Diet-induced Variations Research Articles

Dietary modulation of gut microbiota affects susceptibility to drug-induced liver injury

ABSTRACT The rising incidence of drug-induced liver injury (DILI) parallels contemporary dietary shifts that have transformed the composition of human gut microbiota. The relationship between these phenomena remains unknown. Here, it is unveiled that a high fiber diet (HFiD) provides substantial protection against DILI, whereas a western style diet (WSD) significantly exacerbates DILI. Gut microbiota transplantation further confirms these differing outcomes are mediated by diet-induced variations in gut microbiota. Mechanistically, Lactobacillus acidophilus, enriched by HFiD, alleviates DILI through its metabolite indole-3-lactic acid (ILA), which activates the AhR/Nrf2 signaling pathway, thus enhancing hepatocellular antioxidant defenses and detoxification capacity. In the clinical intervention of subjects with prediabetes (N = 330), dietary fiber intervention enriches intestinal L. acidophilus, elevates serum ILA levels, and improves liver function. Conversely, WSD induces disturbance in bile acid metabolism and dysbiosis in gut microbiota, which impairs the intestinal barrier and facilitates the translocation of lipopolysaccharides (LPS) to the liver, thus triggering inflammatory responses and exacerbating DILI. These results demonstrate that dietary patterns significantly influence the onset of DILI by modulating gut microbiota. This novel insight expands the understanding of DILI risk factors and highlights the potential of dietary modifications as a preventive strategy against DILI.

Host Genetics Background Affects Intestinal Cancer Development Associated with High-Fat Diet-Induced Obesity and Type 2 Diabetes.

Obesity and type 2 diabetes (T2D) promote inflammation, increasing the risk of colorectal cancer (CRC). High-fat diet (HFD)-induced obesity is key to these diseases through biological mechanisms. This study examined the impact of genetic background on the multimorbidity of intestinal cancer, T2D, and inflammation due to HFD-induced obesity. A cohort of 357 Collaborative Cross (CC) mice from 15 lines was fed either a control chow diet (CHD) or HFD for 12 weeks. Body weight was tracked biweekly, and blood glucose was assessed at weeks 6 and 12 via intraperitoneal glucose tolerance tests (IPGTT). At the study's endpoint, intestinal polyps were counted, and cytokine profiles were analyzed to evaluate the inflammatory response. HFD significantly increased blood glucose levels and body weight, with males showing higher susceptibility to T2D and obesity. Genetic variation across CC lines influenced glucose metabolism, body weight, and polyp development. Mice on HFD developed more intestinal polyps, with males showing higher counts than females. Cytokine analysis revealed diet-induced variations in pro-inflammatory markers like IL-6, IL-17A, and TNF-α, differing by genetic background and sex. Host genetics plays a crucial role in susceptibility to HFD-induced obesity, T2D, CRC, and inflammation. Genetic differences across CC lines contributed to variability in disease outcomes, providing insight into the genetic underpinnings of multimorbidity. This study supports gene-mapping efforts to develop personalized prevention and treatment strategies for these diseases.

A First Look at Possible Diet-Induced Variations in the Fecal Microbiota of the Agricultural Pest Diaprepes abbreviatus

A First Look at Possible Diet-Induced Variations in the Fecal Microbiota of the Agricultural Pest Diaprepes abbreviatus

Maternal diet affects utilization of endogenous lipids by red drum Sciaenops ocellatus embryos and early larvae.

Embryonic and early larval development and metabolism of most teleost fishes are fueled entirely by maternally derived nutritional resources (yolk and oil) before the onset of exogenous feeding. The composition of those resources depends, in part, on maternal diet. To examine how diet-induced variations in egg composition affect embryonic and larval utilization of endogenous lipids and fatty acids, we fed red drum (Sciaenops ocellatus) broodstock four different diets to produce distinctive fatty acid compositions in eggs but with no significant difference in total lipid content. We sampled embryos and unfed larvae every 12h from 12h post-fertilization (hpf) until starvation (96-120 hpf; n=5 spawns per diet group). Rates of utilization of the oil globule were significantly different among diet groups, resulting in significant differences in mean oil globule size at the first feeding stage (84 hpf). Utilization rates for 15 fatty acids were significantly different among diet groups and were proportional to their initial concentration. As a result, differences in larval fatty acid compositions among maternal diet groups diminished over time but remained different even at later stages. In addition, larval standard length at 84 hpf was positively correlated with egg total lipid content. This study suggests that the fatty acid composition of yolk and oil affects energy metabolism and tissue composition in red drum larvae. These effects could have consequences for the survival and essential physiological functions of fish larvae during the critical period of transition to exogenous feeding.

Genetic Background and Diet Impact Beef Fatty Acid Composition and Stearoyl‐CoA Desaturase mRNA Expression

The intramuscular fat composition of ruminant meats influences the quality of the final product, which explains the increasing interest in assessing the fatty acid profile of meat from different production systems. In this study, it was hypothesized that there are breed- and diet-induced variations on lipid metabolism in the muscle, which may be, at least partially, modulated by the stearoyl-CoA desaturase (SCD) gene expression levels. Forty purebred young bulls from two phylogenetically distant autochthonous cattle breeds, Alentejana and Barrosã (n=20 for each breed), were assigned to two different diets (low vs. high silage) and slaughtered at 18months of age. Meat fatty acid composition, including the detailed conjugated linoleic acid (CLA) isomeric profile, was determined along with the SCD mRNA levels. Meat from Barrosã bulls fed the low silage diet was richer in monounsaturated fatty acids, CLA and trans fatty acids, when compared to that from Alentejana bulls. The meat content in polyunsaturated fatty acids was similar across experimental groups. Moderate positive correlations between the SCD mRNA levels and the products of this enzyme activity were found, although they were not reflected on the calculated desaturase indices. Overall, these findings highlight the importance of taking into account the genetic background while devising feeding strategies to manipulate beef fatty acid composition.

Short communication: Diet-induced variations in milk fatty acid composition have minor effects on the estimated melting point of milk fat in cows, goats, and ewes: Insights from a meta-analysis

In ruminants, the ability to maintain milk fat melting point within physiological values could play a role in the regulation of milk fat secretion when milk fatty acid (FA) composition varies, such as in response to feeding factors. However, the relationship between milk fat fluidity and changes in milk FA composition is difficult to study experimentally. A meta-analysis was therefore conducted to compare the magnitude of diet-induced variations in milk FA composition and the calculated melting point of milk FA (used as a proxy to estimate the variations in the melting point of milk fat) in 3 dairy ruminant species (cow, goat, and sheep). The coefficient of variation (CV), a scale-free measure of statistical dispersion, was used to compare the variability of criteria differing in their order of magnitude. The analysis of a database of milk FA profiles from cows, goats, and sheep fed different dietary treatments (unsupplemented diets and diets supplemented with lipids rich in oleic acid, linoleic acid, linolenic acid, or C20–22 polyunsaturated FA) revealed that the variability of the calculated melting point of milk FA was narrow (CV of 5%) compared with the variability of milk FA percentages (CV of 18 to 72%). The regulation of the melting point of milk fat is thus probably involved in the control of diet-induced variations in milk fat secretion. The calculated melting point of ewe milk FA was approximately 3°C lower than that of goats or cows across all types of diets, which might be linked to differences in milk fat content (higher in sheep) or the structure of milk triacylglycerides among these species. Lipid supplementation increased the calculated melting point of C18 FA in milk, whereas that of total FA was significantly reduced by supplements rich in oleic, linoleic, and linolenic acids but not C20–22 polyunsaturated FA. However, the slight effects of dietary treatments on the calculated melting point of milk FA did not differ between cows, goats, and ewes.

Abstract 171: Impact of the Mediterranean Diet on Apolipoprotein AI Kinetic in Men with Metabolic Syndrome

The impact of the Mediterranean diet (MedDiet) on HDL metabolism has not been extensively studied to date. The objective of the study was to investigate the effect of the MedDiet consumed under controlled isoenergetic feeding conditions on HDL as well as on apolipoprotein (apo) AI kinetic in men with metabolic syndrome (MetS). The diet of 26 men aged between 24 to 62 years with the MetS (NCEP-ATP III) was first standardized to a North American control diet, which was consumed for 5 weeks. MedDiet was then consumed over a subsequent period of 5 weeks. Both diets were consumed under isoenergetic feeding conditions with all foods, including red wine, provided to participants. During the last week of each diet, participants received a single bolus of [5,5,5- 2 H 3 ] L -leucine and fasting blood samples were collected at predetermined time points over a period of 96 hours. Kinetic parameters were derived using multicompartmental modeling of the enrichment data over time. Although no change in plasma HDL-C concentrations was observed, consumption of the MedDiet led to a significant reduction in plasma apoAI concentration and pool size (both P <0.05) compared with the control diet. The MedDiet was also associated with a trend towards a reduction in apoAI production rate (PR, P =0.07) but had no impact on apoAI fractional catabolic rate (FCR, P =0.64). However, only variations in apoAI FCR correlated with diet-induced variations in plasma HDL-C and in apoAI concentrations ( r = -0.50 and r = -0.49 respectively, P <0.02). Based on the individual HDL-C response to MedDiet, responders and non-responders were identified. Participants among whom HDL-C concentrations were increased with MedDiet (mean ΔHDL-C: +9.9 ± 3.2 %) showed significantly greater reductions in apoAI FCR and in apoB and VLDL-TG concentrations (all P <0.04) than those among whom HDL-C levels were reduced after the MedDiet (mean ΔHDL-C: -11.1 ± 4.5 %). Data from this controlled feeding study suggest that the heterogeneous response of HDL-C and apoAI to MedDiet is primarily determined by variations in apoAI FCR, which in turn may be due to concurrent changes in plasma TG concentrations.

Plasma Levels and Adipose Tissue Messenger Ribonucleic Acid Expression of Retinol-Binding Protein 4 Are Reduced during Calorie Restriction in Obese Subjects but Are Not Related to Diet-Induced Changes in Insulin Sensitivity

Retinol-binding protein 4 (RBP4) may play a role in the development of insulin resistance. We investigated whether RBP4 adipose tissue mRNA expression and plasma level are related to insulin sensitivity during a diet-induced weight loss. Obese women followed a dietary intervention composed of a 4-wk very low-calorie diet (VLCD), a 2-month low-calorie diet, and 3-4 months of a weight maintenance (WM) phase. Clinical investigation was performed before and at the end of each phase. Insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp. Adipose tissue mRNA and plasma levels of RBP4 were determined using reverse transcription-quantitative PCR and ELISA, respectively. Weight and fat mass decreased during VLCD and were stabilized during WM. Glucose disposal rate increased during VLCD and remained elevated thereafter. Plasma levels of RBP4 decreased after VLCD and, although increasing at subsequent phases, remained lower than prediet values. Adipose tissue mRNA levels were diminished after VLCD, and increased during low-calorie diet and WM to reach basal values. Basal RBP4 levels or diet-induced variations of RBP4 were not different in lean women and two groups of obese women with high- and low-insulin sensitivity. Severe calorie restriction promotes a reduction in adipose tissue and plasma levels of RBP4. The study does not bring evidence for a role for RBP4 in the regulation of diet-induced changes in insulin sensitivity.

Cholesterol crystallization in gall-bladder bile of pigs given cholesterol-beta-cyclodextrin-enriched diets with either casein or soyabean concentrate as protein sources.

Cholesterol precipitation from supersaturated bile is the earliest and determinant step in the formation of cholesterol gallstones, which is thought to be diet-dependent. Bile composition, appearance and growth of cholesterol crystals were studied in fresh gall-bladder biles from pigs adapted to four different protein-containing diets over 3 weeks: 160 g dietary protein/kg as casein (C16; n 6), or as soyabean-protein concentrate (S16; n 6), or a mixture of both protein sources (casein-soyabean protein, 70:30, w/w) (CS16; n 6), or 320 g of the mixed protein/kg (CS32; n 6). Moreover, all four diets contained 3 g cholesterol/kg and 50 g beta-cyclodextrin/kg as modifiers of bile composition towards cholesterol pro-crystallization. Cholesterol precipitation was most active after the high-protein diet, CS32, and the casein diet, C16, and lowest after the soyabean-protein diet, S16. It was intermediate after the mixed diet, CS16, but still much lower than in the former two groups. These diet-induced variations were suggested to be mediated through modifications in the biliary profile of bile acids, whereas all other biliary constituents studied were essentially unchanged. The fasting level of plasma cholesterol was lowest in both 160 g protein/kg diets containing soyabean protein (S16 and CS16), highest for the high-protein diet CS32, and intermediate for the C16 diet. These results should encourage clinical studies on the effect of soyabean protein, or other vegetable proteins, for primary or recurrence prevention of cholelithiasis at its earliest stage.

Kinetics of plasma apolipoprotein C-III as a determinant of diet-induced changes in plasma triglyceride levels

To compare the effect of a high monounsaturated fatty acid (MUFA) diet and of a control low-fat diet consumed under ad libitum conditions on plasma apolipoprotein (apo) C-III metabolism. Randomized, two-arm parallel dietary trial. Diets were prepared and consumed at the metabolic kitchen of the Department of Food Sciences and Nutrition, and laboratory analyses were performed at the Institute of Nutraceuticals and Functional Foods at Laval University. Eighteen men were randomly assigned to either the high MUFA diet or the low-fat control diet, which they consumed for 6-7 weeks. Before and after the dietary intervention, subjects received a primed-constant infusion of [5,5,5-D(3)]-L-leucine for 12 h under constant feeding conditions for the determination of plasma apoC-III kinetics. The high-MUFA diet and the low-fat control diet had no significant impact on plasma apoC-III production rate (PR) or fractional catabolic rate. However, diet-induced variations in plasma apoCIII PR predicted the reduction in plasma triglycerides and apoC-III levels (r=0.85, P<0.01 and r=0.73, P<0.05, respectively) in the high MUFA group only. These results suggest that the hypotriglyceridemic effect of a high-MUFA diet may be attributable in part to a reduced hepatic production of apoC-III. This study was supported in part by an operating grant from the Canadian Institutes of Health Research (CIHR), and the Canada Research Chair in Nutrition and Cardiovascular Health (B Lamarche).

Effect of dietary argan oil on fatty acid composition, proliferation, and phospholipase D activity of rat thymocytes

Objective Argan oil is receiving increasing attention due to its potential health benefits in the prevention of cardiovascular risk, but no information to date is available about its possible effect on immune cells and functions. Methods To address this issue male rats were fed one of five diets that contained fish oil, argan oil, olive oil, coconut oil, or sunflower oil for 4 wk. The fatty acid composition of plasma and thymocyte lipids was then analyzed in relation to the mitogen-induced proliferation and phospholipase D (PLD) activity of thymocytes. Results The 18:2ω-6 proportion in thymocyte phospholipids from rats fed argan oil was significantly lower than that observed in phospholipids from rats fed sunflower oil and fish oil but higher than that found in the olive oil and coconut oil groups. Further, a significant positive linear relation was found between thymocyte proliferation and the 18:2ω-6 proportion in thymocyte phospholipids, whatever the diet. The proliferation response of thymocytes to mitogenic activation was also inversely correlated to PLD activity measured in intact thymocytes. Subsequent western blotting experiments indicated that the diet-induced variations in PLD activity mainly reflected variations in the expression of PLD2 protein. Conclusions On the whole, the present study shows that the effects of argan oil on immune cells are very similar to those of olive oil, and that, as a consequence, argan oil can be used as a balanced dietary supply without marked adverse effects on immune cell function.

Variations in plasma apolipoprotein C-III levels are strong correlates of the triglyceride response to a high-monounsaturated fatty acid diet and a high-carbohydrate diet

The objective of this study was to examine how a diet rich in carbohydrates (high-CHO) vs a diet rich in monounsaturated fatty acids (high MUFA) consumed ad libitum modulated plasma apolipoprotein C-III (apo C-III) levels and to examine the extent to which diet-induced changes in plasma apo C-III were associated with concurrent variations in plasma triglyceride (TG) levels. Forty-seven men (mean age, 35.7 ± 11.4 years; body mass index, 29.0 ± 5.1 kg/m 2) were randomly assigned to either a high-CHO diet (CHO, 58%; fat, 26%; n = 23) or a high-MUFA diet (CHO, 45%; fat, 40%; MUFA, 22.5%; n = 24), which they consumed for 6 to 7 weeks. Fasting and postprandial lipemia after an oral fat load and fasting plasma apo C-III were measured at the beginning and at the end of the dietary intervention. Ad libitum consumption of the high-CHO diet induced a significant reduction in body weight (−2.6%, P < .0001), but had no impact on plasma apo C-III concentrations and on fasting and postprandial plasma TG levels. In contrast, ad libitum consumption of the high-MUFA diet also resulted in a significant reduction in body weight (−2.3%, P < .01) as well as in significant reductions in plasma apo C-III (−11%, P = .05) and fasting plasma TG (−17%, P < .01). Diet-induced variations in plasma apo C-III concentrations were correlated with changes in fasting and postprandial TG levels both in the high-CHO ( r > 0.70, P < .001) and the high-MUFA groups ( r > 0.42, P < .05). These results indicate that variations in plasma apo C-III levels are strong correlates of the fasting and postprandial plasma TG responses to high-MUFA and high-CHO diets.

Diet-induced variations in fatty acid content and composition of two on-grown stages ofArtemia Salina

Three species of microalgae, the freshwater Euglena gracilis and themarine Dunaliella salina and Tetraselmis suecica, were fed tothe brine shrimp Artemia salina in order to compare their suitabilityin terms of fatty acid enrichment, and their effect on the biometric parametersof the zooplankter. The fatty acid content and composition were analyzed for the post-larval and pre-adult stages of Artemia fed the algae and theresults compared to the initial content of unfed 24-hour post-hatch nauplii.Differences in the total fatty acid content occurred between the three stages,the fatty acid profile being determined by the composition of the diet. A decreasing trend for almost all the individual fatty acids occurred throughdevelopment from post-larva to pre-adult with each of the three algal diets.Biometrical differences between Artemia fed the marine algae and that fed Euglena were not consistent in the post-larval stage, but became considerable in the pre-adult stage. Artemia fed with Euglena achieved twice the weight of animals fed the marine algae and showed thehighest length. The implications for the use of on-grown Artemia as afeed in larviculture of marine and freshwater fish and crustaceans are considered.

Phospholipid hydroperoxide glutathione peroxidase activity and vitamin E level in the liver microsomal membrane: effects of age and dietary α-linolenic acid deficiency

Age and diet-induced variations of phospholipid hydroperoxide glutathione peroxidase (PHGPx) activity and α-tocopherol concentration in the liver microsomal membrane were studied in male Wistar rats fed a semipurified diet either balanced in n-6 and n-3 polyunsaturated fatty acids (PUFA) (Control) or deprived of α-linolenic acid, i.e. n-3 PUFA (Deficient) over two generations. The animals were studied at the age of 6 months (adult) or 24 months (old). Both PHGPx activity and vitamin E level were significantly higher in 24-month old rats as compared to 6-month old rats. By contrast, the thiobarbituric acid reactive substances (TBARS) following stimulated in vitro peroxidation of membrane lipids were markedly lower (P < 0.01) with aging. The fatty acid composition of microsomal membrane phospholipids (PL) was also considerably modified by age. In particular, the levels of arachidonic acid and total n-6 PUFA were lower (P < 0.001) whereas n-3 PUFA levels were higher (P < 0.001) in most PL main classes. The α-linolenic acid deficiency markedly influenced these age-related changes. The higher PHGPx activity in the old rats as compared to the adult rats was only significant in those fed the control diet. In the 6-month old rats (but not in the 24-month old rats), the deficient diet led to a higher membrane vitamin E level and to lower TBARS production than the control diet. The results suggest that the nature of dietary PUFA may influence the age-related variations in this pair of membrane antioxidants and also in the fatty acid composition of microsomes.

Restricted Feed Intake during Fattening Reduces Intramuscular Lipid Deposition without Modifying Muscle Fiber Characteristics in Rabbits

The present study was conducted to determine the effects of feed restriction during fattening on muscle fiber characteristics and intramuscular lipid traits. From 11 wk of age onward, rabbits were given free access to feed (control group), or received 70% of the control feed intake (restricted group). At the same weight at slaughter, restricted-fed rabbits were 3 wk older than controls (18 vs. 15 wk). The longissimus lumborum (LL, white loin), biceps femoris (BF, white thigh) and semimembranosus proprius (SMP, red thigh) muscles were then removed, and biochemical and histochemical assays were performed. In the three muscles, there was no effect of feed restriction on mean fiber size or percentage of the different fiber types. Restricted vs. control feeding resulted in a significant reduction (P<0.001) in total lipid content in all three muscles. This reduction was paralleled by a decline (P<0.001) in the activities of the malic enzyme and glucose-6 phosphate dehydrogenase (G6PDH), generating NADPH for the support of fatty acid synthesis. The diet-induced variations in lipid concentration and enzyme activities were larger (P<0.05) in the pure oxidative SMP muscle than in the predominantly fast-twitch glycolytic LL and BF muscles. Whatever feeding status, the ratio of malic enzyme to G6PDH activities was sharply lower (P<0.001) in SMP than in BF and LL muscles (averaging 1.5 vs. 9 and 15, respectively). These data indicate that nutritional status regulates intramuscular lipid deposition, without changing fiber-type composition. Further studies are necessary to determine the role of G6PDH in the lipogenic process of oxidative vs. glycolytic muscles.

Effects of dietary fatty acids on lipogenesis and lipid traits in muscle, adipose tissue and liver of growing rabbits

AbstractThe effects of fat source on lipogenesis and lipid traits of longissimus muscle, liver and perirenal adipose tissue, were studied in 48 New Zealand White rabbits, slaughtered at 11 or 15 weeks of age. Rabbits were offered diets with 20 g added fat per kg, containing either medium-chain (COC: coconut oil), saturated and monounsaturated (PAL: palm oil) or polyunsaturated (SUN: sunflower oil) fatty acids as major components. Diets did not affect growth performance, dressing proportion and tissue weights. Intramuscular lipid content was lower for COC than for SUN and PAL (e.g. 10v.13 and 12 glkg, at 11 weeks, respectively,P&lt; 0·05), whereas lipid content was unaffected by diet in liver and perirenal fat. In muscle, the fat source did not influence the activities of acetyl-CoA-carboxylase (CBX), malic enzyme (ME) and glucose-6-phosphodehydrogenase (G6PDH). In liver, activities ofGSPDH and ME were depressed from the SUN diet, as compared with the COC or PAL diets. The diet-induced variations in enzyme activities in perirenal fat were lower than in the liver and were not significant. Medium-chain fatty acids were found only in tissue lipids of animals given COC. The ratio of polyunsaturated to saturated fatty acids decreased in the order SUN &gt; PAL &gt; COC in muscle and perirenal fat. Thus, polyunsaturated fatty acids exert an inhibition of G6PDH and ME activities specifically in liver. Compared with COC, the addition of SUN to the basal diet increased total lipids and polyunsaturated fatty acids contents in the longissimus lumborum muscle, which might improve the organoleptic and dietetic qualities of rabbit meat.

Dietary calcium and blood pressure in experimental models of hypertension. A review.

More than 80 studies have reported lowered blood pressure after dietary calcium enrichment in experimental models of hypertension. The evidence presented here suggests that dietary calcium may act concurrently through a number of physiological mechanisms to influence blood pressure. The importance of any given mechanism may vary depending on the experimental model under consideration. Supplemental dietary calcium is associated with reduced membrane permeability, increased Ca(2+)-ATPase and Na,K-ATPase, and reduced intracellular calcium. These results suggest that supplemental calcium may limit calcium influx into the cell and improve the ability of the VSMC to extrude calcium. This could be a direct effect of calcium on the VSMC or an indirect effect mediated hormonally. The calcium-regulating hormones have all been found to have vasoactive properties and therefore may influence blood pressure. Furthermore, CGRP and the proposed parathyroid hypertensive factor are both vasoactive substances that are responsive to dietary calcium. Therefore, diet-induced variations in calcium-regulating hormones may influence blood pressure. Modulation of the sympathetic nervous system is another important way that dietary calcium can influence blood pressure. There is evidence of altered norepinephrine levels in the hypothalamus as a consequence of manipulations of dietary calcium as well as changes in central sympathetic nervous system outflow. Dietary calcium has also been shown to specifically modify alpha 1-adrenergic receptor activity in the periphery. In some experimental models of hypertension, dietary calcium may alter blood pressure by changing the metabolism of other electrolytes. For example, the ability of calcium to prevent sodium chloride-induced elevations in blood pressure may be attributed to natriuresis. However, natriuresis does not account for all of the interactive effects of calcium and sodium chloride on blood pressure. Sodium chloride-induced hypertension may be due in part to calcium wasting and subsequent elevation of calcium-regulating hormones. Chloride is an important mediator of this effect because it appears that sodium does not cause calcium wasting when it is not combined with chloride. More attention to the central nervous system effects of dietary calcium is needed. Not only can calcium itself influence neural function, but many of the calcium-regulating hormones appear to affect the central nervous system. The influence of calcium and calcium-regulating hormones on central nervous system activity may have important implications for blood pressure regulation and also may extend to other aspects of physiology and behavior.