Myron Winick

Randomized controlled trial of a nonpharmacologic cholesterol reduction program at the worksite

Under experimental clinical conditions diet modification has been shown to reduce serum cholesterol levels. This paper reports such a positive response to a nonpharmacologic, behavioral education program at the worksite. Employees at the New York Telephone Company corporate headquarters were assigned randomly to treatment and control groups. Treatment consisted of an 8-week group cholesterol reduction program conducted during employee lunch hours. It comprised a multiple-treatment approach--food behavior change techniques combined with nutrition education, physical activity planning, and self-management skills. The treatment group showed substantial change compared with the control group at the programs completion. Those treated displayed a significant 6.4% reduction in total serum cholesterol (266 mg% average at baseline) as compared with control subjects with a corresponding decrease in high-density lipoprotein levels. A significant increase in nutrition knowledge and moderate weight loss were also documented for this group. The magnitudes of a participants baseline serum cholesterol level and his/her reduction in percentage of ideal body weight were positively and independently correlated with percentage changes in serum cholesterol levels. Over the same period, decreases in high-density lipoprotein levels and no changes in serum cholesterol, weight, and nutrition knowledge were observed for the control group. Overall, participants in the treatment program successfully reduced the coronary heart disease risk factors of elevated cholesterol and weight. Directions for future study are suggested.

Nutrition and brain development.

It has long been known that malnutrition retards growth. However, when these observations were initially made, it was not clear whether or not a child would recover if he or she subsequently received adequate nourishment. In an experiment done in Cambridge by Kennedy, McCance, and Widdowson, two groups of rats were malnourished for a period of time during growth. The only difference between the two groups was that in one the malnutrition was imposed from birth to weaning, and in the second malnutrition was imposed later, during the growth period. The results demonstrated that the animals malnourished from birth until weaning were small at the end of the period of malnutrition and remained small throughout the rest of their lives, no matter how they were subsequently fed. However, the group malnourished later in the growing period although also small at the end of the period of malnutrition, caught up when refed. So these investigators introduced the element of time into the equation: the earlier the malnutrition, the greater the chance of permanent effect. And yet, when growth was examined in terms of weight or height, or the usual anthropomorphic measurements, we could not break it down in such a way as to explain this dichotomy in recovery.

Prenatal Alcohol Exposure: Abnormalities in Placental Growth and Fetal Amino Acid Uptake in the Rat

On day 20 of gestation, after ethanol feeding (27% ethanol calories, 25% protein), placental weights, DNA, RNA and water content were greater than in controls pair-fed an isocaloric diet without ethanol or those ad lib fed a pellet diet of similar composition. Rat litter size and fetal body, liver and brain weights were similar in all groups. In vivo fetal amino acid accumulation was significantly lower after alcohol exposure despite similar placental uptake. These results indicate that both placental hyperplasia and abnormal fetal amino acid uptake occur at a low alcohol dose when fetal body weight is unaffected.

Maternal nutrition and prenatal growth. Experimental studies of effects of maternal undernutrition on fetal and placental growth.

Recent studies based primarily on rat experiments tend to support the contention that maternal malnutrition results in a nonreversible reduction in cell proliferation infboth fetal and placental tissue. The placenta is apparently ineffective in protecting the fetus from the effects of nutritional deficiencies in the mothers diet. The effect of malnutrition on the total number of brain cells is increased when both prenatal and postnatal nutritional deficiency are experienced. Prenatal nutritional deprivation alone results in a 15% reduction in the number of brain cells postnatal deprivation alone reduces cell number by 15-20% and both prenatal and postnatal deprivation reduce the number of cells by 60%. Possible effects of maternal malnutrition on the human placenta fetus and infant are 1) a reduction in the number of cells and an increase in the RNA/DNA ratios in placenta tissue; 2) a reduction in birth weight and in the number of brain cells at birth; and 3) an increase in the response to postnatal malnutrition. The above conclusions results of an investigation undertaken by the authors of these review articles are also included. The findings of their investigation are suggestive of the mechanism by which malnutrition reduces cell proliferation. Malnutrition may reduce the number of cells by decreasing level of DNA polymerase activity and this decreased activity may interfere with DNA replication. Graphs depict the level of polymerase activity in rat tissues under varying conditions. Other graphs show 1) % of normal placenta cells in reference to DNA content in several human populations and in a single case of anorexia nervosa; 2) % of human DNA in different types of malnutrition; and 3) % of radiothymidine uptake in normal and malnourished brain tissue by region.

Effects of essential fatty acid deficiency during late gestation on brain N-acetylneuraminic acid metabolism and behaviour in the progeny.

1. Rat dams given a diet containing 100 g maize oil/kg for approximately two weeks before mating and during the first 14 d of gestation, were given the same diet or one containing 100 g hydrogenated coconut oil/kg (essential fatty acid (EFA)-deficient) in place of maize oil until parturition. After parturition the dams were given the same diets and all progeny were weaned to the maize oil diet at 21 d of age. Brain N-acetylneuraminic acid (NeuNAc) content as well as neuraminidase (sialidase; (EC 3.2.1.18), and cytidine monophosphate N-acetylneuraminic acid synthetase (CMP-NeuNAc synthetase) activities were measured at days, 7, 14, 21 and 168 in the progeny. Y-maze learning was measured at 168 d. 2. Brain weight was independent of dietary fat at all ages. 3. Lack of EFA in the maternal diet during gestation and lactation depressed ganglioside and glycoprotein NeuNAc levels and the activities of sialidase and CMP-NeuNAc synthetase. 4. Maternal dietary deprivation of EFA irreversibly impaired learning behaviour of the progeny. A relationship exists between early exposure to EFA deficiency and learning potential of the progeny.

The subcellular localization of administered N-acetylneuraminic acid in the brains of well-fed and protein restricted rats

1. This study investigated the subcellular localization of injected N-acetylneuraminic acid (NeuNAc) in brain. Forty pregnant rats were distributed into four groups. Two groups were given a 200 g casein/kg diet and the other two groups a 100 g casein/kg diet throughout gestation. One group from each of the low- and high-protein groups were given their respective diets for the first 11 d of lactation. On day 12 of lactation, 2.5 microCi [14]NeuNAc/kg body-weight were injected intraperitoneally into their pups. After 1 h the pups were killed, their brains removed and subjected to subcellular fractionation. On day 16 of lactation the other two groups were similarly treated. 2. In all groups of animals 80% of the [14C]NeuNAc incorporated into the brains was found in the synaptosomal fraction and the remainder distributed among the other subcellular fractions in proportion to their total NeuNAc content. 3. These results suggest that NeuNAc exerts its effects on behaviour via the synaptic membrane.

Nutrition and Central Nervous System Development

Publisher Summary During the past two decades evidence from a variety of sources has accumulated, which demonstrates that severe early malnutrition can affect both brain structure and brain function. By contrast, animals malnourished after weaning showed smaller brains at the end of the period of malnutrition, but on re-feeding brain weight returned to normal. Subsequent studies have clarified the reason for the different responses. Brain growth is characterized by a series of cellular changes which take place in a sequential pattern. Early growth occurs primarily by repeated cell division as characterized by a linear increase in total organ DNA. Cell size as determined by weight/DNA ratio or protein/DNA ratio remains relatively constant. In animals, malnutrition occurring during the period of rapid cell division (hyperplasia) results in retardation in the overall rate of cell division, and hence ultimately results in fewer cells. This change is permanent. By contrast, malnutrition occurring during the period of hypertrophic growth results in curtailment of cell enlargement, a process which is reversible as soon as rehabilitation is instituted. Data from analysis of brains of children who died of malnutrition during the first year of life demonstrate a reduced number of cells. Thus, in the human, severe early undernutrition curtails cell division and results in fewer cells.

A Possible Relationship between Brain N-Acetylneuraminic Acid Content and Behavior

Summary Repeated intraperitoneal injections of N-acetylneuraminic acid (NANA) into malnourished and well-fed rats during the brain growth spurt were associated with a permanent increase in NANA concentrations in brain gangliosides and glycoproteins. Further, there was an alleviation of some expected behavioral abnormalities in the malnourished group and an above normal behavioral performance shown by the well-fed pups. The results suggest the existence of a relationship between NANA and behavior.

A possible control of food intake during pregnancy in the rat

1. Brain hypothalamic concentrations of serotonin and norepinephrine have been implicated in the control of food intake. During pregnancy and lactation a rat dams food consumption is increased and so a study was performed to ascertain whether this was associated with changes in the hypothalamic content of serotonin and norepinephrine. 2. In the first experiment, forty-eight Sprague Dawley rat dams were given a diet containing 250 g casein/kg adlib. After 2 weeks, eight were killed and their hypothalmic analysed for the previously-mentioned neurotransmitters. The rest were mated and continued on the diet. On each of days 7, 14 and 20 of gestation, day 14 of lactation and 2 weeks after weaning of their pups a further eight dams were killed and their hypothalami assayed as described previously. Food intake was monitored throughout the experimental period. 3. The increase food intake of the dams during gestation and lactation increased to the same extent as elevation in hypothalamic norepinephrine content and depression in serotonin content. After lactation food intake returned to pre-pregnancy levels as did the hypothalamic levels of norepinephrine and serotonin. 4. By using the same experimental design but limiting the increase in food intake in pregnancy and lactation to half the expected amount the same changes were found in hypothalamic norepinephrine and serotonin contents. 5. The possibility of hypothalamic neurotransmitter contents controlling food intake is discussed.

The effects of folic acid supplementation during pregnancy in the rat.

1. Twenty-four Sprague-Dawley female rats were randomly assigned to three groups (groups A, B, C). Group A was given a folic acid-free diet and groups B and C received 0.0018 g folic acid/kg diet. Rats in group C were also given a supplement of 1 mg folic acid/d by intraperitoneal injection. 2. After 14 d of feeding the rats were mated. The diets were continued throughout gestation. On day 21, of gestation the dams were killed and their livers and products of conception assayed for RNA, DNA, protein and tetrahydrofolate dehydrogenase (5,6,7,8-tetrahydrofolate dehydrogenase; EC 1.5.1.3) activity. 3. The foetuses, placentas and livers from supplemented rats (group C) were significantly larger than those from groups A and B and had a higher content of RNA, DNA and protein. Those tissues from group A dams were smaller than those from the other groups and had a correspondingly reduced nucleic acid and protein content. 4. The activity of tetrahydrofolate dehydrogenase, the first and rate-limiting enzyme in the metabolism of folate, was increased in the folate supplemented rats (group C) and reduced in the rats given a folic acid-free diet (group A). These changes in enzyme activity could explain the differences in nucleic acid biosynthesis and growth shown by the different groups.