleraceae) 0·014, brown lentils (Lens culinaris) 0·024, beetroot greens (Beta vulgaris) 0·024 and green lentils (Lens culinaris) 0·032. In contrast, bioavailability was moderate or good with carrot (Daucus carota) 0·098, potato (Solanum tuberosum) 0·115, beetroot (Beta vulgaris) 0·185, pumpkin (Cucurbita mixta) 0·206, broccoli 0·260, tomato (Lycopersicon esculentum) 0·224, cauliflower (Brassica oleraceae) 0·263, cabbage 0·320, turnip (Brassica rapa) 0·327 and sauerkraut 0·327.6. All the vegetables associated with moderate or good Fe bioavailability contained appreciable amounts of one or more of the organic acids, malic, citric and ascorbic acids.7. Poor Fe bioavailability was noted in vegetables with high phytate contents (e.g. wheat germ 0·007, butter beans 0·012, brown lentils 0·024 and green lentils 0·032).8. The fact that a number of vegetables associated with low Fe-absorption turned bluish-black when Fe was added to them, suggested that the total polyphenol content in them was high. The vegetables included aubergine spinach, brown lentils, green lentils and beetroot greens. When the total polyphenol content in all the vegetables tested was formally measured, there was a significant inverse correlation (r 0·859, P < 0·001) between it and Fe absorption. The inverse correlation between the non-hydrolysable polyphenol content and Fe absorption was r 0·901 (P

In groups of four, men and women in their 40s and 50s, some of them lean and some overweight, overate for 30 d by 1000 kcal/d (4186 kJ/d) more than they needed to maintain weight. On an average dietary mixture for Americans they gained a mean of 2.68 kg, and on a diet high in carbohydrate (60 per cent of energy) they gained 2.73 kg. However, on a diet high in protein and fat (70 per cent of energy), they gained significantly less, 1.75 kg. On all three diets the subjects should have gained 5 kg, if adipose tissue has an energy density of 6 kcal/g, and had there been no adaptation. There was adaptation, as evidenced by an average 7 per cent increase in thermogenesis, which was measured by 24-h direct and indirect calorimetry. Energy balances were calculated from: bomb calorimeter values for food and body waste; change in fuel stores from body composition measured by densitometry; and daily expenditure estimated from the net food intake needed to maintain body weight during a 30-d control period. During overeating, energy intake matched energy losses (including fuel storage) for the average diet and the high-carbohydrate diet, but on the diet high in protein and fat energy intake exceeded losses by more than 500 kcal/d (2093 kJ/d). Thus smaller than expected weight gains from overeating (luxuskonsumption) were largely explained by increased thermogenesis, except when the diet was high in protein and fat. Lean and overweight subjects did not differ in weight gain, loss of energy in urine and faeces, or thermogenesis from overeating.

Past studies indicate postmenopausal women who eat meat may experience greater bone mineral loss than lacto-ovo-vegetarian women. The present study extends those findings by comparing bone mineral in adult lacto-ovo-vegetarian and omnivorous males. Bone mineral mass was determined by direct photon absorptiometry in 320 lacto-ovo-vegetarian and 320 omnivorous males 20 to 79 yr old. Lacto-ovo-vegetarians were Seventh-day Adventists committed to their diet for at least 20 yr. Measurements were made at a cortical site along the radius. No statistical differences were identified between bone mineral mass in the lacto-ovo-vegetarian and omnivorous males in any decade examined. When contrasted against significant differences between bone mineral mass in postmenopausal omnivores and lacto-ovo-vegetarians, the data presented here may be interpreted as indicating that some factor associated with meat consumption is increasing bone mineral losses in postmenopausal females while having no observable effect in males.

The concentrations of serum total and free testosterone were studied in 30 healthy, middle-aged men during a dietary intervention program. When men were transferred from their customary diet to an experimental diet, which contained less fat with a higher polyunsaturated/saturated ratio (P/S-ratio) and more fibre, there was a significant decrease in serum total testosterone concentrations (22.7 +/- 1.2 vs 19.3 +/- 1.1 nmol/l SEM, P less than 0.001). Furthermore, serum free, unbound testosterone fell from 0.23 +/- 0.01 to 0.20 +/- 0.01 nmol/l SEM (P less than 0.01). The hormonal changes were reversible. This observation suggests that testosterone activity in plasma can at least partly be modified by changing the composition of the diet.

Weanling (22-day-old) rats fed a low protein (8% casein) diet consumed the same amount of energy as controls (22% casein diet), but intake corrected for body size (kJ/kg0.75) was increased in the former group. Weight gain and the efficiency of gain (g gain/MJ) were markedly reduced in low protein fed rats. Resting oxygen consumption (VO2) was elevated by 15% in the low protein group but this difference was completely abolished by beta-adrenergic blockade with propranolol. Interscapular brown adipose tissue (BAT) mass, protein content, mitochondrial yield and GDP binding were increased in low protein fed rats but mitochondrial alpha-glycophosphate shuttle activity of BAT was unaltered, although shuttle activity was elevated in liver mitochondria. Plasma triiodothyronine levels were increased by 64% in the low protein group, whereas insulin levels were markedly reduced in spite of normal blood glucose levels. Resting VO2 and BAT mass were also increased in older (55-day-old) rats fed the low protein diet, but the changes were smaller than in weanling rats. These data suggest that the decreased metabolic efficiency seen in rats fed protein deficient diets involves sympathetic activation of BAT, and is therefore similar to the thermogenic responses seen in cold adapted and cafeteria-fed animals.

1. The plasma disappearance of 3H-labelled 25-hydroxyvitamin D3 (25(OH)D3) was studied in healthy volunteers on normal and high-fibre diets, using 3H-labelled tracer doses given intravenously. 2. The mean (+/- SEM) plasma half-life in the high-fibre-diet group was 19.2 +/- 1.7 d, which was significantly shorter than in the group on normal diets (27.5 +/- 2.1 d, P less than 0.01). 3. This finding suggests that a high-fibre diet leads to enhanced elimination of 25(OH)D3 by an action within the intestinal lumen. This may involve interference with an enterohepatic circulation of the metabolite, perhaps by binding of 25(OH)D3 to dietary fibre. 4. The reduced plasma half-life of 3H-labelled 25(OH)D3 associated with a high-fibre diet may explain the development of vitamin D deficiency in Asian immigrants with normal exposure to u.v. light.

Macrophages play a significant part in immunity and immune responses. They assume a defensive role exhibited by their ability to carry on phagocytosis of parasites and microbes. They regulate lymphocyte activation and proliferation and they are essential in the activation process of T- and B-lymphocytes by antigens and allogenic cells. Enhanced bactericidal activity of "activated macrophages" is based on immunologically linked mechanisms involving lymphocytes. Macrophages kill ingested microbes but the mechanism by which this is accomplished is not completely understood. This paper discusses the role of macrophages in relation to immunity.

Twenty patients with arthritis and various skin diseases were studied on a metabolic ward during a 2-week period of modified fast followed by a 3-week period of vegetarian diet. During fasting, arthralgia was less intense in many subjects. In some types of skin diseases (pustulosis palmaris et plantaris and atopic eczema) an improvement could be demonstrated during the fast. During the vegan diet, both signs and symptoms returned in most patients, with the exception of some patients with psoriasis who experienced an improvement. The concentrations of lactoferrin in serum reflect the turnover and activity of neutrophil leukocytes. When this protein was initially increased it fell to normal values in most cases. The improvement or impairment of signs and symptoms was related to the lactoferrin levels in serum.

A cancerostatic effect of vegetarian diets is proposed on the basis of a selective alteration of the metabolic pathways of fatty acids in neoplastic cells. Most vegetables lack the enzyme 6-desaturase (6D), which converts linoleic to arachidonic acid. Human cells have 6D, and therefore humans do not need to eat the higher polyunsaturated fatty acids found in animal tissues. Many neoplastic cells have lost the activity of 6D. A vegetarian diet would deprive neoplastic cells of higher-chain fatty acids and inhibit the activity of 6D. Without higher-carbon fatty acids, neoplastic cell membranes would have altered fluidity and thus altered transport properties, receptor activity, sensitivity to external molecules, ability to reproduce, resistance to external agents (drugs, radiation, immune defenses, temperature), and overall survival. These alterations would make the cells easier prey for the self-defense of the body or for attack with therapeutic agents. Thus, a vegetarian diet would alter the tumor cell lipid membranes and decrease neoplastic cell survival.

During an investigation on the effect of fasting and a vegetarian diet on the symptoms and signs in chronic cutaneous and arthritic diseases studies were made of glucose metabolism, liver function and the plasma concentration and urine excretion of some minerals. The study was performed on 27 patients who stayed as in-patients on a metabolic ward for five weeks. After the fasting period the blood glucose and serum insulin concentrations were lower (p less than 0.01) than before the fast. At the end of the period on the vegetarian (vegan) diet (three weeks) the insulin/glucose ratio was lower than at the start of the fast. Serum enzyme concentrations reflecting liver function increased during the fast, but normalized during the vegan diet. The intake of vitamin B12 and of selenium due to the vegan diets was very low, which may give reason for some concern during long-term use of this type of vegetarian diet.

The effect of changes in hydrogen supply on the rate of energy transformation (measured as respiration rate), on the redox state of the NAD(P) and cytochrome c couples and on the extramitochondrial ATP/ADP was investigated with isolated rat liver mitochondria. Hydrogen supply was changed by variation of the beta-hydroxybutyrate/acetoacetate ratio in the incubation medium. In the active state respiration rate was strongly diminished by lowering the beta-hydroxybutyrate/acetoacetate ratio, whereas in the resting state a minor effect was observed. This resulted in a decrease in the respiratory control index (RCI). Even under a metabolic situation of strongly diminished hydrogen supply corresponding to a beta-hydroxybutyrate/acetoacetate ratio equal to 0.5 added ADP was phosphorylated. However, the ATP/ADP ratio generated extramitochondrially amounted to half that obtained at a beta-hydroxybutyrate/acetoacetate ratio of more than 100. Nevertheless at a beta-hydroxybutyrate/acetoacetate ratio of 0.5 the generated extramitochondrial ATP/ADP ratio is near to 100. A comparison of the changes in the available free redox energy with those in the extramitochondrial phosphorylation potential points to a disequilibrium between them in the resting state, too. The experimental results are discussed in the light of the metabolic conditions in vivo.

Among the many biologically active and potentially toxic factors known to be present in plant foodstuffs normally consumed by man, those that are present in legumes have received the most attention. Two categories of legume toxins will be considered - those whose effects have been extensively studied in experimental animals but whose significance in man must remain open to conjecture, and those which are known to produce toxic effects in man but whose identity remains uncertain because similar effects are not readily reproduced in animal models. The protease inhibitors have, over the years, been the object of much study in experimental animals where they have been observed to have an adverse effect on growth and to cause pancreatic enlargement. The relevance of these observations to human nutrition remains obscure, however, because of our lack of knowledge concerning the effect of soybean trypsin inhibitors on the human pancreas. Lectins from certain legumes such as the common bean (Phaseolus vulgaris) have been shown to be toxic to animals upon oral ingestion presumably because of the damage which they inflict upon binding to the cells lining the intestinal mucosa. Lectins may therefore be responsible for reported cases of human intoxication associated with the consumption of inadequately cooked beans. Lathyrism and favism are diseases in man which are associated with the consumption of Lathyrus sativus and Vicia faba respectively. Evidence leading to the probable identification of the causative factors of these diseases and the steps necessary for their elimination will be discussed.

The effects of a 4-day isocaloric isoprotenic dietary replacement of carbohydrate by fats were studied in six healthy subjects, the experimental diet being preceded and followed by a 3-day period of balanced diet. During the ketogenic regimen, the concentrations of fat derived substrates (free fatty acids, glycerol and 3-hydroxybutyrate) rose significantly and glucose levels decreased by 16.5 +/- 3.2% (mean +/- SEM). The hormonal pattern switched towards a catabolic mode with a fall in insulin levels (-44.0 +/- 6.3%) and a rise in glucagon concentration (+39.0 +/- 10.4%). A significant fall in triiodothyronine and rise in reverse triiodothyronine were observed, while thyroxine levels remained unchanged. The average levels of the most important gluconeogenic amino acids (alanine, glutamine, glycine, serine and threonine) were reduced by 8-34% while those of the branched chain amino acids increased by more than 50%. Since these changes reproduce those observed after a few days of total fasting, we suggest that it is the carbohydrate restriction itself which is responsible for the metabolic and hormonal adaptations of brief fasting.

A diagnostic procedure developed for adults and children which includes a week-long fast nutritionally supported with a chemically defined diet was applied to a pilot group of children having ADD/HA syndrome. A probable etiology of food hypersensitivity was shown for a majority of the panel with several standard subjective tests. Three neurological tests, one of which was of the corpus callosum, were evaluated as objective measurements of ADD/HA. Management procedures are not discussed. A follow-up at one year showed substantial continuing control for many of the subjects. It is suggested that this type of general diagnostic procedure be employed to indicate for treatment those having food sensitivity as the primary etiology.

Classic pernicious anemia with abnormal Schilling test results developed in a previously described vegan patient who had coexisting subtle cobalamin malabsorption (demonstrable by abnormal ovalbumin-cobalamin absorption test results but normal Schilling test results). This suggests that the ovalbumin-cobalamin absorption test or a modified version may serve as a prodromal phenomenon to identify patients at risk for developing pernicious anemia. The patient's transformation was also accompanied by the appearance of serum anti-intrinsic factor antibody. A modified assay retrospectively detected this antibody a year earlier than did the standard assay, indicating that such modification enhances the sensitivity of this useful test.

Observations on the deleterious effects of a totally vegetarian diet in infancy are reported and the difficulties encountered in the prevention of nutritional deficiencies in a vegan religious community are discussed. Twenty-five infants of this community who were seen at the hospital showed evidence of protein-calorie malnutrition, iron- and vitamin B12-deficient anemia, rickets, zinc deficiency, and multiple recurrent infections. Evidence of growth retardation was also found in 47 infants seen at the local mother-child health (well-baby) clinic. Samples of breast milk showed low levels of carbohydrate (1.6 to 3.5 gm/100 ml), protein (0.8 to 1.4 gm/100 ml), and fat (2.4 to 4.1 gm/100 ml). The main constituent of the infants' diet after the age of 3 months (a "soya milk" prepared at the community's central kitchen) was extremely dilute with a very low calorific value (13.7 kcal/100 ml). Persistent attempts to find dietary modifications that would satisfy both the vegan philosophy and also the recommended dietary allowances failed. This problem represents a scientific and medicosocial challenge to pediatricians and nutritionists.

Observations on the deleterious effects of a totally vegetarian diet in infancy are reported and the difficulties encountered in the prevention of nutritional deficiencies in a vegan religious community are discussed. Twenty-five infants of this community who were seen at the hospital showed evidence of protein-calorie malnutrition, iron- and vitamin B12-deficient anemia, rickets, zinc deficiency, and multiple recurrent infections. Evidence of growth retardation was also found in 47 infants seen at the local mother-child health (well-baby) clinic. Samples of breast milk showed low levels of carbohydrate (1.6 to 3.5 gm/100 ml), protein (0.8 to 1.4 gm/100 ml), and fat (2.4 to 4.1 gm/100 ml). The main constituent of the infants' diet after the age of 3 months (a "soya milk" prepared at the community's central kitchen) was extremely dilute with a very low calorific value (13.7 kcal/100 ml). Persistent attempts to find dietary modifications that would satisfy both the vegan philosophy and also the recommended dietary allowances failed. This problem represents a scientific and medicosocial challenge to pediatricians and nutritionists.

In several pathophysiologic states, i.e., cirrhosis of liver, protein calorie malnutrition, starvation, carbohydrate deprivation, etc., thyroid hormone metabolism is reported to be altered with a decrease in serum T3 and a reciprocal increase in TR3. Uncontrolled diabetes mellitus is a similar state in which glucose does not enter the cells causing cellular starvation and hyperglycemia ensues. Therefore, serum T4, T3, RT3, T3-resin uptake, TSH, and glucose were determined after an overnight fast in 94 male diabetics (aged 28 to 85 years) during a routine follow-up visit to the outpatient clinic and 24 healthy male adults (aged 24 to 81 years). Glycosylated hemoglobin concentrations were measured as well in normal subjects and 16 newly discovered diabetics. In normal subjects, no significant relationships between fasting plasma glucose and T3 and RRT3 levels were observed. In diabetics there was a significant positive (r = 0.611; p less than 0.001) correlation between glucose and RT3. Similarly, a significant negative relationship was observed between glucose and T3 (r = 0.491; p less than 0.001). T4, free T4, T3-resin uptake, and TSH were normal in diabetics. In 16 newly discovered diabetics, with fasting plasma glucose greater than 200 mg/dl, serum T3 rose (96 +/- 5 to 128 +/- 5 ng/dl) and RT3 declined (26.3 +/- 10.4 +/- 1.4 ng/dl) on improvement of hyperglycemia (fasting plasma glucose less than 140 mg/dl) after intensive therapy for 6 to 8 weeks. Glycosylated hemoglobin levels declined as well (14.6 +/- 0.9% to 9.3 +/- 0.7%). These data indicate: (1) thyroid hormone metabolism may be altered in diabetes mellitus with a fall in serum T3 and a reciprocal rise in RT3; and (2) T3 and RT3 concentrations may serve as indicators of metabolic control in diabetes mellitus.

In cultured human dermal microvessel endothelial cells, the rate of efflux (about twofold greater than for fibroblasts under equivalent conditions) was coupled to an equivalent high rate of sterol net transport from the cells to the medium. This net transport was linked with esterification via lecithin:cholesterol acyltransferase. Since the use of free sterol by plasma transferase is constant, such increased net transport indicates that endothelial cells are highly efficient, in competition with plasma lipoproteins, in supplying free sterol for esterification. These results indicate the marked ability of endothelial cells to regulate and maintain their sterol balance in the face of high sterol levels to which these cells are uniquely exposed in human plasma.