Differences in homeostatic model assessment (HOMA) values and insulin levels after vitamin D supplementation in healthy men: a double-blind randomized controlled trial.

Vitamin D is thought to play a role in glucose metabolism. The aim of the present study was to determine the effect of vitamin D supplementation on markers of insulin sensitivity and inflammation in men without diabetes with vitamin D deficiency/insufficiency. In this 1-year double-blind randomized controlled trial, 130 men aged 20-65 years (mean age 47.52 ± 11.84 years) with serum 25-hydroxyvitamin D levels <50 nmol/l (mean 38.89 ± 8.64 nmol/l) were randomized to treatment (100 000 IU vitamin D bimonthly) or placebo. Anthropometric measurements, demographic questionnaires, and blood indices (fasting glucose, insulin, high-sensitivity C-reactive protein, lipids) were collected and repeated after 6 and 12 months. The compliance rate was 98.5%. Multivariate models, adjusted for baseline levels, age, body mass index, sun exposure, physical activity and LDL, showed significant differences in insulin and homeostatic model assessment of insulin resistance (HOMA-IR) values between groups. Levels of insulin and HOMA-IR values remained steady during the study period in the treatment group but increased by 16% in the control group (p = 0.038 and p = 0.048, respectively). Vitamin D supplementation administered for 12 months in healthy men maintained insulin levels and HOMA-IR values relative to the increase in the control group. Further studies are needed to establish the long-term effect of vitamin D supplementation on the risk of diabetes.

Identifying the threshold for vitamin D insufficiency in relation to cardiometabolic markers.

BACKGROUND AND AIMS: To determine the association between vitamin D status and cardiometabolic indicators, and to determine the vitamin threshold that affects these parameters. METHODS AND RESULTS: High-tech employees were recruited from a periodic occupational health examination clinic and via the study's website. Diastolic and systolic blood pressure (DBP, SBP), body mass index (BMI), and waist circumference were measured. Serum concentrations of 25(OH)D, fasting plasma insulin (FPI), fasting plasma glucose (FPG), triglycerides (TG), and high sensitive C-Reactive Protein (hs-CRP) were measured in fasting blood samples. Of the 400 men who agreed to participate, 358 (90%) completed the study. Mean age was 48.8 ± 10.2 y, BMI 27.0 ± 3.8 k/m(2), serum 25(OH)D 22.1 ± 7.9 ng/l. Deficiency (defined as serum 25(OH)D < 12 ng/ml) was observed among 10.6%, 29.9% were insufficient (12 < 25(OH)D < 20 ng/ml), and 59.5% had sufficient levels (25(OH)D > 20 ng/ml). BMI, waist circumference, FPI, HOMA-IR, TG, hs-CRP levels, DBP, and SBP were negatively associated with serum 25(OH)D. A curved linear association was found with insulin and HOMA-IR with a significant spline knot at 11 ng/ml. For hs-CRP a spline knot at 14 ng/ml was observed. TG, SBP, and DBP exhibited linear associations with 25(OH)D. CONCLUSIONS: Vitamin D status is related to cardiometabolic indicators in healthy men. We suggest a 25(OH)D threshold of 11-14 ng/ml for these outcomes. Future studies are required to address temporal relationships and the impact of vitamin D supplementation.

Link between confusional migraine, hemiplegic migraine and episodic ataxia type 2: hypothesis, family genealogy, gene typing and classification.

An association between hemiplegic migraine (HM) and episodic ataxia type 2 (EA2) has been described; both disorders are linked to mutations in the CACNA1A gene. Although confusion occurs in 21% of patients with HM, we found only one case in the literature of confusional episodes associated with ataxia without hemiplegia. These findings raise the possibility of confusional episodes being part of both the HM and EA2 phenotype. However, a patient with episodic ataxia, confusional spells and CACNA1A gene mutations has not been identified. We describe four individuals, spanning three generations of a family, with episodic ataxia without hemiplegia and confusion, in association with a CACNA1A mutation. We follow with a description of the relationship between the CACNA1A mutations and the three syndromes, suggesting a potential need for a new classification in which the conditions can be subsumed.

New daily persistent headache in the paediatric population.

We conducted a clinic-based study focusing on the clinical features of new-onset chronic daily headaches (CDH) in children and adolescents. The clinical records and headache diaries of 306 children and adolescents were reviewed, to identify 187 with CDH. Relevant information was transferred to a standardized form that included operational criteria for the diagnoses of the headaches. Since we were interested in describing the clinical features of these headaches, we followed the criteria A and B of the 2nd edn of the International Classification of Headache Disorders (ICHD-2) and refer to them as new daily persistent headaches (NDPH) regardless of the presence of migraine features (therefore, this is a modified version of the ICHD-2 criteria). From the 56 adolescents with NDPH, most (91.8%) did not overuse medications. Nearly half (48.1%) reported they could recall the month when their headaches started. NDPH was more common than chronic tension-type headache in both adolescents overusing and not overusing medication. Individuals with NDPH had headaches fulfilling criteria for migraine on an average of 18.5 days per month. On most days, they had migraine-associated symptoms (one of nausea, photophobia or phonophobia)). NDPH is common in children and adolescents with CDH. Most subjects do not overuse medication. Migraine features are common.

Key points in migraine prophylaxis: patient perspective.

Migraine is a chronic neurological condition with heterogeneous presentation. It is associated with significant pain, disability, and diminished quality of life in a large proportion of patients. Patients with severe and/or frequent migraines require prophylaxis, which implies daily administration of anti-migraine compounds for several months, with potential adverse events or contraindications. This paper reviews the main factors influencing patient acceptance of anti-migraine prophylaxis, providing practical suggestions to maximize patient agreement with, and adherence to, preventive treatment.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Relationship of diet to serum lipids.

Serum cholesterol, high-density lipoprotein cholesterol, and triglycerides of three groups of Seventh-day Adventists (SDAs)--true vegetarians, lacto-ovo vegetarians, and nonvegetarians--and the general population were measured and related to age, sex, and diet. True vegetarian SDAs had the lowest cholesterol levels while cholesterol levels of the other three groups were similar. Triglyceride levels were highest in the true vegetarian SDAs and lowest in general population. Cholesterol levels rose with increasing age while percentage of high-density lipoprotein cholesterol fell. Female SDAs in all three dietary groups had higher cholesterol levels than males. In all four groups percentage of high-density lipoprotein cholesterol was higher in females than in males. In the male subjects, cholesterol levels varied linearly and inversely with carbohydrate intake. Protein and fat intake in true vegetarian SDAs and lacto-ovo vegetarian SDA groups were lower than in the nonvegetarian SDA and general population groups. The differences in protein and fat intake were reflected in elevations in serum cholesterol levels. In the female subjects, cholesterol levels were also inversely correlated with carbohydrate intake but not as distinctly as in the males. True vegetarian SDA females ingested less protein and fat than the other three groups and exhibited lower serum cholesterol levels. Cholesterol levels in lacto-ovo vegetarian SDA, nonvegetarian SDA, and general population female subjects were similar and did not reflect differences in protein or fat intake. The true vegetarian dietary lifestyle resulted in lowest cholesterol levels, however, if it was breeched to the least extent, cholesterol levels rose. Thus, intake of skim, low fat, or whole milk resulted in similar serum cholesterol levels as did low or high egg consumption.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Binding of bile salts to dietary residues.

The binding of glycocholic and glycochenodeoxycholic acids to dried defatted residues of homogenized diets consumed by four dietary groups has been measured. The four groups were true vegetarian Seventh-day Adventists (SDA), lacto-ovo vegetarian SDA, nonvegetarian SDA, and the general population. Glycocholic acid was bound to the same extent (7 to 9%) by all four dietary residues. The true vegetarian SDA residues bound significantly more glycochenodeoxycholic acid than those of either lacto-ovo vegetarian SDA (p less than 0.001) or nonvegetarian SDA (p less than 0.001). The general population residue bound significantly more glycochenodeoxycholic acid than did those of nonvegetarian SDA (p less than 0.001). Binding of glycochenodeoxycholic acid was significantly correlated with dietary neutral detergent fiber (p less than 0.001), hemicellulose (p less than 0.01) and cellulose (p = 0.01). There was no correlation between the binding of glycochenodeoxycholic acid and dietary lignin, pectin, or cutin.

Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Comparison of serum hexosaminidase levels.

Elevated levels of serum hexosaminidase (beta-2-acetamido-2-deoxy-D-glucoside; N-acetamidodeoxy-D-glucohydrolase, EC 3.2.1.30)(HEX) have been found in patients with cancer. In view of the reported low levels of colon cancer among Seventh-day Adventists (SDA) we determined levels of total HEX, and its heat-labile (HEX-A) and heat-stable (HEX-B) isozymes in vegetarian SDA, lacto-ovo vegetarian SDA, nonvegetarian SDA, and the general public. Lowest levels of total HEX and highest percentage of HEX-B were found in vegetarian SDA. The levels in the other three groups were comparable, and these differences were seen at all age levels. Female subjects exhibited significantly lower total HEX levels than the males but the percentage of HEX-B was the same.

Influence of whole or skim milk on cholesterol metabolism in rats.

Male Wistar rats were fed commercial ration and given whole milk, skim milk, or water to drink. After 3 weeks the control group showed the greatest weight gain. Rats given whole milk had the smallest livers. Serum cholesterol levels were significantly lower in rats fed either whole or skim milk, but other serum lipids were unaffected. Liver triglyceride levels were lowest in the rats on skim milk. Activities of hepatic fatty acid synthetase, hydroxymethyl-glutaryl coenzyme A reductase and cholesterol 7alpha-hydroxylase were similar in the two milk-fed groups and considerably lower than in the controls.

Dietary fiber and intestinal adaptation: effects on lipid absorption and lymphatic transport in the rat.

Adult male rats fed defined diets containing various fiber supplements or cholestyramine for 4 wk were surgically provided with lymphatic drainage catheters and starved overnight. After duodenal administration of a standard lipid test emulsion, absorption rates and lipoprotein distributions of cholesterol and oleic acid were determined. Prefeeding diets containing cellulose or alfalfa had no significant effect on oleic acid absorption. Diets containing pectin, guar gum, metamucil, mixed fibers (Fibyrax), or cholestyramine caused decreased lymphatic recovery in the initial period; except for the metamucil diet, no decrease was caused in the 24-h recovery, suggesting delayed but not impaired absorption. Fatty acid distribution among lipoproteins and chylomicron size were not altered by diet. All supplements caused a significant reduction in cholesterol absorption during the initial period, and cholesterol absorption remained depressed in animals prefed pectin, guar gum, mixed fibers, metamucil, and cholestyramine.

Cholesterol vehicle in experimental atherosclerosis. Part 15. Randomized butter and randomized lard.

Randomized lard and butter oil were conpared with native lard and butter oil for their effects on cholesterol-induced atherosclerosis in rabbits. In each experiment there was also a group fed corn oil. The diets contained 2% cholesterol and 6% fat and were fed for eight weeks. Randomization of either butter or lard had virtually no effect as regards their atherogenic potential when fed as part of a diet containing 2% cholesterol. The corn oil-containing diet was less atherogenic than any of the other fats.

Cholesterol vehicle in experimental atherosclerosis. Part 16. Effect of peanut oil on pre-established lesions.

Rabbits were fed an atherogenic diet (2% cholesterol and 6% corn oil) for 8 weeks and then divided into groups of equal average serum cholesterol levels. One group was autopsied, and the others were returned to cholesterol-free diets consisting of commercial laboratory ration or ration augmented with 6% corn oil, peanut oil or PGF, a fat designed to resemble peanut oil minus arachidic and behenic acids. The animals were maintained on the diets for 8 more weeks. On all regimens, severity of atherosclerosis was exacerbated. The extent of exacerbation was significantly less in rabbits fed corn oil than in the others. The extent of exacerbation of lesions appears to be a function of the level of unsaturation of the dietary fats.

Flordipine, a calcium channel blocker, which does not influence lipidemia or atherosclerosis in cholesterol-fed rabbits.

Data relating to the effects of calcium channel blockers on experimental atherosclerosis in rabbits are inconsistent with most studies finding no effect on either serum lipids or atherosclerosis. We have administered flordipine (5, 15 or 45 mg/kg/day) for 10 weeks to rabbits fed 1% cholesterol and 4% corn oil. At no level of treatment was there an effect on serum or liver lipids or on aortic sudanophilia.

Experimental atherosclerosis in rabbits fed cholesterol-free diets. Part 7. Interaction of animal or vegetable protein with fiber.

Rabbits were maintained for 10 months on a semipurified, cholesterol-free atherogenic regimen. All diets contained sucrose (40%) and hydrogenated coconut oil (14%). The protein (25%) was either casein or soya protein and the fiber (15%) was either wheat straw, alfalfa, or cellulose. Within either protein group the order for induction of cholesteremia was cellulose=wheat straw greater than alfalfa. For atherogenesis, the effect was cellulose greater than wheat straw greater than alfalfa Soya-wheat straw or soya-cellulose diets were less cholesteremic and atherogenic than their casein counterparts. When alfalfa was the fiber, the two types of protein were almost equivalent. Our results show that casein may be more cholesteremic and atherogenic than soya protein under certain conditions (cellulose or wheat straw as fiber) but the addition of alfalfa to the diet renders the two proteins equivalent.

Experimental atherosclerosis in rabbits fed cholesterol-free diets.

Rabbits were fed a semipurified, cholesterol-free atherogenic diet containing 40% sucrose, 25% casein, 14% fat, 15% fiber, 5% salt mix and 1% vitamin mix. The fats were corn oil (CO), palm kernel oil (PO), cocoa butter (CB), and coconut oil (CNO). The rabbits were bled at 3, 6, and 9 months and killed at 9 months. Serum lipids of rabbits fed CO were unaffected. Serum cholesterol levels (mg/dl) at 9 months were: CO -- 64; PO -- 436; CB -- 220; and CNO -- 474. HDL-cholesterol (%) was: CO -- 37; PO -- 8.6; CB -- 25.1; and CNO -- 7.0. Average atherosclerosis (arch + thoracic/2) was: CO -- 0.15; PO -- 1.28; CB -- 0.53; and CNO -- 1.60. Cocoa butter (iodine value 33) is significantly less cholesterolemic and atherogenic than palm oil (iodine value 17) or coconut oil (iodine value 6). The difference between the atherogenic effects of cocoa butter and palm oil may lie in the fact that about half of the fatty acids of palm oil are C 16 or shorter, whereas 76% of the fatty acids of cocoa butter are C 18 or longer.

Experimental atherosclerosis in rabbits fed cholesterol-free diets. Part 9. Beef protein and textured vegetable protein.

Rabbits were fed a semipurified diet containing 40% sucrose, 25% protein, 15% fiber and 14% tallow. The proteins fed were beef (B), textured vegetable protein (TVP) and casein (C). One diet contained beef-TVP (1 : 1) and in another a soy carbohydrate fraction, spent flakes, was added to the diet; it provided 2.2% protein and 10.5% fiber. TVP provided 6.4% soluble carbohydrate and 10.5% fiber. The diets were fed from 8 months. Diets containing beef protein or casein gave significantly higher serum cholesterol levels and atherosclerosis and significantly lower serum HDL-cholesterol than did the other 3 diets. The beef-TVP (1 : 1) diet gave low serum cholesterol (67% below beef) levels and atherosclerosis (47% below beef). This effect is probably due to the protein. The diet containing spent flakes gave low serum cholesterol levels (44% below beef) and atherosclerosis (45% below beef). This effect is attributed to the different fiber. The lowest serum cholesterol levels and least severe atherosclerosis were observed in the rabbits fed TVP.

Cholesterol vehicle in experimental atherosclerosis. Part 18. Comparison of North American, African and South American peanut oils.

Peanut oils were obtained from the United States (NAPNO), Africa (APNO), and South America (SAPNO) and their effects on atherosclerosis in rabbits fed 2% cholesterol were determined. The major differences among the oils were in the content of oleic (NAPNO, 48.9%; APNO, 58.6%; SAPNO, 36.4%) and linoleic (NAPNO, 29.6%; APNO, 21.7%; SAPNO, 41.1%) acids. In a series of 4 experiments it was found that South American peanut oil was 7% more atherogenic than African peanut oil and 18% more atherogenic than North American peanut oil. American peanut oil was 14% more atherogenic that corn oil (CO). South American peanut oil gave highest serum and liver lipid levels. The differences in atherogenicity may be due to the structure of the triglycerides of the various peanut oils.

Experimental atherosclerosis in rabbits fed cholesterol-free diets. 13. Interaction of proteins and fat.

The atherogenic and cholesterolemic effects of animal protein vis-a-vis plant protein are well documented. Virtually all the studies were carried out using diets high in saturated fat, such as coconut oil. In order to determine if the same effects were seen with less saturated fat, we have compared atherogenic effects of an animal protein (casein) with those of a plant protein (soybean protein isolate) fed with partially hydrogenated soybean oil (PHS) (iodine value 72) or soybean oil (iodine value 134) as part of a cholesterol-free semipurified diet. After 6 months only rabbits fed casein-PHS exhibited elevated levels of plasma and liver cholesterol and triglycerides and atherosclerosis. Rabbits fed soy protein-PHS had slightly higher plasma cholesterol and triglycerides than did those fed soy protein and soybean oil, but values in both groups were in the normal range. The different effects of animal and plant protein on lipidemia and atherosclerosis can be influenced by dietary fat and appear to be dependent on fat saturation.

Experimental atherosclerosis in rabbits fed cholesterol-free diets. Part 12. Comparison of peanut and olive oils.

The atherogenicity of peanut oil is well established as is the fact that the structure of the component triglycerides of peanut oil influences its atherogenicity. This study was carried out to determine if the relative saturation of peanut oil was partly responsible for the observed effects. Rabbits were fed a semipurified, cholesterol-free diet containing 14% of North American peanut oil (iodine value, 100), South American peanut oil (iodine value, 110) or olive oil (iodine value, 83) for 8 months. Rabbits fed olive oil exhibited higher levels of serum and liver lipids than did the two peanut oil-fed groups but significantly lower levels of aortic atherosclerosis. The findings confirm earlier observations that the structure of a fat can have an affect on its atherosclerogenic potential that is independent of its level of unsaturation.

Effects of casein and soy protein on hepatic and serum lipids and lipoprotein lipid distributions in the rat.

Rats fed a semipurified diet containing casein developed higher levels of circulating triglycerides and cholesterol than animals fed a soy protein-containing diet. The increased serum lipid levels in non-fasted rats were associated largely with the d less than 1.006 g/ml lipoprotein particles (e.g. chylomicrons or very low density-like lipoproteins). In addition, casein-fed rats exhibited higher levels of circulating insulin and depressed hepatic 7 alpha-hydroxylase levels compared to soy-fed rats. Supplementation of the casein diet with arginine, to give an arginine/lysine ratio comparable to that in the soy diet, resulted in a reduction of d less than 1.006 g/ml lipids, a reduction in serum insulin levels and an elevation in hepatic 7 alpha-hydroxylase activity. Supplementation of the soy diet with lysine also resulted in modification of these parameters toward those observed with casein diets, albeit the effects were less dramatic. The results suggest that the hyperlipidemia associated with feeding casein-based diet is associated with decreased rates of clearance of chylomicron-like lipoproteins and their component triglycerides and cholesterol. Furthermore, this is largely prevented by addition of arginine to diets containing casein as the sole protein source.